Characterization of ventilatory efficiency during cardiopulmonary exercise testing in healthy athletes.

Abstract

Ventilatory efficiency (⁠V˙E/V˙CO2) during exercise is defined as the ratio of minute ventilation (⁠V˙E) and carbon dioxide output (⁠V˙CO2) and reflects matching of alveolar ventilation and pulmonary perfusion as well as ventilatory drive.1 Abnormally high V˙E/V˙CO2 is important diagnostically and prognostically in the setting of cardiopulmonary disease.1 Current clinical guidelines propose a total slope (⁠V˙E/V˙CO2-total) < 30 as normal,1 with higher cutoffs (⁠V˙E/V˙CO2-total < 34) providing prognostic value in specific diseases.2,3 While some recommend measurement of V˙E/V˙CO2-total slope over only the linear portion of the curve from the start of exercise to the second ventilatory threshold (VT2, also known as the respiratory compensation point),4,5V˙E/V˙CO2-total is often measured over the entirety of the exercise effort given robust prognostic data in heart failure using this technique.2,3,6 Normative values for V˙E/V˙CO2 have been derived from general population cohorts,4,6 but remain limited in athletes.7,8 By virtue of high motivation and cardiorespiratory fitness, athletes are capable of sustaining a graded exercise effort well beyond the VT2 after which V˙E increases relative to V˙CO2 in late exercise even in the absence of cardiopulmonary disease. Resultant elevation in V˙E/V˙CO2-total when measured through the end of exercise may confound assessment for pathology. The primary aims of this study were to define athlete-specific normative values for V˙E/V˙CO2 and to assess the performance of existing cutoffs and predictive equations for V˙E/V˙CO2 in athletes. This prospective cohort study included a select group of athletes who underwent effort-limited clinically indicated cardiopulmonary exercise testing (CPET) on either the treadmill or upright cycle ergometer from 2011 to 2021 in the Massachusetts General Hospital Cardiovascular Performance Program. As previously described, rigorous exclusion criteria were used to generate a cohort free from clinically evident cardiopulmonary disease.9 Endurance sports were defined as distance running, cycling, rowing, triathlon, and/or swimming. V˙E/V˙CO2-total was defined as the V˙E vs. V˙CO2 slope from the ramp start to peak exercise, V˙E/V˙CO2-start-VT1 as the slope from the ramp start to the first ventilatory threshold (VT1), and V˙E/V˙CO2-Nadir as the lowest continuous 30 s average V˙E/V˙CO2 ratio during exercise. Peak V˙O2 (pV˙O2) was defined as the highest oxygen uptake, averaged over 30 s, during the last minute of exercise. Gas exchange data were analysed using a mid-5-of-7 averaging algorithm (i.e. the moving average of five breaths excluding the lowest and highest). Categorical variables are presented as n (%) and continuous variables are presented as mean [standard deviation (SD)]. Linear regression was used to assess the relationship between V˙E/V˙CO2 and other variables. The performance of existing V˙E/V˙CO2 prediction equations was assessed by regressing measured on predicted V˙E/V˙CO2 and by Bland–Altman analysis. The upper limit of normal (ULN) was defined as >90th percentile for predicted V˙E/V˙CO2-total,6 and predicted V˙E/V˙CO2-Nadir +(1.66 × SD).4 Statistical analyses were performed using R (R Core Team, Vienna, Austria, 2022). This study was approved by the Massachusetts General Brigham Institutional Review Board. In 521 athletes (age = 38 ± 15 years, 33% female, 91% white), exercise was completed on the treadmill in 292 (56%) and cycle ergometer in 229 (44%). Most participants were endurance athletes (n = 330, 63%), with the remaining participating in mixed/other sports (n = 191, 37%). Table 1 presents V˙E/V˙CO2 and pV˙O2stratified by age and sex. V˙E/V˙CO2-total exceeded the guideline-recommended cutoff of 30 in 66/172 (38%) females and 106/349 (30%) males and exceeded the prognostic threshold of 34 in 30/172 (17%) females and 40/349 (11%) males. In the total population, V˙E/V˙CO2 exceeded the prognostic threshold of 34 in 70/521 (13%) athletes using V˙E/V˙CO2-total, 10/521 (1.9%) using V˙E/V˙CO2-start-VT1, and 2/521 (0.4%) using V˙E/V˙CO2-Nadir. Of the 70 athletes with V˙E/V˙CO2-total >34, only 8/70 (11.4%) had V˙E/V˙CO2-start-VT1 > 34 and 2/70 (2.9%) had V˙E/V˙CO2-Nadir >34 (Figure 1).