Cases Of Sudden Cardiac Death Research Articles

Harmonization of the definition of sudden cardiac death in longitudinal cohorts of the European Sudden Cardiac Arrest network – towards Prevention, Education, and New Effective Treatments (ESCAPE-NET) consortium

The burden of sudden cardiac death (SCD) in the general population is substantial and SCD frequently occurs among people with few or no known risk factors for cardiac disease. Reported incidences of SCD vary due to differences in definitions and methodology between cohorts. This study aimed to develop a method for adjudicating SCD cases in research settings and to describe uniform case definitions of SCD in an international consortium harmonizing multiple longitudinal study cohorts. The harmonized SCD definitions include both case definitions using data from multiple sources (eg, autopsy reports, medical history, eyewitnesses) as well as a method using only information from registers (eg, cause of death registers, ICD-10 codes). Validation of the register-based method was done within the consortium using the multiple sources definition as gold standard and presenting sensitivity, specificity, accuracy and positive predictive value. Consensus definitions of "definite," "possible" and "probable" SCD for longitudinal study cohorts were reached. The definitions are based on a stratified approach to reflect the level of certainty of diagnosis and degree of information. The definitions can be applied to both multisource and register-based methods. Validation of the method using register-information in a cohort comprising 1335 cases yielded a sensitivity of 74%, specificity of 88%, accuracy of 86%, and positive predictive value of 54%. This study demonstrated that a harmonization of SCD classification across different methodological approaches is feasible. The developed classification can be used to study SCD in longitudinal cohorts and to merge cohorts with different levels of information.

Association between nationwide introduction of public-access defibrillation and sudden cardiac death in Japan: An interrupted time-series analysis

BackgroundThe effectiveness of public-use of automated external defibrillators in reducing the number of sudden cardiac death (SCD) cases at the national level is largely unknown. Our study aimed to evaluate whether the nationwide introduction of public-access-defibrillation (PAD) in 2004 affected the trend of annual sudden cardiac death (SCD) rates in Japan. MethodsThe number of nationwide SCDs occurring in people aged five years and older was extracted from Japanese demographic statistics (1995–2015). Segmented regression analysis was performed on the interrupted time series data stratified by age and sex to evaluate changes in trends of rates of annual SCDs after the PAD introduction in Japan. ResultsAfter the PAD introduction in 2004, we observed a significant decrease in trends of annual SCD rates for those aged 5–19 years (the ratio of trends between pre and post PAD introduction (RT) = 0.886, 95%CI: 0.801 to 0.980), 20–34 years (RT = 0.932; 95%CI: 0.906, 0.958), 35–49 years (RT = 0.953; 95%CI: 0.929, 0.977) and 50–64 years (RT = 0.971; 95%CI: 0.971, 0.991). However, the decrease was not observed for those aged 65 years and older. In the age and sex stratified analysis, there was a significant decrease in RT among males aged 5–64 years, and among females 35–49 years. ConclusionThe nationwide trend of annual rate of SCDs between 5 and 64 years old significantly decreased after the introduction of PAD in 2004 in Japan. Further, the reduction was more evident in males.

515 Exertional syncope and ventricular arrhythmia in a patient with cardiac amyloidosis

Abstract Aims Systemic amyloidosis is a multisystem disorder caused by the misfolding, aggregation, and deposition of certain proteins in various organs and tissues. Cardiac involvement is common and worsens the prognosis. Atrial fibrillation is the most frequent arrhythmia in cardiac amiloidosis (CA), but many cases of ventricular arrhythmias (VA) and sudden cardiac death (SCD) have been described. Methods and results We present a case of a 64-year-old man admitted following exertional syncope occurred after climbing a flight of stairs. In the previous 2 weeks he had experienced fatigue and poor tolerance to exertion; moreover, 2 days before he had another episode of transient loss of consciousness after exertion. His medical history included left gonarthrosis and surgery for right carpal tunnel syndrome one year before. Physical examination did not revealed signs of heart failure. A 12-lead electrocardiogram (ECG) showed a pseudoinfarction pattern with QS waves in V2 and V3 leads and low voltage in all limb leads (Figure 1). Routine blood tests revealed N-terminal pro-bran natriuretic peptide (NT-ProBNP) of 3436 pg/ml (n.v. 0–125) and high-sensitive troponin T of 67 pg/ml (n.v. < 58). A trans-thoracic echocardiogram showed left ventricle (LV) concentric thickening wall with granular and sparkling pattern, mild reduced ejection fraction, reduced global longitudinal strain with apical sparing, grade 3 diastolic disfunction, biatrial enlargement, mild mitral regurgitation, right ventricle free wall thickening (8 mm), mild reduced TAPSE, and mild pericardial effusion. Cardiac magnetic resonance (CMR) confirmed ventricular wall thickening with evidence at T1 mapping of interstitial infiltration more evident in the septum and inferior-lateral wall with apical savings (Figure 2). A total body 99mTc-HDP scintigraphy showed cardiac uptake with intensity similar to bone signal (Perugini Score 2) suggesting ATTR cardiac amyloidosis (Figure 3). Both kappa and lambda concentrations were normal. The genetic testing did not reveled mutations in the TTR gene. We concluded for a diagnosis of ATTR wild-type CA. The Holter ECG monitoring registered numerous ventricular ectopic beats and an episode of non-sustained ventricular tachycardia. A coronary angiography ruled out coronary artery disease. In consideration of the clinical-instrumental picture an ICD was implanted. Conclusions In conclusion, CA is still underdiagnosed. VA and SCD may further complicate the prognosis. Early diagnosis and adequate stratification of the arrhythmic risk are essential to ensure patients the best therapeutic strategies.

Sudden Cardiac Death Caused by Cardiac Small Vessel Vasculitis after COVID-19 Vaccination (BNT162b2 nCov-19): A Case Report

This study presents a case of sudden cardiac death due to cardiac small vessel vasculitis after coronavirus disease 2019 (COVID-19) mRNA vaccination (BNT162b2). The deceased was a 76-year-old woman with diabetes mellitus (DM) and chronic hypertension (HTN), who experienced generalized pain for a month after the first dose of vaccination, and unexpectedly died. Postmortem examination revealed small vessel vasculitis in the heart, lungs and vaccinated site of the left arm. These features were similar to those observed in a previously reported case of a patient with COVID-19 and cardiac endotheliitis and multisystem inflammatory syndrome. In addition, DM and HTN may contribute to vaccine-induced immunologic changes and vascular dysfunction. However, further studies with additional cases are needed.

Abstract 11553: Sudden Cardiac Death in Type 1 and Type 2 Diabetes

Introduction: Diabetes is a known risk factor for sudden cardiac death (SCD). Whether type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) confer a similar risk of SCD remains unclear. Our aim was to determine and compare the association of T1D and T2D with SCD. Hypothesis: Given the differences in the pathophysiology, clinical presentation, and management, the likelihood of having SCD in T1D and T2D is different. Methods: Using data collected from 2002-19, we performed a case-control study of 2,771 cases of SCD (age ≥18 years) from the Oregon Sudden Unexpected Death Study and 8,313 control patients from Kaiser Permanente Northwest (matched for age, sex, and race/ethnicity) who did not have SCD or prior cardiac arrest. We used medical records to determine diabetes status and used logistic regression to evaluate the independent association between diabetes and SCD. Results: Our cases and matched controls had a mean age of 65 ± 16 years, were 33% female and 24% non-White race. In total, 37% (n=1,016) of cases and 24% (n=1,981) of controls had diabetes. In those with diabetes, the proportion of T1D was 6% (n=66) among cases and 2% among controls (n=40; P<0.001). The presence of diabetes was associated with a 1.5- times higher odds of SCD. Compared to those without diabetes, the odds ratio (OR) and 95% confidence interval (CI) for SCD was 4.36 (2.81–6.75; P<0.001) in T1D and 1.45 (95% CI, 1.30–1.63; P<0.001) in T2D after adjustment for age, sex, race/ethnicity, body mass index, and relevant comorbidities. Within the diabetic population (n=2,997), the odds of having SCD were 2.4 times higher in T1D than in T2D (adjusted OR: 2.41; 95% CI, 1.53–3.80; P<0.001). Conclusions: Individuals with T1D and T2D have a higher risk of SCD than those without diabetes. In the diabetic population, T1D is more strongly associated with SCD compared to T2D. These findings have implications for sudden death risk stratification in diabetics.

Abstract 9970: Prevalence of ECG Abnormalities and Association with Arrhythmic Risk and Myocardial Fibrosis in a Large Cohort of Patients with Mitral Valve Prolapse

Background: Inverted or biphasic T-waves (IBTWs) in the inferior leads on a 12-lead electrocardiogram (ECG) have been previously described in small, retrospective samples of MVP with sudden cardiac arrest (SCA) or sudden cardiac death (SCD). However, prior studies are limited by selection of bileaflet involvement, referral bias or targeted autopsies. Moreover, the association of IBTWs with focal fibrosis remains poorly defined. Objective: To assess the rates of IBTWs and their association with arrhythmic risk and late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) in an unselected, longitudinal MVP cohort. Methods: We reviewed available 12-lead ECGs from a cohort of 570 MVP patients with clinical and ambulatory ECG or telemetry monitoring evaluated at the University of California San Francisco between 2012 and 2020. IBTWs were considered clinically relevant if present in at least 2 of 3 inferior ECG leads. Complex ventricular ectopy (ComVE) was defined as >5% burden of premature ventricular contractions, bigeminy, or non-sustained ventricular tachycardia. SCD cases were identified through the National Death Index. In a subset of 86 (15%) patients with available contrast CMR, we assessed the presence and location of LGE. Results: Among 570 MVP patients (52% male, mean age 64±17), 86 (15%) had IBTWs, 160 (28%) had ComVE, and 26 (5%) had severe arrhythmic events (2 sustained VT, 13 SCA, and 11 SCD). Of these 26, 15 (58%) were bileaflet. Rates of IBTWs were similar between MVPs with severe arrhythmic events (9/26, 35%), ComVE (28/160, 18%), and no ventricular arrhythmia (58/410, 14%) ( p= 0.33). Among MVPs with contrast CMR, there were higher rates of IBTWs in those with LGE (papillary muscles or basal inferolateral wall in all) versus without LGE (7/22 vs 6/64, respectively, p = 0.01). Conclusions: In a large, unselected MVP sample inclusive of all arrhythmic presentations and leaflet subtypes, the prevalence of IBTWs is overall low and similar in those with and without ventricular arrhythmia, including SCA/SCD. In those with IBTWs, LGE in the papillary muscles or basal inferolateral wall is common, suggesting focal myocardial traction/fibrosis as the underlying anatomical substrate for repolarization abnormalities in the MVP population.

Abstract 8917: Ankle-Brachial Index and Risk of Sudden Cardiac Death in the Community: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Sudden cardiac death (SCD) is an important public health problem. About 356,000 people suffer SCD in the U.S., accounting for 15% of all deaths. The ankle-brachial index (ABI) is a simple, non-invasive measure of subclinical atherosclerosis. The aim of this study was to determine the relation between ABI and SCD in a middle-aged biracial general population. Methods: All ARIC (Atherosclerosis Risk in Communities) study subjects with a documented ABI measurement between 1987 and 1989 were included in the study. ABI was categorized as abnormal (≤0.9), borderline (0.9-1), normal [1-1.4], and non-compressible (>1.4). SCD was defined as a sudden pulseless condition presumed to be caused by a ventricular tachyarrhythmia in a previously stable individual. All SCD cases were adjudicated by a committee of cardiac electrophysiologists, cardiologists, and internists. Results: Of the 15,135 participants followed for a median of 23.5 years, 558 (3.7%) developed SCD (1.96 cases per 1000 person-years). Abnormal or borderline ABIs were associated with an elevated risk of SCD (HRs with 95 % CIs 2.27 [1.64-3.14] and 1.52 [1.17-1.96], respectively) in comparison to normal ABI. The association between abnormal ABI and SCD remained significant after adjustment for traditional cardiovascular risk factors, but not for borderline ABI (HR 1.63 [1.15-2.32] and 1.24 [0.94-1.63]) (Table). Conclusions: Abnormal ABI is independently associated with risk of SCD in a biracial general population. ABI could be incorporated into a future risk SCD prediction model.

Abstract 13281: Idiopathic Ventricular Fibrillation Endophenotype Determines the Yield of Ultra-Rare RYR2 Variants in Youthful Unexplained Sudden Cardiac Arrest

Introduction: Loss-of-function variants in the RYR2-encoded cardiac calcium release channel underlie a small number of unexplained sudden cardiac arrest and death (SCA/SCD) cases. Objective: To determine if the yield of ultra-rare RYR2 variants in unexplained SCA patients with a default diagnosis of idiopathic ventricular fibrillation (IVF) depends on pre-defined IVF endophenotype and whether RYR2 variant-positive IVF cases have a discernible electrocardiographic phenotype. Methods: All SCA cases referred to Mayo Clinic’s Windland Smith Rice Genetic Heart Rhythm Clinic between 01/2000 and 04/2021 were reviewed. After exclusion of 116 cases where a probable SCA root cause was identified and/or RYR2 genetic testing was not pursued, a total of 64 unexplained SCA cases (36% female; 26 ± 11 years at the time of SCA) were included. Clinical data was extracted from the medical record and patients classified as having i) IVF (no diagnostic clues), N=38 (59%) ii) PVC-triggered ventricular fibrillation (PTVF; documented short coupled PVC-triggered ventricular arrhythmias), N=19 (30%), or iii) early repolarization syndrome (ERS; J-point elevation ≥0.1 mV in ≥2 contiguous leads, excluding leads V 1 -V 3 ), N=7 (11%). The yield of ultra-rare, non-synonymous RYR2 variants (MAF<0.0001 in the Genome Aggregation Database) and electrocardiographic profiles were then compared. Results: Overall, a qualifying, ultra-rare RYR2 non-synonymous variant was identified in 5 out of 64 (7.8%) unexplained SCA patients. Of note, the yield of ultra-rare RYR2 missense variants was significantly higher in individuals with an PTVF endophenotype than those without [4/19 (21%) versus 1/45 (2.2%), p=0.02]. Interestingly, the majority of ultra-rare RYR2 variant-positive unexplained SCA survivors [3/5 (60%)] displayed an exercise stress test pattern characterized by the onset of ventricular ectopy at ~120 bpm with suppression at heart rates ≥140 bpm. Conclusions: The burden of ultra-rare RYR2 variants is higher in unexplained SCA patients with documented PTVF. Collectively, this data suggests that i) a subset of PTVF may have an underlying genetic basis and ii) some IVF- and PTVF-associated RYR2 variants may result in an identifiable electrocardiographic profile.

Abstract 11528: Predictors of Ventricular Arrhythmia in Mitral Valve Prolapse

Introduction: The arrhythmic form of mitral valve prolapse (AMVP) is characterized by complex or frequent ventricular arrhythmia (cfVA) and associated with increased risk of sudden cardiac death (SCD) from ventricular fibrillation, the majority of reported cases of SCD being in premenopausal women. There is limited data on prevalence and predictors of AMVP. Methods: We studied all 645 patients aged 18 to 90 years with mitral valve prolapse (MVP) on echocardiography between 2016-2019 at our institution (median age [IQR] 63.6 [51.9-73] years; 52.4% female; 16.2% African American). Echocardiogram images were reviewed to analyze valve morphology, mitral regurgitation (MR) severity and ventricular structure and function. cfVA was identified from resting and ambulatory ECG tracings. These and cardiovascular risk factors associated with cfVA were analyzed using multivariate logistic regression. Results: cfVA was present in 188 (29.1%) MVP patients. Independent predictors of cfVA were mitral annular disjunction (MAD, odds ratio [OR, 95% CI] 2.45 [1.48 – 4.06], p=0.0005), bi-leaflet prolapse (2.10 [1.42 – 3.11] vs. uni-leaflet, p=0.0002), inferior ECG T-wave inversion (TWI, 1.79 [1.17-2.75], p=0.007) and moderate+ MR (1.52 [1.01-2.27], p=0.044). AMVP, defined as bi-leaflet MVP with cfVA, was present in 102 (15.8%), with MAD in 38 (37.3%, vs. 58 [10.7%] without AMVP, p<0.0001), inferior lead TWI in 45 (44.1%, vs. 97 [17.9%], p<0.0001) and moderate+ MR in 47 (46.1% vs 134 [24.7 %], p<0.0001). After median 1221 (IQR 1013 – 1456) days follow-up, 12 with AMVP died (11.7%, vs. 45 [8.3%] without, p=0.256) with SCD in 2 (2.0%, vs. 4 [0.9%], p=1.00). Conclusion: Ventricular arrhythmia in MVP is predicted by MAD, bi-leaflet prolapse, inferior ECG TWI and MR. These findings may help identify otherwise asymptomatic individuals, such as premenopausal women with MVP, at increased risk of SCD.

Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death.

This study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidental deaths through autopsy. A total of 2784 proteins were obtained from label-free quantitative proteomic analysis. This included a total of 265 differential proteins which were involved in SCD-related processes, such as inflammation, muscle system process regulation, metal ion transport, and lysosomal pathway. Western blotting was carried out to measure the expressions of cathepsin C (CTSC), focal adhesion kinase (FAK), p-FAK, and proteins related to the p38/MAPK signaling pathway, whereas immunohistochemistry was performed to determine the localization and expression of CTSC, TNF-α, and CD206 in arterial tissues. It was found that CTSC were the most expressed proteins with a significant upward trend in SCD cases. Besides, CTSC regulated macrophage polarization to M1 through the FAK-induced p38/MAPK signaling pathway. This promoted the release of inflammatory factors and eventually increased the inflammatory response. In conclusion, this study implies that CTSC may be one of the key molecular targets for promoting macrophage M1 polarization in SCD, which may provide new therapeutic insights into the treatment of inflammatory diseases.

Applicability of the AHA/ACC/HRS guideline for implantable cardioverter defibrillator implantation in Japanese patients with cardiac sarcoidosis

Abstract Background Sarcoidosis is a systemic granulomatous disease that affects multiple organs. Cardiac involvement is a key determinant of poor clinical outcomes in the patients with sarcoidosis, as it causes congestive heart failure, conduction abnormalities, ventricular tachycardia and fibrillation (VT/VF), and sudden cardiac death (SCD). Although implantable cardioverter defibrillators (ICDs) are used to prevent SCD from VT/VF in patients with cardiac sarcoidosis (CS), the generalizability of the AHA/ACC/HRS guidelines for the Japanese CS patients remains unclear. Purpose We aimed to assess, among Japanese patients with CS, the ICD recommendations from the 2017 AHA/ACC/HRS Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. Methods We examined 188 consecutive patients with CS in two tertiary hospitals between 1979 and 2020. The primary outcome was defined as a composite outcome involving SCD or ventricular arrhythmic events. Ventricular arrhythmic events were defined as either emergency treatment for VF or sustained VT, which included appropriate ICD therapy. Results During a median follow-up period of 5.68 (IQR: 4.87–6.70) years, the primary outcome occurred in 44 patients (23%), which included 6 cases of SCD and 38 cases of VT/VF. ICD implant was indicated based on left ventricular ejection fraction (LVEF) of ≤35% (class I recommendation) in 62 patients, with an annualized event rate of 3.93%. A LVEF of >35% with a need for a permanent pacemaker (class IIa recommendation) was observed for 53 patients, with an annualized event rate of 2.54%. A LVEF of >35% with late gadolinium enhancement (LGE) during cardiovascular magnetic resonance (class IIa recommendation) was observed for 62 patients, with an annualized event rate of 2.38% (Figure A). Kaplan-Meier analyses revealed that patients with a class I recommendation for ICD implantation had a significant higher incidence of the primary outcome, compared to patients with a class IIa recommendation and patients with no indication for ICD implantation (P=0.03). However, there were no significant differences in the incidence of the primary outcome between patients with a LVEF of >35% and a need for a permanent pacemaker and patients with a class I recommendation (P=0.08) or patients with a LVEF of ≤35% (P=0.31). Moreover, there was no significant difference in the incidence of the primary outcome between patients with a LVEF of >35% and LGE on cardiovascular magnetic resonance and patients with a class I recommendation (P=0.054) or patients with a LVEF of ≤35% (P=0.22) (Figure B). Conclusions The American guideline recommendations for ICD implantation might be applicable to Japanese patients with CS. Implantation of an ICD may need to be considered in these patients if they require a permanent pacemaker or have LGE, regardless of LVEF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science

Biventricular Myocardial Fibrosis and Sudden Death in Patients With Brugada Syndrome

BackgroundElectrophysiological, imaging, and pathological studies have reported the presence of subtle structural abnormalities in hearts from patients with Brugada syndrome (BrS). However, data concerning disease involvement outside of the right ventricular outflow tract are limited. ObjectivesThis study sought to characterize the presence and distribution of ventricular myocardial fibrosis in a cohort of decedents experiencing sudden cardiac death caused by BrS. MethodsThe authors evaluated 28 whole hearts from consecutive sudden cardiac death cases attributed to BrS and 29 hearts from a comparator group comprised of noncardiac deaths (control subjects). Cardiac tissue from 6 regions across the right and left ventricle were stained with Picrosirius red for collagen and tissue composition was determined using image analysis software. Postmortem genetic testing was performed in cases with DNA retained for analysis. ResultsOf 28 BrS decedents (75% men; median age of death 25 years), death occurred in sleep or at rest in 24 of 28 (86%). The highest proportion of collagen was observed in the epicardial right ventricular outflow tract of the BrS group (23.7%; 95% CI: 20.8%-26.9%). Ventricular myocardium from BrS decedents demonstrated a higher proportion of collagen compared with control subjects (ratio 1.45; 95% CI: 1.22-1.71; P < 0.001), with no significant interactions with respect to sampling location or tissue layer. There was insufficient evidence to support differences in collagen proportion in SCN5A-positive cases (n = 5) when compared with control subjects (ratio 1.23; 95% CI: 0.75-1.43; P = 0.27). ConclusionsBrugada syndrome is associated with increased collagen content throughout right and left ventricular myocardium, irrespective of sampling location or myocardial layer.

Sudden Cardiac Death in Athletes.

Sudden Cardiac Death in Athletes.

Novel cases of pediatric sudden cardiac death secondary to TRDN mutations presenting as long QT syndrome at rest and catecholaminergic polymorphic ventricular tachycardia during exercise: The TRDN arrhythmia syndrome.

TRDN mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT) but may present with abnormal electrocardiogram (ECG) findings provoking a diagnosis of long QT syndrome (LQTS). We report two novel cases of sudden cardiac death in children due to mutations of TRDN, providing further insight into this rare and aggressive inherited arrhythmia syndrome. Whole exome sequencing (WES) was performed in two unrelated children who experienced cardiac arrest during exercise and were negative for targeted testing of LQTS. WES identified a novel homozygous splice-site mutation in both patients, denoted c.22+1G>T, absent from gnomAD and suggesting a founder variant in the Iranian population. We now summarize the genetic architecture of all reported TRDN-related patients, including 27 patients from 21 families. The average age-onset was 30 months (range 1-10) for all cases. Adrenergic-mediated cardiac events were common, occurring in 23 of 27 cases (85%). LQTS was diagnosed in 10 cases (37%), CPVT in 10 (37%) cases, and in 7 cases. No phenotypic diagnosis was provided. Five cases (15%) had evidence for associated skeletal myopathy. Four missense TRDN variants (24%) were observed in diseased cases, while the remaining variants reflect putative loss-of-function (LOF) mutations. No disease phenotype was reported in 26 heterozygous carriers. In conclusion, TRDN mutations cause a rare autosomal recessive arrhythmia syndrome presenting with adrenergic-mediated arrhythmic events, but with ECG abnormalities leading to a diagnosis of LQTS in a proportion of cases. Heterozygous carriers are free of disease manifestations.

The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies.

Cardiomyopathies (CMPs) are a heterogeneous group of myocardial diseases accountable for the majority of cases of heart failure (HF) and/or sudden cardiac death (SCD) worldwide. With the recent advances in genomics, the original classification of CMPs on the basis of morphological and functional criteria (dilated (DCM), hypertrophic (HCM), restrictive (RCM), and arrhythmogenic ventricular cardiomyopathy (AVC)) was further refined into genetic (inherited or familial) and acquired (non-inherited or secondary) forms. Despite substantial progress in the identification of novel CMP-associated genetic variations, as well as improved clinical recognition diagnoses, the functional consequences of these mutations and the exact details of the signaling pathways leading to hypertrophy, dilation, and/or contractile impairment remain elusive. To date, global research has mainly focused on the genetic factors underlying CMP pathogenesis. However, growing evidence shows that alterations in molecular mediators associated with the diagnosis of CMPs are not always correlated with genetic mutations, suggesting that additional mechanisms, such as epigenetics, may play a role in the onset or progression of CMPs. This review summarizes published findings of inherited CMPs with a specific focus on the potential role of epigenetic mechanisms in regulating these cardiac disorders.

Identification of myocardial fibrosis by ATR-FTIR spectroscopy combined with chemometrics

Different degrees of myocardial fibrosis can often be observed in sudden cardiac death cases, so that the identification of myocardial fibrosis is an important step in forensics to identify cardiac death. Previous methods are restricted by complex algorithms, high cost, low sensitivity and high requirements. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy is an efficient and rapid method to identify tissue types, which has been used increasingly in forensics. This study aims to identify novel biophysical biomarkers of myocardial fibrosis and establish a prediction model by using ATR-FTIR analysis combined with chemometrics. A total of 129 tissue blocks taken from human hearts were cut into slices, and then ATR-FTIR spectroscopy and hematoxylin and eosin (HE) staining were performed. By using HE staining, the samples were divided into the experimental group (with myocardial fibrosis) and the control group (without myocardial fibrosis). The chemometrics classification results showed that the sensitivity and specificity of the training dataset were 0.91 and 1.0 respectively, and the sensitivity and specificity of the predictive dataset were 0.862 and 0.900. This study demonstrated that ATR-FTIR spectroscopy combined with chemometrics is a novel method for identifying myocardial fibrosis.

B-AB19-04 DIAGNOSIS OF CORONARY VASOSPASM-INDUCED VENTRICULAR FIBRILLATION DURING PERICARDIAL MAPPING

After excluding cardiac genetic and structural abnormalities, idiopathic VF is estimated to account for ∼5% of cases of sudden cardiac death. In these cases, it may be difficult to identify an etiology for VF. We present a case of idiopathic polymorphic VT/VF (pVT/VF) with the diagnosis made in the EP lab. N/A A 47-year-old man had a witnessed cardiac arrest and was found to be in VF. A work-up including coronary angiography was unrevealing; MRI was largely normal, though suggestive of an inferolateral area of subepicardial scar. A subcutaneous ICD (SICD) was placed. He presented to us with recurrent pVT/VF on sotalol resulting in multiple ICD shocks, some of which failed to immediately defibrillate. At EP study, stimulation did not induce sustained ventricular arrhythmias. Standard pericardial access was obtained to permit epi/endo mapping to identify arrhythmogenic substrate. But immediately upon onset of pericardial mapping, ST segment elevation occurred, and the patient developed non-sustained pVT (Figure). Immediate coronary angiography revealed diffuse coronary spasm, most strikingly in the proximal LAD. With administration of intracoronary nitroglycerin, the LAD spasm and pVT/VF resolved; ST segment abnormalities resolved within minutes. DFT testing revealed a normal functioning SICD. He was discharged on long-acting nifedipine and nitrates for coronary vasospasm. Severe coronary vasospasm may cause idiopathic polymorphic VT/VF. Medical therapy with calcium-channel blockers and oral nitrates are the first-line therapy as ICD therapies alone may be ineffective in the setting of on-going spasm and ischemia.

Histopathological Findings in Sudden Cardiac Death: 5-years Autopsy Experience in a Tertiary Hospital in Bandung, Indonesia

Background: Sudden death (SD) is a sudden and unexpected death with an unknown cause. However, it has been assummed that the most common causes of sudden deaths are cardiovascular or non-cardiovascular causes such as gastrointestinal disease, respiratory disease, genitourinary disease, epilepsy, and trauma. This study aimed to portray histopathological findings and causes of sudden cardiac death (SCD) cases based on 5 year autopsy experience in a tertiary hospital in Bandung, Indonesia. Methods: This study was a descriptive cross-sectional study exploring causes of SCD from 2015 to 2019 at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. All medical records with SCD and histopathology findings were retrieved from September to December 2020. Only cases with histopathological examination results were included.Results: SCD was found in 7 of 16 patients with sudden death. Coronary atherosclerosis was the most common (n=4), followed by myocardial infarction (n=2) and ruptured aortic aneurysm (n=1). Myocarditis and calcific aortic valve diseases were not found.Conclusions: In this study, the most common cause of SCD is coronary atherosclerosis, which is identified mainly in older and male patients.

Ischemic Heart Disease Related Sudden Cardiac Death in Autopsied Cases: An Egyptian perspective.

Diagnosis of the underlying cause of sudden unexpected death in a previously healthy individual remains one of the important challenges in forensic practice. Ischemic heart disease is the most common cause of sudden death. The current study aims to investigate the incidence and pathology of sudden ischemic cardiac death in Egypt. All cases of sudden cardiac death (SCD) examined by different forensic departments throughout Egypt during the period of January 2010 through December 2014 were included. Cases underwent complete autopsy examination including a thorough gross and microscopic examination of the heart and great blood vessels. Of 535 cases of SCD diagnosed during the period of the study, coronary atherosclerosis was the principle finding in 420 (78.5%) cases. The highest numbers of deaths were reported in fifth and sixth decades with male preference. Other causes of SCD included myocarditis, cardiomyopathies, valvular heart disease, and hypertensive heart disease (7.8%, 4.1%, 4.1%, and 2.8%, respectively). There was severe stenosis (>75%) of at least 1 coronary artery in 74% of cases. Type VI atherosclerosis was found in 40.7% of cases. The left anterior descending branch was the most affected artery by atherosclerosis. Acute coronary pathological events were demonstrated in 27.6% of cases. Recent myocardial infarction was evident in 55.5% of cases, whereas old infarcts were demonstrated in 44.5% of cases. Features of hypertensive heart disease were present in 18.3% of cases. In conclusion, ischemic heart disease is the leading cause of SCD in Egypt.

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals

Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined. To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.