Central and Peripheral Determinants of Exercise Capacity in Heart Failure Patients With Preserved Ejection Fraction

E Wolsk, D Kaye, J Komtebedde, SJ Shah, BA Borlaug, D Burkhoff, DW Kitzman, CSP Lam, DJ van Veldhuisen, P Ponikowski, MC Petrie, C Hassager, JE Moller and F Gustafsson
JACC Heart Fail 2019

OBJECTIVES: This study sought to discern which central (e.g., heart rate, stroke volume [SV], filling pressure) and peripheral factors (e.g., oxygen use by skeletal muscle, body mass index [BMI]) during exercise were most strongly associated with the presence of heart failure and preserved ejection fraction (HFpEF) as compared with healthy control subjects exercising at the same workload.

BACKGROUND: The underlying mechanisms limiting exercise capacity in patients with HFpEF are not fully understood.

METHODS: In patients with HFpEF (n = 108), the hemodynamic response at peak exercise was measured using right-sided heart catheterization and was compared with that in healthy control subjects (n = 42) at matched workloads to reveal hemodynamic differences that were not attributable to the workload performed. The patients studied were prospectively included in the REDUCE-LAP HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trials and HemReX (Effect of Age on the Hemodynamic Response During Rest and Exercise in Healthy Humans) study. Univariable and multivariable logistic regression models were used to analyze variables associated with HFpEF versus control subjects. RESULTS: Compared with healthy control subjects, pulmonary capillary wedge pressure (PCWP) and SV were the only independent hemodynamic variables that were associated with HFpEF, a finding explaining 66% (p < 0.0001) of the difference between the groups. When relevant baseline characteristics were added to the base model, only BMI emerged as an additional independent variable, in total explaining of 90% of the differences between groups (p < 0.0001): PCWP (47%), BMI (31%), and SV (12%).

CONCLUSIONS: The study identified 3 key variables (PCWP, BMI, and SV) that independently correlate with the presence of patients with HFpEF compared with healthy control subjects exercising at the same workload. Therapies that decrease left-sided heart filling pressures could improve exercise capacity and possibly prognosis.P

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