Race, ethnicity, and the risk of sudden death.

Sudden cardiac death (SCD) is a major cause of death worldwide, with an estimated U.S. annual incidence of 350,000 [1]. This review will examine the influence of race and ethnicity on SCD burden and risk factors, and review the available literature on resuscitation outcomes and primary prevention of SCD. An improved understanding of associations between race, ethnicity, and SCD may provide clues to mechanisms, lead to improved prevention of SCD, and ultimately reduce racial and ethnic disparities in the burden of SCD.

Unexpected shift in circadian and septadian variation of sudden cardiac arrest: the Oregon Sudden Unexpected Death Study.

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.

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.

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.

Serum Calcium and Risk of Sudden Cardiac Arrest in the General Population.

OBJECTIVE: To evaluate the potential role of low serum Ca levels in the occurrence of sudden cardiac arrest (SCA) in the community. PATIENTS AND METHODS: We compared 267 SCA cases [177 (66%) men] and 445 controls [314 (71%) men] from a large population-based study (catchment population ∼1 million individuals) in the US Northwest from February 1, 2002, through December 31, 2015. Patients were included if their age was 18 years or older with available creatinine clearance (CrCl) and serum electrolyte levels for analyses to enable adjustment for renal function. For cases, creatinine clearance and electrolyte levels were required to be measured within 90 days of the SCA event. RESULTS: Cases of SCA had higher proportions of blacks [31 (12%) vs 14 (3%); P<.001], diabetes mellitus [122 (46%) vs 126 (28%); P<.001], and chronic kidney disease [102 (38%) vs 73 (16%); P<.001] than did controls. In multivariable logistic regression analysis, a 1-unit decrease in Ca levels was associated with a 1.6-fold increase in odds of SCA (odds ratio, 1.63; 95% CI, 1.06-2.51). Blood Ca levels lower than 8.95 mg/dL (to convert to mmol/L, multiply by 0.025) were associated with a 2.3-fold increase in odds of SCA as compared with levels higher than 9.55 mg/dL (odds ratio, 2.33; 95% CI, 1.17-4.61). Cases of SCA had significantly prolonged corrected QT intervals on the 12-lead electrocardiogram than did controls (465±37 ms vs 425±33 ms; P<.001). CONCLUSION: Lower serum Ca levels were independently associated with an increased risk of SCA in the community.

Novel measure of autonomic remodeling associated with sudden cardiac arrest in diabetes.

BACKGROUND: Diabetes is independently associated with an increased risk of sudden cardiac arrest (SCA), with a need to identify novel methods for risk stratification. Diabetic patients can develop autonomic dysfunction that has been associated with an increased risk of ventricular arrhythmogenesis and manifests as reduced heart rate variability (HRV). However, previously published studies have not accounted for resting heart rate (HR), important from both pathophysiological and prognosticating standpoints. OBJECTIVE: We sought to evaluate autonomic remodeling of the sinus node response in SCA and diabetes while accounting for HR. METHODS: We performed a case-control study in SCA cases (age 35-59 years; 2002-2014) from the ongoing Oregon Sudden Unexpected Death Study (catchment population ∼1 million), and archived 12-lead electrocardiograms recorded prior to the SCA event were compared with those of geographic controls. Short-term HRV was calculated from digitized 10-second electrocardiograms by using established methods. We analyzed 313 subjects (mean age 52.0 ± 5.5 years; 216 men, 69.0%) and compared 4 groups: 111 diabetic (49 cases, 62 controls) and 202 nondiabetic (80 cases, 122 controls) subjects. RESULTS: Analysis of covariance showed an absence of the expected interaction between HRV and HR (HRV-HR) in diabetic patients with SCA (regression slope -0.008; 95% confidence interval -0.023 to 0.0071; P = .26). This finding, unique to this population of diabetic patients with SCA, was not detected using traditional HRV measures. CONCLUSION: By incorporating resting HR in this analysis, we observed that this population of diabetic patients with SCA had loss of the expected HRV-HR relationship. This potentially novel noninvasive risk measurement warrants further investigation, especially at the level of the individual patient.

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.

Health Insurance Expansion and Incidence of Out-of-Hospital Cardiac Arrest: A Pilot Study in a US Metropolitan Community.

BACKGROUND: Health insurance has many benefits including improved financial security, greater access to preventive care, and better self-perceived health. However, the influence of health insurance on major health outcomes is unclear. Sudden cardiac arrest prevention represents one of the major potential benefits from health insurance, given the large impact of sudden cardiac arrest on premature death and its potential sensitivity to preventive care. METHODS AND RESULTS: We conducted a pre-post study with control group examining out-of-hospital cardiac arrest (OHCA) among adult residents of Multnomah County, Oregon (2015 adult population 636 000). Two time periods surrounding implementation of the Affordable Care Act were evaluated: 2011-2012 ("pre-expansion") and 2014-2015 ("postexpansion"). The change in OHCA incidence for the middle-aged population (45-64 years old) exposed to insurance expansion was compared with the elderly population (age ≥65 years old) with constant near-universal coverage. Rates of OHCA among middle-aged individuals decreased from 102 per 100 000 (95% CI: 92-113 per 100 000) to 85 per 100 000 (95% CI: 76-94 per 100 000), P value 0.01. The elderly population experienced no change in OHCA incidence, with rates of 275 per 100 000 (95% CI: 250-300 per 100 000) and 269 per 100 000 (95% CI: 245-292 per 100 000), P value 0.70. CONCLUSIONS: Health insurance expansion was associated with a significant reduction in OHCA incidence. Based on this pilot study, further investigation in larger populations is warranted and feasible.

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.

Syncope and risk of sudden cardiac arrest in coronary artery disease.

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±13.8years, 66.9% male) and 746 controls (66.7±11.7years, 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 >5years 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.

Polymorphisms in the GNAS Gene as Predictors of Ventricular Tachyarrhythmias and Sudden Cardiac Death: Results From the DISCOVERY Trial and Oregon Sudden Unexpected Death Study.

BACKGROUND: Population-based studies suggest that genetic factors contribute to sudden cardiac death (SCD). METHODS AND RESULTS: In the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy-arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single-nucleotide polymorphisms (SNPs) in 3 genes coding G-protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter-defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, a community-based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11-1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18-2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26-1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05-1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10-2.13]) genetic models. CONCLUSIONS: GNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community-based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00478933.

Tpeak-to-Tend interval corrected for heart rate: A more precise measure of increased sudden death risk?

BACKGROUND: The Tpeak to Tend (Tpe) interval on the 12-lead electrocardiogram predicts an increased risk of sudden cardiac arrest (SCA). There is controversy over whether Tpe would be more useful if corrected for heart rate (Tpec). OBJECTIVES: We evaluated whether the predictive value of Tpe for SCA improves with heart rate correction and sought to determine an optimal cutoff value for Tpec in the context of SCA risk. METHODS: Cases of SCA (n = 628; mean age 66.4 ± 14.5 years; n = 416, 66.2% men) from the Oregon Sudden Unexpected Death Study with an archived electrocardiogram available prior and unrelated to the SCA event were analyzed. Comparisons were made with control subjects (n = 819; mean age 66.7 ± 11.5 years; n = 559, 68.2% men). The Tpe interval was corrected for heart rate using Bazett (TpecBa) and Fridericia (TpecFd) formulas, and the predictive value of Tpec for SCA was evaluated using logistic regression models. RESULTS: The area under the curve for Tpec predicting SCA improved with both correction formulas. TpecBa and TpecFd were shown to have an area under the curve of 0.695 and 0.672, respectively, as compared with a baseline of 0.601 with an uncorrected Tpe. A TpecBa value of >90 ms was predictive of SCA, independent of age, sex, comorbidities, QRS duration, corrected QT interval, and severely reduced left ventricular ejection fraction (≤35%; odds ratio 2.8; 95% confidence interval 1.92-4.17; P < .0001). CONCLUSION: Correcting Tpe for heart rate, using either the Bazett or the Fridericia formula, improved the independent predictive value of this marker for the assessment of SCA risk. Prolongation of TpecBa beyond 90 ms was associated with a nearly 3-fold increased risk of SCA.