The Role of Infarct Border Zone Remodelling in Ventricular Arrhythmias: Bridging Basic Research and Clinical Applications

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  FIGURE 1. Overview of the fundamental electrophysiological mechanisms of VAs in post‐MI. Multiple mechanisms exist for VAs such as triggered activity, reentry, and automaticity. Scar‐based reentry is a predominant mechanism responsible for most malignant VAs that can ultimately lead to SCD. Some aspects of the structural (myocardial fibrosis and hypertrophy) and electrophysiological (altered gap junction, ion channel and autonomic nervous system) remodelling, especially in the IBZ may lead to impaired impulse generation and conduction. These changes can also significantly affect repolarisation dynamics and repolarisation reserve, rendering the heart more susceptible to arrhythmogenesis. Triggered ventricular activity such as acute ischaemia, infections, drugs and so on, generally develops after depolarisations due to oscillations in membrane potential after an action potential, which meet the threshold for triggering new ventricular action potentials. Cx, connexin; IBZ, infarct border zone; IK1, the inward rectifier K+ current; IKs, the slow delayed rectifier K+ current; Ito, the transient outward current; MI, myocardial infarction; SCD, sudden cardiac death; VAs, ventricular arrhythmias.

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  FIGURE 2. Phenotypic transitions of cardiac fibroblasts in the infarcted myocardium. During the inflammatory phase of infarct healing, necrotic cardiomyocytes undergo necrosis and apoptosis, releasing damage‐associated molecular patterns that activate a pro‐inflammatory response, such as IL‐1β, TNF‐α, and IL‐6. These cytokines stimulate the expression and secretion of MMPs that degrade the ECM, setting the stage for replacing damaged tissue with a collagen‐based scar. Resident cardiac fibroblasts do not express the myofibroblast marker α‐SMA. Matrix‐degrading phenotypes in cardiac fibroblasts contribute to the infiltration and activation of immune cells and fibroblasts at the injury site. The clearance of dead cardiomyocytes stimulates anti‐inflammatory signals, leading to the transition to the proliferative phase of infarct healing. During the proliferative phase, many fibroblasts become activated, proliferate, and differentiate into cardiac myofibroblasts that secrete large amounts of ECM proteins. In the maturation phase of infarct healing, fibroblasts display the disassembly of stress fibres and transition to matrifibrocytes, specialised cells that may play a role in scar maintenance.…

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  FIGURE 3. Prevention and treatment of VAs or SCD in patients with MI. ①Βeta‐blocker can reduce CVD events and improve long‐term prognosis. Amiodarone has no impact on CVD events. ②Early first‐line catheter ablation performed concurrently with ICD implantation probably reduces CVD events. CVD, cardiovascular disease; ICD, implantable cardioverter‐defibrillator; MI, myocardial infarction; SCD, sudden cardiac death; VAs, ventricular arrhythmias.