Abstract 11662: SGLT2 Inhibitor Improved Exercise-induced Pulmonary Hypertension (EIPH) in Heart Failure With Preserved Ejection Fraction

• Published in: Circulation (New York, N.Y.) Vol. 140; no. Suppl_1 Suppl 1; p. A11662
• Main Authors: Satoh, Taijyu, Wang, Longfei, McTiernan, Charles F, Levine, Andrea, Baust, Jeff, Lai, Yen Chun, Gladwin, Mark T
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 19.11.2019
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.11662

BackgroundMetabolic syndrome (MS) and Heart Failure with preserved Ejection Fraction (HFpEF) can lead to pulmonary hypertension (PH). Exercise Induced PH (EIPH), which often accompanies HFpEF, has no effective therapy. The SGLT2 inhibitor Empagliflozin reduces cardiovascular risk and improves clinical outcome in patients with type 2 diabetes and/or MS. We tested the hypothesis that Empagliflozin could improve MS and EIPH in PH-HFpEF model rats.Methods and ResultsEight week (wk) old Obese ZSF-1 rats received SU5416 once to induce PH, and Empagliflozin (10mg/kg/day) via drinking water until 22 wks old (OSE, n=10). Control groups included lean ZSF-1 (Ln, n=5) and obese rats treated with SU5416 only (OS, n=8). At 21 wks old, we implanted a 3 Fr catheter in the right ventricle (RV). At 22 wks we evaluated RV systolic pressure (RVSP) during treadmill exercise. Relative to OS, OSE showed a significant improvement in metabolic syndrome endpoints; body weight (BW, g) (Ln 430+/-17; OS 576+/-16*; OSE 520+/-15g*†; * p<0.05 vs Ln, † p<0.05 vs OS), HgA1c (Ln 4.9+/-0.3; OS 10.9+/-1.1*; OSE 6.8+/-1.3%*†), and insulin resistance (HOMA-iR; Ln 41+/-10; OS 3800+/-1560*; OSE 669+/-443†). At rest (R), OS showed increased RVSP versus Ln. During exercise (EX), OS showed severe PH and exercise intolerance, both of which improved in OSE (R vs EX, Ln 27.5+/-3.2 vs 38.6+/-4.3‡; OS 38.2+/-3.3* vs 65.2+/-4.8‡§; OSE; 35.8+/-3.5* vs 55.7+/-5.9 mmHg‡§