Clinical Utility of the Molecular Microscope Diagnostic System in a Real-World Transplant Cohort: Moving Towards a New Paradigm.

Objectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection. Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection. Methods: Single-center prospective study of 418 consecutive for-cause endomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels. Results: We analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017). Conclusions: In our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.

Current and Emerging Approaches for Primary Prevention of Coronary Artery Disease Using Cardiac Computed Tomography.

PURPOSE OF REVIEW: To summarize the current use of cardiac computed tomography (CT) technologies as well as their pertinent evidence in regards to prevention of coronary artery disease (CAD). RECENT FINDINGS: Cardiac CTA has now become a main non-invasive method for the evaluation of symptomatic CAD. In addition to coronary calcium score, other CT technologies such as atherosclerotic plaque analysis, fractional flow reserve estimation by CT, pericoronary fat attenuation, and endothelial wall shear stress have emerged. Whether the use of CT modalities can enhance risk prediction and prevention in CAD has not been fully answered. We discuss the evidence for coronary artery calcium scoring and coronary CT angiography in primary prevention and the current barriers to their use. We attempt to delineate what can be done to expand use and what studies are needed to broaden adoption in the future. We also examine the potential roles of emerging CT technologies. Finally, we describe potential clinical approaches to prevention that would incorporate cardiac CT technologies.

Pericardiectomy and Pericardial Window for the Treatment of Pericardial Disease in the Contemporary Era.

PURPOSE OF REVIEW: To summarize the contemporary practice of pericardiectomy and pericardial window. We discuss the indications, preoperative planning, procedural aspects, postprocedural management, and outcomes of each procedure. RECENT FINDINGS: Surgical approaches for the treatment of pericardial disease have been around even before the emergence of cardiopulmonary bypass. Since the forthcoming of cardiopulmonary bypass, there have been significant changes in the epidemiology and diagnostic approach of pericardial diseases as well as advancements in the surgical techniques and perioperative management used in the care of these patients. Pericardiectomy has an average mortality of almost 7% and is typically performed in patients with advanced symptoms from constrictive pericarditis and relatively few comorbidities. Pericardial window is a safe procedure for the treatment of pericardial effusion that can be performed with different approaches.