NEAT HFpEF: Organic nitrates fail to deliver

Heart failure with preserved ejection fraction (HFpEF) has emerged as a major cause of cardiovascular morbidity and mortality in last decades.1 The incidence of HFpEF continues to rise and currently it accounts for approximately half of all patients with HF, with morbidity, mortality, and health care costs on par with HF with reduced EF (HFrEF).1,2 HFpEF remains among the most challenging of clinical syndromes for the clinician and scientist, with a multitude of proposed mechanisms involving the heart and other organs and complex interplay with common co-morbidities.2 Unfortunately and to date, there is no effective form of therapy for such patients. The therapeutic picture for HFpEF has been less favorable than HFrEF. Other than an emphasis on rigorous control of hypertension, atrial fibrillation, and fluid retention, there is relatively little new that can be offered to those patients. Regular exercise is one of the few interventions which may offer modest improvement in peak exercise capacity in such patients – as evident in the PARIS study.3 The apparent failure of pharmacotherapy stems from the fact that HFpEF can be multifactorial and the molecular pathways remain largely undefined.