Heart Failure with Preserved Ejection Fraction: Persistent Diagnosis, Therapeutic Enigma

Abstract

Heart failure with preserved ejection fraction (HFPEF) is increasing in prevalence with the aging of the population, and morbidity and mortality rates are comparable to that of heart failure with reduced ejection fraction (HFREF). The diagnosis can be difficult to make, especially in older adults, stemming from the presence of multiple comorbid illnesses with confounding symptoms. New diagnostic tools have resulted in guidelines proposed to define and diagnose HFPEF. Recent literature focusing on the pathophysiology underlying this disease suggests multiple mechanisms are involved in the generation of the phenotype, such as abnormal relaxation and ventricular-vascular coupling, chronotropic incompetence, volume overload, and redistribution and /or endothelial dysfunction. Currently, no clinically proven treatments are shown to decrease morbidity and mortality in this population; however, there may be a novel multidisciplinary and multistage treatment strategy that can be studied to address this complex disease which incorporates pharmacologic and non-pharmacologic therapeutics.

Conflict of interest statement

Disclosure No conflicts of interest relevant to this article were reported.

Figures

Fig. 1

Alternative clinical trial designs for older adult subjects with heart failure with preserved ejection fraction (HFPEF). a Flow chart of traditional randomized placebo-controlled clinical trial (R). b Trial in which several interventions (numbered in the example as 1, 2, and 3) are instituted sequentially with assessment of outcome of interest in comparison to control. Interventions could include diet and lifestyle modifications (eg, salt restriction or cardiac rehabilitation), pharmacologic therapy (eg, treatment aimed at cardiovascular target or non-cardiac target, such as chronic pain) and/or treatment of extra-cardiac factors (eg, mood disorders, sleep-disordered breathing, diabetes). c Trial design in which cohort of interest is randomized to various interventions (indicated by 1, 2 and 3) and the order of interventions is varied in order to evaluate the efficacy of multiple interventions, which are likely to be required in complex clinical conditions such as heart failure with a preserved ejection fraction and to determine if the order of treatment intervention has an effect on outcomes