SGLT2 Inhibitors Are Associated with Left Ventricular Reverse Remodeling in Patients with Non-Compaction Cardiomyopathy—A Prospective Observational Cohort Trial

<b>Background/Objectives:</b> Sodium glucose co-transporter 2 inhibitors (SGLT2is) improve outcomes in heart failure; however, data in left ventricular non-compaction cardiomyopathy (LVNC) patients are limited. We sought to analyze the clinical effects of the SGLT2is dapagliflozin and empagliflozin in patients with LVNC. <b>Methods:</b> Thirty consecutive LVNC patients diagnosed by CMR were prospectively enrolled. Clinical, biochemical and echocardiography data were obtained at the initiation of the SGLT2is and at the 12-month follow-up. All patients were on stable guideline-directed medical therapy. A response to SGLT2i therapy was defined as an improvement in LVEF ≥ 5% at 12 months. <b>Results:</b> Of the 30 enrolled patients, 25 were male, with a mean age of 49 ± 16 years and few comorbidities. Dapagliflozin 10 mg was prescribed to 23 patients and empagliflozin 10 mg to 7 patients. Five patients experiened an adverse event during follow-up (one sudden cardiac death; four heart transplantations or LVAD implantations). During follow-up, significant improvements were observed in LVEF (32.1 ± 6.9% vs. 43.5 ± 9.7%; <i>p</i> = 0.003), LVOT VTI (14.8 ± 6.5 cm vs. 17.6 ± 3.3 cm; <i>p</i> = 0.008), E/e' (14.8 ± 4.7 vs. 10.0 ± 4.1; <i>p</i> < 0.001), and TAPSE (2.0 ± 0.4 cm vs. 2.3 ± 0.4 cm; <i>p</i> = 0.012). NT-proBNP levels decreased significantly (2025 ± 2198 pg/mL vs. 582 ± 803 pg/mL; <i>p</i> = 0.005). Eighteen patients responded favorably to SGLT2i therapy (Group A), whereas seven showed no significant LVEF improvement (Group B). The groups did not differ significantly in age, sex, baseline creatinine, or bilirubin. Compared to Group B, Group A had a smaller baseline LV end-diastolic diameter (6.3 ± 0.8 cm vs. 7.1 ± 0.9 cm; <i>p</i> = 0.025) and lower NT-proBNP levels (1720 ± 1662 pg/mL vs. 4527 ± 4397 pg/mL; <i>p</i> = 0.02). <b>Conclusions:</b> In patients with LVNC, SGLT2i therapy is associated with significant reverse remodeling and functional improvement. Benefits may be greater in those with less advanced disease.