Human biventricular electromechanical simulations on the progression of electrocardiographic and mechanical abnormalities in post-myocardial infarction.

Zhinuo J Wang,Arka Das,Francesca Margara,Chris Kelly,Alfonso Santiago,Mariano Vazquez,Lei Wang,Francesc Levrero-Florencio,Erica Dall'Armellina,Blanca Rodriguez,Xin Zhou

doi:10.1093/europace/euaa405

Abstract

AimsDevelop, calibrate and evaluate with clinical data a human electromechanical modelling and simulation framework for multiscale, mechanistic investigations in healthy and post-myocardial infarction (MI) conditions, from ionic to clinical biomarkers. Methods and resultsHuman healthy and post-MI electromechanical simulations were conducted with a novel biventricular model, calibrated and evaluated with experimental and clinical data, including torso/biventricular anatomy from clinical magnetic resonance, state-of-the-art human-based membrane kinetics, excitation–contraction and active tension models, and orthotropic electromechanical coupling. Electromechanical remodelling of the infarct/ischaemic region and the border zone were simulated for ischaemic, acute, and chronic states in a fully transmural anterior infarct and a subendocardial anterior infarct. The results were compared with clinical electrocardiogram and left ventricular ejection fraction (LVEF) data at similar states. Healthy model simulations show LVEF 63%, with 11% peak systolic wall thickening, QRS duration and QT interval of 100 ms and 330 ms. LVEF in ischaemic, acute, and chronic post-MI states were 56%, 51%, and 52%, respectively. In linking the three post-MI simulations, it was apparent that elevated resting potential due to hyperkalaemia in the infarcted region led to ST-segment elevation, while a large repolarization gradient corresponded to T-wave inversion. Mechanically, the chronic stiffening of the infarct region had the benefit of improving systolic function by reducing infarct bulging at the expense of reducing diastolic function by inhibiting inflation.ConclusionOur human-based multiscale modelling and simulation framework enables mechanistic investigations into patho-physiological electrophysiological and mechanical behaviour and can serve as testbed to guide the optimization of pharmacological and electrical therapies.

Highlights

Coronary heart disease is a leading cause of mortality worldwide, with 7.3 million deaths in 2001.1 One of its consequences is myocardial infarction (MI), caused by coronary artery occlusion or narrowing, which may result in myocardial damage, increased risk of sudden arrhythmic death, and heart failure.[2]
Left ventricular ejection fraction (LVEF) is one of the key metrics used for risk stratification in post-MI, and for decisions on treatment options such as defibrillator implantation.[3]
This is clearly suboptimal as a significant number of sudden deaths occur in patients with relatively preserved left ventricular ejection fraction (LVEF) (36–50%) and a substantial proportion of patients with defibrillators do not make use of them

Summary

Introduction

Coronary heart disease is a leading cause of mortality worldwide, with 7.3 million deaths in 2001.1 One of its consequences is myocardial infarction (MI), caused by coronary artery occlusion or narrowing, which may result in myocardial damage, increased risk of sudden arrhythmic death, and heart failure.[2] The electrocardiogram (ECG) is the most widely used clinical diagnostic tool for cardiac disease and MI. ST-segment elevation and T-wave inversion are markers of cardiac remodelling associated with different stages of MI. It is still partly unclear how ECG abnormalities reflect post-MI properties such as infarct size and location, and arrhythmic risk. A deep mechanistic understanding of the variable substrate in post-MI, and how it reflects in clinical ECG and mechanical markers is needed to improve patients’ risk stratification and management

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Results

Conclusion