enalapril and Heart-Defects--Congenital

While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.. Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman's test.. Median age at echocardiogram was 4.6 (range 2.5-7.4) months. Median ventricular end-diastolic pressure was 7 (range 3-19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range -35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = -0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.. In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.

Topics: Antihypertensive Agents; Cardiac Catheterization; Diastole; Double-Blind Method; Echocardiography, Doppler; Enalapril; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Ventricles; Humans; Infant; Infant, Newborn; Male; Retrospective Studies; Ventricular Function, Left; Ventricular Pressure

To assess the variability in asymmetric growth and its association with neurodevelopment in infants with single ventricle (SV).. We analyzed weight-for-age z-score minus head circumference-for-age z-score (HCAZ), relative head growth (cm/kg), along with individual growth variables in subjects prospectively enrolled in the Infant Single Ventricle Trial. Associations between growth indices and scores on the Psychomotor Developmental Index (PDI) and Mental Developmental Index (MDI) of the Bayley Scales of Infant Development-II (BSID-II) at 14 months were assessed.. Of the 230 subjects enrolled in the Infant Single Ventricle trial, complete growth data and BSID-II scores were available in 168 (73%). Across the cohort, indices of asymmetric growth varied widely at enrollment and before superior cavopulmonary connection (SCPC) surgery. BSID-II scores were not associated with these asymmetry indices. In bivariate analyses, greater pre-SCPC HCAZ correlated with higher MDI (r = 0.21; P = .006) and PDI (r = 0.38; P < .001) and a greater HCAZ increase from enrollment to pre-SCPC with higher PDI (r = 0.15; P = .049). In multivariable modeling, pre-SCPC HCAZ was an independent predictor of PDI (P = .03), but not MDI.. In infants with SV, growth asymmetry was not associated with neurodevelopment at 14 months, but pre-SCPC HCAZ was associated with PDI. Asymmetric growth, important in other high-risk infants, is not a brain-sparing adaptation in infants with SV.. Clinicaltrials.gov: NCT00113087.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Abnormalities; Cephalometry; Double-Blind Method; Enalapril; Female; Growth Disorders; Heart Defects, Congenital; Heart Ventricles; Humans; Infant; Infant, Newborn; Male; Neurodevelopmental Disorders; Prospective Studies

To describe growth patterns in infants with single ventricle physiology and determine factors influencing growth.. Data from 230 subjects enrolled in the Pediatric Heart Network Infant Single Ventricle Enalapril Trial were used to assess factors influencing change in weight-for-age z-score (z) from study enrollment (0.7 ± 0.4 months) to pre-superior cavopulmonary connection (SCPC; 5.1 ± 1.8 months, period 1) and pre-SCPC to final study visit (14.1 ± 0.9 months, period 2). Predictor variables included patient characteristics, feeding regimen, clinical center, and medical factors during neonatal (period 1) and SCPC hospitalizations (period 2). Univariate regression analysis was performed, followed by backward stepwise regression and bootstrapping reliability to inform a final multivariable model.. Weights were available for 197 of 230 subjects for period 1 and 173 of 197 subjects for period 2. For period 1, greater gestational age, younger age at study enrollment, tube feeding at neonatal hospitalization discharge, and clinical center were associated with a greater negative z (poorer growth) in multivariable modeling (adjusted R(2) = 0.39, P < .001). For period 2, younger age at SCPC and greater daily caloric intake were associated with greater positive z (better growth; R(2) = 0.10, P = .002).. Aggressive nutritional support and earlier SCPC are modifiable factors associated with a favorable change in weight-for-age z-score.

Topics: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Growth Disorders; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Prospective Studies

Angiotensin converting enzyme (ACE) inhibitors are known to improve clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology show abnormalities in ventricular function as well as poor growth. The ability of an ACE inhibitor to preserve ventricular function and improve growth in these infants is unknown.. The Pediatric Heart Network designed a randomized, double-blind trial to compare outcomes in infants with single-ventricle physiology receiving enalapril or placebo. Neonates < or =45 days old were eligible. The primary outcome is weight-for-age Z-score at 14 months of age. Secondary outcomes include other measures of somatic growth, laboratory and functional measures of heart failure, developmental indices, measures of ventricular size and function, and the relationship of the renin-angiotensin-aldosterone system genotype to the response to enalapril. The incidence and spectrum of adverse events will also be compared between treatment groups.. A total of 1,245 neonates were screened and 533 (43%) were eligible. The consent rate was 43%; 230 subjects were enrolled. Parental reluctance to participate was the primary reason for non-consent in 79% of the eligible nonconsenting patients. Randomized patients were older, more likely to be male, and more likely to have hypoplastic left heart syndrome than the eligible patients who did not enroll.. The results of this randomized trial will make an important contribution to the management of infants with single-ventricle physiology by determining whether initiation of ACE inhibition therapy in the neonatal period improves growth, clinical outcome, and ventricular function.

Topics: Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Enalapril; Female; Heart Defects, Congenital; Heart Ventricles; Humans; Infant, Newborn; Male

Angiotensin convertase inhibitor (Enalapril) was used in 51 children aged 4 days up to 18 years (mean 4.3 +/- 5.5, years). As many as 27 subjects were newborns (4) and infants (23). The patients suffered from circulatory insufficiency due to congestive cardiomyopathy (13 cases). 6 treated subjects suffered from circulatory insufficiency due to congenital heart malformations before cardiac surgery and 22 after it (including complex malformations operated according to Fontan method). 10 children were treated because of arterial hypertension. 4 subjects suffered form life-threatening arrhythmias coexisting with circulatory insufficiency. (These subjects were already mentioned among the patients suffering from circulatory insufficiency). Enalapril (mainly as a drug named Benalapril) was used in the mean dose of 0.21 mg/kg of body mass daily. 4 patients (8%) died during treatment but their deaths can not be related to angiotensin convertase inhibitor therapy. In the other children (82%) the beneficial influence of angiotensin convertase inhibitor use was found (improvement in comparison with the state before convertase inhibitor introduction). In 10% of subjects enalapril did not show any significant therapeutic effect. According to authors' opinion enalapril use is exceptionally profitable in the subjects surgically treated for complex heart malformations (Fontan operation). The beneficial effect was also found in majority of children suffering from congestive cardiomyopathy. Convertase inhibitor was always successfully used as the unique antihypertensive drug in children suffering from arterial hypertension. In the other cases treatment was combined (mainly with digitalis). This combination seems to be exceptionally useful in children suffering from congestive cardiomyopathy. Only in 1 case unserious side effect was found (persistent cough).

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiac Output, Low; Child; Child, Preschool; Enalapril; Heart Defects, Congenital; Heart Failure; Humans; Hypertension; Infant; Infant, Newborn; Postoperative Care; Premedication; Survival Rate; Treatment Outcome

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

Topics: Angiotensins; Child; Enalapril; Heart Defects, Congenital; Heart Ventricles; Hemodynamics; Humans; Infant; Treatment Outcome; Univentricular Heart

Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of nephrotoxins. This study examines the epidemiology of nephrotoxin exposure and nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS).. This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high nephrotoxin exposure was defined as receipt of ≥ 3 nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥ 2. Poisson models were used to compute adjusted relative risk (aRR) of high nephrotoxin exposure for AKI.. One hundred fifty-four children (median age 20.4 months, IQR 2.3-59.5) were included. One hundred thirty-one (85.1%) received at least one nephrotoxin; 32 (20.8%) received ≥ 3 nephrotoxins. The most commonly administered medications were ketorolac (n = 74, 48.1%), aspirin (n = 62, 40.3%), ibuprofen (n = 51, 33.1%), vancomycin (n = 39, 25.3%), piperacillin/tazobactam (n = 35, 22.7%), and enalapril (n = 14, 9.1%). AKI occurred more commonly in those exposed to ≥ 3 nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR = 1.2, 95% CI 0.9-1.7). Severe AKI was similar between those with and without high nephrotoxin exposure (21.9 vs. 19.7%, p = 0.78).. Nephrotoxin use is common following pediatric CHS. While we found no association between high nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common nephrotoxins, less injurious agents exist and nephrotoxin exposure may represent a modifiable risk factor for AKI.

Topics: Acute Kidney Injury; Adolescent; Aspirin; Cardiac Surgical Procedures; Child; Child, Preschool; Critical Illness; Enalapril; Female; Heart Defects, Congenital; Humans; Ibuprofen; Infant; Ketorolac; Male; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Retrospective Studies; Vancomycin

A few studies have evaluated the impact of clinical trial results on practice in paediatric cardiology. The Infant Single Ventricle (ISV) Trial results published in 2010 did not support routine use of the angiotensin-converting enzyme inhibitor enalapril in infants with single-ventricle physiology. We sought to assess the influence of these findings on clinical practice.. A web-based survey was distributed via e-mail to over 2000 paediatric cardiologists, intensivists, cardiothoracic surgeons, and cardiac advance practice nurses during three distribution periods. The results were analysed using McNemar's test for paired data and Fisher's exact test.. The response rate was 31.5% (69% cardiologists and 65% with >10 years of experience). Among respondents familiar with trial results, 74% reported current practice consistent with trial findings versus 48% before trial publication (p<0.001); 19% used angiotensin-converting enzyme inhibitor in this population "almost always" versus 36% in the past (p<0.001), and 72% reported a change in management or improved confidence in treatment decisions involving this therapy based on the trial results. Respondents familiar with trial results (78%) were marginally more likely to practise consistent with the trial results than those unfamiliar (74 versus 67%, p=0.16). Among all respondents, 28% reported less frequent use of angiotensin-converting enzyme inhibitor over the last 3 years.. Within 5 years of publication, the majority of respondents was familiar with the Infant Single Ventricle Trial results and reported less frequent use of angiotensin-converting enzyme inhibitor in single-ventricle infants; however, 28% reported not adjusting their clinical decisions based on the trial's findings.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiologists; Clinical Trials as Topic; Electronic Mail; Enalapril; Heart Defects, Congenital; Heart Failure; Heart Ventricles; Humans; Pediatrics; Practice Patterns, Physicians'; Surveys and Questionnaires; Translational Research, Biomedical; United States

Angiotensin-converting enzyme inhibitors (ACEi) are commonly used for pediatric cardiology patients. However, studies examining their safety for neonates with cardiac disease are scarce. The current study aimed to test the hypothesis that ACEi-mediated nephrotoxicity occurs in neonates and may be underappreciated in this population. A retrospective review of 243 neonates with cardiac disease between 2007 and 2010 was performed. Demographic data, weight, length, captopril and enalapril dosing, serum [K⁺], serum creatinine, and concomitant medications during ACEi therapy were recorded and analyzed. Body surface area (BSA), creatinine clearance (CrCl), and change in [K⁺] were calculated. The age range of neonates at ACEi initiation was 15.9-18.1 days. The inclusion criteria was met by 206 neonates: 168 term (82%) and 38 preterm (18%) newborns. Of these neonates, 42% were female, and all the patients had a BSA smaller than 0.33 m² (a group known to have relative renal insufficiency). The mean dose of enalapril was 0.08 ± 0.007 mg/kg for the preterm neonates and 0.08 ± 0.003 mg/kg for the term neonates. The mean dose of captopril was 0.07 ± 0.009 mg/kg for the preterm neonates and 0.13 ± 0.019 mg/kg for the term neonates. A significant decrease in CrCl occurred for both the preterm (p < 0.01) and term (p < 0.001) neonates while they were receiving ACEi. However, the two groups did not differ significantly (p = 0.183). Nearly 42% of all the patients showed renal risk, with approximately 30% demonstrating renal failure by modified pRIFLE (pediatric risk, injury, failure, loss, and end-stage renal disease) criteria. Despite the lack of significantly different CrCl, the premature neonates were more likely to experience ACEi-related renal failure by pRIFLE (55%) than their term counterparts (23%; p < 0.001). Despite its common use for term neonates with cardiac disease, ACEi should be used cautiously and only when indications are clear. These results also raise the question whether ACEi should be used at all for preterm neonates.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Creatinine; Enalapril; Female; Heart Defects, Congenital; Humans; Infant, Newborn; Infant, Premature; Kidney Diseases; Male; Retrospective Studies

Angiotensin converting enzyme inhibitors have been used in the neonatal population for both cardiac and renal diseases. Past reports have described deleterious renal and neurological consequences as a result of these drugs. This report describes two infants receiving enalapril for different indications who suffered renal impairments, likely a result of concomitant diuretic use. These cases demonstrate the risks associated with ACE inhibitor use and the importance of vigilant monitoring when using these medications.

Topics: Acute Kidney Injury; Anal Canal; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Esophagus; Heart Defects, Congenital; Heart Septal Defects, Atrial; Humans; Infant; Kidney; Limb Deformities, Congenital; Male; Spine; Trachea; Transposition of Great Vessels

A full-term baby boy developed congestive cardiac failure secondary to left-to-right shunts. He developed acute renal failure following the administration of oral enalapril given for the treatment of cardiac failure. There was no underlying renal disease or renal artery stenosis. He required three peritoneal dialyses, following which he recovered from the renal failure.

Topics: Acute Kidney Injury; Antihypertensive Agents; Enalapril; Heart Defects, Congenital; Heart Failure; Humans; Infant, Newborn; Male; Peritoneal Dialysis

Nephropathy has long been recognized as a potential complication of cyanotic congenital heart disease (CCHD). There have been few large-scale studies or clinical reports on renal impairment in patients with CCHD; similarly, very few studies have examined the drug treatment of nephropathy in CCHD. We examined the clinical characteristics and effectiveness of enalapril, an angiotensin-converting enzyme inhibitor (ACE-I), in patients with CCHD complicated with significant proteinuria.. The clinical records of 37 patients with CCHD were evaluated; all were older than 10 years of age (median 19, range from 10 to 27) and had regular check-ups, including urinalysis. The treatment criteria for enalapril administration included significant proteinuria (urinary excretion > 1.0 g/24 h), stable cardiac condition and blood pressure within the normal range.. Eleven patients (29.7%) had persistent proteinuria, 6 patients met the enalapril treatment criteria and 5 patients were treated for more than 12 months. Enalapril apparently reduced the urinary protein excretion in 4 of the 5 patients (80%). No consistent improvement of renal function, as evidenced in the glomerular filtration rate (GFR), renal plasma flow (RPF) or filtration fraction (FF) was found in these patients, but neither were any significant adverse effects noted.. The incidence of nephropathy among patients with CCHD was about 30%, which was consistent with previous studies. It is worth considering the use of ACE-I when nephropathy accompanies CCHD.

Topics: Adolescent; Adult; alpha-N-Acetylgalactosaminidase; Angiotensin-Converting Enzyme Inhibitors; beta 2-Microglobulin; Biomarkers; Biopsy; Blood Pressure; Child; Creatinine; Enalapril; Female; Glomerular Filtration Rate; Heart Defects, Congenital; Hexosaminidases; Humans; Japan; Kidney; Kidney Function Tests; Male; Nephrotic Syndrome; Proteinuria; Renal Plasma Flow; Serum Albumin; Treatment Outcome

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cyanosis; Enalapril; Female; Heart Defects, Congenital; Heart Diseases; Humans; Male; Treatment Outcome; Ventricular Dysfunction

Enalapril and enalaprilat concentrations were measured after enalapril maleate (0.05 to 0.3 mg/kg) was administered orally to 12 pediatric patients (age range, 10 days to 6 1/2 years) with congestive heart failure caused by congenital heart disease and compared with those obtained from seven normal adults (age range, 21 to 39 years). When normalized to the oral 1 mg/m2 dose of enalapril maleate, the mean +/- SD area under the serum concentration-time curve (AUC) of enalaprilat, a pharmacologically active angiotensin-converting enzyme inhibitor, did not differ significantly between the pediatric group aged > 20 days and adult group (83.1 +/- 47.0 versus 64.6 +/- 17.8 ng.hr/ml per 1 mg/m2). When normalized to the oral 0.1 mg/kg dose, the mean AUC was significantly (p < 0.05) smaller in this pediatric group than in the adult group (138.4 +/- 69.2 versus 245.7 +/- 61.8 ng.hr/ml per 0.1 mg/kg). The AUC observed in three younger (age < 20 days) subjects tended to be much greater compared with infants aged > 20 days. The mean AUC ratio of enalaprilat to enalapril was significantly (p < 0.05) lower in the older pediatric subgroup (2.0 +/- 1.0) than in the adult group (3.4 +/- 1.6), whereas the mean ratios were comparable between the two subdivided pediatric groups. The results suggest that the oral enalapril dose would be better determined on a body surface area rather than on a body weight basis in pediatric patients with congestive heart failure aged > 20 days. The oral dosage should be much reduced in infants with congestive heart failure aged < 20 days compared with those aged > 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Biotransformation; Child; Child, Preschool; Dose-Response Relationship, Drug; Enalapril; Enalaprilat; Female; Heart Defects, Congenital; Heart Failure; Humans; Infant; Infant, Newborn; Male

Eight infants aged between 4 days and 12 weeks with severe heart failure that was refractory to optimal conventional treatment with diuretics were treated with enalapril. The starting dose was 0.1 mg/kg/day, increasing according to response to 0.12-0.43 mg/kg/day. One infant with severe myocarditis did not tolerate enalapril because of hypotension and later died of intractable heart failure. Six of the remaining patients had congenital systemic to pulmonary shunts and one had a simple aortic coarctation. Two weeks after starting enalapril the clinical features of heart failure had improved in all the infants, the mean (SEM) plasma sodium concentration had increased from 129 (2.4) to 136 (1.1) mmol/l and plasma urea concentration had fallen from 7.0 (0.85) to 2.9 (0.85) mmol/l. These data suggest that enalapril is a potentially useful treatment for severe heart failure in infancy.

Topics: Dose-Response Relationship, Drug; Enalapril; Heart Defects, Congenital; Heart Failure; Humans; Infant; Infant, Newborn; Myocarditis; Sodium; Urea

Enalapril was used to treat five patients with pulmonary arterial hypertension secondary to congenital cardiopathy, three with ventricular septal defect, one with arterial septal defect, and one with patent ductus arteriosus. The dose of enalapril was 20 mg/day. All patients underwent pretreatment and posttreatment cardiac catheterization. It was concluded that enalapril may be a useful drug in the treatment of pulmonary arterial hypertension secondary to congenital cardiopathy.

Topics: Adult; Enalapril; Female; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged