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Sodium–Glucose Cotransporter-2 Inhibitors in Cardiogenic Shock with or without Mechanical Circulatory Support: A Scoping Review Protocol Background Sodium–glucose cotransporter-2 (SGLT-2) inhibitors reduce mortality and heart failure hospitalization across chronic and acute heart failure populations. However, patients with cardiogenic shock (CS) have been systematically excluded from pivotal trials. To our knowledge there exists very limited data evaluating SGLT-2 inhibitors in patients receiving inotropic/vasopressor support and/or mechanical circulatory support (MCS), including VA-ECMO, Impella, or intra-aortic balloon pump for cardiogenic shock. Moreover, safety in advanced renal dysfunction (eGFR <20 mL/min/1.73m²) and or during renal replacement therapy (RRT) in with cardiogenic shock states remains poorly characterized. This scoping review will systematically map all available evidence regarding SGLT-2 inhibitor use in cardiogenic shock, with and without mechanical circulatory support and with and without significant renal dysfunction (eGFR <20). Objectives Primary Objective: To identify and characterize all published evidence evaluating SGLT-2 inhibitor use in adults with cardiogenic shock. Secondary Objectives: 1. Describe populations studied (AMI-CS vs non-ischemic CS; SCAI stage where reported). 2. Characterize use in patients receiving mechanical circulatory support. 3. Summarize reported safety outcomes, including acute kidney injury, RRT, hypotension, and ketoacidosis. 4. Identify gaps in evidence to inform future phase 2–3 clinical trials. Methods This protocol follows the Joanna Briggs Institute framework for scoping reviews11 and will be reported according to PRISMA-ScR guidelines. The population (P) included adult patients in cardiogenic shock, the concept (C) will be SGLT inhibitors, and the context (C) intensive care units, coronary care units, cardiothoracic surgery units. A scoping rather than a systematic review design will be used because the objective is to map and summarize the available evidence across multiple domains rather than to evaluate the effect of specific interventions. Given the heterogeneity of study designs and outcomes, a scoping approach was considered most appropriate to identify knowledge gaps and inform future systematic reviews and to help inform grant applications and study design. The review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines12 and with regard to the Ark-sey and O’Malley methodological framework approach for scoping reviews.13 The completed PRISMA-ScR checklist will be available in the Supplemental Material. Eligibility Criteria (PCC Framework) Population: • Adults ≥18 years • Cardiogenic shock defined by SCAI staging, hemodynamic criteria, trial-defined shock, or clinical documentation • Patients with or without mechanical circulatory support (VA-ECMO, Impella, intra-aortic balloon pump, surgical ventricular assist devices) Concept: Exposure to any SGLT-2 inhibitor at any dose or timing relative to shock onset or MCS initiation. Context: Acute hospital settings including intensive care units, coronary care units, and cardiac surgical units. Study Types Included: Randomized controlled trials Non-r-andomized interventional studies Observational cohort studies Registry analyses Case series (≥5 patients) Excluded: Single case reports Narrative reviews Editorials Animal studies Pediatric studies Mechanistic studies Information Sources Electronic databases: - PUBMED - MEDLINE (Ovid) - EMBASE - Cochrane Library - Scopus Trial registries: - ClinicalTrials.gov - WHO ICTRP Grey literature: - Major cardiology and critical care conference abstracts (AHA, ACC, ESC, EuroELSO) No date restriction will be applied. Searches will be limited to English-language publications. Search Strategy Search terms will combine controlled vocabulary and free-text terms for cardiogenic shock, mechanical circulatory support, and individual SGLT-2 inhibitors. Example search string: (cardiogenic shock OR SCAI OR acute heart failure shock) AND (dapagliflozin OR empagliflozin OR canagliflozin OR ertugliflozin OR SGLT2 inhibitor) AND (ECMO OR Impella OR mechanical circulatory support OR IABP) The full strategy will be developed with an academic librarian and reported in the final manuscript. Study Selection Two reviewers will independently screen titles and abstracts. Full-text articles will be assessed against eligibility criteria. Disagreements will be resolved by consensus or third-reviewer adjudication. The selection process will be illustrated using a PRISMA-ScR flow diagram. Data Extraction Data will be extracted independently by two reviewers using a predefined charting form. Variables will include: - Study characteristics (author, year, country, design, sample size) - Shock definition and SCAI stage (if reported) - Aetiology (AMI vs non-AMI) - Baseline renal function and lactate (if reported) - SGLT-2 agent, dose, timing of initiation - MCS type and duration - Mortality outcomes - Acute kidney injury (KDIGO stage) - Major adverse kidney events (MAKE-14, MAKE-30) [composite of death or initiation of renal replacement therapy] - Renal replacement therapy initiation or continuation - Hypotension - Ketoacidosis - Dosing of vasoactive agents (if reported) - Fluid balance (if reported) - ICU and hospital length of stay - Urinary tract infection Risk of Bias As per scoping review methodology, formal risk-of-bias assessment will not determine inclusion. Study design limitations will be described narratively to contextualise findings. Data Synthesis No quantitative meta-analysis is planned due to anticipated heterogeneity. Results will be presented as: 1. Descriptive summary tables 2. Evidence mapping stratified by shock phenotype, MCS use, and renal function strata 3. Gap analysis matrix identifying the absence of prospective CS trials, absence of VA-ECMO cohorts, and lack of data in advanced renal dysfunction Ethics and Dissemination Ethics approval is not required as this review will synthesize published data. Findings will be submitted to a peer-reviewed critical care journal and presented at international cardiology and intensive care conferences. Significance Cardiogenic shock remains associated with high mortality despite advances in revascularization and mechanical circulatory support. No pharmacologic therapy has demonstrated mortality reduction in established CS. This scoping review will define the current evidence landscape and provide a structured foundation for early-phase safety trials in cardiogenic shock, including patients supported with MCS.