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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 β (sβ) = 0.131, P = 0.014], PWAd (sβ = −0.161, P = 0.003), P_NonDipolarABS (sβ = 0.174, P = 0.001), and PWH (sβ = 0.128, P = 0.015) retained independent association, and TWAd (sβ = −0.091, P = 0.074) and TMD (sβ = 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.

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 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.

Background: Nonischemic heart disease (NIHD) is the underlying pathology in about 20% of sudden cardiac deaths (SCDs). Psychotropic medication has been reported as a risk factor for SCD among patients with coronary artery disease, but similar information concerning NIHD is scarce. Objectives: We evaluated the use of psychotropic medication in victims of SCD due to NIHD and compared it to the general medication use in Finland. Method: Study population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) (n = 5,869, mean age 65±12, 79% males; 1,404 victims of SCD due to NIHD, mean age 57±13, 77% males). All deaths occurred in Northern Finland during 1998–2017. All victims underwent a medico-legal autopsy. Data on use of medication was defined using post-mortem toxicology results and patient records. Subjects with neither toxicological analysis nor information of medication use available were excluded. Information on general medication use was derived from Finnish Statistics on Medicines 2018 and presented as defined daily dose/1000 inhabitants/day. Results: Psychotropic medication was used by 579 (41%) subjects with NIHD, whereas in the general population only 12% were estimated to use psychotropics. The results were similar in subgroups of psychotropic medication: 27% vs 2.3% for benzodiazepines, 19% vs 7.5% for antidepressants and 18% vs 2.2% for antipsychotics. Conclusions: Use of psychotropic medication is common in victims of SCD due to NIHD compared to the general population.

Publisher Copyright: © 2022 Heart Rhythm Society 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 β-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.

Introduction Non-ischaemic heart disease (NIHD) is the underlying pathology in∼20% of all sudden cardiac deaths (SCDs). Heavy drinking is known to be associated with SCD due to ischaemic heart disease, but studies on association of recent alcohol consumption and SCD in patients with NIHD are scarce. We evaluated the blood alcohol levels of autopsy verified non-ischaemic SCD victims. Methods Study population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) (n = 5869, mean age 65 ± 12, 79% males). All deaths occurred in Northern Finland during 1998–2017. All victims underwent a medico-legal autopsy. Subjects of SCD due to ischaemic heart disease were excluded. Results A total of 1301 (mean age 57 ± 12, 78% males) victims of SCD due to NIHD were included in the study. The blood ethanol level was elevated in 543 (42%) subjects, out of which the blood alcohol level was ≥0.10%in 339 (62%) subjects and ≥0.15%in 252 (46%) subjects. Male SCD victims had alcohol in blood more frequently compared to females (45% versus 31%, p

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 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.

Myocardial scarring from infarction or nonischemic fibrosis forms an arrhythmogenic substrate. The Selvester QRS score has been developed to estimate myocardial scar from the 12-lead electrocardiogram.; We aimed to assess the value of an automated version of the Selvester QRS score for the prediction of implantable cardioverter-defibrillator (ICD) therapy and death in patients undergoing primary prevention ICD implantation.; Unselected patients undergoing primary prevention ICD implantation were included in this retrospective, observational, multicenter study. The QRS score was calculated automatically from a digital standard preimplantation 12-lead electrocardiogram and was correlated to the occurrence of death and appropriate and inappropriate shocks during follow-up. Analyses were performed in groups defined by QRS duration < 130 ms vs ≥ 130 ms.; Overall, 1047 patients (872 [83%] men; median age 64 years IQR [55-71]) with ischemic (648, 62%) or nonischemic (399, 38%) cardiomyopathy were included. The median QRS duration was 123 ms (interquartile range [IQR] 111-157 ms), and the median QRS score was 5 (IQR 2-8). The QRS duration was

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

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).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.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 duration120 ms, QTc interval450 ms for men and470 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.Sinus rhythm, QRS120 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.

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.The purpose of this study was to investigate whether age and sex influence the prognostic significance of ER.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.ER was present in 367 of the 3305 subjects age50 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 subjects50 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.ER is associated with SCD in subjects younger than 50 years, particularly in women, but not in subjects 50 years and older.

Background: QRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population. Objective: In this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals. Methods: This study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30–61 years. QRS duration and QT interval (Bazett's) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval – QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD. Results: During a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017–1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001–1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996–1.007). Conclusion: Prolonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value. publishedVersion

Publisher Copyright: © 2021 Elsevier Inc. 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

Objective: Cardiac hypertrophy with varying degrees of myocardial fibrosis is commonly associated with coronary artery disease (CAD) related sudden cardiac death (SCD), especially in young victims among whom patterns of coronary artery lesions do not entirely appear to explain the cause of SCD. Our aim was to study the genetic background of hypertrophy, with or without fibrosis, among ischemic SCD victims with single vessel CAD. Methods: The study population was derived from the Fingesture study, consisting of all autopsy-verified SCDs in Northern Finland between the years 1998 and 2017 (n = 5,869). We carried out targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function in 95 ischemic-SCD victims (mean age 63.6 ± 10.3 years; 88.4% males) with single-vessel CAD in the absence of previously diagnosed CAD and cardiac hypertrophy with or without myocardial fibrosis at autopsy. Results: A total of 42 rare variants were detected in 43 subjects (45.3% of the study subjects). Five variants in eight subjects (8.4%) were classified as pathogenic or likely pathogenic. We observed 37 variants of uncertain significance in 39 subjects (40.6%). Variants were detected in myocardial structure protein coding genes, associated with arrhythmogenic right ventricular, dilated, hypertrophic and left ventricular non-compaction cardiomyopathies. Also, variants were detected in ryanodine receptor 2 (RYR2), a gene associated with both cardiomyopathies and catecholaminergic polymorphic ventricular tachycardias. Conclusions: Rare variants associated with cardiomyopathies, in the absence of anatomic evidence of the specific inherited cardiomyopathies, were common findings among CAD-related SCD victims with single vessel disease and myocardial hypertrophy found at autopsies, suggesting that these variants may modulate the risk for fatal arrhythmias and SCD in ischemic disease.

INTRODUCTION The prognostic significance of P-wave morphology in patients with coronary artery disease (CAD) is not well-known. METHODS A total of 1946 patients with angiographically verified CAD were included in the Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study. The P-wave morphology could be analyzed in 1797 patients. RESULTS During 7.4 ± 2.0 years, a total of 168 (9.3%) patients died or experienced resuscitation from sudden cardiac arrest (SCA), 43 (2.4%) patients experienced sudden cardiac death (SCD) or were resuscitated from SCA, 37 (2.1%) patients succumbed to non-SCD (NSCD), and 88 (4.9%) patients to noncardiac death (NCD). Of the P-wave parameters, the absolute P-wave residuum (PWR), the heterogeneity of the P-wave morphology (PWH), and the P-wave duration (Pdur) had the closest univariate association with the risk of SCD/SCA (0.0038 ± 0.0026 vs 0.0022 ± 0.0017, P

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.

Background:Despite recent progress in profiling of risk for sudden cardiac death (SCD) and prevention and intervention of cardiac diseases, SCD remains a major cause of death. Among women, the incidence of SCD is significant, but lower than in men, particularly in the premenopausal and early postmenopausal years. Possibly, as a consequence of the difference in population burden, the mechanisms and risk markers of SCD are not as well defined for women. The aim of this study was to determine the autopsy findings and causes of death among women in a large SCD population. Additionally, we sought to classify prior ECG characteristics in male and female subjects with SCD.Methods:The Fingesture study has systematically collected clinical and autopsy data from subjects with SCD in Northern Finland between 1998 and 2017. The cohort consists of 5869 subjects with SCD. Previously recorded ECGs were available and analyzed in 1101 subjects (18.8% of total population; and in 25.3% of women).Results:Female subjects with SCD were significantly older than men: 70.1±13.1 years versus 63.5±11.8 years (mean ± standard deviation,PP=0.005. In contrast, women were more likely to have nonischemic cause of SCD than men (28.3% versus 24.3%,P=0.005). The prevalence of primary myocardial fibrosis was higher among women (5.2%, n=64) than in men (2.6%, n=120;PPP=0.009). However, ECG markers of left ventricular hypertrophy, with or without repolarization abnormalities, were more common among women (8.2%; 17.9%) than in men (4.9%; 10.6%,P=0.036;PConclusions:Women were considerably older at the time of SCD and more commonly had nonischemic causes. Women were also more likely to have a prior normal ECG than men, but an increased marker for SCD risk based on ECG criteria for left ventricular hypertrophy with repolarization abnormalities was more commonly observed in women.

The debate whether an elevated level of serum uric acid (SUA) is an independent marker of cardiovascular risk is still going on. We examined morbidity and mortality related to SUA and hyperuricemia in a well-characterized population with very long follow-up. Study included 4696 participants (aged 30-59 years at baseline) of the coronary heart disease (CHD) Study of the Finnish Mobile Clinic Health Examination Survey. Adjusted hazard ratios (HRs) of hyperuricemia (defined as ≥360 µmol/l and ≥420 µmol/l) and SUA quintiles for mortality and adverse cardiovascular outcomes are reported. During the mean follow up of 30.6 years there were 2723 deaths, 887 deaths for CHD of which 340 were classified as sudden cardiac deaths, 1642 hospitalizations due to CHD and 798 hospitalizations due to congestive heart failure. After adjusting to baseline risk factors and presence of cardiovascular diseases as well as the use of diuretics there were no significant differences in the risk of any of the outcomes when analyzed either according to quintiles of SUA or using a cut-off point SUA ≥360 µmol/l for hyperuricemia. Only a rare finding of hyperuricemia SUA ≥420 µmol/l among women (n = 17, 0.9%) was independently associated with significantly higher risk of mortality (adjusted HR: 2.59, 95% CI: 1.54-4.34) and a combination end-point of major adverse cardiac events (MACEs) (HR: 2.69; 95% CI: 1.56-4.66). SUA was not an independent indicator of morbidity and mortality, with the exception of particularly high levels of SUA among women.

BackgroundCardiac 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.AimThe 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.MethodsThe 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.ResultsDuring 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.ConclusionSeveral 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.

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.

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.

Background: The association between leisure-time physical activity (LTPA) and the risk of sudden cardiac death (SCD) in coronary artery disease patients is not well known. We aim to assess whether there is an association between LTPA and the risk of SCD and non-SCD in patients with coronary artery disease. Methods: Patients with angiographically verified coronary artery disease (n=1946) underwent a clinical evaluation, including filling in an LTPA questionnaire and extensive risk profiling at the baseline. The patients were classified into 4 groups according to LTPA: (1) inactive; (2) irregularly active; (3) active, exercise regularly 2× to 3× weekly; (4) highly active, exercise regularly ≥4× weekly. Age, sex, body mass index, left ventricular ejection fraction, type 2 diabetes mellitus, history of myocardial infarction, Canadian Cardiovascular Society grading of angina pectoris class, and exercise capacity were used as covariates in the multivariate Cox regression analysis. Results: During follow-up (median 6.3 years), 52 SCDs and 49 non-SCDs occurred. Inactive patients had increased risk for SCD compared with active patients (hazard ratio, 2.45 [95% CI, 1.01–5.98]; P P =0.019 in highly active patients). LTPA was not associated with SCD in patients with Canadian Cardiovascular Society grading of angina pectoris class 1 (n=1107, 18 events). Among patients with Canadian Cardiovascular Society grading of angina pectoris class 2 or higher (n=839, 34 events), increased risk for SCD was encountered in highly active patients (hazard ratio, 7.46 [95% CI, 2.32–23.9]; P P Conclusions: Inactive coronary artery disease patients had increased risk for SCD. In subgroup analysis among symptomatic patients, the risk of SCD was increased in highly active and inactive patients compared with active patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01426685.

Background Asystole (ASY) and pulseless electrical activity (PEA) have a poor outcome during sudden cardiac arrest (SCA). Psychotropic medication has been associated with a risk for sudden cardiac death (SCD). Our aim was to study the association of psychotropic medication with ASY/PEA during SCA. Methods and results A total of 659 SCA subjects were derived from the emergency data of Oulu University Hospital (2007–2012). Subjects with non-cardiac origin of SCA and over 30-minute delay to rhythm recording were excluded. Population included 222 subjects after exclusions (mean age 64 ± 14 years, 78% males). Initial rhythm was ventricular fibrillation (VF) or ventricular tachycardia (VT) in 123 (55%), ASY in 67 (30%) and PEA in 32 (14%) subjects. The delay (collapse to rhythm recording) was similar in VF/VT and ASY/PEA subjects (median 8 min [1st–3rd quartile 3–12 min] versus 10 [0–14] minutes, p = 0.780). Among VF/VT subjects underlying cardiac disease was more often ischemic compared to ASY/PEA subjects (85% versus 68%, p = 0.003). Psychotropic medication was associated with ASY/PEA rhythm (OR 3.18, 95%CI 1.40–7.23, p = 0.006) after adjustment for gender, age and underlying cardiac disease. Subsequently, antipsychotics (OR 4.27, 95%CI 1.28–14.25, p = 0.018) were more common in the ASY/PEA group. Benzodiazepines and antidepressants were not associated with ASY/PEA. Conclusion Psychotropic medication and especially antipsychotics are associated with non-shockable rhythm during SCA and may lower the possibility of survival from the event. This might partly explain the risk of SCD related to psychotropic medication.

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 (p0.001 for all). After adjusting for baseline variables, ECG sign of left ventricular hypertrophy (LVH) (p0.001), and atrial fibrillation (p0.001) 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 (p0.001), abnormal Q-waves (p = 0.002), and atrial fibrillation (p0.001). 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.

Sudden cardiac arrest remains an unexpected and dynamic cardiovascular disease process that continues to present challenges for accurate risk prediction and prevention. The notion of a circadian pattern in the occurrence of sudden cardiac arrest had long been supported by the presence of an early morning peak; however, more recent studies are calling this observation into question. This likely paradigm shift in the presentation and mechanisms of sudden cardiac arrest has major implications and needs to be carefully considered. In this review, we present the current state of the science of circadian and septadian trends in sudden cardiac arrest through an in-depth analysis of the published literature.

Aims Identifying subjects at high and low risk of atrial fibrillation (AF) is of interest. This study aims to assess the risk of AF associated with electrocardiographic (ECG) markers linked to atrial fibrosis: P-wave prolongation, 3rd-degree interatrial block, P-terminal force in lead V1, and orthogonal P-wave morphology. Methods and results P-wave parameters were assessed in a representative Finnish population sample aged ≥30 years (n = 7217, 46.0% male, mean age 51.4 years). Subjects (n = 5489) with a readable ECG including the orthogonal leads, sinus rhythm, and a predefined orthogonal P-wave morphology type [positive in leads X and Y and either negative (Type 1) or ± biphasic (Type 2) in lead Z; Type 3 defined as positive in lead X and ± biphasic in lead Y], were followed 10 years from the baseline examinations (performed 1978–80). Subjects discharged with AF diagnosis after any-cause hospitalization (n = 124) were defined as having developed AF. Third-degree interatrial block was defined as P-wave ≥120 ms and the presence of ≥2 ± biphasic P waves in the inferior leads. Hazard ratios (HRs) and confidence intervals (CIs) were assessed with Cox models. Third-degree interatrial block (n = 103, HR 3.18, 95% CI 1.66–6.13; P = 0.001) and Type 3 morphology (n = 216, HR 3.01, 95% CI 1.66–5.45; P Conclusion P-wave parameters associate with the risk of hospitalization with AF.

Fragmented QRS and inferolateral early repolarization pattern manifested as end-QRS notching or slurring in standard 12-lead electrocardiogram (ECG) have been associated with adverse outcome in several studies spanning different patient populations. Previous studies have explored the sex-related differences of these two ECG markers, in terms of their prevalence and prognostic value, to some extent. However, the current literature is sparse and partly conflicting results have emerged. In this section, we go through the definition and measurement of these two markers as well as the sex differences related to their prevalence and prognostic value, as they are known in the current literature.

We compared the ST elevation myocardial infarction (STEMI) incidence during COVID-19 pandemic (March 2020) to January-February 2020 and to same time period in earlier years 2017-2019 in five Nordic-Baltic tertiary centers. During 2017-2019, there were no marked differences in STEMI incidence between January, February and March. During 2020, there was an average drop of 32% in STEMI incidence in March. The isolation measures may decrease the risk for respiratory virus infection and contribute to the lower STEMI incidence and that we might benefit from firmer suggestions on hand hygiene and social distancing during flu season at least among high-risk individuals.

Previous studies have shown that type 2 diabetes (DM2) is associated with sudden cardiac death (SCD) risk in post-myocardial infarction patients. The treatment of coronary artery disease (CAD) as well as DM2 has changed over time.The purpose of this study was to compare the incidence of SCD in DM2 and nondiabetic patients with CAD and preserved ejection fraction (EF) in a prospective observational study (ARTEMIS study).In 834 DM2 patients and 1112 nondiabetic patients with CAD enrolled, the EF measured ≥3 months after qualifying was 63% ± 10% in DM2 patients and 65% ± 8% in nondiabetic patients (P .01). The primary end point was SCD or resuscitation from sudden cardiac arrest (SCA). All-cause mortality, cardiac mortality, non-SCD, hospitalization for heart failure, and acute coronary syndrome were secondary end points.During a mean follow-up of 6.3 ± 1.6 years, SCDs/SCAs occurred in 50 patients. The prevalence of SCD/SCA was higher in DM2 patients (4.1%) than in nondiabetic patients (1.4%) (adjusted hazard ratio 2.6; 95% confidence interval 1.3-5.3; P.01). However, the non-SCD component of cardiac mortality was not significantly different between DM2 and nondiabetic patients. In addition, heart failure hospitalizations were more common in DM2 patients (8.4%) than in nondiabetic patients (2.9%) (P.001). The annual cardiac mortality in nondiabetic patients with CAD was 0.50%, which was lower than the 0.59% reported in the general Finnish population.DM2 is an independent risk factor for SCD/SCA in CAD patients with preserved EF. Cardiac mortality in nondiabetic CAD patients is slightly lower than that in the general population in the present treatment era.

Background: Myocardial fibrosis is a common postmortem finding among young individuals with sudden cardiac death. Because there is no known single cause, we tested the hypothesis that some cases of myocardial fibrosis in the absence of identifiable causes (primary myocardial fibrosis [PMF]) are associated with genetic variants. Methods: Tissue was obtained at autopsy from 4031 consecutive individuals with sudden cardiac death in Northern Finland, among whom PMF was the only structural finding in 145 subjects with sudden cardiac death. We performed targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function when autopsies did not identify a secondary basis for myocardial fibrosis. All variants with an effect on protein and with a minor allele frequency Results: Among the 96 specimens with DNA passing quality control (66%), postmortem genetic tests identified 24 variants of known or uncertain significance in 26 subjects (27%). Ten were pathogenic/likely pathogenic variants in 10 subjects (10%), and 14 were variants of uncertain significance in 11 genes among 16 subjects (17%). Five variants were in genes associated with arrhythmogenic right ventricular cardiomyopathy, 6 in hypertrophic cardiomyopathy–associated genes, and 11 in dilated cardiomyopathy–associated genes; 2 were not associated with these disorders. Four unique variants of uncertain significance cosegregated among multiple unrelated subjects with PMF. No pathogenic/likely pathogenic variants were detected in ion channel–encoding genes. Conclusions: A large proportion of subjects with PMF at autopsy had variants in genes associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy without autopsy findings of those diseases, suggesting that PMF can be an alternative phenotypic expression of structural disease–associated genetic variants or that risk-associated fibrosis was expressing before the primary disease. These findings have clinical implications for postmortem genetic testing and family risk profiling.

Leisure-time physical activity (LTPA) is associated with longevity in patients with coronary artery disease (CAD). However, less is known about prognostic significance of longitudinally assessed LTPA in patients with stable CAD. The present study assessed the relationship between changes in LTPA and cardiac mortality in patients with CAD. Patients with angiographically documented CAD (n = 1,746) underwent clinical examination and echocardiography at the baseline. Lifestyle factors, including LTPA (inactive, irregularly active, active, highly active), were surveyed at baseline and after 2 years' follow-up. Thereafter, the patients entered the follow-up (median: 4.5 years; first to third quartile: 3.4 to 5.8 years) during which cardiac deaths were registered (n = 68, 3.9%). The patients who remained inactive (n = 114, 18 events, 16%) and became inactive (n = 228, 18 events, 8%) had 7.6- (95% confidence interval [CI] 4.2 to 13.6) and 3.7-fold (95% CI 2.1 to 6.7) univariate risk for cardiac death compared with those who remained at least irregularly active (n = 1,351, 30 events, 2%), respectively. After adjustment for age, gender, body mass index, diabetes, previous myocardial infarction, left ventricular ejection fraction, angina pectoris grading, cardiovascular event during initial 2-year follow-up, smoking and alcohol consumption, the patients who remained inactive and became inactive still had 4.9- (95% CI 2.4 to 9.8, p

BackgroundSudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. While several risk factors are observationally associated with SCA, the genetic architecture of SCA in the general population remains unknown. Furthermore, understanding which risk factors are causal may help target prevention strategies.MethodsWe carried out a large genome-wide association study (GWAS) for SCA (n=3,939 cases, 25,989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA.ResultsNo variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (1) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (2) height and BMI, and (3) electrical instability traits (QT and atrial fibrillation), suggesting etiologic roles for these traits in SCA risk.ConclusionsOur findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in highrisk populations and the general community.

Coronary artery disease (CAD) mortality has declined substantially over the past decades thanks to advancing medical and interventional/surgical treatments; therefore, the prognostic value of the heart rate variability in CAD in the current treatment era is not well established. We evaluated the prognostic significance of baseline heart rate variability in 1,757 ARTEMIS study patients with angiographically verified CAD. During an average follow-up time of 8.7 ± 2.2 years, a total of 285 (16.2%) patients died. Of the patients, 63 (3.6%) suffered sudden cardiac death or were resuscitated from sudden cardiac arrest (SCD/SCA), 60 (3.4%) experienced non-sudden cardiac death (NSCD), and death attributable to non-cardiac causes (NCD) occurred in 162 (9.2%) patients. For every 10 ms decrease in standard deviation of normal to normal intervals the risk for SCD/SCA, NSCD and NCD increased significantly: HR 1.153 (95% CI 1.075–1.236, p

Introduction Little is known about the association between electrocardiographic abnormalities and exercise-related sudden cardiac death. Therefore, our aim was to identify possible electrocardiographic findings related to exercise-induced sudden cardiac death. Methods and results The FinGesture study includes 3,989 consecutive sudden cardiac deaths in northern Finland between 1998 and 2012, out of whom a total of 647 subjects had a previously recorded electrocardiography acquired from the archives of Oulu University Hospital. In 276 of these cases the death was witnessed, and the activity at the time of death was either rest or physical exercise (PE); in 40 (14%) cases sudden cardiac death was exercise-related and in 236 (86%) cases death took place at rest. Fragmented QRS complex in at least two consecutive leads within anterior leads (V1-V3) was more common in the exercise-group compared to rest-group (17/40, 43% vs. 51/236, 22%, p = 0.005). Pathologic Q wave in anterior leads was more common in the PE group (9/40, 23% vs. 26/236, 11%; p = 0.044). Median QRS duration was prolonged in the exercise-group compared to the rest-group (100 ms vs. 94 ms, p = 0.047). QTc interval, the prevalence of inverted T-waves, or other electrocardiographic abnormalities did not differ significantly between the two groups. Conclusions As a conclusion, fragmented QRS complex in the anterior leads is associated with an increased risk of sudden cardiac death during physical exercise. This article is protected by copyright. All rights reserved

We appreciate the comments by Chattopadhyay and John (1) on our recent study on prognostic significance of prediabetes in patients with stable coronary artery disease (CAD) (2). They raise concerns about a self-selected low-risk population, which they claim compromises the generalization of the results. The aim of the Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study was to assess prognostic significance of prediabetes among CAD patients in stable-phase CAD. Approximately half had history of myocardial infarction (MI). Authors Chattopadhyay and John are correct that patients with severe cardiac condition were excluded (2) and some may have even died before enrollment. In this case, it would be interesting to know whether treatment …