Sarkis, Patrick

Introduction: Sex-based differences in outcomes among patients with heart failure with reduced ejection fraction (HFrEF) treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored. This study aimed to evaluate sex-specific differences in cardiovascular outcomes in patients with HFrEF receiving SGLT2 inhibitors alongside guidelinedirected medical therapy (GDMT). Methods: We conducted a retrospective cohort study using the TriNetX global research network. Adults with HFrEF treated with SGLT2is and GDMT were stratified by sex. Propensity score matching (PSM) was used to balance baseline demographics, comorbidities, medications, and laboratory data. Primary outcomes were all-cause mortality and acute heart failure (HF) events; secondary outcomes included hospitalizations, arrhythmias, renal outcomes, and advanced therapies. Results: After PSM, 17,408 male and 17,408 female patients were analyzed. Male patients had lower odds of acute HF events (aOR: 0.949; 95% CI: 0.909–0.991), all-cause hospitalizations (aOR: 0.933; 95% CI: 0.895–0.973), and renal failure (aOR: 0.915; 95% CI: 0.870–0.962). No significant differences were observed in all-cause mortality (aOR: 1.003; 95% CI: 0.926–1.087) or heart transplantation, although LVAD use was more frequent in males (aOR: 1.416; 95% CI: 1.053–1.905). Discussion: The findings highlighted potential sex-based disparities in outcomes for patients with HFrEF on SGLT2is. Differential prescribing patterns, comorbidity burden, or timing of therapy initiation may contribute to observed differences. Conclusion: Among HFrEF patients treated with SGLT2is, males experienced lower risks of HF events, hospitalizations, and renal failure compared to females, despite similar mortality. Further research is needed to understand and address sex-specific disparities in HFrEF management.

Background: Transcatheter aortic valve replacement (TAVR) is a well-established therapeutic option for all risk patients with symptomatic severe aortic stenosis (AS). While TAVR primarily addresses AS, its benefits extend beyond the valve itself. Recent studies suggest possible restoration of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) following TAVR. This study aims to assess changes in LV GLS in patients undergoing TAVR, which may serve as a subclinical indicator of improved LV mechanics. Materials and Methods: This retrospective study included patients with severe AS who underwent TAVR at the American University of Beirut Medical Center from January 2017 to January 2023. Baseline and 1-year echocardiography parameters were compared, and GLS was calculated to assess the impact of TAVR on LV function. Results: A total of 80 patients (mean age: 81.3 ± 7.8 years; 38.8% of women; 88.8% hypertensive) who underwent TAVR for severe AS were included in the final analysis. One-year post-TAVR, echocardiographic studies showed a significant reduction in interventricular septum diameter (13.3 ± 2.3 mm vs. 12 ± 1.8 mm, P < 0.001) and LV mass index (LVMI) (113.6 ± 26.6 g/m 2 vs. 96 ± 30.3 g/m 2 , P < 0.001). LVEF showed a modest improvement (59.2 ± 12.3% vs. 62.1 ± 7.6%, P < 0.01). LV GLS significantly improved from −16.8 ± 4.6% to −19.2 ± 3.3% ( P < 0.001). Baseline LVMI, LVEF, and GLS correlate with the GLS change (ΔGLS) post-TAVR. Conclusion: GLS significantly improves 1 year after TAVR, indicating an overall improvement in LV performance. The degree of improvement in GLS correlates with baseline LVMI and systolic function.

Cardiac cachexia (CC) is a severe complication of advanced heart failure (HF), characterized by involuntary weight loss and muscle wasting, leading to poor outcomes and higher mortality. Despite its severity, CC remains under-recognized and undertreated, lacking targeted therapies specifically addressing its pathophysiology. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), though beneficial in reducing cardiovascular risk in patients with HF, may exacerbate muscle wasting in cachectic patients, necessitating further investigation. Non-pharmacological strategies, including tailored nutritional support and exercise programs, have shown positive effects on body composition and quality of life in patients with CC. However, there remains a gap in recommendations tailored to preventive strategies and pharmacologic therapies for patients with CC and concomitant GLP-1RA use. This review highlights the multifactorial mechanisms underlying CC and current and emerging therapeutic approaches for mitigating HF-related sarcopenia while on GLP-1RAs.