SGLT inhibitors for improving Healthspan and lifespan.

Sodium-glucose cotransporter inhibitor/inhibition (SGLTi), initially approved as a glucose-lowering therapy for type 2 diabetes, is associated with decreased risks for many of the most common conditions of aging, including heart failure, chronic kidney disease, all-cause hospitalization, atrial fibrillation, cancer, gout, emphysema, neurodegenerative disease/dementia, emphysema, non-alcoholic fatty liver disease, atherosclerotic disease, and infections. Studies also show that SGLTi improves overall life expectancy and reduces risks of cardiovascular death and cancer death. These wide-ranging health benefits are largely unexplained by the SGLTi's modest improvements in standard risk factors. SGLTi produces upregulation of nutrient deprivation signaling and downregulation of nutrient surplus signaling. This in turn promotes autophagy, which helps to optimize cellular integrity and prevent apoptotic cell death. SGLTi decreases oxidative stress and endoplasmic reticulum stress, restores of mitochondrial health, stimulates mitochondrial biogenesis, and diminishes proinflammatory and profibrotic pathways. These actions help to revitalize senescent cells, tissues, and organs. In summary, SGLTi appears to slow aging, prevent disease, and improve life expectancy, and its mechanisms of action lend strong biological plausibility to this hypothesis. Further randomized trials are warranted to test whether SGLTi, a safe and well-tolerated, once-daily pill, might improve healthspan and lifespan.

Prognostic Role of Cardiopulmonary Exercise Testing in Wild-Type Transthyretin Amyloid Cardiomyopathy Patients Treated With Tafamidis.

BACKGROUND: The prognostic value of cardiopulmonary exercise testing (CPET) in patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis is unknown. METHODS AND RESULTS: This retrospective study included patients with wtATTR who underwent baseline cardiopulmonary exercise testing and were treated with tafamidis from August 31, 2018, until March 31, 2020. Univariate logistic and multivariate cox-regression models were used to predict the occurrence of the primary outcome (composite of mortality, heart transplant, and palliative inotrope initiation). A total of 33 patients were included (median age 82 years, interquartile range [IQR] 79-84 years), 84% were Caucasians and 79% were males). Majority of patients had New York Heart Association functional class III disease at baseline (67%). The baseline median peak oxygen consumption (VO2) and peak circulatory power (CP) were 11.35 mL/kg/min (IQR 8.5-14.2 mL/kg/min) and 1485.8 mm Hg/mL/min (IQR 988-2184 mm Hg/mL/min), respectively, the median ventilatory efficiency was 35.7 (IQR 31-41.2). After 1 year of follow-up, 11 patients experienced a primary end point. Upon multivariate analysis, the low peak VO2 (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.79, P = .007], peak CP (HR 0.98, 95% CI 0.98-0.99, P = .02), peak oxygen pulse (HR 0.62, 95% CI 0.39-0.97, P = .03), and exercise duration of less than 5.5 minutes (HR 5.82, 95% CI 1.29-26.2, P = .02) were significantly associated with the primary outcome. CONCLUSIONS: Tafamidis-treated patients with wtATTR who had baseline low peak VO2, peak CP, peak O2 pulse, and exercise duration of less than 5.5 minutes had worse outcomes.

In-Hospital Outcomes and Trends of Tricuspid Valve Surgery in Heart Transplant Patients.

INTRODUCTION: Tricuspid valve (TV) regurgitation is the most common valvular pathology after orthotopic heart transplant (OHT). The number of transplants being performed is increasing with patients living longer after heart transplant. Data on TV surgery in OHT recipients is limited. METHODS: We sought to analyze the outcomes of patients undergoing TV surgery from a large diverse, multicentric, nationwide cohort using the Nationwide Inpatient Sample (NIS) database. RESULTS: A total of 42,766 TV repair or replacement (bioprosthetic and mechanical) involving adult patients (age ≥18 years) between 2007 and September 2015 were identified. Of these, 366 were performed in patients with OHT. TV repair was the most common surgery performed in both groups (OHT group and native heart group). Compared to the native group, patients with OHT had a significantly higher incidence of cardiogenic shock (20 vs. 11%, p = 0.024), acute kidney injury (AKI) (59 vs. 30%, p < 0.001), and AKI requiring hemodialysis (13 vs. 4%, p < 0.001). Also, the mean length of stay for the index admission was significantly longer in the OHT group (27 vs. 17 days, p = 0.008). The mortality rate was similar between the two groups (7 vs. 8%, p = 0.753). The number of TV surgeries performed in OHT patients from 2007 to 2014 have remained stable (p = 0.803) compared to those in native heart patients which showed a significantly increasing trend (p = 0.019) during the same time period. CONCLUSIONS: TV surgery remains an important treatment modality among the OHT population and carries a similar mortality during index hospitalization as that in native heart patients undergoing TV surgery.