November 28, 2012

Heart Failure TherapyWhat Should Clinicians Believe?

Author Affiliations

Author Affiliations: University Hospitals Case Medical Center, Cleveland, Ohio.

JAMA. 2012;308(20):2144-2146. doi:10.1001/jama.2012.45418

When you come to a fork in the road, take it.—Yogi Berra

Heart failure with preserved ejection fraction is a syndrome of volume overload and exertional intolerance marked by myocardial stiffness.1 Sophisticated investigations have also delineated multiple other pathophysiologic mechanisms, including vascular and renal dysfunction, chronotropic incompetence, energetic and metabolic derangements, and contractile abnormalities.2,3 However, other than the clinical similarities with heart failure with reduced ejection fraction,4 there is little evidence to support the notion that the 2 conditions are related pathophysiologically. Moreover, these disorders appear to be distinct and not part of a continuum of disease.5 Although basic science, observational studies, and clinical trials support heart failure with reduced ejection fraction as a condition of neurohormonal activation, the same is not true for heart failure with preserved ejection fraction. In fact, renin-angiotensin system antagonism with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in heart failure with preserved ejection fraction has not been effective—although not harmful—in randomized trials to date.69 Yet, these trials have significant limitations, including issues of power, selection bias, and crossovers.10

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