Cardiac Reserve and Exercise Capacity: Insights from Combined Cardiopulmonary and Exercise Echocardiography Stress Testing

Nicola Riccardo Pugliese, Nicolò De Biase, Lorenzo Conte, Luna Gargani, Matteo Mazzola, Iacopo Fabiani, Andrea Natali, Frank L. Dini, Paolo Frumento, Javier Rosada, Stefano Taddei, Barry A. Borlaug, Stefano Masi

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: Cardiopulmonary exercise testing (CPET) represents the gold standard to estimate peak oxygen consumption (VO2) noninvasively. To improve the analysis of the mechanisms behind effort intolerance, we examined whether exercise stress echocardiography measurements relate to directly measured peak VO2 during exercise in a large cohort of patients within the heart failure (HF) spectrum. Methods: We performed a symptom-limited graded ramp bicycle CPET exercise stress echocardiography in 30 healthy controls and 357 patients: 113 at risk of developing HF (American College of Cardiology/American Heart Association stage A-B) and 244 in HF stage C with preserved (HFpEF, n = 101) or reduced ejection fraction (HFrEF, n = 143). Results: Peak VO2 significantly decreased from controls (23, 21.7–29.7 mL/kg/minute; median, interquartile range) to stage A-B (18, 15.4-20.7 mL/kg/minute) and stage C (HFpEF: 13.6, 11.8-16.8 mL/kg/minute; HFrEF: 14.2, 10.7-17.5 mL/kg/minute). A regression model to predict peak VO2 revealed that peak left ventricular (LV) systolic annulus tissue velocity (S′), peak tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (right ventricle-pulmonary artery coupling), and low-load left atrial (LA) reservoir strain/E/e’ (LA compliance) were independent predictors, in addition to peak heart rate, stroke volume, and workload (adjusted R2 = 0.76, P < .0001). The model was successfully tested in subjects with atrial fibrillation (n = 49) and with (n = 224) and without (n = 163) beta-blockers (all P < .01). Peak S′ showed the highest accuracy in predicting peak VO2 < 10 mL/kg/minute (cut point ≤ 7.5 cm/sec, area under the curve = 0.92, P < .0001) and peak VO2 > 20 mL/kg/minute (cut point > 12.5 cm/sec, area under the curve = 0.84, P < .0001) in comparison with the other cardiac variables of the model (P < .05). Conclusions: Peak VO2 is directly related to measures of LV systolic function, LA compliance, and right ventricle-pulmonary artery coupling, in addition to heart rate and stroke volume and independently of workload, age, and sex. The evaluation of cardiac mechanics may provide more insights into the causes of effort intolerance in subjects from HF stages A-C.

Original languageEnglish (US)
Pages (from-to)38-50
Number of pages13
JournalJournal of the American Society of Echocardiography
Issue number1
StatePublished - Jan 2021


  • Cardiac function
  • Cardiopulmonary exercise test
  • Exercise stress echocardiography
  • Heart failure

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine


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