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 Sbarbaro, Robyn Farrell, Rajeev Malhotra, Nicholas E. Houstis, Raghava S. Velagaleti, Stephanie A. Moore, Aaron L. Baggish, George T. O'Connor, Jennifer E. Ho, Martin G. Larson, Ramachandran S. Vasan, Gregory D. Lewis

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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/VCO2pre-VATslope, VE/VCO2post-VATslope), the slope throughout exercise (VE/VCO2overall-slope), and as the lowest 30-second value (VE/VCO2nadir). Results: In the MGH-ExS (N=493, age 56±15 years, 61% women, left ventricular ejection fraction 64±8%), higher VE/VCO2nadirwas associated with lower peak exercise cardiac output and steeper increases in exercise pulmonary capillary wedge pressure (both P<0.0001). VE/VCO2nadir(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/VCO2overall-slope). In FHS (N=1936, age 54±9 years, 53% women), VE/VCO2 measures taken in low-to-moderate intensity exercise (including VE/VCO2pre-VATslope, VE/VCO2nadir) 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.

Original languageEnglish (US)
Pages (from-to)E006729
JournalCirculation: Heart Failure
Issue number5
StatePublished - May 1 2020
Externally publishedYes


  • exercise
  • heart failure
  • physiology
  • population

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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