Dynamic electrocardiogram changes are a novel risk marker for sudden cardiac death.

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.

Temporal Trends in Incidence and Survival From Sudden Cardiac Arrest Manifesting With Shockable and Nonshockable Rhythms: A 16-Year Prospective Study in a Large US Community.

STUDY OBJECTIVE: The proportion of nonshockable sudden cardiac arrests (pulseless electrical activity and asystole) continues to rise. Survival is lower than shockable (ventricular fibrillation [VF]) sudden cardiac arrests, but there is little community-based information on temporal trends in the incidence and survival from sudden cardiac arrests based on presenting rhythms. We investigated community-based temporal trends in sudden cardiac arrest incidence and survival by presenting rhythm. METHODS: We prospectively evaluated the incidence of each presenting sudden cardiac arrest rhythm and survival outcomes for out-of-hospital events in the Portland, Oregon metro area (population of approximately 1 million, 2002 to 2017). We limited inclusion to cases of likely cardiac cause with resuscitation attempted by emergency medical services. RESULTS: Out of 3,723 overall sudden cardiac arrest cases, 908 (24%) presented with pulseless electrical activity, 1,513 (41%) with VF, and 1,302 (35%) with asystole. The incidence of pulseless electrical activity-sudden cardiac arrest remained stable over 4-year periods (9.6/100,000 in 2002 to 2005, 7.4/100,000 in 2006 to 2009, 5.7/100,000 in 2010 to 2013, and 8.3/100,000 in 2014 to 2017; unadjusted beta [ß] -0.56; 95% confidence interval [CI], -3.98 to 2.85). The incidence of VF-sudden cardiac arrests decreased over time (14.6/100,000 in 2002 to 2005, 13.4/100,000 in 2006 to 2009, 12.0/100,000 in 2010 to 2013, and 11.6/100,000 in 2014 to 2017; unadjusted ß -1.05; 95% CI, -1.68 to -0.42) and asystole-sudden cardiac arrests (8.6/100,000 in 2002 to 2005, 9.0/100,000 in 2006 to 2009, 10.3/100,000 in 2010 to 2013, and 15.7/100,000 in 2014 to 2017; unadjusted ß 2.25; 95% CI -1.24 to 5.73) did not change significantly over time. Survival increased over time for pulseless electrical activity-sudden cardiac arrests (5.7%, 4.3%, 9.6%, 13.6%; unadjusted ß 2.8%; 95% CI 1.3 to 4.4) and VF-sudden cardiac arrests (27.5%, 29.8%, 37.9%, 36.6%; unadjusted ß 3.5%; 95% CI 1.4 to 5.6), but not for asystole-sudden cardiac arrests (1.7%, 1.6%, 4.0%, 2.4%; unadjusted ß 0.3%; 95% CI, -0.4 to 1.1). Enhancements in the emergency medical services system's pulseless electrical activity-sudden cardiac arrest management were temporally associated with the increasing pulseless electrical activity survival rates. CONCLUSIONS: Over a 16-year period, the incidence of VF/ventricular tachycardia decreased over time, but pulseless electrical activity incidence remained stable. Survival from both VF-sudden cardiac arrests and pulseless electrical activity-sudden cardiac arrests increased over time with a more than 2-fold increase for pulseless electrical activity-sudden cardiac arrests.

Risk Factors of Sudden Cardiac Death in the Young: Multiple-Year Community-Wide Assessment.

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.

Electrical surrogate for detection of severe left ventricular systolic dysfunction.

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.

Electrical risk score beyond the left ventricular ejection fraction: prediction of sudden cardiac death in the Oregon Sudden Unexpected Death Study and the Atherosclerosis Risk in Communities Study.

AIMS: There is an urgent need to extend sudden cardiac death (SCD) risk stratification beyond the left ventricular ejection fraction (LVEF). We evaluated whether a cumulative electrocardiogram (ECG) risk score would improve identification of individuals at high risk of SCD. METHODS AND RESULTS: In the community-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), 522 SCD cases with archived 12-lead ECG available (65.3 ± 14.5 years, 66% male) were compared with 736 geographical controls to assess the incremental value of multiple ECG parameters in SCD prediction. Heart rate, LV hypertrophy, QRS transition zone, QRS-T angle, QTc, and Tpeak-to-Tend interval remained significant in the final model, which was externally validated in the Atherosclerosis Risk in Communities (ARIC) Study. Sixteen percent of cases and 3% of controls had ≥4 abnormal ECG markers. After adjusting for clinical factors and LVEF, increasing ECG risk score was associated with progressively greater odds of SCD. Overall, subjects with ≥4 ECG abnormalities had an odds ratio (OR) of 21.2 for SCD [95% confidence interval (CI) 9.4-47.7; P < 0.001]. In the LVEF >35% subgroup, the OR was 26.1 (95% CI 9.9-68.5; P < 0.001). The ECG risk score increased the C-statistic from 0.625 to 0.753 (P < 0.001), with net reclassification improvement of 0.319 (P < 0.001). In the ARIC cohort validation, risk of SCD associated with ≥4 ECG abnormalities remained significant after multivariable adjustment (hazard ratio 4.84; 95% CI 2.34-9.99; P < 0.001; C-statistic improvement 0.759-0.774; P = 0.019). CONCLUSION: This novel cumulative ECG risk score was independently associated with SCD and was particularly effective for LVEF >35% where risk stratification is currently unavailable. These findings warrant further evaluation in prospective clinical investigations.

Cardiac structural and functional profile of patients with delayed QRS transition zone and sudden cardiac death.

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.

Left-ventricular geometry and risk of sudden cardiac arrest in patients with preserved or moderately reduced left-ventricular ejection fraction.

AIMS: The majority of sudden cardiac arrests (SCAs) occur in patients with left-ventricular (LV) ejection fraction (LVEF) >35%, yet there are no methods for effective risk stratification in this sub-group. Since abnormalities of LV geometry can be identified even with preserved LVEF, we investigated the potential impact of LV geometry as a novel risk marker for this patient population. METHODS AND RESULTS: In the ongoing Oregon Sudden Unexpected Death Study, SCA cases with archived echocardiographic data available were prospectively identified during 2002-15, and compared with geographical controls. Analysis was restricted to subjects with LVEF >35%. Based on established measures of LV mass and relative wall thickness (ratio of wall thickness to cavity diameter), four different LV geometric patterns were identified: normal geometry, concentric remodelling, concentric hypertrophy, and eccentric hypertrophy. Sudden cardiac arrest cases (n = 307) and controls (n = 280) did not differ in age, sex, or LVEF, but increased LV mass was more common in cases. Twenty-nine percent of SCA cases presented with normal LV geometry, 35% had concentric remodelling, 25% concentric hypertrophy, and 11% eccentric hypertrophy. In multivariate model, concentric remodelling (OR 1.76; 95%CI 1.18-2.63; P = 0.005), concentric hypertrophy (OR 3.20; 95%CI 1.90-5.39; P < 0.001), and eccentric hypertrophy (OR 2.47; 95%CI 1.30-4.66; P = 0.006) were associated with increased risk of SCA. CONCLUSION: Concentric and eccentric LV hypertrophy, but also concentric remodelling without hypertrophy, are associated with increased risk of SCA. These novel findings suggest the potential utility of evaluating LV geometry as a potential risk stratification tool in patients with preserved or moderately reduced LVEF.

A task-based assessment of parental occupational exposure to pesticides and childhood acute lymphoblastic leukemia.

OBJECTIVES: Associations between parental occupational pesticide exposure and childhood acute lymphoblastic leukemia (ALL) vary across studies, likely due to different exposure assessment methodologies. METHODS: We assessed parental occupational pesticide exposure from the year before pregnancy to the child's third year of life for 669 children diagnosed with ALL and 1021 controls. We conducted expert rating using task-based job modules (JM) to estimate exposure to pesticides among farmer workers, gardeners, agricultural packers, and pesticide applicators. We compared this method to (1) partial JM using job titles and a brief description, but without completing the task-based questionnaire, and (2) job exposure matrix (JEM) linking job titles to the International Standard Classifications of Occupation Codes. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for ALL cancer risk and pesticide exposure adjusting for child's sex, age, race/ethnicity and household income. RESULTS: Compared to complete JMs, partial JMs and JEM led to 3.1% and 9.4% of parents with pesticide exposure misclassified, respectively. Misclassification was similar in cases and controls. Using complete JMs, we observed an increased risk of ALL for paternal occupational exposure to any pesticides (OR=1.7; 95% CI=1.2, 2.5), with higher risks reported for pesticides to treat nut crops (OR=4.5; 95% CI=0.9, 23.0), and for children diagnosed before five years of age (OR=2.3; 95% CI: 1.3, 4.1). Exposure misclassification from JEM attenuated these associations by about 57%. Maternal occupational pesticide exposure before and after birth was not associated with ALL. CONCLUSIONS: The risk of ALL was elevated in young children with paternal occupational pesticide exposure during the perinatal period, using more detailed occupational information for exposure classification.

The Romhilt-Estes electrocardiographic score predicts sudden cardiac arrest independent of left ventricular mass and ejection fraction.

BACKGROUND: The Romhilt-Estes point score system (RE) is an established ECG criterion for diagnosing left ventricular hypertrophy (LVH). In this study, we assessed for the first time, whether RE and its components are predictive of sudden cardiac arrest (SCA) independent of left ventricular (LV) mass. METHODS: Sudden cardiac arrest (SCA) cases occurring between 2002 and 2014 in a Northwestern US metro region (catchment area approx. 1 million) were compared to geographic controls. ECGs and echocardiograms performed prior to the SCA and those of controls were acquired from the medical records and evaluated for the ECG criteria established in the RE score and for LV mass. RESULTS: Two hundred forty-seven SCA cases (age 68.3 ± 14.6, male 64.4%) and 330 controls (age 67.4 ± 11.5, male 63.6) were included in the analysis. RE scores were greater in cases than controls (2.5 ± 2.1 vs. 1.9 ± 1.7, p < .001), and SCA cases were more likely to meet definite LVH criteria (18.6% vs. 7.9%, p < .001). In a multivariable model including echocardiographic LVH and LV function, definite LVH remained independently predictive of SCA (OR 2.04, 95% CI 1.16-3.59, p = .013). The model was replicated with the individual ECG criteria, and only SV1.2  ≥ 30 mm and delayed intrinsicoid deflection remained significant predictors of SCA. CONCLUSION: Left ventricular hypertrophy (LVH) as defined by the RE point score system is associated with SCA independent of echocardiographic LVH and reduced LV ejection fraction. These findings support an independent role for purely electrical LVH, in the genesis of lethal ventricular arrhythmias.

Warning Symptoms Are Associated With Survival From Sudden Cardiac Arrest.

BACKGROUND: Survival after sudden cardiac arrest (SCA) remains low, and tools for improved prediction of patients at long-term risk for SCA are lacking. Alternative short-term approaches aimed at preemptive risk stratification and prevention are needed. OBJECTIVE: To assess characteristics of symptoms in the 4 weeks before SCA and whether response to these symptoms is associated with better outcomes. DESIGN: Ongoing prospective population-based study. SETTING: Northwestern United States (2002 to 2012). PATIENTS: Residents aged 35 to 65 years with SCA. MEASUREMENT: Assessment of symptoms in the 4 weeks preceding SCA and association with survival to hospital discharge. RESULTS: Of 839 patients with SCA and comprehensive assessment of symptoms (mean age, 52.6 years [SD, 8]; 75% men), 430 (51%) had warning symptoms (50% of men vs. 53% of women; P = 0.59), mainly chest pain and dyspnea. In most symptomatic patients (93%), symptoms recurred within the 24 hours preceding SCA. Only 81 patients (19%) called emergency medical services (911) to report symptoms before SCA; these persons were more likely to be patients with a history of heart disease (P < 0.001) or continuous chest pain (P < 0.001). Survival when 911 was called in response to symptoms was 32.1% (95% CI, 21.8% to 42.4%) compared with 6.0% (CI, 3.5% to 8.5%) in those who did not call (P < 0.001). LIMITATION: Potential for recall and response bias, symptom assessment not available in 24% of patients, and missing data for some patients and SCA characteristics. CONCLUSION: Warning symptoms frequently occur before SCA, but most are ignored. Emergent medical care was associated with survival in patients with symptoms, so new approaches are needed for short-term prevention of SCA. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Distinctive Clinical Profile of Blacks Versus Whites Presenting With Sudden Cardiac Arrest.

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.

Sudden cardiac arrest during sports activity in middle age.

BACKGROUND: Sports-associated sudden cardiac arrests (SCAs) occur mostly during middle age. We sought to determine the burden, characteristics, and outcomes of SCA during sports among middle-aged residents of a large US community. METHODS AND RESULTS: Patients with SCA who were 35 to 65 years of age were identified in a large, prospective, population-based study (2002-2013), with systematic and comprehensive assessment of their lifetime medical history. Of the 1247 SCA cases, 63 (5%) occurred during sports activities at a mean age of 51.1±8.8 years, yielding an incidence of 21.7 (95% confidence interval, 8.1-35.4) per 1 million per year. The incidence varied significantly by sex, with a higher incidence among men (relative risk, 18.68; 95% confidence interval, 2.50-139.56) for sports SCAs compared with all other SCAs (relative risk 2.58; 95% confidence interval, 2.12-3.13). Sports SCA was also more likely to be a witnessed event (87% versus 53%; P<0.001) with cardiopulmonary resuscitation (44% versus 25%; P=0.001) and ventricular fibrillation (84% versus 51%; P<0.0001). Survival to hospital discharge was higher for sports-associated SCA (23.2% versus 13.6%; P=0.04). Sports SCA cases presented with known preexisting cardiac disease in 16% and ≥1 cardiovascular risk factors in 56%, and overall, 36% of cases had typical cardiovascular symptoms during the week preceding the SCA. CONCLUSIONS: Sports-associated SCA in middle age represents a relatively small proportion of the overall SCA burden, reinforcing the idea of the high-benefit, low-risk nature of sports activity. Especially in light of current population aging trends, our findings emphasize that targeted education could maximize both safety and acceptance of sports activity in the older athlete.

Wide QRS-T Angle on the 12-Lead ECG as a Predictor of Sudden Death Beyond the LV Ejection Fraction.

INTRODUCTION: Improvements in risk stratification for sudden cardiac arrest (SCA) will require discovery of markers that extend beyond the LV ejection fraction (LVEF). The frontal QRS-T angle has been shown to predict risk of SCA but the value of this marker independent of the LVEF has not been investigated. METHODS AND RESULTS: Cases of adult SCA with an archived electrocardiogram (12-lead ECG) available before the event, with a computable frontal QRS-T angle, were identified from the Oregon Sudden Unexpected Death Study (Oregon SUDS) ongoing in the Portland, Oregon metro area. A total of 666 SCA cases (mean age 67.2 years; 95% CI, 52.3-82.1 years; 68.6% males) were compared to 863 controls (mean age 66.6 years, 55.2-78.0 years; 68.1% males; 75.0% had CAD) from the same geographical region. The mean frontal QRS-T angle was wider in cases (74(o) ; 95% CI, 17(o) -131(o) ) compared to controls (51(o) ; 95% CI, 5(o) -97(o;) P< 0.0001). A frontal QRS-T angle of more than 90(o) remained associated with increased risk of SCD after adjusting for age, gender, heart rate, prolonged intraventricular conduction, electrocardiographic left ventricular hypertrophy (ECG LVH), baseline comorbidities, and left ventricular ejection fraction (LVEF) (OR 2.2; 95% CI, 1.60-3.09; P< 0.0001). CONCLUSION: A wide QRS-T angle greater than 90(o) is associated with an increased risk of SCA independent of the left ventricular ejection fraction.

A task-based assessment of parental occupational exposure to organic solvents and other compounds and the risk of childhood leukemia in California.

PURPOSE: Data on parental occupational exposures and risk of childhood leukemia lack specificity. Using 19 task-based job modules, we examined the relationship between occupational exposure to organic solvents and other compounds and the risk of leukemia in children. METHODS: Latino (48%) and non-Latino (52%) children with acute lymphoblastic leukemia (ALL; n=670), acute myeloid leukemia (AML; n=104), and controls (n=1021) were enrolled in a study in California (2000-2008). Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for socio-demographic factors. RESULTS: Among children with non-Latino fathers, none of the exposures evaluated were associated with risks of ALL and AML. In contrast, exposure to any organic solvents in Latino fathers was associated with an increased risk of childhood ALL (OR=1.48; 95% CI: 1.01-2.16); in multivariable analyses, the OR for chlorinated hydrocarbons was 2.28 (95% CI: 0.97-5.37) while the ORs were close to one for aromatic hydrocarbons, glycol ethers, and other hydrocarbon mixtures. We also observed an increased risk of ALL with exposure to combustion exhaust/polycyclic aromatic hydrocarbons (PAHs) (ORs=1.70; 95% CI: 1.16-2.57, and 1.46; 95% CI: 0.94-2.26 with and without adjustment for chlorinated hydrocarbons, respectively). Moderately elevated risks of ALL were seen with exposure to metals, paints, and wood dust, although not statistically significant. An increased risk was reported for asbestos based on small numbers of exposed Latino fathers. No associations were reported between maternal exposures to any exposures and childhood ALL and AML. CONCLUSIONS: Our data support associations between paternal occupational exposures to chlorinated hydrocarbons, combustion exhaust, metals, and possibly asbestos and the risk of ALL in the children of Latino fathers only.

Frequency and determinants of implantable cardioverter defibrillator deployment among primary prevention candidates with subsequent sudden cardiac arrest in the community.

BACKGROUND: The prevalence rates and influencing factors for deployment of primary prevention implantable cardioverter defibrillators (ICDs) among subjects who eventually experience sudden cardiac arrest in the general population have not been evaluated. METHODS AND RESULTS: Cases of adult sudden cardiac arrest with echocardiographic evaluation before the event were identified from the ongoing Oregon Sudden Unexpected Death Study (population approximately 1 million). Eligibility for primary ICD implantation was determined from medical records based on established guidelines. The frequency of prior primary ICD implantation in eligible subjects was evaluated, and ICD nonrecipients were characterized. Of 2093 cases (2003-2012), 448 had appropriate pre- sudden cardiac arrest left ventricular ejection fraction information available. Of these, 92 (20.5%) were eligible for primary ICD implantation, 304 (67.9%) were ineligible because of left ventricular ejection fraction >35%, and the remainder (52, 11.6%) had left ventricular ejection fraction ≤35% but were ineligible on the basis of clinical guideline criteria. Among eligible subjects, only 12 (13.0%; 95% confidence interval, 6.1%-19.9%) received a primary ICD. Compared with recipients, primary ICD nonrecipients were older (age at ejection fraction assessment, 67.1±13.6 versus 58.5±14.8 years, P=0.05), with 20% aged ≥80 years (versus 0% among recipients, P=0.11). Additionally, a subgroup (26%) had either a clinical history of dementia or were undergoing chronic dialysis. CONCLUSIONS: Only one fifth of the sudden cardiac arrest cases in the community were eligible for a primary prevention ICD before the event, but among these, a small proportion (13%) were actually implanted. Although older age and comorbidity may explain nondeployment in a subgroup of these cases, other determinants such as socioeconomic factors, health insurance, patient preference, and clinical practice patterns warrant further detailed investigation.

Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals.

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10(-10)). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).

An ECG-based artificial intelligence model for assessment of sudden cardiac death risk.

BACKGROUND: Conventional ECG-based algorithms could contribute to sudden cardiac death (SCD) risk stratification but demonstrate moderate predictive capabilities. Deep learning (DL) models use the entire digital signal and could potentially improve predictive power. We aimed to train and validate a 12 lead ECG-based DL algorithm for SCD risk assessment. METHODS: Out-of-hospital SCD cases were prospectively ascertained in the Portland, Oregon, metro area. A total of 1,827 pre- cardiac arrest 12 lead ECGs from 1,796 SCD cases were retrospectively collected and analyzed to develop an ECG-based DL model. External validation was performed in 714 ECGs from 714 SCD cases from Ventura County, CA. Two separate control group samples were obtained from 1342 ECGs taken from 1325 individuals of which at least 50% had established coronary artery disease. The DL model was compared with a previously validated conventional 6 variable ECG risk model. RESULTS: The DL model achieves an AUROC of 0.889 (95% CI 0.861-0.917) for the detection of SCD cases vs. controls in the internal held-out test dataset, and is successfully validated in external SCD cases with an AUROC of 0.820 (0.794-0.847). The DL model performs significantly better than the conventional ECG model that achieves an AUROC of 0.712 (0.668-0.756) in the internal and 0.743 (0.711-0.775) in the external cohort. CONCLUSIONS: An ECG-based DL model distinguishes SCD cases from controls with improved accuracy and performs better than a conventional ECG risk model. Further detailed investigation is warranted to evaluate how the DL model could contribute to improved SCD risk stratification.

Sudden cardiac death (SCD) occurs when there are problems with the electrical activity within the heart. It is a common cause of death throughout the world so it would be beneficial to be able to easily identify individuals that are at high risk of SCD. Electrocardiograms are a cheap and widely available way to measure electrical activity in the heart. We developed a computational method that can use electrocardiograms to determine whether a person is at increased risk of having a SCD. Our computational method could allow clinicians to screen large numbers of people and identify those at a higher risk of SCD. This could enable regular monitoring of these people and might enable SCDs to be prevented in some individuals.

Artificial Intelligence Model Predicts Sudden Cardiac Arrest Manifesting With Pulseless Electric Activity Versus Ventricular Fibrillation.

BACKGROUND: There is no specific treatment for sudden cardiac arrest (SCA) manifesting as pulseless electric activity (PEA) and survival rates are low; unlike ventricular fibrillation (VF), which is treatable by defibrillation. Development of novel treatments requires fundamental clinical studies, but access to the true initial rhythm has been a limiting factor. METHODS: Using demographics and detailed clinical variables, we trained and tested an AI model (extreme gradient boosting) to differentiate PEA-SCA versus VF-SCA in a novel setting that provided the true initial rhythm. A subgroup of SCAs are witnessed by emergency medical services personnel, and because the response time is zero, the true SCA initial rhythm is recorded. The internal cohort consisted of 421 emergency medical services-witnessed out-of-hospital SCAs with PEA or VF as the initial rhythm in the Portland, Oregon metropolitan area. External validation was performed in 220 emergency medical services-witnessed SCAs from Ventura, CA. RESULTS: In the internal cohort, the artificial intelligence model achieved an area under the receiver operating characteristic curve of 0.68 (95% CI, 0.61-0.76). Model performance was similar in the external cohort, achieving an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.59-0.84). Anemia, older age, increased weight, and dyspnea as a warning symptom were the most important features of PEA-SCA; younger age, chest pain as a warning symptom and established coronary artery disease were important features associated with VF. CONCLUSIONS: The artificial intelligence model identified novel features of PEA-SCA, differentiated from VF-SCA and was successfully replicated in an external cohort. These findings enhance the mechanistic understanding of PEA-SCA with potential implications for developing novel management strategies.