TY - JOUR T1 - Heart failure therapy: What should clinicians believe? AU - Fang JC Y1 - 2012/11/28 N1 - 10.1001/jama.2012.45418 JO - JAMA SP - 2144 EP - 2146 VL - 308 IS - 20 N2 - 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.6- 9 Yet, these trials have significant limitations, including issues of power, selection bias, and crossovers.10 SN - 0098-7484 M3 - doi: 10.1001/jama.2012.45418 UR - http://dx.doi.org/10.1001/jama.2012.45418 ER -