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Role of genetic heart disease in sentinel sudden cardiac arrest survivors across the age spectrum.

ABSTRACT: BACKGROUND:Sudden cardiac arrest (SCA) may be the sentinel expression of a sudden cardiac death-predisposing genetic heart disease (GHD). Although shown to underlie many unexplained SCAs in the young, the contribution of GHDs to sentinel SCA has never been quantified across the age spectrum. Thus, we sought to determine the contribution of GHDs in single-center referral cohort of non-ischemic SCA survivors. METHODS AND RESULTS:Retrospective analysis of 3037 patients was used to identify all individuals who experienced a sentinel event of SCA. Following exclusion of patients with ischemic or complex congenital heart disease, cases were classified by clinical diagnoses. Overall, 180 (5.9%) referral patients experienced a sentinel SCA (average age at SCA 28?±?15?years, 99 females). An etiology was identified in 113/180 patients (62.8%) including channelopathies in 26.7%, arrhythmogenic bileaflet mitral valve prolapse in 10.6%, cardiomyopathies in 9.4%, other etiologies in 6.7%, acquired long QT syndrome in 6.7%, and multiple disorders in 2.8%. The remaining 67/180 (37.2%) cases were classified as idiopathic ventricular fibrillation (IVF). Interestingly, the contribution of GHDs declined precipitously after the first decade of life [90.0% (age 0-9; n?=?20), 58.7% (age 10-19; n?=?46), 28.1% (age 20-29; n?=?32), 23.8% (age 30-39; n?=?42), 16.7% (age 40-49; n?=?24), and 12.5% (age 50+; n?=?16)]. CONCLUSIONS:Within a referral population enriched for GHDs, the ability of a comprehensive cardiac evaluation, including genetic testing, to elucidate a root cause in non-ischemic SCA survivors declined with age. Although rare, GHDs can underlie SCA into adulthood and merit consideration across the age spectrum.

SUBMITTER: Giudicessi JR

PROVIDER: S-EPMC6364980 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Role of genetic heart disease in sentinel sudden cardiac arrest survivors across the age spectrum.

Giudicessi John R JR Ackerman Michael J MJ

International journal of cardiology 20180530

<h4>Background</h4>Sudden cardiac arrest (SCA) may be the sentinel expression of a sudden cardiac death-predisposing genetic heart disease (GHD). Although shown to underlie many unexplained SCAs in the young, the contribution of GHDs to sentinel SCA has never been quantified across the age spectrum. Thus, we sought to determine the contribution of GHDs in single-center referral cohort of non-ischemic SCA survivors.<h4>Methods and results</h4>Retrospective analysis of 3037 patients was used to id ...[more]

PMID: 29884292

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Project description:BackgroundConsent for data research in acute and critical care is complex as patients become at least temporarily incapacitated or die. Existing guidelines and regulations in the European Union are of limited help and there is a lack of literature about the use of data from this vulnerable group. To aid the creation of a patient-centred framework for responsible data research in the acute setting, we explored views of patients and next-of-kin about the collection, storage, sharing and use of genetic and health-related data for observational research.MethodsWe conducted qualitative interviews (n = 19) with Dutch sudden cardiac arrest survivors who donated clinical and socio-economic data and genetic samples to research. We also interviewed their next-of-kin. Topics were informed by ethics literature and we used scenario-sketches to aid discussion of complex issues.ResultsSudden cardiac arrest survivors displayed limited awareness of their involvement in health data research and of the content of their given consent. We found that preferences regarding disclosure of clinically actionable genetic findings could change over time. When data collection and use were limited to the medical realm, patients trusted researchers to handle data responsibly without concern for privacy or other risks. There was no consensus as to whether deferred consent should be explicitly asked from survivors. If consent is asked, this would ideally be done a few months after the event when cognitive capacities have been regained. Views were divided about the need to obtain proxy consent for research with deceased patients' data. However, there was general support for the disclosure of potentially relevant post-mortem genetic findings to relatives.ConclusionsSudden cardiac arrest patients' donation of data for research was grounded in trust in medicine overall, blurring the boundary between research and care. Our findings also highlight questions about the acceptability of a one-time consent and about responsibilities of patients, researchers and ethics committees. Finally, further normative investigation is needed regarding the (continued) use of participants' data after death, which is of particular importance in this setting. Our findings are thought to be of relevance for other acute and life-threatening illnesses as well.

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.

Project description:BackgroundConditions associated with sudden cardiac arrest/death (SCA/D) in youth often have a genetic etiology. While SCA/D is uncommon, a pro-active family screening approach may identify these inherited structural and electrical abnormalities prior to symptomatic events and allow appropriate surveillance and treatment. This study investigated the diagnostic utility of exome sequencing (ES) by evaluating the capture and coverage of genes related to SCA/D.MethodsSamples from 102 individuals (13 with known molecular etiologies for SCA/D, 30 individuals without known molecular etiologies for SCA/D and 59 with other conditions) were analyzed following exome capture and sequencing at an average read depth of 100X. Reads were mapped to human genome GRCh37 using Novoalign, and post-processing and analysis was done using Picard and GATK. A total of 103 genes (2,190 exons) related to SCA/D were used as a primary filter. An additional 100 random variants within the targeted genes associated with SCA/D were also selected and evaluated for depth of sequencing and coverage. Although the primary objective was to evaluate the adequacy of depth of sequencing and coverage of targeted SCA/D genes and not for primary diagnosis, all patients who had SCA/D (known or unknown molecular etiologies) were evaluated with the project's variant analysis pipeline to determine if the molecular etiologies could be successfully identified.ResultsThe majority of exons (97.6 %) were captured and fully covered on average at minimum of 20x sequencing depth. The proportion of unique genomic positions reported within poorly covered exons remained small (4 %). Exonic regions with less coverage reflect the need to enrich these areas to improve coverage. Despite limitations in coverage, we identified 100 % of cases with a prior known molecular etiology for SCA/D, and analysis of an additional 30 individuals with SCA/D but no known molecular etiology revealed a diagnostic answer in 5/30 (17 %). We also demonstrated 95 % of 100 randomly selected reported variants within our targeted genes would have been picked up on ES based on our coverage analysis.ConclusionsES is a helpful clinical diagnostic tool for SCA/D given its potential to successfully identify a molecular diagnosis, but clinicians should be aware of limitations of available platforms from technical and diagnostic perspectives.

Dataset Information

Role of genetic heart disease in sentinel sudden cardiac arrest survivors across the age spectrum.

Publications

Role of genetic heart disease in sentinel sudden cardiac arrest survivors across the age spectrum.

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