@article {7135, title = {Global Electric Heterogeneity Risk Score for Prediction of Sudden Cardiac Death in the General Population: The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.}, journal = {Circulation}, volume = {133}, year = {2016}, month = {2016 Jun 7}, pages = {2222-34}, abstract = {

BACKGROUND: Asymptomatic individuals account for the majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and noninvasive SCD risk stratification tools is necessary.

METHODS AND RESULTS: Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20 177; age, 59.3{\textpm}10.1 years; age range, 44-100 years; 56\% female; 77\% white) were followed up for 14.0 years (median). Five ECG markers of global electric heterogeneity (GEH; sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient [SVG] magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH electrocardiographic parameters and SCD. An SCD competing risks score was derived from demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes mellitus, hypertension, coronary heart disease, stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C statistic increased from 0.777 to 0.790 (P=0.008), the risk score classified 10-year SCD risk as high (>5\%) in 7.2\% of participants, 10\% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4\% of SCD victims were inappropriately reclassified from high to intermediate risk. The net reclassification index was 18.3\%.

CONCLUSIONS: Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. The addition of GEH parameters to clinical characteristics improves SCD risk prediction.

}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.116.021306}, author = {Waks, Jonathan W and Sitlani, Colleen M and Soliman, Elsayed Z and Kabir, Muammar and Ghafoori, Elyar and Biggs, Mary L and Henrikson, Charles A and Sotoodehnia, Nona and Biering-S{\o}rensen, Tor and Agarwal, Sunil K and Siscovick, David S and Post, Wendy S and Solomon, Scott D and Buxton, Alfred E and Josephson, Mark E and Tereshchenko, Larisa G} } @article {7672, title = {Genome-Wide Associations of Global Electrical Heterogeneity ECG Phenotype: The ARIC (Atherosclerosis Risk in Communities) Study and CHS (Cardiovascular Health Study).}, journal = {J Am Heart Assoc}, volume = {7}, year = {2018}, month = {2018 Apr 05}, abstract = {

BACKGROUND: ECG global electrical heterogeneity (GEH) is associated with sudden cardiac death. We hypothesized that a genome-wide association study would identify genetic loci related to GEH.

METHODS AND RESULTS: We tested genotyped and imputed variants in black (N=3057) and white (N=10~769) participants in the ARIC (Atherosclerosis Risk in Communities) study and CHS (Cardiovascular Health Study). GEH (QRS-T angle, sum absolute QRST integral, spatial ventricular gradient magnitude, elevation, azimuth) was measured on 12-lead ECGs. Linear regression models were constructed with each GEH variable as an outcome, adjusted for age, sex, height, body mass index, study site, and principal components to account for ancestry. GWAS identified 10 loci that showed genome-wide significant association with GEH in whites or joint ancestry. The strongest signal (rs7301677, near ) was associated with QRS-T angle (white standardized β+0.16 [95\% CI 0.13-0.19]; =1.5{\texttimes}10), spatial ventricular gradient elevation (+0.11 [0.08-0.14]; =2.1{\texttimes}10), and spatial ventricular gradient magnitude (-0.12 [95\% CI -0.15 to -0.09]; =5.9{\texttimes}10). Altogether, GEH-SNPs explained 1.1\% to 1.6\% of GEH variance. Loci on chromosomes 4 (near ), 5 (), 11 (11p11.2 region cluster), and 7 (near ) are novel ECG phenotype-associated loci. Several loci significantly associated with gene expression in the left ventricle ( locus-with ; locus-with ), and atria ( locus-with expression of a long non-coding RNA and ).

CONCLUSIONS: We identified 10 genetic loci associated with ECG GEH. Replication of GEH GWAS findings in independent cohorts is warranted. Further studies of GEH-loci may uncover mechanisms of arrhythmogenic remodeling in response to cardiovascular risk factors.

}, issn = {2047-9980}, doi = {10.1161/JAHA.117.008160}, author = {Tereshchenko, Larisa G and Sotoodehnia, Nona and Sitlani, Colleen M and Ashar, Foram N and Kabir, Muammar and Biggs, Mary L and Morley, Michael P and Waks, Jonathan W and Soliman, Elsayed Z and Buxton, Alfred E and Biering-S{\o}rensen, Tor and Solomon, Scott D and Post, Wendy S and Cappola, Thomas P and Siscovick, David S and Arking, Dan E} }