BACKGROUND: The role of left atrial appendage occlusion (LAAO) in patients without previous atrial fibrillation (AF) is not established. This meta-analysis was conducted on patients with normal sinus rhythm who underwent cardiac surgery, with and without concomitant LAAO, to evaluate its effect on the incidence of cerebrovascular accidents (CVAs). METHODS: A systematic review was conducted from inception until December 2023 for randomized and propensity-score studies comparing CVA in patients without AF undergoing cardiac surgery with or without LAAO. RESULTS: Six studies met our inclusion criteria with a total of 4130 patients: 2146 in the LAAO group and 1984 in the no-LAAO group. The risk ratio of postoperative AF was 1.05 (95% CI, 0.86–1.28); P =0.628. The CVA rates at 5 years were 6.8±1.0% in the no-LAAO group and 4.3±0.8% in the LAAO group (log-rank P =0.021). The Cox regression analysis for CVA in patients undergoing LAAO reported a hazard ratio of 0.65 (95% CI, 0.45–0.94); P =0.022. Landmark analysis at 4 years highlighted a significant difference in overall survival between no-LAAO and LAAO groups, 86±12.2% versus 89.6±11.0%; P =0.041. CONCLUSIONS: In this meta-analysis of patients without previous AF undergoing cardiac surgery, LAAO was associated with a decreased risk of CVA, no difference in the incidence of postoperative atrial fibrillation, and a significant overall survival benefit at a 4-year landmark analysis. Although these findings support LAAO, the randomized LeAAPS trial (Left Atrial Appendage Exclusion for Prophylactic Stroke Reduction Trial), LAA-CLOSURE trial (A Randomized Prospective Multicenter Trial for Stroke Prevention by Prophylactic Surgical Closure of the Left Atrial Appendage in Patients Undergoing Bioprosthetic Aortic Valve Surgery), and LAACS-2 trial (Left Atrial Appendage Closure by Surgery-2) will help define the effectiveness of LAAO in patients undergoing cardiac surgery who have risk factors for AF and CVA. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: CRD42024496366.

Thoracic aortic disease (TAD) encompasses a spectrum of life-threatening conditions, including thoracic aortic aneurysm (TAA), acute type A aortic dissection (ATAAD), and bicuspid aortic valve (BAV)-associated aortopathy. While genetic mutations are well-documented contributors, emerging evidence highlights epigenetic mechanisms as critical regulators of TAD pathogenesis. This comprehensive review explores the role of epigenetic modifications—DNA methylation, histone modifications, and microRNA (miRNA) regulation—in vascular remodeling, extracellular matrix degradation, and endothelial dysfunction. Aberrant DNA methylation patterns have been implicated in TAA and ATAAD, influencing genes responsible for vascular integrity and inflammation. Histone modifications modulate smooth muscle cell phenotype switching, impacting aneurysm progression. Additionally, dysregulated miRNA expression contributes to endothelial barrier disruption and extracellular matrix remodeling, presenting novel avenues for biomarker discovery. The reversibility of epigenetic modifications offers a promising therapeutic target, with pharmacological agents such as histone deacetylase inhibitors and miRNA-based therapies showing potential in preclinical models. This review underscores the translational potential of epigenetic biomarkers for early disease detection, risk stratification, and precision medicine approaches. Further research is needed to integrate these findings into clinical practice, paving the way for innovative diagnostic and therapeutic strategies in TAD management.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis, but data are limited on younger, low-risk patients. This analysis compares outcomes in low-surgical-risk patients aged <75 years receiving TAVR versus surgery. METHODS: The Evolut Low Risk Trial randomized 1414 low-risk patients to treatment with a supra-annular, self-expanding TAVR or surgery. We compared rates of all-cause mortality or disabling stroke, associated clinical outcomes, and bioprosthetic valve performance at 3 years between TAVR and surgery patients aged <75 years. RESULTS: In patients <75 years, 352 were randomized to TAVR and 351 to surgery. Mean age was 69.1±4.0 years (minimum 51 and maximum 74); Society of Thoracic Surgeons Predicted Risk of Mortality was 1.7±0.6%. At 3 years, all-cause mortality or disabling stroke for TAVR was 5.7% and 8.0% for surgery ( P =0.241). Although there was no difference between TAVR and surgery in all-cause mortality, the incidence of disabling stroke was lower with TAVR (0.6%) than surgery (2.9%; P =0.019), while surgery was associated with a lower incidence of pacemaker implantation (7.1%) compared with TAVR (21.0%; P <0.001). Valve reintervention rates (TAVR 1.5%, surgery 1.5%, P =0.962) were low in both groups. Valve performance was significantly better with TAVR than surgery with lower mean aortic gradients ( P <0.001) and lower rates of severe prosthesis-patient mismatch ( P <0.001). Rates of valve thrombosis and endocarditis were similar between groups. There were no significant differences in rates of residual ≥moderate paravalvular regurgitation. CONCLUSIONS: Low-risk patients <75 years treated with supra-annular, self-expanding TAVR had comparable 3-year all-cause mortality and lower disabling stroke compared with patients treated with surgery. There was significantly better valve performance in patients treated with TAVR. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT02701283.