Correspondence
Sudden Death in Patients with Myocardial Infarction
N Engl J Med 2005; 353:1294-1297September 22, 2005
- Article
To the Editor:
Solomon and colleagues (June 23 issue)1 report that in the Valsartan in Acute Myocardial Infarction Trial (VALIANT), 19 percent of patients with heart failure, left ventricular dysfunction, or both, after myocardial infarction who died suddenly from cardiac causes or had cardiac arrest with resuscitation did so within the first 30 days after infarction. In the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS),2 involving patients with both heart failure and left ventricular dysfunction (an ejection fraction of ≤40 percent) after myocardial infarction, my colleagues and I recently found that there was a similar high, early incidence of sudden death from cardiac causes and that eplerenone reduced this risk by 37 percent (P=0.051) within 30 days after randomization.3 In patients with an ejection fraction of 30 percent or less after myocardial infarction, who Solomon et al. pointed out had an even higher risk of early sudden death from cardiac causes, we have recently found a 58 percent reduction in sudden death from cardiac causes within 30 days among patients randomly assigned to receive eplerenone (P=0.008).4 We believe that these findings are of special importance in view of the failure of implantable cardioverter–defibrillators to reduce the risk of early sudden death from cardiac causes after myocardial infarction in a similar group of patients.5
Bertram Pitt, M.D.
University of Michigan Medical Center, Ann Arbor, MI 48109
bpitt@med.umich. edu for the EPHESUS Investigators
Dr. Pitt reports having served as a consultant to Pfizer, which sponsored EPHESUS.
5 References1
Solomon SD ,Zelenkofske S ,McMurray JJV , et al. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med 2005;353:2581-2588
Full Text | Web of Science2
Pitt B ,Remme W ,Zannad F , et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-1321[Erratum, N Engl J Med 2003;348:2271.]
Full Text | Web of Science | Medline3
Pitt B ,White H ,Nicolau J , et al. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol 2005;46:425-431
CrossRef | Web of Science | Medline4
van Veldhuisen DJ ,Aschermann M ,Zannad F , et al. Eplerenone benefit at 30 days in high-risk subgroups in the EPHESUS trial. Eur J Heart Fail 2005;4:Suppl 1:79-79 abstract.5
Hohnloser SH ,Kuck KH ,Dorian P , et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-2488
Full Text | Web of Science | Medline
To the Editor:
Solomon and colleagues describe the risk of sudden death after myocardial infarction among patients with left ventricular dysfunction, heart failure, or both. In the accompanying editorial, Buxton pays attention to differences between survivors and patients who died and concludes that there were no useful factors distinguishing those who died suddenly from those who had a nonsudden death.1 However, less than one third of the patients who died received treatment with either thrombolytic therapy or primary angioplasty. In a randomized trial comparing primary angioplasty with thrombolytic therapy, long-term follow-up showed that the rate of death from cardiac causes — in particular, the rate of sudden death — is lower after primary angioplasty than after thrombolytic therapy; this finding directly corresponds to the rates of nonpatent infarct-related arteries, as determined on follow-up coronary angiography.2 In a trial involving 940 patients treated with angioplasty, 50 patients had died after 30 days, but only 3 died suddenly.3 Therefore, the most effective method to prevent sudden death from cardiac causes, as well as death related to heart failure, in patients who have had a myocardial infarction seems to be to send them home with an open infarct-related coronary artery.4
4 ReferencesFelix Zijlstra, M.D., Ph.D.
Iwan C.C. van der Horst, M.D., Ph.D.
Groningen University Medical Center, 30.001 Groningen, the Netherlands
f.zijlstra@thorax. umcg. nl 1
Buxton AE . Sudden death after myocardial infarction -- who needs prophylaxis, and when? N Engl J Med 2005;352:2638-2640
Full Text | Web of Science | Medline2
Zijlstra F ,Hoorntje JCA ,de Boer M-J , et al. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1999;341:1413-1419
Full Text | Web of Science | Medline3
van der Horst IC ,Zijlstra F ,van 't Hof AW , et al. Glucose-insulin-potassium infusion in patients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial. J Am Coll Cardiol 2003;42:784-791
CrossRef | Web of Science | Medline4
Simes RJ ,Topol EJ ,Holmes DR Jr , et al. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion: importance of early and complete infarct artery reperfusion. Circulation 1995;91:1923-1928
Web of Science | Medline
To the Editor:
Solomon and colleagues report that the incidence of sudden death after myocardial infarction among patients with left ventricular dysfunction is greatest in the first 30 days and remains increased for the first several months. The authors also describe various differences in the baseline characteristics between patients who died suddenly from cardiac causes and those who did not. It would be of interest to know if subjects who did not have life-threatening events were more frequently enrolled in exercise programs soon after having a myocardial infarction.
Exercise training reduces mortality from all causes and from cardiovascular causes after myocardial infarction,1 primarily by reducing the rate of sudden death from cardiac causes. Exercise therapy is particularly effective when it is initiated early — within the first two weeks after myocardial infarction.2 The mechanisms behind this reduction in events include improvements in endothelial function, modification of the coagulation system, and, most important, early changes in the autonomic nervous system.3,4 In addition to defibrillator therapy, which Solomon and colleagues discuss eruditely, we suggest that consideration be given to the encouragement of early initiation of cardiac rehabilitation as a cost-effective intervention to reduce the incidence of sudden death from cardiac causes.5
5 ReferencesAmit Khera, M.D.
Benjamin D. Levine, M.D.
University of Texas Southwestern Medical Center, Dallas, TX 75390
amit.khera@utsouthwestern. edu 1
Taylor RS ,Brown A ,Ebrahim S , et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med 2004;116:682-692
CrossRef | Web of Science | Medline2
Kallio V ,Hamalainen H ,Hakkila J ,Luurila OJ . Reduction in sudden deaths by a multifactorial intervention programme after acute myocardial infarction. Lancet 1979;2:1091-1094
CrossRef | Web of Science | Medline3
Malfatto G ,Facchini M ,Bragato R ,Branzi G ,Sala L ,Leonetti G . Short and long term effects of exercise training on the tonic autonomic modulation of heart rate variability after myocardial infarction. Eur Heart J 1996;17:532-538
Web of Science | Medline4
Hull SS Jr ,Vanoli E ,Adamson PB ,Verrier RL ,Foreman RD ,Schwartz PJ . Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia. Circulation 1994;89:548-552
Web of Science | Medline5
Ades PA ,Pashkow FJ ,Nestor JR . Cost-effectiveness of cardiac rehabilitation after myocardial infarction. J Cardiopulm Rehabil 1997;17:222-231
CrossRef | Medline
To the Editor:
Solomon et al., in the report on this study demonstrating the increased risk of sudden death among patients with left ventricular dysfunction or heart failure in the first 30 days after myocardial infarction, note in the Discussion several measures that can identify patients at highest risk for sudden death in the first year after myocardial infarction. The authors neglect, however, to mention T-wave alternans. Studies1,2 have demonstrated a correlation between the presence of T-wave alternans and future arrhythmic events as well as a strong relationship between the absence of T-wave alternans and arrhythmia-free survival. Furthermore, it has been shown that T-wave alternans is a good predictor of arrhythmia-free survival in patients with heart failure.3 Most relevantly, an evaluation of T-wave alternans enhances the prognostic value of the ejection fraction with respect to sudden death from cardiac causes after myocardial infarction.4 Perhaps patients who have recovered from their myocardial infarctions should undergo testing of T-wave alternans to best identify those at highest risk for sudden death from cardiac causes.
4 ReferencesAvrum G. Jacobs, M.D.
University of Chicago, Chicago, IL 60637
ajacobs@medicine.bsd. uchicago. edu 1
Rosenbaum DS ,Jackson LE ,Smith JM ,Garan H ,Ruskin JN ,Cohen RJ . Electrical alternans and vulnerability to ventricular arrhythmias. N Engl J Med 1994;330:235-241
Full Text | Web of Science | Medline2
Gold MR ,Bloomfield DM ,Anderson KP , et al. A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification. J Am Coll Cardiol 2000;36:2247-2253
CrossRef | Web of Science | Medline3
Klingenheben T ,Zabel M ,D'Agostino RB ,Cohen RJ ,Hohnloser SH . Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure. Lancet 2000;356:651-652
CrossRef | Web of Science | Medline4
Ikeda T ,Saito H ,Tanno K , et al. T-wave alternans as a predictor for sudden cardiac death after myocardial infarction. Am J Cardiol 2002;89:79-82
CrossRef | Web of Science | Medline
Author/Editor Response
Although VALIANT highlighted the risk of unexpected sudden death from cardiac causes in the early period after myocardial infarction, we are left with many challenges regarding both the identification of patients at highest risk and the formulation of therapies to reduce this risk. Dr. Pitt and Drs. Zijlstra and van der Horst point out that eplerenone and reperfusion therapy, respectively, reduce sudden death from cardiac causes after infarction; indeed, other therapies (e.g., beta-blockers and angiotensin-converting–enzyme inhibitors) that decrease the rate of death from cardiovascular causes also reduce the rate of sudden death from cardiac causes.1,2 Until more specific therapies to prevent sudden death after myocardial infarction are developed, we agree that combining therapies that are already known to be effective is an essential part of a prevention strategy in the high-risk, early post–myocardial infarction period identified in VALIANT.
Another approach would be to identify more effectively high-risk patients who should receive intensive therapy. Although we did not have measures of electrical instability, such as T-wave alternans, in VALIANT, it is not clear that this or other new assessments have proved robust enough for routine clinical use.
How we might reduce this risk of sudden death after infarction beyond the use of currently proven approaches remains an even greater challenge. Although exercise training, as suggested by Drs. Khera and Levine, may offer long-term benefits in the general post–myocardial infarction population, we could not be certain that exercise during this vulnerable period by patients with heart failure, left ventricular dysfunction, or both, would not increase the risk of sudden death from cardiac causes.3 Much of the progress to be made in the prevention of sudden death from cardiac causes will depend on new technological innovations, but it is also urgent that the role of therapy with implantable cardioverter–defibrillators be evaluated in larger, more definitive clinical trials, since the only major trial involving patients within several months after myocardial infarction did not show a benefit.4 By highlighting an underrecognized, time-sensitive clinical problem, the results of VALIANT and other data5 define a challenge to the cardiovascular community to identify the patients at highest risk, along with effective, tolerable, and cost-effective therapies that can protect these patients during the early, vulnerable period.
5 ReferencesScott D. Solomon, M.D.
Brigham and Women's Hospital, Boston, MA 02115
ssolomon@rics.bwh. harvard. edu Robert M. Califf, M.D.
Duke University Medical Center, Durham, NC 27710Marc A. Pfeffer, M.D., Ph.D.
Brigham and Women's Hospital, Boston, MA 02115for the VALIANT Investigators
1
Domanski MJ ,Exner DV ,Borkowf CB ,Geller NL ,Rosenberg Y ,Pfeffer MA . Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction: a meta-analysis of randomized clinical trials. J Am Coll Cardiol 1999;33:598-604
CrossRef | Web of Science | Medline2
Solomon SD ,Wang D ,Finn P , et al. Effect of candesartan on cause-specific mortality in heart failure patients: the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program. Circulation 2004;110:2180-2183[Erratum, Circulation 2005;111:378.]
CrossRef | Web of Science | Medline3
Albert CM ,Mittleman MA ,Chae CU ,Lee I-M ,Hennekens CH ,Manson JE . Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 2000;343:1355-1361
Full Text | Web of Science | Medline4
Hohnloser SH ,Kuck KH ,Dorian P , et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-2488
Full Text | Web of Science | Medline5
Yap YG ,Duong T ,Bland M , et al. Temporal trends on the risk of arrhythmic vs. non-arrhythmic deaths in high-risk patients after myocardial infarction: a combined analysis from multicentre trials. Eur Heart J 2005;26:1385-1393
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Solomon and his colleagues also concluded that there were no clinically useful factors discriminating patients in their study who died suddenly from those who did not. Drs. Zijlstra and van der Horst comment on the important influence of reperfusion therapy on prognosis after myocardial infarction. No one contests the importance of rapid reperfusion with regard to long-term survival after infarction. Drs. Zijlstra and van der Horst are concerned about the relatively low rate of primary reperfusion therapy in VALIANT. The reality is that a large number of patients with acute myocardial infarction (at least 50 percent in North America) do not receive primary angioplasty or thrombolytic therapy, for a variety of reasons. However, to compare mortality in an unselected series of patients receiving primary angioplasty, in which less than 10 percent were assigned a Killip class higher than 1,1 to a population selected for significant left ventricular dysfunction or heart failure (in the Solomon study) is inappropriate.
1 ReferencesAlfred E. Buxton, M.D.
Brown Medical School, Providence, RI 02806
alfred_buxton@brown.edu 1
Simes RJ ,Topol EJ ,Holmes DR Jr , et al. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion: importance of early and complete infarct artery reperfusion. Circulation 1995;91:1923-1928
Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Andreas Rolf, Birgit Assmus, Volker Schächinger, Johannes Rixe, Susanne Möllmann, Helge Möllmann, Stefanie Dimmeler, Andreas M. Zeiher, Christian W. Hamm, Thorsten Dill. (2011) Maladaptive hypertrophy after acute myocardial infarction positive effect of bone marrow-derived stem cell therapy on regional remodeling measured by cardiac MRI. Clinical Research in Cardiology 100:11, 983-992
CrossRef2
Jeffrey J. Goldberger, Rod Passman. (2009) Implantable Cardioverter-Defibrillator Therapy After Acute Myocardial Infarction. Journal of the American College of Cardiology 54:22, 2001-2005
CrossRef3
Thorsten Dill, Volker Schächinger, Andreas Rolf, Susanne Möllmann, Holger Thiele, Harald Tillmanns, Birgit Assmus, Stefanie Dimmeler, Andreas M. Zeiher, Christian Hamm. (2009) Intracoronary administration of bone marrow-derived progenitor cells improves left ventricular function in patients at risk for adverse remodeling after acute ST-segment elevation myocardial infarction: Results of the Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction study (REPAIR-AMI) cardiac Magnetic Resonance Imaging substudy. American Heart Journal 157:3, 541-547
CrossRef4
Daniel P. Davis, Roger Fisher, Steven Aguilar, Marcelyn Metz, Ginger Ochs, Lana McCallum-Brown, Prasanthi Ramanujam, Colleen Buono, Gary M. Vilke, Theodore C. Chan, James V. Dunford. (2007) The feasibility of a regional cardiac arrest receiving system. Resuscitation 74:1, 44-51
CrossRef
