Search Results (254)

Cardiogenic shock secondary to acute myocardial infarction complicated by mechanical failure remains associated with high mortality despite advances in cardiac surgery and mechanical circulatory support. We report the case of a 42-year-old patient with posterior papillary muscle rupture leading to severe mitral regurgitation, managed with emergency surgical intervention and extracorporeal membrane oxygenation. The patient, with a history of Type I Bipolar Disorder under long-term lithium therapy and chronic Cannabis use, presented in critical condition with cardiogenic shock (Killip IV), acute pulmonary edema, and ST-segment elevation myocardial infarction in the infero-posterior territory. Coronary angiography revealed right coronary artery occlusion and involvement of an obtuse marginal branch. Emergency mitral valve replacement with a mechanical prosthesis and aortocoronary bypass were performed. Due to failure to wean from cardiopulmonary bypass, central veno-arterial ECMO was initiated. The postoperative course was complicated by hemodynamic instability and recurrent pericardial collections requiring repeated surgical interventions and conversion to peripheral ECMO. Multiorgan dysfunction developed, including hepato-renal failure requiring hemofiltration, neurological injury, respiratory impairment, and neuropsychiatric complications. Despite these challenges, progressive recovery was achieved under intensive multidisciplinary management. This case emphasizes the importance of early surgical correction and tailored ECMO support in managing post-infarction mechanical complications. Full article

Background: Cardiogenic shock (CS) is characterized as a state of low cardiac output that is frequently associated with multisystem organ failure. For over two decades, revascularization of the culprit lesion remained the only interventional treatment option to improve outcomes in CS following acute myocardial infarction. However, recently published data provide evidence that the use of a microaxial flow pump for mechanical circulatory support (MCS) in STEMI-related cardiogenic shock significantly reduced mortality after 180 days. Increased rates of complications such as sepsis were observed under MCS. The present study aimed to investigate the influence of sepsis on prognoses in patients with CS receiving temporary MCS with a microaxial flow pump. Methods and Results: This retrospective cohort study included 38 patients who received a microaxial flow pump for CS between 2014 and 2017. All patients were analyzed for the presence of sepsis, defined as infection and an increase in the Sequential Organ Failure Assessment (SOFA) score of ≥2 points. Analyzed clinical outcomes included all-cause mortality after 30 and 365 days and changes in renal function. A total of 38 patients were included in the final analysis. The 30-day all-cause mortality was significantly higher in the sepsis group than in the no-sepsis group (53.9% vs. 8.3%, p = 0.014). The findings were consistent for mortality at 365 days (65.4% vs. 16.7%, p = 0.008). Conclusions: These results indicate that sepsis significantly increases the risk of all-cause mortality at 30 and 365 days among patients with CS following AMI and receiving MCS via a microaxial flow pump. Full article

Background: Segmental arterial mediolysis (SAM) is a non-inflammatory vasculopathy that primarily affects the abdominal visceral arteries leading to hemorrhage, ischemia, or pseudoaneurysms. Its presentation can be mimicked by other vasculopathies including vasculitis involving the medium-sized blood vessels making it difficult to diagnose. Case Presentation: A 55-year-old woman presented with a two-hour history of sudden-onset, severe epigastric pain radiating to the chest. She was noted to be hypotensive with low hemoglobin 8.8 g/dL suspicious for a hemorrhagic cause. Her case was complicated by elevated international normalized ratio 3.7 in the setting of warfarin therapy for the mechanical mitral valve. The remainder of her complete blood count, complete metabolic panel, inflammatory markers, autoantibody serologies, and infectious testing were negative. Abdominal computed tomography angiogram revealed hemoperitoneum, bilateral renal infarctions, a large mesenteric hematoma, aneurysmal disease of the common hepatic and inferior mesenteric arteries, thrombosis and proximal dissection of the superior mesenteric artery, acute thrombosis of the left external iliac vein, and multiple sites of arterial extravasation from the pancreaticoduodenal artery and its branches. Mesenteric artery angiogram showed multivessel visceral artery aneurysms and stenoses characteristic of SAM for which she underwent transcatheter arterial embolization of the bleeding vascular bed. We provide a narrative literature review with a focus on common presentations and differentiating characteristics of vasculopathies that can involve medium-sized blood vessels. It is important to accurately diagnose SAM and its potential mimics as management strategies differ. Conclusions: SAM presents with medium vessel vasculopathy without vasculitis. Differentiation from mimics can be difficult but aided by familiarity of their characteristic findings and differentiating clinical characteristics. Full article

Myocardial infarction initiates complex remodeling processes involving the renin–angiotensin system, through activation of the angiotensin II type 1 receptor (AT₁R). This study correlated AT₁R expression with fibrosis and cardiac function in the heart and kidneys following cardiac ischemic injury in animal models. Male Sprague-Dawley rats underwent Sham surgery, Ischemia/Reperfusion (I/R, 20-min ligation) or Permanent Ligation (PL) of the left anterior descending artery. Cardiac function was assessed by echocardiography. AT₁R expression was measured in the heart (infarct and remote areas) and kidneys (cortex, medulla) via [¹²⁵Iodine]Sarcosine¹-Isoleucine⁸-Angiotensin II autoradiography. Collagen deposition was evaluated through picrosirius red staining. Left ventricular (LV) ejection fraction declined in PL models but remained stable following I/R. Post-I/R, a transient increase in cardiac AT₁R (day-3 to week-5) correlated with an increase in collagen, whereas after PL, elevations persisted through week-12. Infarct areas consistently displayed higher AT₁R and collagen than remote areas. Renal AT₁R and collagen levels were unchanged across groups. In analyses with pooled animals, cardiac AT₁R expression correlated with collagen and inversely correlated with LV Fractional Shortening (LVFS), whereas LVFS inversely correlated with collagen deposition. These findings suggest that cardiac AT₁R levels may serve as a target of cardiac remodeling, while changes in renal AT₁R appear less pronounced. Full article

Background/Objectives: Chronic Obstructive Pulmonary Disease (COPD) is frequently associated with multiple comorbidities that influence prognosis. The comorbidome is a graphical representation of both the prevalence and strength of association of each comorbidity with COPD, allowing rapid identification of the most relevant risk factors. The aim of this study was to evaluate the association between comorbidities and mortality in patients with COPD using a comorbidome approach. Methods: We conducted a retrospective cohort study of 500 patients aged ≥40 years with COPD treated between 2005 and 2020 at Clínica Universidad de La Sabana (Chía, Colombia). Demographic variables, comorbidities, and mortality were recorded. The prevalence of each comorbidity was expressed as a percentage, and their association with mortality was assessed using odds ratios (OR) derived from univariate contingency tables with 95% confidence intervals (95% CI). The comorbidome was constructed by plotting the inverse odds ratio (1/OR) against the prevalence of each condition. Results: The mean age was 76.6 years (SD 11.3). Overall mortality was 28.4%. The most prevalent comorbidities were hypertension (45.2%) and smoking (38%). Comorbidities significantly associated with mortality in unadjusted analyses included congestive heart failure (OR: 4.28; 95% CI: 2.55–7.18), arrhythmias (OR: 2.86; 95% CI: 1.60–5.13), acute myocardial infarction (OR: 2.58; 95% CI: 1.52–4.38), moderate or severe renal disease (OR: 2.08; 95% CI: 1.07–4.04), peripheral vascular disease (OR: 1.94; 95% CI: 1.10–3.40), and hypertension (OR: 1.66; 95% CI: 1.12–2.46). Conclusions: The most prevalent comorbidities were hypertension and smoking. However, the conditions significantly associated with mortality in unadjusted analyses were congestive heart failure, arrhythmias, acute myocardial infarction, moderate or severe renal disease, peripheral vascular disease, and hypertension. Full article

Sodium glucose-1 cotransporter (SGLT1) is a low-capacity, high-affinity glucose transporter expressed in the proximal renal tubule. It is also expressed in different human tissues and, primarily, in the brush border of the small intestine. At this level, SGLT1 inhibition results in an increase in glucose supply to the distal intestine with a reduction in intestinal pH and a consequent alteration of the intestinal microbiota. Specifically, SGLT1 inhibitors (SGLT1is) lead to an intensification of the production of short-chain fatty acids (SCFAs) and an enhancement of the incretin pathway. Potential mechanisms by which SGLT1is could reduce the occurrence of stroke and myocardial infarction may therefore involve the anti-inflammatory, anti-fibrotic and anti-atherosclerotic effects associated with an increased production of endogenous glucagon-like peptide-1 (GLP-1). Full article

Background: Despite advances in reperfusion therapy, ST-segment elevation myocardial infarction (STEMI) remains associated with substantial morbidity and mortality. Early identification of predictors of adverse outcomes is essential for improving risk stratification. Methods: This retrospective study included 512 STEMI patients who underwent coronary revascularization within 6 h of symptom onset. Clinical, laboratory, angiographic and echocardiographic variables were analyzed. The primary endpoint was in-hospital mortality. Secondary outcomes included reduced left ventricular ejection fraction (LVEF < 40%) and moderate-to-severe ischemic mitral regurgitation (IMR). Independent predictors of in-hospital mortality were identified using multivariable logistic regression, while secondary outcomes were described to characterize the study population. Model performance was evaluated using ROC analysis. Results: In-hospital mortality occurred in 9.4% of patients. Reduced LVEF was present in 26.2%, and IMR in 10.9%. Independent predictors of mortality included LVEF < 40% (OR 5.72, 95% CI 2.77–11.80, p < 0.001), IMR (OR 2.61, 95% CI 1.14–5.97, p = 0.023), lower hemoglobin levels (OR 0.74, 95% CI 0.61–0.91, p = 0.003), and reduced glomerular filtration rate (OR 0.96, 95% CI 0.95–0.98, p < 0.001). The model demonstrated good discrimination (AUC 0.88). Complete revascularization was not independently associated with mortality. Conclusions: Left ventricular dysfunction, IMR, anemia, and renal impairment are strong predictors of in-hospital mortality in STEMI patients. Integrating echocardiographic and laboratory parameters may improve early risk stratification and guide clinical decision-making. Full article

Background and Clinical Significance: Nonbacterial thrombotic endocarditis (NBTE) is a sterile fibrin-platelet valvular condition associated with malignancy and hypercoagulable states. It produces friable vegetations prone to systemic embolization, often presenting as multifocal ischemic stroke. While modestly linked to advanced adenocarcinomas, its association with melanoma is exceedingly rare; Case Presentation: We present a 43-year-old man with recently diagnosed metastatic melanoma who presented with fever, confusion and abdominal pain. Brain magnetic resonance imaging (MRI) revealed multifocal bilateral acute infarcts. Additional imaging demonstrated splenic and bilateral renal infarcts. Transesophageal echocardiography (TEE) revealed an 8 mm × 7 mm multilobar lesion on the posterior mitral valve leaflet. Blood cultures remained persistently negative; autoimmune and infectious workup were unrevealing, and positron emission tomography-computed tomography (PET-CT) showed no cardiac hypermetabolism. Despite empiric antibiotics for suspected infective endocarditis (IE), progressive embolic infarcts occurred. After exclusion of infection, NBTE was considered, and therapeutic enoxaparin was initiated, resulting in clinical stabilization without hemorrhagic conversion; Conclusions: Distinguishing NBTE from IE remains challenging due to overlapping and nonspecific imaging findings. TEE is the preferred diagnostic modality because of its high sensitivity for detecting small valvular vegetations. Adjunctive imaging modalities such as brain MRI and PET-CT may support the diagnosis by demonstrating embolic patterns or excluding metabolically active infectious vegetations. Management primarily relies on systemic anticoagulation, while percutaneous vegetation aspiration may represent a potential diagnostic and therapeutic strategy. Clinicians should maintain high suspicion of this condition in patients with advanced melanoma and other malignancies presenting with multifocal embolic phenomena and negative cultures to enable timely anticoagulation. Full article

Background: Patients with advanced chronic kidney disease (CKD) experience disproportionately high ischemic and bleeding risks following acute coronary syndrome (ACS), yet remain markedly underrepresented in randomized trials of antiplatelet therapy. Consequently, real-world data describing antiplatelet prescribing patterns and clinical outcomes in this population are limited. Objectives: To describe real-world antiplatelet use and 12-month clinical outcomes in patients with advanced CKD and end-stage renal disease (ESRD) following ACS. Methods: We conducted a single-center, retrospective cohort study including adults with advanced CKD (stage 4–5) or dialysis-dependent ESRD hospitalized with ACS and discharged on dual antiplatelet therapy. Baseline characteristics, revascularization strategies, and clinical outcomes were collected. Outcomes of interest included all-cause mortality, recurrent ischemic events (recurrent myocardial infarction, stroke or transient ischemic attack, or repeat revascularization), and bleeding events defined by Thrombolysis in Myocardial Infarction (TIMI) criteria over 12 months. All analyses were descriptive in nature. Results: A total of 222 patients were included; clopidogrel was prescribed in 96.0% of patients and ticagrelor in 4.0%. The cohort was elderly, highly comorbid, and predominantly dialysis-dependent. At 12 months, all-cause mortality occurred in approximately one-third of patients, recurrent ischemic events were frequent, and bleeding complications were common. Most bleeding events occurred in dialysis-dependent individuals. Outcomes among ticagrelor-treated patients are reported descriptively only due to the very small sample size. Conclusions: In this real-world cohort of patients with advanced CKD and ESRD following ACS, a substantial burden of mortality, recurrent ischemic events, and bleeding complications was observed, underscoring the narrow therapeutic window in this high-risk population. These findings are descriptive and hypothesis-generating, supporting the need for individualized antiplatelet strategies and prospective studies specifically enrolling patients with advanced CKD. Full article

Background: Critically ill cardiac patients who require invasive mechanical ventilation represent a high-risk population with persistently elevated in-hospital mortality, despite advances in cardiovascular and critical care management. Real-world data describing clinical profiles and prognostic patterns in this population remain limited. Objectives: The aim of this study was to characterize clinical profiles and prognostic patterns among critically ill cardiac patients requiring invasive mechanical ventilation and to identify variables associated with in-hospital mortality. Methods: We conducted a five-year retrospective observational cohort study, including 492 adult patients admitted to a tertiary cardiovascular intensive care unit who required invasive mechanical ventilation. The demographic characteristics, cardiovascular risk factors, primary cardiac diagnoses, major in-hospital complications, duration of mechanical ventilation, length of hospital stay, and in-hospital mortality were analyzed. Results: The overall in-hospital mortality was 53.9%. Acute myocardial infarction was the most frequent primary diagnosis. Advanced age, diabetes mellitus, cardiogenic shock, acute renal dysfunction, hepatic dysfunction and prolonged hospitalization were significantly associated with increased mortality (p < 0.05 for all comparisons). Cardiogenic shock showed the strongest association (p < 0.001). Ventilator-associated respiratory infections occurred in 16.9% of patients, and were associated with a prolonged hospital stay (p < 0.05), without a statistically significant association with mortality. Conclusions: Critically ill cardiac patients requiring invasive mechanical ventilation exhibit distinct high-risk clinical profiles characterized by advanced age, cardiogenic shock, metabolic comorbidities, and the development of multi-organ dysfunction. These findings highlight prognostic patterns that may support risk stratification and generate hypotheses for future prospective studies in cardiac intensive care. Full article

Background: Fibroblast growth factor-23 (FGF23) is a key regulator of phosphate homeostasis and an emerging biomarker in cardiovascular disease. Emerging data suggest that FGF23 may also contribute to the pathophysiology of myocardial infarction (MI), but existing studies have largely focused on non-acute stages. To address this gap, we investigated early FGF23 regulation by characterizing serum concentration kinetics over the first 24 h following MI, using both a clinical MI model (TASH) and a cohort of patients with ST-elevation myocardial infarction (STEMI). Methods: Circulating FGF23 concentrations (cFGF23; RU/mL) were determined by C-terminal ELISA in patients with preserved renal function (eGFR > 30 mL/min/1.73 m²). TASH (transcoronary septal ablation) was carried out in patients with hypertrophic obstructive cardiomyopathy (n = 38). Venous serum samples were taken at baseline (pre-TASH) and at 30′, 60′, 2 h, 4 h and 24 h post-TASH. For the STEMI cohort (n = 18), serum was sampled immediately before and 3 h after coronary recanalization. All samples were processed using standardized procedures prior to analysis. Changes over time were assessed using the Friedman test with Bonferroni-corrected pairwise Wilcoxon comparisons. Results: FGF23 concentrations changed significantly over time after TASH (Friedman test, p < 0.000001, Kendall’s W = 0.518). Baseline FGF23 was 28.9 (19.4–71.0) RU/mL and increased significantly at 30′ (68.2 (36.2–178.7) RU/mL, adjusted p < 0.0001 **) after TASH. Concentrations remained elevated at 60′ (54.8 (31.6–118.3) RU/mL; adjusted p = 0.0019 *), returned to baseline at 2 h (30.9 (20–71.2) RU/mL; adjusted p = 1.0 vs. baseline) and decreased significantly below baseline at 4 h (24 (12.13–37.5) RU/mL, adjusted p = 0.0215 *). By 24 h, FGF23 had returned to baseline levels (28.8 (12.8–57.3) RU/mL; adjusted p = 1.0 vs. baseline). Although concentrations were numerically higher than at the 4 h nadir, this recovery did not reach statistical significance (adjusted p = 0.136 vs. 4 h). In STEMI patients, a non-significant decrease was observed from baseline (27 (15.5–35.75) RU/mL) to 3 h after recanalization (15.5 (6.75–34.25) RU/mL; p = 0.074, effect size r = 0.422). In an exploratory normalized analysis, the decline reached significance (p = 0.0241). Conclusions: The triphasic kinetics of circulating FGF23 in TASH patients—characterized by an early rise, transient undershoot, and a recovery toward baseline with a continuing upward trend—are consistent with a dynamic release-and-clearance pattern following myocardial injury. These findings are hypothesis-generating and warrant further investigation in larger cohorts with additional biomarkers to elucidate the source, regulation, and potential functional significance of FGF23 in the acute phase of myocardial infarction. Full article

Objectives: Malperfusion is a major determinant of outcome in acute type A aortic dissection (ATAAD), yet its heterogeneous patterns and prognostic impact remain incompletely defined. We investigated the association between malperfusion burden, territory-specific involvement, and early outcomes after emergency ATAAD repair. Methods: We performed a retrospective single-center study including 483 consecutive patients undergoing emergency surgery for ATAAD (2010–2022). Malperfusion was classified by coronary, visceral, and peripheral territories and stratified as none, single-territory, or multidistrict (≥2 territories). The primary outcome was in-hospital mortality. Secondary outcomes included stroke, renal replacement therapy, peri-procedural myocardial infarction, major vascular events, and a composite endpoint of major adverse events (MAEs). Multivariable logistic regression identified independent predictors. Results: Overall, 68.5% of the population were male with a mean age of 65.4 ± 12.1 years. Malperfusion was present in 151 patients (31.3%), including 131 (27.1%) with single-territory and 20 (4.1%) with multidistrict involvement. In-hospital mortality increased stepwise with malperfusion burden (12.7%, 19.8%, and 50.0%; p < 0.001). MAEs occurred in 36.6% of patients, with a similar gradient (31.2%, 46.2%, and 65.0%, p < 0.001). In multivariable analysis, preoperative shock, neurological deficit, descending aortic involvement, and redo surgery were independent predictors of MAEs, whereas malperfusion burden showed an attenuated association after adjustment. Territory-specific analyses revealed strong associations between coronary malperfusion and peri-procedural myocardial infarction, visceral malperfusion and postoperative dialysis, and peripheral malperfusion and major vascular events. Conclusions: Malperfusion burden is associated with worse early outcomes after ATAAD repair but largely reflects underlying clinical severity. Distinct malperfusion territories confer specific postoperative risks, supporting a pattern-based approach to perioperative risk stratification. Full article

Background/Objectives: Acute coronary syndromes (ACS) encompass a spectrum of clinical entities from unstable angina to non–ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI), all associated with significant morbidity and mortality. Inflammation plays a central role in the pathophysiology of ACS, contributing to atherosclerotic plaque destabilization, myocardial injury, and adverse clinical outcomes. Inflammatory biomarkers, together with N-terminal pro–B-type natriuretic peptide (NT-proBNP), are increasingly used for risk stratification, yet their prognostic value across different ACS presentations remains unclear. This study aimed to assess the prognostic value of inflammatory status in patients with acute coronary syndromes in a single-center cohort. Methods: This prospective observational study included 100 consecutive patients with ACS and elevated inflammatory biomarkers, enrolled in 2024–2025 at a tertiary cardiovascular center. Inflammatory status was assessed by using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII); NT-proBNP was also measured. The primary endpoint was in-hospital MACE, defined as cardiovascular death, recurrent myocardial infarction, stroke, urgent coronary revascularization, or acute heart failure requiring escalation of therapy. Multivariable logistic regression and ROC analyses were performed. Results: Among the 100 ACS patients, half experienced in-hospital MACE. Compared with those without events, patients with MACE were older (p = 0.003) and had higher inflammatory biomarkers—CRP (p < 0.001; strongest association), NLR (p = 0.030), and SII (p = 0.042)—as well as higher NT-proBNP (p = 0.002). Patients with MACE also showed reduced renal function (p < 0.001) and lower left ventricular systolic function, reflected by reduced LVEF (p = 0.001), indicating concomitant renal impairment and ventricular dysfunction. Hypertension was more prevalent in the MACE group (p = 0.028), and new-onset atrial fibrillation was significantly more common among these patients (p < 0.001). In multivariable analysis, LVEF emerged as an independent predictor of short-term outcomes (OR 0.934 per 1% increase; p = 0.047). Conclusions: Inflammatory activation appears closely linked to the occurrence of in-hospital adverse events in patients with acute coronary syndromes. While left ventricular ejection fraction remained an independent determinant of short-term outcomes, inflammatory biomarkers may provide complementary insight into the inflammatory burden accompanying ACS. Full article

Background: The endothelial activation and stress index (EASIX), derived from the serum lactate dehydrogenase, creatinine, and platelet counts, is a composite biomarker for endothelial dysfunction and systemic stress. It has been developed to predict clinical outcomes in hematologic malignancies. This study aimed to investigate the EASIX’s predictive role in contrast-induced nephropathy (CIN) and in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: A total of 1552 patients with STEMI who underwent primary PCI were retrospectively included. The patients were divided into two groups: CIN (+) and CIN (−). Baseline demographic, laboratory, clinic, and procedural variables were compared between the two groups. Logistic regression analysis was performed to identify independent predictors of CIN and in-hospital mortality, while receiver operating characteristic (ROC) curves were used to determine the optimal EASIX cut-off values. Results: CIN developed in 7.6% (n = 118) of the study population, and these patients had significantly increased EASIX scores. Those with CIN were older and exhibited higher rates of diabetes mellitus, chronic kidney disease (CKD), and decreased left ventricular ejection fraction (LVEF) (all p < 0.001). In multivariable analysis, age (OR 1.053), CKD (OR 1.338), reduced LVEF (OR 0.965), and EASIX (OR 2.467) independently predicted CIN. EASIX > 0.93 demonstrated strong discriminatory ability (AUC 0.785; sensitivity 72% and specificity 72%). EASIX also independently predicted in-hospital mortality (OR 3.592), with an optimal cut-off > 0.88 (AUC 0.774). Conclusions: By integrating markers of renal function, endothelial activation, and systemic stress, EASIX may serve as a useful and reliable indicator for predicting CIN development and in-hospital mortality in STEMI patients undergoing primary PCI. Full article

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. Full article