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.

Left Ventricular Geometry and Risk of Sudden Cardiac Arrest in Patients With Severely Reduced Ejection Fraction.

BACKGROUND: Recent reports indicate that specific left ventricular (LV) geometric patterns predict recurrent ventricular arrhythmias in patients with implantable cardioverter-defibrillators and reduced left ventricular ejection fraction (LVEF). However, this relationship has not been evaluated among patients at risk of sudden cardiac arrest (SCA) in the general population. METHODS AND RESULTS: Adult SCA cases from the Oregon Sudden Unexpected Death Study were compared with geographic controls with no prior history of SCA. Archived echocardiograms performed closest and prior to the SCA event were reviewed. LV geometry was defined as normal (normal LV mass index [LVMI] and relative wall thickness [RWT]), concentric remodeling (normal LVMI and increased RWT), concentric hypertrophy (increased LVMI and RWT), or eccentric hypertrophy (increased LVMI and normal RWT). Analysis was restricted to those with LVEF ≤40%. A total of 246 subjects were included in the analysis. SCA cases (n=172, 68.6±13.3 years, 78% male), compared to controls (n=74, 66.8±12.1 years, 73% male), had lower LVEF (29.4±7.9% vs 30.8±6.3%, P=0.021). Fewer cases presented with normal LV geometry (30.2% vs 43.2%, P=0.048) and more with eccentric hypertrophy (40.7% vs 25.7%, P=0.025). In a multivariate model, eccentric hypertrophy was independently predictive of SCA (OR 2.15, 95% CI 1.08-4.29, P=0.03). CONCLUSIONS: Eccentric LV hypertrophy was independently associated with increased risk of SCA in subjects with EF ≤40%. These findings, now consistent between device-implanted and non-implanted populations, indicate the potential of improving SCA risk stratification from the same noninvasive echocardiogram at no additional cost.

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.

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.

Mitral valve prolapse and sudden cardiac arrest in the community.

BACKGROUND: Mitral valve prolapse (MVP) is relatively common in the general population with recently reported prevalence of 1% and familial clustering (Framingham Heart Study). However, its association with ventricular arrhythmias and sudden cardiac arrest (SCA) remains controversial. OBJECTIVES: The purpose of this study was to characterize the frequency and clinical profile of patients with MVP who suffer SCA in the community. METHODS: Patients with SCA cases were prospectively identified in the population-based Oregon Sudden Unexpected Death Study (population ~1 million). The presence of MVP was identified from echocardiograms recorded prior but unrelated to the SCA event. The detailed clinical profile of patients with SCA and MVP was compared with that of SCA patients without MVP to identify potential differences. RESULTS: A total of 729 SCA patients were evaluated over a 12-year period (mean age 69.5 ± 14.8 years; 64.6% men). MVP was observed in 17 (2.3%) prior to the SCA event (95% confidence interval 1.2%-3.4%). Mitral regurgitation was present in 14 SCA patients with MVP (82.3%) and was moderate or severe in 10 (58.8%). Compared with SCA patients without MVP, SCA patients with MVP were younger (mean age 60.9 ± 16.4 years vs 69.7 ± 14.7 years; P = .02), with fewer risk factors (diabetes 5.9% vs 46.4%; P = .001; hypertension 41.2% vs 78.9%; P = .001) or known coronary disease (29.4% vs 65.6%; P < .001). CONCLUSION: MVP was observed in a small proportion (2.3%) of SCA patients in the general population, suggesting a low risk overall. Since SCA patients with MVP were characterized by younger age and relatively low cardiovascular comorbidity, a focus on imaging for valve structure/insufficiency as well as genetics could aid future risk stratification approaches.

T-wave reversal in the augmented unipolar right arm electrocardiographic lead is associated with increased risk of sudden death.

BACKGROUND: Repolarization abnormalities are associated with ventricular arrhythmias, and published studies report that a reversal of T wave polarity (positive or flat T wave) in lead aVR may be linked to increased cardiovascular mortality. We evaluated whether a positive or flat T wave in aVR is a risk marker for sudden cardiac death (SCD). METHODS: SCD cases from the Oregon Sudden Unexpected Death Study (catchment population ~1 million) were compared to geographic controls with coronary artery disease and no history of SCD. Archived electrocardiograms performed prior and unrelated to the SCD event were evaluated. RESULTS: SCD cases (n = 691, 67.6 ± 14.9 years, 69% male) were more likely than controls (n = 663, 66.2 ± 11.6 years, 67% male) to have diabetes (40 vs 32%; p < 0.01), left ventricular ejection fraction (LVEF) ≤35% (27 vs 11 %; p < 0.01), prolonged QTc (≥450 ms; 54 vs 28%; p < 0.01) and positive (19 vs 13%; p < 0.01) or flat T wave (14 vs 7%; p < 0.01) in aVR. On multivariable analysis, a positive/flat T wave in aVR was independently associated with SCD (OR 1.9, 95% CI 1.3-2.8, p < 0.01). However, a positive T wave alone lost statistical significance in patients with LVEF ≤ 35% and QTc ≥ 450 ms. In a subgroup analysis among patients with normal LVEF, QTc, and no diabetes, a positive T wave in aVR (but not a flat T wave) remained associated with SCD (OR 2.8, 95% CI 1.2-6.1, p < 0.01). CONCLUSIONS: A positive or flat T wave in lead aVR was associated with SCD in subsets of patients. This simple ECG marker in this often-ignored lead may contribute to enhancement of SCD risk stratification, and warrants further evaluation.

Delayed intrinsicoid deflection of the QRS complex is associated with sudden cardiac arrest.

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

Occupation and risk of sudden death in a United States community: a case-control analysis.

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.

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.

Cumulative effects of common genetic variants on risk of sudden cardiac death.

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

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.

QRS fragmentation and sudden cardiac death in the obese and overweight.

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.

Chronic Obstructive Pulmonary Disease and Risk of Sudden Cardiac Death.

OBJECTIVES: The purpose of this study was to determine whether chronic obstructive pulmonary disease (COPD) is associated with sudden cardiac death (SCD) in the community. BACKGROUND: COPD is linked to cardiovascular mortality; an association with SCD has not been systematically investigated in the general population. METHODS: In the Oregon Sudden Unexpected Death Study (approximately 1 million population), adult SCD case subjects were compared with geographic control subjects with coronary artery disease. Detailed clinical and electrocardiographic risk marker information was obtained from medical records. The association of COPD with SCD in the overall population and in a propensity score-matched dataset was assessed with logistic models. RESULTS: SCD case subjects (n = 728; age 69.9 ± 13.7 years) were more likely than control subjects (n = 548; age 67.2 ± 11.3 years) to have left ventricular ejection fraction ≤35% (27.5% vs. 12.0%; p < 0.0001), COPD (30.8% vs. 12.8%, p < 0.0001), diabetes mellitus (47.7% vs. 31.8%; p < 0.0001), use short-acting beta-2 agonist agents (SBAs) (22.3% vs. 12.6%; p < 0.0001), and less likely to use beta-blockers (60.6% vs. 66.4%; p = 0.03). In multivariable analysis, COPD was significantly associated with SCD (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.4 to 3.5; p < 0.001). There was no significant interaction between COPD and medications, but an interaction was identified between SBAs and beta-blockers (p = 0.04); SBAs were strongly associated with SCD in subjects not taking beta-blockers (OR: 3.3; 95% CI: 1.4 to 7.7; p = 0.005) but not in those taking beta-blockers (OR: 1.3; 95% CI: 0.7 to 2.3; p = 0.39). The COPD-SCD association was maintained in a propensity score-matched analysis. CONCLUSIONS: COPD is associated with SCD risk in the community independent of medications, electrocardiographic risk markers, and left ventricular ejection fraction. Among other mechanisms, pro-arrhythmogenic right ventricular remodeling and systemic inflammation warrant further investigation.

Electrocardiographic Markers and the Left Ventricular Ejection Fraction have Cumulative Effects on Risk of Sudden Cardiac Death.

OBJECTIVES: To assess potential improvement in SCD risk prediction by adding selected risk markers from the 12-lead ECG to measurement of the left ventricular ejection fraction (LVEF). BACKGROUND: Novel strategies to improve risk stratification for sudden cardiac death (SCD) are needed. Given the modest odds associated with most individual risk markers, combining multiple markers may be a useful approach. METHODS: From the ongoing Oregon Sudden Unexpected Death Study, SCD cases with pre-event LVEF available were compared to matched control subjects with coronary artery disease. Resting heart rate, QRS duration (QRSD), and JTc intervals were measured from archived ECGs prior and unrelated to the SCD event. Independent odds of SCD for individual and combined ECG markers were calculated. RESULTS: SCD cases (n= 317; 67.9 ± 12.9 years) were more likely than controls (n=317; 67.9 ± 12.8 years) to have LVEF ≤ 35% (26% vs. 11%). Mean heart rate, QRSD, and JTc were significantly higher in cases (all p<0.0001). In adjusted analyses, higher heart rate [OR 2.6 (1.8 - 3.7)], QRSD [OR 1.5 (1.0 - 2.5)] and JTc [OR 2.3 (1.6 - 3.4)] were independently associated with SCD. When ECG markers were combined, SCD odds progressively increased with one [OR 3.4 (2.1 - 5.4)] and ≥ 2 elevated markers [OR 6.3 (3.3 - 12.1)]. Addition of ECG markers to an adjusted model with LVEF improved discrimination (C statistic 0.724 vs. 0.642) and net reclassification (by 22.7%) (p<0.0001). CONCLUSIONS: Combining selected 12-lead ECG markers with LVEF improves SCD risk prediction, and warrants further investigation in prospective studies.

Ischemic heart disease diagnosed before sudden cardiac arrest is independently associated with improved survival.

BACKGROUND: Sudden cardiac arrest (SCA) is a significant public health problem, and rates of survival after resuscitation remain well below 10%. While several resuscitation-related factors are consistently associated with survival from SCA, the impact of specific comorbid conditions has not been assessed. METHODS AND RESULTS: The Oregon Sudden Unexpected Study is an ongoing, multisource, community-based study in Portland, Oregon. Patients with SCA who underwent attempted resuscitation between 2002 and 2012 were included in this analysis if there were both arrest and prearrest medical records available. Information from the emergency medical services system, medical examiner, public health division, hospitals, and clinics was used to adjudicate SCA, evaluate comorbidities, and identify medical treatments. Univariate and multivariate analyses were performed to investigate the influence of prearrest comorbidities on survival to hospital discharge. Among 1466 included patients, established resuscitation-related predictors (Utstein factors) were associated with survival, consistent with prior reports. When a panel of prearrest comorbidities was evaluated along with Utstein factors, recognized coronary artery disease was significantly associated and predicted higher odds of survival (unadjusted odds ratio 1.5, P<0.001; adjusted odds ratio 1.5, P=0.02). In multivariable logistic models, prearrest coronary artery disease modified the survival effects of bystander cardiopulmonary resuscitation, but did not modify other Utstein factors. CONCLUSIONS: An established diagnosis of coronary artery disease was associated with 50% higher odds of survival from resuscitated SCA after adjustment for all arrest-related predictors. These findings raise novel potential mechanistic insights into survival after SCA, while highlighting the importance of early recognition and treatment of coronary artery disease.

Left ventricular diameter and risk stratification for sudden cardiac death.

BACKGROUND: Left ventricular (LV) diameter is routinely measured on the echocardiogram but has not been jointly evaluated with the ejection fraction (EF) for risk stratification of sudden cardiac death (SCD). METHODS AND RESULTS: From a large ongoing community-based study of SCD (The Oregon Sudden Unexpected Death Study; population ≈1 million), SCD cases were compared with geographic controls. LVEF and LV diameter, measured using the LV internal dimension in diastole (categorized as normal, mild, moderate, or severe dilatation using American Society of Echocardiography definitions) were assessed from echocardiograms prior but unrelated to the SCD event. Cases (n=418; 69.5±13.8 years), compared with controls (n=329; 67.7±11.9 years), more commonly had severe LV dysfunction (EF ≤35%; 30.5% versus 18.8%; P<0.01) and larger LV diameter (52.2±10.5 mm versus 49.7±7.9 mm; P<0.01). Moderate or severe LV dilatation (16.3% versus 8.2%; P=0.001) and severe LV dilatation (8.1% versus 2.1%; P<0.001) were significantly more frequent in cases. In multivariable analysis, severe LV dilatation was an independent predictor of SCD (odds ratio 2.5 [95% CI 1.03 to 5.9]; P=0.04). In addition, subjects with both EF ≤35% and severe LV dilatation had higher odds for SCD compared with those with low EF only (odds ratio 3.8 [95% CI 1.5 to 10.2] for both versus 1.7 [95% CI 1.2 to 2.5] for low EF only), suggesting that severe LV dilatation additively increased SCD risk. CONCLUSION: LV diameter may contribute to risk stratification for SCD independent of the LVEF. This readily available echocardiographic measure warrants further prospective evaluation.

Sex hormone levels in patients with sudden cardiac arrest.

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.

The association between atrial fibrillation and sudden cardiac death: the relevance of heart failure.

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.