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Posts Tagged ‘CABG’


Patients with Heart Failure & Left Ventricular Dysfunction: Life Expectancy Increased by coronary artery bypass graft (CABG) surgery: Poor Outcomes on Medical Therapy alone

Curator: Aviva Lev-Ari, PhD, RN

CABG improves survival for individuals with coronary artery disease and compromised left ventricular function,” said NHLBI Director Gary H. Gibbons, MD

Monday, April 4, 2016

Original article

http://www.nejm.org/doi/full/10.1056/NEJMoa1602001

Study results show bypass surgery extends lives of patients with heart failure

Research may lead to improved outcomes for large number of patients who previously had limited therapeutic options.

Scientists funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health have found that a greater number of patients with coronary artery disease may benefit from coronary artery bypass graft (CABG) surgery than previously thought.

CABG — a surgical procedure to help improve blood flow to the heart by bypassing arteries clogged with cholesterol plaques — was thought to be too risky for patients with the long-term effects of coronary artery disease: left ventricular dysfunction (when the left side of the heart is unable to pump normally) and heart failure. Studies of the safety and effectiveness of CABG in the 1970s excluded most patients with these two conditions. The procedure was typically used to relieve angina, or chest pain.

“With limited data showing any benefit for patients with left ventricular dysfunction and heart failure, physicians and patients were less likely to engage in such an invasive, and thus risky, procedure as CABG for diagnosis and treatment,” said lead author Eric J. Velazquez, MD, FACP, FACC, FASE, FAHA, of Duke University Medical Center. “Patients with these conditions largely received medical therapy alone and had poor outcomes.”

Dr. Velazquez and his team conducted a five-year global, randomized controlled clinical trial, called the Surgical Treatment for Ischemic Heart Failure (STICH) study, and a five-year extension study (STICHES(link is external)), to evaluate whether CABG plus guideline-directed medical therapy had a durable benefit over medical therapy alone for patients with coronary artery disease and left ventricular dysfunction. The researchers found that CABG added to medical therapy led to significantly lower rates of death and hospitalization among patients with coronary artery disease, left ventricular dysfunction, and heart failure.

“Our results usher in a new era in the treatment of coronary artery disease because we now have evidence that with CABG and medical therapy, there is a 16 percent reduction in the risk of death from any cause over 10 years,” Dr. Velazquez said.

He added that there is also a median survival benefit of nearly a year and a half, and that he and his team saw that the addition of CABG to medical therapy prevented a death from any cause for every 14 patients they treated. Their data further suggest that the reduction in the risk of death could be even greater in real-world practice.

“Conducting this trial was critically important to determine in a scientifically rigorous study that CABG improves survival for individuals with coronary artery disease and compromised left ventricular function,” said NHLBI Director Gary H. Gibbons, MD. “The current 10-year follow-up provides new important insights about patient subgroups that are more likely to benefit from CABG as compared to medical therapy alone. As such, we now have a solid evidence base to inform patient care and the future development of clinical practice recommendations.”

Dr. Velazquez noted that the results are particularly important because the prevalence of left ventricular dysfunction and heart failure is expected to increase to approximately 8 million individuals by 2030 in the U.S. alone. The increase in the projected prevalence is a result of advances in the management of cardiovascular disease and its risk factors, increasingly transforming coronary artery disease into a chronic disease with long-term effects such as left ventricular dysfunction and heart failure.

George Sopko, MD, MPH, the program director in NHLBI’s Division of Cardiovascular Sciences who administered the study grant, added that this investigation, published in The New England Journal of Medicine (April 2016), is one of only a few cardiovascular trials with 10 years of follow-up and with approximately 98 percent of the patients followed throughout the study period.

“It is unusual to have this quality of follow-up for so long,” said Dr. Sopko. “It speaks to the rigor of the results.” He added that the results are very generalizable, as the study included a diverse patient population spread across 22 countries and various health systems.

SOURCE

http://www.nih.gov/news-events/news-releases/study-results-show-bypass-surgery-extends-lives-patients-heart-failure

http://www.nejm.org/doi/full/10.1056/NEJMoa1602001

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

Articles on Heart Failure N=6

https://pharmaceuticalintelligence.com/?s=Heart+Failure

Articles on coronary artery bypass graft CABG N=36

https://pharmaceuticalintelligence.com/?s=CABG

Articles on Pharmacotherapy of Cardiovascular Diseases N=296

https://pharmaceuticalintelligence.com/?s=Pharmacotherapy+of+Cardiovascular+Disease

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Call for the abandonment of the Off-pump CABG surgery (OPCAB) in the On-pump / Off-pump Debate, +100 Research Studies

Curator: Aviva Lev-Ari, PhD, RN

The curator shadowed Dr. J. Walker @MGH performing On-pump CABG in 1/2005 and On-pump CABG performed @Texas Heart Institute in 2/2005, and attended demos of ECMO at Vanderbilt Medical Center, Department of Surgery, Perfusion Program, 8/2005.

 

Public release date: 22-Jul-2013

Contact: Gina Orlando
gina.orlando@bmc.org
617-638-8490
Boston University Medical Center

BMC surgeon recommends off-pump coronary artery bypass grafting be abandoned

(Boston) – In a Special Report in the current issue of Circulation, Boston Medical Center cardiothoracic surgeon Harold Lazar, MD, has found that off-pump coronary artery bypass graft (OPCAB) surgery has failed to show any significant improvement in short-term morbidity or mortality as compared to the traditional on-pump coronary artery bypass graft (CABG) surgery. He recommends that the technique be abandoned, unless surgeons who perform off-pump surgery can show that their own results are as good as results reported with the traditional on-pump surgery.

During off-pump coronary artery bypass graft surgery, the heart is still beating while the graft attachments are made to bypass a blockage. While performing on-pump CABG surgery, the heart is stopped and a heart-lung machine takes over the work for the heart and lungs. This method has been an effective, safe and time-proven technique and is considered the gold standard with which all other surgical revascularization methods have been compared. However, performing coronary revascularization this way can result in myocardial ischemic injury, neurocognitive deficits, and strokes and activate inflammatory pathways that contribute to pulmonary, renal and hematologic complications.

In order to accurately compare the advantages and disadvantages of OPCAB and to determine what, if any, role it should have in the practice of surgical coronary artery revascularization, Lazar examined clinical data from numerous studies worldwide and found the OPCAB technique had failed to show any significant improvement in short-term morbidity or mortality.

According to Lazar a major impetus for performing OPCAB was to avoid the possible detrimental effects of cardiopulmonary bypass, which include activation of inflammatory pathways, changes in neurological and cognitive function and alterations in quality of life. “However, patients undergoing OPCAB have not shown any benefits in these areas,” said Lazar, a professor of surgery at Boston University School Medicine. “Even in those studies in which OPCAB has resulted in a small improvement in early postoperative outcomes, these improvements are no longer apparent on long-term follow-up,” he added.

In fact, several studies suggest that long-term survival may be significantly reduced in OPCAB patients compared with patients in whom on-pump techniques were used. Lazar explains that this may be attributable to the significant increase in incomplete revascularization seen in OPCAB patients and may be responsible for the increase in recurrent angina and need for revascularization procedures seen in OPCAB patients.

“Unless individual surgeons can demonstrate that they can achieve short- and long-term outcomes with OPCABG that are comparable to on-pump CABG results, they should abandon this technique,” said Lazar.

 

The debate over abandoning off-pump CABG surgery

JULY 29, 2013 

Boston, MA Off-pump coronary artery bypass graft (OPCAB) surgery is not as durable or as effective as coronary surgery performed with cardiopulmonary bypass (CPB) and should be abandoned in favor of conventional CABG surgery, according to one expert.

In the July 23, 2013 issue of CirculationDr Harold Lazar (Boston Medical Center, MA) argues that the primary focus of surgical coronary revascularization is complete revascularization and a technically perfect anastomosis that uses the best conduits with a minimal amount of hemodynamic instability. He adds that the procedure should be able to be performed “under all circumstances, on all patients, at all institutions, regardless of their cardiac volume.

“We must not forget that patients are sent for surgical revascularization because medical management has failed, their cardiologists believe that stents will not result in complete revascularization, and the goal is for optimal long-term survival and enhanced freedom from recurrent angina and the need for [repeat] revascularization,” writes Lazar. “These goals can be best achieved with on-pump CABG surgery.”

Dr Robbin Cohen (University of Southern California, LA), on the other hand, said that many physicians are routine off-pump CABG surgeons and the data suggest that results achieved by experienced operators are excellent. It is also a cheaper operation in experienced hands. He does not believe that OPCAB should be abandoned but acknowledged there is a need to better identify the ideal patient who would benefit from the procedure.

While there is yet no consensus and no studies have identified subgroups with better results, the ideal OPCAB candidate is one with a severely diseased descending aorta and those with single-vessel or two-vessel disease—in other words, a patient with favorable anatomy that doesn’t require moving the heart around too much, he said.

“I don’t doubt that I have treated some patients with off-pump surgery where if I had put them on the pump I would have killed them,” Cohen told heartwire.

Looking at the big picture

In his perspective, Lazar analyzes previously published retrospective studies and prospective, randomized controlled clinical trials, including the Randomized On/Off Bypass (ROOBY), Smart Management of Arterial Revascularization Therapy (SMART), and Coronary Artery Bypass Surgery Off- or On-Pump Revascularization (CORONARY) studies.

In ROOBY, the primary short-term end point of death and major cardiovascular events at 30 days was similar in the on-pump and off-pump treatment arms, while cardiac-related mortality and major adverse events were higher in the OPCAB arm at one year. The SMART trial also failed to show a mortality benefit with OPCAB. The CORONARY investigators reported no difference in the composite of death, nonfatal cerebrovascular accidents, nonfatal MIs, or new renal failure requiring dialysis between OPCAB and on-pump CABG surgery. In CORONARY, there was also no difference in quality-of-life scores and neurocognitive function at one year.

Importantly, Lazar says the data from published meta-analyses show that OPCAB patients tend to receive fewer grafts and have a higher incidence of incomplete revascularization. “Despite advances in stabilizers and other equipment, it may be difficult to graft inferior and posterolateral vessels because of right and left ventricular distension and hemodynamic changes,” he writes.

Abandoned? Not so fast, says another expert

So, will OPCAB be abandoned? Not likely, says Cohen. OPCAB is performed often in other countries, mainly because the procedure is quicker and has lower costs than conventional CABG surgery. Cohen had high praise for the systematic review by Lazar, however, noting that the OPCAB vs on-pump CABG debate is a complicated topic and nearly each month brings a new review, journal article, or other analysis in the medical journals.

“Early on, most of us assumed that the morbidity associated with cardiac surgery, that being stroke, renal failure, and so on, was the result of cardiopulmonary bypass,” said Cohen. “And when we started doing off-pump procedures, we assumed that the morbidity would be eliminated. That wasn’t the case. Some of the early studies showed an advantage with blood use and sometimes with the utilization of resources, but morbidity and mortality with the two surgeries were the same.”

Cohen addressed the criticism that OPCAB provides incomplete revascularization compared with on-pump CABG and that the anastomoses are not as good, saying these are all valid criticisms of the procedure. He agreed with Lazar’s point that if surgeons must cross over from OPCAB to conventional bypass, the outcomes are poor. To date, however, OPCAB “has been a moving target,” he added, noting that there has been a move toward addressing these shortcomings.

At one point, Cohen said his group was performing up to 90% of cardiac surgeries with OPCAB but now do just 10% of procedures off-pump. The reasons for decline in use include all of the previously cited reasons:

  • incomplete revascularization,
  • poorer anastomoses, and
  • no reduction in morbidity and mortality to show it is better than conventional CABG, as well the fact that
  • it is difficult to teach to residents.

For OPCAB to move forward, he said that research needs to provide evidence that the procedure is as least as effective and as durable as on-pump CABG. There is also a need to identify specific patient subgroups that would benefit from OPCAB, such as

  • older patients, those with
  • existing renal failure, or
  • patients who have previously had a stroke.
Source

  1. Lazar HL. Should off-pump coronary artery bypass grafting be abandoned? Circulation 2013; 128:406-413. 

 

Related links

Lazar and Cohen report no conflicts of interest. 

http://www.theheart.org/article/1564393.do?utm_medium=email&utm_source=20130731_heartwire&utm_campaign=newsletter

REVIEWS in

http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_reviews&from_uid=23877063

Should off-pump coronary artery bypass grafting be abandoned?

Lazar HL.

Circulation. 2013 Jul 23;128(4):406-13. doi: 10.1161/CIRCULATIONAHA.113.003388. No abstract available.

PMID: 23877063 [PubMed – in process]

Related citations

 

Off-pump coronary artery bypass grafting: simple concept but potentially sublime scientific value.

Ngaage DL.

Med Sci Monit. 2004 Mar;10(3):RA47-54. Epub 2004 Mar 1. Review.

PMID: 14976442 [PubMed – indexed for MEDLINE]

Related citations

 

Coronary artery surgery: conventional coronary artery bypass grafting versus off-pump coronary artery bypass grafting.

Salzberg SP, Adams DH, Filsoufi F.

Curr Opin Cardiol. 2005 Nov;20(6):509-16. Review.

PMID: 16234622 [PubMed – indexed for MEDLINE]

Related citations

 

Outcomes of off-pump coronary artery bypass surgery: current best available evidence.

Raja SG, Berg GA.

Indian Heart J. 2007 Jan-Feb;59(1):15-27. Review.

PMID: 19098331 [PubMed – indexed for MEDLINE]

Related citations

 

Off-pump coronary artery bypass grafting through sternotomy: for whom?

Noora J, Puskas JD.

Curr Opin Cardiol. 2006 Nov;21(6):573-7. Review.

PMID: 17053406 [PubMed – indexed for MEDLINE]

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Reoperative off-pump coronary artery bypass grafting: current outcomes, concerns and controversies.

Raja SG, Amrani M.

Expert Rev Cardiovasc Ther. 2010 May;8(5):685-94. doi: 10.1586/erc.10.14. Review.

PMID: 20450302 [PubMed – indexed for MEDLINE]

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Off-pump versus on-pump coronary artery bypass grafting.

Halkos ME, Puskas JD.

Surg Clin North Am. 2009 Aug;89(4):913-22, ix. doi: 10.1016/j.suc.2009.06.015. Review.

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Myocardial revascularization for the elderly: current options, role of off-pump coronary artery bypass grafting and outcomes.

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Current status of off-pump coronary artery bypass surgery.

Raja SG, Dreyfus GD.

Asian Cardiovasc Thorac Ann. 2008 Apr;16(2):164-78. Review.

PMID: 18381881 [PubMed – indexed for MEDLINE]

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Cochrane Database Syst Rev. 2012 Mar 14;3:CD007224. doi: 10.1002/14651858.CD007224.pub2. Review.

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PMID: 22436497 [PubMed]

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Rationale, design and methodology for a Prospective Randomized Study of graft patency in Off-pump and On-pump MultI-vessel coronary artery bypasS Surgery (PROMISS) using multidetector computed tomography.

Uva MS, Matias F, Cavaco S, Magalhães MP.

Trials. 2008 Jul 17;9:44. doi: 10.1186/1745-6215-9-44.

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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

REFERENCES

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  2. Heart Disease and Stroke Statistics — 2011 Update. American Heart Association, 2011.
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  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.
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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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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

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

Larry H. Bernstein, MD, Writer
And
Aviva Lev-Ari, PhD, RN, Curator

 

This is a summary of several studies, mostly reviewing one decade of work at Texas Heart Institute, Houston, TX.

Seminal treatments of the evolving methods, leading to a recent review of options for

  • Survival comparison of CABD vs PCI
  • Mitral valve repair or mitral valve replacement for the treatment of ischemic mitral regurgitation. This might further consolidate a series of articles in these chapters.

SOURCES

1. Bypass, Angioplasty Similar in Survival 10 Years After Heart Procedures, Survival Rates Differ Little. K Doheny. WebMD Health News   Oct. 15, 2007
3. Will Stent Revascularization Replace Coronary Artery Bypass Grafting? JM Wilson Tex Heart Inst J. 2012; 39(6): 856–859
4. Coronary Artery Bypass Surgery versus Coronary Stenting. Risk-Adjusted Survival Rates in 5,619 Patients. RP Villlareal,V-V Lee, MA Elayda, JM Wilson.  Tex Heart Inst J. 2002; 29(1): 3–9.
5. Should all ischemic mitral regurgitation be repaired? When should we replace?  DJ LaPar, IL Kron. Curr Opin Cardiol. 2011 March; 26(2): 113–117
6. Hybrid Cath Lab Combines Nonsurgical, Surgical Treatments

Bypass, Angioplasty Similar in Survival 10 Years After Heart Procedures

The survival rates 10 years after coronary artery bypass surgery and angioplasty are similar, according to a new analysis of nearly 10,000 heart patients. Five years after the procedures, 90.7% of the bypass patients and 89.7% of the angioplasty patients were still alive, says  Mark A. Hlatky, MD, senior author of the analysis and a professor of health research and policy and professor of medicine at Stanford University School of Medicine in Palo Alto.

Hlatky and colleagues stress that their analysis only applies to a select group of heart patients: those for whom either procedure would be considered a reasonable choice. For patients who are eligible for either heart intervention, “either is feasible,” Hlatky tells WebMD. The report is released early online and will be published in the Nov. 20 issue of the Annals of Internal Medicine.

CABG vs. Angioplasty

The researchers evaluated the results of 23 clinical trials in which 5,019 patients (average age 61 years; 73% men) were randomly assigned to get angioplasty with or without stents (PCI), and 4,944 were assigned to get coronary artery bypass graft surgery (CABG) In angioplasty, interventional cardiologists push a balloon-like device into the coronary arteries and inflate the balloon to widen the vessel. An expandable wire mesh tube called a stent may be inserted to keep the vessel open. Some stents are coated with drugs meant to help prevent the artery from clogging up. In 2005, about 645,000 angioplasty procedures were done in the U.S. In bypass surgery, cardiac surgeons harvest a segment of a healthy blood vessel from another part of the body and use it to bypass the clogged artery or arteries, rerouting the blood to improve blood flow to the heart. About 261,000 bypass procedures were done in the U.S. in 2005.

Findings

Besides similar survival rates overall, the researchers found no significant survival differences between the two procedures for patients with diabetes, although earlier research had seemed to favor bypass surgery. Similar numbers of patients suffered heart attacks within five years of the procedures. While 11.9 of those who got angioplasty had a heart attack within five years, 10.9% of those who got bypass did. Repeat procedures were more common in angioplasty patients. While 46.1% of angioplasty patients who didn’t get a stent needed repeat procedures, 40.1% of those who got a stent did. But just 9.8% of surgery patients needed another procedure.  The study didn’t include information on drug-coated stents.

Second Opinions

The new analysis is “very complete,” says Kim A. Eagle, MD, director of the Cardiovascular Center and Albion Walter Hewlett Professor of Internal Medicine at the University of Michigan, Ann Arbor. The study shows, he says, that if either procedure is considered appropriate for an individual patient, the decision can rest on patient attitudes and preferences. Patients preferences might be based on lower need to repeat in favor of surgery, or on avoidance of surgery in favor of angioplasty. But it is important to note, acoording to Curtis Hunter at Santa-Monica-UCLA, that the studies cover the least sick with heart disease, so the two procedures are shown to be equal in a very small subset of the patients.

Coronary Artery Bypass Surgery versus Coronary Stenting – Risk-Adjusted Survival Rates in 5,619 Patients  THIJ. 2002

We used the Texas Heart Institute Cardiovascular Research Database to retrospectively identify patients who had undergone their 1st revascularization procedure with coronary artery bypass surgery (CABG; n=2,826) or coronary stenting (n=2,793) between January 1995 and December 1999. Patients were classified into 8 anatomic groups according to the number of diseased vessels and presence or absence of proximal left anterior descending coronary artery disease. Mortality rates were adjusted with proportional hazards methods to correct for baseline differences in severity of disease and comorbidity.
We found that in-hospital mortality was significantly greater in patients undergoing CABG than in those undergoing stenting (3.6% vs 0.75%; adjusted OR 8.4; P <0.0001). At a mean 2.5-year follow-up, risk-adjusted survival was equivalent (CABG 91%, stenting 95%; adjusted OR 1.26; P = 0.06). When subgroups matched for severity of disease were compared, no differences in risk-adjusted survival were seen. A survival advantage of stenting was noted in 3 categories of patients: those >65 years of age (OR 1.33, P = 0.049), those with non-insulin-requiring diabetes (OR 2.06, P = 0.002), and those with any noncoronary vascular disease (OR 1.59, P = 0.009).
In this nonrandomized observational study, CABG had a higher periprocedural mortality rate than did percutaneous stenting. At 2.5 years, however, the survival advantage of stenting was no longer evident. These data suggest that there is no intermediate-term survival advantage of CABG over stenting in patients who have multivessel disease with lesions that can be treated percutaneously. (Tex Heart Inst J 2002;29:3–9)

Fig. 1 Adjusted and unadjusted survival rates in all patients treated with CABG or PCI-stenting
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/table/t3-2/?report=previmg

survival rates  of CABG or PCI-stenting

TABLE III. Multivariate Correlates of Intermediate-Term (2.5-Year) Mortality
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/table/t3-2/?report=previmg

Fig. 2 Adjusted odds ratios comparing the results of CABG and PCI-stenting in the 8 anatomic subgroups.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2FF2.jpg

Adjusted odds ratios comparing the results of CABG and PCI-stenting in the 8 anatomic subgroups

TABLE IV. Intermediate-Term (2.5-Year) Survival According to Treatment in Each of the 8 Anatomic Groups
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2TT4.jpg

Intermediate-Term (2.5-Year) Survival According to Treatment in Each of the 8 Anatomic Groups

Fig. 3 Adjusted odds ratios comparing the results of CABG and PCI-stenting in the various prespecified subsets.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC101260/bin/2FF3.gif

Adjusted odds ratios comparing the results of CABG and PCI-stenting in the various prespecified subsets.

Will Drug-Eluting Stents Replace Coronary Artery Bypass Surgery?

Abstract

Introduction
The growth of the PCI industry and the consequent decline in the number of patients referred for CABG has produced much speculation about the future role of each type of intervention. Because the new drug-eluting stents allow PCI to be performed with lower rates of early restenosis than do bare-metal stents or percutaneous transluminal coronary angioplasty (PTCA) alone, 2–8 some have predicted that surgical revascularization will soon be obsolete.

CABG vs Pharmaco-Therapy

Randomized clinical trials performed during the 1970s and early 1980s clearly established the advantages of CABG over medical therapy in patients with triple-vessel CAD, left main coronary artery stenosis, double-vessel CAD with proximal left anterior descending (LAD) coronary artery stenosis, or left ventricular dysfunction. Problems arose subsequently because of the limitations built into the trial so that the results were biased in favor of medical therapy.  These were:
  • stringent exclusion criteria that eliminated a large percentage of potential participants
  • left main CAD and an ejection fraction of less than 0.40, eliminated patients for whom CABG would have been beneficial
  • the high rate of crossover from the medical to the surgical groups

The numerous technical and technological advances made since these trials were completed limit the degree to which their results resemble those of the CAD treatments used today. The maximal medical therapy used during the trials did not routinely include lipid-lowering agents, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, clopidogrel, or some of the other drugs currently used for CAD. Nor did the CABG groups benefit from advances that were subsequently made in preoperative imaging, perfusion and myocardial protection, anesthesia, and perioperative and intensive care practices. CABG did not then include the use of left internal mammary artery (LIMA) grafts, much less other arterial conduits. Finally, PCIs, including balloon angioplasty and stenting, were not included in these trials.

CABG vs PTCA

Randomized trials comparing PTCA with CABG revealed dramatically higher re-intervention rates in the PTCA groups and better angina relief in the CABG groups, although there were no significant differences in death or myocardial infarction rates. The Duke database study. 9 showed better survival rates with PTCA than with CABG in patients with single-vessel CAD, whereas CABG produced better survival than did PTCA in patients with severe, triple-vessel CAD.
These results are not necessarily representative of the results obtainable today with PTCA and CABG, for several reasons.
1.  stents were not used in the PTCA patients in these trials
2.  operative mortality rates for the CABG groups were higher than the rates currently found in the Society of Thoracic Surgeons (STS) database
3.  the inclusion/exclusion criteria of these studies eliminated a high percentage of those patients who might have benefited more from CABG than from PTCA

CABG vs Stents

The introduction of coronary artery stenting resulted in better outcomes than those produced by balloon angioplasty or by other adjuncts, including rotational atherectomy, brachytherapy, and laser angioplasty.  Since then, stent designs and delivery techniques have advanced considerably. The use of coronary stents has greatly decreased the necessity of emergent CABG for technical failure of PCI and for dissection or rupture of coronary arteries during PCI. Another major advance in the application of PCI is the use of the antiplatelet agent clopidogrel in addition to aspirin after PCI, as well as the use of glycoprotein (GP) IIb/IIIa receptor inhibitors during the procedure. These adjuncts have significantly reduced the incidence of acute and subacute thrombosis after PTCA with stenting.
Randomized trials comparing PTCA plus stenting with PTCA alone have shown that stenting significantly reduces rates of restenosis and re-intervention, as well as the frequency of emergent CABG.  On the other hand, randomized trials of stenting versus surgery have produced less conclusive results regarding the mid-term survival and freedom from adverse events.  For example, the Stent or Surgery (SOS) trial reported a greater need for repeat revascularization in the stent group (21%) than in the CABG group (6%) and a survival advantage in the CABG group (hazard ratio, 2.91; 95% CI, 1.29–6.53; P = 0.01) during the 3-year follow-up period. Additionally, angina and the use of anti-angina medications were less common in the CABG group at 1-year follow-up.
The ARTS and ERACI trials also reported an increased need for revascularization in the stent groups but did not show a survival advantage in the CABG groups. This was due in part to a higher operative mortality rate in the CABG group than reported in the STS database. Like the PCI versus CABG trials mentioned previously, these randomized trials involved a select group of patients with relatively low expected mortality rates and relatively high expected technical success with PCI.
Observational data in retrospective analyses of large patient databases comparing CABG with PCI plus stenting does indicate that, because of the greater invasiveness of surgical revascularization, CABG produces greater operative mortality than does PCI. However, in patients with multivessel CAD, the risk-adjusted survival rates at 2.5 years of follow-up are no better for PCI than for CABG, and 3 recent risk-adjusted observational studies showed that the CABG patients had a significant survival advantage at 3- to 8-year follow-up.   The CABG patients had significantly more preoperative risk factors than did the PCI patients in each study, so that unadjusted, the CABG groups in each study included significantly more patients with triple-vessel disease and fewer patients with double-vessel disease than did the PCI groups. Again, we have a moving target with recent advances in both surgery and PCI technology.

Disadvantages of Stenting

The Achilles’ heel of PCI is restenosis and the need for repeat revascularization. Stents have decreased the rate of acute and subacute  periprocedural thrombosis. The newer, drug-eluting stents (DESs) have improved in-stent restenosis rates, especially in the carefully selected patient populations studied in the early DES trials. In the RAVEL trial, the early reports of zero in-stent restenosis compared favorably with the 27% in-stent restenosis rates in the bare-metal stent control group at 6-month follow-up. However, the RAVEL trial excluded patients with lesions longer than 18 mm, ostial targets, calcified or thrombosed targets, or target arteries less than 2.5 mm in diameter.
The media frenzy that followed the release of these findings created a public demand for these new “miracle” stents that apparently did not re-occlude. Stories of CAD patients refusing conventional PCI and CABG —instead, adding their names to the list of patients waiting for U.S. Food and Drug Administration (FDA) approval of DESs—appeared to change the practice patterns of cardiologists and cardiac surgeons overnight.  And then there were the calls for class-action lawsuits and recall of various DES models. After the FDA approved the Cordis Cypher™ DES (Cordis Corporation, a Johnson & Johnson company; Miami Lakes, Fla), a few reports of subacute thrombosis and hypersensitivity reactions prompted the FDA to release a public health notification on 29 October 2003.
The SIRIUS trial had slightly less strict exclusion criteria than did the RAVEL trial, admitting patients with target lesions 2.5 to 3.5 mm in diameter and 15 to 30 mm long, as well as patients with diabetes mellitus (who constituted 26% of the total group).  The SIRIUS trial also differed from the RAVEL trial in that the reported end-point was in-segment restenosis, rather than in-stent restenosis. The results showed a significant advantage of DESs over bare-metal stents for preventing in-segment restenosis (9.2% vs 32.3%) and target failures (10.5% vs 19.5%), but major adverse cardiac events were more frequent in the DES group than in the bare-metal stent group (3.7% vs 1.0%). Interestingly, the 6-month restenosis rates of the bare-metal stents in the RAVEL and SIRIUS control groups were much higher than the 19% 12-month restenosis rate associated with bare-metal stents in an earlier study comparing bare-metal stents with PTCA. In fact, the restenosis rates in the RAVEL and SIRIUS control groups more closely resembled the 40% restenosis rate reported for the PTCA control group in the earlier study.
The practical advantages of DESs over bare-metal stents are evident; nonetheless, we still do not have sufficient mid-term or long-term clinical data to argue that PTCA with DESs is preferable to CABG in “real-world” patients who require revascularization. Although DESs will likely provide better outcomes than bare-metal stents for many patients for whom stenting is indicated, a general extrapolation of existing data to justify the use of DESs in patients for whom CABG is currently indicated is unknown, perhaps undeterminable because the lesion and patient characteristics that lead to the failure of PCI are multifactorial, and the size of the population with lesions having unfavorable characteristics , such as,
  • longer
  • total occlusion
  • branch
  • small-diameter
  • calcified
  • multiple
  • left main
  • ostial, and
  • diffuse lesions
are being treated with PCI more often, as well as diabetics, multiple lesions, and patients with multiple comorbidities.

Advantages of CABG

Over the last 4 decades, surgical coronary artery revascularization techniques and technology have advanced significantly. As a result, despite an increasingly older and sicker patient population, CABG outcomes continue to improve. Observed operative mortality rates have decreased because advances in preoperative evaluation, including more precise coronary artery and myocardial imaging and diagnostic techniques, have allowed more appropriate patient selection and surgical planning. In addition, preoperative, intraoperative, and postoperative monitoring and therapeutic interventions have made CABG safer, even for critically ill and high-risk patients. Improvements in cardiopulmonary perfusion and careful myocardial protection, as well as the use of off-pump and on-pump beating- heart techniques in selected patients, have also decreased perioperative morbidity and mortality rates.

LIMA-to-LAD Long-Term Patency

The long-term benefits of CABG with regard to survival and quality of life are dependent on prolonged graft patency. The LIMA-to-LAD bypass, which is now performed in more than 90% of CABG procedures, shows excellent patency in 10- to 20-year angiographic follow-up studies, setting the gold standard with which other revascularization strategies should be compared. Tatoulis et al. reported that LIMA-to-LAD grafts had a 97.1% patency rate in patients who underwent angiography for cardiac symptoms. Those authors also found high patency rates at 5-year (98%), 10-year (95%), and 15-year (88%) follow-up. However, there are not yet long-term data on bare-metal stents or DESs, and by the time 10- or 20-year data are available, DESs probably will have been replaced by a newer, more advanced technology.
Because of the reported success of the LIMA-to-LAD bypass, other types of arterial conduits are also being used much more frequently. Conduit selection has become an area of great interest to cardiac surgeons, and conduit studies are expanding our understanding of the mechanisms of graft failure and ways to improve bypass graft patency. For example, studies have shown that patients who undergo CABG with both LIMA and right internal mammary artery (RIMA) conduits have better results than those who undergo CABG with one IMA and one or more saphenous vein grafts.

Techniques to Improve Conduit Patency

To maximize the odds of long-term graft patency, surgeons carefully harvest the graft as a pedicled or skeletonized conduit using “no touch” techniques. Using careful anastomotic technique to avoid excessive turbulence at the anastomosis site will prolong graft patency, and the quality of the conduit is crucial. Long-term graft patency depends not only on the conduit chosen but also on the target artery and the degree of stenosis proximal to the anastomosis. Maintaining flow patterns in the native artery, including residual flow (that is, competitive flow) and outflow, is important to avoid stasis in the graft, turbulence at the anastomosis, and vasospasm, especially in arterial conduits. Studies have shown an inverse relationship between the degree of proximal stenosis and graft patency. Targeting the LAD produces the highest patency rates. The characteristics of the target artery also determine graft patency, including –
1. the diameter of the target artery,
2. the presence or absence of diffuse disease within the artery,
3. whether or not the artery requires endarterectomy
Surgeons can avoid atheroembolic events by handling the aorta carefully or not at all. They can also improve safety by
1. using aggressive myocardial protection techniques;
2. avoiding the induction of inflammatory mediators; and
3. carefully controlling
  • blood pressure,
  • body temperature, and
  • electrolyte and glucose levels.
Although there have been major innovations that have enabled surgeons to perform cardiac surgery (including CABG) less invasively, minimally invasive surgical procedures are useful only if they are at least as efficacious as conventional surgery. New technology is being developed to enhance the evolving field of minimally invasive coronary bypass surgery.

Hybrid Coronary Revascularization

As PCI technology improves and techniques of LIMA-to-LAD grafting become less invasive, hybrid coronary revascularization is becoming a distinct possibility. For example, a minimally invasive, off-pump, direct LIMA-to-LAD anastomosis can be combined with DES placement in a focal mid-right-coronary-artery lesion in a patient with complex proximal LAD lesions. Hybrid coronary revascularization procedures are currently being performed, with promising early results. A few centers now have hybrid operating rooms with cardiac surgical and coronary angiographic capabilities that make it possible to perform simultaneous hybrid coronary revascularizations.

Although coronary artery bypass grafting (CABG) remains the treatment of choice for certain types of coronary artery disease (CAD), percutaneous coronary intervention (PCI)—particularly coronary angioplasty with stenting—has become the most popular nonmedical treatment approach to CAD. Some have speculated that, with the advent of drug-eluting stents (DESs), PCI will replace CABG entirely. However, the complete disappearance of CABG is both unlikely and unwarranted, for several reasons. Published randomized trials of CABG, PCI, and medical approaches to CAD compared only highly selected subgroups of patients because of strict exclusion criteria that often favored the PCI cohorts. Therefore, their results do not constitute sufficient evidence for the superiority of PCI over CABG in all CAD patients requiring revascularization. As PCI indications broaden to include more complex lesions and more high-risk patients, outcomes will not remain as favorable. In addition, although PCI is less invasive than surgery, CABG offers more complete revascularization and better freedom from repeat revascularization. Furthermore, no long-term patency data on DESs yet exist, whereas excellent 10- and 20-year patency rates have been reported for the left internal mammary artery-to-left anterior descending artery graft used in most CABG procedures. While PCI has been changing, CABG has not been stagnant; recently, advances in many aspects of the CABG procedure have improved short- and long-term outcomes in CABG patients. Both CABG and PCI technologies will continue to advance, not necessarily exclusive of one another, but no data yet exist to suggest that DESs will render CABG obsolete any time soon. 

Will Stent Revascularization Replace Coronary Artery Bypass Grafting?

When we discuss revascularization outcomes, we are talking about 3 major endpoints: death, myocardial infarction, and symptom control. With respect to death, we know that revascularization benefits patients who have severe multivessel disease and left ventricular dysfunction or other physiologic indicators of high risk. 2-vessel disease with proximal left anterior descending coronary artery (LAD) stenosis has been accepted as an indication for revascularization, even though the supporting data come from a small subgroup in a single trial. There has been no success in proving that endovascular treatment has a positive impact on stable CAD, but it is relevant because we leave the native arteries relatively intact. Attempts to improve graft performance beyond the relatively spectacular performance of the pedicled internal mammary artery (IMA) graft to the LAD have been disappointing.

Fig. 1 Graph of graft patency shows deterioration rates over 10 years and the comparative superiority of using the internal mammary artery (IMA) instead of the saphenous vein (SVG).http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25FF1.gif

graft patency of IMA vs SVG

Percutaneous Transluminal Coronary Angioplasty

When angioplasty was introduced, the hope was for a method of revascularization that would rival coronary artery bypass grafting. However, the results were mixed. Angioplasty worked well in patients with no major risk factors, such as diabetes mellitus, but failed miserably in diabetic patients. In fact, the Bypass Angioplasty Revascularization Investigation (BARI)  taught us this: if revascularization is needed, regardless of physiologic markers of high risk, the use of percutaneous coronary intervention (PCI) is potentially harmful in comparison with an IMA bypass for the LAD.

Stents and Short-Term Outcomes

The use of stents drastically reduced the probability of emergent surgery after attempted; however, the probability of new lesion formation or restenosis after intervention did not decrease.

Fig. 2 Diagrams  show the calculated success (after percutaneous revascularization) of A) percutaneous transluminal coronary angioplasty (PTCA), and B) bare-metal and C) drug-eluting stenting in patients with 3-vessel coronary artery disease (CAD).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25FF2.gif

At the same time, surgeons got better. Myocardial preservation techniques improved, and the use of the pedicled IMA graft changed the game. As a result, successful revascularization, meaning long-term success, became the domain of the surgeon. We at the Texas Heart Institute/St. Luke’s Episcopal Hospital (THI/SLEH) examined our long-term outcomes after stenting or surgery, and we initially reported that stenting was just as beneficial as surgery. This was in accord with the results of several trials: whenever placing a stent was feasible, stent therapy and surgery had the same outcome.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25TT1.jpg

success after PTCA vs bare-metal and drug-eluting stents

Stents and Long-Term Outcomes

Later, when we looked at longer-term follow-up data and the effects of multiple procedures, this picture began to change. Stented patients underwent more procedures. When the risk of one surgical procedure was compared with that of multiple endovascular procedures, the outcomes became more similar, especially in patients with bifurcation lesions or lesions with severe calcification. Drug-eluting stents, with their promise of no restenosis, substantially increased interventional cardiologists’ reach, but not their grasp. In patients with multivessel disease and high-risk lesions, DES placement was almost as risky as surgery and did not yield the same long-term benefit.

Nevertheless, we found locally that the introduction of the DES, with its lower risk of restenosis, was treated as a blessing to proceed with stenting (Table I). This did not follow the data, but cardiologists continued anyway, given the promise of less restenosis. Early risk was discounted, glycoprotein IIb/IIIa inhibitor use declined overnight, and the rate of endovascular procedural complications rose to meet that of surgery without the promise of an IMA graft in our future.

Table I. Independent Predictors of 30-Day Major Adverse Cardiac Events and 3-Year Survival after Drug-Eluting Stent Placement
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528239/bin/25TT1.jpg

Comparing Stenting and Surgery

For decades, methods have been sought to quantify lesion complexity in order to compare the early and late risks associated with stenting versus surgery. Although no perfect system has been devised, the SYNTAX was an important step forward. The SYNTAX score is a simple, computer-based tool for evaluating the risk of complications or failure after PCI. And there are other tools for estimating the same complications after surgery. These estimates enable cardiologists to give patients objective advice regarding the revascularization method that has the best short- and long-term probability of success.
In the patient with non-life-threatening disease (that is, not left main or severe multivessel CAD with left ventricular dysfunction or severely impaired function), stent revascularization has become a reasonable, although not ideal, alternative to surgical revascularization. However, this is true only if stenting is confined to patients whose anatomy and physiology are suited to it—considerations that are well quantified in the SYNTAX score. Whenever questions arise as to the most appropriate therapy, the SYNTAX score should be weighed against clinical characteristics that affect surgical risk. This will guide discussions between the cardiologist, cardiovascular surgeon, patient, and treating physician.
I think that our THI risk is more useful than the other available scores. It uses simple clinical data and can be easily calibrated to the geographic location of its use. Other scores require data that might not be available at the time of clinical decision-making or at all—making such predictions hazardous, at best.

Conclusion

With regard to the chosen mode of revascularization, it is perhaps safe to say that the decision goes beyond the individual physician and must become collective. When a patient has multivessel disease, a reasoned approach must be taken, using these predictive tools and considering the patient’s wishes. Treatment decisions should include all interested parties: the patient, cardiologist, cardiovascular surgeon, and anesthesiologist. The time of ad hoc angioplasty for the patient with multivessel CAD has passed.

Should all ischemic mitral regurgitation be repaired? When should we replace?   Curr Opin Cardiol. 2011

Abstract

Purpose of review

Ischemic mitral regurgitation (IMR) is a major source of morbidity and mortality. Although mitral valve repair has become recently popularized for the treatment of IMR, select patients may derive benefits from replacement. The purpose of this review is to describe current surgical options for IMR and to discuss when mitral valve replacement (MVR) may be favored over mitral valve repair.

Recent findings

Current surgical options for the treatment of IMR include surgical revascularization alone, mitral valve repair, or MVR. Although surgical revascularization alone may benefit patients with mild–moderate IMR, most surgeons advocate the performance of revascularization in combination with either mitral valve repair or replacement. In the current era, mitral valve repair has proven to offer improved short-term and long-term survival, decreased valve-related morbidity, and improved left ventricular function compared with MVR. However, MVR should be considered for high-risk patients and those with specific underlying mechanisms of IMR.

Summary

In the absence of level one evidence, mitral valve repair offers an effective and durable surgical approach to the treatment of mitral insufficiency and remains the operation of choice for IMR. MVR, however, is preferred for select patients. Future randomized, prospective clinical trials are needed to directly compare these surgical techniques.

Introduction

Ischemic mitral regurgitation (IMR) describes insufficiency of the mitral valve in the setting of myocardial ischemia, resulting from coronary artery disease. Although IMR may present in the acute setting, usually as a papillary rupture (Carpentier type II), it is usually a consequence of chronic myocardial ischemia that typically presents weeks following a complete infarction. IMR describes mitral insufficiency in the absence of degenerative (structural) mitral valve disease. The underlying pathophysiologic mechanisms of IMR are often complex, resulting from several different structural changes involving left ventricular geometry, the mitral annulus, and the valvular/subvalvular apparatus. Although changes to any one component may result in detectable mitral valve insufficiency, moderate-to-severe IMR requiring surgical correction often involves the complex interplay of several co-existent anatomic changes. These underlying mechanisms result in clinically significant valve incompetence due to the combined effects of decreased ventricular function and restricted motion of the valve itself due to tethering.
IMR is a major source of patient morbidity and mortality. Although the frequency of IMR differs based upon imaging modality, estimates have suggested that nearly 20–30% of patients experience mitral insufficiency following myocardial infarction. Furthermore, its intimate association with heart failure and poor outcomes for suboptimal medical management further complicates the management of clinically significant IMR. Recent evidence suggests that moderate or severe mitral regurgitation may be associated with a three-fold increase in the adjusted risk of heart failure and a 1.6-fold increase in risk-adjusted mortality at 5-year follow-up. In addition, unfavorable patient profiles and co-existing comorbid disease, including renal failure, chronic obstructive pulmonary disease, diabetes, and impaired left ventricular function, further complicate the clinical picture for those with IMR. Consequently, surgical correction of this condition is often required.
The purpose of this review is to analyze published results for the surgical correction of IMR and to provide current opinion regarding the selection of mitral valve procedure in the setting of myocardial ischemia. Herein, we review current surgical options for IMR and discuss when MVR may be favored over mitral valve repair.

Surgical options for ischemic mitral regurgitation: surgical revascularization alone

Surgical revascularization alone with CABG may be beneficial for some patients. Although CABG alone may be performed in cases of mild-to-moderate IMR, for the treatment of severe IMR, evidence supports performance of CABG with a mitral valve. In fact, a lack of evidence exists to support the performance of CABG alone for severe IMR. In one retrospective review of propensity-matched cohorts, Diodato et al. suggested that addition of a mitral valve procedure to patients undergoing CABG for moderately severe to severe IMR did not increase mortality or improve survival over the performance of CABG alone. This study, however, was limited by small sample sizes (51 CABG + mitral valve repair vs. 51 CABG alone) and 3-year follow-up. To the contrary, substantial evidence exists to support the performance of surgical revascularization alone in cases of mild-to-moderate IMR.
A study by Aklog et al. investigated the role of CABG alone in the correction of moderate IMR. In their series of 136 patients with moderate IMR, they demonstrated that performance of revascularization alone conferred improvement of mitral regurgitation in 51% of patients with complete resolution in an additional 9%. Despite these results, 40% of patients remained with 3–4+ mitral regurgitation, leading the authors to conclude that CABG alone may not be the optimal therapy for most patients and suggest that concomitant mitral annuloplasty may improve results. Other series similarly suggest that complete resolution of functional IMR is uncommon following revascularization alone. Despite the presence of residual mitral regurgitation following revascularization, the impact of performance of CABG without a valve procedure on long-term survival remains ill defined. Currently, on-going prospective evaluation may help to define the potential role of revascularization alone for patients with moderate IMR. Until the completion of these trials, however, evidence supports the performance of surgical revascularization combined with a mitral valve procedure for moderate-to-severe mitral regurgitation.

Surgical revascularization with a mitral valve procedure

The majority of patients with moderate-to-severe IMR require surgical revascularization with a concomitant mitral valve procedure (MVR or mitral valve repair). Historically, these procedures have been associated with high morbidity and mortality as well as poor long-term. However, improved surgical techniques and postoperative management have improved contemporary outcomes. Those favoring mitral valve repair promote its beneficial effects on survival, preserved ventricular function, and the avoidance of long-term anticoagulation, whereas those favoring MVR argue that it ensures long-term freedom from recurrent mitral insufficiency.

Mitral valve replacement vs. mitral valve repair

The use of MVR for IMR eliminates the possibility of recurrent IMR. In addition, previous literature suggests improvements in surgical technique for MVR 29–32. For patients with IMR, MVR with preservation of the subvalvular apparatus using a chordal sparing technique has been shown to be beneficial 33. David and Ho 33 demonstrated a significant survival benefit for patients undergoing MVR with preservation of chordae tendineae (89%) compared with complete excision of the mitral valves (59%) in a cohort of 51 patients with IMR. In addition, Cohn et al. suggested disproportionate survival benefits favoring MVR in a cohort of 150 patients with both functional and structural IMR, concluding that survival following performance of mitral valve procedures for IMR was more dependent on underlying pathophysiology rather than surgical technique. More recently, series have suggested equivalent results for the MVR and mitral valve repair. Mantovani et al. report that prosthetic MVR and mitral valve repair offer very similar results for chronic IMR, demonstrating similar operative mortality and 5-year actuarial survival for both techniques. In a similar report, Magne et al.•• compared short-term and long-term outcomes for 370 patients undergoing mitral valve repair (n = 186) and MVR (n = 184) for IMR. Although operative mortality was lower for mitral valve repair compared with MVR (9.7 vs. 17.4%, P = 0.03), 6-year survival was similar for both operations (73 ± 4 vs. 67 ± 4%, P = 0.17). Type of procedure was also not an independent predictor of mortality following risk adjustment. As a result, the authors suggest that mitral valve repair is not superior to MVR for patients with IMR.
In contrast, other series favor the performance of mitral valve repair for functional IMR. Although several repair techniques exist, restrictive annuloplasty remains the most commonly performed operation 37• and has been shown to be beneficial in both functional and chronic IMR 38•. The purported benefits of improved survival, decreased valve-related morbidity, and improved left ventricular function have been previously established, and several series have reported lower hospital mortality with mitral valve repair compared with MVR.
The Cleveland Clinic published a landmark review of 482 patients undergoing mitral valve procedures for IMR to study the influence of mitral valve procedure type on survival 1. In this series, propensity-matched cohorts were compared: mitral valve repair (n = 397) vs. MVR (n = 85). Concomitant CABG was performed in 95% of operations, and annuloplasty for repair occurred in 98% of cases. After matching, patients were risk stratified into five quintiles. Group 1 represented the highest-risk patients with higher degrees of heart failure and emergent operations, and group 5 represented the lowest-risk patients. Subsequent survival analysis revealed that overall 5-year survival was poor for patients with IMR (58% mitral valve repair vs. 36% MVR, P = 0.08). Moreover, within matched quintiles, the highest-risk patients (quintile 1) had the worst survival, but survival was similar (P = 0.4) despite mitral valve procedure type. In contrast, survival favored mitral valve repair over replacement for quintiles III–V (P = 0.003).
In the absence of published randomized trials, two recently published meta-analyses provide more robust comparisons of the influence of surgical mitral valve repair or replacement. Shuhaiber and Anderson  compared outcomes of 29 studies, including over 10 000 patients. Study groups were stratified based upon mitral valve etiology into ischemic, degenerative/myxomatous, rheumatic, and mixed groups. Summary analyses indicated worse overall survival for MVR (early mortality odds ratio = 2.24 and total survival hazard ratio = 1.58) compared with repair. Mitral valve repair was also associated with lower rates of thromboembolism. Moreover, a nonsignificant trend toward lower 30-day mortality favored mitral valve repair for those with IMR. The most recent meta-analysis to date compared short-term and long-term survival of mitral valve repair vs. replacement specifically for IMR ••. In this analysis, nine studies were included based upon stringent exclusion criteria to ensure direct comparisons of survival for mitral valve procedures exclusively performed for IMR. Interestingly, in this series, although patients undergoing MVR were older, those undergoing repair often had higher rates of hypertension and diabetes with lower ejection fractions. Further, the proportion of patients with severe ventricular dysfunction was similar between procedure groups. These findings conflict with a common assumption that an inherent selection bias exists within published studies for the performance of mitral valve repair in healthier patients. Nevertheless, MVR was associated with worse short-term mortality (odds ratio = 2.667) and long-term mortality (hazard ratio = 1.35) compared with mitral valve repair, and the authors advocate that choice in mitral procedure should be based upon individual patient profile.

When not to repair ischemic mitral regurgitation?

Within the context of published literature and current dogma among practicing surgeons, the fundamental question of when not to repair an ischemic mitral valve remains. For several years, accumulated evidence supports the performance of mitral valve repair over replacement for the surgical treatment of functional IMR. The aforementioned benefits of repair include improved long-term survival, durability and efficacy, improved ventricular function, and avoidance of chronic anticoagulation therapy. Nevertheless, MVR still plays a select role in the treatment of IMR.
With respect to the performance of MVR, the use of bioprosthetic valves and the avoidance of mechanical valve replacement are preferred. This choice is largely driven by the avoidance of complications due to long-term anticoagulation use as well as by the belief that it is unlikely that the majority of patients requiring MVR are likely to encounter bioprosthetic deterioration in their lifetime. In addition, MVR with techniques to preserve the subvalvular apparatus should be performed when possible.

Summary

Undoubtedly, the debate regarding when to perform repair or replacement for IMR remains unsettled. In the recent era, mitral valve repair has proven efficacious and remains the preferred surgical strategy for most cases of IMR. MVR should be considered for severe tethering, complex or uncertain mechanisms of mitral insufficiency, regurgitation due to papillary muscle rupture, and perhaps for the sickest and highest-risk patients.
The present review was supported by Award Number 2T32HL007849-11A1 (D.J.L.) from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors.
Hybrid Cath Lab Combines Nonsurgical, Surgical Treatments  2008
A new cardiac treatment facility that couples the benefits of interventional cardiology with cardiothoracic surgery for critically ill newborns, children and adults has opened at Rush University Medical Center, Chicago.  Toshiba’s new biplane hybrid cardiac suite, which is one of only three facilities of its kind in the U.S., is equipped with the latest in continuous, real-time imaging technology and radio frequency identification (RFID) technology which allows “all-in-one-room” care. The suite allows collaboration between the surgeon and interventional cardiologist on complex heart problems. For example, fixing a very large hole in the heart can be done by inserting a catheter through a small incision in the chest rather than relying on major surgery to open the chest to reach the heart. “Now, interventional cardiologists and cardiothoracic surgeons working together in this suite will reduce the amount of time required to correct complex heart problems and reduce the emotional and physical stress placed on a patient and their family – which translates into less pain, less scarring and a faster recovery time,” Ziyad Hijazi, M.D., director of the new Rush Center for Congenital and Structural Heart Disease. The hybrid suite is equipped with the latest technology for minimally invasive interventional cardiology that involves the use of a catheter and an image-guidance system to thread tiny instruments through blood vessels to repair the heart. Through these special catheters, physicians at Rush can implant stents, artificial heart valves and insert patches for holes in the heart. In many complex cardiac cases, patients who would otherwise have no other option but to undergo open-heart bypass surgery can now have minimally invasive procedures that would otherwise not be available to them. “We can now communicate with colleagues and obtain their expertise in real time for very complex situations,” said Dr. Hijazi. “If physicians decide another procedure is needed, even surgery, the suite can be converted into an operating room and the surgical team can be assembled in the new suite ”Patients at Rush will stay in one place in the new hybrid cardiac suite where all the imaging technology and implantable devices that might be needed are stored and located. The additional ability it gives us to provide surgical treatments allows us to provide the most comprehensive care in the most sensitive manner for patients with often extremely fragile conditions.”  The new hybrid cardiac catheterization suite has the most advanced imaging technologies and can still get a precise, optimal image of any region of the heart regardless of the size or complexity of congenital heart disease. The imaging system also features eight-inch cardiac flat panel detectors designed to deliver distortion-free images. The suite also includes intravascular ultrasound machines, which takes real-time images to allow physicians to see the progress of the procedure taking place inside the patient’s body. A high-tech, automated clinical resource management system located in the suite stores and tracks the medication, surgical tools, medical devices, and implantable devices and supplies using the latest RFID enabled technology.

Hybrid Cath Lab/ORs Are the Way of the Future

Recent developments in cardiac surgery and interventional cardiology with new percutaneous alternatives for aneurysm repair, valve replacements, shunt closure devices and aortic arch reconstruction have led to the creation of integrated, hybrid cath lab/operating rooms (OR) that allow both surgical and intravascular procedures. These rooms offer both surgical equipment and high-end angiographic equipment. Creating such rooms requires special planning and design from both surgical and interventional cardiologists working closely together. Cath labs have high-quality fluoroscopy equipment, but generally are smaller rooms and lack the sterile requirements and equipment needed for surgical procedures. ORs tend to use lower quality mobile C-arms, which are not ideal for interventional procedures. The hybrids aim to provide the best of both worlds. The trend toward hybrid labs has been reinforced by digital angiography manufacturers partnering with surgical equipment companies to create easy-to-integrate hybrid room solutions with coordinated installation. Philips partners with both Skytron and Steris. Toshiba partners with MAQUET. GE Healthcare, Siemens and Toshiba also offer hybrid installations. Philips said while some hospitals want to combine interventional procedures with minimally invasive surgeries, they also want a properly equipped room in case emergency surgery is needed.
Philips said hybrids also allow hospitals with lower PCI numbers to get a bigger bang for their buck by allowing the same room to serve the needs of surgeons. Penn Presbyterian Medical Center in Philadelphia, PA, created a hybrid lab with help from Siemens, which opened in November. Wilson Szeto, M.D., cardio-thoracic surgeon, and William Matthai, M.D., interventionalist, both from Penn Presbyterian said hybrid labs are ideally suited for procedures that require both percutaneous and surgical interventions, percutaneous valve replacements, deploying percutaneous septal occluders or installing aortic stent grafts. Interventionalists can also be called in after cardiac surgery to perform a completion angiography.

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56•. Goland S, Czer LS, Siegel RJ, et al. Coronary revascularization alone or with mitral valve repair: outcomes in patients with moderate ischemic mitral regurgitation. Tex Heart Inst J. 2009;36:416–424. This series documents current outcomes for the performance of CABG alone with/without concomitant mitral valve repair for ischemic mitral regurgitation. The authors report similar 5-year survival rates for both techniques; however, revascularization with repair resulted in significantly reduced mitral regurgitation grade, improved left ventricular function, and functional class compared with revascularization alone. This study provides an important comparison of these two techniques in the current surgical era. [PMC free article] [PubMed]
57••. Magne J, Girerd N, Senechal M, et al. Mitral repair versus replacement for ischemic mitral regurgitation: comparison of short-term and long-term survival. Circulation. 2009;120(11 Suppl):S104–S111. In this study, the authors compare postoperative outcomes for mitral valve repair and replacement for ischemic mitral regurgitation. Despite lower operative mortality following mitral valve repair, long-term survival was equivalent between surgical groups. This study adds important long-term comparisons of mitral valve procedures to accumulating data examining surgical treatments for ischemic mitral regurgitation. [PubMed]
58. Silberman S, Klutstein MW, Sabag T, et al. Repair of ischemic mitral regurgitation: comparison between flexible and rigid annuloplasty rings. Ann Thorac Surg. 2009;87:1721–1726. discussion 1726–1727. This study provides a contemporary comparison between the use of flexible and rigid annuloplasty rings for the surgical treatment of IMR. The authors report significantly improved clinical and hemodynamic results for rigid mitral annuloplasty rings compared with flexible rings. [PubMed]
59•. Tekumit H, Cenal AR, Uzun K, et al. Ring annuloplasty in chronic ischemic mitral regurgitation: encouraging early and midterm results. Tex Heart Inst J. 2009;36:287–292. This study reports early and midterm results for the use of flexible annuloplasty rings for the surgical treatment of chronic IMR. The authors demonstrate that use of flexible mitral valve annuloplasty conferred a reduction in left ventricular diameter with improved New York Heart Association functional class. This study reports current, encouraging results and provides a context for future investigations comparing flexible and rigid annuloplasty rings for chronic IMR. [PMC free article] [PubMed]
60. Shuhaiber J, Anderson RJ. Meta-analysis of clinical outcomes following surgical mitral valve repair or replacement. Eur J Cardiothorac Surg. 2007;31:267–275. [PubMed]
61••. Vassileva CM, Boley T, Markwell S, Hazelrigg S. Meta-analysis of short-term and long-term survival following repair versus replacement for ischemic mitral regurgitation. Eur J Cardiothorac Surg. 2010 [Epub ahead of print] This meta-analysis provides a comparison of nine published series specifically addressing the performance of mitral valve repair vs. replacement for IMR. The authors demonstrate worse short-term and long-term mortality for MVR. Their analysis offers an up-to-date and robust comparison of these two surgical techniques. [PubMed]

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Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Coronary Artery Disease (LMCAD)

Writer: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN

Significant, defined as a greater than 50 percent narrowing, left main coronary artery disease (LMCAD) is found in 4 to 6 percent of all patients who undergo coronary arteriography [1]. When present, it is associated with multivessel coronary artery disease (MVCAD) about 70 percent of the time [2,3].

Most patients are symptomatic and at high risk of cardiovascular events, since occlusion of this vessel compromises flow to at least 75 percent of the left ventricle, unless it is protected by collateral flow or a patent bypass graft to either the left anterior descending or circumflex artery. Studies performed before revascularization with coronary artery bypass graft surgery (CABG) became the standard of care revealed a poor prognosis for these patients, with three-year survival as low as 37 percent [4]. CABG, when directly compared to medical therapy, is associated with significantly better cardiovascular outcomes, including mortality [5].

Percutaneous coronary intervention (PCI) with stenting has generally been restricted to such patients considered inoperable or at high risk for CABG, or with prior CABG and at least one patent graft to the left anterior descending or circumflex artery (so-called “protected” left main disease). Graft patency is important in this setting in the event of acute or late closure after PCI. However, evidence is increasing to support the use of PCI with stenting in some cases. (See ‘PCI versus CABG’ below.)

Asymptomatic patients with left main lesions felt to not be hemodynamically significant should be managed with preventative therapies. Patients with anginal symptoms attributable to lesions elsewhere should be managed with therapies similar to those used in other patients with coronary artery disease. (See “Overview of the care of patients with stable ischemic heart disease”.)

This topic will discuss most aspects of the management of patients with LMCAD. The approach to patients with multivessel coronary artery disease without LMCAD is discussed elsewhere. (See “Bypass surgery versus percutaneous intervention in the management of stable angina pectoris: Recommendations”.)

http://www.uptodate.com/contents/management-of-left-main-coronary-artery-disease

 

Management of significant left main coronary disease before and after trans-apical transcatheter aortic valve replacement in a patient with severe and complex arterial disease.

Source

Columbia University Medical Center, New York, New York; Cardiovascular Research Foundation, New York, New York.

Abstract

We report the case of an 81-year-old woman with symptomatic severe aortic stenosis, extremely significant peripheral arterial disease, and obstructive coronary artery disease who underwent percutaneous coronary intervention via a transaxillary conduit immediately before a trans-apical transcatheter aortic valve replacement performed with a transfemoral device. After deployment of the transcatheter heart valve, there was a left main coronary obstruction and the patient required an emergent PCI. This multifaceted case clearly underlines the importance of a well functioning heart team including the interventional cardiologist, the cardiovascular surgeon, and the echocardiographer. © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.

This is an interesting surgical case presented by the Columbia University Cardiovascular Surgery team, illustrating the importance of combined team skills in the most difficult of cases.  It is part of a series on cardiovascular surgery.

Management of significant left main coronary disease before and after trans-apical transcatheter aortic valve replacement in a patient with severe and complex arterial disease.

Paradis JM, George I, and Kodali S
Catheterization and Cardiovascular Interventions  (2013)

Introduction

Transcatheter aortic valve replacement (TAVR) with the Edwards SAPIEN transcatheter heart valve (THV) (Edwards Lifesciences, Irvin, CA) has been shown to reduce mortality when compared to medical therapy alone for patients with symptomatic severe aortic stenosis deemed unsuitable for surgical aortic valve replacement due to multiple co-morbidities. The Edwards SAPIEN THV, sizes 23 and 26 mm, and the RetroFlex 3 transfemoral delivery system, have been recently approved by the US Food and Drug Administration (FDA) for commercial use outside of the PARTNER clinical trial for patients considered inoperable.  However, an alternative site needs to be selected for patients with peripheral arteries inadequate for transfemoral TAVR.  Although not fully validated, the transapical approach or the transaortic route using a balloon expandable THV,  appears to be appropriate for this specific purpose.  Significant coronary artery disease (CAD) is often found in patients with severe aortic stenosis. in > 50% of patients with aortic stenosis over 70 years of age and in > 65% of patients who are  over 80 years of age. There is no established guideline for managing significant CAD in the context of TAVR, including the appropriate revascularization strategy as well as the timing of interventions.

Case Report

An 81-year-old woman  presented with symptomatic severe aortic stenosis, extremely significant peripheral arterial disease, and obstructive coronary artery disease. She had a six-month history prior to admission of progressive exertional shortness of breath and fatigue, and a long history fo hypertension, hyperlipidemia, obesity, and severe peripheral vascular disease.  In 2003, she underwent a coronary artery bypass graft (CABG) surgery, with grafting of the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery, a saphenous vein graft (SVG) to the first obtuse marginal (OM) branch, and a SVG to the right coronary artery (RCA). Due to associated severe mitral regurgitation, a mitral valve ring annuloplasty was also performed. A transthoracic echocardiogram (TTE) revealed severe aortic stenosis with a peak gradient across the aortic valve of 63 mm Hg, a mean gradient of 39 mm Hg, and an aortic valve area of 0.8 cm2.  The left ventricular ejection fraction (LVEF) was 64% while the pulmonary artery systolic pressure was measured at 28 mm Hg.  Extreme calcification and tortuosity precluded the advancement of any wire, catheter, or sheath, contributing to two attempts at cardiac catheterization prior to transfer with a total occlusion of the distal abdominal aorta, at the level of the aorto-iliac bifurcation, and the left main, proximal LAD, proximal left circumflex, and the proximal RCA all had greater than 70% coronary lesions. In addition, ostial total occlusions were seen in both SVGs.
left main coronary artery
After transfer, a cardiac catheterization through the right radial artery was attempted without success due to calcification and tortuosity in the arterial bed.  An 80% distal left main lesion was clearly identified with a Judkins left 3.5 guiding catheter.  There was non-flow limiting coronary disease in the left circumflex and competitive retrograde flow seen in the LIMA graft, but they still were unable to cannulate the RCA and the SVGs. It was determined that the patient was inoperable, on grounds of her significant frailty, reoperative status and overall comorbid state (Society of Thoracic Surgeons (STS) risk score of 11%). Furthermore, due to the occlusion of the distal aorta, the patient was unsuitable for a TAVR via the transfemoral approach.
They chose to approach her PCI via a conduit on the right axillary artery and perform a concomitant TAVR from a trans-apical approach due to the serious limiting condition of the patient.  She underwent percutaneous coronary intervention via a transaxillary conduit immediately before a trans-apical transcatheter aortic valve replacement performed with a transfemoral device.  Excellent flow from the conduit was noted. A 7 French (Fr) sheath was connected to the end of the conduit, which was kept long to allow better maneuverability (Fig. 1). A Rosen wire was passed with some difficulty to the aortic root, and was switched to a stiff wire in an attempt to straighten the vessel.
PowerPoint Presentation
Fig. 1. Transaxillary conduit used during the procedure. A 7 French sheath was connected to an 8 mm dacron graft, which was previously sewn to the axillary artery.
After deployment of the transcatheter heart valve, there was a left main coronary obstruction and the patient required an emergent PCI.  This multifaceted case clearly underlines the importance of a well functioning heart team including the interventional cardiologist, the cardiovascular surgeon, and the echocardiographer. A Xience
V everolimus eluting stent 3.5 mm  18 mm was implanted starting 2 mm distal to the ostium of the left main, extending in the proximal portion of the left circumflex artery. After one post-dilatation with a non-compliant balloon, the final angiographic result was excellent.
They used a Retroflex 3 transfemoral delivery sheath to perform the trans-apical TAVR. They estimated the size and length of the ventricular cavity, and then placed markers on the delivery sheath (prior to insertion) indicating the appropriate length of sheath to remain outside the heart (Fig. 2).
PowerPoint Presentation
Fig. 2. Marker placed on the RetroFlex 3 transfemoral sheath to safely guide its insertion inside the left ventricular cavity during the trans-apical transcatheter aortic valve replacement.
A 23 mm Edwards SAPIEN valve was selected and deployed under fluoroscopic and transesophageal echocardiographic guidance. Immediately after deployment, turbulent flow was noted within the left main with the color Doppler on TEE, indicating a new obstruction of the left main, which a left coronary angiogram showed to be a severe proximal lesion.  Through the trans-axillary conduit, a  guiding catheter was laboriously brought in the ascending aorta and cannulated the left main artery which permitted a predilation and a stent insertion in the ostial portion of the left main.  She was discharged to a rehabilitation facility 7 days after the procedure.
On follow-up TTE, the LVEF was 55% without any significant wall motion abnormality. There was no aortic regurgitation, and the peak and mean gradients were 14.9 mm Hg and 8.0 mm Hg, respectively. The patient is still doing well more than 6 months after the procedure. She is now in NYHA class 2 and has not had any recurrent hospitalization for congestive heart failure.
Discussion
This report is a case of a complex percutaneous coronary intervention of the left main coronary artery via a right axillary conduit followed immediately by an off label commercial transapical TAVR using the Retro-Flex 3 trans-femoral introducer sheath, complicated finally by a new left main coronary obstruction mandating another PCI. It is the first description of a TAVR procedure preceded and followed by a left main trans-axillary PCI. The role of TEE (color Doppler) in the diagnosis of a very rare TAVR complication is also noteworthy. In a recent meta-analysis of 3,519 patients from 16 studies using the Valve Academic Research Consortium (VARC) definitions, the pooled estimate rate of coronary
obstruction following TAVR was only 0.7%. Obviously, the early recognition and treatment of this hazard is imperative.
The surgical management of this patient also warrants discussion. The hybrid surgical approach of accessing the axillary artery via a conduit provides numerous advantages:
(1) the ascending aorta, coronaries, and aortic valve are easily accessible;
(2) transition to cardiopulmonary bypass or extra-corporeal membrane oxygenation, if needed, is quick; and
(3) long-term morbidity is minimal for the patient when compared to aorto-iliac, aortic, or femoral conduits.
Finally, the heart team approach not only allowed the realization of a difficult coronary
stent implantation through an unusual transaxillary graft followed by a transapical TAVR in a patient with significant peripheral arterial disease, but also permitted the early  recognition and management of a potentially fatal left main obstruction. Considerations such as team-based care, close communication between the different specialties
involved and careful planning for outlining management of potential complications are therefore essential for the success of a TAVR program.

REFERENCES

 1. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597–1607.
2. Iung B. Interface between valve disease and ischaemic heart disease. Heart 2000;84:347–352.
3. Wenaweser P, Pilgrim T, Guerios E, Stortecky S, Huber C, Khattab AA, et al. Impact of coronary artery disease and percutaneous coronary intervention on outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.
EuroIntervention 2011;7:541–548.
4. Genereux P, Head SJ, Van Mieghem NM, Kodali S, Kirtane AJ, Xu K, et al. Clinical outcomes after transcatheter aortic valve replacement using valve academic research consortium definitions: A weighted meta-analysis of 3,519 patients from 16 studies.
J Am Coll Cardiol 2012;59:2317–2326.
Three coronary artery bypass grafts, a LIMA to...

Three coronary artery bypass grafts, a LIMA to LAD and two saphenous vein grafts – one to the right coronary artery (RCA) system and one to the obtuse marginal (OM) system. (Photo credit: Wikipedia)

heart with coronary arteries

heart with coronary arteries (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)

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

Investigational Devices: Edwards Sapien Transcatheter Aortic Valve Transapical Deployment

Aviva Lev-Ari, PhD, RN 6/6/2012

https://pharmaceuticalintelligence.com/2012/06/04/investigational-devices-edwards-sapien-transcatheter-heart-valve/

Lev-Ari, A. 2/12/2013 Clinical Trials on transcatheter aortic valve replacement (TAVR) to be conducted by American College of Cardiology and the Society of Thoracic Surgeons

https://pharmaceuticalintelligence.com/2013/02/12/american-college-of-cardiologys-and-the-society-of-thoracic-surgeons-entrance-into-clinical-trials-is-noteworthy-read-more-two-medical-societies-jump-into-clinical-trial-effort-for-tavr-tech-f/

Lev-Ari, A. 8/13/2012 Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents 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/

Lev-Ari, A. 7/18/2012 Percutaneous Endocardial Ablation of Scar-Related Ventricular Tachycardia

https://pharmaceuticalintelligence.com/2012/07/18/percutaneous-endocardial-ablation-of-scar-related-ventricular-tachycardia/

Lev-Ari, A. 6/22/2012 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)

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/

Lev-Ari, A. 6/19/2012 Executive Compensation and Comparator Group Definition in the Cardiac and Vascular Medical Devices Sector: A Bright Future for Edwards Lifesciences Corporation in the Transcatheter Heart Valve Replacement Market

https://pharmaceuticalintelligence.com/2012/06/19/executive-compensation-and-comparator-group-definition-in-the-cardiac-and-vascular-medical-devices-sector-a-bright-future-for-edwards-lifesciences-corporation-in-the-transcatheter-heart-valve-replace/

Lev-Ari, A. 6/22/2012 Global Supplier Strategy for Market Penetration & Partnership Options (Niche Suppliers vs. National Leaders) in the Massachusetts Cardiology & Vascular Surgery Tools and Devices Market for Cardiac Operating Rooms and Angioplasty Suites

https://pharmaceuticalintelligence.com/2012/06/22/global-supplier-strategy-for-market-penetration-partnership-options-niche-suppliers-vs-national-leaders-in-the-massachusetts-cardiology-vascular-surgery-tools-and-devices-market-for-car/

 We reported on the following Medical Devices News:

Lev-Ari A. 4/6/2012.  Investigational-devices-edwards-sapien-transcatheter-heart-valve. 

https://pharmaceuticalintelligence.com/2012/06/04/investigational-devices-edwards-sapien-transcatheter-heart-valve/

Cardiac Surgery Theatre in China vs. in the US: Cardiac Repair Procedures, Medical Devices in Use, Technology in Hospitals, Surgeons’ Training and Cardiac Disease Severity”    https://pharmaceuticalintelligence.com/2013/01/08/cardiac-surgery-theatre-in-china-vs-in-the-us-cardiac-repair-procedures-medical-devices-in-use-technology-in-hospitals-surgeons-training-and-cardiac-disease-severity/

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/

FDA Pending 510(k) for The Latest Cardiovascular Imaging Technology
https://pharmaceuticalintelligence.com/2013/01/28/fda-pending-510k-for-the-latest-cardiovascular-imaging-technology/

PCI Outcomes, Increased Ischemic Risk associated with Elevated Plasma Fibrinogen not Platelet Reactivity
https://pharmaceuticalintelligence.com/2013/01/10/pci-outcomes-increased-ischemic-risk-associated-with-elevated-plasma-fibrinogen-not-platelet-reactivity/

The ACUITY-PCI score: Will it Replace Four Established Risk Scores — TIMI, GRACE, SYNTAX, and Clinical SYNTAX
https://pharmaceuticalintelligence.com/2013/01/03/the-acuity-pci-score-will-it-replace-four-established-risk-scores-timi-grace-syntax-and-clinical-syntax/

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/

Ablation Devices Market to 2016 – Global Market Forecast and Trends Analysis by Technology, Devices & Applications
https://pharmaceuticalintelligence.com/2012/12/23/ablation-devices-market-to-2016-global-market-forecast-and-trends-analysis-by-technology-devices-applications/

Heart Renewal by pre-existing Cardiomyocytes: Source of New Heart Cell Growth Discovered
https://pharmaceuticalintelligence.com/2012/12/23/heart-renewal-by-pre-existing-cardiomyocytes-source-of-new-heart-cell-growth-discovered/

To Stent or Not? A Critical Decision
https://pharmaceuticalintelligence.com/2012/10/23/to-stent-or-not-a-critical-decision/

Transcatheter Aortic-Valve Replacement for Inoperable Severe Aortic Stenosis

https://pharmaceuticalintelligence.com/2012/09/03/transcatheter-aortic-valve-replacement-for-inoperable-severe-aortic-stenosis/

New Definition of MI Unveiled, Fractional Flow Reserve (FFR)CT for Tagging Ischemia

https://pharmaceuticalintelligence.com/2012/08/27/new-definition-of-mi-unveiled-fractional-flow-reserve-ffrct-for-tagging-ischemia/

New Drug-Eluting Stent Works Well in STEMI
https://pharmaceuticalintelligence.com/2012/08/22/new-drug-eluting-stent-works-well-in-stemi/

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Read Full Post »


Revascularization: PCI, Prior History of PCI vs CABG

Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED 9/25/2013

Table. Comparison of Surgical Therapy and Coronary Angioplasty (Open Table in a new window)

Endpoint Pocock et al* Pocock et al BARI Study
CABG(N=358) PTCA(N=374) CABG(N=1303) PTCA(N=1336) CABG(N=914) PTCA(N=915)
Death (%) 0.3 1.9 2.8 3.1 10.7 13.7
Death or MI 4.5 7.2 8.5 8.1 11.7 10.9
Repeat CABG 1.4 16.0§ 0.8 18.3§ 0.7 20.5§
Repeat CABG or PTCA 3.6 30.5§ 3.2 34.5§ 8.0 54.0§
More than mild angina 6.5 14.6§ 12.1 17.8§
*Meta-analysis of results of 3 trials at 1 year. Patients with single-vessel disease were studied.[22] †Meta-analysis of results of 3 trials at 1 year. Patients with multivessel disease were studied.[22] 

‡Reported results are for 5-year follow-up. Patients with multivessel disease were studied.[21] 

§ P < .05.

BARI = Bypass Angioplasty Revascularization Investigation; CABG = coronary artery bypass grafting; MI = myocardial infarction; PTCA = percutaneous transluminal coronary angioplasty.

SOURCE

http://emedicine.medscape.com/article/161446-overview#aw2aab6b2b5

Percutaneous coronary intervention (PCI), also known as coronary angioplasty, is a nonsurgical technique for treating multiple conditions, including unstable angina, acute myocardial infarction (MI), and multivessel coronary artery disease (CAD).

Essential update: Cangrelor decreases periprocedural complications of PCI

According to a pooled analysis of 3 CHAMPION trials—CHAMPION-PCI , CHAMPION-PLATFORM , and CHAMPION-PHOENIX—cangrelor can reduce the risk of periprocedural thrombotic complications of PCI.[1, 2, 3] The 3 trials included patients with ST-elevation MI (STEMI), non-STEMI, and stable CAD who were randomly assigned to receive either cangrelor or control therapy consisting of either clopidogrel or placebo.

The primary outcome in this analysis was a composite of death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours.[2] The frequency of this outcome was significantly lower in cangrelor-treated patients than in control subjects (absolute difference, 1.9%; relative risk reduction [RRR], 19%). Stent thrombosis was also reduced in the cangrelor-treated group (absolute difference, 0.3%; RRR, 41%). Primary safety outcomes were comparable in the 2 groups, but cangrelor-treated patients had a higher rate of mild bleeding.

Indications and contraindications

Clinical indications for PCI include the following:

In an asymptomatic or mildly symptomatic patient, objective evidence of a moderate-sized to large area of viable myocardium or moderate to severe ischemia on noninvasive testing is an indication for PCI. Angiographic indications include hemodynamically significant lesions in vessels serving viable myocardium (vessel diameter >1.5 mm).

Clinical contraindications for PCI include the presence of any significant comorbid conditions (this is a relative contraindication). Angiographic contraindications include the following:

  • Left main stenosis in a patient who is a surgical candidate (except in carefully selected patients[4] )
  • Diffusely diseased small-caliber artery or vein graft
  • Other coronary anatomy not amenable to PCI

In patients with stable angina, medical therapy is recommended as first-line therapy unless one or more of the following indications for cardiac catheterization and PCI or CABG are present:

  • A change in symptom severity
  • Failed medical therapy
  • High-risk coronary anatomy
  • Worsening left ventricular (LV) dysfunction

American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines on the management of unstable angina/non-STEMI recommend that an early invasive approach (angiography and revascularization within 24 hours) should be used to treat patients presenting with the following high-risk features[5] :

  • Recurrent angina at rest or low level of activity
  • Elevated cardiac biomarkers
  • PCI in the past 6 months or prior CABG
  • New ST-segment depression
  • Elevated cardiac biomarkers
  • High-risk findings on noninvasive testing
  • Signs or symptoms of heart failure or new or worsening mitral regurgitation
  • Hemodynamic instability
  • Sustained ventricular tachycardia
  • LV systolic function < 40%
  • High risk score (eg, Thrombolysis in Myocardial Infarction [TIMI] score >2) (see the TIMI Score for Unstable Angina Non ST Elevation Myocardial Infarction calculator)

See Overview for more detail.

Equipment

Balloon catheters for PCI have the following features:

  • A steerable guide wire precedes the balloon into the artery and permits navigation through the coronary tree
  • Inflation of the balloon compresses and axially redistributes atheromatous plaque and stretches the vessel wall
  • The balloon catheter also serves as an adjunctive device for many other interventional therapies

Atherectomy devices have the following features:

  • These devices are designed to physically remove coronary atheroma, calcium, and excess cellular material
  • Rotational atherectomy, which relies on plaque abrasion and pulverization, is used mostly for fibrotic or heavily calcified lesions that can be wired but not crossed or dilated by a balloon catheter
  • Atherectomy devices may be used to facilitate stent delivery in complex lesions
  • Directional coronary atherectomy (DCA) has been used to debulk coronary plaques
  • Laser atherectomy is not widely used at present
  • Atherectomy is typically followed by balloon dilation and stenting

Intracoronary stents have the following features:

  • Stents differ with respect to composition (eg, stainless steel, cobalt chromium, or nickel chromium), architectural design, and delivery system
  • Drug-eluting stents have demonstrated significant reductions in restenosis and target-lesion revascularization rates
  • In the United States, stents are available that elute the following drugs: sirolimus (Cypher), paclitaxel (Taxus), zotarolimus (Endeavor), and everolimus (Xience V)
  • Stents are conventionally placed after balloon predilation, but in selected coronary lesions, direct stenting may lead to better outcomes

Other devices used for PCI include the following:

  • Thrombus aspiration limits the adverse effects that prolonged time to treatment has on myocardial reperfusion[6]
  • Distal embolic protection during saphenous vein graft intervention has become the standard of care

See Periprocedural Care and Devices for more detail.

Technique

Intravascular ultrasonography (IVUS) is used in PCI as follows:

  • Provide information about the plaque, the vessel wall, and the degree of luminal narrowing
  • Assessment of indeterminate lesions
  • Evaluation of adequate stent deployment

Intracoronary Doppler pressure wires are used in PCI as follows:

  • To characterize coronary lesion physiology and estimate lesion severity
  • Comparison of pressure distal to a lesion with aortic pressure enables determination of fractional flow reserve (FFR)
  • An FFR measurement below 0.75-0.80 during maximal hyperemia (induced via administration of adenosine) is consistent with a hemodynamically significant lesion

Antithrombotic therapy

  • Aspirin and heparin have been the traditional adjunctive medical therapies
  • Direct thrombin inhibitors (ie, hirudin, bivalirudin) are slightly better than heparin in preventing ischemic complications during balloon angioplasty but do not affect restenosis rates
  • Low-molecular-weight heparins (LMWHs) are substituted for standard heparin at some centers

Antiplatelet therapy

Patients receiving stents are treated with a combination of aspirin and clopidogrel. Duration of therapy is as follows:

  • Bare-metal stents: A minimum of 4 weeks
  • Drug-eluting stents: A minimum of 12 months

Use of proton pump inhibitors is appropriate in patients with multiple risk factors for GI bleeding who require antiplatelet therapy.

Glycoprotein inhibitor therapy

  • Abciximab, tirofiban, and eptifibatide have all been shown to reduce ischemic complications in patients undergoing balloon angioplasty and coronary stenting
  • In primary PCI, GPIIb/IIIa receptor inhibitors have also been shown to improve flow and perfusion and to reduce adverse events
  • Abciximab may improve outcomes in patients when given before arrival in the catheterization lab for primary PCI[7]

See Technique and Medication for more detail.

SOURCE & References for the UPDATE, in

http://emedicine.medscape.com/article/161446-overview#aw2aab6b2b5

Outcomes comparison between PCI and CABG was explored in the past by authors on this Open Access Online Scientific Journal, in the following articles:

CABG or PCI: Patients with Diabetes – CABG Rein Supreme

https://pharmaceuticalintelligence.com/2012/11/05/cabg-or-pci-patients-with-diabetes-cabg-rein-supreme/

To Stent or Not? A Critical Decision

https://pharmaceuticalintelligence.com/2012/10/23/to-stent-or-not-a-critical-decision/

PCI Outcomes, Increased Ischemic Risk associated with Elevated Plasma Fibrinogen not Platelet Reactivity

https://pharmaceuticalintelligence.com/2013/01/10/pci-outcomes-increased-ischemic-risk-associated-with-elevated-plasma-fibrinogen-not-platelet-reactivity/

New Definition of MI Unveiled, Fractional Flow Reserve (FFR)CT for Tagging Ischemia

https://pharmaceuticalintelligence.com/2012/08/27/new-definition-of-mi-unveiled-fractional-flow-reserve-ffrct-for-tagging-ischemia/

Age-Dependent Depression in Circulating Endothelial Progenitor Cells in Coronary Artery Bypass Grafting Patients

https://pharmaceuticalintelligence.com/2012/08/17/age-dependent-depression-in-circulating-endothelial-progenitor-cells-in-coronary-artery-bypass-grafting-patients/

Now we are reporting  an Original Contribution on this subject which includes also Prior History of PCI, a factor NOT included in the other studies. The major conclusions are the following three:

  1. In a contemporary cohort of STEMI patients undergoing primary PCI, a history of prior CABG was found to be an independent predictor of in-hospital mortality.
  2. In contrast, despite more comorbidities at the time of STEMI, patients with prior PCI had no significant difference in the rates of death, stroke, or periprocedural MI when compared to a STEMI population without prior coronary revascularization.
  3. Thus, only prior surgical — and not percutaneousrevascularization should be considered a significant risk factor in the setting of primary PCI.

Number 1, above is related to patient medical history of cardiovascular disease SEVERITY prior to CABG

Number 2, above indicates that patients can tolerate and benefit several cycles of PCI and stent implantation rather than PCI being a determinant predictor of future prognosis

Number 3, above is as well related to patient medical history of cardiovascular disease SEVERITY prior to CABG

The Original Contribution on this subject is present, below.

The Impact of Previous Revascularization on Clinical Outcomes in Patients Undergoing Primary Percutaneous Coronary Intervention

Travis J. Bench, MD1, Puja B. Parikh, MD1, Allen Jeremias, MD1, Sorin J. Brener, MD2, Srihari S. Naidu, MD3,

Richard A. Shlofmitz, MD4, Thomas Pappas, MD4, Kevin P. Marzo, MD3, Luis Gruberg, MD1

Authors Affiliations:

1Division of Cardiovascular Medicine, Stony Brook University Medical Center, Stony Brook, New York,

2Department of Cardiology, Methodist Hospital, Brooklyn, New York,

3Division of Cardiology, Winthrop University Hospital, Mineola,

New York, and

4The Heart Center, St Francis Hospital, Roslyn, New York.

The authors report no conflicts of interest regarding the content herein.

Manuscript submitted October 10, 2012, provisional acceptance given October 20, 2012, final version accepted November 28, 2012.

Address for correspondence: 

Luis Gruberg, MD, FACC, Department of Medicine, Division of Cardiology, Health Sciences Center, T16-080, Stony Brook, NY 11794- 8160. Email: luis.gruberg@stonybrook.edu

 

Abstract : While the impact of prior coronary artery bypass graft surgery (CABG) on in-hospital outcomes in patients with STelevation myocardial infarction (STEMI) has been described, data are limited on patients with prior percutaneous coronary intervention (PCI) undergoing primary PCI in the setting of an STEMI. The aim of the present study was to assess the effect of previous revascularization on in-hospital outcomes in STEMI patients undergoing primary PCI. Between January 2004 and December 2007, a total of 1649 patients underwent primary PCI for STEMI at four New York State hospitals. Baseline clinical and angiographic characteristics and in-hospital outcomes were prospectively collected as part of the New York State PCI Reporting System (PCIRS). Patients with prior surgical or percutaneous coronary revascularization were compared to those without prior coronary revascularization. Of the 1649 patients presenting with STEMI, a total of 93 (5.6%) had prior CABG, 258 (15.7%) had prior PCI, and 1298 (78.7%) had no history of prior coronary revascularization. Patients with prior CABG were significantly older and had higher rates of peripheral vascular disease, diabetes mellitus, congestive heart failure, and prior stroke. Additionally, compared with those patients with a history of prior PCI as well as those without prior coronary revascularization, patients with previous CABG had more left main interventions (24% vs 2% and 2%; P<.001), but were less often treated with drug-eluting stents (47% vs 61% and 72%; P<.001).

Despite a low incidence of adverse in-hospital events, prior CABG was associated with higher all-cause in-hospital mortality (6.5% vs 2.2%; P=.012), and as a result, higher overall MACE (6.5% vs 2.7%; P=.039). By multivariate analysis, prior CABG (odds ratio, 3.40; 95% confidence interval, 1.15-10.00) was independently associated with in-hospital mortality. In contrast, patients with prior PCI had similar rates of MACE (4.3% vs 2.7%; P=.18) and inhospital mortality (3.1% vs 2.2%; P=.4) when compared to the de novo population. Patients with a prior history of CABG, but not prior PCI, undergoing primary PCI in the setting of STEMI have significantly worse in-hospital outcomes when compared with patients who had no prior history of coronary artery revascularization. Thus, only prior surgical — and not percutaneous — revascularization should be considered a significant risk factor in the setting of primary PCI.

J INVASIVE CARDIOL 2013;25(4):166-169

Key words: PCI risk factor, CABG

Demographics and Angiographic Characteristics

Between 2004 and 2007, a total of 25,025 patients underwent PCI at these medical institutions, and their data were prospectively collected and submitted as required by the New York State Department of Health. Of these patients, a total of 1649 underwent primary PCI in the setting of an STEMI and constituted our study population. In this group, a total

No Prior Revascularization (n = 1298)

Prior PCI (n = 258)

Prior CABG (n = 93)

Demographics

Age (years) 61 ± 13 62 ± 12 67 ± 12 <.001

Male gender 956 (73.6%) 194 (75.2%) 76 (81.7%) .21

White 1165 (89.8%) 231 (89.5%) 87 (93.5%) .51

African-American 78 (6%) 18 (7%) 1 (1.1%) .51

Hispanic 91 (7%) 11 (4.3%) 4 (4.3%) .51

Medical history

Ejection fraction (%) 43 ± 12 44 ± 13 45 ± 11 .079

Diabetes mellitus 196 (15.1%) 69 (26.7%) 27 (29%) <.001

Peripheral vascular disease 53 (4.1%) 25 (9.7%) 12 (12.9%) <.001

Chronic lung disease 47 (3.6%) 17 (6.6%) 4 (4.3%) .09

Congestive heart failure 74 (5.7%) 25 (9.7%) 10 (10.8%) .02

Prior myocardial infarction 3 (0.2%) 1 (0.4%) 1 (1.1%) .35

Prior cerebrovascular event 56 (4.3%) 9 (3.5%) 10 (11%) .01

Chronic dialysis 6 (0.5%) 6 (2.3%) 0 (0%) .004

Creatinine (mg/dL) 1.1 ± 0.8 1.3 ± 1.4 1.3 ± 1.1 .002

Glomerular filtration rate (mL/min/1.73 m2) 79 ± 26 75 ± 28 71 ± 27 .002

Angiographic characteristics

Left main 19 (1.5%) 5 (1.9%) 22 (23.7%) <.001

Left anterior descending 942 (72.6%) 178 (69%) 69 (74.2%) .45

Left circumflex 579 (44.6%) 122 (47.3%) 70 (75.3%) <.001

Right coronary 806 (62.1%) 187 (72.5%) 67 (72%) .002

Graft (arterial or venous) n/a n/a 20 (21.5%)

Stent type

Bare-metal stent 241 (18.6%) 52 (20.2%) 23 (24.7%) .31

Drug-eluting stent 928 (71.5%) 158 (61.2%) 44 (47.3%) <.001

of 1298 patients (78.7%) had no prior history of revascularization,

while 93 patients (5.6%) had a history of previous

CABG and 258 (15.7%) had a history of previous PCI. Considerable

differences in baseline clinical and procedural characteristics were noted among these groups (Table 1).

Discussion

While STEMI patients with prior CABG are well known to have worse clinical outcomes than those without prior revascularization, a direct comparison between patients who underwent primary PCI in the setting of prior CABG or prior PCI has not yet been reported. The principal findings from the present analysis suggest that in a contemporary, unrestricted patient population presenting with STEMI and undergoing primary PCI, patients with a prior history of CABG are:

(1) usually older and have multiple comorbidities, including peripheral vascular disease, diabetes, and chronic obstructive lung disease;

(2) are more likely to undergo intervention on a native vessel and not a bypass graft;

(3) are more likely to be treated with bare-metal stents; and (4) have higher rates of in-hospital mortality without a significant increase in stroke or MI rates, when compared with patients with a prior history of PCI or patients with no previous history of coronary artery revascularization. Interestingly, these outcomes did not apply to patients with a history of prior PCI in this analysis. Instead, this cohort of patients had no significant difference in the rate of death, stroke, or periprocedural infarction when compared to a STEMI population without prior coronary revascularization, despite a significantly higher burden of comorbidities than those with no prior revascularization.

Our findings concur with previous studies that have shown higher mortality rates among patients with prior surgical bypass presenting with acute MI.7,9,14 Despite changes in revascularization strategies over the past 30 years, invasive therapies to treat acute coronary syndromes in patients with prior bypass surgery appear to have yielded less robust results than in other populations. In fact, Stone and colleagues already described in the Primary Angioplasty in Myocardial Infarction (PAMI-2) study that patients with a previous CABG undergoing primary PCI in the setting of an acute MI had significantly greater in-hospital mortality than patients without previous CABG, especially if the infarct-related vessel was a bypass conduit. However, by logistic regression analysis, only advanced age (P=.004), triple-vessel disease (P=.004), and Killip class ≥2 (P=.02) were independent predictors of in-hospital mortality in that study.13 In a more contemporary study of 128 STEMI patients with prior CABG, who were enrolled in the Assessment of PEXelizumab in Acute

Figure 1. In-hospital major adverse cardiac and cerebrovascular events (MACCE), mortality, and stroke rates for patients without prior history of coronary revascularization (light grey bars), prior percutaneous coronary revascularization (PCI) (dark grey bars), and prior coronary artery bypass graft (CABG) (black bars). Vol. 25, No. 4, April 2013 169

STEMI and Prior Revascularization Myocardial Infarction (APEX-AMI) trial, Welsh and colleagues reported that post-CABG patients are less likely to undergo acute reperfusion (only 79% underwent primary PCI), have worse angiographic outcomes following primary PCI, and have higher 90-day mortality rates (19.0% vs 5.7%; P=.05). This difference was even more apparent when the infarct-related artery was a bypass graft that was not successfully reperfused (23.1% vs 8.5%; P=.03).3 These results are similar to our current analysis, where in-hospital mortality rates for patients who underwent primary PCI of a graft were numerically roughly 4 times as high as those undergoing PCI of a native vessel. Likewise, Gurfinkel et al reported a significant reduction in hard endpoints, such as all-cause death and MI at 6 months in patients treated with an invasive approach in the Global Registry of Acute Coronary Events (GRACE).15 In this large, multinational, observational study of 3853 patients with prior bypass surgery presenting with an acute coronary syndrome, only 497 (12.9%) were managed invasively and the rest were treated medically.

Despite significant differences in baseline characteristics, including a higher rate of STEMI in patients treated invasively (14% vs 27%; P<.001), in-hospital mortality was similar in both groups (3.4% vs 3.2%; P=.86). However, at 6-month follow-up, mortality was significantly higher in those patients treated medically (6.5% vs 3.4%; P<.02) as was the combined endpoint of death or MI (11% vs 5.8%; P<.01).

Whether these results apply to patients with a prior history of PCI has not been well defined. By the nature of vascular disease, patients with prior PCI are more likely to have more comorbidities than those without prior revascularization, a finding confirmed in our study. Despite considerable differences in baseline characteristics, however, these differences did not translate into a differential risk after STEMI. In fact, the cohort of patients presenting with STEMI who had a history of prior PCI had no statistically significant difference in in-hospital mortality or overall MACCE when compared to a population of patients presenting with STEMI in the absence of any prior revascularization.

Study limitations. The database utilized was derived from four New York State teaching hospitals and was designed to track quality of care and clinical outcomes. As all studies involving multicenter databases and registries, there is potential error in data entry and availability. Potential confounding comorbidities, including smoking status and family history of coronary artery disease, were not collected in this database, and information regarding long-term follow-up is not available, all of which are important limitations of this analysis. As such, deficiencies such as these limit the conclusions that can be drawn from our multivariate analysis. Additionally, there is no audit of data quality, and the low overall event rates limit effective statistical comparison.

Conclusions

In a contemporary cohort of STEMI patients undergoing primary PCI, a history of prior CABG was found to be an independent predictor of in-hospital mortality. In contrast, despite more comorbidities at the time of STEMI, patients with prior PCI had no significant difference in the rates of death, stroke, or periprocedural MI when compared to a STEMI population without prior coronary revascularization. Thus, only prior surgical — and not percutaneous — revascularization should be considered a significant risk factor in the setting of primary PCI.

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