果冻传媒

Ventricular tachycardia (VT) is a life-threatening cardiac arrhythmia that is more common in patients after a heart attack. The heart tissue damaged by the heart attack forms a substrate for abnormal electrical activity, which can lead to re-entry activation circuits and VT. These VTs often develop 7 to 10 years after the initial heart attack. By predicting the long-term risk of VT in patients after a heart attack, more tailored therapies can be developed, reducing over- and under-treatment in this patient group. In her thesis, describes how long-term mechanical and electrical remodeling of the left ventricle after a heart attack can influence the development of VT. By integrating mechanical and electrophysiological aspects of the left ventricle using finite element models, this research increases our understanding of the progression of VT risk.

In a model of left ventricular mechanics, the infarct area was modeled by increasing passive stiffness and eliminating contraction. The transition zone around the infarct area showed a linear transition of these properties from infarct values to healthy values. In an electrophysiological model, the infarct area was implemented as a non-conductive area and the transition zone as an area with reduced impulse conduction and altered ion channel properties, which regulate various characteristics of the action potential.

Finally, electrical pacing was used to evaluate the risk of VT.

Risk of Ventricular Tachycardia

Central to this thesis is the hypothesis that stretch-induced changes in the conduction velocity of electrical activity influence the risk of VT. Willems tested this with simulations in which local stretch amplitudes, derived from the mechanical model of the ventricle with a chronic infarction, alter the electrical impulse conduction velocity transverse to the fiber direction in an electrophysiological model. In the first study of this thesis, a relationship between strain amplitude and transverse impulse conduction velocity was proposed and the effect of implementing this relationship on the definition of the electrophysiological substrate was investigated. This relationship between strain and conduction velocity was then applied with two different implementations for cardiac mechanics, and convergence tests were performed for both. Next, long-term remodeling after infarction was investigated by evaluating the effect of infarction stiffening on strain amplitudes and, consequently, on transverse impulse conduction and the risk of VT.

Finally, Willems investigated whether the proposed hypothesis could underlie the discrepancy between acute and definitive ablation treatment outcomes observed in the clinic. Based on this work, she concluded that investigating the influence of mechanical remodeling on electrical impulse conduction has made a new contribution to the field of computational cardiac arrhythmias.

The results show that including biomechanics can lead to a functional infarct zone in the electrophysiological model that extends beyond the anatomical zone of the infarct. Furthermore, the inclusion of infarct stiffening leads to a subtle increase in the VT risk, which may be related to the slow progression and thus the long period between the moment of the heart attack and the onset of VT, as observed in the clinic. When implementing chronic ablation scars, both pro- and anti-arrhythmic effects of the changes in conductivity resulting from strain affected by ablation scars were found, which may partially explain the process behind the period between therapy and the final treatment outcome.

The findings from Willem's thesis can be used to guide future research toward a better understanding of the role of cardiac mechanics in the progression of VT risk after a heart attack or after ablation treatment.

Title of PhD thesis: 鈥�鈥� (Under embargo until December 20, 2025)

Supervisors: Frans van de Vosse, Lukas Dekker and (Maastricht UMC+)