Arrhythmogenic substrate, modulating factors, and triggering factors (the so-called Coumel’s triangle concept) play a primary role in atrial fibrillation (AF) pathophysiology. Several years have elapsed since Coumel and co-workers advanced the concept of the relevance of autonomic nervous system (ANS) influences on atrial cells’ electrophysiological characteristics. The ANS is not only associated with cardiac rhythm regulation but also exerts an important role in the triggering and maintenance of atrial fibrillation. This review aims to describe in detail the autonomic mechanisms involved in the pathophysiology of atrial fibrillation (AF), starting from the hypothesis of an “Autonomic Coumel Triangle” that stems from the condition of the fundamental role played by the ANS in all phases of the pathophysiology of AF. In this article, we provide updated information on the biomolecular mechanisms of the ANS role in Coumel’s triangle, with the molecular pathways of cardiac autonomic neurotransmission, both adrenergic and cholinergic, and the interplay between the ANS and cardiomyocytes’ action potential. The heterogeneity of the clinical spectrum of the ANS and AF, with the ANS playing a relevant role in situations that may promote the initiation and maintenance of AF, is highlighted. We also report on drug, biological, and gene therapy as well as interventional therapy. On the basis of the evidence reviewed, we propose that one should speak of an “Autonomic Coumel’s Triangle” instead of simply “Coumel’s Triangle”.

Drug-coated balloons (DCBs) have emerged as a promising alternative therapeutic strategy to traditional drug-eluting stent (DES) implantation in various coronary artery lesion scenarios, aiming to minimize complications associated with permanent metallic scaffolds, such as chronic inflammation, delayed vessel healing, and stent thrombosis. This review systematically evaluates the current clinical evidence supporting the use of DCBs across diverse anatomical and clinical contexts, including small-vessel disease, in-stent restenosis, bifurcation lesions, diffuse coronary lesions, acute coronary syndromes, and chronic total occlusions, as well as in special patient populations such as individuals with diabetes mellitus or at high bleeding risk. The literature analysis incorporated recent randomized controlled trials, observational studies, and real-world registries, highlighting the clinical efficacy, safety profiles, and specific advantages of DCB angioplasty. The findings consistently demonstrated non-inferior clinical outcomes of DCBs compared to DESs across multiple lesion types, with particular benefits observed in special populations, including reduced restenosis rates and comparable major adverse cardiac events (MACEs). Nevertheless, clinical data gaps remain, emphasizing the need for larger, longer-term randomized trials to refine patient selection and procedural techniques. In conclusion, DCB angioplasty represents a viable and effective alternative to conventional stenting, particularly advantageous in complex lesions and specific patient subsets, pending further definitive evidence.

Background/Objectives: Polymer-free drug-eluting stents (PF-DESs) aim to mitigate long-term adverse effects associated with polymer-based platforms. However, clinical comparisons with biodegradable polymer DESs (BP-DESs) remain limited. The objective of this review is to assess the efficacy and safety of PF-DESs versus thin-struts (<100 μm) BP-DESs in patients undergoing percutaneous coronary intervention (PCI). Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PF-DESs and BP-DESs in adults undergoing PCI. PubMed, Embase, and CENTRAL were searched up to 1 February 2025. A random-effects model was used to calculate pooled risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). Outcomes included myocardial infarction (MI), all-cause and cardiac death, target lesion revascularization (TLR), stent thrombosis, and angiographic/OCT parameters. Subgroup and sensitivity analyses were conducted for outcomes with high heterogeneity (I² > 50%). Results: Nine RCTs (n = 9597) were included. At 12 months, no significant differences were found between PF-DESs and BP-DESs for TLR (RR 1.51; 95% CI: 0.83–2.75), MI, or stent thrombosis. At 24 months, MI and all-cause death were similar between groups. A subgroup analysis showed lower cardiac death with the BioFreedom stent (RR 0.57; 95% CI: 0.35–0.90), not observed in non-BioFreedom devices. No significant differences were detected in angiographic or OCT outcomes, though heterogeneity was high. Conclusions: PF-DESs and BP-DESs demonstrated comparable clinical performance. The observed benefit in cardiac death with BioFreedom may reflect device-specific effects and merits further investigation.

Cardioneuroablation (CNA) is now recognized as a safe and effective method in patients with cardioinhibitory neurocardiogenic syncope (CNCS), especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Several investigations have shown beneficial and very satisfactory results with a standard non-extensive endocardial ablation, aimed at identifying high-amplitude fragmented signals in the right and left atria. Despite this, the current scientific debate is focused about a proposal on an ablative method, even more individualized than CNA (at least as a first approach), considering that a standardized approach, especially in the left atrium, could expose CNCS patients with a good prognosis to an excessive risk of complications. These findings, moving from the concept of CNA to a new concept of ‘cardioneuromodulation’, opened a new era, aimed at a non-extensive and individualized treatment of different clinical CNCS scenarios or vagally-mediated atrioventricular block or sinus-atrial node dysfunction.