Background Recurrence of acute myocarditis (AM) is challenging. The management and natural history of patients who experience a recurrence of AM (Re‐AM) remain poorly characterized. The aim of this study is to investigate clinical characteristics and outcomes of patients with Re‐AM. Methods In this international multicenter study, 141 consecutive patients with biopsy‐proven or cardiac magnetic resonance‐proven Re‐AM (35 [26–45] years, 77% male, median left ventricular ejection fraction 55%) were investigated and compared with 372 consecutive patients with single acute myocarditis (S‐AM). The primary outcome was a composite of all‐cause mortality, heart transplant and major ventricular arrhythmias. Results Patients with Re‐AM had more frequently a family history of cardiomyopathy (19% in Re‐AM versus 2.8% in S‐AM, P<0.001) and a diffuse late gadolinium enhancement compared with patients with S‐AM (46% in Re‐AM versus 34% in S‐AM, P=0.019). The extent of late gadolinium enhancement also increased between the first and the second AM episode in patients with Re‐AM (P=0.001). During a median follow‐up of 33 months (interquartile range, 23–52) patients with Re‐AM had a higher risk of primary outcome (P=0.001) compared with patients with S‐AM, as well as a significantly elevated competing risk of major ventricular arrhythmias (P<0.001), which remained independently associated even after adjustment (hazard ratio, 2.15 [95% CI, 1.15–4.04], P=0.017). A family history of cardiomyopathy, autoimmune diseases, and ring‐like late gadolinium enhancement was independently associated with a higher risk of recurrent AM. Conclusions Re‐AM is a distinct clinical subgroup of AM associated with generally worse prognosis and a specific increased arrhythmic risk compared with S‐AM.

INTRODUCTION:Elevated leucocytes, particularly neutrophils, are strongly associated with poor prognosis after acute myocardial infarction (AMI). However, inflammatory indices are not included in established post-AMI risk scores. We aimed to derive a novel, inflammation-based risk score with superior performance to contemporary scores to predict in-hospital mortality after AMI. METHODS AND RESULTS:This was a retrospective, multicentre, longitudinal cohort study including a derivation cohort of consecutive patients presenting with AMI between 2016 and 2023. The primary outcome was in-hospital mortality. Primary outcome risk estimates were derived by regularized machine learning techniques, incorporating leucocyte subpopulations, which we termed the INFLammation in Acute Myocardial diseases risk Estimation for Myocardial Infarction (INFLAME-MI) score. The INFLAME-MI score was validated in an external international cohort and compared to the Global Registry of Acute Coronary Events (GRACE) score. The INFLAME-MI score was derived from a cohort of 3028 AMI patients and tested in an external validation cohort of 682 AMI patients. It demonstrated strong internal discrimination (area under the curve [AUC] 0.88) and maintained excellent external predictive performance for the primary outcome, achieving a non-inferior AUC of 0.92 relative to the GRACE score (AUC 0.94, P = 0.256). Furthermore, INFLAME-MI demonstrated superior calibration and improved reclassification compared to the GRACE score (Hosmer-Lemeshow χ²₈ = 6.2 (P = 0.102) vs. χ²₈ = 22.9 (P < 0.001), respectively). CONCLUSION:INFLAME-MI is a novel, rapid, and easy-to-use risk score for in-hospital mortality after AMI, derived from common inflammatory indices. In external validation, it demonstrates comparable discrimination, improved calibration, and higher net benefit at ≤7% thresholds compared with the GRACE score, particularly within key decision-making ranges. Further work is needed to establish the INFLAME-MI score through validation of these findings in diverse, prospective patient cohorts.

Background Poorer cardiovascular outcomes among ethnic minorities have been reported, particularly during the COVID-19 pandemic. However, the relationship between ethnicity and quality of care after hospitalization for heart failure (HF) and long-term outcomes is largely unknown. Objectives The aim of this analysis is to investigate quality of care and longer-term outcomes of patients hospitalized with acute HF according to ethnicity. Methods Routinely collected data for England from the National Heart Failure Audit, National Health Service Hospital Episode Statistics, and Office for National Statistics death register from 2018 to 2023 were used to investigate the quality of care and outcomes after hospitalization with HF according to ethnicity. Results National Heart Failure Audit data for 239,890 patients admitted with HF were grouped by ethnicity as White (215,800), Black (6,610), Asian (12,940), and mixed/other (4,540), with median ages of 81 years (IQR: 73-88 years),75 years (IQR: 60-84 years), 77 years (IQR: 67-84 years), and 75 years (IQR: 61-84 years), respectively. Overall, patients had a median of 3 comorbidities (IQR: 2-4 comorbidities), with Asians having the greatest number. About 50% of patients had HF with reduced ejection fraction in all ethnic groups. For HF with reduced ejection fraction, White patients were least likely to be discharged on guideline-recommended therapies. Over a median follow-up of 68 weeks (IQR: 20-142 weeks), 122,980 (57%) White patients died, as did 2,860 (43%) Black patients, 6,270 (48%) Asian patients, and 1,900 (42%) patients of other/mixed ethnicity. About 90% of deaths were due to cardiovascular or respiratory causes. After adjusting for age, sex, socioeconomic factors, and variables associated with HF severity, all ethnic groups had lower mortality compared with White patients, including those who were Black (HR: 0.81; 95% CI: 0.78-0.84), Asian (HR: 0.77; 95% CI: 0.75-0.79), or from mixed/other ethnic groups (HR: 0.72; 95% CI: 0.69-0.75). Conclusions In a universal health care system, treating an ethnically diverse population hospitalized for HF, non-White patients received better pharmacological management, which was associated with better long-term outcomes.

BACKGROUND:No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS:In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS:Median age at presentation was 48 years (first to third quartile, 34-59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (first to third quartile, 25%-48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.9% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis-associated form (13.1%) at 3 years (P=0.15). CONCLUSIONS:Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06447935.

aSchool of Cardiovascular and Metabolic Medicine & Sciences, King's College London British Heart Foundation Centre of Excellence, James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK. bDepartment of Cardiology, King's College Hospital London, Denmark Hill, Brixton, London, SE5 9RS, UK. Corresponding author: Dr Daniel Bromage, School of Cardiovascular Medicine and Sciences, King's College London British Heart Foundation Centre of Excellence, James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK; Tel: +44 (0)20 7848 5189; e-mail: [email protected]. nothnig to disclose

Background: Heart failure with preserved ejection fraction is challenging to diagnose, precluding the initiation of prognostic medications. A deeper understanding of HFpEF phenotypes and trajectories could address this, however previous studies analyzed trial cohorts, limiting generalizability. Here we apply artificial intelligence (AI) algorithms to longitudinal electronic health record data (EHR) to characterize reproducible real-world HFpEF phenogroups. Methods: We applied natural language processing (NLP) to extract structured and unstructured data from EHRs at a multi-site hospital network, including comorbidities, echocardiographic measurements, and all-cause mortality outcomes. HFpEF cases were identified by applying contemporaneous guideline-directed criteria. Phenogroups were derived at the first documented mention of ?heart failure? using latent class analysis, then reassigned annually to quantify the frequency and directionality of transitions. External validation was performed at an independent hospital network. Results: We identified 2,223 patients (median age 75 years; 60% female) meeting HFpEF diagnostic criteria, with a median follow-up of 4 years. A clinician-recorded HFpEF diagnosis was present for only 10.4%. Four phenogroups were identified: Elderly-Atrial Dysfunction (32%), Cardio-Renal-Metabolic (23%), Obesity-Predominant (24%), and Young-Low Comorbidity (22%). The Young-Low Comorbidity group had the lowest rate of clinician-assigned HFpEF diagnosis (3%), and more than half of patients transitioned phenogroups within five years, suggesting this may represent an early-stage HFpEF phenotype. By contrast, Elderly-Atrial Dysfunction and Cardio-Renal-Metabolic groups displayed stable group membership (<10% transitioned), with high mortality rates (adjusted hazard ratio = 1.30 [1.02?1.67] and 1.49 [1.18?1.87] respectively). Phenogroup reproducibility was validated externally (n=3,349), demonstrating consistent clinical features and survival trends. Conclusion: AI-enabled phenotyping of real-world data identified reproducible, prognostically significant HFpEF phenogroups. The identification of an underrecognized, early-stage subgroup underscores a critical opportunity for earlier diagnosis and targeted intervention to alter the clinical trajectory. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Adrian Beecroft British Heart Foundation Cardiovascular Catalyst Award (CC/22/250022 to AMS, KOG, RJD and JT) with further support from the British Heart Foundation (CH/1999001/11735, RG/20/3/34823 and RE/18/2/34213 to AMS) and King?s College Hospital Charity (D/3003/122022/Shah/1188 to AMS). BSB is supported by an MRC Experimental Medicine grant (MR/W026198/1). KOG and DIB are each supported by MRC Clinician Scientist Fellowships (MR/Y001311/1 to KOG, MR/X001881/1 to DB). CAM, Advanced Fellowship, NIHR301338 is funded by the National Institute for Health and Care Research (NIHR). CAM further acknowledges support from the University of Manchester British Heart Foundation Research Excellence Award (RE/24/130017) and the NIHR Manchester Biomedical Research Centre (NIHR203308). The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: London South-East Research Ethics Committee approval (18/LO/2048) granted to the King's Electronic Records Research Interface (KERRI). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available from the corresponding author upon reasonable request.

Heart failure is a complex clinical syndrome affecting around 70 million individuals globally. It has a prevalence of 2% in Europe and North America and approximately 1% in Asia and South America. Accurate diagnosis relies on the presence of typical signs and symptoms, elevated natriuretic peptide concentrations, and evidence of cardiac structural or functional abnormalities using cardiac imaging techniques. Approximately half of all heart failure cases are attributed to reduced left ventricular systolic function-classified as heart failure with reduced ejection fraction (HFrEF). Current guideline-directed medical therapy has markedly improved survival and quality of life for patients with HFrEF. Contemporary management emphasises early initiation and rapid uptitration of four foundational drug classes-renin-angiotensin system inhibitors or angiotensin receptor-neprilysin inhibitors, β blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors-alongside diuretics for the symptom relief of volume overload. Despite advances in management, heart failure remains a leading cause of cardiovascular morbidity and mortality, partly due to absence of implementation of, and poor adherence to, medications. Future directions to improve outcomes include the integration of personalised medicine approaches, multiomic profiling, and innovative clinical trial designs to address residual risk and identify novel therapeutic targets. This Seminar provides an overview of the current diagnostic and pharmacological management of patients with HFrEF, highlighting the progress and outlining the challenges that remain.

AIMS:Elevated neutrophils are associated with a poor prognosis after acute myocardial infarction (AMI) but it is not known if ethnicity influences the association between neutrophil count and outcome. We aimed to describe the temporal dynamics of neutrophils after AMI, and assess the interaction between ethnicity, neutrophil count, and outcomes after AMI. METHODS:Consecutive patients presenting with AMI between 2016 and 2023 were divided into two groups according to their median neutrophil count. Ethnicity was dichotomised as white and other ethnic groups combined (referred to as 'ethnic minorities'). The primary outcome was in-hospital mortality, with a secondary outcome of 60-day mortality. RESULTS:In our study of 3062 AMI patients (76 % white, 24 % from ethnic minority groups), we found that neutrophil counts rose early post AMI, which coincided with a nadir of the other cell groups. We identified a relative baseline neutropenia in ethnic minority individuals, compared to white individuals (6.85 vs 8.42 × 109/L). We observed a significant, independent association between elevated neutrophils at baseline and the primary outcome of in-hospital mortality (OR 2.06, p < 0.001) and secondary outcome of 60-day all-cause mortality (HR 1.08, p = 0.002). Sub-group analysis revealed a significant interaction between ethnicity and elevated neutrophils (p = 0.004), indicating that a comparable neutrophil count conferred an increased risk for ethnic minority patients for both outcomes. CONCLUSIONS:We report ethnicity-specific leucocyte dynamics after AMI. Furthermore, neutrophil count is associated with a disproportionate risk in ethnic minority compared with white individuals. Understanding post-AMI inflammation and its interaction with ethnicity is essential in providing personalised prognostication and patient management.

BACKGROUND:The complication risk of procedures may be influenced by operator and institutional characteristics. Our aim was to assess whether supervising consultant seniority and operative volume, and hospital volume were associated with the risk of reintervention following complex device implantation. METHODS:A nationwide population-based study was performed using the National Institute for Cardiovascular Outcomes Research registry including all patients receiving their first transvenous implantable cardioverter defibrillator or cardiac resynchronisation therapy (CRT) implant in England over 5 years (April 2014-March 2019). The primary endpoint was 1-year reintervention. We evaluated the association between reintervention and supervising consultant annualised complex device volume, supervising consultant seniority and hospital annualised complex device volume, using multilevel logistic regression. RESULTS:47 630 implants were included. The 1-year reintervention rate was 6.1% (N=2916). There was no difference in reintervention risk with increasing supervising consultant volume (OR 0.89 Q4 vs Q1; 95% CI 0.76 to 1.05, p=0.17). When CRT-pacemakers/defibrillators implants were analysed separately (N=26 108), there was an association between operator volume and 1-year reintervention, but this was of borderline statistical significance and only evident in the highest compared with the lowest volume quartile of operators (adjusted OR 0.79 Q4 vs Q1; 95% CI 0.63 to 0.98, p=0.03). There was a non-linear relationship between reintervention risk and supervising consultant seniority, with the operators in the middle two quartiles of seniority having a lower risk (OR 0.87 Q2 vs Q1, p=0.02; OR 0.81 Q3 vs.Q1; p=0.003) while the most and least senior operators had a similar reintervention risk (OR 0.93 Q4 vs Q1, p=0.31). Hospital volume was not associated with 1-year reintervention. CONCLUSIONS:There is a U-shaped curve between operator seniority and reintervention risk for complex devices. Although there are several potential explanations, these data suggest that while newly qualified consultants may benefit from mentoring, all operators should continuously evaluate their outcomes and share them within their centre and more widely through the national audit.

Congestion in patients with heart failure (HF) predicts adverse outcomes and is a leading cause of hospitalisation. Understanding congestion mechanisms helps in HF management and underscores the importance of tailored therapies to treat vascular and tissue congestion, improving patient outcomes. In this setting, several tools are available to detect congestion. Biomarker measurement is a simple, valid and affordable method to evaluate congestion in patients with HF. Natriuretic peptides are the most widely available tool in acute and chronic HF, helping diagnosis, risk stratification and management. Novel biomarkers can potentially become reliable allies in diagnosing and monitoring patients with HF. This review aims to assess the current scientific literature on biomarkers for managing HF, evaluate their clinical utility and explore future perspectives in this field

Background Neutrophil-to-lymphocyte ratio (NLR) is an easy-to-use inflammatory biomarker. Baseline NLR is independently associated with incident cardiovascular events and all-cause mortality. However, whether this applies to acute myocarditis (AM) has not been evaluated. Objectives The present study aimed to investigate the prognostic value of NLR in patients with AM. Methods A total of 1,150 consecutive patients with a diagnosis of AM admitted to 10 international tertiary referral cardiac centers were included in the study. The diagnosis was confirmed using cardiac magnetic resonance or endomyocardial biopsy. The primary outcome measure was a composite of all-cause mortality or heart transplantation. Patients were divided into 2 groups according to an NLR cutoff of 4 derived from spline regression analysis and 70:30 train-test split algorithm. Results Patients with an NLR <4 were younger and more likely to present with chest pain, and those with an NLR ≥4 were more likely to present with breathlessness and have other comorbidities. Over a median follow-up of 228 weeks, a NLR ≥4 was associated with a worse prognosis (P < 0.0001). After adjustment for prognostic variables, NLR emerged as an independent predictor of outcome (HR: 3.03 [95% CI: 1.30-7.04]; P = 0.010). Elevated NLR remained associated with worse outcomes among patients with preserved ejection fraction at baseline, who are conventionally considered to be at lower risk of adverse events (P < 0.0001). Conclusions In patients with AM, elevated NLR is associated with worse prognosis and may be valuable for stratifying patients, even those conventionally considered at low risk.

Aims The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) is well recognized as a master regulator of antioxidant responses and cytoprotective genes. Previous studies showed that NRF2 enhances the resistance of mouse hearts to chronic haemodynamic overload, at least in part by reducing oxidative stress. Evidence from other tissues suggests that NRF2 may modulate glucose intermediary metabolism but whether NRF2 has such effects in the heart is unclear. Here, we investigate the role of NRF2 in regulating glucose intermediary metabolism and cardiac function during disease stress.Methods and results Cardiomyocyte-specific Keap1 knockout (csKeap1KO) mice, deficient in the endogenous inhibitor of NRF2, were used as a novel model of constitutively active NRF2 signalling. Targeted metabolomics and isotopomer analysis were employed in studies with 13C6-glucose in csKeap1KO and wild-type mice. Pharmacological and genetic approaches were utilized in neonatal rat ventricular myocytes (NRVMs) to explore molecular mechanisms. We found that cardiac-specific activation of NRF2 redirected glucose metabolism towards the pentose phosphate pathway (PPP), a branch pathway of glycolysis, and mitigated pressure overload-induced cardiomyocyte death and cardiac dysfunction. Activation of NRF2 also protected against myocardial infarction-induced DNA damage in remote myocardium and cardiac dysfunction. In vitro, knockdown of Keap1 upregulated PPP enzymes and reduced cell death in NRVM subjected to chronic neurohumoral stimulation. These pro-survival effects were abolished by pharmacological inhibition of the PPP or silencing of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase. Knockdown of NRF2 in NRVM increased stress-induced DNA damage, which was rescued by supplementing the cells with either nicotinamide adenine dinucleotide phosphate (NADPH) or nucleosides, the two main products of the PPP.Conclusion These results indicate that NRF2 regulates cardiac metabolic reprogramming by stimulating the diversion of glucose into the PPP, thereby generating NADPH and providing nucleotides to prevent stress-induced DNA damage and cardiac dysfunction.

BACKGROUND For patients with acute heart failure (HF), specialist HF care during admission improves diagnosis and treatments. OBJECTIVES The authors aimed to investigate the association of HF specialist care with in-hospital and longer term prognosis. METHODS The authors used data from the National Heart Failure Audit from January 1, 2018, to December 31, 2022, linked to electronic records for hospitalization and deaths. All-cause mortality was the primary outcome measure and in-hospital mortality the secondary outcome measure. RESULTS Data for 227,170 patients admitted to hospital with HF (median age: 81 years; IQR: 72-88 years), were analyzed. Approximately 80% of acute HF admissions received support from HF specialists. Thirty-nine percent of patients (n = 70,720) were seen by a multidisciplinary team (HF physicians and heart failure specialist nurses [HFSNs]), 22% (n = 40,330) were seen by HFSNs alone, and the remaining 39% (n = 71,700) were seen exclusively by specialist HF physicians. At discharge, more patients who received HF specialist care were prescribed medical therapy for HF and had specialized follow-up. Conversely, diuretic agents were prescribed to fewer patients. HF specialist care was independently associated with a higher rate of prescribing HF therapies at discharge and a lower likelihood of receiving diuretic therapy (OR: 0.90 [95% CI: 0.86-0.95]; P < 0.001). HF specialist care was associated with better long-term survival (HR: 0.89 [95% CI: 0.87-0.90]; P < 0.001) and lower in-hospital mortality (OR: 0.92 [95% CI: 0.0.88-0.97]; P < 0.001). CONCLUSIONS Receiving HF specialist care during admission for HF is associated with a higher rate of implementation of medical therapy, fewer discharges on diuretic therapy, and lower in-hospital and long-term mortality across the left ventricular ejection fraction spectrum, especially for patients with heart failure with reduced ejection fraction. (JACC Heart Fail. 2025;13:402-413) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

AIMS:Cardiovascular disease and cancer represent significant global health challenges. An overlap between oncology and cardiology is compounded by cancer therapies, which are known to have cardiotoxic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for treating diabetes, have shown promising cardiovascular benefits in non-cancer populations, particularly in preventing heart failure (HF) and reducing HF-related hospitalization and mortality in large randomized controlled trials (RCTs) across the spectrum of left ventricular ejection fraction. However, their potential cardioprotective role in cancer patients remains unclear. This systematic review and meta-analysis evaluated cardiovascular outcomes in cancer patients with type 2 diabetes undergoing chemotherapy with concomitant use of SGLT2i compared with those not using SGLT2i. Subgroup analyses were performed to explore patients without baseline HF and patients treated exclusively with anthracyclines. METHODS AND RESULTS:A systematic review identified 11 observational retrospective studies (n = 104 327 patients). Based on the National Institutes of Health Quality Assessment Tool checklist, two studies were at moderate risk of bias, while all other included studies had a low risk of bias. Meta-analysis indicated that the use of SGLT2i was associated with a significant reduction in all-cause mortality [0.47, 95% confidence interval (CI) 0.33-0.67, P < 0.0001] and risk of HF hospitalization (0.44, 95% CI 0.27-0.72, P = 0.001). CONCLUSION:The use of SGLT2i may be associated with a significant reduction in all-cause mortality and risk of HF hospitalization in actively treated cancer patients with Type 2 diabetes. Our study highlights the need for further investigation through prospective RCTs to confirm the efficacy and safety of SGLT2i in attenuating cardiotoxicity and supporting cardiovascular health in oncology settings.