QRS-T angle: is it a specific parameter associated with sudden cardiac death in type 2 diabetes? Results from the SURDIAGENE and the Mini-Finland prospective cohorts.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with a high risk of sudden cardiac death (SCD), but the risk of dying from another cause (non-SCD) is proportionally even higher. The aim of the study was to identify easily available ECG-derived features associated with SCD, while considering the competing risk of dying from non-SCD causes. METHODS: In the SURDIAGENE (Survie, Diabete de type 2 et Genetique) French prospective cohort of individuals with type 2 diabetes, 15 baseline ECG parameters were interpreted among 1362 participants (mean age 65 years; HbA1c 62±17 mmol/mol [7.8±1.5%]; 58% male). Competing risk models assessed the prognostic value of clinical and ECG parameters for SCD after adjusting for age, sex, history of myocardial infarction, N-terminal pro b-type natriuretic peptide (NT-proBNP), HbA1c and eGFR. The prospective Mini-Finland cohort study was used to externally validate our findings. RESULTS: During median follow-up of 7.4 years, 494 deaths occurred including 94 SCDs. After adjustment, frontal QRS-T angle ≥90° (sub-distribution HR [sHR] 1.68 [95% CI 1.04, 2.69], p=0.032) and NT-proBNP level (sHR 1.26 [95% CI 1.06, 1.50] per 1 log, p=0.009) were significantly associated with a higher risk of SCD. Nevertheless, frontal QRS-T angle was the only marker not to be associated with causes of death other than SCD (sHR 1.08 [95% CI 0.84, 1.39], p=0.553 ). These findings were replicated in the Mini-Finland study subset of participants with diabetes (sHR 2.22 [95% CI 1.05, 4.71], p=0.04 for SCD and no association for other causes of death). CONCLUSIONS/INTERPRETATION: QRS-T angle was specifically associated with SCD risk and not with other causes of death, opening an avenue for refining SCD risk stratification in individuals with type 2 diabetes.

Predicting risk of AF in ischaemic stroke using sinus rhythm ECG abnormalities: A meta-analysis.

OBJECTIVE: To identify ECG changes in sinus rhythm that may be used to predict subsequent development of new AF. METHOD: We identified prospective and retrospective cohort or case control studies evaluating ECG patterns from a 12-lead ECG in sinus rhythm taken in hospital or community predicting subsequent development of new AF. For each identified ECG predictor, we then identify absolute event rates and pooled risk ratios (RR) using an aggregate level random effects meta-analysis. RESULTS: We identified 609,496 patients from 22 studies. ECG patterns included P wave terminal force V1 (PTFV1), interatrial block (IAB) and advanced interatrial block (aIAB), abnormal P wave axis (aPWA), PR prolongation and atrial premature complexes (APCs). Pooled risk ratios reached significance for each of these; PTFV1 RR 1.48 (95% CI 1.04-2.10), IAB 2.54 (95% CI 1.64-3.93), aIAB 4.05 (95% CI 2.64-6.22), aPWA 1.89 (95% CI 1.25-2.85), PR prolongation 2.22 (95% CI 1.27-3.87) and APCs 3.71 (95% CI 2.23-6.16). Diabetes reduced the predictive value of PR prolongation. CONCLUSION: APC and aIAB were most predictive of AF, while IAB, PR prolongation, PTFV1 and aPWA were also significantly associated with development of AF. These support their use in a screening tool to identify at risk cohorts who may benefit from further investigation, or following stroke, with empirical anticoagulation.

Percutaneous coronary intervention with drug-coated balloon-only strategy combined with single antiplatelet treatment in patients at high bleeding risk: Single center experience of a novel concept.

OBJECTIVES: At least 1 month of dual antiplatelet therapy is required after coronary stenting. The aim of this all-comers retrospective registry study was to assess the efficacy and safety of percutaneous coronary intervention (PCI) using drug-coated balloon (DCB) with single antiplatelet treatment (SAPT). METHODS: Between 2011 and 2020, 232 PCIs were performed in 172 patients using the DCB-only strategy and discharged with SAPT. RESULTS: The mean age of the patients was 75 ± 11 years and 59% were male. The clinical presentation was stable coronary artery disease (CAD) in 42% of the patients and acute coronary syndrome (ACS) in 58%. The lesions were mainly de novo (96%). The majority (58%) of treated lesions were in large coronary arteries (≥3.0 mm). Most (87%) of the patients were at high bleeding risk (HBR) with at least one major or two minor Academic Research Consortium (ARC) risk factors for bleeding. Periprocedural DAPT was used in 49% of the patients. The 12-month major adverse cardiac events (MACE, the composition of cardiovascular death, nonfatal myocardial infarction, and target-lesion revascularization) rate was 1.4% in stable CAD and 7.1% in ACS. The 12-month all-cause mortality after DBC only + SAPT strategy was 4.1% in stable CAD and 12.1% in ACS. The rate of ischemia-driven target lesion revascularisation (TLR) was 0% in stable CAD and 3.0% in ACS at 12 months. The 12-month rate of significant bleeding (BARC type 2-5) was 10.5%. There were no acute or subacute vessel closures. CONCLUSIONS: Despite the aged patient population with comorbidities, the TLR, MACE, and bleeding rates were low with DCB-only PCI combined with SAPT. This novel approach could reduce the post-PCI bleeding risk in patients with CAD and HBR compared to stenting.

Drug-coated balloon-only strategy for percutaneous coronary intervention of de novo left main coronary artery disease: the importance of proper lesion preparation.

This retrospective single-center registry study included all consecutive patients who underwent percutaneous coronary intervention (PCI) for a de novo left main coronary artery lesion using drug coated-balloon (DCB)-only strategy between August 2011 and December 2018. To best of our knowledge, no previous studies of DCB-only strategy of treating de novo left main coronary artery disease, exist. The primary endpoint was major adverse cardiovascular events (MACEs) including cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR). The cohort was divided into two groups depending on weather the lesion preparation was done according to the international consensus group guidelines. Sixty-six patients (mean age 75±8.6, 72% male), 52% of whom had acute coronary syndrome, underwent left main PCI with the DCB-only strategy. No procedural mortality and no acute closures of the treated left main occurred. At 12 months, MACE and TLR occurred in 24% and 6% of the whole cohort, respectively. If the lesion preparation was done according to the guidelines, the MACE and TLR rates were 21.2% and 1.9%. Left main PCI with the DCB only-strategy is safe leading to acceptable MACE and low TLR rates at one year, if the lesion preparation is done according to the guidelines.

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.

Interatrial block and P terminal force in the general population - Longitudinal changes, risk factors and prognosis.

BACKGROUND: Partial and advanced interatrial block (IAB) and P terminal force (PTF) in lead V1 are markers of atrial remodeling and risk factors for atrial fibrillation (AF). There is a lack of information about constancy and possible factors influencing the development of these P-wave abnormalities. METHODS: The study sample consisted of 6058 Finnish participants (mean age 52.16 ± 14.60 years, 45.0% male) from the general population with an ECG taken in a health examination, and from 3224 of these participants, who had a re-examination 11 years later. Risk factors for incident partial and advanced IAB and PTF were studied using binomial logistic regression analysis, and the prognostic significance of these ECG changes for new AF was studied using time-varying Cox regression analysis. RESULTS: The rate of reversal to normal of the studied ECG parameters were 47.4% for partial IAB, 40.0% for advanced IAB and 79.3% for PTF. Age, male sex, hypertension, higher BMI, higher LDL cholesterol, ECG left ventricular hypertrophy, use of beta blocker, and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist were independently associated with a risk to develop incident P-wave abnormality. Partial IAB was independently associated with increased AF risk (HR 1.28 [95% CI 1.04-1.58]), as was also advanced IAB (HR 1.72 [95% CI 1.07-2.75]). CONCLUSION: Traditional cardiovascular risk factors increase the risk of a new P-wave abnormality. Partial and advanced IAB are associated with increased AF risk. Surprisingly, P-wave abnormalities are often reversible during long-term follow-up in the general population.

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.

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

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

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.

Intentional weight loss as a predictor of type 2 diabetes occurrence in a general adult population.

INTRODUCTION: Observational and intervention studies have verified that weight loss predicts a reduced type 2 diabetes (T2D) risk. At the population level, knowledge on the prediction of self-report intentional weight loss (IWL) on T2D incidence is, however, sparse. We studied the prediction of self-report IWL on T2D incidence during a 15-year follow-up in a general adult population. RESEARCH DESIGN AND METHODS: The study sample from the representative Finnish Health 2000 Survey comprised 4270 individuals, aged 30-69 years. IWL was determined with questions concerning dieting attempts and weight loss during the year prior to baseline. Incident T2D cases during a 15-year follow-up were drawn from national health registers. The strength of the association between IWL and T2D incidence was estimated with the Cox model. RESULTS: During the follow-up, 417 incident cases of T2D occurred. IWL predicted an increased risk of T2D incidence (HR 1.44; 95% CI 1.11 to 1.87, p=0.008) in a multivariable model. In interaction analyses comparing individuals with and without IWL, a suggestively elevated risk emerged in men, the younger age group, among less-educated people and in individuals with unfavorable values in several lifestyle factors. CONCLUSIONS: Self-report IWL may predict an increased risk of T2D in long-term, probably due to self-implemented IWL tending to fail. The initial prevention of weight gain and support for weight maintenance after weight loss deserve greater emphasis in order to prevent T2D.

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.

The prevalence and prognostic significance of interatrial block in the general population.

Introduction: Partial and advanced interatrial block (IAB) in the electrocardiographic (ECG) represents inter-atrial conduction delay. IAB is associated with atrial fibrillation (AF) and stroke in the general population.Material and methods: A representative sample of Finnish subjects (n = 6354) aged over 30 years (mean: 52.2 years, standard deviation: 14.6) underwent a health examination including a 12-lead ECG. Five different IAB groups based on automatic measurements were compared to normal P waves using multivariate-adjusted Cox proportional hazard model. Follow-up lasted up to 15 years.Results: The prevalence of advanced and partial IAB was 1.0% and 9.7%, respectively. In the multivariate model, both advanced (hazard ratio (HR): 1.63 (95% confidence interval (CI): 1.00-2.65)) and partial IAB (HR: 1.39 (1.09-1.77)) were associated with increased risk of AF. Advanced IAB was associated with increased risk of stroke or transient ischaemic attack (TIA) independently of associated AF (HR: 2.22 (1.20-4.13)). Partial IAB was also associated with increased risk of being diagnosed with coronary heart disease (HR: 1.26 (1.01-1.58)).Discussion: IAB is a rather frequent finding in the general population. IAB is a risk factor for AF and is associated with an increased risk of stroke or TIA independently of associated AF.Key messagesBoth partial and advanced interatrial block are associated with increased risk of atrial fibrillation in the general population.Advanced interatrial block is an independent risk factor for stroke and transient ischaemic attack.The clinical significance of interatrial block is dependent on the subtype classification.

Metastable Atrial State Underlies the Primary Genetic Substrate for MYL4 Mutation-Associated Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common clinical arrhythmia and is associated with heart failure, stroke, and increased mortality. The myocardial substrate for AF is poorly understood because of limited access to primary human tissue and mechanistic questions around existing in vitro or in vivo models. METHODS: Using an MYH6:mCherry knock-in reporter line, we developed a protocol to generate and highly purify human pluripotent stem cell-derived cardiomyocytes displaying physiological and molecular characteristics of atrial cells. We modeled human MYL4 mutants, one of the few definitive genetic causes of AF. To explore non-cell-autonomous components of AF substrate, we also created a zebrafish Myl4 knockout model, which exhibited molecular, cellular, and physiologic abnormalities that parallel those in humans bearing the cognate mutations. RESULTS: There was evidence of increased retinoic acid signaling in both human embryonic stem cells and zebrafish mutant models, as well as abnormal expression and localization of cytoskeletal proteins, and loss of intracellular nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide + hydrogen. To identify potentially druggable proximate mechanisms, we performed a chemical suppressor screen integrating multiple human cellular and zebrafish in vivo endpoints. This screen identified Cx43 (connexin 43) hemichannel blockade as a robust suppressor of the abnormal phenotypes in both models of MYL4 (myosin light chain 4)-related atrial cardiomyopathy. Immunofluorescence and coimmunoprecipitation studies revealed an interaction between MYL4 and Cx43 with altered localization of Cx43 hemichannels to the lateral membrane in MYL4 mutants, as well as in atrial biopsies from unselected forms of human AF. The membrane fraction from MYL4-/- human embryonic stem cell derived atrial cells demonstrated increased phospho-Cx43, which was further accentuated by retinoic acid treatment and by the presence of risk alleles at the Pitx2 locus. PKC (protein kinase C) was induced by retinoic acid, and PKC inhibition also rescued the abnormal phenotypes in the atrial cardiomyopathy models. CONCLUSIONS: These data establish a mechanistic link between the transcriptional, metabolic and electrical pathways previously implicated in AF substrate and suggest novel avenues for the prevention or therapy of this common arrhythmia.

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.

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.

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.

Risk Factors Associated With Atrioventricular Block.

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

Long-term prognostic impact of hyperuricemia in community.

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.

Prevalence and Prognostic Significance of Negative U-waves in a 12-lead Electrocardiogram in the General Population.

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 <0.05 mV) or discordant U-waves in 1,004 subjects (15.4%), normal positive U-waves in 3,950 (60.6%) subjects, and no U-waves were observed in 603 subjects (9.3%). In 730 subjects (11.2%), U-waves were unassessable. When adjusted for age and gender, negative U-waves were associated with all end points (p <0.01). In an analysis adjusted for multiple demographic and clinical factors, in men, negative U-waves were associated with increased risk of all-cause mortality (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.26 to 2.03; p <0.001), cardiac mortality (HR 1.74; 95% CI 1.26 to 2.39; p = 0.001), and cardiac hospitalization (HR 1.67; 95% CI 1.27 to 2.18; p <0.001), but not with sudden cardiac death, whereas women did not show a significant association to any of the end points (p >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.