Ciro Indolfi

Atrial fibrillation (AF) is an arrhythmia that affects the left atrium, cardiac function, and the patients’ survival rate. Due to empowered diagnostics, it has become increasingly recognized among young individuals as well, in whom it is influenced by a complex interplay of autoimmune, inflammatory, and electrophysiological mechanisms. Deepening our understanding of these mechanisms could contribute to improving AF management and treatment. Inflammation is a complexly regulated process, with interactions among various immune cell types, signaling molecules, and complement components. Addressing circulating antibodies and designing specific autoantibodies are promising therapeutic options. In cardiomyopathies or channelopathies, the first manifestation could be paroxysmal AF; persistent forms tend not to respond to antiarrhythmic drugs in these conditions. Further research, both in vitro and in vivo, on the use of genomic biotechnology could lead to new therapeutic approaches. Additional triggers that can be encountered in AF patients below 60 years of age are systemic hypertension, overweight, diabetes, and alcohol abuse. The aims of this review are to briefly report evidence from basic science and results of clinical studies that might explain the juvenile burden of the most encountered sustained supraventricular tachyarrhythmias in the general population.

To date, no medical therapy can slow the progression of aortic stenosis. Fibrocalcific stenosis is the most frequent form in the general population and affects about 6% of the elderly population. Over the years, diagnosis has evolved thanks to echocardiography and computed tomography assessments. The application of artificial intelligence to electrocardiography could further implement early diagnosis. Patients with severe aortic stenosis, especially symptomatic patients, have valve repair as their only therapeutic option by surgical or percutaneous technique (TAVI). The discovery that the pathogenetic mechanism of aortic stenosis is similar to the atherosclerosis process has made it possible to evaluate the hypothesis of medical therapy for aortic stenosis. Several drugs have been tested to reduce low-density lipoprotein (LDL) and lipoprotein(a) (Lp(a)) levels, inflammation, and calcification. The Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9-i) could decrease the progression of aortic stenosis and the requirement for valve implantation. Great interest is related to circulating Lp(a) levels as causally linked to degenerative aortic stenosis. New therapies with ASO (antisense oligonucleotides) and siRNA (small interfering RNA) are currently being tested. Olpasiran and pelacarsen reduce circulating Lp(a) levels by 85–90%. Phase 3 studies are underway to evaluate the effect of these drugs on cardiovascular events (cardiovascular death, non-fatal myocardial injury, and non-fatal stroke) in patients with elevated Lp(a) and CVD (cardiovascular diseases). For instance, if a reduction in Lp(a) levels is associated with aortic stenosis prevention or progression, further prospective clinical trials are warranted to confirm this observation in this high-risk population.

Common triggers for sudden cardiac death (SCD) are transient ischemia, hemodynamic fluctuations, neurocardiovascular influences, and environmental factors. SCD occurs rapidly when sinus rhythm degenerates into ventricular tachycardia (VT) and/or ventricular fibrillation (VF), followed by asystole. Such progressive worsening of the cardiac rhythm is in most cases observed in the setting of ischemic heart disease and often associated with advanced left ventricular (LV) impairment. Revascularization prevents negative outcomes including SCD and heart failure (HF) due to LV dysfunction (LVD). The implantable cardioverter–defibrillator (ICD) on top of medical therapy is superior to antiarrhythmic drugs for patients with LVD and VT/VF. The beneficial effects of ICD have been demonstrated in primary prevention of SCD as well. However, yet debated is the temporal management for patients with LVD who are eligible to ICD prior to revascularization, either through percutaneous or surgical approach. Restoration of coronary blood flow has a dramatic impact on adverse LV remodeling, while it requires aggressive long-term antiplatelet therapy, which might increase complication for eventual ICD procedure when percutaneous strategy is pursued; on the other hand, when LV and/or multiorgan dysfunction is present and coronary artery bypass grafting is chosen, the overall risk is augmented, mostly in HF patients. The aims of this review are to describe the pathophysiologic benefits of revascularization, the studies addressing percutaneous, surgical or no revascularization and ICD implantation, as well as emerging defibrillation strategies for patients deemed at transient risk of SCD and/or at higher risk for transvenous ICD implantation.