Genetic Basis and Prognostic Value of Exercise QT Dynamics

Overview

Journal Circ Genom Precis Med

Specialties Cardiology & Vascular Diseases
Genetics

Date 2020 Jun 13

PMID 32527199

Citations 9

Authors

Stefan van Duijvenboden

Julia Ramirez

William J Young

Borbala Mifsud

Michele Orini

Andrew Tinker

Patricia B Munroe

Pier D Lambiase

Affiliations

Soon will be listed here.

Abstract

Background: Abnormal QT interval responses to heart rate (QT dynamics) is an independent risk predictor for cardiovascular disease in patients, but its genetic basis and prognostic value in a population-based cohort have not been investigated.

Methods: QT dynamics during exercise and recovery were derived in 56 643 individuals from UK Biobank without a history of cardiovascular events. Genome-wide association studies were conducted to identify genetic variants and bioinformatics analyses were performed to prioritize candidate genes. The prognostic value of QT dynamics was evaluated for cardiovascular events (death or hospitalization) and all-cause mortality.

Results: Heritability of QT dynamics during exercise and recovery were 10.7% and 5.4%, respectively. Genome-wide association studies identified 20 loci, of which 4 loci included genes implicated in mendelian long-QT syndrome. Five loci did not overlap with previously reported resting QT interval loci; candidate genes included and . Genetic risk scores were not associated with cardiovascular events in 357 882 unrelated individuals from UK Biobank. We also did not observe associations of QT dynamics during exercise and recovery with cardiovascular events. Increased QT dynamics during recovery was significantly associated with all-cause mortality in the univariate Cox regression analysis (hazard ratio, 1.09 [95% CI, 1.05-1.13], =2.28×10), but the association was not significant after adjusting for clinical risk factors.

Conclusions: QT interval dynamics during exercise and recovery are heritable markers but do not carry independent prognostic information for clinical outcomes in the UK Biobank, a population-based cohort. Their prognostic importance may relate to cardiovascular disease cohorts where structural heart disease or ischemia may influence repolarization dynamics. The strong overlap between QT dynamics and resting QT interval loci suggests common biological pathways; however, nonoverlapping loci suggests alternative mechanisms may exist that underlie QT interval dynamics.

Citing Articles

Long-term association of ultra-short heart rate variability with cardiovascular events.

Orini M, van Duijvenboden S, Young W, Ramirez J, Jones A, Hughes A Sci Rep. 2023; 13(1):18966.

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Premature atrial and ventricular contractions detected on wearable-format electrocardiograms and prediction of cardiovascular events.

Orini M, van Duijvenboden S, Young W, Ramirez J, Jones A, Tinker A Eur Heart J Digit Health. 2023; 4(2):112-118.

PMID: 36974269 PMC: 10039429. DOI: 10.1093/ehjdh/ztad007.

A large genome-wide association study of QT interval length utilizing electronic health records.

Hoffmann T, Lu M, Oni-Orisan A, Lee C, Risch N, Iribarren C Genetics. 2022; 222(4).

PMID: 36271874 PMC: 9713425. DOI: 10.1093/genetics/iyac157.

ECG T-Wave Morphologic Variations Predict Ventricular Arrhythmic Risk in Low- and Moderate-Risk Populations.

Ramirez J, Kiviniemi A, van Duijvenboden S, Tinker A, Lambiase P, Junttila J J Am Heart Assoc. 2022; 11(17):e025897.

PMID: 36036209 PMC: 9496440. DOI: 10.1161/JAHA.121.025897.

Prediction of Coronary Artery Disease and Major Adverse Cardiovascular Events Using Clinical and Genetic Risk Scores for Cardiovascular Risk Factors.

Ramirez J, van Duijvenboden S, Young W, Tinker A, Lambiase P, Orini M Circ Genom Precis Med. 2022; 15(5):e003441.

PMID: 35861959 PMC: 9584057. DOI: 10.1161/CIRCGEN.121.003441.

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