Ghazal, Rachad

This study uncovers a previously unrecognized role for NAV3 in TGF-β1-driven cardiac fibroblast activation. We show that NAV3 facilitates profibrotic remodeling through noncanonical signaling and cell cycle arrest, independently of SMAD2/3. These findings position NAV3 as a novel regulator of fibroblast phenotype and a potential modulator of cardiac fibrosis.

Background. Acute cellular rejection (ACR) remains a major cause of morbidity after heart transplantation despite advances in immunosuppression. Whole genome transcriptomic profiling offers a systems-based, unbiased approach to elucidate the molecular mechanisms underlying ACR. However, noninvasive, longitudinal biomarker assessments capable of capturing the temporal dynamics of rejection biology remain scarce. Methods. RNA sequencing of peripheral blood from heart transplant recipients before, during, and after ACR was compared with nonrejection controls. Pathway analysis was conducted using differentially expressed genes (DEGs), and a machine learning approach was applied to assess gene-based prediction of ACR. Results. A total of 235 rejection-specific significant DEGs and 863 postrejection DEGs (false discovery rate < 0.05) were identified. During ACR, DEGs were enriched for T-cell activation/differentiation, apoptosis, and B-cell receptor signaling pathways. By combining the 2 sets of DEGs, a panel of 71 common genes was identified that reflected the significant, longitudinal transcriptomic dynamics of ACR. In an elastic net machine learning–based classifier, DYNLL1 and SERF2 were identified as ACR predictive genes, and achieved a cross-validated area under the receiver operating characteristic curve of 0.63. Conclusions. Peripheral blood transcriptomics identify dynamic temporal responses in ACR including T- and B-cell pathways with potential ACR predictive genes that warrant further investigation.

Background: Transcatheter aortic valve replacement (TAVR) is a well-established therapeutic option for all risk patients with symptomatic severe aortic stenosis (AS). While TAVR primarily addresses AS, its benefits extend beyond the valve itself. Recent studies suggest possible restoration of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) following TAVR. This study aims to assess changes in LV GLS in patients undergoing TAVR, which may serve as a subclinical indicator of improved LV mechanics. Materials and Methods: This retrospective study included patients with severe AS who underwent TAVR at the American University of Beirut Medical Center from January 2017 to January 2023. Baseline and 1-year echocardiography parameters were compared, and GLS was calculated to assess the impact of TAVR on LV function. Results: A total of 80 patients (mean age: 81.3 ± 7.8 years; 38.8% of women; 88.8% hypertensive) who underwent TAVR for severe AS were included in the final analysis. One-year post-TAVR, echocardiographic studies showed a significant reduction in interventricular septum diameter (13.3 ± 2.3 mm vs. 12 ± 1.8 mm, P < 0.001) and LV mass index (LVMI) (113.6 ± 26.6 g/m 2 vs. 96 ± 30.3 g/m 2 , P < 0.001). LVEF showed a modest improvement (59.2 ± 12.3% vs. 62.1 ± 7.6%, P < 0.01). LV GLS significantly improved from −16.8 ± 4.6% to −19.2 ± 3.3% ( P < 0.001). Baseline LVMI, LVEF, and GLS correlate with the GLS change (ΔGLS) post-TAVR. Conclusion: GLS significantly improves 1 year after TAVR, indicating an overall improvement in LV performance. The degree of improvement in GLS correlates with baseline LVMI and systolic function.

Cardiac fibrosis, a hallmark of heart failure and various cardiomyopathies, represents a complex pathological process that has long challenged therapeutic intervention. High-throughput omics technologies have begun revolutionizing our understanding of the molecular mechanisms driving cardiac fibrosis and are providing unprecedented insights into its heterogeneity and progression. This review provides a comprehensive analysis of how techniques—encompassing genomics, epigenomics, transcriptomics, proteomics, and metabolomics—are providing insight into our understanding of cardiac fibrosis. Genomic studies have identified novel genetic variants and regulatory networks associated with fibrosis susceptibility and progression, and single-cell transcriptomics has unveiled distinct cardiac fibroblast subpopulations with unique molecular signatures. Epigenomic profiling has revealed dynamic chromatin modifications controlling fibroblast activation states, and proteomic analyses have identified novel biomarkers and potential therapeutic targets. Metabolomic studies have uncovered important alterations in cardiac energetics and substrate utilization during fibrotic remodeling. The integration of these multi-omic data sets has led to the identification of previously unrecognized pathogenic mechanisms and potential therapeutic targets, including cell-type-specific interventions and metabolic modulators. We discuss how these advances are driving the development of precision medicine approaches for cardiac fibrosis while highlighting current challenges and future directions in translating multi-omic insights into effective therapeutic strategies. This review provides a systems-level perspective on cardiac fibrosis that may inform the development of more effective, personalized therapeutic approaches for heart failure and related cardiovascular diseases.

Background and purpose: Aortic stenosis (AS) poses significant healthcare challenges, particularly in aging populations like Lebanon. Aortic valve replacement (AVR) is the primary treatment; however the choice between transcatheter aortic valve replacement (TAVR) and surgical AVR (SAVR) varies based on patient-specific factors. This study aimed to compare clinical outcomes between TAVR and SAVR in patients with severe AS at a Lebanese tertiary care center. Methods: This retrospective study included 453 patients aged ≥60 with severe AS who underwent either TAVR or SAVR at the American University of Beirut Medical Center from 2011 to 2022. Primary outcomes were 30-day mortality and hospital readmission rates. Secondary outcomes included length of stay, complications, and changes in echocardiographic parameters. Statistical analysis included Chi-squared tests, t-tests, and propensity score matching. Results: Of the 453 patients, 306 underwent TAVR, and 147 underwent SAVR, with a mean age of 79.0 ± 6.8 years. The TAVR group had higher Society of Thoracic Surgeons (STS) scores (4.7 ± 3.2 vs. 2.6 ± 1.7; P < 0.001). TAVR patients had shorter hospital stays (2 [0-93] vs. 6 [4-41] days; P < 0.001), lower 30-day readmission rates (8.2% vs. 18.5%; P = 0.002), and similar all-cause mortality rates (hazard ratio [HR]: 0.69; 95% confidence interval [95% CI]: 0.14–3.42; P = 0.647). Post-procedural new-onset left bundle branch block (LBBB) was more common in TAVR group (13.0% vs. 0.6%; P < 0.001), and new-onset atrial fibrillation (Afib) was more frequent in the SAVR group (34% vs. 1%; P < 0.001). There were no significant differences in the rates of complete heart block (CHB) or pacemaker implantation. The effective orifice area index (EOAi) was higher in the TAVR group (1.2 ± 0.4 vs. 0.9 ± 0.2 cm2/m2; P < 0.001). Major bleeding complications were significantly lower in TAVR patients (7.9% vs. 65.8%; P < 0.001), with no significant differences in neurological events. Conclusions: Both TAVR and SAVR show comparable safety and efficacy, with TAVR offering advantages in terms of recovery time and bleeding risk. These findings support a tailored approach to procedural choice based on individual patient risk profiles.