Mavacamten in Right Ventricular Outflow Tract Obstruction.

Right ventricular outflow tract (RVOT) obstruction is a rare complication of ventricular hypertrophy in patients with hypertrophic cardiomyopathy (HCM). This study presents an unusual case of a patient with HCM with severe RVOT obstruction that was relieved successfully through the use of mavacamten.

Assessing athletes beyond routine screening: Incorporating essential factors to optimize cardiovascular health and performance.

The American Heart Association (AHA) has devised Life's Essential 8, a set of eight evidence-based health behaviors that play a crucial role in optimizing cardiovascular health and overall well-being. In addition to Life's Essential 8, enhanced screening for Cardiovascular-Kidney-Metabolic (CKM) Syndrome risk factors into routine athlete screening also provides a more comprehensive approach for ensuring athlete safety and long-term health. Incorporating Life's Essential 8 and CKM Syndrome metrics into athlete health evaluations will improve the sports performance of athletes and help optimize their long-term health.

Shared decision making for participation in elite athletes with cardiovascular conditions. Where are we now?

Sudden Cardiac Death is a leading medical cause of death in athletes of all ages. Recently there has been a shift from an authoritarian approach to that of using a Shared Decision Making (SDM) model in eligibility decisions of athletes with cardiovascular decisions. SDM in elite athletics can be complex and collaboration amongst the athlete, family, physicians, athletic trainers, and institutional stakeholders is critical. SDM acknowledges the complexities of a collaboration between sports cardiologists bringing disease and sport-specific expertise, and team physicians, in complementary fashion to integrate medical knowledge, clinical uncertainty, athlete and family values, and institutional philosophies and risk tolerance.

2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.

2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.

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: This study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM. METHODS: Patients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient <30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption <80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The 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 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) of patients in the placebo group. From baseline to 12 weeks, ninerafaxstat was associated with significantly better VE/Vco2 (ventilatory efficiency) slope compared with placebo with a least-squares (LS) mean difference between the groups of -2.1 (95% CI: -3.6 to -0.6; P = 0.006), with no significant difference in peak VO2 (P = 0.90). The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score was directionally, though not significantly, improved with ninerafaxstat vs placebo (LS mean 3.2; 95% CI: -2.9 to 9.2; P = 0.30); however, it was statistically significant when analyzed post hoc in the 35 patients with baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score ≤80 (LS mean 9.4; 95% CI: 0.3-18.5; 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.

Exercise After Acute Myocarditis: When and How to Return to Sports.

Myocarditis is an inflammatory disease of the myocardium secondary to infectious and noninfectious insults. The most feared consequence of myocarditis is sudden cardiac death owing to electrical instability and arrhythmia. Typical presenting symptoms include chest pain, dyspnea, palpitations and/or heart failure. Diagnosis is usually made with history, electrocardiogram, biomarkers, echocardiogram, and cardiac MRI (CMR). Application of the Lake Louise criteria to CMR results can help identify cases of myocarditis. Treatment is usually supportive with medical therapy, and patients are recommended to abstain from exercise for 3 to 6 months. Exercise restrictions may be lifted after normalization on follow-up testing.

A Multicenter Evaluation of the Impact of Therapies on Deep Learning-based Electrocardiographic Hypertrophic Cardiomyopathy Markers.

Background: Artificial intelligence-enhanced electrocardiography (AI-ECG) can identify hypertrophic cardiomyopathy (HCM) on 12-lead ECGs and offers a novel way to monitor treatment response. While the surgical or percutaneous reduction of the interventricular septum (SRT) represented initial HCM therapies, mavacamten offers an oral alternative. Objective: To evaluate biological response to SRT and mavacamten. Methods: We applied an AI-ECG model for HCM detection to ECG images from patients who underwent SRT across three sites: Yale New Haven Health System (YNHHS), Cleveland Clinic Foundation (CCF), and Atlantic Health System (AHS); and to ECG images from patients receiving mavacamten at YNHHS. Results: A total of 70 patients underwent SRT at YNHHS, 100 at CCF, and 145 at AHS. At YNHHS, there was no significant change in the AI-ECG HCM score before versus after SRT (pre-SRT: median 0.55 [IQR 0.24-0.77] vs post-SRT: 0.59 [0.40-0.75]). The AI-ECG HCM scores also did not improve post SRT at CCF (0.61 [0.32-0.79] vs 0.69 [0.52-0.79]) and AHS (0.52 [0.35-0.69] vs 0.61 [0.49-0.70]). Among 36 YNHHS patients on mavacamten therapy, the median AI-ECG score before starting mavacamten was 0.41 (0.22-0.77), which decreased significantly to 0.28 (0.11-0.50, p <0.001 by Wilcoxon signed-rank test) at the end of a median follow-up period of 237 days. Conclusions: The lack of improvement in AI-based HCM score with SRT, in contrast to a significant decrease with mavacamten, suggests the potential role of AI-ECG for serial monitoring of pathophysiological improvement in HCM at the point-of-care using ECG images.

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.

Longitudinal cardiac remodeling in collegiate American football players as assessed by echocardiography during their collegiate career.

BACKGROUND: Studies on the longitudinal effects of intense physical training on cardiac remodeling are limited, especially in American collegiate football players. HYPOTHESIS: College-level American football training will result in remodeling in a pattern consistent of a sport with moderate static and dynamic demands with increases in both wall and chamber sizes. METHODS: We studied 85 American collegiate football players who underwent transthoracic echocardiogram (TTE) for asymptomatic or mild COVID-19-related illness and compared the changes in echo dimensions to their preparticipation screening TTE. Pre- and posttraining variables were compared using a paired t-test for normally distributed variables. RESULTS: Mean age was 19 years ± 1 and 61% of athletes were Black. Mean follow-up between TTEs was 21 ± 13 months. There was an increase in left atrial volume index (26.4 ± 5.5 to 32.8 ± 8.4 mL/m2 , p < .001), LV end diastolic diameter (5.13 ± 0.4 to 5.27 ± 0.4 cm, p = .003), basal RV diameter (3.28 ± 0.7 to 3.83 ± 0.5 cm, p = <.001), LV mass index (86.7 ± 15.3 to 90.1 ± 15.3, p = .015), and aortic root diameter (3.1 ± 0.4 to 3.2 ± 0.3 cm, p = .03) from pre- to posttraining, with a slightly greater magnitude in athletes with >2 years of training. Presence of left atrial enlargement (≥35 mL/m2 ) increased from 2.9% to 29% pre- to postparticipation in athletes with >2 years training. No significant changes in wall thickness, diastolic function, or right ventricular systolic function were observed. CONCLUSION: American football players college-level training was associated with increases in left and right ventricular chamber sizes, left atrial size, and aortic root diameter.

Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is one of the most common genetic causes of heart disease. Since the initial description of HCM, there have been minimal strides in management options. Obstructive HCM constitutes a larger subset of patients with increased left ventricular outflow tract gradients causing symptoms. Septal reduction therapy (SRT) has been successful, but it is not the answer for all patients and is not disease modifying. AREAS COVERED: Current guideline recommendations include beta-blockers, calcium channel blockers, or disopyramides for medical management, but there lacks evidence of much benefit with these drugs. In recent years, there has been the emergence of cardiac myosin inhibitors (CMI) which have demonstrated positive results in patients with both obstructive and non-obstructive HCM. In addition to CMIs, other drugs have been investigated as we have learned more about HCM's pathological mechanisms. Drugs targeting sodium channels and myocardial energetics, as well as repurposed drugs that have demonstrated positive remodeling are being investigated as potential therapeutic targets. Gene therapy is being explored with vast potential for the treatment of HCM. EXPERT OPINION: The armamentarium of therapeutic options for HCM is continuously increasing with the emergence of CMIs as mainstays of treatment. The future of HCM treatment is promising.

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.

Exercise recommendations for patients with hypertrophic cardiomyopathy.

Individuals with hypertrophic cardiomyopathy (HCM) have historically been advised to limit exercise and sports participation to mild-intensity activities due to concerns for sudden cardiac arrest (SCA). However, more contemporary data have shown SCA is rare in patients with HCM and emerging data is shifting towards support for the safety of exercise in this patient population. Recent guidelines endorse exercise in patients with HCM after a comprehensive evaluation and shared-decision making with an expert provider.

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.

Exercise and cardiovascular health: A state-of-the-art review.

Cardiovascular (CV) disease (CVD) is the leading cause of global morbidity and mortality, and low levels of physical activity (PA) is a leading independent predictor of poor CV health and associated with an increased prevalence of risk factors that predispose to CVD development. In this review, we evaluate the benefits of exercise on CV health. We discuss the CV adaptations to exercise, focusing on the physiological changes in the heart and vasculature. We review the impact and benefits of exercise on specific CV prevention, including type II diabetes, hypertension, hyperlipidemia, coronary artery disease, and heart failure, in addition to CVD-related and all-cause mortality. Lastly, we evaluate the current PA guidelines and various modes of exercise, assessing the current literature for the effective regimens of PA that improve CVD outcomes.