A randomized clinical trial of omega-3 fatty acid and vitamin D supplementation on electrocardiographic risk profiles.

Beneficial and adverse associations with arrhythmias have been reported for omega-3 fatty acids (omega-3 FA) and Vitamin D. The 12 lead electrocardiogram (ECG) contains quantitative measures reflecting diverse aspects of electrophysiology that might provide insights into mechanisms underlying these associations. In a pre-specified ancillary study of the VITaminD and omegA-3 (VITAL) trial, we examined the effect of 1 g of marine omega-3 FA per day, comprised of 460 mg eicosapentanoic acid and 380 mg of docosahexaenoic acid, and 2000 IU VitaminD3 per day on ECG characteristics associated with atrial and ventricular arrhythmias among individuals age 50 years or greater. A total of 911 study participants underwent ECGs at baseline and again at 2 years after the randomization. Individuals randomized to active omega-3 FA demonstrated significant net increase in PR-interval duration (p = 0.005) and P-wave duration (p = 0.03) as well significant net decrease in P-wave amplitude (p = 0.037) as compared to placebo. RMSSD increased to a greater extent in the omega-3 FA arm compared to placebo (p = 0.040). For Vitamin D3, the Cornell voltage increased to a lesser extent in the participants assigned to active treatment as compared to placebo (p = 0.044). There were no other significant differences in QRS, QTc, Cornell voltage or heart rate. Thus, randomized treatment with omega-3 FA supplements resulted in changes on the ECG that are potentially reflective of heightened vagal tone and/or slowing of intraatrial and AV conduction. Vitamin D3 supplementation resulted in modest reductions in progressive LV voltage suggestive of a potential antihypertrophic effect.Trial registration ClinicalTrials.gov Identifiers: NCT01169259, NCT02178410 (06/26/2010 and 06/30/2014).

Risk of sudden cardiac death associated with QRS, QTc, and JTc intervals in the general population.

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.

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.

Markers of Myocardial Stress, Myocardial Injury, and Subclinical Inflammation and the Risk of Sudden Death.

BACKGROUND: The majority of sudden cardiac deaths (SCDs) occur in low-risk populations often as the first manifestation of cardiovascular disease (CVD). Biomarkers are screening tools that may identify subclinical cardiovascular disease and those at elevated risk for SCD. We aimed to determine whether the total to high-density lipoprotein cholesterol ratio, high-sensitivity cardiac troponin I, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity C-reactive protein individually or in combination could identify individuals at higher SCD risk in large, free-living populations with and without cardiovascular disease. METHODS: We performed a nested case-control study within 6 prospective cohort studies using 565 SCD cases matched to 1090 controls (1:2) by age, sex, ethnicity, smoking status, and presence of cardiovascular disease. RESULTS: The median study follow-up time until SCD was 11.3 years. When examined as quartiles or continuous variables in conditional logistic regression models, each of the biomarkers was significantly and independently associated with SCD risk after mutually controlling for cardiac risk factors and other biomarkers. The mutually adjusted odds ratios for the top compared with the bottom quartile were 1.90 (95% CI, 1.30-2.76) for total to high-density lipoprotein cholesterol ratio, 2.59 (95% CI, 1.76-3.83) for high-sensitivity cardiac troponin I, 1.65 (95% CI, 1.12-2.44) for NT-proBNP, and 1.65 (95% CI, 1.13-2.41) for high-sensitivity C-reactive protein. A biomarker score that awarded 1 point when the concentration of any of those 4 biomarkers was in the top quartile (score range, 0-4) was strongly associated with SCD, with an adjusted odds ratio of 1.56 (95% CI, 1.37-1.77) per 1-unit increase in the score. CONCLUSIONS: Widely available measures of lipids, subclinical myocardial injury, myocardial strain, and vascular inflammation show significant independent associations with SCD risk in apparently low-risk populations. In combination, these measures may have utility to identify individuals at risk for SCD.

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.

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.

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.

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.

ECG left ventricular hypertrophy as a risk predictor of sudden cardiac death.

BACKGROUND: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is an established risk factor for cardiovascular events. However, limited data is available on the prognostic values of different ECG LVH criteria specifically to sudden cardiac death (SCD). Our goal was to assess relationships of different ECG LVH criteria to SCD. METHODS: Three traditional and clinically useful (Sokolow-Lyon, Cornell, RaVL) and a recently proposed (Peguero-Lo Presti) ECG LVH voltage criteria were measured in 5730 subjects in the Health 2000 Survey, a national general population cohort study. Relationships between LVH criteria, as well as their selected composites, to SCD were analyzed with Cox regression models. In addition, population-attributable fractions for LVH criteria were calculated. RESULTS: After a mean follow-up of 12.5 ±â€¯2.2 years, 134 SCDs had occurred. When used as continuous variables, all LVH criteria except for RaVL were associated with SCD in multivariable analyses. When single LVH criteria were used as dichotomous variables, only Cornell was significant after adjustments. The dichotomous composite of Sokolow-Lyon and Cornell was also significant after adjustments (hazard ratio for SCD 1.82, 95% confidence interval 1.20-2.70, P = 0.006) and was the only LVH measure that showed statistically significant population-attributable fraction (11.0%, 95% confidence interval 1.9-19.2%, P = 0.019). CONCLUSIONS: Sokolow-Lyon, Cornell, and Peguero-Lo Presti ECG, but not RaVL voltage, are associated with SCD risk as continuous ECG voltage LVH variables. When SCD risk assessment/adjustment is performed using a dichotomous ECG LVH measure, composite of Sokolow-Lyon and Cornell voltages is the preferred option.

Waveform prototype-based feature learning for automatic detection of the early repolarization pattern in ECG signals.

OBJECTIVE: Our aim was to develop an automated detection method, for prescreening purposes, of early repolarization (ER) pattern with slur/notch configuration in electrocardiogram (ECG) signals using a waveform prototype-based feature vector for supervised classification. APPROACH: The feature vectors consist of fragments of the ECG signal where the ER pattern is located, instead of abstract descriptive variables of ECG waveforms. The tested classifiers included linear discriminant analysis, k-nearest neighbor algorithm, and support vector machine (SVM). MAIN RESULTS: SVM showed the best performance in Friedman tests in our test data including 5676 subjects representing 45 408 leads. Accuracies of the different classifiers showed results well over 90%, indicating that the waveform prototype-based feature vector is an effective representation of the differences between ECG signals with and without the ER pattern. The accuracy of inferior ER was 92.74% and 92.21% for lateral ER. The sensitivity achieved was 91.80% and specificity was 92.73%. SIGNIFICANCE: The algorithm presented here showed good performance results, indicating that it could be used as a prescreening tool of ER, and it provides an additional identification of critical cases based on the distances to the classifier decision boundary, which are close to the 0.1 mV threshold and are difficult to label.

Electrocardiogram as a predictor of sudden cardiac death in middle-aged subjects without a known cardiac disease.

BACKGROUND: Abnormal 12­lead electrocardiogram (ECG) findings and proposing its ability for enhanced risk prediction, majority of the studies have been carried out with elderly populations with prior cardiovascular diseases. This study aims to denote the association of sudden cardiac death (SCD) and various abnormal ECG morphologies using middle-aged population without a known cardiac disease. METHODS: In total, 9511 middle-aged subjects (mean age 42 ±â€¯8.2 years, 52% males) without a known cardiac disease were included in this study. Risk for SCD was assessed after 10 and 30-years of follow-up. RESULTS: Abnormal ECG was present in 16.3% (N = 1548) of subjects. The incidence of SCD was distinctly higher among those with any ECG abnormality in 10 and 30-year follow-ups (1.7/1000 years vs. 0.6/1000 years, P < 0.001; 3.4/1000 years vs. 1.9/1000 years, P < 0.001). At 10-year point, competing risk multivariate regression model showed HR of 1.62 (95% CI 1.0-2.6, P = 0.05) for SCD in subjects with abnormal ECG. QRS duration ≥ 110 ms, QRST-angle > 100°, left ventricular hypertrophy, and T-wave inversions were the most significant independent ECG risk markers for 10-year SCD prediction with up to 3-fold risk for SCD. Those with ECG abnormalities had a 1.3-fold risk (95% CI 1.07-1.57, P = 0.007) for SCD in 30-year follow-up, whereas QRST-angle > 100°, LVH, ER ≥ 0.1 mV and ≥0.2 mV were the strongest individual predictors. Subjects with multiple ECG abnormalities had up to 6.6-fold risk for SCD (P < 0.001). CONCLUSION: Several ECG abnormalities are associated with the occurrence of early and late SCD events in the middle-age subjects without known history of cardiac disease.

Repolarization Heterogeneity Measured With T-Wave Area Dispersion in Standard 12-Lead ECG Predicts Sudden Cardiac Death in General Population.

BACKGROUND: We developed a novel electrocardiographic marker, T-wave area dispersion (TW-Ad), which measures repolarization heterogeneity by assessing interlead T-wave areas during a single cardiac cycle and tested whether it can identify patients at risk for sudden cardiac death (SCD) in the general population. METHODS AND RESULTS: TW-Ad was measured from standard digital 12-lead ECG in 5618 adults (46% men; age, 50.9±12.5 years) participating in the Health 2000 Study-an epidemiological survey representative of the Finnish adult population. Independent replication was performed in 3831 participants of the KORA S4 Study (Cooperative Health Research in the Region of Augsburg; 49% men; age, 48.7±13.7 years; mean follow-up, 8.8±1.1 years). During follow-up (7.7±1.4 years), 72 SCDs occurred in the Health 2000 Survey. Lower TW-Ad was univariately associated with SCD (0.32±0.36 versus 0.60±0.19; P<0.001); it had an area under the receiver operating characteristic curve of 0.809. TW-Ad (≤0.46) conferred a hazard ratio of 10.8 (95% confidence interval, 6.8-17.4; P<0.001) for SCD; it remained independently predictive of SCD after multivariable adjustment for clinical risk markers (hazard ratio, 4.6; 95% confidence interval, 2.7-7.4; P<0.001). Replication analyses performed in the KORA S4 Study confirmed an increased risk for cardiac death (unadjusted hazard ratio, 5.5; 95% confidence interval, 3.2-9.5; P<0.001; multivariable adjusted hazard ratio, 1.9; 95% confidence interval, 1.1-3.5; P<0.05). CONCLUSION: Low TW-Ad, reflecting increased heterogeneity of repolarization, in standard 12-lead resting ECGs is a powerful and independent predictor of SCD in the adult general population.

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.

The ability of an electrocardiogram to predict fatal and non-fatal cardiac events in asymptomatic middle-aged subjects.

INTRODUCTION: The long-term prognostic value of a standard 12-lead electrocardiogram (ECG) for predicting cardiac events in apparently healthy middle-aged subjects is not well defined. MATERIALS AND METHODS: A total of 9511 middle-aged subjects (mean age 43 ± 8.2 years, 52% males) without a known cardiac disease and with a follow-up 40 years were included in the study. Fatal and non-fatal cardiac events were collected from the national registries. The predictive value of ECG was separately analyzed for 10 and 30 years. Major ECG abnormalities were classified according to the Minnesota code. RESULTS: Subjects with major ECG abnormalities (N = 1131) had an increased risk of cardiac death after 10-years (adjusted hazard ratio [HR] 1.7; 95% confidence interval [95% CI], 1.1-2.5, p = 0.009) and 30-years of follow-up (HR 1.3, 95% CI, 1.1-1.5, p < 0.001). Model discrimination measured with the C-index showed only a minor improvement with the inclusion of ECG abnormalities: 0.851 versus 0.853 and 0.742 versus 0.743 for 10- and 30-year follow-up, respectively. ECG did not predict non-fatal cardiac events after 10-years or 30-years of follow-up. DISCUSSION: Major ECG abnormalities are associated with an increased risk of short and long-term cardiac mortality in middle-aged subjects. However, the improvement in discrimination between subjects with and without fatal cardiac events was marginal with abnormal ECG. KEY MESSAGES: Abnormalities observed on 12-lead electrocardiogram are shown to have prognostic significance for cardiac events in elderly subjects without known cardiac disease. Our results suggest that ECG abnormalities increase the risk of fatal cardiac events also in middle-aged healthy subjects.

12-Lead electrocardiogram as a predictor of sudden cardiac death: from epidemiology to clinical practice.

Sudden cardiac death (SCD) causes a high burden of premature deaths in the population affecting subjects of all ages. The identification of subjects at high risk for SCD is of great importance as the prevention of many of these events would be possible with the treatment of underlying cardiac diseases and the use of implantable cardioverter-defibrillators (ICD). However, the current selection of patients for ICD therapy is based solely on left ventricular ejection fraction, and thus a substantial portion of patients at high risk does not qualify for the therapy. Role of the standard electrocardiogram (ECG) in SCD risk stratification has been under active research during the last decade and multiple abnormalities of depolarization and repolarization on the ECG associated with an increased risk of SCD have been identified. In this review, we describe the basic pathophysiological principles behind these changes. We also review the current knowledge of the prognostic significance of ECG predictors of SCD in the general population, and in patients with coronary heart disease (CHD), heart failure, cardiomyopathies, and in inheritable arrhythmia syndromes. Also, insights into the novel digital ECG signal processing techniques are provided.

Diabetes, glucose tolerance, and the risk of sudden cardiac death.

BACKGROUND: Diabetes predisposes to sudden cardiac death (SCD). However, it is uncertain whether greater proportion of cardiac deaths are sudden among diabetes patients than other subjects. It is also unclear whether the risk of SCD is pronounced already early in the course of the disease. The relationship of impaired glucose tolerance (IGT) and SCD is scarcely documented. METHODS: A general population cohort of 10594 middle-aged subjects (mean age 44 years, 52.6 % male, follow-up duration 35-41 years) was divided into diabetes patients (n = 82), subjects with IGT (n = 3806, plasma glucose ≥9.58 mmol/l in one-hour glucose tolerance test), and controls (n = 6706). RESULTS: Diabetes patients had an increased risk of SCD after adjustment confounders (hazard ratio 2.62, 95 % confidence interval 1.46-4.70, p = 0.001) but risk for non-sudden cardiac death was similarly increased and the proportion of SCD of cardiac deaths was not increased. The SCD risk persisted after exclusion of subjects with baseline cardiac disease or non-fatal cardiac events during the follow-up. Subjects with IGT were at increased risk for SCD (univariate hazard ratio 1.51; 95 % confidence interval 1.31-1.74; p < 0.001) and also for non-sudden cardiac deaths and non-fatal cardiac events but adjustments for other risk factors attenuated these effects. CONCLUSIONS: Diabetes was associated with increased risk of SCD but also the risk of non-sudden cardiac death was similarly increased. The proportion of cardiac deaths being sudden in subjects with diabetes was not increased. The higher SCD risk in diabetes patients was independent of known cardiac disease at baseline or occurrence of non-fatal cardiac event during the follow-up.

Prevalence and prognosis of ECG abnormalities in normotensive and hypertensive individuals.

OBJECTIVE: To define the prevalence and prognosis of ECG abnormalities in hypertensive individuals. METHODS: ECG, blood pressure and other cardiovascular risk factors were recorded in a nationwide population sample of 5800 Finns. The presence of 15 ECG abnormalities was evaluated. Participants were divided into categories by blood pressure and followed for coronary heart (CHD) and cardiovascular disease (CVD) events. RESULTS: Mean follow-up was 10.4 ±â€Š2.2 years. The age- and sex-adjusted prevalence rates of ECG abnormalities were generally higher in the hypertensive participants than in normotensive individuals. In multivariable-adjusted Cox models, the following ECG abnormalities predicted CHD in hypertensive participants: left ventricular hypertrophy (LVH) by Sokolow-Lyon criteria [hazard ratio, 1.47; 95% confidence interval (CI), 1.07-2.01; P = 0.02], LVH with ST-depression and negative T wave (ST/T changes) (hazard ratio, 2.31; 95% CI, 1.20-4.43, P = 0.01), ST/T changes (hazard ratio, 2.12; 95% CI, 1.34-3.36; P = 0.001), positive T wave in lead aVR (AVRT+) (hazard ratio, 1.74; 95% CI, 1.15-2.64; P = 0.009) and poor R-wave progression (hazard ratio, 2.02; 95% CI, 1.27-3.22; P = 0.003). These ECG abnormalities were also significant predictors of CVD in hypertensive participants (P ≤ 0.03 for all). Nonspecific intraventricular conduction delay predicted CVD in the whole population (hazard ratio, 1.50; 95% CI, 1.06-2.13; P = 0.02). Prolonged QT interval, abnormal P-wave indices, left axis deviation and early repolarization pattern were not associated with CHD or CVD. CONCLUSION: ECG abnormalities are highly prevalent in hypertensive individuals. LVH is still the cornerstone of cardiovascular risk assessment in hypertensive patients. The additional assessment of ST/T changes, AVRT+ and poor R-wave progression in ECGs could improve risk prediction in hypertensive patients.