BACKGROUND: Clinical practice recommendations for participation in sports and exercise among young competitive athletes with cardiovascular conditions at risk for sudden death are based largely on expert consensus with a paucity of prospective outcomes data. Recent guidelines have taken a more permissive approach, using a shared decision-making model. However, the impact and outcomes of this strategy remain unknown. METHODS: The ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) study is a prospective, multicenter, longitudinal, observational cohort study designed to monitor clinical outcomes in athletes with potentially life-threatening cardiovascular conditions. The study will assess sports eligibility decision-making, exercise habits, psychosocial well-being, and long-term cardiovascular outcomes among young competitive athletes with cardiovascular conditions. Competitive athletes aged 18 to <35 years diagnosed with a confirmed cardiovascular condition or borderline finding with potential increased risk of major adverse cardiovascular events are eligible. Outcomes will be monitored for an initial 5-year follow-up period or until age 35, and metrics of psychosocial well-being and composite adverse cardiovascular events including arrhythmias, sudden cardiac arrest/sudden cardiac death, and evidence of disease progression will be compared among athletes who continue versus discontinue competitive sports participation. CONCLUSIONS: The ORCCA study aims to assess the process and results of return to sport decision-making and to monitor major adverse cardiovascular events, exercise habits, and the psychosocial well-being among young competitive athletes diagnosed with confirmed cardiovascular conditions or borderline findings with potential increased risk of major adverse cardiovascular events. The results of this work will generate an evidence base to inform future guidelines.

BACKGROUND: Clinically relevant aortic dilatation (>40 mm) and increased cardiovascular risk are common among retired professional American-style football athletes. Among younger athletes, the effect of American-style football participation on aortic size is incompletely understood. We sought to determine changes in aortic root (AR) size and associated cardiovascular phenotypes across the collegiate career. METHODS AND RESULTS: This was a multicenter, longitudinal repeated-measures observational cohort study of athletes across 3 years of elite collegiate American-style football participation. A total of 247 athletes (119 [48%] Black, 126 [51%] White, 2 [1%] Latino; 91 [37%] linemen, 156 [63%] non-linemen) were enrolled as freshmen and studied at pre-and postseason year 1, postseason year 2 (N=140 athletes), and postseason year 3 (N=82 athletes). AR size was measured with transthoracic echo-cardiography. AR diameter increased over the study period from 31.7 (95% CI, 31.4–32.0) to 33.5 mm (95% CI, 33.1–33.8; P<0.001). No athlete developed an AR ≥40 mm. Athletes also demonstrated increased weight (cumulative mean Δ, 5.0 [95% CI, 4.1–6.0] kg, P<0.001), systolic blood pressure (cumulative mean Δ, 10.6 [95% CI, 8.0–13.2] mm Hg, P<0.001), pulse wave velocity (cumulative mean Δ, 0.43 [95% CI, 0.31–0.56] m/s, P<0.001), and left ventricular mass index (cumulative mean Δ, 21.2 [95% CI, 19.2–23.3] g/m2, P<0.001), and decreased E′ velocity (cumulative mean Δ, −2.4 [95%CI, −2.9 to −1.9] cm/s, P<0.001). Adjusting for height, player position, systolic blood pressure, and diastolic blood pressure, higher weight (β=0.030, P=0.003), pulse wave velocity (β=0.215, P=0.02), and left ventricular mass index (β=0.032, P<0.001) and lower E′ (β=−0.082, P=0.001) were associated with increased AR diameter. CONCLUSIONS: Over the collegiate American-style football career, athletes demonstrate progressive AR dilatation associated with cardiac and vascular functional impairment. Future studies delineating aortic outcomes are necessary to determine whether AR dilation is indicative of maladaptive vascular remodeling in this population.

As the popularity of scuba diving increases internationally, physicians interacting with divers in the clinical setting must be familiar with the cardiovascular stresses and risks inherent to this activity. Scuba presents a formidable cardiovascular challenge by combining unique environmental conditions with the physiologic demands of underwater exercise. Haemodynamic stresses encountered at depth include increased hydrostatic pressure leading to central shifts in plasma volume coupled with cold water stimuli leading to simultaneous parasympathetic and sympathetic autonomic responses. Among older divers and those with underlying cardiovascular risk factors, these physiologic changes increase acute cardiac risks while diving. Additional scuba risks, as a consequence of physical gas laws, include arterial gas emboli and decompression sickness. These pathologies are particularly dangerous with altered sensorium in hostile dive conditions. When present, the appropriate management of patent foramen ovale (PFO) is uncertain, but closure of PFO may reduce the risk of paradoxical gas embolism in divers with a prior history of decompression sickness. Finally, similar to other Masters-level athletes, divers with underlying traditional cardiovascular risk should undergo complete cardiac risk stratification to determine 'fitness-to-dive'. The presence of undertreated coronary artery disease, occult cardiomyopathy, channelopathy and arrhythmias must all be investigated and appropriately treated in order to ensure diver safety. A patient-centred approach facilitating shared decision-making between divers and experienced practitioners should be utilised in the management of prospective scuba divers.

Myocarditis is a leading cause of sudden death in athletes. Early data demonstrating increased prevalence of cardiac injury in hospitalized patients with COVID-19 raised concerns for athletes recovered from COVID-19 and the possibility of underlying myocarditis. However, subsequent large registries have provided reassuring data affirming low prevalence of myocarditis in athletes convalesced from COVID-19. Although the clinical significance of subclinical myocarditis detected by cardiac MRI remains uncertain, clinical outcomes have not demonstrated an increase in acute cardiac events in athletes throughout the pandemic. Future directions include defining mechanisms underlying "long-haul" COVID-19 and the potential impact of new viral variants.

OBJECTIVES: American-style football (ASF) athletes are at risk for the development of concentric left ventricular hypertrophy (C-LVH), an established cardiovascular risk factor in the general population. We sought to address whether black race is associated with acquired C-LVH in collegiate ASF athletes. METHODS: Collegiate ASF athletes from two National Collegiate Athletic Association Division-I programmes were recruited as freshmen between 2014 and 2019 and analysed over 3 years. Demographics (neighbourhood family income) and repeated clinical characteristics and echocardiography were recorded longitudinally at multiple timepoints. A mixed-modelling approach was performed to evaluate acquired C-LVH in black versus white athletes controlling for playing position (linemen (LM) and non-linemen (NLM)), family income, body weight and blood pressure. RESULTS: At baseline, black athletes (N=124) were more often NLM (72% vs 54%, p=0.005) and had lower median neighbourhood family income ($54 119 vs $63 146, p=0.006) compared with white athletes (N=125). While both black and white LM demonstrated similar increases in C-LVH over time, among NLM acquired C-LVH was more common in black versus white athletes (postseason year-1: N=14/89 (16%) vs N=2/68 (3%); postseason year-2: N=9/50 (18%) vs N=2/32 (6%); postseason year-3: N=8/33 (24%) vs N=1/13 (8%), p=0.005 change over time). In stratified models, black race was associated with acquired C-LVH in NLM (OR: 3.70, 95% CI 1.12 to 12.21, p=0.03) and LM was associated with acquired C-LVH in white athletes (OR: 3.40, 95% CI 1.03 to 11.27, p=0.048). CONCLUSIONS: Independent of family income and changes in weight and blood pressure, black race was associated with acquired C-LVH among collegiate ASF NLM and LM was associated with acquired C-LVH in white athletes.

Repeated bouts of exercise condition muscle mitochondria to meet increased energy demand—an adaptive response associated with improved metabolic fitness. We found that the type 2 cytokine interleukin-13 (IL-13) is induced in exercising muscle, where it orchestrates metabolic reprogramming that preserves glycogen in favor of fatty acid oxidation and mitochondrial respiration. Exercise training–mediated mitochondrial biogenesis, running endurance, and beneficial glycemic effects were lost in Il13–/– mice. By contrast, enhanced muscle IL-13 signaling was sufficient to increase running distance, glucose tolerance, and mitochondrial activity similar to the effects of exercise training. In muscle, IL-13 acts through both its receptor IL-13Ra1 and the transcription factor Stat3. The genetic ablation of either of these downstream effectors reduced running capacity in mice. Thus, coordinated immunological and physiological responses mediate exercise-elicited metabolic adaptations that maximize muscle fuel economy.

Background: As the population of adults with congenital heart disease (CHD) grows, cardiologists continue to encounter patients with complex anatomies that challenge the standard treatment of care. Single ventricle Fontan palliated patients are the most complex within CHD, with a high morbidity and mortality burden. Factors driving this early demise are largely unknown. Methods and Results: We analyzed biomarker expression in 44 stable Fontan outpatients (29.2 ± 10.7 years, 68.2% female) seen in the outpatient Emory Adult Congenital Heart Center and compared them to 32 age, gender and race matched controls. In comparison to controls, Fontan patients had elevated levels of multiple cytokines within the inflammatory pathway including Tumor Necrosis Factor-α (TNF-α) (p<0.001), Interleukin-6 (IL-6) (p<0.011), Growth Derived Factor-15 (GDF-15) (p<0.0001), β2-macroglobulin, (p=0.0006), stem cell mobilization: SDF-1α (p=0.006), extracellular matrix turnover: Collagen IV (p<0.0001), neurohormonal activation: Renin (p<0.0001), renal dysfunction: Cystatin C (p<0.0001) and Urokinase receptor (uPAR) (p=0.022), cardiac injury: Troponin-I (p<0.0004) and metabolism: Adiponectin (p=0.0037). Within our baseline -stable- Fontan patients, 50% had hospitalizations, arrhythmias and worsening hepatic function within 1 year. GDF-15 was significantly increased in Fontan patients with clinical events (p<0.0001). In addition, GDF-15 moderately correlated with longer duration of Fontan (r=0.55, p=0.01) and was elevated in atriopulmonary (AP) Fontan circulation. Finally, in a multivariate model, VEGF-D and Collagen IV levels were found to be associated with a change in MELDXI, a marker of liver function. Conclusion: Multiple clinical and molecular biomarkers are upregulated in Fontan patients, suggesting a state of chronic systemic dysregulation.

The associations between high-sensitivity troponin I (hsTnI) levels and coronary artery disease (CAD) severity and progression remain unclear. We investigated whether there is an association between hsTnI and angiographic severity and progression of CAD and whether the predictive value of hsTnI level for incident cardiovascular outcomes is independent of CAD severity. Methods and Results--In 3087 patients (aged 63±12 years, 64% men) undergoing cardiac catheterization without evidence of acute myocardial infarction, the severity of CAD was calculated by the number of major coronary arteries with ≥50% stenosis and the Gensini score. CAD progression was assessed in a subset of 717 patients who had undergone ≥2 coronary angiograms > 3 months before enrollment. Patients were followed up for incident all-cause mortality and incident cardiovascular events. Of the total population, 11% had normal angiograms, 23% had nonobstructive CAD, 20% had 1-vessel CAD, 20% had 2-vessel CAD, and 26% had 3-vessel CAD. After adjusting for age, sex, race, body mass index, smoking, hypertension, diabetes mellitus history, and renal function, hsTnI levels were independently associated with the severity of CAD measured by the Gensini score (log 2 β=0.31; 95% confidence interval, 0.18-0.44; P < 0.001) and with CAD progression (log 2 β=0.36; 95% confidence interval, 0.14-0.58; P=0.001). hsTnI level was also a significant predictor of incident death, cardiovascular death, myocardial infarction, revascularization, and cardiac hospitalizations, independent of the aforementioned covariates and CAD severity. Conclusions--Higher hsTnI levels are associated with the underlying burden of coronary atherosclerosis, more rapid progression of CAD, and higher risk of all-cause mortality and incident cardiovascular events. Whether more aggressive treatment aimed at reducing hsTnI levels can modulate disease progression requires further investigation.

The COVID-19 pandemic brought the global world of sports to a staggering halt. In unprecedented fashion and with few exceptions, professional leagues, mass participation endurance events, and youth sport around the globe went silent. In the face of a rapidly evolving health crisis, the decision to cancel or postpone sporting events was a logical and necessary step. COVID-19 is a highly contagious, potentially fatal virus that is transmitted primarily through contact with aerosolised or surface-dwelling respiratory secretions, a process that requires close human contact.1 Competitive sport as we know it, from athletes ‘elbowing’ one another for position on the pitch to arenas packed with fans, may be the quintessential antithesis of social distancing. There is concern that the Champions League match between Atalanta and Valencia in Milan may have influenced the trajectory of COVID-19 cases in Europe.2 In the absence of a vaccination or curative intervention, physical distancing emerged as the key step to slow or stop the spread of COVID-19. Thus, the decision to turn off the lights and to silence competitive athletics represented a logical, essential and highly visible component in the global fight against COVID-19.

Background--Being unmarried is associated with decreased survival in the general population. Whether married, divorced, separated, widowed, or never-married status affects outcomes in patients with cardiovascular disease has not been well characterized. Methods and Results--A prospective cohort (inception period 2003-2015) of 6051 patients (mean age 63 years, 64% male, 23% black) undergoing cardiac catheterization for suspected or confirmed coronary artery disease was followed for a median of 3.7 years (interquartile range: 1.7-6.7 years). Marital status was stratified as married (n=4088) versus unmarried (n=1963), which included those who were never married (n=451), divorced or separated (n=842), or widowed (n=670). The relationship between marital status and primary outcome of cardiovascular death and myocardial infarction was examined using Cox regression models adjusted for clinical characteristics. There were 1085 (18%) deaths from all causes, 688 (11%) cardiovascular-related deaths, and 272 (4.5%) incident myocardial infarction events. Compared with married participants, being unmarried was associated with higher risk of all-cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI] , 1.06-1.47), cardiovascular death (HR: 1.45; 95% CI, 1.18-1.78), and cardiovascular death or myocardial infarction (HR: 1.52; 95% CI, 1.27-1.83). Compared with married participants, the increase in cardiovascular death or myocardial infarction was similar for the participants who were divorced or separated (HR: 1.41; 95% CI, 1.10-1.81), widowed (HR: 1.71; 95% CI, 1.32-2.20), or never married (HR: 1.40; 95% CI, 0.97-2.03). The findings persisted after adjustment for medications and other socioeconomic factors. Conclusions--Marital status is independently associated with cardiovascular outcomes in patients with or at high risk of cardiovascular disease, with higher mortality in the unmarried population. The mechanisms responsible for this increased risk require further study.