Angiotensin-converting enzyme inhibition and pre-superior cavopulmonary connection haemodynamics in infants with single-ventricle physiology. Al Balushi A, Averin K, Hsu DT, Mackie AS. Cardiol Young. 2021 Feb 16:1-5. doi: 10.1017/S1047951121000305. PMID: 33588974
Take Home Points:
- ACE inhibitors did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to Superior Cavo-pulmonary connection (Glenn) palliation.
- The pathophysiology of pulmonary vascular remodeling in these infants is complex, and this study suggests that enalapril plays no role in that process in this population.
Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch:
Angiotensin-converting enzyme inhibitors have been used in pediatric heart failure associated with left-to-right shunts or chronic valvular regurgitation because they reduce systemic vascular resistance and left-to-right shunt. Amongst single-ventricle patients, ACEi have been shown to decrease ventricular filling pressure in older children with Fontan physiology while pulmonary hypertension therapies aimed at modulating the pulmonary vascular resistance in this patient population have yielded mixed results. Adults with chronic heart failure treated with ACEi have been shown to have lower PA pressure with short term use.
Material and methods:
Using the Pediatric Heart Network Infant Single Ventricle trial (ISV trial) dataset, the original ISV trial showed that enalapril in the first year of life was not associated with improved somatic growth, ventricular function, or heart failure severity, but the ISV trial did not explore the impact of ACEi on measures of pulmonary vascular health. The authors hypothesized that infants enrolled in the ISV trial who received enalapril would have lower mean PA pressure compared to those who received placebo.
The study enrolled infants at 10 centers in the United States of America and Canada from August 2003, to May 2007. Inclusion criteria were infants with single ventricle physiology between 1 week and 45 days of age with stable systemic and pulmonary blood flow in whom a superior Cavo pulmonary connection (SCPC) was planned.
The primary outcome of this analysis was:
- Invasively measured mean PA pressure at the time of the pre-SCPC catheterization. If the mean PA pressure was not recorded in the catheterization dataset, a pulmonary venous wedge pressure was taken as a representative of mean PA pressure if < 18 mmHg.
- Transpulmonary gradient and pulmonary-to-systemic blood flow ratio recorded during pre-SCPC catheterization and oxygen saturation post-SCPC (7 days after surgery) were secondary outcomes.
The initial enalapril dose prescribed in the ISV trial was 0.1 mg/kg/day. The dose was up titrated as tolerated over a period of 2 weeks to the target dose of 0.4 mg/kg/day, given in two divided doses per day. Patients on enalapril were grouped into low- and high dose, based on a cut-off of 0.3 mg/kg/day.
Within the ISV trial, 179 of 230 patients underwent pre-SCPC cardiac catheterization and were included in the current analysis. There were 94 patients (53%) in the placebo group and 85 (47%) in the enalapril group. Baseline patient characteristics were similar between the two groups.
Results are provided as n (%) unless otherwise specified.
DKS = Damus–Kaye–Stansel.
PAB = pulmonary artery band.
SD = standard deviation.
*No direct measurement of pulmonary artery pressure and pulmonary vein wedge pressure > 18 mmHg
Hemodynamic outcomes The primary analysis showed no difference in the mean PA pressure between the enalapril and placebo groups (13.1 ± 2.9 versus 13.7 ± 3.4 mmHg, p = 0.31).
Secondary outcome variables also did not differ between study groups. There was no difference in the enalapril versus placebo groups for any of the outcome measures according to the morphology of the ventricle.
Pre-specified subgroup analysis was also performed according to the type of shunt. In infants who had a Sano shunt (Table 4), the mean PA pressure was 13.0 ± 2.5 in the enalapril group versus 14.0 ± 3.6 in the placebo group (p = 0.25). In the Sano shunt patients, the post-SCPC oxygen saturation was 84 ± 4% in the enalapril group versus 82 ± 5% in the placebo group (p = 0.007). In infants who received an aortopulmonary shunt, the mean PA pressure was 14.0 ± 3.2 in the enalapril group versus 14.0 ± 3.4 in the placebo group (p = 0.75), and post-SCPC oxygen saturation was similar in the enalapril and placebo groups (83 ± 6 versus 82 ± 6, respectively, p = 0.96).
Impact of high-dose enalapril: The mean PA pressure was 13.2 ± 3.6 in the high-dose enalapril group (0.3–0.4 mg/kg/day) versus 13.2 ± 3.5 in the low-dose group (0.1–0.2 mg/kg/day) (p = 0.98).
Conclusion: ACE inhibitors did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to Glenn palliation.