Molecular mechanisms of heart failure progression associated with implantable cardioverter-defibrillator shocks for ventricular tachyarrhythmias

AbstractImplantable cardioverter-defibrillators (ICDs) are highly effective in reducing mortality related to ventricular tachyarrhythmias (VTAs). Despite this benefit, the occurrence of ICD shocks for VTAs in patients with heart failure (HF) and depressed left ventricular function has been associated with adverse outcomes. Patients with shocked VTAs are at an elevated risk of HF and death. While VTAs may be markers for high-risk patients, it is possible that the harmful effects of electrical shocks and VTAs are involved in HF progression and associated mortality. Some investigators have speculated that shocked VTAs may activate signaling pathways in the molecular cascade of HF. We recently reported in an experimental model of ventricular fibrillation storm that multiple ICD shocks for recurrent ventricular fibrillation caused striking activation of Ca2+/calmodulin-dependent protein kinase II, a validated signaling molecule for HF. This review article describes the harmful effects of shocks and VTAs and proposes that Ca2+/calmodulin-dependent protein kinase II could connect shocked VTAs to adverse outcomes