3-Month Enalapril Treatment in Pediatric Fontan Patients With Moderate to Good Systolic Ventricular Function

Abstract

Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderate-good systolic ventricular function. Fontan patients between 8 and 18 years with moderate-good systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B–type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 ± 0.1 mg/kg/d. A total of 6 patients (21%) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B–type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function. Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderate-good systolic ventricular function. Fontan patients between 8 and 18 years with moderate-good systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B–type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 ± 0.1 mg/kg/d. A total of 6 patients (21%) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B–type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function. Although survival of Fontan patients has improved, life expectancy is still less than normal, and many patients suffer from morbidities. Exercise performance, diastolic and systolic ventricular function are already reduced at a young age.1Atz AM Zak V Mahony L Uzark K D'Agincourt N Goldberg DJ Williams RV Breitbart RE Colan SD Burns KM Margossian R Henderson HT Korsin R Marino BS Daniels K Mccrindle BW Pediatric Heart Network InvestigatorsLongitudinal outcomes of patients With single ventricle after the Fontan procedure.J Am Coll Cardiol. 2017; 69: 2735-2744Crossref PubMed Scopus (131) Google Scholar,2Cheung YF Penny DJ Redington AN. Serial assessment of left ventricular diastolic function after Fontan procedure.Heart. 2000; 83: 420-424Crossref PubMed Scopus (130) Google Scholar Because severe diastolic and systolic dysfunction may not be present yet, both functions deteriorate over time in these patients, which may eventually result in heart failure.1Atz AM Zak V Mahony L Uzark K D'Agincourt N Goldberg DJ Williams RV Breitbart RE Colan SD Burns KM Margossian R Henderson HT Korsin R Marino BS Daniels K Mccrindle BW Pediatric Heart Network InvestigatorsLongitudinal outcomes of patients With single ventricle after the Fontan procedure.J Am Coll Cardiol. 2017; 69: 2735-2744Crossref PubMed Scopus (131) Google Scholar,2Cheung YF Penny DJ Redington AN. Serial assessment of left ventricular diastolic function after Fontan procedure.Heart. 2000; 83: 420-424Crossref PubMed Scopus (130) Google Scholar In patients with biventricular heart circulation, angiotensin-converting enzyme (ACE) inhibitors have become the cornerstone of systolic heart failure treatment as they have been shown to improve exercise performance, diastolic and systolic ventricular function, and decrease systemic vascular resistance in adult and pediatric patients with mild to severe systolic heart failure.3Creager MA Massie BM Faxon DP Friedman SD Kramer BL Weiner DA Ryan TJ Topic N Melidossian CD. Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure.J Am Coll Cardiol. 1985; 6: 163-173Crossref PubMed Scopus (117) Google Scholar, 4Eronen M Pesonen E Wallgren EI Tikkanen I Fyhrquist F Andersson S. Enalapril in children with congestive heart failure.Acta Paediatr Scand. 1991; 80: 555-558Crossref PubMed Scopus (15) Google Scholar, 5Kinugawa T Osaki S Kato M Ogino K Shimoyama M Tomikura Y Igawa O Hisatome I Shigemasa C. Effects of the angiotensin-converting enzyme inhibitor alacepril on exercise capacity and neurohormonal factors in patients with mild-to-moderate heart failure.Clin Exp Pharmacol Physiol. 2002; 29: 1060-1065Crossref PubMed Scopus (22) Google Scholar, 6Mori 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: 270-275Crossref PubMed Scopus (71) Google Scholar, 7Pouleur H Rousseau MF van Eyll C Stoleru L Hayashida W Udelson JA Dolan N Kinan D Gallagher P Ahn S. SOLVD InvestigatorsEffects of long-term enalapril therapy on left ventricular diastolic properties in patients with depressed ejection fraction.Circulation. 1993; 88: 481-491Crossref PubMed Scopus (66) Google Scholar, 8SOLVD Investigators Yusuf S Pitt B Davis CE Hood Jr WB Cohn JN Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions [published correction appears in N Engl J Med 1992;327:1768].N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3479) Google Scholar, 9Tang WH Vagelos RH Yee YG Benedict CR Willson K Liss CL Fowler MB. Neurohormonal and clinical responses to high- versus low-dose enalapril therapy in chronic heart failure.J Am Coll Cardiol. 2002; 39: 70-78Crossref PubMed Scopus (97) Google Scholar, 10The NETWORK InvestigatorsClinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison.Eur Heart J. 1998; 19: 481-489Crossref PubMed Scopus (194) Google Scholar Because its effectiveness in biventricular heart patients, many Fontan patients are currently treated with ACE inhibitors, including those without overt systolic ventricular dysfunction, despite the lack of evidence of its efficacy in this patient population.11Anderson PA Breitbart RE Mccrindle BW Sleeper LA Atz AM Hsu DT Lu M Margossian R Williams RV. The Fontan patient: inconsistencies in medication therapy across seven pediatric heart network centers.Pediatr Cardiol. 2010; 31: 1219-1228Crossref PubMed Scopus (46) Google Scholar,12Wilson TG Iyengar AJ Winlaw DS Weintraub RG Wheaton GR Gentles TL Ayer J Grigg LE Justo RN Radford DJ Bullock A Celermajer DS Dalziel K Schilling C d'Udekem Y Australia and New Zealand Fontan RegistryUse of ACE inhibitors in Fontan: rational or irrational?.Int J Cardiol. 2016; 210: 95-99Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Therefore, in this study we evaluated the effect of ACE inhibition in pediatric Fontan patients with moderate-good systolic ventricular function and hypothesized that it may improve exercise performance and ventricular and vascular function. Additionally, adverse events and tolerability were evaluated. Fontan patients from 8 to 18 years old who were operated at the Leiden University Medical Center were recruited from July 2017 to October 2019. Patients with pre-existent ACE inhibitor use and those unable to exercise were excluded. Written informed consent was obtained from all participants or their parents or guardians. The study was approved by the Medical Ethical Committee Leiden-Den Haag-Delft. For this study patients were treated with enalapril, an ACE inhibitor, for 3 months. This period was chosen as previous studies have shown beneficial effects of ACE inhibitors within 12 weeks of treatment, especially on exercise capacity, the primary end point of this study.3Creager MA Massie BM Faxon DP Friedman SD Kramer BL Weiner DA Ryan TJ Topic N Melidossian CD. Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure.J Am Coll Cardiol. 1985; 6: 163-173Crossref PubMed Scopus (117) Google Scholar,5Kinugawa T Osaki S Kato M Ogino K Shimoyama M Tomikura Y Igawa O Hisatome I Shigemasa C. Effects of the angiotensin-converting enzyme inhibitor alacepril on exercise capacity and neurohormonal factors in patients with mild-to-moderate heart failure.Clin Exp Pharmacol Physiol. 2002; 29: 1060-1065Crossref PubMed Scopus (22) Google Scholar,13Abdulla J Abildstrom SZ Christensen E Kober L Torp-Pedersen C. A meta-analysis of the effect of angiotensin-converting enzyme inhibitors on functional capacity in patients with symptomatic left ventricular systolic dysfunction.Eur J Heart Fail. 2004; 6: 927-935Crossref PubMed Scopus (24) Google Scholar,14Seguchi M Nakazawa M Momma K. Effect of enalapril on infants and children with congestive heart failure.Cardiol Young. 1992; 2: 14-19Crossref Scopus (22) Google Scholar Initial enalapril dosage was 5 mg/day and was titrated, as tolerated, to the target dose of 0.5 mg/kg/day or a maximum of 20 mg/day. Enalapril dosage was titrated by blood pressure measured weekly for at least 2 weeks after initiation of treatment. If systolic blood pressure (SBP) fell >20%, or if patients experienced side effects, the dosage was lowered. Renal function (urea and creatinine blood levels) was assessed at baseline, after 2 weeks of treatment with the maximal tolerated dosage, and at the end of the study. At baseline patients were asked if they were familiar with syncope, dizziness, low blood pressure, or if they experienced other complaints, such as palpitations. During the titration period and after 3 months of treatment, patients were asked about it again. At baseline, and after 3 months of treatment, a cardiopulmonary exercise test, echocardiography, arterial stiffness measurement, and blood sample were performed, as described later. Exercise testing was performed on an upright bicycle ergometer with a V volume and or and were by the age of the Patients were to exercise were performed the was exercise were assessed in patients with a maximal heart at the to and the were from the exercise C L of maximal and exercise performance in Fontan patients 15 years of J Cardiol. Full Text Full Text PDF PubMed Scopus Google Scholar was performed on a were and of 3 were for were performed across the to and diastolic and the of those from the of the single and ventricular were obtained to systolic and and diastolic the between the and diastolic of the was systolic performance, was obtained from the ventricle from the as van T of time in children Am Full Text Full Text PDF PubMed Scopus Google Scholar at least 5 of 6 to if the ventricular was than the was from both The was to of the of the and were performed in a with the on the left The and the of the with an was not of or we the were after a and a be with an SD of the of the a plasma and N-terminal pro-B–type natriuretic peptide levels were was performed New were for with and are as mean ± SD or as with first to in of are as a with A sample or a for were for between and A p was The primary end point for this study was exercise performance and the D of as effect with mean and SD from N M AJ T Exercise capacity in children after total versus Full Text Full Text PDF PubMed Scopus Google Scholar an of and we that be to a in A total of Fontan patients were for of which to Patients who did not from those who did not in of age (median of years to for participants years to for p = and of the single ventricle = 6 patients in the baseline measurements, a total of patients were in this study and with enalapril treatment. During the study patient at the of parents and patient was for of medication The remaining 28 patients completed the study of baseline are in Initial and ventricular in the of the study = (21%) left left heart ventricle at at Fontan Fontan or by as mean and = = total with an in a as mean and = = total with an of blood pressure and plasma and creatinine levels is shown in SBP was during the study as with levels of and creatinine did not patients not the dosage of a decrease in SBP = or other adverse of = = and = patient a after of the study which after of This that of the patients experienced adverse events other than the drop in which was with baseline 2 patients that they were familiar with = and = patients completed the study with a mean dosage of ± 0.1 from 5 to 20 blood pressure and plasma and creatinine levels during plasma and for between and is as mean or = blood SBP = systolic blood is as mean or = blood SBP = systolic blood from for between and is as mean or = blood SBP = systolic blood in a of the exercise are shown in A total of 3 patients were not to a and were for of the maximal exercise The Fontan patients on a low exercise capacity at baseline, by a low and A 3-month treatment with enalapril did not improve of the exercise exercise exercise exercise as mean or = maximal heart at = at = = maximal = of to = = maximum in a as mean or = maximal heart at = at = = maximal = of to = = maximum the of the and vascular function. echocardiography, all patients a to systolic ventricular function. At baseline, systolic were and was with as was already in a previous C van of exercise in Fontan patients with an J Cardiol. Full Text Full Text PDF PubMed Scopus Google Scholar ventricular function was at baseline as with a low and with from previous was in 6 and mild in was in 3 and mild in 2 systolic and did not with enalapril treatment. The of already low at baseline, after treatment with SBP Although the of the of the to this did not the for of the no of and vascular function = function E A function SBP as mean or = diastolic = diastolic = of the E = diastolic = diastolic = from the = N-terminal natriuretic = of the = systolic SBP = systolic blood = in a as mean or A = diastolic = diastolic = of the E = diastolic = diastolic = from the = N-terminal natriuretic = of the = systolic SBP = systolic blood = study the effect of a 3-month enalapril treatment in pediatric Fontan patients no of exercise capacity systolic and diastolic ventricular function, and arterial stiffness. SBP and did a of patients significant side ACE inhibition has been the cornerstone of the treatment of congestive heart failure in adult have shown beneficial effects of enalapril in patients with reduced ejection with from to MA Massie BM Faxon DP Friedman SD Kramer BL Weiner DA Ryan TJ Topic N Melidossian CD. Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure.J Am Coll Cardiol. 1985; 6: 163-173Crossref PubMed Scopus (117) Google H Rousseau MF van Eyll C Stoleru L Hayashida W Udelson JA Dolan N Kinan D Gallagher P Ahn S. SOLVD InvestigatorsEffects of long-term enalapril therapy on left ventricular diastolic properties in patients with depressed ejection fraction.Circulation. 1993; 88: 481-491Crossref PubMed Scopus (66) Google Scholar, 8SOLVD Investigators Yusuf S Pitt B Davis CE Hood Jr WB Cohn JN Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions [published correction appears in N Engl J Med 1992;327:1768].N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3479) Google Scholar, 9Tang WH Vagelos RH Yee YG Benedict CR Willson K Liss CL Fowler MB. Neurohormonal and clinical responses to high- versus low-dose enalapril therapy in chronic heart failure.J Am Coll Cardiol. 2002; 39: 70-78Crossref PubMed Scopus (97) Google Scholar, 10The NETWORK InvestigatorsClinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison.Eur Heart J. 1998; 19: 481-489Crossref PubMed Scopus (194) Google Scholar of these studies no between the dose of enalapril and clinical WH Vagelos RH Yee YG Benedict CR Willson K Liss CL Fowler MB. Neurohormonal and clinical responses to high- versus low-dose enalapril therapy in chronic heart failure.J Am Coll Cardiol. 2002; 39: 70-78Crossref PubMed Scopus (97) Google NETWORK InvestigatorsClinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison.Eur Heart J. 1998; 19: 481-489Crossref PubMed Scopus (194) Google Scholar However, the of ACE inhibition in patients with diastolic heart failure with ejection is as a meta-analysis that have not a survival of ACE inhibitors in these H T K T Effect of inhibition on and function and exercise capacity in heart failure with ejection a meta-analysis of controlled PubMed Scopus Google Scholar In pediatric patients with and heart with congestive heart failure and patients with a biventricular circulation, enalapril between and 0.5 mg/kg/day have been M Pesonen E Wallgren EI Tikkanen I Fyhrquist F Andersson S. Enalapril in children with congestive heart failure.Acta Paediatr Scand. 1991; 80: 555-558Crossref PubMed Scopus (15) Google 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: 270-275Crossref PubMed Scopus (71) Google Scholar,14Seguchi M Nakazawa M Momma K. Effect of enalapril on infants and children with congestive heart failure.Cardiol Young. 1992; 2: 14-19Crossref Scopus (22) Google AM and dosage of enalapril in and heart PubMed Scopus Google Scholar In the present study, we for a maximal enalapril dose of 0.5 mg/kg/day with a maximum of 20 The dosage after the from 5 to 20 mg/day with a mean of ± 0.1 which with pediatric and adult in the ACE inhibitors are in Fontan In 2 previous and of the Fontan patients were treated with ACE PA Breitbart RE Mccrindle BW Sleeper LA Atz AM Hsu DT Lu M Margossian R Williams RV. The Fontan patient: inconsistencies in medication therapy across seven pediatric heart network centers.Pediatr Cardiol. 2010; 31: 1219-1228Crossref PubMed Scopus (46) Google Scholar,12Wilson TG Iyengar AJ Winlaw DS Weintraub RG Wheaton GR Gentles TL Ayer J Grigg LE Justo RN Radford DJ Bullock A Celermajer DS Dalziel K Schilling C d'Udekem Y Australia and New Zealand Fontan RegistryUse of ACE inhibitors in Fontan: rational or irrational?.Int J Cardiol. 2016; 210: 95-99Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar In the study by PA Breitbart RE Mccrindle BW Sleeper LA Atz AM Hsu DT Lu M Margossian R Williams RV. The Fontan patient: inconsistencies in medication therapy across seven pediatric heart network centers.Pediatr Cardiol. 2010; 31: 1219-1228Crossref PubMed Scopus (46) Google Scholar the use of ACE inhibitors in pediatric Fontan patients with severe and ventricular not with the of ventricular In in the study by TG Iyengar AJ Winlaw DS Weintraub RG Wheaton GR Gentles TL Ayer J Grigg LE Justo RN Radford DJ Bullock A Celermajer DS Dalziel K Schilling C d'Udekem Y Australia and New Zealand Fontan RegistryUse of ACE inhibitors in Fontan: rational or irrational?.Int J Cardiol. 2016; 210: 95-99Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar of the patients enalapril did not have systolic ventricular dysfunction that in Fontan patients ACE inhibitors are as a of effectiveness is In this study, we that a 3-month enalapril treatment no on exercise capacity, on systolic or diastolic function in pediatric Fontan patients with moderate-good systolic ventricular function. did a in blood pressure and levels of after a 3-month enalapril treatment. The effect on blood pressure a in vascular However, both stiffness including and did not both are by blood pressure, a be on blood pressure which not that is a in stiffness. studies were unable to an in function in pediatric Fontan patients during treatment with ACE vascular function in patients with Fontan J Cardiol. Full Text Full Text PDF PubMed Scopus Google K function the Fontan J Cardiol. Full Text Full Text PDF PubMed Scopus Google Scholar did a decrease in levels which Although did not may have been an effect on which were not measured in this study. A study a of after enalapril treatment in patients with before or after Fontan an of diastolic d'Udekem Y Effect of failure therapy on diastolic function in children with Young. PubMed Scopus Google Scholar effect of enalapril be the of function in Fontan patients as shown in a P W in patients after Fontan J Cardiol. Full Text Full Text PDF PubMed Scopus Google Scholar previous studies have evaluated the effect of enalapril in and 18 pediatric Fontan patients, JA Mahony Enalapril not exercise capacity in patients after Fontan PubMed Scopus Google H S K O Y S. after the Fontan [published correction appears in PubMed Scopus Google Scholar that no including vascular at diastolic and systolic ventricular function, exercise capacity, and after a 3 to enalapril treatment these are with Although no effect on functional outcome was after months of treatment, long-term enalapril treatment have a beneficial A previous study with enalapril in biventricular patients with congestive heart failure that survival did not 18 months of Investigators Yusuf S Pitt B Davis CE Hood Jr WB Cohn JN Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions [published correction appears in N Engl J Med 1992;327:1768].N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3479) Google Scholar Long-term beneficial effects on ventricular failure may be of the inhibition of the and F B F of congestive heart the PubMed Scopus Google Scholar levels of and be in adult patients with heart including patients with R W M M AJ SD Neurohormonal and the chronic heart failure in with heart 2002; PubMed Scopus Google Scholar levels of and have been shown to with and ventricular dysfunction in these R W M M AJ SD Neurohormonal and the chronic heart failure in with heart 2002; PubMed Scopus Google Scholar and may a in the of the Fontan However, if long-term treatment with ACE inhibition or other inhibition may have beneficial effects in Fontan patients study that a of patients experienced a significant adverse which may ACE inhibition is tolerated by this patient blood pressure in a chronic volume with of the lack of a is to Because of the or not to as in biventricular in a Fontan may a decrease in which be M B R J W A M The Fontan who 2010; PubMed Scopus Google Scholar previous study in pediatric Fontan patients has shown a in during exercise after treatment with JA Mahony Enalapril not exercise capacity in patients after Fontan PubMed Scopus Google Scholar Because many Fontan patients are treated with ACE inhibitors, the ventricular function be to in a Fontan M B R J W A M The Fontan who 2010; PubMed Scopus Google Scholar has been as of the factors of in Fontan patients, of which vascular resistance is of the Because low vascular resistance is a for a Fontan circulation, have as a therapy in the of Fontan The effect of in Fontan patients has already been in a studies and an in of to after M van the for in Fontan PubMed Scopus Google Scholar This study has study a sample with the target not being despite many it is the study of enalapril in Fontan patients yet, and the to that enalapril has no beneficial effect was by Although the cardiovascular were as in other Fontan sample was as pediatric patients with and moderate-good systolic ventricular function were did not study the effect of ACE inhibition in Fontan patients with significant ventricular The treatment period chosen have been the treatment period was chosen on previous studies which a beneficial effect on exercise within to 12 weeks after treatment with ACE inhibitors, which was the primary end point of MA Massie BM Faxon DP Friedman SD Kramer BL Weiner DA Ryan TJ Topic N Melidossian CD. Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure.J Am Coll Cardiol. 1985; 6: 163-173Crossref PubMed Scopus (117) Google Scholar,5Kinugawa T Osaki S Kato M Ogino K Shimoyama M Tomikura Y Igawa O Hisatome I Shigemasa C. Effects of the angiotensin-converting enzyme inhibitor alacepril on exercise capacity and neurohormonal factors in patients with mild-to-moderate heart failure.Clin Exp Pharmacol Physiol. 2002; 29: 1060-1065Crossref PubMed Scopus (22) Google Scholar,13Abdulla J Abildstrom SZ Christensen E Kober L Torp-Pedersen C. A meta-analysis of the effect of angiotensin-converting enzyme inhibitors on functional capacity in patients with symptomatic left ventricular systolic dysfunction.Eur J Heart Fail. 2004; 6: 927-935Crossref PubMed Scopus (24) Google Scholar,14Seguchi M Nakazawa M Momma K. Effect of enalapril on infants and children with congestive heart failure.Cardiol Young. 1992; 2: 14-19Crossref Scopus (22) Google Scholar has its in diastolic function or ventricular However, both and have the in the present study were In conclusion, study that a 3-month enalapril treatment period in pediatric Fontan patients with moderate-good systolic ventricular function not exercise capacity or improve vascular and ventricular function. did SBP and enalapril was not as a of patients experienced adverse events. on these we that short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function.

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