Genetic Associations With Tpe Of The Heart T-Wave Under Different Conditions In UK Biobank

Public Domain | Source: Anthony Atkielski , Modified.
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Sudden cardiac death (SCD) is an unexpected death due to heart failure which occurs rapidly, often within 1 hour of symptom presentation. In the vast majority of SCD cases there were no long term warning signs of risk. Globally, SCD accounts for more than 7 million deaths per year, with over 300,000 in the USA alone. 

Heart rhythm problems can alert medical practitioners to a patient at high risk of heart attack. Surface electrocardiogram (ECG) is a non-invasive tool widely used for this purpose. The ECG Tpeak to Tend (Tpe) is an independent risk factor for ventricular arrhythmic mortality and all-cause mortality.  New studies are needed to understand the biology underpinning the Tpe in the intact human heart.

Andrew Tinker of Queen Mary University of London, UK, and colleagues aimed to identify genetic variants significantly associated with Tpe under different states of activity. To achieve this they employed two cohorts of the UK biobank, one sub-cohort of 58,839 individuals completed an exercise test using a stationary bicycle in conjunction with an ECG recording (EST-UKB), the other 35,225 individuals participated in an imaging study (IMAGE-UKB). The results were published in The American Journal of Human Genetics.

For resting Tpe, 28 genetic loci were identified, 10 of which were specific to resting Tpe, which explained 3.20% of its variance, corresponding to 21% of its estimated heritability. Two loci for Tpe response to exercise, that explained 0.16% of its variance, and one for Tpe response to recovery, that explained 0.06% of its variance were identified. 

Low heritability of the traits might explain the low number of identified variants for Tpe response to exercise and to recovery. The results would benefit from outside validation due to the limited samples available in the current study.

“In summary, our findings provide additional loci for Tpe interval traits and reveal the role of ventricular repolarization and cardiac conduction and contraction in modulating them. Our work may guide future studies identifying new therapeutic targets to modulate resting Tpe and its dynamics to prevent and treat ventricular arrhythmias,” concluded the authors.

Source

  1. https://www.cell.com/ajhg/pdf/S0002-9297(20)30118-X.pdf