Machine Learning for Sudden Cardiac Death Prediction in the Atherosclerosis Risk in Communities Study

Introduction Sudden cardiac death (SCD) is a devastating consequence often without antecedent expectation. Current risk stratification methods derived from baseline independently modeled risk factors are insufficient. Novel random forest machine learning (ML) approach incorporating time-dependent variables and complex interactions may improve SCD risk prediction. Methods Atherosclerosis Risk in Communities (ARIC) study participants were followed for adjudicated SCD. ML models were compared to standard Poisson regression models for interval data, an approximation to Cox regression, with stepwise variable selection. Eighty-two time-varying variables (demographics, lifestyle factors, clinical characteristics, biomarkers, etc.) collected at four visits over 12 years (1987-98) were used as candidate predictors. Predictive accuracy was assessed by area under the receiver operating characteristic curve (AUC) through out-of-bag prediction for ML models and 5-fold cross validation for the Poisson regression models. Results Over a median follow-up time of 23.5 years, 583 SCD events occurred among 15,661 ARIC participants (mean age 54 years and 55% women). Compared to different Poisson regression models (AUC at 6-year ranges from 0.77-0.83), the ML model improved prediction (AUC at 6-year 0.89). Top predictors identified by ML model included prior coronary heart disease (CHD), which explained 47.9% of the total phenotypic variance, diabetes mellitus, hypertension, and T wave abnormality in any of leads I, aVL, or V6. Using the top ML predictors to select variables, the Poisson regression model AUC at 6-year was 0.77 suggesting that the non-linear dependencies and interactions captured by ML, are the main reasons for its improved prediction performance. Conclusions Applying novel ML approach with time-varying predictors improves the prediction of SCD. Interactions of dynamic clinical characteristics are important for risk-stratifying SCD in the general population.

Wellens’ Syndrome: Incidence, Characteristics, and Long-Term Clinical Outcomes

Background: Sparse study of large sample size are available on patients with Wellens’ syndrome. We sought to assess the current incidence, risk factors, clinical presentation and long-term outcomes of this population. Methods: Among a total of 3528 patients with ACS underwent angioplasty from 2017 to 2019 in our center, 2127 NSTE-ACS patients with culprit vessel of LAD were enrolled in this study. According to electrocardiographic criteria, they were divided into Wellens’ group (n = 200) and non-Wellens’ group (n =1927). The primary endpoint was cardiac death; the secondary endpoint was MACCE, a composite of all-cause death, cardiac death, recurrent myocardial infarction, target lesion revascularization, heart failure and stroke. Results: The incidence of Wellens’ syndrome was 5.7% (200 of 3528) in all the ACS patients. Wellens’ syndrome was more often manifested as NSTEMI (69% vs 17.5%, P＜0.001). Percent of preexisting coronary heart disease (39.6% vs 23%) and previous PCI (19.5% vs 9%) were significantly higher in the non-Wellens’ group than in Wellens’ group (all P<0.001). More importantly, the proportion of early PCI was higher in Wellens’ group (68% vs 59.3%, P=0.017). At a median follow-up of 24 months, Wellens’ syndrome was not a factor that affects the prognosis of MACCE (P=0.05) and cardiac death (P=0.188). Conclusions: In patients with NSTE-ACS, Wellens’ syndrome does not affect the prognosis. The presence of age≥65years, diabetes, NSTEMI, eGFR< 60ml/min and left main disease were associated with an incidence of cardiac death. Early recognition and aggressive intervention are critical as they may help to attenuate adverse outcomes.

A Novel Multiple Risk Score Model for Prediction of Long-Term Ischemic Risk in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: Insights From the I-LOVE-IT 2 Trial

Backgrounds: A plug-and-play standardized algorithm to identify the ischemic risk in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) could play a valuable step to help a wide spectrum of clinic workers. This study intended to investigate the ability to use the accumulation of multiple clinical routine risk scores to predict long-term ischemic events in patients with CAD undergoing PCI.Methods: This was a secondary analysis of the I-LOVE-IT 2 (Evaluate Safety and Effectiveness of the Tivoli drug-eluting stent (DES) and the Firebird DES for Treatment of Coronary Revascularization) trial, which was a prospective, multicenter, and randomized study. The Global Registry for Acute Coronary Events (GRACE), baseline Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX), residual SYNTAX, and age, creatinine, and ejection fraction (ACEF) score were calculated in all patients. Risk stratification was based on the number of these four scores that met the established thresholds for the ischemic risk. The primary end point was ischemic events at 48 months, defined as the composite of cardiac death, nonfatal myocardial infarction, stroke, or definite/probable stent thrombosis (ST).Results: The 48-month ischemic events had a significant trend for higher event rates (from 6.61 to 16.93%) with an incremental number of risk scores presenting the higher ischemic risk from 0 to ≥3 (p trend &lt; 0.001). In addition, the categories were associated with increased risk for all components of ischemic events, including cardiac death (from 1.36 to 3.15%), myocardial infarction (MI) (from 3.31 to 9.84%), stroke (3.31 to 6.10%), definite/probable ST (from 0.58 to 1.97%), and all-cause mortality (from 2.14 to 6.30%) (all p trend &lt; 0.05). The net reclassification index after combined with four risk scores was 12.5% (5.3–20.0%), 9.4% (2.0–16.8%), 12.1% (4.5–19.7%), and 10.7% (3.3–18.1%), which offered statistically significant improvement in the performance, compared with SYNTAX, residual SYNTAX, ACEF, and GRACE score, respectively.Conclusion: The novel multiple risk score model was significantly associated with the risk of long-term ischemic events in these patients with an increment of scores. A meaningful improvement to predict adverse outcomes when multiple risk scores were applied to risk stratification.

Methylation of f2rl3, cdkn2a genes and sudden cardiac death

The aim of the study was to evaluate the association of methylation of the F2RL3, CDKN2A gene with sudden cardiac death (SCD). Material and methods. Case-control study design. The SCD group included 150 deceased men (mean age 46.7 ± 9.2 years) with the main pathological diagnoses of acute circulatory failure, acute coronary insufficiency, which meets the SCD criteria of the European Society of Cardiology. The control group included 150 men who died suddenly, but not due to cardiovascular pathology (mean age 42.6 ± 1.2 years). DNA was isolated by phenol-chloroform extraction from myocardial tissue in both groups. The methylation status of the F2RL3 gene (19: 16890405-16890606, GRCh38.p13) and the CDKN2A gene (9: 21974726-21974877, GRCh38.p13) was assessed by methyl-specific polymerase chain reaction. Results. In the SCD group, 17.3 % (26/150) had the F2RL3 gene completely methylated (MM); in 6.0 % (9/150) it is completely unmethylated (UU); 76.7 % (115/150) had both methylated and unmethylated F2RL3 (MU) gene. In the control group, 16 % (24/150) had the F2RL3 gene completely methylated (MM); in 5.3 % (8/150), it is completely unmethylated (UU); 78.7 % (118/150) had both methylated and unmethylated F2RL3 (MU) gene. When comparing the groups, there were no statistically significant differences in the methylation status of the F2RL3 gene between the groups (p > 0.05). In all subjects in the SCD group and the control group, the CDKN2A gene is completely unmethylated. Conclusions. Methylation of genes F2RL3, CDKN2A is not associated with sudden cardiac death.

Genetic Variants Associated With Sudden Cardiac Death in Victims With Single Vessel Coronary Artery Disease and Left Ventricular Hypertrophy With or Without Fibrosis

Objective: Cardiac hypertrophy with varying degrees of myocardial fibrosis is commonly associated with coronary artery disease (CAD) related sudden cardiac death (SCD), especially in young victims among whom patterns of coronary artery lesions do not entirely appear to explain the cause of SCD. Our aim was to study the genetic background of hypertrophy, with or without fibrosis, among ischemic SCD victims with single vessel CAD.Methods: The study population was derived from the Fingesture study, consisting of all autopsy-verified SCDs in Northern Finland between the years 1998 and 2017 (n = 5,869). We carried out targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function in 95 ischemic-SCD victims (mean age 63.6 ± 10.3 years; 88.4% males) with single-vessel CAD in the absence of previously diagnosed CAD and cardiac hypertrophy with or without myocardial fibrosis at autopsy.Results: A total of 42 rare variants were detected in 43 subjects (45.3% of the study subjects). Five variants in eight subjects (8.4%) were classified as pathogenic or likely pathogenic. We observed 37 variants of uncertain significance in 39 subjects (40.6%). Variants were detected in myocardial structure protein coding genes, associated with arrhythmogenic right ventricular, dilated, hypertrophic and left ventricular non-compaction cardiomyopathies. Also, variants were detected in ryanodine receptor 2 (RYR2), a gene associated with both cardiomyopathies and catecholaminergic polymorphic ventricular tachycardias.Conclusions: Rare variants associated with cardiomyopathies, in the absence of anatomic evidence of the specific inherited cardiomyopathies, were common findings among CAD-related SCD victims with single vessel disease and myocardial hypertrophy found at autopsies, suggesting that these variants may modulate the risk for fatal arrhythmias and SCD in ischemic disease.

A Single Coronary Artery Originating from the Right Coronary Sinus with a Typical Course of the Right Coronary Artery and the Interarterial Course of the Left Main, Left Anterior Descending, and Left Circumflex as an Example of a Rare Case of High-Risk Coronary Anomaly

In the typical course of the coronary arteries, the right coronary artery comes from the right coronary sinus and descends in the right atrioventricular groove. The left coronary artery trunk begins from the left coronary sinus. It crosses the pulmonary trunk and divides into left anterior descending and left circumflex arteries. Anatomical differences of the coronary arteries can be observed in 0.3–5.6% of the population. The interarterial course of coronary branches between the aorta and the pulmonary trunk is a malignant anomaly of the coronary arteries. Such abnormalities have been associated with an increased risk of sudden cardiac death. We present a rare case of coronary arteries anomaly involving the presence of a single right coronary artery and the interarterial course of its atypical branches documented by computed tomography angiography (CTA). In summary, the accurate assessment of the anatomical topography of coronary anomalies, possible in CTA, is necessary in the analysis of the risk of sudden cardiac death and its prevention.

Factores de riesgos de muerte súbita cardiaca en adolescentes: una revisión sistemática

Introducción: La muerte súbita cardiaca es un resultado poco común siendo en adolescentes incluso más catastrófico tanto para su entorno familiar como la sociedad, por lo cual es de vital importancia identificar los factores que pueden conllevar a una persona estar en riesgo de tener esta muerte devastadora. Objetivos: Determinar los factores de riesgo de muerte súbita cardiaca en adolescentes. Métodos: Se realizó una revisión sistemática donde se tomaron en cuenta todos los artículos en el idioma inglés y español los cuales fueron publicados desde el año 2020 hasta el año 2021, en los sitios de búsqueda PubMed y Google Scholar. Se utilizó la siguiente pregunta PEO: Población: Adolescentes, Exposición: Factores de riesgo, Outcome: Muerte súbita cardiaca. Las palabras clave fueron: “youth”, en combinación con “Risk Factors” y “Sudden Cardiac Death” (utilizados en PubMed). En google scholar se utilizaron los siguientes términos para la búsqueda avanzada: “Adolescentes”, “Muerte súbita Cardiaca” y “Factores de riesgo”. Se seleccionaron los artículos pblicados desde el año 2015 que cumplieran con los criterios de exclusión. Resultados: De los 13 artículos para esta revisión con respecto a la muerte súbita cardiaca en adolescentes se encontró una variedad de causas o factores de riesgo que hicieron desencadenar esta patología encontrando entre estas ciertas causantes con mayor repetición. Conclusión: La muerte súbita cardiaca tienen como principales factores de riesgo a las cardiopatías congénitas y la carga genética; los cuales debemos identificar y así poder actuar de una manera preventiva disminuyendo su incidencia de muertes.