Cause Of Cardiac Death Research Articles

The gender difference in cause of death in Japanese atrial fibrillation patients: The Fushimi AF Registry

Abstract Background Previously we reported that incident rate of heart failure (HF) hospitalization was higher in female than male and stroke was comparable between female and male in Japanese atrial fibrillation (AF) patients. We also reported cardiovascular death was mainly related to HF but not stroke. However, the gender difference in cause of death in Japanese AF patients is little known. Method The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, which is a typical urban district of Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. In the entire cohort, 2,677 were male and 1,819 were female. We compared clinical characteristics and cause and incidence rate of death between two groups. Result Female patients were older (female vs. male; 76.7 years vs. 71.5 years, p<0.01), less in body weight (51.2 kg vs. 65.0 kg, p<0.01), had higher pulse rate (79.4 bpm vs. 77.5 bpm, p<0.01), less often persistent/permanent type (48.2% vs. 52.0%, p=0.04), less likely to have previous stroke/systemic embolism (18.6% vs. 21.1%, p=0.04), diabetes mellitus (19.9% vs. 26.2%, p<0.01), coronary artery disease (12.3% vs. 16.0%, p<0.01) and more likely to have prior HF (32.2% vs. 24.0%, p<0.01), chronic kidney disease (39.3% vs. 33.7%, p<0.01)and had higher CHADS2 score (2.15 vs. 1.96, p<0.01). In prescription data, female patients less often received oral anticoagulant (52.1% vs. 58.2%, p<0.01) and antiplatelet drug (23.8% vs. 29.0%, p<0.01). Systolic blood pressure, hypertension and major bleeding were comparable between two groups. During the median follow-up of 2,093 days, the incidence rate of all cause death was comparable between female group and male group (5.20 vs. 4.86 % per person-year, log rank p=0.32). The incidence rate of cardiac death was significantly higher in female group than male group (0.98 vs. 0.70 % per person-year, log rank p=0.02) and the incidence rate of vascular death was also significantly higher in female group than male group (0.43 vs. 0.26 % per person-year, log rank p=0.03). The incidence rate of death due to HF, which was main cause of cardiac death, was higher in female group but not significant (0.86 vs. 0.66 % per person-year, log rank p=0.08). We analyzed the proportion of cause of death in each gender, cardiac death and stroke were higher and non-cardiovascular death was lower in female than male group. Conclusion The incidence rates of cardiac death and vascular death were significantly higher in female group than male group, and death due to HF was non-significantly higher in female group. Concerning the proportion of cause of death in each gender, cardiac death and stroke were higher in female than male. The impact of cardiovascular events may be stronger and prevention of them may be more important in female.

Ferroptosis and its Potential Determinant Role in Myocardial Susceptibility to Ischemia/Reperfusion Injury in Diabetes.

Myocardial ischemia/reperfusion injury (MIRI) is a major cause of cardiac death particularly in patients with diabetes. When the coronary artery is partially or completely blocked, restoration of blood perfusion can normally be achieved within a certain time due to the development of advanced techniques such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery. However, cardiac tissue injury may aggravate progressively even after the ischemic myocardium is restored to normal perfusion. MIRI is often associated with various forms of cell death, including apoptosis, autophagy, programmed necrosis, pyroptosis, and ferroptosis, among others. Ferroptosis is known as iron-dependent cell death that is distinct from other programmed modes of cell death. Ferroptosis is under constitutive control by glutathione peroxidase 4 (GPX4), and the reduction of GPX4 may result in ferroptosis even if iron homeostasis is physiologically maintained. The essences of ferroptosis are substantial iron accumulation and lipid peroxidation that trigger cell death. Under impaired antioxidant system, cellular reactive oxygen species (ROS) accumulation leads to lipid peroxidation which consequently results in ferroptosis. Ferroptosis shares a few common features with several types of cell death and interplays with various forms of cell death such as autophagy and apoptosis in the development of cardiovascular diseases. More and more recent studies have demonstrated that ferroptosis plays an important role in MIRI. However, few studies have addressed the relative importance of ferroptosis in MIRI relative to other forms of cell deaths. In this review, we summarized the basic aspects and advances regarding the molecular pathogenesis of ferroptosis, evaluated its role in MIRI, and propose that the levels of ferroptosis may function as a major determinant of myocardial susceptibility to ischemia/reperfusion injury (IRI) in general and of the enhanced vulnerability to MIRI specifically in diabetes.

The Impact of Body Mass Index on the Mortality of Myocardial Infarction Patients With Nonobstructive Coronary Arteries.

Myocardial infarction without significant stenosis or occlusion of the coronary arteries carries a high risk of recurrent major adverse cardiovascular events and poor prognosis. This study aimed to investigate the association between body mass index and outcomes in patients with a suspected myocardial infarction with nonobstructive coronary artery disease (MINOCA). Patients were recruited at Bergmannsheil University Hospital from January 2010 to April 2021. The primary outcomes were in-hospital and long-term mortality. Secondary outcomes consisted of adverse events during hospitalization and during follow-up. A total of 373 patients were included in the study, with a mean follow-up time of 6.2 years. The patients were divided into different BMI groups: < 25 kg/m² (n = 121), 25-30 kg/m² (n = 140), and > 30 kg/m² (n = 112). In-hospital mortality was 1.7% versus 2.1% versus 4.5% (p = 0.368). However, long-term mortality tended to be higher in the < 25 kg/m² group compared to the 25-30 and > 30 kg/m² groups (log-rank p = 0.067). Subgroup analysis using Kaplan-Meier analysis showed a higher rate of cardiac cause of death in the < 25 kg/m² group compared to the 25-30 and > 30 kg/m² groups: 5.7% versus 1.1% versus 0.0% (log-rank p = 0.042). No significant differences were observed in other adverse events between the different BMI groups during hospitalization and long-term follow-up. Patients with a BMI < 25 kg/m² who experience a suspected myocardial infarction without significant coronary artery disease may have higher all-cause mortality and cardiovascular cause of death. However, further data are needed to confirm these findings.

Assessment of Risk for Sudden Cardiac Death Among Adolescents and Young Adults After Receipt of COVID-19 Vaccine - Oregon, June 2021-December 2022.

COVID-19 vaccination has been associated with myocarditis in adolescents and young adults, and concerns have been raised about possible vaccine-related cardiac fatalities in this age group. In April 2021, cases of myocarditis after COVID-19 vaccination, particularly among young male vaccine recipients, were reported to the Vaccine Adverse Event Reporting System. To assess this possibility, investigators searched death certificates for Oregon residents aged 16-30 years who died during June 2021-December 2022 for cardiac or undetermined causes of death. For identified decedents, records in Oregon's immunization information system were reviewed for documentation of mRNA COVID-19 vaccination received ≤100 days before death. Among 1,292 identified deaths, COVID-19 was cited as the cause for 30. For 101 others, a cardiac cause of death could not be excluded; among these decedents, immunization information system records were available for 88, three of whom had received an mRNA COVID-19 vaccination within 100 days of death. Of 40 deaths that occurred among persons who had received an mRNA COVID-19 vaccine dose, three occurred ≤100 days after vaccination. Two of these deaths were attributed to chronic underlying conditions; the cause was undetermined for one. No death certificate attributed death to vaccination. These data do not support an association between receipt of mRNA COVID-19 vaccine and sudden cardiac death among previously healthy young persons. COVID-19 vaccination is recommended for all persons aged ≥6 months to prevent COVID-19 and complications, including death.

Preventing Atrial Fibrillation in Hypertrophic Cardiomyopathy using Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs)

Hypertrophic cardiomyopathy (HCM), a genetic cardiovascular disease, is the leading cause of cardiac death in young people, often due to atrial fibrillation (AF). AF is generally treated using antiarrhythmics and anticoagulants, which have adverse side effects after long-term use, and are therefore unsuitable for young HCM patients. AF is characterized by a rapid and irregular atrial heartbeat, marked by a short action potential duration and atrial effective refractory period in atrial cardiomyocytes. Prior studies have indicated that the renin-angiotensin system is involved in lowering both, so it has been hypothesized that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which inhibit the renin-angiotensin system, could prevent AF. Therefore, in this study, we propose a research protocol to examine the viability of ACE inhibitors and ARBs as prophylactic measures against the development of AF in HCM patients. To test this, we suggest extracting atrial cardiomyocytes from HCM patients by performing enzyme dissociation on myocardial tissue. The isolated cardiomyocytes will then be treated in vitro with an ACE inhibitor, an ARB, a combination of both, or a control saline solution, and the patch-clamp technique will be used to determine the frequency and duration of their action potentials. We expect action potential duration and atrial effective refractory period to be longer in treated cells, while neither medication will provide a greater advantage, and, as prior research suggests, the combination will not yield significant benefits. The study will continue by testing the effects of ACE inhibitors and ARBs on the function of atrial myocardial organoids created from differentiated stem cells with an HCM mutation. The results of this study could present a new preventative measure against AF for HCM patients which would be safe for long-term use.

Granulomatous myocarditis arising from intravesical Bacillus Calmette–Guérin therapy leading to death diagnosed by postmortem examination: a case report

BackgroundIntravesical Bacillus Calmette–Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach.Case presentationWe present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus.ConclusionGranulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.

Anticoagulants versus Left Atrial Appendage Occlusion in Patients with Atrial Fibrillation and Co-Morbid Thrombocytopenia.

Left atrial appendage closure (LAAC) is an alternative approach to anticoagulants. Nonetheless, data regarding the outcomes of LAAC procedures in patients with thrombocytopenia remain lacking. The primary objective was to determine the incidence of the composite endpoint comprising ischemic stroke, intracranial hemorrhage, major bleeding, and cardiac cause of death among patients with atrial fibrillation (AF) and thrombocytopenia who were either undergoing LAAC or receiving oral anticoagulants. The secondary endpoint was the determination of total mortality. Data from a prospective, single-center registry of patients undergoing LAAC procedures were analyzed. A subset of 50 consecutive patients with thrombocytopenia were selected. Thrombocytopenia was defined as a thrombocyte count below 150,000. Subsequently, from patients hospitalized with AF receiving oral anticoagulants, 50 patients were further chosen based on propensity score matching, ensuring comparability with the study group. The primary endpoint occurred in 2% of patients in the LAAC group and 10% of patients in the non-LAAC group (p = 0.097). Additionally, a significant difference was noted in the occurrence of the secondary endpoint, which was observed in 0% of patients in the LAAC group and 10% of patients in the non-LAAC group (p = 0.025). In patients with thrombocytopenia the LAAC procedure improves prognosis compared with continued anticoagulant treatment.

Prevalence of atrial septal defects and patent foramen ovale in a large cohort of sudden cardiac death patients undergoing autopsy

Abstract Background The prevalence of patent foramen ovale and atrial septal defects has previously been described in early autopsy series and transoesophageal echocardiograms as ranging from 25 to 30%. Updated pathologic data is lacking. Methods A state-wide prospective out-of-hospital cardiac arrest registry identified all patients aged 1 to 50 years who experienced a sudden cardiac arrest in Victoria, Australia from April 2019 to April 2022 and subsequently underwent autopsy with a cardiac cause of death identified. A comprehensive autopsy assessment was performed including visual description of any atrial septal defect and identification of probe patency of the foramen ovale. Results 517 patients underwent autopsy in the setting of sudden cardiac death with documentation of their atrial septal status. 36 patients (6.9%) had a probe-patent foramen ovale, 2 patients (0.4%) had secundum atrial septal defects, and 2 patients (0.4%) had a simultaneous atrial septal defect and patent foramen ovale (1 of whom had undergone percutaneous repair of both lesions). 12 patients (2.3%) had a prior history of cerebrovascular accident either recorded on medical history or detected on neuropathological examination; however none of these patients had atrial septal defects or patent foramen ovale. Conclusions The combined rate of atrial septal defects and patent foramen ovale in a cohort of approximately 500 patients undergoing autopsy was 7.7%. None of these patients had experienced a cerebrovascular accident. This appears lower than earlier reports, and warrants further investigation in expanded cohorts of patients.

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.

Abstract 16681: Echocardiogram-Based Screening and Prevalence of Rheumatic Heart Disease in Children and Adolescents From Endemic Areas: A Systematic Review and Updated Meta-Analysis

Background: Rheumatic heart disease (RHD) is the leading cause of cardiac death in children, posing a significant burden to health systems, particularly in developing countries. Echocardiogram is a sensitive tool to identify early RHD patients, who may benefit from secondary prevention. Therefore, we performed an updated meta-analysis to determine the prevalence of latent RHD using echocardiogram-based screening performed in endemic regions across the globe. Methods: PubMed, Embase, Cochrane, and Lilacs databases were searched for cross-sectional studies reporting the prevalence of RHD in individuals aged 5-20 years, through echocardiogram-based screening programs in endemic areas. Studies with screening based on auscultation were excluded. Echocardiography-detected RHD was considered as borderline or definite by World Heart Federation (WHF) criteria and possible, probable or definite by World Heart Organization (WHO) criteria. We used random-effects models to assess the prevalence of RHD according to the geographic distribution. Results: A total of 57 studies were included, with a total of 224,100 screened subjects. WHF criteria for RHD echocardiographic diagnosis were used in 46 studies, WHO criteria in 6, and others in 3. The overall prevalence of echocardiography detected RHD was 23 per 1,000 individuals (95% CI 18 to 29 per 1,000), with a pooled prevalence of definitive RHD of 9 per 1,000 individuals (95% CI 7 to 12 per 1,000). Analysis of the prevalence of echocardiography detected RHD in different continents yielded an overall prevalence of 21 per 1,000 (95% CI 14 to 31 per 1,000) in Africa, 28 per 1,000 (95% CI 18 to 42 per 1,000) in Oceania, 21 per 1,000 (95% CI 15 to 30 per 1,000) in Asia, and 22 per 1,000 (95% CI 6 to 76 per 1,000) in Latin America. Conclusion: Screening programs incorporating echocardiography found a significant prevalence of RHD, in the range of 20 to 30 per 1,000 children and adolescents screened in endemic areas across different continents.

Prevalence of atrial septal defects and patent foramen ovale in a cohort of sudden cardiac death patients undergoing autopsy

BackgroundPatent foramen ovale (PFO) and atrial septal defects (ASD) have been described in up to 30 % of subjects in autopsy series but contemporary data are scarce. It is important to confirm the prevalence of ASD/PFO in the general population given the potential associated stroke risk and the increasing availability of intervention via PFO closure. MethodsA state-wide prospective out-of-hospital cardiac arrest registry (OHCA) identified all patients aged 1 to 50 years who experienced OHCA in Victoria, Australia from April 2019 to April 2022 and subsequently underwent autopsy with a cardiac cause of death identified. Autopsy was performed including visual description of any ASD and identification of probe patency of foramen ovale. ResultsA total of 517 patients underwent autopsy in the setting of sudden cardiac death; 36 patients (6.9 %) had a probe-patent foramen ovale, 2 patients (0.4 %) had secundum ASD, and 2 patients (0.4 %) had both a PFO and ASD (1 of whom had undergone percutaneous repair of both lesions). Twelve patients (2.3 %) had a prior history of cerebrovascular accident either recorded on medical history or detected on neuropathological examination; however none of these patients had a PFO or ASD. ConclusionsThe combined rate of PFO and ASD in a cohort of 517 patients undergoing autopsy was 7.9 %. None of these patients had experienced a cerebrovascular accident. This rate of PFOs appears lower than earlier reports and raises the possibility that the relative risk of an associated stroke could be higher than previously estimated.

Impact of mineralocorticoid receptor gene NRC2 on the prediction of arrhythmia after acute myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients with acute myocardial infarction (AMI) suffer from distress that causes a rise in cortisol (stress hormone) which acts through glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). Both receptors are present in cardiomyocyte nuclei (1-4). The animal model study in 2017 showed that activated MR increases cardiomyocyte oxidative stress leading to adverse electrophysiological remodelling that causes arrhythmias. 1.4% of tachyarrhythmias which is the main cause of cardiac death occur within the first month in AMI patients. MR are encoded by the human gene NR3C2 (nuclear receptor subfamily 3 group C member (5-6). Thus, we hypothesized that NR3C2 rs2070950, rs4635799 and rs5522 gene polymorphisms might have an extensive impact on rhythm disorders that occur in a cohort of AMI patients. Aim The aim is to evaluate the impact of the NR3C2 rs2070950, rs4635799 and rs5522 genes polymorphism in patients that developed rhythm and conduction disorders after suffering AMI. Methods The study included 301 patients treated at our hospital after suffering from AMI; all study subjects underwent primary percutaneous coronary intervention (PCI) and guideline-directed medical treatment (1). Patients' blood samples that were collected upon arrival had cortisol and troponin I levels checked and SNPs of the NR3C2 gene (rs2070950, rs4635799 and rs5522) assessed. To avoid inaccuracies all patients with a previous history of coronary syndrome or PCI were excluded. Rhythm conduction disorders and NR3C2 gene polymorphism were analyzed using the exact Fisher’s test. All the statistical analyses were performed with SPSS 27.0 software. The value of p &amp;lt; 0.05 was considered statistically significant. Results Patients with ventricular and atrial events in the early phase of AMI had higher levels of serum cortisol than the patients that did not have rhythm disorders (p=0.001) (Table 1). Rhythm disorders such as ventricular tachycardia (VT), ventricular flutter (VF) and atrial flutter or atrial fibrillation (AF/AFL) that occurred during hospitalization for AMI were notably associated with rs5522 gene polymorphism. During a hospital stay for AMI higher rs5522 TT genotype frequency was noticed in patients with AF/AFL than in patients without. C allele recurrence was 19.6%. Moreover, the protective effect was detected for AF/AFL there is also a protective effect in VA. (Table 2). Despite this, the gene polymorphism and high-grade atrioventricular block (HAVB) were unrelated. Genes rs2070950 and rs4635799 were not found significant to rhythm and conduction disorders. Conclusions Patients with the rs5522 TT allele are more prone to experience a higher frequency of arrhythmias. However, if at least one rs5522 C is found it associates with a smaller risk of arrhythmias post-AMI, meaning that this gene possibly limits damaging effects on cardiomyocytes that are caused by cortisol.

Comparative Structure of Male Mortality From Cardiac Causes in Five-Year Age Groups.

Aim To study the nosological structure of male mortality in 5-year age groups (15-85+) and the contribution of cardiac causes to all-cause mortality in 2020; to discuss the correctness of statistical recording of causes of cardiac death.Material and methods Data source: Center for Demographic Research of the Russian School of Economy http://demogr.nes.ru / index.php / ru / demogr_indicat / agreement. The selected indexes were all-cause death, causes of the class of circulatory diseases (CD) according to the International Classification of Diseases, Tenth Revision (ICD-10) (class IX, codes I00-I99), and cardiac causes of death (codes I00-I40, I70, I67.4, Q20-28) in 5-year age groups.Results Proportions of CD and cardiac causes in the male all-cause mortality were almost identical in the age groups younger than 30 years. Then the proportion of cardiac deaths remained almost unchanged (30-34 %) in contrast to the rapid growth of the CD proportion (to 51 % with a maximum at 75-79 years). Until the age of 45 years, more than 50% of cardiac deaths were caused by heart defects and cardiomyopathies and more than 25% by acute forms of ischemic heart disease (IHD); in older groups, their proportions decreased but the mortality increased. In the age groups younger than 50 years, the mortality from "Other forms of acute IHD" (ICD codes I20, I24.1-9 counted as one line) was higher than the mortality from myocardial infarction (MI); after 50 years, the MI mortality became higher. The combined proportion of two groups in the mortality from cardiac causes was maximal at the age of 20-24 years (31 %), then it decreased to a minimum of 9 % at the age of 85+. The mortality from and the proportions of chronic forms of IHD (more than 50% of which have no clear criteria for diagnosis and death), arterial hypertension, "Myocardial degeneration" (ICD code I51.5), and "Pulmonary heart and pulmonary circulation disorders" (ICD codes I26-I28) rapidly grow with increasing age. Existing approaches to recording the causes of death do not allow assessment of the contribution and mortality rates from a number of cardiac diseases.Conclusion Mortality reduction programs should provide more accurate recording of the causes of death and take into account age-related features of the nosological structure of cardiac mortality.

Relationships between neighborhood disadvantage and cardiovascular findings at autopsy in subjects with sudden death

Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland. State of Maryland investigation reports from 2,278 subjects within the CVPath Sudden Death Registry were screened for street addresses and 9-digit zip codes. Area deprivation index (ADI), used as metric for neighborhood disadvantage, was available for 1,464 subjects; 650 of whom self-identified as Black and 814 as White. The primary study outcome measurements were causes of death and gross and histopathologic findings of the heart. Subjects from most disadvantaged neighborhoods (i.e., ADI ≥ 8; n=607) died at younger age compared with subjects from less disadvantaged neighborhoods (i.e., ADI ≤ 7; n=857; 46.07 ± 14.10 vs 47.78 ± 13.86 years; P=0.02) and were more likely Black or women. They were less likely to die from cardiac causes of death (61.8% vs 67.7%; P=0.02) and had less severe atherosclerotic plaque features, including plaque burden, calcification, intraplaque hemorrhage, and thin-cap fibroatheromas. In addition, subjects from most disadvantaged neighborhoods had lower frequencies of plaque rupture (18.8% vs 25.1%, P=0.004). However, these associations were omitted after adjustment for traditional risk factors and race. Neighborhood disadvantage did not associate with cause of death or coronary histopathology after adjustment for cardiovascular risk factors and race, implying that social determinants of health other than neighborhood disadvantage play a more prominent role in sudden cardiac death.

Abstract 13995: Relationships Between Neighborhood Disadvantage and Cardiovascular Findings at Autopsy in Subjects With Sudden Death

Introduction: Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland. Methods: State of Maryland investigation reports from 2,278 subjects within the CVPath Sudden Death Registry were screened for street addresses and 9-digit zip-codes. Area Deprivation Index (ADI), used as metric for neighborhood disadvantage, was available for 1,464 subjects; 650 of whom self-identified as Black and 814 as White. The primary study outcome measurements were causes of death and gross and histopathologic findings of the heart. Results: Subjects from most disadvantaged neighborhoods ( i.e. , ADI ≥ 8; n = 607) died at younger age compared with subjects from less disadvantaged neighborhoods ( i.e. , ADI ≤ 7; n = 857; 46.07 ± 14.10 versus 47.78 ± 13.86 years; p = 0.02) and were more likely Black or women. They were, however, less likely to die from cardiac causes of death (61.8% versus 67.7%; p = 0.02) and had less severe atherosclerotic plaque features, including plaque burden, calcification, intraplaque hemorrhage, and thin-cap fibroatheromas. In addition, subjects from most disadvantaged neighborhoods had lower frequencies of plaque rupture (18.8% versus 25.1%, p = 0.004). However, these associations were omitted after adjustment for traditional risk factors and race. Conclusion: Neighborhood disadvantage did not associate with cause of death or coronary histopathology after adjustment for cardiovascular risk factors and race, implying that social determinants of health other than neighborhood disadvantage play a more prominent role in cardiovascular pathology.

Cardiovascular Causes of Death in Patients Treated for Localized Prostate Cancer

<h3>Purpose/Objective(s)</h3> From two trials in localized prostate cancer, cardiovascular disease represented the second cause of death. Based on our own data, we retrieved and reviewed the clinical information on those patients labelled by investigators as dying from cardiovascular disease (CVD) aiming to confirm and precisely define the cause/diagnosis of their cardiovascular death. <h3>Materials/Methods</h3> From October 2000 to September 2010, 1230 patients were randomized into two prostate cancer trials. Causes of death compiled up to January 2022, were based on data from clinical records, death certificates, obituaries, family members, and family physicians. Patients who were reported dying from CVD were classified into 2 groups: cardiac events proper and vascular events outside the heart. <h3>Results</h3> With a median follow up of 13.4 years, 663/1230 (53.9%) patients had died, 274 in IRPC and 389 in HRPC. 6 of the 136 patients reported dead from CVD were excluded: 3 pulmonary embolisms, 1 thrombosis, 1 severe veno-occlusive disease and 1 aorto-thoracic dissection. A total of 130/663 (19.6%) patients died from CVD. No significant differences were seen in the group of cardiac events proper [47/274 (17.2%) vs 56/389 (14.4%), p=0.4], or in vascular events outside the heart [15/274 (5.5%) vs 12/389 (3.1%), p=0.2] between IRPC and HRPC patients, respectively. The group of CVD deaths from cardiac events accounted for 79.2% (103/130) of all deaths. Many different diagnoses were attributed as potential cause of cardiac death; coronary heart disease was the most frequent 70.8%, followed by heart rhythm disorders 5.4% and heart valve disease 3.1%. The second group of CVD deaths made of vascular events outside the heart represented 20.8% (27/130) of all CVD deaths. <h3>Conclusion</h3> In localized prostate cancer, deaths from CVD represented almost 20% of all causes of death as per original definition from investigators. Of these, deaths linked to a truly cardiac event occurred in 79.2% of the cohort with the remaining deaths attributed to vascular events outside the heart. Notwithstanding potential caveats related to the retrospective nature of this review, this differentiation seems appropriate and may aid in better assessing the possible relationship between ADT and its real impact on the heart.

Post-Mortem Cardiac Magnetic Resonance in Explanted Heart of Patients with Sudden Death.

Background: We sought to evaluate the diagnostic accuracy of post-mortem cardiac magnetic resonance (PMCMR) of explanted hearts to detect the cardiac causes of sudden death. Methods: PMCMR was performed in formalin-fixed explanted hearts of 115 cases of sudden death. Histological sampling of myocardium was performed using two different approaches: (1) guideline-based sampling; (2) guideline-based plus PMCMR-driven sampling. Results: Forensic diagnosis of cardiac cause of death was ascertained in 72 (63%) patients. When the guideline-driven histological sampling was used, the PMCMR interpretation matched with final forensic diagnosis in 93 out of 115 cases (81%) with sensitivity of 88% (79–95%), specificity of 65% (47–80%), PPV of 84% (78–90%), NPV of 73% (58–84%), accuracy of 81% (72–88%), and AUC of 0.77 (0.68–0.84). When a PMCMR-driven approach was added to the guideline-based one, the matching increased to 102 (89%) cases with a PMCMR sensitivity of 89% (80–94%), a specificity of 86% (67–96%), PPV of 95% (89–98%), NPV of 73% (59–83%), accuracy of 89% (81–93%), and AUC of 0.88 (0.80–0.93). Conclusions: PMCMR has high accuracy to identify the cardiac cause of sudden death and may be considered a valid auxilium for forensic diagnosis. PMCMR could improve histological diagnosis in conditions with focal myocardial involvement or demonstrating signs of myocardial ischemia.

Heart dose and cardiac comorbidities influence death with a cardiac cause following hypofractionated radiotherapy for lung cancer.

BackgroundThere is increasing evidence of cardiac toxicity of thoracic radiotherapy however, it is difficult to draw conclusions on cardiac dose constraints due to the heterogeneity of published studies. Moreover, few studies record data on cause of death. The aim of this paper is to investigate the relationship between conventional cardiac dosimetric parameters and death with cardiac causes using data from the UK national cause of death registry.MethodsData on cancer diagnosis, treatment and cause of death following radical lung cancer radiotherapy were obtained from Public Health England for all patients treated at the Christie NHS Foundation Trust between 1/1/10 and 31/12/16. Individuals with metastatic disease and those who received multiple courses of thoracic radiotherapy where excluded. All patients who received > 45Gy in 20 fractions were included. Cardiac cause of death was defined as the following ICD-10 codes on death certificate: I20-I25; I30-I32; I34-I37; I40-I52. Cardiac V5Gy, V30Gy, V50Gy and mean heart dose (MHD) were extracted. Cumulative incidence of death with cardiac causes were plotted for each cardiac dosimetric parameter. Multi-variable Fine and Gray competing risk analysis was used to model predictors for cardiac death with non-cardiac death as a competing risk.ResultsCardiac dosimetric parameters were available for 967 individuals, 110 died with a cardiac cause (11.4%). Patients with a cardiac comorbidity had an increased risk of death with a cardiac cause compared with those without a cardiac comorbidity (2-year cumulative incidence 21.3% v 6.2%, p<0.001). In patients with a pre-existing cardiac comorbidity, heart V30Gy ≥ 15% was associated with higher cumulative incidence of death with a cardiac cause compared to patients with heart V30Gy <15% (2-year rate 25.8% v 17.3%, p=0.05). In patients without a cardiac comorbidity, after adjusting for tumour and cardiac risk factors, MHD (aHR 1.07, 1.01-1.13, p=0.021), heart V5Gy (aHR 1.01, 1-1.13, p=0.05) and heart V30Gy (aHR 1.04, 1-1.07, p=0.039) were associated with cardiac death.ConclusionThe effect of cardiac radiation dose on cardiac-related death following thoracic radiotherapy is different in patients with and without cardiac comorbidities. Therefore patients’ cardiovascular risk factors should be identified and managed alongside radiotherapy for lung cancer.

Effect of time on characterics and cause of death in unwitnessed, young sudden cardiac death cases

Abstract Introduction Around 50% of all sudden cardiac death (SCD) cases are unwitnessed. According to the World Health Organization's definition of sudden cardiac death, any unwitnessed death is considered SCD if the person was last seen alive and well within 24 hours of death and with confirmed or suspected cardiac cause of death. The length of this timespan has been debated, as the nature of death in unwitnessed cases is less certain compared to witnessed cases. The effect of time on the composition of the group of unwitnessed SCD cases has not previously been assessed. Purpose This study aimed to compare clinical characteristics and causes of death among unwitnessed SCD cases last seen alive within 1 hour or 24 hours. Methods This nationwide, retrospective study conducted in Denmark included all deceased persons aged 1–35 from 2000–2014. The highly descriptive Danish death certificates were utilized to identify all sudden and unexpected deaths. Through subsequent examination of autopsy reports and discharge summaries, we identified all SCD cases. In addition, witnessed status and time since last seen alive (1 vs. 24 hours) were recorded. Information on comorbidities was collected from the Danish Health Registries. Results During the 15-year study period, we identified 857 SCD. Of these, 353 (41%) were witnessed, and 441 (51%) were unwitnessed; 62 (7%) cases had unknown witnessed status. Among the unwitnessed SCD, 75 (17%) were last seen alive within 1 hour, and the remaining 366 (83%) were seen alive within 24 hours. Comparison of clinical characteristics and cause of death revealed few but distinct differences. Cases seen within 1 hour were of male predominance (82% vs. 65%, p=0.005). The comorbidity burden was similar, except for epilepsy which was significantly more prevalent among the group last seen alive within 24 hours. Circumstances regarding death also differed among the groups: Cases seen alive within 1 hour were more often awake at the time of death (72% vs. 36%, p&amp;lt;0.001) when compared to cases seen alive within 24 hours, and they were less often autopsied (61% vs. 75%, p=0.02). Among autopsied cases, structural heart disease was more often the cause of death among persons last seen alive within 1 hour (58% vs. 40%, p=0.02). In both groups. The most common cause of death was sudden unexpected death, but the proportion was significantly higher in the 24-hour group (60% vs 42%, p=0.03). Arrhythmogenic cardiomyopathy and thoracic aortic dissection were significantly more prevalent among cases seen within 1 hour (11% vs. 3%, p=0.002 for both). Conclusions In this 15-year nationwide study of SCD in Denmark, we found few, marked differences in cause of death and clinical characteristics between unwitnessed SCD last seen alive within 1 and 24 hours. Male sex predominated in cases seen within 1 hour, and the autopsy rate was significantly lower. In the autopsied cases structural heart disease was more common in cases seen alive within 1 hour. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Copenhagen

Exercise-induced signaling pathways to counteracting cardiac apoptotic processes.

Cardiovascular diseases are the most common cause of death in the world. One of the major causes of cardiac death is excessive apoptosis. However, multiple pathways through moderate exercise can reduce myocardial apoptosis. After moderate exercise, the expression of anti-apoptotic proteins such as IGF-1, IGF-1R, p-PI3K, p-Akt, ERK-1/2, SIRT3, PGC-1α, and Bcl-2 increases in the heart. While apoptotic proteins such as PTEN, PHLPP-1, GSK-3, JNK, P38MAPK, and FOXO are reduced in the heart. Exercise-induced mechanical stress activates the β and α5 integrins and subsequently, focal adhesion kinase phosphorylation activates the Akt/mTORC1 and ERK-1/2 pathways, leading to an anti-apoptotic response. One of the reasons for the decrease in exercise-induced apoptosis is the decrease in Fas-ligand protein, Fas-death receptor, TNF-α receptor, Fas-associated death domain (FADD), caspase-8, and caspase-3. In addition, after exercise mitochondrial-dependent apoptotic factors such as Bid, t-Bid, Bad, p-Bad, Bak, cytochrome c, and caspase-9 are reduced. These changes lead to a reduction in oxidative damage, a reduction in infarct size, a reduction in cardiac apoptosis, and an increase in myocardial function. After exercising in the heart, the levels of RhoA, ROCK1, Rac1, and ROCK2 decrease, while the levels of PKCε, PKCδ, and PKCɑ are activated to regulate calcium and prevent mPTP perforation. Exercise has an anti-apoptotic effect on heart failure by increasing the PKA-Akt-eNOS and FSTL1-USP10-Notch1 pathways, reducing the negative effects of CaMKIIδ, and increasing the calcineurin/NFAT pathway. Exercise plays a protective role in the heart by increasing HSP20, HSP27, HSP40, HSP70, HSP72, and HSP90 along with increasing JAK2 and STAT3 phosphorylation. However, research on exercise and factors such as Pim-1, Notch, and FAK in cardiac apoptosis is scarce, so further research is needed. Future research is recommended to discover more anti-apoptotic pathways. It is also recommended to study the synergistic effect of exercise with gene therapy, dietary supplements, and cell therapy for future research.