Contributions of Nondiastolic Factors to Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

BackgroundHeart failure with preserved ejection fraction (HFpEF) has a complex etiology. Factors responsible for development of impaired exercise tolerance and disease progression are incompletely defined.ObjectivesThe authors sought to define the contributions of contractile reserve, ventriculo-arterial coupling (VAC) reserve, and chronotropic response to the progression of HFpEF.MethodsWe performed echocardiography at rest and immediately post-cardiopulmonary exercise test in 207 patients (63 ± 8 years of age) with stage C heart failure (HF) (exertional dyspnea, New York Heart Association functional class II to III, exercise capacity <80% of normal, left ventricular ejection fraction >50%, and diastolic dysfunction) and 60 patients with stage B HF (normal exercise tolerance with left ventricular hypertrophy, and/or reduced global longitudinal strain, with diastolic dysfunction).ResultsSymptomatic patients were grouped as stage C1 (ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity [E/e′] <13 both at rest and exercise; n = 63), C2 (E/e′ >13 only at exercise; n = 118), and C3 (E/e′ >13 both at rest and exercise; n = 26) HF. Exercise capacity and cardiovascular functional reserve were less impaired in stage C1 than in stages C2 and C3. Chronotropic response was more disturbed in stage C3 than C1 and C2. Changes from rest to exercise in E/e′ (−0.6 ± 1.7 vs. 3.7 ± 2.8; p < 0.0001), global longitudinal strain (2.9 ± 2.0 vs. 1.6 ± 2.8; p < 0.002), VAC (−0.21 ± 0.17 vs. −0.09 ± 0.15; p < 0.0001), and in VO2-HR gradient (0.30 ± 0.07 vs. 0.26 ± 0.11; p < 0.01) were significantly different in stages B and C.ConclusionsNormal E/e′ response to exertion in symptomatic HFpEF is associated with less profound impairment of exercise capacity and is accompanied by derangements of contractile state and VAC. The transition from asymptomatic to overt HFpEF is linked to diastolic, systolic, and chronotropic deficits and an increasing degree of hemodynamic disturbances in stage C HF.