Effect of dapagliflozin on coronary microcirculation in patients with ejection fraction preserved heart failure
Z Zhang, S X Chen, G H Ma, Y U Li, W Q OuAbstract
Background
Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure, with coronary microvascular dysfunction (CMD) playing a key pathogenic role and representing a promising therapeutic target. Although sodium–glucose cotransporter-2 inhibitors (SGLT2i) are recommended as first-line therapy for HFpEF, the mechanisms underlying their clinical benefits—particularly their effects on the coronary microcirculation remain unclear.
Objective
This study is the first to use cardiac magnetic resonance imaging (CMR) to evaluate the impact of six months of dapagliflozin therapy on coronary microvascular function in patients with HFpEF, to assess whether clinical benefits are mediated by improvements in CMD.
Methods
This single-center, prospective study enrolled patients with HFpEF. All participants received guideline-directed medical therapy and dapagliflozin (10 mg/day) for six months. Coronary microcirculation was primarily assessed using CMR. Segmental analysis of left ventricular short-axis images was performed according to the AHA 6-segment model. Quantitative myocardial perfusion parameters—including arrival time, peak time，slope, maximum slope, and signal intensity ratio were derived. Secondary outcomes included echocardiographic parameters (left ventricular ejection fraction [LVEF] and left ventricular end-diastolic diameter [LVED]), plasma B-type natriuretic peptide (BNP), urinary albumin-to-creatinine ratio (UACR), 6-minute walk test (6MWT) distance, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, and body mass index (BMI). Statistical analyses were performed using SPSS version 27.0, with a two-sided P < 0.05 considered statistically significant.
Results
29 patients completed the follow-up. CMR analysis demonstrated no significant changes in myocardial perfusion parameters across any segments (all P > 0.05). Echocardiographic indices likewise remained stable, with no significant differences (LVEF: 61.96 ± 6.03% vs. 63.57 ± 5.87%, P = 0.21) or LVED: 44.14 ± 6.57 mm vs. 44.29 ± 7.45 mm, P = 0.89). Contrastly, significant clinical improvements were observed. BNP levels decreased (267.25 ± 194.49 pg/mL vs. 215.19 ± 175.93 pg/mL, P = 0.036), and UACR declined [15.64 (3.44, 34.49) vs. 6.28 (2.64, 17.79) mg/g, P = 0.023]. Functional capacity improved, as evidenced by an increase in 6MWT distance (361.79 ± 100.25 m vs. 386.33 ± 96.58 m, P = 0.03), along with lower MLHFQ scores [20.48 (8.25, 35) vs. 16.73 (14.25, 16.93), P = 0.048]. BMI showed a non-significant downward trend (23.77 ± 4.9 vs. 23.26 ± 4.05, P = 0.133).
Conclusion
Six-month dapagliflozin therapy didn't improve coronary microvascular function or cardiac structure in HFpEF but significantly reduced BNP and urinary protein excretion, improved exercise capacity and quality of life. These benefits appear independent of CMVD, highlighting the need for further studies to define phenotype-specific mechanisms of SGLT2 inhibitors in HFpEF.Comparison of CMR parametersFor image description, please refer to the figure legend and surrounding text.Comparison of cardiac function parameterFor image description, please refer to the figure legend and surrounding text.