Rate-Adaptive Pacing for Heart Failure With Preserved Ejection Fraction

In this issue of JAMA, Borlaug and colleagues 1 report the results of a important clinical trial, which are likely to alter paradigms and clinical guidelines for heart failure with preserved ejection fraction (HFpEF). 1 The prevalence of this syndrome has progressively increased, and HFpEF has become the most common form of heart failure, particularly in older persons, women, and Black individuals.2,3 It affects more than 3 million people in the US and is associated with severe symptoms of exertional dyspnea and fatigue (exercise intolerance), impaired health-related quality of life, severely reduced exercise capacity (the primary outcome in the current trial), and increased rates of rehospitalizations and death.2,3 HFpEF is not only one of the most common cardiovascular disorders but also one of the most poorly understood.Many initial assumptions regarding the pathophysiology of HFpEF have been disproved by careful mechanistic studies.3 Collectively, these studies support that HFpEF is a systemic syndrome, initiated and promoted by undetermined circulating factors but likely related to systemic inflammation arising from excess, maladapted adipose tissue and resulting in widespread mitochondrial dysfunction and loss of tissue capillarity, which are critical to organ perfusion and energy metabolism. 2 These in turn impair the function not only of the heart but of other organs, such that HFpEF is now viewed as a quintessential systemic, multiorgan disorder.2,3