Galectin-3 Is Associated with Cardiac Fibrosis and an Increased Risk of Sudden Death.

BACKGROUND: Myocardial fibrosis is a common postmortem finding among individuals with Sudden Cardiac Death (SCD). Numerous in vivo and in vitro studies have shown that increased galectin-3 (gal3) expression into the myocardium is associated with higher incidence of fibrosis. Although elevated gal3 expression is linked with myocardial fibrosis, its role in predicting the risk of SCD is unknown. METHODS: We reviewed the clinical datasets and post-mortem examination of 221 subjects who had died suddenly. We examined myocardial pathology including the extent of cardiac hypertrophy, fibrosis, and the degree of coronary atherosclerosis in these subjects. In a select group of SCD subjects, we studied myocardial gal3 and periostin expression using immunohistochemistry. To further examine if a higher level of circulating gal3 can be detected preceding sudden death, we measured serum gal3 in a porcine model of subtotal coronary artery ligation which shows an increased tendency to develop lethal cardiac arrhythmias, including ventricular tachycardia or fibrillation. RESULTS: Of the total 1314 human subjects screened, 12.7% had SCD. Comparison of age-matched SCD with non-SCD subjects showed that SCD groups had excessive myocardial fibrosis involving both the left ventricular free wall and interventricular septum. In pigs with subtotal coronary artery ligation and SCD, we detected significantly elevated circulating gal3 levels approximately 10 days preceding the SCD event. Immunohistochemistry showed increased myocardial gal3 and periostin expression in pigs that died suddenly, compared to the controls. CONCLUSION: Our study shows that increased gal3 is associated with a higher risk of myocardial fibrosis and the risk of SCD. This supports the importance of larger translational studies to target gal3 to prevent cardiac fibrosis and attenuate the risk of SCD.

Energy loss index as a predictor of all-cause mortality after transcatheter aortic valve replacement: A long-term follow-up.

BACKGROUND: As transcatheter aortic valve replacement (TAVR) procedures become more widely available, there is a growing need to monitor and evaluate postoperative outcomes accurately. The energy loss index (ELI) of the ascending aorta has been commonly used to examine the agreement between the echocardiographic and Gorlin measurement of the aortic valve area. OBJECTIVES: This project aims to demonstrate a link between ELI values and mortality following implanted TAVR valves and determine an ELI cutoff value associated with post-TAVR events. METHOD: We retrospectively reviewed patients undergoing TAVR from 2012 to 2017. We calculated ELI values for patients immediately postoperative after a TAVR procedure. Using Receiver-Operator Characteristic and Cox Regression analyses, we identified a cutoff value to distinguish between "High ELI" (≥ 1.34) and "Low ELI" (< 1.34) patients. RESULTS: This study showed low ELI (hazard ratio, 2.30; 95% confidence interval 1.57-3.36, p < .001) as representative of patients with a high risk of mortality post-TAVR. Additionally, post-TAVR, ejection fraction increased by 3.6% (p < .001), and the aortic valve effective orifice area increased by 1.41 cm squared (p < .001) while the mean transvalvular gradient decreased by 32.8 mmHg (p < .001) and the peak transvalvular gradient decreased by 49.0 mmHg (p < .001). CONCLUSION: ELI is an additional prognostic factor that should be considered during risk assessment before TAVR. This study shows that patients with Low ELI had decreased cumulative survival post-TAVR. These patients almost had a fivefold increased risk of death following TAVR.