Clinical and Hemodynamic Associations and Prognostic Implications of Ventilatory Efficiency in Patients With Preserved Left Ventricular Systolic Function
Matthew Nayor, Vanessa Xanthakis, Melissa Tanguay, Jasmine B Blodgett, Ravi V. Shah, Mark Schoenike, John A. Sbarbaro, Robyn Farrell, Rajeev Malhotra, Nicholas Houstis, Raghava S. Velagaleti, Stephanie Moore, Aaron L. Baggish, George O'connor, Jennifer E. Ho, Martin G. Larson, Ramachandran S. Vasan, Gregory D. Lewis
Abstract
Background: Ventilatory efficiency (minute ventilation required to eliminate carbon dioxide, VE/VCO2) during exercise potently predicts outcomes in advanced heart failure with reduced ejection fraction, but its prognostic significance for at-risk individuals with preserved left ventricular systolic function is unclear. We aimed to characterize mechanistic determinants and prognostic implications of VE/VCO2 in a single-center dyspneic referral cohort (MGH-ExS [Massachusetts General Hospital Exercise Study]) and in a large sample of community-dwelling participants in the FHS (Framingham Heart Study). Methods: Maximum incremental cardiopulmonary exercise tests were performed. VE/VCO2 was assessed as the slope pre- and post-ventilatory anaerobic threshold (VE/VCO2 pre-VATslope , VE/VCO2 post-VATslope ), the slope throughout exercise (VE/VCO2 overall-slope ), and as the lowest 30-second value (VE/VCO2 nadir ). Results: In the MGH-ExS (N=493, age 56±15 years, 61% women, left ventricular ejection fraction 64±8%), higher VE/VCO2 nadir was associated with lower peak exercise cardiac output and steeper increases in exercise pulmonary capillary wedge pressure (both P <0.0001). VE/VCO2 nadir (hazard ratio, 1.34 per 1-SD unit [95% CI, 1.10–1.62] P =0.003) was associated with future cardiovascular hospitalization/death and outperformed classical VE/VCO2 measures used in heart failure with reduced ejection fraction (VE/VCO2 overall-slope ). In FHS (N=1936, age 54±9 years, 53% women), VE/VCO2 measures taken in low-to-moderate intensity exercise (including VE/VCO2 pre-VATslope , VE/VCO2 nadir ) were directly associated with cardiovascular risk factor burden (smoking, Framingham cardiovascular disease risk score, and lower fitness; all P <0.001). Conclusions: Impaired ventilatory efficiency is associated with cardiovascular risk in the community and with adverse hemodynamic profiles and future hospitalizations/death in a referral population, highlighting the prognostic importance of easily acquired submaximum exercise ventilatory gas exchange measurements in broad populations with preserved left ventricular systolic function.