Sudden cardiac death (SCD) is a major public health concern, accounting for 400,000 deaths in the US each year. Clinical and autopsy studies have consistently demonstrated a predominant, common pathophysiology in Western populations, showing that the most common electrophysiologic mechanism for SCD is ventricular fibrillation (VF) and the most common pathologic substrate is coronary heart disease (CHD). In about half of SCD cases, death is the first clinical manifestation of CHD. Yet risk factors of SCD early in the natural history of conditions predisposing SCD have not been fully identified, and SCD risk stratification strategy in general population has not been developed. ECG is easy available, non-expensive and noninvasive tool, which carries valuable information on electrophysiological properties of the heart. However, traditional analysis of ECG includes very limited assessment of the arrhythmogenic substrate. Recently we developed novel 12-lead ECG SCD risk score, composed of parameters that measure (1) slow discontinued conduction, (2) temporal repolarization lability, and (3) adverse electrical remodeling. Preliminary gender-, race-, and age-matched case-control analysis of the Atherosclerosis In Community (ARIC) study showed a total continuous net reclassification improvement of 86.0% as compared to the Framingham risk score alone. We hypothesize that (1) the ?SCD ECG risk score?, comprised of the mechanistic ECG markers of arrhythmogenic substrate derived in the resting 12-lead ECG analysis accurately stratify persons into high-, intermediate- and low-risk groups and improve classification in comparison to the risk stratification on the basis of traditional CHD risk factors;(2) heritable factors of the novel ECG phenotype are associated with the increased SCD risk. This application bridges a critical gap between understanding of the SCD mechanisms and SCD risk stratification in a general population. We will leverage 2 unique large NIH-funded prospective community-dwelling GWAS cohorts with an available digital 12-lead ECG repository: ARIC and CHS. Baseline digital 12-lead ECG will be analyzed by customized Matlab software in PI's laboratory. The SCD ECG risk score will be developed in ARIC and validated in the CHS cohort. Net reclassification improvement will be assessed. Longitudinal changes in studied ECG parameters over 20 years of follow-up will be evaluated as predictors of cardiac structural and functional phenotype, assessed by echocardiography at the 5th ARIC visit. Our study will identify genes, associated with specific ECG traits, which will lead to novel targets for treatments and in the future will enable SCD prevention.
The objective of this ancillary ARIC and CHS study is to develop and validate the novel resting 12-lead ECG risk score of sudden cardiac death risk in the analysis of community-dwelling cohorts of asymptomatic adults and discover genetic factors associated with the novel ECG phenotypes (repolarization lability, slow discontinued conduction and adverse remodeling).
|Thomas, Jason A; A Perez-Alday, Erick; Junell, Allison et al. (2018) Vectorcardiogram in athletes: The Sun Valley Ski Study. Ann Noninvasive Electrocardiol :e12614|
|Tereshchenko, Larisa G; Sotoodehnia, Nona; Sitlani, Colleen M et al. (2018) Genome-Wide Associations of Global Electrical Heterogeneity ECG Phenotype: The ARIC (Atherosclerosis Risk in Communities) Study and CHS (Cardiovascular Health Study). J Am Heart Assoc 7:|
|Perez-Alday, Erick Andres; Li-Pershing, Yin; Bender, Aron et al. (2018) Importance of the heart vector origin point definition for an ECG analysis: The Atherosclerosis Risk in Communities (ARIC) study. Comput Biol Med 104:127-138|
|Tereshchenko, Larisa G; Posnack, Nikki G (2018) Does plastic chemical exposure contribute to sudden death of patients on dialysis? Heart Rhythm :|
|Fitzpatrick, Jessica; Sozio, Stephen M; Jaar, Bernard G et al. (2018) Association of Abdominal Adiposity with Cardiovascular Mortality in Incident Hemodialysis. Am J Nephrol 48:406-414|
|Thomas, Jason A; Perez-Alday, Erick Andres; Hamilton, Christopher et al. (2018) The utility of routine clinical 12-lead ECG in assessing eligibility for subcutaneous implantable cardioverter defibrillator. Comput Biol Med 102:242-250|
|Perez-Alday, Erick A; Thomas, Jason A; Kabir, Muammar et al. (2018) Torso geometry reconstruction and body surface electrode localization using three-dimensional photography. J Electrocardiol 51:60-67|
|Biering-Sørensen, Tor; Kabir, Muammar; Waks, Jonathan W et al. (2018) Global ECG Measures and Cardiac Structure and Function: The ARIC Study (Atherosclerosis Risk in Communities). Circ Arrhythm Electrophysiol 11:e005961|
|Junell, Allison; Thomas, Jason; Hawkins, Lauren et al. (2017) Screening entire healthcare system ECG database: Association of deep terminal negativity of P wave in lead V1 and ECG referral with mortality. Int J Cardiol 228:219-224|
|Patel, Siddharth; Kwak, Lucia; Agarwal, Sunil K et al. (2017) Counterclockwise and Clockwise Rotation of QRS Transitional Zone: Prospective Correlates of Change and Time-Varying Associations With Cardiovascular Outcomes. J Am Heart Assoc 6:|
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