Cardiopulmonary Remodeling In Nondiabetic Patients with Systolic Heart Failure Using Sodium-Glucose Cotransporter 2 Inhibitors: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Introduction: Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drugs that have demonstrated cardiovascular risk improvement in patients with heart failure. Current evidence suggests that they can also reduce mortality, hospitalization, and renal disease progression. In this study, we aimed to evaluate the cardiac reverse remodeling potential of SGLT2 inhibitors in nondiabetic heart failure patients with reduced ejection fraction (HFrEF).

Method: We systematically searched various databases, including Web of Science, Pub- Med/Medline, Scopus, Cochrane, and ProQuest. After screening, five randomized controlled trials were retrieved from the initial search (8442 citations).

Results: The meta-analysis revealed statistically significant and positive effects of SGLT2 inhibitors on left ventricular mass and function, cardiac matrix and cells, and cardiopulmonary fitness.

Discussion: SGLT2 inhibitor users experienced a reduction in left ventricular (LV) mass (mean difference (MD): -20.06 grams, confidence interval (CI) 95%: -24.94 to -10.18, p-value< 0.01), LV mass index (MD: -9.79 g/m2, CI 95%: -13.47 to -6.11, p-value < 0.01), LV end diastolic volume (MD: -17.42 ml, CI 95%: -29.00 to -5.83, p-value < 0.01), and LV end systolic volume (MD: -17.30 ml, CI 95%: -34.35 to -0.25, p-value: 0.05). Correspondingly, cardiac extracellular volume (MD: -1.47, CI 95%: -2.49 to -0.46, p-value < 0.01), cardiac cellular volume (MD: - 7.74, CI 95%: -12.30 to -3.19, p-value< 0.01), and cardiac matrix volume (MD: -5.33 ml, CI 95%: -8.33 to -2.33, p-value< 0.01) significantly decreased. Markers of cardiorespiratory fitness, including maximal oxygen consumption (VO2) (MD: 1.58 ml/kg/min, CI 95%: 0.60 to 2.55, pvalue< 0.01) and the minute ventilation (VE)/carbon dioxide consumption (VCO2) slope (MD: - 1.64, CI 95%: -3.18 to -0.09, p-value: 0.04), also improved. Moreover, LV ejection fraction indicated a statistically and clinically negligible rise (MD: 2.97 %, CI 95%: -0.24 to 6.19, p-value: 0.07).

Conclusion: The meta-analysis supports the potential role of SGLT2 inhibitors in enhancing LV function and reducing LV mass in HFrEF patients. These drugs can benefit HFrEF patients by improving pulmonary function and oxygenation. Treatment with SGLT2 inhibitors may be effective for outcomes associated with pulmonary and left ventricular function.