Federico Breviario

Bruton tyrosine kinase inhibitors have transformed the management of chronic lymphocytic leukemia and other B-cell malignancies, but their clinical use is increasingly influenced by cardiovascular safety. In contemporary practice, patients receiving these therapies are typically older and characterized by a high burden of comorbidities, including cardiovascular disease, metabolic disorders, and renal impairment. In this setting, cardiovascular complications should not be interpreted as isolated adverse events, but rather as clinical expressions of underlying patient vulnerability and frailty. Atrial fibrillation and arterial hypertension represent the most frequent complications, while heart failure, ventricular arrhythmias, and bleeding, although less common, may carry significant prognostic implications. Importantly, these events often arise from the interaction between drug exposure and pre-existing comorbidities, and may lead to treatment interruption, dose reduction, or discontinuation, ultimately compromising the long-term benefit of otherwise highly effective therapies. This review provides a comprehensive overview of the clinical burden, mechanisms, and management of cardiovascular complications associated with these agents, and proposes a practical, patient-centered framework to guide clinical decision-making. A structured approach based on risk assessment, early detection, and proactive management is essential to prevent complications, optimize treatment continuity, and preserve the long-term benefit of therapy in a complex and vulnerable population.

Erdheim–Chester Disease (ECD) constitutes a rare and clinically heterogeneous non-Langerhans cell histiocytosis, characterized by the systemic infiltration of tissues by foamy, lipid-laden histiocytes. These cells typically exhibit an immunophenotypic profile positive for CD68 and negative for CD1a. The disease’s multifaceted presentation, which can span from isolated bone lesions to fulminant multi-organ failure, frequently results in considerable diagnostic delay. In this case-based review, we describe the case of a 58-year-old who presented with a primary complaint of exertional dyspnoea and fatigue. The initial diagnostic evaluation revealed a hemodynamically significant circumferential pericardial effusion and imaging findings suggestive of aortitis. Clinical presentation of ECD depends on the organs and tissues involved, and may range from bone pain to neurological symptoms, endocrine dysfunction, and cardiac involvement. Cardiovascular involvement occurs in at least 40% of ECD patients, although it is frequently underdiagnosed. Cardiac ECD is heterogeneous and may mimic many alternative aetiologies. The infiltration of the right atrioventricular sulcus, right atrial walls, or interatrial septum is one of the most typical cardiac manifestations of ECD. Recognition of pseudo-tumour intra-atrial mass, pericardial involvement, as well as the circumferential encasement of the entire aorta, the so-called coated aorta, are other frequent findings. Diagnosis often requires a multimodal approach, in particular when cardiac symptoms represent the onset of clinical manifestation of ECD. The combined use of computed tomography, fluorodeoxyglucose positron emission tomography, dedicated cardiac and abdominal magnetic resonance imaging, and X-ray of long bones can collectively reveal a constellation of findings diagnostic of ECD.

Background: Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome that represents an increasing global health challenge due to its high rates of morbidity, hospitalization, and mortality. In this context, cardiopulmonary exercise testing (CPET) has emerged as a valuable diagnostic modality, particularly in patients presenting with unexplained exertional dyspnea and inconclusive resting imaging results. Objectives and Clinical Implications: This narrative review examines current evidence on the clinical relevance and prognostic value of CPET parameters in HFpEF. Peak VO₂, a marker of aerobic capacity and cardiovascular fitness, has established prognostic value in heart failure with reduced ejection fraction (HFrEF). However, its prognostic significance in HFpEF remains less well defined. Oxygen pulse has emerged as another important measure for evaluating functional capacity and predicting response to exercise-based interventions, offering potential prognostic insight into adverse outcomes in HFpEF. Finally, the VE/VCO₂ slope, an index of ventilatory efficiency during exercise, also holds clinical relevance in HFpEF, particularly with concomitant pulmonary hypertension, though evidence remains heterogeneous. Conclusions: CPET-derived variables are valuable parameters for HFpEF assessment. Their systematic integration into clinical evaluation of HFpEF patients could guide individualized management strategies and inform clinicians for improving outcomes in this challenging condition.

Heart failure represents a complex clinical syndrome characterized by progressive ventricular dysfunction, systemic congestion, and high mortality despite significant advances in pharmacological and device-based therapy. This review explores recent developments across the heart failure continuum, with a focus on therapeutic advances across the continuum of care, with emphasis on both established and emerging strategies. In patients with reduced ejection fraction, early initiation of the four pillars markedly lowers cardiovascular events, yet real-world implementation remains limited by therapeutic inertia and underdosing. Novel agents such as finerenone provide cardiorenal benefits in patients with diabetes and chronic kidney disease, while glucagon-like peptide-1 receptor agonists show promise in preserved or mildly reduced ejection fraction, particularly with obesity. Tricuspid regurgitation, once considered a secondary phenomenon, is now recognized as a modifiable contributor to disease progression, with transcatheter interventions offering new therapeutic avenues. In advanced disease, innovations including donation after circulatory death and the development of total artificial heart systems offer promising solutions to overcome organ shortages and improve access to transplantation. Together, these advances highlight a shift toward precision-guided, multidisciplinary heart failure care.