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BackgroundGenome-wide association studies and candidate-gene based approaches have identified multiple common variants associated with increased risk of sudden cardiac death (SCD). However, the independent contribution of these individual loci to disease risk is modest.ObjectiveTo investigate the cumulative effects of genetic variants previously associated with SCD risk.MethodsA total of 966 SCD cases from the Oregon-Sudden Unexpected Death Study and 1,926 coronary artery disease controls from the Wellcome Trust Case-Control Consortium were investigated. We generated genetic risk scores (GRS) for each trait composed of variants previously associated with SCD or with abnormalities in specific electrocardiographic traits such as QRS duration, QTc interval and heart rate. GRSs were calculated using a weighted approach based on the number of risk alleles weighted by the beta coefficients derived from the original studies. We also compared the highest and lowest quintiles for the GRS composed of SCD SNPs.ResultsIncreased cumulative risk was observed for a GRS composed of 14 SCD-SNPs (OR=1.17 [1.05-1.29], P = 0.002). The risk for SCD was 1.5 fold higher in the highest quintile when compared to the lowest quintile (OR = 1.46[1.11-1.92]). We did not observe significant associations with SCD for SNPs that determine electrocardiographic traits.ConclusionsA modest but significant effect on SCD risk was identified for a GRS composed of 14 previously associated SCD SNPs. While next generation sequencing methodology will continue to identify additional novel variants, these findings represent proof of concept for the additive effects of gene variants on SCD risk.

BackgroundIn cohort studies, elevated levels of plasma nonesterified free fatty acids (NEFAs) have been associated with increased risk of sudden cardiac death (SCD) in men, but blood samples were drawn several years before SCD.ObjectiveTo confirm this relationship by evaluating levels of plasma NEFAs at the time of the SCD event in a group of both men and women.MethodsFrom the ongoing Oregon Sudden Unexpected Death Study, we compared levels of plasma NEFAs in 149 SCD cases presenting with ventricular fibrillation (mean age 64 ± 12 years; 73% men) and 149 age- and sex-matched controls with coronary artery disease. Plasma was processed from blood drawn at the time of arrest (cases) and at a routine visit (controls). The levels of plasma NEFAs were compared after categorizing into quartiles on the basis of control values. Conditional logistic regression was used to predict adjusted odds ratio for SCD associated with plasma NEFA levels per increased quartile.ResultsThe plasma NEFA levels were significantly higher in SCD cases than in controls (median 0.39 mmol/L [interquartile range 0.28-0.60 mmol/L] vs 0.32 mmol/L [interquartile range 0.20-0.49 mmol/L]; P = .002). There were no significant differences in body mass index, smoking, and diabetes. The odds ratio for SCD was 1.42 (95% confidence interval 1.14-1.78) per quartile increase in the plasma NEFA level (P = .002). Individuals with plasma NEFA levels above the prespecified cutoff point of 0.32 mmol/L were at increased risk of SCD (odds ratio 2.00; 95% confidence interval 1.20-3.34; P = .008).ConclusionThese findings strengthen the role of plasma NEFA as a potential biomarker for the assessment of SCD risk.

Background and Aims Electrocardiogram (ECG) abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD), but the potential importance of dynamic ECG remodelling has not been investigated. In this study, the nature and prevalence of dynamic ECG remodelling were studied among individuals who eventually suffered SCD. Methods The study population was drawn from two prospective community-based SCD studies in Oregon (2002, discovery cohort) and California, USA (2015, validation cohort). For this present sub-study, 231 discovery cases (2015–17) and 203 validation cases (2015–21) with ≥2 archived pre-SCD ECGs were ascertained and were matched to 234 discovery and 203 validation controls based on age, sex, and duration between the ECGs. Dynamic ECG remodelling was measured as progression of a previously validated cumulative six-variable ECG electrical risk score. Results Oregon SCD cases displayed greater electrical risk score increase over time vs. controls [+1.06 (95% confidence interval +0.89 to +1.24) vs. −0.05 (−0.21 to +0.11); P <.001]. These findings were successfully replicated in California [+0.87 (+0.7 to +1.04) vs. −0.11 (−0.27 to 0.05); P <.001]. In multivariable models, abnormal dynamic ECG remodelling improved SCD prediction over baseline ECG, demographics, and clinical SCD risk factors in both Oregon [area under the receiver operating characteristic curve 0.770 (95% confidence interval 0.727–0.812) increased to area under the receiver operating characteristic curve 0.869 (95% confidence interval 0.837–0.902)] and California cohorts. Conclusions Dynamic ECG remodelling improved SCD risk prediction beyond clinical factors combined with the static ECG, with successful validation in a geographically distinct population. These findings introduce a novel concept of SCD dynamic risk and warrant further detailed investigation. [ABSTRACT FROM AUTHOR]

Out-of-hospital cardiac arrest (OHCA) remains a major public health problem. Even in high-income countries, survival rates have plateaued in the range of ten percent, stimulating an ongoing interest in developing novel approaches to resuscitation. Emergency Medical Services (EMS)-witnessed OHCAs constitute a subgroup of overall OHCA that occur after the arrival of EMS, leading to rapid initiation of resuscitation and significantly improved survival. In this narrative review we summarize and interpret recent developments in knowledge of EMS-witnessed OHCA regarding prevalence, demographics, location, circumstances, survival outcomes and clinical profile. We examine the possibility of informing novel resuscitation approaches and enhancing mechanistic knowledge by studying EMS-witnessed OHCA, with the goal of improving overall survival from OHCA. [ABSTRACT FROM AUTHOR]

Background: Patients with shockable sudden cardiac arrest (SCA; ventricular fibrillation/tachycardia) have significantly better resuscitation outcomes than do those with nonshockable rhythm (pulseless electrical activity/asystole). Heart failure (HF) increases the risk of SCA, but presenting rhythms have not been previously evaluated.Objective: We hypothesized that based on unique characteristics, HFpEF (HF with preserved ejection fraction; left ventricular ejection fraction [LVEF] ≥50%), bHFpEF (HF with borderline preserved ejection fraction; LVEF >40% and <50%), and HFrEF (HF with reduced ejection fraction; LVEF ≤40%) manifest differences in presenting rhythm during SCA.Methods: Consecutive cases of SCA with HF (age ≥18 years) were ascertained in the Oregon Sudden Unexpected Death Study (2002-2019). LVEF was obtained from echocardiograms performed before and unrelated to the SCA event. Presenting rhythms were identified from first responder reports. Logistic regression was used to evaluate the independent association of presenting rhythm with HF subtype.Results: Of 648 subjects with HF and SCA (median age 72 years; interquartile range 62-81 years), 274 had HFrEF (23.4% female), 92 had bHFpEF (35.9% female), and 282 had HFpEF (42.5% female). The rates of shockable rhythms were 44.5% (n = 122), 48.9% (n = 45), and 27.0% (n = 76) for HFrEF, bHFpEF, and HFpEF, respectively (P < .001). Compared with HFpEF, the adjusted odds ratios for shockable rhythm were 1.86 (95% confidence interval 1.27-2.74; P = .002) in HFrEF and 2.26 (95% CI 1.35-3.77; P = .002) in bHFpEF. The rates of survival to hospital discharge were 10.6% (n = 29) in HFrEF, 22.8% (n = 21) in bHFpEF, and 9.9% (n = 28) in HFpEF (P = .003).Conclusion: The rates of shockable rhythm during SCA depend on the HF clinical subtype. Patients with bHFpEF had the highest likelihood of shockable rhythm, correlating with the highest rates of survival. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have reported both early morning and Monday peaks in occurrence of sudden cardiac arrest (SCA) in the community and appropriate defibrillator shocks in patients with an implantable cardioverter-defibrillator (ICD). However, a more recent analysis of ICD shocks reported absence of these peaks.Objective: The purpose of this study was to perform a contemporary evaluation of the circadian and septadian variation of SCA in the general population.Methods: The analysis was performed from an ongoing, population-based study of SCA in a Northwestern US community of approximately 1 million residents. To maximize accuracy, we focused on consecutive patients who presented with witnessed SCA and were attended by emergency medical services (EMS). The specific time of each SCA event was determined based on the time of the 911 call to EMS.Results: During 2002-2014, we identified 1535 patients age ≥18 years who suffered witnessed SCA, with time of first EMS contact recorded. There was no morning (6 AM to 12 PM) peak, and we observed a nadir in SCA events during 12 AM to 6 AM, with only 13.9% of events occurring during this 6-hour block (P <.0001). There was no peak on Mondays, but a nadir was observed on Sundays that accounted for only 11.3% of SCA events during the week (P = .004).Conclusion: in this contemporary community-based study, we failed to observe the expected morning peak or the Monday peak in SCA, duplicating recent findings in primary prevention defibrillator patients. The significant public health implications of these findings merit further investigation. [ABSTRACT FROM AUTHOR]

Aims: Delayed QRS transition zone in the precordial leads of the 12-lead electrocardiogram (ECG) has been recently associated with increased risk of sudden cardiac death (SCD), but the underlying mechanisms are unknown. We correlated echocardiographic findings with ECG and clinical characteristics to investigate how alterations in cardiac structure and function contribute to this risk marker.Methods and Results: From the ongoing population-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), SCD cases with prior ECG available (n = 627) were compared with controls (n = 801). Subjects with delayed transition at V5 or later were identified, and clinical and echocardiographic patterns associated with delayed transition were analysed. Delayed transition was present in 31% of the SCD cases and 17% of the controls. These subjects were older and more likely to have cardiovascular risk factors and history of myocardial infarction. Delayed transition was associated with increased left ventricular (LV) mass (122.7 ± 40.2 vs. 102.9 ± 33.7 g/m2; P < 0.001), larger LV diameter (53.3 ± 10.4 vs. 49.2 ± 8.0 mm; P < 0.001), and lower LV ejection fraction (LVEF) (46.4 ± 15.7 vs. 55.6 ± 12.5%; P < 0.001). In multivariate analysis, delayed transition was independently associated with myocardial infarction, reduced LVEF, and LV hypertrophy. The association between delayed transition and SCD was independent of the LVEF (OR 1.57; 95% CI 1.04-2.38; P = 0.032).Conclusion: The underpinnings of delayed QRS transition zone extend beyond previous myocardial infarction and reduced LVEF. Since the association with sudden death is independent of these factors, this novel marker of myocardial electrical remodelling should be explored as a potential risk predictor of SCD. [ABSTRACT FROM AUTHOR]

Background: Prolongation of initial ventricular depolarization on the 12-lead electrocardiogram (ECG), or delayed intrinsicoid deflection (DID), can indicate left ventricular hypertrophy (LVH). The possibility that this marker could convey distinct risk of sudden cardiac arrest (SCA) has not been evaluated.Objective: To evaluate the association of DID and SCA in the community.Methods: In the ongoing prospective, population-based Oregon Sudden Unexpected Death Study (Oregon SUDS; catchment area approximately 1 million), SCA cases were compared to geographic controls with no SCA. Archived ECGs (closest and unrelated to SCA event for cases) were evaluated for the presence of DID, defined as ≥0.05 second in leads V5 or V6. Left ventricular (LV) mass and function were evaluated from archived echocardiograms.Results: SCA cases (n = 272, 68.7 ± 14.6 years, 63.6% male) as compared to controls (n = 351, 67.6 ± 11.4 years, 63.3% male) were more likely to have DID on ECG (28.3% vs. 17.1%, P = .001). DID was associated with increased SCA odds (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.31-2.81; P = .001), but showed poor correlation with LV mass and echocardiographic LVH (kappa 0.13). In multivariate analysis adjusted for clinical and ECG markers, reduced LV ejection fraction, and echocardiographic LVH, DID remained an independent predictor of SCA (OR 1.82; 95% CI 1.12-2.97; P = .016). Additionally, in a sensitivity analysis restricted to narrow QRS, DID and ECG LVH by voltage were each independently associated with SCA risk.Conclusion: DID was associated with increased SCA risk independent of echocardiographic LVH, ECG LVH, and reduced LV ejection fraction, potentially reflecting unique electrical remodeling that warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Both schizophrenia and epilepsy have been linked to increased risk of sudden cardiac death (SCD). We hypothesized that DNA variants within genes previously associated with schizophrenia and epilepsy may contribute to an increased risk of SCD. Objective: To investigate the contribution to SCD susceptibility of DNA variants previously implicated in schizophrenia and epilepsy. Methods: From the ongoing Oregon Sudden Unexpected Death Study, comparisons were performed among 340 SCD cases presenting with ventricular fibrillation and 342 controls. We tested for the association between 17 single-nucleotide polymorphisms (SNPs) mapped to 14 loci previously implicated in schizophrenia and epilepsy by using logistic regression and assuming additive, dominant, and recessive genetic models. Results: The minor allele of the nonsynonymous SNP rs10503929 within the neuregulin 1 gene was associated with SCD under all 3 investigated models, with the strongest association for the recessive genetic model (recessive P = 4.01 × 10−5, odds ratio [OR] 4.04; additive P = 2.84 × 10−7, OR 1.9; and dominant P = 9.01 × 10−6, OR 2.06). To validate our findings, we further explored the association of this variant in the Harvard Cohort SCD study. The SNP rs10503929 was associated with an increased risk of SCD under the recessive genetic model (P = .0005, OR 2.7). This missense variation causes a methionine to threonine change and functional effects are currently unknown. Conclusions: The observed association between a schizophrenia-related neuregulin 1 gene variant and SCD may represent the first evidence of coexisting genetic susceptibility between 2 conditions that have an established clinical overlap. Further investigation is warranted to explore the molecular mechanisms of this variant in the pathogenesis of SCD. [Copyright &y& Elsevier]

Background Left ventricular hypertrophy (LVH) has been associated with increased risk of sudden cardiac death (SCD), and improvements in risk stratification methodology are warranted. Methods We evaluated electrocardiographic intervals as potential markers of SCD risk in LVH. Corrected QT, QRS, and JT intervals were evaluated in consecutive cases with SCD and LVH from the ongoing Oregon Sudden Unexpected Death study who underwent a 12-lead electrocardiogram (EKG) and echocardiogram prior to and unrelated to the SCD event. Comparisons of age, gender, body mass index, LV ejection fraction, and EKG intervals together with clinical conditions (hypertension and diabetes) were conducted with geographically matched controls that had coronary artery disease but no history of ventricular arrhythmias or cardiac arrest. LVH was determined using the modified American Society of Echocardiography equation for LV mass. Independent samples t-test, Pearson's chi-square test, and multiple logistic regression were used for statistical comparisons. Results Of the 109 cases and 49 controls who met study criteria, age, gender, and comorbidities were similar among cases and controls. The mean LV mass index was not significantly different in cases compared to controls. However mean QTc (470.6 ± 53.6 ms vs 440.7 ± 38.7 ms; P < 0.0001) and QRS duration (113.6 ± 30.0 ms vs 104.9 ± 18.7 ms; P = 0.03) were significantly higher in cases than controls. In logistic regression analysis, prolonged QTc was the only EKG interval significantly associated with SCD (OR 1.72 [1.23-2.40]). Conclusion Prolonged QTc was independently associated with SCD among subjects with LVH and merits further evaluation as a predictor of SCD in LVH. [ABSTRACT FROM AUTHOR]

Sudden Cardiac Death. Introduction: Sudden cardiac death (SCD) is a large public health problem that warrants on-going evaluation in the general population. While single-year community-based studies have been performed there is a lack of studies that have extended evaluation to multiple years in the same community. Methods and Results: From the on-going Oregon Sudden Unexpected Death Study, we analyzed prospectively identified SCD cases in Multnomah County, Ore, (population ≈700,000) from February 1, 2002 to January 31, 2005. Detailed information ascertained from multiple sources (first responders, clinical records, and medical examiner) was analyzed. A total of 1,175 SCD cases were identified (61% male) with a mean age of 65 ± 18 years for men versus 70 ± 20 for women (P < 0.001). The overall incidence rate for the period was 58/100,000 residents/year. One-quarter (24.6%) was ≤55 years of age. The most common initial rhythm was ventricular tachycardia or fibrillation (39% of cases, survival 27%) followed by asystole (36%, survival 0.7%) and pulseless electrical activity (23%, survival 6%). Among subjects that underwent resuscitation, the rate of survival to hospital discharge was 12% and overall survival to hospital discharge irrespective of resuscitation was 8%. Of the 68 survivors, 16 (24%) received a secondary prevention ICD. Conclusion: We report annualized SCD incidence from a multiple-year, multiple-source community-based study, with higher than expected rates of women and subjects age ≤55 years. The low implantation rate of secondary prevention ICDs is likely to be multifactorial, but there are potential implications for recalibration of the projected need for ICD implantation; larger and more detailed studies are warranted. (J Cardiovasc Electrophysiol, Vol. 24, pp. 60-65, January 2013) [ABSTRACT FROM AUTHOR]

Background: Abnormalities of ventricular repolarization as well as depolarization have been associated with increased risk of ventricular arrhythmias. Objective: To evaluate the relative contribution of these predictors to risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD). Methods: In the ongoing Oregon Sudden Unexpected Death Study, adult residents from the Portland, Oregon, metropolitan area (population ∼1 million) who suffered SCD were identified prospectively (2002–2007). Of these, we analyzed the subgroup of SCDs that had a resting 12-lead ECG prior to SCD and also had associated CAD. Comparisons were conducted with a control group of subjects with known CAD but no history of SCD from the same geographic region. Corrected QT interval (QTc), JT interval (JTc), QRS duration (QRSd), and other parameters were measured from ECG prior and unrelated to SCD. Analysis of left ventricular function was limited to those subjects who had undergone echocardiography prior to and remote from SCD. Results: A total of 642 SCD cases (71 ± 13 years, 62% male) were compared to 450 controls (66 ± 12 years, 64% male). SCD cases had significantly longer QRSd (102 ± 25 ms vs 97 ± 20 ms, P = .0008) as well as JTc (348 ± 44 ms vs 339 ± 34 ms, P = .0006) vs controls. In cases with prolonged QRSd, 38% had severe left ventricular systolic dysfunction and 62% had normal, mild, or moderately decreased left ventricular systolic function. In a multivariable model, QRSd, JTc, age, and severe left ventricular systolic dysfunction were independent predictors. There was minimal overlap between prolonged QRSd and JTc in both case and control groups (3% and 4%, respectively). Conclusion: Prolonged QRSd, JTc, and severe left ventricular systolic dysfunction had independent contributions to risk of SCD in coronary disease, in this community-based setting. [ABSTRACT FROM AUTHOR]

Background: There is a lack of prospective population-based data regarding sudden death in children. Objective: The purpose of this study was to assess the burden of sudden cardiac arrest (SCA) in the pediatric population in a 3-year community-wide study. Methods: During 2002–2005, all residents of Multnomah County, Oregon (population 660,486) who underwent SCA were ascertained from emergency medical services, the medical examiner, and emergency rooms of 16 area hospitals. A comprehensive evaluation was performed, including analysis of circumstances of death, medical records, and available autopsy data. Annual incidence rates were calculated for all residents age <18 years using the 2000 U.S. Census data. Results: A total of 33 children met the criteria for SCA (58% female, median age 0.37 years, range 0.03–12.3 years). The majority of SCAs (76%) occurred in children age <1 year. At least 90% of this subgroup also met the criteria for the sudden infant death syndrome (SIDS). Pediatric SCAs constituted 2.8% of all SCAs. The pediatric annual incidence rate per 100,000 population was 1.7 (95% confidence interval [CI] 1.1–2.3), compared with 60/100,000 for all ages. The pediatric annual incidence rate per 100,000 children was 7.5 (95% CI 5.1–10.5). The annual incidence rate of SIDS was 0.8/1000 live births. In contrast to an adult survival rate of 8%, none of the children survived to be discharged from the hospital. Conclusions: The burden of pediatric sudden death was low (3% of all sudden deaths), but 90% occurred before the age of 1 year, and the majority were diagnosed as SIDS (70% of overall sudden deaths in children). Population education to prevent SIDS and enhanced postnatal diagnosis of occult heart disease are likely to have the greatest impact on the prevention of pediatric sudden death. [Copyright &y& Elsevier]

Abstract: Background: Sudden cardiac arrest (SCA) is a significant public health problem and better understanding of triggers could enhance prevention. Vigorous physical activity has been suggested as a prominent trigger but has not been well-evaluated in the general population. We performed a community-based study to analyze the role of physical activity as a potential trigger of SCA. Methods: Medical records of 1180 subjects who sustained SCA during the ongoing Oregon Sudden Unexpected Death Study (Multnomah County, Oregon, USA; 2002–05) were reviewed. Analysis was limited to first responder and hospital records of patients who experienced witnessed SCA, with information available regarding physical activity immediately prior to SCA. An estimated metabolic equivalent (MET) score was used to classify levels of physical activity. Results: A total of 304 adults met criteria for analysis (mean age 69 years, 67% male). The majority (n =193, 63%) were performing light activities, 51 (17%) subjects were sleeping, 39 (13%) were performing moderate activities, 14 (5%) were performing heavy activities, and 7 (2%) were engaged in sexual activity. Light activities were associated with older age (72 years) and heavy activities with the youngest (51 years, p <0.001). Males were more likely to be involved in heavy activity (93% male) and the sexual activity group was exclusively male (p =0.04). Conclusion: Vigorous physical activity was a potential trigger of SCA in a minority (5%). The vast majority (80%) of subjects were asleep or were performing light activities. The traditional view of SCA triggers may have to be re-visited, with renewed focus on factors such as emotional stress and sleep-related disorders. [Copyright &y& Elsevier]

Summary: Background: A potential effect of socioeconomic status on occurrence of sudden cardiac arrest in the community is likely, but has not been evaluated fully. Methods: All cases of sudden cardiac arrest in Multnomah County Oregon (population 660,486; February 2002–January 2004) were identified prospectively and categorized by census tract based on the address of residence and specific geographic location of occurrence of cardiac arrest. Each census tract was assigned to quartiles of median income, poverty level, median home value, and educational attainment. Results: Of 714 cases (annual incidence 54 per 100,000), 697 (98%) had residential addresses that matched a county census tract successfully. For each socioeconomic status measure, the incidence of cardiac arrest was 30–80% higher in the lowest compared to the highest socioeconomic status census tracts. Annual incidence in census tracts in the lowest compared to the highest quartiles of median home value was 60.5 versus 35.1 per 100,000 (RR 1.7, 95% CI 1.4–2.2). This gradient was exaggerated significantly for age <65 years (34.5 versus 15.1 per 100,000, RR 2.3, 95% CI 1.6–3.3). Identical trends were observed for sudden cardiac arrest based on location, with 60% of all cases and 66% of cases age<65 years occurring in the two quartiles with lowest socioeconomic status. Conclusions: Low neighborhood socioeconomic status was associated with a significantly higher incidence of sudden cardiac arrest based on address of residence as well as location of cardiac arrest. For effective deployment of strategies for community-based prevention such as the automated external defibrillator, neighborhood socioeconomic status is likely to be an important consideration. [Copyright &y& Elsevier]

Introduction: Patients who suffer sudden cardiac arrest (SCA) can present with shockable (ventricular tachycardia/ventricular fibrillation) or non-shockable rhythms, with major implications for survival outcomes as well as future utilization of implantable defibrillators. At least 25% of HFpEF and 50% of HFrEF patients will die suddenly, but modes of SCA in HFpEF have not been previously evaluated. Hypothesis: We hypothesized that the significant differences in cardiac function between HFpEF (LV EF ≥50%) vs. HFrEF (LV EF ≤35%) reflect in significant differences in distribution of presenting rhythm or mode of SCA. Methods: Consecutive cases of SCA with established HF (age ≥18 years) were enrolled from a large ongoing population-based study of out-of-hospital SCA in the Northwestern US. LV EF was measured from echocardiogram, angiogram, or MUGA performed prior and unrelated to the SCA event. Presenting rhythms were identified from review of first responder reports and in-the-field electrocardiographic recordings. Univariate comparisons between HFpEF and HFrEF cases were evaluated using Pearson's chi-square tests and independent samples t-tests. Logistic regression was used to evaluate the independent association of presenting rhythm with HFpEF vs. HFrEF. Results: A total of 214 HFpEF and 204 HFrEF cases were included in this analysis. HFpEF were older (71.2 ± 13.0 vs. 68.7 ± 13.0, p = 0.05) and more likely to be female (42.5% vs. 20.1%, p < 0.0001). Presenting arrhythmia among HFpEF group was 34.1% VF/VT, 31.8% PEA and 34.1% asystole; while among HFrEF group was 52.9% VF/VT, 26.0% PEA and 21.1% asystole (p = 0.0003). There were no significant differences in the arrest location, witnessed status, bystander CPR or response time (p ≥ 0.31) with similar survival rates (p = 0.63) between the two groups. HFpEF cases had a higher odds of presenting with a non-shockable rhythm (odds ratio 1.9, 95% CI 1.28-2.90, p = 0.002), after adjustment for age and sex. Conclusions: HFpEF patients have double the risk of presenting with a non-shockable rhythm during SCA, with major implications for resuscitation as well as primary and secondary prevention. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) has a prevalence of 90/100,000 (0.09%) in the US general population. Patients often have major impairments of the autonomic nervous system with potential mechanistic implications for lethal ventricular arrhythmias and sudden cardiac death (SCD). However, there are no existing population-based studies that have evaluated this association. Hypothesis: To evaluate the prevalence of multiple sclerosis in a large population-based cohort of SCD patients. Methods: Out-of-hospital SCD cases age ≥18 yrs from an ongoing prospective community-based evaluation of SCD in the Portland, OR metro area (population approx. 1 million, 2002-2017) were evaluated for diagnosis of multiple sclerosis. Results: Out of 3144 adjudicated SCD cases with medical records available for review, we identified 15 (0.5%; 500/100,000) cases with a diagnosis of multiple sclerosis. MS cases were 60% female, 93% white, with a mean age of 56.33 yrs. In comparison, the total SCD population was 33% female, 87% white with a mean age of 66.18 yrs. Of the 15 MS cases, 1 had DNR status, 12 had resuscitation attempted and 2 survived to hospital discharge. The presenting rhythms at time of cardiac arrest were VF (n=5), asystole (n=4), and PEA (n=2); no data on rhythm was available for 4 cases. Regarding clinical characteristics, 11 patients had varying degrees of muscular dystrophy, 3 had visual problems, 2 with dizziness/orthostatic hypotension, 2 with bladder incontinence and 2 had a history of seizures. Four patients had known coronary artery disease and 2 presented with acute ischemia at arrest; 11 had ECGs available with a mean QTc interval of 490 ms, and T-peak to T-end interval of 106 ms. Conclusions: The prevalence of multiple sclerosis in this large population-based SCD cohort was over 5-fold higher than in the general US population. A proportion of MS patients who suffered SCD had abnormal markers of electrical risk, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Introduction: The time duration of warning symptoms may be a potential determinant of survival from sudden cardiac arrest (SCA), but this has not been evaluated. Hypothesis: Duration of warning symptoms influences outcome of sudden cardiac arrest. Methods: Cases of out-of-hospital SCA age ≥35 yrs were identified from an ongoing prospective community-based study of SCA in the Portland OR metro area (catchment population approx. 1 million, 2002-2015). We identified details of symptoms from virtual interviews performed by paramedic personnel at the scene combined with a detailed review of the resuscitation data, the medical examiner's report and hospital medical records when available. The nature and duration of symptoms occurring during the 4 week interval prior to the SCA event were evaluated, and correlated with survival to hospital discharge. Results: We identified 444 patients (70% male, mean age 56.6 ± 11.6 yrs) who had symptoms within the 4 weeks prior to arrest. Of these, 357 had information on symptom duration and survival outcome. The types of symptoms identified were angina and its equivalent (34%), dyspnea (17%), palpitations (1%), syncope (2%), abdominal discomfort (4%), others (37%) and unknown (5%). Men were more likely to suffer angina; women were more likely to have dyspnea and other symptoms. Overall, duration of symptoms longer than one hour was associated with lower survival compared to symptoms within an hour of the SCA event [11% (n=28) vs. 19% (n=21); p=0.06]. Conclusions: Longer duration of symptoms was associated with lower survival from SCA. [ABSTRACT FROM AUTHOR]

Introduction: Patients with echocardiographic (echo) left ventricular hypertrophy (LVH) are at moderately increased risk of sudden cardiac death (SCD). Since this is a common condition, further clinical risk stratification is needed to identify the pool of patients at highest risk. Hypothesis: We hypothesized that a recently developed and externally-validated electrocardiographic (ECG) risk score will improve SCD risk stratification among patients with echo LVH. Methods: From a community-based study of SCD in the Pacific Northwest, we included SCD cases and controls (2002 - 2016) who were age ≥18 with ECGs and echocardiograms available prior to cardiac arrest. The ECG risk score included six markers: heart rate >75 bpm, ECG LVH by voltage, delayed QRS transition (lead V5 or later), QRS-T angle >90 degrees, QTc >450 ms for men and >460 ms for women, and Tpeak-to-Tend interval >89 ms. We used logistic regression to evaluate echo LVH and the ECG risk score as independent predictors of SCD. We then assessed whether the ECG score predicted risk in patients with echo LVH. Results: Among 193 SCD cases (61% male, mean age 66.4) and 282 controls (63% male, mean age 66.4), cases had a higher prevalence of echo LVH (41% vs. 18%, p<0.001). Cases were also more likely to have diabetes (51% vs 34%, p<0.001) and severely reduced left ventricular ejection fraction (LVEF≤35%) (20% vs. 10%, p=0.002). An ECG risk score of ≥3 was observed in 49% of cases and 14% of controls (p<0.001). Adjusting for age, sex, diabetes, and LVEF, both LVH and the ECG risk score were significant predictors of SCD (odds ratio (OR) for LVH: 2.1, 95% CI 1.3-3.3, p=0.003; OR for a 1-unit increase in ECG risk score: 2.2, 95% CI 1.8-2.6, p<0.001). Among individuals with LVH (80 cases, 50 controls), the ECG risk score predicted SCD (p=0.001); those with an ECG risk score of ≥3 (vs. ≤2) had a significantly higher odds of SCD (OR 6.4, 95% CI 1.3-31.2, p=0.02). Conclusions: In patients with LVH at moderately increased risk of SCD, an elevated ECG risk score identified a subgroup with a markedly elevated SCD risk. These findings highlight the potential utility of a simple and widely available ECG risk score to sequester LVH patients at highest risk of SCD, with implications for clinical risk stratification. [ABSTRACT FROM AUTHOR]

Introduction: Both obesity and left ventricular hypertrophy (LVH) are associated with increased risk of sudden cardiac death (SCD). Since the increased risk of SCD in obesity independent of coronary artery disease remains unexplained, we evaluated the pathophysiological overlap between the two conditions. Hypothesis: LVH explains increased risk of SCD in obesity. Methods: From an ongoing prospective, population-based study of SCD in the Portland OR metro area (catchment population approx. 1 million, 2002-2016), we compared cases and controls age ≥18 who had detailed clinical phenotyping available including, body mass index (BMI) and echocardiographic LV mass measurements (performed prior and unrelated to the SCD event). Results: Among 596 SCD cases (64% male, mean 70.2 years) and 424 controls (69% male, mean 67.7 years), cases were more likely to have a higher mean BMI (31.4 ± 11.4 vs. 29.8 ± 6.4, p=0.004), diabetes, and hypertension. When compared to controls across all BMI categories, cases had higher mean LV mass (LVM, 240 vs 203, p<0.001), mean LVM indexed for body surface area (LVMi, 120 vs 101, p<0.001) and prevalence of echo LVH (38 vs 17%, p<0.001). After adjustment for age, sex, DM, HTN and heavy drinking, there was a 26% increased risk of SCD for every 40-unit increase in LVM, a 29% increased risk for every 20-unit increase in LVMi, and a more than two-fold (2.57x) increase with echo LVH diagnosis. All these findings remained unchanged after further adjustment for BMI. Conclusions: The independent, elevated risk of SCD in obesity, is not explained by LVH. Other factors such as increased myocardial fat content, hormonal factors and ion-channel remodeling at the cardiac myocyte level warrant further investigation. [ABSTRACT FROM AUTHOR]

Background Syncope has been associated with increased risk of sudden cardiac arrest (SCA) in specific patient populations, such as hypertrophic cardiomyopathy, heart failure, and long QT syndrome, but data are lacking on the risk of SCA associated with syncope among patients with coronary artery disease (CAD), the most common cause of SCA. We investigated this association among CAD patients in the community. Methods All cases of SCA due to CAD were prospectively identified in Portland, Oregon (population approximately 1 million) as part of the Oregon Sudden Unexpected Death Study 2002–2015, and compared to geographical controls. Detailed clinical information including history of syncope and cardiac investigations was obtained from medical records. Results 2119 SCA cases (68.4 ± 13.8 years, 66.9% male) and 746 controls (66.7 ± 11.7 years, 67.0% male) were included in the analysis. 143 (6.8%) of cases had documented syncope prior to the SCA. SCA cases with syncope were > 5 years older and had more comorbidities than other SCA cases. After adjusting for clinical factors and left ventricular ejection fraction (LVEF), syncope was associated with increased risk of SCA (OR 2.8; 95%CI 1.68–4.85). When analysis was restricted to subjects with LVEF ≥ 50%, the risk of SCA associated with syncope remained significantly elevated (adjusted OR 3.1; 95%CI 1.68–5.79). Conclusions Syncope was associated with increased risk of SCA in CAD patients even with preserved LV function. These findings suggest a role for this clinical marker among patients with CAD and normal LVEF, a large sub-group without any current means of SCA risk stratification. [ABSTRACT FROM AUTHOR]

Introduction: Over time, the effectiveness of severely reduced left ventricular ejection fraction (LVEF <35%) as a predictor of SCD has diminished, and improvements in risk stratification await discovery of novel markers. Right ventricular (RV) abnormalities can be observed in conditions like chronic obstructive pulmonary disease and sleep apnea, both of which have also been linked to SCD. Hypothesis: Abnormalities of RV dysfunction can be observed in patients who eventually suffer SCD. Methods: In a large, prospective ongoing community-based study of SCD in the Portland OR metro area, SCD cases (age ≥18, 2002-2014) were compared to geographic controls with coronary artery disease but no SCD. We assembled a novel archive of digital echocardiograms performed in SCD cases, before and unrelated to their lethal event. All images were read using a standardized 2-physician blinded protocol in a core lab. We assessed the following parameters of RV function: basal RV diameter (RVD), RV end-diastolic area (EDA), and RV fractional area change (FAC). Multivariable logistic regression analyses were performed; all models were adjusted for age, sex, and LVEF. Results: A total of 401 subjects were studied, including SCD cases (n=88, 68.0 ± 13.4 years, 70% male) and controls (n=313, 65.5 ± 10.1 years, 68% male). In logistic regression analyses with each RV marker separately, significant associations were observed for a 5-mm increase in RVD (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.01-1.13; p=0.04), a 5 cm2 increase in EDA (OR: 1.19; 95% CI: 1.01-1.14; p=0.04), and a 5% decrease in FAC (OR: 1.16; 95% CI: 1.06-1.27; p=0.002). In a multivariable logistic regression model with both EDA and FAC, a 5% decrease in RV FAC was significantly associated with SCD (OR: 1.14; 95% CI: 1.04-1.25; p=0.005) but no significant association was identified for increase in RV EDA (OR: 0.89; 95% CI: 0.75-1.05; p=0.16). Conclusion: RV dysfunction, as measured by decreased RV FAC, was associated with a significantly increased risk of SCD independent of the LV ejection fraction, in a community-based study. This novel marker warrants further evaluation as a potential clinical risk predictor that could enhance SCD clinical risk stratification. [ABSTRACT FROM AUTHOR]