Lack of Prognostic Value of T-Wave Alternans for Implantable Cardioverter-Defibrillator Benefit in Primary Prevention.

BACKGROUND: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention. METHODS AND RESULTS: In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 µV and <60 µV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 µV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P=0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit. CONCLUSIONS: T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.

Prognostic significance of beat-to-beat variability of spatial heterogeneity of repolarization analyzed from a 5-minute resting electrocardiogram in coronary artery disease.

BACKGROUND: Data on the prognostic significance of temporal variability of spatial heterogeneity of electrocardiographic repolarization in coronary artery disease (CAD) are limited. OBJECTIVE: The purpose of this study was to evaluate the prognostic value of temporal variability of T-wave morphology analyzed from a 5-minute resting electrocardiogram in CAD. METHODS: The standard deviation (SD) of T-wave morphology dispersion (TMD-SD) and the SD of total cosine R-to-T were analyzed on a beat-to-beat basis from a 5-minute period of the standard resting 12-lead electrocardiogram obtained before the clinical stress test in 1702 patients with angiographically verified CAD and well-preserved left ventricular function. RESULTS: During an average of 8.7 ± 2.2 years of follow-up, 60 patients experienced sudden cardiac death/arrest (SCD/SCA) (3.5%), 69 patients nonsudden cardiac death (NSCD) (4.1%), and 161 patients noncardiac death (9.5%). TMD-SD was significantly higher in patients who experienced SCD/SCA than in other patients (1.72 ± 2.00 vs 1.12 ± 1.75; P = .01) and higher in patients who succumbed to NSCD than in other patients (1.57 ± 1.74 vs 1.12 ± 1.76; P = .04), but it did not differ significantly between patients who experienced noncardiac death and those without such an event (1.16 ± 1.42 vs 1.14 ± 1.79; P = .86). In the Cox multivariable hazards model, TMD-SD retained its significant association with the risk of SCD/SCA (hazard ratio 1.119; 95% confidence interval 1.015-1.233; P = .024) but not with the risk of NSCD (hazard ratio 1.089; 95% confidence interval 0.983-1.206; P = .103). CONCLUSION: TMD-SD is independently associated with the long-term risk of SCD/SCA in patients with CAD.

Association of electrocardiographic spatial heterogeneity of repolarization and spatial heterogeneity of atrial depolarization with left ventricular fibrosis.

AIMS: To evaluate the relationship between spatial heterogeneity of electrocardiographic repolarization and spatial heterogeneity of atrial depolarization with arrhythmic substrate represented by left ventricular fibrosis. METHODS AND RESULTS: We assessed the associations of T- and P-wave morphology parameters analysed from the standard 12-lead electrocardiograms with left ventricular fibrosis in 378 victims of unexpected sudden cardiac death (SCD) who underwent medico-legal autopsy. Based on autopsy findings, the SCD victims were categorized into four different groups according to different stages of severity of left ventricular fibrosis (substantial fibrosis, moderate patchy fibrosis, scattered mild fibrosis, no fibrosis). T-wave and P-wave area dispersion (TWAd: 0.0841 ± 0.496, 0.170 ± 0.492, 0.302 ± 404, 0.296 ± 0.476, P = 0.008; PWAd: 0.574 ± 0.384, 0.561 ± 0.367, 0.654 ± 0.281, 0.717 ± 0.257, P = 0.011, respectively; low values abnormal), non-dipolar components of T-wave and P-wave morphology (T_NonDipolarABS: 0.0496 ± 0.0377, 0.0571 ± 0.0487, 0.0432 ± 0.0476, 0.0380 ± 0.0377, P = 0.027; P_NonDipolarABS: 0.0132 ± 0.0164, 0.0130 ± 0.0135, 0.0092 ± 0.0117, 0.0069 ± 0.00472, P = 0.005, respectively, high values abnormal), T-wave morphology dispersion (TMD: 45.9 ± 28.3, 40.5 ± 25.8, 35.5 ± 24.9, 33.0 ± 24.6, P = 0.030, respectively, high values abnormal), and P-wave heterogeneity (PWH: 20.0 ± 9.44, 19.7 ± 8.87, 17.9 ± 9.78, 15.4 ± 4.60, P = 0.019, respectively, high values abnormal) differed significantly between the groups with different stages of left ventricular fibrosis. After adjustment with heart weight, T_NonDipolarABS [standardized ß (sß) = 0.131, P = 0.014], PWAd (sß = -0.161, P = 0.003), P_NonDipolarABS (sß = 0.174, P = 0.001), and PWH (sß = 0.128, P = 0.015) retained independent association, and TWAd (sß = -0.091, P = 0.074) and TMD (sß = 0.097, P = 0.063) tended to retain their association with the degree of myocardial fibrosis. CONCLUSION: Our findings suggest that abnormal values of T- and P-wave morphology are associated with arrhythmic substrate represented by ventricular fibrosis partly explaining the mechanism behind their prognostic significance.

Prognostic value of P-wave morphology in general population.

AIMS: To evaluate the prognostic significance of novel P-wave morphology descriptors in general population. METHODS AND RESULTS: Novel P-wave morphology variables were analyzed from orthogonal X-, Y-, Z-leads of the digitized electrocardiogram using a custom-made software in 6906 middle-aged subjects of the Mini-Finland Health Survey. A total of 3747 (54.3%) participants died during the follow-up period of 24.3 ± 10.4 years; 379 (5.5%) of the study population succumbed to sudden cardiac death (SCD), 928 (13.4%) to non-SCD (NSCD) and 2440 (35.3%) patients to non-cardiac death (NCD). In univariate comparisons, most of the studied P-wave morphology parameters had a significant association with all modes of death (P from <0.05 to <0.001). After relevant adjustments in the Cox multivariate hazards model, P-wave morphology dispersion (PMD) still tended to predict SCD [hazard ratio (HR): 1.006, 95% confidence interval (CI): 1.000-1.012, P = 0.05) but not NSCD (HR: 0.999, 95% CI: 0.995-1.003, P = 0.68) or NCD (HR: 0.999, 95% CI: 0.997-1.001, P = 0.44). The P-wave maximum amplitude in the lead Z (P-MaxAmp-Z) predicted SCD even after multivariate adjustments (HR: 1.010, 95% CI: 1.005-1.015, P = 0.0002) but also NSCD (HR: 1.005, 95% CI: 1.002-1.009, P = 0.0005) and NCD (HR: 1.002, 95% CI: 1.000-1.005, P = 0.03). CONCLUSION: Abnormalities of P-wave morphology are associated with the risk of all modes of death in general population. After relevant adjustments, PMD was still closely associated with the risk of SCD but not with NSCD or NCD. P-MaxAmp-Z predicted SCD even after adjustments, however, it also retained its association with NSCD and NCD.

Association of atrial depolarization variability and cardiac autonomic regulation with sudden cardiac death in coronary artery disease.

AIMS: To evaluate the prognostic significance of the temporal variability of P-wave morphology, specifically in relation to cardiac autonomic regulation. METHODS AND RESULTS: We analyzed the standard deviation of P-wave residuum (PWRSD) from five consecutive beats of the standard 12-lead ECG in 1236 patients with angiographically verified coronary artery disease (CAD). We evaluated the prognostic value of PWRSD, of PWRSD and PWR in relation to the 24 h standard deviation of normal-to-normal intervals (PWRSD/SDNN and PWR/SDNN). After 8.7 ± 2.2 years of follow-up on average, 43 patients (3.5%) experienced sudden cardiac death (SCD) or were resuscitated from sudden cardiac arrest (SCA), 34 (2.8%) succumbed to non-sudden cardiac death (NSCD) and 113 (9.1%) to non-cardiac death (NCD). In the Cox regression analysis, PWRSD (≥0.002727) had a significant univariate (uv) [hazard ratio (HR): 4.27, 95% confidence interval (CI): 2.26-8.08, P = 0.000008] and multivariate (mv) (HR: 2.58, 95% CI: 1.31-5.08, P = 0.006) association with SCD/SCA but not with NSCD (uv P = 0.76, mv P = 0.33) or NCD (uv P = 0.57, mv P = 0.66). All the studied P-morphology parameters retained a significant association with the risk of SCD/SCA after relevant adjustment (mv P-values from 0.00003 to <0.05) but not with NSCD or NCD. When dichotomized PWRSD, PWR, PWRSD/SDNN, and PWR/SDNN were added to the clinical risk model for SCD/SCD, the C-index increased from 0.799 to 0.834 and integrated discrimination index and net reclassification index improved significantly (P < 0.001). CONCLUSION: Variability of P-morphology representing temporo-spatial heterogeneity of atrial depolarization, specifically when combined with cardiac autonomic regulation, independently predicts the risk of SCD in patients with CAD.

Poor R-wave progression as a predictor of sudden cardiac death in the general population and subjects with coronary artery disease.

BACKGROUND: Poor R-wave progression (PRWP) is a common clinical finding on the standard 12-lead electrocardiogram (ECG), but its prognostic significance is unclear. OBJECTIVE: The purpose of this study was to examine the prognosis associated with PRWP in terms of sudden cardiac death (SCD), cardiac death, and all-cause mortality in general population subjects with and without coronary artery disease (CAD). METHODS: Data and 12-lead ECGs were collected from a Finnish general population health examination survey conducted during 1978-1980 with follow-up until 2011. The study population consisted of 6854 subjects. Main end points were SCD, cardiac death, and all-cause mortality. PRWP was defined as R-wave amplitude ≤ 0.3 mV in lead V3 and R-wave amplitude in lead V2 ≤ R-wave amplitude in lead V3. RESULTS: PRWP occurred in 213 subjects (3.1%). During the follow-up period of 24.3 ± 10.4 years, 3723 subjects (54.3%) died. PRWP was associated with older age, higher prevalence of heart failure and CAD, and ß-blocker medication. In multivariate analyses, PRWP was associated with SCD (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.34-3.39), cardiac death (HR 1.75; 95% CI 1.35-2.15), and all-cause mortality (HR 1.29; 95% CI 1.08-1.54). In the subgroup with CAD, PRWP had a stronger association with cardiac mortality (HR 1.71; 95% CI 1.19-2.46) than in the subgroup without CAD, while the association with SCD was significant only in the subgroup with CAD (HR 2.62; 95% CI 1.38-4.98). CONCLUSION: PRWP was associated with adverse prognosis in the general population and with SCD in subjects with CAD.

Q waves are the strongest electrocardiographic variable associated with primary prophylactic implantable cardioverter-defibrillator benefit: a prospective multicentre study.

AIM: The association of standard 12-lead electrocardiogram (ECG) markers with benefits of the primary prophylactic implantable cardioverter-defibrillator (ICD) has not been determined in the contemporary era. We analysed traditional and novel ECG variables in a large prospective, controlled primary prophylactic ICD population to assess the predictive value of ECG in terms of ICD benefit. METHODS AND RESULTS: Electrocardiograms from 1477 ICD patients and 700 control patients (EU-CERT-ICD; non-randomized, controlled, prospective multicentre study; ClinicalTrials.gov Identifier: NCT02064192), who met ICD implantation criteria but did not receive the device, were analysed. The primary outcome was all-cause mortality. In ICD patients, the co-primary outcome of first appropriate shock was used. Mean follow-up time was 2.4 ± 1.1 years to death and 2.3 ± 1.2 years to the first appropriate shock. Pathological Q waves were associated with decreased mortality in ICD patients [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.35-0.84; P < 0.01] and patients with pathological Q waves had significantly more benefit from ICD (HR 0.44, 95% CI 0.21-0.93; P = 0.03). QTc interval increase taken as a continuous variable was associated with both mortality and appropriate shock incidence, but commonly used cut-off values, were not statistically significantly associated with either of the outcomes. CONCLUSION: Pathological Q waves were a strong ECG predictor of ICD benefit in primary prophylactic ICD patients. Excess mortality among Q wave patients seems to be due to arrhythmic death which can be prevented by ICD.

Prognostic significance of flat T-waves in the lateral leads in general population.

BACKGROUND: Negative T-waves are associated with sudden cardiac death (SCD) risk in the general population. Whether flat T-waves also predict SCD is not known. The aim of the study was to examine the clinical characteristics and risk of SCD in general population subjects with flat T-waves. METHODS: We examined the electrocardiograms of 6750 Finnish general population adults aged ≥30 years and classified the subjects into 3 groups: 1) negative T-waves with an amplitude ≥0.1 mV in ≥2 of the leads I, II, aVL, V4-V6, 2) negative or positive low amplitude T-waves with an amplitude <0.1 mV and the ratio of T-wave and R-wave <10% in ≥2 of the leads I, II, aVL, V4-V6, and 3) normal positive T-waves (not meeting the aforesaid criteria). The association between T-wave classification and SCD was assessed during a 10-year follow-up. RESULTS: A total of 215 (3.2%) subjects had negative T-waves, 856 (12.7%) flat T-waves, and 5679 (84.1%) normal T-waves. Flat T-wave subjects were older and had more often cardiovascular morbidities compared to normal T-wave subjects, while negative T-wave subjects were the oldest and had most often cardiovascular morbidities. After adjusting for multiple factors, both flat T-waves (hazard ratio [HR] 1.81; 95% confidence interval [CI] 1.13-2.91) and negative T-waves (HR 3.27; 95% CI 1.85-5.78) associated with SCD. CONCLUSIONS: Cardiovascular risk factors and disease are common among subjects with flat T-waves, but these minor T-wave abnormalities are also independently associated with increased SCD risk.

Temporal variability of T-wave morphology and risk of sudden cardiac death in patients with coronary artery disease.

BACKGROUND: The possible relationship between temporal variability of electrocardiographic spatial heterogeneity of repolarization and the risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD) is not completely understood. METHODS: The standard deviation of T-wave morphology dispersion (TMD-SD), of QRST angle (QRSTA-SD), and of T-wave area dispersion (TW-Ad-SD) were analyzed on beat-to-beat basis from 10 min period of the baseline electrocardiographic recording in ARTEMIS study patients with angiographically verified CAD. RESULTS: After on average of 8.6 ± 2.3 years of follow-up, a total of 66 of the 1,678 present study subjects (3.9%) had experienced SCD or were resuscitated from sudden cardiac arrest (SCA). TMD-SD was most closely associated with the risk for SCD and was significantly higher in patients who had experienced SCD/SCA compared with those who remained alive (3.61 ± 2.83 vs. 2.64 ± 2.52, p = .008, respectively), but did not differ significantly between the patients who had experienced non-SCD (n = 71, 4.2%) and those who remained alive (3.20 ± 2.73 vs. 2.65 ± 2.53, p = .077, respectively) or between the patients who succumbed to non-cardiac death (n = 164, 9.8%) and those who stayed alive (2.64 ± 2.17 vs. 2.68 ± 2.58, p = .853). After adjustments with relevant clinical risk indicators of SCD/SCA, TMD-SD still predicted SCD/SCA (HR 1.107, 95% CIs 1.035-1.185, p = .003). CONCLUSIONS: Temporal variability of electrocardiographic spatial heterogeneity of repolarization represented by TMD-SD independently predicts long-term risk of SCD/SCA in patients with CAD.

Increased Beat-to-Beat Variability of T-Wave Heterogeneity Measured From Standard 12-Lead Electrocardiogram Is Associated With Sudden Cardiac Death: A Case-Control Study.

INTRODUCTION: The prognostic significance of beat-to-beat variability of spatial heterogeneity of repolarization measured from standard 12-lead ECG is not well-understood. METHODS: We measured the short-term variability of repolarization parameters, such as T-wave heterogeneity in leads V4-V6 (TWH) and QT interval (QT), from five consecutive beats of previously recorded standard 12-lead ECG in 200 victims of unexpected sudden cardiac death (SCD) confirmed to be due to complicated atherosclerotic coronary artery disease (CAD) in medico-legal autopsy and 200 age- and sex-matched controls with angiographically confirmed CAD. The short-term variability of repolarization heterogeneity was defined as the standard deviation (SD) of the measured repolarization parameters. All ECGs were in sinus rhythm, and no premature ventricular contractions were included in the measured segment. RESULTS: TWH-SD and QT-SD were significantly higher in SCD victims than in subjects with CAD (6.9 ± 5.6 µV vs. 3.8 ± 2.6 µV, p = 1.8E-11; 8.3 ± 13.1 ms vs. 3.8 ± 7.1 ms, p = 0.00003, respectively). After adjusting in the multivariate clinical model with factors, such as diabetes, RR interval, and beta blocker medication, TWH-SD and QT-SD retained their significant power in discriminating between the victims of SCD and the patients with CAD (p = 0.00003, p = 0.006, respectively). TWH-SD outperformed QT-SD in identifying the SCD victims among the study subjects (area under the curve in the receiver operating characteristics curve 0.730 vs. 0.679, respectively). CONCLUSION: Increased short-term variability of repolarization heterogeneity measured from standard 12-lead ECG is associated with SCD.

Electrocardiographic Risk Markers for Heart Failure in Women Versus Men.

Heart failure (HF) is one of the leading causes of hospitalization in the Western world. Women have a lower HF hospitalization rate and mortality compared with men. The role of electrocardiography as a risk marker of future HF in women is not well known. We studied association of electrocardiographic (ECG) risk factors for HF hospitalization in women from a large middle-aged general population with a long-term follow-up and compared the risk profile to men. Standard 12-lead ECG markers were analyzed from 10,864 subjects (49% women), and their predictive value for HF hospitalization was analyzed. During the follow-up (30 ± 11 years), a total of 1,743 subjects had HF hospitalization; of these, 861 were women (49%). Several baseline characteristics, such as age, body mass index, blood pressure, and history of previous cardiac disease predicted the occurrence of HF both in women and men (p <0.001 for all). After adjusting for baseline variables, ECG sign of left ventricular hypertrophy (LVH) (p <0.001), and atrial fibrillation (p <0.001) were the only baseline ECG variables that predicted future HF in women. In men, HF was predicted by fast heart rate (p = 0.008), T wave inversions (p <0.001), abnormal Q-waves (p = 0.002), and atrial fibrillation (p <0.001). Statistically significant gender interactions in prediction of HF were observed in ECG sign of LVH, inferolateral T wave inversions, and heart rate. In conclusion, ECG sign of LVH predicts future HF in middle-aged women, and T wave inversions and elevated heart rate are associated with HF hospitalization in men.

Gender differences in prevalence and prognostic value of fragmented QRS complex.

BACKGROUND: Fragmented QRS (fQRS) on 12-lead electrocardiogram (ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. METHODS: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 ± 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of ≥50% (70% men; 66.6 ± 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 ± 8.5 yrs). RESULTS: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p < 0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p < 0.001), CAD patients without prior MI (39.9% vs. 26.4%, p < 0.001), CAD patients with prior MI (42.9% vs. 31.2%, p < 0.001), and victims of SCD (56.4% vs. 44.4%, p < 0.001). CONCLUSIONS: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men.

Electrocardiogram as a predictor of survival without appropriate shocks in primary prophylactic ICD patients: A retrospective multi-center study.

BACKGROUND: Abnormal 12-lead electrocardiogram (ECG) can predict cardiovascular events, including sudden cardiac death. We tested the hypothesis that ECG provides useful information on guiding implantable cardioverter defibrillator (ICD) therapy into individuals with impaired left ventricular ejection fraction (LVEF). METHODS: Retrospective data of primary prevention ICD implantations from 14 European centers were gathered. The registry included 5111 subjects of whom 1687 patients had an interpretable pre-implantation ECG available (80.0% male, 63.3 ± 11.4 years). Primary outcome was survival without appropriate ICD shocks or heart transplantation. A low-risk ECG was defined as a combination of ECG variables that were associated with the primary outcome. RESULTS: A total of 1224 (72.6%) patients survived the follow-up (2.9 ± 1.7 years) without an ICD shock, 224 (13.3%) received an appropriate shock and 260 (15.4%) died. Low-risk ECG defined as QRS duration <120 ms, QTc interval <450 ms for men and <470 ms for women, and sinus rhythm, were met by 515 patients (30.5%). Multivariable Cox regression showed that the hazard (HR) for death, heart transplantation or appropriate shock were reduced by 42.5% in the low-risk group (HR 0.575; 95% CI 0.45-0.74; p < 0.001), compared to the high-risk group. The HR for the first appropriate shock was 42.1% lower (HR 0.58; 95% CI 0.41-0.82; p = 0.002) and the HR for death was 48.0% lower (HR 0.52; 95% CI 0.386-0.72; p < 0.001) in the low-risk group. CONCLUSION: Sinus rhythm, QRS <120 ms and normal QTc in standard 12-lead ECG provides information about survival without appropriate ICD shocks and might improve patient selection for primary prevention ICD therapy.

Electrocardiographic Risk Markers of Cardiac Death: Gender Differences in the General Population.

BACKGROUND: Cardiac death is one of the leading causes of death and sudden cardiac death (SCD) is estimated to cause approximately 50% of cardiac deaths. Men have a higher cardiac mortality than women. Consequently, the mechanisms and risk markers of cardiac mortality are not as well defined in women as they are in men. AIM: The aim of the study was to assess the prognostic value and possible gender differences of SCD risk markers of standard 12-lead electrocardiogram in three large general population samples. METHODS: The standard 12-lead electrocardiographic (ECG) markers were analyzed from three different Finnish general population samples including total of 20,310 subjects (49.9% women, mean age 44.8 ± 8.7 years). The primary endpoint was cardiac death, and SCD and all-cause mortality were secondary endpoints. The interaction effect between women and men was assessed for each ECG variable. RESULTS: During the follow-up (7.7 ± 1.2 years), a total of 883 deaths occurred (24.5% women, p < 0.001). There were 296 cardiac deaths (13.9% women, p < 0.001) and 149 SCDs (14.8% women, p < 0.001). Among those who had died due to cardiac cause, women had more often a normal electrocardiogram compared to men (39.0 vs. 27.5%, p = 0.132). After adjustments with common cardiovascular risk factors and the population sample, the following ECG variables predicted the primary endpoint in men: left ventricular hypertrophy (LVH) with strain pattern (p < 0.001), QRS duration > 110 ms (p < 0.001), inferior or lateral T-wave inversion (p < 0.001) and inferolateral early repolarization (p = 0.033). In women none of the variables remained significant predictors of cardiac death in multivariable analysis, but LVH, QTc ≥ 490 ms and T-wave inversions predicted SCD (p < 0.047 and 0.033, respectively). In the interaction analysis, LVH (HR: 2.4; 95% CI: 1.2-4.9; p = 0.014) was stronger predictor of primary endpoint in women than in men. CONCLUSION: Several standard ECG variables provide independent information on the risk of cardiac mortality in men but not in women. LVH and T-wave inversions predict SCD also in women.

Appropriate Shocks and Mortality in Patients With Versus Without Diabetes With Prophylactic Implantable Cardioverter Defibrillators.

OBJECTIVE: Diabetes increases the risk of all-cause mortality and sudden cardiac death (SCD). The exact mechanisms leading to sudden death in diabetes are not well known. We compared the incidence of appropriate shocks and mortality in patients with versus without diabetes with a prophylactic implantable cardioverter defibrillator (ICD) included in the retrospective EU-CERT-ICD registry. RESEARCH DESIGN AND METHODS AND RESULTS: A total of 3,535 patients from 12 European EU-CERT-ICD centers with a mean age of 63.7 ± 11.2 years (82% males) at the time of ICD implantation were included in the analysis. A total of 995 patients (28%) had a history of diabetes. All patients had an ICD implanted for primary SCD prevention. End points were appropriate shock and all-cause mortality. Mean follow-up time was 3.2 ± 2.3 years. Diabetes was associated with a lower risk of appropriate shocks (adjusted hazard ratio [HR] 0.77 [95% CI 0.62-0.96], P = 0.02). However, patients with diabetes had significantly higher mortality (adjusted HR 1.30 [95% CI 1.11-1.53], P = 0.001). CONCLUSIONS: All-cause mortality is higher in patients with diabetes than in patients without diabetes with primary prophylactic ICDs. Subsequently, patients with diabetes have a lower incidence of appropriate ICD shocks, indicating that the excess mortality might not be caused primarily by ventricular tachyarrhythmias. These findings suggest a limitation of the potential of prophylactic ICD therapy to improve survival in patients with diabetes with impaired left ventricular function.

Impact of age and sex on the long-term prognosis associated with early repolarization in the general population.

BACKGROUND: Early repolarization (ER) has been linked to the risk of sudden cardiac death (SCD) in the general population, although controversy remains regarding risks across various subgroups. OBJECTIVE: The purpose of this study was to investigate whether age and sex influence the prognostic significance of ER. METHODS: We evaluated the 12-lead electrocardiograms of 6631 Finnish general population subjects age ≥30 years (mean age 50.1 ± 13.9 years; 44.5% men) for the presence of ER (J-point elevation ≥0.1 mV in ≥2 inferior/lateral leads) and followed them for 24.4 ± 10.3 years. We analyzed the association between ER and the risk of SCD, cardiac death, and all-cause mortality in subgroups according to age (<50 or ≥50 years) and sex. RESULTS: ER was present in 367 of the 3305 subjects age <50 years and in 426 of 3326 subjects ≥50 years. ER was not associated with any of the endpoints in the entire study population. After adjusting for clinical factors, ER was associated with SCD (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.16-3.07) in subjects <50 but not in older subjects (interaction between ER and age group, P = .048). In the younger subgroup, women with ER had a high risk of SCD (HR 4.11; 95% CI 1.41-12.03), whereas among men ER was not associated with SCD. Finally, ER was not associated with cardiac mortality or all-cause mortality in either age group. CONCLUSION: ER is associated with SCD in subjects younger than 50 years, particularly in women, but not in subjects 50 years and older.

Predicting sudden cardiac death in a general population using an electrocardiographic risk score.

OBJECTIVE: We investigated whether combining several ECG abnormalities would identify general population subjects with a high sudden cardiac death (SCD) risk. METHODS: In a sample of 6830 participants (mean age 51.2±13.9 years; 45.5% male) in the Mini-Finland Health Survey, a general population cohort representative of the Finnish adults aged ≥30 years conducted in 1978-1980, we examined their ECGs, following subjects for 24.3±10.4 years. We analysed the association between individual ECG abnormalities and 10-year SCD risk and developed a risk score using five ECG abnormalities independently associated with SCD risk: heart rate >80 beats per minute, PR duration >220 ms, QRS duration >110 ms, left ventricular hypertrophy and T-wave inversion. We validated the score using an external general population cohort of 10 617 subjects (mean age 44.0±8.5 years; 52.7% male). RESULTS: No ECG abnormalities were present in 4563 subjects (66.8%), while 96 subjects (1.4%) had ≥3 ECG abnormalities. After adjusting for clinical factors, the SCD risk increased progressively with each additional ECG abnormality. Subjects with ≥3 ECG abnormalities had an HR of 10.23 (95% CI 5.29 to 19.80) for SCD compared with those without abnormalities. The risk score similarly predicted SCD risk in the validation cohort, in which subjects with ≥3 ECG abnormalities had HR 10.82 (95% CI 3.23 to 36.25) for SCD compared with those without abnormalities. CONCLUSION: The ECG risk score successfully identified general population subjects with a high SCD risk. Combining ECG risk markers may improve the risk stratification for SCD.

Association of Silent Myocardial Infarction and Sudden Cardiac Death.

Importance: Myocardial infarction in the absence of major or unrecognized symptoms are characterized as silent (SMI). The prevalence of SMI among individuals who experience sudden cardiac death (SCD), with or without concomitant electrocardiographic (ECG) changes, has not previously been described in detail from large studies to our knowledge. Objective: To determine the prevalence of SMI in individuals who experience SCD without a prior diagnosis of coronary artery disease (CAD) and to detect ECG abnormalities associated with SMI-associated SCD. Design, Setting, and Participants: This case-control study compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in a consecutive cohort of individuals in the Finnish Genetic Study of Arrhythmic Events (Fingesture) study population who were verified to have had SCD. The Fingesture study consists of individuals who had autopsy-verified SCD in Northern Finland between 1998 and 2017. Individuals who had SCD with CAD and evidence of SMI were regarded as having had cases; those who had SCD with CAD without SMI were considered control participants. Analyses of ECG tests were carried out by investigators blinded to the SMI data. Data analysis was completed from October 2018 through November 2018. Main Outcomes and Measures: Silent MI was defined as a scar detected by macroscopic and microscopic evaluation of myocardium without previously diagnosed CAD. Clinical history was obtained from medical records, previously recorded ECGs, and a standardized questionnaire provided to the next of kin. The hypothesis tested was that SMI would be prevalent in the population who had had SCD with CAD, and it might be detected or suspected from findings on ECGs prior to death in many individuals. Results: A total of 5869 individuals were included (2459 males [78.8%]; mean [SD] age, 64.9 [12.4] years). The cause of SCD was CAD in 4392 individuals (74.8%), among whom 3122 had no history of previously diagnosed CAD. Two individuals were excluded owing to incomplete autopsy information. An ECG recorded prior to SCD was available in 438 individuals. Silent MI was detected in 1322 individuals (42.4%) who experienced SCD without a clinical history of CAD. The participants with SMI were older than participants without MI scarring (mean [SD] age, 66.9 [11.1] years; 65.5 [11.6] years; P < .001) and were more often men (1102 of 1322 [83.4%] vs 1357 of 1798 [75.5%]; P < .001). Heart weight was higher in participants with SMI (mean [SD] weight, 483 [109] g vs 438 [106] g; P < .001). In participants with SMI, SCD occurred more often during physical activity (241 of 1322 [18.2%] vs 223 of 1798 [12.4%]; P < .001). A prior ECG was abnormal in 125 of the 187 individuals (66.8%) who had SCD after SMI compared with 139 of 251 (55.4%) of those who had SCD without SMI (P = .02). Conclusions and Relevance: Many individuals who experienced SCD associated with CAD had a previously undetected MI at autopsy. Previous SMI was associated with myocardial hypertrophy and SCD during physical activity. Premortem ECGs in a subset with available data were abnormal in 67% of the individuals who had had a SCD after an SMI.

Prediabetes and Risk for Cardiac Death Among Patients With Coronary Artery Disease: The ARTEMIS Study.

OBJECTIVE: To compare cardiac mortality in patients with CAD and prediabetes with that in CAD patients with normal glycemic status and type 2 diabetes. RESEARCH DESIGN AND METHODS: The Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included patients with CAD after revascularization (79%), optimal medical therapy, or both. Patients had type 2 diabetes (n = 834), impaired glucose tolerance (IGT; n = 314), impaired fasting glucose (IFG; n = 103), or normal glycemic status (n = 697) as defined on the basis of the results of an oral glucose tolerance test. The primary end point was cardiac death. Major adverse cardiac event (MACE: cardiac death, heart failure, or acute coronary syndrome) and all-cause mortality were secondary end points. RESULTS: During a mean ± SD follow-up of 6.3 ± 1.6 years, 101 cardiac deaths, 385 MACEs, and 208 deaths occurred. Patients with IGT tended to have 49% lower adjusted risk for cardiac death (P = 0.069), 32% lower adjusted risk for all-cause mortality (P = 0.076), and 36% lower adjusted risk for MACE (P = 0.011) than patients with type 2 diabetes. The patients with IFG had 82% lower adjusted risk for all-cause mortality (P = 0.015) than the patients with type 2 diabetes, whereas risks for cardiac death and MACE did not differ significantly between the two groups. The adjusted risks for cardiac death, MACE, and all-cause mortality among patients with IGT and IFG did not significantly differ from those risks among patients with normal glycemic status. CONCLUSIONS: Cardiac mortality or incidence of MACE in patients with CAD with prediabetes (i.e., IGT or IFG after revascularization, optimal medical therapy, or both) does not differ from those values in patients with normal glycemic status.

Risk Factors Associated With Atrioventricular Block.

Importance: Pacemaker implantations as a treatment for atrioventricular (AV) block are increasing worldwide. Prevention strategies for AV block are lacking because modifiable risk factors have not yet been identified. Objective: To identify risk factors for AV block in community-dwelling individuals. Design, Setting, and Participants: In this population-based cohort study, data from the Mini-Finland Health Survey, conducted from January 1, 1978, to December 31, 1980, were used to examine demographics, comorbidities, habits, and laboratory and electrocardiographic (ECG) measurements as potential risk factors for incident AV block. Data were ascertained during follow-up from January 1, 1987, through December 31, 2011, using a nationwide registry. A total of 6146 community-dwelling individuals were included in the analysis performed from January 15 through April 3, 2018. Main Outcomes and Measures: Incidence of AV block (hospitalization for second- or third-degree AV block). Results: Among the 6146 participants (3449 [56.1%] women; mean [SD] age, 49.2 [12.9] years), 529 (8.6%) had ECG evidence of conduction disease and 58 (0.9%) experienced a hospitalization with AV block. Older age (hazard ratio [HR] per 5-year increment, 1.34; 95% CI, 1.16-1.54; P < .001), male sex (HR, 2.04; 95% CI, 1.19-3.45; P = .01), a history of myocardial infarction (HR, 3.54; 95% CI, 1.33-9.42; P = .01), and a history of congestive heart failure (HR, 3.33; 95% CI, 1.10-10.09; P = .03) were each independently associated with AV block. Two modifiable risk factors were also independently associated with AV block. Every 10-mm Hg increase in systolic blood pressure was associated with a 22% higher risk (HR, 1.22; 95% CI, 1.10-1.34; P = .005), and every 20-mg/dL increase in fasting glucose level was associated with a 22% higher risk (HR, 1.22; 95% CI, 1.08-1.35; P = .001). Both risk factors remained statistically significant (HR for systolic blood pressure, 1.26 [95% CI, 1.06-1.49; P = .007]; HR for glucose level, 1.22 [95% CI, 1.04-1.43; P = .01]) after adjustment for major adverse coronary events during the follow-up period. In population-attributable risk assessment, an estimated 47% (95% CI, 8%-67%) of AV blocks may have been avoided if all participants exhibited ideal blood pressure and 11% (95% CI, 2%-21%) may have been avoided if all had a normal fasting glucose level. Conclusions and Relevance: In this analysis of data from a population-based cohort study, suboptimal blood pressure and fasting glucose level were associated with AV block. These results suggest that a large proportion of AV blocks are assocated with these risk factors, even after adjusting for other major adverse coronary events.