Raslan, Mohammed Alaa

Background/Objectives: Thoracic aortic aneurysm (TAA) often results from structural degeneration of the aortic wall. Traditional management focuses on hemodynamic control using beta-blockers (BB) and angiotensin receptor blockers (ARBs). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for diabetes and weight management, may offer additional vascular protective benefits through anti-inflammatory, antioxidative, and matrix-stabilizing mechanisms. However, their role in reducing mortality and thoracic aortic dissection (TAD) risk in patients with TAA has not been evaluated in human populations. In this study, we aimed to assess the association between GLP-1 RA use and the risks of mortality and thoracic aortic dissection. Methods: We conducted a retrospective cohort study of adults diagnosed with TAA between 2018 and 2024 across three Mayo Clinic sites. Patients receiving GLP-1 RAs were compared with non-users using 1:1 propensity score matching. Outcomes included all-cause mortality, cardiovascular mortality, and incident TAD. Kaplan–Meier and Cox proportional hazards analyses were performed. Results: A total of 32,279 patients with TAA, with a median age of 68.0 [IQR: 59.0–76.0] and 70.7% male, were included in a 1:1 propensity score match. This yielded a balanced cohort of 588 GLP-1 RA users and 588 non-users. Through a median follow-up of 4.1 (2.2, 5.9) years, GLP-1 RA use was associated with significantly lower 5-year cumulative incidence of all-cause mortality (5.0% vs. 14.5%, HR: 0.31; 95% CI: 0.19–0.50; p < 0.001), cardiovascular mortality (1.9% vs. 5.5%, HR: 0.30; 95% CI: 0.13–0.70; p = 0.005), and TAD (0.9% vs. 4.0%, HR: 0.19; 95% CI: 0.06–0.60; p < 0.0004). Conclusions: GLP-1 RAs are associated with reduced incidence of all-cause mortality, cardiovascular mortality, and TAD incidence in patients with TAA. Prospective studies are needed to confirm these findings and evaluate effects on aneurysm progression.

Background: Loeys–Dietz syndrome (LDS) is an autosomal dominant aortopathy characterized by aggressive aneurysm formation and arterial dissections. Pregnancy-related outcomes and timing of LDS diagnosis remain poorly characterized. Methods: Demographics, genetic, obstetric, and vascular data was collected from genetically or clinically confirmed individuals with LDS seen at the three Mayo Clinic sites from 2018 to 2025. Aneurysm progression, new aneurysm formation, and arterial dissections were recorded across all vascular beds. Vascular events were assessed during pregnancy, within 12 months postpartum, and during breastfeeding. Comparative analyses were performed between women with and without a history of pregnancy, and a single-arm descriptive analysis was conducted among patients who experienced vascular complications during the peripartum period. Continuous variables were compared using the Mann–Whitney U test, while categorical variables were analyzed using chi-square or Fisher exact tests. Results: Of 47 women with LDS, 24 had a history of pregnancy, accounting for 54 pregnancies. In the comparative analysis, age at LDS diagnosis differed significantly between women with and without a prior pregnancy: women without prior pregnancy were diagnosed at a younger age (median 23.5 years [IQR 10.8–41.0], n = 23) than those who had been pregnant (median 53.5 years [IQR 43.0–59.3], n = 24). Among pregnant women, the median age at first pregnancy was 28 years (IQR 23–34); only 4 (16.7%) knew their diagnosis before pregnancy. Of 54 pregnancies, 40 (74.1%) resulted in live birth, with 23 (57.5%) vaginal and 17 (42.5%) cesarean deliveries; preterm delivery occurred in 1 (2.5%) pregnancy, and postpartum hemorrhage in 2 (5.0%). No maternal deaths, aortic dissections, or uterine ruptures occurred during gestation or the first postpartum year. In addition, 14 women (58.3%) developed aneurysms, 6 (25.0%) experienced at least one arterial dissection, and 7 (29.2%) required surgical repair, predominantly involving the ascending and abdominal aorta. The prevalence of vascular complications did not differ significantly between groups. Conclusions: In this LDS cohort, pregnancy and the early postpartum period were not accompanied by acute aortic catastrophes, despite frequent diagnostic delay. Although women without prior pregnancy were diagnosed at a younger age, the overall burden of vascular and morphologic complications did not differ significantly by pregnancy history. These findings highlight the importance of long-term cardiovascular follow-up in women with LDS.

Background: Transthyretin (TTR) cardiac amyloidosis is a progressive cardiomyopathy with high mortality; however, the role of implantable cardioverter-defibrillators (ICDs) in this population remains unclear. Methods: This retrospective cohort study included patients with confirmed TTR cardiac amyloidosis, with or without ICDs, from January 1, 2001, to December 31, 2024, across all three Mayo Clinic sites (Arizona, Florida, and Minnesota). Diagnosis was confirmed by endomyocardial biopsy or abnormal technetium pyrophosphate (PYP) scintigraphy. A 1:4 propensity score-matched cohort of non-ischemic cardiomyopathy (NICM) patients with ICDs served as a control group. The primary outcome was all-cause mortality, comparing transthyretin cardiac amyloidosis (TTR-CA) patients by ICD status and against matched NICM patients. Secondary analyses evaluated predictors of mortality, including the use of tafamidis and the indication for ICD (primary vs. secondary prevention). Kaplan–Meier and Cox regression analyses were used to assess predictors of survival and mortality. Results: A total of 463 patients with confirmed TTR cardiac amyloidosis were included. The median follow-up duration was 7.4 years (interquartile range (IQR): 5.3–9.2 years) for the non-ICD group and 6.8 years (IQR: 4.5–9.0 years) for the ICD group. The median age was 74.5 years (IQR: 68.0–80.0 years), and 92.9% of patients were male. Among them, 206 (44.5%) received ICDs and 257 (55.5%) did not. ICD recipients were younger (71.0 vs. 77.0 years; p = 0.001) and had higher rates of hypertension (62.6% vs. 45.6%; p = 0.001), chronic kidney disease (CKD) (62.6% vs. 44.4%; p = 0.001), and diabetes (30.1% vs. 21.8%; p = 0.043). Median left ventricular ejection fraction was lower in the ICD groups (43% vs. 54%; p = 0.007), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the ICD group (2259.0 pg/mL vs. 1503.0 pg/mL; p = 0.007). Among ICD recipients, 157 (76.2%) received the device for primary prevention, while 48 (23.3%) received the ICD for secondary prevention. Appropriate shocks were delivered in 22 patients (10.6%), primarily for ventricular tachycardia (n = 18) and ventricular fibrillation (n = 4). Inappropriate shocks occurred in six patients (3.0%), and 12 patients (5.8%) experienced device-related complications. Over 10 years of follow-up, ICD implantation did not confer a survival benefit for patients with TTR-CA compared to those without an ICD (p = 0.74). In contrast, a 1:4 propensity-matched NICM cohort with ICDs, which had a median follow-up of 7.1 years (IQR: 4.6–8.8 years), showed significantly improved survival than TTR-CA patients with ICDs (p = 0.034). Among the TTR-CA patients with ICDs, neither the use of tafamidis (p = 0.10) nor the ICD indication (primary vs. secondary prevention; p = 0.85) influenced mortality. In the Cox regression analysis, predictors of mortality in TTR-CA patients included older age (hazard ratio (HR) 1.048; p = 0.001), CKD (HR 1.637; p = 0.029), troponin T >50 ng/L (HR 1.594; p = 0.031), NT-proBNP >3000 pg/mL (HR 1.514; p = 0.050), and ejection fraction <40% (HR 1.935; p = 0.003). ICD implantation was not associated with improved survival (HR 0.932; p = 0.763). Conclusions: In conclusion, our data suggest that ICD therapy may not provide a significant overall survival benefit in older TTR-CA patients with impaired pump function; thus, prospective studies are warranted before any changes to clinical practice are considered. Key predictors of mortality included reduced ejection fraction and elevated cardiac biomarkers. Additional prospective studies are needed to clarify the role of ICDs in treatment strategies for patients with TTR-CA.