Immune checkpoint molecules like cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1), play a critical role in regulating the immune response, and immune checkpoint inhibitors (ICIs) targeting these checkpoints have shown clinical efficacy in cancer treatment; however, their use is associated with immune-related adverse events (irAEs), including cardiac complications. The prevalence of cardiac irAEs, particularly myocarditis, is relatively low, but they can become a severe and potentially life-threatening condition, usually occurring shortly after initiating ICI treatment; moreover, diagnosing ICI-related myocarditis can be challenging. Diagnostic tools include serum cardiac biomarkers, electrocardiography (ECG), echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB). The treatment of ICI-induced myocarditis involves high-dose corticosteroids, which have been shown to reduce the risk of major adverse cardiac events (MACE). In refractory cases, second-line immunosuppressive drugs may be considered, although their effectiveness is based on limited data. The mortality rates of ICI-induced myocarditis, particularly in severe cases, are high (38–46%). Therapy rechallenge after myocarditis is associated with a risk of recurrence and severe complications. The decision to rechallenge should be made on a case-by-case basis, involving a multidisciplinary team of cardiologists and oncologists. Further research and guidance are needed to optimize the management of cancer patients who have experienced such complications, evaluating the risks and benefits of therapy rechallenge. The purpose of this review is to summarize the available evidence on cardiovascular complications from ICI therapy, with a particular focus on myocarditis and, specifically, the rechallenge of immunotherapy after a cardiac adverse event.

Thalassemia is an inherited blood disorder with worldwide distribution. Transfusion and chelation therapy have radically improved the prognosis of β-thalassemic patients in the developed world, but this has led to the development of new chronic cardiac complications like atrial fibrillation (AF). Prevalence of AF in patients with β-thalassemia is higher than in the general population, ranging from 2 to 33%. Studies are lacking, and the little evidence available comes from a small number of observational studies. The pathophysiology is not well understood but, while iron overload seems to be the principal mechanism, AF could develop even in the absence of iron deposition. Furthermore, the clinical presentation is mainly paroxysmal, and patients are highly symptomatic. The underlying disease, the pathophysiology, and the clinical presentation require a different management of AF in β-thalassemia than in the general population. Rhythm control should be preferred over rate control, and the most important antiarrhythmic therapy is represented by chelation drugs. Thromboembolic risk is high, but the available risk scores are not validated in β-thalassemia, and the choice of anticoagulation therapy should be considered early. The main purpose of this review is to summarize the actual knowledge about AF in β-thalassemia, with a specific focus on the clinical management of these complex patients.

This study compiles data to determine if procalcitonin (PCT) values may predict both the risk of bacterial infection and potentially negative long-term outcomes in patients with acute coronary syndromes (ACS). All patients with a diagnosis of ACS that had PCT levels assessed during the first 24 h of hospitalization were enrolled in this study. The primary outcome was to detect the presence of bacterial infection defined as the occurrence of fever and at least one positive blood or urinary culture with clinical signs of infection. The secondary outcome was to monitor the occurrence after 1 year of the composite outcome of all-cause mortality, stroke and myocardial infarction. Overall, 569 patients were enrolled (mean age 69.37 ± 14 years, 30% females). Of these, 44 (8%) met the criteria for bacterial infection. After multivariate analysis, PCT and SBP were found to be independent predictors of bacterial infections (OR for PCT above the cut-off 2.67, 95% CI 1.09–6.53, p = 0.032 and OR for SBP 0.98, 95% CI 0.97–0.99, p = 0.043). After 1 year, the composite outcome of all-cause death, MI and stroke occurred in 104 patients (18%). PCT was not found to be an independent predictor of these outcomes. In conclusion, when assessing ACS, we found that testing for PCT levels during hospital admissions procedures was a good predictor of bacterial infections but not of all-cause mortality, stroke, or myocardial infarction. Clinicaltrial.org identifier: NCT02438085.

Aims: The aim of this study is to investigate the prognostic role of T1 mapping techniques in predicting major adverse cardiovascular events (MACE) in patients affected by non-ischaemic dilated cardiomyopathy (NIDCM) by performing a meta-analysis of available studies. Methods and results: Data from 12 observational studies exploring the prognostic role of native T1 mapping and extracellular volume (ECV) were analysed with random effect generic inverse variance. The primary endpoint was MACE defined as a composite of heart failure or arrhythmic-related events, expressed as hazard ratio (HR) with 95% confidence interval (CI). Secondary main outcomes were heart failure-related events, arrhythmic-related events, and weighted mean difference of native T1 mapping values or ECVs between patients with or without MACE. Overall, 4025 patients with NIDCM were included. The median follow-up length was 22 (IQR 14–22) months. The primary outcome of MACE occurred in 610 patients with a pooled HR for native T1 mapping values of 1.07 (95% CI 1.04–1.09, I2 31.5%) and a pooled HR for ECV of 1.37 (95% CI 1.29–1.44, I2 0%). HF-related events occurred in 492 patients, with a pooled HR for T1 mapping of 1.05 (95% CI 1.03–1.07, I2 1%) and a pooled HR for ECVs of 1.43 (95% CI 1.25–1.61, I2 63%). Arrhythmic-related events occurred in 118 patients, with a pooled HR for T1 mapping values of 1.09 (95% CI 1.07–1.12, I2 0%). The weighted mean difference of native T1 mapping between patients with and without MACE was 30.91 (95% CI 18.45–43.16, I2 16.72%), while the mean difference of ECV was 4.52 (95% CI 2.78–6.26, I2 86%). Conclusions: In NIDCM patients, native T1 mapping and ECV were associated with increased risk of the composite primary endpoint of MACE and the secondary endpoint of heart failure and arrhythmic-related events.

Severe aortic stenosis represents a significant prognostic burden, particularly in symptomatic patients. The advent of transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of patients previously considered ineligible for surgical aortic valve replacement (SAVR). TAVR provides a relatively safe intervention that leads to improvements in survival, symptoms, and functional status within months of implantation. A major complication following TAVR is the occurrence of paravalvular leaks (PVLs), which have been associated with increased mortality and higher rates of heart failure-related hospitalizations. PVLs refer to abnormal blood flow between the implanted valve and the aortic wall, which can compromise the functionality of the device. Careful pre-procedural planning enables the identification of patients at higher risk for PVL development. Although the incidence of PVLs has decreased with the introduction of newer-generation transcatheter valves, the condition remains clinically relevant. Due to the complex anatomy of the aortic valve apparatus and interference from the prosthetic frame, accurate evaluation of PVLs requires a multimodal diagnostic approach. Current evidence on PVL management is limited. In most cases, a conservative approach is adopted, while interventional strategies (such as pre- and post-dilatation, percutaneous PVL closure, and TAVR-in-TAVR) are reserved for selected patients. We performed a systematic literature review to summarize the incidence, predictors, diagnostic techniques, and management strategies of PVLs following TAVR.