Clinical Implications of Resting Metabolic Rate in Heart Failure With Preserved Ejection Fraction.

BACKGROUND

Heart failure with preserved ejection fraction (HFpEF) is causally related to obesity. Adipose tissue accumulates when energy intake exceeds expenditure. Resting metabolic rate (RMR) is a key determinant of energy expenditure, but it has not been evaluated in HFpEF.

METHODS

Patients with HFpEF undergoing invasive hemodynamic exercise testing were categorized into lower- or higher-than-expected measured RMR groups based on the difference between directly measured RMR, calculated using the Weir equation (indirect calorimetry) and predicted RMR, estimated using the Mifflin-St. Jeor equation.

RESULTS

Of 472 patients with HFpEF, 212 had lower-than-expected RMRs, and 260 had higher-than-expected RMRs. Compared with patients with lower-than-expected RMRs, those with higher-than-expected RMRs were older (69 ± 10 vs 65 ± 11 years; P < 0.001), more commonly women (66.2% vs 43.9%; P <0.001), and less likely to be obese (53.9% vs 75.0%; P < 0.001). At rest, patients with higher-than-expected RMRs displayed hemodynamic adaptations consistent with increased metabolic demand, including left ventricular dilation, higher stroke work and stroke volume index, and vasodilation. However, during exercise, patients with higher-than-expected RMRs displayed blunted augmentation in cardiac performance and inadequate vasodilation, indicating impaired cardiovascular reserve. Over a median follow-up of 4.6 (2.2, 6.4) years, patients with higher-than-expected RMRs had greater risks of cardiovascular death or hospitalization due to HF compared with those with lower-than-expected RMRs (HR 2.66 [95% CI 1.43-4.94]; P = 0.002).

CONCLUSIONS

Patients with HFpEF and lower-than-expected RMRs have a greater prevalence of obesity, and those with higher-than-expected RMRs display circulatory adaptations to heightened metabolic demand at rest, which are coupled with blunted reserve capacity during exercise and increased risk for adverse clinical outcomes. Further studies are warranted to elucidate the underlying mechanisms by which RMRs contribute to the pathophysiology of HFpEF and to clarify its potential use in therapeutic strategies.