Sexual dimorphism in the relationships between intramyocardial fat, myocardial fibrosis, and exercise intolerance in heart failure with preserved ejection fraction.

Ng ACT ，Dong X ，Koepp KE ，Obokata M ，Sorimachi H ，Galloway G ，Araoz P ，Delgado V ，Bax JJ ，Borlaug BA ... -  《-》

Myocardial adipose deposition and the development of heart failure with preserved ejection fraction.

It has been proposed that an increase of myocardial adiposity is related to left ventricular (LV) diastolic dysfunction. The specific roles of myocardial steatosis including epicardial fat and intramyocardial fat for diastolic function are unknown in those patients suffering heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF). This study aims to determine the complex relationship between myocardial adiposity in patients with HFrEF or HFpEF. Using cardiac magnetic resonance imaging (CMRI), myocardial steatosis was measured in 305 subjects (34 patients with HFrEF, 163 with HFpEF, and 108 non-HF controls). We also evaluated cardiac structure and diastolic and systolic function by echocardiography and CMRI. Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non-HF controls [intramyocardial fat content (%), 1.56 (1.26, 1.89) vs. 0.75 (0.50, 0.87) and 1.0 (0.79, 1.15), P < 0.05]. Intramyocardial fat amount (%) was higher in HFpEF women than in men [1.91% (1.17%, 2.32%) vs. 1.22 (0.87%, 2.02%), P = 0.01]. When estimated by CMRI (left ventricular peak filling rate), echocardiographic E/e' level, or left atrial volume index, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients, and this was independent of age, co-morbidities, body mass index, gender, and myocardial fibrosis (standardized coefficient: β = -0.34, P = 0.03; β = 0.29, P = 0.025; and β = 0.25, P = 0.02, respectively). Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non-HF controls. Independent of risk factors or gender, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients.

Wu CK ，Lee JK ，Hsu JC ，Su MM ，Wu YF ，Lin TT ，Lan CW ，Hwang JJ ，Lin LY ... -  《-》

Vitamin D Status and Exercise Capacity in Older Patients with Heart Failure with Preserved Ejection Fraction.

Older patients with heart failure with preserved ejection fraction have severe exercise intolerance. Vitamin D may play a role in cardiovascular and skeletal muscle function, and may therefore be implicated in exercise intolerance in heart failure with preserved ejection fraction. However, there are few data on vitamin D status and its relationship to exercise capacity in heart failure with preserved ejection fraction patients. Plasma 25-hydroxyvitamin D (25[OH]D) and exercise capacity (peak oxygen consumption, [VO2], 6-minute walk distance) were measured in 112 older heart failure with preserved ejection fraction patients (mean ± SD age = 70 ± 8 years) and 37 healthy age-matched controls. General linear models were used to compare 25(OH)D between heart failure with preserved ejection fraction patients and healthy controls, and to determine the cross-sectional association between 25(OH)D and exercise capacity. The association between 25(OH)D and left ventricular function was evaluated secondarily in heart failure with preserved ejection fraction patients. 25(OH)D concentrations were significantly lower in heart failure with preserved ejection fraction vs healthy controls (11.4 ± 0.6 ng/mL vs 19.1 ± 2.1 ng/mL; P = .001, adjusted for age, race, sex, body mass index, season). More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency (<20 ng/mL) and 30% had frank 25(OH)D deficiency (<10 ng/mL). In heart failure with preserved ejection fraction patients, but not healthy controls, 25(OH)D was significantly correlated with peak VO2 (r = 0.26; P = 0.007) and 6-minute walk distance (r = 0.34; P < .001). More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency, and 30% were frankly deficient. Lower 25(OH)D was associated with lower peak VO2 and 6-minute walk distance in heart failure with preserved ejection fraction, suggesting that 25(OH)D insufficiency could contribute to exercise intolerance in this patient population. These findings provide the data and rationale for a future randomized trial designed to test the potential for vitamin D supplementation to improve exercise intolerance in heart failure with preserved ejection fraction.

Pandey A ，Kitzman DW ，Houston DK ，Chen H ，Shea MK ... -  《-》

Regional Adipose Distribution and its Relationship to Exercise Intolerance in Older Obese Patients Who Have Heart Failure With Preserved Ejection Fraction.

This study sought to test the hypothesis that older obese patients with heart failure with preserved ejection fraction (HFpEF) have significantly greater abdominal, cardiac, and intermuscular fat than healthy, age-matched controls, out of proportion to total body fat, and that these abnormalities are associated with objective measurements of physical function. Recent studies indicate that excess total body adipose tissue contributes to exercise intolerance in patients with HFpEF. However, the impact of the pattern of regional (abdominal, cardiac, intermuscular) adipose deposition on exercise intolerance in patients with HFpEF is unknown. We measured total body adiposity (using dual-energy x-ray absorptiometry) and regional adiposity (using cardiac magnetic resonance), peak oxygen uptake (Vo2), 6-min walk distance (6MWD), short physical performance battery (SPPB), and leg press power in 100 older obese patients with HFpEF and 61 healthy controls (HCs) and adjusted for age, sex, race, and body surface area. Peak Vo2 (15.7 ± 0.4 ml/kg/min vs. 23.0 ± 0.6 ml/kg/min, respectively; p < 0.001), 6MWD (427 ± 7 m vs. 538 ± 10 m, respectively; p < 0.001), SPPB (10.3 ± 0.2 vs. 10.9 ± 0.2, respectively; p < 0.05), and leg power (117 ± 5 W vs. 152 ± 9 W, respectively; p = 0.004) were significantly lower in patients with HFpEF than HCs. Total fat mass, total percent fat, abdominal subcutaneous fat, intra-abdominal fat, and thigh intermuscular fat were significantly higher, whereas epicardial fat was significantly lower in patients with HFpEF than in HC. After we adjusted for total body fat, intra-abdominal fat remained significantly higher, while epicardial fat remained significantly lower in patients with HFpEF. Abdominal subcutaneous fat, thigh subcutaneous fat, and thigh intermuscular fat:skeletal muscle ratio were inversely associated, whereas epicardial fat was directly associated with peak Vo2, 6MWD, SPPB, and leg power. Using multiple stepwise regression, we found intra-abdominal fat was the strongest independent predictor of peak Vo2 and 6MWD. In metabolic obese HFpEF, the pattern of regional adipose deposition may have important adverse consequences beyond total body adiposity. Interventions targeting intra-abdominal and intermuscular fat could potentially improve exercise intolerance. (Exercise Intolerance in Elderly Patients With Diastolic Heart Failure [SECRET]; NCT00959660).

Haykowsky MJ ，Nicklas BJ ，Brubaker PH ，Hundley WG ，Brinkley TE ，Upadhya B ，Becton JT ，Nelson MD ，Chen H ，Kitzman DW ... -  《-》

Myocardial fibrosis and prognosis in heart failure with preserved ejection fraction: a pooled analysis of 12 cohort studies.

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with significant clinical heterogeneity. Myocardial fibrosis has been considered a common pathological process in the development and progress of HFpEF. This study aimed to consolidate data on the prognostic effect of myocardial fibrosis, evaluated by cardiovascular magnetic resonance (CMR) imaging in patients with HFpEF. Three medical databases were searched for potentially related articles up to February 28, 2023. Cohort studies reporting associations between myocardial fibrosis and risk of all-cause mortality or composite major adverse cardiac outcomes (MACE) were included. Cardiac fibrosis was evaluated by CMR metrics, including late gadolinium enhancement (LGE) or myocardial extracellular volume (ECV). The hazard ratios (HRs) and 95% confidence intervals (CI) of the outcomes for higher myocardial fibrosis were calculated. Twelve studies with 2787 patients with HFpEF were included for analysis. After a median follow-up duration of 31.2 months, a higher level of cardiac fibrosis was associated with a significant increase in the risk of MACE (HR = 1.34, 95% CI = 1.14-1.57) and all-cause mortality (HR = 1.74, 95% CI = 1.27-2.39), respectively. Furthermore, the increased risk of outcomes was both observed when cardiac fibrosis was defined according to LGE or ECV, respectively. Higher burden of myocardial fibrosis evaluated by CMR can predict a poor prognosis in patients with HFpEF. Evaluation of LGE or ECV based on CMR could be recommended in these patients for risk stratification and guiding further treatment. Inclusion of cardiovascular magnetic resonance examination in the diagnostic and risk-evaluation algorithms in patients with heart failure with preserved ejection fraction should be considered in clinical practice and future studies. • Myocardial fibrosis is a common pathological process in heart failure with preserved ejection fraction. • A higher myocardial fibrosis burden on cardiac magnetic resonance predicts a poor prognosis in patients with heart failure with preserved ejection fraction. • Evaluation of myocardial fibrosis may be useful in patients with heart failure with preserved ejection fraction for risk stratification and treatment guidance.

Zhang X ，Yang S ，Hao S ，Li J ，Qiu M ，Chen H ，Huang Y ... -  《-》