Mohamed, Mohamed Reyad

Background: Heart transplantation (HT) remains the definitive therapy for end-stage heart failure, yet rejection and cardiac allograft vasculopathy (CAV) continue to limit long-term outcomes. Beyond donor-specific HLA antibodies, non-HLA antibodies, particularly anti-angiotensin II type 1 receptor antibodies (AT1R-Abs), have been implicated in allograft injury, but published findings are heterogeneous. Aim: The aim of this study is to systematically evaluate the evidence linking AT1R gene expression and anti-AT1R antibodies with key post-heart transplant outcomes. Methods: We conducted a systematic review in accordance with PRISMA guidelines. Scopus, PubMed, Web of Science, and the Cochrane Library were searched (December 2025) for cohort and case–control studies evaluating AT1R gene expression and/or AT1R-Ab status in HT recipients and their association with post-transplant outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the NIH Quality Assessment Tool. Results: Twelve studies encompassing 951 recipients met the inclusion criteria. Five studies evaluated AT1R mRNA expression, reporting variable patterns: several observed reduced AT1R/AT2R transcription after transplantation without clear clinical correlation, whereas others associated higher donor or recipient AT1R expression with transplant coronary artery disease and recurrent rejection. AT1R-Ab prevalence varied widely and appeared to increase after mechanical circulatory support, with substantial seroconversion reported during LVAD support in initially antibody-negative patients. Associations between AT1R-Ab and acute cellular rejection and antibody-mediated rejection were inconsistent across studies, and survival findings were inconclusive; however, some reports linked elevated AT1R-Abs to poorer long-term freedom from adverse events. Evidence regarding CAV was mixed, with signals of increased vasculopathy risk in some cohorts but not others. Conclusions: Current evidence suggests a potential role for AT1R expression and AT1R-Abs in cardiac allograft dysfunction, including rejection phenotypes and vasculopathy. Larger prospective studies with harmonized testing strategies are needed to define clinically meaningful AT1R-Ab cutoffs and clarify their utility in risk stratification and targeted therapeutic trials.

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality. Accurate diagnosis of ischemia-causing coronary stenoses is essential for guiding revascularization and improving outcomes. Although invasive fractional flow reserve (FFR) remains the gold standard for functional lesion assessment, its use is limited by procedural invasiveness, cost, and complexity. CT-derived FFR (FFRct), based on computational fluid dynamics (CFD), was the first major advance in noninvasive physiological assessment, but its adoption has been hindered by intensive off-site computation and dependence on high-quality imaging. This review summarizes the evolution from invasive FFR to AI-driven functional assessment of coronary lesions. We examine the principles and validation of CFD-based FFRct and then focus on the shift toward artificial intelligence, including both machine learning (ML) and deep learning (DL) approaches. These methods range from models using engineered geometric and plaque features trained on large synthetic datasets to end-to-end systems that learn directly from imaging data. We discuss key validation studies evaluating diagnostic accuracy, prognostic value, and clinical utility, with attention to performance in challenging settings such as intermediate stenoses, heavy calcification, and patients with comorbidities. We also highlight major barriers to widespread adoption, including dependence on input data quality, limited explainability, regulatory hurdles, and integration into clinical workflows. Finally, we outline future directions, including AI-enabled virtual PCI planning, multimodal risk stratification, and broader access to functional cardiac assessment. AI has the potential to transform noninvasive coronary imaging by enabling a single CCTA scan to provide rapid, integrated evaluation of anatomy, plaque characteristics, and physiological significance, supporting more personalized care and better clinical outcomes.

Background/Objectives: Esaxerenone, a novel non-steroidal mineralocorticoid receptor antagonist, has shown promising results in the treatment of essential hypertension (HTN). This study aims to comprehensively analyze the effectiveness of esaxerenone to control BP in patients with essential HTN. Methods: A systematic search was performed on PubMed, Scopus, Web of Science (WOS), and Cochrane Library from inception until January 2025 for randomized controlled trials (RCTs) comparing esaxerenone with standard HTN usual care. The primary outcome of interest was mean changes in sitting systolic (SBP) and diastolic blood pressure (DBP). Other secondary outcomes were mean changes in 24 h-SBP and 24 h-DBP, and target BP achievement. Safety outcomes, such as adverse events and increased levels of potassium/uric acid, were also assessed. Results: Our meta-analysis included four studies with a total of 1981 patients, all conducted in Japan. Esaxerenone demonstrated dose-dependent blood pressure reductions. At 5 mg, sitting DBP decreased by 4.22 mmHg (95% CI −8.72 to 0.29; p = 0.07) and SBP by 9.07 mmHg (95% CI −17.69 to −0.45; p = 0.04), while the 1.25 mg dose showed smaller, non-significant reductions. For 24 h measurements, only the 5 mg dose achieved significant reductions. Target BP achievement increased by 48% overall (RR 1.48, 95% CI 1.11 to 1.96; p = 0.007), with stronger effects at 5 mg (RR 2.05, 95% CI 1.03 to 4.08; p = 0.04). Esaxerenone significantly reduced nocturnal SBP by 10.62 mmHg (95% CI −14.01 to −7.23; p < 0.001). Conclusions: In patients with essential HTN, esaxerenone was shown to be safe and well-tolerated compared with usual care. Long-term data on safety is warranted.