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.

Electrocardiographic Findings in Female Professional Basketball Athletes.

Importance: Previous studies of professional basketball athletes have characterized manifestations of athletic remodeling by echocardiography and electrocardiography (ECG) in males and echocardiography in females. There is a paucity of female, basketball-specific ECG data. Objective: To generate reference range ECG data for female professional basketball athletes. Design, Setting, and Participants: This is a cross-sectional study of ECGs performed on female professional basketball athletes. The Women's National Basketball Association mandates annual preseason ECGs and echocardiograms for each athlete and has partnered with Columbia University Irving Medical Center to annually review these studies. Data for this study were collected during preseason ECG and echocardiography cardiac screening between April and May 2022. Data analysis was performed between February and July 2023. Exposure: Athlete ECGs and echocardiograms were sent to Columbia University Irving Medical Center for core lab analysis. Main Outcomes and Measures: Quantitative ECG variables were measured. ECG data were qualitatively analyzed for training-related and abnormal findings using the International Recommendations for Electrocardiographic Interpretation in Athletes. Findings from ECGs were compared with corresponding echocardiographic data. Results: There were a total of 173 athletes (mean [SD] age 26.5 [4.1] years; mean [SD] height, 183.4 [9.1] cm; mean [SD] body surface area, 2.0 [0.2] m2), including 129 Black athletes (74.5%) and 40 White athletes (23.1%). By international criteria, 136 athletes (78.6%) had training-related ECG changes and 8 athletes (4.6%) had abnormal ECG findings. Among athletes with at least 1 training-related ECG finding, left ventricular structural adaptations associated with athletic remodeling were present in 64 athletes (47.1%). Increased relative wall thickness, reflecting concentric left ventricular geometry, was more prevalent in athletes with the repolarization variant demonstrating convex ST elevation combined with T-wave inversions in leads V1 to V4 (6 of 12 athletes [50.0%]) than in athletes with early repolarization (5 of 42 athletes [11.9%]) (odds ratio, 7.40; 95% CI, 1.71-32.09; P = .01). Abnormal ECG findings included T-wave inversions (3 athletes [1.7%]), Q waves (2 athletes [1.2%]), prolonged QTc interval (2 athletes [1.2%]), and frequent premature ventricular contractions (1 athlete [0.6%]). Conclusions and Relevance: This cross-sectional study provides reference ECG data for elite female basketball athletes. International criteria-defined training-related findings were common, whereas abnormal ECG findings were rare in this athlete group. These reference data may assist basketball programs and health care professionals using ECGs in screening for female athletes and may be used as a stimulus for future female-specific ECG inquiries.

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.

Impact of Sex on Cardiovascular Adaptations to Exercise: JACC Review Topic of the Week.

Routine exercise leads to cardiovascular adaptations that differ based on sex. Use of cardiac testing to screen athletes has driven research to define how these sex-based adaptations manifest on the electrocardiogram and cardiac imaging. Importantly, sex-based differences in cardiovascular structure and outcomes in athletes often parallel findings in the general population, underscoring the importance of understanding their mechanisms. Substantial gaps exist in the understanding of why cardiovascular adaptations and outcomes related to exercise differ by sex because of underrepresentation of female participants in research. As female sports participation rates have increased dramatically over several decades, it also remains unknown if differences observed in older athletes reflect biological mechanisms vs less lifetime access to sports in females. In this review, we will assess the effect of sex on cardiovascular adaptations and outcomes related to exercise, identify the impact of sex hormones on exercise performance, and highlight key areas for future research.

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.

Rationale and Design of the ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) Study.

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.

A Practical Approach to Echocardiographic Imaging in Patients With Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is frequently unrecognized or misdiagnosed. The recently published consensus recommendations from the American Society of Echocardiography provided recommendations for the utilization of multimodality imaging in the care of patients with HCM. This document provides an additional practical framework for optimal image and measurement acquisition and guidance on how to tailor the echocardiography examination for individuals with HCM. It also provides resources for physicians and sonographers to use to develop HCM imaging protocols.

Shared Decision-Making in Athletes Diagnosed With a Cardiovascular Condition: A Scoping Review.

This scoping review summarizes existing approaches, benefits, and barriers to shared decision-making (SDM) in the context of sports cardiology. Among 6,058 records screened, 37 articles were included in this review. Most included articles defined SDM as an open dialogue between the athlete, healthcare team, and other stakeholders. The benefits and risks of management strategies, treatment options, and return-to-play were the focus of this dialogue. Key components of SDM were described through various themes, such as emphasizing patient values, considering nonphysical factors, and informed consent. Benefits of SDM included enhancing patient understanding, implementing a personalized management plan, and considering a holistic approach to care. Barriers to SDM included pressure from institutions, consideration of multiple perspectives in decision-making, and the potential liability of healthcare providers. The use of SDM when discussing management, treatment, and lifestyle modification for athletes diagnosed with a cardiovascular condition is necessary to ensure patient autonomy and engagement.

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.

Post-systolic shortening index by echocardiography evaluation of dyssynchrony in the non-dilated and hypertrophied left ventricle.

BACKGROUND: Post-systolic shortening index (PSI) is defined as myocardial shortening that occurs after aortic valve closure, and is an emerging measure of regional LV contractile dysfunction. PSI measurement variability amongst software vendor and its relationship with mechanical dyssynchrony and mechanical dispersion index (MDI) remains unknown. We evaluated PSI by speckle-tracking echocardiography from several vendors in patients with increased left ventricular wall thickness, and associations with MDI. METHODS: This is a prospective cross-sectional study of 70 patients (36 hypertrophic cardiomyopathy [HCM], 18 cardiac amyloidosis and 16 healthy controls) undergoing clinically indicated echocardiography. PSI was measured using QLAB/aCMQ (Philips), QLAB/LV auto-trace (Philips), EchoPAC (GE), Velocity Vector Imaging (Siemens), and EchoInsight (EPSILON) software packages, and calculated as 100%×(post systolic strain-end-systole strain)/post systolic strain. RESULTS: There was a significant difference in mean PSI among controls 2.1±0.6%, HCM 6.1±2.6% and cardiac amyloidosis 6.8±2.7% (p <0.001). Variations between software vendors were significant in patients with pathologic increases in LV wall thickness (for HCM p = 0.03, for amyloidosis p = 0.008), but not in controls (p = 0.11). Furthermore, there were moderate correlations between PSI and both MDI (r = 0.77) and left ventricular global longitudinal strain (r = 0.69). CONCLUSION: PSI was greater in HCM and cardiac amyloidosis patients than controls, and a valuable tool for dyssynchrony evaluation, with moderate correlations to MDI and strain. However, there were significant variations in PSI measurements by software vendor especially in patients with pathological increase in LV wall thickness, suggesting that separate vendor-specific thresholds for abnormal PSI are required.

Recommendations for Multimodality Cardiovascular Imaging of Patients with Hypertrophic Cardiomyopathy: An Update from the American Society of Echocardiography, in Collaboration with the American Society of Nuclear Cardiology, the Society for Cardiovascular Magnetic Resonance, and the Society of Cardiovascular Computed Tomography.

Hypertrophic cardiomyopathy (HCM) is defined by the presence of left ventricular hypertrophy in the absence of other potentially causative cardiac, systemic, syndromic, or metabolic diseases. Symptoms can be related to a range of pathophysiologic mechanisms including left ventricular outflow tract obstruction with or without significant mitral regurgitation, diastolic dysfunction with heart failure with preserved and heart failure with reduced ejection fraction, autonomic dysfunction, ischemia, and arrhythmias. Appropriate understanding and utilization of multimodality imaging is fundamental to accurate diagnosis as well as longitudinal care of patients with HCM. Resting and stress imaging provide comprehensive and complementary information to help clarify mechanism(s) responsible for symptoms such that appropriate and timely treatment strategies may be implemented. Advanced imaging is relied upon to guide certain treatment options including septal reduction therapy and mitral valve repair. Using both clinical and imaging parameters, enhanced algorithms for sudden cardiac death risk stratification facilitate selection of HCM patients most likely to benefit from implantable cardioverter-defibrillators.

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.

Sex-based differences in left ventricular remodeling in patients with chronic aortic regurgitation: a multi-modality study.

BACKGROUND: Significant aortic regurgitation (AR) leads to left ventricular (LV) remodeling; however, little data exist regarding sex-based differences in LV remodeling in this setting. We sought to compare LV remodeling and AR severity, assessed by echocardiography and cardiovascular magnetic resonance (CMR), to discern sex-based differences. METHODS: Patients with ≥ moderate chronic AR by echocardiography who underwent CMR within 90 days between December 2005 and October 2015 were included. Nonlinear regression models were built to assess the effect of AR regurgitant fraction (RF) on LV remodeling. A generalized linear model and Bland Altman analyses were constructed to evaluate differences between CMR and echocardiography. Referral for surgical intervention based on symptoms and LV remodeling was evaluated. RESULTS: Of the 243 patients (48.3 ± 16.6 years, 58 (24%) female), 119 (49%) underwent surgical intervention with a primary indication of severe AR, 97 (82%) men, 22 (18%) women. Significant sex differences in LV remodeling emerged on CMR. Women demonstrated significantly smaller LV end-diastolic volume index (LVEDVI) (96.8 ml/m2 vs 125.6 ml/m2, p < 0.001), LV end-systolic volume index (LVESVI) (41.1 vs 54.5 ml/m2, p < 0.001), blunted LV dilation in the setting of increasing AR severity (LVEDVI p value < 0.001, LVESVI p value 0.011), and LV length indexed (8.32 vs 9.69 cm, p < 0.001). On Bland Altman analysis, a significant interaction with sex and LV diameters was evident, demonstrating a significant increase in the difference between CMR and echocardiography measurements as the LV enlarged in women: LVEDVI (p = 0.006), LVESVI (p < 0.001), such that echocardiographic measurements increasingly underestimated LV diameters in women as the LV enlarged. LV length was higher for males with a linear effect from RF (p < 0.001), with LV length increasing at a higher rate with increasing RF for males compared to females (two-way interaction with sex p = 0.005). Sphericity volume index was higher for men after adjusting for a relative wall thickness (p = 0.033). CONCLUSIONS: CMR assessment of chronic AR revealed significant sex differences in LV remodeling and significant echocardiographic underestimation of LV dilation, particularly in women. Defining optimal sex-based CMR thresholds for surgical referral should be further developed. TRIAL REGISTRATION: NA.