Diastolic dysfunction and structural response to SGLT2 inhibition in chronic kidney disease: the DECODE-CKD trial
TL;DR
It is suggested that SGLT2 inhibitors may preferentially attenuate ventricular remodeling in patients with early HFpEF-related structural changes.
Abstract
Chronic kidney disease (CKD) is associated with abnormalities in diastolic function, predisposing to heart failure with preserved ejection fraction (HFpEF). In DECODE-CKD, dapagliflozin induced significant left ventricular mass index (LVMI) regression in patients with CKD, representing a novel structural cardiac benefit in this population. As sodium glucose-transporter 2 (SGLT2) inhibitors reduce preload and interstitial volume, patients with more advanced diastolic or structural remodeling may exhibit differential regression of LVMI. In DECODE-CKD, a 6-months randomized placebo-controlled trial of patients with CKD, comprehensive echocardiography was performed at baseline and follow-up. Treatment effects on LVMI were evaluated using regression models adjusted for baseline LVMI, including interaction analyses with HFpEF status and echocardiographic measures of diastolic function. HFpEF was defined per ESC criteria as LVEF ≥50%, NT-proBNP >125 pg/mL, ≥1 symptom, and ≥1 structural/functional echocardiographic abnormality. Among 222 patients with CKD (age 66.9±13.2 years), 7% had HFpEF according to the ESC criteria (Table 1). The presence of abnormal measures of diastolic function was well-balanced across treatment groups (LAVI>35: 6% vs 8%, E/e’>9: 11% vs 8%, TR peak velocity>2.8: 14% vs 15%; all p>0.05). Regression of LVMI was consistent irrespective of HFpEF status, E/e’, and TR peak velocity. However, there was suggestion of effect modification by baseline LAVI (pinteraction=0.064), such that the magnitude of LVMI reduction increased progressively with higher baseline LAVI (Figure). Overt HFpEF was infrequent in this CKD cohort, yet subclinical structural and diastolic abnormalities were present in a larger subset. SGLT2 inhibition significantly reduced LVMI, with a numerically greater effect in individuals with increased LAVI. These findings suggest that SGLT2 inhibitors may preferentially attenuate ventricular remodeling in patients with early HFpEF-related structural changes.