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Cardiovascular Predictive Value and Genetic Basis of Ventricular Repolarization Dynamics
Julia Ramírez1,2, Stefan van Duijvenboden1,2, Nay Aung3,4
1Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry (J.R., S.v.D., A.T., M.O., P.B.M.), Queen Mary University of London, United Kingdom.
T-wave morphology restitution (TMR) predicts cardiovascular events in middle-aged UK adults. TMR genetic risk scores also identify individuals at higher cardiovascular risk, validating TMR as a prognostic tool.
Area of Science:
- Cardiology
- Genetics
- Electrocardiography
Background:
- Early cardiovascular risk prediction in the general population is crucial.
- T-wave morphology restitution (TMR), an ECG marker of ventricular repolarization dynamics, is linked to cardiovascular mortality in heart failure patients.
Purpose of the Study:
- To evaluate the cardiovascular prognostic value of TMR in a UK middle-aged population.
- To identify any genetic contribution to TMR and its association with cardiovascular risk.
Main Methods:
- Analysis of ECG recordings from 55,222 individuals from the UK Biobank (UKB) undergoing exercise stress tests.
- Measurement of TMR during exercise (TMR extsuperscript{ex}) and recovery (TMR extsuperscript{rec}).
- Genome-wide association studies for TMR extsuperscript{ex} and TMR extsuperscript{rec}, and derivation of genetic risk scores.
Main Results:
- TMR extsuperscript{rec} was significantly associated with cardiovascular events (HR, 1.11; P=5×10 extsuperscript{-7}), independent of clinical variables and other ECG markers.
- TMR extsuperscript{rec} also correlated with all-cause mortality (HR, 1.10) and ventricular arrhythmias (HR, 1.16).
- Individuals with a high TMR extsuperscript{rec} genetic risk score had a significantly higher likelihood of cardiovascular events (HR, 1.07; P=6×10 extsuperscript{-3}).
Conclusions:
- TMR and its genetic risk scores are significantly associated with cardiovascular risk in a UK middle-aged population.
- These findings support TMR as a valid cardiovascular risk predictor, linked to ventricular repolarization heterogeneity.
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