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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.

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

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). Conclusions: PRWP was associated with adverse prognosis in the general population and with SCD in subjects with CAD.

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

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: 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.

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 (

Background Sudden cardiac death (SCD) remains a major cause of premature mortality worldwide, so there has been an ongoing pursuit for tools for SCD risk stratification. Coronary artery disease is the major cause for SCD in adults, but the level of risk associated with multiple cardiovascular risk factors is not well established. Purpose To create a clinical risk score for estimating SCD risk in the general population. Methods Using data from a Finnish general population cohort of 7200 adults (mean age 51y, 46% male) with a mean follow-up of 24±11 years, we assessed the incremental SCD risk associated with the presence of several cardiovascular risk factors. SCD events were adjudicated based on death certificates according to the established criteria (autopsy was performed on 48% of SCD cases). Hazard ratios (HR) for SCD and all-cause mortality were calculated using the Cox proportional hazards model. Of the multiple parameters analysed, male sex, increasing age, diabetes, hypertension, smoking and previously diagnosed cardiac disease were independently associated with SCD in a multivariable model. Based on the magnitude of risk, a SCD risk score was created (2 points: age >70y; 1 point: male sex, age 60–70y, diabetes, hypertension, smoking, cardiac disease). Results 75.2% of the study subjects had 0–2 risk points, 12.8% 3 risk points, and 12.0% >3 risk points. During the follow-up, 400 SCDs occurred. Increasing risk score was associated with a progressively greater risk for SCD (Figure). Compared with subjects without risk factors, those with a risk score of 3 had a HR of 21.2 (95% CI 12.7–35.4, p3 had a HR of 52.6 (95% CI 31.3–88.3, p3 [95% CI 27.6–35.9, p Risk of SCD according to the risk score Conclusions Accumulation of multiple cardiovascular risk factors is associated with a markedly elevated risk for SCD in the general population. This highlights the need for SCD prevention efforts with lifestyle interventions and medical therapy in the high-risk subjects. Studies on focused SCD risk stratification may be warranted in the subjects at highest risk.

ObjectiveWe investigated whether combining several ECG abnormalities would identify general population subjects with a high sudden cardiac death (SCD) risk.MethodsIn 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).ResultsNo 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.ConclusionThe ECG risk score successfully identified general population subjects with a high SCD risk. Combining ECG risk markers may improve the risk stratification for SCD.

Negative U-waves are a relatively rare finding in an electrocardiogram (ECG), but are often associated with cardiac disease. The prognostic significance of negative U-waves in the general population is unknown. We evaluated 12-lead ECGs of 6,518 adults (45% male, mean age 50.9 +/- 13.8 years) for the presence of U-waves, and followed the subjects for 24.5 +/- 10.3 years. Primary end points were all-cause mortality, cardiac mortality, and sudden cardiac death; secondary end point was hospitalization due to cardiac causes. Negative U-waves (amplitude >= 0.05 mV) were present in 231 subjects (3.5%), minor negative (amplitude 0.30). In conclusion, negative U-waves are associated with adverse events in the general population. In men, this association is independent of cardiovascular risk factors. (C) 2018 Elsevier Inc. All rights reserved.

Background QRS transition zone is related to the electrical axis of the heart in the horizontal plane and is easily determined from the precordial leads of a standard 12-lead ECG. However, whether delayed QRS transition, or clockwise rotation of the heart, carries prognostic implications and predicts sudden cardiac death (SCD) is unclear. Objective The purpose of this study was to study whether delayed transition is associated with mortality and SCD. Methods We evaluated 12-lead ECGs of 10,815 Finnish middle-aged subjects from the general population (52% men, mean age 44 ± 8.5 years) and followed them for 30 ± 11 years. Main end-points were mortality and SCD. Results Delayed QRS transition at lead V 4 or later occurred in 1770 subjects (16.4%) and markedly delayed transition at lead V 5 or later in 146 subjects (1.3%). Delayed transition zone was associated with older age, male gender, higher body mass index, hypertension, baseline cardiovascular disease, leftward shift of the frontal QRS axis, wider QRS-T angle, and ECG left ventricular hypertrophy. After adjusting for several clinical and ECG variables, delayed transition was associated with overall mortality (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.07–1.22, P P = .029). Markedly delayed transition at V 5 or later predicted significantly SCD (HR 1.89, 95% CI 1.18–3.03, P = .008) and all-cause mortality (HR 1.30, 95% CI 1.07–1.58, P = .01). However, further adjustments for repolarization abnormalities attenuated this effect. Conclusion Delayed QRS transition in the precordial leads of an ECG seems to be a novel ECG risk marker for SCD. In particular, markedly delayed transition was associated with significantly increased risk of SCD, independent of confounding factors.

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.

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

Evidence of the role of body mass index (BMI) as a risk factor for sudden cardiac death (SCD) is conflicting, and how electrocardiographic (ECG) SCD risk markers perform in subjects with different BMIs is not known. In this study, a general population cohort consisting of 10,543 middle-aged subjects (mean age 44 years, 52.7% men) was divided into groups of lean (BMI20, n = 374), normal weight (BMI 20.0 to 24.9, n = 4,334), overweight (BMI 25.0 to 29.9, n = 4,390), and obese (BMI30, n = 1,445) subjects. Cox proportional hazards models adjusted for confounders were used to assess the risk for SCD associated with BMI and the risk for SCD associated with ECG abnormalities in subjects with different BMIs. The overweight and obese subjects were at increased risk for SCD (hazard ratios [95% CIs] were 1.33 [1.13 to 1.56], p = 0.001 and 1.79 [1.44 to 2.23], p0.001 for overweight and obese subjects, respectively). The risk of non-SCD had a similar relation with BMI as SCD. Hazard ratios associated with ECG abnormalities were 3.03, 1.75, 1.74, and 1.34 in groups of lean, normal weight, overweight, and obese subjects, respectively, but no statistical significance was reached in the obese. ECG abnormalities improved integrated discrimination indexes and continuous net reclassification indexes statistically significantly only in the normal weight group. In conclusion, the overweight and obese are at increased risk for SCD but also for non-SCD, and ECG abnormalities are associated with increased risk of SCD also in normal weight subjects presenting with less traditional cardiovascular risk factors.