Cardiovascular response to exercise training in the systemic right ventricle of adults with transposition of the great arteries

We aimed to assess the haemodynamic effects of exercise training in transposition of the great arteries (TGA) patients with systemic right ventricles (SRVs). TGA patients have limited exercise tolerance and early mortality due to systemic (right) ventricular failure. Whether exercise training enhances or injures the SRV is unclear. Fourteen asymptomatic patients (34 ± 10 years) with TGA and SRV were enrolled in a 12 week exercise training programme (moderate and high-intensity workouts). Controls were matched on age, gender, BMI and physical activity. Exercise testing pre- and post- training included: (a) submaximal and peak; (b) prolonged (60 min) submaximal endurance and (c) high-intensity intervals. Oxygen uptake (; Douglas bag technique), cardiac output (, foreign-gas rebreathing), ventricular function (echocardiography and cardiac MRI) and serum biomarkers were assessed. TGA patients had lower peak , , and stroke volume (SV), a blunted / slope, and diminished SV response to exercise (SV increase from rest: TGA = 15.2%, controls = 68.9%, P < 0.001) compared with controls. After training, TGA patients increased peak by 6 ± 8.5%, similar to controls (interaction P = 0.24). The magnitude of SV reserve on initial testing correlated with training response (r = 0.58, P = 0.047), though overall, no change in peak was observed. High-sensitivity troponin T (hs-TnT) and N-terminal prohormone of brain naturetic peptide (NT pro-BNP) were low and did not change with acute exercise or after training. Our data show that TGA patients with SRVs in this study safely participated in exercise training and improved peak . Neither prolonged submaximal exercise, nor high-intensity intervals, nor short-term exercise training seem to injure the systemic right ventricle. Key Points Patients with transposition of the great arteries (TGA) and systemic right ventricles have premature congestive heart failure; there is also a growing concern that athletes who perform extraordinary endurance exercise may injure the right ventricle. Therefore we felt it essential to determine whether exercise training might injure a systemic right ventricle which is loaded with every heartbeat. Previous studies have shown that short term exercise training is feasible in TGA patients, but its effect on ventricular function is unclear. We demonstrate that systemic right ventricular function is preserved (and may be improved) in TGA patients with exercise training programmes that are typical of recreational and sports participation, with no evidence of injury on biomarker assessment. Stroke volume reserve during exercise correlates with exercise training response in our TGA patients, identifying this as a marker of a systemic right ventricle (SRV) that may most tolerate (and possibly even be improved by) exercise training. Introduction Patients with transposition of the great arteries (TGA) with systemic right ventricles (SRVs) have limited exercise tolerance and depressed systemic right ventricular function that is associated with adverse outcomes (Kempny et al. 2012; Gallego et al. 2012; Diller et al. 2012). Among adults with congenital heart disease, it has been reported that SRV patients have a high incidence of sudden death which can occur during exercise (Kammeraad et al. 2004; Gallego et al. 2012; Koyak et al. 2012). Therefore, TGA patients are often restricted from most exercise and sports participation (Graham et al. 2005; Baumgartner et al. 2010). However, two recent randomized controlled studies in TGA patients showed that low to moderate-intensity, short duration exercise training is safe and, importantly, increased exercise capacity as indicated by peak oxygen uptake (); but these studies did not evaluate cardiac output response and lacked comprehensive description of the training response on the SRV (Goda et al. 2009; Winter et al. 2012; Westhoff-Bleck et al. 2013). Exercise training improves clinical outcomes in adults with systemic left ventricular dysfunction without congenital heart disease (O'Connor et al. 2009; Belardinelli et al. 2012). The use of high-intensity ‘interval’ type training may actually be more beneficial for improving cardiac and metabolic function in these populations (Rognmo et al. 2012; Weston et al. 2013). However, given the unique structure and function of the right ventricle, findings in the systemic left ventricle or the subpulmonic right ventricle cannot be extrapolated to this TGA population. The SRV is loaded against systemic level resistance with every heartbeat, which may affect ventricular performance and safety in response to the high haemodynamic loads associated with vigorous-intensity exercise. Indeed, in the usual subpulmonic position the right ventricle may be particularly sensitive to exercise-induced cardiac fatigue and possibly even injury in competitive athletes, including those performing at high levels of exercise (Oxborough et al. 2011; La Gerche et al. 2012; Claessen et al. 2014). The current study was designed to comprehensively examine the cardiovascular and metabolic responses to acute exercise and 3 months of moderate- to high-intensity exercise training in the SRV in those patients with TGA. Measurements of ventricular function and stress (biomarkers, non-invasive imaging and haemodynamics) were collected at rest, during and after prolonged submaximal exercise, peak exercise, and after high-intensity intervals in order to comprehensively determine whether novel training techniques can be applied to this patient population with equivalent safety, and perhaps better efficacy.