To our knowledge, this is the first prospective evaluation of CPET and CWRET in TR patients undergoing TTVI. The main findings are fourfold. First, CPET revealed a severely impaired cardiopulmonary exercise capacity in our cohort of severe TR patients. Second, TTVI does not result in a statistically significant improvement of peak VO2 oxygen during exercise. Third, CWRET revealed a significant improvement of SEC regardless of baseline RV function. Finally, this improvement correlates with a reduction of TR parameters, increased left ventricular stroke volume, and QOL.

Baseline CPET analysis confirmed that the health condition in our cohort of TR patients was severely limited and unsuitable/high risk for surgery. It is known that VT1 is a valid risk predictor for non-thoracic surgery, with threshold values of lower than 9–12 ml VO2/kg/min for a worse post-surgical outcome [21, 22]. VO2 at VT1 is well below this threshold in our cohort. Interestingly, after TTVI patients did not present with a significant detectable improvement in maximum exercise capacity, despite significant functional improvements such as NYHA class, 6MWD and QOL. The underlying reason may be multifactorial and remains to be elucidated [23]. Pathophysiological considerations on the critical power concept suggest that treatment effects may be first seen in the submaximal endurance part of the power–duration curve (Fig. 1), and less pronounced in maximal exercise capacity [10]. This is in line with mixed results from previous trials in heart failure and pulmonary arterial hypertension that have used peak VO2 as a measure of treatment effects [11, 24]. In addition, there is published data from a previous retrospective analysis of functional improvement after interventional valve repair showing an improvement in peak VO2 at 3 months [25]. However, the respective patient cohort was younger and probably more impaired before the procedure, as the average peak VO2 at baseline was lower than in our patients. Interestingly, the absolute peak VO2 values at follow-up were comparable to our results. TR patients undergoing TTVI are generally elderly patients with several comorbidities which may also negatively affect exercise capacity. Considering the left ventricle, Benito-Gonzáles et al. reported that transcatheter mitral valve repair in patients with severe mitral regurgitation may result in an improvement in maximum oxygen uptake 6 months post-procedurally (9.8 [9.1; 13.4] ml/kg/min vs. 13.5 [12.1; 16.8] ml/kg/min; p = 0.033) [26]. This study comprised a very small cohort consisting of 11 patients while explicitly excluding patients with advanced age and severe comorbidities. This may be an additional explanation for the varying results. Furthermore, besides the hemodynamic dimension, exercise capacity also depends on the muscular and cellular oxidative systems. Patients suffering from the aforementioned comorbidities certainly do not often exercise on maximum levels in their daily lives. This could explain that improvements in peak VO2 were not significant due to chronic muscular deconditioning. Whether or not a customized exercise regimen could increase peak VO2 should be part of future prospective trials.

On the other hand, endurance time at constant work rate (CWRET) increased significantly after TTVI. As predicted by the critical power concept, this confirms that submaximal endurance capacity increases in this patient cohort before any relevant changes in maximal exercise capacity may be visible [27].

The fractional improvement in SEC, which is more likely to reflect daily life exercise challenges, was much greater and therefore detected more easily than any improvement in peak VO2. The 6MWD, which also reflects a self-paced maximal sustainable power [27], also shows a significant improvement, as expected. However, in contrast to the 6MWD, improvements in SEC correlate with a reduction in TR (TR-EROA), improved cardiac output, and improved QOL.

Despite the aforementioned advantages of CWRET, this method is more complex, needs more clinical resources, and suffers from limited patient compliance, compared to the 6MWD. Patients have to be motivated to undergo a preliminary incremental ramp CPET to determine an individual constant work rate which may also be time-consuming for patients and clinicians. Nevertheless, little is known about the causes and severity of exercise intolerance in these individuals. Since CWRET provides a more detailed insight in patients’ submaximal exercise capacity, it may represent the most appropriate tool to quantify clinical improvements after TTVI, preserving the acquisition of metabolic exercise data by gas exchange measurements and providing insights into potential mechanisms of exercise limitation. Even though the improvement of CWRET is of interest, the lack of improvement in peak VO2 is another meaningful finding, supporting the importance of other, non-TR-related mechanisms of exercise limitation in these patients.

The TRILUMINATE pivotal trial has shown that TTVI appears to have clinical rather than prognostic benefit in patients with severe TR and improves QOL [28]. Given the high morbidity and advanced age of this patient population, the clinical benefit might be of greater importance to patients, possibly even more than survival benefit.

With that in mind, CWRET might be a sensitive examination to assess functional improvement in patients undergoing TTVI and could help elucidate non-TR-related mechanisms of exercise limitation, including chronic muscular deconditioning. Based on these findings, individual treatment strategies of comorbidities and exercise prescription may be optimized.

Some studies have shown that in advanced heart failure, exercise training does not appear to have a significant effect on exercise capacity in the maximal exercise range [29]. Whether exercise training can achieve improvements in the submaximal range needs to be investigated in future studies.