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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]

Background: The ECG is a critical diagnostic tool for the management of immediate sudden cardiac arrest (SCA) survivors, but can be altered as a consequence of the SCA event. A limited number of studies report that electrical remodeling post SCA is due to prolonged myocardial repolarization, but a better understanding of this phenomenon is needed.Aim: To identify specific ECG abnormalities that follow SCA in immediate survivors.Methods: SCA survivors with a pre-arrest ECG and an ECG obtained within 48 h post-SCA were prospectively collected in the Oregon Sudden Unexpected Death Study (Portland metro region) from 2002-2015. Ventricular depolarization and repolarization measurements were compared between pre-arrest and post-arrest ECGs using paired t-tests and assessed for association with survival using unpaired t-tests and Pearson's chi-square tests.Results: A pre-arrest ECG and post-arrest ECG were available for 297 SCA cases (67.8 ± 13.4 years; 65.3% male). From the pre- to post-arrest setting, there was a significant mean increase in QRS (21 ms, p < 0.001) and QTc (35 ms, p < 0.001) in each SCA case, while there was no significant change in the JTc (4 ms, p = 0.361). Post-arrest QRS duration was significantly shorter in cases who survived to hospital discharge compared with those who did not survive (mean QRSD 115 ± 29 ms vs 127 ± 34 ms; p = 0.006).Conclusions: Contrary to expectations, electrical remodeling of the ECG due to SCA occurs due to prolongation of ventricular depolarization (QRSD), and not repolarization (JTc). Prolonged QRSD may also assist with prognostication and warrants further evaluation. [ABSTRACT FROM AUTHOR]

Keywords: sex differences; sudden cardiac arrest; sudden death EN sex differences sudden cardiac arrest sudden death 606 608 3 04/20/20 20200218 NES 200218 The incidence of sudden cardiac death (SCD) declined significantly between 1950 and 1999,[1] mirroring a decline in overall cardiovascular mortality. Last, we evaluated rates of SCD with known heart disease and those with SCD as first manifestation of heart disease. In men, the subset of SCD occurring in the setting of identifiable prearrest heart disease was responsible for 55% of the rebound in overall SCD incidence. [Extracted from the article]

Background: Prevention of sudden cardiac arrest (SCA) in the young remains a largely unsolved public health problem, and sports activity is an established trigger. Although the presence of standard cardiovascular risk factors in the young can link to future morbidity and mortality in adulthood, the potential contribution of these risk factors to SCA in the young has not been evaluated.Methods: We prospectively ascertained subjects who experienced SCA between the ages of 5 and 34 years in the Portland, Oregon, metropolitan area (2002-2015, catchment population ≈1 million). We assessed the circumstances, resuscitation outcomes, and clinical profile of subjects who had SCA by a detailed evaluation of emergency response records, lifetime clinical records, and autopsy examinations. We specifically evaluated the association of standard cardiovascular risk factors and SCA, and sports as a trigger for SCA in the young.Results: Of 3775 SCAs in all age groups, 186 (5%) occurred in the young (mean age 25.9±6.8, 67% male). In SCA in the young, overall prevalence of warning signs before SCA was low (29%), and 26 (14%) were associated with sports as a trigger. The remainder (n=160) occurred in other settings categorized as nonsports. Sports-related SCAs accounted for 39% of SCAs in patients aged ≤18, 13% of SCAs in patients aged 19 to 25, and 7% of SCAs in patients aged 25 to 34. Sports-related SCA cases were more likely to present with shockable rhythms, and survival from cardiac arrest was 2.5-fold higher in sports-related versus nonsports SCA (28% versus 11%; P=0.05). Overall, the most common SCA-related conditions were sudden arrhythmic death syndrome (31%), coronary artery disease (22%), and hypertrophic cardiomyopathy (14%). There was an unexpectedly high overall prevalence of established cardiovascular risk factors (obesity, diabetes mellitus, hypertension, hyperlipidemia, smoking) with ≥1 risk factors in 58% of SCA cases.Conclusions: Sports was a trigger of SCA in a minority of cases, and, in most patients, SCA occurred without warning symptoms. Standard cardiovascular risk factors were found in over half of patients, suggesting the potential role of public health approaches that screen for cardiovascular risk factors at earlier ages. [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]

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]

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]

Background: Early diagnosis and therapy improves outcomes in heart failure with severely reduced left ventricular ejection fraction (LVEF ≤35%), but some patients may remain undiagnosed. We hypothesized that a combination of electrocardiogram (ECG) markers may identify individuals with severely reduced LVEF.Methods: From a community-based study in the Northwest US (the Oregon Sudden Unexpected Death Study), we evaluated the prevalence of conventional ECG markers by LVEF. We then evaluated the association of nine additional ECG markers and LVEF. We validated the correlation of these ECG markers and LVEF in a separate, large health system in Los Angeles, California.Results: In the discovery population (n = 1,047), patients with LVEF ≤35% were twice as likely as those with LVEF >35% to have ≥1 conventional ECG abnormality. In the subset without conventional ECG abnormalities, ≥4 abnormal ECG markers from the expanded panel were found in 12% vs. 1% of patients with LVEF ≤35% and >35%, respectively. In the validation population (n = 9,742), 44% with LVEF ≤35% and 17% with LVEF >35% had ≥1 conventional ECG abnormality. In patients without conventional ECG abnormalities (n = 7,601), 40% with LVEF ≤35% and 5% with LVEF >35% had ≥4 abnormal ECG markers from the expanded panel. Each additional abnormal ECG marker from the expanded panel (range 0 to ≥4) more than doubled the odds of LVEF ≤35%.Conclusions: An expanded panel of easily obtained ECG markers correlated strongly with severely reduced LVEF in two separate populations. This electrical surrogate score could facilitate diagnosis of severely reduced LVEF, and warrants prospective evaluation. [ABSTRACT FROM AUTHOR]

Background: In the absence of apparent triggers, sudden cardiac death (SCD) during nighttime hours is a perplexing and devastating phenomenon. There are few published reports in the general population, with insufficient numbers to perform sex-specific analyses. Smaller studies of rare nocturnal SCD syndromes suggest a male predominance and implicate sleep-disordered breathing., Objective: The purpose of this study was to identify mechanisms of nighttime SCD in the general population., Methods: From the population-based Oregon Sudden Unexpected Death Study, we evaluated SCD cases that occurred in the community between 10 PM and 6 AM (nighttime) and compared them with daytime cases. Univariate comparisons were evaluated using Pearson χ 2 tests and independent samples t tests. Logistic regression was used to further assess independent SCD risk., Results: A total of 4126 SCD cases (66.2% male, 33.8% female) met criteria for analysis and 22.3% (n = 918) occurred during nighttime hours. Women were more likely to present with nighttime SCD than men (25.4% vs 20.6%; P < .001). In a multivariate regression model, female sex (odds ratio [OR] 1.3 [confidence interval (CI) 1.1-1.5]; P = .001), medications associated with somnolence/respiratory depression (OR 1.2 [CI 1.1-1.4]; P = .008) and chronic obstructive pulmonary disease/asthma (OR 1.4 [CI 1.1-1.6]; P < .001) were independently associated with nighttime SCD. Women were taking more central nervous system-affecting medications than men (1.9 ± 1.7 vs 1.4 ± 1.4; P = .001)., Conclusion: In the general population, women were more likely than men to suffer SCD during nighttime hours and female sex was an independent predictor of nighttime events. Respiratory suppression is a concern, and caution is advisable when prescribing central nervous system-affecting medications to patients at an increased risk of SCD, especially women., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to evaluate the potential impact of the coronavirus disease-2019 (COVID-19) pandemic on out-of-hospital cardiac arrest (OHCA) responses and outcomes in 2 U.S. communities with relatively low infection rates., Background: Studies in areas with high COVID-19 infection rates indicate that the pandemic has had direct and indirect effects on community responses to OHCA and negative impacts on survival. Data from areas with lower infection rates are lacking., Methods: Cases of OHCA in Multnomah County, Oregon, and Ventura County, California, with attempted resuscitation by emergency medical services (EMS) from March 1 to May 31, 2020, and from March 1 to May 31, 2019, were evaluated., Results: In a comparison of 231 OHCA in 2019 to 278 in 2020, the proportion of cases receiving bystander cardiopulmonary resuscitation (CPR) was lower in 2020 (61% to 51%, respectively; p = 0.02), and bystander use of automated external defibrillators (AEDs) declined (5% to 1%, respectively; p = 0.02). EMS response time increased (6.6 ± 2.0 min to 7.6 ± 3.0 min, respectively; p < 0.001), and fewer OHCA cases survived to hospital discharge (14.7% to 7.9%, respectively; p = 0.02). Incidence rates did not change significantly (p > 0.07), and coronavirus infection rates were low (Multnomah County, 143/100,000; Ventura County, 127/100,000 as of May 31) compared to rates of ∼1,600 to 3,000/100,000 in the New York City region at that time., Conclusions: The community response to OHCA was altered from March to May 2020, with less bystander CPR, delays in EMS response time, and reduced survival from OHCA. These results highlight the pandemic's indirect negative impact on OHCA, even in communities with relatively low incidence of COVID-19 infection, and point to potential opportunities for countering the impact., Competing Interests: Author Disclosures Dr. Chugh was funded by National Institutes of Health, National Heart Lung and Blood Institute (NHLBI) grants R01 HL147358 and R01 HL145675. Dr. Chugh holds the Pauline and Harold Price Chair in Cardiac Electrophysiology at Cedars-Sinai, Los Angeles. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The effectiveness of severely reduced left ventricular ejection fraction (LVEF <35%) as a predictor of sudden cardiac death (SCD) has diminished, and improvements in risk stratification await discovery of novel markers. Right ventricular (RV) abnormalities can be observed in conditions such as chronic obstructive pulmonary disease and sleep apnea, which have been linked to SCD., Objective: The purpose of this study was to evaluate whether RV abnormalities were associated with SCD after accounting for LVEF and other patient characteristics., Methods: In a large, prospective ongoing community-based study of SCD in the Portland, Oregon, metropolitan area, SCD cases (age ≥18 years; 2002-2014) were compared to controls with coronary artery disease but no SCD. Using a novel archive of digital echocardiograms, a standardized approach was used to evaluate RV basal diameter, RV end-diastolic area, and right ventricular fractional area change (RVFAC)., Results: A total of 350 subjects were studied, including 81 SCD cases (age 68.7 ± 13.6 years; 73% male) and 269 controls (age 66.5 ± 10.2 years; 69% male). In multivariate analysis, RVFAC was significantly associated with SCD (odds ratio 1.14 for each 5% decrease; 95% confidence interval 1.03-1.25; P = .01). When modeled with LVEF ≤35%, RVFAC ≤35% was significantly associated with increased risk of SCD. Individuals with both left ventricular and RV dysfunction had a 3× higher odds of SCD than those with neither (odds ratio 3.19; 95% confidence interval 1.33-7.68; P = .01)., Conclusion: RV dysfunction was associated with a significantly increased risk of SCD independent of LVEF and, when combined with LVEF, had additive effects on SCD risk., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: Work environment is said to influence cardiovascular risk. We assessed whether nature of occupation affects risk of sudden cardiac death (SCD) in the general population., Methods: In the ongoing, prospective Oregon Sudden Unexpected Death Study (catchment population 1 million), working-age SCD cases (18-65 years) were compared with controls who died from any cause. Usual occupation obtained from death certificates was classified using the US Census Bureau standard occupational classification descriptions and categorised as white collar, blue collar or homemaker. Odds ratio (OR) for SCD by occupation category was obtained and clinical profile of SCD cases was compared by occupation type., Results: Among SCD cases (n=646; 74% male) compared to controls (n=622; 73.6% male), the proportion of white collar workers was higher among male SCD cases (52.7% vs 43.7%; p=0.01); the difference in females was smaller (59.5% vs 55%; p=0.62). Adjusting for race and smoking status, male white collar workers had a higher risk of SCD compared to blue collar workers (OR=1.67, (1.26 to 2.23), p<0.001). A similar, non-significant trend was observed among females (OR 1.49 (0.81 to 2.75); p=0.20). White collar SCD cases were less likely to be current smokers (34.7% vs 45.3%, p=0.008), drug misusers (13.1% vs 18.5%) or have diabetes (21.4% vs 28.2%, both p=0.07) compared to blue collar workers. Other cardiac risk factors were similar., Conclusions: A white collar occupation was associated with increased risk of SCD, when compared to blue collar occupations. Since differences in conventional risk factors did not explain this elevated risk, work-related behavioural and psychosocial stressors warrant a closer evaluation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Sudden cardiac arrest (SCA) is a major contributor to mortality, but data are limited among nonwhites. Identification of differences in clinical profile based on race may provide opportunities for improved SCA prevention., Methods and Results: In the ongoing Oregon Sudden Unexpected Death Study (SUDS), individuals experiencing SCA in the Portland, OR, metropolitan area were identified prospectively. Patient demographics, arrest circumstances, and pre-SCA clinical profile were compared by race among cases from 2002 to 2012 (for clinical history, n=126 blacks, n=1262 whites). Incidence rates were calculated for cases from the burden assessment phase (2002-2005; n=1077). Age-adjusted rates were 2-fold higher among black men and women (175 and 90 per 100 000, respectively) compared with white men and women (84 and 40 per 100 000, respectively). Compared with whites, blacks were >6 years younger at the time of SCA and had a higher prearrest prevalence of diabetes mellitus (52% versus 33%; P<0.0001), hypertension (77% versus 65%; P=0.006), and chronic renal insufficiency (34% versus 19%; P<0.0001). There were no racial differences in previously documented coronary artery disease or left ventricular dysfunction, but blacks had more prevalent congestive heart failure (43% versus 34%; P=0.04) and left ventricular hypertrophy (77% versus 58%; P=0.02) and a longer QTc interval (466±36 versus 453±41 milliseconds; P=0.03)., Conclusions: In this US community, the burden of SCA was significantly higher in blacks compared with whites. Blacks with SCA had a higher prearrest prevalence of risk factors beyond established coronary artery disease, providing potential targets for race-specific prevention., (© 2015 American Heart Association, Inc.)

Background: Obesity has been associated with significantly greater risk of sudden cardiac death (SCD); however, identifying the obese patient at highest risk remains a challenge. We evaluated the association between QRS fragmentation on the 12-lead electrocardiogram and SCD, in obese/overweight subjects., Methods and Results: In the ongoing prospective, community-based Oregon Sudden Unexpected Death Study (population approximately 1 million), we performed a case-control analysis, comparing obese/overweight SCD victims with obese/overweight controls from the same geographic region. Archived ECGs prior and unrelated to the SCD event were used for cases and all ECG measurements were assessed in blinded fashion. Fragmentation was defined as the presence of RSR' patterns and/or notching of the R/S wave in at least 2 contiguous leads. Analysis was limited to ECGs with QRS duration <120 ms. Overall prevalence of fragmentation was higher in cases (n=185; 64.9±13.8 years; 67.0% male) compared with controls (n=405; 64.9±11.0 years; 64.7% male) (34.6% versus 26.9%, P=0.06). Lateral fragmentation was significantly more frequent in cases (8.1% versus 2.5%; P<0. 01), with non-significant differences in anterior and inferior territories. Fragmentation in multiple territories (≥2) was also more likely to be observed in cases (9.7% versus 4.9%, P=0.02). In multivariable analysis with consideration of established SCD risk factors, lateral fragmentation was significantly associated with SCD (OR 2.84; 95% CI 1.01 to 8.02; P=0.05)., Conclusion: QRS fragmentation, especially in the lateral territory is a potential risk marker for SCD independent of the ejection fraction, among obese/overweight subjects in the general population., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Sex hormones are known to have significant effects on the pathophysiology of cardiovascular disease., Objective: The purpose of this study was to study the association between sex hormone levels and sudden cardiac arrest (SCA)., Methods: In the ongoing Oregon Sudden Unexpected Death Study (catchment population approximately 1 million), cases of SCA were compared with matched controls. Testosterone and estradiol levels were measured from blood samples drawn at the time of the SCA event in cases and during a routine visit in controls., Results: Among cases (n = 149, age 64.1 ± 11.7 years, 73.2% male), compared to controls (n = 149, 64.2 ± 11.6 years, 72.5% male), median testosterone levels were significantly lower in males (4.4 vs 5.4 ng/mL, P = .01). Median estradiol levels were higher in male (68 vs 52 pg/mL, P <.001) and female cases (54 vs 36 pg/mL, P <.001). In multivariate analysis, higher testosterone levels were associated with lower SCA odds only in males (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.58-0.96, P = .02). Higher estradiol levels were associated with higher SCA odds in both males (OR 2.0, 95% CI 1.5-2.6, P <.001) and females (OR 3.5, 95% CI 1.9-6.4, P <.001). A higher testosterone/estrogen ratio was associated with lower SCA odds in males only (OR 0.5, 95% CI 0.4-0.7, P <.001). In a canine model of SCA, plasma testosterone levels were not significantly altered by the cardiac arrest event., Conclusion: We observed significant differences in sex hormone levels in patients who suffered SCA, with potential mechanistic implications. The role of sex hormones in the genesis of fatal ventricular arrhythmias warrants further exploration., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to evaluate the role of congestive heart failure (CHF) in the association between atrial fibrillation (AF) and sudden cardiac death (SCD)., Background: Recent studies have reported the possibility of an independent association between AF and SCD. We hypothesized that a history of CHF is a significant confounder of this association., Methods: In a prospective case-control analysis from the community (The Oregon-SUDS [Sudden Unexpected Death Study], 2002 to 2012), SCD cases (n = 652) with clinical records available (including electrocardiography and/or echocardiography) were compared with age- and sex-matched control patients with coronary artery disease. The association between AF and SCD was analyzed using multivariable logistic regression and propensity score matching., Results: Cases (age 67.3 ± 11.7 years, 65% male) were more likely than control patients (age 67.2 ± 11.4 years, 65% male) to have a history of AF (p = 0.0001), myocardial infarction (p = 0.007), CHF (p < 0.0001), stroke (p < 0.0001), and diabetes (p < 0.0001). In multivariate analysis without considering CHF, AF was a significant predictor of SCD (odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.2 to 2.0; p = 0.002). However, in a model that included CHF, the AF-SCD association was no longer significant (OR: 1.1; 95% CI: 0.8 to 1.5; p = 0.45), whereas CHF was a significant predictor of SCD (OR: 3.1; 95% CI: 2.4 to 4.1; p < 0.0001). Results on the basis of propensity score matching were consistent., Conclusions: Our findings suggest that a history of CHF, including both systolic and diastolic symptomatic dysfunction, may partially explain the AF-SCD association., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Among patients with epilepsy, sudden cardiac arrest (SCA) is a major cause of death. It is commonly thought that SCA in epilepsy occurs after a seizure, though the strength of evidence supporting this is limited. We sought to evaluate the relationship between seizures and SCA in patients with epilepsy., Methods and Results: From the ongoing Oregon Sudden Unexpected Death Study, cases of SCA identified using prospective, multisource ascertainment (Portland metropolitan area, Oregon; population≈1 million; February 1, 2002, to March 1, 2012) were evaluated for history of epilepsy. In the subset with witnessed SCA, clinical presentations were analyzed for evidence of seizure activity immediately before the event as well as lifetime clinical history, including nature of seizures before SCA. Only 34% of patients with history of epilepsy and a witnessed arrest had evidence of seizure activity before the arrest. Rates of survival to hospital discharge after attempted resuscitation were 2.7% in patients with history of epilepsy versus 11.9% for patients without epilepsy (P=0.014). Patients with epilepsy had a significantly lower rate of presentation with ventricular tachycardia/ventricular fibrillation as opposed to pulseless electrical activity/asystole (epilepsy, 26%; no epilepsy, 44%; P=0.002), despite nearly identical response times., Conclusions: In the majority (66%) of epilepsy patients, there was no relationship between seizure and SCA, implying that SCA in epilepsy patients often may not involve seizure as a trigger. The significantly worse rate of survival from SCA in epilepsy patients warrants urgent investigation.

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 © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There has been a paradigm shift in the manifestation of sudden cardiac arrest (SCA), with steadily decreasing rates of ventricular fibrillation/tachycardia (VF/VT) and a significant increase in the proportion of pulseless electrical activity (PEA) and asystole., Objective: Since PEA is marked by failure of myocardial contractility, we evaluated the potential role of drugs that affect cardiac contractility in the pathophysiology of human PEA., Methods: Subjects with out-of-hospital SCA (aged≥18 years) who underwent attempted resuscitation were evaluated in the ongoing Oregon Sudden Unexpected Death Study (2002-2009). Specific classes of medications with either negative or positive cardiac inotropic effects were evaluated for association with occurrence of PEA vs VF/VT by using Pearson χ(2) tests and logistic regression., Results: PEA cases (n = 309) were older than VF/VT cases (n = 509; 68±14 years vs 64±15 years; P<.0001) and were more likely to be women (39% vs 25%; P<.0001). In a logistic regression model adjusting for age, sex, comorbidities, disease burden, and resuscitation variables, antipsychotic drugs (odds ratio 2.40; 95% confidence interval 1.26-4.53) were significant predictors of PEA vs VF/VT. Conversely, use of digoxin was associated with the occurrence of VF/VT (P<.0001)., Conclusions: When drugs modifying myocardial contractility were evaluated in a comprehensive analysis of patients who suffered SCA, use of antipsychotic agents was a significant and independent predictor of manifestation with PEA., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: Studies evaluating a possible survival advantage from sudden cardiac arrest (SCA) in women have produced mixed results possibly due to a lack of comprehensive analyses. We hypothesized that race, socioeconomic status (SES), and elements of the lifetime clinical history influence gender effects and need to be incorporated within analyses of survival., Methods: Cases of SCA were identified from the ongoing, prospective, multiple-source Oregon Sudden Unexpected Death Study (population approximately one million). Subjects included were age ≥18 years who underwent attempted resuscitation by EMS providers. Pearson's chi-square tests and independent samples t tests or analysis of variance were used for univariate comparisons. We evaluated gender and race differences in survival adjusted for age, circumstances of arrest, disease burden, and socioeconomic status using a logistic regression model predicting survival., Results: A total of 1,296 cases had resuscitation attempted (2002-2007; mean age 65 years, male 67%). Women were older than men (68 vs. 63 years, p < 0.0001) and were more likely to have return of spontaneous circulation (41% vs. 33%, p = 0.004). Women were more likely to present with pulseless electrical activity (PEA) and asystole (p < 0.0001), and overall, PEA was more common among African Americans (p = 0.04). Higher survival to hospital discharge was observed in women compared to men presenting with ventricular fibrillation/tachycardia (34% vs. 24%, p = 0.02) or with PEA (10% vs. 3%, p = 0.007). In a multivariate model adjusting for age, race, presenting arrhythmia, arrest circumstances, arrest location, disease burden, and SES, women were more likely than men to survive to hospital discharge [odds ratio 1.85; 95% confidence interval (1.12-3.04)]., Conclusions: Despite older age, higher prevalence of SCA in the home, and higher rates of PEA, women had a survival advantage from ventricular fibrillation and pulseless electrical activity.

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., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Recent evidence suggests a genetic component for sudden cardiac death (SCD) in subjects with coronary artery disease (CAD). We conducted a systematic candidate-gene approach using haplotype-tagging single nucleotide polymorphisms (htSNPs) to identify genes associated with SCD risk in the context of CAD., Methods and Results: We investigated 1424 htSNPs representing 18 genes with mutations described in patients with ventricular arrhythmias in 291 subjects from the Oregon Sudden Unexpected Death Study (Ore-SUDS). The Ore-SUDS is an ongoing prospective investigation of SCD in the Portland, OR, metropolitan area (population, 1 000 000). SCD cases were ascertained from multiple sources and medical records were reviewed to determine the presence of CAD. A total of 36 SNPs were associated with risk of SCD (uncorrected probability values <0.01) in the initial study sample. These SNPs were subsequently tested for replication in an independent case-control study sample from the Ore-SUDS (n=688). The association analysis in the replication stage revealed 6 SNPs associated with SCD: CASQ2 region (rs17500488, P=0.04; rs3010396, P=0.007; rs7366407; P=0.04), NOS1AP (rs12084280, P=0.04; rs10918859, P=0.02), and 1 SNP located ≈26 kb upstream of GPD1L (rs9862154, P=0.04)., Conclusions: Common variations in or near CASQ2, GPD1L, and NOS1AP are associated with increased risk of SCD in patients with CAD. These findings provide further evidence for overlap between the genetic architecture of rare and common forms of SCD, and replication in additional populations is warranted.

Background: Corresponding with a continuing decline in the prevalence of sudden cardiac arrest cases presenting with ventricular fibrillation (VF), there has been a significant rise in the prevalence of pulseless electrical activity (PEA). Given significantly lower survival from PEA versus VF, we comprehensively investigated PEA correlates by incorporating first-responder data with lifetime clinical history information., Methods and Results: In the Portland, Ore, metropolitan area (population ≈1 million), cases of out-of-hospital sudden cardiac arrest who underwent attempted resuscitation were identified prospectively (2002-2007). Those presenting with PEA versus VF and asystole were compared with χ² tests, ANOVA, and logistic regression. A total of 1277 cases aged ≥18 years underwent resuscitation by first responders (mean age, 65±16 years; 67% male). Presenting arrhythmia was VF in 48%, PEA in 25%, and asystole/other in the remainder. Compared with VF cases, PEA cases were older (mean age, 68 versus 63 years; P=0.0002), more likely to be female (37% versus 26%; P=0.0008), and less likely to survive to hospital discharge (6% versus 25%; P<0.0001). A history of syncope was strongly associated with PEA (odds ratio, 2.6; confidence interval, 1.3 to 5.3) after adjustment for age, gender, response time, and arrest circumstances. Black race was also independently associated with PEA (odds ratio, 2.6; confidence interval, 1.3 to 5.4). Pulmonary disease and female gender were significant factors associated with PEA (P for interaction=0.04). In a subgroup analysis of resting ECGs (n=391), there were no differences in cardiac clinical history or prevalence of cardiac conduction system disease (PEA, 31.6% versus VF, 32.2%; P=0.48)., Conclusions: PEA cases had a significantly higher prevalence of syncope in their lifetime, with other correlates, including black race, that were distinct from VF cases. Potential mechanistic links between syncope and future manifestation with PEA warrant further exploration.

Background: Existing studies indicate a significant genetic component for sudden cardiac arrest (SCA) and genome-wide association studies (GWAS) provide an unbiased approach for identification of novel genes. We performed a GWAS to identify genetic determinants of SCA., Methodology/principal Findings: We used a case-control design within the ongoing Oregon Sudden Unexpected Death Study (Oregon-SUDS). Cases (n = 424) were SCAs with coronary artery disease (CAD) among residents of Portland, OR (2002-07, population approximately 1,000,000) and controls (n = 226) were residents with CAD, but no history of SCA. All subjects were of White-European ancestry and GWAS was performed using Affymetrix 500K/5.0 and 6.0 arrays. High signal markers were genotyped in SCA cases (n = 521) identified from the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) (combined n = 19,611). No SNPs reached genome-wide significance (p<5x10(-8)). SNPs at 6 loci were prioritized for follow-up primarily based on significance of p<10(-4) and proximity to a known gene (CSMD2, GPR37L1, LIN9, B4GALNT3, GPC5, and ZNF592). The minor allele of GPC5 (GLYPICAN 5, rs3864180) was associated with a lower risk of SCA in Oregon-SUDS, an effect that was also observed in ARIC/CHS whites (p<0.05) and blacks (p<0.04). In a combined Cox proportional hazards model analysis that adjusted for race, the minor allele exhibited a hazard ratio of 0.85 (95% CI 0.74 to 0.98; p<0.01)., Conclusions/significance: A novel genetic locus for SCA, GPC5, was identified from Oregon-SUDS and successfully validated in the ARIC and CHS cohorts. Three other members of the Glypican family have been previously implicated in human disease, including cardiac conditions. The mechanism of this specific association requires further study.

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.

Background: In a recent cohort study, prolongation of the corrected QT interval (QTc) was associated with an independent increased risk of sudden cardiac death (SCD). We evaluated determinants of prolonged QTc and the relationship of prolonged QTc to SCD risk among patients with coronary artery disease in the general population., Methods and Results: A case-control design was used. Cases were SCD patients with coronary artery disease among a metropolitan area of 1 000 000 residents (2002 to 2006); controls were area residents with coronary artery disease but no history of SCD. All cases were required to have an ECG suitable for QTc analysis before and unrelated to the occurrence of SCD. A total of 373 cases and 309 controls met criteria for analysis. Mean QTc was significantly longer in cases than in controls (450+/-45 versus 433+/-37 ms; P<0.0001). In a multivariate model, gender, diabetes mellitus, and QTc-prolonging drugs were significant determinants of QTc prolongation in controls. In a logistic regression model predicting SCD, diabetes mellitus (odds ratio, 1.97; 95% confidence interval, 1.32 to 2.96) and use of QTc-prolonging drugs (odds ratio, 2.90; 95% confidence interval, 1.92 to 4.37) were significant predictors of SCD among subjects with normal or borderline QTc. However, abnormally prolonged QTc in the absence of diabetes and QT-prolonging medications was the strongest predictor of SCD (odds ratio, 5.53; 95% confidence interval, 3.20 to 9.57)., Conclusions: Diabetes mellitus and QTc-affecting drugs determined QTc prolongation and were predictors of SCD in coronary artery disease. However, idiopathic abnormal QTc prolongation was associated with 5-fold increased odds of SCD. A continued search for novel determinants of QTc prolongation such as genomic factors is likely to enhance risk stratification for SCD in coronary artery disease.

Background: Published case reports have associated the therapeutic use of methadone with the occasional occurrence of sudden cardiac death. Because of the established utility of this drug and with the eventual goal of enhancing safety of use, we performed a community-based study to evaluate this association., Methods: During a 4-year period, we prospectively evaluated all patients who consecutively had sudden cardiac death and underwent investigation by the medical examiner in the metropolitan area of Portland, Ore. Case subjects of interest were those with a therapeutic blood level of methadone (<1 mg/L), and case comparison subjects were those with no methadone identified. Patients with recreational drug use or any drug overdose were excluded from either group. Detailed autopsies were conducted, including the detection and quantification of all substances in the blood., Results: A total of 22 sudden cardiac death cases with therapeutic levels of methadone (mean 0.48+/-0.22 mg/L; range 0.1-0.9 mg/L) were identified (mean age 37.0+/-10 years, 68% were male) and compared with 106 consecutive sudden cardiac death cases without evidence of methadone (mean age 42+/-13 years, 69% were male). The most common indication for methadone use was pain control (n=12, 55%). Among cases receiving methadone therapy, sudden death-associated cardiac abnormalities were identified in only 23% (n=5), with no clear cause of sudden cardiac death in the remaining 77% (n=17). Among cases with no methadone, sudden death-associated cardiac abnormalities were identified in 60% (n=64, P=.002)., Conclusion: The significantly lower prevalence of cardiac disease in the case group implicates methadone, even at therapeutic levels, as a likely cause of sudden death. These findings point toward an association between methadone and occurrence of sudden death in the community. Clinical safeguards and further prospective studies specifically designed to enhance safety of methadone use are warranted.