Background: Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the etiology has been attributed to central factors, including ventilation-perfusion mismatch, increased pulmonary vascular resistance and right heart dysfunction and uncoupling. Pulmonary endarterectomy and, balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. However, despite normalization of pulmonary hemodynamics, exercise capacity often does not return to age-predicted. By systematically evaluating the oxygen (O 2 ) pathway we aimed to elucidate the cause/s of functional limitations in CTEPH patients before and after pulmonary vascular intervention. Methods: Using exercise cardiac magnetic resonance (CMR) imaging with simultaneous invasive hemodynamic monitoring, we sought to quantify the steps of the O2 transport cascade from the mouth to the mitochondria in patients with CTEPH (n=20) as compared to healthy subjects (n=10). Furthermore we evaluated the effect of pulmonary vascular intervention (pulmonary endarterectomy or balloon angioplasty) on the individual components of the cascade (n=10). Results: Peak VO2 was significantly reduced in CTEPH patients relative to controls (56±17 vs 112±20% of predicted, p<0.0001). The difference was due to impairments in multiple steps of the O 2 cascade, including O 2 delivery (product of cardiac output and arterial O 2 content), skeletal muscle diffusion capacity, and pulmonary diffusion. The total O 2 extracted in the periphery, i.e. ΔAVO 2 , was not different. Following pulmonary vascular intervention, peak VO 2 increased significantly (12.5±4.0 to 17.8±7.5 ml/kg/min, p=0.036) but remained below age-predicted (70±11%). The O 2 delivery was improved due to an increase in peak cardiac output and lung diffusion capacity. However, peak exercise ΔAVO2 was unchanged, as was skeletal muscle diffusion capacity. Conclusions: We demonstrated that CTEPH patients have significant impairment of all steps in the O 2 utilisation cascade resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increased peak VO 2 , by partly correcting O 2 delivery but having no impact on abnormalities in peripheral O 2 extraction. This suggests that current interventions only partially address patients' limitations and that additional therapies may improve functional capacity.

Background and Aims The impact of long-term endurance sport participation (on top of a healthy lifestyle) on coronary atherosclerosis and acute cardiac events remains controversial. Methods The Master@Heart study is a well-balanced prospective observational cohort study. Overall, 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile, were included. Peak oxygen uptake (VO2peak) quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on computed tomography coronary angiography. Analyses were corrected for multiple cardiovascular risk factors. Results The median age was 55 (50–60) years in all groups. Lifelong and late-onset athletes had higher VO2peak than non-athletes (159 [143-177] vs 155 [138-169] vs 122 [108-138] % predicted). Lifelong endurance sports was associated with having ≥1 coronary plaque (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.17–2.94), ≥1 proximal plaque (OR 1.96, 95% CI 1.24–3.11), ≥1 calcified plaques (OR 1.58, 95% CI 1.01–2.49), ≥1 calcified proximal plaque (OR 2.07, 95% CI 1.28–3.35), ≥1 non-calcified plaque (OR 1.95, 95% CI 1.12–3.40), ≥1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39–5.65) and ≥1 mixed plaque (OR 1.78, 95% CI 1.06–2.99) as compared to a healthy non-athletic lifestyle. Conclusion Lifelong endurance sport participation is not associated with a more favorable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum.

Aims Athletes with right ventricular (RV) arrhythmias, even in the absence of desmosomal mutations, may have subtle RV abnormalities which can be unmasked by deformation imaging. As exercise places a disproportionate stress on the right ventricle, evaluation of cardiac function and deformation during exercise might improve diagnostic performance. Methods and results We performed bicycle stress echocardiography in 17 apparently healthy endurance athletes (EAs), 12 non-athletic controls (NAs), and 17 athletes with RV arrhythmias without desmosomal mutations (EI-ARVCs) and compared biventricular function at rest and during low (25% of upright peak power) and moderate intensity (60%). At rest, we observed no differences in left ventricular (LV) or RV function between groups. During exercise, however, the increase in RV fractional area change (RVFAC), RV free wall strain (RVFWSL), and strain rate (RVFWSRL) were significantly attenuated in EI-ARVCs as compared to EAs and NAs. At moderate exercise intensity, EI-ARVCs had a lower RVFAC, RVFWSL, and RVFWSRL (all P < 0.01) compared to the control groups. Exercise-related increases in LV ejection fraction, strain, and strain rate were also attenuated in EI-ARVCs (P < 0.05 for interaction). Exercise but not resting parameters identified EI-ARVCs and RVFWSRL with a cut-off value of >−2.35 at moderate exercise intensity had the greatest accuracy to detect EI-ARVCs (area under the curve 0.95). Conclusion Exercise deformation imaging holds promise as a non-invasive diagnostic tool to identify intrinsic RV dysfunction concealed at rest. Strain rate appears to be the most accurate parameter and should be incorporated in future, prospective studies to identify subclinical disease in an early stage.

BackgroundExercise-induced cardiac remodelling (EICR) results from the structural, functional and electrical adaptations to exercise. Despite similar sports participation, EICR varies and some athletes develop phenotypic features that overlap with cardiomyopathies. Training load and genotype may explain some of the variation; however, exercise ‘dose’ has lacked rigorous quantification. Few have investigated the association between EICR and genotype.Objectives(1) To identify the impact of training load and genotype on the variance of EICR in elite endurance athletes and (2) determine how EICR and its determinants are associated with physical performance, health benefits and cardiac pathology.MethodsThe Pro@Heart study is a multicentre prospective cohort trial. Three hundred elite endurance athletes aged 14–23 years will have comprehensive cardiovascular phenotyping using echocardiography, cardiac MRI, 12-lead ECG, exercise-ECG and 24-hour-Holter monitoring. Genotype will be determined using a custom cardiomyopathy gene panel and high-density single-nucleotide polymorphism arrays. Follow-up will include online tracking of training load. Cardiac phenotyping will be repeated at 2, 5, 10 and 20 years.ResultsThe primary endpoint of the Pro@Heart study is the association of EICR with both training load and genotype. The latter will include rare variants in cardiomyopathy-associated genes and polygenic risk scores for cardiovascular traits. Secondary endpoints are the incidence of atrial and ventricular arrhythmias, physical performance and health benefits and their association with training load and genotype.ConclusionThe Pro@Heart study is the first long-term cohort study to assess the impact of training load and genotype on EICR.Trial registration numberNCT05164328; ACTRN12618000716268.

IntroductionLow and moderate endurance exercise is associated with better control of cardiovascular risk factors, a decreased risk of coronary artery disease and atrial fibrillation (AF). There is, however, a growing proportion of individuals regularly performing strenuous and prolonged endurance exercise in which the health benefits have been challenged. Higher doses of endurance exercise have been associated with a greater coronary atherosclerotic plaque burden, risk of AF and myocardial fibrosis (MF).Methods and analysisMaster@Heart is a multicentre prospective cohort study aiming to assess the incidence of coronary atherosclerosis, AF and MF in lifelong endurance athletes compared to late-onset endurance athletes (initiation of regular endurance exercise after the age of 30 years) and healthy non-athletes.The primary endpoint is the incidence of mixed coronary plaques. Secondary endpoints include coronary calcium scores, coronary stenosis >50%, the prevalence of calcified and soft plaques and AF and MF presence. Tertiary endpoints include ventricular arrhythmias, left and right ventricular function at rest and during exercise, arterial stiffness and carotid artery intima media thickness.Two hundred male lifelong athletes, 200 late-onset athletes and 200 healthy non-athletes aged 45–70 will undergo comprehensive cardiovascular phenotyping using CT, coronary angiography, echocardiography, cardiac MRI, 12-lead ECG, exercise ECG and 24-hour Holter monitoring at baseline. Follow-up will include online tracking of sports activities, telephone calls to assess clinical events and a 7-day ECG recording after 1 year.Ethics and disseminationLocal ethics committees approved the Master@Heart study. The trial was launched on 18 October 2018, recruitment is complete and inclusions are ongoing.Trial registration numberNCT03711539.