Exercise-Induced Reduction in Left Ventricular Ejection Fraction in the Absence of Coronary Artery Disease: Clinical Characteristics and Outcomes

Background: During exercise stress echocardiography (ESE), there are patients with normal left ventricular ejection fraction (LVEF) who paradoxically develop reduced LVEF during exercise despite absence of coronary artery disease (CAD) and a significant hypertensive response. This study sought to describe the clinical features and outcomes of this population. Methods: Among ESEs performed between 2003 and 2022, patients without CAD by angiogram within 90 days of ESE and resting LVEF ≥50% with a ≥5% LVEF decrease during ESE were included. Outcomes assessed were all-cause mortality, heart failure (HF) hospitalization, and atrial fibrillation (AF). Kaplan-Meier and Cox regression methods were used to analyze time-to-event outcomes. Results: Among 213,643 ESE, 134 patients met the eligibility criteria. The mean age of the population was 66 ± 10 years, 76% were women, and 16% had AF at baseline. Mean LVEF was 58% ± 4% at rest and 43% ± 4% at peak stress. Stress ECG met the criteria for ischemia in 14% of these patients. The 10-year estimated incidence of HF hospitalization was 17.6% (95% CI, 9.0%-26.2%). Among the subgroup without AF at baseline, the 10-year estimated incidence of developing AF was 23.4% (95% CI, 13.4%-33.4%). The 10-year estimated incidence of all-cause mortality was 12.9% (95% CI, 5.5%-20.3%), with 89% of deaths occurring due to noncardiovascular causes. Conclusion: Patients with exercise-induced reduction in LVEF in the absence of obstructive CAD have a high incidence of HF hospitalizations and AF. The underlying pathophysiology of this disease process needs to be further investigated.