Factors That Determine VO2 Max Importance as Measure of Heart Failure Severity

Right ventricular systolic function evaluated through VO2 max is a more accurate measure of functional capacity of persons with heart failure compared with left ventricular systolic function.

VO2 max, or an individual’s maximum oxygen uptake during intense exercise, is a measure of right ventricular systolic function, and in a recent study published in ESC Heart Failure, several factors were identified that cemented its ability to more accurately gauge the functional capacity of patients with heart failure vs left ventricular systolic function.

This retrospective, observational, single-center study from Spain used cardiopulmonary exercise testing (CPET) to evaluate outcomes among 362 patients via 2 treadmill-based stress tests: Bruce’s protocol (n = 360) and Naughton’s protocol (n = 2). The investigators also used multivariable linear regression analysis (MLRA) “to identify the independent clinical predictors associated with peak VO2 max.”

“This parameter represents an objective estimation of the functional capacity in patients with cardiovascular disease,” the authors stated, “and, in addition, it allows prognostic stratification in patients with heart failure.” Their primary study objective was to identify factors that determine the value of VO2 max in heart failure.

The mean (SD) patient age was 57.3 (10.9) years, and 75.4% were male. Their mean (SD) body mass index (BMI) was 28.1 (4.8) kg/m2; systolic blood pressure, 112.1 (17.3) mm Hg; and resting heart rate, 67.3 (11.5) beats/min. Most had New York Heart Association (NYHA) functional class II (56.1%) or III (34.5%) disease, and comorbidities included hypertension (44.5%), obesity (32.6%), anemia (32.3%), ischemic heart disease (31.5%), and chronic kidney disease (30.7%). Beta-blockers were the most common medication class.

Overall, more patients had heart failure with reduced ejection fraction than had midrange or preserved ejection fraction: 72.1% vs 16% vs 11.9%, respectively. Mean (SD) measures as a result of the stress tests were 19.8 (5.2) mL/kg/min for VO2 max, 75.9% (21%) for VO2 max/%pp VO2 ratio, and 8.4 (3.9) min for exercise duration.

Of the 12 factors investigated through MLRA—age, BMI, atrial fibrillation/flutter, hypertension, diabetes, NYHA class, creatinine, urea, hemoglobin, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), tricuspid annular plane systolic excursion (TAPSE), and ivabradine use—the following remained as statistically significant independent factors of lower VO2 max:

  • Older age (P < .001)
  • Worse NYHA class (P < .001)
  • Higher NT-proBNP (P = .019)
  • Higher BMI (P = .002)

Just TAPSE (P < .001) and higher hemoglobin (P = .007) were statistically significant independent factors of higher VO2 max.

VO2 max was overall higher in male vs female patients and younger (<60 years) than vs older (>60 years) patients: 20.4 (5.3) mL/kg/min vs 18.1 4.2 mL/kg/min (P = .027) and 21.6 (5.2) mL/kg/min vs 17.9 (4.7) mL/kg/min (P <.001), respectively. It was lower in patients with anemia compared with everyone else in the study: 16.8 (3.9) mL/kg/min vs 20.3 (5.4) mL/kg/min (P < .001).

Despite study limitations that include its observational and retrospective nature, that the CPET was performed during a routine check-up and not according to research protocol, and a possible insufficient sample size missing additional risk factors, the authors note that their results support the strength of VO2 max as an indicator of heart failure. This in turn elevates right ventricular systolic function over left ventricular systolic function as a measure of heart failure.

“These results seem to suggest that in patients with heart failure, the preservation of the contractile function of the right ventricle would be a more determining factor for keeping the ability to exercise than the systolic function of the left ventricle itself,” the authors concluded.


Pravio JR, Caballero EB, Caamaño CB, et al. Determinants of maximal oxygen uptake in patients with heart failure. ESC Heart Fail. Published online March 27, 2021. doi:10.1002/ehf2.13275

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