Connelly, Kim A, Wu, Ellen, Visram, Aylin, Friedberg, Mark K, Batchu, Sri Nagarjun, Yerra, Veera Ganesh, Thai, Kerri, Nghiem, Linda, Zhang, Yanling, Kabir, Golam, Desjardins, J F, Advani, Andrew and Gilbert, Richard E (2022) The SGLT2i dapagliflozin reduces RV mass independent of changes in RV pressure induced by pulmonary artery banding. Cardiovascular drugs and therapy. ISSN 1573-7241

Abstract

BACKGROUND

Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class is efficacious in the treatment and prevention of right heart failure has not been explored.

HYPOTHESIS

We hypothesized that SGLT2 inhibition would reduce the structural, functional, and molecular responses to pressure overload of the right ventricle.

METHODS

Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (0.5 mg/kg/day) or vehicle by oral gavage. After 6 weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses.

RESULTS

PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content, and alteration in calcium handling protein expression (all p < 0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, phospho-AMPK and LC3I/II ratio expression (all p < 0.05).

SIGNIFICANCE

Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined.

Item Type:	Article
Date Deposited:	05 Nov 2022 00:46
Last Modified:	05 Nov 2022 00:46
URI:	https://oak.novartis.com/id/eprint/48895