Digital twin reconstruction of ventricular repolarisation identifies regional causes of T-wave abnormalities in hypertrophic cardiomyopathy
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Abnormal ventricular repolarisation in hypertrophic cardiomyopathy (HCM) may predispose patients to lethal arrhythmias, but repolarisation in HCM remains poorly spatially characterised. Integrating spatial cardiac magnetic resonance with ECG data has the potential to map electrical function throughout the ventricles. This study applied novel digital twin inverse ECG methods to map repolarisation patterns underlying abnormal T-waves in HCM.
Methods
Patient-specific full ventricular electrophysiological models were iteratively refined to match the patient 12-lead ECG. Data from 32 healthy volunteers and 69 HCM patients were analysed, with inferred substrates incorporating activation times, repolarisation times, and rate-corrected action potential durations (APD c s). Patients were stratified by T-wave phenotype to identify distinct spatial repolarisation signatures associated with different ECG presentations.
Results
Clinical 12-lead ECGs were accurately reproduced by the inferred ventricular models in 95 of 101 cases. Healthy volunteers (N=30) and HCM patients with normal T-waves (N=33) were characterised by apex-to-base APD c gradients of 60 ms (40–80) and 60 ms (30–80), respectively. HCM patients with V1-V3 T-wave abnormalities (N=6) had attenuated apex-to-base APD c gradients of 30 ms (-20–40) driven by apical-to-mid anterior APD c prolongation, greatest at the apical segment (ΔAPD c vs. healthy: 54 ms; 95% CI: 23–84 ms). HCM patients with V4-V6 T wave abnormalities (N=21) had reversed apex-to-base APD c gradients of -20 ms (-40–0) driven by apical-to-mid APD c prolongation, most severe at the apical segment (ΔAPD c vs. healthy: 94 ms; 95% CI: 74–120 ms). Despite significant APD c prolongation, only 4 of 69 HCM patients had QT c > 480 ms, due to masking by the intrinsically healthy longer APD c s at the ventricular base.
Conclusions
Distinct spatial distributions of APD c prolongation, not necessarily mirroring the distribution of hypertrophy, underlie different ECG repolarisation phenotypes in HCM and may be missed by the QT c interval.
Clinical Perspective
What is Known
-
T-wave abnormalities on ECG occur in 50% of HCM patients, but the drivers of these ECG changes remain only partially understood.
-
Abnormal prolonged repolarisation is thought to occur in HCM, but QT c > 480 ms on ECG occurs only in 13% of HCM patients.
What the Study Adds
-
This study uses a simulation-based inference framework to reconstruct patient-specific spatially resolved electrophysiological substrates in HCM from routine 12-lead ECG and CMR.
-
By comparing to healthy volunteers, the framework identifies prolongation of ventricular repolarisation in mid-to-apical regions underlying T-wave abnormalities in HCM, indicating a regionally impaired electrical substrate.
-
The framework identifies that the QT c interval fails to capture regional prolongation of repolarisation in HCM, particularly in mid-to-apical ventricular regions.
