Posts Tagged ‘NEJM’

Treatment for Infective Endocarditis

Curator: Larry H Bernstein, MD, FACP

UPDATED on 3/4/2019



Tricuspid Valve Reconstruction for Infective Endocarditis: Operative Highlights (Video)

There are no easy solutions for acute infective tricuspid valve endocarditis in IV drug users, as the risk of prosthetic endocarditis in this population is high. Complete valve resection without replacement is feasible but leads to progressive right-sided heart failure. Reconstruction of the tricuspid valve with autologous pericardium is an alternative option, as demonstrated in the video case study below.

A 29-year-old female drug abuser with fever, hemoptysis and MRSA bacteremia was started on IV antibiotics. She looked frail and had prominent jugular venous pressure as well as 95 percent saturation on 2 liters of nasal cannula oxygen. She was not on inotropes and had a pulmonary artery pressure of 40/20 mmHg with a good cardiac index. Chest CT showed a large left pleural effusion with associated atelectasis of the left lung. The right lung had manifestations of septic emboli and a smaller pleural effusion.

A Cleveland Clinic surgical team led by cardiothoracic surgeon Faisal Bakaeen, MD, proceeded to excise the patient’s extensive infected and devitalized tissue around the tricuspid valve, leaving only a portion of the anterior leaflet to serve as a reference for reconstruction using autologous pericardium. Dr. Bakaeen walks us through the essential surgical steps — and their underlying rationale — in the narrated operative video below.




An article that appeared in NEJM compares early surgery versus conventional treatment for infective endocarditis.
Early Surgery versus Conventional Treatment for Infective Endocarditis
Duk-Hyun Kang, Yong-Jin Kim, Sung-Han Kim, Byung Joo Sun, et al.

N Engl J Med June 28, 2012; 366:2466-2473. http://doi.org/10.1056/NEJMoa1112843

Background and Purpose: While current guidelines advocate surgical management for complicated left-sided infective endocarditis and early surgery for patients with infective endocarditis and congestive heart failure, the indications for surgical intervention to prevent systemic embolism remain unclear. Surgery is favored by experience with complete excision of infected tissue and valve repair, and low operative mortality, but it does not remove concerns about residual active infection, which results in two sets of guidelines, the 2006 ACC-AHA for class IIa indication only for recurrent emboli and persistent vegetation, and the 2009 ESC guidelines for class IIb indication for very large, isolated vegetations. The Early Surgery versus Conventional Treatment in Infective Endocarditis (EASE) trial was conducted to determine whether early surgical intervention woulddecrease rate of death or embolic events.

Patient Enrollment: The study enrolled 76 consecutive patients, 18 years of age or older, with left-sided, native-valve infective endocarditis and a high risk of embolism. For all patients with suspected infective endocarditis, blood cultures were obtained and transthoracic echocardiography was performed within 24 hours after hospitalization. Patients were only eligible for enrollment if they had received a diagnosis of definite infective endocarditis and had severe mitral valve or aortic valve disease and vegetation with a diameter greater than 10 mm. Patients were excluded if they had moderate-to-severe congestive heart failure, infective endocarditis complicated by heart block, annular or aortic abscess, destructive penetrating lesions requiring urgent surgery, or fungal endocarditis, or were over 80 years age, or coexisting major embolic stroke with a risk of hemorrhagic transformation at the time of diagnosis, and a serious coexisting condition. Patients were also excluded if they had infective endocarditis involving a prosthetic valve, right-sided vegetations, or small vegetations (diameter, ≤10 mm) or had been referred from another hospital more than 7 days after the diagnosis of infective endocarditis.
The protocol specified that patients who were assigned to the early-surgery group should undergo surgery within 48 hours after randomization. Patients assigned to the conventional-treatment group were treated according to the AHA guidelines, and surgery was performed only if complications requiring urgent surgery developed during medical treatment or if symptoms persisted after the completion of antibiotic therapy. Details of the study procedures are provided in the Supplementary Appendix, available at NEJM.org.

Study End Points: The primary end point was a composite of in-hospital death or clinical embolic events that occurred within 6 weeks after randomization. An embolic event was defined as a systemic embolism fulfilling both prespecified criteria: the acute onset of clinical symptoms or signs of embolism and the occurrence of new lesions, as confirmed by follow-up imaging studies. Prespecified secondary end points, at 6 months of follow-up, included death from any cause, embolic events, recurrence of infective endocarditis, and repeat hospitalization due to the development of congestive heart failure.

Clinical and Echocardiographic Characteristics of the Patients at Baseline, According to Treatment Group:

The mean age of the patients was 47 years, and 67% were men. The mitral valve was involved in 45 patients, the aortic valve in 22, and both valves in 9. Severe mitral regurgitation was observed in 45 patients, severe aortic regurgitation in 23, severe aortic stenosis in 3, severe mitral regurgitation and stenosis in 1, and both severe mitral regurgitation and aortic regurgitation in 4. The median diameter of vegetation was 12 mm (interquartile range, 11 to 17). All patients met the Duke criteria for definite endocarditis; the most common pathogens in both groups were viridans streptococci (in 30% of all patients), other streptococci (in 30%), and Staphylococcus aureus (in 11%). Characteristics of Antibiotic Therapy, According to Treatment Group: There were no significant between-group differences in terms of control of the underlying infection, the antibiotic regimen used, or the duration of antibiotic therapy.

Surgical Procedures: All patients in the early-surgery group underwent valve surgery within 48 hours after randomization; the median time between randomization and surgery was 24 hours (interquartile range, 7 to 45). Of the 22 patients with involvement of the mitral valve, 8 patients underwent mitral-valve repair and 14 underwent mitral-valve replacement with a mechanical valve. Of the 15 patients with involvement of the aortic valve or both the mitral and aortic valves, 14 underwent mechanical-valve replacement and 1 underwent valve replacement with a biologic prosthesis. Concomitant coronary-artery bypass grafting at the time of valve surgery was performed in 2 patients (5%).

Conventional Therapy: Of the 39 patients assigned to the conventional-treatment group, 30 (77%) underwent surgery during the initial hospitalization (27 patients) or during follow-up (3). The surgical procedures included 11 mitral-valve repairs, 6 mitral-valve replacements (with 5 patients receiving a mechanical valve and 1 a biologic prosthesis), 11 aortic-valve replacements (with 9 patients receiving a mechanical valve and 2 a biologic prosthesis), and 2 combined aortic-valve replacements (with 1 patient receiving a mechanical valve and 1 a biologic prosthesis) and mitral-valve repairs. In 8 patients (21%), indications for urgent surgery developed during hospitalization (median time to surgery after randomization, 6.5 days [interquartile range, 6 to 10]). Elective surgery was performed in an additional 22 patients owing to symptoms or left ventricular dysfunction more than 2 weeks after randomization. Surgical results are shown in the Supplementary Appendix.

Primary End Point: The primary end point of in-hospital death or embolic events within the first 6 weeks after randomization occurred in one patient (3%) in the early-surgery group, as compared with nine (23%) in the conventional-treatment group (hazard ratio, 0.10; 95% confidence interval [CI], 0.01 to 0.82; P=0.03). In the early-surgery group, one patient died in the hospital and no patients had embolic events; in the conventional-treatment group, one patient died in the hospital and eight patients had embolic events (Table 3TABLE 3).

At 6 weeks after randomization, the rate of embolism was 0% in the early-surgery group, as compared with 21% in the conventional-treatment group (P=0.005). No patient in either group had an embolic event or was hospitalized for congestive heart failure during follow-up. Recurrence of infective endocarditis within 6 months after discharge was not observed in any patient in the early-surgery group but was reported in 1 patient in the conventional-treatment group. Among the 11 patients (28%) in the conventional-treatment group who were treated medically and discharged without undergoing surgery, 1 (3%) died suddenly, 7 (18%) had symptoms related to severe valve disease or recurrence of infective endocarditis (3 of whom underwent surgery during follow-up), and 3 (8%) had no symptoms or embolic events (Table S3 in the Supplementary Appendix).
There was no significant difference between the early-surgery and conventional-treatment groups in all-cause mortality at 6 months (3% and 5%, respectively; hazard ratio, 0.51; 95% CI, 0.05 to 5.66; P=0.59) (Figure 2AFIGURE 2).
Kaplan–Meier Curves for the Cumulative Probabilities of Death and of the Composite End Point at 6 Months, According to Treatment Group.

At 6 months, the rate of the composite of death from any cause, embolic events, recurrence of infective endocarditis, or repeat hospitalization due to the development of congestive heart failure was 3% in the early-surgery group, as compared with 28% in the conventional-treatment group (hazard ratio, 0.08; 95% CI, 0.01 to 0.65; P=0.02). The estimated actuarial rate of end points was significantly lower in the early-surgery group than in the conventional-treatment group (P=0.009 by the log-rank test) (Figure 2B).

Conclusion: Early surgery performed within 48 hours after diagnosis reduced the composite primary end point of death from any cause or embolic events by effectively reducing the risk of systemic embolism. Moreover, these improvements in clinical outcomes were achieved without an increase in operative mortality or recurrence of infective endocarditis.

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Evidence for Overturning the Guidelines in Cardiogenic Shock

Reporter: Aviva Lev-Ari, PhD, RN


Christopher M. O’Connor, M.D., and Joseph G. Rogers, M.D.

August 27, 2012 (10.1056/NEJMe1209601)

Cardiogenic shock complicating acute myocardial infarction continues to be a devastating event associated with extremely high mortality. The results of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial,1 now reported in the Journal, show that in patients with acute myocardial infarction and hemodynamic compromise who undergo revascularization, the routine use of an intraaortic balloon pump (IABP), as compared with standard therapy, does not improve survival.1

Introduced nearly five decades ago,2 IABP is now routinely used as an adjuvant treatment for myocardial infarction complicated by cardiogenic shock, on the basis of evidence that it is associated with hemodynamic improvements accompanied by enhanced coronary blood flow, increased perfusion of vital organs, maintenance of infarct-artery patency, and decreased systemic inflammation.3 Until recently, few alternatives have been available to support patients with severely compromised hemodynamics. Despite a lack of robust data from outcomes trials and meta-analyses4,5 that have shown limited efficacy, international guidelines endorse the use of IABP for treating post-myocardial infarction shock, with a class I recommendation.6,7

The IABP-SHOCK II trial could have affirmed contemporary clinical practice and guidelines. Instead, it revealed surprising results. In a comparison of IABP with standard therapy, the investigators found no difference in 30-day mortality or in any key secondary end points. Although IABP was safe, there was no evidence that it was associated with hemodynamic improvement — a mechanistic effect of IABP that has long been considered to be critical for its clinical application. Moreover, there were no benefits with respect to renal function or attenuation in lactate or C-reactive protein levels.

Conducting a randomized clinical trial in the emergency setting of acute myocardial infarction with shock is exceptionally difficult. In an era of rapid intervention in the catheterization laboratory and a pervasive perception of lack of equipoise, the IABP-SHOCK II investigators should be commended for completing a moderate-sized trial in 3 years at 37 sites. The results of the trial have important clinical implications, but several issues must be addressed. First, this 600-patient study could be considered too small to be definitive. However, the conclusions are bolstered by more than 240 primary end-point events, making them far more robust than might be surmised from the sample size alone. Second, the patients represented a moderate-risk cohort, with a 30-day mortality of 40%. This rate is lower than that reported in other trials involving patients with cardiogenic shock, so the results may not be applicable to the highest-risk patients. In the decade since the original Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial was reported,8 emphasis on early revascularization and increased use of background medical therapies would be anticipated to have favorably altered the natural history of cardiogenic shock occurring after myocardial infarction, leading to lower 30-day mortality. Third, asymmetry in the number of crossovers may have influenced the final results analyzed according to the intention-to-treat principle. However, a per-protocol analysis (which included all the patients who had confirmed acute myocardial infarction, with the exclusion of those who crossed over) and an adjusted multivariate model showed similar nonsignificant results. Finally, favorable trends with IABP were observed in younger patients and in those with a first myocardial infarction, although these findings can be considered only as hypothesis-generating. Given the concordance of data from the meta-analyses and the current trial, the data do not support the routine use of IABP in patients with acute myocardial infarction complicated by cardiogenic shock, and the level I guideline recommendation is now strongly challenged. Members of guideline committees and clinicians should take note of another example of a recommendation that is based on insufficient data.

The results of the IABP-SHOCK II trial parallel those from many recent outcome trials that have challenged our understanding of the management of acute and chronic heart failure, including those regarding the use of pulmonary artery catheters9 and the role of revascularization in ischemic cardiomyopathy.10

Therapeutic strategies for patients with cardiogenic shock have changed abruptly and are ready for renewed growth and development. Although many will find the results of the IABP-SHOCK II trial disappointing, we must recognize the opportunity to develop novel and innovative strategies to treat this condition. Integrated systems to ensure rapid reperfusion may reduce the incidence of shock among patients who have had an acute myocardial infarction.11 Secondary analyses of data from the IABP-SHOCK II trial may help us understand the mechanisms of the failed response. Comparing the patient populations and outcomes of the IABP-SHOCK II study groups and the concurrent registry cohort may yield important insights, with therapeutic implications for the use of other mechanical devices for circulatory support. On the basis of the findings of the IABP-SHOCK II trial, we must move forward with the understanding that a cardiovascular condition with 40% mortality at 30 days remains unacceptable. Most important, we hope that the results of this trial will galvanize a broadly based mandate to address this devastating clinical problem by reestablishing equipoise and international engagement in research on novel devices and pharmacologic therapies.

This article was published on August 27, 2012, at NEJM.org.

Source Information

From Duke University, Durham, NC.



Intraaortic Balloon in Cardiogenic Shock 

Original Article

Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock

H. Thiele and Others

In current international guidelines, intraaortic balloon counterpulsation (IABP) is considered to be a class I treatment for cardiogenic shock complicating acute myocardial infarction. However, evidence is based mainly on registry data, and there is a paucity of randomized clinical trials.

Clinical Pearls

  What were the results of this study, which compared intraaortic balloon counterpulsation or no intraaortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction?

At 30 days, mortality was similar among patients in the IABP group and those in the control group (39.7% and 41.3%, respectively; relative risk with IABP, 0.96; 95% confidence interval, 0.79 to 1.17; P=0.69).

Table 3.Clinical Outcomes.

Figure 1. Time-to-Event Curves for the Primary End Point.

  Among patients who received IABP, did results differ between those who had the IABP inserted before versus after revascularization?

Among patients in the IABP group, there was no significant difference in mortality between the patients (13.4%) in whom the balloon pump was inserted before revascularization and the patients (86.6%) in whom the balloon pump was inserted after revascularization (mortality, 36.4% and 36.8%, respectively; P=0.96).

Morning Report Questions

Q. Did safety end points differ between the two groups? 

A. There were no significant differences between the IABP group and the control group with respect to the rates of stroke, bleeding, sepsis, or peripheral ischemic complications requiring intervention in the hospital. There were also no significant differences in the rates of reinfarction or stent thrombosis.

Q. How do the authors explain the effect of intraaortic balloon counterpulsation in this trial on the factors that are known to cause death in patients with cardiogenic shock? 

A. Death in patients with cardiogenic shock can result from one or more of three factors: hemodynamic deterioration, occurrence of multiorgan dysfunction, and development of the systemic inflammatory response syndrome. There was no immediate improvement in blood pressure or heart rate among patients in whom an intraaortic balloon pump was inserted, as compared with those who did not have a balloon pump inserted. Although there was a positive effect of intraaortic balloon counterpulsation on multiorgan dysfunction at day 2 and day 3, this effect was not evident at day 4. There were also no significant effects on C-reactive protein level or serum lactate level, which were assessed as measures of inflammation and tissue oxygenation. Experimental and clinical studies have indicated that intraaortic balloon counterpulsation results in a hemodynamic benefit as a result of afterload reduction and diastolic augmentation with improvement in coronary perfusion. The authors postulate that the effects on cardiac output are modest and might not be sufficient to reduce mortality.


NEJM Resident E-Bulletin <resebulletin@nejm.org> on 10/3/2012


    1. 1Thiele H, Zeymer U, Neumann F-J, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012. DOI: 10.1056/NEJMoa1208410.

    1. 2Kantrowitz A, Tjonneland S, Freed PS, Phillips SJ, Butner AN, Sherman JL Jr. Initial clinical experience with intraaortic balloon pumping in cardiogenic shock. JAMA 1968;203:113-118
      CrossRef | Web of Science | Medline

    1. 3Ohman EM, George BS, White CJ, et al. Use of aortic counterpulsation to improve sustained coronary artery patency during acute myocardial infarction: results of a randomized trial. Circulation 1994;90:792-799
      CrossRef | Web of Science

    1. 4Sjauw KD, Engstrom AE, Vis MM, et al. A systematic review and meta-analysis of intra-aortic balloon pump therapy in ST-elevation myocardial infarction: should we change the guidelines? Eur Heart J 2009;30:459-468
      CrossRef | Web of Science

    1. 5Unverzagt S, Machemer MT, Solms A, et al. Intra-aortic balloon pump counterpulsation (IABP) for myocardial infarction complicated by cardiogenic shock. Cochrane Database Syst Rev 2011;7:CD007398-CD007398

    1. 6Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004;110:e82-e292[Erratum, Circulation 2005;111:2013-4, 2007;115(5):e411, 2010;121(23):e441.]
      CrossRef | Medline

    1. 7Van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. Eur Heart J 2008;29:2909-2945
      CrossRef | Web of Science | Medline

    1. 8Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. N Engl J Med 1999;341:625-634
      Full Text | Web of Science | Medline

    1. 9Binanay C, Califf RM, Hasselblad V, et al. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA 2005;294:1625-1633
      CrossRef | Web of Science | Medline

    1. 10Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011;364:1607-1616
      Full Text | Web of Science | Medline

  1. 11Jollis JG, Roettig ML, Aluko AO, et al. Implementation of a statewide system for coronary reperfusion for ST-segment elevation myocardial infarction. JAMA 2007;298:2371-2380
    CrossRef | Web of Science | Medline

Related posts to this topic on this Scientific Web Site:

Foreseen changes in Guideline of Treatment of Cardiogenic Shock with Intra-aortic Balloon counterPulsation (IABP)


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