Impact of SGLT2 Inhibitors on PA Pressures in D-TGA after Atrial Switch Operations

Abstract

Heart failure (HF) is the leading cause of mortality in adults with congenital heart disease (ACHD), including patients with systemic right ventricles, such as those with dextro-transposition of the great arteries with an atrial switch (DTGA-AS). With more ACHD patients surviving well into adulthood, there is an increase in advanced heart failure (HF) and pulmonary hypertension (PH), many of whom are being treated with SGLT2-inhibitors (SGLT2-i). However, there is a paucity of data supporting SGLT2-i inhibitor use in the ACHD population and on how they may impact pulmonary artery pressures (PAP). This single center retrospective study aimed to evaluate the impact of SGLT2-i on (PAP) in patients with DTGA-AS. Six patients were studied, all male (mean age 41 [range 38-52] years), with a mean systemic right ventricular ejection fraction of 27% (range 22-32%), with an implanted hemodynamic CardioMEMs monitor data were recorded one month prior to medication start and six months afterwards. Half of the patients had normal PAP, and the addition of SGLT2i did not result in a significant change in PAP in all patients. However, half of the patients demonstrated a trend towards improvement. In conclusion, in this study with a small sample size of DTGA-AS patients, there was no significant reduction in PAP.

Keywords

Heart failure / Pulmonary hypertension / CardioMEMS / Adult congenital heart disease (ACHD) / Dextro-transposition of the great arteries atrial switch (DTGA-AS) / Implanted hemodynamic monitor (IHM) / SGLT2-inhibitors

Author Contributions

Conceptualization, M.L. and W.H.M.V; Methodology, M.L. and W.H.M.V; Software, W.H.M.V; Validation, M.L., W.H.M.V; Formal Analysis, M.L. and W.H.M.V; Investigation, M.L. and W.H.M.V; Resources, M.L. and W.H.M.V Data Curation, M.L. and W.H.M.V; Writing—Original Draft Preparation, M.L.; Writing—M.L. and W.H.M.V; Visualization, M.L. and W.H.M.V Supervision, W.H.M.V; Project Administration, M.L.; Funding Acquisition, W.H.M.V.

Ethics Statement

This study was approved with waivered consent by The Ohio State University Biomedical Institutional Review Board (ID: 2022H0297).

Informed Consent Statement

Patient consent was waived due to the retrospective fashion of the study.

Data Availability Statement

Accessibility of research data is available upon request.

Funding

This research received no external funding.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this paper.

References

[1] Broberg CS, van Dissel AC, Minnier J, Aboulhosn J, Kauling RM, Ginde S, et al. Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries. J. Am. Coll. Cardiol. 2022, 80, 951-963.

[2] Zaragoza-Macias E, Zaidi AN, Dendukuri N, Marelli A. Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J. Am. Coll. Cardiol. 2019, 73, 1564-1578.

[3] Fusco F, Scognamiglio G, Merola A, Iannuzzi A, Palma M, Grimaldi N, et al. Safety and Efficacy of Sacubitril/Valsartan in Patients with a Failing Systemic Right Ventricle: A Prospective Single-Center Study. Circ. Heart Fail. 2023, 16, e009848.

[4] McMurray JJ, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N. Engl. J. Med. 2019, 381, 1995-2008.

[5] Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N. Engl. J. Med. 2020, 383, 1413-1424.

[6] Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N. Engl. J. Med. 2021, 385, 1451-1461.

[7] Solomon SD, McMurray JJ, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N. Engl. J. Med. 2022, 387, 1089-1098.

[8] Marshall WH, Wright L. Sodium-Glucose Cotransporter 2 Inhibitors in Adult and Pediatric Congenital Heart Disease: Review of Emerging Data and Future Directions. Congenit. Heart Dis. 2024, 19, 419-433.

[9] Rosenkranz S, Gibbs JS, Wachter R, De Marco T, Vonk-Noordegraaf A, Vachiery JL. Left ventricular heart failure and pulmonary hypertension. Eur. Heart J. 2016, 37, 942-954.

[10] Nassif ME, Qintar M, Windsor SL, Jermyn R, Shavelle DM, Tang F, et al. Empagliflozin Effects on Pulmonary Artery Pressure in Patients with Heart Failure: Results from the EMBRACE-HF Trial. Circulation 2021, 143, 1673-1686.

[11] Kirschbaum K, Vasa-Nicotera M, Zeiher AM, Cremer S. SGLT2 inhibitor therapy and pulmonary artery pressure in patients with chronic heart failure-further evidence for improved hemodynamics by continuous pressure monitoring. Clin. Res. Cardiol. 2022, 111, 469-472.

[12] Marshall WH, Daniels CJ. Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Systemic Right Ventricles: Incrementally Building the Evidence Base. J. Am. Heart Assoc. 2025, 14, e043096.

[13] Guazzi M, Naeije R. Pulmonary Hypertension in Heart Failure: Pathophysiology, Pathobiology, and Emerging Clinical Perspectives. J. Am. Coll. Cardiol. 2017, 69, 1718-1734.

[14] Alshnbari AS, Millar SA, O’Sullivan SE, Idris I. Effect of Sodium-Glucose Cotransporter-2 Inhibitors on Endothelial Function: A Systematic Review of Preclinical Studies. Diabetes Ther. 2020, 11, 1947-1963.

[15] Lee MM, Brooksbank KJ, Wetherall K, Mangion K, Roditi G, Campbell RT, et al. Effect of Empagliflozin on Left Ventricular Volumes in Patients with Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction (SUGAR-DM-HF). Circulation 2021, 143, 516-525.

[16] Omar M, Jensen J, Frederiksen PH, Kistorp C, Videbæk L, Poulsen MK, et al. Effect of Empagliflozin on Hemodynamics in Patients with Heart Failure and Reduced Ejection Fraction. J. Am. Coll. Cardiol. 2020, 76, 2740-2751.

[17] Durante W, Behnammanesh G, Peyton KJ. Effects of Sodium-Glucose Co-Transporter 2 Inhibitors on Vascular Cell Function and Arterial Remodeling. Int. J. Mol. Sci. 2021, 22, 8786.

[18] Kayano H, Koba S, Hirano T, Matsui T, Fukuoka H, Tsuijita H, et al. Dapagliflozin Influences Ventricular Hemodynamics and Exercise-Induced Pulmonary Hypertension in Type 2 Diabetes Patients—A Randomized Controlled Trial. Circ. J. 2020, 84, 1807-1817.

[19] Ebenroth ES, Hurwitz RA, Cordes TM. Late onset of pulmonary hypertension after successful Mustard surgery for d-transposition of the great arteries. Am. J. Cardiol. 2000, 85, 127-130.

[20] Van De Bruaene A, Toh N, Hickey EJ, Benson L, Horlick E, Granton JT, et al. Pulmonary hypertension in patients with a subaortic right ventricle: Prevalence, impact and management. Heart 2019, 105, 1471-1478.

[21] Chaix MA, Dore A, Mercier LA, Mongeon FP, Marcotte F, Ibrahim R, et al. Late Onset Postcapillary Pulmonary Hypertension in Patients with Transposition of the Great Arteries and Mustard or Senning Baffles. J. Am. Heart Assoc. 2017, 6, e006481.

[22] Cowgill JA, Moran AM. Stiff “Left Atrial” syndrome post-mustard procedure. J. Cardiol. Cardiovasc. Med. 2021, 6, 69-73.