Developing a Pan-Canadian Registry of Sudden Cardiac Arrest: Challenges and Opportunities.
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SUBMITTER: Allan K
PROVIDER: S-EPMC7063603 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Developing a Pan-Canadian Registry of Sudden Cardiac Arrest: Challenges and Opportunities.
Allan Katherine K Dorian Paul P Lin Steve S
CJC open 20190220 2
Sudden cardiac arrest (SCA) has a devastating impact on both the family of the patient with SCA and his or her community. Because of various methodological differences between studies, reported incidence rates for SCA can vary widely, emphasizing the lack of clarity with respect to the true scope of this phenomenon. In recognition of the importance of accurately ascertaining the incidence and causes of SCA, there have been repeated calls for the development of national, prospective, population-b ...[more]
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Project description:BackgroundSudden cardiac arrest (SCA) in young people represents a dramatic event, often leading to severe neurologic outcomes or sudden cardiac death (SCD), and is frequently caused by genetic heart diseases. In this study, we report the results of the Tuscany registry of sudden cardiac death (ToRSADE) registry, aimed at monitoring the incidence and investigating the genetic basis of SCA and SCD occurring in subjects < 50 years of age in Tuscany, Italy.Methods and resultsCreation of the ToRSADE registry allowed implementation of a repository for clinical, molecular and genetic data. For 22 patients, in whom a genetic substrate was documented or suspected, blood samples could be analyzed; 14 were collected at autopsy and 8 from resuscitated patients after SCA. Next generation sequencing (NGS) analysis revealed likely pathogenetic (LP) variants associated with cardiomyopathy (CM) or channelopathy in four patients (19%), while 17 (81%) carried variants of uncertain significance in relevant genes (VUS). In only one patient NGS confirmed the diagnosis obtained during autopsy: the p.(Asn480Lysfs*20) PKP2 mutation in a patient with arrhythmogenic cardiomyopathy (AC).ConclusionSystematic genetic screening allowed identification of LP variants in 19% of consecutive patients with SCA/SCD, including subjects carrying variants associated with hypertrophic cardiomyopathy (HCM) or AC who had SCA/SCD in the absence of structural cardiomyopathy phenotype. Genetic analysis combined with clinical information in survived patients and post-mortem evaluation represent an essential multi-disciplinary approach to manage juvenile SCD and SCA, key to providing appropriate medical and genetic assistance to families, and advancing knowledge on the basis of arrhythmogenic mechanisms in inherited cardiomyopathies and channelopathies.
| S-EPMC9795053 | biostudies-literature
Project description:MicroRNAs (miRNAs) have regulatory functions in organs critical in resuscitation from sudden cardiac arrest due to ventricular fibrillation (VF-SCA); therefore, circulating miRNAs may be markers of VF-SCA outcome.We measured candidate miRNAs (N=45) in plasma using qRT-PCR among participants of a population-based VF-SCA study. Participants were randomly selected cases who died in the field (DF, n=15), died in hospital (DH, n=15), or survived to discharge (DC, n=15), and, age-, sex-, and race-matched controls (n=15). MiRNA levels were compared using ANOVA, t-tests, and fold-changes.Mean age of groups ranged from 66.9 to 69.7. Most participants were male (53-67%) and white (67%). Comparing cases to controls, plasma levels of 17 miRNAs expressed in heart, brain, liver, and other tissues (including miR-29c, -34a, -122, -145, -200a, -210, -499-5p, and -663b) were higher and three non-specific miRNAs lower (miR-221, -330-3p, and -9-5p). Among DH or DC compared with DF cases, levels of two miRNAs (liver-specific miR-122 and non-specific miR-205) were higher and two heart-specific miRNAs (miR-208b and -499-5p) lower. Among DC vs. DF cases, levels of three miRNAs (miR-122, and non-specific miR-200a and -205) were higher and four heart-specific miRNAs (miR-133a, -133b, -208b, and -499-5p) lower. Among DC vs. DH cases, levels of two non-specific miRNAs (miR-135a and -9-3p) were lower.Circulating miRNAs expressed in heart, brain, and other tissues differ between VF-SCA cases and controls and are related to resuscitation outcomes. Measurement of miRNAs may clarify mechanisms underlying resuscitation, improve prognostication, and guide development of therapies. Results require replication.
| S-EPMC4996717 | biostudies-literature
Project description:ObjectiveEthnic differences in sudden cardiac arrest resuscitation have not been fully explored and studies have yielded inconsistent results. We examined the association of ethnicity with factors affecting sudden cardiac arrest outcomes.MethodsRetrospective cohort study of 3551 white, 440 black and 297 Asian sudden cardiac arrest cases in Seattle and King County, Washington, USA.ResultsCompared with whites, blacks and Asians were younger, had lower socioeconomic status and were more likely to have diabetes, hypertension and end-stage renal disease (all p<0.001). Blacks and Asians were less likely to have a witnessed arrest (whites 57.6%, blacks 52.1%, Asians 46.1%, p<0.001) or receive bystander cardiopulmonary resuscitation (whites 50.9%, blacks 41.4%, Asians 47.1%, p=0.001), but had shorter average emergency medical services response time (mean in minutes: whites 5.18, blacks 4.75, Asians 4.85, p<0.001). Compared with whites, blacks were more likely to be found in pulseless electrical activity (blacks 20.9% vs whites 16.6%, p<0.001), and Asians were more likely to be found in asystole (Asians 41.1% vs whites 30.0%, p<0.001). One of the strongest predictors of resuscitation outcomes was initial cardiac rhythm with 25% of ventricular fibrillation, 4% of patients with pulseless electrical activity and 1% of patients with asystole surviving to hospital discharge (adjusted OR of resuscitation in pulseless electrical activity compared with ventricular fibrillation: 0.30, 95% CI 0.24 to 0.34, p<0.001, adjusted OR of resuscitation in asystole relative to ventricular fibrillation 0.21, 95% CI 0.17 to 0.26, p<0.001). Survival to hospital discharge was similar across all three ethnicities.ConclusionsWhile there were differences in some prognostic characteristics between blacks, whites and Asians, we did not detect a significant difference in survival following sudden cardiac arrest between the three ethnic groups. There was, however, an ethnic difference in presenting rhythm, with pulseless electrical activity more prevalent in blacks and asystole more prevalent in Asians.
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Project description:Studies of miRNA profiling to predict outcome in cardiac arrest patients treated with therapeutic hypothermia (TH) Venous blood was collected in citrated tubes prior discharge. Plasma was harvested by centrifugation and stored at -80°C until assayed. Identical volumes of plasma from the 14 patients of a group (cerebral performance category (CPC): 1-2 or CPC: 3-5) were pooled to reach a final volume of 400µL for each group. The two pools were processed conjointly. Total RNA was extracted using miRVana isolation kit (Applied Biosystems), dephosphorylated and labeled using miRNA Complete Labeling and hybridization kit (Agilent). Hybridization was performed on miRNA Human Microarray Release 12.0 slides (Agilent). 4 arrays per pool were hybridized. Scanning was achieved with the Genepix 4000B Scanner (Molecular Devices, Sunnyvale, USA). Raw data were acquired with the Genepix Pro software (Molecular Devices).
2013-01-11 | E-GEOD-34643 | biostudies-arrayexpress
Project description:Studies of miRNA profiling to predict outcome in cardiac arrest patients treated with therapeutic hypothermia (TH)
2013-01-11 | GSE34643 | GEO
Project description:BACKGROUND:The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes. METHODS:In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members. RESULTS:Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening. CONCLUSIONS:In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac arrest during participation in competitive sports was 0.76 cases per 100,000 athlete-years. The occurrence of sudden cardiac arrest due to structural heart disease was uncommon during participation in competitive sports. (Funded by the National Heart, Lung, and Blood Institute and others.).
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Project description:Low socioeconomic status is associated with poor cardiovascular health. We evaluated the association between socioeconomic status and the incidence of sudden cardiac arrest, a condition that accounts for a substantial proportion of cardiovascular-related deaths, in seven large North American urban populations.Using a population-based registry, we collected data on out-of-hospital sudden cardiac arrests occurring at home or at a residential institution from Apr. 1, 2006, to Mar. 31, 2007. We limited the analysis to cardiac arrests in seven metropolitan areas in the United States (Dallas, Texas; Pittsburgh, Pennsylvania; Portland, Oregon; and Seattle-King County, Washington) and Canada (Ottawa and Toronto, Ontario; and Vancouver, British Columbia). Each incident was linked to a census tract; tracts were classified into quartiles of median household income.A total of 9235 sudden cardiac arrests were included in the analysis. For all sites combined, the incidence of sudden cardiac arrestin the lowest socioeconomic quartile was nearly double that in the highest quartile (incidence rate ratio [IRR] 1.9, 95% confidence interval [CI] 1.8-2.0). This disparity was greater among people less than 65 years old (IRR 2.7, 95% CI 2.5-3.0) than among those 65 or older (IRR 1.3, 95% CI 1.2-1.4). After adjustment for study site and for population age structure of each census tract, the disparity across socioeconomic quartiles for all ages combined was greater in the United States (IRR 2.0, 95% CI 1.9-2.2) than in Canada (IRR 1.8, 95% CI 1.6-2.0) (p<0.001 for interaction).The incidence of sudden cardiac arrest at home or at a residential institution was higher in poorer neighbourhoods of the US and Canadian sites studied, although the association was attenuated in Canada. The disparity across socioeconomic quartiles was greatest among people younger than 65. The association between socioeconomic status and incidence of sudden cardiac arrest merits consideration in the development of strategies to improve survival from sudden cardiac arrest, and possibly to identify opportunities for prevention.
| S-EPMC3193117 | biostudies-literature
Project description:AimsData on sports-related sudden cardiac arrest (SrSCA) among young adults in the general population are scarce. We aimed to determine the overall SrSCA incidence, characteristics, and outcomes in young adults.Methods and resultsProspective cohort study of all cases of SrSCA between 2012 and 2019 in Germany and Paris area, France, involving subjects aged 18-35 years. Detection of SrSCA was achieved via multiple sources, including emergency medical services (EMS) reporting and web-based screening of media releases. Cases and aetiologies were centrally adjudicated. Overall, a total of 147 SrSCA (mean age 28.1 ± 4.8 years, 95.2% males) occurred, with an overall burden of 4.77 [95% confidence interval (CI) 2.85-6.68] cases per million-year, including 12 (8.2%) cases in young competitive athletes. While bystander cardiopulmonary resuscitation (CPR) was initiated in 114 (82.6%), automated external defibrillator (AED) use by bystanders occurred only in a minority (7.5%). Public AED use prior to EMS arrival (odds ratio 6.25, 95% CI 1.48-43.20, P = 0.02) was the strongest independent predictor of survival at hospital discharge (38.1%). Among cases that benefited from both immediate bystander CPR and AED use, survival rate was 90.9%. Coronary artery disease was the most frequent aetiology (25.8%), mainly through acute coronary syndrome (86.9%).ConclusionSports-related sudden cardiac arrest in the young occurs mainly in recreational male sports participants. Public AED use remains disappointingly low, although survival may reach 90% among those who benefit from both bystander CPR and early defibrillation. Coronary artery disease is the most prevalent cause of SrSCA in young adults.
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Project description:Despite remarkable successes in the clinic, cancer targeted therapy development remains challenging and the failure rate is disappointingly high. This problem is partly due to the misapplication of the targeted therapy paradigm to therapeutics targeting pan-essential genes, which can result in therapeutics whereby efficacy is attenuated by dose-limiting toxicity. Here we summarize the key features of successful chemotherapy and targeted therapy agents, and use case studies to outline recurrent challenges to drug development efforts targeting pan-essential genes. Finally, we suggest strategies to avoid previous pitfalls for ongoing and future development of pan-essential therapeutics.
| S-EPMC8157671 | biostudies-literature
Project description:Patients on dialysis are 20 times more likely to have a cardiac arrest compared with the general population. We considered whether inherited factors associate with cardiac arrest among patients on dialysis. From a sample of 647,457 patients on chronic dialysis, we identified 5117 pairs of patients who came from the same family. These patients were each matched to a control subject from the same population. McNemar's tests were used to compare the risk of cardiac arrest between the familial related and unrelated pairs. Genetically related family members who did not cohabitate had an odds ratio of 1.88 (95% confidence interval [95% CI], 1.25 to 2.84) for cardiac arrest compared with their phenotypically matched unrelated controls. Genetically related family members who lived together in the same environment had an odds ratio of 1.66 (95% CI, 1.20 to 2.28). Spouses, who are genetically unrelated but live together in the same environment, had an odds ratio of 0.95 (95% CI, 0.60 to 1.59) for cardiac arrest. The risk of cardiac arrest in patients on dialysis may be attributable to inherited factors. Additional studies are needed to identify such candidate genes that modify cardiovascular risk in ESRD.
| S-EPMC4625678 | biostudies-literature