Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particularly vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a difficult outcome to target, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD; however, the optimal intensity of such therapy is still a topic of debate, particularly in the post-acute and long-term setting. Recent well-powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and selection of patients is a key issue. The aim of this review is, therefore, to discuss and summarize the most up-to-date available evidence for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both types of atherosclerotic disease and comparing a higher- versus a lower-intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improve precision medicine.

Cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy in which extracellular amyloid deposition leads to progressive structural and functional impairment. Beyond myocardial infiltration, growing evidence highlights the central role of autonomic nervous system dysfunction (ANS) —particularly the vagal nerve involvement—as a contributor to orthostatic intolerance, syncope, exercise limitation, arrhythmias, and reduced quality of life. Emerging data suggest that autonomic impairment may precede overt cardiac manifestations, offering a potential window for earlier recognition. This narrative review summarizes current knowledge on the mechanisms and clinical relevance of autonomic dysfunction in CA, emphasizing the novelty of the “vagal link” as a unifying framework connecting with a specific focus on the vagus nerve (VN) and its complex interplay with cardiac structure and function. We further discuss diagnostic approaches and the potential role of autonomic assessment in early detection, risk stratification, and personalized treatment strategies. A clearer understanding of vagal dysfunction may provide new insights into disease progression and identify opportunities for therapeutic innovation.

Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particular vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a hard outcome to be targeted, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD however, the optimal intensity of such therapy is still topic of debate, particularly in the post-acute and long-term setting. Recent well powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and patients selection is a key issue. The aim of this review is therefore to discuss and summarize the most updated available evidences for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both type of atherosclerotic disease and comparing a higher versus a lower intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improving precision medicine.

Arrhythmogenic cardiomyopathy (ACM; MIM #107970) is a primitive heart muscle disease characterized by progressive myocardial loss and fibrosis or fibrofatty replacement, predisposing patients to ventricular arrhythmias, sudden cardiac death, and heart failure. Despite advances in imaging and genetics, early diagnosis remains challenging due to incomplete penetrance, variable phenotypic expressivity, and the fact that fatal arrhythmic events may often occur in the early stages of the disease. In this context, the identification of reliable biomarkers could enhance diagnostic accuracy, support risk stratification, and guide clinical management. This narrative review examines the current landscape of potential and emerging biomarkers in ACM, including troponins, natriuretic peptides, inflammatory proteins, microRNAs, fibrosis-related markers, and other molecules. Several of these biomarkers have demonstrated associations with disease severity, arrhythmic burden, or structural progression, although their routine clinical utility remains limited. The increasing relevance of genetic testing and non-invasive tissue characterization—particularly through cardiac imaging techniques—should also be emphasized as part of a multimodal diagnostic strategy in which biomarkers may play a complementary role. Although no single biomarker currently meets the criteria for a standalone diagnostic application, ongoing research into multi-marker panels and novel molecular targets offers promising perspectives. In conclusion, the integration of circulating biomarkers with imaging findings, genetic data, and clinical parameters may open new avenues for improving early detection and supporting personalized therapeutic strategies in patients with suspected ACM.

Background: While it's has already been demonstrated that cardiovascular mortality increases in patients with reduced ejection fraction (EF), there is no evidence that this parameter identifies with high sensitivity those who will experience sudden cardiac death (SCD). Cardiac magnetic resonance (CMR), through myocardial scar characterization, could enhance risk stratification for arrhythmic events in such patients. Purpose: The study's objective was to identify factors, independent of EF, capable of stratifying arrhythmic risk in a population of patients undergoing implantable cardioverter-defibrillator (ICD) placement. Methods: This is an observational, retrospective, longitudinal, cohort study. Demographic, clinical, and radiological data were collected for all patients undergoing ICD implantation between 2014 and 2021. Deaths from all causes and significant arrhythmic events (non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation) were recorded during routine device controls and remote monitoring. To define the prognostic value of various factors was performed an univariate Kaplan-Meier analysis in relation to the composite primary endpoint, consisting of ventricular arrhythmias [VA] and all-cause mortality. Results: Among 700 patients (82% males, mean age 69 ± 13 years) who underwent ICD implantation (46% single-chamber, 15% dual-chamber, 36% cardiac resynchronization therapy, 3% subcutaneous ICD) pre-implantation CMR was available in 354 of the total, with 69% of them implanted for primary prevention and 52% with non-ischemic cardiomyopathy. Late gadolinium enhancement (LGE) was present in 67% of them; and 30% of these patients had it in fewer than 5 segments. At the end of the mean 8-year follow-up, 30.6% of patients died. Patients with LGE showed increased all-cause mortality and incidence of VA compared to those without LGE (HR=2.17 [1.78-2.60]; p<0.05); this data was mainly driven by the difference in mortality, as the incidence of VA alone did not exhibit significant variation between the two groups (HR=0.7 [0.65-1.02]; p=0.23). In patients with fewer than 5 cardiac segments involved by LGE, the risk of all-cause death and significant VA was higher than in those with more than 5 segments involved (HR=2.46 [2.09-9.07]; p<0.05). Conclusions: The presence of LGE emerged as a significant prognostic factor for both arrhythmic events and overall mortality. This suggests the possibility that assessing myocardial fibrosis serves as a comprehensive predictor of the patient's future clinical outcome, extending beyond merely predicting arrhythmic events. Notably, the relevance of LGE is heightened when observed in fewer than 5 segments, indicating a focal substrate, making it a crucial prognostic factor for anticipating arrhythmic events. In patients with reduced EF, pre-implantation CMR proves valuable in effectively stratifying arrhythmic risk and all-cause mortality.

Background: The implantation of defibrillators (ICDs) in patients over 80 years old is becoming increasingly common; however, evidence-based data regarding the actual clinical benefit in this population remain limited and contradictory. While age seems not to affect mortality and arrhythmia risk in octogenarians undergoing secondary prevention, the mortality reduction benefit given by ICD implantation for primary prevention appears to decrease with advancing age, likely due to the high number of non-arrhythmic deaths. Purpose: This study aims to assess the long-term incidence of ventricular arrhythmias and mortality in a real-world cohort of octogenarian patients undergoing ICD implants. Methods: This was an observational, retrospective, longitudinal cohort study. Demographic, clinical, and radiological data were collected for all patients undergoing ICD implantation between 2014 and 2021. Deaths from all causes and significant arrhythmic events (sustained ventricular tachycardias and ventricular fibrillation) detected during routine device controls and remote monitoring were recorded. Then was performed an univariate Kaplan-Meier analysis, stratifying the population by age in relation to the two study endpoints: ventricular arrhythmias and all-cause mortality. Results: Out of a total of 700 patients, 512 underwent ICD implantation before the age of 80 (mean age at implantation 64±12), while 188 underwent ICD implantation after the age of 80 (mean age at implantation 82±3.2). No significant differences were found between these two groups in terms of gender (82% vs. 83% male; p 0.12), indication for implantation (74% vs. 75% primary prevention; p 0.79), and the presence of late gadolinium enhancement (LGE) on cardiac MRI (68% vs. 77%; p 0.14). Octogenarians were more frequently affected by ischemic heart disease (54% vs. 65%; p 0.01) and were more frequently treated with Amiodarone (17% vs. 24%; p 0.02). At the end of the average 8-year follow-up, octogenarians had significantly higher all-cause mortality than younger patients (HR=2.35 [1.88-3.16]; p<0.05), with survival curves diverging from 3 years after implantation. However, ventricular arrhythmic events were significantly reduced in octogenarian patients (HR=0.88 [0.87-0.89]; p<0.05). Conclusions: In a real-world population of octogenarian patients, the clinical benefit of ICD implantation for primary prevention appears diminished, considering the trade-off between ventricular arrhythmias and mortality, in both ischemic and non-ischemic cardiomyopathy patients.