When, Why and How to Re-challenge Clozapine in Schizophrenia Following Myocarditis.

Clozapine-induced myocarditis (CIM) is among the most important adverse events limiting the use of clozapine as the most effective treatment for schizophrenia. CIM necessitates the immediate termination of clozapine, often resulting in its permanent discontinuation with considerable detrimental effects on patients' psychopathology and long-term outcome. Consequently, a clozapine re-challenge after CIM is increasingly regarded as a viable alternative, with published reports indicating a success rate of approximately 60%. However, published cases of re-challenges after CIM remain limited. Here, we provide a narrative review of the current state of research regarding the epidemiology, pathophysiology, risk factors, diagnosis and clinical management of CIM as well as a synthesis of current recommendations for re-challenging patients after CIM. This includes a step-by-step guide for this crucial procedure based on the current evidence regarding the pathophysiology and risk factors for CIM. Slow dose titration regimes and addressing risk factors including concomitant valproate and olanzapine are crucial both to prevent CIM and to ensure a safe and successful re-challenge. Furthermore, we discuss the utility of C-reactive protein, troponin, N-terminal-pro hormone and brain natriuretic peptide, therapeutic drug-monitoring and cardiac magnetic resonance imaging for CIM screening and diagnosis as well as for post-CIM re-challenges.

Coronary Artery Disease Assessment via On-Site CT Fractional Flow Reserve in Patients Undergoing Transcatheter Aortic Valve Replacement.

Purpose To examine the clinical feasibility of workstation-based CT fractional flow reserve (CT-FFR) for coronary artery disease (CAD) evaluation during preprocedural planning in patients undergoing transcatheter aortic valve replacement (TAVR). Materials and Methods In this retrospective single-center study, 434 patients scheduled for TAVR between 2018 and 2020 were screened for study inclusion; a relevant proportion of patients (35.0% [152 of 434]) was not suitable for evaluation due to insufficient imaging properties. A total of 112 patients (mean age, 82.1 years ± 6.7 [SD]; 58 [52%] men) were included in the study. Invasive angiography findings, coronary CT angiography results, and Agatston score were acquired and compared with on-site CT-FFR computation for evaluation of CAD and prediction of major adverse cardiovascular events (MACE) within a 24-month follow-up. Results Hemodynamic relevant CAD, as suggested by CT-FFR of 0.80 or less, was found in 41 of 70 (59%) patients with stenosis of 50% or more. MACE occurred in 23 of 112 (20.5%) patients, from which 14 of 23 had stenoses with CT-FFR of 0.80 or less (hazard ratio [HR], 3.33; 95% CI: 1.56, 7.10; P = .002). CT-FFR remained a significant predictor of MACE after inclusion in a multivariable model with relevant covariables (HR, 2.89; 95% CI: 1.22, 6.86; P = .02). An Agatston score of 1000 Agatston units or more (HR, 2.25; 95% CI: 0.98, 5.21; P = .06) and stenoses of 50% or more determined via invasive angiography (HR, 0.94; 95% CI: 0.41, 2.17; P = .88) were not significant predictors of MACE. Conclusion Compared with conventional CAD markers, CT-FFR better predicted adverse outcomes after TAVR. A relevant portion of the screened cohort, however, was not suitable for CT-based CAD evaluation. Keywords: CT, Transcatheter Aortic Valve Implantation/Replacement (TAVI/TAVR), Cardiac, Coronary Arteries, Outcomes Analysis © RSNA, 2024 See also the commentary by Weir-McCall and Pugliese in this issue.

DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts.

Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A), play a pivotal role in driving clonal hematopoiesis of indeterminate potential (CHIP), and are associated with unfavorable outcomes in patients suffering from heart failure (HF). However, the precise interactions between CHIP-mutated cells and other cardiac cell types remain unknown. Here, we identify fibroblasts as potential partners in interactions with CHIP-mutated monocytes. We used combined transcriptomic data derived from peripheral blood mononuclear cells of HF patients, both with and without CHIP, and cardiac tissue. We demonstrate that inactivation of DNMT3A in macrophages intensifies interactions with cardiac fibroblasts and increases cardiac fibrosis. DNMT3A inactivation amplifies the release of heparin-binding epidermal growth factor-like growth factor, thereby facilitating activation of cardiac fibroblasts. These findings identify a potential pathway of DNMT3A CHIP-driver mutations to the initiation and progression of HF and may also provide a compelling basis for the development of innovative anti-fibrotic strategies.

Resonancia magnética cardiovascular en la práctica cardiológica: una guía concisa para la adquisición de imágenes y la interpretación clínica / Cardiovascular Magnetic Resonance in Cardiology Practice: A Concise Guide to Image Acquisition and Clinical Interpretation

La resonancia magnética cardiovascular está adquiriendo un papel cada vez más relevante en la práctica clínica habitual en cardiología. Se trata de una modalidad de diagnóstico por imagen versátil que permite una evaluación exacta, amplia y profunda de la función y la estructura cardiacas y que aporta información sobre cuestiones clínicas relevantes, en enfermedades como la cardiopatía isquémica, las miocardiopatías no isquémicas y la insuficiencia cardiaca, a la vez que permite indicaciones especiales, como la evaluación y/o cuantificación de la sobrecarga de hierro o la infiltración miocárdica. La creciente evidencia que respalda el papel de la resonancia magnética cardiovascular, junto con la difusión del conocimiento y la pericia en su uso fuera de los centros expertos, ha permitido un mayor acceso de los pacientes a esta técnica y la obtención de una experiencia clínica más amplia. En esta revisión se refleja la situación de la resonancia magnética cardiovascular en la práctica clínica moderna relacionando la adquisición y el posprocesado de las imágenes con una descripción efectiva de su significado clínico (AU)

Cardiovascular magnetic resonance plays an increasingly important role in routine cardiology clinical practice. It is a versatile imaging modality that allows highly accurate, broad and in-depth assessment of cardiac function and structure and provides information on pertinent clinical questions in diseases such as ischemic heart disease, nonischemic cardiomyopathies, and heart failure, as well as allowing unique indications, such as the assessment and quantification of myocardial iron overload or infiltration. Increasing evidence for the role of cardiovascular magnetic resonance, together with the spread of knowledge and skill outside expert centers, has afforded greater access for patients and wider clinical experience. This review provides a snapshot of cardiovascular magnetic resonance in modern clinical practice by linking image acquisition and postprocessing with effective delivery of the clinical meaning (AU)