Heart failure with preserved ejection fraction: molecular pathways of the aging myocardium

Abstract

Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, HFpEF is now as common as heart failure with reduced ejection fraction. We now have many successful treatments for heart failure with reduced ejection fraction, while specific treatment options for HFpEF patients remain elusive. The lack of treatments for HFpEF reflects our very incomplete understanding of this constellation of diseases. There are many pathophysiological factors in HFpEF, but aging appears to play an important role. Here, we propose that aging of the myocardium is itself a specific pathophysiological process. New insights into the aging heart, including hormonal controls and specific molecular pathways, such as microRNAs, are pointing to myocardial aging as a potentially reversible process. While the overall process of aging remains mysterious, understanding the molecular pathways of myocardial aging has never been more important. Unraveling these pathways could lead to new therapies for the enormous and growing problem of HFpEF.

Keywords: aging; diastolic dysfunction; heart failure, diastolic.

Figure 1. Aging itself leads to molecular changes that contribute to diastolic impairment

Age is associated with systemic changes and myocardial molecular dysfunction that translate into structural changes believed to contribute to HFpEF.

Figure 2. New molecular pathways in aging biology could lead to new treatments of age-related diastolic heart failure

Existing therapies for systolic heart failure have been unsuccessful at treating HFpEF. Novel therapeutic pathways including microRNAs, metabolic factors and age-dependent circulating hormones offer the new opportunities for developing successful treatments.