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.

Plaque histology and myocardial disease in sudden coronary death: the Fingesture study.

AIMS: At least 50% of deaths due to coronary artery disease (CAD) are sudden cardiac deaths (SCDs), but the role of acute plaque complications on the incidence of sudden death in CAD is somewhat unclear. The present study aimed to investigate plaque histology and concomitant myocardial disease in sudden coronary death. METHODS AND RESULTS: The study population is derived from the Fingesture study, which has collected data from 5869 consecutive autopsy-verified SCD victims in Northern Finland (population ≈600 000) between 1998 and 2017. In this substudy, histological examination of culprit lesions was performed in 600 SCD victims whose death was due to CAD. Determination of the cause of death was based on the combination of medical records, police reports, and autopsy data. Plaque histology was classified as either (i) plaque rupture or erosion, (ii) intraplaque haemorrhage, or (iii) stable plaque. The mean age of the study subjects was 64.9 ± 11.2 years, and 82% were male. Twenty-four per cent had plaque rupture or plaque erosion, 24% had an intraplaque haemorrhage, and 52% had a stable plaque. Myocardial hypertrophy was present in 78% and myocardial fibrosis in 93% of victims. The presence of myocardial hypertrophy or fibrosis was not associated with specific plaque histology. CONCLUSION: Less than half of sudden deaths due to CAD had evidence of acute plaque complication, an observation which is contrary to historical perceptions. The prevalence of concomitant myocardial disease was high and independent of associated plaque morphology.

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.

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.

Cardiovascular responses to dynamic and static upper-body exercise in a cold environment in coronary artery disease patients.

PURPOSE: Upper-body exercise performed in a cold environment may increase cardiovascular strain, which could be detrimental to patients with coronary artery disease (CAD). This study compared cardiovascular responses of CAD patients during graded upper-body dynamic and static exercise in cold and neutral environments. METHODS: 20 patients with stable CAD performed 30 min of progressive dynamic (light, moderate, and heavy rating of perceived exertion) and static (10, 15, 20, 25 and 30% of maximal voluntary contraction) upper body exercise in cold (- 15 °C) and neutral (+ 22 °C) environments. Heart rate (HR), blood pressure (BP) and electrocardiographic (ECG) responses were recorded and rate pressure product (RPP) calculated. RESULTS: Dynamic-graded upper-body exercise in the cold increased HR by 2.3-4.8% (p = 0.002-0.040), MAP by 3.9-5.9% (p = 0.038-0.454) and RPP by 18.1-24.4% (p = 0.002-0.020) when compared to the neutral environment. Static graded upper-body exercise in the cold resulted in higher MAP (6.3-9.1%; p = 0.000-0.014), lower HR (4.1-7.2%; p = 0.009-0.033), but unaltered RPP compared to a neutral environment. Heavy dynamic exercise resulted in ST depression that was not related to temperature. Otherwise, ECG was largely unaltered during exercise in either thermal condition. CONCLUSIONS: Dynamic- and static-graded upper-body exercise in the cold involves higher cardiovascular strain compared with a neutral environment among patients with stable CAD. However, no marked changes in electric cardiac function were observed. The results support the use of upper-body exercise in the cold in patients with stable CAD. TRIAL REGISTRATION: Clinical trial registration NCT02855905 August 2016.

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.

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.

Simple electrocardiographic measures improve sudden arrhythmic death prediction in coronary disease.

AIMS: To determine whether the combination of standard electrocardiographic (ECG) markers reflecting domains of arrhythmic risk improves sudden and/or arrhythmic death (SAD) risk stratification in patients with coronary heart disease (CHD). METHODS AND RESULTS: The association between ECG markers and SAD was examined in a derivation cohort (PREDETERMINE; N = 5462) with adjustment for clinical risk factors, left ventricular ejection fraction (LVEF), and competing risk. Competing outcome models assessed the differential association of ECG markers with SAD and competing mortality. The predictive value of a derived ECG score was then validated (ARTEMIS; N = 1900). In the derivation cohort, the 5-year cumulative incidence of SAD was 1.5% [95% confidence interval (CI) 1.1-1.9] and 6.2% (95% CI 4.5-8.3) in those with a low- and high-risk ECG score, respectively (P for Δ < 0.001). A high-risk ECG score was more strongly associated with SAD than non-SAD mortality (adjusted hazard ratios = 2.87 vs. 1.38 respectively; P for Δ = 0.003) and the proportion of deaths due to SAD was greater in the high vs. low risk groups (24.9% vs. 16.5%, P for Δ = 0.03). Similar findings were observed in the validation cohort. The addition of ECG markers to a clinical risk factor model inclusive of LVEF improved indices of discrimination and reclassification in both derivation and validation cohorts, including correct reclassification of 28% of patients in the validation cohort [net reclassification improvement 28 (7-49%), P = 0.009]. CONCLUSION: For patients with CHD, an externally validated ECG score enriched for both absolute and proportional SAD risk and significantly improved risk stratification compared to standard clinical risk factors including LVEF. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01114269. ClinicalTrials.gov ID NCT01114269.

Sudden Cardiac Death in Women.

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, P<0.001). The most frequently identified cause of death was ischemic heart disease in both sexes: 71.7% among women versus 75.7% among men, P=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; P<0.001). Female subjects with SCD were more likely to have normal prior ECG tracings (22.2% versus 15.3% in men, P<0.001). A normal ECG was even more common among nonischemic female subjects with SCD (27.8% versus 16.2% in men, P=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; P<0.001, respectively). CONCLUSIONS: 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.

Orthogonal P-wave morphology, conventional P-wave indices, and the risk of atrial fibrillation in the general population using data from the Finnish Hospital Discharge Register.

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 < 0.001) were independently associated with the risk of hospitalization with AF. Subjects with P-wave <110 ms and Type 1 morphology (n = 2074) were at low risk (HR 0.46, 95% CI 0.26-0.83; P = 0.006), compared to the rest of the subjects. CONCLUSION: P-wave parameters associate with the risk of hospitalization with AF.

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.

Prognostic significance of P-wave morphology in patients with coronary artery 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 < .001; 11.0 ± 5.2 vs 8.6 ± 3.6, P < .01; 142.7 ± 16.9 vs 134.8 ± 14.3 milliseconds, P < .01; SCD/SCA vs no SCD/SCA, respectively). After adjustments with factors that were associated with the risk of SCD/SCA, such as diabetes, smoking, left bundle branch block, high-sensitivity C-reactive protein, and high-sensitivity troponin T, PWR (P < .001), PWH (P < .05), and Pdur (P < 0.01) still predicted SCD/SCA but not non-sudden cardiac death. When these parameters were added to the SCD/SCA clinical risk model, the discrimination and reclassification accuracy of the risk model increased significantly (P < .05, P < .001) and the C-index increased from 0.745 to 0.787. CONCLUSION: The P-wave morphology parameters independently predict SCD/SCA in patients with CAD.

Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project.

BACKGROUND: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12­lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION: The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.

Cardiovascular responses to cold and submaximal exercise in patients with coronary artery disease.

Regular year-round exercise is recommended for patients with coronary artery disease (CAD). However, the combined effects of cold and moderate sustained exercise, both known to increase cardiac workload, on cardiovascular responses are not known. We tested the hypothesis that cardiac workload is increased, and evidence of ischemia would be observed during exercise in the cold in patients with CAD. Sixteen men (59.3 ± 7.0 yr, means ± SD) with stable CAD each underwent 4, 30 min exposures in a randomized order: seated rest and moderate-intensity exercise [walking, 60%-70% of max heart rate (HR)] performed at +22°C and -15°C. Systolic brachial blood pressure (SBP), HR, electrocardiogram (ECG), and skin temperatures were recorded throughout the intervention. Rate pressure product (RPP) and ECG parameters were obtained. The combined effects of cold and submaximal exercise were additive for SBP and RPP and synergistic for HR when compared with rest in a neutral environment. RPP (mmHg·beats/min) was 17% higher during exercise in the cold (18,080 ± 3540) compared with neutral (15,490 ± 2,940) conditions ( P = 0.001). Only a few ST depressions were detected during exercise but without an effect of ambient temperature. The corrected QT interval increased while exercising in the cold compared with neutral temperature ( P = 0.023). Recovery of postexercise blood pressure was similar regardless of temperature. Whole body exposure to cold during submaximal exercise results in higher cardiac workload compared with a neutral environment. Despite the higher RPP, no signs of myocardial ischemia or abnormal ECG responses were observed. The results of this study are useful for planning year-round exercise-based rehabilitation programs for stable CAD patients.

Fragmented QRS complex as a predictor of exercise-related sudden cardiac death.

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 of 40, 43% vs. 51 of 236, 22%, P  =  0.005). Pathologic Q wave in anterior leads was more common in the PE group (9 of 40, 23% vs. 26 of 236, 11%; P  =  0.044). Median QRS duration was prolonged in the exercise-group compared to the rest-group (100 milliseconds vs. 94 milliseconds, 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 PE.

Inferolateral early repolarization among non-ischaemic sudden cardiac death victims.

Aim: Inferolateral early repolarization (ER) has been associated with an increased risk of sudden cardiac death (SCD). However, this association is thought to be mainly due to ischaemic SCD. The association of ER and non-ischaemic SCD has not been studied. The aim was to evaluate whether inferolateral ER is associated with non-ischaemic SCD. Methods and results: Study population consists of 275 consecutive victims of non-ischaemic SCD with 12-lead ECG and control group of general population cohort with 10 864 subjects. Sudden cardiac deaths were verified as non-ischaemic by medicolegal autopsy. Hypertensive cardiomyopathy (HTCMP) (25%), alcohol related dilated cardiomyopathy (ACMP) (24%), obesity associated cardiomyopathy (OCMP) (23%), and idiopathic myocardial fibrosis (IMF) (15%) were the most common causes of non-ischaemic SCD. A structurally normal heart was seen in only 1.5%. The prevalence of inferolateral ER was 20.7% among patients with non-ischaemic SCD compared to 5.3% in the general population (P < 0.001). The ECG pattern was accompanied with a horizontal/descending ST segment in 95% of the cases. The prevalence of inferolateral ER was slightly higher in the HTCMP group (26%) and the ACMP group (24%) than in the IMF group (20%) and the OCMP group (13%). The history of previously diagnosed cardiac diseases was not higher among subjects with ER (55%) than those without (59%, P = 0.59). Conclusion: The prevalence of inferolateral ER among non-ischaemic SCD victims is high. Almost all ER patterns are accompanied with the malignant horizontal/descending ST segment morphology suggesting that inferolateral ER is not only associated with an ischaemic SCD but also a non-ischaemic SCD.

Prognostic value of T-wave morphology parameters in coronary artery disease in current treatment era.

BACKGROUND: The prognostic value of T-wave morphology parameters in coronary artery disease in the current treatment era is not well established. METHODS: The Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included 1,946 patients with angiographically verified coronary artery disease (CAD). The study patients underwent thorough examinations including 12-lead digital electrocardiogram (ECG) at baseline. RESULTS: During a follow-up period of 73 ± 22 months, a total of 201 (10.3%) patients died. Of the study patients, 95 (4.9%) experienced cardiac death (CD) consisting of 44 (2.3%) sudden cardiac deaths (SCD) and 51 (2.6%) nonsudden cardiac deaths (NSCD), and 106 (5.4%) patients experienced noncardiac death (NCD). T-wave morphology dispersion (TMD), T-wave area dispersion (TWAD), and total cosine R-to-T (TCRT) had a significant association with CD even after adjustment with relevant clinical risk markers in the Cox regression analysis (multivariate HRs: 1.015, 95% CI 1.007-1.023, p = .0003; 0.474, 95% CI 0.305-0.737, p = .0009; 0.598, 95% CI 0.412-0.866, p = .006, respectively). When including these parameters to the clinical risk model for CD, the C-index increased from 0.810 to 0.823 improving the discrimination significantly (integrated discrimination index [IDI] = 0.0118, 95% CI 0.0028-0.0208, p = .01). These parameters were more closely associated with NSCD (multivariate p-values from .016 to .001) than with SCD (univariate/multivariate p-values for TMD .015/.197 and for TCRT .012/.43). CONCLUSION: T-wave morphology parameters describing repolarization heterogeneity improve the predictive power of the clinical risk model for CD in patients with CAD in the current treatment era.

Experiences in digitizing and digitally measuring a paper-based ECG archive.

BACKGROUND: No established method for digitizing and digital measuring of paper electrocardiograms (ECG) exists. We describe a paper ECG digitizing and digital measuring process, and report comparability to manual measurements. METHODS: A paper ECG was recorded from 7203 health survey participants in 1978-1980. With specific software, the ECGs were digitized (ECG Trace Tool), and measured digitally (EASE). A sub-sample of 100 ECGs was selected for manual measurements. RESULTS: The measurement methods showed good agreement. The mean global (EASE)-(manual) differences were 1.4ms (95% CI 0.5-2.2) for PR interval, -1.0ms (95% CI -1.5-[-0.5]) for QRS duration, and 11.6ms (95% CI 10.5-12.7) for QT interval. The mean inter-method amplitude differences of RampV5, RampV6, SampV1, TampII and TampV5 ranged from -0.03mV to 0.01mV. CONCLUSIONS: The presented paper-to-digital conversion and digital measurement process is an accurate and reliable method, enabling efficient storing and analysis of paper ECGs.

Supraventricular premature beats and risk of new-onset atrial fibrillation in coronary artery disease.

INTRODUCTION: The significance of premature atrial contraction (PAC) count and supraventricular runs (SVR) for the risk of development of new-onset atrial fibrillation (AF) in patients with coronary artery disease (CAD) is not well established. METHODS: The Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study cohort consisted of 1,946 patients with CAD who underwent clinical and echocardiographic examinations, 24-hour ambulatory ECG monitoring, and laboratory tests. After excluding patients who were not in sinus rhythm at baseline or were lost from the follow-up, the present study included 1,710 patients. SVR was defined as at least four PACs in a row with a duration <30 seconds. RESULTS: During a follow-up for an average 5.6 ± 1.5 years, new-onset AF was identified in 143 (8.4%) patients. In the univariate analysis, both SVR and PAC count were associated with the development of new-onset AF. When SVR and PAC count were adjusted with the established AF risk markers of the modified CHARGE-AF model in the Cox multivariate regression analysis, both parameters remained significant predictors of the occurrence of new-onset AF (HR = 2.529, 95 % CI = 1.763-3.628, P ˂ 0.001 and HR = 8.139 for ≥1,409 PACs [the fourth quartile] vs. ≤507 PACs [the first quartile], 95 % CI = 3.967-16.696, P ˂ 0.001, respectively). Together these parameters improved the C-index of the established AF risk model from 0.649 to 0.718, P < 0.001. CONCLUSION: Including SVR and PAC count to the established AF risk model improves the discrimination accuracy in predicting AF in patients with CAD.