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J Am Coll Cardiol, 2003; 41:224-226
© 2003 by the American College of Cardiology Foundation
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EDITORIAL COMMENT

The less familiar face of heart failure*

Mariell Jessup, MD, FACC{dagger},*

{dagger} Heart Failure/Transplant Program, Cardiovascular Disease, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

* Reprint requests and correspondence: Dr. Mariell Jessup, Heart Failure/Transplant Program, 6 Penn Tower, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
jessupm{at}uphs.upenn.edu

Nearly five million Americans have heart failure (HF) today, an incidence approaching 10 per 1,000 population after the age of 65 years. Heart failure is the reason for at least 20% of all hospital admissions in persons above the age of 65 years; hospitalizations for HF have increased by 159% (1). Substantial efforts have been made to identify and treat those factors that predict recurrent hospitalization for HF, in addition to the identification of therapies that improve overall survival. Indeed, over the past decade, multiple clinical trials have unequivocally demonstrated a significant reduction in mortality for patients with systolic HF. Simultaneously, however, large epidemiologic or cohort registries have not observed an equivalent impact on overall death rates from HF (2–4). Clearly, as has been noted by a number of investigators, the patients entered into recent clinical trials of HF have not been entirely representative of the "typical" patient with HF in the U.S. (5).

It is in the context of a further description of patients with HF who are utilizing our hospitals that the study by Masoudi et al. (6) in this issue of the Journal is of great interest. They abstracted charts from 37,500 Medicare beneficiaries hospitalized primarily for HF from the National Heart Failure Project (NHF) database. They report three important observations.

  1. Only 57% of patients had an assessment of left ventricular function to determine ejection fraction (EF) during their index hospitalization. Guidelines for the management of HF have outlined the need for a measurement of ventricular function since 1994 (7).
  2. Of the 19,710 patients with a documented EF, 66% had HF associated with systolic dysfunction. Approximately a third of all patients had HF with a preserved EF (an EF of ≥50% in this study), a syndrome that has been termed diastolic HF (8,9).
  3. Diastolic HF was present almost twice as frequently in women as in men. This correlation was consistent across a wide range of patient characteristics, including age and etiology of cardiac disease.

These investigators are not the first to report the higher prevalence of diastolic HF in elderly women, as the authors acknowledge in their discussion. Likewise, the incidence of diastolic HF in hospitalized patients is also not a new observation. However, this analysis comprises a several-fold higher number of patients than previous studies, and Masoudi et al. (6) have attempted to eliminate potential flaws or biases of previous, smaller studies.

There are a number of implications in these data, some of which have been emphasized by the authors. Table 1 depicts the age and gender characteristics of some representative cardiovascular trials, the majority of which were multicenter, randomized studies involving patients with systolic dysfunction (10–18), with or without (19–22) symptomatic HF. Other studies depicted in Table 1 examine the cause of unexplained cardiomyopathy (23), or those factors that best predict survival after the onset of HF (24). Two pivotal trials examining the impact of intervention in high-risk populations with vascular disease or acute coronary syndromes are also included (25,26). The mean age of the populations studied was usually <65 years, and women were typically underrepresented. (The number of women from races other than Caucasian is not usually reported.) Even in trials structured to investigate the response of an older population (14), or in cardiovascular syndromes such as aortic stenosis (27), often associated with elderly women, fewer than half of the participants were female. It is only in the large population-based studies that the natural history of the elderly and women has been explored (2,4,28–30).


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  		Table 1 Age and Gender Characteristics of Representative Heart Failure or Cardiovascular Trials

 
Is there any reason to think that elderly patients or women respond differently to therapy for HF? Several studies in Table 1 noted a prognostic impact of age, so that clinical outcome worsened as patients advanced in years (4,23,27). The impact of age on decisions to proceed with thrombolysis or catheter-based intervention after myocardial infarction has become important as a result of clinical trials including very elderly patients. Management algorithms for patients with cardiomyopathy, with or without symptoms, may also need to consider age as a valuable determinant, especially when the cost of defibrillators or ventricular assist devices may be applied. Elderly patients tend to have a higher prevalence of comorbidities, and an increased incidence of adverse effects to medications, in addition to the altered pathophysiology of the aging myocardium and conduction system (31–33).

A growing body of literature suggests that there are gender differences in the biologic response to chronic hypertension, pressure overload such as seen in aortic stenosis, and myocyte loss after myocardial infarction (34). Hypertension and diabetes seem to confer a greater risk of HF for women compared to men, despite the usual finding of less coronary disease in females (35). Conclusive data for the reduction of mortality and morbidity after angiotensin-converting enzyme inhibition exist only for men with HF; beta-blockers appear to be effective for both genders with systolic dysfunction and symptoms of HF (36). Everything from apoptosis to arrhythmias appears to exhibit gender-specific characteristics.

If diastolic HF is often a disease of elderly women (8,9), and we have little information acquired from clinical trials to date about the elderly or about women, it should not be unexpected that there is a mounting sense of urgency to become more familiar with this group of patients (37). To make a meaningful dent in the cost to our economy from HF admissions, we are obligated to begin clinical trials in patients with diastolic HF. Federal efforts to increase the representation of women in clinical trials have been moderately successful, primarily because of a small number of large, single-gender trials involving coronary disease. There has been little change in the gender composition of cohorts in the majority of other studies of cardiovascular disease (38). This could change dramatically if we started to enroll subjects in a trial on diastolic HF.


   Footnotes
 
* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. Back


   References
Top
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