AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Real-World Predictors of Non-Response to SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: A Retrospective Cohort Study from a Tertiary Care Center in Central India of 4723 Patients
By Juneja M, Bhagwatkar H, Kiyimba DM et al.
Introduction: SGLT2 inhibitors reduce heart failure hospitalizations and mortality in HFrEF, yet 30-50% of patients fail to achieve reverse remodeling. Most prediction models derive from Western trials with limited ethnic diversity. Using India’s largest real-world HFrEF cohort (n=4,723), we aimed to identify clinical predictors of non-response to SGLT2i in a South Asian tertiary care setting. Methods: Retrospective cohort study of 4,723 HFrEF (LVEF ≤40%) adults initiated on empagliflozin/dapagliflozin (2020-2025). Non-response defined as <5% absolute LVEF increase or <10% LVESVi reduction at 6-12 months. Multivariable logistic regression identified independent predictors from 40+ clinical, laboratory, and echocardiographic variables. Bootstrap internal validation performed. Results: Among 4,723 patients (mean age 58.1±11.4 years, 38% female, 46% ischemic etiology), non-response to SGLT2i occurred in 1,946 patients (41.2%). On multivariable analysis, independent predictors of non-response were: ischemic etiology (adjusted OR 2.31, 95% CI 1.87-2.86), baseline LVEF ≤25% (OR 1.89, 95% CI 1.53-2.34), NT-proBNP ≥3000 pg/mL (OR 1.82, 95% CI 1.46-2.27), HbA1c ≥8.0% in diabetics (OR 1.65, 95% CI 1.31-2.08), eGFR <45 mL/min/1.73m ² (OR 1.57, 95% CI 1.24-1.99), and anemia (OR 1.46, 95% CI 1.18-1.81). Concurrent ARNI use was protective (OR 0.68, 95% CI 0.54-0.85). Non-ischemic dilated cardiomyopathy and peripartum cardiomyopathy showed highest response rates (74% and 81%, respectively). The prediction model demonstrated good discrimination (AUC 0.80, 95% CI 0.77-0.83) and calibration (Hosmer-Lemeshow p=0.34). Bootstrap internal validation confirmed minimal optimism (corrected AUC 0.79, 95% CI 0.76-0.82). Conclusion: In this largest real-world Indian HFrEF cohort, 41% failed to achieve reverse remodeling with SGLT2i. Ischemic etiology, severe LV dysfunction, elevated NT-proBNP, poor glycemic control, renal impairment, and anemia independently predicted non-response. These readily available clinical variables enable bedside risk stratification in resource-limited settings.