Genetic Deletion of Galectin-3 Exacerbates Age-Related Myocardial Hypertrophy and Fibrosis in Mice.

BACKGROUND/AIMS: Aging is accompanied by progressive and adverse cardiac remodeling characterized by myocardial hypertrophy, fibrosis, and dysfunction. We previously reported that galectin-3 (Gal-3) is a critical regulator of inflammation and fibrosis associated with hypertensive heart disease and myocardial infarction. Nevertheless, the role and mechanism of Gal-3 in age-related cardiac remodeling have not been previously investigated. We hypothesized that Gal-3 plays a critical role in cardiac aging and that its deficiency exacerbates the underlying mechanisms of myocardial hypertrophy and fibrosis. METHODS: Male C57BL/6 (control) (n=24) and Gal-3 knockout (KO) (n=29) mice were studied at 24 months of age to evaluate the role of Gal-3 in cardiac aging. We assessed 1) survival rate; 2) systolic blood pressure (SBP) by plethysmography; 3) myocardial hypertrophy, apoptosis, and fibrosis by quantification of histological and immunohistochemical analysis; 4) cardiac expression of angiotensin (Ang) II, Ang (1-7) by Radioimmunoassay; 5) transforming growth factor-ß (TGF-ß), sirtuin (SIRT) 1, SIRT 7 and metalloproteinase 9 (MMP-9) by RT-qPCR and 6) ventricular remodeling and function by echocardiography. RESULTS: We found that aged Gal-3 KO mice had a lower survival rate and exhibited exacerbated myocardial hypertrophy and fibrosis without changes in SBP. Similarly, myocardial apoptosis and MMP-9 mRNA expression was significantly increased in the hearts of Gal-3 KO mice compared to controls. Additionally, cardiac Ang II and TGF-ß expression were higher in aged Gal-3 KO mice while SIRT1 and SIRT7 expression were reduced. CONCLUSION: Our findings strongly suggest that Gal-3 is involved in age-related cardiac remodeling by regulating critical mechanisms associated with the development of pathological hypertrophy. The gene deletion of Gal-3 reduced the lifespan and markedly increased age-dependent mechanisms of myocardial hypertrophy, apoptosis, and fibrosis, including Ang-II, TGF-ß, and MMP-9. At the same time, there was diminished cardiac-specific expression of SIRT1 and SIRT7, which are extensively implicated in delaying age-dependent cardiomyopathies.

Sarcopenia index as a predictor of clinical outcomes in older patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Sarcopenia is a prevalent condition in elderly patients and has been associated with adverse outcomes following transcatheter aortic valve replacement (TAVR). The present study aimed to determine the predictive value of serum creatinine-cystatin C ratio, that is, "Sarcopenia Index" (SI) as a surrogate marker of sarcopenia, and investigate its association with clinical outcomes after TAVR. METHODS: We conducted a retrospective observational study of patients undergoing TAVR between January, 2016 and December, 2018 at Hospital Italiano de Buenos Aires, Argentina. Patients were excluded if <65-years old, presented previous surgical aortic valve replacement, severe chronic kidney disease, or hemodialysis requirement. The SI was obtained at baseline before TAVR. All-cause mortality and/or readmissions for congestive heart failure (CHF) were defined as the primary endpoint. RESULTS: In total 100 patients met inclusion criteria for the purpose of the study. Sarcopenia Index was significantly correlated with Timed Up and Go (r = -0.272, p = .010) and Gait Speed (r = -0.278, p = .005). During follow-up, 5/100 patients died within 30 days and a total of 10/100 patients died at 1-year follow-up. Moreover, survival curves were significantly worse (Log-rank test = p = .02) and CHF readmissions were more prevalent in the lowest SI tertile (Log-rank test = p = .01). In multivariate Cox regression analysis, we identified low SI (cutoff ≤66) as an independent predictor of long-term adverse outcomes (HR = 4.01, 95% CI = 1.31-12.27, p = .015) at 1-year follow-up. CONCLUSION: Sarcopenia Index, surrogate for the degree of skeletal muscle mass (SMM), could be used as a predictor of adverse outcomes in patients undergoing TAVR.

Additive prognostic value of carbohydrate antigen-125 over frailty in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: To evaluate the additive prognostic value of myocardial, inflammatory, and renal biomarkers according to frailty status in patients undergoing transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS). METHODS: A total of 111 subjects who underwent TAVR at Hospital Italiano de Buenos Aires, Argentina between January 2016 and December 2018 were retrospectively reviewed. Plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity troponin T (hs-cTnT), C-reactive protein (CRP), cystatin-c (Cys-C) and carbohydrate antigen-125 (CA-125) were assessed prior to TAVR. Frailty status was assessed according to the fried physical frailty phenotype (FPFP). The primary endpoint was defined as all-cause death and/or readmission for worsening congestive heart failure (CHF) within the first year after TAVR. RESULTS: Of the 111 patients included, 48/111 (43%) were considered to be "frail" according to the FPFP. Among biomarkers, we found CA-125 to be strongly associated with the primary endpoint (p = .006). CA-125 ≥ 18.2 U/ml was present in 41% and was associated with a higher rate of the primary endpoint (31% vs. 9%; p = .003). After multivariable adjustment, CA-125 ≥ 18.2 U/ml (hazard ratio [HR] 3.17; p = .024) was the only independent predictor of the primary endpoint. Finally, the inclusion of CA-125 to frailty significantly improved C-index (0.68-0.74; p < .05), and provided a Net Reclassification Improvement (NRI) of 0.34 (95% CI 0.19-0.49, p = .031), largely through reductions in risk estimates among pre-frail and frail patients. CONCLUSIONS: CA-125, a tumor biomarker, outperformed frailty for predicting the primary endpoint within the first year after TAVR.

Stroke risk after transcatheter aortic valve replacement in patients with carotid stenosis: A systematic review and meta-analysis.

BACKGROUND: Stroke is a feared complication of transcatheter aortic valve replacement (TAVR). Patients undergoing TAVR typically have multiple comorbidities, such as carotid artery stenosis (CAS). We conducted the present meta-analysis to determine the risk of stroke and mortality following TAVR in patients with CAS. METHODS: We searched PubMed/Medline, Scopus, ScienceDirect, and Cochrane Clinical Trials databases for clinical studies that compared CAS ≥50% and CAS ≥70% versus non-CAS TAVR population. The endpoints included the 30-day incidence of stroke or transient ischemic attack (TIA) and 30-day all-cause of mortality. RESULTS: We identified seven studies that included 12,418 patients in the CAS group and 102,316 in the control group. CAS ≥50% was not associated with an increased risk of 30-day stroke or TIA after TAVR [risk ratio (RR): 1.38; 95% confidence interval (95% CI): 0.95-2.02; p = 0.09]. However, patients with CAS ≥70% had an increased risk of stroke or TIA (RR: 1.43; 95% CI: 1.02-2.01; p = 0.04). No difference in 30-day all-cause mortality was observed between CAS ≥50% or CAS ≥70% and control groups (RR: 1.09; 95% CI: 0.79-1.52; p = 0.59 and RR: 1.11; 95% CI: 0.85-1.45; p = 0.43, respectively). CONCLUSIONS: CAS ≥70% was associated with an increased risk of stroke or TIA following TAVR compared with patients without CAS.

Transcatheter Aortic Valve Replacement Through a Single Femoral Access: A Multicenter Experience.

OBJECTIVES: During the past few years, physicians have optimized transcatheter aortic valve replacement and its periprocedural management, with the minimalist approach becoming popular. We aimed to further simplify the procedure using a single femoral access (the "all-in-one" technique). Here, we report a multicenter experience with TAVR with Acurate neo/neo2 transcatheter heart valves (Boston Scientific) through a single, large-bore, femoral sheath. METHODS: Patients underwent TAVR with the Acurate neo or neo2 through a single femoral access at 4 centers. The large sheath was used for both the delivery catheter and the pigtail used to visualize the aortic root. RESULTS: A total of 157 patients (59% women) with a mean age of 82 ± 6 years underwent TAVR with the Acurate neo (n = 100) or the Acurate neo2 (n = 57). The procedure was successfully performed through a single large sheath in all patients. Median duration of hospitalization stay was 2 days (interquartile range, 1-3 days). On echocardiography before discharge, the mean gradient was 7 ± 3 mm Hg and 7 patients (4.4%) had more than mild paravalvular leak. At 30 days, a major vascular complication had occurred in 2 patients (1.3%), 2 patients (1.3%) had suffered a stroke, and only 4 patients (2.5%) had required new permanent pacemaker implantation. A total of 3 patients (1.9%) had died. CONCLUSIONS: An all-in-one access technique allows safe implantation of Acurate neo and neo2 transcatheter heart valves, with low rates of periprocedural complications and favorable short-term outcomes.