Abstract
BackgroundHeart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.MethodsTwenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.ResultsWhen compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max.ConclusionsMyocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.
Highlights
Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation and lipotoxicity
The diagnostic criteria of HF with preserved ejection fraction (HFpEF) is based on clinical features of HF and normal left ventricular (LV) ejection fraction (EF) together with evidence of diastolic dysfunction, LV hypertrophy, left atrial (LA) enlargement and raised plasma brain natriuretic peptides (BNP) according to the current European Society of Cardiology (ESC) guidelines [3]
In addition we found that reduced PCr/adenosine triphosphate (ATP) correlated with impaired peak systolic circumferential strain (r = − 0.55, p = 0.002) but no significant correlations with age, body mass index (BMI), systolic blood pressure (SBP) or BNP
Summary
Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. Almost half of all patients who present with clinical features of heart failure (HF) have preserved left ventricular (LV) ejection fraction (HFpEF). Its prevalence is on the rise, representing a major burden for health care services [1]. These patients are often elderly, female with multiple co-morbidities such as hypertension and obesity, and typically show a non-dilated LV, concentric remodelling and abnormal diastolic function [2]. The diagnostic criteria of HFpEF is based on clinical features of HF and normal LV ejection fraction (EF) together with evidence of diastolic dysfunction, LV hypertrophy, left atrial (LA) enlargement and raised plasma brain natriuretic peptides (BNP) according to the current European Society of Cardiology (ESC) guidelines [3]. There is a real need for novel and, effective therapeutic targets to improve the management of the increasing number of patients with HFpEF
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