Myocardial relaxation, left ventricular filling, and exercise capacity in older subjects with dyspnea

With aging, left ventricular (LV) early diastolic lengthening declines. Delayed or dyssynchronous untwisting and relaxation may slow and reduce filling and contribute to elevated diastolic pressures. Segmental variations in the timing of early diastolic relaxation may impair LV suction during exercise and impact LV stroke volume reserve, especially in heart failure with preserved ejection fraction (HFpEF). To determine possible mechanisms causing dyspnea, we investigated 106 subjects aged ≥ 60 yr, including 38 patients with HFpEF, 26 breathless, 19 hypertensive, and 23 healthy controls, at rest and during submaximal exercise stress echocardiography. Global and regional early diastolic function were assessed by LV isovolumic relaxation time (IVRT), the deceleration time (DT) and propagation velocity of mitral inflow, and segmental variations in times-to-peak early diastolic myocardial velocity (e'). Global IVRT and DT were similar between groups at rest and during stress. During exercise, increments in mean segmental e' were similar between groups, whereas times-to-peak e' shortened variably, being 13%-20% longer in the midseptal and 30%-35% longer in the midlateral segments in HFpEF than in healthy or hypertensive subjects (P < 0.001). There were moderate inverse correlations between time-to-peak e' and LV inflow velocity, cardiac output on exercise, and 6-min walk distance (ρ -0.42, P < 0.001). Slower early diastolic relaxation on exercise is associated with less stroke volume reserve and reduced exercise capacity. Machine learning might be able to identify subtle changes in timing of relaxation as a diagnostic or therapeutic target in subjects with HFpEF.NEW & NOTEWORTHY Dyspnea in older subjects and patients with HFpEF is usually attributed to elevated LV filling pressures caused by reduced end-diastolic compliance. This study demonstrates that during exercise, slow early diastolic relaxation and reduced ventricular suction limit increments in early diastolic filling and impair stroke volume reserve, thereby reducing exercise capacity. Lowering late systolic pressure and augmenting early diastolic filling may be important targets for pharmacologic therapy to reduce dyspnea.