doi: 10.1161/CIRCHEARTFAILURE.108.796250
Editorials |
Does It Matter Why and How Patients With Heart Failure Die?
A Debate That Lives On
From the Division of Cardiology, Saint Louis University School of Medicine, St Louis, Mo.
Correspondence to Paul J. Hauptman, MD, Saint Louis University Hospital, 3635 Vista Ave, St Louis, MO 63110. E-mail hauptmpj{at}slu.edu
Key Words: Editorials • heart failure • death
Our interest in death and illness is nothing but a way of expressing an interest in life" —Thomas Mann, The Magic Mountain.1
Is the retort to the declarative statement that "dead is dead"2 now dead? Simply answered, not at all. In the heart failure discipline, whether data are derived from clinical trials, registries, or epidemiological studies, delineating "why" and "how" patients die remains a keen interest for investigators. Cross-reference "cause of death" with "heart failure" in an online publication database, and you will find almost 60 papers in the 10 years since the "dead is dead" issue was raised. Why are we so engaged in this task? Perhaps it is because the underlying goals are sound: to understand the impact of interventions according to treatment assignment and to better understand the pathophysiology and natural history of heart failure.
Article see p 91
We have in fact learned a great deal from a long list of studies: For example, patients with nonischemic cardiomyopathy can die of ischemic complications,3 implantable defibrillators may shift death from a sudden arrhythmic cause to progressive heart failure,4 and sudden death is clustered in the early period after myocardial infarction.5 Such analyses can also raise interesting hypotheses or help to demonstrate the robustness of a treatment effect, as, for example, when an intervention reduces both sudden and nonsudden causes of cardiovascular death.6 Many of these concepts apply not only to death as an end point but to any number of other cardiovascular events, such as stroke or nonfatal myocardial infarction.
We also know that there are implicit limitations in all such studies, which are based in part on the lack of availability of comprehensive and relevant clinical data and on the definitions themselves.7 Long the purview of clinical trial events committees, these definitions may not be "user friendly" across clinical trials or be easily translated for use in large epidemiological databases. Even the simplest classification schema, such as arrhythmic death versus circulatory failure, can be criticized because of overlap and difficulties recreating the events that lead to death.8,9 Indeed, the fact that necropsy findings often do not correlate with "best estimates" from clinical data, including medical records,2 leads to even more uncertainty about whether we are really measuring what we think we are measuring. In addition, when it comes to categorizing a death, arguments can reach almost philosophical levels. What constitutes an arrhythmic death? Can a death be sudden if the patient has severe functional limitations and leads a New York Heart Association class IV existence? What does it mean if a drug or intervention causes a redistribution among the various causes of death without meaningfully affecting overall death rates?
Now, in the present issue of Circulation: Heart Failure, Henkel and colleagues10 come into the fray, using data from Olmsted County, Minn, to examine the causes of death in a community cohort with incident heart failure between 1979 and 2002. Great effort was expended to ascertain whether death occurred; the sample is also unusual in that death certificates were completed in the majority of cases by a medical examiner or Mayo Clinic pathologist. Of particular note, death due to noncardiovascular causes increased with time from diagnosis and was more likely among patients with preserved rather than reduced ejection fraction (49% versus 36%). Interestingly, one of the lessons appears to be that although quantitative differences existed between the 2 groups, noncardiovascular causes were remarkably common regardless of ejection fraction, and thus, it appears reasonable to posit that there is a need to address comorbidities to a greater degree than previously appreciated.
Despite these provocative findings, the naysayers can maintain that nothing has fundamentally changed, because we should be thinking more about how patients die than about cause. Indeed, it may be that we have not spent enough time finding out what death with advanced heart failure actually looks like.11,12
If that is the case, should we continue to explore the cause of death in heart failure? A reasonable argument can be made that we must first establish some uniformity of definitions, even while acknowledging the artificiality of such an exercise, at the very least to facilitate study-to-study comparisons. This may allow for some unexpected benefits, including modification of risk-stratification models that currently predict all-cause death.13,14 Second and most importantly, if we gain better insight into what patients want or expect from chronic illness, we can certainly justify further study.15 While doing so, we should avoid the temptation in clinical trials and registries to examine the cause of death in small subgroups, especially if they are not prespecified. Furthermore, analyses should have meaning beyond the fulfillment of a regulatory requirement. Patients (and their physicians who care for them) should know more about what to expect as heart failure progresses and how various therapeutic options can affect not only the duration and quality of life but the quality of death as well. Therefore, "why" and "how" patients with heart failure die matter, not only to us on a macroscopic level but almost certainly to the patients who live with heart failure but may or may not die of it.
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Acknowledgments |
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Disclosures
None.
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Footnotes |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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References |
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 TOP References |
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- Mann T. The Magic Mountain. Woods JE, translator. New York, NY: Knopf; 1995: 486.
- Gottlieb SS. Dead is dead: artificial definitions are no substitute. Lancet. 1997; 349: 662–663.[CrossRef][Medline]
- Poole-Wilson PA, Uretsky BF, Thygesen K, Cleland JGF, Massie BM, Ryden L. Mode of death in heart failure: findings from the ATLAS trial. Heart. 2003; 89: 42–48.
[Abstract/Free Full Text] - Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002; 346: 877–883.
[Abstract/Free Full Text] - Solomon SD, Zelenkofske S, McMurray JJ, Finn PV, Velazquez E, Ertl G, Harsanyi A, Rouleau JL, Maggioni A, Kober L, White H, Van de Werf F, Pieper K, Califf RM, Pfeffer MA; Valsartan in Acute Myocardial Infarction Trial (VALIANT) Investigators. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med. 2005; 352: 2581–2588.
[Abstract/Free Full Text] - Remme WJ, Cleland JG, Erhardt L, Spark P, Torp-Pedersen C, Metra M, Komajda M, Moullet C, Lukas MA, Poole-Wilson P, Di Lenarda A, Swedberg K. Effect of carvedilol and metoprolol on the mode of death in patients with heart failure. Eur J Heart Fail. 2007; 9: 1128–1135.[CrossRef][Medline]
- Narang R, Cleland JG, Erhardt L, Ball SG, Coats AJ, Cowley AJ, Dargie HJ, Hall AS, Hampton JR, Poole-Wilson PA. Mode of death in chronic heart failure: a request and proposition for more accurate classification. Eur Heart J. 1996; 17: 1390–1403.
[Abstract/Free Full Text] - Packer M. Lack of relation between ventricular arrhythmias and sudden death in patients with chronic heart failure. Circulation. 1992; 85 (suppl): I-50–I-56.[Medline]
- Cleland JGF, Massie B, Packer M. Sudden death in heart failure: vascular or electrical? Eur J Heart Fail. 1999; 1: 41–45.[CrossRef][Medline]
- Henkel DM, Redfield MM, Weston SA, Gerber Y, Roger VL. Death in heart failure: a community perspective. Circ Heart Fail. 2008; 1: 91–97.
[Abstract/Free Full Text] - Teuteberg JJ, Lewis EF, Nohria A, Tsang SW, Fang JC, Givertz MM, Jarcho JA, Mudge GH, Baughman KL, Stevenson LW. Characteristics of patients who die with heart failure and a low ejection fraction in the new millennium. J Card Fail. 2006; 12: 47–53.[CrossRef][Medline]
- Derfler MC, Jacob M, Wolf RE, Bleyer F, Hauptman PJ. Mode of death from congestive heart failure: implications for clinical management. Am J Ger Cardiol. 2004; 13: 299–306.[CrossRef]
- Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV. Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. J Am Med Assoc. 2003; 290: 2581–2587.
[Abstract/Free Full Text] - Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB, Anand I, Maggioni A, Burton P, Sullivan MD, Pitt B, Poole-Wilson PA, Mann DL, Packer M. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation. 2006; 113: 1424–1433.
[Abstract/Free Full Text] - Califf RM, Vidaillet H, Goldman L. Advanced congestive heart failure: what do patients want? Am Heart J. 1998; 135: S320–S326.[CrossRef][Medline]
Related Article
- Death in Heart Failure: A Community Perspective
- Danielle M. Henkel, Margaret M. Redfield, Susan A. Weston, Yariv Gerber, and Véronique L. Roger
Circ Heart Fail 2008 1: 91-97.[Abstract] [Full Text] [PDF]
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