Cause Of Sudden Cardiac Death Research Articles

Sudden sustained monomorphic ventricular tachycardia in a previously healthy adult with many causes for it, but which one is the correct? A case report

Introduction. Sustained monomorphic ventricular tachycardia (VT) ? SMVT is a rare, underdiagnosed pathology with a very poor prognosis. Along with ventricular fibrillation, SMVT is responsible for nearly all of the arrhythmic sudden cardiac deaths (SCD). The most common cause of VT is ischemic heart disease, but there are many other reasons, among which are arrhythmogenic right ventricular cardiomyopathy (ARVD) and myocardial bridging phenomenon. Treatment options include a hybrid approach consisting of antiarrhythmic drugs, catheter ablation, and implantable cardioverter defibrillators (ICD). Case report. We present a case of a 46-year-old man, a military officer, who experienced chest pain, palpitations, and nausea during regular physical activity at home. Due to the symptoms described, he was examined immediately and diagnosed with SMVT. Shortly after the diagnosis, he lost consciousness and was successfully resuscitated. A complete non-invasive and invasive cardiology examination was performed. It revealed that the patient had stable coronary disease and a muscle bridge on the left anterior descending artery. An ARVD was suspected after transthoracic echocardiography and heart magnetic resonance imaging. Genetic testing for ARVD was negative, but according to the Heart Rhythm Society expert consensus criteria, we had enough for a definitive diagnosis. The patient was hospitalized for ten days and treated with drugs without recurring VT or other disorders. We implanted an implantable loop recorder before the discharge and monitored the heart rhythm for one year. During a three-year follow-up, all of his electrocardiographic findings presented sinus rhythm without heart rhythm disorders. Conclusion. Sudden SMVT is the most common cause of SCD. It is of inestimable importance to carry out a detailed examination and determine the immediate cause of the arrhythmia and the right therapy, which, for these patients, is a life-saving form of treatment. Therapy includes medications, electrophysiology or ICD, or a combination of these treatment approaches.

SYSTEM OF DETECTION OF VENTRICULAR ARRHYTHMIYS

Determining the boundaries of QRS complexes in ECG signals is of fundamental importance in the diagnosis of arrhythmias and in the recognition of signals in clinical manifestations in general. Existing systems of mobile diagnostics of arrhythmias do not meet modern requirements: some algorithms are too complicated for software implementation, others are not sufficiently resistant to interference. Ventricular extrasystoles, as one of the most important studies in arrhythmology, are currently considered one of the main causes of sudden cardiac death, and their timely detection and objective diagnosis, as well as proper prevention, remain one of the most pressing issues. One of the urgent issues is the development of simple (acceptable for mobile devices – which can be implemented online) algorithms for the recognition and classification of ventricular arrhythmias. The aim of the work is to develop a system for determining the informative parameters of the ECG signal in real time for the diagnosis of ventricular extrasystoles and parameters of heart rate variability. An algorithm for recognition of arrhythmias (ventricular extrasystoles) is proposed, which is characterized by ease of implementation and minimal requirements for computing resources, while maintaining high values of sensitivity and specificity for ECG signals with sinus rhythm and single ventricular extrasystoles. The algorithm is implemented in the Labview software environment. Using ECG files taken from international databases, the algorithm and system were tested to determine the parameters of heart rate variability. Keywords: electrocardiographic signal, arrhythmia, heart rate variability, ventricular extrasystole

Forensic Pathological Diagnosis of Acute and Old Myocardial Infarction Using Fourier Transform Infrared Spectroscopy.

Fourier transform infrared spectroscopy (FTIR) was used to analyze myocardial infarction tissues at different stages of pathological change to achieve the forensic pathology diagnosis of acute and old myocardial infarction. FTIR spectra data of early ischemic myocardium, necrotic myocardium, and myocardial fibrous tissue in the left ventricular anterior wall of the sudden death group of atherosclerotic heart disease and the myocardium of the normal control group were collected using hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining as a reference, and the data were analyzed using multivariate statistical analysis. The mean normalized spectra of control myocardium, early ischemic myocardium and necrotic myocardium were relatively similar, but the mean second derivative spectra were significantly different. The peak intensity of secondary structure of proteins in early ischemic myocardium was significantly higher than in other types of myocardium, and the peak intensity of the α-helix in necrotic myocardium was the lowest. The peaks of amide Ⅰ and amide Ⅱ in the mean normalized spectra of myocardial fibrous tissue significantly shifted towards higher wave numbers, the peak intensities of amide Ⅱ and amide Ⅲ were higher than those of other types of myocardium, and the peak intensities at 1 338, 1 284, 1 238 and 1 204 cm-1 in the mean second derivative spectra were significantly enhanced. Principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) showed that FTIR could distinguish different types of myocardium. FTIR technique has the potential to diagnose acute and old myocardial infarction, and provides a new basis for the analysis of the causes of sudden cardiac death.

Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy

BackgroundDilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure. Up to 50% of all DCM cases have a genetic background, with variants in over 250 genes reported in association with DCM. Whole-exome sequencing (WES) is a powerful tool to identify variants underlying genetic cardiomyopathies. Via WES, we sought to identify DCM causes in a family with 2 affected patients.MethodsWES was performed on the affected members of an Iranian family to identify the genetic etiology of DCM. The candidate variant was segregated via polymerase chain reaction and Sanger sequencing. Computational modeling and protein-protein docking were performed to survey the impact of the variant on the structure and function of the protein.ResultsA novel single-nucleotide substitution (G > A) in exon 9 of MED12, c.1249G > A: p.Val417Ile, NM_005120.3, was identified. The c.1249G > A variant was validated in the family. Bioinformatic analysis and computational modeling confirmed that c.1249G > A was the pathogenic variant responsible for the DCM phenotype.ConclusionWe detected a novel DCM-causing variant in MED12 using WES. The variant in MED12 may decrease binding to cyclin-dependent kinase 8 (CDK8), affect its activation, and cause alterations in calcium-handling gene expression in the heart, leading to DCM.

Anomalous origin of left main coronary artery from the right sinus of Valsalva

BackgroundAnomalous coronary arteries are rare congenital variations with cases ranging from asymptomatic to life-threatening. Given the wide variability of coronary anomalies, it is challenging to predict their clinical consequences. Here, we present the ‘malignant’ variant – interarterial course of the left coronary artery between the aorta and pulmonary trunk – given the highest risk of sudden cardiac death among the various coronary anomalies.Case presentationOur case presents a 22-year-old male presenting to the emergency department after a syncopal episode that occurred while the patient was driving a motor vehicle. Initial Computed Tomography (CT) of the chest performed as part of the trauma work-up revealed a rare case of an anomalous origin of the left main coronary artery (LMCA) originating from a common ostium with the right coronary artery (RCA). The LMCA was found to have a malignant course, as it was positioned between the aorta and pulmonary artery. Given the high risk of sudden cardiac arrest with this congenital variant, the patient underwent coronary artery bypass grafting.ConclusionAnomalous coronary arteries remain the second leading cause of sudden cardiac death in young adult patients. The risk of sudden cardiac death depends on the congenital variant of the anomalous coronary artery as well as the course these vessels take. This case highlights a rare congenital variant featuring both the LMCA and RCA originating from a common ostium, with the LMCA having a malignant course, a variant with the highest risk of sudden cardiac death.

Using Genomics to Identify Novel Therapeutic Targets for Aortic Disease.

Aortic disease, including dissection, aneurysm, and rupture, carries significant morbidity and mortality and is a notable cause of sudden cardiac death. Much of our knowledge regarding the genetic basis of aortic disease has relied on the study of individuals with Mendelian aortopathies and, until recently, the genetic determinants of population-level variance in aortic phenotypes remained unclear. However, the application of machine learning methodologies to large imaging datasets has enabled researchers to rapidly define aortic traits and mine dozens of novel genetic associations for phenotypes such as aortic diameter and distensibility. In this review, we highlight the emerging potential of genomics for identifying causal genes and candidate drug targets for aortic disease. We describe how deep learning technologies have accelerated the pace of genetic discovery in this field. We then provide a blueprint for translating genetic associations to biological insights, reviewing techniques for locus and cell type prioritization, high-throughput functional screening, and disease modeling using cellular and animal models of aortic disease.

ALCAPA syndrome, arare cause of sudden cardiac death.

ALCAPA syndrome, arare cause of sudden cardiac death.

Genotype-Phenotype Taxonomy of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes, but there is no systematic framework for classifying morphology or assessing associated risks. Here, we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression. We enrolled 436 patients with HCM (median age, 60 years; 28.8% women) with clinical, genetic, and imaging data. An independent cohort of 60 patients with HCM from Singapore (median age, 59 years; 11% women) and a reference population from the UK Biobank (n=16 691; mean age, 55 years; 52.5% women) were also recruited. We used machine learning to analyze the 3-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree. Carriers of pathogenic or likely pathogenic variants for HCM had lower left ventricular mass, but greater basal septal hypertrophy, with reduced life span (mean follow-up, 9.9 years) compared with genotype negative individuals (hazard ratio, 2.66 [95% CI, 1.42-4.96]; P<0.002). Four main phenotypic branches were identified using unsupervised learning of 3-dimensional shape: (1) nonsarcomeric hypertrophy with coexisting hypertension; (2) diffuse and basal asymmetrical hypertrophy associated with outflow tract obstruction; (3) isolated basal hypertrophy; and (4) milder nonobstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for pathogenic or likely pathogenic variants, 2.18 [95% CI, 1.93-2.28]; P=0.0001). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalizable to an independent cohort (trustworthiness, M1: 0.86-0.88). We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk, and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.

P38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia.

Ventricular fibrillation (VF) is a leading immediate cause of sudden cardiac death. There is a strong association between aging and VF, although the mechanisms are unclear, limiting the availability of targeted therapeutic interventions. Here we found that the stress kinases p38γ and p38δ are activated in the ventricles of old mice and mice with genetic or drug-induced arrhythmogenic conditions. We discovered that, upon activation, p38γ and p38δ cooperatively increase the susceptibility to stress-induced VF. Mechanistically, our data indicate that activated p38γ and p38δ phosphorylate ryanodine receptor 2 (RyR2) disrupt Kv4.3 channel localization, promoting sarcoplasmic reticulum calcium leak, Ito current reduction and action potential duration prolongation. In turn, this led to aberrant intracellular calcium handling, premature ventricular complexes and enhanced susceptibility to VF. Blocking this pathway protected genetically modified animals from VF development and reduced the VF duration in aged animals. These results indicate that p38γ and p38δ are a potential therapeutic target for sustained VF prevention.

Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A 20-Year Study.

Understanding the incidence, causes, and trends of sudden cardiac death (SCD) among young competitive athletes is critical to inform preventive policies. This study included National Collegiate Athletic Association athlete deaths during a 20-year time frame (July 1, 2002, through June 30, 2022). Athlete deaths were identified through 4 separate independent databases and search strategies (National Collegiate Athletic Association resolutions list, Parent Heart Watch database and media reports, National Center for Catastrophic Sports Injury Research database, and insurance claims). Autopsy reports and medical history were reviewed by an expert panel to adjudicate causes of SCD. A total of 143 SCD cases in National Collegiate Athletic Association athletes were identified from 1102 total deaths. The National Collegiate Athletic Association resolutions list identified 117 of 143 (82%), the Parent Heart Watch database or media reports identified 89 of 143 (62%), the National Center for Catastrophic Sports Injury Research database identified 63 of 143 (44%), and insurance claims identified 27 of 143 (19%) SCD cases. The overall incidence of SCD was 1:63 682 athlete-years (95% CI, 1:54 065-1:75 010). Incidence was higher in male athletes than in female athletes (1:43 348 [95% CI, 1:36 228-1:51 867] versus 1:164 504 [95% CI, 1:110 552-1:244 787] athlete-years, respectively) and Black athletes compared with White athletes (1:26 704 [1:20 417-1:34 925] versus 1:74 581 [1:60 247-1:92 326] athlete-years, respectively). The highest incidence of SCD was among Division I male basketball players (1:8188 [White, 1:5848; Black, 1:7696 athlete-years]). The incidence rate for SCD decreased over the study period (5-year incidence rate ratio, 0.71 [95% CI, 0.61-0.82]), whereas the rate of noncardiovascular deaths remained stable (5-year incidence rate ratio, 0.98 [95% CI, 0.94-1.04]). Autopsy-negative sudden unexplained death (19.5%) was the most common postmortem examination finding, followed by idiopathic left ventricular hypertrophy or possible cardiomyopathy (16.9%) and hypertrophic cardiomyopathy (12.7%), in cases with enough information for adjudication (118 of 143). Eight cases of death were attributable to myocarditis over the study period (1 case from January 1, 2020, through June 30, 2022), with none attributed to COVID-19 infection. SCD events were exertional in 50% of cases. Exertional SCD was more common among those with coronary artery anomalies (100%) and arrhythmogenic cardiomyopathy (83%). The incidence of SCD in college athletes has decreased. Male sex, Black race, and basketball are associated with a higher incidence of SCD.

Proof of concept for monoclonal antibody therapy in a cellular model of acquired long QT syndrome type 3.

Long QT syndrome (LQTS) type 3 although less common than the first two forms, differs in that arrhythmic events are less likely triggered by adrenergic stimuli and are more often lethal. Effective pharmacological treatment is challenged by interindividual differences, mutation dependence, and adverse effects, translating into an increased use of invasive measures (implantable cardioverter-defibrillator, sympathetic denervation) in patients with LQTS type 3. Previous studies have demonstrated the therapeutic potential of polyclonal KCNQ1 antibody for LQTS type 2. Here, we sought to identify a monoclonal KCNQ1 antibody that preserves the electrophysiological properties of the polyclonal form. Using hybridoma technology, murine monoclonal antibodies were generated, and patch clamp studies were performed for functional characterization. We identified a monoclonal KCNQ1 antibody able to normalize cardiac action potential duration and to suppress arrhythmias in a pharmacological model of LQTS type 3 using human-induced pluripotent stem cell-derived cardiomyocytes.NEW & NOTEWORTHY Long QT syndrome is a leading cause of sudden cardiac death in the young. Recent research has highlighted KCNQ1 antibody therapy as a new treatment modality for long QT syndrome type 2. Here, we developed a monoclonal KCNQ1 antibody that similarly restores cardiac repolarization. Moreover, the identified monoclonal KCNQ1 antibody suppresses arrhythmias in a cellular model of long QT syndrome type 3, holding promise as a first-in-class antiarrhythmic immunotherapy.

Interleukin-17 and interferon-gamma in patients with different forms of non-ischemic cardiomyopathies

Abstract Introduction Dilated cardiomyopathy (DCM) characterized by left ventricular dilation and impaired left ventricular function represents a common and severe cause of heart failure (HF). Predominantly affecting younger patients, it is considered a leading cause for sudden cardiac death and heart transplantation. Several studies identified myocarditis as a substantive precursor and potential cause of DCM. Inflammatory cardiomyopathy (DCMi) can lead to cardiomyocytal damage and exposure of cardiac myosin and other heart proteins. This cascade can in susceptible individuals trigger an altered immune response consecutively leading to autoimmunity and chronic inflammation. A variety of inflammatory and immunologic agents are discussed to be involved in the pathophysiology of myocardial inflammation. Several studies suggested a role of Interleukin -17 (IL-17) and Interferon-γ (IFN-γ) in chronic HF, myocardial infarction and other cardiovascular diseases. Underlying pathomechanisms, however, are poorly understood. Methods In this study we measured IL-17 and IFN-γ levels in serum by ELISA in patients in which an endomyocardial biopsy (EMB) was performed due to chronic unexplained heart failure symptoms after exclusion of ischemic or valvular heart disease at our center. All patients underwent transthoracic echocardiography prior to EMB sampling. Patients were classified according to the histological presence of inflammation into DCMi, DCM and patients with preserved left ventricular ejection fraction (LVEF) without inflammation. EMB specimens were analyzed including histology, immunohistochemistry and molecular virology. Results A total of 289 patients were included into the final analysis. Mean age was 47 years and 71% were male. Mean LVEF was 50% and mean left ventricular end-diastolic diameter (LVEDD) was 57 mm. Based on EMB results, 71 (25%) samples were categorized as DCMi and 113 (39%) as DCM. 105 (36%) samples were assigned to the group without myocardial inflammation and normal LVEF. The groups differed significantly in their inflammatory profiles. Levels of IL-17 (p &amp;lt; 0.001) and IFN-γ (p &amp;lt; 0.01) were significantly higher in patients with DCMi compared to the DCM as well as the normal LVEF group (Figure 1, Figure 2). Therefore, this effect is not specific for heart failure, but seems to be an important mediator in inflammatory cardiomyopathy. Conclusion Our data showed a significant elevation of IL-17 and IFN-γ in patients with inflammatory dilated cardiomyopathy. These findings suggest that these agents play an important role in the disease entity development and progression that remains poorly understood. So far treatment strategies in DCMi are unspecific. Therefore, blocking IL-17 expression could be an interesting potential therapeutic target in future (personalized) treatment for a wide group of patients with heart failure generated by inflammatory causes.Serum IL-17 levels.t-SNE analysis of the different groups.

Cardiac magnetic resonance imaging in athletes with suspected structural myocardial disease: results of a high volume single-center study

Abstract Introduction Structural heart disease is one of the leading causes of sudden cardiac death in athletes. Cardiac magnetic resonance imaging (CMR) has a key role in the diagnosis, providing accurate functional and morphological information. Aim To investigate the prevalence of structural heart disease and the etiology of sudden cardiac death (SCD) in athletes. Methods We enrolled athletes (training ≥6 hours/week) who underwent CMR due to suspected structural myocardial disease at our Heart and Vascular Center between 2009 and 2022. We also performed cardiogenetic testing with new-generation sequencing (174 genes) in athletes with confirmed structural heart disease and/or malignant arrhythmia who gave consent. Results CMR was performed on a total of 556 athletes (445 male, 24±10 age). The indications for CMR were as follows: aborted sudden cardiac death/sustained ventricular tachycardia (3%), ECG (46%) or echocardiographic abnormality (36%), positive family history of SCD or cardiomyopathy (CMP) (3%), or athletes' complaints (31%). Structural myocardial abnormalities were confirmed in 99 athletes: hypertrophic (HCM) in 27, arrhythmogenic (AC) in 11, dilated (DCM) CMP in 7, and left ventricular non-compaction (LVNC) in 9 cases. MR images consistent with Fabry disease were found in 5 patients. We have discovered post-myocardial infarction scars in 10 cases, and atypical non-ischemic scarring (excluding hinge point fibrosis) was observed in 32 athletes. Besides pathological abnormalities, minor alterations were identified in 76 patients. Among the athletes examined after aborted sudden cardiac death/sustained ventricular tachycardia (n=18), we found structural heart disease in 14 patients, AC was confirmed in 7, HCM in two, non-ischemic fibrosis in three cases and LVNC in one athlete. Cardiogenetic test was performed in 26 athletes, we found pathogenic or likely pathogenic mutations in 5 cases, typical of HCM, AC, DCM (MYBPC3, PKP2, LMNA, TTN). The genetic test showed VUS (variant of unknown significance) in 15 additional athletes. Conclusions HCM was identified as the most frequent CMP, whereas AC and nonischaemic scar was the leading cause of SCD or SVT in our athletes.Figure A)Short axis late gadolinium ehancement CMR image of a 26-year-old female tennis player with hypertrophic cardiomyopathy and nonischemic fibrosis (arrow) and MYBPC3 pathogenic variant.Figure B)Short axis late gadolinium enhancement CMR image of a 40-year-old male elite discus thrower with sustained ventricular tacchycardia and nonischaemic scar formation (arrows). LMNA and titin pathogenic variants could be detected.

Sudden cardiac death in women: causes of death at premenopausal and postmenopausal age

Abstract Background Among women the incidence of sudden cardiac death (SCD) is lower than in men but still significant. On average menopause occurs at the age of 51.4 years. During the last decades the proportion of nonischemic SCD seems to have increased in both sexes. In postmenopausal women both the incidence and severity of the coronary artery disease (CAD) increase unpredictably 3-fold compared to premenopausal women of similar age. Purpose The aim of this study was to determine whether the causes of SCD differ among women at premenopausal and postmenopausal age. Methods The Fingesture study has systematically collected clinical and autopsy data from SCD victims in Northern Finland between 1998 and 2017. The cohort consists of 5,869 SCD victims of which 1,238 are women (21.1%). Women aged ≥52 years were considered as postmenopausal and ≤51 years old as premenopausal as the direct information of the menopause lacked due to the retrospective nature of this autopsy-based data. Results Approximately one fifth of the SCD victims were women (21.1%; P&amp;lt;0.001). The mean age of female subjects was 70.1±13.1 years (P&amp;lt;0.001). Only 7.9% of the women experienced SCD under the age of 52 years (P&amp;lt;0.001). Causes of death among women at premenopausal and postmenopausal age are represented in Table 1. Amongst all women 71.7% of the SCDs were ischemic (P&amp;lt;0.001). Majority of those women were at postmenopausal age but CAD caused still one third of the SCDs of the women at premenopausal age (33.7%, P&amp;lt;0.001). Overall nonischemic causes of death were more common at premenopausal age compared to postmenopausal women. Statistically significant nonischemic causes of death were primary myocardial fibrosis (PMF), obesity cardiomyopathy (CM), myocarditis, arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated CM. PMF was considerably more common cause of death among premenopausal women than in postmenopausal women (19.4 % vs. 3.9%, P&amp;lt;0.001), as was also the obesity CM (16.3% vs. 5.3%, P&amp;lt;0.001). Myocarditis caused the death of 5.1% of the premenopausal women but only 1.3% of the postmenopausal women (P=0.004). Both dilated CM (P=0.021) and ARVC (P=0.008) were the cause of death of 2.0% of the premenopausal women and 0.3-0.4% of the postmenopausal women. Subjects with anatomically and histologically normal finding at autopsy were mainly at premenopausal age (2.0% vs. 0.3%, P=0.008) even though the overall amount of cases remained low. Conclusions SCD at premenopausal age is rare. One third of the premenopausal SCDs are ischemic even though majority of the SCDs at premenopausal age are nonischemic etiology. Especially the prevalence of PMF and obesity CM were remarkably higher among premenopausal women compared to the postmenopausal age group emphasizing the role of genetics and lifestyle behind the SCD of premenopausal women.Table 1.

Conventional cardiovascular risk factors in young individuals with three-vessel coronary artery disease experiencing sudden cardiac death

Abstract Background Coronary artery disease (CAD) is a major cause of sudden cardiac death (SCD) in young victims under 50 years of age. Despite the young age, highly advanced CAD is a common finding at autopsies. Purpose We aimed to determine the prevalence of conventional cardiovascular risk factors in ischemic SCD victims under the age of 50 years with a three-vessel CAD detected at autopsy. Methods The study population was derived from the Fingesture study, consisting of consecutive victims of SCD in Northern Finland between years 1998-2017 (n=5,869). All victims underwent medico-legal autopsy with histological examinations, and toxicology investigations was performed if necessary. Pre-mortem clinical history was obtained from available medical records and medication, questionnaires to closest family members and police reports about the conditions of the death. Results In the Fingesture study, a total of 266 SCDs caused by CAD were observed in victims under 50 years of age. Three-vessel disease was detected in 118 victims (44%). The victims with three-vessel disease had more commonly a history of diabetes (26% vs. 14%, p=0.017) compared with victims with fewer major coronary arteries affected. No statistically significant difference was detected in the prevalence of known dyslipidemia (16% vs. 9%, p=0.134), hypertension (29% vs. 19%, p=0.103), male gender (88% vs. 91%, p=0.552), family history of SCD (33% vs. 36%, p=0.841), smoking (81% vs. 72%, p=0.371), or mean age (45 years vs. 44 years, p=0.120). Conclusions The history of diabetes was the only conventional risk factor associated with three-vessel disease in young individuals who experienced SCD determined to be caused by CAD. Along with previous studies, these results highlight the role of diabetes in the development of CAD and adverse outcomes in young people.

Abstract 12529: Exercise Patterns and Body Mass Index in a Large Cohort of Patients With Anomalous Aortic Origins of Coronary Arteries

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden cardiac death in the young. Exercise patterns in relation to BMI and surgery status are lacking. Hypothesis: Exercise patterns are variable in AAOCA and relate to BMI and surgery. Aim: To identify differences in exercise patterns and BMI in patients with AAOCA and their relation to surgery status. Methods: Single-center retrospective study of 573 patients with AAOCA (median age = 11.9 years, IQR 6-15), 63% males. Exercise patterns were classified as recreational or organized/competitive. BMI percentiles were stratified as normal (5 th to ≤ 85 th %ile), overweight (85 th to ≤ 95 th %) and obese (≥ 95 th %ile). Exercise patterns and BMI were compared across demographic parameters, presence of ischemia, and surgery status. Mann-Whitney U test was for non-parametric and χ 2 test for categorical variables. Results: Two-thirds of patients exercise recreationally, 1/3 are overweight (BMI &gt; 85 th %ile) and 20% are obese (BMI &gt;95 th %ile) (Table 1). Those who had surgery were more likely to exercise competitively (24% vs 15%, p=0.026). Myocardial ischemia was more likely in those who were exercise restricted (34% vs 14%, p=&lt;0.001). There was no difference in BMI percentile in those with ischemia or who exercised competitively (Table 2). Conclusion: Most patients with AAOCA exercise recreationally and 1 in 5 is obese. Surgery positively relates to competitive exercise. BMI or exercise patterns are unrelated to ischemia but associated with exercise restriction. Future studies are needed to determine optimal exercise recommendations to promote active lifestyle while minimizing the risk of sudden death.

Abstract 19071: An Agitated Young Heart: A Rare Presentation With a Favorable Outcome Under the Right Circumstances

Introduction: Commotio cordis (Latin: agitation of heart) is sudden death triggered by a blunt, often innocent-appearing blow to the chest. It is the third most common cause of sudden cardiac death (SCD) in young athletes, after hypertrophy cardiomyopathy, and coronary anomalies. Around 10-20 cases are added to the Commotio Cordis (CC) registry annually. Ventricular fibrillation seems to be the most common arrhythmia in commotio cordis in 40% of cases. Case Presentation: A 22-year-old male with no known medical illness presented after sudden cardiac arrest. According to a bystander, he fell to the ground and lost consciousness within a few seconds of being “elbowed in his chest” during a basketball game. EMS provided bag valve mask ventilation for respiratory distress but were unable to record the rhythm. On initial presentation to the emergency room, he was found to be in ventricular tachycardia (VT) with hemodynamic instability. He was cardioverted, and his VT deteriorated to ventricular fibrillation. He was intubated for airway protection, received two rounds of CPR and another 200 J defibrillation that restored his sinus rhythm with return ofspontaneous circulation (ROSC). Bedside echocardiogram revealed global hypokinesis with EF 30-35%. EKG showed marked ST elevation in AvR with deep ST depression in other leads. Code STEMI was activated, and an emergent coronary angiogram was done which revealed normal coronary arteries and anatomy. Subsequent EKG within an hour was essentially normal. A repeat echocardiogram on the next day showed an improved EF of 65%. Discussion: Commotio cordis is fatal, with only about 25% of the cases on CC registry resulting in survival. A chest blow must be confined to a small area of the precordium within a 20 msec window during upstroke of T wave that results in ventricular fibrillation. Sustained ventricular tachycardia is even rare, with only one case report found on literature review. It is likely that his VT favored a better prognosis.

Abstract 12668: Prevalence of Phenotypic Hypertrophic Cardiomyopathy Among Students Referred for Sport Pre-Participation Cardiovascular Screening

Background: Although rare, sudden cardiac death (SCD) is a tragic event for young sports participants and has catastrophic impact on the community. Hypertrophic cardiomyopathy (HCM) is a leading cause of SCD in sports. Comprehensive initial pre-participation physical evaluation (CIPPE) is mandated for middle school, and junior and senior high school students by Pennsylvania Interscholastic Athletic Association (PIAA) primarily for reducing potential sports-related injuries and SCD. Prospective data has been limited in this age group in regard to the prevalence of HCM. Methods: Between 2015 and 2023, we prospectively screened 424 students [age 10-21 (15±2) years, 60% male, 64% Caucasian) referred for cardiovascular disease pre-participation screening based on at least one positive response on the 14-point AHA questionnaire during CIPPE. Evaluation included 12-lead ECG and rhythm strip (100%), transthoracic echo (96.4%), ambulatory heart rhythm monitor (3.8%), treadmill exercise ECG (14.5%), stress echo (2.1%), and cardiac MRI (0.9%). Results: Overall, 1 (0.24%) student was diagnosed with definitive and two were diagnosed with probable HCM [Table-1]. Conclusion: In this prospective cohort of middle school and junior and senior high school students with at least one positive response to the 14-point AHA questionnaire, 1 (0.24%) had definitive and 2 (0.47%) had probable phenotypic HCM.

Abstract 13937: Socioeconomic Status in Pediatric Patients With Anomalous Aortic Origins of Coronary Arteries: An Individual- and Zip Code-Level Analysis

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden cardiac death in the young. Limited data is available on potential disparities on access to care and whether socioeconomic status is associated with AAOCA. Hypothesis: AAOCA occurrence, severity, and treatment relate to socioeconomic status and may unfold inequities to care. Methods: Single-center retrospective study of 553 pediatric patients with AAOCA residing in Texas. Zip code socioeconomic characteristics were extracted from American Community Survey 2021 5-year estimates. All Texas zip codes were ordered into quartiles by characteristic. Age at diagnosis, signs of ischemia, and surgery status were compared by race and zip code parameters. Mann-Whitney U test was for non-parametric variables and χ 2 test, Fisher’s test, or one-way ANOVA for categorical variables. Results: Table 1 depicts patients’ demographics. AAOCA patients tended to reside in zip codes at the 4 th quartile of income (39%, p=&lt;0.001), education (29%, p=0.003), and employment (42%, p=&lt;0.001) (Table 2). There was no difference in age at diagnosis, signs of ischemia, or occurrence of coronary surgery by individual race or zip code socioeconomic parameters. Conclusions: AAOCA pediatric patients tend to live in zip codes with higher socioeconomic status (SES). These differences may reflect disparities in access to diagnosis and care. Further studies are needed to determine the burden of AAOCA in low SES populations.

Abstract 14902: Prevalence and Characteristics of Myocarditis-Related Sudden Death in the General Population

Introduction: Myocarditis is a frequent cause of sudden cardiac death (SCD) in young individuals (&lt;35 years), but the frequency of myocarditis in middle-aged (35-65 years) and older SCD victims (&gt;65 years) is unclear. Objective: We aimed to investigate the prevalence and characteristics of myocarditis-related sudden death in the general population. Methods: Our study population is drawn from the Fingesture study, which has prospectively collected all out-of-hospital SCD cases from Northern Finland (population ~700,000) since 1998. As required by Finnish law, all sudden deaths undergo a medicolegal autopsy. All out-of-hospital sudden death cases in the community with a verified cardiac cause of death at autopsy are included in the Fingesture study. By 2017, the Fingesture study had collected data on 5,869 SCD victims. Results: In total, 60 SCD victims had evidence of acute myocarditis at autopsy (1.0% of all SCD cases). The mean age of SCD victims with myocarditis was 55.9±18.2, which was significantly lower than among the rest SCD victims (65.0±12.3; p&lt;0.001). Myocarditis cases were also more often female in comparison to the rest SCD cases (33.3% vs. 21.0%; p=0.02). The proportion of myocarditis was highest among young (&lt;35 years) SCD cases (n=6/73; 8.2%), and the proportion decreased in middle aged (35-65 years) (n=34/2,948; 1.2%) and older (&gt;65 years) SCD cases (n=20/2,848; 0.7%) (p&lt;0.001), although the absolute number was higher. The most common diagnosis was undetermined acute myocarditis (n=42/60; 70%) followed by infective myocarditis (n=10/60; 16.7%) and pericarditis (n=5/60; 8.3%). In addition, two SCD cases had sarcoidosis and one had giant cell myocarditis. Five SCD cases due to myocarditis (8.3%) occurred during physical exercise. Conclusions: Myocarditis is a rare cause of SCD in the general population. Although the relative proportion of myocarditis was highest among young SCD victims, the absolute number was highest among middle-aged SCD victims.