Evolution of Left Ventricular Size in Late Survivors of Surgery for Hypoplastic Left Heart Syndrome.

BACKGROUND: Aortic atresia and mitral atresia are predictors of adverse events in early life in patients with hypoplastic left heart syndrome, but it is unclear whether late outcomes are also affected, and whether this impact is related to a small hypertrophied left ventricle (LV) that impairs right ventricle (RV) function. METHODS: Thirty patients with hypoplastic left heart syndrome surviving with a Fontan procedure were identified. Follow-up echocardiograms were available at birth, before the Fontan procedure, and several years after. Mean follow-up time was 10.9 ± 3.1 years. Measurements included interventricular septum thickness and ventricular length. The LV/RV length ratio at birth was calculated, and its impact on later LV and septal growth was examined. The primary endpoint was a composite of death, transplantation, or Fontan takedown. RESULTS: A cutoff LV/RV length ratio of 0.55 was identified: length ratio was 0.55 or less in group A (18 patients) and more than 0.55 in group B (12 patients) The LV/RV length ratio and interventricular septum thickness decreased over time in group A while remaining static in group B. The LV length at birth did not affect late adverse outcomes (hazard ratio 2.7, 95% confidence interval: 0.31 to 23.4, p = 0.37), whereas aortic atresia and mitral atresia were the most potent predictors of death or transplantation or takedown (hazard ratio 8.5, 95% confidence interval: 1.2 to 57.7, p = 0.029). CONCLUSIONS: Patients with aortic atresia and mitral atresia have worse outcomes even after Fontan independently of a small, thick, hypertrophied LV. The most severely hypoplastic LVs do not grow proportionally as much as the RVs.

Intravenous sildenafil in the management of pulmonary hypertension associated with congenital diaphragmatic hernia.

BACKGROUND: Pulmonary artery hypertension (PAH) is a significant cause of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). The phosphodiesterase-5 inhibitor sildenafil may be beneficial as a pulmonary vasodilator in CDH. Use of oral preparations of sildenafil may be restricted by feeding delays and intolerance. This study assessed the cardiorespiratory effects of a newly available intravenous (IV) preparation of sildenafil in CDH. OBJECTIVES: The objective of the article is to assess the acute effects of IV sildenafil infusion on myocardial function, pulmonary artery pressure (PAP), and oxygenation in infants with CDH. METHODS: Retrospective case review of infants with CDH who received continuous IV sildenafil. Physiological and echocardiographic data were reviewed to obtain oxygenation index (OI), PAP, patent ductus arteriosus (PDA) flow, myocardial tissue Doppler velocities, and right ventricular output (RVO) at 48 hours presildenafil, and at 24 to 48 hours and 72 to 96 hours after commencing IV sildenafil. RESULTS: A total of nine infants received IV sildenafil at a dose of 100 to 290 µg/kg/h after CDH repair but before enteral feeding. Pre-IV sildenafil PAP was ≥ systemic blood pressure in all infants, systolic and diastolic right ventricular myocardial velocities were impaired. After 72 to 96 hours of IV sildenafil, OI and Fio 2 were significantly reduced. Ratio of right-to-left to left-to-right PDA flow was > 1 pre-IV sildenafil and < 1 post-IV sildenafil. CONCLUSIONS: IV sildenafil infusion was associated with improved oxygenation. Prospective trials of IV sildenafil are required to determine effects on longer term outcome.

Plasma vascular endothelial growth factor A and placental growth factor: novel biomarkers of pulmonary hypertension in congenital diaphragmatic hernia.

Pulmonary hypertension (PH) due to abnormal pulmonary vascular development is an important determinant of illness severity in congenital diaphragmatic hernia (CDH). Vascular endothelial growth factor A (VEGFA) and placental growth factor (PLGF) may be important mediators of pulmonary vascular development in health and disease. This prospective study investigated the relationship between plasma VEGFA and PLGF and measures of pulmonary artery pressure, oxygenation, and cardiac function in CDH. A cohort of 10 infants with CDH consecutively admitted to a surgical neonatal intensive care unit (NICU) was recruited. Eighty serial plasma samples were obtained and analyzed by multiplex immunoassay to quantify VEGFA and PLGF. Concurrent assessment of pulmonary artery pressure (PAP) and cardiac function were made by echocardiography. Plasma VEGFA was higher and PLGF was lower in CDH compared with existing normative data. Combined plasma VEGFA:PLGF ratio correlated positively with measures of PAP, diastolic ventricular dysfunction, and oxygenation index. Nonsurvivors had higher VEGFA:PLGF ratio than survivors at days 3-4 of life and in the second week of life. These findings suggest that increased plasma VEGFA and reduced PLGF correlate with clinical severity of pulmonary vascular disease and may be associated with adverse outcome in CDH. This potential role for combined plasma VEGFA and PLGF in CDH as disease biomarkers, pathogenic mediators, and therapeutic targets merits further investigation.

Right ventricular diastolic function measured by tissue Doppler imaging predicts early outcome in congenital diaphragmatic hernia.

OBJECTIVE: To investigate the relationship between early right ventricular function measured by tissue Doppler imaging and early outcome measures in newborn infants with congenital diaphragmatic hernia. DESIGN: Retrospective cohort study. SETTING: Surgical neonatal ICU within a regional pediatric center. PATIENTS: Twenty newborn infants with congenital diaphragmatic hernia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis of serial echocardiograms in a cohort of 20 infants with congenital diaphragmatic hernia was done. Tissue Doppler early diastolic and systolic myocardial velocities were measured to assess diastolic and systolic function, respectively, in the basal right ventricle. Pulmonary:systemic peak pressure ratio was estimated using velocity of tricuspid regurgitation. Physiologic, treatment, and early outcome data (duration of respiratory support and length of stay) were recorded. For analysis, duration of respiratory support was selected as the main outcome measure, and infants were divided into two groups based on median duration of respiratory support of 21 days: duration of respiratory support more than 21 days and duration of respiratory support less than 21 days. In 16 surviving infants, mean right ventricular early diastolic myocardial velocity on days 1 and 2 of life correlated with length of stay and duration of respiratory support (r = -0.75, p = 0.002 and r = -0.84, p = 0.0001, respectively). Mean pulmonary:systemic peak pressure ratio on days 1 and 2 of life did not significantly correlate with outcome measures. At receiver-operating characteristics analysis, averaged right ventricular early diastolic myocardial velocity on days 1 and 2 of life of less than 4.6 cm/s predicted duration of respiratory support more than 21 days, with 100% sensitivity and 88% specificity (area under the curve = 0.96, p = 0.002). Right ventricular early diastolic myocardial velocity was significantly lower in the first week of life in the duration of respiratory support more than 21-day group on days 1 and 2 and days 7 and 8. After surgery, right ventricular early diastolic myocardial velocity decreased in the duration of respiratory support more than 21-day group and was significantly lower at days 3 and 4 postoperative. CONCLUSIONS: Tissue Doppler imaging mean right ventricular early diastolic myocardial velocity on days 1 and 2 of life predicted early outcome in surviving infants with congenital diaphragmatic hernia. Right ventricular diastolic dysfunction is associated with disease severity in congenital diaphragmatic hernia. Right ventricular function may be optimized by delaying surgical repair in infants with severe congenital diaphragmatic hernia.