Arrhythmogenic right ventricular cardiomyopathies (ARVC): Diagnostic challenges from imaging to genetics.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary cardiomyopathy, predominantly affecting young males, regardless of ethnicity or race. Due to its variable penetrance, females usually have milder and less malignant phenotypes and it may be diagnosed in older individuals. Accordingly, some affected individuals may remain asymptomatic, while in others sudden cardiac death represents the inaugural symptom. Exercise-related palpitations and syncope are red-flag symptoms in otherwise healthy adolescents and young adults and should be fully investigated, considering ARVC as a potential diagnosis. Clinicians should adopt a cardiomyopathy-oriented mindset which is focused on recognizing suspicious electrocardiogram, structural abnormalities and family history of sudden cardiac death. Complete baseline-investigations should be performed in all individuals in whom ARVC is suspected, regardless of their symptoms. These include multi-modality imaging (echocardiogram, cardiac magnetic resonance imaging), electrocardiogram monitors and maximal exercise tolerance tests. Genetic testing should be regarded as the final piece of the puzzle and offered in individuals with a high pre-test probability. A clinically actionable result allows for predictive family testing and pre-implantation diagnosis. Importantly, it should be offered only with appropriate pre and post-test counselling. Both clinicians and patients should understand that not identifying a disease-causing variant does not exclude ARVC. Finally, three clinical cases illustrating the potential caveats in diagnosing ARVC are discussed.

Myocardial Fibrosis in Young and Veteran Athletes: Evidence from a Systematic Review of the Current Literature.

Background: Exercise is associated with several cardiac adaptations that can enhance one's cardiac output and allow one to sustain a higher level of oxygen demand for prolonged periods. However, adverse cardiac remodelling, such as myocardial fibrosis, has been identified in athletes engaging in long-term endurance exercise. Cardiac magnetic resonance (CMR) imaging is considered the noninvasive gold standard for its detection and quantification. This review seeks to highlight factors that contribute to the development of myocardial fibrosis in athletes and provide insights into the assessment and interpretation of myocardial fibrosis in athletes. Methods: A literature search was performed using the PubMed/Medline database and Google Scholar for publications that assessed myocardial fibrosis in athletes using CMR. Results: A total of 21 studies involving 1642 endurance athletes were included in the analysis, and myocardial fibrosis was found in 378 of 1595 athletes. A higher prevalence was seen in athletes with cardiac remodelling compared to control subjects (23.7 vs. 3.3%, p < 0.001). Similarly, we found that young endurance athletes had a significantly higher prevalence than veteran athletes (27.7 vs. 19.9%, p < 0.001), while male and female athletes were similar (19.7 vs. 16.4%, p = 0.207). Major myocardial fibrosis (nonischaemic and ischaemic patterns) was predominately observed in veteran athletes, particularly in males and infrequently in young athletes. The right ventricular insertion point was the most common fibrosis location, occurring in the majority of female (96%) and young athletes (84%). Myocardial native T1 values were significantly lower in athletes at 1.5 T (p < 0.001) and 3 T (p = 0.004), although they had similar extracellular volume values to those of control groups. Conclusions: The development of myocardial fibrosis in athletes appears to be a multifactorial process, with genetics, hormones, the exercise dose, and an adverse cardiovascular risk profile playing key roles. Major myocardial fibrosis is not a benign finding and warrants a comprehensive evaluation and follow-up regarding potential cardiac disease.

Sport PRactice and its Effects on aortic size and valve function in bicuspid Aortic valve Disease: a cross-sectional report from the SPREAD study.

OBJECTIVE: Concerns exist about the possible detrimental effects of exercise training on aortic size and valve function in individuals with bicuspid aortic valve (BAV). This multicentre international study aimed to determine the characteristics of aortic size and valve function in athletes versus non-athletes with BAV and athletes with tricuspid aortic valve (TAV). METHODS: We enrolled competitive athletes with BAV and age- and sex-matched athletes with TAV and non-athletes with BAV. We assessed valve function, aortic size and biventricular measures using echocardiography. Individuals with established moderate-severe AV stenosis, regurgitation or significant aortic dilation were excluded from the study. RESULTS: The study population comprised 504 participants: 186 competitive athletes with BAV (84% males; age 30±11 years), 193 competitive athletes with TAV and 125 non-athletes with BAV. The aortic annulus was greater in athletes with BAV than athletes with TAV and non-athletes with BAV (p<0.001). Both athletic and non-athletic individuals with BAV had greater sinuses of Valsalva, sino-tubular junction and ascending aorta diameters than athletes with TAV (p<0.001). However, no significant differences were found between athletes and non-athletes with BAV. Left ventricular index volumes and mass were greater in athletes with BAV than in the other two groups (p<0.001). Individuals with BAV (athletes and non-athletes) had greater mean gradients than TAV athletes. CONCLUSION: This multicentre international study demonstrates no differences between athletes with BAV and non-athletes with BAV regarding aortic valve function or aortic dimensions. However, athletes with BAV have larger aortic diameters and a relatively worse valvular function than athletes with TAV.

The future of education in Preventive Cardiology. A Statement of the European Association of Preventive Cardiology (EAPC) of the ESC.

In recent years, major advances in our understanding of risk factors implicated in the development of cardiovascular disease (CVD), in available tools for early detection of CVD, and in effective interventions to prevent subclinical or clinically manifest disease, have led to an increasing appreciation of prevention as a major pillar of cardiovascular medicine. Preventive cardiology has evolved into a dynamic sub-specialty focused on the promotion of cardiovascular health through all stages of life, and on the management of individuals at risk of developing CVD or experiencing recurrent cardiovascular events, through interdisciplinary care in different settings. As the level of knowledge, specialized skills, experience, and committed attitudes related to cardiovascular prevention has exceeded core cardiology training, the European Association of Preventive Cardiology (EAPC) has placed major emphasis on continuous education and training of physicians and allied professionals involved in cardiovascular prevention, with the aim of setting standards for practice and improving quality of care. The EAPC recognizes the need for comprehensive educational offer across different levels of training (from core cardiology to sub-specialty to expert training) as well as the need for interdisciplinary approaches that will promote synergies among allied professionals involved in cardiovascular prevention. This statement by the EAPC aims to highlight current gaps and unmet needs, and to describe the framework to help standardize, structure, and deliver comprehensive, up-to-date, interactive, high-quality education using a combination of traditional and novel educational tools. The document aims to form the basis for ongoing refinements of the EAPC educational offer, with the ultimate goal to ensure that new evidence in the field will translate to better cardiovascular practice and improved outcomes for our patients.

Left ventricular morphology and geometry in élite athletes characterised by extreme anthropometry.

OBJECTIVE: The aim of the study was to explore the individual impact of BMI and height on LV size and geometry in a cohort of healthy athletes. METHODS: From a total cohort of 1857 healthy élite athletes (21 ± 5 years, males 70%) investigated with ECG and echocardiogram, we considered three groups: Group 1 n = 50: BMI ≥ 30 and height < 1.90 m; Group 2 n = 87: height ≥ 1.95 m and BMI < 30; control Group 3 n = 243: height < 1.90 m and BMI = 20-29. RESULTS: BSA was ≤2.3 m2 in 52% of athletes in group 1 and 47% of athletes in group 2. Athletes in group 1 and in group 2 showed an enlarged LV end-diastolic diameter (LVEDD) (57 ± 6 vs 57 ± 4 vs 53 ± 4 mm in Group 3); 50% of athletes in group 1 and 38% of athletes in group 2 exhibited a LVEDD > 57 mm (p = 0.23). LV wall thickness was higher in group 1 (11 ± 1 vs 10 ± 2 mm in Group 2, p = 0.001). Concentric hypertrophy or concentric remodelling was found in 20% of athletes in group 1 vs 7% of athletes in group 2 (p = 0.04). Athletes of group 1 with BSA ≤ 2.3 m2 showed lower LVEDD (53 ± 5 vs 60 ± 5 mm, p < 0.001), similar LV wall thickness (10 ± 1 vs 11 ± 1 mm, p = 0.128) and higher prevalence of concentric hypertrophy or concentric remodelling (31% vs 8%, p = 0.04) compared to those with BSA > 2.3 m2. CONCLUSION: Athletes with high BMI have similar LV dimensions but greater wall thickness and higher prevalence of concentric remodelling compared to very tall athletes. Athletes with high BMI and large BSA have the widest LV dimensions.

Prevalence of Abnormal Cardiovascular Magnetic Resonance Findings in Athletes Recovered from COVID-19 Infection: A Systematic Review and Meta-Analysis.

Background: Competitive sports and high-level athletic training result in a constellation of changes in the myocardium that comprise the 'athlete's heart'. With the spread of the COVID-19 pandemic, there have been concerns whether elite athletes would be at higher risk of myocardial involvement after infection with the virus. This systematic review and meta-analysis evaluated the prevalence of abnormal cardiovascular magnetic resonance (CMR) findings in elite athletes recovered from COVID-19 infection. Methods: The PubMed, Cochrane and Web of Science databases were systematically search from inception to 15 November 2023. The primary endpoint was the prevalence of abnormal cardiovascular magnetic resonance findings, including the pathological presence of late gadolinium enhancement (LGE), abnormal T1 and T2 values and pericardial enhancement, in athletes who had recovered from COVID-19 infection. Results: Out of 3890 records, 18 studies with a total of 4446 athletes were included in the meta-analysis. The pooled prevalence of pathological LGE in athletes recovered from COVID-19 was 2.0% (95% CI 0.9% to 4.4%, I2 90%). The prevalence of elevated T1 and T2 values was 1.2% (95% CI 0.4% to 3.6%, I2 87%) and 1.2% (95% CI 0.4% to 3.7%, I2 89%), respectively, and the pooled prevalence of pericardial involvement post COVID-19 infection was 1.1% (95% CI 0.5% to 2.5%, I2 85%). The prevalence of all abnormal CMR findings was much higher among those who had a clinical indication of CMR. Conclusions: Among athletes who have recently recovered from COVID-19 infection, there is a low prevalence of abnormal CMR findings. However, the prevalence is much higher among athletes with symptoms and/or abnormal initial cardiac screening. Further studies and longer follow up are needed to evaluate the clinical relevance of these findings and to ascertain if they are associated with adverse events.

International Criteria for Reporting Study Quality for Sudden Cardiac Arrest/Death Tool.

BACKGROUND: Studies reporting on the incidence of sudden cardiac arrest and/or death (SCA/D) in athletes commonly lack methodological and reporting rigor, which has implications for screening and preventative policy in sport. To date, there are no tools designed for assessing study quality in studies investigating the incidence of SCA/D in athletes. METHODS AND RESULTS: The International Criteria for Reporting Study Quality for Sudden Cardiac Arrest/Death tool (IQ-SCA/D) was developed following a Delphi process. Sixteen international experts in sports cardiology were identified and invited. Experts voted on each domain with subsequent moderated discussion for successive rounds until consensus was reached for a final tool. Interobserver agreement between a novice, intermediate, and expert observer was then assessed from the scoring of 22 relevant studies using weighted and unweighted κ analyses. The final IQ-SCA/D tool comprises 8 domains with a summated score of a possible 22. Studies are categorized as low, intermediate, and high quality with summated IQ-SCA/D scores of ≤11, 12 to 16, and ≥17, respectively. Interrater agreement was "substantial" between all 3 observers for summated IQ-SCA/D scores and study categorization. CONCLUSIONS: The IQ-SCA/D is an expert consensus tool for assessing the study quality of research reporting the incidence of SCA/D in athletes. This tool may be used to assist researchers, reviewers, journal editors, and readers in contextualizing the methodological quality of different studies with varying athlete SCA/D incidence estimates. Importantly, the IQ-SCA/D also provides an expert-informed framework to support and guide appropriate design and reporting practices in future SCA/D incidence trials.

Ethnicity and sudden cardiac death in athletes: insights from a large United Kingdom registry.

AIMS: The relationship between ethnicity and causes of sudden cardiac death (SCD) in athletes is poorly understood. OBJECTIVES: To investigate aetiology of SCD among different ethnicities in a large cohort of athletes. METHODS AND RESULTS: 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. Most of athletes were white (n = 758; 89%). Black and Asian athletes were in number of 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%), 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. n = 1; 2%; 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. CONCLUSION: 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 focuses 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.

The role for ambulatory electrocardiogram monitoring in the diagnosis and prognostication of Brugada syndrome: a sub-study of the Rare Arrhythmia Syndrome Evaluation (RASE) Brugada study.

AIMS: Brugada syndrome (BrS) diagnosis and risk stratification rely on the presence of a spontaneous type 1 (spT1) electrocardiogram (ECG) pattern; however, its spontaneous fluctuations may lead to misdiagnosis and risk underestimation. This study aims to assess the role for repeat high precordial lead (HPL) resting and ambulatory ECG monitoring in identifying a spT1, and evaluate its prognostic role. METHODS AND RESULTS: HPL resting and ambulatory monitoring ECGs of BrS subjects were reviewed retrospectively, and the presence of a spT1 associated with ventricular dysrhythmias and sudden cardiac death (SCD). Three-hundred and fifty-eight subjects (77 with spT1 pattern at presentation, Group 1, and 281 without, Group 2) were included. In total, 1651 resting HPL resting and 621 ambulatory monitoring ECGs were available for review, or adequately described. Over a median follow-up of 72 months (interquartile range - IQR - 75), 42/77 (55%) subjects in Group 1 showed a spT1 in at least one ECG. In Group 2, 36/281 subjects (13%) had a newly detected spT1 (1.9 per 100 person-year) and 23 on an HPL ambulatory recording (8%). Seven previously asymptomatic subjects, five of whom had a spT1 (four at presentation and one at follow-up), experienced arrhythmic events; survival analysis indicated that a spT1, either at presentation or during lifetime, was associated with events. Univariate models showed that a spT1 was consistently associated with increased risk [spT1 at presentation: hazard ratio (HR) 6.3, 95% confidence interval (CI) 1.4-28, P = 0.016; spT1 at follow-up: HR 3.1, 95% CI 1.3-7.2, P = 0.008]. CONCLUSION: Repeated ECG evaluation and HPL ambulatory monitoring are vital in identifying transient spT1 Brugada pattern and its associated risk.

Current Insights and Novel Cardiovascular Magnetic Resonance-Based Techniques in the Prognosis of Non-Ischemic Dilated Cardiomyopathy.

Cardiac magnetic resonance (CMR) imaging has an important emerging role in the evaluation and management of patients with cardiomyopathies, especially in patients with dilated cardiomyopathy (DCM). It allows a non-invasive characterization of myocardial tissue, thus assisting early diagnosis and precise phenotyping of the different cardiomyopathies, which is an essential step for early and individualized treatment of patients. Using imaging techniques such as late gadolinium enhancement (LGE), standard and advanced quantification as well as quantitative mapping parameters, CMR-based tissue characterization is useful in the differential diagnosis of DCM and risk stratification. The purpose of this article is to review the utility of CMR in the diagnosis and management of idiopathic DCM, as well as risk prediction and prognosis based on standard and emerging CMR contrast and non-contrast techniques. This is consistent with current evidence and guidance moving beyond traditional prognostic markers such as ejection fraction.

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.

The Acute Impact of Endurance Exercise on Right Ventricular Structure and Function: A Systematic Review and Meta-analysis.

There have been many studies since the late 1980s investigating the effect of endurance exercise on the left ventricle. More recently, attention has shifted to the right heart, with suggestions that endurance exercise may have a detrimental effect on the right ventricle. This systematic review and meta-analysis summarizes and critiques 26 studies, including 649 athletes, examining the acute impact of endurance exercise on the right ventricle. We also present a subanalysis contrasting ultraendurance with endurance exercise. Finally, we identify areas for future research, such as the influence of sex, ethnicity, and age.

Sudden Cardiac Death in Young Athletes: JACC State-of-the-Art Review.

Athletes epitomize the healthiest segment of society. Despite this premise, sudden cardiac death may occur in apparently healthy athletes, attracting significant attention not only in the medical community but also in laypersons and media. The incidence of sudden cardiac death is variably reported, and epidemiological burden differs among cohorts. Athletes appear to be at risk of developing fatal arrhythmias when harboring a quiescent cardiac disorder. Primary cardiomyopathies, ion channelopathies, and coronary artery anomalies are prevalent causes in young individuals. Cardiac assessment of athletes can be challenging because these individuals exhibit a plethora of electrical, structural, and functional physiological changes that overlap with cardiac pathology. A diagnosis of cardiac disease in a young athlete is not necessarily an indication to terminate competition and sports participation. International guidelines, traditionally focused on disqualification of individuals with cardiac disease, have recently adopted a more liberal attitude, based on a careful assessment of the risk and on a shared-decision making approach.

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.

Seasonal Variation in Sudden Cardiac Death: Insights from a Large United Kingdom Registry.

BACKGROUND: Sudden cardiac death (SCD) is relatively common and may occur in apparently healthy individuals. The role of seasonal variation as a risk factor for SCD is poorly understood. The aim of this study was to investigate whether SCD exhibits a predilection for specific seasons. METHODS: We reviewed a database of 4751 cases of SCD (mean age 38 ± 17 years) referred to our Center for Cardiac Pathology at St George's University of London between 2000 and 2018. Clinical information was obtained from referring coroners who were asked to complete a detailed questionnaire. All cases underwent macroscopic and histological evaluation of the heart, by expert cardiac pathologists. RESULTS: SCD was more common during winter (26%) and rarer during summer (24%), p = 0.161. Significant seasonal variation was not observed among cases of sudden arrhythmic death syndrome (SADS, 2910 cases) in which the heart is structurally normal. In contrast, a significant difference in seasonal distribution among decedents exhibiting cardiac structural abnormalities at the post-mortem examination (n = 1841) was observed. In this subgroup, SCDs occurred more frequently during winter (27 %) compared to summer (22%) (p = 0.007). In cases diagnosed with a myocardial disease (n = 1399), SCD was most common during the winter (27%) and least common during the summer (22%) (p = 0.027). CONCLUSIONS: While SADS occurs throughout the year with no seasonal variation, SCD due to structural heart disease appears to be more common during the winter. Bio-meteorological factors may be potential triggers of SCD in individuals with an underlying structural cardiac abnormality.