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Angiotensin-converting enzyme inhibition and pre-superior cavopulmonary connection haemodynamics in infants with single-ventricle physiology

Published online by Cambridge University Press:  16 February 2021

Asim Al Balushi
Affiliation:
Division of Cardiology, Stollery Children’s Hospital, Department of Pediatrics, University of Alberta, Edmonton, Canada
Konstantin Averin
Affiliation:
Division of Cardiology, Stollery Children’s Hospital, Department of Pediatrics, University of Alberta, Edmonton, Canada
Daphne T. Hsu
Affiliation:
The Children’s Hospital at Montefiore, Albert Einstein College of Medicine, New York, NY, USA
Andrew S. Mackie*
Affiliation:
Division of Cardiology, Stollery Children’s Hospital, Department of Pediatrics, University of Alberta, Edmonton, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, Canada
*
Author for correspondence: Dr A. S. Mackie, Division of Cardiology, Stollery Children’s Hospital, Department of Pediatrics, 4C2 Walter Mackenzie Center, 8440-112th St. NW, Edmonton, AB T6G 2B7, Canada. Tel: +780 407 8361; Fax: +780 407 3954. E-mail: [email protected]

Abstract

Introduction:

Preliminary animal and human data suggest that angiotensin-converting enzyme inhibition has a role in pulmonary vascular remodelling. We sought to assess the effect of ACEi versus placebo on pulmonary artery pressure and transpulmonary gradient amongst infants undergoing single-ventricle palliation.

Materials and methods:

Using the publicly available Pediatric Heart Network Infant Single-Ventricle trial dataset, we compared mean PA pressure at pre-superior cavopulmonary connection catheterisation (primary outcome), transpulmonary gradient, pulmonary-to-systemic flow ratio, and post-SCPC oxygen saturation (secondary outcomes) in infants receiving enalapril versus placebo.

Results:

A total of 179 infants underwent pre-SCPC catheterisation, of which 85 (47%) received enalapril. There was no difference between the enalapril and placebo group in the primary and the secondary outcomes. Mean PA pressure in the enalapril group was 13.1 ± 2.9 compared to 13.7 ± 3.4 mmHg in the placebo group. The transpulmonary gradient was 6.7 ± 2.5 versus 6.9 ± 3.2 mmHg in the enalapril and placebo groups, respectively. The pulmonary-to-systemic flow ratio was 1.1 ± 0.5 in the enalapril group versus 1.0 ± 0.5 in the placebo group and the post-SCPC saturation was 83.1 ± 5.0% in the enalapril group versus 82.2 ± 5.3% in the placebo group. In the pre-specified subgroup analyses comparing enalapril and placebo according to ventricular morphology and shunt type, there was no difference in the primary and secondary outcomes.

Conclusion:

ACEi did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to SCPC palliation.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Ridderbos, FJ, Wolff, D, Timmer, A, et al. Adverse pulmonary vascular remodeling in the Fontan circulation. J Heart Lung Transplant 2015; 34: 404413.CrossRefGoogle ScholarPubMed
La Gerche, A, Gewillig, M. What limits cardiac performance during exercise in normal subjects and in healthy Fontan patients? Int J Pediatr 2010; 2010: 791291.CrossRefGoogle ScholarPubMed
Zhao, L, Al-Tubuly, R, Sebkhi, A, Owji, AA, Nunez, DJ, Wilkins, MR. Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung. Br J Pharmacol 1996; 119: 12171222.CrossRefGoogle ScholarPubMed
Nong, Z, Stassen, JM, Moons, L, Collen, D, Janssens, S. Inhibition of tissue angiotensin-converting enzyme with quinapril reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Circulation 1996; 94: 19411947.CrossRefGoogle ScholarPubMed
Rondelet, B, Kerbaul, F, Van Beneden, R, et al. Prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 2005; 289: H2319H2324.CrossRefGoogle ScholarPubMed
Morrell, NW, Upton, PD, Kotecha, S, et al. Angiotensin II activates MAPK and stimulates growth of human pulmonary artery smooth muscle via AT1 receptors. Am J Physiol 1999; 277: L440L448.Google ScholarPubMed
Shaddy, RE, Teitel, DF, Brett, C. Short-term hemodynamic effects of captopril in infants with congestive heart failure. Am J Dis Child 1988; 142: 100105.Google ScholarPubMed
Montigny, M, Davignon, A, Fouron, JC, Biron, P, Fournier, A, Elie, R. Captopril in infants for congestive heart failure secondary to a large ventricular left-to-right shunt. Am J Cardiol 1989; 63: 631633.CrossRefGoogle ScholarPubMed
Mori, Y, Nakazawa, M, Tomimatsu, H, Momma, K. Long-term effect of angiotensin-converting enzyme inhibitor in volume overloaded heart during growth: a controlled pilot study. J Am Coll Cardiol 2000; 36: 270275.CrossRefGoogle ScholarPubMed
Momma, K. ACE inhibitors in pediatric patients with heart failure. Paediatr Drugs 2006; 8: 5569.CrossRefGoogle ScholarPubMed
Yim, DL, Jones, BO, Alexander, PM, d’Udekem, Y, Cheung, MM. Effect of anti-heart failure therapy on diastolic function in children with single-ventricle circulations. Cardiol Young 2015; 25: 12931299.CrossRefGoogle ScholarPubMed
Wilson, TG, Iyengar, AJ, d’Udekem, Y. The use and misuse of ACE inhibitors in patients with single ventricle physiology. Heart Lung Circ 2016; 25: 229236.CrossRefGoogle ScholarPubMed
Giardini, A, Balducci, A, Specchia, S, Gargiulo, G, Bonvicini, M, Picchio, FM. Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Eur Heart J 2008; 29: 16811687.CrossRefGoogle ScholarPubMed
Goldberg, DJ, French, B, McBride, MG, et al. Impact of oral sildenafil on exercise performance in children and young adults after the Fontan operation: a randomized, double-blind, placebo-controlled, crossover trial. Circulation 2011; 123: 11851193.CrossRefGoogle Scholar
Schuuring, MJ, Vis, JC, van Dijk, AP, et al. Impact of Bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial. Eur J Heart Fail 2013; 15: 690698.CrossRefGoogle ScholarPubMed
Hebert, A, Mikkelsen, UR, Thilen, U, et al. Bosentan improves exercise capacity in adolescents and adults after Fontan operation: the TEMPO (treatment with endothelin receptor antagonist in Fontan Patients, a randomized, placebo-controlled, double-blind study measuring peak oxygen consumption) study. Circulation 2014; 130: 20212030.CrossRefGoogle ScholarPubMed
Rhodes, J, Ubeda-Tikkanen, A, Clair, M, et al. Effect of inhaled iloprost on the exercise function of Fontan patients: a demonstration of concept. Int J Cardiol 2013; 168: 24352440.CrossRefGoogle ScholarPubMed
Goldberg, DJ, Zak, V, Goldstein, BH, et al. Results of the Fontan udenafil exercise longitudinal (FUEL) trial. Circulation 2019; 141: 641651. doi: 10.1161/CIRCULATIONAHA.119.044352 CrossRefGoogle ScholarPubMed
Tavli, T, Gocer, H. Effects of cilazapril on endothelial function and pulmonary hypertension in patients with congestive heart failure. Jpn Heart J 2002; 43: 667674.CrossRefGoogle ScholarPubMed
Hsu, DT, Zak, V, Mahony, L, et al. Enalapril in infants with single ventricle: results of a multicenter randomized trial. Circulation 2010;122:333340.CrossRefGoogle ScholarPubMed
Hsu, DT, Mital, S, Ravishankar, C, et al. Rationale and design of a trial of angiotensin-converting enzyme inhibition in infants with single ventricle. Am Heart J 2009; 157: 3745.CrossRefGoogle ScholarPubMed
Mori, Y, Nakanishi, T, Ishii, T, Imai, Y, Nakazawa, M. Relation of pulmonary venous wedge pressures to pulmonary artery pressures in patients with single ventricle physiology. Am J Cardiol 2003; 91: 772774.CrossRefGoogle ScholarPubMed
Fratz, S, Fineman, JR, Gorlach, A, et al. Early determinants of pulmonary vascular remodeling in animal models of complex congenital heart disease. Circulation 2011; 123: 916923.CrossRefGoogle ScholarPubMed
Reddy, VM, McElhinney, DB, Moore, P, Petrossian, E, Hanley, FL. Pulmonary artery growth after bidirectional cavopulmonary shunt: is there a cause for concern? J Thorac Cardiovasc Surg 1996; 112: 11801190.CrossRefGoogle Scholar
Tocco, DJ, deLuna, FA, Duncan, AE, Vassil, TC, Ulm, EH. The physiological disposition and metabolism of enalapril maleate in laboratory animals. Drug Metab Dispos 1982; 10: 1519.Google ScholarPubMed
Morrell, NW, Grieshaber, SS, Danilov, SM, Majack, RA, Stenmark, KR. Developmental regulation of angiotensin converting enzyme and angiotensin type 1 receptor in the rat pulmonary circulation. Am J Respir Cell Mol Biol 1996; 14: 526537.CrossRefGoogle ScholarPubMed
Fratz, S, Geiger, R, Kresse, H, et al. Pulmonary blood pressure, not flow, is associated with net endothelin-1 production in the lungs of patients with congenital heart disease and normal pulmonary vascular resistance. J Thorac Cardiovasc Surg 2003; 126: 17241729.CrossRefGoogle Scholar
Wedgwood, S, Mitchell, CJ, Fineman, JR, Black, SM. Developmental differences in the shear stress-induced expression of endothelial NO synthase: changing role of AP-1. Am J Physiol Lung Cell Mol Physiol 2003; 284: L650L662.CrossRefGoogle ScholarPubMed
Aggarwal, S, Gross, C, Fineman, JR, Black, SM. Oxidative stress and the development of endothelial dysfunction in congenital heart disease with increased pulmonary blood flow: lessons from the neonatal lamb. Trends Cardiovasc Med 2010; 20: 238246.CrossRefGoogle ScholarPubMed
Mital, S, Chung, WK, Colan, SD, et al. Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle. Circulation 2011; 123: 23532362.CrossRefGoogle ScholarPubMed
Levy, M, Danel, C, Tamisier, D, Vouhe, P, Leca, F. Histomorphometric analysis of pulmonary vessels in single ventricle for better selection of patients for the Fontan operation. J Thorac Cardiovasc Surg 2002; 123: 263270.CrossRefGoogle ScholarPubMed
Adachi, I, Ueno, T, Hori, Y, Sawa, Y. Alterations in the medial layer of the main pulmonary artery in a patient with longstanding Fontan circulation. Interact Cardiovasc Thorac Surg 2010; 11: 682683.CrossRefGoogle Scholar
Tarkiainen, EK, Tornio, A, Holmberg, MT, et al. Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril. Br J Clin Pharmacol 2015; 80: 11311138.CrossRefGoogle ScholarPubMed
Tian, L, Liu, H, Xie, S, et al. Effect of organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphism on the single- and multiple-dose pharmacokinetics of enalapril in healthy Chinese adult men. Clin Ther 2011; 33: 655663.CrossRefGoogle ScholarPubMed
Pike, NA, Pemberton, V, Allen, K, et al. Challenges and successes of recruitment in the “angiotensin-converting enzyme inhibition in infants with single ventricle trial” of the Pediatric Heart Network. Cardiol Young 2013; 23: 248257.CrossRefGoogle ScholarPubMed