Dynamic electrocardiogram changes are a novel risk marker for sudden cardiac death.

BACKGROUND AND AIMS: Electrocardiogram (ECG) abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD), but the potential importance of dynamic ECG remodelling has not been investigated. In this study, the nature and prevalence of dynamic ECG remodelling were studied among individuals who eventually suffered SCD. METHODS: The study population was drawn from two prospective community-based SCD studies in Oregon (2002, discovery cohort) and California, USA (2015, validation cohort). For this present sub-study, 231 discovery cases (2015-17) and 203 validation cases (2015-21) with ≥2 archived pre-SCD ECGs were ascertained and were matched to 234 discovery and 203 validation controls based on age, sex, and duration between the ECGs. Dynamic ECG remodelling was measured as progression of a previously validated cumulative six-variable ECG electrical risk score. RESULTS: Oregon SCD cases displayed greater electrical risk score increase over time vs. controls [+1.06 (95% confidence interval +0.89 to +1.24) vs. -0.05 (-0.21 to +0.11); P < .001]. These findings were successfully replicated in California [+0.87 (+0.7 to +1.04) vs. -0.11 (-0.27 to 0.05); P < .001]. In multivariable models, abnormal dynamic ECG remodelling improved SCD prediction over baseline ECG, demographics, and clinical SCD risk factors in both Oregon [area under the receiver operating characteristic curve 0.770 (95% confidence interval 0.727-0.812) increased to area under the receiver operating characteristic curve 0.869 (95% confidence interval 0.837-0.902)] and California cohorts. CONCLUSIONS: Dynamic ECG remodelling improved SCD risk prediction beyond clinical factors combined with the static ECG, with successful validation in a geographically distinct population. These findings introduce a novel concept of SCD dynamic risk and warrant further detailed investigation.

Association of electrocardiographic spatial heterogeneity of repolarization and spatial heterogeneity of atrial depolarization with left ventricular fibrosis.

AIMS: To evaluate the relationship between spatial heterogeneity of electrocardiographic repolarization and spatial heterogeneity of atrial depolarization with arrhythmic substrate represented by left ventricular fibrosis. METHODS AND RESULTS: We assessed the associations of T- and P-wave morphology parameters analysed from the standard 12-lead electrocardiograms with left ventricular fibrosis in 378 victims of unexpected sudden cardiac death (SCD) who underwent medico-legal autopsy. Based on autopsy findings, the SCD victims were categorized into four different groups according to different stages of severity of left ventricular fibrosis (substantial fibrosis, moderate patchy fibrosis, scattered mild fibrosis, no fibrosis). T-wave and P-wave area dispersion (TWAd: 0.0841 ± 0.496, 0.170 ± 0.492, 0.302 ± 404, 0.296 ± 0.476, P = 0.008; PWAd: 0.574 ± 0.384, 0.561 ± 0.367, 0.654 ± 0.281, 0.717 ± 0.257, P = 0.011, respectively; low values abnormal), non-dipolar components of T-wave and P-wave morphology (T_NonDipolarABS: 0.0496 ± 0.0377, 0.0571 ± 0.0487, 0.0432 ± 0.0476, 0.0380 ± 0.0377, P = 0.027; P_NonDipolarABS: 0.0132 ± 0.0164, 0.0130 ± 0.0135, 0.0092 ± 0.0117, 0.0069 ± 0.00472, P = 0.005, respectively, high values abnormal), T-wave morphology dispersion (TMD: 45.9 ± 28.3, 40.5 ± 25.8, 35.5 ± 24.9, 33.0 ± 24.6, P = 0.030, respectively, high values abnormal), and P-wave heterogeneity (PWH: 20.0 ± 9.44, 19.7 ± 8.87, 17.9 ± 9.78, 15.4 ± 4.60, P = 0.019, respectively, high values abnormal) differed significantly between the groups with different stages of left ventricular fibrosis. After adjustment with heart weight, T_NonDipolarABS [standardized ß (sß) = 0.131, P = 0.014], PWAd (sß = -0.161, P = 0.003), P_NonDipolarABS (sß = 0.174, P = 0.001), and PWH (sß = 0.128, P = 0.015) retained independent association, and TWAd (sß = -0.091, P = 0.074) and TMD (sß = 0.097, P = 0.063) tended to retain their association with the degree of myocardial fibrosis. CONCLUSION: Our findings suggest that abnormal values of T- and P-wave morphology are associated with arrhythmic substrate represented by ventricular fibrosis partly explaining the mechanism behind their prognostic significance.

Temporal Trends in Incidence and Survival From Sudden Cardiac Arrest Manifesting With Shockable and Nonshockable Rhythms: A 16-Year Prospective Study in a Large US Community.

STUDY OBJECTIVE: The proportion of nonshockable sudden cardiac arrests (pulseless electrical activity and asystole) continues to rise. Survival is lower than shockable (ventricular fibrillation [VF]) sudden cardiac arrests, but there is little community-based information on temporal trends in the incidence and survival from sudden cardiac arrests based on presenting rhythms. We investigated community-based temporal trends in sudden cardiac arrest incidence and survival by presenting rhythm. METHODS: We prospectively evaluated the incidence of each presenting sudden cardiac arrest rhythm and survival outcomes for out-of-hospital events in the Portland, Oregon metro area (population of approximately 1 million, 2002 to 2017). We limited inclusion to cases of likely cardiac cause with resuscitation attempted by emergency medical services. RESULTS: Out of 3,723 overall sudden cardiac arrest cases, 908 (24%) presented with pulseless electrical activity, 1,513 (41%) with VF, and 1,302 (35%) with asystole. The incidence of pulseless electrical activity-sudden cardiac arrest remained stable over 4-year periods (9.6/100,000 in 2002 to 2005, 7.4/100,000 in 2006 to 2009, 5.7/100,000 in 2010 to 2013, and 8.3/100,000 in 2014 to 2017; unadjusted beta [ß] -0.56; 95% confidence interval [CI], -3.98 to 2.85). The incidence of VF-sudden cardiac arrests decreased over time (14.6/100,000 in 2002 to 2005, 13.4/100,000 in 2006 to 2009, 12.0/100,000 in 2010 to 2013, and 11.6/100,000 in 2014 to 2017; unadjusted ß -1.05; 95% CI, -1.68 to -0.42) and asystole-sudden cardiac arrests (8.6/100,000 in 2002 to 2005, 9.0/100,000 in 2006 to 2009, 10.3/100,000 in 2010 to 2013, and 15.7/100,000 in 2014 to 2017; unadjusted ß 2.25; 95% CI -1.24 to 5.73) did not change significantly over time. Survival increased over time for pulseless electrical activity-sudden cardiac arrests (5.7%, 4.3%, 9.6%, 13.6%; unadjusted ß 2.8%; 95% CI 1.3 to 4.4) and VF-sudden cardiac arrests (27.5%, 29.8%, 37.9%, 36.6%; unadjusted ß 3.5%; 95% CI 1.4 to 5.6), but not for asystole-sudden cardiac arrests (1.7%, 1.6%, 4.0%, 2.4%; unadjusted ß 0.3%; 95% CI, -0.4 to 1.1). Enhancements in the emergency medical services system's pulseless electrical activity-sudden cardiac arrest management were temporally associated with the increasing pulseless electrical activity survival rates. CONCLUSIONS: Over a 16-year period, the incidence of VF/ventricular tachycardia decreased over time, but pulseless electrical activity incidence remained stable. Survival from both VF-sudden cardiac arrests and pulseless electrical activity-sudden cardiac arrests increased over time with a more than 2-fold increase for pulseless electrical activity-sudden cardiac arrests.

Use of Psychotropic Medication in Victims of Sudden Cardiac Death with Nonischemic Heart Disease.

BACKGROUND: Nonischemic heart disease (NIHD) is the underlying pathology in about 20% of sudden cardiac deaths (SCDs). Psychotropic medication has been reported as a risk factor for SCD among patients with coronary artery disease, but similar information concerning NIHD is scarce. OBJECTIVES: We evaluated the use of psychotropic medication in victims of SCD due to NIHD and compared it to the general medication use in Finland. METHOD: Study population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) (n = 5,869, mean age: 65 ± 12, 79% males; 1,404 victims of SCD due to NIHD, mean age: 57 ± 13, 77% males). All deaths occurred in Northern Finland during 1998-2017. All victims underwent a medicolegal autopsy. Data on use of medication were defined using postmortem toxicology results and patient records. Subjects with neither toxicological analysis nor information of medication use available were excluded. Information on general medication use was derived from Finnish Statistics on Medicines 2018 and presented as defined daily dose/1,000 inhabitants/day. RESULTS: Psychotropic medication was used by 579 (41%) subjects with NIHD, whereas in the general population, only 12% were estimated to use psychotropics. The results were similar in subgroups of psychotropic medication: 27% versus 2.3% for benzodiazepines, 19% versus 7.5% for antidepressants, and 18% versus 2.2% for antipsychotics. CONCLUSIONS: Use of psychotropic medication is common in victims of SCD due to NIHD compared to the general population.

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

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

Temporal Trends in the Incidence and Characteristics of Sudden Cardiac Death among Subjects under 40 Years of Age in Northern Finland during 1998-2017.

BACKGROUND: Although the mean age of sudden cardiac death (SCD) victims has increased during recent decades, overall incidence has remained relatively stable. Small but very important proportion of SCDs occur in subjects under 40 years of age and temporal trends in the incidence and characteristics of SCD in this age-group are not well known. METHODS: The Fingesture study has prospectively gathered data from 5,869 consecutive autopsy verified SCD victims in Northern Finland during 1998-2017. On the basis of Finnish law, all who die unexpectedly undergo autopsy. RESULTS: Out of total 5,869 SCDs, 160 occurred in subjects under 40 years of age (3%) indicating a total incidence of 2.9/100,000/year. Incidence decreased during the study period: 4.0/100,000/year (n = 50) in 1998-2002, 3.7/100,000/year (n = 45) in 2003-2007, 2.5/100,000/year (n = 36) in 2008-2012, and 1.5/100,000/year (n = 29) in 2013-2017. Coronary artery disease (CAD) was the cause of death in 46 SCD victims (29%). Among nonischemic causes, most common were obesity-related hypertrophic myocardial disease (24%), primary myocardial fibrosis (19%), and hypertensive myocardial disease (6%). The incidence of SCD caused by CAD decreased as follows: 1.5/100,000/year in 1998-2002, 1.2/100,000/year in 2003-2007, 0.6/100,000/year in 2008-2012, and 0.2/100,000/year in 2013-2017. Proportion of male gender (81%) and obesity as a comorbidity (body mass index >30 kg/m2, 40%) remained relatively stable during the period (p = 0.58 and p = 0.79, respectively). CONCLUSIONS: The incidence of SCD in subjects under 40 years of age has decreased in Northern Finland during 1998-2017. According to autopsy data, most of the deaths are due to nonischemic myocardial diseases and relative proportion of CAD has decreased.

Sudden Cardiac Death in Women.

BACKGROUND: Despite recent progress in profiling of risk for sudden cardiac death (SCD) and prevention and intervention of cardiac diseases, SCD remains a major cause of death. Among women, the incidence of SCD is significant, but lower than in men, particularly in the premenopausal and early postmenopausal years. Possibly, as a consequence of the difference in population burden, the mechanisms and risk markers of SCD are not as well defined for women. The aim of this study was to determine the autopsy findings and causes of death among women in a large SCD population. Additionally, we sought to classify prior ECG characteristics in male and female subjects with SCD. METHODS: The Fingesture study has systematically collected clinical and autopsy data from subjects with SCD in Northern Finland between 1998 and 2017. The cohort consists of 5869 subjects with SCD. Previously recorded ECGs were available and analyzed in 1101 subjects (18.8% of total population; and in 25.3% of women). RESULTS: Female subjects with SCD were significantly older than men: 70.1±13.1 years versus 63.5±11.8 years (mean ± standard deviation, P<0.001). The most frequently identified cause of death was ischemic heart disease in both sexes: 71.7% among women versus 75.7% among men, P=0.005. In contrast, women were more likely to have nonischemic cause of SCD than men (28.3% versus 24.3%, P=0.005). The prevalence of primary myocardial fibrosis was higher among women (5.2%, n=64) than in men (2.6%, n=120; P<0.001). Female subjects with SCD were more likely to have normal prior ECG tracings (22.2% versus 15.3% in men, P<0.001). A normal ECG was even more common among nonischemic female subjects with SCD (27.8% versus 16.2% in men, P=0.009). However, ECG markers of left ventricular hypertrophy, with or without repolarization abnormalities, were more common among women (8.2%; 17.9%) than in men (4.9%; 10.6%, P=0.036; P<0.001, respectively). CONCLUSIONS: Women were considerably older at the time of SCD and more commonly had nonischemic causes. Women were also more likely to have a prior normal ECG than men, but an increased marker for SCD risk based on ECG criteria for left ventricular hypertrophy with repolarization abnormalities was more commonly observed in women.

Gender differences in prevalence and prognostic value of fragmented QRS complex.

BACKGROUND: Fragmented QRS (fQRS) on 12-lead electrocardiogram (ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. METHODS: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 ± 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of ≥50% (70% men; 66.6 ± 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 ± 8.5 yrs). RESULTS: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p < 0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p < 0.001), CAD patients without prior MI (39.9% vs. 26.4%, p < 0.001), CAD patients with prior MI (42.9% vs. 31.2%, p < 0.001), and victims of SCD (56.4% vs. 44.4%, p < 0.001). CONCLUSIONS: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men.

Primary Myocardial Fibrosis as an Alternative Phenotype Pathway of Inherited Cardiac Structural Disorders.

BACKGROUND: Myocardial fibrosis is a common postmortem finding among young individuals with sudden cardiac death. Because there is no known single cause, we tested the hypothesis that some cases of myocardial fibrosis in the absence of identifiable causes (primary myocardial fibrosis [PMF]) are associated with genetic variants. METHODS: Tissue was obtained at autopsy from 4031 consecutive individuals with sudden cardiac death in Northern Finland, among whom PMF was the only structural finding in 145 subjects with sudden cardiac death. We performed targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function when autopsies did not identify a secondary basis for myocardial fibrosis. All variants with an effect on protein and with a minor allele frequency <0.01 were classified as pathogenic or variants of uncertain significance on the basis of American College of Medical Genetics consensus guidelines. RESULTS: Among the 96 specimens with DNA passing quality control (66%), postmortem genetic tests identified 24 variants of known or uncertain significance in 26 subjects (27%). Ten were pathogenic/likely pathogenic variants in 10 subjects (10%), and 14 were variants of uncertain significance in 11 genes among 16 subjects (17%). Five variants were in genes associated with arrhythmogenic right ventricular cardiomyopathy, 6 in hypertrophic cardiomyopathy-associated genes, and 11 in dilated cardiomyopathy-associated genes; 2 were not associated with these disorders. Four unique variants of uncertain significance cosegregated among multiple unrelated subjects with PMF. No pathogenic/likely pathogenic variants were detected in ion channel-encoding genes. CONCLUSIONS: A large proportion of subjects with PMF at autopsy had variants in genes associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy without autopsy findings of those diseases, suggesting that PMF can be an alternative phenotypic expression of structural disease-associated genetic variants or that risk-associated fibrosis was expressing before the primary disease. These findings have clinical implications for postmortem genetic testing and family risk profiling.

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

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

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

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

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

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

Day-of-the-week variation of sudden unexpected cardiac death.

Background: There has been some controversy about the day-of-the-week (septadian) variation of unexpected sudden cardiac death (SCD). Methods: We evaluated the incidence of unexpected SCD on different days of the week in a consecutive series of 5869 SCD victims from Northern Finland [the FINGESTURE study (Finnish Genetic Study of Arrhythmic Events)]. As it is mandatory in Finland, a medico-legal autopsy was performed on all unexpected sudden death victims. The autopsies were performed between the years 1998-2017. Results: The mean incidence of unexpected SCD was higher at weekends (during the days from Friday to Sunday, peaking on Saturday) than during the days from Monday to Thursday (8.54 ± 0.72 vs. 7.22 ± 0.19 SCDs per day of the week per 100,000 inhabitants per year, p < 0.001). Regardless of sex or ischemic versus non-ischemic etiology of SCD, the distribution of the occurrence of SCD among the days of the week was similar compared with the whole SCD cohort. Conclusion: The incidence of unexpected SCD was highest at weekends (during the days from Friday to Sunday, peaking on Saturday).

An ECG-based artificial intelligence model for assessment of sudden cardiac death risk.

BACKGROUND: Conventional ECG-based algorithms could contribute to sudden cardiac death (SCD) risk stratification but demonstrate moderate predictive capabilities. Deep learning (DL) models use the entire digital signal and could potentially improve predictive power. We aimed to train and validate a 12 lead ECG-based DL algorithm for SCD risk assessment. METHODS: Out-of-hospital SCD cases were prospectively ascertained in the Portland, Oregon, metro area. A total of 1,827 pre- cardiac arrest 12 lead ECGs from 1,796 SCD cases were retrospectively collected and analyzed to develop an ECG-based DL model. External validation was performed in 714 ECGs from 714 SCD cases from Ventura County, CA. Two separate control group samples were obtained from 1342 ECGs taken from 1325 individuals of which at least 50% had established coronary artery disease. The DL model was compared with a previously validated conventional 6 variable ECG risk model. RESULTS: The DL model achieves an AUROC of 0.889 (95% CI 0.861-0.917) for the detection of SCD cases vs. controls in the internal held-out test dataset, and is successfully validated in external SCD cases with an AUROC of 0.820 (0.794-0.847). The DL model performs significantly better than the conventional ECG model that achieves an AUROC of 0.712 (0.668-0.756) in the internal and 0.743 (0.711-0.775) in the external cohort. CONCLUSIONS: An ECG-based DL model distinguishes SCD cases from controls with improved accuracy and performs better than a conventional ECG risk model. Further detailed investigation is warranted to evaluate how the DL model could contribute to improved SCD risk stratification.

Sudden cardiac death (SCD) occurs when there are problems with the electrical activity within the heart. It is a common cause of death throughout the world so it would be beneficial to be able to easily identify individuals that are at high risk of SCD. Electrocardiograms are a cheap and widely available way to measure electrical activity in the heart. We developed a computational method that can use electrocardiograms to determine whether a person is at increased risk of having a SCD. Our computational method could allow clinicians to screen large numbers of people and identify those at a higher risk of SCD. This could enable regular monitoring of these people and might enable SCDs to be prevented in some individuals.

The burden of sudden cardiac arrest in the setting of acute coronary syndrome.

BACKGROUND: The incidence of sudden cardiac arrest (SCA) during acute coronary syndrome is somewhat unclear, since often subjects dying before the first healthcare contact are not included in the estimates. We aimed to investigate the complete incidence of SCA during ACS. METHODS: The study population consists of two cohorts. The first cohort includes 472 ACS patients from Northern Ostrobothnia, Finland from year 2016 and the second cohort 162 autopsy-verified SCD subjects (extrapolated) from the same region and year, whose death was attributable to coronary artery disease (CAD) and ACS. An extrapolation of SCA incidence during ACS was done by utilizing autopsy data and data from prior autopsy study on this sample. RESULTS: The overall incidence of SCA in the setting of ACS was 17.5%. The incidence of SCA was 20.6% in all ACS subjects without prior CAD diagnosis, and 25.4% in STEMI subjects without prior CAD diagnosis. In subjects with previously diagnosed CAD, the incidence of SCA was 10.9% in all ACS subjects and 16.1% in STEMI subjects. There was a statistically significant difference in the incidence of SCA between subjects with and without prior CAD diagnosis (p = 0.0052). CONCLUSION: The inclusion of ACS-SCA subjects dying before the first emergency medical service (EMS) contact results in a higher and likely more accurate estimation of SCA during ACS. The incidence of SCA was higher among subjects without prior CAD diagnosis. The high mortality rate highlights the importance of early ACS detection to reduce the burden of CAD-related premature deaths.

Artificial Intelligence Model Predicts Sudden Cardiac Arrest Manifesting With Pulseless Electric Activity Versus Ventricular Fibrillation.

BACKGROUND: There is no specific treatment for sudden cardiac arrest (SCA) manifesting as pulseless electric activity (PEA) and survival rates are low; unlike ventricular fibrillation (VF), which is treatable by defibrillation. Development of novel treatments requires fundamental clinical studies, but access to the true initial rhythm has been a limiting factor. METHODS: Using demographics and detailed clinical variables, we trained and tested an AI model (extreme gradient boosting) to differentiate PEA-SCA versus VF-SCA in a novel setting that provided the true initial rhythm. A subgroup of SCAs are witnessed by emergency medical services personnel, and because the response time is zero, the true SCA initial rhythm is recorded. The internal cohort consisted of 421 emergency medical services-witnessed out-of-hospital SCAs with PEA or VF as the initial rhythm in the Portland, Oregon metropolitan area. External validation was performed in 220 emergency medical services-witnessed SCAs from Ventura, CA. RESULTS: In the internal cohort, the artificial intelligence model achieved an area under the receiver operating characteristic curve of 0.68 (95% CI, 0.61-0.76). Model performance was similar in the external cohort, achieving an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.59-0.84). Anemia, older age, increased weight, and dyspnea as a warning symptom were the most important features of PEA-SCA; younger age, chest pain as a warning symptom and established coronary artery disease were important features associated with VF. CONCLUSIONS: The artificial intelligence model identified novel features of PEA-SCA, differentiated from VF-SCA and was successfully replicated in an external cohort. These findings enhance the mechanistic understanding of PEA-SCA with potential implications for developing novel management strategies.

Novel Genetic Variants Associated with Primary Myocardial Fibrosis in Sudden Cardiac Death Victims.

Myocardial fibrosis is a common finding in victims of sudden cardiac death (SCD). Whole exome sequencing was performed in 127 victims of SCD with primary myocardial fibrosis as the only pathological finding. These cases are derived from the Fingesture study which has collected data from autopsy-verified SCD victims in Northern Finland. A computational approach was used to identify protein interactions in cardiomyocytes. Associations of the identified variants with cardiac disease endpoints were investigated in the Finnish national genetic study (FinnGen) dataset. We identified 21 missense and one nonsense variant. Four variants were estimated to affect protein function, significantly associated with SCD/primary myocardial fibrosis (Fingesture) and associated with cardiac diseases in Finnish population (FinnGen). These variants locate in cartilage acidic protein 1 (CRATC1), calpain 1 (CAPN1), unc-45 myosin chaperone A (UNC45A) and unc-45 myosin chaperone B (UNC45B). The variants identified contribute to function of extracellular matrix and cardiomyocytes.

Artificial Intelligence in Ventricular Arrhythmias and Sudden Death.

Sudden cardiac arrest due to lethal ventricular arrhythmias is a major cause of mortality worldwide and results in more years of potential life lost than any individual cancer. Most of these sudden cardiac arrest events occur unexpectedly in individuals who have not been identified as high-risk due to the inadequacy of current risk stratification tools. Artificial intelligence tools are increasingly being used to solve complex problems and are poised to help with this major unmet need in the field of clinical electrophysiology. By leveraging large and detailed datasets, artificial intelligence-based prediction models have the potential to enhance the risk stratification of lethal ventricular arrhythmias. This review presents a synthesis of the published literature and a discussion of future directions in this field.