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Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): The Finnish Foundation for Cardiovascular Research, and Helsinki and Uusimaa Hospital District research fund. Background and aims Direct oral anticoagulants (DOACs) have largely replaced warfarin in patients with atrial fibrillation (AF) to reduce risk of stroke. However, it is not known whether DOACs are more efficacious in preventing stroke or safer than good-quality warfarin treatment with high time in therapeutic range (TTR). Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients that combines data from several Finnish health care registers. We analyzed all new-onset AF patients in Finland from January 2011 to December 2018 with laboratory data available. Comorbidities, concomitant medications and CHA2DS2-VASc -scores were recorded until date of AF diagnosis. OAC purchases from diagnosis of AF to the end of study were analyzed. ICD-10 diagnoses for stroke (ischemic or hemorrhagic) or transient ischemic attack during OAC use were analyzed until maximum follow-up of 730 days. Confounding factors by baseline characteristics as well as medications were taken in account by use of an inverse probability of treatment weighted analysis. For warfarin users, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. Rate of stroke in different TTR quartiles for warfarin users were compared to standard dose dabigatran (150 mg bd.), apixaban (5mg bd.) and rivaroxaban (20mg od.). Results Altogether, 74 008 new-onset AF patients with OAC therapy (50.4 % male, mean age 73.0 years, 43 549 on warfarin, with mean TTR 66% and median TTR 72%) were followed for 109 143 patient years (py). Rate of stroke among patients with standard dose direct oral anticoagulants was 6.0/100 py for dabigatran (n=4545), 6.2/100 py for apixaban (n=12 426) and 4.0/100 py for rivaroxaban (n=12 950). In the TTR quartiles of patients on warfarin, rates of stroke were 9.3, 7.2, 5.5 and 4.3/100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of stroke were 6.3, 6.1 and 4.5/100 py for dabigatran, apixaban and rivaroxaban, respectively, and for warfarin from the lowest to the highest quartile: 8.8, 7.0, 5.5 and 4.2/100 py, respectively. The Figure provides survival probabilities (crude rates) of stroke with confidence intervals of the analysed OAC groups. Conclusion Rates of stroke were evidently the highest among patients on warfarin in the two lowest TTR quartiles, while the differences between high TTR groups and standard dose DOACs were only modest.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District (TYH2019309) and The Finnish Foundation for Cardiovascular Research Background and aims Elderly patients with atrial fibrillation (AF) and patients with renal failure – for example – are recommended to use reduced doses of direct oral anticoagulants (DOACs) to minimize risk of ischemic stroke and hemorrhagic complications. However, it is not known whether DOACs used with reduced doses are better than warfarin when the quality of warfarin treatment is available by means of time in therapeutic range (TTR). Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients that combines data from several Finnish health care registers. Here all new-onset AF patients from 2011 to 2018 on reduced dose DOAC in Finland and patients on warfarin with TTR data were analyzed. Comorbidities, concomitant medications and CHA2DS2-VASc -scores were recorded until date of AF diagnosis. OAC purchases from diagnosis of AF to the end of study were analyzed. ICD-10 diagnoses for stroke (ischemic or hemorrhagic) or transient ischemic attack during OAC-use were analyzed until maximum follow-up of 730 days. Crude rates of stroke as well as weighted rates are provided. To avoid confounding by baseline characteristics as well as medications, an inverse probability of treatment weighted analysis was made. For warfarin users with sufficient laboratory data, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. Results Altogether, 52 204 new-onset AF patients with OAC therapy (46.1 % male, mean age 75.7 years, 43 549 on warfarin - with mean TTR 66%, median TTR 72%) were followed for 91 549 patient-years (py). Rate of stroke among patients on lower dose DOACs was 5.2/100 patient years (py) for dabigatran (n=2 672), 4.3/100 py for apixaban (n=3 936), 3.9 /100 py for rivaroxaban (n=1 866). In the TTR-quartiles of patients on warfarin, the rates of stroke were 9.3, 7.2, 5.5 and 4.3 /100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of stroke were 5.1, 3.5 and 3.1/100 py for dabigatran, apixaban and rivaroxaban, respectively and for warfarin from the lowest to the highest quartile: 8.7, 7.0, 5.4 and 4.1/100 py. Figure provides survival probabilities of the OAC groups with confidence limits. Conclusion In AF patients treated with OAC, the rates of stroke were highest among patients on warfarin at the lowest TTR quartiles, while the differences between high TTR groups and lower dose DOACs were only modest.

Background Patients with aortic stenosis (AS) have been underrepresented in the trials evaluating direct oral anticoagulants (DOACs) in atrial fibrillation (AF). We aimed to assess whether AS impacts outcomes in patients with AF and estimate the effects of DOACs versus warfarin in patients with AF and AS. Methods and Results The registry‐based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covered all patients with AF diagnosed during 2007 to 2018 in Finland. Hazard ratios (HRs) of first‐ever gastrointestinal bleeding, intracranial bleeding, any bleeding, ischemic stroke, and death were estimated with cause‐specific hazards regression adjusted for anticoagulant exposure variables. We identified 183 946 patients (50.5% women; mean age, 71.7 [SD, 13.5] years) with incident AF without prior bleeding or ischemic stroke, of whom 5231 (2.8%) had AS. The crude incidence rate of all outcomes was higher in patients with AS than in patients without AS. After propensity score matching, AS was associated with the hazard of any bleeding, gastrointestinal bleeding, and death but not with intracranial bleeding or ischemic stroke (adjusted HRs, 1.36 [95% CI, 1.25–1.48], 1.63 [95% CI, 1.43–1.86], 1.32 [95% CI, 1.26–1.38], 0.96 [95% CI, 0.78–1.17], and 1.11 [95% CI, 0.99–1.25], respectively). Among patients with AS, DOACs were associated with a lower risk of ischemic stroke when compared with warfarin, while bleeding and mortality did not differ between DOACs and warfarin. Conclusions AS is associated with substantially higher risk of gastrointestinal bleeding in patients with AF. DOACs may be more effective in preventing ischemic stroke than warfarin in patients with AF and AS. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04645537.

Aims To evaluate the prognostic significance of novel P-wave morphology descriptors in general population. Methods and results Novel P-wave morphology variables were analyzed from orthogonal X-, Y-, Z-leads of the digitized electrocardiogram using a custom-made software in 6906 middle-aged subjects of the Mini-Finland Health Survey. A total of 3747 (54.3%) participants died during the follow-up period of 24.3 ± 10.4 years; 379 (5.5%) of the study population succumbed to sudden cardiac death (SCD), 928 (13.4%) to non-SCD (NSCD) and 2440 (35.3%) patients to non-cardiac death (NCD). In univariate comparisons, most of the studied P-wave morphology parameters had a significant association with all modes of death (P from Conclusion Abnormalities of P-wave morphology are associated with the risk of all modes of death in general population. After relevant adjustments, PMD was still closely associated with the risk of SCD but not with NSCD or NCD. P-MaxAmp-Z predicted SCD even after adjustments, however, it also retained its association with NSCD and NCD.

Guidelines on the management of atrial fibrillation (AF) have evolved significantly during the past two decades, but the concurrent developments in real-life management and prognosis of AF are unknown. We assessed trends in the treatment and outcomes of patients with incident AF between 2007 and 2017.The registry-based nationwide FinACAF (Finnish AntiCoagulation in Atrial Fibrillation) cohort covers all patients with AF in Finland from all levels of care. We determined the proportion of patients who were treated with oral anticoagulants (OACs) or rhythm control therapies, experienced an ischemic stroke or bleeding event requiring hospitalization, or died within a one-year follow-up after AF diagnosis. We identified 206,909 patients (mean age 72.6 years) with incident AF. During the study period, use of OACs increased from 43.6 to 76.3%, and the increase was most evident in patients with at least moderate stroke risk. One-year mortality decreased from 13.3 to 10.6%, and the ischemic stroke rate from 5.3 to 2.2%. The prognosis especially improved in patients over 75 years of age. Concurrently, a small increase in major bleeding events was observed. Use of catheter ablation increased continuously over the study period, but use of other rhythm-control therapies decreased after 2013.Stroke prevention with OACs in patients with incident AF improved considerably from 2007 to 2017 in Finland. This development was accompanied by decreasing one-year mortality and the reduction of the ischemic stroke rate by more than half, particularly among elderly patients, whereas there was only slight increase in severe bleeding events.

Aims Guidelines on the management of atrial fibrillation (AF) have evolved significantly during the past two decades, but the concurrent developments in real-life management and prognosis of AF are unknown. We assessed trends in the treatment and outcomes of patients with incident AF between 2007 and 2017. Methods and results The registry-based nationwide FinACAF (Finnish AntiCoagulation in Atrial Fibrillation) cohort covers all patients with AF in Finland from all levels of care. We determined the proportion of patients who were treated with oral anticoagulants (OACs) or rhythm control therapies, experienced an ischaemic stroke or bleeding event requiring hospitalization, or died within 1-year follow-up after AF diagnosis. We identified 206 909 patients (mean age 72.6 years) with incident AF. During the study period, use of OACs increased from 43.6 to 76.3%, and the increase was most evident in patients with at least moderate stroke risk. One-year mortality decreased from 13.3 to 10.6%, and the ischaemic stroke rate from 5.3 to 2.2%. The prognosis especially improved in patients over 75 years of age. Concurrently, a small increase in major bleeding events was observed. Use of catheter ablation increased continuously over the study period, but use of other rhythm-control therapies decreased after 2013. Conclusion Stroke prevention with OACs in patients with incident AF improved considerably from 2007 to 2017 in Finland. This development was accompanied by decreasing 1-year mortality and the reduction of the ischaemic stroke rate by more than half, particularly among elderly patients, whereas there was only slight increase in severe bleeding events.

Aim Women with atrial fibrillation (AF) have been reported to receive less antiarrhythmic therapies (AAT) than men. We assessed sex differences in AAT use in Finland. Methods The FinACAF registry linked data from several nationwide registries covering all levels of care in addition to drug purchases and included records on all patients diagnosed with incident AF in Finland during 2007–2018. The outcomes of interest (use of antiarrhythmic drugs (AAD), cardioversions (CV), catheter ablation procedures and any AAT including all aforementioned rhythm control modalities) were identified based on procedure-specific codes and drug purchases. Sex differences in AAT use were analyzed in the entire cohort and separately in three age groups: Results Altogether, 229565 patients (50.0% female; mean age 68.90±13.44 in men and 76.57±11.79 in women) with incident AF were identified. In the entire patient population, female sex was associated a higher incidence of AAD use and lower incidence of CVs and ablation procedures contributing to an overall slightly lower incidence of any AAT compared to men (Table 1). In the age group specific analyses, the lower incidence of CVs and higher incidence of AAD use in females were observed only in patients Conclusion Our nationwide data showed no considerable sex difference in overall use of AAT in Finland. Despite a lower number of CVs in women, ablation procedures were performed almost equally and AADs were used more frequently in women compared to men. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Sydäntutkimussäätiö

Funding Information: Konsta Teppo: Research grants: The Finnish Foundation for Cardiovascular Research. Jussi Jaakkola: none. Fausto Biancari: none Olli Halminen: none. Jukka Putaala: Putaala reports personal fees from Boehringer-Ingelheim, personal fees and other from Bayer, grants and personal fees from BMS-Pfizer, personal fees from Portola, other from Amgen, personal fees from Herantis Pharma, personal fees from Terve Media, other from Vital Signum, personal fees from Abbott, outside the submitted work. Pirjo Mustonen: Consultant: Roche, BMS-Pfizer-alliance, Novartis Finland, Boehringer Ingelheim, MSD Finland. Jari Haukka: Consultant: Research Janssen R&D; Speaker: Bayer Finland. Miika Linna: Speaker: BMSPfizer-alliance, Bayer, Boehringer-Ingelheim. Juha Hartikainen: Research grants: The Finnish Foundation for Cardiovascular Research, EU Horizon 2020, EU FP7. Advisory Board Member: BMS-Pfizer-alliance, Novo Nordisk, Amgen. Speaker: Cardiome, Bayer. K.E. Juhani Airaksinen: Research grants: The Finnish Foundation for Cardiovascular Research; Speaker: Bayer, Pfizer and Boehringer-Ingelheim. Member in the advisory boards: Bayer, Pfizer and AstraZeneca. Mika Lehto: Consultant: BMS-Pfizer-alliance, Bayer, Boehringer-Ingelheim, and MSD; Speaker: BMS-Pfizer-alliance, Bayer, Boehringer Ingelheim, MSD, Terve Media and Orion Pharma. Research grants: Aarne Koskelo Foundation, The Finnish Foundation for Cardiovascular Research, and Helsinki and Uusimaa Hospital District research fund, Boehringer-Ingelheim. Funding Information: This work was supported by the Aarne Koskelo Foundation, The Finnish Foundation for Cardiovascular Research, and Helsinki and Uusimaa Hospital District research fund (TYH2019309). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2022 by the authors. Background: Rural–urban disparities have been reported in the access, utilization, and quality of healthcare. We aimed to assess whether use of antiarrhythmic therapies (AATs) in patients with atrial fibrillation (AF) differs between those with rural and urban residence. Methods: The registry-based FinACAF cohort covers all patients with AF from all levels of care in Finland. Patients were divided into rural and urban categories and into urbanization degree tertiles based on their municipality of residence at the time of AF diagnosis. The primary outcome was the use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription. Results: We identified 177,529 patients (49.9% female, mean age 73.0 (SD13.0) years) with incident AF during 2010–2018. Except for AADs, the differences in AAT use were nonsignificant when patients were stratified according to the rural–urban classification system (urban vs. rural adjusted incidence rate ratios (aIRRs) with 95% CIs for anyAAT 1.01 (0.99–1.03), AADs 1.11 (1.07–1.15), cardioversion 1.01 (0.98–1.03), catheter ablation 1.05 (0.98–1.12)). However, slightly higher use of all rhythm control modalities was observed in the highest urbanization degree tertile when compared to the lowest tertile (aIRRs with 95% Cis for any AAT 1.06 (1.03–1.08), AADs 1.18 (1.14–1.23), cardioversion 1.05 (1.02–1.08), catheter ablation 1.10 (1.02–1.19)). Conclusions: This nationwide retrospective cohort study observed that urban residence is associated with higher use of AADs in patients with incident AF. Otherwise, the observed disparities were only marginal, suggesting that in the use of rhythm control therapies, no large rural–urban inequity exists in Finland.

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.

Background: Atrial fibrillation (AF) patients with mental health conditions (MHCs) have higher incidence of ischaemic stroke (IS) than patients without MHC, but whether this results from direct impact of MHCs or relates to higher prevalence of comorbidities and differences in the use of oral anticoagulant (OAC) therapy is unclear. We assessed the hypothesis that MHCs independently increase the risk of IS in patients with incident AF. Methods: The nationwide FinACAF cohort covered all 203,154 patients diagnosed with incident AF without previous IS or transient ischaemic attack in Finland during 2007–2018. MHCs of interest were depression, bipolar disorder, anxiety disorder, schizophrenia and any MHC. The outcomes were first-ever IS and all-cause death. Results: The patients' (mean age 73.0 ± 13.5 years, 49.0% female) mean follow-up time was 4.3 (SD 3.3) years and 16,272 (8.0%) experienced first-ever IS and 63,420 (31.2%) died during follow-up. After propensity score matching and adjusting for OAC use, no MHC group was associated with increased IS risk (adjusted SHRs (95% CI): depression 0.961 (0.857–1.077), bipolar disorder 1.398 (0.947–2.006), anxiety disorder 0.878 (0.718–1.034), schizophrenia 0.803 (0.594–1.085) and any MHC 1.033 (0.985–1.085)). Lower rate of OAC use partly explained the observed higher crude IS incidence in patients with any MHC. Depression, schizophrenia and any MHC were associated with higher all-cause mortality (adjusted HRs [95% CI]: 1.208 [1.136–1.283], 1.543 [1.352–1.761] and 1.149 [1.116–1.175], respectively). Conclusions: In this nationwide retrospective cohort study, MHCs were not associated with the incidence of first-ever IS in patients with AF. publishedVersion

Aims Little is known about the effects of mental health conditions (MHCs) on the utilization of oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients. We aimed to assess whether MHCs affect initiation of OAC therapy among AF patients with special focus on non-vitamin K antagonist oral anticoagulants (NOACs). Methods and results The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) registry included all 239 222 patients diagnosed with incident AF during 2007–18 in Finland identified from national registries covering primary to tertiary care and drug purchases. Patients with previous depression, bipolar disorder, anxiety disorder, or schizophrenia diagnosis or a fulfilled psychiatric medication prescription within the year preceding the AF diagnosis were classified to have any MHC. The main outcome was OAC initiation, defined as first fulfilled OAC prescription after AF diagnosis. The patients’ mean age was 72.7 years and 49.8% were female. The prevalence of any MHC was 19.9%. A lower proportion of patients with any MHC compared with those without MHCs were initiated on OAC therapy (64.9% vs. 73.3%, P Conclusion MHCs are common among AF patients, and they are associated with a lower rate of OAC initiation even during the NOAC era.

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

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: In patients with atrial fibrillation (AF), socioeconomic disparities have been reported in the use of oral anticoagulant therapy and outcomes, but whether income also affects the utilization of antiarrhythmic therapies (AATs) for rhythm control is unknown. We assessed the hypothesis that AF patients with higher income are more likely to receive AATs.Methods: The nationwide retrospective registry based FinACAF cohort study covers all patients with AF from all levels of care in Finland. Patients were divided in AF diagnosis year and age-group specific income quintiles according to their highest annual income during 2004-2018. The primary outcome was the use of any AAT, including cardioversion, catheter ablation, and fulfilled antiarrhythmic drug (AAD) prescription.Results: We identified 188 175 patients (mean age 72.6 +/- 13.0 years; 49.6% female) with incident AF during 2010-2018. Patients in higher income quintiles had consistently higher use of all AAT modalities. When compared to patients in the lowest income quintile, the adjusted incidence rate ratios (95% CI) in the highest quintile were 1.53 (1.48-1.59) for any AAT, 1.71 (1.61-1.81) for AADs, 1.43 (1.37-1.49) for cardioversion, and 2.00 (1.76-2.27) for catheter ablation. No temporal change during study period was observed in the magnitude of income disparities in AAT use, except for a decrease in income-related differences in the use of AADs.Conclusion: Profound income-related disparities exist in AAT use among patients with AF in Finland, especially in the use catheter ablation.

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

Publisher Copyright: © 2021 Elsevier Inc. Background: Negative T-waves are associated with sudden cardiac death (SCD) risk in the general population. Whether flat T-waves also predict SCD is not known. The aim of the study was to examine the clinical characteristics and risk of SCD in general population subjects with flat T-waves. Methods: We examined the electrocardiograms of 6750 Finnish general population adults aged ≥30 years and classified the subjects into 3 groups: 1) negative T-waves with an amplitude ≥0.1 mV in ≥2 of the leads I, II, aVL, V4–V6, 2) negative or positive low amplitude T-waves with an amplitude

Introduction Atrial fibrillation (AF) is a chronic condition, and once diagnosed, most of the patients need life-long treatment for AF; rate and rhythm control for symptom relief and oral anticoagulation to mitigate the associated risk of stroke. Incidence of AF is strongly associated with age, and with longer life-expectancy the number of AF patients is worldwide rapidly increasing. Purpose The FinACAF study is a nationwide registry study including all AF patients searched from comprehensive national health care registers. To our knowledge, FinACAF is the first nationwide study including both primary, secondary, and tertiary health care register data. The aim of this study was to assess the incidence of new-onset AF in unselected nationwide population in Finland. Methods In the FinACAF study we gathered data (hospitalizations, outpatient specialist and primary health care visits, and drug reimbursement) from all national health care registers to identify new-onset AF patients from 01st January 2004 to 31st December 2018. To minimize the risk of misclassification, we considered a patient to have incident AF only if the new-onset AF diagnosis emerged after 1st January 2007 allowing at least three years of registration in Finnish health care registers without diagnosis of AF. Furthermore, patients with warfarin prescriptions during 2004–2006 were excluded. Raw incidence rates (1/100 000) were calculated using the total number of incident AF cases during a given year as numerator, and the total number of Finnish population free of AF on the last day of that year as denominator. The age-standardized incidence rates (1/100 000) were calculated using the total number of new-onset AF cases per year compared to the Nordic population free of AF age distribution. Results In total, 411 080 patients with the diagnosis of AF were documented during 2004–2018 in Finland, and the number of new-onset AF patients during 2007–2018 was 256 323. The incidence of AF in relation to age is shown in the Figure 1, and the increasing incidence with advancing age is outstandingly seen. Incidence of AF was more than 2000/100 000 in the population 80 years or older. The incidence of new-onset AF in the whole Finnish population increased during the study period from 330/100 000 and peaked to 456/100 000 in 2018. However, after adjustment for age, the age-adjusted AF incidence remained unchanged during 2007–2018 (Figure 2), but an obvious leap in the incidence emerged during 2011–2013 when the national primary care register was established. Conclusions In 2018 the incidence of AF per the whole population was 456/100 000. Based on very novel data and including all the known, diagnosed AF patients in Finland, this is the highest reported incidence rate of AF. Incidence of AF is strongly age-dependent, but the age-standardized incidence was not significantly changed from 2007 to 2018. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District research fundThe Finnish Foundation for Cardiovascular Research The incidence of AF in relation to ageAge-adjusted annual incidence of AF

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital district Finnish foundation for cardiovascular research Introduction Atrial fibrillation (AF) is a major cause of ischemic stroke. The risk of stroke is strongly associated with age, sex and comorbidities of the patients. Therefore, it is crucial that the comorbidities are consistently recorded in medical records as well as health care registries. Purpose This study aims to evaluate the prevalence of the comorbidities related to AF stroke risk in Finnish nationwide population registries, and assess how the use and combination of these registries affect the calculated CHA2DS2-VASc risk score. The comorbidities evaluated were Hypertension, Diabetes, Stroke or TIA, Heart Failure, and Vascular Disease. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study collected data on all Finnish AF patients from 1st January 2004 to 31st December 2018. Due to the initiation of the national primary care register in 2012, this substudy uses the data of patients with a new AF diagnosis during 2012-2018 (n = 168 353). Using a unique personal identification code, individual patient data were linked from the Finnish national health care registries "AvoHILMO" (primary care) and "HILMO" (secondary and tertiary care), National Prescription Register (ATC codes of purchased medication) and the National Reimbursement Register for reimbursed medication upheld by the Social Insurance Institute (KELA). Results The average CHA2DS2-VASc risk score when entering the cohort, and including information from all registries, equaled 2.91 for men (mean age 70.0 years) and 4.42 for women (mean age 76.9 years). The highest prevalence of diabetes and hypertension were found based on the National Reimbursement Register (ATC codes). Stroke or TIA and heart failure were identified almost exclusively based on secondary and tertiary hospital records. The table represents our results. Conclusion Comprehensive registry analysis of AF patients requires the inclusion of both hospital and medication data. The role of primary care information was limited. Comorbidity and CHA2DS2-VASc weight Total Prevalence Primary care ICD-10 codes Primary care ICPC-2 codes Secondary and tertiary care ICD-10 codes ATCcodes Medication reimbursement codes Hypertension 1 82%137 317 28%47 337 13%21 427 39%66 252 77%130 400 7%10 957 Diabetes 1 24%41 017 13%22 666 13%22 547 14%23 793 21%35 942 12%20 295 Stroke or TIA 2 17%28 653 4%6 254 1%1 968 16%27 379 - - Heart Failure 1 18%29 827 5%7 630 1%1 398 16%26 366 - 1%1 908 Vascular Disease1 28%47 420 12%19 581 2%3 265 25%41 647 - 7%11 802 Average CHA2DS2-VASc contribution 1.86 0.65 0.31 1.26 0.99 0.26 The prevalence of the comorbidities and average CHA2DS2-VASc risk score contribution by registry and combined.

Introduction Finnish gelsolin amyloidosis (AGel amyloidosis) is an inherited systemic amyloidosis with well-known ophthalmological, neurological and cutaneous symptoms. Additionally, cardiomyopathies, conduction disorders and need of cardiac pacemakers occur in some patients. This study focuses on electrocardiographic (ECG) findings in AGel amyloidosis and their relation to cardiac magnetic resonance (CMR) changes. We also assessed whether ECG abnormalities were associated with pacemaker implantation and mortality. Materials and methods In this cohort study, 51 genetically verified AGel amyloidosis patients (mean age 66 years) without cardiac pacemakers underwent 12-lead ECG and CMR imaging with contrast agent in 2017. Patients were followed-up for 3 years. Results Conduction disturbances were found in 22 patients (43%). Nine (18%) presented with first-degree atrioventricular block, six (12%) with left anterior hemiblock, seven (14%) with left or right bundle branch block and two (4%) with non-specific intraventricular conduction delay. Low QRS voltage was present in two (4%) patients. Late gadolinium enhancement (LGE) concentrating on the interventricular septum and inferior parts of the heart was present in 19 (86%) patients with conduction abnormalities. During the follow-up, only one patient received a pacemaker, and one patient died. Discussion Conduction disorders and septal LGE are common in AGel amyloidosis, whereas other ECG and CMR findings typically observed in most common cardiac amyloidosis types were rare. Septal pathology seen in CMR may interfere with the cardiac conduction system in AGel amyloidosis, explaining conduction disorders, although pacemaker therapy is rarely required.

To investigate whether clockwise rotation (CWR) and counterclockwise rotation (CCWR) of electrocardiographic QRS transition zone is associated with mortality from all causes and cardiovascular diseases (CVD).Studies were identified from searching of PubMed, EMBASE and the reference lists of relevant papers. Summary multivariate-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) and 95% prediction intervals (PIs) were computed through meta-analysis.A total of five observational cohort studies fulfilled the inclusion criteria, which included 47,252 participants from the general population (8.8% CWR; 44.1% CCWR). Pooling data revealed that CWR was significantly associated with the increased risk of all-cause mortality (HR, 1.18; 95% CI: 1.12-1.24; 95% PI: 1.03-1.37) and CVD mortality (HR, 1.18; 95% CI: 1.08-1.29; 95% PI: 0.98-1.42) compared to NR pattern, with low heterogeneity among studies (P = 0.29, IOur meta-analysis demonstrated CWR was positively associated with higher risk of mortality from all-cause and CVD, while CCWR was negatively associated with the risk of all-cause mortality and no significant association with CVD mortality. These findings suggested that QRS transition zone carries important prognostic value, more attention should be paid in clinical practice.

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 Negative T-waves are associated with sudden cardiac death (SCD) in the general population. Whether also low amplitude T-waves link to SCD risk in the general population is unknown. Purpose We investigated the prognostic significance of T-wave abnormalities in a general population cohort. Methods We evaluated the ECGs of 6584 Finnish general population subjects aged ≥30 years (mean age 51.2±13.9, 45.6% men) and classified them according to the T-wave morphology to 3 classes: 1) negative T-waves (negative T-wave with amplitude ≥0.1mV in ≥2 of the leads I, II, aVL, V4-V6), 2) low amplitude T-waves (negative or positive T-wave with amplitude Results A total of 239 subjects (3.5%) had negative T-waves, 869 (12.7%) low amplitude T-waves, and 5746 (83.8%) normal T-waves. The Table shows the baseline characteristics. Subjects with T-wave abnormalities were older and had more often cardiovascular morbidities than subjects with normal T-waves. Cardiovascular morbidities were most common in subjects with negative T-waves. After adjusting for multiple clinical factors, negative T-waves (HR 3.91; 95% CI 2.30–6.64) and low amplitude T-waves (HR 1.80; 95% CI 1.13–2.86) were associated with SCD, when compared to normal T-waves. Furthermore, both negative T-waves and low amplitude T-waves associated with cardiac death (HR 2.34; 95% CI 1.75–3.13 and HR 1.49; 95% CI 1.17–1.91, respectively) and death from any cause (HR 1.85; 95% CI 1.50–2.27 and HR 1.45; 95% CI 1.24–1.70, respectively). The Figure displays the survival plots for SCD according to T-wave group. Conclusion In addition to negative T-waves, low amplitude T-waves also associate with SCD risk in the general population. Focus should be also placed on these minor T-wave abnormalities in the future. Kaplan-Meier plot Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Finnish Medical Foundation, Aarne Koskelo Foundation

Background Nonvitamin K antagonist oral anticoagulants (NOACs) are increasingly used in patients with atrial fibrillation (AF) undergoing elective cardioversion (ECV). The aim was to investigate the use of NOACs and warfarin in ECV in a real‐life setting and to assess how the chosen regimen affected the delay to ECV and rate of complications. Methods Consecutive AF patients undergoing ECVs in the city hospitals of Helsinki between January 2015 and December 2016 were studied. Data on patient characteristics, delays to cardioversion, anticoagulation treatment, acute (

Heart failure (HF) is one of the leading causes of hospitalization in the Western world. Women have a lower HF hospitalization rate and mortality compared with men. The role of electrocardiography as a risk marker of future HF in women is not well known. We studied association of electrocardiographic (ECG) risk factors for HF hospitalization in women from a large middle-aged general population with a long-term follow-up and compared the risk profile to men. Standard 12-lead ECG markers were analyzed from 10,864 subjects (49% women), and their predictive value for HF hospitalization was analyzed. During the follow-up (30 ± 11 years), a total of 1,743 subjects had HF hospitalization; of these, 861 were women (49%). Several baseline characteristics, such as age, body mass index, blood pressure, and history of previous cardiac disease predicted the occurrence of HF both in women and men (p0.001 for all). After adjusting for baseline variables, ECG sign of left ventricular hypertrophy (LVH) (p0.001), and atrial fibrillation (p0.001) were the only baseline ECG variables that predicted future HF in women. In men, HF was predicted by fast heart rate (p = 0.008), T wave inversions (p0.001), abnormal Q-waves (p = 0.002), and atrial fibrillation (p0.001). Statistically significant gender interactions in prediction of HF were observed in ECG sign of LVH, inferolateral T wave inversions, and heart rate. In conclusion, ECG sign of LVH predicts future HF in middle-aged women, and T wave inversions and elevated heart rate are associated with HF hospitalization in men.

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

There is an urgent need to extend sudden cardiac death (SCD) risk stratification beyond the left ventricular ejection fraction (LVEF). We evaluated whether a cumulative electrocardiogram (ECG) risk score would improve identification of individuals at high risk of SCD.In the community-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), 522 SCD cases with archived 12-lead ECG available (65.3 ± 14.5 years, 66% male) were compared with 736 geographical controls to assess the incremental value of multiple ECG parameters in SCD prediction. Heart rate, LV hypertrophy, QRS transition zone, QRS-T angle, QTc, and Tpeak-to-Tend interval remained significant in the final model, which was externally validated in the Atherosclerosis Risk in Communities (ARIC) Study. Sixteen percent of cases and 3% of controls had ≥4 abnormal ECG markers. After adjusting for clinical factors and LVEF, increasing ECG risk score was associated with progressively greater odds of SCD. Overall, subjects with ≥4 ECG abnormalities had an odds ratio (OR) of 21.2 for SCD [95% confidence interval (CI) 9.4-47.7; P 0.001]. In the LVEF35% subgroup, the OR was 26.1 (95% CI 9.9-68.5; P 0.001). The ECG risk score increased the C-statistic from 0.625 to 0.753 (P 0.001), with net reclassification improvement of 0.319 (P 0.001). In the ARIC cohort validation, risk of SCD associated with ≥4 ECG abnormalities remained significant after multivariable adjustment (hazard ratio 4.84; 95% CI 2.34-9.99; P 0.001; C-statistic improvement 0.759-0.774; P = 0.019).This novel cumulative ECG risk score was independently associated with SCD and was particularly effective for LVEF35% where risk stratification is currently unavailable. These findings warrant further evaluation in prospective clinical investigations.

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

Sudden cardiac death (SCD) is a major cause of premature mortality worldwide, and intensive research efforts have focused on finding ways to recognise high-risk individuals before the fatal event. Ventricular tachycardia degenerating into ventricular fibrillation is the most common pathophysiological cascade leading to sudden death from arrhythmia. Presence of myocardial fibrosis leads to susceptibility for life-threatening reentrant ventricular arrhythmias by creating anatomical and/or functional abnormalities in the electrical impulse conduction that may serve as an arrhythmogenic substrate. Therefore, detecting cardiac fibrosis has been under considerable interest, as this could help to identify patients with cardiac disease at high risk of SCD. Late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) acts as an in vivo marker of replacement fibrosis and scar. The presence of fibrosis in CMR has been emerging as a powerful prognostic tool, and several studies have demonstrated increased risk of arrhythmias in cardiac patients with LGE. This risk appears to be at least partly independent from reduced left ventricular ejection fraction (LVEF), SCD risk marker that is currently used to guide implantable cardioverter-defibrillator (ICD) therapy for primary prevention. In a recent meta-analysis, fibrosis detected by LGE was associated with a fourfold risk of ventricular arrhythmias or SCD in ischaemic as well as in non-ischaemic cardiomyopathy, and the risk was similar both in LVEF ≤35% and LVEF >35% patients.1 In hypertrophic cardiomyopathy, extensive LGE increases the risk of …

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

Background Heart failure (HF) is one the leading causes of hospitalization in the Western world. Women have a lower rate of HF hospitalization and mortality compared to men. Role of 12-lead electrocardiography (ECG) as a risk marker of future HF in women is not well known. Purpose We studied the association of standard 12-lead ECG and clinical risk factors to HF hospitalization in women and in men separately from a large middle aged general population sample with a long-term follow-up. Methods Standard 12-lead ECG markers were analyzed from 10,864 subjects (48.8% women, N=5,215) of the prospective Mobile Clinic Study, and their predictive value for HF hospitalization was analyzed. Results During the follow-up (29.6±11.2 yrs.), a total of 1,743 subjects had HF hospitalization; out of these, 861 were women (49.4%). Several baseline characteristics, such as age, body mass index, blood pressure, and history of prior cardiac disease predicted the occurrence of HF both in women and men (P Conclusions ECG sign of LVH predicts future HF in middle-aged women independently, and T wave inversions and elevated heart rate are associated with HF hospitalization in men in. Acknowledgement/Funding Finnish Cultural Foundation, The University of Oulu Scholarship Foundation, Juho Vainio Foundation

Background Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in patients with atrial fibrillation (AF) undergoing elective cardioversion (ECV). The real-life data evaluating the safety and efficacy of ECV in patients receiving NOACs is sparse. Purpose The aim was to investigate the use of NOACs and warfarin in ECV in a real-life setting and to assess how the chosen regimen affected the delay to ECV and rate of complications. Methods Consecutive AF patients undergoing ECVs in a large city in Finland between January 2015 and December 2016 were studied. Data on patient characteristics, delays to cardioversion, anticoagulation treatment, acute ( Results Nine hundred patients (59.2% men; mean age, 68.0±10.0) underwent 992 ECVs, of which 596 (60.0%) were performed using NOACs and 396 (40.0%) using warfarin. The mean CHA2DS2-VASc score was 2.5 (±1.6). In patients without previous anticoagulation treatment, NOACs were associated with a shorter mean time to cardioversion than warfarin (51 vs. 68 days, respectively; P2 when thromboembolic complications occurred. Clinically relevant bleeding events occurred in 3 patients (0.5%) receiving NOACs and 7 patients (1.8%) receiving warfarin. Anticoagulation treatment was altered for 99 patients (11.0%) during the study period, with the majority (88.2%) of changes from warfarin to NOACs. Conclusion In this real-life study, the rates of thromboembolic and bleeding complications were low in AF patients undergoing ECV. Patients receiving NOAC therapy had a shorter time to cardioversion and fewer postponements of scheduled elective cardioversion compared with warfarin. Furthermore, patients receiving NOAC therapy had less anticoagulation treatment changes than patients on warfarin. Acknowledgement/Funding Finnish Foundation for Cardiovascular Research, Helsinki University Hospital District research fund, Boehringer-Ingelhem, Finnish Medical Foundation

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.

Background A substantial portion of the risk of atrial fibrillation (AF) remains unexplained by the established risk markers. However, accurate assessment of AF risk would be beneficial, especially among stroke patients and subjects with symptoms attributable to arrhythmia. Purpose To study the associations of P-wave indices with AF risk in the general population. Methods Electrocardiograms, including orthogonal leads, of 7217 Finnish subjects aged over 30 years who took part in the baseline examinations of the Mini-Finland Health Survey in 1978–80, were digitized. P-wave duration, third-degree interatrial block (IAB), and P terminal force (PTF) were assessed manually. PTF was considered abnormal when the amplitude of the negative terminal part of the P wave in lead V1 was ≥0.1mV and duration ≥40ms. Third-degree IAB was defined as P-wave duration ≥120ms and the presence of ≥2 +/− biphasic P-waves in the inferior leads. Orthogonal P-wave morphology, which is related to left atrial breakthrough site and affected by atrial fibrosis (1 being considered benign, 2 borderline, and 3 shown to be associated with adverse events), was assessed with an automated algorithm, and ascertained manually. Subjects were followed 10 years for AF hospitalization and mortality. The risk of AF associated with P wave parameters was assessed using Cox proportional hazards models. Model discrimination improvement was quantified by the change in C index, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results There were 5489 subjects (47.8% male, mean age 50.5 years) with a readable ECG, sinus rhythm, no missing data, and a predefined orthogonal P-wave morphology. Type 3 orthogonal P morphology (n=216, multivariate adjusted HR [maHR] 3.01, 95% confidence interval [CI] 1.66–5.45, p Conclusions P-wave indices and orthogonal P-wave morphology can be used to identify subjects at high and low risk for AF and possibly direct extensive AF screening protocols towards high-risk subjects in the general population in order to decrease the risk of cardioembolic stroke. However, more research is needed in this topic. Acknowledgement/Funding Finnish Medical Foundation, Onni and Hilja Tuovinen's Foundation, Orion Research Foundation, Paavo Nurmi's Foundation, Veritas Foundation

Background Early repolarization (ER) in the electrocardiogram (ECG) has been associated with increased sudden cardiac death (SCD) risk in the general population. However, controversy remains about the risk associated with ER in different population subgroups. Purpose We evaluated whether age and sex affect the prognostic significance of ER in general population subjects. Methods The study population consisted of Finnish general population subjects aged over 30 years participating in the Mini-Finland Health Survey in 1978–80. Subjects underwent extensive baseline health examinations including a resting 12-lead ECG and were followed for 24±10 years. After excluding ECGs with QRS duration >110ms, the presence of ER (J-point elevation ≥0.1 mV in ≥2 inferior/lateral leads) was assessed from the remaining 6,631 subjects. The association between ER and SCD risk was analysed in subgroups according to age ( Results ER was present in 250 (15.7%) of the 1,592 male subjects aged Conclusion Our results suggest that among adults Acknowledgement/Funding Aarne Koskelo foundation and Paavo Ilmari Ahvenainen Foundation

Radium

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.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.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.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.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.

Introduction: Ischemic stroke (IS) in a young patient is a disaster and recurrent cardiovascular events could add further impairment. Identifying patients with high risk of such events is therefore important. The prognostic relevance of ECG for this population is unknown. Materials and methods: A total of 690 IS patients aged 15–49 years were included. A 12-lead ECG was obtained 1–14 d after the onset of stroke. We adjusted for demographic factors, comorbidities, and stroke characteristics, Cox regression models were used to identify independent ECG parameters associated with long-term risks of (1) any cardiovascular event, (2) cardiac events, and (3) recurrent stroke. Results: Median follow-up time was 8.8 years. About 26.4% of patients experienced a cardiovascular event, 14.5% had cardiac events, and 14.6% recurrent strokes. ECG parameters associated with recurrent cardiovascular events were bundle branch blocks, P-terminal force, left ventricular hypertrophy, and a broader QRS complex. Furthermore, more leftward P-wave axis, prolonged QTc, and P-wave duration >120 ms were associated with increased risks of cardiac events. No ECG parameters were independently associated with recurrent stroke. Conclusion: A 12-lead ECG can be used for risk prediction of cardiovascular events but not for recurrent stroke in young IS patients.KEY MESSAGESECG is an easy, inexpensive, and useful tool for identifying young ischemic stroke patients with a high risk for recurrent cardiovascular events and it has a statistically significant association with these events even after adjusting for confounding factors.Bundle branch blocks, P-terminal force, broader QRS complex, LVH according to Cornell voltage duration criteria, more leftward P-wave axis, prolonged QTc, and P-wave duration >120 ms are predictors for future cardiovascular or cardiac events in these patients.No ECG parameters were independently associated with recurrent stroke. ECG is an easy, inexpensive, and useful tool for identifying young ischemic stroke patients with a high risk for recurrent cardiovascular events and it has a statistically significant association with these events even after adjusting for confounding factors. Bundle branch blocks, P-terminal force, broader QRS complex, LVH according to Cornell voltage duration criteria, more leftward P-wave axis, prolonged QTc, and P-wave duration >120 ms are predictors for future cardiovascular or cardiac events in these patients. No ECG parameters were independently associated with recurrent stroke.

QRST-angle and Sudden Cardiac DeathIntroduction Improvements in risk stratification for sudden cardiac arrest (SCA) will require discovery of markers that extend beyond the LV ejection fraction (LVEF). The frontal QRS-T angle has been shown to predict risk of SCA but the value of this marker independent of the LVEF has not been investigated. Methods and Results Cases of adult SCA with an archived electrocardiogram (12-lead ECG) available before the event, with a computable frontal QRS-T angle, were identified from the Oregon Sudden Unexpected Death Study (Oregon SUDS) ongoing in the Portland, Oregon metro area. A total of 666 SCA cases (mean age 67.2 years; 95% CI, 52.3–82.1 years; 68.6% males) were compared to 863 controls (mean age 66.6 years, 55.2–78.0 years; 68.1% males; 75.0% had CAD) from the same geographical region. The mean frontal QRS-T angle was wider in cases (74o; 95% CI, 17o–131o) compared to controls (51o; 95% CI, 5o–97o; P< 0.0001). A frontal QRS-T angle of more than 90o remained associated with increased risk of SCD after adjusting for age, gender, heart rate, prolonged intraventricular conduction, electrocardiographic left ventricular hypertrophy (ECG LVH), baseline comorbidities, and left ventricular ejection fraction (LVEF) (OR 2.2; 95% CI, 1.60–3.09; P< 0.0001). Conclusion A wide QRS-T angle greater than 90o is associated with an increased risk of SCA independent of the left ventricular ejection fraction.

Hypertrophic cardiomyopathy (HCM) is a genetically transmitted cardiac disease, characterized by increased left ventricular (LV) wall thickness in the absence of abnormal loading conditions.1 The estimated prevalence of HCM is ≈1 per 500 in the general population,2 with a diverse clinical course including heart failure and sudden cardiac arrest (SCA), but also asymptomatic survival to normal life expectancy.3 SCA attributable to ventricular arrhythmias is a major cause of mortality in young and middle-aged patients with HCM.4 With modern management strategies, including implantable cardioverter-defibrillator therapy for high-risk individuals, contemporary disease-related mortality has been reported to be ≈0.5% annually.4 These estimates are derived from several HCM patient registries, representing a somewhat selected patient population. However, the absence of symptoms causes HCM to remain undetected in a large proportion of patients. Because few data exist on the burden of HCM-related SCA in the community, in the present study we assessed the incidence and characteristics of HCM-related SCA in the young and middle-aged general population from the ongoing Oregon SUDS (Oregon Sudden Unexpected Death Study). This study was approved by the institutional review boards of Cedars-Sinai Medical Center, Oregon Health …

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.

The last two decades have witnessed significant developments in the diagnosis and management of supraventricular and ventricular arrhythmias, especially in the high-income countries. Due to several factors that include the dynamic nature of these conditions, epidemiology and surveillance have not advanced to the same extent. In this chapter, the goal is to collate the existing literature on epidemiology and global burden of arrhythmias, recognizing that these data are also available from only a few of the world regions, mostly the high-income nations.

Background: Abnormal 12‑lead 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 ± 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 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