Nicola Potere

The rapid development of novel cancer therapies has considerably improved the care of cancer patients and cancer-related survival; however, these therapies are associated with a broad range of adverse events that have become a major burden in this population. Alongside other cancer-related factors, vascular toxicity from anticancer therapies contributes to an increased risk of venous thromboembolism. Among anticancer drugs, chemotherapeutic agents (eg, anthracyclines, platinum-based drugs, antimetabolites), hormonal therapies (eg, selective estrogen receptor modulators), agents used for multiple myeloma (including immunomodulatory drugs and proteasome inhibitors), asparaginase, as well as targeted inhibitors to immune checkpoints, vascular endothelial growth factor, epidermal growth factor receptor, tyrosine kinases, cyclin-dependent kinases, and poly(ADP-ribose) polymerase are primarily associated with increased risk of venous thromboembolism. Vascular adverse events associated with anticancer drugs are frequently underestimated, and significant gaps remain in the risk stratification, prevention, and management of thromboembolic events in patients receiving systemic anticancer therapies. This review examines the evidence linking anticancer drug exposure to the incidence of venous thromboembolism, summarizes the key underlying pathobiological mechanisms, and highlights current guideline recommendations for the prevention and treatment of cancer-associated thrombosis. Arterial thrombotic events are also discussed where clinically or mechanistically relevant. This review also offers advanced cardio-oncology perspectives on the identification, risk stratification, and therapeutic targeting of drug-induced vascular toxicity.

Background: Acute myocarditis is an inflammatory disease of the myocardium with an annual incidence of 4–14 per 100,000 individuals, predominantly affecting young adults. Its clinical features are frequently nonspecific, mimicking acute coronary syndrome, which makes early recognition and management challenging. The disease results from infectious (predominantly viral) and noninfectious triggers, including autoimmune disorders, immune checkpoint inhibitors and mRNA vaccines. Pathophysiology involves a dysregulated interplay between innate immunity and adaptive immunity. Clinical Features and Diagnosis: Presentation is typically dominated by chest pain, with dyspnea and syncope reported less frequently. Cardiac magnetic resonance (CMR), with the 2018 updated Lake Louise criteria, has become the cornerstone of noninvasive diagnosis, whereas endomyocardial biopsy (EMB), in experienced centres, remains the gold standard for histological characterization and guiding immunosuppressive therapy. Outcomes and Management: Uncomplicated myocarditis usually resolves spontaneously. However, approximately 25% of patients with myocarditis have left ventricular systolic dysfunction, ventricular arrhythmias or acute heart failure. Mortality ranges from 1% to 7%, depending on presentation, aetiology and specific populations. Treatment centers on guideline‐directed heart failure therapy, with immunosuppression reserved for complicated presentations and virus‐negative, autoimmune or histologically specific subtypes. Mechanical circulatory support is critical in fulminant cases, where mortality is high. Conclusions: This clinical review synthesizes recent guideline updates and emerging trial data, primarily from literature published in the past 10 years, to support a phenotype‐driven approach to acute myocarditis, in which management is guided by clinical severity, suspected aetiology, selective use of CMR and EMB and targeted therapy. Ongoing trials investigating corticosteroids, targeted biologics and novel therapies may further refine personalized immunomodulatory strategies.

Duplex ultrasonography is the preferred non-invasive imaging technique for diagnosing lower extremity deep vein thrombosis (DVT), but considered largely unreliable for determining thrombus-specific features. Elastosonography techniques including real-time strain elastography (RT-SE) are widely used in clinical practice to assess tissue elasticity, but its potential remains largely unrealized in DVT, where RT-SE might provide adjunct information on thrombus biomechanical properties potentially aiding clinical decision-making. This single-center prospective pilot study investigates the use of modern RT-SE imaging enhanced with an advanced quantification software for reconstructive tissue elasticity analysis in patients with symptomatic acute lower-extremity DVT objectively diagnosed within 6 months of enrollment. Between-group differences in median thrombus elasticity, assessed via a newly proposed elasticity biomarker, namely thrombus tissue deformation index, were evaluated using Mann–Whitney U or Kruskal–Wallis tests. Relationships between thrombus elasticity and patient-, DVT- and anticoagulation-related factors were assessed through Spearman’s rank-order correlation. Thirty-eight deep venous thrombi were analyzed using advanced RT-SE, in addition to standard duplex ultrasonography (i.e., triplex ultrasonography). Median thrombus elasticity was 25.7% (interquartile range [IQR], 22.1–26.1), 20.8% (IQR, 17.1–22.1), and 3.8% (IQR, 1.3–6.6) in acute, sub-acute, and chronic DVT, respectively ( p < 0.001). Thrombus elasticity robustly correlated with the period of DVT diagnosis (i.e., lower elasticity with increasing thrombus chronological age; ρ = −0.70, p < 0.0001). Elasticity of chronic thrombi inversely correlated with dynamic changes in residual vein obstruction (i.e., higher elasticity of thrombi undergoing smaller size reduction over time; ρ = 0.85, p < 0.0001). These findings preliminarily identify modern advanced RT-SE imaging as a viable and easily-implementable tool for enhanced non-invasive thrombus characterization, with the potential to inform thrombus-guided management strategies in patients with DVT. Graphical Abstract Framework for thrombus elasticity assessment via advanced real-time strain elastography, and potential clinical usefulness of enhanced non-invasive DVT characterization.

Cardiovascular disease (CVD) remains a major health burden despite significant therapeutic advances accomplished over the last decades. It is widely and increasingly recognized that systemic inflammation not only represents a major cardiovascular risk and prognostic factor but also plays key pathogenic roles in CVD development and progression. Despite compelling preclinical evidence suggesting large potential of anti-inflammatory pharmacological interventions across numerous CVDs, clinical translation remains incomplete, mainly due to (1) yet undefined molecular signaling; (2) challenges of safety and efficacy profile of anti-inflammatory drugs; and (3) difficulties in identifying optimal patient candidates and responders to anti-inflammatory therapeutics, as well as optimal therapeutic windows. Randomized controlled trials demonstrated the safety/efficacy of canakinumab and colchicine in secondary cardiovascular prevention, providing confirmation for the involvement of a specific inflammatory pathway (NLRP3 [NACHT, LRR, and PYD domain-containing protein 3] inflammasome/IL [interleukin]-1β) in atherosclerotic CVD. Colchicine was recently approved by the US Food and Drug Administration for this indication. Diverse anti-inflammatory drugs targeting distinct inflammatory pathways are widely used for the management of other CVDs including myocarditis and pericarditis. Ongoing research efforts are directed to implementing anti-inflammatory therapeutic strategies across a growing number of CVDs, through repurposing of available anti-inflammatory drugs and development of novel anti-inflammatory compounds, which are herein concisely discussed. This review also summarizes the main characteristics and findings of completed and upcoming randomized controlled trials directly targeting inflammation in CVDs, and discusses major challenges and future perspectives in the exciting and constantly expanding landscape of cardioimmunology.

Venous thromboembolism (VTE) is a relatively common complication in cancer patients with potentially dire consequences. Anticoagulants are the mainstay of treatment of cancer-associated VTE. The anticoagulants most often used are low-molecular-weight heparin (LMWH) and direct oral factor (F) Xa inhibitors, which include apixaban, edoxaban, and rivaroxaban. Most guidelines recommend primary VTE prophylaxis with LMWH, apixaban, or rivaroxaban after abdominal or pelvic cancer surgery, or in high-risk ambulatory cancer patients. Both oral FXa inhibitors and LMWH have limitations. LMWH requires daily subcutaneous injections, and because of its renal clearance, its use may be problematic in patients with severe kidney disease. The risk of bleeding with oral FXa inhibitors may be higher than with LMWH in patients with intraluminal gastrointestinal or genitourinary cancers. Other problems with oral FXa inhibitors include potential drug-drug interactions and dosing issues in patients with thrombocytopenia or severe kidney or liver disease. Therefore, there remains a need for convenient and safer anticoagulants for VTE treatment in cancer patients. FXI has emerged as a potentially safer target for anticoagulants than FXa because FXI is essential for thrombosis, but mostly dispensable for hemostasis. This review summarizes the currently available therapeutic options for cancer-associated VTE, highlights knowledge gaps, and discusses the potential of FXI inhibitors to address key unmet clinical needs in this vulnerable patient population.

Not applicable (no abstract required for this article type) Received: 28 November 2023 Accepted after revision: 18 January 2024 Accepted Manuscript online: 19 January 2024 © . Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany