Diastolic dysfunction

Abstract

Despite the growing number of patients affected, the understanding of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) is still poor. Clinical trials, largely based on successful treatments for systolic heart failure, have been disappointing, suggesting that HFpEF has a different pathology to that of systolic dysfunction. In this review, general concepts, epidemiology, diagnosis, and treatment of diastolic dysfunction are summarized, with an emphasis on new experiments suggesting that oxidative stress plays a crucial role in the pathogenesis of at least some forms of the disease. This observation has lead to potential new diagnostics and therapeutics for diastolic dysfunction and heart failure caused by diastolic dysfunction.

Figure 1

Relationship of diastolic dysfunction to HFpEF and HFrEF. Diastolic heart failure is a subset of HFpEF, diastolic dysfunction can exist in HFrEF, and many patients with diastolic dysfunction are asymptomatic. HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.

Figure 2

Major risk factors for diastolic dysfunction, which can lead to asymptomatic or symptomatic diastolic dysfunction. HTN, hypertension; LVH, left ventricular hypertrophy.

Figure 3

Selected possible mechanisms of diastolic dysfunction. Hypertension (HTN) and diabetes lead to oxidative modification of proteins including cMyBP-C and a decreased myofilament relaxation rate. Targeted antioxidants appear to prevent or treat oxidant stress-induced diastolic dysfunction in animal models, and circulating modified cMyBP-C may serve as a biomarker of disease. Independent of myocyte biology, increased extracellular matrix may cause abnormal LV relaxation. BH4, tetrahydrobiopterin; cMyBP-C, cardiac myosin binding protein C; CTGF, connective tissue growth factor; MMP, matrix metalloprotease; NOS, nitric oxide synthase; ROS, reactive oxygen species; TIMP, tissue inhibitors of MMP; TGF, transforming growth factor.