Safety and Efficacy of Metabolic Modulation With Ninerafaxstat in Patients With Nonobstructive Hypertrophic Cardiomyopathy.

BACKGROUND: In nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and exercise limitation. Ninerafaxstat, a novel cardiac mitotrope, enhances cardiac energetics. OBJECTIVES: To evaluate the safety and efficacy of ninerafaxstat in nHCM. METHODS: Patients with HCM and left ventricular (LV) outflow gradient <30 mmHg, ejection fraction ≥50% and peak VO2 <80% predicted, were randomized to ninerafaxstat 200 mg BID or placebo (1:1) for 12 weeks. Primary endpoint was safety and tolerability with efficacy outcomes also assessed as secondary endpoints. RESULTS: A total of 67 patients with nHCM were enrolled at 12 centers (57 yrs ± 11.8; 55% women). Serious adverse events occurred in 11.8% (4/34) in the ninerafaxstat group and 6.1% of patients (2/33) in placebo. From baseline to 12 weeks, ninerafaxstat was associated with significantly better ventilatory efficiency (VE/VCO2 slope) compared to placebo with a least square (LS) mean difference between the groups of -2.1 (95% CI, -3.4, -0.6; p=0.006), with no significant difference in pVO2 (p=0.9). KCCQ-CCS was directionally though not significantly improved with ninerafaxstat vs. placebo (LS mean, 3.2 [95% CI, -2.9, 9.2; p=0.2]), though was statistically significant when analyzed post-hoc in the 35 patients with baseline KCCQ-CSS ≤80 (LS mean, 9.4 [95% CI, 0.2, 18.5; p=0.04]). CONCLUSIONS: In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a Phase 3 study.

Return-to-Play for Elite Athletes With Genetic Heart Diseases Predisposing to Sudden Cardiac Death.

BACKGROUND: People diagnosed with genetic heart diseases (GHDs) associated with sudden cardiac death (SCD) have historically been restricted from competitive sports. Recent data documenting return-to-play (RTP) experiences following shared decision making (SDM) suggest that cardiac event rates for athletes with a GHD are lower than previously described, thereby suggesting an opportunity to reconsider this paradigm. OBJECTIVES: The purpose of this study was to evaluate clinical outcomes among National Collegiate Athletic Association Division I university and professional athletes diagnosed with a GHD. METHODS: A multicenter retrospective analysis was performed to examine demographics, clinical characteristics, RTP outcomes, and cardiac events among elite athletes with a GHD. RESULTS: A total of 76 elite (66%, Division I, 34% professional) athletes (age 19.9 ± 5 years, 28% women) diagnosed with a GHD (hypertrophic cardiomyopathy [53%], long QT syndrome, long QT syndrome [26%]) comprise this cohort. Most athletes were asymptomatic (48 of 76, 63%) before diagnosis and had their GHD detected during routine preparticipation cardiovascular screening. Most athletes (55 of 76, 72%) were initially disqualified from their sport but subsequently opted for unrestricted RTP after comprehensive clinical evaluation and SDM. To date, (mean follow-up 7 ± 6 years), only 1 exercise-related (1.3%) and 2 nonexercise-related GHD-associated adverse cardiac events occurred. There have been no fatalities during follow-up. CONCLUSIONS: This is the first study describing the experience of athletes with a known SCD-predisposing GHD who are competing at the elite level. After careful evaluation, risk stratification, and tailoring of their GHD therapy, RTP following SDM appears associated with low, nonfatal events rates at elite levels of sport.

Wearable technology in the sports medicine clinic to guide the return-to-play and performance protocols of athletes following a COVID-19 diagnosis.

The coronavirus disease 2019 (COVID-19) pandemic has enabled the adoption of digital health platforms for self-monitoring and diagnosis. Notably, the pandemic has had profound effects on athletes and their ability to train and compete. Sporting organizations worldwide have reported a significant increase in injuries manifesting from changes in training regimens and match schedules resulting from extended quarantines. While current literature focuses on the use of wearable technology to monitor athlete workloads to guide training, there is a lack of literature suggesting how such technology can mediate the return to sport processes of athletes infected with COVID-19. This paper bridges this gap by providing recommendations to guide team physicians and athletic trainers on the utility of wearable technology for improving the well-being of athletes who may be asymptomatic, symptomatic, or tested negative but have had to quarantine due to a close exposure. We start by describing the physiologic changes that occur in athletes infected with COVID-19 with extended deconditioning from a musculoskeletal, psychological, cardiopulmonary, and thermoregulatory standpoint and review the evidence on how these athletes may safely return to play. We highlight opportunities for wearable technology to aid in the return-to-play process by offering a list of key parameters pertinent to the athlete affected by COVID-19. This paper provides the athletic community with a greater understanding of how wearable technology can be implemented in the rehabilitation process of these athletes and spurs opportunities for further innovations in wearables, digital health, and sports medicine to reduce injury burden in athletes of all ages.

Does cardiovascular preparticipation screening cause psychological distress in athletes? A systematic review.

OBJECTIVE: To evaluate the psychological implications of cardiovascular preparticipation screening (PPS) in athletes. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE, PubMed, CINAHL, SPORTDiscus, APA PsycInfo, Cochrane Library and grey literature sources. STUDY ELIGIBILITY CRITERIA: Observational and experimental studies assessing a population of athletes who participated in a cardiovascular PPS protocol, where psychological outcomes before, during and/or after PPS were reported. METHODS: Results of included studies were synthesised by consolidating similar study-reported measures for key psychological outcomes before, during and/or after screening. Summary measures (medians, ranges) were computed across studies for each psychological outcome. RESULTS: A total of eight studies were included in this review (median sample size: 479). Study cohorts consisted of high school, collegiate, professional and recreational athletes (medians: 59% male, 20.5 years). Most athletes reported positive reactions to screening and would recommend it to others (range 88%-100%, five studies). Increased psychological distress was mainly reported among athletes detected with pathological cardiac conditions and true-positive screening results. In comparison, athletes with false-positive screening results still reported an increased feeling of safety while participating in sport and were satisfied with PPS. A universal conclusion across all studies was that most athletes did not experience psychological distress before, during or after PPS, regardless of the screening modality used or accuracy of results. CONCLUSION: Psychological distress associated with PPS in athletes is rare and limited to athletes with true-positive findings. To mitigate downstream consequences in athletes who experience psychological distress, appropriate interventions and resources should be accessible prior to the screening procedure. PROSPERO REGISTRATION NUMBER: CRD42021272887.

Wearable Sensor Technology to Predict Core Body Temperature: A Systematic Review.

Heat-related illnesses, which range from heat exhaustion to heatstroke, affect thousands of individuals worldwide every year and are characterized by extreme hyperthermia with the core body temperature (CBT) usually > 40 °C, decline in physical and athletic performance, CNS dysfunction, and, eventually, multiorgan failure. The measurement of CBT has been shown to predict heat-related illness and its severity, but the current measurement methods are not practical for use in high acuity and high motion settings due to their invasive and obstructive nature or excessive costs. Noninvasive predictions of CBT using wearable technology and predictive algorithms offer the potential for continuous CBT monitoring and early intervention to prevent HRI in athletic, military, and intense work environments. Thus far, there has been a lack of peer-reviewed literature assessing the efficacy of wearable devices and predictive analytics to predict CBT to mitigate heat-related illness. This systematic review identified 20 studies representing a total of 25 distinct algorithms to predict the core body temperature using wearable technology. While a high accuracy in prediction was noted, with 17 out of 18 algorithms meeting the clinical validity standards. few algorithms incorporated individual and environmental data into their core body temperature prediction algorithms, despite the known impact of individual health and situational and environmental factors on CBT. Robust machine learning methods offer the ability to develop more accurate, reliable, and personalized CBT prediction algorithms using wearable devices by including additional data on user characteristics, workout intensity, and the surrounding environment. The integration and interoperability of CBT prediction algorithms with existing heat-related illness prevention and treatment tools, including heat indices such as the WBGT, athlete management systems, and electronic medical records, will further prevent HRI and increase the availability and speed of data access during critical heat events, improving the clinical decision-making process for athletic trainers and physicians, sports scientists, employers, and military officers.

Myocarditis in the Athlete: A Focus on COVID-19 Sequelae.

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.

A Video-Enhanced, Electronic Modality for Preparticipation Examination of Young Athletes.

ABSTRACT: We developed a video-enhanced preparticipation evaluation symptom questionnaire (the V-PPE), intended to help screen athletes for heart disease. We now report results of a pilot quality improvement study evaluating V-PPE's performance. In a prospective before-and-after study, approximately 5700 high-school athletes were prompted to voluntarily fill out the V-PPE questionnaire. We compared symptom frequencies on standard PPE to those on V-PPE. Of 5700 athletes, 46 (0.8%), 117 (2.0%), 33 (0.6%), and 101 (1.8%) reported syncope, angina, palpitations, and dyspnea, respectively on routine screening. Four hundred and ninety-two (8.6%) voluntarily filled out the V-PPE. Athletes were more likely to report palpitations on V-PPE than PPE, but not angina, dyspnea, syncope, or at least one symptom. Symptom frequencies on electronic PPE questionnaires are lower than recent reports suggest. Embedded videos can alter screening yield. More research is necessary to evaluate the predictive value of the V-PPE for clinically relevant cardiac pathology.

Hypertrophic Cardiomyopathy: Updates Through the Lens of Sports Cardiology.

PURPOSE OF REVIEW: This review will summarize the distinction between hypertrophic cardiomyopathy (HCM) and exercise-induced cardiac remodeling (EICR), describe treatments of particular relevance to athletes with HCM, and highlight the evolution of recommendations for exercise and competitive sport participation relevant to individuals with HCM. RECENT FINDINGS: Whereas prior guidelines have excluded individuals with HCM from more than mild-intensity exercise, recent data show that moderate-intensity exercise improves functional capacity and indices of cardiac function and continuation of competitive sports may not be associated with worse outcomes. Moreover, recent studies of athletes with implantable cardioverter defibrillators (ICDs) demonstrated a safer profile than previously understood. In this context, the updated American Heart Association/American College of Cardiology (AHA/ACC) and European Society of Cardiology (ESC) HCM guidelines have increased focus on shared decision-making and liberalized restrictions on exercise and sport participation among individuals with HCM. SUMMARY: New data demonstrating the safety of exercise in individuals with HCM and in athletes with ICDs, in addition to a focus on shared decision-making, have led to the most updated guidelines easing restrictions on exercise and competitive athletics in this population. Further athlete-specific studies of HCM, especially in the context of emerging therapies such as mavacamten, are important to inform accurate risk stratification and eligibility recommendations.

Outcomes of Pulmonary Vein Isolation in Athletes.

OBJECTIVES: The aims of this study were to assess outcomes of pulmonary vein isolation (PVI) performed on athletes at a tertiary care center and to characterize its efficacy and physiological effects. BACKGROUND: The incidence of atrial fibrillation (AF) is increased in highly trained athletes and poses unique management challenges. METHODS: Athletes were identified through a database of patients undergoing PVI from January 2000 through October 2015. Outcomes of AF ablation were defined in accordance with published guidelines. Available electrocardiographic, echocardiographic, and exercise treadmill testing data were also analyzed. RESULTS: The study population included 144 athletes (93% men; mean age 50.4 ± 8.6 years; 97 paroxysmal, 38 persistent, and 9 long-standing persistent) with median follow-up of 3 years. Single-procedure freedom from arrhythmia was 75%, 68%, and 33% at 1 year for paroxysmal, persistent, and long-standing persistent AF, respectively. Multiple-procedure freedom from arrhythmia off antiarrhythmic drugs was 86%, 76%, and 56% in respective groups at the end of follow-up (mean 1.4 ± 0.7 ablations per athlete). Compared with a matched cohort of nonathletes who underwent PVI, there was no difference in arrhythmia recurrence (log-rank p = 0.23). Excluding long-standing persistent AF, longer diagnosis-to-ablation time was the only variable in Cox proportional hazards analyses associated with arrhythmia recurrence (adjusted heart rate per log increase: 1.92; 95% confidence interval: 1.40 to 2.73; p < 0.0001), and PVI within 2 years of diagnosis was notably associated with successful outcomes (log-rank p = 0.002). Sinus rate increased following the index ablation (mean 54 beats/min vs. 64 beats/min at >1 year; p < 0.0001), but maximum metabolic equivalents on exercise treadmill testing were unchanged (13.1 ± 1.2 vs. 12.7 ± 1.4; p = 0.44). CONCLUSIONS: PVI is an effective therapy in athletes with paroxysmal and persistent AF, and arrhythmia recurrence was no different from that among matched nonathletes. Early ablation was associated with improved success rates. Sustained cardioautonomic effects were observed following ablation, but exercise capacity was preserved.

Mitral and tricuspid stenosis caused by light chain cardiac amyloid deposition.

Cardiac amyloidosis results in an infiltrative restrictive cardiomyopathy, with a number of characteristic features: biventricular hypertrophy, abnormal myocardial global longitudinal strain with relative apical sparing, biatrial dilation, and small pericardial effusion along with conduction abnormalities. Amyloid deposits leading to hemodynamically significant valvular heart disease are very rare. We describe a rare case of concomitant moderately severe tricuspid and mitral valve stenosis because of ongoing amyloid deposition in a patient with progressive multiple myeloma and fat pad biopsy-proven light chain amyloidosis. Worsening infiltrative cardiomyopathy and valvulopathy despite evidence-based chemotherapy and heart failure pharmacotherapy led to end-stage disease and death. Valvular involvement in cardiac amyloidosis requires early recognition of the underlying disease condition to guide directed medical therapy and prevent its progression. In this instance, valvuloplasty or valve replacement is not a viable option.

Wearable Technology and Analytics as a Complementary Toolkit to Optimize Workload and to Reduce Injury Burden.

Wearable sensors enable the real-time and non-invasive monitoring of biomechanical, physiological, or biochemical parameters pertinent to the performance of athletes. Sports medicine researchers compile datasets involving a multitude of parameters that can often be time consuming to analyze in order to create value in an expeditious and accurate manner. Machine learning and artificial intelligence models may aid in the clinical decision-making process for sports scientists, team physicians, and athletic trainers in translating the data acquired from wearable sensors to accurately and efficiently make decisions regarding the health, safety, and performance of athletes. This narrative review discusses the application of commercial sensors utilized by sports teams today and the emergence of descriptive analytics to monitor the internal and external workload, hydration status, sleep, cardiovascular health, and return-to-sport status of athletes. This review is written for those who are interested in the application of wearable sensor data and data science to enhance performance and reduce injury burden in athletes of all ages.

Ascending Aortic Dimensions in Former National Football League Athletes.

BACKGROUND: Ascending aortic dimensions are slightly larger in young competitive athletes compared with sedentary controls, but rarely >40 mm. Whether this finding translates to aortic enlargement in older, former athletes is unknown. METHODS AND RESULTS: This cross-sectional study involved a sample of 206 former National Football League (NFL) athletes compared with 759 male subjects from the DHS-2 (Dallas Heart Study-2; mean age of 57.1 and 53.6 years, respectively, P<0.0001; body surface area of 2.4 and 2.1 m2, respectively, P<0.0001). Midascending aortic dimensions were obtained from computed tomographic scans performed as part of a NFL screening protocol or as part of the DHS. Compared with a population-based control group, former NFL athletes had significantly larger ascending aortic diameters (38±5 versus 34±4 mm; P<0.0001). A significantly higher proportion of former NFL athletes had an aorta of >40 mm (29.6% versus 8.6%; P<0.0001). After adjusting for age, race, body surface area, systolic blood pressure, history of hypertension, current smoking, diabetes mellitus, and lipid profile, the former NFL athletes still had significantly larger ascending aortas (P<0.0001). Former NFL athletes were twice as likely to have an aorta >40 mm after adjusting for the same parameters. CONCLUSIONS: Ascending aortic dimensions were significantly larger in a sample of former NFL athletes after adjusting for their size, age, race, and cardiac risk factors. Whether this translates to an increased risk is unknown and requires further evaluation.

Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone.

OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF). BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown. METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained. RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide. CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).