Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated significant cardiovascular benefits in clinical trial. While their role in reducing heart failure hospitalizations and cardiovascular mortality is well established, the precise mechanisms underlying their direct cardiac effects remain unclear. This literature review aims to synthesize current knowledge on the molecular and physiological pathways by which SGLT2 inhibitors may exert effects on cardiac tissue, independent of glycemic control. Methods: A comprehensive review of peer-reviewed articles, randomized controlled trials, meta-analyses, and mechanistic studies published in PubMed and related databases was conducted. The search focused on studies examining the direct impact of SGLT2 inhibitors on cardiac function, remodeling, metabolism, and intracellular signaling pathways. Only studies evaluating the cardiac effects separate from their glucose-lowering action were included in the analysis. Results: This review identified several key mechanisms by which SGLT2 inhibitors may benefit the heart directly, including reductions in oxidative stress, inflammation, and myocardial fibrosis. Emerging evidence suggests that these drugs modulate key pathways such as sodium-hydrogen exchange (NHE) inhibition, improvement of mitochondrial function, and promotion of ketone body utilization in cardiomyocytes. Conclusions: SGLT2 inhibitors appear to confer direct cardioprotective effects. These include anti-inflammatory, anti-fibrotic, and energy efficiency improvements in the myocardium. The findings highlight new potential therapeutic mechanisms and provide a foundation for further research into the non-diabetic use of SGLT2 inhibitors in heart failure and other cardiac conditions. Understanding these direct effects could lead to optimized treatment strategies for patients with and without diabetes.

Background: Sarcopenia, or loss of skeletal muscle mass, has been associated with poor outcomes (e.g., functional decline, increased mortality, and low quality of life), but its role in CTEPH remains unclear. The psoas muscle index (PMI) is a validated measure of sarcopenia. We investigated the incidence of sarcopenia using PMI in CTEPH. Methods: Retrospective analysis of a single-center cohort of patients with CTEPH with an available computed tomography of the abdomen and pelvis (CTAP). PMI was measured at the L3 level of the CTAP and was then calculated using the formula (left psoas area + right psoas area/height²). Patients in the first quartile of PMI were classified as sarcopenic. Results: We reviewed 558 patients with CTEPH, and 97 patients had an available CTAP before intervention. Sarcopenia was identified in 26 (24.8%) of the patients and was associated with worse baseline functional status (p = 0.008), higher mean pulmonary artery pressure (48 vs. 39 mmHg; p = 0.002), and higher pulmonary vascular resistance (9.9 vs. 6.8 WU; p = 0.013). Post-PTE, patients with sarcopenia exhibited longer intensive care unit (ICU) (9 vs. 4 days, p < 0.001) and overall hospital stays (24 vs. 11 days, p < 0.001), despite similar post-operative hemodynamics achieved compared to non-sarcopenic patients. Conclusions: CTEPH patients with sarcopenia have worse baseline functional class and hemodynamics. For those with sarcopenia requiring surgery, there is longer ICU and total hospitalization stays, but they achieve significant functional improvements and hemodynamics comparable to that of non-sarcopenic patients. Hence, the risk of longer perioperative hospitalization days is justified by the longer-term benefit of hemodynamic improvement. The use of PMI as part of routine pre-operative assessments could improve clinical decision-making in CTEPH patients undergoing surgical or medical intervention.

Background: Sarcopenia is associated with adverse surgical outcomes across multiple specialties. The psoas muscle index (PMI), a radiologic marker of sarcopenia, may offer prognostic value in patients undergoing left ventricular assist device (LVAD) implantation, a population frequently characterized by frailty and high perioperative risk. Methods: We conducted a single-center retrospective study of 32 patients who underwent LVAD implantation between 2017 and 2022 and had preoperative CT imaging within 45 days. PMI was calculated from bilateral psoas muscle area at the L3 vertebral level, normalized to height. Sarcopenia was defined as the lowest sex-specific quartile of PMI. Primary outcomes were overall survival (OS), 90-day mortality, and postoperative length of stay (LOS). Results: Eight patients (25%) met criteria for sarcopenia. Sarcopenic and non-sarcopenic groups had similar demographics, comorbidities, and nutritional status. While there were no significant differences in overall, 90-day, or 1-year mortality between groups, among those who died post-implantation, the sarcopenic group had significantly shorter OS (median 38 vs. 597 days, p = 0.006). All sarcopenic deaths occurred within 90 days post-implant. LOS did not differ significantly between groups. Conclusions: PMI-defined sarcopenia was associated with early postoperative mortality among LVAD recipients, though not with overall or long-term mortality.