HFpEF: cardiovascular abnormalities not just comorbidities.

T wenty-five years ago, the understanding of heart failure (HF) was straightforward. HF was a clinical syndrome due to left ventricular (LV) systolic dysfunction apparent as a reduced ejection fraction (EF). Based on this understanding , large randomized trials were conducted using an EF<0.30 or 0.35 as a key entry criterion. These studies demonstrated that the use of angiotensin-converting enzyme inhibitors, β-adrenergic blockers, aldosterone blockers, and cardiac resynchronization improved morbidity and mortality in patients with HF and a reduced EF (HFrEF). 1 The benefit of these interventions (except for aldosterone blockade) was associated with reversal of the LV dilation (eccentric remodel-ing) present in HFrEF. 2 In contrast, the use of positive inotro-pic agents to improve systolic function was either of no benefit or actually detrimental in HFrEF. 1 This suggested that there was more to HF than just systolic dysfunction. The concept that all HF was due to systolic dysfunction apparent as a reduced EF was further challenged by the subsequent recognition that HF occurs in patients with the entire range of EFs, including EF>0.50, an EF that is in the normal or near-normal range (ie, preserved EF). 3 Many features of the HF syndrome are similar across the EF spectrum including elevated left atrial pressure, abnormal LV filling dynamics, neurohormonal activation, dyspnea, impaired exercise tolerance , frequent hospitalization, and reduced survival. There are also clear clinical differences between HF with a preserved EF (HFpEF) and HFrEF. Patients with HFpEF are older, more likely to be women, less likely to have ischemia, and there is a very strong association with systolic hyperten-sion. In addition, there are differences in cardiac structure and function. 6,7 In HFrEF, the LV is dilated with eccentric remodeling. In contrast, the LV end-diastolic volume is not increased relative to the stroke volume in HFpEF, and concentric remodeling (with or without LV hypertrophy) is present in many patients. In addition, in HFrEF, LV systolic elastance is reduced and arterial elastance is elevated so that there is impaired ventricular–vascular coupling. In contrast, both LV and arterial elastance are increased in HFpEF so that the coupling between them is preserved. In fact, the presence of a normal EF indicates that the coupling of the LV and arterial system is nearly optimal to convert the energy of contraction into the stroke work. Thus, arterial vasodilation improves LV systolic performance in HFrEF, but not in HFpEF. 12 Patients with both HFpEF …