Ventricular Arrhythmias in Ischemic Cardiomyopathy—New Avenues for Mechanism-Guided Treatment

Abstract

Ischemic heart disease is the most common cause of lethal ventricular arrhythmias and sudden cardiac death (SCD). In patients who are at high risk after myocardial infarction, implantable cardioverter defibrillators are the most effective treatment to reduce incidence of SCD and ablation therapy can be effective for ventricular arrhythmias with identifiable culprit lesions. Yet, these approaches are not always successful and come with a considerable cost, while pharmacological management is often poor and ineffective, and occasionally proarrhythmic. Advances in mechanistic insights of arrhythmias and technological innovation have led to improved interventional approaches that are being evaluated clinically, yet pharmacological advancement has remained behind. We review the mechanistic basis for current management and provide a perspective for gaining new insights that centre on the complex tissue architecture of the arrhythmogenic infarct and border zone with surviving cardiac myocytes as the source of triggers and central players in re-entry circuits. Identification of the arrhythmia critical sites and characterisation of the molecular signature unique to these sites can open avenues for targeted therapy and reduce off-target effects that have hampered systemic pharmacotherapy. Such advances are in line with precision medicine and a patient-tailored therapy.

Anomalous Origin of the Right Coronary Artery: An Uncommon Presentation

“…During physical exercise, emotional burden, and tachycardia, myocardial oxygen demand increases while coronary flow decreases. This mismatch leads to cumulative myocardial ischemia [13] and fibrotic scar, eventual lethal ventricular arrhythmia, myocardial ischemia, and sudden cardiac death [14]. This theory was confirmed by the pathological feature of postmortem sudden cardiac death victims of anomalous origin coronary artery demonstrates histopathologic finding of left ventricular subendocardial myocardial fibrosis [15].…”

Ticagrelor Can Regulate the Ion Channel Characteristics of Superior Cervical Ganglion Neurons after Myocardial Infarction

“…The sympathetic nervous system (SNS) plays an important role in the regulation of cardiac function after MI [ 17 , 18 ]. MI can lead to excessive excitement of sympathetic nerves, leading to neurotransmitter accumulation [ 1 , 2 ], which is an important reason for the cardiac arrhythmias observed post-MI [ 3 , 4 ].…”

Electrical Remodelling in Cardiac Disease

“…Mutations in the gene encoding β-cardiac myosin heavy chain increase myofilament Ca 2+ sensitivity which leads to dysfunctional diastolic Ca 2+ handling and further increases arrhythmogenic risk [30]. Amoni and Sipido approach their review of ventricular arrhythmias in ischemic cardiomyopathy from a therapeutic viewpoint [31]. They provide novel mechanistic insight to molecular alterations of the vulnerable myocardial infarction boarder zone with the implicit aim to arrive at new avenues for treatment.…”