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Posts Tagged ‘Percutaneous coronary intervention’


Ischemic Stable CAD: Medical Therapy and PCI no difference in End Point: Meta-Analysis of Contemporary Randomized Clinical Trials

Reporter: Aviva Lev-Ari, PhD, RN

 

SOURCE

Stergiopoulos K, Boden WE, Hartigan P, et al. Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: A collaborative meta-analysis of contemporary randomized clinical trialsJAMA Intern Med 2013; DOI:10.1001/jamainternmed.2013.12855. Available at:http://www.jamainternalmedicine.com.

 

PCI No Benefit Over Medical Therapy in Ischemic Stable CAD

December 02, 2013

NEW YORK, NY — A new analysis is calling into question the de facto rationale for many of the revascularization procedures taking place today, at least in patients with stable coronary artery disease[1]. In a meta-analysis of more than 5000 patients, PCI was no better than medical therapy in patients with documented ischemia by stress testing or fractional flow reserve (FFR).

“Cardiology has a long history of finding a marker of a bad outcome and treating that marker of that bad outcome as if it were the cause of the bad outcome,” senior author on the study, Dr David Brown (State University of New York [SUNY]–Stony Brook School of Medicine), told heartwire . In the case of proceeding to PCI on the basis of documented ischemia, that stems from evidence that patients with ischemia have a worse prognosis than patients who don’t.”It has gotten to the point that a positive stress test [is the gateway] to doing an intervention, even if the ischemia is not in the same ischemic territory as the vessel being treated,” he said. “The medical/industrial complex in cardiology is now focused on finding and treating ischemia, and I think that’s not justified, and these data suggest that that’s not justified.”

Brown and colleagues, with first author Dr Kathleen Stergiopoulus (SUNY–Stony Brook School of Medicine), reviewed the literature for randomized clinical trials of PCI and medical therapy for stable CAD conducted over the past 40 years, ultimately including five trials of 5286 patients. These were a small German trial published in 2004, plus MASS II COURAGE , BARI 2D , and FAME 2 . In all, 4064 patients had myocardial ischemia documented by exercise, nuclear or echo stress imaging, or FFR.

Over a median follow-up of five years, mortality, nonfatal MI, unplanned revascularization, and angina were no different between patients treated medically vs those treated with PCI.

Odds Ratio, PCI vs Medical Therapy

Outcome Odds ratio 95% CI
Death 0.90 0.71–1.16
Nonfatal MI 1.24 0.99–1.56
Unplanned revascularization 0.64 0.35–1.17
Angina 0.91 0.57–1.44

“These findings are unique in that this is the first meta-analysis to our knowledge limited to patients with documented, objective findings of myocardial ischemia, almost all of whom underwent treatment with intracoronary stents and disease-modifying secondary-prevention therapy,” Stergiopoulus et al write.

The findings, they continue, “strongly suggest that the relationship between ischemia and mortality is not altered or ameliorated by catheter-based revascularization of obstructive, flow-limiting coronary stenosis.”

To heartwire , Brown pointed out that their analysis could not separate out patients who had small amounts of ischemia from those with larger ischemic territories. “Maybe that’s where the differentiating factor will be,” he acknowledged, adding that the 8000-patient ISCHEMIA trial, still ongoing, will hopefully yield some insights.

Current practice, however, is to check for ischemia and to proceed with catheterization and, usually, revascularization when ischemia is confirmed by stress testing or during FFR. “But if that doesn’t improve outcomes, why are we doing it?” Brown asked. “We think that needs to be rethought.”

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Information from Industry

Commenting on the study for heartwire Dr Peter Berger(Geisinger Health System, Danville, PA) pointed out: “There is no question that PCI is more effective than medical therapy for relief of symptoms: the more severe the angina and the more active the patient, the greater the superiority of PCI.” And, as Berger noted, most of the studies included in this analysis documented ischemia but did not report on the frequency or severity of angina at baseline.

That said, “Patients with minimal angina—and certainly those with silent ischemia but no angina—are unlikely to have a significantly greater reduction of symptoms with PCI, and PCI is rarely beneficial in such patients.”

Moreover, Berger continued, it has been clearly established that PCI does not reduce the risk of death or MI in most such patients.

“I very much agree with the authors, however, that just because more severe ischemia has been shown to be associated with a worse long-term prognosis, reducing the ischemic burden ought not be assumed to reduce the likelihood of death or MI. In most such patients, it does not.”

Stergiopoulos and Brown had no disclosures. Disclosures for the coauthors are listed in the paper.

SOURCE 

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Stent Design and Thrombosis:  Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents

Curator: Aviva Lev-Ari, PhD, RN

UPDATED 2/8/2014

Reva Completes Drug-Eluting Bioresorbable Stent Trial Enrollment

January 24, 2014
Reva Medical Clinical Trial ReZolve2 Bioresorbable Stent
January 24, 2014 — Reva Medical Inc. has completed enrollment in the clinical trial of the ReZolve2 drug-eluting bioresorbable scaffold. A total of 112 patients from three continents have been enrolled in the trial to provide the data needed to apply for CE marking.

The company anticipates filing a CE mark application before the end of 2014. It plans to report an update on trial data at the Paris Course on Revascularization (EuroPCR) in Paris, France, May 2014.

For more information: http://www.teamreva.com

This article has the following SIX Parts:

Part I: Bifurcation Intervention – Stent Design and Thrombosis

Part II: Biodegradable Polymer DES Reduce Stent Thrombosis Rates vs. Durable Polymer DES

Part III: Stent Flexibility versus Stent Concertina Longitudinal Deformation Effect on Outcomes

Part IV: Stent Thrombosis Through the Generations of Stent Design

Part V: Stent Thrombosis in Randomized Trials of Drug-Eluting Stents: Reappraisal of the Synthesis of Evidence!

Part VI. Duration of Dual Antiplatelet Therapy following Zotarolimus-Eluting Stents and A New Strategy for Discontinuation of Dual Antiplatelet Therapy

Conclusions by Larry H Bernstein, MD, FCAP

 

Part I

Bifurcation Intervention – Stent Design and Thrombosis

 

The 5 Ts of Bifurcation Intervention: Type, Technique, Two Stents, T-Stenting, Trials

Ron Waksman, MD, FACC; Laurent Bonello, MD

Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.

J Am Coll Cardiol Intv. 2008;1(4):366-368. doi:10.1016/j.jcin.2008.06.006

http://interventions.onlinejacc.org/article.aspx?articleid=1110233

Bifurcation, the division of an artery into 2 branches, is a common anatomy feature of the human coronary tree and is recognized as a common site for atherosclerotic plaque buildup due to the differences in coronary flow, turbulence, and shear stress at the site of the bifurcation. The prevalence of bifurcation stenosis in the human coronary tree is reported to be between 15% to 20% of all interventions and is considered complex and challenging for percutaneous intervention.

Numerous techniques and devices have been proposed to address the treatment of bifurcation lesions: balloon angioplasty, metallic stents, drug-eluting stents (DES), newly designed stents with dedicated access to the side branch, and full bifurcated stents. Clearly, the interest in the treatment of bifurcation stenting has increased with the availability to significantly reduce the recurrence rate, but this was associated with the increasing fear of stent thrombosis. Despite this extensive body of work and the latest innovations of 2008, there is not a “one size fits all” solution to the bifurcation puzzle, while the optimal percutaneous coronary intervention technique remains undetermined.

In this issue of JACC: Cardiovascular Interventions, Routledge et al. (1) present 2-year outcome data of 477 patients treated for bifurcation coronary disease with provisional side branch T-stenting using DES, and claim a systematic approach feasible for 90% of the patients, with acceptable efficacy and safety profiles. This editorial is written in response to this provocative study and will cover the 5 Ts of bifurcation stenting: Type of bifurcation, Techniques, Two stents versus one, T-stenting, and Trial design.

Types Of Bifurcation

Part of the complexity in treating bifurcation lesions and applying technique standardization is in regard to the numerous anatomic patterns of bifurcation stenosis and the lack of consistent, reliable methodology. Further, the variations in anatomy, angulations, and location of the disease within the bifurcation have led to the development of numerous classifications of bifurcation lesions, with differentiation between “true” bifurcation (both the main and the branch are diseased) and “false” bifurcation (either the main or the branch is disease) based on angiography. The most popular and intuitive classification is that of Medina et al. (2), which identifies at least 7 types of bifurcation involving the proximal main branch, the distal main branch, and the side branch, with different variations. If we add this to the classification of the various potential angulations between the main and the side branches, the sizes of the parent vessel and the side branch, and the different potential morphologies of the diseased segment (calcification, fibrosis, and so on), we can identify nearly endless anatomic and morphologic configurations of bifurcations types (3).

Technique

2 stents versus 1

Numerous techniques have been proposed for the treatment of bifurcation lesions. The first decision that the operator must make is whether the procedure will involve 1 or 2 stents. The most important information relates to the size of the side branch and the degree of the disease in this branch. Or do we really care about the side branch? Initially, the thought of using 2 stents for all bifurcated lesions was appealing because this approach usually resulted in an optimal angiographic success rate. Among the most popular techniques that employed the use of 2 stents are the culotte, crush, V-stenting, T-stenting, and simultaneous kissing stents (4). However, after numerous reports of high rates of late complications, including an increase in stent thrombosis and restenosis frequency, systematical use of 2 stents did not live up to expectations (58). These poor outcomes were observed regardless of the technique used and thus discouraged the liberal use of 2 stents. Therefore, the provisional strategy gained ground: try 1 stent first, and, if the result is not acceptable (dissection, impaired lumen, or flow of the other branch), use a second stent for the side branch. The superiority of such a provisional approach over a 2-stent technique was confirmed by the Nordic Bifurcation study (9). The results of this study had operators favoring the provisional rather than the 2-stent approach. However, many questions still remain regarding this approach: can we predict which bifurcation will require 2, rather than 1 stent? In how many patients is the provisional approach feasible? If a second stent is required, what then is the optimal technique for implantation of the second stent? Is provisional stenting still superior to the 2-stent approach with the new generation of stents available? And lastly, are the latest technique modifications, including pre- and post-kissing, clinically beneficial?

The present study demonstrated that provisional stenting is feasible in 90% of all patients, and those who received a second stent in the side branch, 28%, had similar long-term outcomes as those treated with 1 stent. The outcome of this study is similar to that of the Nordic Bifurcation study, which observed no difference in outcomes at 6 months’ follow-up between 1 and 2 stents (9). Finally, the latest Nordic Bifurcation Stent Technique study, comparing the culotte and crush techniques, reported low rates of angiographic restenosis and major adverse cardiac events for both techniques (10), with similar angiographic and clinical outcomes as the provisional approach with T-stenting reported in the Routledge et al. study (1). This leaves us with the question of whether, in 2008, provisional stenting is still superior to 2 stents when an improved technique is applied and new-generation stents are used?

T-stenting

Use of the provisional T-stenting technique is gaining interest because of its simplicity and subsequent reports of good mid-term outcomes (1113). As illustrated in the present report by Routledge et al. (1), it is feasible in a large majority of patients and is associated with low rates of recurrent events during long-term follow-up. In the past, the technique was described to resolve dissections of a side branch (8) or as a new technique for the use of 2 stents for the treatment of bifurcation lesions (11). In the present study, the authors used provisional T-stenting as the default technique. From a technical point of view, provisional T-stenting offers several advantages compared with other bifurcation techniques: it is simple to perform in most cases, and it limits the need for a second stent, as illustrated by the low rate of stenting in the side branch in the present study. One technical aspect of the procedure remains in question: is kissing post-procedure mandatory in the provisional T-stenting approach with 1 or 2 stents? Bench testing observed that the final kissing balloon may have several interesting advantages: it opens the stent cells to the side branch, it allows the side branch ostium to be at least partially covered by stent struts, and it prevents the main branch stent from becoming deformed by side branch dilation. Further, in previous studies involving crush stenting, kissing balloon was shown to be critical in preventing restenosis (14). Nevertheless, the clinical impact of a final kissing balloon in provisional T-stenting must be established in future trials. Several limitations should be considered with T-stenting: it is not applicable for all lesions, it is dependent on the bifurcation angle and cannot be applied to angles <40°; the second stent, if needed, may not be able to fully cover the ostium, which will result in switching to a mini-crush technique, and like other techniques, there is a learning curve. Nevertheless, among today’s available options, the provisional T-stenting technique seems to be the simplest and is associated with favorable long-term outcomes.

Table 1 Comparison of Bifurcation Studies in the DES Era

Bifurcation stenting continues to challenge the interventional cardiologist. Despite the recent literature, including the present manuscript, there is a lack of consensus on an array of important issues, such as: Which branches deserve protection? Should provisional stenting be the default strategy of bifurcation stenting? Should we always pre-dilate the side branch? And if 2 stents are required, which technique would be the best? Is kissing always mandatory for both branches? Are DES more thrombogenic? And finally, how will the special dedicated bifurcated stents be integrated into current practice? With further trials and perhaps the sixth T in bifurcation stenting (Time), the answers to these important questions will be answered.

References

1 Routledge  H.C., Morice  M.-C., Lefèvre  T.; 2-year outcome of patients treated for bifurcation coronary disease with provisional side branch T-stenting using drug-eluting stents. J Am Coll Cardiol Intv. 1 2008:358-365.

2 Medina  A., Suárez de Lezo  J., Pan  M.; A new classification of coronary bifurcation lesions. Rev Esp Cardiol. 59 2006:183

3 Thomas  M., Hildick-Smith  D., Louvard  Y.; Percutaneous coronary intervention for bifurcation disease. A consensus view from the first meeting of the European bifurcation club. Euro Intervention. 2 2006:149-153.

4 Louvard  I., Lefevre  T., Morice  M.C.; Percutaneous coronary intervention for bifurcation coronary disease. Heart. 90 2004:713-722.

5 Iakovou  I., Schmidt  T., Bonizzoni  E.; Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 293 2005:2126-2130.

6 Finn  A.V., Kolodgie  F.D., Harnek  J.; Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus- or paclitaxel-eluting stents. Circulation. 112 2005:270-278.

7 Daemen  J., Wenaweser  P., Tsuchida  K.; Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet. 369 2007:667-678.

8 Carrie  D., Karouny  E., Chouairi  S., Puel  J.; “T” shaped stent placement: a technique for the treatment of dissected bifurcation lesions. Cathet Cardiovasc Diagn. 37 1996:311-313.

9 Steigen  T.K., Maeng  M., Wiseth  R.; Randomized study on simple versus complex stenting of coronary artery bifurcation lesions: the Nordic Bifurcation study. Circulation. 114 2006:1955-1961.

10 Gunnes P, Niemela M, Kervinen K, et al, for the Nordic-Baltic PCI Study Group. Eight months angiographic follow-up in patients randomized to crush or culotte stenting of coronary artery bifurcation lesions. The Nordic Bifurcation Stent Technique study. Paper presented at: ACC 2008 Late Breaking Trials; April 1, 2008; Chicago, IL.

11 Palvakis  G., de Man  F., Hamer  B., Doevendas  P., Stella  P.R.; Registry of new technique on coronary bifurcation lesions: the Utrech-“T” experience. Euro Intervention. 3 2007:262-268.

12 Pan  M., Suárez de Lezo  J., Medina  A.; Drug-eluting stents for the treatment of bifurcation lesions: a randomized comparison between paclitaxel and sirolimus stents. Am Heart J. 153 2007:15-17.

13 Ormiston  J.A., Webster  M.W., El Jack  S.; Drug-eluting stents for coronary bifurcations: bench testing of provisional side-branch strategies. Catheter Cardiovasc Interv. 67 2006:49-55.

14 Ge  L., Airoldi  F., Iakovou  I.; Clinical and angiographic outcome after implantation of drug-eluting stents in bifurcation lesions with the crush stent technique: importance of final kissing balloon post-dilation. J Am Coll Cardiol. 46 2005:613-620.

15 Hoye  A., Iakovou  I., Ge  L.; Long-term outcomes after stenting of bifurcation lesions with the “crush” technique: predictors of an adverse outcome. J Am Coll Cardiol. 47 2006:1949-1958.

16 Sharma  S.K.; Simultaneous kissing drug-eluting stent technique for percutaneous treatment of bifurcation lesions in large-size vessels. Catheter Cardiovasc Interv. 65 2005:10-16.

17 Moussa  I., Costa  R.A., Leon  M.B.; A prospective registry to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions using the “crush technique”. Am J Cardiol. 97 2006:1317-1321.

18 Yanagi  D., Shirai  K., Takamiya  Y.; Results of provisional stenting with a sirolimus-eluting stent for bifurcation lesion: multicenter study in Japan. J Cardiol. 51 2008:89-94.

19 Di Mario  C., Morici  N., Godino  C.; Predictors of restenosis after treatment of bifurcational lesions with paclitaxel eluting stents: a multicenter prospective registry of 150 consecutive patients. Catheter Cardiovasc Interv. 69 2007:416-424.

20 Tsuchida  K., Colombo  A., Lefèvre  T.; The clinical outcome of percutaneous treatment of bifurcation lesions in multivessel coronary artery disease with the sirolimus-eluting stent: insights from the Arterial Revascularization Therapies Study part II (ARTS II). Eur Heart J. 28 2007:433-442.

SOURCE

J Am Coll Cardiol Intv. 2008;1(4):366-368. doi:10.1016/j.jcin.2008.06.006

http://interventions.onlinejacc.org/article.aspx?articleid=1110233

 

Bifurcation Stenting

David Hildick-Smith, MD

Consultant Cardiologist and Director of Cardiac Research

Brighton-Sussex University Hospital NHS Trust

Brighton, UK

Slide 1

Bifurcation stenting and its various ramifications in the modern cardiology world. The objectives of this presentation are to talk about some of the difficulties of bifurcation stenting, to summarize the recent study data, and to talk a little bit about dedicated stent systems, as well.

Dedicated Bifurcation Stent Systems – Main types:

Side branch facilitation

Side branch stenting incorporated

Main branch stenting with enhanced access

True dedicated systems

Slide 32

So we then have the issue of dedicated stent systems. Are they the answer to some of these questions? Are they going to bail us out of these difficult geometric issues of bifurcations? There are a number of dedicated stent systems in development and available at the moment, and they fall into a few different groups. There are systems which simply facilitate side branch access. There are systems which actually incorporate side branch stenting as the primary philosophy. There are those which are essentially a main branch stent with enhanced access. And then there are the truly dedicated systems.

Bifurcation Stenting: Should You Keep it Simple

You Keep it Simple

Facilitation

Increasing success of provisional T

Slide 33

If we look at the facilitation group, there are stent systems available where there’s a wire that is integral to the balloon system, and will perhaps then facilitate getting into the side branch, and may certainly facilitate making sure that you are,

Side Branch Ostial Coverage Stents:

Scaffold side branch ostium

Allow subsequent main vessel stenting

The side branch ostial coverage stents are intended to scaffold the side branch and retain main vessel stenting capabilities. There are a couple of stents of this nature on the market at the moment which are undergoing clinical trials to see their general applicability.

Main Vessel Enhanced Access Stents

Pop-up/expand into side vessel

Improve subsequent or immediate access to side branch

Slide 35

The next group is the main vessel enhanced access stents, which, either through a pop-up mechanism with mechanical scaffolding of the side branch ostium, or with a proximal stent which is self-expanding, enhance the access to the side branch, so that you have both immediate access and subsequent access. Which is one of the things that people worry about in this situation, which is, what happens if you have to come back to that side branch vessel a few months later? Will you be able to gain access to it? So these tools may have a role there.

True Dedicated Bifurcation Stent

Stenting of both branches

Slide 36

The fourth group is the true dedicated bifurcation stent. These are clearly the most useful, but of course, mechanically and from an engineering point of view, the most difficult to create and make work. They will certainly have a potential role in bifurcation stenting, but there’s a little  way to go before they could be used in a wide manner.

Slide 37

The dedicated systems, while most are quite ingenious, unfortunately most will not survive in their current format. But the true dedicated bifurcation stent will certainly have a role in the left main. And, as we come back increasingly from these bifurcations to the left main and get a mandate to be able to treat that, this is an area where there will be a significant place for dedicated bifurcation stent systems.

Conclusions

• Bifurcations remain troublesome

• Provisional T stenting is the gold standard

• Subsets of bifurcations require complex strategies

• Large side branches

• Longer ostial disease

• Current complex strategies fail us

• Crush fails more than culotte

• Dedicated devices will have a role

• Large bifurcations in main coronary tree

• Left main

Slide 38

In conclusion, bifurcation stenting is still a troublesome area. Provisional T stenting is the gold standard approach across the board, but we mustn’t forget that there may well be, and I believe there are, subsets of bifurcations which do require a complex strategy. These are the ones with large side branches and significant length of disease at the ostium of that side branch. The current complex strategies do fail from a mechanical point of view, and in that respect crush fails more than culotte. Although it’s a difficult time for dedicated devices at the moment, I think they will have a role, particularly in large bifurcations in the main coronary tree and, most particularly of all, in the left main stem.

SOURCE

http://www.theheart.org/documents/satellite_programs/intervsurgery/913801/BifurcationStenting_REVISED_FINAL.pdf

Part II

Biodegradable Polymer DES Reduce Stent Thrombosis Rates vs. Durable Polymer DES

March 27, 2012 — Biodegradable polymer drug-eluting stents (DES) provide better long-term safety and efficacy than durable polymer DES, according to findings from an analysis of three major clinical trials

  • ISAR-TEST 3,
  • ISAR-TEST 4 and
  • LEADERS.

The data were presented at at the American College of Cardiology’s 61st Annual Scientific Session. The findings provide the first combined long-term data on the comparison between biodegradable polymer DES and durable polymer DES. Designed to improve long-term clinical outcomes while also shortening healing time, biodegradable polymer DES are a new generation of DES that have undergone little research and thus have yet to substantiate its claims. The three analyzed studies showed that after four years, use of biodegradable polymer DES resulted in

  • lower rates of target lesion revascularization,
  • definite stent thrombosis and
  • cardiac death and
  • heart attack than durable polymer DES.

“Because it is often difficult to design individual trials to test for differences in rarely occurring adverse events [like stent clotting], we pooled the data from the three largest trials to see if any differences between the two stent types could be seen,” said co-lead investigator Robert A. Byrne, M.B., B.Ch., Ph.D., a cardiologist at Deutsches Herzzentrum in Munich, Germany. “In addition, by including surveillance out to four years, this helped us better capture the differences between the two stents, as benefit was expected to first emerge with long-term follow-up.”

Among all three analyzed trials, 2,358 patients were randomly assigned to angioplasty with a biodegradable polymer DES (sirolimus-eluting = 1,501; biolimus-eluting = 857), while 1,704 patients were treated with a durable polymer SES (all sirolimus-eluting).

At the four-year follow-up point, the researchers found that the risk of target lesion revascularization (the study’s primary efficacy endpoint) was significantly lower among those patients treated with a biodegradable polymer DES than for those treated with a durable polymer DES (hazard ratio [HR] 0.82, 95 percent confidence interval [CI] 0.68-0.98, P=0.029). In addition, the risk of having a blood clot, called stent thrombosis (the study’s primary safety endpoint), was also significantly lower for those patients treated with a biodegradable polymer DES compared to those treated with a durable polymer DES (HR 0.56, 95 percent CI 0.35-0.90, P=0.015). This was driven by a lower risk of very late stent thrombosis (clots occurring more than one year after angioplasty) for the biodegradable polymer group (HR 0.22, 95 percent CI 0.08-0.61, P=0.004).

Furthermore, the incidence of heart attack late after stenting was lower for patients treated with biodegradable polymer versus durable polymer stents (HR 0.59, 95 percent CI 0.73-0.95, P=0.031).

While the arrival of DES has allowed interventionalists to provide treatment for more complex patients, concerns have arisen about the stents’ long-term safety, particularly concerning stent thrombosis. As a result, the polymer coating on the first-generation stents was targeted as an area for improvement. Specifically, the durable polymer remains in the coronary artery wall beyond the time when its useful function is served. This may cause delayed healing and a hypersensitivity reaction, leading to inflammation and stent thrombosis.

As a potential solution to these problems, new-generation stents with a bioabsorbable polymer were created. This polymer, which fully degrades and leaves a bare-metal stent in place, has been suggested to shorten healing time and cause less inflammation and subsequent stent thrombosis.

“These findings show that biodegradable polymer DES can provide better long-term safety and efficacy,” said Byrne. “This advantage, coupled with a shortened healing time compared with durable polymer DES, means that biodegradable polymer stents look to become an important tool for the interventional cardiologist in everyday practice.”

The current analysis was industry independent, supported in part by a grant from the Swiss National Science Foundation, and conducted at the ISAR Research Center in Munich, Germany, and the Clinical Trials Unit in Bern, Switzerland.

This study was simultaneously published in the European Heart Journal and was released online at the time of presentation.

The results offer a promising outlook for Boston Scientific’s Synergy DES, now in development. It uses the same platform stent as the Ion and Promus, but instead of a duable polymer it uses abluminal biodegradable polymer containing everolimus. The company presented its first-in-man study at TCT 2011 and hopes to begin its EVOLVE II U.S. Food and Drug Administration (FDA) investigational decive exemption trial later this year.

For more information: www.acc.org

Biosensensors BioMatrix Flex was among the stents included in this study. It uses an abluminal, biodegradable polymer as a carrier for its BA9 drug.

http://www.dicardiology.com/article/biodegradable-polymer-des-reduce-stent-thrombosis-rates

First Patient Enrolled in Dissolving Drug-Polymer Coronary Stent Trial

February 21, 2011 – The first patient has been enrolled the DESSOLVE II study to support CE mark for a coronary stent that uses a bioresorbable drug polymer. The MiStent drug-eluting coronary stent system (MiStent DES), by Micell Technologies.

The trial involves treatment of patients with de novo lesions in the native coronary arteries. Stefan Verheye, M.D., Ph.D. at Middelheim Hospital, Antwerp, Belgium enrolled the first patient in the study.

The MiStent DES employs supercritical fluid technology, which applies a precisely controlled absorbable polymer – active drug (sirolimus) matrix onto a cobalt-chromium stent. The polymer dissolves and releases the drug into the surrounding tissue in a controlled manner, designed to optimize dosing of the drug throughout the affected artery. In preclinical trials, the drug completely elutes and the polymer is eliminated from the stent within 45 to 60 days in-vivo, resulting in a bare-metal stent.

DESSOLVE II is a prospective, controlled, 2:1 unbalanced randomized, multicenter study of approximately 270 patients. Patients will be enrolled at 26 clinical sites in Europe, New Zealand and Australia. Candidates for the trial are patients with documented stable or unstable angina pectoris or ischemia. The primary endpoint is superiority of MiStent DES in minimizing in-stent late lumen loss at nine months, compared to Medtronic’s Endeavor DES, as measured with angiography in treated de-novo lesions ranging in diameter from 2.5 to 3.5 mm and amenable to treatment with a maximum 23 mm long stent.

Along with secondary clinical endpoints such as major adverse cardiac events and revascularization rates, the extent of stent coverage and re-endothelialization, via optical coherence tomography (OCT), and endothelial function (vasomotor response) will be evaluated in a subgroup of patients at nine months.

“Drug-eluting stents have significantly improved and expanded our ability to treat coronary atherosclerotic lesions compared to bare-metal stents,” said William Wijns, M.D., Cardiovascular Center, Aalst, Belgium, and principal investigator of the study. “However, cardiologists are still looking for options to improve safety and outcomes. The MiStent DES may address some of these issues directly. Based on recent GLP animal data, the polymer and drug are gone from the stent within 45 to 60 days. This may reduce the risk of late-stent thrombosis related to long-term exposure to DES nonerodible polymers. Given the relatively short residence time of polymer on the stent, MiStent DES may allow for a shorter duration of dual antiplatelet therapy and be a safer choice for noncompliant patients. These performance-enhancing properties are what interventional cardiologists are looking for in a new drug-eluting stent.”

For more information: www.micell.com

http://www.dicardiology.com/article/first-patient-enrolled-dissolving-drug-polymer-coronary-stent-trial

 

Part III

Stent Flexibility versus Stent Concertina Effect

 

Stent flexibility versus concertina effect: mechanism of an unpleasant trade-off in stent design and its implications for stent selection in the cath-lab.

Foin N, Di Mario C, Francis DP, Davies JE.

Abstract

The “concertina effect”, longitudinal deformation of the proximal segments of a deployed stent when force is applied from a guide catheter or other equipment, is a recently recognised problem which seems to particularly affect more recent stent designs. Until now, flexibility and deliverability have been paramount aims in stent design. Developments have focused on optimizing these features which are commonly evaluated by clinicians and demanded by regulatory bodies. Contemporary stent designs now provide high flexibility by reducing the number of connecting links between stent segments and by allowing the connecting links to easily change their length. These design evolutions may, however, simultaneously reduce longitudinal strength and have the unintended effect of inducing some risk of longitudinal compression of the stent (the “concertina effect”) during difficult clinical cases. Progress in stent design and elimination of restenosis by drug coating has improved PCI outcome and enabled new applications. Here we discuss design trade-offs that shaped evolution and improvement in stent design, from early bare metal designs to the latest generation of drug eluting stent (DES) platforms. Longitudinal strength was not recognised as a critical parameter by clinicians or regulators until recently. Measurements, only now becoming publically available, seem to confirm vulnerability of some modern designs to longitudinal deformation. Clinicians could be more guarded in their assumption that changes in technology are beneficial in all clinical situations. Sometimes a silent trade-off may have taken place, adopting choices that are favourable for the vast majority of patients but exposing a few patients to unintended hazard.

Int J Cardiol. 2013 Apr 15;164(3):259-61. doi: 10.1016/j.ijcard.2012.09.143. Epub 2012 Oct 22.

http://www.ncbi.nlm.nih.gov/pubmed/23084111

 

Stent “Concertina:” Stent Design Does Matter

On-Hing Kwok, MBBS

From the Cardiac Catheterization & Intervention Center, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong.

ABSTRACT: The development of modern coronary stent platforms has transformed the landscape of interventional cardiology. Contemporary coronary stents are much more deliverable than older-generation stents. However, longitudinal deformation has emerged as a “new” complication in modern coronary stent platforms. Although most reported cases of longitudinal stent deformation involve mechanical or technical mishaps, it appears that it is more frequently associated with a particular stent design: the “offset peak-to-peak” stent design. This review summarizes the latest data around stent performance. Within this context, two clinical cases where longitudinal deformation was observed in the absence of any mechanical mishaps are also presented. Collectively, this evidence suggests that stent design may be a major determinant of stent performance.

SOURCE

Journal Cardiology, Volume 25 – Issue 6 – June 2013

Key words: longitudinal deformation, stent design, stent concertina, drug-eluting stent

Over the past decades, stent design and material has undergone significant evolution. The introduction of the drug-eluting stent (DES) has also made “drug delivery” another major determinant in modern stent design.1

Coronary stent design. The majority of early coronary stents were made of stainless steel. These designs were associated with variable basic manufacture, cell geometry, and strut thickness.2 Use of alloys such as cobalt chromium and platinum chromium has enabled stents to have thinner struts, while maintaining strength and radioopacity.3 Thin-strut stents improve deliverability and conformability. However, there is limited evidence suggesting that thinner struts may result in less vessel wall damage and hence less risk of restenosis.4-6 Although thin-strut DESs have never been shown to have lower restenosis rates than thick-strut DESs, the trend of thinner strut platforms has triggered innovative designs to maintain stent radial strength. The development of longer, thinner, more flexible, and easier-to-deliver stent platforms made percutaneous coronary intervention (PCI) possible even in the most tortuous anatomy and calcified vessels.7 However, longitudinal stent strength may be compromised with these modern designs.3 Stent design requires careful consideration of several performance characteristics, including crimped and expanded stent flexibility, shortening upon expansion, trackability, scaffolding, radioopacity, longitudinal strength, radial strength, and recoil.8

Stent longitudinal flexibility and deliverability prior to deployment, and vessel conformability after deployment, are widely dependent on the number, orientation, shape, thickness, and material of the crests and links.9 These parameters also determine the longitudinal strength of the stent, defined as maintenance of intact stent architecture upon exposure to compressing or elongating forces.9 Alteration of any one feature of a stent platform will undoubtedly impact other aspects of stent performance and may result in clinical complications. For instance, thinner struts improve deliverability, but reduce radio-opacity of the cobalt chromium stents. In addition, reduction of the number of fixed links between cells or alteration of their geometry may enhance flexibility and conformability, but as a consequence may compromise longitudinal strength.7

Although stent flexibility may be influenced by a variety of factors, it has been shown that stent longitudinal integrity, defined by the number of links between hoops, correlates with stent stiffness. In addition, the alignment of the links with the long axis of the stent may also be an important factor for longitudinal integrity.9

Architectural design differences are major factors affecting resistance against longitudinal compression. The peak-to-peak or peak-to-valley strut architectures of platforms result in variation between the longitudinal stiffness and strength of stents. It is highly likely that the occurrence of longitudinal deformation is dependent on a particular stent design.10

Longitudinal stent deformation. Until recently, the longitudinal strength of coronary stents has never been considered a standard parameter of stent performance. However, recent evidence identified longitudinal compression, or postdeployment stent shortening, as a newly observed complication. Longitudinal stent deformation is defined as the distortion or shortening of a stent in the longitudinal axis following successful stent deployment.3 This phenomenon describes the effect of a longitudinal compression force on the stent rings, causing them to nest or concertinate.

PCI procedures involve multiple and complex techniques that may increase the risk for longitudinal stent compression. These include the use of extra-support guide catheters, aggressive guide catheter manipulation (deep-seat), mother and child catheter systems, multiple balloon postdilations, bifurcation stent techniques, and adjunctive devices such as intravascular ultrasound (IVUS), distal protection devices, etc.7 In a clinical setting, longitudinal compression may occur in various situations (Table 1),8 and it may simply represent an angiographic detection of an exceptional PCI complication. Protrusion of struts into the lumen and extensive malapposition of struts due to longitudinal deformation may result in disruption of flow and increasing the risk of stent thrombosis. Moreover, longitudinal deformation of a DES may result in uneven drug delivery and increase the risk for in-stent restenosis (ISR).9

Clinical reports of longitudinal deformation. Hanratty and Walsh recently described 3 cases where longitudinal compression of a previously deployed stent resulted in stent deformation. Two cases were detected angiographically, while 1 was detected on adjunctive imaging. The complication was first reported with the Promus Element (Boston Scientific) platform. However, Hanratty and Walsh noted that this phenomenon has since been observed with all modern DES platforms. They concluded that such deformation could potentially result in a suboptimal technical result for the medium- to long-term and increase the risk for stent thrombosis and ISR if left undetected.7

References

1. Htay T, Liu MW. Drug-eluting stent: a review and update. Vasc Health Risk Manag. 2005;1(4):263-276.

2. Colombo A, Stankovic G, Moses JW. Selection of coronary stents. J Am Coll Cardiol. 2002;40(6):1021-1033.

3. Williams PD, Mamas MM, Morgan K, et al. Longitudinal stent deformation — a retrospective analysis of frequency and mechanisms. EuroIntervention. 2012;8(2):267-274. Epub AOP 2011.

4. Pache J, Kastrati A, Mehilli J, et al. Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO-2) trial. J Am Coll Cardiol. 2003;41(8):1283-1288.

5. Moreno R, Jimenez-Valero S, Sanchez-Recalde A. Periprocedural (30-day) risk of myocardial infarction after drug-eluting coronary stent implantation: a meta-analysis comparing cobalt-chromium and stainless steel drug-eluting coronary stents. EuroIntervention. 2011;6(8):1003-1010.

6. Kastrati A, Mehilli J, Dirschinger J, et al. Strut thickness effect on restenosis outcome (ISAR-STEREO) trial. Circulation. 2001;103(23):2816-2821.

7. Hanratty CG, Walsh SJ. Longitudinal compression: a “new” complication with model coronary stent platforms — a time to think beyond deliverability. EuroIntervention. 2011;7(7):872-877. Epub AOP 2011.

8. Prabhu S, Schikorr T, Mahmoud T, Jacobs J, Potgieter A, Simonton C. Engineering assessment of the longitudinal compression behavior of contemporary coronary stents. EuroIntervention. 2012;8(2):275-281.

9. Ormiston JA, Webber B, Webster MWI. Stent longitudinal integrity — bench insights into a clinical problem. JACC Cardiovasc Interv. 2011;4(12):1310-1317.

10. Mortier P, De Beule M. Stent design back in the picture: an engineering perspective on longitudinal stent compression. EuroIntervention. 2011;7(7):773-776.

11. Stone GW, Teirstein PS, Meredith IT, et al; PLATINUM Trial Investigators. A prospective randomised evaluation of a novel everolimus-eluting coronary stent: the PLATINUM trial. J Am Coll Cardiol. 2011;57(16):1700-1708.

12. Pitney M, Pitney K, Jepson N, et al. Major stent deformation/pseudofracture of 7 Crown Endeavor/Micro Driver stent platform: incidence and causative factors. EuroIntervention. 2011;7(2):256-262.

13. Finet G, Rioufol G. Coronary stent longitudinal deformation by compression: is this a new global stent failure, a specific failure of a particular stent design, or simply an angiographic detection of an exceptional complication. Eurointervention. 2012;8(2):177-181. Epub AOP 2011.

Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The author reports no conflicts of interest regarding the content herein.

Manuscript submitted September 12, 2012, provisional acceptance given October 31, 2012, final version accepted January 14, 2013.

Address for correspondence: On-Hing Kwok, MBBS, FRCP, FACC, FSCAI, Cardiology Center, 6/F Li Shu Fan Building, Hong Kong Sanatorium & Hospital, 2 Village Road, Happy Valley, Hong Kong. Email:vohkwok@hksh.com

SOURCE

J INVASIVE CARDIOL 2013;25(6):E114-E119

 

Part IV

Stent Thrombosis Through the Generations of Stent Design

A recent retrospective analysis provided further valuable information on the frequency and mechanisms of longitudinal stent deformation. The study involved 4455 interventional cases performed during a 4-year period. Stent deformation occurred in a total of 9 cases (0.2%) and affected 0.097% of stents deployed. In 6 cases, the Promus Element stent was involved, and there was 1 case each involving Endeavor (Medtronic), Biomatrix (Biosensors Interventional Technologies), and Taxus Liberté (Boston Scientific) stents. Stent deformation varied from 0% in several stent types to 0.86% in the case of Promus Element.3 It was virtually unseen in the Cypher and Xience (Abbott Vascular) platforms. Longitudinal stent deformation is probably not a “class effect,” but highly dependent on a particular stent design.

http://www.invasivecardiology.com/articles/stent-“concertina”-stent-design-does-matter

Author(s): 

Lawrence Rajan, MD and David J. Moliterno, MD

From the Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky.

Stent thrombosis (ST), while infrequent, remains a dreaded complication of percutaneous coronary revascularization because of the associated rates of

  • major myocardial infarction (60%-70%) and
  • early mortality (20%-25%).1

As coronary stents became more widely used in clinical practice during the late 1990s to treat acute vessel closure and to reduce restenosis, the emergence of ST redirected the efforts of the cardiology community to mitigate or eliminate this potentially catastrophic event. Advances in

  • stent design and strut thinness,
  • the advent of drug-eluting stent (DES) options, and
  • more potent antithrombotic therapy

have been substantial influences on ST.

  • DESs have been associated with higher ST rates as compared to their bare-metal counterparts, particularly when utilized among high-risk groups and high-risk lesions.

More recently, early meta-analyses of smaller studies have suggested

  • reduced ST rates with newer-generation DESs versus prior versions.2 Similarly, observations from a randomized trial suggested
  • lower ST rates with the newer-generation everolimus-eluting stent (<1%) compared to rates for the older-generation paclitaxel-eluting stent (3%).3

So while this uncommon but catastrophic complication persists in contemporary practice, its low frequency has made it difficult to study, particularly in the real-world setting.

In the current issue of the Journal of Invasive Cardiology, Dores et al have analyzed the outcome data from a large-volume, single-center prospective registry evaluating the incidence of definite ST.4 The study consisted of 3806 patients who underwent percutaneous coronary intervention between January 2003 and December 2010. In the registry, a total of 2388 patients (62.7%) were treated with first-generation DESs (sirolimus-eluting and paclitaxel-eluting stents), while 1418 patients (37.3%) were treated with second-generation DESs (everolimus-eluting and zotarolimus-eluting stents). The overall occurrence of Academic Research Consortium (ARC)-defined definite ST at 12 months was 1.2% (46 events). After correction for baseline differences between study groups and other variables deemed to influence the occurrence of ST, Dores et al concluded that the

  • use of first-generation DESs was associated with a 2.4-fold increase in the risk of definite ST. Among the cases receiving a first-generation DES,
  • the risk of ST was higher for paclitaxel-eluting versus sirolimus-eluting stents.

The observations from Dores et al are consistent with prior reports, in that the rates of definite ST are low and decreasing in recent years. As can be seen in Dores’s Figure 3 considering annual frequency of definite ST, the numerically highest years were 2003 and 2004, and over the most recent years, rates have averaged closer to 1%. Questions will remain in the field of ST, some of which will require large-scale registry data to help consider their relevance and possible answers.

The underlying challenge remains how to afford to study such low-frequency events with multifactorial and variable etiologies. Beyond the events during the interventional procedure and device utilized (ie, type of DES), many other factors that affect the rate of ST (eg, patient genotype and phenotype) are still being unraveled. Considerable research has gone into finding predictive subsets for those at increased risk for ST.5 Among identified factors are the timing and acuity of presentation. Patients presenting with an ACS are known to be more vulnerable to early ST than patients with chronic stable disease. The initial plaque rupture of ACS triggers a prothrombotic avalanche of events, from platelet activation to local thrombus formation and occlusion, spasm, and distal embolization of microcirculatory debris.6 It is interesting to note in the Dores et al. registry that patients receiving second-generation DESs more often presented with an ACS, making their observations reassuring that ST rates can be kept low with evolving care strategies.

In an analysis of the ACUITY trial, which particularly enrolled patients with ACS,7 early ST occurred with similar frequency after anticoagulation with either heparin plus glycoprotein IIb/IIIa inhibitors or bivalirudin (with or without IIb/IIIa inhibitors), and not surprisingly was predicted by diffuse atherosclerosis, suboptimal angiographic results, and inadequate pharmacotherapy. Such patients also had a higher incidence of renal insufficiency and insulin-dependent diabetes mellitus. The ACUITY subanalysis found that the rate of ST within 30 days was 1.4%, significantly higher than the 0.3%-0.5% ST rates reported among patients with stable coronary artery disease.

Among the most critical factors in mitigating the risk of ST are adequate and consistent dual-antiplatelet therapy (DAPT). A remarkable interpatient variability in the antiplatelet response to clopidogrel has been well documented. The frequency of

  • clopidogrel hyporesponsiveness has been reported among as many as 30% of patients undergoing PCI, yet the clinical relevance of antiplatelet responsivity is modest,8 again since the factors related to ST are many.
  • Loss-of-function alleles have been identified for clopidogrel metabolism, and these have been associated with an increased risk of adverse cardiovascular events, including ST.
  • Among patients with ACS, the need for more rapid and potent pharmacological suppression of platelet reactivity in the prevention of early ST is highlighted in clinical trials testing newer antiplatelet therapies.

In a landmark trial,

  • prasugrel, a more potent, consistent, and faster-acting third-generation thienopyridine has shown a significant reduction in overall ST rates compared to clopidogrel (1.1% vs 2.4%).9 Similarly,
  • ticagrelor, an oral, reversible, direct-acting inhibitor of the ADP receptor P2Y12 that has a more rapid onset and greater potency of platelet inhibition than clopidogrel was recently studied in a large clinical trial.
  • In the Platelet Inhibition and Patient Outcomes (PLATO) study, there was a significant reduction in ST in the ticagrelor group vs the clopidogrel group, with definite ST rates of 1.3% and 1.9%, respectively.10

It is becoming clear that there has been a generational improvement in DESs that has reduced the risk of ST. This has been paralleled by advances in DAPT regimens and interventional techniques that have collectively reduced the risk of ST. While the field will continue to search for answers to the

  • optimum duration of DAPT, and whether this is dependent on
  • stent type and
  • acuity of patient presentation,

DES polymers, design characteristics, and the antiproliferative drugs will also continue to evolve. Understanding incremental improvements in techniques, devices, and drugs will remain quite challenging as the rate of ST slowly moves closer to zero.

References

1. Cutlip DE, Baim DS, Ho KK, et al. Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation. 2001;103(15):1967-1971.

2. Palmerini T, Biondi-Zoccai G, Della Riva D, et al. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet. 2012;379(9824):1393-1402.

3. Kedhi E, Joesoef KS, McFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet. 2010;375(9710):201-209.

4. Dores H, Raposo L, Teles RC, et al. Stent thrombosis with second versus first generation drug eluting stents in real world coronary percutaneous intervention. J Invasive Cardiol. 2013;25(7):330-336.

5. Holmes DR Jr, Kereiakes DJ, Garg S, et al. Stent thrombosis. J Am Coll Cardiol. 2010;56(17):1357-1365.

6. Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R. Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol. 2010;30(7):1282-1292.

7. Aoki J, Lansky AJ, Mehran R, et al. Early stent thrombosis in patients with acute coronary syndromes treated with drug-eluting and bare metal stents: the Acute Catheterization and Urgent Intervention Triage Strategy trial. Circulation. 2009;119(5):687-698.

8. Holmes DR Jr, Dehmer GJ, Kaul S, Leifer D, O’Gara PT, Stein CM. ACCF/AHA clopidogrel clinical alert: approaches to the FDA “boxed warning.” A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. J Am Coll Cardiol. 2010;56(4):321-341.

9. Wiviott SD, Braunwald E, McCabe CH, et al; TRITON-TIMI 38 Investigators. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet. 2008;371(9621):1353-1363.

10. Wallentin L, Becker RC, Budaj A, et al; the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndrome. N Engl J Med. 2009;361(11):1045-1057.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Address for correspondence: David J. Moliterno, MD, Department of Internal Medicine, The University of Kentucky, 900 S. Limestone Avenue, 329 Wethington Building, Lexington, KY 40536-0200. Email: moliterno@uky.edu

Journal of invasive Cardiology, Volume 25 – Issue 7 – July 2013

http://www.invasivecardiology.com/articles/stent-thrombosis-through-generations

Stent Thrombosis With Second- Versus First-Generation Drug-Eluting Stents in Real-World Percutaneous Coronary Intervention: Analysis of 3806 Consecutive Procedures From a Large-Volume Single-Center Prospective Registry

Stent thrombosis (ST) is a serious and often fatal event limiting the efficacy of percutaneous coronary intervention (PCI). The pathophysiology of ST is multifactorial, and underlying causes including stent-, procedure-, lesion-, and patient-related factors seem to play different roles at different time points after the index procedure.1,2 When compared to first-generation (1stGEN) drug-eluting stents (DESs), newer DESs have been associated with a lower rate of ST in several randomized clinical trials, subsequent meta-analyses, and also in some registries, such as the recently published Swedish Coronary Angiography and Angioplasty Registry (SCAAR).3-7 New, second-generation (2ndGEN) DESs have been developed with improved design and materials, both of which may contribute to overcome some of the limitations of the older DESs. Decreased strut thickness — resulting in higher flexibility, conformability, and deliverability — and optimized polymer biocompatibility and drug delivery kinetics have been shown to contribute to a low late-loss rate and to a lower thrombotic risk.1 Despite the evidence pointing in this direction, most of the data comes from post hoc analysis and meta-analysis, mainly because studies defining ST as a primary endpoint are scarce.

We aimed to assess whether or not the systematic use of a 2ndGEN DES, relative to the 1stGEN DES, translates into a higher safety rate in a real-world population where DES implantation was indicated. For that purpose, we conducted an analysis of a single-center prospective registry, evaluating the incidence of definite ST, as defined by the Academic Research Consortium (ARC), at 12 months of follow-up as the primary outcome measure.

Author(s): 

Helder Dores, MD, Luís Raposo, MD, Rui Campante Teles, MD, Carina Machado, MD, Sílvio Leal, MD, Pedro Araújo Gonçalves, MD, Henrique Mesquita Gabriel, MD, Manuel Sousa Almeida, MD, Miguel Mendes, MD

Abstract

Background and Aims. When compared to their first-generation (1stGEN) counterparts, second-generation (2ndGEN) drug-eluting stents (DESs) have been associated with better clinical outcomes in randomized clinical trials, namely by reducing the rates of stent thrombosis (ST). Our goal was to investigate whether or not the broad use of newer devices would translate into higher safety in a real-world population. For that purpose, we compared the occurrence of definite ST at 12 months between two patient subsets from a large-volume single-center registry, according to the type of DES used. Total mortality was a secondary endpoint.

Methods and Results. Between January 2003 and December 2010, a total of 3806 patients were submitted to percutaneous coronary intervention (PCI) with only 1stGEN or 2ndGEN DES: 2388 patients (62.7%) were treated with 1stGEN DES only (sirolimus-eluting stent [SES] = 1295 [34.0%]; paclitaxel-eluting stent [PES] = 943 [24.8%]; both stent types were used in 150 patients) and 1418 patients (37.3%) were treated with 2ndGEN DESs only. The total incidence of definite ST (as defined by the Academic Research Consortium) at 12 months was 1.2% (n = 46). After correction for baseline differences between study groups and other variables deemed to influence the occurrence of ST, the use of 1stGEN DES was associated with a significant 2.4-fold increase in the risk of definite ST (95% confidence interval [CI], 1.05-5.42; P=.039) at 12 months; adjusted risk was higher with PES (hazard ratio [HR], 3.6; 95% CI, 1.48-8.70; P=.005) than with SES (HR, 2.3; 95% CI, 0.92-5.65; P=.074). Total mortality (3.7% vs 3.5%) did not differ significantly between groups (adjusted HR, 1.2; 95% CI, 0.81-1.84, P=.348).

Conclusions. Our data suggest that in the real-world setting of contemporary PCI, the unrestricted use of newer 2ndGEN DESs translates into an improvement in PCI safety (relative to 1stGEN DESs), with a significantly lower risk of definite ST at 12 months.

Journal of Invasive Cardiology                    Volume 25 – Issue 7 – July 2013

J INVASIVE CARDIOL 2013;25(7):330-336

Key words: stent thrombosis, drug-eluting stent

http://www.invasivecardiology.com/articles/stent-thrombosis-second-versus-first-generation-drug-eluting-stents-real-world-percutaneous

 

Part V

Stent Thrombosis in Randomized Trials of Drug-Eluting Stents:

Reappraisal of the Synthesis of Evidence!

Stent Thrombosis in Randomized Clinical Trials of Drug-Eluting Stents

Laura Mauri, M.D., Wen-hua Hsieh, Ph.D., Joseph M. Massaro, Ph.D., Kalon K.L. Ho, M.D., Ralph D’Agostino, Ph.D., and Donald E. Cutlip, M.D.

N Engl J Med 2007; 356:1020-1029February 12, 2007DOI: 10.1056/NEJMoa067731

http://www.nejm.org/doi/full/10.1056/NEJMoa067731?goback=%2Egde_675087_member_263490750

 

EDITORIAL on  bare-metal stents (BMS) vs sirolimus-eluting stents (SES)

With full interest, we read the article “Stent thrombosis in randomized clinical trials (RCT) of drug-eluting stents (DES)” by Mauri L et al, previously published in the New England Journal of Medicine in 2007 [1]. The authors concluded that “The incidence of stent thrombosis (ST) did not differ significantly between patients with DES and those with bare-metal stents (BMS) in RCT, although the power to detect small differences in rates was limited” [1]. 
I have the following concerns. First and foremost, ST in the BMS groups occurred more frequently among patients who underwent intervening target lesion revascularization (TLR) versus those who did not [1]. And since brachytherapy was the standard of care for treatment of restenosis at that time, it was used more frequently in patients with restenosis following BMS (9 out of 11 patients with BMS who underwent intervening TLR and subsequently developed definite/probable ST), in whom restenosis occurred more frequently and more diffusely, compared with DES [1]. In an observational study, brachytherapy was associated with a high risk of late (thrombotic) total occlusion of the index vessel at 6-month angiographic follow-up [2]. In that study, the mean time from brachytherapy to late total occlusion was 5.4 ± 3.2 months [2]. Therefore, brachytherapy may constitute selection bias for devices with higher rates of restenosis, by increasing the risk of late ST following intervening procedures for these devices. This might explain the much higher rate of late (beyond 30 days to 1 year) definite/probable ST following BMS compared with sirolimus-eluting stents (SES) (1% versus 0.1%, respectively), which was obviously responsible for the higher overall rate of definite/probable ST following BMS compared with SES at 4-year follow-up (1.7% versus 1.5%, respectively, p=0.7) [1]. It is worth mentioning that

  • BMS was associated with a lower rate of very late (beyond 1 year) definite/probable ST compared with SES (0.4% versus 0.9%, respectively) [1]. Second,
  • the study included 4 RCT of SES published from 2002 to 2004, and 4 RCT of paclitaxel-eluting stents (PES) published from 2003 to 2005, all of which were published before the Academic Research Consortium (ARC) report that put forward the current standard definitions of ST [3].

Thus, the ARC definitions were applied to all of these trials retrospectively, and therefore, might have missed some of the ST events.

  • Third, the study enrolled 878 patients with SES versus 870 treated with the corresponding BMS, 1400 patients with PES versus 1397 treated with the corresponding BMS; thus, it was clearly underpowered for detection of a difference in rare-by-nature events such as ST.  Forth, the
  • RCT included in the study were the earliest RCT of SES and PES; hence, they enrolled relatively low-risk patient, lesion, and clinical subsets, that do not reflect real-world practice.
  • Finally, the individual databases of RCT of PES were managed by Boston Scientific, which might introduce another source of bias!

References

1. Mauri L, Hsieh WH, Massaro JM, et al. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007;356:1020-9.

2. Waksman R, Bhargava B, Mintz GS, et al. Late total occlusion after intracoronary brachytherapy for patients with in-stent restenosis. J Am Coll Cardiol. 2000;36:65-8.

3. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115:2344-51.

Part VI

Duration of Dual Antiplatelet Therapy following Zotarolimus-Eluting Stents and A New Strategy for Discontinuation of Dual Antiplatelet Therapy

Dr. Pearlman: Drug eluting stents decrease in stent stenosis from endothelial exuberant growth at the cost of increased propensity to thrombosis, offset by prolonged use of dual anti platelet medication. The net effect depends on compliance which if good results in net decrease. The risk has increased due to drug eluting stent prevalence, but that is offset by management with dual anti platelet agents, so the net incidence is reduced. There have been a number of presentations based on angioscopy showing thrombus inside bare metal and drug eluting stents that supported the general concensus also supported by TIMI trials that stent thrombosis is promoted by metal stents until they endothelialize, and that drug-eluting stents impede the endothelialization “too well” prolonging that issue, so minimal dual platelet agent duration in practice is 3 months for BMS, 6-12 months for DES, but benefit fades to 2% at 1 year, 1% at 2 years at which point risk-benefit is unconvincing and many stop plavix, while some insist it is a lifetime medication.

With full interest, we read the article “Dual antiplatelet therapy duration and clinical outcomes following treatment with zotarolimus-eluting stents (ZES)” by Kandzari DE, et al [1]. The authors concluded that “Among patients treated with ZES, late-term events of death, myocardial infarction (MI), stroke, and stent thrombosis (ST) do not significantly differ between patients taking 6 months dual antiplatelet therapy (DAPT) compared with continuation beyond 1 year” [1].
I have the following concerns. First, although the authors claimed that their study was based on a pooled analysis of patients who received ZES in 5 ‘clinical trials’; actually, 2 out of 5 were not ‘trials’. One was a registry of direct stenting with ZES [2], and the other was a study of pharmacokinetics of ABT 578 in a subset of the ENDEAVOR II trial, that was not published in a medical journal [3]! Second, patients were classified by “DAPT adherence according to the most recent report of compliance with aspirin and thienopyridine”. Evidence supports that premature discontinuation clopidogrel is the most powerful independent predictor of late ST [4].

There is no evidence, however, that stopping aspirin predisposes to ST following drug-eluting stent implantation. Third, follow-up of DAPT adherence was done at 30 days, 6 months, then annually for 3 years. Reporting DAPT adherence based on “the last reported follow-up interval of compliance with both aspirin and clopidogrel” does not reflect the actual duration of clopidogrel received in any of the comparison groups. Forth, in the second comparison of “6 months on/24 months off” (on DAPT at 6 but not at 24 months) versus “≥24 months” (on DAPT at 6 and 24 months)”, the first group included, by definition, patients who were also on DAPT at 12 months (but not at 24 months). Thus, it cannot be taken to reflect a comparison between 6-month DAPT and 24-month DAPT!  Fifth, the ENDEAVOR II and ENDEAVOR III trials were published in 2006, before the publication of ARC report [5,6]. Therefore, the ARC definitions of ST were applied retrospectively in many patients, which might explain the absence of ‘probable’ ST in all comparison groups, in all time points. Sixth, major bleeding was defined exclusively as “any hemorrhagic event that required blood product transfusion”. This might explain why such rates were 0% in all groups, in all time points. Finally, the study involved low-risk patient and lesion subsets, and was statistically underpowered for rare events such as ST, cardiac death, or MI.

References

1. Kandzari DE, Barker CS, Leon MB, et al. Dual antiplatelet therapy duration and clinical outcomes following treatment with zotarolimus-eluting stents. JACC Cardiovasc Interv 2011;4:1119-28.
2. Schultheiss HP, Grube E, Kuck KH, et al. Endeavor II Continued Access Investigators. Safety of direct stenting with the Endeavor stent: results of the Endeavor II continued access registry. EuroIntervention 2007;3:76–81.
3. Pharmacokinetics of ABT-578 in patients from Endeavor stent: results from a subset of a double-blind, randomized, multicenter (ENDEAVOR-II) trial. In: The ENDEAVOR II Study 30-Day Pharmacokinetic Report. Abbot Park, IL: Abbott Laboratories, 2004.
4. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126-30.
5. Fajadet J, Wijns W, Laarman GJ, et al. ENDEAVOR II Investigators. Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial. Circulation 2006;114:798–806.
6. Kandzari DE, Leon MB, Popma JJ, et al. ENDEAVOR III Investigators. Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial. J Am Coll Cardiol 2006;48:2440–7.
SOURCE
interventions.onlinejacc.org <http://interventions.onlinejacc.org> interventions.onlinejacc.org <http://interventions.onlinejacc.org>

A New Strategy for Discontinuation of Dual Antiplatelet Therapy

With interest, we read the article “A New Strategy for Discontinuation of Dual Antiplatelet Therapy: REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation (RESET) Trial” by Kim B-K, et al [1]. The authors concluded that Endeavor zotarolimus-eluting stent (E-ZES) with 3-month dual antiplatelet therapy (DAPT) was noninferior to other drug-eluting stents (DES) with 12-month DAPT (standard therapy) with respect to the occurrence of the primary endpoint (a composite of cardiovascular death, myocardial infarction (MI), stent thrombosis (ST), target vessel revascularization (TVR), or bleeding at 1 year) [1]. 
I have the following concerns. First, the study design was defective since the comparator group should have been composed of patients who received the same stent (E-ZES) and took DAPT for 12 months. Moreover, the comparator group was not homogeneous, since it was composed of patients who received sirolimus-eluting stents (SES, Cypher, 28.5%), everolimus-eluting stents (EES, Xience, 30%), and ZES with a biocompatible polymer (R-ZES, Resolute, 41.5%). This would further complicate the comparison since it dilutes the results of the comparator group by mixing first- (Cypher) with second-generation (Xience and Resolute) DES. Further confusion was added with the unjustified stratified randomization of the comparator group: patients with Diabetes mellitus (DM) and those with acute coronary syndrome (ACS) were assigned to R-ZES; those with short lesions to SES; those with long lesions to EES. Second, whereas the trial compared two regimens (short versus long) of DAPT following DES, the primary endpoint adopted by the authors included ischemia-driven TVR; an event completely unrelated to the safety or efficacy of a DAPT regimen. Third, the authors could not explain why the event rates were very low (cardiovascular death 0.2%, MI 0.2%, ARC definite/probable ST 0.2%) compared with previous reports of the E-ZES at a similar time point: ENDEAVOR II trial (total death 1.2%, MI 2.7%, ST 0.5% at 9 months); ENDEAVOR IV trial (cardiac death 0.5%, MI 1.6%, ARC definite/probable ST 0.9% at 12 months) [2,3]. Forth, unexpectedly, both TVR and ST rates in patients with DM who received E-ZES were lower than the rates for the whole E-ZES group! And in the ACS subgroup, patients who received the standard therapy (R-ZES) had rates of cardiovascular death 0%, MI 0%, and ST 0%, at 12 months! And surprisingly, in the subset of short lesions, despite the shorter duration of DAPT, bleeding rates were higher with E-ZES + 3-month DAPT versus standard therapy (0.6% versus 0%)! Fifth, based on the current low 12-month rates of primary composite endpoint (4.7%) compared with the figure used for statistical power calculation (10-11%), the trial was underpowered for the primary endpoint. Additionally, the non-inferiority margin of 4% was very wide for the 12-month rates of primary endpoint (4.7%). Finally, enrollment of 2117 patients in 26 centers over 20 months speaks of a low enrollment rate of 4.1 patients/center/month, that reflects an overt selection bias.

References 


1. Kim BK, Hong MK, Shin DH, et al. A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol 2012;60:1340-8.

2. Fajadet J, Wijns W, Laarman GJ, et al. Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial. Circulation 2006;114:798-806.

3. Leon MB, Mauri L, Popma JJ, et al. A randomized comparison of the ENDEAVOR zotarolimus-eluting stent versus the TAXUS paclitaxel-eluting stent in de novo native coronary lesions 12-month outcomes from the ENDEAVOR IV trial.

SOURCE

J Am Coll Cardiol 2010;55:543-54.

content.onlinejacc.org content.onlinejacc.org

http://digitalreprints.elsevier.com/i/85787/6

Conclusions

by Larry H Bernstein, MD, FCAP

This has been a six part discussion on the progress of stent design, and the decreasing problem of stent thrombosis, which evades elimination with a tradeoff in greater utility and somewhat greater risk.  However, the risk of thrombotic events has become low enough that accurate comparisons of stent technologies, method of placement, and antithrombotic techniques to avoid thrombotic complications is burdened by statistical power limitations.  In addition to the issue of sample size, there is an issue of patient characteristics that probably confer increased risk.

In the first part we found that stent placement is done in 15-20% of cases at a bifurcation site, where it is most favorable for plaque buildup from turbulent flow and shear stress.  Recall that Routledge et al. (1) presented 2-year outcome data of 477 patients treated for bifurcation coronary disease with provisional side branch T-stenting using drug-eluting stents (DES), and they concluded that a systematic approach is feasible for 90% of the patients, with acceptable efficacy and safety profiles.  There are several inherent problems that encumbered any analysis.  These were: numerous anatomic configurations of bifurcation types, with the concern for late complications, restenosis, and its frequency, leading to the dilemma of placing two stents versus one stent, and then another as a side branch, if needed.  The study (1) did indicate that provisional stenting is feasible in 90% of all patients, and those who received a second stent in the side branch, 28%, had similar long-term outcomes as those treated with 1 stent. The outcome of this study is similar to that of the Nordic Bifurcation study, which observed no difference in outcomes at 6 months’ follow-up between 1 and 2 stents (9).  As for technique, the latest Nordic Bifurcation Stent Technique study, comparing the culotte and crush techniques, reported low rates of angiographic restenosis and major adverse cardiac events for both techniques (10). However, kissing balloon was shown to be critical in preventing restenosis. Provisional T-stenting offers several advantages compared with other bifurcation techniques. It seems to be the simplest and is associated with favorable long-term outcomes.  It has also been shown that side branches and osteal disease are most problematic and that dedicated devices will have a role in left main disease.

The next issue for consideration is the use of biodegradable drug-eluting stents versus durable polymer DES. Biodegradable polymer DES resulted in lower rates than durable polymer DES of

  • target lesion revascularization (hazard ratio [HR] 0.82, 95 percent confidence interval [CI] 0.68-0.98, P=0.029).
  • definite stent thrombosis (the study’s primary safety endpoint), (HR 0.56, 95 percent CI 0.35-0.90, P=0.015).
  • very late stent thrombosis (clots occurring more than one year after angioplasty) for the biodegradable polymer group (HR 0.22, 95 percent CI 0.08-0.61, P=0.004).
  • cardiac death and heart attack (HR 0.59, 95 percent CI 0.73-0.95, P=0.031).

The third topic for consideration is the tradeoff between stent flexibility versus the concertina effect. Longitudinal strength was not recognized as a critical parameter by clinicians or regulators until recently. Measurements, only now becoming publically available, seem to confirm vulnerability of some modern designs to longitudinal deformation. Stent designs now provide high flexibility by reducing the number of connecting links between stent segments and by allowing the connecting links to easily change their length.  However, this design results in reduced longitudinal strength with the unintended effect of inducing some risk of longitudinal compression of the stent (the “concertina effect”).  While contemporary coronary stents are much more deliverable than older-generation stents, longitudinal deformation has emerged as a “new” complication in modern coronary stent platforms. This is more frequently associated with a particular stent design: the “offset peak-to-peak” stent design.  Thin-strut stents improve deliverability and conformability. There is only limited evidence that thinner struts may result in less vessel wall damage reducing risk of restenosis. The trend of thinner strut platforms has triggered innovative designs to maintain stent radial strength. The development of longer, thinner, more flexible, and easier-to-deliver stent platforms made percutaneous coronary intervention (PCI) possible even in the most tortuous anatomy and calcified vessels.  Longitudinal stent deformation, the distortion or shortening of a stent in the longitudinal axis is the effect of a longitudinal compression force on the stent rings, causing them to nest or concertinate.

The fourth question is the effect of stent design on stent thrombosis.  A recent retrospective analysis provided further valuable information on the frequency and mechanisms of longitudinal stent deformation. The study involved 4455 interventional cases performed during a 4-year period. Stent deformation occurred in a total of 9 cases (0.2%) and affected 0.097% of stents deployed.   Longitudinal stent deformation is probably not a “class effect,” but highly dependent on a particular stent design.

Stent thrombosis (ST), while infrequent, remains a dreaded complication of percutaneous coronary revascularization because of the associated rates of

  • major myocardial infarction (60%-70%) and
  • early mortality (20%-25%).1

the emergence of ST redirected the efforts of the cardiology community to mitigate or eliminate this potentially catastrophic event by

  • stent design and strut thinness,
  • the advent of drug-eluting stent (DES) options, and
  • more potent antithrombotic therapy

DESs have been associated with higher ST rates as compared to their bare-metal counterparts, particularly when utilized among high-risk groups and high-risk lesions.

The overall occurrence of Academic Research Consortium (ARC)-defined definite ST at 12 months was 1.2% (46 events). After correction for baseline differences between study groups and other variables deemed to influence the occurrence of ST, Dores et al concluded that the

  • use of first-generation DESs was associated with a 2.4-fold increase in the risk of definite ST. Among the cases receiving a first-generation DES,
  • the risk of ST was higher for paclitaxel-eluting versus sirolimus-eluting stents.

It should not be a surprise that patients presenting with an ACS are known to be more vulnerable to early ST than patients with chronic stable disease. The initial plaque rupture of ACS triggers a prothrombotic avalanche of events, from platelet activation to local thrombus formation and occlusion, spasm, and distal embolization of microcirculatory debris.6 It is interesting to note in the Dores et al. registry that patients receiving second-generation DESs more often presented with an ACS, making their observations reassuring that ST rates can be kept low.   Patients who had early ST were characterized by diffuse atherosclerosis, angiography, inadequate pharmacotherapy, and had a higher incidence of renal insufficiency and insulin-dependent diabetes mellitus.  The ACUITY subanalysis found that the rate of ST within 30 days was 1.4%, significantly higher than the 0.3%-0.5% ST rates reported among patients with stable coronary artery disease.

Among the most critical factors in mitigating the risk of ST are adequate and consistent dual-antiplatelet therapy (DAPT).  Among patients with ACS, the need for more rapid and potent pharmacological suppression of platelet reactivity in the prevention of early ST is highlighted in clinical trials testing newer antiplatelet therapies.  In the Platelet Inhibition and Patient Outcomes (PLATO) study, there was a significant reduction in ST in the ticagrelor group vs the clopidogrel group, with definite ST rates of 1.3% and 1.9%, respectively.

This brings us to ST in randomized trials of DES.  There was a much higher rate of late (beyond 30 days to 1 year) definite/probable ST following BMS compared with sirolimus-eluting stents (SES) (1% versus 0.1%, respectively).  BMS was associated with a lower rate of very late (beyond 1 year) definite/probable ST compared with SES (0.4% versus 0.9%, respectively) [1].  The different overall rate of definite/ probable ST following BMS compared with SES is nearly equal at 4-year follow-up (1.7% versus 1.5%, respectively), is indeterminate (p=0.7) [1]. The study was underpowered for detection of a difference in rare-by-nature events such as ST.

Finally, Dr. Pearlman analyzes the published studies concerning whether there should be a reduction in the length of dual antiplatelet therapy to six months.  Drug eluting stents decrease in stent stenosis from endothelial exuberant growth at the cost of increased propensity to thrombosis, offset by prolonged use of dual anti-platelet medication.  The risk has increased due to drug eluting stent prevalence, but that is offset by management with dual anti platelet agents, so the net incidence is reduced. Stent thrombosis is promoted by metal stents until they endothelialize, but drug-eluting stents impede the endothelialization, so minimal dual platelet agent duration in practice is 3 months for BMS, 6-12 months for DES, but benefit fades to 2% at 1 year, 1% at 2 years at which point risk-benefit is unconvincing.  Evidence supports that premature discontinuation clopidogrel is the most powerful independent predictor of late ST.

So here we have the status in a nutshell.

  • ST has driven the design of stents to be simpler to insert effectively, with a clear goal to minimize ST
  • The stent designs have resulted in thinner, and multi-segmented longer insertions as needed.
  • The result of improved stent design has been an effect of local vessel distortion.
  • The standard of practice is provisional T-branch DES
  • The use of dual antiplatelet therapy for not less than 1 year is determined by the time required for endothelialization of the artery.
  • There is a risk difference incurred by ACS versus stable disease, and by adequacy of antithrombotic therapy prior to an acute event.

Other related articles published on this Open Access Online Scientific Journal, include the following:

AHA, ACC Change in requirement for surgical support:  Class IIb -> Class IIa Level of Evidence A: Supports Nonemergent PCI without Surgical Backup (Change of class IIb, level of Evidence B).

Larry H Bernstein, MD, FCAP and Justin D Pearlman, MD, PhD, FACC

Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Coronary Reperfusion Therapies: CABG vs PCI – Mayo Clinic preprocedure Risk Score (MCRS) for Prediction of5. in-Hospital Mortality after CABG or PCI

Larry H. Bernstein, MD, FCAP  and Aviva Lev-Ari, PhD, RN

Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents

Aviva Lev-Ari, PhD, RN

Absorb™ Bioresorbable Vascular Scaffold: An International Launch by Abbott Laboratories

Aviva Lev-Ari, PhD, RN

CABG or PCI: Patients with Diabetes – CABG Rein Supreme

Aviva Lev-Ari, PhD, RN

To Stent or Not? A Critical Decision

Aviva Lev-Ari, PhD, RN

New Drug-Eluting Stent Works Well in STEMI

Aviva Lev-Ari, PhD, RN

Revascularization: PCI, Prior History of PCI vs CABG

Aviva Lev-Ari, PhD, RN

Drug Eluting Stents: On MIT’s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES

Larry H Bernstein, MD, FCAP and  Aviva Lev-Ari, PhD, RN

Outcomes in High Cardiovascular Risk Patients: Prasugrel (Effient) vs. Clopidogrel (Plavix); Aliskiren (Tekturna) added to ACE or added to ARB

Aviva Lev-Ari, PhD, RN

Read Full Post »


Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

Author, Introduction and Summary: Justin D Pearlman, MD, PhD, FACC

and

Article Curator: Aviva Lev-Ari, PhD, RN

The Curator recommends the e-Reader to read the following book on Surgical Complications:

Complications
“Essential Reading For Anyone Involved In Medicine”–Amazon.com –  2002

Cardiovascular Complications:

I. Reoperative Sternotomy after prior CABG, MVR, AVR, or radiation therapy

IIa. PCI, and

IIb. PAD Endovascular Interventions: Carotid Artery Endarterectomy

III. Incidence of Sepsis (circulation infection with serious consequences)

UPDATED 11/2/2013

As minimally interventional techniques improve, patients are offered a choice of invasive surgical remedies or less invasive procedures (video assisted, robotic, or percutaneous). The decision should not rest on the size of the scar or even the up front risk and discomfort, but rather should weigh all aspects of the risks and benefits. In addition to the risks and benefits for the current problem, one should also consider why the problem occurred and its likelihood of recurrence. Open chest surgery has a clear disadvantage when it comes to recurrences, as the scars from first surgery interfere with second surgery. Opening the chest (sternotomy) for a second or third time poses elevated risks analyzed herein. This article reviews data from major centers addressing the risks from repeat sternotomy and from minimally invasive cardiovascular surgeries. Any invasion of the body elevates risk of infection, which can lead to sepsis and possible death, so that risk is also addressed.

I. Risk of Injury During Repeat Sternotomy for CABG or Aortic Valve Replacement, Open Heart Surgery

II. Complications After Percutaneous Coronary intervention (PCI) and endovascular surgery for Peripheral Artery Disease (PAD)

  • (a) Post PCIand 
  • (b) PAD Endovascular Interventions: Carotid Artery Endarterectomy

III. Cardiac Failure During Systemic Sepsis

This article addresses specific reports of complications but does not cover numerous other complications that may occur, such as lung collapse, cardiogenic shock, blood loss, local infection, emboli, thrombus, stroke.

I. Risk of Injury During Open Heart Surgery after prior Coronary Artery Bypass Grafting (CABG), Aortic Valve Replacement, Mitral Valve Replacement, or Radiation Therapy 

Conclusions of a Study conducted @Mayo Clinic on Reoperative (Repeat) Sternotomy (opening of the chest through the sternum):

Chan B. Park, MD,a,b Rakesh M. Suri, MD,a Harold M. Burkhart, MD,a Kevin L. Greason, MD,a

Joseph A. Dearani, MD,a Hartzell V. Schaff, MD,a and Thoralf M. Sundt III, MDa

Identifying patients at particular risk of injury during repeat sternotomy: Analysis of 2555 cardiac reoperations

Authors Affiliations: From the Division of Cardiovascular Surgery,

a Mayo Clinic, Rochester, Minn; and the Department of Thoracic and Cardiovascular Surgery,

b St. Paul’s Hospital, The Catholic University of Korea, Seoul, Korea.

Disclosures: None.

Read at the 90th Annual Meeting of The American Association for Thoracic Surgery, Toronto, Ontario, Canada, May 1–5, 2010. Received for publication April 6, 2010; revisions received July 19, 2010; accepted for publication July 30, 2010.

doi:10.1016/j.jtcvs.2010.07.086

Particular attention to protective strategies should be considered during reoperative sternotomy among patients with multiple previous sternotomies, previous mediastinal radiotherapy, and those with patent internal thoracic artery grafts. (J Thorac Cardiovasc Surg 2010;140:1028-35)

Of the 2555 patients,

  • 1537 (60%) had undergone previous coronary artery bypass grafting,
  • 700 (27%) previous mitral valve surgery, and
  • 643 (25%) previous aortic valve replacement (AVR).
  • 61 (2%) had prior mediastinal radiotherapy, and
  • 424 (17%) had more than one previous sternotomy.

 Injury Analysis – 9% events in 231 Patient in the study

In 231 patients, 267 injuries (9.0%) occurred.

Injury occurred

  • during sternotomy in 87 patients (33%) and
  • during prepump dissection in 135 (51%).

Hospital mortality rate was

6.5% among those without injury and

18.5% among those with injury (P < .001);

25% when injury occurred during sternal division

Injuries were more common

1. after previous coronary artery bypass grafting

  • 11% with previous coronary artery bypass grafting vs
  • 7% without, (P = .0012)

but not

  • previous aortic valve surgery,
  • previous mitral valve surgery, or
  • previous aorta surgery.

2.  Injury was also more common when the current operation was aortic valve replacement (AVR)

  • 10% with AVR vs
  • 8% without, (P = .04) or

3.  aorta surgery

  • 14% vs
  • 8% (P = .004).

Predicted injury by multivariate analysis –

Injury was an independent risk factor of hospital death (odds ratio, 2.6).

4.   previous radiotherapy (odds ratio, 4.9)

5.  a greater number of previous sternotomies (odds ratio 1.7), and

6.  a patent internal thoracic artery (odds ratio, 1.8)

J Thorac Cardiovasc Surg. 2010 Nov;140(5):1028-35. doi: 10.1016/j.jtcvs.2010.07.086.

Identifying patients at particular risk of injury during repeat sternotomy: analysis of 2555 cardiac reoperations.

Source

Division of Cardiovascular Surgery, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

OBJECTIVES:

A variety of protective strategies during repeat sternotomy been proposed; however, it remains unclear for which patients they are warranted.

METHODS:

We identified adults undergoing repeat median sternotomy for routine cardiac surgery at our institution between January 1, 1996, and December 31, 2007. The operative notes and perioperative outcomes were reviewed.

RESULTS:

Of the 2555 patients, 1537 (60%) had undergone previous coronary artery bypass grafting, 700 (27%) previous mitral valve surgery, and 643 (25%) previous aortic valve replacement (AVR). Sixty-one patients (2%) had prior mediastinal radiotherapy, and 424 (17%) had more than one previous sternotomy. In 231 patients, 267 injuries (9.0%) occurred. Injury occurred during sternotomy in 87 patients (33%) and during prepump dissection in 135 (51%). The hospital mortality rate was 6.5% among those without injury and 18.5% among those with injury (P < .001); when injury occurred during sternal division, the mortality rate was 25%. Injuries were more common after previous coronary artery bypass grafting (11% with previous coronary artery bypass grafting vs 7% without, P = .0012) but not previous AVR, mitral valve surgery, or aortic surgery. Injury was also more common when the current operation was AVR (10% with AVR vs 8% without, P = .04) or aortic surgery (14% vs 8%, P = .004). On multivariate analysis, previous radiotherapy (odds ratio, 4.9), a greater number of previous sternotomies (odds ratio 1.7), and a patent internal thoracic artery (odds ratio, 1.8) predicted injury. Injury was an independent risk factor of hospital death (odds ratio, 2.6).

CONCLUSIONS:

Particular attention to protective strategies should be considered during reoperative sternotomy among patients with multiple previous sternotomies, previous mediastinal radiotherapy, and those with patent internal thoracic artery grafts.

Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Comment in

TABLE 2. Hospital mortality according to Timing of Injury

Timing Mortality rate with injury P value

  • Re-entry 19/76 (25.0%) <.001
  • Prepump 20/121 (16.5%) <.001
  • Cardiopulmonary bypass (CPB)  3/14 (21.4%) .05
  • Aortic CrossClamp (ACC 1/11) (9.1%) .85
  • Closing 5/17 (29.4%) <.001

TABLE 1. Preoperative patient characteristics

Characteristic No injury (n 1/4 2324) Injury (n 1/4 231) P value

Age (y) 66.9  12.4 67.7  11.5 .509

Men 1583 (68.1%) 167 (72.3%) .192

Diabetes mellitus 499 (21.5%) 61 (26.4%) .084

Hypertension 1536 (66.2%) 158 (68.4%) .490

Hypercholesterolemia 1656 (71.4%) 171 (74.0%) .395

Myocardial infarction 633 (27.3%) 68 (29.4%) .480

Congestive heart failure 758 (32.6%) 89 (38.5%) .069

NYHA .064

I-II 492 (21.2%) 37 (16.0%)

III-IV 1830 (78.8%) 184 (84.0%)

Previous operation No injury (n 1/4 2324) Injury (n 1/4 231) P value

CABG 1375 (59.2%) 162 (70.1%) .001

Aortic valve surgery 586 (25.2%) 57 (24.7%) .857

Mitral valve surgery 645 (27.8%) 55 (23.8%) .200

Tricuspid valve surgery 64 (2.8%) 9 (3.9%) .320

Aorta surgery 167 (7.2%) 20 (8.7%) .413

Current operation No injury (n 1/4 2324) Injury (n 1/4 231) P value

CABG 897 (38.6%) 104 (45.0%) .056

Aortic valve surgery 1020 (43.9%) 118 (51.1%) .036

Mitral valve surgery 821 (35.3%) 80 (34.6%) .833

Tricuspid valve surgery 414 (17.8%) 52 (22.5%) .078

Aortic surgery 232 (10.0%) 37 (16.0%) .004

DISCUSSION

The results of the present study have confirmed the significant risk of cardiovascular injury during reoperative cardiac surgery. The death rate from such injury can be 10-30%, particularly  when occurring during division of the sternum. These risks are greatest among patients with multiple previous sternotomies or prior chest radiotherapy.

Current PROTOCOL at Virginia University, now suggested to be considered for adoption @Mayo Clinic:

The Mayo Clinic’s Authors write: Our findings are more consistent with those reported by Roselli and colleagues.2 The explanation of these institutional differences is unclear, although a number of practice differences are likely present between these institutions in terms of both patient substrate and surgical practice. Compared with the series from the University of Virginia, the Mayo series we have reported represents a greater percentage of total cases performed at the institution (13.5% vs 7.8%), with a somewhat greater percentage of those reoperations being for CABG (41% vs 60%). In the Mayo series, a lower percentage were first-time repeat sternotomies (83% vs 90%) and a greater percentage were the fourth time or more (2.7% vs 1.1%).

The incidence of previous radiotherapy in the University of Virginia series was not reported.

It is also unclear to what degree the differences in surgical practice, including the role of the assistant surgeons in performing the repeat sternotomy, could account for these differences. In the present retrospective study, we were unable to demonstrate an effect of experience or expertise in either the occurrence of injury or the outcome. However, it is clear to all practicing surgeons that, when injury occurs, the judgment and expertise of the operating surgeon is critical to expeditious institution of CPB or other ‘‘rescue’’ maneuvers.

Perhaps of more practical value and broad applicability, however, is the standardized approach to repeat sternotomy advocated by the group at the University of Virginia, including routine preoperative CT scanning if the procedure is the third or fourth sternotomy and insertion of a femoral arterial line by which emergent percutaneous arterial inflow cannulation can be accomplished, if necessary. In their series, emergent institution of CPB using the femoral route was instituted in 1.8% of reoperative patients, constituting 19% of the patients with injury. Most notably, in their series, no deaths occurred among these patients. Serious consideration should be given to adopting such protocols.

Our high mortality rate associated with SVG injury during sternotomy, however, supports the  recommendation by others to carefully assess the course of bypass grafts by preoperative angiography. Routine preoperative CT imaging of all patients with more than one previous sternotomy has been advocated by Morishita and colleagues,3 with a demonstrable reduction in operative complications. Roselli and colleagues2 identified a lack of preparative imaging as the most common ‘‘lapse’’ in the preventive strategy among patients with injury. Our data suggest that CT scanning might be particularly helpful in the subset of patients with multiple previous sternotomies or radiotherapy and would support the institution of a policy of routine scanning for these patients.

FIGURE 1. Hospital mortality according to emergent cardiopulmonary bypass (CPB) in The Journal of Thoracic and Cardiovascular Surgery c November 2010, pp. 1032

TABLE 5. Postoperative results

No injury (n 1/4 2324) —  Injury (n 1/4 231) — P value

Postoperative transfusion (U)

PRCs 4.5  7.2 6.5  8.9 .046

ICU stay (h) 102.3  228.6 146.3 +/- 346.9 <.001

Reoperation for bleeding 127 (5.5%) 21 (9.1%) .024

Sepsis 86 (3.7%) 16 (6.9%) .017

Stroke 56 (2.4%) 11 (4.8%) .033

Prolonged ventilation 505 (21.7%) 97 (42.0%) <.001

Pneumonia 123 (5.3%) 25 (10.8%) <.001

ARDS 32 (1.4%) 8 (3.5%) .015

Postoperative renal failure 237 (10.2%) 51 (22.1%) <.001

Multisystem failure 45 (1.9%) 13 (5.6%) <.001

Perioperative MI 9 (0.4%) 2 (0.9%) .289

Hospital death 151 (6.5%) 43 (18.6%) <.001

Abbreviations:

IABP, intra-aortic balloon pump; ICU, intensive care unit; ARDS, acute respiratory

distress syndrome; MI, myocardial infarction.

SOURCE
The Journal of Thoracic and Cardiovascular Surgery c November 2010, pp. 1032

Independent predictors for injury during repeat median sternotomy

The structures injured and the timing of injury in our study were similar to those reported by Roselli and colleagues.2  Bypass grafts were the most commonly injured and, perhaps in contrast to expectations, most injuries occurred during dissection, not during sternal division. Unlike their study, however, we found injury during sternal division to carry a greater mortality risk. We observed a remarkably high mortality rate associated with injury to the right ventricle, as did Roselli and colleagues.2  This may be particularly true in the presence of pulmonary hypertension, when attempts to repair the injury are hampered by inadequate access, progressive tearing of the ventricle secondary to traction injury, and what can be a relatively thin and friable free wall. The incidence of injury to the Internal thoracic artery (ITA) in our series (4.9%) was comparable to the 4.4%–5.3% reported by other investigators.11-14 Because the ITA was damaged more often during prepump dissection (20.7%) than during re-entry (11.5%), these data support the trend to avoid dissecting and isolating the ITA during AVR after previous CABG.12,13

FOUR CONCLUSIONS

1. On the basis of these data, we would advocate preoperative axial CT imaging to define the proximity of cardiovascular structures to the sternum of patients who have undergone more than one previous sternotomy and those who have undergone radiotherapy because these patients statistically have the greatest risk of injury.

2. We would also advocate considering percutaneous or open access of the femoral vessels, if not the institution of CPB, before sternotomy in these same patients, as well as those with significant pulmonary hypertension.

3. Because injury is common during prepump dissection, we support a philosophy of leaving patent ITA grafts undisturbed by attempts to gain control during AVR after previous CABG.

4. Finally, given the mortality rate associated with graft injury, patients with previous CABG should be considered for graft angiography or high-resolution CT.

Summary 

This is a very important study  on the Outcomes and the Complications involved in Cardiac Surgery @Mayo Clinic.

Study’s Objectives: A variety of protective strategies during repeat sternotomy been proposed; however, it remains unclear for which patients they are warranted.

Authors @Mayo Clinic reported:

We were unable to definitively assess the effect of any specific protective strategies on the incidence of injury. Because we do not have standardized or uniform prospective institutional policies in this regard, it was not possible to account for the confounding factor of the clinician’s judgment in the decision to use these strategies in particularly highrisk patients.

Our high mortality rate associated with saphenous vein graft (SVG) injury during sternotomy, however, supports the  recommendation by others to carefully assess the course of bypass grafts by preoperative angiography. Routine preoperative CT imaging of all patients with more than one previous sternotomy has been advocated by Morishita and colleagues,3 with a demonstrable reduction in operative complications.

The reader is advised to review another article Co-Curated by us on the following related study by Mayo Clinic researches, This article examines 10-year to 15-year survivals from arterial bypass grafts using arterial vs saphenous venous grafts.

CABG Survival in Multivessel Disease Patients: Comparison of Arterial Bypass Grafts vs Saphenous Venous Grafts

The conclusions in this article are:

In patients undergoing isolated coronary artery bypass graft surgery with LIMA to left anterior descending artery,

  • arterial grafting of the non-left anterior descending vessels conferred a survival advantage at 15 years compared with Saphenous Venous grafting (SVG).

It is still unproven whether these results apply to higher-risk subgroups of patients.

Related study

Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents,

REFERENCES

1. Sabik JF III, Blackstone EH, Houghtaling PL,Walts PA, LytleBW. Is reoperation

still a risk factor in coronary artery bypass surgery? Ann Thorac Surg. 2005;80:

1719-27.

2. Roselli EE, Pettersson GB, Blackstone EH, Brizzio ME, Houghtaling PL,

Lauck R, et al. Adverse events during reoperative cardiac surgery: Frequency,

characterization, and rescue. J Thorac Cardiovasc Surg. 2008;135:316-23.

3. Morishita K, Kawaharada N, Fukada J, Yamada A, Masaru T, Kuwaki K, et al.

Three or more median sternotomies for patients with valve disease: Role of computed

tomography. Ann Thorac Surg. 2003;75:1476-81.

4. Luciani N, Anselmi A, De Geest R, Martinelli L, Perisano M, Possati G. Extracorporeal

circulation by peripheral cannulation before redo sternotomy: Indications

and results. J Thorac Cardiovasc Surg. 2008;136:572-7.

5. Potter DD, Sundt TM III, Zehr KJ, Dearani JA, Daly RC, Mullany CJ, et al. Risk

of repeat mitral valve replacement for failed mitral valve prostheses. Ann Thorac

Surg. 2004;78:67-72.

6. Potter DD, Sundt TM III, Zehr KJ, Dearani JA, Daly RC, Mullany CJ, et al. Operative

risk of reoperative aortic valve replacement. J Thorac Cardiovasc Surg.

2005;129:94-103.

7. Sundt TM III, Murphy SF, Barzilai B, Schuessler RB, Mendeloff EN,

Huddleston CB, et al. Previous coronary artery bypass grafting is not a risk factor

for aortic valve replacement. Ann Thorac Surg. 1997;64:651-7.

8. Ellman PI, Smith RL, Girotti ME, Thompson PW, Peeler BB, Kern JA, et al. Cardiac

injury during resternotomy does not affect perioperative mortality. JAm Coll

Surg. 2008;206:993-9.

9. Chang ASY, Smedira NG, Chang CL, Benavides MM, Myhre U, Feng J, et al.

Cardiac surgery after mediastinal radiation: Extent of exposure influences outcome.

J Thorac Cardiovasc Surg. 2007;133:404-13.

10. Schmuziger M, Christenson JT, Maurice J, Mosimann E, Simonet F, Velebit V.

Reoperative myocardial revascularization: An analysis of 458 reoperations and

2645 single operations. Cardiovasc Surg. 1994;2:623-9.

11. Gillinov AM, Casselman FP, Lytle BW, Blackstone EH, Parsons EM, Loop FD,

et al. Injury to a patent left internal thoracic artery graft at coronary reoperation.

Ann Thorac Surg. 1999;67:382-6.

12. Byrne JG, Karavas AN, Filsoufi F, Mihaljevic T, Aklog L, Adams DH, et al. Aortic

valve surgery after previous coronary artery bypass grafting with functioning

internal mammary artery grafts. Ann Thorac Surg. 2002;73:779-84.

13. Smith RL, Ellman PI, Thompson PW, Girotti ME, Mettler BA, Ailawadi G, et al.

Do you need to clamp a patent left internal thoracic artery—Left anterior descending

graft in reoperative cardiac surgery? Ann Thorac Surg. 2009;87:742-7.

14. Coltharp WH, Decker MD, Lea JWIV, Petracek MR, Glassford DM,

Thormas CS, et al. Internal mammary artery graft at reoperation: Risks, benefits,

and methods of preservation. Ann Thorac Surg. 1991;52:225-9.

15. O’Brien MF, Harrocks S, Clarke A, Garlick B, Barnett AG. How to do safe sternal

reentry and the risk factors of redo cardiac surgery: A 21-year review with

zero major cardiac injury. J Cardiac Surg. 2002;17:4-13.

16. Klein G. Naturalistic decision making. Human Factors. 2008;50:456-60.

II. Complications After Percutaneous Coronary intervention (PCI) and endovascular surgery for Peripheral Artery Disease (PAD)

(a) after prior PCI, and

(b) after prior PAD Endovascular Interventions: Carotid Artery Endarterectomy

II(a)  PCI  After Prior PCI – Major occurring Complications include the following:

 

  • Hematoma (a firm collection of blood greater than 2 cm around or in the proximity of the access site).
  • Pseudoaneurysm / dissection,
  • A-V fistula and ischemic leg were also considered along with
  • Retroperitoneal bleed. Retroperitoneal bleeding was defined by any amount of bleeding in the retroperitoneum diagnosed by computer tomography.
  • Inflammation of the Lower extremity on the side of the access site to the femoral artery

UPDATED 11/2/2013

VIEW VIDEO

Impact of Intra-procedural Stent Thrombosis during Percutaneous Coronary Intervention: Insights from the CHAMPION PHOENIX Trial ONLINE FIRST

Philippe Généreux, MD1; Gregg W. Stone, MD1; Robert A. Harrington, MD4; C. Michael Gibson, MD5; Ph. Gabriel Steg, MD6; Sorin J. Brener, MD10; Dominick J. Angiolillo, MD, PhD11; Matthew J. Price, MD12; Jayne Prats, PhD13; Laura LaSalle, MPH2; Tiepu Liu, MD, PhD12; Meredith Todd, B.Sc12; Simona Skerjanec, Pharm.D12; Christian W. Hamm, MD14; Kenneth W. Mahaffey, MD4; Harvey D. White, DSc15; Deepak L. Bhatt, MD, MPH16
J Am Coll Cardiol. 2013;():. doi:10.1016/j.jacc.2013.10.022

Abstract

Objective  We sought to evaluate the clinical impact of intra-procedural stent thrombosis (IPST), a relatively new endpoint.

Background  In the prospective, double-blind, active-controlled CHAMPION PHOENIX trial, cangrelor significantly reduced periprocedural and 30-day ischemic events in patients undergoing percutaneous coronary intervention (PCI), including IPST.

Methods  An independent core laboratory blinded to treatment assignment performed a frame-by-frame angiographic analysis in 10,939 patients for the development of IPST, defined as new or worsening thrombus related to stent deployment anytime during the procedure. Adverse events were adjudicated by an independent, blinded clinical events committee.

Results  IPST developed in 89 patients (0.8%), including 35/5470 (0.6%) and 54/5469 (1.0%) in the cangrelor and clopidogrel arms, respectively (OR [95%CI] = 0.65 [0.42,0.99], p=0.04). Compared to patients without IPST, IPST was associated with a marked increase in composite ischemia (death, myocardial infarction [MI], ischemia-driven revascularization, or new onset out-of-lab stent thrombosis [ARC]) at 48 hours and at 30 days (29.2% vs. 4.5% and 31.5% vs. 5.7%, P<0.0001 for both). After controlling for potential confounders, IPST remained a strong predictor of all adverse ischemic events at both time points.

Conclusion  In the large-scale CHAMPION PHOENIX trial, the occurrence of IPST was strongly predictive of subsequent adverse cardiovascular events. The potent intravenous ADP antagonist cangrelor substantially reduced IPST, contributing to its beneficial effects at 48 hours and 30 days.

Clinical trial info  CHAMPION PHOENIX; NCT01156571

Bleeding and Vascular Complications at the Femoral Access Site Following Percutaneous Coronary Intervention (PCI): An Evaluation of Hemostasis Strategies

Author(s):

Dale R. Tavris, MD, MPH1, Yongfei Wang, MS2, Samantha Jacobs, BS1, Beverly Gallauresi, MPH, RN1, Jeptha Curtis, MD2, John Messenger, MD3, Frederic S. Resnic, MD, MSc4, Susan Fitzgerald, MS, RN5

Authors Affiliation

From the 1US Food and Drug Administration (FDA), Silver Spring, Maryland, 2Yale University, New Haven, Connecticut, 3University of Colorado, Boulder, Colorado, 4Brigham and Women’s Hospital, Boston, Massachusetts, and 5the American College of Cardiology, Bethesda, Maryland.

Abstract: Background. Previous research found at least one vascular closure device (VCD) to be associated with excess vascular complications, compared to manual compression (MC) controls, following cardiac catheterization. Since that time, several more VCDs have been approved by the Food and Drug Administration (FDA). This research evaluates the safety profiles of current frequently used VCDs and other hemostasis strategies. Methods. Of 1089 sites that submitted data to the CathPCI Registry from 2005 through the second quarter of 2009, a total of 1,819,611 percutaneous coronary intervention (PCI) procedures performed via femoral access site were analyzed. Assessed outcomes included bleeding, femoral artery occlusion, embolization, artery dissection, pseudoaneurysm, and arteriovenous fistula. Seven types of hemostasis strategy were evaluated for rate of “any bleeding or vascular complication” compared to MC controls, using hierarchical multiple logistic regression analysis, controlling for demographic factors, type of hemostasis, several indices of co-morbidity, and other potential confounding variables. Rates for different types of hemostasis strategy were plotted over time, using linear regression analysis.Results. Four of the VCDs and hemostasis patches demonstrated significantly lower bleeding or vascular complication rates than MC controls: Angio-Seal (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.65-0.70); Perclose (OR, 0.54; CI, 0.51-0.57); StarClose (OR, 0.77; CI, 0.72-0.82); Boomerang Closure Wire (OR, 0.63; CI, 0.53-0.75); and hemostasis patches (OR, 0.70; CI, 0.67-0.74). All types of hemostasis strategy, including MC, exhibited reduced complication rates over time. All trends were statistically significant except one. Conclusions. This large, nationally representative observational study demonstrated better safety profiles for most of the frequently used VCDs, compared to MC controls.

J INVASIVE CARDIOL 2012;24(7):328-334

Key words: hemostasis patch, mechanical compression, vascular closure device

Problems and Complications of the Transradial Approach for Coronary Interventions: A Review

The Journal of invasive Cardiology

Elizabeth Bazemore, BS and J. Tift Mann, III, MD

The benefits of the transradial approach have clearly been documented in numerous studies in the past ten years.1–9 Access site bleeding complication rates are lower and early ambulation results in a significant reduction in patient morbidity and a lower total procedure cost.3,4 Both patients undergoing the procedure and staff caring for these patients overwhelmingly prefer the transradial approach.10
As a result of these benefits, there has been an increase in the use of the radial artery for interventional procedures worldwide in the past several years. This experience has led to an understanding of the problems and complications that can result from the transradial approach. The purpose of the present manuscript is to review these issues.
Radial artery occlusion. Although this complication is a major concern, the consequences of radial artery occlusion are usually benign. The dual blood supply to the hand is an extremely protective mechanism (Figure 1). Hand ischemia with necrosis has occurred following prolonged cannulation of the radial artery for hemodynamic monitoring in critically ill patients; however, this complication has not been reported thus far after transradial coronary procedures.
The absence of ischemic complications is largely the result of the original recommendation by Kiemeneij that the transradial procedure be performed only in patients with a documented patent ulnar artery and palmar arch.1 This has traditionally been evaluated using the Allen’s test, but ultrasound, Doppler, and plethysmography prior to the procedure are more accurate methods.11
Plethysmography is probably the simplest and most effective method. A pulse oximetry test is performed with the probe placed on the patient’s thumb (Figure 2). The persistence of waveform and high oximetry readings after digital occlusion of the radial artery is very strong evidence that the patient will have sufficient collateral flow to prevent hand ischemia if the radial artery should become occluded as a result of the procedure. Barbeau has demonstrated the reappearance of the waveform and a high oximetry reading two minutes after initial negative results.11 This delayed recruitment of collaterals may be an additional explanation for the absence of hand ischemia with radial occlusion.
Several variables influence the incidence of radial artery occlusion. Adequate anticoagulation is extremely important. This is usually not an issue in patients undergoing interventional procedures, but the incidence of radial occlusion was as high as 30% in patients receiving only 1,000 units of heparin during diagnostic catheterization.12 The incidence of radial occlusion is reduced significantly by administering at least 5,000 units of heparin during the procedure.12,13 Due to this risk of radial occlusion, we tend to reserve the use of the radial artery for interventional procedures and “look-see” diagnostic catheterization. Elective diagnostic catheterizations are performed transradially only when there is an increased risk of femoral complications.
Catheter size has been shown to be an important predictor of post-procedure radial artery occlusion. Saito has studied the ratio of the radial artery internal diameter to the external diameter of the arterial sheath.14 The incidence of occlusion was 4% in patients with a ratio of greater than 1, as compared to 13% in those with a ratio of less than 1. Radial procedures have traditionally been performed using 6 Fr catheters, and most patients have an internal radial artery diameter larger than the 2.52 mm external 6 Fr sheath diameter.14 The incidence of radial occlusion following 6 Fr procedures is less than 5%, but the rate increases with larger sheath sizes.4,13 Virtually all interventional procedures can now be performed through large-bore, 6 Fr guide catheters, and larger-sized catheters are rarely necessary. For straightforward procedures, 5 Fr guide catheters may be utilized and are particularly useful in smaller women.
When the radial artery is utilized for hemodynamic monitoring in critically ill patients, the incidence of radial occlusion is significantly higher in patients with cannulation times greater than 24 hours, as compared to those under 20 hours.15 Since catheters are virtually always removed at the conclusion of a catheterization or interventional procedure, the time of cannulation may not be a factor. However, prolonged post-procedure compression times, particularly with high pressure using a mechanical device, may be a factor. We use sufficient pressure only to achieve hemostasis and try to remove the device as quickly as possible. Even in patients with intensive anticoagulation, it is rarely necessary to maintain mechanical compression for longer than one to two hours. A compression dressing using non-occlusive pressures can then be applied.
In summary, post-procedure radial occlusion occurs only in a small percentage of patients and is virtually always asymptomatic because of the dual blood supply to the hand. Patients with generalized vascular disease, diabetes mellitus, and those undergoing repeat procedures are more susceptible. The incidence can be minimized with appropriate anticoagulation, proper sheath selection, and avoiding prolonged high-pressure compression following the procedure.
Non-occlusive radial artery injury. Recent studies have demonstrated that permanent radial artery injury without occlusion may occur following transradial intervention in some patients. Mean radial artery internal diameter as measured by ultrasound was smaller in patients undergoing repeat transradial interventional procedures as compared to the initial procedure.16 This smaller diameter was not present on the day following the procedure, but developed during a mean follow up of 4.5 months. Wakeyama et al. demonstrated with intravascular ultrasound that this progressive narrowing is due to intimal hyperplasia, presumably induced by trauma from the cannulation sheath or catheter.17 The studies in our laboratory show that this hyperplasia is usually segmental rather than diffuse and is not present in all patients with a previous transradial procedure (Figure 3). The incidence of subsequent intimal hyperplasia in patients undergoing radial procedures is yet to be determined.
The ramifications of this injury are important not only in patients undergoing repeat interventional procedures, but also in patients in whom the radial artery may be used as a conduit for coronary artery bypass surgery. At our center, this is not an issue as most procedures are performed from the right radial artery and surgeons use the left radial artery for bypass graft purposes. At present, it would seem prudent not to use a radial artery that previously has been used for a catheterization as a bypass graft.
Radial artery spasm. Much of the morbidity of the transradial procedure is related to vasospasm induced by the introduction of a sheath or catheter into the radial artery. The vessel has a prominent medial layer that is largely dominated by alpha-1 adenoreceptor function.18 Thus, increased levels of circulating catecholamines are a cause of radial artery spasm. Local anesthesia and adequate sedation to control anxiety during catheter insertion are important preventative measures.
It has been demonstrated in isolated radial artery ring segments that nitroglycerin and verapamil are effective agents in preventing arterial spasm.19 Indeed, a vasodilator cocktail consisting of 3–6 mg of verapamil injected intra-arterially prior to sheath insertion is extremely effective in preventing radial artery spasm. The effect of the drug is immediate and significant arterial dilatation can be seen within minutes of its administration (Figure 4).
Intra-arterial verapamil and nitroglycerin have virtually eliminated vasospasm as a cause of significant morbidity of the procedure. It is now possible to perform transradial procedures using short sheaths and arm discomfort generally occurs only in patients with very small or tortuous radial arteries, particularly if guide catheter manipulation is excessive.
Spasm distal to the access site may be a cause of access failure. Occasionally, guide wire or guide catheter induced focal spasm may occur in a tortuous segment. Angiographic visualization of these areas is important as they generally respond to repeat verapamil administration and can be traversed with an angled hydrophilic coated guide wire. A soft-tipped coronary guide wire may also be used to cross these areas (Figure 5).
Sheath-induced spasm is also minimized by the use of sheaths with hydrophilic coating. Kiemeneij has documented that both patient discomfort and the force required to remove a sheath as measured by an automatic pull-back device was significantly less with hydrophilic coated sheaths as opposed to non-coated sheaths.20
Local access bleeding. The most important benefit of transradial procedures is the elimination of access site bleeding complications.1–4 The radial artery puncture site is located over bone and can easily be compressed with minimal pressure. Thus, bleeding from the radial access site can virtually always be prevented. Although manual pressure from an experienced operator is the ideal method to obtain hemostasis, several compression devices have been developed in an attempt to maximize operator and staff efficiency. Local hematomas may occur as a result of improper device application or device failure. It is important to emphasize that compression of the radial artery both proximally and distally to the puncture site must be performed because of retrograde flow from the palmar arch collaterals.
Forearm hematoma. Bleeding may occur from a site in the radial artery remote from the access site. The most common cause is perforation of a small side branch by the guide wire in patients receiving a platelet glycoprotein IIb/IIIa inhibitor (Figure 6). Avulsion of a small radial recurrent artery arising from a radial loop is another important cause of this syndrome.21,22 Hydrophilic guidewires preferentially select this small arterial remnant in patients with a radial loop and forceful advancement of the guide catheter can result in avulsion of the vessel. Radial artery perforation has been described in 1% of patients although in our experience the incidence is substantially lower. A low threshold to perform a radial artery arteriogram when any resistance to guide wire or catheter insertion is encountered will help prevent this complication.
Recognition of this bleeding remote from the access site is important as hemostatic pressure must be applied to an area other than the access site. Hemostasis is usually easily accomplished by the application of an Ace bandage to the forearm. A blood pressure sphygmomanometer may also be utilized. The latter is inflated to systolic pressure and then gradually released over a period of one to two hours. Sealing of a perforation with a long sheath is also an option, but this is rarely necessary.22
Compartment syndrome is the most dreaded complication of radial artery hemorrhage. A large hematoma causes hand ischemia due to pressure-induced occlusion of both the radial and ulnar arteries. Fasciotomy with hematoma evacuation must be performed as an emergency procedure to prevent chronic ischemic injury. This complication is rare, occurring only once in our early experience; it should always be preventable.

Access failure. Failure to cannulate the radial artery using a 20 gauge needle and a 0.025 mm straight Terumo guide wire occurs in less than 5% of patients with an experienced operator. The importance of adequate patient sedation and local anesthesia in the prevention of radial artery spasm has previously been emphasized. In addition, meticulous attention to detail is important as the probability of failure increases as the number of unsuccessful attempts to puncture the artery increases. It should be emphasized that the puncture site is proximal to the styloid process of the radius bone. The radial artery distally usually bifurcates and becomes less superficial and attempting to puncture the vessel too distally is a common cause of access failure (Figure 7).
The radial loop is the most common congenital anomaly of the radial artery and may be a cause of access failure. It occurs in 1–2% of patients and may be unilateral or bilateral.21 Wide loops can occasionally be traversed with hydrophilic guidewires and 5 Fr catheters without excessive patient discomfort.23 However, in most cases, it is preferable to consider an alternative access site.
Radial arteries that are smaller than 2 mm in diameter are difficult to access. These are generally seen in smaller women and patients with previous radial procedures. The use of a 5 Fr guide in this situation may be an option. However, complex or difficult procedures cannot be performed through a 5 Fr guide catheter.
Miscellaneous complications. Pseudoaneurysm formation may rarely occur at the radial artery access site. This is usually easily managed with thrombin injection and/or mechanical compression. However, surgery may be required. Radial artery avulsion due to intense spasm has been described but this complication should virtually never occur using contemporary techniques. Sterile abscesses rarely occur with the use of hydrophilic coated sheaths.24
Conclusion. The radial artery is an excellent access site for coronary interventions. Although technically more challenging with a definite learning curve, there are significant advantages to this approach. Complications are infrequent and many are preventable with careful technique.

 http://www.invasivecardiology.com/article/3821

J Invasive Cardiol. 2010 Apr;22(4):175-8.

Vascular complications after percutaneous coronary intervention following hemostasis with the Mynx vascular closure device versus the AngioSeal vascular closure device.

Source

Department Cardiology, New York Medical College, Macy Pavilion, Valhalla, NY 10595, USA.

Abstract

We investigated the prevalence of vascular complications after PCI following hemostasis in 190 patients (67% men and 33% women, mean age 64 years) treated with the AngioSeal vascular closure device (St. Jude Medical, Austin, Texas) versus 238 patients (67% men and 33% women, mean age 64 years) treated with the Mynx vascular closure device (AccessClosure, Mountain View, California).

RESULTS:

Death, myocardial infarction or stroke occurred in none of the 190 patients (0%) treated with the AngioSeal versus none of 238 patients (0%) treated with the Mynx. Major vascular complications occurred in 4 of 190 patients (2.1%) treated with the AngioSeal versus 5 of 238 patients (2.1%) treated with the Mynx (p not significant). Major vascular complications in patients treated with the AngioSeal included removal of a malfunctioning device (1.1%), hemorrhage requiring intervention (0.5%) and hemorrhage with a loss of > 3g Hgb (0.5%). The major vascular complications in patients treated with the Mynx included retroperitoneal bleeding requiring surgical intervention (0.8%), pseudoaneurysm with surgical repair (0.8%) and hemorrhage with a loss of > 3g Hgb (0.4%). These complications were not significantly different between the two vascular closure devices (p = 0.77). Minor complications included hematoma > 5 cm (0.5%, n = 1) within the AngioSeal group, as well as procedure failure requiring > 30 minutes of manual compression after device deployment, which occurred in 7 out of 190 patients (3.7%) treated with the AngioSeal versus 22 of 238 patients with the Mynx (9.2%) (p = 0.033).

CONCLUSIONS:

Major vascular complications after PCI following hemostasis with vascular closure devices occurred in 2.1% of 190 patients treated with the AngioSeal vascular closure device versus 2.1% of 238 patients treated with the Mynx vascular closure device (p not significant). The Mynx vascular closure device appears to have a higher rate of device failure.

Comment in

http://www.ncbi.nlm.nih.gov/pubmed/20351388

Z Kardiol. 2005 Jun;94(6):392-8.

Incications and complications of invasive diagnostic procedures and percutaneous coronary interventions in the year 2003. Results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

Source

Herzzentrum Ludwigshafen, Bremserstrasse 79, 67063 Ludwigshafen, Germany. Uwe.Zeymer@t-online.de

Abstract

BACKGROUND:

The ALKK registry contains about 20% of the invasive and interventional cardiological procedures performed in Germany.

METHODS:

In 2003 a total of 82,282 consecutive diagnostic invasive and 30,689 interventional procedures from 75 hospitals were centrally collected and analyzed.

RESULTS:

The main indication for an invasive diagnostic procedure was coronary artery disease in 92.5% of cases, myocardial disease in 1.6%, impaired left ventricular function in 4.0%, valve disease in 4% and other indications in 1.9%. An acute coronary syndrome was present in 25% of the patients. The rate of severe complications in patients with a lone diagnostic invasive procedure was low (<0.5%). The indication for percutaneous coronary intervention (n=30,689) was stable angina in 44.1%, ST elevation myocardial infarction in 22.3%, non ST elevation myocardial infarction in 14.8%, unstable angina in 10.0%, silent ischemia in 2.2%, prognostic in 5.2% of patients. The majority of interventions were performed directly after the diagnostic procedure (n=23,887=78.6%). The intervention was successful in 94.6% of cases. Stent implantation was performed in 77.2%, with 1 stent in 88.4%, two stents in 7.6% and 3 or more stents in 3.3%. A drug-eluting stent was implanted in 3.6% of the cases. The complication rate after PCI was influenced by the indication for the intervention. The in-hospital mortality in patients with cardiogenic shock was 33%, while in patients with stable angina, silent ischemia and prognostic indication only 0.2% died.

CONCLUSION:

There is an increase of invasive diagnostic and interventional procedures in patients with acute coronary syndromes, with 47% of PCIs performed in these patient. PCIs were performed in 75% of the cases directly after the diagnostic procedure. The rate of stent implantation seems to have reached a plateau at around 80%, while drug-eluting stents were implanted only in a minority of cases. The complication rate is mainly dependent on the clinical presentation of the patients and the indication for PCI.

http://www.ncbi.nlm.nih.gov/pubmed/15940439

Coronary arterial complications after percutaneous coronary intervention in Behçet’s disease

Authors: Kinoshita T, Fujimoto S, Ishikawa Y, Yuzawa H, Fukunaga S, Toda M, Wagatsuma K, Akasaka Y, Ishii T, Ikeda T

Published Date February 2013 Volume 2013:4 Pages 9 – 12

DOI: http://dx.doi.org/10.2147/RRCC.S41240,

Published: 05 February 2013
Toshio Kinoshita,1 Shinichiro Fujimoto,Yukio Ishikawa,2 Hitomi Yuzawa,1 Shunji Fukunaga,1Mikihito Toda,3 Kenji Wagatsuma,3 Yoshikiyo Akasaka,2 Toshiharu Ishii,2 Takanori Ikeda1
1Department of Cardiovascular Medicine, 2Department of Pathology, 3Division of Interventional Cardiology, Toho University Faculty of Medicine, Ohta City, Tokyo, Japan

Abstract: Behçet’s disease is a multisystemic vascular inflammatory disease, but concurrent cardiac diseases, such as acute myocardial infarction, are rare. Several complications may arise after coronary intervention for coronary lesions that interfere with treatment, and the incidence of coronary arterial complications due to invasive therapy remains unclear. Further, the long-term outcomes in patients with Behçet’s disease after stenting for acute myocardial infarction have not been described. The present report describes a 35-year-old Japanese man with Behçet’s disease who developed acute myocardial infarction. A coronary aneurysm developed at the stenting site of the left anterior descending coronary artery, along with stenosis in the left anterior descending segment proximal to the site. Although invasive therapy was considered, medication including immunosuppressants was selected because of the high risk of vascular complications after invasive therapy. The coronary artery disease has remained asymptomatic for the 4 years since the patient started medication. This case underscores the importance of considering the incidence of coronary arterial complications and of conservative treatment when possible.

Keywords: Behçet’s disease, myocardial infarction, coronary arterial complications, percutaneous coronary intervention, immunosuppressants

http://www.dovepress.com/coronary-arterial-complications-after-percutaneous-coronary-interventi-peer-reviewed-article-RRCC-recommendation1

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  4. United States Food and Drug Administration (US FDA). Manufacturer and user facility device experience; MAUDE Database, 2001: Accessed atwww.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/TextResults.cfm
  5. Tavris DR, Dey S, Gallauresi B, et al. Risk of local adverse events following cardiac catheterization by hemostasis device use — phase II. J Invasive Cardiol. 2005;17(12):644-650.
  6. An initiative of the American College of Cardiology Foundation, the NCDR, National Cardiovascular Data Registry, is a comprehensive, outcomes-based suite of registries focused on quality improvement. www.ncdr.com. 
  7. Applegate RJ, Sacrinty MT, Kutcher MA, et al. Propensity score analysis of vascular complications after diagnostic cardiac catheterization and percutaneous coronary intervention 1998-2003. Catheter Cardiovasc Interv. 2006;67(4):556-562.
  8. Applegate RJ, Sacrinty M, Kutcher MA, et al. Vascular complications with newer generations of Angio-Seal vascular closure devices. J Interv Cardiol. 2006;19(1):67-74.
  9. Applegate RJ, Sacrinty MT, Kutcher MA, et al. Propensity score analysis of vascular complications after diagnostic cardiac catheterization and percutaneous coronary intervention using thrombin hemostatic patch-facilitated manual compression. J Invasive Cardiol. 2007;19(4):164-170.
  10. Sulzbach-Hoke LM, Ratcliffe SJ, Kimmel SE, et al. Predictors of complications following sheath removal with percutaneous coronary intervention. J Cardiovasc Nurs. 2010;25(3):E1-E8.
  11. Legrand V, Doneux P, Martinez C, et al. Femoral access management: comparison between two different vascular closure devices after percutaneous coronary intervention. Acta Cardiol. 2005;60(5):482-488.
  12. Hermiller JB, Simonton C, Hinohara T, et al. The StarClose Vascular Closure System: interventional results from the CLIP study. Catheter Cardiovasc Interv. 2006;68(5):677-683.
  13. Martin JL, Pratsos A, Magargee E, et al. A randomized trial comparing compression, Perclose Proglide and Angio-Seal VIP for arterial closure following percutaneous coronary intervention: the CAP trial. Catheter Cardiovasc Interv. 2008;71(1):1-5.
  14. Deuling JH, Vermeulen RP, Anthonio RA, et al. Closure of the femoral artery after cardiac catheterization: a comparison of Angio-Seal, StarClose, and manual compression. Catheter Cardiovasc Interv. 2008;71(4):518-523.
  1. Wong SC, Bachinsky W, Cambier P, et al; ECLIPSE Trial Investigators. A randomized comparison of a novel bioabsorbable vascular closure device versus manual compression in the achievement of hemostasis after percutaneous femoral procedures: the ECLIPSE (Ensure’s Vascular Closure Device Speeds Hemostasis Trial). JACC Cardiovasc Interv. 2009;2(8):785-793.
  2. Arora N, Matheny ME, Sepke C, Resnic FS. A propensity analysis of the risk of vascular complications after cardiac catheterization procedures with the use of vascular closure devices. Am Heart J. 2007;153(4):606-611.
  3. Castillo-Sang M, Tsang AW, Almaroof B, et al. Femoral artery complications after cardiac catheterization: a study of patient profile. Ann Vasc Surg. 2010;24(3):328-335.
  4. Sanborn TA, Ebrahimi R, Manoukian SV, et al. Impact of femoral vascular closure devices and antithrombotic therapy on access site bleeding in acute coronary syndromes: the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. Circ Cardiovasc Interv. 2010;3(1):57-62.
  5. Iqtidar AF, Li D, Mather J, McKay RG. Propensity matched analysis of bleeding and vascular complications associated with vascular closure devices vs standard manual compression following percutaneous coronary intervention. Conn Med. 2011;75(1):5-10.
  6. Marso SP, Amin AP, House JA, et al; National Cardiovascular Data Registry. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. JAMA. 2010;303(21):2156-2164.
  7. Ahmed B, Piper WD, Malenka D, et al. Significantly improved vascular complications among women undergoing percutaneous coronary intervention: a report from the Northern New England Percutaneous Coronary Intervention Registry. Circ Cardiovasc Interv. 2009;2(5):423-429.
  8. Trimarchi S, Smith DE, Share D, et al; BMC2 Registry. Retroperitoneal hematoma after percutaneous coronary intervention: prevalence, risk factors, management, outcomes, and predictors of mortality: a report from the BMC2 (Blue Cross Blue Shield of Michigan Cardiovascular Consortium) registry. JACC Cardiovasc Interv. 2010;3(8):845-850.
  9. Vaitkus PT. A meta-analysis of percutaneous vascular closure devices after diagnostic catheterization and percutaneous coronary intervention. J Invasive Cardiol. 2004;16(5):243-246.
  10. Koreny M, Riedmuller E, Nikfardjam M, et al. Arterial puncture closing devices compared with standard manual compression after cardiac catheterization — systematic review and meta-analysis. JAMA. 2004;291(3):350-357.
  11. Nikolsky E, Mehran R, Halkin A, et al. Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: a meta-analysis. J Am Coll Cardiol. 2004;44(6):1200-1209.
  12. Biancari F, D’Andrea V, Di Marco C, et al. Meta-analysis of randomized trials on the efficacy of vascular closure devices after diagnostic angiography and angioplasty. Am Heart J. 2010;159(4):518-531.
  13. Tavris DR, Dey S, Gallauresi B, et al. Risk of local adverse events following cardiac catheterization by hemostasis device use — phase II. J Invasive Cardiol. 2005;17(12): 644-650.

Frequency and Costs of Ischemic and Bleeding Complications After Percutaneous Coronary Interventions: Rationale for New Antithrombotic Therapy

Journal of Invasive Cardiology

http://www.invasivecardiology.com/article/2489

Author(s):

Mauro Moscucci, MD

Recent advances in catheter technology and antithrombotic therapy have led to a continuous improvement in outcomes of percutaneous coronary intervention (PCI). These improved outcomes have been associated with broadening of the indications for PCI, with an exponential growth in number of procedures performed, but they have also been paralleled by incremental procedure costs. The estimated costs of PCI currently range from $8,000–$13,000.1 With over 800,000 cases performed each year in the United States (US) alone, this represents over $10 billion annually for the US Healthcare System.2 Roughly half of these costs are incurred by the Center for Medicare and Medicaid Services (CMS, formerly known as the Health Care Financing Administration).3 Total costs of PCI include disposable equipment used during the procedure (balloons, catheters, stents, etc.), cardiac catheterization laboratory overhead and depreciation, nursing and pharmacy costs, laboratory costs and physician services. In addition, factors that have been found to be associated with increased PCI costs include the use of special devices such as atherectomy or vascular closure devices, the use of multiple stents, the use of platelet glycoprotein (GP) IIb/IIIa inhibitors, and the presence of certain patient demographic characteristics including advanced age, gender and other comorbidities.1,4,5 Finally, complications related to the procedure have been identified in several studies as the single most significant contributor to increased costs of PC.5–7

Methods to reduce the cost of PCI include re-use of balloon catheters,8 percutaneous revascularization performed at the same time as diagnostic catheterization,9 reduced anticoagulation, the use of new devices or pharmacological interventions to reduce restenosis and complications, and the use of competitive bidding for cardiac cath lab supplies.10 For example, the evolution of anticoagulation therapy in stented patients from a regime of post-procedural heparin and warfarin to one of thienopyridines and aspirin,11 and the subsequent reduction of length of stay from 4 days in 1995 to 2 days in 2000, have helped keep total procedure costs down.12 In addition, a reduction in complication rates appears to be a key target for cost reduction efforts. In support of this statement, in the economic assessment of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) trial in high-risk patients, Mark et al. identified bleeding complications, urgent and non-urgent coronary artery bypass graft surgery (CABG), and urgent and non-urgent percutaneous transluminal coronary angioplasty (PTCA) as important correlates of incremental costs.7 Unfortunately, standard aggressive antithrombotic therapy aimed toward a reduction of ischemic complications is often associated with an increase in bleeding complications. In the analysis of the EPIC trial, the benefits of abciximab in decreasing procedure costs through a reduction of ischemic complications were offset by drug acquisition costs and by an increase in bleeding complications.7 Thus, with ischemic complications becoming more rare as a result of improvement in PCI technology and more aggressive antithrombotic therapy, bleeding has become a rather common and costly complication of PCI, with a blood transfusion estimated to add up to $8,000 to the cost of care for the PCI patient.13

Based on these premises, it appears that the next challenge in the care of PCI patients will be to determine how to continue to prevent ischemic complications without increasing the risk of bleeding. This paper examines the frequency of PCI complications in both recent clinical trials and actual practice, discusses the costs of complications, and explores improvements in patient management and particularly changes in anticoagulation therapy that might impact total costs of PCI.

Complication rates in clinical trials

Ischemic complications in clinical trials. Despite advances in PCI technology and adjunctive pharmacotherapy, data from clinical trials indicate that ischemic complications still occur in 5–15% of patients.14–19 Typically, clinical trials define ischemic complications as a combination of death, myocardial infarction (MI; both Q-wave and non-Q wave) and either urgent or any target vessel revascularization (TVR). Different definitions of MI or revascularization can make comparisons across trials difficult. However, comparisons may still be possible through the application of strict meta-analysis methodology. A recent meta-analysis combined data from 6 double-blind PCI trials conducted predominantly in North America between 1993 and 1998.20 A total of 16,546 patients were enrolled in these trials (Table 1). Protocols and case report forms for trials included in the analysis were compared to ensure reasonable consistency of study methods, patient management, data reporting and data structure. Integration of the databases from the trials enabled a direct comparison of key event rates at 7 days, using standard classifications and criteria for severity. The meta-analysis showed that the use of high-dose heparin (175 U/kg) was associated with significantly less frequent clinical ischemic events (8.1%) than lower doses of heparin (100 U/kg; 10.3%). In this same meta-analysis, event rates in patients treated with low-dose heparin (70 U/kg) plus a GP IIb/IIIa inhibitor was 6.5%.20 Although not included in this meta-analysis, it is worth noting that the incidence of death, MI and revascularization in the ESPRIT trial was 9.3% in patients treated with low-dose heparin alone (60 U/kg).21

Bleeding complications in clinical trials. In clinical trials of antiplatelet and anti-thrombotic therapy in PCI, bleeding complications are generally defined using either thrombolysis in myocardial infarction (TIMI)22 or global utilization of streptokinase or tPA outcomes (GUSTO)23 criteria (Table 2). Rates of major bleeding in clinical trials using these criteria are generally less than 2% (Table 3).14–19,21,24,25 However, these restrictive definitions may not capture all clinically significant bleeding. For example, neither the TIMI nor the GUSTO major bleeding definition includes the need for a blood transfusion as part of the criteria. Thus, a broader measure of bleeding using a combination of both major and minor bleeding defined by TIMI or GUSTO criteria appears more likely to be representative of bleeding rates in clinical practice.

In the meta-analysis of contemporary PCI trials, TIMI criteria were used to classify hemorrhagic events, permitting direct comparisons between trials. In the high-dose heparin group, the combination of TIMI major and minor bleeding occurred in 10.5% of patients compared with a rate of 10.7% in the low-dose heparin group, while the bleeding rate was 14.3% in patients receiving a combination of GP IIb/IIIa inhibitors and low-dose heparin.

As shown in Table 3, when both TIMI major and minor bleeding are combined in contemporary PCI trials, bleeding complications average 4–14%, depending on patient characteristics and the drug regime used. In addition, when transfusions are included in the definition, the frequency of bleeding complications increases substantially. For example, in NICE-3, bleeding complications were 10.5% when transfusions were included in the criteria, but only 2% of the patients experienced TIMI major bleeding.26

Notably, the only adjunctive anti-thrombotic agent shown to reduce both ischemic and bleeding complications in PCI is bivalirudin. In the Bivalirudin Angioplasty Trial,27 the risk of bleeding was decreased 62% in the bivalirudin group compared with high-dose heparin. The combined rate of TIMI major and TIMI minor bleeding in bivalirudin patients (n = 2,161) was found to be 4.3% in the meta-analysis of contemporary PCI trials with a corresponding ischemic event rate of 6.6%.20

Complications in practice

Ischemic complications in practice. Rates of ischemic complications in clinical practice are difficult to determine. Although several investigators have published data from multicenter databases, these data tend to be 3–5 years old by the time manuscripts are in print. Since trends in the published literature do show continued reduction in PCI complications over time, the frequency of complications noted in these publications may overestimate the actual rate of complications in clinical practice today. In addition, rates of complications can vary widely across institutions due to differences in practice patterns, definitions, operator skills and resource utilization. For example, in the Society for Cardiac Angiography and Interventions (SCA&I) registry, stent use among laboratories varied from 29–95%.28 Others have found lower complication rates in patients whose procedure was performed by a high-volume operator or in a high-volume institution.29 We identified 6 published reports of PCI complications in clinical practice reporting a variety of ischemic outcomes.1,28–31

Saucedo et al. prospectively collected data on 900 patients undergoing successful elective stent placement in native coronary arteries between January 1994 and December 1995.30 The purpose of this study was to evaluate the incidence and long-term clinical consequences of patients with creatine kinase (CK) myocardial isoenzyme band (CK-MB) elevations after stenting. By design, all patients in this observational study had a successful procedure defined as an increase of > 20% in luminal diameter with final percent diameter stenosis of < 50%, without the occurrence of any major complications (death, Q-wave MI and CABG). Nevertheless, 26.4% of patients had CK-MB elevations 1–5 times the upper limit of normal (ULN) and 8.5% had CK-MB elevations > 5 times ULN. In total, 3.9% of patients required a repeat diagnostic catheterization for recurrent ischemia and 1.2% required urgent target vessel revascularization. In this study, patients requiring the use of GP IIb/IIIa inhibitors were excluded.

The Northern New England group (NNE) collected data on 14,498 patients undergoing PCI between 1994 and 1996.29 In this study, outcomes included the in-hospital occurrence of death; emergency CABG (eCABG) or non-eCABG; or new MI (defined as chest pain, diaphoresis, dyspnea or hypotension associated with the development of new Q-waves or ST-T wave changes and a rise in CK to at least twice normal with a positive CK-MB). Overall, death occurred in 1.2% of patients, CABG in 2.6% (0.8% eCABG and 1.8% non-eCABG), and MI in 2%. Stents were used in 22% of patients enrolled in this registry.

In the National Cardiovascular Network database (NCN), Batchelor et al. reported complications of PCI in 109,708 patients who underwent PCI between 1994 and 1997.31 In this observational study, in-hospital mortality was defined as the occurrence of death after the procedure, MI was defined as the appearance of new Q-waves in 2 contiguous leads on a 12-lead electrocardiogram (ECG) for up to 30 days post-PCI, and repeat revascularization was defined as the need for CABG or additional PCI prior to discharge. In this study, death occurred in 1.3% of patients, Q-wave MI in 1.4% and repeat revascularization in 4.5%. Half of the patients underwent stenting in this study. Notably, this database did not record myocardial enzymes or the use of GP IIb/IIIa inhibitors.

Aronow and colleagues observed outcomes in a cohort of consecutive registry patients undergoing coronary stent placement between 1995 and 1997.32 A total of 373 patients underwent PCI during this time period, with death occurring in 9 patients (2.4%), CABG in 3 (0.8%) and MI in 19 (5.1%, including both QWMI and NQWMI). Repeat diagnostic catheterization was performed in 3.2% of patients and repeat PCI in 0.8%.

The SCA&I registry evaluated outcomes in 16,811 patients undergoing either balloon angioplasty (n = 6,121) or stenting (n = 10,690) between July 1996 and December 1998.28 In this observational analysis, 12.9% of patients received a GP IIb/IIIa inhibitor, 87% of patients enrolled in the database underwent PCI between 1997 and 1998, and 60% of the stent patients were enrolled in 1998. Outcomes reported included in-hospital death (occurring at any time during the hospitalization) and eCABG, defined as CABG occurring immediately after PCI. Death occurred in 0.4% of patients and eCABG in 0.5%.

Finally, Cohen and others recorded in-laboratory complications in 26,421 patients at 70 different centers undergoing PCI in 1998.1 In-laboratory complications were rare, with death occurring in 0.17%, cardiac arrest in 0.32%, stroke in 0.03%, ventricular fibrillation or tachycardia in 0.94%, abrupt closure in 0.71%, and eCABG in 0.53%. Overall, 72% of patients received stents and 20% received GP IIb/IIIa inhibitors.

In addition to published reports of PCI complications, data from unpublished sources can be used to determine outcomes in a more contemporary cohort of patients undergoing PCI.33 The MQ-Profile (MQ-Pro) Database [Cardinal Information Corporation (CIC), Marlborough, Massachusetts] is maintained by CIC, which sells and distributes software to US acute-care hospitals for the collection of detailed clinical and administrative data. Data from 5,373 PCI procedures performed between July 1, 1998 and June 30, 1999 were obtained from the database using International Classification of Diseases 9th Edition (ICD-9) procedure codes for PCI (36.01, 36.02, 36.05). Demographic, clinical and economic data were collected on each patient using a combination of database retrieval and chart review. In this analysis, death was defined as discharge disposition of “deceased”, MI as the presence of ECG changes consistent with MI (new Q-waves or ST-segment changes) or an increase in CK-MB of at least 2 times the testing facility’s ULN. CABG was identified by the presence of ICD-9 procedure code 36.1 and repeat PCI by either code 36.01, 36.02, or 36.05. Failed PCI was defined by the term “failed PTCA” in chart notes (for patients without a previous history of PCI) and recurrent ischemia documented by ECG changes. Death occurred in 2.0% of patients, MI in 3.1%, CABG in 1.3% and repeat PCI in 5.5%. Translated into a combined endpoint similar to those used in clinical trials, the rate of death/MI/revascularization was 11.9%.

Data from these published and unpublished observations of contemporary PCI practice indicate that while in-laboratory ischemic complications are exceedingly rare, in-hospital ischemic complications still occur in a substantial number of patients. Using an approximation of outcomes from these published and unpublished reports, mortality averages 1%, Q-wave MI occurs in 2% of patients, NQWMI in 6%, CABG in 2% and repeat PCI occurs in 3–5% of patients. It is important to underscore that although most deaths following PCI are due to underlying comorbidities (i.e., acute MI, cardiogenic shock, etc.) rather than to the procedure itself, few deaths still occur as a complication of the procedure.34,35 Extrapolated to the estimated PCI population of 800,000 cases per year, then 8,000 people will die and 64,000 will experience an MI. In addition, approximately 16,000 will require CABG and as many as 40,000 will need a repeat PCI before hospital discharge.

II(b) PAD Endovascular Interventions: Carotid Artery Endarterectomy

  • Original Contributions

Medical Complications Associated With Carotid Endarterectomy

Stroke.1999; 30: 1759-1763  doi: 10.1161/​01.STR.30.9.1759

  1. Maurizio Paciaroni, MD;
  2. Michael Eliasziw, PhD;
  3. L. Jaap Kappelle, MD;
  4. Jane W. Finan, BScN;
  5. Gary G. Ferguson, MD;
  6. Henry J. M. Barnett, MD;
  7. for the North American Symptomatic Carotid Endarterectomy Trial (NASCET) Collaborators

+Author Affiliations


  1. From the John P. Robarts Research Institute (M.P., M.E., L.J.K., J.W.F., H.J.M.B) and the Departments of Epidemiology and Biostatistics (M.E.) and Clinical Neurological Sciences (M.E., G.G.F., H.J.M.B.), University of Western Ontario, London, Ontario, Canada.
  1. Correspondence to Dr H.J.M. Barnett, John P. Robarts Research Institute, PO Box 5015, 100 Perth Dr, London, ON N6A 5K8, Canada. E-mail barnett@rri.on.ca

Abstract

Background and Purpose—Carotid endarterectomy (CE) has been shown to be beneficial in patients with symptomatic high-grade (70% to 99%) internal carotid artery stenosis. To achieve this benefit, complications must be kept to a minimum. Complications not associated with the procedure itself, but related to medical conditions, have received little attention.

Methods—Medical complications that occurred within 30 days after CE were recorded in 1415 patients with symptomatic stenosis (30% to 99%) of the internal carotid artery. They were compared with 1433 patients who received medical care alone. All patients were in the North American Symptomatic Carotid Endarterectomy Trial (NASCET).

Results—One hundred fifteen patients (8.1%) had 142 medical complications: 14 (1%) myocardial infarctions, 101 (7.1%) other cardiovascular disorders, 11 (0.8%) respiratory complications, 6 (0.4%) transient confusions, and 10 (0.7%) other complications. Of the 142 complications, 69.7% were of short duration, and only 26.8% prolonged hospitalization. Five patients died: 3 from myocardial infarction and 2 suddenly. Medically treated patients experienced similar complications with one third the frequency. Endarterectomy was ≈1.5 times more likely to trigger medical complications in patients with a history of myocardial infarction, angina, or hypertension (P<0.05).

Conclusions—Perioperative medical complications were observed in slightly fewer than 1 of every 10 patients who underwent CE. The majority of these complications completely resolved. Most complications were cardiovascular and occurred in patients with 1 or more cardiovascular risk factors. In this selected population, the occurrence of perioperative myocardial infarction was uncommon.

Key Words:

The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Endarterectomy Trial showed unequivocal benefit of carotid endarterectomy (CE) in symptomatic patients with high-grade internal carotid artery (ICA) stenosis (70% to 99%).1 2 The parallel study dealing with symptomatic patients with moderate-grade stenosis (30% to 69%) showed benefits of CE only in a carefully selected group of patients.3 Currently, CE is the most common elective peripheral vascular procedure, which in 1997 was performed in ≈130 000 patients in the United States.4

Despite benefit in the long term, CE may cause complications either by the operation itself or by concomitant medical conditions. The challenge for the future is to reduce the perioperative risk as much as possible. The incidence and type of complications that are directly related to the surgical procedure have been the subject of many reports,5 6 7 8 910 whereas medical complications that are not directly caused by the procedure have received less attention. The aim of the present study is to describe the incidence and type of medical complications that occurred in patients randomized into NASCET and to determine their association with baseline risk factors.

Subjects and Methods

The methods of the NASCET have been described in detail elsewhere.1 11 Briefly, NASCET was a randomized clinical trial designed to compare the benefit of best medical therapy alone with best medical therapy plus CE in patients with recent transient or nondisabling neurological deficit caused by cerebral or retinal ischemia in the territory of the ICA. Among the exclusions were patients with recent history (6 months) of myocardial infarction, unstable angina pectoris, atrial fibrillation, recent congestive heart failure, and valvular heart disease. For inclusion, the ICA had to have a 30% to 99% stenosis as assessed by selective carotid angiography and to be technically suitable for CE. Baseline evaluations included a detailed medical history and complete physical and neurological examination.

Surgeons were invited to join NASCET if the center had a documented CE stroke and death rate of ≤6% in a minimum of 50 consecutive cases over a 2-year period. Surgery was completed at the earliest opportunity after randomization, and patients underwent a second complete physical and neurological examination 30 days after surgery. All medical and surgical complications that caused transient or permanent disability within the 30-day period were recorded.

Medical complications consisted of myocardial infarction (based on ECG and cardiac enzyme changes), arrhythmia (requiring antiarrhythmic medication), congestive heart failure, angina pectoris, hypertension (diastolic blood pressure >100 mm Hg requiring intravenous medication), hypotension (systolic pressure <90 mm Hg requiring administration of vasopressor agent), sudden death, respiratory problems (pneumonia, atelectasis, pulmonary edema, or exacerbation of chronic obstructive pulmonary disease), renal failure (doubling of preoperative urea and/or creatinine), depression, and confusion (requiring restraint). Complications were considered mild if they were transient and did not prolong hospital stay, moderate if they were transient but caused delay in hospital discharge, and severe if they were associated with permanent disability or death.

In the present study, patients were excluded from the analyses if they had serious complications that were directly attributable to the surgical procedure, such as those due to anesthesia, thrombosis at the operative site, wound hematomas requiring surgical intervention, or deficits from a vagus nerve injury interfering with swallowing. These surgical complications are described in detail elsewhere.12 For comparative purposes, a list of complications that occurred in the medically treated arm of NASCET was compiled for the 32-day period after randomization (ie, the 30-day period plus the average 2 days that lapsed from randomization to CE in the surgical arm). In both the surgical and medical arms, patients were censored at the time of a stroke, since the subsequent medical complications are commonly the result of the stroke.

Cox proportional hazards regression modeling was used to identify baseline factors that increased the risk of perioperative medical complications. Adjusted hazard rates and adjusted hazard ratios were used to summarize the results. The estimated hazard ratio (or relative hazard) is a measure of association that can be interpreted as a relative risk. Hazard ratios with corresponding probability value of <0.05 were considered statistically significant. Adjusted hazard rates were obtained from the regression model by using the mean value for a factor being adjusted.

The modeling strategy consisted of initially fitting a “full” model, which included all factors. A “final” model was determined by eliminating all factors that were not significantly predictive of the medical complications, using a backward selection approach. The “change-in-estimate” strategy was used to determine whether the remaining factors in the final model were independent risk factors. A factor was considered an independent risk factor if the change in hazard ratios between the full and final models was <10%.

Results

A total of 1436 eligible patients were randomized to the surgical arm and 1449 to the medical arm of the NASCET. In the surgical arm, 21 patients were not operated on for various reasons.12 In the medical arm 16 patients crossed over to surgical therapy within 30 days, leaving 1433 patients for analysis. CE was performed in 1415 patients (328 patients with severe stenosis and 1087 with moderate stenosis). Of the 1415, 59 (4.2%) patients had serious surgical complications that excluded them from further analyses, and 115 (8.1%) had medical complications (Table 1). Of the 142 complications, 69.7% were mild, 26.8% were moderate, and 3.5% were severe. Twenty patients had ≥2 complications. No patient had pulmonary embolus, renal failure, or depression requiring medication. Cardiovascular disorders were >4 times as common as all other conditions combined. All 5 severe complications were fatal and were caused by cardiovascular disorders: 3 patients had fatal myocardial infarction, and 2 patients died suddenly. Of the patients with fatal myocardial infarction, 2 patients had massive myocardial infarctions on the day of surgery. In the other patient, CE was prolonged (7 hours) because of intraoperative occlusion of the ICA. Twenty-four hours after CE, the patient had a myocardial infarction followed by cardiac arrest, leaving the patient in a vegetative state. The patient died 2 months later. Two patients died suddenly on days 3 and 6 after CE, and both had a history of previous myocardial infarction. All patients with fatal medical complications were male, and all had multiple cardiovascular risk factors.

http://stroke.ahajournals.org/content/30/9/1759.full

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  19. Feinberg WM, Albers GW, Barnett HJ, Biller J, Caplan LR, Carter LP, Hart RG, Hobson RW II, Kronmal RA, Moore WS, Robertson JT, Adams HP, Mayberg M. Guidelines for the management of transient ischemic attacks: from the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart Association. Circulation. 1994;89:2950–2965.
  20. Hankey GJ, Warlow CP. Cost-effective investigation of patients with suspected transient ischaemic attacks. J Neurol Neurosurg Psychiatry. 1992;55:171–176.
  21. Wong JH, Findlay JM, Suarez-Almazor ME. Regional performance of carotid endarterectomy: appropriateness, outcomes, and risk factors for complications.Stroke. 1997;28:891–898.
  22. Holton P, Wood JB. The effect of bilateral removal of the carotid bodies and denervation of the carotid sinuses in two human subjects. J Physiol (Lond).1965;181:365–378.
  23. Lilly MP, Brunner MJ, Wehberg KE, Rudolphi DM, Queral LA. Jugular venous vasopressin increases during carotid endarterectomy after cerebral reperfusion. J Vasc Surg. 1992;16:1–9.
  24. Smith BL. Hypertension following carotid endarterectomy: the role of cerebral renin production. J Vasc Surg. 1984;1:623–627.
  25. Eliasziw M, Spence JD, Barnett HJM. Carotid endarterectomy does not affect long-term blood pressure: observations from the NASCET. Cerebrovasc Dis.1998;8:20–24.
  26. Solomon RA, Loftus CM, Quest DO, Correll JW. Incidence and etiology if intracerebral hemorrhage following carotid endarterectomy. J Neurosurg.1986;64:29–34.
  27. Hafner DH, Smith RB, King OW, Perdue GD, Stewart MT, Rosenthal D, Jordan WD. Massive intracerebral hemorrhage following carotid endarterectomy. Arch Surg.1987;122:305–307.
  28. Piepgras DG, Morgan MK, Sundt TM, Yanagihara T, Mussman LM. Intracerebral hemorrhage after carotid endarterectomy. J Neurosurg. 1988;68:532–536.
  29. Jansen C, Sprengers AM, Moll FL, Vermeulen FE, Hamerlijnck RP, van Gijn J, Ackerstaff RG. Prediction of intracerebral hemorrhage after carotid endarterectomy by clinical criteria and intraoperative transcranial Doppler monitoring. Eur J Vasc Surg. 1994;8:303–308.
  30. Chambers BR, Smidt U, Koh O. Hyperperfusion post-endarterectomy.Cerebrovasc Dis. 1994;4:32–37.
  31. Penn AA, Schomer DF, Steinberg GK. Imaging studies of cerebral hyperperfusion after carotid endarterectomy: case report. J Neurosurg. 1995;83:133–137.
  32. Baptista MV, Maeder P, Dewarrat A, Bogousslavsky J. Conflicting images.Lancet. 1998;351:414.

Intraoperative use of dextran is associated with cardiac complications after carotid endarterectomy.

J Vasc Surg. 2013 Mar;57(3):635-41. doi: 10.1016/j.jvs.2012.09.017. Epub 2013 Jan 18.

Source

Section of Vascular and Endovascular Surgery, Boston University Medical Center, Boston, MA, USA. Alik.Farber@bmc.org

Abstract

OBJECTIVE:

Although dextran has been theorized to diminish the risk of stroke associated with carotid endarterectomy (CEA), variation exists in its use. We evaluated outcomes of dextran use in patients undergoing CEA to clarify its utility.

METHODS:

We studied all primary CEAs performed by 89 surgeons within the Vascular Study Group of New England database (2003-2010). Patients were stratified by intraoperative dextran use. Outcomes included perioperative death, stroke, myocardial infarction (MI), and congestive heart failure (CHF). Group and propensity score matching was performed for risk-adjusted comparisons, and multivariable logistic and gamma regressions were used to examine associations between dextran use and outcomes.

RESULTS:

There were 6641 CEAs performed, with dextran used in 334 procedures (5%). Dextran-treated and untreated patients were similar in age (70 years) and symptomatic status (25%). Clinical differences between the cohorts were eliminated by statistical adjustment. In crude, group-matched, and propensity-matched analyses, the stroke/death rate was similar for the two cohorts (1.2%). Dextran-treated patients were more likely to suffer postoperative MI (crude: 2.4% vs 1.0%; P = .03; group-matched: 2.4% vs 0.6%; P = .01; propensity-matched: 2.4% vs 0.5%; P = .003) and CHF (2.1% vs 0.6%; P = .01; 2.1% vs 0.5%; P = .01; 2.1% vs 0.2%; P < .001). In multivariable analysis of the crude sample, dextran was associated with a higher risk of postoperative MI (odds ratio, 3.52; 95% confidence interval, 1.62-7.64) and CHF (odds ratio, 5.71; 95% confidence interval, 2.35-13.89).

CONCLUSIONS:

Dextran use was not associated with lower perioperative stroke but was associated with higher rates of MI and CHF. Taken together, our findings suggest limited clinical utility for routine use of intraoperative dextran during CEA.

J Vasc Surg. 2008 Nov;48(5):1139-45. doi: 10.1016/j.jvs.2008.05.013. Epub 2008 Jun 30.

Factors associated with stroke or death after carotid endarterectomy in Northern New England.

Source

Section of Vascular Surgery Dartmouth-Hitchcock Medical Center, Lebanon, NH 03765, USA. philip.goodney@hitchcock.org

Abstract

OBJECTIVE:

This study investigated risk factors for stroke or death after carotid endarterectomy (CEA) among hospitals of varying type and size participating in a regional quality improvement effort.

METHODS:

We reviewed 2714 patients undergoing 3092 primary CEAs (excluding combined procedures or redo CEA) at 11 hospitals in Northern New England from January 2003 through December 2007. Hospitals varied in size (25 to 615 beds) and comprised community and teaching hospitals. Fifty surgeons reported results to the database. Trained research personnel prospectively collected >70 demographic and clinical variables for each patient. Multivariate logistic regression models were used to generate odds ratios (ORs) and prediction models for the 30-day postoperative stroke or death rate.

RESULTS:

Across 3092 CEAs, there were 38 minor strokes, 14 major strokes, and eight deaths (5 stroke-related) < or =30 days of the index procedure (30-day stroke or death rate, 1.8%). In multivariate analyses, emergency CEA (OR, 7.0; 95% confidence interval [CI], 1.8-26.9; P = .004), contralateral internal carotid artery occlusion (OR, 2.8; 95% CI, 1.3-6.2; P = .009), preoperative ipsilateral cortical stroke (OR, 2.4; 95% CI, 1.1-5.1; P = .02), congestive heart failure (OR, 1.6; 95% CI, 1.1-2.4, P = .03), and age >70 (OR, 1.3; 95% CI, 0.8-2.3; P = .315) were associated with postoperative stroke or death. Preoperative antiplatelet therapy was protective (OR, 0.4; 95% CI, 0.2-0.9; P = .02). Risk of stroke or death varied from <1% in patients with no risk factors to nearly 5% with patients with > or =3 risk factors. Our risk prediction model had excellent correlation with observed results (r = 0.96) and reasonable discriminative ability (area under receiver operating characteristic curve, 0.71). Risks varied from <1% in asymptomatic patients with no risk factors to nearly 4% in patients with contralateral internal carotid artery occlusion (OR, 3.2; 95% CI, 1.3-8.1; P = .01) and age >70 (OR, 2.9; 95% CI, 1.0-4.9, P = .05). Two hospitals performed significantly better than expected. These differences were not attributable to surgeon or hospital volume.

CONCLUSION:

Surgeons can “risk-stratify” preoperative patients by considering the variables (emergency procedure, contralateral internal carotid artery occlusion, preoperative ipsilateral cortical stroke, congestive heart failure, and age), reducing risk with antiplatelet agents, and informing patients more precisely about their risk of stroke or death after CEA. Risk prediction models can also be used to compare risk-adjusted outcomes between centers, identify best practices, and hopefully, improve overall results.

III. Cardiac Failure During Systemic Sepsis

CHANGES IN HEART FUNCTION DURING SEPSIS

The patient with sepsis has severely altered physiology in a number of ways, which can influence cardiac function. Firstly, there is a

  • Loss of intravascular volume due to excessive third space loss that results in a decrease in preload. Systemic vascular resistance is decreased which results in a fall in afterload. In addition,
  • end diastolic volumes often increase and
  • ejection fraction falls. However, many of these changes are overcome by an
  • increase in heart rate that may result in an increase in cardiac output. However, it should be remembered that even in the presence of high cardiac outputs it is usually always possible to demonstrate
  • ventricular dysfunction in patients with sepsis. Echocardiographic studies consistently confirm that there is decreased left ventricular systolic function in humans with sepsis.

In addition, there have been many studies in animals and a few in humans which have confirmed the presence of

  • diastolic dysfunction – particularly in those patients that go on to die from sepsis.

In the presence of adequate fluid resuscitation there is an increase in end diastolic volume and this is probably a normal response to a decrease in contractility. However, in the non-survivors of sepsis there is a normal or low end diastolic volume that is the result of a decrease in ventricular diastolic compliance. Thus, there is a decreased end diastolic volume at the same filling pressure.

During sepsis, a

  • decrease in contractility results in a shift to the right of the end-systolic pressure / volume curve and if this is not compensated for results in a
  • decrease in stroke volume and cardiac output.

When patients with sepsis are appropriately fluid resuscitated there is an

  • increase in end diastolic pressure that increases stroke volume. In addition, the
  • decrease in afterload will also increase stroke volume and will prevent a decrease in ejection fraction.

Alas, because there is a decrease in systolic contractility it would be expected that there would also be a decrease in diastolic stiffness which would allow cardiac output to be maintained despite the relatively low filling pressures. However, if this diastolic compliance change does not occur (as in the nonsurvivors of sepsis) then it is apparent  that the ability of the ventricle to generate a stroke volume is impaired at both ends of the curve.

The cause of the altered cardiac function in sepsis remains unknown although there are many theoretical explanations. Clearly, one of the most important mechanisms which can be readily corrected is hypovolaemia.

  • Myocardial oedema may contribute to a decrease in contractility.
  • Increased circulating catecholamines can result in a decrease in diastolic compliance, particularly important since these agents are often used to improve myocardial contractility.
  • Increased intrathoracic pressure caused by positive pressure ventilation can also result in decreased diastolic compliance. In addition, many of the
  • mediators of the inflammatory response, including products of activated endothelial cells and polymorphonuclear leucocytes (e.g. nitric oxide, tumour necrosis factor and interleukins 1 and 2) have all been postulated as negative inotropes and negative lusitropes.

Another, as yet, unidentified agent which is believed to be released from the splanchnic bed –

  • myocardial depressant factor – is postulated to play a role.

Treatments aimed at correcting the effects of these various inflammatory mediators may be eventually found but until these approaches have been proven to be beneficial the septic patient will continue to be managed according to the physiological principles outlined by Starling.

http://www.rcsed.ac.uk/RCSEDBackIssues/journal/vol46_1/4610005.htm

Sepsis and the Heart – Cardiovascular Involvement in General Medical Conditions

  1. M.W. Merx, MD;
  2. C. Weber, MD

+Author Affiliations


  1. From the Department of Medicine (M.W.M.), Division of Cardiology, Pulmonary Diseases and Vascular Medicine and the Institute of Molecular Cardiovascular Research (IMCAR) at the University Hospital (C.W.), RWTH Aachen University, Aachen, Germany.
  1. Correspondence to Marc W. Merx, MD, Medizinische Klinik I, Universitätsklinikum der RWTH Aachen, Pauwelstraße 30, 52057 Aachen, Germany (e-mailmmerx@ukaachen.de), or Christian Weber, MD, Institut für Kardiovaskuläre Molekularbiologie, Universitätsklinikum der RWTH Aachen, Pauwelstraße 30, 52057 Aachen, Germany (e-mail cweber@ukaachen.de).
Circulation.2007; 116: 793-802doi: 10.1161/​CIRCULATIONAHA.106.678359

Abstract

Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual. As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date. There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis; however, in septic patients with coexistent and possibly undiagnosed coronary artery disease, regional myocardial ischemia or infarction secondary to coronary artery disease may certainly occur.

A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include

  • cytokines,
  • prostanoids, and
  • nitric oxide, among others.
  • Endothelial activation and
  • induction of the coagulatory system also contribute to the pathophysiology in sepsis.

Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. The purpose of this review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.

Key Words:

Sepsis, defined by consensus conference as “the systemic inflammatory response syndrome (SIRS) that occurs during infection,”1 is generally viewed as a disease aggravated by the inappropriate immune response encountered in the affected individual (for review, see Hotchkiss and Karl2 and Riedemann et al,3). The Table gives the current criteria for the establishment of the diagnosis of systemic inflammatory response syndrome, sepsis, and septic shock.1,4 Morbidity and mortality are high, resulting in sepsis and septic shock being the 10th most common cause of death in the United States.5 The incidence of sepsis and sepsis-related deaths appears to be increasing by 1.5% per year.6 In a recent study,6 the total national hospital cost invoked by severe sepsis in the United States was estimated at approximately $16.7 billion on the basis of an estimated severe sepsis rate of 751 000 cases per year with 215 000 associated deaths annually. A recent study from Britain documented a 46% in-hospital mortality rate for patients presenting with severe sepsis on admission to the intensive care unit.7

Current Criteria for Establishment of the Diagnosis of SIRS, Sepsis, and Septic Shock1,4

As an important organ system frequently affected by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. In 1951, Waisbren was the first to describe cardiovascular dysfunction due to sepsis.8 He recognized a hyperdynamic state with full bounding pulses, flushing, fever, oliguria, and hypotension. In addition, he described a second, smaller patient group who presented clammy, pale, and hypotensive with low volume pulses and who appeared more severely ill. With hindsight, the latter group might well have been volume underresuscitated, and indeed, timely and adequate volume therapy has been demonstrated to be one of the most effective supportive measures in sepsis therapy.9

Under conditions of adequate volume resuscitation, the profoundly reduced systemic vascular resistance typically encountered in sepsis10 leads to a concomitant elevation in cardiac index that obscures the myocardial dysfunction that also occurs. However, as early as the mid-1980s, significant reductions in both stroke volume and ejection fraction in septic patients were observed despite normal total cardiac output.11 Importantly, the presence of cardiovascular dysfunction in sepsis is associated with a significantly increased mortality rate of 70% to 90% compared with 20% in septic patients without cardiovascular impairment.12 Thus, myocardial dysfunction in sepsis has been the focus of intense research activity. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear.

The purpose of the present review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches. This review is not intended to be all inclusive.

Characteristics of Myocardial Dysfunction in Sepsis

Using portable radionuclide cineangiography, Calvin et al13 were the first to demonstrate myocardial dysfunction in adequately volume-resuscitated septic patients with decreased ejection fraction and increased end-diastolic volume index. Adding pulmonary artery catheters to serial radionuclide cineangiography, Parker and colleagues11 extended these observations with the 2 major findings that (1) survivors of septic shock were characterized by increased end-diastolic volume index and decreased ejection fraction, whereas nonsurvivors typically maintained normal cardiac volumes, and (2) these acute changes in end-diastolic volume index and ejection fraction, although sustained for several days, were reversible. More recently, echocardiographic studies have demonstrated impaired left ventricular systolic and diastolic function in septic patients.14–16 These human studies, in conjunction with experimental studies ranging from the cellular level17 to isolated heart studies18,19 and to in vivo animal models,20–22 have clearly established decreased contractility and impaired myocardial compliance as major factors that cause myocardial dysfunction in sepsis.

Notwithstanding the functional and structural differences between the left and right ventricle, similar functional alterations, as discussed above, have been observed for the right ventricle, which suggests that right ventricular dysfunction in sepsis closely parallels left ventricular dysfunction.23–26 However, the relative contribution of the right ventricle to septic cardiomyopathy remains unknown.

Myocardial dysfunction in sepsis has also been analyzed with respect to its prognostic value. Parker et al,27 reviewing septic patients on initial presentation and at 24 hours to determine prognostic indicators, found a heart rate of <106 bpm to be the only cardiac parameter on presentation that predicted a favorable outcome. At 24 hours after presentation, a systemic vascular resistance index >1529 dyne · s−1 · cm−5 · m−2, a heart rate <95 bpm or a reduction in heart rate >18 bpm, and a cardiac index >0.5 L · min−1 · m−2 suggested survival.27 In a prospective study, Rhodes et al28 demonstrated the feasibility of a dobutamine stress test for outcome stratification, with nonsurvivors being characterized by an attenuated inotropic response. The well-established biomarkers in myocardial ischemia and heart failure, cardiac troponin I and T, as well as B-type natriuretic peptide, have also been evaluated with regard to sepsis-associated myocardial dysfunction. Although B-type natriuretic peptide studies have delivered conflicting results in septic patients (for review, see Maeder et al29), several small studies have reported a relationship between elevated cardiac troponin T and I and left ventricular dysfunction in sepsis, as assessed by echocardiographic ejection fraction30–33 or pulmonary artery catheter–derived left ventricular stroke work index.34 Cardiac troponin levels also correlated with the duration of hypotension35 and the intensity of vasopressor therapy.34In addition, increased sepsis severity, measured by global scores such as the Simplified Acute Physiology Score II (SAPS II) or the Acute Physiology And Chronic Health Evaluation II score (APACHE II), was associated with increased cardiac troponin levels,31,33 as was poor short-term prognosis.32,33,35,36 Despite the heterogeneity of study populations and type of troponin studied, the mentioned studies were univocal in concluding that elevated troponin levels in septic patients reflect higher disease severity, myocardial dysfunction, and worse prognosis. In a recent meta-analysis of 23 observational studies, Lim et al37 found cardiac troponin levels to be increased in a large percentage of critically ill patients. Furthermore, in a subset of studies that permitted adjusted analysis and comprised 1706 patients, this troponin elevation was associated with an increased risk of death (odds ratio, 2.5; 95% CI, 1.9 to 3.4, P<0.001)37; however, the underlying mechanisms clearly require further research.

Thus, it appears reasonable to recommend inclusion of cardiac troponins in the monitoring of patients with severe sepsis and septic shock to facilitate prognostic stratification and to increase alertness to the presence of cardiac dysfunction in individual patients. However, it remains to be shown whether risk stratification based on cardiac troponins can identify patients in whom aggressive therapeutic regimens might reap the greatest benefit and so translate into a survival benefit.

Mechanisms Underlying Myocardial Dysfunction in Sepsis

Cardiac depression during sepsis is probably multifactorial (Figure). Nevertheless, it is important to identify individual contributing factors and mechanisms to generate worthwhile therapeutic targets. As a consequence, a vast array of mechanisms, pathways, and disruptions in cellular homeostasis have been examined in septic myocardium.

Figure

View larger version:

Synopsis of potential underlying mechanisms in septic myocardial dysfunction. MDS indicates myocardial depressant substance.

Global Ischemia

An early theory of myocardial depression in sepsis was based on the hypothesis of global myocardial ischemia; however, septic patients have been shown to have high coronary blood flow and diminished coronary artery–coronary sinus oxygen difference.38 As in the peripheral circulation, these alterations can be attributed to disturbed flow autoregulation or disturbed oxygen utilization.39,40 Coronary sinus blood studies in patients with septic shock have also demonstrated complex metabolic alterations in septic myocardium, including increased lactate extraction, decreased free fatty acid extraction, and decreased glucose uptake.41 Furthermore, several magnetic resonance studies in animal models of sepsis have demonstrated the presence of normal high-energy phosphate levels in the myocardium.42,43 It has also been proposed that myocardial dysfunction in sepsis may reflect hibernating myocardium.44 To reach this conclusion, Levy et al44 studied a murine cecal ligation and double-puncture model and observed diminished cardiac performance, increased myocardial glucose uptake, and deposits of glycogen in a setting of preserved arterial oxygen tension and myocardial perfusion. Although all of the above-mentioned findings reflect important alterations in coronary flow and myocardial metabolism, mirroring effects observed in peripheral circulation during sepsis, there is no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis. However, in septic patients with coexistent and possibly undiagnosed coronary artery disease (CAD), regional myocardial ischemia or infarction secondary to CAD may certainly occur. The manifestation of myocardial ischemia due to CAD might even be facilitated by the volatile hemodynamics in sepsis, as well as by the generalized microvascular dysfunction so frequently observed in sepsis.45 Additional CAD-aggravating factors encountered in sepsis encompass generalized inflammation and the activated coagulatory system. Furthermore, the endothelium plays a prominent role in sepsis (see below), but little is known of the impact of preexisting, CAD-associated endothelial dysfunction in this context. In a postmortem study of 21 fatal cases of septic shock, previously undiagnosed myocardial ischemia at least contributed to death in 7 of the 21 cases (all 21 patients were males, with a mean age of 60.4 years).46 It certainly appears prudent to remain wary of CAD complications while treating sepsis, especially in patients with identifiable risk factors and in view of the ever-increasing mean age of intensive care unit patients and including septic patients.

Myocardial Depressant Substance

A circulating myocardial depressant factor in septic shock was first proposed more than 50 years ago.47 Parrillo et al48 quantitatively linked the clinical degree of septic myocardial dysfunction with the effect the serum, taken from respective patients, had on rat cardiac myocytes, with clinical severity correlating well with the decrease in extent and velocity of myocyte shortening. These effects were not seen when serum from convalescent patients whose cardiac function had returned to normal was applied or when serum was obtained from other critically ill, nonseptic patients.48 In extension of these findings, ultrafiltrates from patients with severe sepsis and simultaneously reduced left ventricular stroke work index (<30 g · m−1 · m−2) displayed cardiotoxic effects and contained significantly increased concentrations of interleukin (IL)-1, IL-8, and C3a.49Recently, Mink et al50 demonstrated that lysozyme c, a bacteriolytic agent believed to originate mainly from disintegrating neutrophilic granulocytes and monocytes, mediates cardiodepressive effects during Escherichia coli sepsis and, importantly, that competitive inhibition of lysozyme c can prevent myocardial depression in the respective experimental sepsis model. Additional potential candidates for myocardial depressant substance include other cytokines, prostanoids, and nitric oxide (NO). Some of these will be discussed below.

Cytokines

Infusion of lipopolysaccharide (LPS, an obligatory component of Gram-negative bacterial cell walls) into both animals and humans51 partially mimics the hemodynamic effects of septic shock.51,52 However, only a minority of patients with septic shock have detectable LPS levels, and the prolonged time course of septic myocardial dysfunction and the chemical characteristics of LPS are not consistent with LPS representing the sole myocardial depressant substance.48,53 Tumor necrosis factor-α (TNF-α) is an important early mediator of endotoxin-induced shock.54 TNF-α is derived from activated macrophages, but recent studies have shown that TNF-α is also secreted by cardiac myocytes in response to sepsis.55 Although application of anti-TNF-α antibodies improved left ventricular function in patients with septic shock,56 subsequent studies using monoclonal antibodies directed against TNF-α or soluble TNF-α receptors failed to improve survival in septic patients.57–59 IL-1 is synthesized by monocytes, macrophages, and neutrophils in response to TNF-α and plays a crucial role in the systemic immune response. IL-1 depresses cardiac contractility by stimulating NO synthase (NOS).60 Transcription of IL-1 is followed by delayed transcription of IL-1 receptor antagonist (IL-1-ra), which functions as an endogenous inhibitor of IL-1. Recombinant IL-1-ra was evaluated in phase III clinical trials, which showed a tendency toward improved survival61 and increased survival time in a retrospective analysis of the patient subgroup with the most severe sepsis62; however, to date, this initially promising therapy has failed to deliver a statistically significant survival benefit. IL-6, another proinflammatory cytokine, has also been implicated in the pathogenesis of sepsis and is considered a more consistent predictor of sepsis than TNF-α because of its prolonged elevation in the circulation.63 Although cytokines may very well play a key role in the early decrease in contractility, they cannot explain the prolonged duration of myocardial dysfunction in sepsis, unless they result in the induction or release of additional factors that in turn alter myocardial function, such as prostanoids or NO.64,65

Prostanoids

Prostanoids are produced by the cyclooxygenase enzyme from arachidonic acid. The expression of cyclooxygenase enzyme-2 is induced, among other stimuli, by LPS and cytokines (cyclooxygenase enzyme-1 is expressed constitutively).66 Elevated levels of prostanoids such as thromboxane and prostacyclin, which have the potential to alter coronary autoregulation, coronary endothelial function, and intracoronary leukocyte activation, have been demonstrated in septic patients.67 Early animal studies with cyclooxygenase inhibitors such as indomethacin yielded very promising results.68,69Along with other positive results, these led to an important clinical study involving 455 septic patients who were randomized to receive intravenous ibuprofen or placebo.70Unfortunately, that study did not demonstrate improved survival for the treatment arm. Similarly, a more recent, smaller study on the effects of lornoxicam failed to provide evidence for a survival benefit through cyclooxygenase inhibition in sepsis.71 Animal studies aimed at elucidating possible benefits of isotype-selective cyclooxygenase inhibition have so far produced conflicting results.72,73

Endothelin-1

Endothelin-1 (ET-1; for an in-depth review of endothelin in sepsis, see Gupta et al74) upregulation has been demonstrated within 6 hours of LPS-induced septic shock.75Cardiac overexpression of ET-1 triggers an increase in inflammatory cytokines (among others, TNF-α, IL-1, and IL-6), interstitial inflammatory infiltration, and an inflammatory cardiomyopathy that results in heart failure and death.76 The involvement of ET-1 in septic myocardial dysfunction is supported by the observation that tezosentan, a dual endothelin-A and endothelin-B receptor antagonist, improved cardiac index, stroke volume index, and left ventricular stroke work index in endotoxemic shock.77 However, higher doses of tezosentan exhibited cardiotoxic effects and led to increased mortality.77Although ET-1 has been demonstrated to be of pathophysiological importance in a wide array of cardiac diseases through autocrine, endocrine, or paracrine effects, its biosynthesis, receptor-mediated signaling, and functional consequences in septic myocardial dysfunction warrant further investigation to assess the therapeutic potential of ET-1 receptor antagonists.

Nitric Oxide

NO exerts a plethora of biological effects in the cardiovascular system.78 It has been shown to modulate cardiac function under physiological and a multitude of pathophysiological conditions. In healthy volunteers, low-dose NO increases LV function, whereas inhibition of endogenous NO release by intravenous infusion of the NO synthase (NOS) inhibitor NG-monomethyl-L-arginine reduced the stroke volume index.79 Higher doses of NO have been shown to induce contractile dysfunction by depressing myocardial energy generation.80 The absence of the important NO scavenger myoglobin (Mb) in Mb knockout mice results in impaired cardiac function that is partially reversible by NOS inhibition.81 Endogenous NO contributes to hibernation in response to myocardial ischemia by reducing oxygen consumption and preserving calcium sensitivity and contractile function.82 NO also represents a potent modulator of myocardial ischemia/reperfusion injury. However, as in sepsis-related NO research, the reported effects of NO on ischemia/reperfusion injury are inconsistent owing to a multitude of confounding experimental factors.83

Sepsis leads to the expression of inducible NOS (iNOS) in the myocardium,84,85 followed by high-level NO production, which in turn importantly contributes to myocardial dysfunction, in part through the generation of cytotoxic peroxynitrite, a product of NO and superoxide (for an excellent review, see Pacher et al86). In iNOS-deficient mice, cardiac function is preserved after endotoxin challenge.87 Nonspecific NOS inhibition restores cardiac output and stroke volume after LPS injection.88 Strikingly, in septic patients, infusion of methylene blue, a nonspecific NOS inhibitor, improves mean arterial pressure, stroke volume, and left ventricular stroke work and decreases the requirement for inotropic support but, unfortunately, does not alter outcome.89 An interesting study comparing the inhibition of NO superoxide and peroxynitrite in cytokine-induced myocardial contractile failure found peroxynitrite to indeed be the most promising therapeutic target.90 It has also been proposed that the constitutively expressed mitochondrial isoform of NOS (mtNOS), the expression of which can be augmented by induction, controls rates of oxidative phosphorylation by inhibiting various steps of the respiratory chain.91 Although this hypothesis would provide a plausible explanation for the reduced coronary oxygen extraction observed during sepsis (see above), the effects of sepsis on expression of mtNOS and NO generation remain to be explored. Furthermore, the constitutively expressed endothelial NOS (eNOS), previously neglected in the context of sepsis, has been shown to be an important regulator of iNOS expression, resulting in a more stable hemodynamic status in eNOS-deficient mice after endotoxemia.92 Very recently, a functional NOS in red blood cells (rbcNOS) was identified that regulates deformability of erythrocyte membranes and inhibits activation of platelets.93 With both effect targets thus far demonstrated for rbcNOS lying at the core of microvascular dysfunction in sepsis, this discovery opens a whole new window to NO-related sepsis research. Given the existence of different NOS isoforms and their various modulating interactions, dose-dependent NO effects, and the precise balance of NO, superoxide, and thus peroxynitrite generated in subcellular compartments, further advances in our understanding of the complex NO biology and its derived reactive nitrogen species hold the promise of revealing new, more specific and effective therapeutic targets.

Adhesion Molecules

Surface-expression upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 has been demonstrated in murine coronary endothelium and cardiomyocytes after LPS and TNF-α stimulation.94 After cecal ligation and double puncture, myocardial intercellular adhesion molecule-1 expression increases in rats.95Vascular cell adhesion molecule-1 blockade with antibodies has been shown to prevent myocardial dysfunction and decrease myocardial neutrophil accumulation,94,96 whereas both knockout and antibody blockade of intercellular adhesion molecule-1 ameliorate myocardial dysfunction in endotoxemia without affecting neutrophil accumulation.94 In addition, neutrophil depletion does not protect against septic cardiomyopathy, which suggests that the cardiotoxic potential of neutrophils infiltrating the myocardium is of lesser importance in this context.94 Other aspects of adhesion molecules are discussed in conjunction with possible statin effects below.

The e-Reader is advised to consider the following expansion on the subject matter carrying the discussion to additional related clinical issues:

Advanced Topics in Sepsis and the Cardiovascular System at its End Stage

Author: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-sepsis-and-the-cardiovascular-system-at-its-end-stage/

Therapeutic Approaches: The Present and the Future

A detailed discussion of therapeutic options in septic patients would clearly be beyond the scope of this review, and readers are kindly referred to the multiple excellent reviews published on the subject (eg, Hotchkiss and Karl,2 Annane et al,4 and Dellinger et al97). Although a number of preventive measures, such as prophylactic antibiotics, maintenance of normoglycemia, selective digestive tract decontamination, vaccines, and intravenous immunoglobulin, have shown benefit in distinct patient populations, preventive strategies with a broader aim remain elusive. Once sepsis is manifest (see the Table for criteria), prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. Supportive therapy encompasses early and goal-directed fluid resuscitation,9 vasopressor and inotropic therapy, red blood cell transfusion, mechanical ventilation, and renal support when indicated. It is very likely beneficial to monitor cardiac performance in these patients. A wide array of techniques are available for this purpose, ranging from echocardiography to pulmonary catheters, thermodilution techniques, and pulse pressure analysis.98 Because none of these techniques have demonstrated superiority, physicians should use the method with which they are most familiar. Whichever method is chosen, it should be applied frequently to tailor supportive therapy to the individual patient and to achieve the “gold standard” of early goal-directed therapy. In recent years, several attempts have been made to therapeutically address myocardial dysfunction in sepsis. Although the combination of norepinephrine as vasopressor and dobutamine as inotropic agent is probably the most frequently applied in septic shock, there is currently no evidence to recommend one catecholamine over the other.97 In human endotoxemia, epinephrine has been demonstrated to inhibit proinflammatory pathways and coagulation activation, as well as to augment antiinflammatory pathways,99,100 whereas no immunomodulatory or coagulant effects could be demonstrated for dobutamine in a similar setting.101 Isoproterenol has recently been applied successfully in a small group of patients with septic shock, no known history of CAD, and inappropriate mixed venous oxygen concentration despite correction of hypoxemia and anemia.102 In a cecal ligation and double-puncture model of sepsis, the β-blocker esmolol given continuously after sepsis induction improved myocardial oxygen utilization and attenuated myocardial dysfunction,103 which suggests that therapeutic strategies proven in ischemic heart failure might also hold promise in septic cardiomyopathy. However, the optimal mode of β-receptor stimulation (or indeed inhibition) to limit myocardial dysfunction remains a wide-open field for inspired investigation.

Given the generally accepted view of sepsis as a disease largely propelled by an inappropriate immune response, numerous basic research and clinical trials have been undertaken to curb the lethal toll of sepsis through modulation of this uncontrolled immune response.2,3 To date, activated protein C104 and low-dose hydrocortisone105 have emerged as the only inflammation-modulating substances that have been confirmed to be of benefit in patients with severe sepsis and septic shock. Over the past years, increasing evidence has accumulated that suggests that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, or statins, have therapeutic benefits independent of cholesterol lowering, termed “pleiotropic” effects. These have added a wide scope of potential targets for statin therapy that range from decreasing renal function loss106 and lowering mortality in patients with diastolic heart failure107 to prevention and treatment of stroke,108 to name just a few. These pleiotropic effects include antiinflammatory and antioxidative properties, improvement of endothelial function, and increased NO bioavailability and thus might contribute to the benefit observed with statin therapy. Notably, these important immunomodulatory effects of statins have been demonstrated to be independent of lipid lowering109 and appear to be mediated via interference with the synthesis of mevalonate metabolites (nonsteroidal isoprenoid products). Blockade of the mevalonate pathway has been shown to suppress T-cell responses,110 reduce expression of class II major histocompatibility complexes on antigen presenting cells,109 and inhibit chemokine synthesis in peripheral blood mononuclear cells.111 Furthermore, CD11b integrin expression and CD11b-dependent adhesion of monocytes have been found to be attenuated by the initiation of statin treatment in hypercholesterolemic patients.112 In this context, Yoshida et al113 have reported that statins reduce the expression of both monocytic and endothelial adhesion molecules, eg, the integrin leukocyte function-associated antigen-1 (LFA-1), via an inhibition of Rho GTPases, in particular their membrane anchoring by geranylation. In addition, mechanisms for antiinflammatory actions of statins have been revealed that are not related to the isoprenoid metabolism. For instance, Weitz-Schmidt et al114 have identified that some statins act as direct antagonists of LFA-1 owing to their capacity to bind to the regulatory site in the LFA-1 i-domain. In addition to these multifaceted antiinflammatory effects, statins may interfere with activation of the coagulation cascade, as illustrated by the suppression of LPS-induced monocyte tissue factor in vitro.115 Beyond their immunomodulatory functions, statins have been shown to exert direct antichlamydial effects during pulmonary infection with Chlamydia pneumoniae in mice,116 and a recent report suggests the benefit of statins may also extend to viral pathogens.117

Given the strong impact of statins on inflammation, statins might represent a welcome enforcement in the battle against severe infectious diseases such as sepsis. Consequently, several investigators have evaluated the role of statins in the prevention and treatment of sepsis. In a retrospective analysis, Liappis et al118 demonstrated a reduced overall and attributable mortality in patients with bacteremia who were treated concomitantly with statins. Pretreatment with simvastatin has been shown to profoundly improve survival in a polymicrobial murine model of sepsis by preservation of cardiovascular function and inhibition of inflammatory alterations.19 Encouraged by these findings, the same model was used to successfully treat sepsis in a clinically feasible fashion, ie, treatment was initiated several hours after the onset of sepsis. With different statins (atorvastatin, pravastatin, and simvastatin) being effective, the therapeutic potential of statins in sepsis appears to be a class effect.22 Recently, Steiner et al119observed that pretreatment with simvastatin can suppress the inflammatory response induced by LPS in healthy human volunteers. Furthermore, in a prospective observational cohort study in patients with acute bacterial infections performed by Almog et al,120previous treatment with statins was associated with a considerably reduced rate of severe sepsis and intensive care unit admissions. A total of 361 patients were enrolled in that study, and 82 of these patients had been treated with statins for at least 4 weeks before their admission. Severe sepsis developed in 19% of patients in the no-statin group compared with only 2.4% in patients who were taking statins. The intensive care unit admission rates were 12.2% for the no-statin group and 3.7% for the statin group. Because of the number of patients enrolled, the study was not powered to detect differences in mortality, although the large effect on sepsis rate and intensive care unit admission were at least suggestive. As the most recent development in this field, Hackam et al121 have produced an impressive observational study by initial evaluation of 141 487 cardiovascular patients, which resulted in a well-paired and homogenous study cohort of 69 168 patients after propensity-based matching. Drawing from this solid base, Hackam and coauthors were able to support the conclusion that statin therapy is associated with a considerably decreased rate of sepsis (hazard ratio, 0.81; 95% CI, 0.72 to 0.90), severe sepsis (hazard ratio, 0.83; 95% CI, 0.70 to 0.97), and fatal sepsis (hazard ratio, 0.75; 95% CI, 0.61 to 0.93). This protective effect prevailed at both high and low statin doses and for several clinically important subpopulations, such as diabetic and heart failure patients.

As has been suggested previously,122 statins might provide cumulative benefit by reducing mortality from cardiovascular and infectious diseases such as sepsis. However, statins may have detrimental effects in distinct subsets of patients. Therefore, caution should prevail, and the use of statins in patients with sepsis must be accompanied by meticulous monitoring of unexpected side effects and well-designed randomized, controlled clinical trials.

Beyond an apparent rationale for randomized trials on statins in sepsis, it is notable that the results with other immunomodulatory approaches in sepsis have yielded rather limited success. For instance, use of the anti-TNF antibody F(ab′)2 fragment afelimomab led to a significant but rather modest reduction in risk of death and to improved organ-failure scores in patients with severe sepsis and elevated IL-6 levels.123 Moreover, a selective inhibitor of group IIA secretory phospholipase A2 failed to improve clinical outcome for patients with severe sepsis, with a negative trend most pronounced among patients with cardiovascular failure.124 Hence, because none of the available strategies proven to be effective in sepsis are designed specifically to target myocardial dysfunction, one might conclude that strategies that preferentially address cardiac morbidity in sepsis may be a promising area for investigation. For instance, lipoteichoic acid, a major virulence factor in Gram-positive sepsis, causes cardiac depression by activating myocardial TNF-α synthesis via CD14 and induces coronary vascular disturbances by activating thromboxane 2 synthesis. It thus contributes to cardiac depression and may therefore be a worthwhile and cardiac-specific target.125 The implications of intensified efforts in the search for successful novel approaches to the treatment of myocardial dysfunction in sepsis may be considerable with regard to improved patient care that results in reduced mortality. This is of major significance in view of the substantial economic consequences of increasing sepsis morbidity in an aging population.

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Circulation.2007; 116: 793-802doi: 10.1161/​CIRCULATIONAHA.106.678359

Other articles on Sepsis published on this Open Access Online Scientific Journal, include the following:

Advanced Topics in Sepsis and the Cardiovascular System at its End Stage

Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-sepsis-and-the-cardiovascular-system-at-its-end-stage/

Nitric Oxide and Sepsis, Hemodynamic Collapse, and the Search for Therapeutic Options

Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2012/10/20/nitric-oxide-and-sepsis-hemodynamic-collapse-and-the-search-for-therapeutic-options/

Sepsis, Multi-organ Dysfunction Syndrome, and Septic Shock: A Conundrum of Signaling Pathways Cascading Out of Control

Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2012/10/13/sepsis-multi-organ-dysfunction-syndrome-and-septic-shock-a-conundrum-of-signaling-pathways-cascading-out-of-control/

Automated Inferential Diagnosis of SIRS, sepsis, septic shock

Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2012/08/01/automated-inferential-diagnosis-of-sirs-sepsis-septic-shock/

The role of biomarkers in the diagnosis of sepsis and patient management

Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2012/07/28/the-role-of-biomarkers-in-the-diagnosis-of-sepsis-and-patient-management/

Bernstein, HL, Pearlman, JD and A. Lev-Ari  Alternative Designs for the Human Artificial Heart: The Patients in Heart Failure – Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community

https://pharmaceuticalintelligence.com/2013/08/05/alternative-designs-for-the-human-artificial-heart-the-patients-in-heart-failure-outcomes-of-transplant-donorimplantation-artificial-and-monitoring-technologies-for-the-transplantimplant-pat/

Pearlman, JD and A. Lev-Ari 7/22/2013 Cardiac Resynchronization Therapy (CRT) to Arrhythmias: Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion

https://pharmaceuticalintelligence.com/2013/07/22/cardiac-resynchronization-therapy-crt-to-arrhythmias-pacemakerimplantable-cardioverter-defibrillator-icd-insertion/

Lev-Ari, A. 7/19/2013 3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy

https://pharmaceuticalintelligence.com/2013/07/19/3d-cardiovascular-theater-hybrid-cath-labor-suite-hybrid-surgery-complications-post-pci-and-repeat-sternotomy/

Pearlman, JD and A. Lev-Ari 7/17/2013 Emerging Clinical Applications for Cardiac CT: Plaque Characterization, SPECT Functionality, Angiogram’s and Non-Invasive FFR

https://pharmaceuticalintelligence.com/2013/07/17/emerging-clinical-applications-for-cardiac-ct-plaque-characterization-spect-functionality-angiograms-and-non-invasive-ffr/

Lev-Ari, A. 7/14/2013 Vascular Surgery: International, Multispecialty Position Statement on Carotid Stenting, 2013 and Contributions of a Vascular Surgeon at Peak Career – Richard Paul Cambria, MD

https://pharmaceuticalintelligence.com/2013/07/14/vascular-surgery-position-statement-in-2013-and-contributions-of-a-vascular-surgeon-at-peak-career-richard-paul-cambria-md-chief-division-of-vascular-and-endovascular-surgery-co-director-thoracic/

Lev-Ari, A. 7/9/2013 Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers

https://pharmaceuticalintelligence.com/2013/07/09/research-programs-george-m-linda-h-kaufman-center-for-heart-failure-cleveland-clinic/

Lev-Ari, A. 7/8/2013 Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications 

https://pharmaceuticalintelligence.com/2013/07/08/becoming-a-cardiothoracic-surgeon-an-emerging-profile-in-the-surgery-theater-and-through-scientific-publications/

Pearlman, JD and A. Lev-Ari  7/4/2013 Fractional Flow Reserve (FFR) & Instantaneous wave-free ratio (iFR): An Evaluation of Catheterization Lab Tools (Software Validation) for Ischemic Assessment (Diagnostics) – Change in Paradigm: The RIGHT vessel not ALL vessels

https://pharmaceuticalintelligence.com/2013/07/04/fractional-flow-reserve-ffr-instantaneous-wave-free-rario-ifr-an-evaluation-of-catheterization-lab-tools-for-ischemic-assessment/

Lev-Ari, A. 7/1/22013 Endovascular Lower-extremity Revascularization Effectiveness: Vascular Surgeons (VSs), Interventional Cardiologists (ICs) and Interventional Radiologists (IRs)

https://pharmaceuticalintelligence.com/2013/07/01/endovascular-lower-extremity-revascularization-effectiveness-vascular-surgeons-vss-interventional-cardiologists-ics-and-interventional-radiologists-irs/

Lev-Ari, A. 6/10/2013 No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A Way To Know If I Have it?

https://pharmaceuticalintelligence.com/2013/06/10/no-early-symptoms-an-aortic-aneurysm-before-it-ruptures-is-there-a-way-to-know-if-i-have-it/

Lev-Ari, A. 6/9/2013 Congenital Heart Disease (CHD) at Birth and into Adulthood: The Role of Spontaneous Mutations

https://pharmaceuticalintelligence.com/2013/06/09/congenital-heart-disease-at-birth-and-into-adulthood-the-role-of-spontaneous-mutations-the-genes-and-the-pathways/

Lev-Ari, A. 6/3/2013 Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care

https://pharmaceuticalintelligence.com/2013/06/03/clinical-indications-for-use-of-inhaled-nitric-oxide-ino-in-the-adult-patient-market-clinical-outcomes-after-use-therapy-demand-and-cost-of-care/

Lev-Ari, A. 6/2/2013 Inhaled Nitric Oxide in Adults: Clinical Trials and Meta Analysis Studies – Recent Findings

https://pharmaceuticalintelligence.com/2013/06/02/inhaled-nitric-oxide-in-adults-with-acute-respiratory-distress-syndrome/

Pearlman, JD and A. Lev-Ari 5/24/2013 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

https://pharmaceuticalintelligence.com/2013/05/24/imaging-biomarker-for-arterial-stiffness-pathways-in-pharmacotherapy-for-hypertension-and-hypercholesterolemia-management/

Pearlman, JD and A. Lev-Ari 5/22/2013 Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone

https://pharmaceuticalintelligence.com/2013/05/22/acute-and-chronic-myocardial-infarction-quantification-of-myocardial-viability-fdg-petmri-vs-mri-or-pet-alone/

Lev-Ari, A. 5/17/2013 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

https://pharmaceuticalintelligence.com/2013/05/17/synthetic-biology-on-advanced-genome-interpretation-for-gene-variants-and-pathways-what-is-the-genetic-base-of-atherosclerosis-and-loss-of-arterial-elasticity-with-aging/

Justin D Pearlman, HL Bernstein and A. Lev-Ari 5/15/2013 Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

https://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/

Pearlman, JD and A. Lev-Ari 5/11/2013 Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus

https://pharmaceuticalintelligence.com/2013/05/11/arterial-elasticity-in-quest-for-a-drug-stabilizer-isolated-systolic-hypertension-caused-by-arterial-stiffening-ineffectively-treated-by-vasodilatation-antihypertensives/

Pearlman, JD and A. Lev-Ari 5/7/2013 On Devices and On Algorithms: Arrhythmia after Cardiac Surgery Prediction and ECG Prediction of Paroxysmal Atrial Fibrillation Onset

https://pharmaceuticalintelligence.com/2013/05/07/on-devices-and-on-algorithms-arrhythmia-after-cardiac-surgery-prediction-and-ecg-prediction-of-paroxysmal-atrial-fibrillation-onset/

Pearlman, JD and A. Lev-Ari 5/4/2013 Cardiovascular Diseases: Decision Support Systems for Disease Management Decision Making

https://pharmaceuticalintelligence.com/2013/05/04/cardiovascular-diseases-decision-support-systems-for-disease-management-decision-making/

Lev-Ari, A. 5/3/2013 Gene, Meis1, Regulates the Heart’s Ability to Regenerate after Injuries.

https://pharmaceuticalintelligence.com/2013/05/03/gene-meis1-regulates-the-hearts-ability-to-regenerate-after-injuries/

Lev-Ari, A. 4/30/2013 Prostacyclin and Nitric Oxide: Adventures in Vascular Biology – A Tale of Two Mediators

https://pharmaceuticalintelligence.com/2013/04/30/prostacyclin-and-nitric-oxide-adventures-in-vascular-biology-a-tale-of-two-mediators/

Lev-Ari, A. 4/28/2013 Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

https://pharmaceuticalintelligence.com/2013/04/28/genetics-of-conduction-disease-atrioventricular-av-conduction-disease-block-gene-mutations-transcription-excitability-and-energy-homeostasis/

Lev-Ari, A. 4/25/2013 Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association

https://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/

Lev-Ari, A. 4/24/2013 Harnessing New Players in Atherosclerosis to Treat Heart Disease

https://pharmaceuticalintelligence.com/2013/04/25/harnessing-new-players-in-atherosclerosis-to-treat-heart-disease/

Lev-Ari, A. 4/25/2013 Revascularization: PCI, Prior History of PCI vs CABG

https://pharmaceuticalintelligence.com/2013/04/25/revascularization-pci-prior-history-of-pci-vs-cabg/

Lev-Ari, A. 4/7/2013 Cholesteryl Ester Transfer Protein (CETP) Inhibitor: Potential of Anacetrapib to treat Atherosclerosis and CAD

https://pharmaceuticalintelligence.com/2013/04/07/cholesteryl-ester-transfer-protein-cetp-inhibitor-potential-of-anacetrapib-to-treat-atherosclerosis-and-cad/

Lev-Ari, A. 4/4/2013 Hypertriglyceridemia concurrent Hyperlipidemia: Vertical Density Gradient Ultracentrifugation a Better Test to Prevent Undertreatment of High-Risk Cardiac Patients

https://pharmaceuticalintelligence.com/2013/04/04/hypertriglyceridemia-concurrent-hyperlipidemia-vertical-density-gradient-ultracentrifugation-a-better-test-to-prevent-undertreatment-of-high-risk-cardiac-patients/

Lev-Ari, A. 4/3/2013 Fight against Atherosclerotic Cardiovascular Disease: A Biologics not a Small Molecule – Recombinant Human lecithin-cholesterol acyltransferase (rhLCAT) attracted AstraZeneca to acquire AlphaCore

https://pharmaceuticalintelligence.com/2013/04/03/fight-against-atherosclerotic-cardiovascular-disease-a-biologics-not-a-small-molecule-recombinant-human-lecithin-cholesterol-acyltransferase-rhlcat-attracted-astrazeneca-to-acquire-alphacore/

Lev-Ari, A. 3/31/2013 High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk

https://pharmaceuticalintelligence.com/2013/03/31/high-density-lipoprotein-hdl-an-independent-predictor-of-endothelial-function-artherosclerosis-a-modulator-an-agonist-a-biomarker-for-cardiovascular-risk/

Lev-Ari, A. 3/10/2013 Acute Chest Pain/ER Admission: Three Emerging Alternatives to Angiography and PCI

https://pharmaceuticalintelligence.com/2013/03/10/acute-chest-painer-admission-three-emerging-alternatives-to-angiography-and-pci/

Lev-Ari, A. and L H Bernstein 3/7/2013 Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013

https://pharmaceuticalintelligence.com/2013/03/07/genomics-genetics-of-cardiovascular-disease-diagnoses-a-literature-survey-of-ahas-circulation-cardiovascular-genetics-32010-32013/

Lev-Ari, A. 2/28/2013 The Heart: Vasculature Protection – A Concept-based Pharmacological Therapy including THYMOSIN

https://pharmaceuticalintelligence.com/2013/02/28/the-heart-vasculature-protection-a-concept-based-pharmacological-therapy-including-thymosin/

Lev-Ari, A. 2/27/2013 Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel

https://pharmaceuticalintelligence.com/2013/02/27/arteriogenesis-and-cardiac-repair-two-biomaterials-injectable-thymosin-beta4-and-myocardial-matrix-hydrogel/

Lev-Ari, A. 12/29/2012. Coronary artery disease in symptomatic patients referred for coronary angiography: Predicted by Serum Protein Profiles

https://pharmaceuticalintelligence.com/2012/12/29/coronary-artery-disease-in-symptomatic-patients-referred-for-coronary-angiography-predicted-by-serum-protein-profiles/

Bernstein, HL and Lev-Ari, A. 11/28/2012. Special Considerations in Blood Lipoproteins, Viscosity, Assessment and Treatment

https://pharmaceuticalintelligence.com/2012/11/28/special-considerations-in-blood-lipoproteins-viscosity-assessment-and-treatment/

Lev-Ari, A. 11/13/2012 Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes

https://pharmaceuticalintelligence.com/2012/11/13/peroxisome-proliferator-activated-receptor-ppar-gamma-receptors-activation-pparγ-transrepression-for-angiogenesis-in-cardiovascular-disease-and-pparγ-transactivation-for-treatment-of-dia/

Lev-Ari, A. 10/19/2012 Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?

https://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/

Lev-Ari, A. 10/4/2012 Endothelin Receptors in Cardiovascular Diseases: The Role of eNOS Stimulation

https://pharmaceuticalintelligence.com/2012/10/04/endothelin-receptors-in-cardiovascular-diseases-the-role-of-enos-stimulation/

Lev-Ari, A. 10/4/2012 Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production, stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography

https://pharmaceuticalintelligence.com/2012/10/04/inhibition-of-et-1-eta-and-eta-etb-induction-of-no-production-and-stimulation-of-enos-and-treatment-regime-with-ppar-gamma-agonists-tzd-cepcs-endogenous-augmentation-for-cardiovascular-risk-reduc/

Lev-Ari, A. 8/29/2012 Positioning a Therapeutic Concept for Endogenous Augmentation of cEPCs — Therapeutic Indications for Macrovascular Disease: Coronary, Cerebrovascular and Peripheral

https://pharmaceuticalintelligence.com/2012/08/29/positioning-a-therapeutic-concept-for-endogenous-augmentation-of-cepcs-therapeutic-indications-for-macrovascular-disease-coronary-cerebrovascular-and-peripheral/

Lev-Ari, A. 8/28/2012 Cardiovascular Outcomes: Function of circulating Endothelial Progenitor Cells (cEPCs): Exploring Pharmaco-therapy targeted at Endogenous Augmentation of cEPCs

https://pharmaceuticalintelligence.com/2012/08/28/cardiovascular-outcomes-function-of-circulating-endothelial-progenitor-cells-cepcs-exploring-pharmaco-therapy-targeted-at-endogenous-augmentation-of-cepcs/

Lev-Ari, A. 8/27/2012 Endothelial Dysfunction, Diminished Availability of cEPCs, Increasing CVD Risk for Macrovascular Disease – Therapeutic Potential of cEPCs

https://pharmaceuticalintelligence.com/2012/08/27/endothelial-dysfunction-diminished-availability-of-cepcs-increasing-cvd-risk-for-macrovascular-disease-therapeutic-potential-of-cepcs/

Lev-Ari, A. 8/24/2012 Vascular Medicine and Biology: CLASSIFICATION OF FAST ACTING THERAPY FOR PATIENTS AT HIGH RISK FOR MACROVASCULAR EVENTS Macrovascular Disease – Therapeutic Potential of cEPCs

https://pharmaceuticalintelligence.com/2012/08/24/vascular-medicine-and-biology-classification-of-fast-acting-therapy-for-patients-at-high-risk-for-macrovascular-events-macrovascular-disease-therapeutic-potential-of-cepcs/

Lev-Ari, A. 7/19/2012 Cardiovascular Disease (CVD) and the Role of agent alternatives in endothelial Nitric Oxide Synthase (eNOS) Activation and Nitric Oxide Production

https://pharmaceuticalintelligence.com/2012/07/19/cardiovascular-disease-cvd-and-the-role-of-agent-alternatives-in-endothelial-nitric-oxide-synthase-enos-activation-and-nitric-oxide-production/

Lev-Ari, A. 4/30/2012 Resident-cell-based Therapy in Human Ischaemic Heart Disease: Evolution in the PROMISE of Thymosin beta4 for Cardiac Repair

https://pharmaceuticalintelligence.com/2012/04/30/93/

Lev-Ari, A. 5/29/2012 Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes

https://pharmaceuticalintelligence.com/2012/05/29/445/

Lev-Ari, A. 7/2/2012 Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk

https://pharmaceuticalintelligence.com/2012/07/02/macrovascular-disease-therapeutic-potential-of-cepcs-reduction-methods-for-cv-risk/

 

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3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy

Curator: Aviva Lev-Ari, PhD, RN

This article has THREE Parts: 

Part One:  Hybrid Cath Lab/OR Suite for Hybrid Surgery

Part Two: Cardiac Surgery 

Part Three: Invasive Interventions with Complications

1. Repeat Sternotomy Post CABG and/or Aortic Valve Replacement

2. Complications Post PCI – Pump Catheter in Use

The voice of Series A Content Consultant, Justin D Pearlman, MD, PhD, FACC

The leading cause of death and disability from any cause is cardiovascular disease, principally, heart attacks and strokes. Both the heart and brain typically allow only 10 minutes or so of inadequate blood supply before starting a committed course of permanent tissue injury, progressing in severity as time goes by without successful interruption of the disease process. Thus there is great time urgency to get patients to a definitive treatment that can stop the injury and restore adequate nutrient blood supply. Many patients can benefit from a catheterization to identify blockages and insert a small balloon within the blockage to expand the narrow channel, often followed by placement of a stent (wire cage) to maintain the expanded vessel diameter. Chemicals released over time from drug-eluting stents can prevent tissue in growth that may obstruct stents. These emergeny interventions are not always successful. There may be complications from the attempt to access an entry artery, and the blockages may not be amenable to a balloon. When such limitations are encountered, the next chance to help is surgical, with continued time pressure.

The fastest way to make the transition from a diagnostic catheterization to a timely intervention is a hybrid intervention suite that offers non-invasive imaging, catheterization and surgery all in one location. The following articles present the current state of hybrid “do it all” intervention suites. Additional articles address the risks of bad outcomes from such interventions.

Part One 

Hybrid Cath Lab/OR Suite for Hybrid Surgery

In ACC.10 and i2 Summit, 59th Annual Scientific Session, 3/14-3/16, 2010, Alfred A. Bove, M.D., Ph.D., F.A.C.C., ACC President addressed the conference attendees:

Welcome to the all-new Hybrid Cath Lab/OR and 3D CV Theater. Recent developments in cardiac surgery and interventional cardiology have led to the creation of integrated, hybrid cath lab/operating rooms (OR), which provide significant advantages in the diagnosis and treatment of patients requiring cardiac procedures—helping to facilitate a rapid-response approach. These multimodality rooms are designed to support a variety of integrated surgical and endovascular procedures. We are excited to provide you with this opportunity to get a first-hand look—and feel—of the latest technologies. We hope you take the time to explore this interactive, multivendor venue. Learning is at the core of the ACC Annual Scientific Session and we invite you to expand your educational experience in this dynamic learning environment.

In the Hybrid Cath Lab/OR Suite, you’ll discover how integrating cutting edge angiographic and surgical equipment and technologies can facilitate a broad range of procedures within one location. Additionally, you will learn how hybrid suites are providing solutions that enable interventionalists and surgeons to work collaboratively to provide the best treatment options for patients. The adjoining 3D CV Theater features presentations by physicians currently performing intravascular and surgical procedures in hybrid suites. Each live presentation pairs a cardiologist with a surgeon, allowing you to hear perspectives from both sides on a variety of hybrid suite procedures and cases. In addition, the Theater offers video presentations of cases from around the world.

The ACC thanks the supporters of the Hybrid Suite for providing us with the opportunity to share this unique learning destination with you.

http://www.expo.acc.org/acc12/CUSTOM/images/ACC12/ACC.10%20Hybrid%20Suite%20Directory.pdf

Hybrid Cath Lab/OR Suite for Hybrid Surgery

Procedures Performed in a Hybrid Suite

The treatment of cardiovascular diseases has undergone a paradigm shift within the last few years, from

  • open surgery to minimally invasive surgical procedures and from
  • limited percutaneous catheter-based interventions to hybrid interventions for the entire cardiovascular tree.

The Hybrid Suite

are perfect examples of procedures that could, and should, be carried out in a hybrid OR. High-risk patients who require less invasive interventions are the best candidates for treatment in a hybrid suite.

As cardiac surgery becomes less invasive, incisions are becoming smaller and smaller, and even totally endoscopic heart surgery is now possible. Cardiac surgeons have started to perform procedures that include catheter-based skills, such as transapical valve replacement. For these operations, surgeons need more sophisticated imaging techniques, fluoroscopy and contrast injections. The hybrid OR offers all these facilities. Perhaps the most obvious and easiest procedure that can be performed in a hybrid OR is coronary revascularization combining coronary artery bypass grafting with on-table intra-operative completion angiography for quality control. If the surgeon detects a problem during the procedure, he or she can revise the graft immediately and thereby prevent potential perioperative and long-term complications. Currently, cardiologists and cardiovascular surgeons have shown special interest in so-called hybrid coronary interventions, which are combinations of minimally invasive coronary artery bypass grafting and percutaneous coronary interventions. In these procedures, cardiovascular surgeons place a left-internal mammary artery bypass graft to the left-anterior descending artery through small incisions (MIDCAB) or completely endoscopically (TECAB), while any remaining obstructed coronary arteries are treated with stents by an interventional cardiologist. This procedure is an attractive alternative to multivessel open coronary artery bypass grafting. Transcatheter heart-valve replacement and repair are especially suited to a hybrid suite because percutaneous transfemoral and transapical aortic valve repairs include risks that can only be treated successfully by immediate surgical intervention, such as coronary artery obstruction, aortic dissection and aortic perforations.

In addition, endovascular aortic stent grafting for the repair of abdominal aortic aneurysms is a suitable procedure for a hybrid operating room. Endovascular aneurysm repair has become an established alternative to open repair and is increasingly used for thoracic aorta repair as well. Some

  • emergency procedures for traumatic lesions of the thoracic aorta and
  • fulminant pulmonary embolism may also be performed in a hybrid OR. Several
  • pediatric interventions can be carried out in a hybrid suite as well, such as implantation of closure devices for atrial and ventricular septal defects in small children and
  • treatments for hypoplastic left-heart syndrome.

http://www.expo.acc.org/acc12/CUSTOM/images/ACC12/ACC.10%20Hybrid%20Suite%20Directory.pdf

In a recent article we reported on the Change in Requirement for Surgical Support by Cath Labs for performance of Nonemergent PCI without Surgical Backup, that increases the autonomy of Interventional Cardiologists. In the Hybrid OR that change is irrelevant since the presence of a Cardiac Surgeon is a fact of the division of labor between the two types of specialties. Cardiac Surgeons are involved with  percutaneous transfemoral and transapical aortic valve repairs and intervention for endoscopic aorta, AAA and Thoracic AA grafting.

AHA, ACC Change in Requirement for Surgical Support:  Class IIb -> Class III, Level of Evidence A: Supports Nonemergent PCI without Surgical Backup (Change of class IIb, level of Evidence B).

What is a Cardiovascular Hybrid Suite?

Cardiovascular hybrid suite is a state-of-the-art operating room equipped with a fully functional catheterization laboratory, thus allowing surgical procedures and catheter-based interventions to be carried out in the same room. Hybrid suites provide a place where treatments traditionally available only in a cath lab and procedures only available in an operating room can be performed together to provide patients with the best available combination of therapies for cardiovascular disease. These multidisciplinary, integrated cardiovascular procedural suites bring the best of two worlds together by combining all the advantages of a modern cath lab with an up-to-date cardiovascular surgery operating room (OR).

Hybrid suites began to evolve in the mid to late 1990s, when some groups of interventional cardiologists started sharing operating rooms with cardiovascular surgeons. The appeal of the hybrid suite concept has grown as have catheter based devices (stents, coils, balloons and lasers) have been developed that enable interventional cardiologists to advance the invasiveness and effectiveness and applications of percutaneous transcatheter interventions. The interest in these suites has also increased as cardiovascular surgeons have developed a variety of techniques for

  • Minimally invasive procedures, such as minimally invasive direct coronary artery bypass grafting (MIDCAB) or
  • Totally endoscopic coronary artery bypass grafting (TECAB).

With the advent of more tools, interventional cardiologists are becoming more like surgeons, and with less invasive tools, cardiovascular surgeons are becoming more like interventionalists. Rather than separating surgical procedures from interventional procedures performed in traditional operating rooms and cath labs, hybrid suites provide a high-tech environment that allows cardiologists and surgeons to work together to offer patients complex, minimally invasive therapies.

Some experts believe that hybrid suites represent the wave of the future in cardiovascular care and that most heart centers will eventually install hybrid suites to offer patients the latest cardiovascular procedures safely and effectively with minimal surgical trauma. The rooms can be costly to build and equip, but if a medical center is considering building a new operating room or cath lab, setting up a hybrid suite makes sense. Medical centers that have a hybrid suite available can clearly differentiate themselves in a positive way from centers that do not have such capabilities.

The Benefits of a Hybrid Suite for Medical Centers

While building a hybrid suite is more expensive than building a traditional operating room or cath lab, a hybrid suite can potentially be used for all types of cardiovascular procedures, including

  • traditional cardiac and vascular surgery,
  • interventional coronary procedures,
  • endovascular aortic procedures and
  • electrophysiology procedures.

Hybrid suites reinforce the trend in cardiovascular care toward less invasive, comprehensive hybrid procedures. Once a hybrid suite is in place, the demand for its use will likely grow due to increasing indications and referrals for these innovative treatments, many of which are increasingly covered by third-party payers.

http://www.expo.acc.org/acc12/CUSTOM/images/ACC12/ACC.10%20Hybrid%20Suite%20Directory.pdf

What Equipment is Needed?

Interventional cath labs usually have excellent imaging capabilities but lack the sterile facilities and staff needed for a formal OR, while operating rooms frequently lack high-level imaging equipment. Some of the essential equipment for a hybrid suite includes:

• A state-of-the-art imaging system capable of performing 3D rotational angiography, CT scanning, and ultrasound is advantageous. Floor-mounted and ceiling-mounted systems are available, but many hospitals use ceiling-mounted systems because access to the patient is slightly easier. Some ceiling-mounted systems provide 3D imaging from the surgeon’s position perpendicular to the patient. However, some hospitals prefer floor-mounted systems because having mechanical parts running above the operative field may cause dust to fall, resulting in infections. An important aspect is that the C-arm can be parked away when it is not used. This especially enhances access of the anesthesia team to the patient.

• An operating table that meets the needs of both surgeons and interventionalists by electronically integrating the table with the imaging system is also essential. These tables should have retractable rails for retractors and other surgical tools. To perform 3D imaging on the operating table, the C-arm of the imaging system should allow fast and precise rotation around the patient.

• A variety of other surgical and interventional systems and equipment may also be needed, including a robotic surgical system, a heart-lung machine, an image integration system, an endoscopic imaging system, a radiology display system, an audiovisual system to move images to different monitors and an anesthesia monitoring system, including transesophageal echocardiography. Some equipment like the integrated OR table and the angiography unit need to be fixed parts of the hybrid OR. Some equipment will be mobile in order to maintain some flexibility in workflow.

Hybrid1

Hybrid2

Hybrid3

Hybrid4

Hybrid5

Who are the Equipment Vendors?

Philips Healthcare

Phone: 800-934-7372

Email: healthcare@philips.com

Web: http://www.philips.com/healthcare

Philips is one of the world’s leading technology companies, with a long history of practical innovation and visionary design. In healthcare, we are committed to understanding the human and technological needs of patients and caregivers. We believe this understanding will help us deliver solutions that not only enable more confident diagnoses and more efficient delivery of care, but also improve the overall experience of care. We offer equipment, software and services for imaging, patient monitoring, resuscitation and much more.  A Hybrid OR can help make life simpler for the interdisciplinary teams who operate in this environment every day. As a world leader in cardiovascular X-ray, Philips has the experience and expertise to deliver the first class technology you need to perform minimally invasive procedures with speed, accuracy and confidence. A long history of innovation has enabled Philips to develop pioneering imaging solutions that really make a difference.

For example, Philips Allura Xper cardiovascular X-ray systems are designed to deliver enhanced imaging with superb performance for all cardiac projections, and our iE33 ultrasound system with Live 3D TEE and QLAB can assist interventional procedures and provide comprehensive quantitative information to support critical decisions. Our cardiology informatics solutions help you manage patient information throughout the cardiovascular care continuum. Philips solutions allow minimally invasive and catheter-based procedures to take place in the same suite as conventional cardiac surgery.

Phillips EchoNavigator – X-Ray and 3-D Ultrasound is described in:

Minimally Invasive Structural CVD Repairs: FDA grants 510(k) Clearance to Philips’ EchoNavigator – X-ray and 3-D Ultrasound Image Fused.

Intuitive Surgical, Inc. 

da Vinci.Surgery by Intuitive Surgical, Inc. 

Phone: 800-876-1310

Email: info@intusurg.com

Web: http://www.intuitivesurgical.com

Intuitive Surgical, Inc. is the global technology leader in robotic-assisted, minimally invasive surgery. The company’s da Vinci® Surgical System offers breakthrough capabilities that enable cardiac surgeons to use a minimally invasive approach and avoid median sternotomy.

Content of FDA Warning Letter, following  FDA Inspection on dates 04/01/2013 – 05/30/2013 – it discussed in

Hybrid Cath Lab/OR Suite’s da Vinci Surgical Robot of Intuitive Surgical gets FDA Warning Letter on Robot Track Record

 

MAVIG GmbH 

Phone: 631-266-2229,

585-247-1212 ext. 60

Email: info@mavig.com

Web: http://www.mavig.com

MAVIG’s specialty is ceiling/boom suspension systems for lighting (exam, surgical and LED), monitor-suspension systems—single, multibank (one to eight) systems and widescreen, overhead radiation shielding and contrast injector adapters. MAVIG also manufactures radiation protection products such as aprons, gloves, table-attachable lower body shields, adjustable- and fixed-height mobile and modular barriers.

Toshiba America Medical Systems, Inc.

Phone: 714-730-5000

Email: mktgcomm@tams.com

Web: http://www.medical.toshiba.com

Creating a hybrid lab may be complicated, but having an experienced partner that listens makes all the difference. Toshiba’s unique blend of hybrid experience and industry recognized Infinix™-i imaging systems for the Cath Lab.

Hybrid Cath Lab/OR Suite in Leading Hospitals in the US

  • The  Hybrid Cath Lab/OR Suite at New York Presbyterian Hospital/Columbia University Medical Center, New York, NY is presented in

Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications

  • The  Hybrid Cath Lab/OR Suite at Cleveland Clinic, Cleveland, Ohio is presented in

Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers

Speakers at 3D CV Theater, 2010 are working in Hospitals where Hybrid Cath Lab/OR Suite are in operations at the present time. The list include the following Hospitals with a Hybrid Cath Lab/OR Suite:

  • Vanderbilt Medical Center, Nashville, TN
  • University of Maryland Heart Center, Baltimore, MD
  • The Heart Center at Nationwide Children’s Hospital, Columbus, Ohio
  • The Robotic Surgical Center, East Carolina University Department of Surgery, Greenville, N.C.
  • University of Washington Medicine Regional Heart Center, Seattle, WA
  • Brigham and Women’s Hospital, Boston, MA
  • Saint Joseph’s Hospital and Peachtree Cardiovascular and Thoracic Surgery, Atlanta, GA
  • Emory University Hospital, Atlanta, GA
  • Beth Israel Deaconess Medical Center, Boston, MA
  • Boston Medical Center, Boston, MA
  • Mayo Graduate School of Medicine, Mayo Clinic, Rochester, MN
  • Lankenau Hospital, Lancaster, PA
  • Cardiac Non-Invasive Laboratory at Cedars-Sinai Medical Center, Los Angeles, CA
  • Robotic Surgery at St. Joseph’s Hospital, Atlanta, GA

Speakers at 3D CV Theater, 2010, included the following Cardiovascular Interventionists leading the adoption process of Hybrid Surgery in Hybrid Cath Lab/OR Suite into care modalities for cardiovascular disease:

Johannes O. Bonatti, M.D., is professor of surgery and director of coronary surgery and advanced coronary interventions at the University of Maryland Heart Center, Baltimore. He received his training in general surgery and cardiac surgery at the department of surgery at Innsbruck Medical University in Austria. Prior to his arrival at the University of Maryland, he worked at this institution as an attending surgeon and associate professor. Dr. Bonatti’s main interest is the development of minimally invasive, totally endoscopic coronary artery bypass grafting (TECAB) procedures using robotic technology.

As one of the international leaders in this field, he performed the largest series of robotic TECAB on the arrested heart, including single-, double- and triple-vessel TECAB. He has published significantly on procedure development and the implementation process of completely endoscopic coronary surgery using the da Vinci robotic system. Together with colleagues from interventional cardiology, Dr. Bonatti is working on integrated concepts for treatment of coronary artery disease. He was the first to perform a simultaneous hybrid coronary intervention using TECAB and placement of a coronary stent. He is organizing international meetings on hybrid interventions in cardiovascular medicine (http://www.icrworkshop.com). He has trained heart surgeons from around the world in the use of the da Vinci robot for heart surgery and he has introduced TECAB procedures in Austria, the Czech Republic, Greece, Turkey, India and Australia.

John G. Byrne, M.D., is the William S. Stoney Professor of Cardiac Surgery at Vanderbilt University School of Medicine and chair of the department of cardiac surgery at Vanderbilt Medical Center, Nashville, TN.

Before moving to Vanderbilt, he was associate chief and residency program director in the division of cardiac surgery at Brigham and Women’s Hospital, and associate professor of surgery at Harvard Medical School, Cambridge, MA. A graduate of the University of California, Davis, he received his medical degree in 1987 from Boston University. His postdoctoral training was completed at the University of Illinois affiliated hospitals and Brigham and Women’s Hospital in Boston.

Dr. Byrne is the author of more than 100 scientific articles on cardiac surgery and related areas. His patient care emphasis is

  • aortic root surgery,
  • coronary artery disease and
  • valve surgery

He is board-certified in general surgery and thoracic surgery.

John P. Cheatham, M.D., is director of cardiac catheterization and interventional therapy and codirector of The Heart Center at Nationwide Children’s Hospital, Columbus, Ohio. He is also the George H. Dunlap Endowed Chair in Interventional Cardiology and professor of pediatrics and internal medicine at The Ohio State University College of Medicine. Dr. Cheatham’s area of expertise is transcatheter intervention and hybrid therapy of newborns, children and adults with complex congenital heart disease. He has pioneered several new techniques and devices in non-surgical intervention and is a leader in developing hybrid therapies. He has been a principal investigator in numerous FDA-sponsored clinical trials evaluating non-surgical closure devices and stent therapy over the past two decades. Additionally, Dr. Cheatham designed the first hybrid cardiac catheterization suites and advanced imaging equipment at Nationwide Children’s Hospital. He serves as a consultant to various medical companies and proctors new transcatheter techniques and devices to other physicians around the world. Dr. Cheatham has implemented a formal physician exchange program with two of the leading medical institutions in China. In cooperation with China Red Cross, he is also the foreign director of the International Training Center for treatment of congenital heart disease in poor children. Dr. Cheatham has written more than 120 manuscripts, 16 book chapters, 300 national and international presentations and is co-editor of the book, Complications in Percutaneous Interventions for Congenital and Structural Heart Disease. After graduating from the University of Oklahoma College of Medicine, he completed his residency at Boston Children’s Hospital, followed by a fellowship in Pediatric Cardiology at Texas Children’s Hospital in Houston.

W. Randolph Chitwood, Jr., M.D., is senior associate vice chancellor for health sciences and chief of cardiovascular services at East Carolina University Department of Surgery, Greenville, N.C. Dr. Chitwood is a leading international pioneer in minimally invasive and robotic heart surgery. The Robotic Surgical Center at East Carolina University has trained more than 350 surgeons. His research activities relate to myocardial preservation, simulation in surgery and endoscopic/robotic cardiac surgery. He was the principal investigator of the FDA robotic mitral valve trials that led to approval for use in the U.S. He is the son and grandson of “southwestern Virginia mountain doctors” who set the guidelines for his professional life. He graduated from Hampden-Sydney College and received his medical degree from the University of Virginia. After medical school, he completed the surgical residency at Duke University Medical Center under David C. Sabiston, M.D., an influential surgical educator of the era. At Duke he spent 10 years training in general and cardiothoracic surgery, as well as basic science research.

After his chief residency at Duke in 1984, he was selected to begin and head the new cardiac surgery program at the East Carolina University School of Medicine. Because of his prolific publication record as a resident and clinical acumen, his initial appointment was as a full professor of surgery. Except for a two-year hiatus as the chief of cardiothoracic surgery at the University of Kentucky, he has spent his entire career at East Carolina University, where he also served as chairman of the department of surgery. In 2003, he was named to be in charge of the development of the East Carolina Heart Institute, which now includes an integrated department of cardiovascular sciences as well as a $200 million heart hospital, outpatient, research and education center.

Larry S. Dean, M.D., is director of the University of Washington Medicine Regional Heart Center and is professor of medicine and of surgery at the University of Washington School of Medicine, Seattle. In addition to general cardiology, he is an expert in cardiac catheterization and interventional cardiology. He also conducts research on stents to keep blocked heart arteries open and on ways to prevent restenosis after stents are inserted. He is currently involved in the evaluation of percutaneous aortic valve replacement. Dr. Dean earned his M.D. from the University of Alabama School of Medicine, Birmingham, and served his internship and residency at the University of Washington. He then returned to the University of Alabama Hospital for fellowships in cardiovascular disease and in angioplasty. After nearly 15 years as a faculty member at the University of Alabama, he returned to the University of Washington to direct the Regional Heart Center. He is a fellow of the American College of Cardiology and is board-certified in internal medicine, cardiovascular disease and interventional cardiology. He is also a fellow of the American Heart Association and president-elect of the Society of Cardiovascular Angiography and Interventions.

Andrew Craig Eisenhauer, M.D., is director of the interventional cardiovascular medicine service at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School. His specialties are

  • interventional cardiology,
  • vascular medicine and
  • congenital and inherited diseases.

He earned his medical degree at New York University School of Medicine and served a residency at Peter Bent Brigham Hospital and a fellowship at Massachusetts General Hospital. He is certified in internal medicine, cardiovascular disease and interventional cardiology. His clinical interests are

  • endovascular therapy,
  • complex coronary disease,
  • peripheral vascular disease,
  • cerebrovascular disease,
  • congenital heart disease and structural heart disease

Douglas A. Murphy, M.D., is chief of cardiothoracic surgery at Saint Joseph’s Hospital and a cardiothoracic surgeon at Peachtree Cardiovascular and Thoracic Surgery, Atlanta. His areas of interest are robotically assisted heart surgery with an emphasis on repairing the mitral valve rather than replacing it. A graduate of the University of Pennsylvania Medical School, Philadelphia, he served an internship and residency at Massachusetts General Hospital, Boston, and at Emory University, Atlanta.

Khusrow Niazi, M.D., is an assistant professor at Emory University School of Medicine and director of peripheral and carotid intervention at Emory University Hospital Midtown, Atlanta. He earned his medical degree at King Edward Medical College, Lahore, Pakistan, and served an internship at Kettering Medical Center, Dayton, Ohio, and a fellowship at William Beaumont Hospital, Royal Oak, MI. He has published papers on stenting following rotational atherectomy, small vessel stenting for coronary arteries, imaging of lower extremities and treatment of peripheral arterial disease.

Jeffrey J. Popma, M.D., is director of innovations in interventional cardiology, a senior attending physician at Beth Israel Deaconess Medical Center and an associate professor of medicine at Harvard Medical School in Boston. Dr. Popma received his bachelor’s degree in economics from Stanford University, and his M.D. from Indiana University School of Medicine. He completed his internship, residency, chief residency and fellowship at University of Texas Southwestern Medical Center. He also completed an interventional cardiology fellowship at the University of Michigan. Dr. Popma is the past president of the Society for Cardiac Angiography and Intervention and is the co-chair of the ACC Interventional Council. He sits on the editorial boards of several publications, and reviews for several cardiology periodicals. Dr. Popma has more than 300 published peer-reviewed manuscripts.

Dr. Popma also directs the BIDMC Angiographic Core Laboratory and is principal investigator for more than 65 ongoing multicenter device studies within the research laboratory. Over the past 15 years, these trials have included a broad array of new technology, including bare-metal stents, drug-eluting stents, distal-protection devices, total-occlusion devices and carotid and peripheral revascularization procedures. His primary clinical interest currently is the use of percutaneous aortic valve replacement for patients with high-risk aortic stenosis.

Robert S. Poston, M.D., is chief of cardiac surgery at Boston Medical Center and associate professor of cardiothoracic surgery at Boston University School of Medicine. He has a strong background in minimally invasive cardiac bypass surgery and is a pioneer in using robotics, specifically the da Vinci Surgical System, to treat coronary artery disease. A graduate of the Johns Hopkins School of Medicine, Baltimore, Dr. Poston completed a residency in general surgery at the University of California, San Francisco, and continued his training with a research fellowship in cardiothoracic surgery at Stanford University School of Medicine, Palo Alto, CA, and a cardiothoracic residency at the University of Pittsburgh Medical Center.

Charanjit S. Rihal, M.D., is professor of medicine and director of the cardiac catheterization laboratory at Mayo Graduate School of Medicine, Mayo Clinic, Rochester, MN. A graduate of the University of Winnipeg, Dr. Rihal did his residency and fellowship at the Mayo Graduate School of Medicine and also earned an MBA at the Carlson School of Management, University of Minnesota. His medical interests are interventional cardiology, structural heart disease interventions and the management of quality and costs in healthcare.

Timothy A. Shapiro, M.D., is director of the Interventional Cardiology Fellowship Program and campus chief, interventional cardiology, at Lankenau Hospital, Lancaster, PA. A graduate of Yale University School of Medicine, he served his residency and a fellowship at the Hospital of the University of Pennsylvania.

Robert J. Siegel, M.D., is director of the Cardiac Non-Invasive Laboratory at Cedars-Sinai Medical Center, cardiology director of the Cedars-Sinai Marfan Center, and Rexford S. Kennamer, M.D., chair in cardiac ultrasound at Cedars-Sinai Medical Center, Los Angeles. Dr. Siegel is also professor of medicine in residence at the David Geffen School of Medicine at University of California, Los Angeles. He previously served as senior staff fellow in cardiac pathology at the Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, MD. Internationally recognized as one of the leading experts in the field of cardiovascular ultrasound, Dr. Siegel specializes in cardiovascular ultrasound, including transthoracic, transesophageal and intravascular methodologies. His research interests include

  • valvular heart disease,
  • therapeutic applications of ultrasound energy,
  • transesophageal and intraoperative echocardiography, and the
  • development and use of hand-held portable echocardiographic systems for clinical innovations.

In addition, he is involved with clinical research studies related to the diagnosis, assessment and management of patients with

  • Marfan syndrome,
  • hypertrophic cardiomyopathy and
  • pericardial and valvular heart disease.

Dr. Siegel is a fellow, and has previously served as the president of the California Chapter of the American College of Cardiology and president of the Los Angeles Society of Echocardiography. He has been active in numerous cardiovascular societies, including the American Heart Association, the American College of Cardiology and the American Society of Echocardiography. Dr. Siegel received his medical degree at Baylor College of Medicine, Houston, where he developed an interest in cardiology. He completed his medical residency at Emory University and at Los Angeles County + USC Medical Center. He completed his cardiology fellowship at Harbor-UCLA Medical Center.

Over the last two years Dr. Siegel has worked extensively with live 3D transesophageal echo in the cardiac intervention center and the operating room. He and his echocardiologist colleagues, doctors Shiota, Biner, Tolstrup and Gurudevan, have worked closely at Cedars-Sinai Medical Center in Los Angeles with the interventional cardiologists, doctors Kar and Makkar, as well as with the cardiac surgeons, doctors Trento and Fontana. They use live 3D TEE extensively for the assessment of structural heart disease. In addition, it is used on a regular basis for the guidance of percutaneous procedures for mitral valve e-clip repair, mitral balloon valvuloplasty, aortic and pulmonic valve replacement, left atrial appendage exclusion by the Watchman device as well as for ASD closure.

Sudhir P. Srivastava, M.D., president of the International College of Robotic Surgery at St. Joseph’s Hospital, Atlanta, is a pioneer in performing beating heart totally endoscopic coronary artery bypass surgeries. Previously, he was assistant professor of surgery and director of robotic and minimally invasive cardiac surgery at the University of Chicago Medical Center. Dr. Srivastava specializes in robotically assisted totally endoscopic coronary artery bypass surgery. He has performed approximately 1,000 robotic cardiothoracic surgical procedures, of which 450  have been single- and multivessel beating heart totally endoscopic coronary bypass (BH TECAB) procedures. He has keen interest in hybrid coronary revascularization in TECAB patients to achieve complete revascularization.

Dr. Srivastava has helped launch robotic revascularization programs throughout the world. He has performed numerous live BH TECAB demonstrations both in the U.S. and abroad, and continues to be a presenter and invited speaker at numerous national and international scientific meetings. He earned his medical degree at the Jawahar Lal Nehru Medical College in Ajmer, India and immigrated to the U.S. in 1972. He completed his cardiothoracic surgery residency at the hospitals associated with the University of British Columbia, Vancouver, Canada.

Francis P. Sutter, D.O., F.A.C.S., is clinical professor of surgery at Thomas Jefferson University-Jefferson Medical College, Philadelphia, and chief of cardiothoracic surgery at Lankenau Hospital, Main Line Health System, Wynnewood, PA. A graduate of Philadelphia College of Osteopathic Medicine, his surgical residency and a cardiothoracic fellowship were completed at Thomas Jefferson University Hospital.

Mark R. Vesely, M.D., is an assistant professor of medicine at the University of Maryland School of Medicine. He completed medical school at the George Washington University and postgraduate training—an internal medicine residency and fellowships in cardiovascular disease and interventional cardiology—at the University of Maryland. He is board-certified in internal medicine, cardiovascular disease, nuclear cardiology and interventional cardiology. Dr. Vesely is the associate program director of the Interventional Cardiology fellowship at University of Maryland. His special interests include the partnered approach (interventional cardiologists and cardiac surgeons) for hybrid coronary revascularization and structural heart disease interventions. Additional research interests include investigation of techniques to minimize acute myocardial infarction injury with ventricular-assist devices and adult stem cell therapies.

David X. M. Zhao, M.D., Ph.D., is an associate professor of medicine and cardiac surgery, Harry and Shelley Page Chair in Interventional Cardiology, director of the Cardiac Catheterization Laboratories and interventional cardiology director of the Interventional Cardiology Fellowship Training Program, Vanderbilt University School of Medicine, Nashville, TN. He earned his medical degree at Shanghai Medical University, Shanghai, P.R. China, and his Ph.D. in immunology at Queensland University, Brisbane, Australia. His postdoctoral training was at Zhongshan Hospital, Shanghai Medical University, Shanghai, P.R. China, The Prince Charles Hospital, Brisbane, Australia, and Brigham and Women’s Hospital, Boston.

http://www.expo.acc.org/acc12/CUSTOM/images/ACC12/ACC.10%20Hybrid%20Suite%20Directory.pdf

Part Two

Cardiac Surgery

 

Cardiac Surgery @ Cleveland Clinic: Traditional OR & Hybrid Cath Lab/OR Suite

Nation #1 for 19 consecutive years – The Heart Center: Miller Family Heart & Vascular Institute @ Cleveland Clinic

The Sydell and Arnold Miller Family Heart & Vascular Institute is one of the largest, most experienced cardiovascular specialty groups in the world. Our physicians are committed to providing the most advanced diagnostic and treatment options, better outcomes and improved quality of life. U.S.News & World Reporthas ranked Cleveland Clinic as the No.1 heart program in America every year since 1995.

Departments & Centers:

Below we present two articles on Cardiac Surgery @ Mayo Clinic 

Cardiac Surgery @ Mayo Clinic: Traditional OR & Hybrid Cath Lab/OR Suite 

Coronary Reperfusion Therapies: CABG vs PCI – Mayo Clinic preprocedure Risk Score (MCRS) for Prediction of in-Hospital Mortality after CABG or PCI

Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Comparison of the 10-year and 15-year survivals after CABG demonstrated benefit from a change in graft sources used at the Mayo Clinic and widely adapted by others: vascular grafts from the left internal mammary artery (LIMA) instead of just leg veins, for multiple grafts (up to 3), LIMA-to-LAD plus grafts using LIMA or radial artery vs LIMA/saphenous vein (SV).

CABG Survival in Multivessel Disease Patients: Comparison of Arterial Bypass Grafts vs Saphenous Venous Grafts

Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Part Three 

Invasive Interventions with Complications

In the following article we covered multiple etiologies for cardiovascular complications related to invasive interventions: cardiovascular and peripheral arterial or peri- and post- cardiac surgery of the open heart type.

Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

This article covers types of Cardiovascular Complications derived from the following THREE types of assault on the Human body, two related to cardiac invasive interventions, the last due to its systemic nature is taking a fatal Cardiac toll: the Sepsis condition causing cardiac failure.

Three types of Cardiovascular Complications:

I. Risk of Injury During Repeat Sternotomy – following CABG orAortic Valve Replacement, both done in Open Heart Surgery

II. Complications After Percutaneous Coronary intervention (PCI) and endovascular surgery for Peripheral Artery Disease (PAD)

  • (a) Post PCI, and
  • (b) PAD Endovascular Interventions: Carotid Artery Endarterectomy

III. Cardiac Failure During Systemic Sepsis

This article does NOT cover the following two types of Cardiovascular Complications:

1. Trauma Injury causing cardiac arrest, lung collapse or cardiogenic shock

2. Surgical Complication of Non-cardiac surgery type causing cardiac arrest, i.e, Surgery of Joint Replacement causing sepsis causing death or death caused by complications of surgery i.e., blood loss, viral infection, emboli, thrombus, stroke, or cardiogenic shock not related to Cardiovascular and Cardiac invasive interventions

The e-Reader is advised to consider the following expansion on the subject matter carrying the discussion to additional related clinical issues:

Larry H Bernstein, Advanced Topics in Sepsis and the Cardiovascular System at its End Stage

https://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-sepsis-and-the-cardiovascular-system-at-its-end-stage/

Bernstein, HL, Pearlman, JD and A. Lev-Ari  Alternative Designs for the Human Artificial Heart: The Patients in Heart Failure – Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community

https://pharmaceuticalintelligence.com/2013/08/05/alternative-designs-for-the-human-artificial-heart-the-patients-in-heart-failure-outcomes-of-transplant-donorimplantation-artificial-and-monitoring-technologies-for-the-transplantimplant-pat/

Pearlman, JD and A. Lev-Ari Cardiac Resynchronization Therapy (CRT) to Arrhythmias: Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion

https://pharmaceuticalintelligence.com/2013/07/22/cardiac-resynchronization-therapy-crt-to-arrhythmias-pacemakerimplantable-cardioverter-defibrillator-icd-insertion/

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AHA, ACC Change in Requirement for Surgical Support for PCI Performance: Class IIb -> Class III, Level of Evidence A: Support Nonemergent PCI without Surgical Backup (Change of class IIb, Level of evidence B).


AHA, ACC Change in Requirement for Surgical Support:  Class IIb -> Class III, Level of Evidence A: Supports Nonemergent PCI without Surgical Backup (Change of class IIb, Level of Evidence B).

Larry H Bernstein, MD, FCAP, Author, Curator, Volumes 1,2,3,4,5,6 Co-Editor and Author, Volume Two & Five, Co-Editor and Justin Pearlman, MD, PhD, FACC, Content Consultant to Six-Volume e-SERIES A: Cardiovascular Diseases

 

Voice of content consultant: Justin Pearlman, MD, PhD, FACC

The American Heart Association (AHA) and the American College of Cardiology (ACC) have convened teams of experts to summarize evidence and opinion regarding a wide range of decisions relevant to cardiovascular disease. The system accounts for some of the short comings of “evidence based medicine” by allowing for expert opinion in areas where evidence is not sufficient. The main argument for evidence-based medicine is the existence of surprises, where a plausible decision does not actually appear to work as desired when it is tested. A major problem with adhesion to evidence based medicine is that it can impede adaptation to individual needs (we are all genetically and socially/environmentally unique) and impede innovation. Large studies carry statistical weight but do not necessary consider all relevant factors. Commonly, the AFFIRM trial is interpreted as support that rate control suffices for most atrial fibrillation (AFIB), but half of those randomized to rhythm control were taken off anticoagulation without teaching patients to check their pulse daily for recurrence of AFIB. Thus the endorsed “evidence” may have more to do with the benefits of anticoagulation for both persisting and recurring AFIB and rhythm control may yet prove better than rate control. However, with wide acceptance of a particular conclusion, randomizing to another treatment may be deemed unethical, or may simply not get a large trial due to lack of economic incentive, leaving only the large trial products as the endorsed options. A medication without patent protection, such as bismuth salts for H Pylori infection, lacks financial backing for large trials.

The American Heart Association Evidence-Based Scoring System
Classification of Recommendations

● Class I: Conditions for which there is evidence, general

agreement, or both that a given procedure or treatment is

useful and effective.

● Class II: Conditions for which there is conflicting evidence,

a divergence of opinion, or both about the usefulness/

efficacy of a procedure or treatment.

● Class IIa: Weight of evidence/opinion is in favor of

usefulness/efficacy.

● Class IIb: Usefulness/efficacy is less well established by

evidence/opinion.

● Class III: Conditions for which there is evidence, general

agreement, or both that the procedure/treatment is not useful/

effective and in some cases may be harmful.

Level of Evidence

● Level of Evidence A: Data derived from multiple randomized

clinical trials

● Level of Evidence B: Data derived from a single randomized

trial or nonrandomized studies

● Level of Evidence C: Consensus opinion of experts

Circulation 2006 114: 1761 – 1791.

Assessment of Coronary Artery Disease by Cardiac Computed Tomography

A Scientific Statement From the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology

Reported by Chris Kaiser, Cardiology Editor, MedPage  7/2013  

 

Action Points

  1. Patients with indications for nonemergency PCI who presented at hospitals without on-site cardiac surgery, were randomly assigned to undergo PCI at a hospital without on-site cardiac surgery or at a hospital with on-site cardiac surgery.
  2. The rates of death, myocardial infarction, repeat revascularization, and stroke did not differ significantly between the groups.
  3. Community hospitals without surgical services can safely perform percutaneous coronary intervention (PCI) in low-risk patients — and not refuse higher-risk patients either, the MASS COMM trial found.

Summary

  • The co-primary endpoint of major adverse cardiac events (MACE) at 30 days occurred at a rate of 9.5% in the 10 hospitals without surgical backup versus 9.4% in the seven hospitals with onsite surgery (P<0.001 for noninferiority), Alice K. Jacobs, MD, of Boston University School of Medicine, and colleagues found.
  • The other co-primary endpoint of MACE at 12 months was also significant, occurring in 17.3% of patients in hospitals without backup versus 17.8% in centers with surgical services (P<0.001 for non-inferiority), they reported in the study published online by the New England Journal of Medicine. The findings were also reported at the American College of Cardiology meeting.

Study Characteristics and Results

Primary Endpoints

  1. death
  2. myocardial infarction
  3. repeat revascularization
  4. stroke
no significant differences between the two groups at 30 days and at 12 months.

Rate of stent thrombosis at 30 days

similar in both groups (0.6% versus 0.8%) and at 12 months (1.1% versus 2.1%).
Jacobs and colleagues noted that the 2011 PCI guidelines lacked evidence to fully support nonemergent PCI without surgical backup (class IIb, level of evidence B).

CPORT – E trial

Even though those guidelines came out before the results of the CPORT-E trial were published, CPORT-E trial showed similar non-inferiority at 9 months between centers that perform PCI with or without surgical backup in a cohort of nearly 19,000 non-emergent patients. The CPORT-E results were published in the March 2012 issue of the New England Journal of Medicine, and in May three cardiology organizations published an update to cath lab standards allowing for PCI without surgical.

 MASS COMM study

To further the evidence, Jacobs and colleagues in 2006  had designed and carried out the Randomized Trial to Compare Percutaneous Coronary Intervention between Massachusetts Hospitals with Cardiac Surgery On-Site and Community Hospitals without Cardiac Surgery On-Site (MASS COMM) in collaboration with the Massachusetts Department of Public Health who collaborated to obtain “evidence on which to base regulatory policy decisions about performing non-emergent PCI in hospitals without on-site cardiac surgery.”

  • Hospitals without backup surgery were required to perform at least 300 diagnostic catheterizations per year, and operators were mandated to have performed a minimum of 75 PCI procedures per year.
  • The researchers randomized 3,691 patients to each arm in a 3:1 ratio (without/with backup). The median follow-up was about 1 year.
  • The median age of patients was 64, one-third were women, and 92% were white. Both groups had similar median ejection fractions at baseline (55%).
  • The mean number of vessels treated was 1.17 and most patients (84%) had one vessel treated. The mean number of lesions treated was 1.45 and most patients (67%) had one lesion treated.

The indications for PCI were:

1. ST-segment elevated MI (>72 hours before PCI of infarct-related or non–infarct-related artery — 19% and 17%
2. Unstable angina — 45% and 47%
3. Stable angina — 27% and 28%
4. Silent ischemia — 5% and 6%
5. Other — 2.5% and 2.8%
Regarding secondary endpoints, both groups had similar rates of emergency CABG and urgent or emergent PCI at 30 days. Results at 30 days and 12 months were similar for rates of ischemia-driven target-vessel revascularization and target-lesion revascularization. Other endpoints as well were similar at both time points, including
  • all-cause death
  • repeat revascularization
  • stroke
  • definite or probable stent thrombosis
  • major vascular complications
Researchers adjusted for a 1.3 greater chance of MACE occurring at a randomly selected hospital compared with another randomly selected hospital and found
  • the relative risks at 30 days and 12 months “were consistent with those of the primary results” (RR 1.02 and 0.98, respectively).

However, they cautioned that new sites perhaps should be monitored as they gain experience.

A prespecified angiographic review of 376 patients who were in the PCI-without-backup arm and 87 in the other arm showed no differences in
  1. rates of procedural success,
  2. proportion with complete revascularization, or
  3. the proportion of guideline-indicated appropriate lesions for PCI.
Such results show consistent practice patterns between the groups, they noted.
The study had several limitations including the
  • loss of data for 13% of patients, the
  • exclusion of some patients for certain clinical and anatomical features, and
  • not having the power to detect non-inferiority in the separate components of the primary endpoint, researchers wrote.

Cardio Notes: Score Predicts PCI Readmission

Published: Jul 15, 2013

By Chris Kaiser, Cardiology Editor, MedPage Today
  

A simple calculation of patient variables before PCI may help stem the tide of readmission within the first month. Also this week, two blood pressure drugs that benefit diabetics and imaging cardiac sympathetic innervation.

Pre-PCI Factors Predict Return Trip

A new 30-day readmission risk prediction model for patients undergoing percutaneous coronary intervention (PCI) showed it’s possible to predict risk using only variables known before PCI, according to a study published online in Circulation: Cardiovascular Quality and Outcomes.

After multivariable adjustment, the 10 pre-PCI variables that predicted 30-day readmission were older age (mean age 68 in this study), female sex, insurance type (Medicare, state, or unknown), GFR category (less than 30 and 30-60 mL/min per 1.73m2), current or history of heart failure, chronic lung disease, peripheral vascular disease, cardiogenic shock at presentation, admit source (acute and non-acute care facility or emergency department), and previous coronary artery bypass graft surgery.

Additional significant variables post-discharge that predicted 30-day readmission were beta-blocker prescribed at discharge, post-PCI vascular or bleeding complications, discharge location, African American race, diabetes status and modality of treatment, any drug-eluting stent during the index procedure, and extended length of stay.

A risk score calculator using the pre-PCI variables will be available online soon, according to Robert W. Yeh, MD, MSc, of Massachusetts General Hospital in Boston, and colleagues.

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Treatment Options for Left Ventricular Failure  –  Temporary Circulatory Support: Intra-aortic balloon pump (IABP)Impella Recover LD/LP 5.0 and 2.5, Pump Catheters (Non-surgical) vs Bridge Therapy: Percutaneous Left Ventricular Assist Devices (pLVADs) and LVADs (Surgical) 

Author: Larry H Bernstein, MD, FCAP
And
Curator: Justin D Pearlman, MD, PhD, FACC

 

UPDATED on 12/2/2013 – HeartMate II – LVAD

http://www.nytimes.com/2013/11/28/business/3-hospital-study-links-heart-device-to-blood-clots.html?pagewanted=1&_r=0&emc=eta1

Hospital Studies Link Heart Device to Clots

David Maxwell for The New York Times

Dr. Randall Starling, right, said that he could only speculate about the reason for the rapid rise in early blood clots.

By 
Published: November 27, 2013

Doctors at the Cleveland Clinic began to suspect in 2012 that something might be wrong with a high-tech implant used to treat patients with advanced heart failure like former Vice President Dick Cheney.

Thoratec Corportation

The HeartMate II is a left ventricular assist device, which contains a pump that continuously pushes blood through the heart.

The number of patients developing potentially fatal blood clots soon after getting the implant seemed to be rising. Then early this year, researchers completed a check of hospital records and their concern turned to alarm.

The data showed that the incidence of blood clots among patients who got the device, called the HeartMate II, after March 2011 was nearly four times that of patients who had gotten the same device in previous years. Patients who developed pump-related clots died or needed emergency steps like heart transplants or device replacements to save them.

“When we got the data, we said, ‘Wow,’ ” said Dr. Randall C. Starling, a cardiologist at Cleveland Clinic.

On Wednesday, The New England Journal of Medicineposted a study on its website detailing the findings from the Cleveland Clinic and two other hospitals about the device. The HeartMate II belongs to a category of products known as a left ventricular assist device and it contains a pump that continuously pushes blood through the heart.

The abrupt increase in pump-related blood clots reported in the study is likely to raise questions about whether its manufacturer, Thoratec Corporation, modified the device, either intentionally or accidentally. By March, the Cleveland Clinic had informed both Thoratec and the Food and Drug Administration about the problems seen there, Dr. Starling said.

Officials at Thoratec declined to be interviewed. But in a statement, the company, which is based in Pleasanton, Calif., said that the HeartMate II had been intensively studied and used in more 16,000 patients worldwide with excellent results. It added that the six-month survival rate of patients who received the device had remained consistently high.

“Individual center experience with thrombosis varies significantly, and Thoratec actively partners with clinicians at all centers to minimize this risk,” the company said in a statement.

Thoratec and other cardiologists also pointed to a federally funded registry that shows a smaller rise in the rate of blood clots, or thrombosis, among patients getting a HeartMate II than the one reported Wednesday by the three hospitals. In the registry, which is known as Intermacs, the rate of pump-related blood clot associated with the HeartMate II rose to about 5 percent in devices implanted after May 2011 compared with about 2 percent in previous years.

The data reported on Wednesday in The New England Journal of Medicine found rates of clot formation two months after a device’s implant had risen to 8.4 percent after March 2011 from 2.2 percent in earlier years. Researchers also suggested in the study that the Intermacs registry might not capture all cases of pump-related blood clots, such as when patients gets emergency heart transplants after a clot forms.

Not only did the rate of blood clots increase, but the clots also occurred much sooner than in the past, according to the study. After March 2011, the median time before a clot was 2.7 months, compared with 18.6 months in previous years. In addition to the Cleveland Clinic, the report on Wednesday included data from Duke University and Washington University in St. Louis.

All mechanical heart implants are prone to producing blood clots that can form on a device’s surface. And experts say that the rate of blood clot formation can be affected by a variety of factors like changes in the use of blood-thinning drugs or the health of a patient.

In a telephone interview, Dr. Starling described the Thoratec officials as cooperative, adding that they have been looking into the problem since March to understand its cause. He said that he could only speculate about the reason for the rapid rise in early blood clots but believed it was probably device-related.

“My belief is that it is something as subtle as a change in software that affects pump flow or heat dissipation near a bearing,” said Dr. Starling, who is a consultant to Thoratec.

Asked about his comments, Thoratec responded that it had yet to determine the reason for even the smaller rise in blood clots seen in the federally funded database. “We have performed extensive analysis on HeartMate II and have not identified any change that would cause the increase observed in the Intermacs registry,” the company said.

In a statement, the F.D.A. said that it was reviewing the findings of the study. “The agency shares the authors concerns about the possibility of increased pump thrombosis,” the F.D.A. said in a statement.

The fortunes of Thoratec, which has been a favorite of Wall Street investors, may depend on its ability to find an answer to the apparent jump in pump-related blood clots. Over the last two years, the company’s stock has climbed from about $30 a share to over $43 a share. In trading Wednesday, Thoratec stock closed at $42.12 a share, up 61 cents. (The New England Journal of Medicine article was released after the stock market closed.)

The HeartMate II has been a lifesaver for many patients like Mr. Cheney in the final stages of heart failure, who got his device in 2010, sustaining them until they get a heart transplant or permanently assisting their heart. Dr. Starling said that he planned to keep using the HeartMate II in appropriate patients at the Cleveland Clinic because those facing death from heart failure had few options.

But the company has also been pushing to expand the device’s use beyond patients who face imminent death from heart failure. For example, the F.D.A. approved a clinical trial for patients with significant, but less severe, heart failure to receive a HeartMate II to compare their outcomes with patients who take drugs for the same condition. Researchers at the University of Michigan Medical Center who are leading the trial said on Wednesday that, based on the lower rates of blood clots seen in the Intermacs registry, they are planning to move forward with the trial.

Dr. Starling and researchers at the Cleveland Clinic tried this spring to get The New England Journal of Medicine to publish a report about the findings at that hospital, but the publication declined, saying the data might simply represent the experience of one facility. As a result, Dr. Starling contacted Duke University and Washington University for their data. When analyzed, it mirrored events at the Cleveland Clinic, he said.

The problems seen with the HeartMate II at the three hospitals were continuing as recently as this summer, when researchers paused the collection of data to prepare Wednesday’s study. The study also noted that a preliminary analysis of data provided by a fourth hospital, the University of Pennsylvania, showed the same pattern of blood clot formation, but that the data had been submitted too late for full analysis.

 SOURCE

 

This article presents the following four Sections:

I.     Impella LD – ABIOMED, Inc.

II.   IABP VS. Percutaneous LVADS

III. Use of the Impella 2.5 Catheter in High-Risk Percutaneous Coronary Intervention

IV.  PROTECT II Study – Experts Discussion

This account is a vital piece of recognition of very rapid advances in cardiothoracic interventions to support cardiac function mechanically by pump in the situation of loss of contractile function and circulatory output sufficient to sustain life, as can occur with the development of cardiogenic shock.  This has been mentioned and its use has been documented in other portions of this series.   On the one hand, PCI has a long and steady history in the development of interventional cardiology. This necessitated the availability of thoracic-surgical operative support. The situation is changed, and is more properly, conditional.

I. Impella LD – ABIOMED, Inc.

This micro-axial blood pump can be inserted into the left ventricle via open chest procedures. The Impella LD device has a 9 Fr catheter-based platform and a 21 Fr micro-axial pump and is  inserted through the ascending aorta, across the aortic and mitral valves and into the left ventricle.  It requires minimal bedside support and a 9 Fr single-access point  requires no priming outside the body.

Impella.LD_

Impella Recover LD/LP 5.0

The Impella Recover miniaturized impeller pump located within a catheter. The Impella Recover LD/LP 5.0 Support System has been developed to address the need for ventricular support in patients who develop heart failure after heart surgery (called cardiogenic shock) and who have not responded to standard medical therapy. The system is designed to provide immediate support and restore hemodynamic stability for a period of up to 7 days. Used as a bridge to therapy, it allows time for developing a definitive treatment strategy.

The Pump

The Impella Recover LD 5.0 showing implantation via direct placement into the left ventricle.
 Insert B – location in LV
imeplla-LD-video
The Impella Recover system is a miniaturized impeller pump located within a catheter. The device can provide support for the left side of the heart using either the
  • Recover LD 5.0 (implanted via direct placement into the left ventricle) or the
  • Recover LP 5.0 LV (placed percutaneously through the groin and positioned in the left ventricle).
The microaxial pump of the Recover LP/LD 5.0 can pump up to 4.5 liters per minute at a speed of 33,000 rpm. The pump is located at the distal end of a 9 Fr catheter.

II.   IABP VS. Percutaneous LVADS

An intra-aortic balloon pump (IABP) remains the method of choice for mechanical assistance1 in patients experiencing LV failure because of its

  • proven hemodynamic capabilities,
  • prompt time to therapy, and
  • low complication rates.

Percutaneous left ventricular assist devices (pLVADs), such as described above, represent an emerging option for partial or total circulatory support2 and several studies have compared the and efficacy of these devices with intra-aortic balloon pump (IABP) (IABP.)

Despite some randomized controlled trials demonstrating better hemodynamic profiles for pLVADs compared with IABP, there is no difference in  30-day survival or trend toward a reduced 30-day mortality rate associated with pLVADs.  Patients treated with pLVADs tended to have a
  • higher incidence of leg ischemia and
  • device related bleeding.3
Further, no differences have been detected in the overall use of
  • positive inotropic drugs or
  • vasopressors in patients with pLVADs.4,5
However, pLVADs may increase their use for patients not responding to
  • PCI,
  • fluids,
  • inotropes, and
  • IABP
Therefore, the decision making process on how to treat requires an integrated stepwise approach. A pLVAD might be considered on the basis of
  • anticipated individual risk,
  • success rates, and for
  • postprocedural events.6

Potential Algorithm for Device Selection during High-Risk PCI

PADS_HRPCI cardiac assist device selection

Potential Algorithm for Device Selection during Cardiogenic Shock
device_selection_CS
Until an alternative modality, characterized by improved efficacy and safety features compared with IABP, is developed, IABP remains the cornerstone of temporary circulatory support.2

Device Comparison for Treatment of Cardiogenic Shocktraditional intra-aortic balloon therapy with Impella 2.5 percutaneous ventricular assist device

 
1. Percutaneous LVADs in AMI complicated by cardiogenic shock. H Thiele, et al. EHJ 2007;28:2057-2063
2. Cardiogenic shock current concepts and improving outcomes. H R Reynolds et al. Circulation 2008 ;117 :686-697
3. Percutaneous left ventricular assist devices vs. IABP counterpulsation for treatment of cardiogenic shock. J M Cheng, et al. EHJ doi:10.1093/eurheart/ehp292
4. A randomized clinical trial to evaluate the safety and efficacy of a pLVAD vs. IABP for treatment of cardiogenic shock caused by MI. M Seyfarth, et al. JACC 2008;52:1584-8
5. A randomized multicenter clinical study to evaluate the safety and efficacy of the tandem heart pLVAD vs. conventional therapy with IABP for treatment of cardiogenic shock.
6. Percutaneous LVADs in AMI complicated by cardiogenic shock. H Thiele, et al. EHJ 2007;28:2057-2063

III. Use of the Impella 2.5 Catheter in High-Risk Percutaneous Coronary Intervention

Brenda McCulloch, RN, MSN
Sutter Heart and Vascular Institute, Sutter Medical Center, Sacramento, California
Crit Care Nurse 2011; 31(1): e1-e16    http://dx.doi.org/10.4037/ccn2011293
Abstract
The Impella 2.5 is a percutaneously placed partial circulatory assist device that is increasingly being used in high-risk coronary interventional procedures to provide hemodynamic support. The Impella 2.5 is able to unload the left ventricle rapidly and effectively and increase cardiac output more than an intra-aortic balloon catheter can. Potential complications include bleeding, limb ischemia, hemolysis, and infection. One community hospital’s approach to establishing a multidisciplinary program for use of the Impella 2.5 is described.
Patients who undergo high-risk percutaneous coronary intervention (PCI), such as procedures on friable saphenous vein grafts or the left main coronary artery, may have an intra-aortic balloon catheter placed if they require hemodynamic support during the procedure. Currently, the intra-aortic balloon pump (IABP) is the most commonly used device for circulatory support. A newer option that is now available for select patients is the Impella 2.5, a short-term partial circulatory support device or percutaneous ventricular assist device (VAD).
In this article, I discuss the Impella 2.5, review indications and contraindications for its use, delineate potential complications of the Impella 2.5, and discuss implications for nursing care for patients receiving extended support from an Impella 2.5. Additionally, I share our experiences as we developed our Impella program at our community hospital. Routine management of patients after PCI is not addressed.

IABP Therapy: Background

  • decreases after-load,
  • decreases myocardial oxygen consumption,
  • increases coronary artery perfusion, and
  • modestly enhances cardiac output.1,2
The IABP cannot provide total circulatory support. Patients must have some level of left ventricular function for an IABP to be effective.
Optimal hemodynamic effect from the IABP is dependent  on:
  • the balloon’s position in the aorta,
  • the blood displacement volume,
  • the balloon diameter in relation to aortic diameter,
  • the timing of balloon inflation in diastole and deflation in systole, and
  • the patient’s own blood pressure and vascular resistance.3,4

Impella 2.5 Catheter – ABIOMED, Inc.

Effect
  • reduces myocardial oxygen consumption,
  • improves mean arterial pressure, and
  • reduces pulmonary capillary wedge pressure.2

The Impella 2.5 has been used for

  • hemodynamic support during high-risk PCI and for
  • hemodynamic support of patients with
  1. myocardial infarction complicated by cardiogenic shock or ventricular septal defect,
  2. cardiomyopathy with acute decompensation,
  3. postcardiotomy shock,
  4. off-pump coronary artery bypass grafting surgery, or
  5. heart transplant rejection and
  6. as a bridge to the next decision.9
The Impella provides a greater increase in cardiac output than the other IABP provides. In one trial5 in which an IABP was compared with an Impella in cardiogenic shock patients, after 30 minutes of therapy, the cardiac index (calculated as cardiac output in liters per minute divided by body surface area in square meters) increased by 0.5 in the patients with the Impella compared with 0.1 in the patients with an IABP.
Unlike the IABP, the Impella does not require timing, nor is a trigger from an electrocardiographic rhythm or arterial pressure needed (Table 1). The device received 510(k) clearance from the Food and Drug Administration in June 2008 for providing up to 6 hours of partial circulatory support. In Europe, the Impella 2.5 is approved for use up to 5 days. Reports of longer duration of therapy in both the United States and Europe have been published.8,9
Table IABT vs Impella

Clinical Research and Registry Findings

Abiomed has sponsored several trials, including PROTECT I, PROTECT II, RECOVER I, RECOVER II, and ISAR-SHOCK.
The PROTECT I study was done to assess the safety and efficacy of device placement in patients undergoing high-risk PCI.10

Twenty patients who had

  • poor ventricular function (ejection fraction =35%) and had
  • PCI on an unprotected left main coronary artery or the
  • last remaining patent coronary artery or graft.

The device was successfully placed in all patients, and the duration of support ranged from 0.4 to 2.5 hours. Following this trial, the Impella 2.5 device received its 510(k) approval from the Food and Drug Administration.

The ISAR-SHOCK trial was done to evaluate the safety and efficacy of the Impella 2.5 versus the IAPB in patients with cardiogenic shock due to acute myocardial infarction.5 Patients were randomized to support from an IABP (n=13) or an Impella (n=12).

The trial’s primary end point of hemodynamic improvement was defined as improved cardiac index at 30 minutes after implantation.

  1. Improvements in cardiac index were greater with the Impella (P=.02).
  2. The diastolic pressure increased more with Impella (P=.002).
  3. There was a nonsignificant difference in the MAP (P=.09), as was the use of inotropic agents and vasopressors similar in both groups of patients.

Device Design: Impella 2.5 Catheter

The Impella 2.5 catheter contains a nonpulsatile microaxial continuous flow blood pump that pulls blood from the left ventricle to the ascending aorta, creating increased forward flow and increased cardiac output. An axial pump is one that is made up of impellar blades, or rotors, that spin around a central shaft; the spinning of these blades is what moves blood through the device.13

The Impella 2.5 catheter has 2 lumens. A tubing system called the Quick Set-Up has been developed for use in the catheterization laboratory. It is a single tubing system that bifurcates and connects to each port of the catheter. This arrangement allows rapid initial setup of the console so that support can be initiated quickly. When the Quick Set-Up is used, the 10% to 20% dextrose solution used to purge the motor is not heparinized. One lumen carries fluid to the impellar blades and continuously purges the motor to prevent the formation of thrombus. The proximal port of this lumen is yellow. The second lumen ends near the motor above the level of the aortic valve and is used to monitor aortic pressure.
The components required to run the device are assembled on a rolling cart and include the power source, the Braun Vista infusion pump, and the Impella console. The Impella console powers the microaxial blood pump and monitors the functioning of the device, including the purge pressure and several other parameters. The console can run on a fully charged battery for up to 1 hour.

Placement of the Device

The Impella 2.5 catheter is placed percutaneously through the common femoral artery and advanced retrograde to the left ventricle over a guidewire. Fluoroscopic guidance in the catheterization laboratory or operating room is required. After the device is properly positioned, it is activated and blood is rapidly withdrawn by the microaxial blood pump from the inlet valve in the left ventricle and moved to the aorta via the outlet area, which sits above the aortic valve in the aorta.
If the patient tolerates the PCI procedure and hemodynamic instability does not develop, the Impella 2.5 may be removed at the end of the case, or it can be withdrawn, leaving the arterial sheath in place, which can be removed when the patient’s activated clotting time or partial thromboplastin time has returned to near normal levels. For patients who become hemodynamically unstable or who have complications during the PCI (eg, no reflow, hypotension, or lethal arrhythmias), the device can remain in place for continued partial circulatory support, and the patient is transported to the critical care setting.

Potential Complications of Impella Therapy

The most commonly reported complications of Impella 2.5 placement and support include

  • limb ischemia,
  • vascular injury, and
  • bleeding requiring blood transfusion.6,9
Hemolysis is an inherent risk of the axial construction, and results in transfusions.5,10
Hemolysis can be mechanically induced when red blood cells are damaged as they pass through the microaxial pump. Other potential complications include
  • aortic valve damage,
  • displacement of the distal tip of the device into the aorta,
  • infection, and
  • sepsis.
  • Device failure, although not often reported, can occur.
Patients on Impella 2.5 support who may require
  • interrogation of a permanent pacemaker or
  • implantable cardioverter defibrillator
present an interesting situation. In order for the interrogator to connect with the permanent pacemaker or implantable cardioverter defibrillator, the Impella console must be turned off for a few seconds while the signal is established. As soon as the signal has been established, Impella support is immediately restarted.

Impella 2.5 Console Management

The recommended maximum performance level for continuous use is P8. At P8, the flow rate is 1.9 to 2.6 L/min and the motor is turning at 50000 revolutions per minute. When activated, the console is silent. No sound other than alarms is audible during Impella support, unlike the sound heard with an IABP. Ten different performance levels ranging from P0 to P9 are available. As the performance level increases, the flow rate and number of revolutions per minute increase. At maximum performance (P9), the pump rotates at 50000 revolutions per minute and delivers a flow rate of 2.1 to 2.6 L/min. P9 can be activated only for 5-minute intervals when the Impella 2.5 is in use.

IV.  PROTECT II Study – Experts Discussion

the use of the Impella support device and the intraortic balloon pump for high-risk percutaneous coronary intervention
 
DR. SMALLING: Well, the idea about the PROTECT trial is that it would show that using the Impella device to support high-risk angioplasty was not inferior to utilizing the balloon pump for the same patient subset. Ejection fraction’s were in the 30%–35% range. Supposedly last remaining vessel or left main disease or left-main plus three-vessel disease and low EF; so I think that was the screening for entry into the trial.
major adverse cardiac event endpoints
  1. Acute myocardial infarction,
  2. mortality,
  3. bleeding,
mortality was the same. Their endpoints really didn’t show that much difference. In subgroup analysis, they felt that they Impella may have had a little advantage over balloon pump.
DR. KERN: So do you think this study would tip the interventionalist to move in one direction or the other for high-risk angioplasty?
DR. SMALLING: That’s an interesting concept, you know? One has to get to: What is really a high-risk angioplasty. I think you and I are both old enough to remember that back in the mid-’80s, we determined that high-risk angioplasty was a patient with an ejection fraction of 25% or less, with a jeopardy score over 6. The EFs were a little higher. And, I guess, based on our prior experience with other support devices — like, for instance, CPS and then, later on, the Tandem Heart — there really was not an advantage of so-called more vigorous support systems. And so, the balloon pump served as well.
DR. SMALLING:
Those of us that have looked carefully at what it can really do, I think it may get one liter a minute at most, maybe more.1-6 But I think, for all intents and purposes, it doesn’t support at a very vigorous level. So I think personally, if I had someone I was really worried about, I would opt for something more substantial like, for instance, a Tandem Heart device.
DR. KERN: I think this is a really good summary of the study and the. Are there any final thoughts for those of us who want to read the PROTECT II study when it comes out?
DR. SMALLING: We have to consider a $20,000, $25,000 device. Is that really necessary to do something that we could often do without any support at all, or perhaps with a less costly device like a balloon pump.
DR. KERN: We’re going to talk for a few minutes about the PROTECT II study results that were presented here in their form. And Ron, I know you’ve been involved with following the work of the PROTECT II investigators. Were you a trial site for this study?
DR. WAKSMAN: No, actually, we were not, but we have a lot of interest in high-risk PCI and using devices to make this safe — mainly safe — and also effective. We were not investigators, but we did try to look, based on the inclusion/exclusion criteria, on our own accord with the balloon pump. If you recall, this study actually was comparing balloon time to the Impella device for patients who are high-risk PCI.
The composite endpoint was very complicated. They added like probably nine variables there, which is unusual for a study design. … They basically estimated that the event rate on the balloon pump would be higher than what we thought it should be. So we looked at our own data, and we found out that the actual — if you go by the inclusion/exclusion criteria and their endpoints — the overall event rate in the balloon pump would be much lower than they predicted and built in their sample size.
DR. KERN: And, so, the presentation of the PROTECT II trial, was it presented as a positive study or a negative study.
DR. WAKSMAN: Overall the study did not meet the endpoint. So the bottom line, you can call it the neutral study, which is a nice way to say it.
if you go and do all those analyses, you may find some areas that you can tease a P value, but I don’t think that this has any scientific value, and people should be very careful. We’re not playing now with numbers or with statistics, this is about patient care. You’re doing a study — the study, I think, has some flaws in the design to begin with — and we actually pointed that out when we were asked to participate in the study. But if the study did not meet the endpoint, then I think all those subanalyses, subgroups, you extract from here, you add to there, and you get a P value, that means nothing. So we have to be careful when we interpret this, other than as a neutral study that you basically cannot adopt any of the … it did not meet the hypothesis, that’s the bottom line.

A first-in-man study of the Reitan catheter pump for circulatory support in patients undergoing high-risk percutaneous coronary intervention.

Smith EJ, Reitan O, Keeble T, Dixon K, Rothman MT.
Department of Cardiology, London Chest Hospital, United Kingdom.
Catheter Cardiovasc Interv. 2009 Jun 1;73(7):859-65.
http://dx.doi.org/10.1002/ccd.21865.

To investigate the safety of a novel percutaneous circulatory support device during high-risk percutaneous coronary intervention (PCI).

BACKGROUND:

The Reitan catheter pump (RCP) consists of a catheter-mounted pump-head with a foldable propeller and surrounding cage. Positioned in the descending aorta the pump creates a pressure gradient, reducing afterload and enhancing organ perfusion.

METHODS:

Ten consecutive patients requiring circulatory support underwent PCI; mean age 71 +/- 9; LVEF 34% +/- 11%; jeopardy score 8 +/- 2.3. The RCP was inserted via the femoral artery. Hemostasis was achieved using Perclose sutures. PCI was performed via the radial artery. Outcomes included in-hospital death, MI, stroke, and vascular injury. Hemoglobin (Hb), free plasma Hb (fHb), platelets, and creatinine (cre) were measured pre PCI and post RCP removal.

RESULTS:

The pump was inserted and operated successfully in 9/10 cases (median 79 min). Propeller rotation at 10,444 +/- 1,424 rpm maintained an aortic gradient of 9.8 +/- 2 mm Hg.  Although fHb increased,

  • there was no significant hemolysis (4.7 +/- 2.4 mg/dl pre vs. 11.9 +/- 10.5 post, P = 0.04, reference 20 mg/dl).
  • Platelets were unchanged (pre 257 +/- 74 x 10(9) vs. 245 +/- 63, P = NS).
  • Renal function improved (cre pre 110 +/- 27 micromol/l vs. 99 +/- 28, P = 0.004).

All PCI procedures were successful with no deaths or strokes, one MI, and no vascular complications following pump removal.

14F RCP first in man mechanical device post PCI LVEF 25% JS 10

CONCLUSIONS:

The RCP can be used safely in high-risk PCI patients.

(c) 2009 Wiley-Liss, Inc.  PMID: 19455649

Todd J. Brinton, MD and Peter J. Fitzgerald, MD, PhD, Chapter 14: VENTRICULAR ASSIST TECHNOLOGIES

http://www.sis.org/docs/2006Yearbook_Ch14.pdf

Other related articles published on this Open Access Online Scientific Journal include the following:

A coronary angiogram that shows the LMCA, LAD ...

A coronary angiogram that shows the LMCA, LAD and LCX. (Photo credit: Wikipedia)

English: Simulation of a wave pump human ventr...

English: Simulation of a wave pump human ventricular assist device (Photo credit: Wikipedia)

English: Figure A shows the structure and bloo...

English: Figure A shows the structure and blood flow in the interior of a normal heart. Figure B shows two common locations for a ventricular septal defect. The defect allows oxygen-rich blood from the left ventricle to mix with oxygen-poor blood in the right ventricle. (Photo credit: Wikipedia)

 

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CABG Survival in Multivessel Disease Patients: Comparison of Arterial Bypass Grafts vs Saphenous Venous Grafts

Writer and Curator: Larry H. Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN 

 

This article examines 10-year to 15-year survivals from arterial bypass grafts using arterial vs saphenous venous grafts.

Locker C, Schaff HV, Dearani JA, Joyce LD, Park SJ, et al.
Division of Cardiovascular Surgery, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. lekerlocker.chaim@mayo.edu
Circulation. 2012 Aug 28;126(9):1023-30.   PMID: 22811577 http://dx.doi.org/10.1161/CIRCULATIONAHA.111.084624. Epub 2012 Jul 18. Review.
Coronary artery bypass surgery (CABG) , is performed to relieve angina and reduce the risk of death from coronary artery disease. Arteries or veins from elsewhere in the patient’s body are grafted to the coronary arteries to bypass atherosclerotic narrowings and improve the blood supply to the coronary circulation supplying the myocardium. This surgery is usually performed with the heart stopped, necessitating the usage of cardiopulmonary bypass; techniques are available to perform CABG on a beating heart, so-called “off-pump” surgery.
Russian cardiac surgeon, Dr. Vasilii Kolesov, performed the first successful internal mammary artery–coronary artery anastomosis in 1964. Using a standard suture technique in 1964, and over the next five years he performed 33 sutured and mechanically stapled anastomoses in St. Petersburg, Russia.
Dr. René Favaloro, an Argentine surgeon, achieved a physiologic approach in the surgical management of coronary artery disease—the bypass grafting procedure—at the Cleveland Clinic in May 1967. His new technique used a saphenous vein autograft to replace a stenotic segment of the right coronary artery, and he later successfully used the saphenous vein as a bypassing channel, which has become the typical bypass graft technique we know today; in the U.S., this vessel is typically harvested endoscopically, using a technique known as endoscopic vessel harvesting (EVH). Soon Dr. Dudley Johnson extended the bypass to include left coronary arterial systems. In 1968, Doctors Charles Bailey, Teruo Hirose and George Green used the internal mammary artery instead of the saphenous vein for the grafting.
A person with a large amount of coronary artery disease (CAD) may receive fewer bypass grafts owing to the lack of suitable “target” vessels. A coronary artery may be unsuitable for bypass grafting if
  • it is small (< 1 mm or < 1.5 mm depending on surgeon preference),
  • heavily calcified (meaning the artery does not have a section free of CAD) or
  • intramyocardial (the coronary artery is located within the heart muscle rather than on the surface of the heart).
Similarly, a person with a single stenosis (“narrowing”) of the left main coronary artery requires only two bypasses (to the LAD and the LCX). However, a left main lesion places a person at the highest risk for death from a cardiac cause.
  • Both PCI and CABG are more effective than medical management at relieving symptoms, (e.g. angina, dyspnea, fatigue).
  • CABG is superior to PCI for some patients with multivessel CAD.
The Surgery or Stent (SoS) trial was a randomized controlled trial that compared CABG to PCI with bare-metal stents. The SoS trial demonstrated CABG is superior to PCI in multivessel coronary disease.
The SYNTAX trial was a randomized controlled trial of 1800 patients with multivessel coronary disease, comparing CABG versus PCI using drug-eluting stents (DES). The study found that
  • rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the DES group (17.8% versus 12.4% for CABG; P=0.002).
This was primarily driven by
  • higher need for repeat revascularization procedures in the PCI group with no difference in repeat infarctions or survival.
  • Higher rates of strokes were seen in the CABG group.

http://upload.wikimedia.org/wikipedia/commons/thumb/c/c3/Coronary_artery_bypass_surgery_Image_657C-PH.jpg/230px-Coronary_artery_bypass_surgery_Image_657C-PH.jpg

http://upload.wikimedia.org/wikipedia/commons/thumb/3/30/Heart_saphenous_coronary_grafts.jpg/220px-Heart_saphenous_coronary_grafts.jpg

220px-Heart_saphenous_coronary_grafts

Left Internal Mammary Artery Usage in Coronary Artery Bypass Grafting: A Measure of Quality Control

S Karthik and BM Fabri
Ann R Coll Surg Engl 2008; 85(4):367-69.

Over the last two decades, many studies have shown better long-term patency rates and survival in patients undergoing coronary artery bypass grafting (CABG) with left internal mammary artery (LIMA) to the left anterior descending artery (LAD).
Although the current focus in the UK is on mortality rates, we believe that it will not be long before this will also include the incidence of major morbidity after CABG such as stroke, myocardial infarction (MI), renal failure and sternal wound problems. We also believe that we should now consider LIMA usage as a marker of quality control in CABG. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964611/

This study very clearly demonstrated that:

  1. Approximately 4% of all patients undergoing first-time CABG do not need a graft to the LAD.
  2. Of the rest, about 92% receive LIMA to LAD.

Six sub-groups of patients in whom LIMA usage was significantly less were:

(i) the elderly (> 70 years of age);

(ii) females;

(iii) diabetics;

(iv) patients having emergency CABG;

(v) poor left ventricular (LV) function (ejection fraction [EF] < 30%); and

(vi) respiratory disease.

LIMA usage was also reduced in patients undergoing combined CABG and valve procedures.

Multiple arterial grafts improve late survival of patients undergoing CABG

BACKGROUND: Use of the left internal mammary artery (LIMA) in multivessel coronary artery disease improves survival after coronary artery bypass graft surgery; however, the survival benefit of multiple arterial (MultArt) grafts is debated. (Perhaps not without reason. One problem is the small size of the left circumflex artery, and where does the right coronary artery have a place?)
METHODS : We reviewed 8622 Mayo Clinic patients who had isolated primary coronary artery bypass graft surgery for multivessel coronary artery disease from 1993 to 2009. Patients were stratified by number of arterial grafts into the LIMA plus saphenous veins (LIMA/SV) group (n=7435) or the MultArt group (n=1187). Propensity score analysis matched 1153 patients.
RESULTS: Operative mortality was 0.8% (n=10) in the MultArt and 2.1% (n=154) in the LIMA/SV (P=0.005) group.This result was not statistically different (P=0.996) in multivariate analysis or the propensity-matched analysis (P=0.818).
Late survival was greater for MultArt versus LIMA/SV (10- and 15-year survival rates were 84% and 71% versus 61% and 36%, respectively [P<0.001], in unmatched groups and 83% and 70% versus 80% and 60%, respectively [P=0.0025], in matched groups). The large difference between the MultiArt versus the LIMA/SV appears to be the 61% and 36% in unmatched and 80% and 60% in matched, evident at 15-years, favorable for the MultiArt group.
MultArt subgroups with bilateral internal mammary artery/SV (n=589) and

  • bilateral internal mammary artery only (n=271) had improved 15-year survival (86% and 76%; 82% and 75% at 10 and 15 years [P<0.001]), and
  • bilateral internal mammary artery/radial artery (n=147) and LIMA/radial artery (n=169) had greater 10-year survival (84% and 78%; P<0.001) versus LIMA/SV.

In multivariate analysis, MultArt grafts remained a strong independent predictor of survival (hazard ratio, 0.79; 95% confidence interval, 0.66-0.94; P=0.007).

CONCLUSIONS:

In patients undergoing isolated coronary artery bypass graft surgery with LIMA to left anterior descending artery,

  • arterial grafting of the non-left anterior descending vessels conferred a survival advantage at 15 years compared with Saphenous Venous (SV) grafting.

It is still unproven whether these results apply to higher-risk subgroups of patients.

Other related articles published on this Open Access Online Scientific Journal, include the following:

Competition in the Ecosystem of Medical Devices in Cardiac and Vascular Repair: Heart Valves, Stents, Catheterization Tools and Kits for Open Heart and Minimally Invasive Surgery (MIS) (Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2012/06/22/competition-in-the-ecosystem-of-medical-devices-in-cardiac-and-vascular-repair-heart-valves-stents-catheterization-tools-and-kits-for-open-heart-and-minimally-invasive-surgery-mis/
Bioabsorbable Drug Coating Scaffolds, Stents and Dual Antiplatelet Therapy (Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2013/05/29/bioabsorbable-drug-coating-scaffolds-stents-and-dual-antiplatelet-therapy/

Vascular Repair: Stents and Biologically Active Implants (larryhbern)
https://pharmaceuticalintelligence.com/2013/05/04/stents-biologically-active-implants-and-vascular-repair/

Drug Eluting Stents: On MIT’s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES (larryhbern)
https://pharmaceuticalintelligence.com/2013/04/25/contributions-to-vascular-biology/

Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents (Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2012/08/13/coronary-artery-disease-medical-devices-solutions-from-first-in-man-stent-implantation-via-medical-ethical-dilemmas-to-drug-eluting-stents/

Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty (larryhbern)
https://pharmaceuticalintelligence.com/2013/06/23/comparison-of-cardiothoracic-bypass-and-percutaneous-interventional-catheterization-survivals

Svelte Medical Systems’ Drug-Eluting Stent: 0% Clinically-Driven Events Through 12-Months in First-In-Man Study (Aviva Lev-Ari
https://pharmaceuticalintelligence.com/2013/05/28/svelte-medical-systems-drug-eluting-stent-0-clinically-driven-events-through-12-months-in-first-in-man-study/

Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone (Justin Pearlman, Aviva Lev-Ari)
https://pharmaceuticalintelligence.com/2013/05/22/acute-and-chronic-myocardial-infarction-quantification-of-myocardial-viability-fdg-petmri-vs-mri-or-pet-alone/

Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization (larryhbern)
https://pharmaceuticalintelligence.com/2013/05/05/bioengineering-of-vascular-and-tissue-models/

Revascularization: PCI, Prior History of PCI vs CABG (A Lev-Ari)
https://pharmaceuticalintelligence.com/2013/04/25/revascularization-pci-prior-history-of-pci-vs-cabg/

Accurate Identification and Treatment of Emergent Cardiac Events (larryhbern)
https://pharmaceuticalintelligence.com/2013/03/15/accurate-identification-and-treatment-of-emergent-cardiac-events/

FDA Pending 510(k) for The Latest Cardiovascular Imaging Technology (A Lev-Ari)
https://pharmaceuticalintelligence.com/2013/01/28/fda-pending-510k-for-the-latest-cardiovascular-imaging-technology/

The ACUITY-PCI score: Will it Replace Four Established Risk Scores — TIMI, GRACE, SYNTAX, and Clinical SYNTAX (A Lev-Ari)
https://pharmaceuticalintelligence.com/2013/01/03/the-acuity-pci-score-will-it-replace-four-established-risk-scores-timi-grace-syntax-and-clinical-syntax/

CABG or PCI: Patients with Diabetes – CABG Rein Supreme (A Lev-Ari)
https://pharmaceuticalintelligence.com/2012/11/05/cabg-or-pci-patients-with-diabetes-cabg-rein-supreme/

To Stent or Not? A Critical Decision (A Lev-Ari)
https://pharmaceuticalintelligence.com/2012/10/23/to-stent-or-not-a-critical-decision/

The internal mammary artery and its branches.

The internal mammary artery and its branches. (Photo credit: Wikipedia)

Coronary artery bypass surgery, the usage of c...

Coronary artery bypass surgery, the usage of cardiopulmonary bypass Русский: Коронарное шунтирование (Photo credit: Wikipedia)

A coronary angiogram that shows the LMCA, LAD ...

A coronary angiogram that shows the LMCA, LAD and LCX. (Photo credit: Wikipedia)

Micrograph of an artery that supplies the hear...

Micrograph of an artery that supplies the heart with significant atherosclerosis and marked luminal narrowing. Tissue has been stained using Masson’s trichrome. (Photo credit: Wikipedia)

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