Pulmonary hypertension in heart failure with preserved ejection fraction: a plea for proper phenotyping and further research.

Abstract

Heart failure (HF) with preserved ejection fraction (HFpEF) is a common disease affecting the elderly in particular. Up to 80% of these patients develop pulmonary hypertension (PH), which is associated with worse symptoms and increased mortality.1 It is a matter of concern that drugs approved for pulmonary arterial hypertension (PAH) are sometimes used in such patients despite insufficient data for their safety and efficacy. On the other hand, the impact of PH and right ventricular (RV) dysfunction on morbidity and mortality in HFpEF call for proper attention both at the clinical and scientific level. Here we discuss the clinical problem, pathophysiology, diagnostic shortfalls, gaps in evidence, and future strategies for PH-HFpEF. HFpEF is currently the dominant form of HF in aging societies globally. Epidemiologic trends over the past two decades showed that HFpEF increased relative to HF with reduced ejection fraction (HFrEF).2 Overall mortality did not improve over time, with more than 50% dead in 5 years from diagnosis.2 Differences between epidemiologic and trial populations of HFpEF reflect potential selection bias and lack of uniformity of diagnostic criteria. Epidemiologic studies utilize the most widely applicable definition of HFpEF: (i) clinically diagnosed HF (e.g. by Framingham criteria) and (ii) preserved EF (e.g. ≥50%).2 While such definitions capture the broad unselected population with the syndrome of HFpEF, they are rarely specific enough for clinical trials since the accurate diagnosis relies on symptoms and signs of HFpEF, both non-discriminating particularly in elderly patients with multiple comorbidities. The ESC guidelines included additional criteria, i.e. elevated levels of natriuretic peptides or objective evidence of left ventricular (LV) hypertrophy, left atrial enlargement, and/or LV diastolic dysfunction.3 Yet, the diagnosis of HFpEF remains difficult as many presumably healthy elderly patients fulfil at least some of these echocardiographic criteria. Invasive demonstration of increased pulmonary …