Patrizio Mazzone

Despite major advances in cardiovascular medicine, ischemic heart disease (IHD) in women remains underrecognized and undertreated. A substantial proportion of symptomatic women have no flow-limiting epicardial stenosis, and ischemia may arise from coronary microvascular dysfunction, vasospasm, diffuse atherosclerosis, plaque-related mechanisms, spontaneous coronary artery dissection (SCAD), or combinations of these processes. Female-specific biological factors—including hormonal transitions, vascular aging, inflammation, metabolic changes, and reproductive cardiovascular risk enhancers—modify the coronary substrate across the life course. This review integrates these determinants with contemporary coronary phenotyping and proposes a clinically oriented, mechanism-based framework for IHD in women. Multimodality imaging, invasive coronary functional testing, and intracoronary imaging are considered complementary tools for identifying predominant and coexisting mechanisms. Management should combine guideline-directed cardiovascular prevention with mechanism-targeted antianginal therapy and women-specific considerations, including reproductive planning, pregnancy counseling, medication safety, and psychosocial care. This framework is intended as a practical synthesis rather than a validated classification system and aims to support more precise diagnosis and individualized treatment of women with ischemic symptoms.

Aims: Atrial fibrillation (AF) is highly prevalent among cardiac amyloidosis (CA) patients and contributes significantly to their morbidity and mortality. Evidence regarding AF ablation efficacy and safety in CA patients remains limited. The aim of our study is to evaluate baseline characteristics, clinical course and outcomes of AF ablation in a series of patients with transthyretin (ATTR) or light-chain (AL) CA from a multicentre international registry. Methods and results: Patients with CA who underwent AF ablation were included. Co-primary endpoints were: (i) atrial arrhythmia (AA) recurrence; (ii) a composite endpoint of all-cause mortality and heart failure hospitalization (HFH). 109 patients (mean age 72.4 ± 7.4 years, females 17.4%, persistent AF 64.2%, ATTR 78%, AL 22%) were included. Radiofrequency, cryo-balloon and pulsed-field ablation were performed in 67%, 15% and 18% of patients, respectively; 49.5% received pulmonary vein isolation plus additional ablations. Low voltage zones were documented in 34 out of 44 patients undergoing electro-anatomical mapping (77.3%). During a median follow-up of 22.7 months, 63 patients (58.3%) experienced AA recurrence (32.4% persistent AF recurrence), with no significant differences between CA subtypes (ATTR 59.5% vs. AL 54.2%, log-rank P = 0.55). The composite endpoint of HFH and all-cause death occurred in 27 patients (25%). Recurrence of persistent AF was associated with three-fold higher risk (OR 2.9, P = 0.02) of the composite endpoint. Conclusion: CA patients undergoing AF ablation present high prevalence of persistent AF. Freedom from AA after AF ablation is achieved in 42% of patients after a two-year follow-up. Patients with persistent AF recurrence have a three-fold higher risk of HFH and death.

Background/Objectives: Sacubitril/Valsartan is a cornerstone therapy to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate the effect of Sacubitril/Valsartan on cardiac autonomic balance using physiological sensor data obtained from implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds). Methods: This observational study involved 54 ICD and CRT-D patients who initiated Sacubitril/Valsartan therapy to treat HFrEF. The evaluated key parameters included heart rate variability (HRV), 24 h mean heart rate (24 h-HR), and nocturnal heart rate (nHR). Device electrical parameters and ventricular arrhythmias were also assessed. The data were collected by remote monitoring and averaged over a 7-day window at baseline (before treatment) and at 3 and 12 months after treatment initiation. Results: Sacubitril/Valsartan significantly improved HRV at 3 months (from 78.6 ms [interquartile range: 54.2–104.6] to 80.8 ms [60.8–108.0]; p = 0.041), reduced 24 h-HR (from 73.2 bpm [67.3–77.7] to 69.9 bpm [64.2–75.7]; p = 0.016), and reduced nHR (from 63.0 bpm [58.1–70.0] to 60.4 bpm [56.0–68.6]; p = 0.028). No significant changes in HRV, 24 h-HR, and nHR were observed between 3- and 12-month follow-up. The device electrical parameters were not influenced by the treatment. While the overall ventricular arrhythmia burden did not change post-treatment, patients with pre-treatment arrhythmias experienced a significant reduction in episodes from 2.97 (pre-treatment) to 0.82 (post-treatment) events per 100 patient years (p = 0.008). Conclusions: Sacubitril/Valsartan therapy in HFrEF patients was associated with statistically significant changes in cardiac autonomic indices, including a small increase in HRV and a slight reduction in heart rate, mainly during the first three months of treatment.

Background: Cardiovascular disease (CVD) in pregnancy is a major cause of maternal morbidity and mortality, accounting for nearly one-third of pregnancy-related deaths worldwide. Physiological adaptations—expanded plasma volume, increased cardiac output, and a prothrombotic state—represent a natural cardiovascular stress test that may precipitate decompensation or unmask subclinical disease. Aim: This review critically examines contemporary evidence and international guidelines on the management of pregnancy-related cardiovascular disorders, focusing on pathophysiological mechanisms, diagnostic challenges, and therapeutic controversies. Content: The discussion centers on three high-impact clinical domains: (1) peripartum and preexisting cardiomyopathies, emphasizing mechanisms, prognosis, and the role of bromocriptine; (2) anticoagulation management in women with mechanical prosthetic valves, balancing maternal safety and fetal protection; and (3) hypertensive disorders of pregnancy, highlighting recent evidence from the CHAP and WILL trials and their implications for long-term cardiovascular prevention. Comparative analysis of ESC 2025 and AHA 2020 recommendations reveals broad consensus but persistent discrepancies in anticoagulation targets, postpartum surveillance, and follow-up strategies. Perspectives: Endothelial dysfunction, angiogenic imbalance, and systemic inflammation emerge as shared mechanisms linking diverse pregnancy-related cardiovascular conditions. Strengthening multidisciplinary care through Pregnancy Heart Teams, integrating obstetric and cardiologic expertise, and establishing structured postpartum follow-up pathways are essential to improve outcomes.

Background: Mitral annular disjunction (MAD) is an anatomical abnormality associated with an increased risk of major arrhythmic events, regardless of the presence of mitral valve prolapse. Cardiac magnetic resonance (CMR) plays a key role in diagnosing MAD and identifying myocardial fibrosis, a marker of arrhythmic vulnerability. Aim: This study reports the experience of the De Gasperis Cardiology Centre at Niguarda Hospital (Milan, Italy) in managing high-risk MAD patients who underwent implantable cardioverter–defibrillator (ICD) implantation and describes their main clinical characteristics. Methods: Between January 2020 and April 2025, five patients with MAD who received ICDs were identified and monitored remotely. Although the small sample size limits generalizability, the objective was to characterize factors associated with arrhythmic susceptibility. Results: Four patients exhibited documented ventricular arrhythmias: two with non-sustained and two with sustained ventricular tachycardia. Notably, CMR did not reveal myocardial fibrosis in two symptomatic cases, suggesting that arrhythmic vulnerability may precede detectable structural abnormalities. The observed coexistence of MAD with arrhythmogenic cardiomyopathies and channelopathies underscores the relevance of comprehensive genetic evaluation in these patients. Conclusions: MAD should be considered a potential arrhythmogenic substrate rather than a benign anatomical variant. A multimodal diagnostic approach and individualized risk stratification—potentially integrating genetic findings—are essential for optimal patient management.

Premature ventricular contractions (PVCs) originating from the left ventricular summit (LVS) present a diagnostic and therapeutic challenge due to their complex anatomical location. The LVS includes an epicardial area of the left ventricle bordered by major coronary arteries, which has been increasingly recognized as an arrhythmic focus. Idiopathic ventricular arrhythmias from this area may exhibit specific electrocardiographic characteristics, making accurate localization essential for effective management. Methods: This narrative review explores the primary features of this arrhythmia, emphasizing key diagnostic and therapeutic aspects, including both pharmacological and interventional approaches, considering the recent technological advances in cardiac mapping and ablations. Conclusions: PVCs originating from the left ventricular summit (LVS) exhibit characteristic electrocardiographic features. Prompt recognition of this arrhythmia may facilitate appropriate referral for targeted treatment.