Audrey Uy-Evanado

Prolonged Tpeak-to-Tend Interval on the Resting ECG Is Associated With Increased Risk of Sudden Cardiac Death

Background— Early studies indicate that prolongation of the interval between the peak and the end of the T wave (Tpeak to Tend [TpTe]) on the 12-lead ECG is a marker of ventricular arrhythmogenesis. However, community-based studies have not been conducted. Methods and Results— TpTe and other ECG predictors were evaluated in the ongoing Oregon Sudden Unexpected Death Study based in the Portland, Oregon, metropolitan area using a case-control design. Cases of sudden cardiac death (SCD) (n=353; mean age, 66.6 years; 95% CI, 65.1 to 68.1 years; 67% men) were compared with living controls with coronary artery disease (n=342; mean age, 64.7 years; 95% CI, 63.4 to 66.0 years; 69% men) from the same region. Analysis of TpTe and selected ECG intervals was limited to sinus rhythm 12-lead ECGs. For cases, these were obtained before and unrelated to SCD. Independent-samples t tests and multiple logistic regression were used. Mean TpTe was significantly greater in cases (89.4 ms; 95% CI, 87.7 to 91.2 ms; P<0.0001) than in controls (76.1 ms; 95% CI, 74.8 to 77.4 ms). The other ECG intervals (corrected QT interval [QTc], QRS duration [QRSD], and TpTe/QT ratio) also were significantly prolonged among cases versus controls (P⩽0.01). TpTe remained a significant predictor of SCD after adjusting for age, sex, QTc, QRSD, and left ventricular function. Odds of SCD increased more with a 1-SD increase in TpTe (12 ms) among subjects with prolonged QRSD (odds ratio, 3.49; 95% CI, 2.06 to 5.91) than with a 1-SD increase in TpTe among subjects with normal QRSD (odds ratio, 1.96; 95% CI, 1.65 to 2.32). TpTe remained significantly associated with SCD in subjects with normal QTc. Conclusions— Prolongation of the TpTe interval measured in lead V5 was independently associated with SCD, with particular utility when the QTc was normal or not measurable because of prolonged QRSD.

Public Health Burden of Sudden Cardiac Death in the United States

Background—Sudden cardiac death (SCD) is a leading cause of death in the United States, but the relative public health burden is unknown. We estimated the burden of premature death from SCD and compared it with other diseases. Methods and Results—Analyses were based on the following data sources (using most recent sources that provided appropriately stratified data): (1) leading causes of death among men and women from 2009 US death certificate reporting; (2) individual cancer mortality rates from 2008 death certificate reporting from the Centers for Disease Control and Prevention’s National Program of Cancer Registries; (3) county, state, and national population data for 2009 from the US Census Bureau; and (4) SCD rates from the Oregon Sudden Unexpected Death Study (SUDS) population-based surveillance study of SCD between 2002 and 2004. Cases were identified from multiple sources in a prospectively designed surveillance program. Incidence, counts, and years of potential life lost for SCD and other major diseases were compared. The age-adjusted national incidence of SCD was 60 per 100 000 population (95% confidence interval, 54–66 per 100 000). The burden of premature death for men (2.04 million years of potential life lost; 95% uncertainty interval, 1.86–2.23 million) and women (1.29 million years of potential life lost; 95% uncertainty interval, 1.13–1.45 million) was greater for SCD than for all individual cancers and most other leading causes of death. Conclusions—The societal burden of SCD is high relative to other major causes of death. Accordingly, improved national surveillance with the goal of optimizing and monitoring SCD prevention and treatment should be a high priority.

Women Have a Lower Prevalence of Structural Heart Disease as a Precursor to Sudden Cardiac Arrest: The Ore-SUDS (Oregon Sudden Unexpected Death Study)

OBJECTIVES Our aim was to utilize a community-based approach to identify sex-related differences in risk factors for sudden cardiac arrest (SCA). BACKGROUND There are significant sex-based differences in prevalence and manifestation of SCA. Any differences related to predictors of SCA in women versus men are likely to have implications for risk stratification and prevention. METHODS The Ore-SUDS (Oregon Sudden Unexpected Death Study) is an ongoing prospective investigation of SCA in the Portland, Oregon, metropolitan area (population approximately 1 million). All cases meeting criteria for SCA were ascertained using multiple sources. Medical records were reviewed to identify clinical conditions that may contribute to SCA risk, and comparisons were made between male and female SCA cases using Pearsons chi-square tests for categorical variables, t tests for continuous variables, and multivariate logistic regression analysis. RESULTS During 2002 to 2007, 1,568 adult SCA cases were identified (women 36% vs. men 64%; p < 0.0001) and women were older (mean age 71 +/- 14 years vs. 65 +/- 14 years, p < 0.0001). There were no significant sex differences in prevalence of obesity, dyslipidemia, history of chronic obstructive pulmonary disease/asthma, left ventricular (LV) hypertrophy, or history of myocardial infarction. In multivariate analysis, women were significantly less likely to have severe LV dysfunction (odds ratio: 0.51; 95% confidence interval: 0.31 to 0.84) or previously recognized coronary artery disease (odds ratio: 0.34; 95% confidence interval: 0.20 to 0.60) compared with men. CONCLUSIONS Women were significantly less likely than men to have a diagnosis of structural heart disease (LV dysfunction or coronary artery disease) before SCA. These findings suggest that fewer women may be eligible for prophylactic implantable cardioverter-defibrillator placement based on current guidelines and therefore may not have equal opportunity for prevention. Enhancement of SCA risk stratification may have even higher importance for women.

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).

Population-based analysis of sudden death in children: The Oregon Sudden Unexpected Death 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.

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.

Factors Associated With Pulseless Electric Activity Versus Ventricular Fibrillation The Oregon Sudden Unexpected Death Study

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 &khgr;2 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.

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.

Frequency and Determinants of ICD 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.

Prolonged QRS duration on the resting ECG is associated with sudden death risk in coronary disease, independent of prolonged ventricular repolarization

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.