Yield of molecular autopsy in sudden cardiac death in athletes: data from a large registry in the UK.

AIMS: Sudden cardiac death (SCD) may occur in apparently healthy individuals, including athletes. The aim was to investigate the diagnostic role of post-mortem genetic testing, molecular autopsy (MA), in elucidating the cause of SCD in athletes. METHODS AND RESULTS: We reviewed a database of 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre. All cases underwent detailed cardiac autopsy, and 748 were deemed to be athletes. Of these, 42 (6%) were investigated with MA (28 using a targeted sequencing, 14 exome sequencing). Variants were classified as pathogenic, likely pathogenic, or variant of unknown significance using international guidelines. Clinical information was obtained from referring coroners who completed a detailed health questionnaire. Out of the 42 decedents (average age 35 years old, 98% males) who were investigated with MA, the autopsy was in keeping with a structurally normal heart [sudden arrhythmic death syndrome (SADS)] in n = 33 (78%) cases, followed by arrhythmogenic cardiomyopathy (ACM) in eight (19%) individuals and idiopathic left ventricular fibrosis in one (2%). Death occurred during exercise and at rest in 26 (62%) and 16 (38%) individuals, respectively. Variants that were adjudicated clinically actionable were present in seven cases (17%). There was concordance between the genetic and phenotypic findings in two cases of ACM (in FLNC and TMEM43 genes). None of the variants identified in SADS cases were previously linked to channelopathies. Clinically actionable variants in cardiomyopathy-associated genes were found in five cases of SADS. CONCLUSION: The yield of MA in athletes who died suddenly is 17%. In SADS cases, clinically actionable variants were found in cardiomyopathy-associated genes and not in channelopathy-associated genes. Arrhythmogenic cardiomyopathy is a common cause of SCD in athletes, and one in four decedents with this condition had a clinically actionable variant in FLNC and TMEM43 genes.

Diagnostic yield and financial implications of a nationwide electrocardiographic screening programme to detect cardiac disease in the young.

AIMS: There is limited information on the role of screening with electrocardiography (ECG) for identifying cardiovascular diseases associated with sudden cardiac death (SCD) in a non-select group of adolescents and young adults in the general population. METHODS AND RESULTS: Between 2012 and 2014, 26 900 young individuals (aged 14-35 years) were prospectively evaluated with a health questionnaire and ECG. Individuals with abnormal results underwent secondary investigations, the costs of which were being based on the UK National Health Service tariffs. Six hundred and seventy-five (2.5%) individuals required further investigation for an abnormal health questionnaire, 2175 (8.1%) for an abnormal ECG, and 114 (0.5%) for both. Diseases associated with young SCD were identified in 88 (0.3%) individuals of which 15 (17%) were detected with the health questionnaire, 72 (81%) with ECG and 2 (2%) with both. Forty-nine (56%) of these individuals received medical intervention beyond lifestyle modification advice in the follow-up period of 24 months. The overall cost of the evaluation process was €97 per person screened, €17 834 per cardiovascular disease detected, and €29 588 per cardiovascular disease associated with SCD detected. Inclusion of ECG was associated with a 36% cost reduction per diagnosis of diseases associated with SCD compared with the health questionnaire alone. CONCLUSION: The inclusion of an ECG to a health questionnaire is associated with a five-fold increase in the ability to detect disease associated with SCD in young individuals and is more cost effective for detecting serious disease compared with screening with a health questionnaire alone.

Ethnicity and Sudden Cardiac Death in Athletes: Insights from a Large United Kingdom Registry.

BACKGROUND AND AIMS: The relationship between ethnicity and causes of sudden cardiac death (SCD) in athletes is poorly understood. OBJECTIVES: To investigate etiology of SCD among different ethnicities in a large cohort of athletes. METHODS: Between 1994 and November 2022, 7880 cases of SCD were consecutively referred from all over the United Kingdom to our national cardiac pathology centre; 848 (11%) were athletes. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners. RESULTS: Most of athletes were white (n = 758; 89%). Black and Asian athletes were 51 (6%) and 39 (5%) respectively. A structurally normal heart, indicative of sudden arrhythmic death syndrome (SADS) was the most common autopsy finding (n = 385, 45%), followed by myocardial diseases (n = 275; 32%) cases, atherosclerotic coronary artery disease (CAD) (n = 58, 7%) and coronary artery anomalies (n = 29, 3%). In most of cases, death occurred during exercise (n = 737; 87%) . Arrhythmogenic cardiomyopathy (ACM) was more common in black (n = 13; 25%) than in white (n = 109; 14%) and Asian (n = 3; 8%) athletes (p = 0.03 between black and white athletes; p = 0.04 between black and Asian athletes); in contrast, CAD was more common in Asians (n = 6; 15% vs n = 51; 7% in whites vs 2% n = 1; in blacks, p = 0.02 between Asian and black athletes). Among white athletes, ACM was more common in individuals who died during exercise than in the ones who died at rest (p = 0.005). Such a difference was not observed in Asian and black athletes. In Asian athletes, CAD was the diagnosis at autopsy in 18% of individuals who died during exercise and in none of individuals who died at rest. CONCLUSIONS: A structurally normal heart at autopsy and myocardial diseases are the most common findings in athletes who died suddenly. While ACM is more common in black athletes, atherosclerotic CAD is more common in Asian athletes, with a strong association with exercise-induced SCD. ACM appears to be a driver of exercise-induced SCD in white athletes, however this is not the case in black and Asian athletes.

A sudden death in an athlete is an uncommon but highly tragic event which appears almost paradoxical, as athletes epitomize the healthiest segment of society. Inherited and familiar cardiac conditions are the main causes of sudden death in young individuals and athletes. Studies on this matter have mainly focused on Caucasian athletes and the frequency or the causes of sudden death in athletes of other ethnicities is largely unknown. Our study focusses on this aspect and reveals that causes of sudden death may highly vary among athletes of different race. The circumstances of death differ significantly among various ethnicities, even looking at the same underlying cardiac condition.

Coronary artery anomalies and the role of echocardiography in pre-participation screening of athletes: a practical guide.

Transthoracic echocardiography is an essential and widely available diagnostic tool for assessing individuals reporting cardiovascular symptoms, monitoring those with established cardiac conditions and for preparticipation screening of athletes. While its use is well-defined in hospital and clinic settings, echocardiography is increasingly being utilised in the community, including in the rapidly expanding sub-speciality of sports cardiology. There is, however, a knowledge and practical gap in the challenging area of the assessment of coronary artery anomalies, which is an important cause of sudden cardiac death, often in asymptomatic athletic individuals. To address this, we present a step-by-step guide to facilitate the recognition and assessment of anomalous coronary arteries using transthoracic echocardiography at the bedside; whilst recognising the importance of performing dedicated cross-sectional imaging, specifically coronary computed tomography (CTCA) where clinically indicated on a case-by-case basis. This guide is intended to be useful for echocardiographers and physicians in their routine clinical practice whilst recognising that echocardiography remains a highly skill-dependent technique that relies on expertise at the bedside.

Sex-related differences in the association between septal wall thickness and survival.

Background: In many conditions characterised by septal hypertrophy, females have been shown to have worse outcomes compared to males. In clinical practice and research, similar cutoff points for septal hypertrophy are still used for both sexes. Here, we explore the association between different cutoff points for septal hypertrophy and survival in relation to sex. Methods and results: We performed a retrospective analysis of consecutive patients undergoing echocardiography between March 2010 and February 2021 in a large tertiary referral centre. A total of 70,965 individuals were included. Over a mean follow-up period of 59.1 ± 37 months, 9631 (25 %) males and 8429 (26 %) females died. When the same cutoff point for septal hypertrophy was used for both sexes, females had worse prognosis than males. The impact of septal hypotrophy on survival became statistically significant at a lower threshold in females compared to males: 11.1 mm (HR 1.13, CI 95 %:1.03-1.23, p = 0.01) vs 13.1 mm (HR 1.21, CI 95 %: 1.12-1.32, p < 0.001). However, when indexed wall thickness was used, the cutoff points were 6 mm/body surface area (BSA) (HR 1.08, CI 95 %: 1-1.18, p = 0.04) and 6.2 mm/BSA (HR 1.07, CI 95 %: 1-1.15, p = 0.05) for females and males, respectively. Conclusions: Septal hypertrophy is associated with increased mortality at a lower threshold in females than in males. This may account for the worse prognosis reported in females in many conditions characterised by septal hypertrophy. Applying a lower absolute value or using indexed measurements may facilitate early diagnosis and improve prognostication in females.

An Athlete With Bicuspid Aortic Valve Regurgitation and Left Ventricular Dilatation: A Clinical Conundrum.

The physiologic cardiac adaptations caused by intensive exercise and the pathophysiologic changes caused by significant regurgitant valvular lesions can be challenging to differentiate. We describe the clinical course of an asymptomatic 31-year-old elite triathlete with a moderately regurgitant bicuspid aortic valve and severe left ventricular and aortic dilatation. (Level of Difficulty: Intermediate.).

Ethnic and sex-related differences at presentation in apical hypertrophic cardiomyopathy: An observational cross-sectional study.

BACKGROUND: We investigated whether ethnicity and sex are associated with different clinical presentations and cardiovascular magnetic resonance (CMR) findings in individuals with apical hypertrophic cardiomyopathy (ApHCM). METHODS: A retrospective observational cohort study of consecutive ApHCM patients from a large tertiary referral center in the United Kingdom (UK). Demographic, clinical, 12­lead electrocardiogram (ECG) and CMR findings were collected. Participants presented in our clinics between 2010 and 2020. 'Pure' ApHCM was defined as isolated apical hypertrophy and 'mixed' with both apical and septal hypertrophy but with the apical segments of a greater wall thickness. Deep T-wave inversion was defined as ≥5 mm in any electrocardiogram lead. RESULTS: A total of 150 consecutive ApHCM patients (75% men, 25% women; 37% White, 25% Black, 24% Asian and 15% of Mixed/Other ethnicity) were included. Females were diagnosed at an older age compared to men, had less prominent ECG changes, had higher left atrial area index, and were more hypertensive. Black patients had higher left ventricular mass index, more hypertension, and more of the 'mixed' type of ApHCM. The majority of hypertensive male patients showed the 'mixed' phenotype. CONCLUSIONS: Individuals of Black ethnicity and hypertensive male patients are more likely to present with mixed apical and basal hypertrophy, whereas White, Asian and non-hypertensive male patients tend to have hypertrophy limited to the apex. Females present at an older age and are less likely to have deep T wave inversion on ECG.

Prevalence and diagnostic significance of de-novo 12-lead ECG changes after COVID-19 infection in elite soccer players.

BACKGROUND AND AIM: The efficacy of pre-COVID-19 and post-COVID-19 infection 12-lead ECGs for identifying athletes with myopericarditis has never been reported. We aimed to assess the prevalence and significance of de-novo ECG changes following COVID-19 infection. METHODS: In this multicentre observational study, between March 2020 and May 2022, we evaluated consecutive athletes with COVID-19 infection. Athletes exhibiting de-novo ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all players (n=30) following COVID-19 infection, despite the absence of cardiac symptoms or de-novo ECG changes. RESULTS: 511 soccer players (median age 21 years, IQR 18-26 years) were included. 17 (3%) athletes demonstrated de-novo ECG changes, which included reduction in T-wave amplitude in the inferior and lateral leads (n=5), inferior leads (n=4) and lateral leads (n=4); inferior T-wave inversion (n=7); and ST-segment depression (n=2). 15 (88%) athletes with de-novo ECG changes revealed evidence of inflammatory cardiac sequelae. All 30 athletes who underwent a mandatory CMR scan had normal findings. Athletes revealing de-novo ECG changes had a higher prevalence of cardiac symptoms (71% vs 12%, p<0.0001) and longer median symptom duration (5 days, IQR 3-10) compared with athletes without de-novo ECG changes (2 days, IQR 1-3, p<0.001). Among athletes without cardiac symptoms, the additional yield of de-novo ECG changes to detect cardiac inflammation was 20%. CONCLUSIONS: 3% of athletes demonstrated de-novo ECG changes post COVID-19 infection, of which 88% were diagnosed with cardiac inflammation. Most affected athletes exhibited cardiac symptoms; however, de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms.

Mending the broken valentine heart: a case report.

Background: Mortality from myocardial infarction (MI) has been decreasing since the introduction of primary percutaneous intervention. Late complications still pose a dilemma, such as deterioration of left ventricle (LV) function, LV aneurysms, and LV thrombus formation. If not adequately managed in a timely manner, this can result in life-threatening consequences. Restoration of LV function by surgical resection of the infarcted LV wall is an option for a few complicated cases, with variable outcomes. Case summary: A 66-year-old man presented with dyspnoea 2 years after his initial MI, which was treated with a drug-eluting stent to his left circumflex artery. His Warfarin had been stopped after 6 months of treatment of a small LV thrombus, which was noted at the time of his initial infarction. His echocardiogram on admission demonstrated severe LV systolic impairment of 23% (which had deteriorated from 40%) with a giant true aneurysm of the basal to mid-lateral wall, which resembled a Valentine heart. The presence of a large, organized thrombus filling the aneurysm complicated the case further. The patient underwent a resection of the LV aneurysm and thrombus. He remained asymptomatic and maintained a significant improvement of his LV function to 47% at his 5 months scan. Discussion: The importance of imaging post-large MI and follow-up imaging once thrombus resolution has occurred is crucial. Patients with large LV aneurysm associated with severe refractory LV impairment and LV thrombus should be considered for LV aneurysmectomy for prognostic benefit and symptom relief.

Evaluating the role of transthoracic echocardiography in hospitalised patients with COVID-19 infection.

OBJECTIVE: To identify the most common transthoracic echocardiogram (TTE) parameters in patients hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) and their association with myocardial injury and outcomes. METHODS: A retrospective, single-centre, observational, exploratory cohort study was performed at the height of the COVID-19 pandemic. All SARS-CoV-2 polymerase chain reaction (PCR) positive patients who underwent a TTE during their inpatient admission between 1 March 2020 and 31 October 2020 were analysed. The most frequent cardiovascular risk factor profile and echocardiographic features were investigated. RESULTS: A total of 87 patients met the eligibility criteria. A salient 41.4% (n=36) of our cohort succumbed to this devastating virus. More than half of our hospital population (58.6%) were admitted to the intensive care unit (ITU) and this was significantly associated with inpatient mortality (OR: 7.14, CI 2.53 to 20.19, p<0.001). Hypertension was the most common cardiovascular risk factor (51.7%) with no additional prominence in non-survivors (OR: 2.33, CI 0.97 to 5.61, p=0.059). Remarkably, 90.8% of our cohort demonstrated a preserved left ventricular ejection fraction, although 69.1% had elevated troponin levels. Only 1 patient (1.1%) was given a diagnostic label of myocarditis. A raised pulmonary artery systolic pressure (36.8%) andright ventricle (RV) dysfunction (26.4%) were the most common echocardiographic features. In particular, the presence of RV dysfunction was significantly related to adverse outcomes (OR: 2.97, CI 1.11 to 7.94, p<0.03). CONCLUSIONS: In this cohort of extremely unwell patients hospitalised with COVID-19 pneumonitis, the presence of RV dysfunction or admission to ITU was significantly associated with inpatient case fatality ratio. Moreover, COVID-19-induced myocarditis remains extremely rare.

Exercise in the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) era: A Question and Answer session with the experts Endorsed by the section of Sports Cardiology & Exercise of the European Association of Preventive Cardiology (EAPC).

Regular exercise has multiple benefits for physical and mental health, including the body's ability to combat infections. The current COVID-19 pandemic and the social distancing measures employed to curtail the impact of the infection are likely to reduce the amount of usual physical activity being performed by most individuals, including habitual exercisers. The uncertainties relating to the impact of the SARS-CoV-2 virus on the heart may cause increased anxiety, particularly in athletes who need to sustain a vigorous exercise regime in order to maintain their skills and fitness in preparation for return to competition after a short re-training period. The aim of this document is to provide practical answers to pertinent questions being posed by the sporting community, in an attempt to offer reassurance, promote safe participation in exercise during as well as after the COVID-19 pandemic and provide a framework of management for physicians caring for athletes.