The Bear is Out of the Lair: The Emerging Importance of Diastolic Heart Failure

Abstract & Commentary

By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.

Heart failure today is the focus of enormous growth of interest in research, clinical trials, and improved care. A number of factors are responsible for the increasing prominence of congestive heart failure (CHF). The Swan-Ganz catheter, the development of drugs that interact with the renin-angiotensin system, ie, the ACE inhibitors and, subsequently, the ARBs, and the use of β-blockers have been key factors. Echocardiography, allowing for immediate assessment of left ventricular (LV) function, provides an opportunity to differentiate between classic or systolic heart failure vs diastolic heart failure. The recently established Heart Failure Society has contributed to the increasing prominence of CHF, as has the development of new drugs and, recently, device therapy for end-stage CHF patients (bi-ventricular pacing, defibrillators). National treatment guidelines for systolic HF are widely available, but attention to diastolic HF has been limited.

Two database analyses, one from the Mayo Clinic and the other from the University of Toronto, provide useful information about CHF patients with both systolic and diastolic HF. Both demonstrate the importance of diastolic heart failure, as well as emphasizing data that support a poor prognosis for these patients, almost as lethal as systolic HF. These studies are observational, retrospective analyses of outcomes in large groups of patients with clinical CHF, focusing on the differences and similarities between systolic and diastolic HF. Owan and colleagues from the Mayo Clinic analyzed the outcomes of consecutive patients admitted to Mayo hospitals between 1987 and 2001 who were found to have diastolic HF, ie, an ejection fraction (EF) of 50% or greater.1 They found that 4596 patients met appropriate ICD codes, and had an echocardiogram within 30 days of admission. Patients with preserved EF were older, more likely to be female, and had a higher mean body mass index than CHF patients with reduced EF. Half of patients 65 or older had diastolic HF, and 40% of those younger than 65 had preserved EF. Clinical factors common in the preserved LV function cohort include hypertension, diabetes, atrial fibrillation, and/or the presence of structural or coronary heart disease.

Results: Over the 14-year study period, the prevalence of preserved EF increased from 38% to 54%, with no change in the number of individuals with systolic HF. Survival data are striking. Although mortality was higher in the systolic HF cohort, the difference from the preserved EF cohort was small, with survival only 3% lower in the impaired LV function cohort; 29% vs 32% at one year and 65% vs 68% at 5 years. The likelihood of survival increased during the study period for those with reduced EF, but not for the preserved EF cohort. The difference in survival between the 2 groups was greater in individuals younger than 65. Owan et al reviewed the recent literature and note that there has been considerable variability with respect to survival of systolic vs diastolic HF patients. They stress that physician awareness and acceptance of preserved EF as being an adverse marker increased over the study, as more emphasis on diastolic dysfunction has appeared in the literature. They point out that of the studies reporting a greater difference in survival between the 2 types of HF, most included outpatients or hospitalized individuals who were not specifically admitted for CHF, as well as other methodological differences. This study only included hospitalized patients. Owan et al note that overall survival in systolic HF patients is improving, but not in preserved LVEF patients. They call for greater understanding of he pathophysiology of diastolic HF, as well as for the development of "unspecified therapeutic strategies against it." They suggest that current trends suggest that diastolic heart failure may become the dominant form of CHF.

The Canadian study, while of different design, reaches essentially the same conclusions. Bhatia and colleagues from Toronto assessed the one-year status of HF patients admitted to 103 hospitals from 1999 to 2001, characterized by EF status.2 Follow-up data were documented in patients with low LVEF (< 40%) and preserved LVEF (> 50%). Subjects with an EF of 40-50% were excluded. The primary end-point was death from any cause following index hospitalization for heart failure. Secondary outcomes included 30-day and one-year re-admission rates.

Results: Of the 10,000 patients admitted with CHF, the study group was narrowed to 2450 eligible subjects; intermediate EF patients were not included. As with the Mayo Clinic cohort, preserved EF patients were older, more likely to be female, had a greater incidence of hypertension and, of interest, had lower rates of modifiable cardiac risk factors. Higher rates of atrial fibrillation and COPD also were found. "The presenting symptoms in patients with preserved EF were largely similar to those in patients with reduced EF." The preserved EF group did have lower rates of acute pulmonary edema, severe HF, or a third heart sound. Mortality at 30 days was only slightly higher in the reduced EF group; 7.1% vs 5.3% (ns). At one year, mortality rates were 25.5% and 22.2%, respectively (P = 0.07). Re-admission rates were only slightly higher in the reduced EF group; 16.1% vs 15.5% at one year. Predictors of death in the preserved EF group included age, systolic blood pressure, history of vascular disease, and number of adverse renal markers. Bhatia et al stress that one third of patients admitted with HF for the first time had preserved EF and, in contrast to other studies, had a high rate of diabetes and CAD. They suggest that sub-clinical myocardial infarction/ischemia may play a role in some of these individuals. Physical exam findings and symptoms were not different. Thus, preserved EF patients "had complication rates that were similar to those… with a reduced EF, including in their type of clinical presentation." Such patients were less likely to get primary care from a cardiologist.

Bhatia et al discuss the considerable variation in the literature regarding systolic vs diastolic HF and mortality. All patients had a similarity of signs and symptoms upon presentation. There were no clinical markers other than the echocardiogram that distinguished the 2 groups who had similar in-hospital complications and one-year mortality rates. The absolute mortality rate in the diastolic HF cohort was higher than previously reported studies.

An insightful editorial by Dr. Aurigemma is well worth reading.3 He discusses the terminology, ie, preserved ejection fraction vs diastolic heart failure, and appears to prefer the latter. He reminds the reader that "ejection fraction is not a good predictor of clinical disability," and stresses the abnormal diastolic properties of the LV. He also focuses on the somewhat surprising finding that survival rates were only slightly better at one and 5 years for the diastolic HF group. He points out some limitations of the 2 studies, including the ethnic similarities of the populations and the fact that out-patients were not included. The Canadian study "is a reminder that we are facing a lethal condition, regardless of its name." Aurigemma calls for aggressive anti-hypertensive therapy and increased clinical research to determine to best treatment for diastolic HF.

Commentary

Until recently, I had considered diastolic HF to be relatively unusual and significantly more benign than the more common HF with depressed EF. However, the data from these 2 retrospective studies are concordant with worse overall outcome and survival than one would expect, while multiple pharmacologic and device therapies for depressed systolic function patients are changing the natural history of HF in these patients. Experienced clinicians have long recognized that a high quality echocardiogram is essential in the initial assessment of any patient who presents with CHF, in or out of the hospital. Dismissal of the importance of heart failure symptoms in an individual with an EF of 50% or greater is no longer accepted. Rigorous search for risk factors, particularly hypertension, is mandated; while we have no specific therapies, some would suggest that an angiotensin receptor blocker should be included in the regimen of these patients, based in part on the CHARM study. The bad news is that diastolic heart failure does not appear to be particularly amenable to therapeutic interventions. There may be confusion among many physicians regarding the terms diastolic dysfunction or diastolic abnormalities, given the eagerness of echocardiographers to report on E and A wave, abnormalities, relaxation parameters, etc. Diastolic dysfunction is an echo disease, while diastolic heart failure is a clinical syndrome of congestive heart failure with preserved LVEF. The nomenclature remains the subject of debate; Aurigemma favors the older term, diastolic heart failure, but recent guidelines stress the term heart failure with preserved EF. Either would appear acceptable until there is complete consensus. Finally, the striking mortality similarities between systolic and diastolic failure noted in both databases is a sobering wake-up call for those of us who have been dismissive of the clinical importance of patients with a good EF who manifest CHF.

References

1. Owan TE, et al. Trends in Prevalence and Outcome of Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2006;355:251-259.

2. Bhatia RS, et al. Outcome of Heart Failure with Preserved Ejection Fraction in a Population-Based Study. N Engl J Med. 2006;355:260-269.

3. Aurigemma GP. Diastolic Heart Failure—A Common and Lethal Condition by Any Name. N Engl J Med. 2006;355:308-310.