Novel paradigms in the therapeutic management of heart failure with preserved ejection fraction: clinical perspectives

Heart failure with preserved ejection fraction (HFpEF) is a pathological complexity that decreases cardiac output and elevates the ventricular filling pressure. HFpEF is usually misdiagnosed and maltreated. HFpEF is usually correlated with excessive morbidity and mortality. The prevalence of HFpEF is growing, and there is a deficiency of evidence-based therapy, creating challenges for the physician with no effective management guidelines. Moreover, HFpEF is not equivalent to diastolic heart failure as previously thought, as diastolic dysfunction is not the only underlying mechanism related to HFpEF and sometimes may be absent. Several other mechanisms may work in concert to produce HFpEF syndrome, either cardiac related (chronotropic incompetence, a longitudinal left ventricular (LV) systolic dysfunction despite a normal ejection fraction) or extracardiac related (pulmonary hypertension, abnormal ventricular-arterial coupling, abnormal exercise-induced vasodilation, extracardiac volume overload). These complex pathophysiologic mechanisms indicate that HFpEF is heterogeneous and that this syndrome might be related to a vascular or an endothelial dysfunction or might be considered a cardiac manifestation of one or more systemic illnesses. The heterogeneity of HFpEF necessitates excluding many differential diagnoses. In addition, the multiple comorbidities that are inherent to this condition need to be controlled in order to achieve effective management. Taken together, these key mechanisms might contribute to the multiple difficulties in the management of HFpEF patients; these mechanisms also explain why medications used in patients with other heart conditions may or may not be successful in these patients. Novel therapies and clinical trials including paradigm shifts in therapeutic management are needed to effectively manage HFpEF. The current review article sheds light on novel paradigms related to pathologies, diagnoses, and strategies, along with some proposed recommendations and clinical options for effective management of HFpEF.