Incidence Of Sudden Death Research Articles

Association between QT prolongation and cardiovascular mortality in cancer patients

BackgroundCancer patients’ vulnerability to QT prolongation contradicts certain anti-cancer drug usage. Until now, the QT prolongation’s impact on CV mortality in cancer patients remains unclear, potentially biasing therapeutic decisions.MethodsThis retrospective observational cohort included adult cancer patients with an electrocardiogram (ECG) performed in a tertiary hospital in Taiwan. The first performed ECGs after cancer diagnosis (n = 59,568) were analyzed. The corrected QT intervals by Bazett (QTcB), Fridericia (QTcFri), and Framingham (QTcFra) formulae were used to predict the 90-day and one-year CV mortality according to the Taiwan death registry.ResultsThe AUC of QTcB (90 days: 0.70, 1 year: 0.68) for predicting CV mortality was better than QTcFri and QTcFra (90 days: 0.63 and 0.50, 1 year: 0.65 and 0.56). Using the restricted cubic spline regression model adjusted by age and comorbidities, QTcB increased a significant but trivial risk of CV mortality at 90 days (hazard ratio, 1.007, P = 0.02) and one year (1.006, P < 0.01). Compared to those with QTcB < 500ms, the patients with QTcB ≥ 500ms were older and had more comorbidities and mortalities within one year. The incidence of sudden death and ventricular arrhythmias was only 0.2%. After adjusting for comorbidities, QTcB was neither associated with 90-day nor one-year CV mortality. In the patients already with QTcB ≥ 500ms, the patients receiving the unexpected uses of QT-prolonging drugs were not associated with higher one-year CV mortality than those without (P = 0.14).ConclusionsRather than a prolonged QT interval per se, comorbidities contributed to CV mortality and irreversible outcomes in cancer patients.

Looking for the ideal medication for heart failure with reduced ejection fraction: a narrative review.

The main goals of the pharmacological treatment of Heart failure with reduced ejection fraction (HFrEF) are the reduction of mortality and the prevention of hospitalizations. However, other outcomes such as improvements in cardiac remodeling and clinical status, functional capacity and quality of life, should be taken into account. Also, given the significant inter-individual and intra-individual variability of HF, and the fact that patients usually present with comorbidities, an appropriate treatment for HFrEF should exert a clinical benefit in most patient profiles irrespective of their characteristics or the presence of comorbidities, while providing organ protection beyond the cardiovascular system. The aim of this narrative review is to determine which are the proven effects of the guideline-directed treatments for HFrEF on five key clinical outcomes: cardiovascular mortality and hospitalization due to HF, sudden death, reverse cardiac remodeling, renal protection and evidence in hospitalized patients. Publications that fulfilled the pre-established selection criteria were selected and reviewed. Renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a benefit in terms of mortality and hospitalization rates. ARNI, BB, and MRA have demonstrated a significant positive effect on the incidence of sudden death. ARB, ARNI, BB and SGLT2i have been associated with clear benefits in reverse cardiac remodeling. Additionally, there is consistent evidence of renal protection from ARB, ARNI, and SGLT2i in renal protection and of benefits for hospitalized patients from ARNI and SGLT2i. In conclusion, the combination of drugs that gather most beneficial effects in HFrEF, beyond cardiovascular mortality and hospitalization, would be ideally pursued.

Death in a bathtub of an adolescent with neurofibromatosis type 2 exhibiting meningioangiomatosis with white matter involvement.

Neurofibromatosis type 2 (NF2) is a neurocutaneous syndrome characterized by the development of multiple benign tumors, including vestibular schwannomas and meningiomas, in the nervous system. Seizures are rarely associated with NF2, and the lethality of this condition typically stems from tumor growth and related complications, leaving the incidence of sudden death largely unreported. This report discribes a 16-year-old girl with a history of NF2 and occasional seizures who died unexpectedly in a bathtub. Postmortem examination revealed multiple tumors in the cranial nerves (schwannoma), under the dura mater (meningioma), and in the upper cervical cord (neurofibroma). Typical signs of drowning, such as foam in the airways, were not present. Upon histological examination, meningioangiomatosis (MA) was observed in the cerebellum and the cerebral cortex, specifically in the frontal lobe, temporal lobe, and insula. The MA extended into the white matter, exhibiting severe perivascular fibrosis and cystic dilatation of perivascular spaces in the frontal lobe and cerebellum. Additionally, glial microhamartomas were detected both around and separate from the MA. These autopsy findings suggest that sudden unexpected death in epilepsy (SUDEP) was the cause of death rather than drowning. Moreover, while NF2-associated MA is typically asymptomatic, unlike sporadic MA, which commonly presents with seizures, the spread of MA into the white matter is unusual in an NF2 patient. Therefore, MA with the white matter involvement could have been a factor causing the seizures and the occurrence of SUDEP in this NF2 patient.

Abstract We018: The Molecular Mechanism of Coronary Collateral Growth Induced by Repetitive Ischemia by Single Cell-RNA Sequencing

Coronary heart diseases (CHD) are the leading cause of mortality and morbidity in the United States. A well-developed coronary collateral circulation ameliorates the consequences of CHD, reducing the incidence of sudden death and infarct sizes following coronary occlusion. Stimulation of coronary collateral growth (CCG) is also an alternative therapeutic approach for patients with intractable angina pectoris. The importance of CCG is undisputable, but the process and mechanism underlying the CCG is unclear. We developed a mouse model of CCG by repetitive ischemia (RI) in adults, and the CCG was validated with contrast echo to measure the coronary blood flow 3D images of micro-CT to quantitate the CCG. In this study, we use single cell-RNA sequencing (scRNA-Seq) to analyze the molecular signaling of CCG at different time points during the RI process. We digested the hearts from RI days 5, 10, and 17 and control (naïve) mice, harvested non-cardiomyocytes, performed scRNA-Seq with 10x Genomics and sequenced with Next-Seq 500 (Illumina).The fastq files are converted to a gene count matrix using kallisto|bustools with refdata-gex-mm10-2020-A employed as the reference mouse genome. The Kallisto bustools output is then converted in R to files compatible for uploading to Cellenics, an open-source platform for single-cell RNA-Seq analysis. Dimensionality reduction is done with Principal Components Analysis (PCA) with 30 principal components. We will use UMAP to visualize cell clusters. Cellenics uses scType to annotate the cell populations automatically when building clusters of cell populations. Our preliminary data show dynamic kinetics of non-cardiomyocytes induced by RI over the timeline of CCG and different cell populations of non-cardiomyocytes and EC expression profiling varied in response to RI throughout CCG. We will validate the critical signaling in CCG and explore the potential targets to induce CCG.

Prevalence of cardiovascular implantable electronic devices in children with type 1 myotonic dystrophy.

Type 1 myotonic dystrophy (DM1) is a neuromuscular disorder of multiple organ systems with important electrophysiologic (EP) manifestations, leading to a cumulative incidence of sudden death of 6.6%. Due to genetic anticipation, there is a pediatric subset of this patient population. However, most EP research on DM1 patients has been in adults, making cardiac care for pediatric patients difficult and directed by adult guidelines which often leads to cardiovascular implantable electronic device (CIED) implants. We sought to investigate the prevalence of CIEDs in the pediatric DM1 population. The Vizient® Clinical Data Base was queried from October 2019 to October 2023 for admissions with and without ICD-10 code for myotonic dystrophy (G71.11), with and without codes for presence of a pacemaker or ICD (Z95.0, Z95.810). Patients who were identified were stratified by age: Pediatric (0-21 years) and Adult (22-50 years). Prevalence of CIED in pediatric DM1 was 2.1% and in adult DM1 was 15.8%. When comparing to pediatric and adult patients with CIED and without DM1, the odds ratio for CIED in pediatric DM1 was 48.8, compared to 23.3 for CIED in adult DM1. There are pediatric DM1 patients who have received CIED despite a lack of data to inform this decision-making. Further research will be important to ensure appropriate use of CIED in this population and to develop appropriate guidelines to direct management.

Cardiomyocyte-stromal cell interplay modulates the pathogenesis of arrhythmogenic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Transnational Research Projects on Cardiovascular Diseases Background Arrhythmogenic Cardiomyopathy (ACM) is an inherited heart disorder characterized by a high incidence of sudden death at young age. Mutations linked to ACM occur primarily in desmosomal genes (e.g. PKP2) [1]. Different cell types individually contribute to set the ACM phenotype with either functional abnormalities (cardiomyocytes; CM) [2]; or fibro-fatty substitution (cardiac mesenchymal stromal cells; cMSC) [3]. The relative contribution of the different cell type derangements to determine disease evolution and electrical instability is still unclear. Purpose We hypothesize that the use of a multicellular cardiac system, modelling the functional interaction between CM and cMSC, will allow the understanding of the relative contribution of the different cell types to the ACM phenotypes. Methods Primary cMSC (carrier of the PKP2 mutation c.2013delC) have been collected from a right ventricle biopsy sample; control cMSC obtained from a biobank. iPSC reprogrammed from the same ACM patient and the isogenic line in which the PKP2 mutation was corrected [4] were used. Cardiac cocultures (cc) were assembled by combining 85% iPSC-CM and 15% primary cMSC (as in Figure 1A), either mutated or control, in different combination (as in Figure 1B). Fibro-fatty accumulation have been evaluated by immunofluorescence analysis. Movies of contracting clusters have been collected and analysed by the MUSCLEMOTION tool [5]. Cell-cell communication was studied in silico by InterCellar analysis [6] on the single culture transcriptomes. The assessment of the paracrine interactions was performed on the cc secretome by Olink technology. Results Immunofluorescence analysis highlighted that ACM cc (cc 4) accumulate more lipids and collagen than healthy control (HC) ones (cc 1). Since intermediate fibro-fatty levels were observed in ‘mixed cc’ (cc 2 and 3), we conclude that ACM iPSC-CM are able to influence fibro-adipo-commitment of cMSC. Contraction studies showed a high propensity for cc monolayers which include ACM iPSC-CM (cc3 and cc4) to display arrhythmic events. An increase in the percentage of arrhythmic events was triggered when the ACM cMSC were replacing HC cMSC, indicating that ACM cMSC can affect iPSC-CM rhythm. The most abundant ligand-receptor couplets regarded cell-cell adhesion, cell-matrix coupling, cell differentiation and inflammation. Differential abundance between the four cc was observed mainly for secreted factors involved in cardiac fibrosis, inflammation, adipogenesis / lipid metabolism and heart failure. In particular, DLK-1, secreted only by HC CM, is validated as novel inhibitor of ACM fibro-adipose differentiation. Conclusion Overall, our novel simple multicellular ACM cell model can recapitulate different phenotypes of ACM and contributed to understand the relative contribution of the different cell types to ACM features (e.g. fibro-adipose replacement, contractile defects and proarrhythmic events).

Fine particulate matter-sudden death association modified by ventricular hypertrophy and inflammation: a case-crossover study.

Sudden death accounts for approximately 10% of deaths among working-age adults and is associated with poor air quality. Objectives: To identify high-risk groups and potential modifiers and mediators of risk, we explored previously established associations between fine particulate matter (PM2.5) and sudden death stratified by potential risk factors. Sudden death victims in Wake County, NC, from 1 March 2013 to 28 February 2015 were identified by screening Emergency Medical Systems reports and adjudicated (n = 399). Daily PM2.5 concentrations for Wake County from the Air Quality Data Mart were linked to event and control periods. Potential modifiers included greenspace metrics, clinical conditions, left ventricular hypertrophy (LVH), and neutrophil-to-lymphocyte ratio (NLR). Using a case-crossover design, conditional logistic regression estimated the OR (95%CI) for sudden death for a 5 μg/m3 increase in PM2.5 with a 1-day lag, adjusted for temperature and humidity, across risk factor strata. Individuals having LVH or an NLR above 2.5 had PM2.5 associations of greater magnitude than those without [with LVH OR: 1.90 (1.04, 3.50); NLR > 2.5: 1.25 (0.89, 1.76)]. PM2.5 was generally less impactful for individuals living in areas with higher levels of greenspace. LVH and inflammation may be the final step in the causal pathway whereby poor air quality and traditional risk factors trigger arrhythmia or myocardial ischemia and sudden death. The combination of statistical evidence with clinical knowledge can inform medical providers of underlying risks for their patients generally, while our findings here may help guide interventions to mitigate the incidence of sudden death.

Analysis of ventricular arrhythmias and sudden death from prospective, randomized clinical trials of acalabrutinib.

This analysis investigated the incidence of sudden deaths (SDs) and non-fatal and fatal ventricular arrhythmias (VAs) in five acalabrutinib clinical trials. In total, 1299 patients received acalabrutinib (exposure, 4568.4 patient-years). Sixteen (1.2%) patients experienced SD or VA (event rate, 0.350/100 patient-years). Non-fatal VAs occurred in 11 (0.8%) patients, nine (0.7%) of whom had premature ventricular contractions only. SD and fatal VAs occurred in five (0.4%) patients (event rate, 0.109/100 patient-years; median time to event: 46.2 months). SDs and VAs with acalabrutinib occurred at low rates, and there are insufficient data to point to an increased risk of SD or VA with acalabrutinib.

An In Silico Cardiomyocyte Reveals the Impact of Changes in CaMKII Signalling on Cardiomyocyte Contraction Kinetics in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias, and cardiomyocyte dysfunction that may cause sudden death. HCM is associated with mutations in sarcomeric proteins and is usually transmitted as an autosomal-dominant trait. The aim of this in silico study was to assess the mechanisms that underlie the altered electrophysiological activity, contractility, regulation of energy metabolism, and crossbridge cycling in HCM at the single-cell level. To investigate this, we developed a human ventricular cardiomyocyte model that incorporates electrophysiology, metabolism, and force generation. The model was validated by its ability to reproduce the experimentally observed kinetic properties of human HCM induced by (a) remodelling of several ion channels and Ca2+-handling proteins arising from altered Ca2+/calmodulin kinase II signalling pathways and (b) increased Ca2+ sensitivity of the myofilament proteins. Our simulation showed a decreased phosphocreatine-to-ATP ratio (-9%) suggesting a negative mismatch between energy expenditure and supply. Using a spatial myofilament half-sarcomere model, we also compared the fraction of detached, weakly bound, and strongly bound crossbridges in the control and HCM conditions. Our simulations showed that HCM has more crossbridges in force-producing states than in the control condition. In conclusion, our model reveals that impaired crossbridge kinetics is accompanied by a negative mismatch between the ATP supply and demand ratio. This suggests that improving this ratio may reduce the incidence of sudden death in HCM.

Long QT Syndrome and the Risk of Sudden Death in Adult Patients: An In-depth Analysis of Clinical Correlates and Prognostic Factors

Long QT Syndrome (LQTS) is a hereditary or acquired cardiac disorder characterized by delayed ventricular repolarization, predisposing affected individuals to life-threatening arrhythmias. While extensively studied in the pediatric population, there is a paucity of comprehensive research focusing on the clinical implications and prognostic markers of LQTS in adults. This article aims to elucidate the association between Long QT Syndrome and the heightened risk of sudden death in adult patients, exploring pertinent clinical correlates and potential prognostic factors. A systematic literature review was conducted to identify relevant studies published between 2000 and 2024, utilizing databases such as PubMed, MEDLINE, and Cochrane Library. Eligible articles were critically appraised for methodological quality and relevance to adult populations with Long QT Syndrome. Data extraction encompassed demographics, genetic predispositions, clinical presentations, electrocardiographic findings, and outcomes, focusing on the incidence of sudden death. Preliminary findings underscore the significance of a prolonged QT interval as a critical marker for adverse cardiovascular events in adults with Long QT Syndrome. Additionally, the study examines the impact of genotype-phenotype correlations, gender-related differences, and the influence of comorbidities on the risk of sudden death. Furthermore, potential therapeutic interventions and risk stratification strategies will be discussed in light of recent advancements in the field. This review aims to bridge the existing knowledge gap regarding Long QT Syndrome in the adult population, emphasizing the need for heightened clinical awareness, risk stratification, and targeted interventions to mitigate the risk of sudden death in affected individuals. The synthesis of current evidence will contribute to a more nuanced understanding of the complex interplay between Long QT Syndrome and adverse outcomes in adults, facilitating the development of tailored therapeutic approaches and improved patient outcomes

The real incidence of sudden death: Fair estimations or futile speculations?

BackgroundThe true incidence of sudden death remains undetermined, with controversial results from various publications over time and countries. AimTo investigate if different estimations would reach the values usually reported for France. MethodsThree different kinds of estimations were used. First, the number of resuscitated sudden deaths and necropsies for sudden death in the Haute-Garonne French administrative department (i.e. county) over the last 10years was expanded to the national level. Second, sudden death coding of death certificates was collected at the national level. Third, the total number of out-of-hospital cardiac arrests leading to any emergency call (with/without intervention) in Haute-Garonne over the last 10years was expanded to the national level. ResultsThere was a mean of 26 resuscitated sudden deaths and 145 necropsies for sudden death each year in Haute-Garonne, i.e. 12 to 14 sudden deaths for 100,000 inhabitants, and 7700 to 9400 sudden deaths yearly when related to the whole French population, according to the year of inclusion. Based on death certificates, a mean of 6584 sudden deaths was registered each year in France. Finally, there were about 600 yearly calls/interventions for out-of-hospital cardiac arrests in Haute-Garonne, i.e. 40 to 50 sudden deaths for 100,000 inhabitants, and 16,000 to 27,000 sudden deaths yearly for the whole French territory, according to the year of inclusion. ConclusionsThe incidence of sudden death ranges from 6500 to 27,000 in France according to the calculation methods. This huge difference raises the question of the true current incidence of sudden death, which may have been overestimated previously or may be underestimated in France. More straight prospective surveys are needed to solve this question, because of relevant implications for priorities that should be given to sudden death.

Incidence of sudden death in epilepsy (SUDEP): update and limitations

Sudden unexpected death in epilepsy (SUDEP) is in most cases probably due to afatal complication of tonic-clonic seizures and plays asignificant role in the premature mortality of individuals with epilepsy. The reported risks of SUDEP vary considerably depending on the study population, so that an up-dated systematic review of SUDEP incidence including most recent studies is required to improve the estimated SUDEP risk and the counseling of individuals with epilepsy. To provide an overview of the current research landscape concerning SUDEP incidence across different patient populations and discuss potential conclusions and existing limitations. Asystematic literature review on SUDEP incidence was conducted in MEDLINE and EMBASE, supplemented by amanual search in June 2023. Out of atotal of 3324 publications, 50were reviewed for this study. The analyzed studies showed significant heterogeneity concerning cohorts, study design and data sources. Studies conducted without specific criteria and relying on comprehensive registers indicated an incidence of 0.78-1.2 per 1000 patient-years. Research providing incidences across various age groups predominantly show an increase with age, peaking in middle age. Due to varying methods of data collection and incidence calculation, comparing between studies is challenging. The association with age might be due to an underrepresentation of children, adolescents and patients over 60years. Considering all age groups and types of epilepsy it is estimated that about 1 in 1000 individuals with epilepsy dies of SUDEP annually. With an assumed epilepsy prevalence of 0.6% in Germany, this could lead to more than one SUDEP case daily. Standardization of research methods is essential to gain more profound insights.

The Heart of Rett Syndrome: A Quantitative Analysis of Cardiac Repolarization.

Rett syndrome (RTT) is a developmental encephalopathy disorder that is associated with a high incidence of sudden death presumably from cardiorespiratory etiologies. Electrocardiogram (ECG) abnormalities, such as prolonged heart-rate corrected QT (QTc) interval, are markers of cardiac repolarization and are associated with potentially lethal ventricular arrhythmias. This study investigates the cardiac repolarization characteristics of RTT patients, including QTc and T-wave morphology characteristics. A retrospective quantitative analysis on 110 RTT patients and 124 age and sex-matched healthy controls was conducted. RTT patients had longer QTc, more abnormal T-wave morphology, and greater heterogeneity of cardiac repolarization parameters compared to controls. Even RTT patients without prolonged QTc had more abnormal ECG and T-wave characteristics than controls. Among RTT patients, MECP2 patients had prolonged QTc compared to CDKL5 and FOXG1 patients. A subset of five RTT patients who died had normal QTc, but more abnormal T-wave morphology than the remaining RTT patients. Cardiac repolarization abnormalities are present in RTT patients, even without long QTc. T-wave morphology is related to RTT genotype and may be predictive of mortality. These findings could be used to help the management and monitoring of RTT patients.

Population-specific and cross-ancestry genome-wide association study identifies shared genetic architecture and 6 new risk loci including CAMK2D associated for Brugada syndrome

Abstract Introduction The Brugada syndrome (BrS) is an inherited arrhythmia characterized by coved-type ST-segment elevation in the right precordial leads and an increased risk for sudden cardiac death. Genome-wide association studies (GWAS) of BrS, mainly performed in European ancestry, have illustrated its complex genetic architecture as an polygenic disease besides a monogenic trait due to mutations in the major responsible cardiac sodium channel gene SCN5A. Clinical manifestations of BrS including the disease prevalence and the incidence of sudden death are known to be variable between Asian and European populations, however, its underlying mechanisms are largely unknown. Objectives We aimed to identify novel BrS-associated loci and to assess ancestry-dependent genetic heterogeneity that may underlie the variable clinical manifestations of BrS patients across different populations. Methods We performed a genome-wide meta-analysis of BrS in the Japanese ancestry (940 cases and 1,634 controls), followed by a cross-ancestry meta-analysis of Japanese and European GWAS (total of 3,760 cases and 11,635 controls) to identify novel risk loci and compared the allelic effects between two ancestries. We characterized the novel loci based on fine-mapping of potential causal variants, and expression and splicing quantitative trait associations using the Genotype-Tissue Expression (GTEx) database. Results The Japanese-specific genome-wide meta-analysis identified a novel association signal near the ZSCAN20 (lead variant, rs2336244; P=1.0E-08) besides previously reported 4 association signals at the SCN5A-SCN10A and HEY2 loci. Cross-ancestry genome-wide meta-analysis identified 17 association signals including 6 novel loci. The effect directions were consistent for 94.1% of the variants (16 of 17; P for sign test = 0.00027) and their allelic effects were highly correlated across ancestries (Pearson’s R=0.91 [P=2.9E-07]). The genetic risk score (GRS) derived from European-ancestry GWAS of BrS was significantly associated with the risk of BrS in the Japanese populations (odds ratio, 2.12 [95% confidence interval, 1.94–2.31]; P=1.2E-61), suggesting the shared genetic architecture across ancestries. The functional characterization of the 6 novel loci showed that one lead SNP on CAMK2D promotes an alternative splicing resulting in an isoform switch of calmodulin kinase II that favors up-regulation of the pro-inflammatory isoform δ9 and down-regulation of the pro-survival isoform δ3. Conclusions Our results identified 6 novel susceptible loci associated with BrS and revealed shared genetic architecture across ancestries.GWAS Manhattan plotShared genetic architecture

Cardiomyocyte - stromal cells interplay as a novel platform for mechanistic insights in arrhythmogenic cardiomyopathy

Abstract Background Arrhythmogenic Cardiomyopathy (ACM) is an inherited heart disorder characterized by a high incidence of sudden death at young age. Mutations linked to ACM occur primarily in desmosomal genes (e.g. PKP2) [1]. Different cell types individually contribute to set the ACM phenotype with either functional abnormalities (cardiomyocytes; CM) [2]; or fibro-fatty substitution (cardiac mesenchymal stromal cells; CMSC) [3]; these two cell types interact and show a reciprocal influence [4]. The relative contribution of the different cell type derangements to determine disease evolution and electrical instability is still unclear. Purpose Based on this evidence, we hypothesize that the use of a multicellular cardiac system, modelling the functional interaction between CM and CMSC, will allow the understanding of the relative contribution of the different cell types to the ACM phenotypes. Methods Primary stromal cells (carrier of the PKP2 mutation c.2013delC) have been collected from a right ventricle biopsy sample; control stromal cells obtained from a biobank. iPSC reprogrammed from the same ACM patient and the isogenic line in which the PKP2 mutation c.2013delC was corrected [5] were used. Cardiac cocultures (cc) were assembled by combining 85% iPSC-CM and 15% primary CMSC, either mutated or control, in different combination (as in Table 1). Movies of contracting clusters have been collected and analysed by the MUSCLEMOTION tool [6]. Fibro-fatty accumulation have been evaluated by immunofluorescence analysis by confocal microscopy. Results Immunofluorescence analysis highlighted that ACM cc (cc 4) accumulate more lipids and collagen than healthy control (HC) ones (cc 3). Since intermediate fibro-fatty levels were observed in ‘mixed cc’ (cc 1 and 4), we conclude that ACM iPSC-CM are able to influence fibro-adipo-commitment of CMSC. Contraction studies showed a high propensity for cc monolayers which include ACM iPSC-CM (cc1 and cc2) to display arrhythmic events. An increase in the percentage of arrhythmic events was triggered when the ACM CMSC were replacing HC CMSC, indicating that ACM CMSC can affect iPSC-CM rhythm. Conclusion Overall, our data confirm the importance of the cardiomyocytes and stromal cells interplay during ACM pathogenesis. Furthermore, our novel advanced ACM cell model can recapitulate different phenotypes of ACM and offers a unique opportunity for validating pharmacological therapies to modulate ACM-related characteristics (e.g. fibro-adipose replacement, contractile defects and proarrhythmic events).

Abstract 12178: Association Between QT Prolongation and Cardiovascular Mortality in Cancer Patients

Introduction: The QT interval (QT) is a safeguard criterion to avoid detrimental arrhythmias. Cancer patients are vulnerable to QT prolongation. However, its prognostic impact on cardiovascular (CV) mortality in cancer patients is not clear. Research questions: Which is the best QTc formula to predict CV mortality in cancer patients? Whether a QT interval would be a suitable predictor for CV mortality in cancer patients? Methods: This retrospective observational cohort included adult cancer patients who had an electrocardiogram (ECG) performed in a tertiary hospital in Taiwan. The first performed ECGs after cancer diagnosis (n=59,568) were analyzed. The corrected QT intervals by Bazett (QTcB), Fridericia (QTcFri), and Framingham (QTcFra) formulae were used to predict the 90-day and one-year CV mortality according to the Taiwan death registry. Results: The AUC of QTcB (0.70) for predicting CV mortality at 90 days was better than QTcFri and QTcFra (0.63 and 0.50). The AUC of QTcB (0.68) for predicting CV mortality at one year was also better than QTcFri and QTcFra (0.65 and 0.56).Using the restricted cubic spline regression model adjusted by age and comorbidities, QTcB increased a significant but trivial risk of CV mortality at 90 days (hazard ratio, 1.007, P= 0.02) and one year (1.006, P &lt;0.01). Compared to those with QTcB &lt;500ms, the patients with QTcB ≥500ms were older, had more comorbidities, and higher CV (1.74%), cancer (24.5%), and all-cause mortalities (32.5%) within one year. The incidence of sudden death and ventricular arrhythmias was only 0.2%. After adjusting for comorbidities, QTcB was neither associated with 90-day nor one-year CV mortality. Conclusions: Rather than a long QT interval per se, comorbidities contributed to CV mortality and irreversible outcome in cancer patients.

Sudden death in the southern region of Saudi Arabia: A retrospective study.

Sudden death is unanticipated, non-violent death taking place within the first 24 h after the onset of symptoms. It is a major public health problem worldwide. Moreover, the effects of living at moderate altitude on mortality are poorly understood. To retrospectively report the frequency and the main causes of sudden deaths in relation to total deaths at Asir Central Hospital, 2255 m above sea level, in the southern region of Saudi Arabia over a period of 4 years from 2013 to 2016. The medical records of 1821 deaths were examined and showed 353 cases (19.4%) of sudden death. The highest incidence of sudden death was among the elderly (51%), whereas, the lowest was among children and adolescents (6.5%). With regard to gender, the incidence of sudden death was higher in males (54.4%) compared to 45.6% in females. In this study, we found that the most common direct causes of sudden death were cardiovascular diseases (29.2%), respiratory disease (22.7%), infectious disease (12.2%), cancer (9.4%) and hematological diseases (6.2%). With respect to seasonal variation, the highest incidence was during winter (31.32%) followed by summer (25.8%). The results of this study will help emergency physicians and health care providers to exercise due care to reduce the incidence of sudden death and raise public awareness about the impact of sudden death.

Electrocardiogram Changes in the Postictal Phase of Epileptic Seizure: Results from a Prospective Study.

The brain and heart are strictly linked and the electrical physiologies of these organs share common pathways and genes. Epilepsy patients have a higher prevalence of electrocardiogram (ECG) abnormalities compared to healthy people. Furthermore, the relationship between epilepsy, genetic arrhythmic diseases and sudden death is well known. The association between epilepsy and myocardial channelopathies, although already proposed, has not yet been fully demonstrated. The aim of this prospective observational study is to assess the role of the ECG after a seizure. From September 2018 to August 2019, all patients admitted to the emergency department of San Raffaele Hospital with a seizure were enrolled in the study; for each patient, neurological, cardiological and ECG data were collected. The ECG was performed at the time of the admission (post-ictal ECG) and 48 h later (basal ECG) and analyzed by two blinded expert cardiologists looking for abnormalities known to indicate channelopathies or arrhythmic cardiomyopathies. In all patients with abnormal post-ictal ECG, next generation sequencing (NGS) analysis was performed. One hundred and seventeen patients were enrolled (females: 45, median age: 48 ± 12 years). There were 52 abnormal post-ictal ECGs and 28 abnormal basal ECGs. All patients with an abnormal basal ECG also had an abnormal post-ictal ECG. In abnormal post-ictal ECG, a Brugada ECG pattern (BEP) was found in eight patients (of which two had BEP type I) and confirmed in two basal ECGs (of which zero had BEP type I). An abnormal QTc interval was identified in 20 patients (17%), an early repolarization pattern was found in 4 patients (3%) and right precordial abnormalities were found in 5 patients (4%). Any kind modification of post-ictal ECG was significantly more pronounced in comparison with an ECG recorded far from the seizure (p = 0.003). A 10:1 higher prevalence of a BEP of any type (particularly in post-ictal ECG, p = 0.04) was found in our population compared to general population. In three patients with post-ictal ECG alterations diagnostic for myocardial channelopathy (BrS and ERP), not confirmed at basal ECG, a pathogenic gene variant was identified (KCNJ8, PKP2 and TRMP4). The 12-lead ECG after an epileptic seizure may show disease-related alterations otherwise concealed in a population at a higher incidence of sudden death and channelopathies. Post-ictal BEP incidence was higher in cases of nocturnal seizure.

Incidence and autopsy rates of sudden cardiac death in Northern Finland

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Sigrid Juselius foundation. Finnish foundation for cardiovascular research. Background/Introduction Sudden cardiac death (SCD) is one of the most common modes of death in Western societies. The exact incidence and etiological background of SCD is somewhat unknown due to the low number of autopsies performed in sudden death victims. In prior autopsy studies approximately 40% of sudden death victims have other than cardiac cause for the event and in most countries autopsy rates are between 5-25%. Purpose Determine the incidence of SCD and autopsy rates for sudden death in Northern Finland. Methods We performed a death certificate review of all out of hospital or hospice deaths in 2016 in Northern Finland. Death was determined to be sudden if it occurred within one hour of occurrence of symptoms or if the victim was found dead. Information on autopsy, cause of death, and demographical data were collected. Results From a total of 6620 deaths 1412 occurred out of hospital/hospice. Death was classified as sudden in 1067 (16.1%) victims. Mean age was 70.1 yrs (±16.5 yrs) and 66.9% were male. Autopsy rate for all sudden deaths was 73.7%. Among victims under 70yrs autopsy rate was 90.8% and in under 50 yrs 96.2%. In all 785 autopsied sudden deaths 421 (53.6%) were SCD i.e. cardiac cause for death. In a population of 740 000 out of hospital/hospice sudden death incidence in 2016 was 144/100 000 and SCD incidence on 2016 was 77/100 000. Autopsied sudden cardiac death (N=421) was caused by ischemic heart disease (310, 73.6%), hypertensive heart disease (48, 11.4%), cardiomyopathy (50, 11.9%) or other cardiac causes (13, 3.1%). Conclusions Autopsy rates of sudden death in Northern Finland are high. The utilization of autopsies in sudden death provide the premises for accurate SCD incidence calculations. The results confirm the assumption that a large part of sudden deaths are non-cardiac and common cardiac diseases are the most frequent cause of SCD in unselected general population.

PO-03-227 INCIDENCE AND AUTOPSY RATES OF SUDDEN CARDIAC DEATH IN NORTHERN FINLAND

Sudden cardiac death (SCD) is one of the most common modes of death in Western societies. The exact incidence and etiological background of SCD is somewhat unknown due to the low number of autopsies performed in sudden death victims. In prior autopsy studies approximately 40% of sudden death victims have other than cardiac cause for the event and in most countries autopsy rates are between 5-25%. Determine the incidence of SCD and autopsy rates for sudden death in Northern Finland. We performed a death certificate review of all out of hospital or hospice deaths in 2016 in Northern Finland. Death was determined to be sudden if it occurred within one hour of occurrence of symptoms or if the victim was found dead. Information on autopsy, cause of death, and demographical data were collected. From a total of 6620 deaths 1412 occurred out of hospital/hospice. Death was classified as sudden in 1067 (16.1%) victims. Mean age was 70.1 yrs (±16.5 yrs) and 66.9% were male. Autopsy rate for all sudden deaths was 73.7%. Among victims under 70yrs autopsy rate was 90.8% and in under 50 yrs 96.2%. In all 785 autopsied sudden deaths 421 (53.6%) were SCD i.e. cardiac cause for death. In a population of 740 000 out of hospital/hospice sudden death incidence in 2016 was 144/100 000 and SCD incidence on 2016 was 77/100 000. Autopsied sudden cardiac death (N=421) was caused by ischemic heart disease (310, 73.6%), hypertensive heart disease (48, 11.4%), cardiomyopathy (50, 11.9%) or other cardiac causes (13, 3.1%). Autopsy rates of sudden death in Northern Finland are high. The utilization of autopsies in sudden death provide the premises for accurate SCD incidence calculations. The results confirm the assumption that a large part of sudden deaths are non-cardiac and common cardiac diseases are the most frequent cause of SCD in unselected general population.