Dapagliflozin enhances systolic and diastolic function in concordance with clinical response in patients with left ventricular dysfunction

A.E. Abou Warda, J.D. Duarte, M. Nabil Salem, H.F. Salem, A.N. Moharram, A.S. Alanazi, A.I. Alzarea, T.G. Alsahli, H. Sultan, M.A. Alrashdi, A.F. Altebainawi, B. Emil Ibrahim, S. Ibrahim Alnahrawi, K. Kamel Megalaa, B. Zarif, R.M. Sarhan

Department of Clinical Pharmacy, Faculty of Pharmacy, October 6 University, Giza, Egypt. asdalananzi@ju.edu.sa

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• Cardiology

OBJECTIVE: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have reshaped heart failure (HF) management. However, evidence regarding their effects on cardiac structure, particularly for dapagliflozin, remains inconsistent. This study evaluates dapagliflozin’s impact on echocardiographic parameters and its concordance with clinical response.

MATERIALS AND METHODS: A prospective, randomized controlled study included HF patients with left ventricular (LV) dysfunction, divided into dapagliflozin-treated and dapagliflozin-naïve groups. Echocardiography and speckle-tracking strain analysis were conducted at baseline and six months. The primary outcome was the change in indexed LV mass. Secondary outcomes included LV function, volumes, dimensions, functional mitral regurgitation, global longitudinal strain (GLS), diastolic function, right ventricular (RV) function, and clinical response assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) score.

RESULTS: Among 240 participants, 160 received dapagliflozin in addition to guideline-directed medical therapy, while 80 were dapagliflozin-naïve. Adjusted regression analysis showed significant improvements in LV mass index (-43.51 g/m², 95% CI: -59.4 to -27.5, p < 0.0001), end-systolic volume (-29.45 mL, 95% CI: -43.9 to -14.9, p < 0.0001), and end-diastolic volume (-29.44 mL, 95% CI: -47.9 to -10.9, p = 0.0021). Improvements were also observed in LV ejection fraction (5.15%, 95% CI: 2.84 to 7.45, p < 0.0001), GLS (-1.99%, 95% CI: -2.87 to -1.11, p < 0.0001), E/A ratio (-0.56, 95% CI: -1.01 to -0.10, p = 0.016), effective regurgitant orifice area (EROA) (-0.18 cm², 95% CI: -0.28 to -0.081, p = 0.0006), tricuspid annular plane systolic excursion (TAPSE) (0.38 cm, 95% CI: 0.15 to 0.62, p = 0.0024), and composite clinical outcome (HR 0.65, 95% CI: 0.43-0.98, p = 0.043). LVEF, GLS, E/A ratio, TAPSE, inferior vena cava diameter, and left atrial area correlated with clinical response.

CONCLUSIONS: Dapagliflozin emerges as a potential therapy for patients with left ventricular dysfunction, enhancing LV systolic function and diastolic performance, alongside a favorable clinical response. Future studies with more extensive assessment of right ventricular function and longer follow-up are warranted.

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