Michele Marchetta

Was not provided for this article.

Was not provided for this article.

Transcatheter aortic valve implantation (TAVI) elicits a sterile inflammatory response that is almost universal, yet highly heterogeneous in both magnitude and clinical impact. Initiated by endothelial injury, ischemia–reperfusion, and residual bioprosthetic immunogenicity, peri-procedural inflammation converges on activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and downstream interleukin-1β (IL-1β) and IL-6 signaling, leading to increased C-reactive protein levels. This response is further modulated by patient susceptibility, procedural complexity, and device-specific characteristics. While a controlled response promotes tissue repair and healing, exaggerated activation, which manifests as systemic inflammatory response syndrome in up to two-thirds of patients, has been consistently associated with higher mortality, conduction disturbances, new-onset atrial fibrillation, acute kidney injury (AKI), and subclinical leaflet thrombosis. Emerging evidence also implicates gut microbiome-derived metabolites and xenoantigen-driven adaptive immunity as additional contributors to the overall inflammatory burden. Serial biomarker assessment, including C-reactive protein trajectories, neutrophil-to-lymphocyte ratio, cancer antigen 125 (CA-125), and novel composite indices such as the neutrophil percentage-to-albumin ratio, combined with multimodality imaging, allows increasingly refined risk stratification. However, no anti-inflammatory therapy is currently established for routine use after TAVI. Colchicine has shown proof-of-concept signals, sodium–glucose cotransporter 2 inhibitors have demonstrated clinical benefit with pleiotropic anti-inflammatory properties, and lessons from IL-1 and IL-6 inhibition trials in ischemic heart disease provide a translational roadmap. This narrative review synthesizes the epidemiology, mechanisms, clinical consequences, and assessment of peri-TAVI inflammation. Moreover, this review proposes a pragmatic inflammatory subphenotyping framework that integrates baseline risk, procedural exposure, and biomarker kinetics. Such a framework may help bridge the gap between observational associations and precision-based therapeutic strategies, shifting peri-TAVI inflammation from a prognostic marker to a modifiable determinant of outcome.

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.

Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) are two conditions presenting as acute coronary syndromes that predominantly affect women and are frequently triggered by emotional or physical stress. While traditionally considered distinct entities, emerging evidence suggests that these conditions may coexist more frequently than previously recognized, sharing common pathophysiological mechanisms centered on catecholamine-mediated pathways, vascular vulnerability, and hormonal influences. Their overlapping presentations create significant diagnostic challenges that may lead to misdiagnosis and suboptimal management. This narrative review examines the pathophysiological convergence between SCAD and TTS, addresses the diagnostic complexity arising when these entities coexist, and proposes a novel stepwise diagnostic algorithm integrating clinical risk stratification, coronary angiography, intracoronary imaging, and cardiac magnetic resonance imaging. The review also provides scenario-dependent management guidance and outlines priorities for future research.

Background: C-reactive protein (CRP) is commonly used to assess systemic inflammation, yet its prognostic value in acute myocarditis remains uncertain. Evidence is limited by heterogeneous populations, variable CRP thresholds and differing outcome definitions. We therefore aimed to evaluate whether CRP levels measured at presentation are associated with 90-day clinical outcomes in adults hospitalised with acute myocarditis. Methods: Using the TriNetX Research Network, we identified 3615 adults hospitalised with acute myocarditis between 2005 and 2025. Patients were stratified according to baseline CRP <10 mg/L (n=1001) vs ≥10 mg/L (n=2614). Propensity score matching (1:1) was performed using age, sex and race. The primary outcome was a 90-day composite of all-cause death and tachyarrhythmias (atrial fibrillation, ventricular tachycardia, ventricular fibrillation or torsades de pointes). Secondary outcomes included the individual components. Results: In the unmatched cohort, patients with CRP <10 mg/L had a numerically higher 90-day incidence of the primary composite outcome compared with those with CRP ≥10 mg/L (16.4% vs 14.0%; log-rank p=0.087; HR 1.17, 95% CI 0.98 to 1.41), driven by a borderline higher incidence of tachyarrhythmias (14.1% vs 11.7%; log-rank p=0.059; HR 1.21, 95% CI 0.99 to 1.48), while all-cause mortality was similar between groups. After propensity score matching, the 90-day incidence of the primary composite outcome was virtually identical in the CRP <10 mg/L and CRP ≥10 mg/L groups (16.4% vs 16.9%; log-rank p=0.735; HR 0.96, 95% CI 0.78 to 1.19). Individual endpoints (tachyarrhythmias and all-cause mortality) were also similar, with no statistically significant differences. Conclusion: In this large dataset analysis, elevated baseline CRP was frequent in patients with acute myocarditis and was not consistently associated with 90-day adverse outcomes. A single CRP measurement at presentation appears to have limited value for risk stratification in this setting.

Pericarditis is the most frequent manifestation of pericardial disease and accounts for up to 5% of emergency department visits for chest pain. Although traditionally considered a benign and self-limited condition, it is a heterogeneous syndrome with a broad aetiological spectrum and potentially significant morbidity. While mortality is low, the burden of complications like recurrent disease, cardiac tamponade or constrictive pericarditis, and the frequent need for hospitalisation underscore its clinical relevance. The growing availability of multimodality imaging and the publication of updated international guidelines in 2025 have recently renewed attention to pericardial diseases, refining diagnostic criteria, risk stratification and therapeutic approaches. In high-income settings, idiopathic or presumed viral pericarditis remains the most common presentation. However, a substantial proportion of patients harbour alternative aetiologies that carry distinct prognostic implications and require tailored diagnostic and management strategies. In this review, we use the ABCDE mnemonic as a pragmatic framework to highlight five clinically important and often under-recognised forms of pericardial disease. Pericarditis associated with autoimmune and systemic inflammatory diseases is typically characterised by recurrent or refractory inflammatory courses and frequent extracardiac involvement. Bacterial pericarditis , although rare, represents a life-threatening condition requiring rapid aetiological identification and aggressive therapy. Cancer-related pericardial disease often presents with large pericardial effusions or cardiac tamponade and is associated with a poor prognosis largely determined by the underlying malignancy. Damage-related and drug-related pericarditis encompasses postcardiac injury syndromes and pharmacological toxicity. Finally, endocrine and metabolic disorders, including uraemia, hypothyroidism and infiltrative conditions such as amyloidosis, are associated with pericardial disease that manifests with atypical features and effusion. Early recognition of these entities is critical, as management extends beyond standard anti-inflammatory therapy and often requires correction of the underlying cause and close multidisciplinary collaboration. This ABCDE approach can aid clinicians in identifying these uncommon high-risk forms of pericarditis and optimising patient-centred care.

Myocarditis is an inflammatory disease of the heart muscle that can be triggered by various causes, including viruses, autoimmune response, molecular mimicry and exposure to immune-stimulating drugs or vaccines. Most cases of myocarditis heal, and cardiac dysfunction, if present, recovers; however, selected forms may require targeted therapy to improve outcomes. We herein review five conditions presenting with or mimicking myocarditis that require targeted diagnostic approaches, including endomyocardial biopsy, and/or targeted treatments. Giant cell myocarditis is an intense and unresolving inflammation of the heart, characterised by rapid progression, significant arrhythmias, heart failure and shock, that is unlikely to resolve without immunosuppression therapy. Myocarditis related to immune checkpoint inhibitors is a rare but potentially fatal adverse effect of the use of cancer immunotherapy with checkpoint inhibitors, requiring immunosuppressive therapy. Eosinophilic myocarditis can be triggered by allergy, hypersensitivity reactions, infections or can be idiopathic and is characterised by eosinophilic infiltrates in the heart and other organs, associated with thrombosis and necessitating targeted therapy. Myocarditis is a frequent cardiovascular manifestation of systemic immune-mediated inflammatory diseases such as systemic lupus erythematosus, and injury is caused by an autoimmune response in the myocardium and cytokine-mediated damage, requiring targeted therapy. Genetic pathogenic mutations in desmoplakin and other desmosomal genes can present with ‘hot phases’ mimicking myocarditis associated with an increased risk of arrhythmias, heart failure, and sudden cardiac death.