Cause Of Sudden Cardiac Death Research Articles

Spectrum of Disorders Leading to Sudden Cardiac Death

Objective: To determine the frequency of disorders leading to sudden cardiac death (SCD).
 Study Design: Cross-sectional study.
 Place and duration of study: Pathology Lab in collaboration with the Cardiology Department, AFIC & NIHD, Rawalpindi Pakistan, from Jan 2017 to Dec 2018.
 Methodology: A total of 305 cases of sudden cardiac death reported within the last 24 hours of a death to AFIC Rawalpindi were included consecutively. Cases with a history of extracardiac diseases leading to sudden death were excluded. Most of the included cases were diagnosed phenotypically based on clinical examination, biochemistry, ECG, echocardiography, angiography, thallium scan, electro-physiological studies, cardiac CT scan, MRI and routine autopsy whenever recommended.
 Results: Out of 305 cases, 197 (65%) were males and 108 (35%) females. Disorders leading to SCD were found in 178 (58.3%) cases due to ischemic heart disease (IHD), aortic dissection (0.7%), hypertrophic cardiomyopathy (HCM) (0.3%), dilated cardiomyopathy (DCM) (10.5%), congenital heart disease (12.1%) and valvular heart disease (7.9%). While in cardiac channelopathies, catecholaminergic polymorphic ventricular tachycardia (CPVT) in 5 (1.6%) and congenital long QT syndrome (LQTS) in 2 (0.7%) cases. However, 24 (7.9%) cases remained as sudden unexplained deaths (SUD).
 Conclusion: In our setup, ischemic heart disease and dilated cardiomyopathy were the commonest causes of sudden cardiac death, followed by congenital heart disease and valvular heart diseases.

Coronary unroofing does not fits all anomalous aortic origin of coronary arteries.

Anomalous aortic origin of coronary artery (AAOCA) is the second leading cause of sudden cardiac death in children and young adults. Intramural-interarterial course is the most frequent anatomic variation and coronary unroofing is widest adopted for surgical management. Symptoms recurrence is described regardless of the technique used. This study aims to describe how an anatomic patient-centered approach aimed to restore a normal coronary artery take-off is associated with symptoms resolution. From 2008 to 2021, 25 patients were operated on for an AAOCA at a median age of 20 years. Nineteen patients had a right AAOCA and six had left AAOCA. Intramural course was present in 18 patients. Seventy-six percent were symptomatic. No episodes of aborted sudden cardiac death before surgery was described in the population. Surgical technique used were coronary unroofing in 18 patients, coronary neo-ostioplasty in 3, coronary Reimplantation in 3, and main pulmonary artery re-location in 1. No hospital mortality or reoperation was observed in our experience as well as major complications related to surgery. Mean hospital length of stay was 8.5 days. None of patients reported symptoms recurrence at follow-up. Young athletes returned to play competitive sport. Postoperative computed tomography scan evaluation showed a general improvement of the take-off angle. AAOCA requires a patient anatomic-based surgical management. There is not a single surgical technique that can fits all anatomic subtype of AAOCA. Surgical techniques may be selected on the base of the preoperative images and intraoperative findings. In our experience, this policy is associated with no symptoms recurrence.

αSMA-Cre-mediated Ogt deletion leads to heart failure and vascular smooth muscle cell dysfunction in mice

Dilated cardiomyopathy, a type of heart muscle disease defined by the presence of left ventricular dilatation and contractile dysfunction, is an important cause of sudden cardiac death and heart failure. O-GlcNAcylation is an important post-translational modification of proteins by the addition of O-GlcNAc moieties at serine or threonine residues. Several studies have shown that proper control of O-GlcNAcylation is required for maintaining physiological function of heart by using Ogt (O-GlcNAc transferase) cardiomyocyte-specific knockout mouse models. In this study, we generated a new mouse model (αSMA-Ogt KO) in which Ogt was deleted in both cardiomyocytes and smooth muscle cells by crossing Ogt floxed mice with αSMA-Cre mice. αSMA-Cre-mediated Ogt deletion in mice led to severe postnatal lethality; the survived mice were smaller than control mice, had dilated hearts, and showed observable signs of heart failure. Moreover, the αSMA-Ogt KO heart had more apoptotic cells and fibrosis. The arteries of αSMA-Ogt KO mice exhibited significantly reduced expression of contractile genes and a trend towards arterial stiffness. In conclusion, our data emphasize the importance of OGT in maintaining normal heart function and reveal a novel role of OGT in regulating arterial contractility.

Blood-based biomarkers for the prediction of hypertrophic cardiomyopathy prognosis: a systematic review and meta-analysis.

Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease. HCM is an important cause of sudden cardiac death and may also lead to outflow tract obstruction and heart failure. Disease severity is highly variable and risk stratification remains limited. Therefore, we aimed to review current knowledge of prognostic blood-based biomarkers in HCM. A systematic literature search was performed on PubMed, Embase, and the Cochrane library to identify studies assessing plasma or serum biomarkers for outcomes involving malignant ventricular arrhythmia, outflow tract obstruction, and heart failure. Risk of bias was assessed using the QUIPS tool. Meta-analyses were performed using the random effects method. A total of 26 unique cohort studies assessing 42 biomarkers were identified. Overall risk of bias was moderate. Thirty-two biomarkers were significantly associated to an HCM outcome in at least one study (nine biomarkers in at least two studies). In pooled analyses, cardiovascular mortality was predicted by N-terminal prohormone of brain natriuretic peptide (hazard ratio [HR] 5.38 per log[pg/mL], 95% confidence interval [CI] 2.07-14.03, P<0.001, I2 =0%) and high-sensitivity C-reactive protein (HR 1.30 per μg/mL, 95% CI 1.00-1.68, P=0.05, I2 =78%), all-cause mortality by low-density lipoprotein cholesterol (HR 0.63 per μmol/mL, 95% CI 0.49-0.80, P<0.001, I2 =0%), and a combined congestive heart failure, malignant ventricular arrhythmia, and stroke outcome by high-sensitivity cardiac troponin T (pooled HR 4.19 for ≥0.014ng/mL, 95% CI 2.22-7.88, P<0.001, I2 =0%). Quality of evidence was low-moderate. Several blood-based biomarkers were identified as predictors of HCM outcomes. Additional studies are required to validate their prognostic utility within current risk stratification models.

Genotype-Specific ECG-Based Risk Stratification Approaches in Patients With Long-QT Syndrome.

BackgroundCongenital long-QT syndrome (LQTS) is a major cause of sudden cardiac death (SCD) in young individuals, calling for sophisticated risk assessment. Risk stratification, however, is challenging as the individual arrhythmic risk varies pronouncedly, even in individuals carrying the same variant.Materials and MethodsIn this study, we aimed to assess the association of different electrical parameters with the genotype and the symptoms in patients with LQTS. In addition to the heart-rate corrected QT interval (QTc), markers for regional electrical heterogeneity, such as QT dispersion (QTmax-QTmin in all ECG leads) and delta Tpeak/end (Tpeak/end V5 – Tpeak/end V2), were assessed in the 12-lead ECG at rest and during exercise testing.ResultsQTc at rest was significantly longer in symptomatic than asymptomatic patients with LQT2 (493.4 ms ± 46.5 ms vs. 419.5 ms ± 28.6 ms, p = 0.004), but surprisingly not associated with symptoms in LQT1. In contrast, post-exercise QTc (minute 4 of recovery) was significantly longer in symptomatic than asymptomatic patients with LQT1 (486.5 ms ± 7.0 ms vs. 463.3 ms ± 16.3 ms, p = 0.04), while no such difference was observed in patients with LQT2. Enhanced delta Tpeak/end and QT dispersion were only associated with symptoms in LQT1 (delta Tpeak/end 19.0 ms ± 18.1 ms vs. −4.0 ms ± 4.4 ms, p = 0.02; QT-dispersion: 54.3 ms ± 10.2 ms vs. 31.4 ms ± 10.4 ms, p = 0.01), but not in LQT2. Delta Tpeak/end was particularly discriminative after exercise, where all symptomatic patients with LQT1 had positive and all asymptomatic LQT1 patients had negative values (11.8 ± 7.9 ms vs. −7.5 ± 1.7 ms, p = 0.003).ConclusionDifferent electrical parameters can distinguish between symptomatic and asymptomatic patients in different genetic forms of LQTS. While the classical “QTc at rest” was only associated with symptoms in LQT2, post-exercise QTc helped distinguish between symptomatic and asymptomatic patients with LQT1. Enhanced regional electrical heterogeneity was only associated with symptoms in LQT1, but not in LQT2. Our findings indicate that genotype-specific risk stratification approaches based on electrical parameters could help to optimize risk assessment in LQTS.

Management of the patient with a wearable cardiac defibrillator in a virtual remote monitoring clinic

Abstract Funding Acknowledgements Type of funding sources: None. Background the risk of sudden cardiac death (SCD) currently represents a severe problem that significantly involves the population. The implantable cardiac defibrillator (ICD) has been used to prevent SCD among patients with a high risk for life-threatening sustained ventricular arrhythmias. However, there are a number of patients at risk for SCD either awaiting a work-up for reversible causes of SCD or with acute contraindications to ICD implantation. Nevertheless, ICD implantation is dependent on defining ventricular substrate, evaluating the future risk of SCD and estimation of the patient’s overall survival. The wearable cardiac defibrillator (WCD) provides an option for protection during this vulnerable period when the risk of SCD is unclear. Methods our virtual device control clinic is managed by 3 cardiovascular technicians and 3 electrophysiologists. From August 2017 to January 2022, we included 29 patients who received WCD, 6 women (21%), with an average age of 66 years. The indications for the use of WCD were: ischemic cardiomyopathy (62,1%) and non-ischemic cardiomyopathy (17,24%),during cardiovascular rehabilitation pending eventual recovery of the ejection fraction (EF), waiting for genetic test result (10,34%) or ICD explant for infection awaiting reimplantation (10,34%).The patient is trained by technician staff to ensure the correct wearing of the WCD, the management of any alarms, the management of the device in case of arrhythmia and shock, as well as the daily replacement of the battery and the management of the remote monitoring system. Results in virtual control device clinic Cardiovascular Technician checks the transmissions from the WCD site: only clinical parameters such as recorded ECGs (manual, asystolic, events detected but not treated and events treated with shock) and patient compliance (wearing hours per day) can be verified.The average wearing duration has been 37 days, with a daily average of 23.1 hours. We received and controlled a total of 1097 transmissions, of which 22 with events, of which 7 were generated for VT, 4 for TSV, 10 for T wave oversensing and 1 for inappropriate Shock; in all these cases, the patient has been contacted by the clinic staff for clinical management. At the end of wearing period, technical staff schedules a check-up with echocardiogram monitoring the EF to evaluate the patient's clinical path. Following the clinical evaluation, a recovery of cardiac function has been possible for 13 patients, without any implantation of ICD, whereas 16 patients underwent a defined implantation of ICD. Conclusions the WCD has been shown to be an effective device in protecting SCD from VT/VF. Despite the small number of patients, it was necessary to take them in charge at the virtual remote monitoring clinic for proper clinical management, which generated a workload increase. Therefore, it will be important to propose a recognition of the service and its reimbursement.

Cardiac Multislice Computed Tomography in the Detection of Phenotypic Polymorphism of Hypertrophic Cardiomyopathy

Background. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease with a prevalence of 1 case per 500 people and is the most common cause of sudden cardiac death in young patients. As clinical manifestations and electrocardiographic data are nonspecific and diverse, noninvasive imaging techniques play a key role in the detection of HCM and the understanding of its pathophysiology.&#x0D; The aim. To evaluate the possibilities of ECG-synchronized cardiac multislice computed tomography (MSCT) as a highly informative diagnostic tool for assessing the morpho-functional state of the heart in patients with HCM.&#x0D; Materials and methods. This was a retrospective analysis conducted at the National Amosov Institute of Cardiovascular Surgery from January 2020 to December 2021. We examined 221 cardiac MSCT scans of patients who underwent the examination to assess the spread of myocardial hypertrophy. Particular attention was paid to the presence of crypts at different levels of the left ventricle (LV), anatomical features of the mitral valve and subvalvular apparatus. The presence of systolic pulling of the anterior mitral valve to the interventricular septum, myocardial mass, LV end-diastolic, LV end-systolic volumes and the corresponding indices of body surface area, ejection fraction were determined and calculated during the functional analysis. Additionally, the anatomy and patency of the coronary arte­ ries were assessed. The studies were performed on a 640-slice Canon Aquilion One CT scanner with retrospective ECG gating and subsequent image processing. The studies were transferred to a workstation for review and evaluation by a team of radiologists.&#x0D; Results. The mean patient age was 46 ± 23 years, 48% were male. Mean maximal LV wall thickness was 19 mm (range 16–34). In 159 patients (71.9%), there was an asymmetric form of HCM with a predominant thickening of the anterior and anteroseptal segments of the left ventricle at the basal and midventricular levels. Fifty-four (24.4%) patients had symmetric form of HCM. The midventricular form of HCM was detected in 4 patients (1.8%). Apical form of HCM was detected in 3 patients (1.3%). One patient was diagnosed with a tumor-like variant of HCM (0.5%). In 198 patients (89.6%), systolic anterior motion of the mitral valve to the interventricular septum was found. In 95 cases (42.9%), morphological abnormality, abnormality of the number or attachment of the papillary muscles were detected. Forty-eight myocardial crypts were detected in 44 patients (21.7%). In 194 patients (87.7%), patent coronary arteries without signs of stenosis were found, 68 patients (30.7%) had 74 myocardial bridges (33.4%).&#x0D; Conclusions. HCM is a genetic heart disease with enormous phenotypic diversity. Due to its high spatial resolution, cardiac MSCT is an accurate diagnostic tool, which allows to assess the morphofunctional state of the LV, mitral valve, subvalvular apparatus, as well as to analyze the anatomy and narrowing of coronary arteries in patients with HCM.

Development and diseases of the coronary microvasculature and its communication with the myocardium.

We review the current understanding of formation and development of the coronary microvasculature which supplies oxygen and nutrients to the heart myocardium and removes waste. We emphasize the close relationship, mutual development, and communication between microvasculature endothelial cells and surrounding cardiomyocytes. The first part of the review is focused on formation of microvasculature during embryonic development. We summarize knowledge about establishing the heart microvasculature density based on diffusion distance. Then signaling mechanisms which are involved in forming the microvasculature are discussed. This includes details of cardiomyocyte-endothelial cell interactions involving hypoxia, VEGF, NOTCH, angiopoietin, PDGF, and other signaling factors. The microvasculature is understudied due to difficulties in its visualization. Therefore, currently available imaging methods to delineate the coronary microvasculature in development and in adults are discussed. The second part of the review is dedicated to the importance of the coronary vasculature in disease. Coronary microvasculature pathologies are present in many congenital heart diseases (CHD), especially in pulmonary atresia, and worsen outcomes. In CHDs, where the development of the myocardium is impaired, microvasculature is also affected. In adult patients coronary microvascular disease is one of the main causes of sudden cardiac death, especially in women. Coronary microvasculature pathologies affect myocardial ischemia and vice versa; myocardial pathologies such as cardiomyopathies are closely connected with coronary microvasculature dysfunction. Microvasculature inflammation also worsens the outcomes of COVID-19 disease. Our review stresses the importance of coronary microvasculature and provides an overview of its formation and signaling mechanisms and the importance of coronary vasculature pathologies in CHDs and adult diseases. This article is categorized under: Cardiovascular Diseases > Stem Cells and Development Congenital Diseases > Molecular and Cellular Physiology Cardiovascular Diseases > Molecular and Cellular Physiology.

An Atypical Anomalous Aortic Origin of the Left Coronary Artery With Intra-Arterial Wall Course Pretending a Normal Migration on Imaging Screening: A Case Report

BackgroundAn anomalous aortic origin of a coronary artery (AAOCA) has been considered as a dominant cause of sudden cardiac death (SCD) among young age children. Therefore, it is critical to identify AAOCA timely to avoid lethal events. Recently, accumulating cases of right or left coronary arteries originating from inappropriate locations at the sinus of Valsalva have been identified. Here, we report a rare case of AAOCA with an intra-arterial wall course pretending normal migration on imaging screening in a patient who suffered from syncope.Case summaryA 7-year-old male without a previous history of cardiovascular and cerebrovascular diseases suddenly suffered from sharp chest pain and syncope after intensive exercise. The electrocardiogram showed that the ST segment of multiple leads was depressed by more than 0.05 mV, and biomarkers indicated severe myocardial injuries. The left ventricular ejection fraction (LVEF) decreased dramatically to 23%. Fulminant myocarditis and cardiomyopathy were therefore excluded. However, a relatively normal coronary artery origin, which arose from the left coronary sinus, presented on echocardiography and cardiac CT angiography (CTA). It is difficult to draw an association between severe clinical manifestations and slight malformations on echocardiography and CTA. Furthermore, selective coronary angiography revealed that an anomalous left coronary artery arose from the superior margin of the inappropriate sinus, developed an intramural wall course and finally exits the left sinus of Valsalva and migrated between the aorta and the pulmonary artery, which induced severe myocardial infarction during exercise. Then, the patient received surgical correction with a modified unroofing procedure. After 2 months of intensive treatment, the patient was discharged and remained asymptomatic through 18 months of follow-up.ConclusionAAOCA, especially anomalous left coronary artery (ALCA), represents a major potential risk of SCD. We reported an atypical manifestation of ALCA arising from the inappropriate sinus of Valsalva and merging into the intra-arterial wall to develop a strange course and then sprout between the aorta and the pulmonary artery. The diversity of AAOCA might present as a relatively normal course under non-invasive radiological imaging scanning.

Pharmacologic Management for Ventricular Arrhythmias: Overview of Anti-Arrhythmic Drugs.

Ventricular arrhythmias (Vas) are a life-threatening condition and preventable cause of sudden cardiac death (SCD). With the increased utilization of implantable cardiac defibrillators (ICD), the focus of VA management has shifted toward reduction of morbidity from VAs and ICD therapies. Anti-arrhythmic drugs (AADs) can be an important adjunct therapy in the treatment of recurrent VAs. In the treatment of VAs secondary to structural heart disease, amiodarone remains the most well studied and current guideline-directed pharmacologic therapy. Beta blockers also serve as an important adjunct and are a largely underutilized medication with strong evidentiary support. In patients with defined syndromes in structurally normal hearts, AADs can offer tailored therapies in prevention of SCD and improvement in quality of life. Further clinical trials are warranted to investigate the role of newer therapeutic options and for the direct comparison of established AADs.

Sincope ricorrente: attenti alla coronaria

Anomalous aortic origin of coronary artery (AAOCA) is a rare condition and the second cause of sudden cardiac death among young athletic patients. Suspicion should arise in the presence of exertional syncope without prodrome, chest pain and/or dyspnea. An accurate transthoracic echocardiogram with Doppler colour flow mapping is the best and first method to identify AAOCA, followed by cardiac CT or MRI to define the coronary anatomy that could benefit from corrective cardiac surgery.

Income and education are associated with incidence of sudden cardiac death in a general population cohort

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No 733381 Introduction Socioeconomic status is associated to all-cause mortality and common cardiac risk factors. The association between socioeconomic status and sudden cardiac death (SCD) taking prevalence of other risk factors into account has not been fully established. Objective The aim of this study was to investigate the association between income and education level and incidence of SCD. Methods All participants in the third wave of the Copenhagen City Heart Study were followed from 1993 to 2016 and all deaths were adjudicated using high quality death certificates, autopsy reports, and national registry data. Medical history and social demographics were self-reported. Hazard ratios (HR) were calculated using Cox proportional hazards regression and adjusted cumulative incidences were predicted using cause specific cox models. Results The study enrolled 10099 participants who were alive at start of follow up (median age at entry (IQR): 61 (48-72) years, 56% female). During 24 years of follow up, there were 5575 deaths of which 834 were classified as SCD. Compared with lowest income group and adjusted for age, sex, job, and education, higher income was associated with lower HR of SCD: middle income HR 0.82 (95% CI: 0.69-0.98) and high income HR 0.62 (0.47-0.81). This effect was attenuated, but still present, when adjusting for common cardiac risk factors (smoking, alcohol, BMI, physical activity, AMI, diabetes, hypertension, hypercholesterolemia). Compared with no education, increasing length of education was associated with lower HR of SCD: apprenticeship HR 0.82 (0.68-0.98), short education HR 0.80 (0.67-0.96), bachelor’s degree HR 0.56 (0.41-0.76), master’s degree HR 0.41 (0.28-0.59). This effect was also attenuated when adjusting for risk factors, job, and income. Adjusted cumulative incidences of SCD during the first 10 years of follow up according to income and education are shown in the figures. Conclusions In this study we found an association between lower income and shorter education and increased risk of SCD, an association not fully explained by prevalence of common cardiac risk factors, calling for further research into competing causes of SCD.

SAECG - advances in Brugada stratification

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Brugada syndrome (BrS) is a relevant cause of sudden cardiac death (SCD) in young adults. Several risk factors have been identified, but clinical decision making remains extremely challenging, particularly in asymptomatic patients. Purpose To explore the usefulness of the non-invasive assessment of late potentials (LPs) based signal-averaged ECG (SAECG) for risk stratification in BrS. Methods Prospective single-center study of patients with BrS included from 2003 to 2021. LPs were evaluated by SA-ECG with determination of the total filtered QRS duration (fQRS), root mean square voltage of the 40ms terminal portion of the QRS (RMS40) and duration of the low amplitude electric potential component of the terminal portion of the QRS (LAS40) in conventional and modified right precordial leads. The primary endpoint was the occurrence of malignant arrhythmic events (MAEs), defined as a composite of SCD or appropriate shocks. Uni- and multivariate Cox regression survival analyses were used to identify significant prognostic predictors considering the clinical, genetic, and electrocardiographic characteristics as well as the tercile distribution of the SAECG parameters. A risk score was computed incorporating the significant LPs variables and its usefulness for prognostic stratification was explored using Kaplan Meier survival analysis. Results Our cohort consisted of 117 patients (mean age: 47±13 years, 33% male), including 75 (65%) with type 1 spontaneous pattern and 92 (79%) asymptomatic individuals. Symptoms at presentation included syncope in 16 pts (14%) and polymorphic VT/cardiac arrest in 4 (3.4%). During a median follow-up of 4.1±0.3 years, 8 pts (6.8%) suffered MAEs: 3 (2.6%) with SCD and 5 (4.3%) with appropriate shocks. The risk of events differed in relation to the several SAECG parameters (Table 1), increasing linearly with the fQRS duration determined either in the conventional (HR 1.03, 95% CI 1.01-1.06, p=0.008) or modified leads (HR: 1.03, 95% CI 1.01- 1.05, p=0.003). The SAECG score incorporated as risk markers a fQRS ≥113ms and a RMS40 &amp;lt;13 μV. Patients with both risk markers presented a 7-fold increased risk (HR 7.17, 95% CI 1.29-40, p = 0.025), independently of the baseline symptomatic status and ECG pattern. Conclusion This study shows that the non-invasive assessment of LPs based on SAECG is useful for prognostic stratification of BrS. It was possible to identify a subset of patients presenting a high risk of events who may deserve individualized preventive strategies.

Rare and Common Genetic Variation Underlying the Risk of Hypertrophic Cardiomyopathy in a National Biobank

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death in young people. Although rare genetic variants are well-established contributors to HCM risk, common genetic variants have recently been implicated in disease pathogenesis. To assess the contributions of rare and common genetic variation to risk of HCM in the general population. This cohort study of the UK Biobank (data from 2006-2010) and the Mass General Brigham Biobank (2010-2019) assessed the relative and joint contributions of rare genetic variants and a common variant (polygenic) score to risk of HCM. Both rare and common variant predictors were then evaluated in the context of relevant clinical risk factors. Data analysis was conducted from May 2021 to February 2022. Pathogenic rare variants, common-variant (polygenic) score, and clinical risk factors. Risk of HCM. The primary study population comprised 184 511 individuals from the UK Biobank. Mean (SD) age was 56 (8) years, 83 690 (45%) of participants were men, and 204 (0.1%) participants had HCM. Of 51 genes included in clinical genetic testing panels for HCM, pathogenic or likely pathogenic variants in 14 core genes (designated by the American College of Medical Genetics and Genomics [ACMG]) were associated with 55-fold higher odds (95% CI, 35-83) of HCM, while those in the remaining 37 non-ACMG genes were not significantly associated with HCM (OR, 1.8; 95% CI, 0.6-4.0). ClinVar pathogenic or likely pathogenic mutations in MYBPC3 (OR, 72; 95% CI, 39-124) and MYH7 (OR, 61; 95% CI, 26-121) were strongly associated with HCM, as were loss-of-function variants in ALPK3 (OR, 13; 95% CI, 4.4-28). A polygenic score was strongly associated with HCM (OR per SD increase in score, 1.6; 95% CI, 1.4-1.8), with concordant results in the Mass General Brigham Biobank. Genetic factors enhanced clinical risk prediction for HCM: addition of rare variant carrier status and the polygenic score to clinical risk factors (obesity, hypertension, atrial fibrillation, and coronary artery disease) improved the area under the receiver operator characteristic curve from 0.71 (95% CI, 0.65-0.77) to 0.82 (95% CI, 0.77-0.87). Both rare and common genetic variants contribute substantially to HCM susceptibility in the general population and improve HCM risk prediction beyond that achieved with clinical factors.

P27 MONOMORPHIC VENTRICULAR TACHYCARDIA INDUCED BY BLUNT CHEST TRAUMA IN A YOUNG MAN WITHOUT STRUCTURAL HEART DISEASE: A CASE REPORT

Abstract Introduction Life–threatening ventricular arrhythmias secondary to chest trauma without structural cardiac damage (i.e. commotio cordis [CC]) are a rare but dramatic cause of sudden cardiac death. We present a case of fast ventricular tachycardia (VT) induced by blunt chest trauma in a healthy man during sports activity. Case Presentation A 22–year–old man, competitive soccer player, was admitted to our hospital for VT. A few hours before admission, after a heavy ball impact in the chest during a soccer match, he suddenly reported fast and regular palpitation with lightheadedness and dyspnea, without loss of consciousness. The emergency medical service was activated, and the evaluation revealed a hemodynamically tolerated monomorphic VT with a rate of almost 285 bpm (Fig.A). Amiodaron infusion was ineffective and sinus rhythm (SR) was restored by electrical cardioversion. At the time of admission, he was asymptomatic. Familiar history, past medical history and physical examination were unremarkable. ECG revealed regular SR, with minimal right bundle branch conduction delay (Fig.B). Blood samples showed normal blood cells count, electrolyte concentrations and liver, kidney, and thyroid function; seriate high sensitivity troponin I determinations were negative. Echocardiography and cardiac magnetic resonance showed normal findings. Computed tomography angiography excluded coronary anomalies. Exercise test revealed no signs of cardiac ischemia and no effort–induced arrhythmias. The fluoroscopy–free unipolar and bipolar voltage maps showed normal electrograms throughout the right ventricle (Fig.C). No sustained arrhythmias were induced by programmed ventricular stimulation. The patient was then discharged with the indication to cardiology follow–up and the advice to avoid contact sports activities. Discussion VT is a rare presentation of CC. It has been proposed that CC occurs when a chest strike timed at the upstroke of the T–wave causes both ventricular depolarization trigger and altered dispersion of repolarization, mainly via activation of KATP channels. In the absence of structural heart disease (SHD), the usual presenting rhythm is ventricular fibrillation and there are no accepted mechanisms to explain monomorphic VT in this context. Some authors reported monomorphic VT after chest trauma as the first manifestation of arrhythmogenic cardiomyopathy. Therefore, a careful follow–up will be needed to exclude future development of SHD in this patient.

Metabolite Signature in the Carriers of Pathogenic Genetic Variants for Cardiomyopathy: A Population-Based METSIM Study.

Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are among the leading causes of sudden cardiac death. We identified 38 pathogenic or likely pathogenic variant carriers for HCM in three sarcomere genes (MYH7, MYBPC3, TPMI) among 9.928 participants of the METSIM Study having whole exome sequencing data available. Eight of them had a clinical diagnosis of HCM. We also identified 20 pathogenic or likely pathogenic variant carriers for DCM in the TTN gene, and six of them had a clinical diagnosis of DCM. The aim of our study was to investigate the metabolite signature in the carriers of the pathogenic or likely pathogenic genetic variants for HCM and DCM, compared to age- and body-mass-index-matched controls. Our novel findings were that the carriers of pathogenic or likely pathogenic variants for HCM had significantly increased concentrations of bradykinin (des-arg 9), vanillactate, and dimethylglycine and decreased concentrations of polysaturated fatty acids (PUFAs) and lysophosphatidylcholines compared with the controls without HCM. Additionally, our novel findings were that the carriers of pathogenic or likely pathogenic variants for DCM had significantly decreased concentrations of 1,5-anhydrogluticol, histidine betaine, N-acetyltryptophan, and methylsuccinate and increased concentrations of trans-4-hydroxyproline compared to the controls without DCM. Our population-based study shows that the metabolite signature of the genetic variants for HCM and DCM includes several novel metabolic pathways not previously described.

PO-717-07 A FAMILY WITH SUDDEN CARDIAC DEATH, LEFT VENTRICULAR FIBROSIS AND MITRAL VALVE PROLAPSE

Arrhythmic mitral valve prolapse (AMVP) is a rare cause of sudden cardiac death (SCD) however, the prevalence of MVP in victims of unexplained SCD is 11.7%. Mechanisms of arrhythmia include tugging of the prolapsing valve, which can tigger premature ventricular beats, polymorphic ventricular tachycardia (VT) and ventricular fibrillation. This may lead to fibrosis of the myocardium over time and re-entrant arrhythmia. No guidelines exist on SCD risk stratification and treatment of AMVP.

PO-700-04 PREDICTING RISK OF SUDDEN CARDIAC DEATH BY ARRHYTHMIA IN HYPERTROPHIC CARDIOMYOPATHY PATIENTS BY APPLYING MACHINE LEARNING TO CARDIAC MAGNETIC RESONANCE IMAGES AND CLINICAL COVARIATES

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) by ventricular arrhythmia (VA) in young adults. Current clinical criteria outlined in AHA/ACC and ESC guidelines fail to accurately identify HCM patients at risk for SCD. Mechanistically, myocardial fibrosis, a hallmark of HCM, creates substrates for VA. However, few studies have explored whether features of myocardial fibrosis visualized on late gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMR) can be used, in combination with other clinical data, to forecast VA in a large cohort of HCM patients. This study aims to predict risk of VA in HCM patients by applying machine learning (ML) to LGE-CMR images and clinical covariates. In a single-center retrospective study, LGE-CMR images and clinical covariates were acquired from 819 patients with HCM to develop an algorithm for VA (tachycardia or fibrillation) risk prediction. The left ventricular (LV) myocardium was automatically segmented from LGE-CMR images by a pre-validated deep learning model which preserves the shape of the LV with anatomical fidelity. Multiple features quantifying fibrosis burden were calculated using various standard thresholding techniques. These were fed, together with most discriminative clinical covariates selected in a univariate analysis with outcome, into a tree-based ensemble learning model to identify patients who experienced VA. In the univariate analysis, 9 numerical covariates exhibited significant (p<0.05) discrimination of the outcome in Mann-Whitney U test. The top 3 covariates were maximum interventricular septal thickness, LV global longitudinal systolic strain and LV outflow tract stress. The model incorporating LGE-CMR-derived information and clinical covariates identified HCM patients with VA with area under the ROC curve (AUC) of 0.69 and 0.72, respectively, in a 5-fold cross validation (n=570) and a held-out test (n=143). As a comparison, a model we developed using only demographic covariates and major risk factors outlined in AHA/ACC guidelines had AUC of 0.63 and 0.60.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Our ML algorithm offers improved and generalizable prediction of VA in HCM patients compared with current clinical guidelines. It could be used to identify HCM patients at high risk for SCD.

PO-691-08 ASSESSING THE MECHANISTIC ROLE OF DIFFUSE FIBROSIS TOWARDS ARRHYTHMOGENESIS IN HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in the young and is a significant cause of SCD in adults. Myocardial fibrosis takes the form of both dense (focal) and diffuse fibrosis, with histopathological evidence showing diffuse fibrosis as the hallmark feature of the disease. Diffuse fibrosis, however, is not well captured by standard LGE-CMR and its contribution to arrhythmogenic propensity in HCM patients has never been assessed before. We introduce information from post-contrast T1 mapping, a quantitative and parametric imaging modality to represent the extensive diffuse fibrotic remodeling in HCM. To investigate the mechanistic role of diffuse fibrosis towards arrhythmogenesis with personalized, image-based models of fibrotic remodeling. In this retrospective study, we reconstructed 3D left ventricular models using contrast-enhanced LGE-MRI from 26 HCM patients, but with only 13 having experienced VA. We incorporated parametric post-contrast T1 mapping to define new, personalized thresholds of the LGE-MRI signal intensity to delineate regions of non-fibrotic myocardium, and diffuse and dense fibrosis at the tissue level. At the cellular level, we incorporated HCM-specific cell remodeling (Fig A). Rapid pacing was used to assess VA inducibility from the personalized distributions of diffuse fibrosis. Clinical characteristics, amount of fibrotic remodeling, and distribution of hypertrophy were not significantly associated with clinical VA (Fig B). T1-based thresholding increased the amount of diffuse fibrosis to 40.5 ± 9.4% from 8.9 ± 9.4% achieved by standard LGE-MRI thresholding (p<0.0001), but the amount of dense scar did not change significantly (3.8 ± 2.3 vs 3.2 ± 1.3, p=0.30). An average of 1.5 [0-3] unique VAs were induced in models reconstructed from patients with clinical VA compared to 0.3 [0-2] in models reconstructed from patients without clinical VA (p<0.001). Overall, one or more VA was induced in 11/13 models with clinical VA compared to 2/13 without clinical VA. The arrhythmogenic propensity of the ventricular substrate with diffuse fibrosis is patient-specific; it is not the amount of fibrosis, but its distribution (shape and location) that determines inducibility of arrhythmia.

A Case Series of Hypertrophic Cardiomyopathy Conducted in Vietnam Revealing a Novel Pathogenic Variant of the TNNT2 Gene

Background: Hypertrophic Cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death in adults.HCM is inherited in an autosomal dominant manner; however, the genetic etiology of the disease is not fully explained and studies on the hereditary characteristics in family trees are still underway. Methods: Ten HCM patients and 31 of their relatives were recruited. Targeted sequencing for 4 HCM related-genes, including MYH7, MYBPC3, TNNT2, and TNNI3, using targeted next-generation sequencing (NGS) was carried out. Demographic, clinical, electrocardiography, and echocardiography characteristics were also characterized. Results: Among the 10 HCM patients, 5 were identified with the HCM pathogenic variants in MYH7 (3 patients), MYBPC3 (1 patient), and TNNT2 (1 patient) genes. Eleven out of 31 relatives from these 5 genotype-positive patients carried the same pathogenic variants. We found the novel c.822-2 A&gt;G variant in the splicing site of the TNNT2 gene responsible for HCM disease in a family with 7 subjects genotype positive and 3 others who suffered from sudden cardiac death. Conclusion: This case series highlighted the importance of genetic testing for clinically confirmed HCM patients and family members. The genetic information can be used as a molecular marker to complement the clinical presentation in the diagnosis of HCM, as well as a prognostic tool for the patients and their family members.