We present the case of a 51-year-old male with known congestive heart failure and acute myocarditis who presented to the emergency department (ED) with swollen testicles and urinary symptoms two weeks after the initiation of sodium glucose cotransporter 2 (SGLT2) inhibitor treatment. Abdominal and pelvic computed tomography (CT) scan was consistent with the diagnosis of Fournier’s gangrene (FG). Intravenous antibiotics were administered and surgical exploratory intervention and excision of necrotic tissue were performed, stopping the evolution of necrotizing fasciitis. FG, a reported adverse event, may rarely occur when SGLT2 inhibitors are administered in patients with diabetes. To our knowledge, there have been no reported cases of FG in Romania since SLGT2 inhibitors were approved. The distinguishing feature of this case is that the patient was not diabetic, which emphasizes that patients without diabetes who are treated for heart failure with SGLT2 inhibitors may also be at risk of developing genitourinary infections. The association of predisposing factors may have contributed to the development of FG in this case and even though the benefits of SGLT2 inhibitors outweigh the risks, serious adverse events need to be voluntarily reported in order to intervene promptly, verify the relationship, and minimize the risk of bias.

Background and Objectives: This systematic review and meta-analysis aims to evaluate whether the benefits of sodium–glucose co-transporter-2 (SGLT2) inhibitors on cardiovascular outcomes extend when initiated in patients with acute coronary syndrome (ACS), regardless of diabetic status. Materials and Methods: PubMed, Embase, and the Cochrane Library were searched from 2015 up to July 2025, according to PRISMA 2020 guidelines. Eligible studies were randomized controlled trials (RCTs) and observational studies comparing SGLT2 inhibitors with controls in post-ACS patients. Articles without full-text data for extraction, with unavailable outcome data or evaluating patients with stable coronary artery disease (CAD) were excluded. Primary outcomes were all-cause and cardiovascular (CV) mortality. Secondary outcomes included recurrent myocardial infarction (MI), rehospitalization for ACS, revascularization and stroke. Meta-analysis was conducted using the R statistical software (Version 4.5.1). Subgroup analysis was performed by study design to evaluate outcomes in type 2 diabetes mellitus (T2DM) populations. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2.0 and Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results: A total of 16 studies were included in the meta-analysis, encompassing over 130,000 patients. Initiation of SGLT2 inhibitors after ACS was associated with a significant reduction in the primary outcome of all-cause mortality [hazard ratio (HR) = 0.77; (95% confidence interval (CI): 0.67–0.89)] and CV mortality [HR = 0.83; (95% CI: 0.70–0.99)]. In subgroup analyses, patients with T2DM experienced a significant reduction in all-cause mortality [HR = 0.73, (95% CI: 0.62–0.86)] and recurrent MI [HR = 0.83, (95% CI: 0.69–0.99)]. Conclusions: Initiation of SGLT2 inhibitors after ACS is associated with a significant reduction in all-cause and CV mortality. Subgroup analysis further demonstrated a reduction in all-cause mortality and recurrent myocardial infarction among patients with T2DM, while in patients without diabetes, no significant effects were observed. Although evidence certainty ranged from low to moderate and large RCTs are still ongoing, these findings support the early introduction of SGLT2 inhibitors in eligible patients with T2DM following ACS, pending confirmation by large, prospective clinical trials.

Background/Objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors provide well-established cardiovascular and renal benefits in heart failure (HF), type 2 diabetes (T2DM), and chronic kidney disease (CKD). Although emerging trials suggest potential value after acute myocardial infarction (AMI), SGLT2 inhibitors currently have no formal indication for AMI, and real-world prescribing patterns in this setting remain uncharacterized. This study aimed to evaluate in-hospital and post-discharge prescribing patterns and clinical predictors of SGLT2 inhibitor initiation among AMI patients eligible for therapy based on guideline-supported indications. Methods: We conducted a retrospective cohort study including 244 consecutive AMI patients hospitalized between January 2023 and July 2024. A total of 180 (73.7%) met guideline-based eligibility criteria for SGLT2 inhibitors. Four multivariable logistic regression models were developed to identify independent predictors of SGLT2 inhibitor prescription. Results: A total of 117 patients (65%) received SGLT2 inhibitors and 63 (35%) remained untreated. Receivers were more frequently male (81% vs. 65%) and exhibited lower left ventricular ejection fraction (LVEF) (38.2 ± 6.7% vs. 42.4 ± 8.3%), larger ventricular volumes, and higher Killip class at presentation. HF patients with preserved ejection fraction (HFpEF) were markedly undertreated (25.9%) compared with mid-range (HFmrEF) (69.8%) or reduced (HFrEF) (73.7%). Across all models, HFpEF was a strong negative predictor of prescribing (OR 0.071–0.081, p < 0.001), while male sex and markers of clinical severity were associated with higher likelihood of initiation. Many untreated patients had T2DM or CKD despite guideline-based eligibility. No serious adverse events attributable to SGLT2 inhibitors were reported. Conclusions: In this real-world AMI cohort, SGLT2 inhibitors were prescribed primarily in relation to established indications for HF, T2DM, and CKD, yet their use remained highly variable in the absence of a dedicated recommendation for AMI. Significant therapeutic gaps were observed in HFpEF and high-risk cardiometabolic profiles, underscoring the need for clearer guidance and standardized pathways to support consistent initiation in eligible patients after MI.

Background and Objectives: SGLT2 inhibitors are foundational in heart failure therapy, yet their impact on left ventricular (LV) remodeling immediately following acute coronary syndrome (ACS) remains less defined. This study evaluated the association between early SGLT2 inhibitor initiation and structural recovery in a real-world post-ACS cohort. Materials and Methods: We conducted a retrospective observational study including 238 revascularized ACS patients, stratified into an SGLT2 inhibitor group (n = 71) and a control group (n = 167). Changes in LV ejection fraction (LVEF) and indexed LV mass (LVMi) were assessed by echocardiography at baseline and follow-up (mean 286 days). Multivariable regression models were adjusted for baseline imbalances and tested for interactions with diabetes status. Results: A significant “confounding by indication” was observed; the SGLT2 group presented a high-risk phenotype with higher diabetes prevalence (56.3% vs. 25.7%, p < 0.001), lower baseline LVEF (38.3% vs. 43.3%), and greater hypertrophy. After adjustment, statistical independence was attenuated by baseline severity, yet the SGLT2 group achieved follow-up structural outcomes comparable to lower-risk controls. Interaction analysis indicated these trends were consistent regardless of diabetes status (p > 0.05). Conclusions: In this high-risk ACS population, early SGLT2 inhibitor therapy was associated with stabilization of cardiac structure. Despite a profound baseline disadvantage, the recovery trajectory effectively aligned with that of a lower-risk population, highlighting a clinically relevant pattern of structural stabilization consistent across metabolic subgroups.

Background: Guideline-directed medical therapy (GDMT) is recommended after acute myocardial infarction (AMI), particularly in patients with left ventricular systolic dysfunction, yet real-world implementation remains suboptimal. Whether greater early GDMT intensity is associated with post-infarction ventricular remodeling has not been fully established. We aimed to quantify the guideline-to-practice gap and evaluate the association between GDMT intensity, cardiac remodeling, and clinical outcomes after AMI. Methods: In this single-center retrospective cohort study, 186 consecutive patients hospitalized for AMI who underwent successful percutaneous coronary intervention and had baseline plus follow-up transthoracic echocardiography were included. GDMT intensity was defined as the number of prescribed foundational therapy classes at discharge (renin–angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter 2 inhibitors; range 0–4). The primary endpoint was change in left ventricular end-diastolic diameter (ΔLVEDD). Secondary endpoints included changes in left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular mass, and heart failure rehospitalization. Multivariable models adjusted for relevant clinical covariates were applied. Results: Only 18.8% of the overall cohort and 26.2% of patients with baseline left ventricular ejection fraction ≤ 40% received all four GDMT pillars. A graded association was observed between higher GDMT intensity and more favorable remodeling. In adjusted analyses, each additional GDMT pillar was associated with a greater reduction in LVEDD (β = 0.120 cm, p = 0.004). In the prespecified reduced-ejection-fraction subgroup, the association was stronger (β = 0.204 cm, p < 0.001). Higher GDMT intensity was also associated with lower odds of heart failure rehospitalization (odds ratio 0.384, 95% CI 0.195–0.754; p = 0.006). Conclusions: In this real-world post-AMI cohort, broader implementation of foundational GDMT at discharge was associated with more favorable early ventricular reverse remodeling and lower odds of heart failure rehospitalization. These findings highlight a persistent implementation gap and support prospective studies evaluating rapid comprehensive GDMT initiation after AMI.

Background/Objectives: Sodium–glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits beyond glycemic control, yet the specific biological pathways potentially linking SGLT2 inhibitor exposure to cardiovascular outcomes after acute myocardial infarction (AMI) remain incompletely characterized. Two biologically plausible pathways, serum uric acid (SUA) reduction and renal functional preservation, have been proposed, but not directly compared in a unified analytical framework. This study aimed to explore whether associations between SGLT2 inhibitor exposure and recurrent post-AMI outcomes may be more strongly linked to SUA reduction and to renal functional changes, using a hypothesis-generating causal mediation analysis. Methods: This retrospective observational cohort study included 142 consecutive patients hospitalized for AMI who underwent percutaneous coronary intervention (PCI) during the index hospitalization, reflecting standard-of-care management for AMI in this tertiary center. Patients were categorized by SGLT2 inhibitor exposure (n = 57) vs. controls (n = 85). Both diabetic (47.2%) and non-diabetic (52.8%) patients were included. The primary endpoint was change in SUA (ΔUA); the secondary endpoint was myocardial infarction (MI) recurrence. Causal mediation analysis with nonparametric bootstrap simulation tested both mechanistic pathways. Results: SGLT2 inhibitor therapy was associated with significant SUA reduction (ΔUA = −0.99 mg/dL vs. +0.56 mg/dL in controls; p < 0.001), consistent across diabetic and non-diabetic subgroups and independent of AMI recurrence. Each 1 mg/dL decrease in SUA was associated with lower odds of recurrent MI in the initial model (β = −0.25; p = 0.041). However, after incorporation of renal functional change, the uric acid-mediated pathway lost significance (ACME p = 0.462), whereas the renal-mediated pathway remained significant (ACME p = 0.038). Serum creatinine change emerged as the strongest independent predictor of MI recurrence (β = 2.22; p = 0.015). Conclusions: The findings are more consistent with a renal-mediated pathway than with an independent uric acid-mediated pathway in explaining the observed associations between SGLT2 inhibitor exposure and recurrent post-AMI outcomes. These hypothesis-generating results from a retrospective design warrant prospective validation.