Ventricular Arrhythmias in Ischemic Cardiomyopathy-New Avenues for Mechanism-Guided Treatment.
Matthew AmoniEef DriesSebastian IngelaereDylan VermoorteleH Llewelyn RoderickPiet ClausRik WillemsKarin R SipidoPublished in: Cells (2021)
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.
Keyphrases
- heart failure
- left ventricular
- catheter ablation
- congenital heart disease
- end stage renal disease
- chronic kidney disease
- ejection fraction
- newly diagnosed
- risk factors
- smoking cessation
- acute myocardial infarction
- minimally invasive
- atrial fibrillation
- peritoneal dialysis
- oxidative stress
- ischemia reperfusion injury
- mesenchymal stem cells
- combination therapy
- single molecule
- blood brain barrier