Why Don’t We Have Proven Treatments for HFpEF?
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The lack of effective treatments for heart failure with preserved ejection fraction represents a large and growing unmet need in cardiology today. A critical obstacle to therapeutic innovation in heart failure with preserved ejection fraction has been the absence of animal models that accurately recapitulate the complexities of the human disease. Here, we propose that more comprehensive multi organ system and functional phenotyping of preclinical models is essential if we are to maximize our chances of discovering and validating novel targets for effective therapeutic development in heart failure with preserved ejection fraction.
At this time in human history, we are witnessing an unprecedented aging of populations around the world. By 2050, the number of individuals >65 years will nearly triple to ≈1.5 billion, accounting for ≈16% of the world’s population.1 Although cardiology, and medicine more generally, can appropriately take enormous pride in the progress made in extending human lifespan, we must also recognize that as our populations age, so will the clinical landscape.
Perhaps the quintessential example of how the evolution of human longevity is changing the face of medicine is the emerging epidemic of heart failure with preserved ejection fraction (HFpEF). Often described as a disease of the elderly, trends in HFpEF have closely paralleled the change in global ageing demographics. In the United States, the prevalence of HFpEF, relative to heart failure with reduced ejection fraction (HFrEF), is increasing at an alarming rate of 1%/y with the overwhelming majority of patients being >65 years.2 Importantly, the prognosis for HFpEF remains poor with mortality rates comparable with HFrEF.2
Unfortunately, although tremendous strides have been made in improving mortality in HFrEF, no pharmacological therapy, including our armament of neurohormonal antagonists, has demonstrated similar benefits in HFpEF. In fact, no large-scale clinical trial of medical therapy has …