Letter by Psaty et al Regarding Article, “Heart Failure With Recovered Ejection Fraction: Clinical Description, Biomarkers, and Outcomes”
To the Editor:
Basuray and colleagues1 assembled a cross-sectional sample of patients who, having survived heart failure for an average of ≈6 years, were referred to 1 of 3 heart-failure specialty centers. On the basis of echocardiography at enrollment, eligible patients (n=1878) were classified according to current and historical ejection fractions (EF). Those with an EF <50% were classified as heart failure with reduced ejection fraction (HF-REF, n=1523). Among the 355 with EF ≥50%, the authors excluded 57 without available historical data, and classified the rest into 2 groups: (1) EF always ≥50% (HF-PEF, n=122), and (2) EF previously <50% (HF-Recovered, n=176). During an average of 3.6 years of follow-up, the prognosis defined in terms of the composite end point of death, cardiac transplantation, or placement of ventricular assist device was significantly worse for both the HF-REF and HF-PEF patients than for the HF-Recovered patients. The authors conclude that “the HF-Recovered EF population presents a distinct phenotype with biochemical properties and natural history that differ from the traditional HF-REF and HF-PEF populations.” Because of limitations in design, the evidence for this claim is perhaps weaker or less complete than acknowledged.
Although recruiting a convenience sample of referred patients and looking retrospectively to examine recovery of ejection fraction is natural for specialty centers, the optimal method for studying the natural history of heart failure involves assembling an inception cohort of patients at the time of their initial presentation.2 The recruitment of patients at a uniform time early in the course of their disease assures that both those who die and those who recover completely are included in the cohort so that all the new-onset heart failure patients from a defined population contribute information to the natural history of disease and its prognosis. A cross-sectional sample of heart failure patients who have survived 6 years and who are sufficiently ill to require referral to a specialty center may not provide valid unbiased estimates of the relative prognosis among the 3 groups of interest.
An inception-cohort design is especially important in the study of the baseline factors that predict prognosis. Consider, for instance, prognostic factors for patients within any of the HF groups. If a risk factor is associated with a high case fatality rate early in the course of the disease, the susceptible patients are likely to be depleted from the cohort before enrollment, and in longitudinal follow-up of such a cross-sectional sample, the risk factor may be associated with improved long-term prognosis, but primarily by the mechanism of early mortality.
The findings of the study by Basuray and colleagues may be generalizable to heart failure patients in other specialty centers, but perhaps not to those in general cardiology and general medicine, where most cases of HF-PEF are identified and managed. Indeed, referral of HF-PEF cases to tertiary care centers suggests the possibility of greater disease severity or progression than in the general population. Advancing our understanding of the natural history of heart failure phenotypes will require additional studies that use a higher-quality, prospective, inception-cohort design.
Bruce M. Psaty, MD, PhD
Cardiovascular Health Research Unit
Departments of Medicine, Epidemiology, and Health Services
University of Washington
Group Health Research Institute
Group Health Cooperative
Sanjiv J. Shah, MD
Division of Cardiology
Department of Medicine
Northwestern University Feinberg School of Medicine
John Gottdiener, MD
Division of Cardiology
Department of Medicine
University of Maryland
Sources of Funding
This work was supported in part by grants HL078888, HL080295, HL103612, and HL105756 from the National Heart, Lung, and Blood Institute (to Dr Psaty).
Dr Psaty serves on the Data Safety and Monitoring Board for a clinical trial of a device funded by Zoll LifeCor and on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute, the National Institutes of Health. The other authors report no conflicts.
- © 2015 American Heart Association, Inc.
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