Prognostic Value of Exercise-Induced Left Ventricular Functional Reserve Assessed by Left Ventricular Global Strain in Heart Failure With Preserved Ejection Fraction

In patients with heart failure with preserved ejection fraction (HFpEF), resting echocardiographic indices often fail to capture functional abnormalities that emerge only during stress. This study aimed to determine the prognostic significance of left ventricular functional reserve (LVFR) in HFpEF patients. We retrospectively analyzed 211 patients with HFpEF who underwent treadmill stress echocardiography at Samsung Medical Center between 2010 and 2017. LVFR was calculated as change in global longitudinal strain (ΔGLS) (%) = (|left ventricular global longitudinal strain LV GLS| after exercise − |LV GLS| at rest)/|LV GLS| at rest × 100. Patients were divided by the median ΔGLS (10.3%) and followed for a median of 8.0 years (interquartile range, 6.0–11.0). The primary outcome was a composite of cardiovascular death or unplanned heart failure (HF) hospitalization. A total of 41 patients (19.4%) experienced the primary outcome. Lower LVFR correlated with higher N-terminal pro-B-type natriuretic peptide, higher post-exercise ratio of peak early mitral inflow velocity to early diastolic mitral annular velocity, and lower exercise capacity. Conventional receiver-operating characteristic analysis at 8 years showed that LVFR had the highest prognostic performance for the primary outcome, outperforming static strain and diastolic indices. In multivariable analysis, each 1% increase in LVFR was associated with a 6.3% lower risk of cardiovascular death or HF hospitalization (hazard ratio, 0.94; 95% confidence interval, 0.91–0.96; p<0.001). In HFpEF patients, LVFR, assessed by exercise-induced left ventricular strain augmentation, provides independent and incremental prognostic value in HFpEF, outperforming conventional echocardiographic and clinical parameters.