Mark H.D. Danton

Pre-operative sildenafil and pulmonary endothelial-related complications following cardiopulmonary bypass : a randomised trial in children undergoing cardiac surgery*

In a randomised trial, we compared the effects of oral sildenafil (0.5 mg.kg−1) and placebo, administered the day before cardiac surgery, in 24 children. In sildenafil vs placebo patients, pre‐cardiopulmonary bypass median (IQR [range]) cyclic‐guanosine‐monophosphate was not significantly different (29.9 (2.1–208.1 [0.5–391.5]) vs 5.2 (0.3–54.6 [0–628.9]) pmol.ml−1, respectively). Post‐cardiopulmonary bypass, nitrate/nitrite levels were also not significantly different (0.7 (0–8.0 [0–142.8]) vs 0 (0–2.7 [0–52.7]) μM, respectively). Postoperatively, mean (SD) pulmonary vascular resistance (2.64 (2.28) vs 1.90 (1.12) WU.m−2, respectively and oxygenation index (5.29 (4.60) vs 3.38 (2.54), respectively) remained unchanged, whilst oxygen delivery (57.18 (21.24) vs 74.13 (35.46) ml.min−1.m−2, respectively) and bi‐ventricular systolic function (left ventricle 3.78 (0.94) vs 4.55 (1.08) cm.s−1, respectively; p = 0.002; right ventricle 6.93 (1.47) vs 8.09 (2.25) cm.s−1, respectively; p < 0.001) were significantly reduced in the sildenafil group. In this trial, pre‐operative sildenafil did not affect postoperative pulmonary vascular resistance. There was, however, a negative impact on ventricular function and oxygenation.

Tissue Doppler imaging following paediatric cardiac surgery: early patterns of change and relationship to outcome

In this study, tissue Doppler imaging (TDI) was used to assess changes in ventricular function following repair of congenital heart defects. The relationship between TDI indices, myocardial injury and clinical outcome was explored. Forty-five children were studied; 35 with cardiac lesions and 10 controls. TDI was performed preoperatively, on admission to paediatric intensive care unit (PICU) and day 1. Regional myocardial Doppler signals were acquired from the right ventricle (RV), left ventricle (LV) and septum. TDI indices included: peak systolic velocities, isovolumetric velocities (IVV) and isovolumetric acceleration (IVA). Preoperatively, bi-ventricular TDI velocities in the study group were reduced compared with normal controls. Postoperatively, RV velocities were significantly reduced and this persisted to day-1 (PreOp vs. PICU and day-1: 7.7+/-2.2 vs. 3.4+/-1.0, P<0.0001 and 3.55+/-1.29, P<0.0001). LV velocities initially declined but recovered towards baseline by day-1 (PreOp vs. PICU: 5.31+/-1.50 vs. 3.51+/-1.23, P<0.0001). Isovolumetric parameters in all regions were reduced throughout the postoperative period. Troponin-I release correlated with longer X-clamp times (r=0.82, P<0.0001) and reduced RV velocities (r=0.42, P=0.028). Reduced pre- and postoperative LV velocities correlated with longer ventilation (PreOp: r=0.54, P=0.002; PostOp: r=0.42, P=0.026). This study identified reduced postoperative RV velocities correlated with myocardial injury while reduced LV TDI correlated with longer postoperative ventilation.

Synergistic interaction between right ventricular mechanical dyssynchrony and pulmonary regurgitation determines early outcome following tetralogy of Fallot repair

OBJECTIVE The ability of the right ventricle to tolerate acute pulmonary regurgitation (PR) following tetralogy of Fallot (TOF) repair is variable and the mechanisms that underlie this are not completely understood. We hypothesise that dyssynchronous wall mechanics affects the RV tolerance to postoperative PR with adverse effect on early surgical outcome. METHODS Twenty-four TOFs (mean age 19.5+/-15.5 months) undergoing elective repair were prospectively recruited. Ventricular wall mechanics was studied by tissue Doppler echocardiography following induction (preop) and postoperative day one (POD1) and compared with a control group (10 VSD/AVSD). Segmental dyssynchrony, defined as out-of-phase peak myocardial contraction, was determined at the base, mid, apical segments of the septum, RV and LV free walls and scored by the total number of affected segments. PR was graded from absent to severe and RV dimension was quantified by end-diastolic area index (RVEDAI). Cardiac index (CI) was measured by pulse contour cardiac output analysis. Outcome measures were CI, mixed venous oxygen saturation (SvO2), lactate, and duration of ventilation and critical care stay. RESULTS Preoperatively, biventricular free-wall motion was synchronous in both groups. Following surgery, TOF developed RV-septal dyssynchrony (>2 segments in 11 (46%) vs none in control, p=0.01), while the LV free wall remained normal in both groups. RV-septal dyssynchrony correlated with the ventilation time (rho=0.69, p=0.003), critical care stay (rho=0.58, p=0.02) in the presence of PR (n=16), but not with other outcome measures. The relationships between dyssynchrony and early outcome were not seen when PR was absent. In the presence of PR, median RVEDAI was greater with higher dyssynchrony score (>3 segments; p=0.009). The degree of PR did not affect critical care/ventilation time or RVEDAI. The presence of transannular patch (p=0.007) or at least moderate PR (p=0.01) was associated with a more severe dyssynchrony. CONCLUSIONS Dyssynchronous RV-septal wall mechanics occurs early after Fallot repair. The magnitude of dyssynchrony appears to interact synergistically with pulmonary regurgitation to influence RV dimension and early outcome.

Impact of modified ultrafiltration on morbidity after pediatric cardiac surgery.

Cardiopulmonary bypass is a double-edged sword. Without it, corrective cardiac surgery would not be possible in the majority of children with congenital heart disease. However, much of the perioperative morbidity that occurs after cardiac surgery can be attributed to a large extent to pathophysiologic processes engendered by extracorporeal circulation. One of the challenges that has confronted pediatric cardiac surgeons has been to minimize the consequences of cardiopulmonary bypass. Ultrafiltration is a strategy that has been used for many years in an effort to attenuate the effects of hemodilution that occur when small children undergo surgery with cardiopulmonary bypass. Over the past several years, a modified technique of ultrafiltration, commonly known as modified ultrafiltration, has been used with increasing enthusiasm. Multiple studies have been undertaken to assess the effects of modified ultrafiltration on organ function and postoperative morbidity following repair of congenital heart defects. This review attempts to evaluate current available scientific evidence on the impact of modified ultrafiltration on organ function and morbidity after pediatric cardiac surgery.

Impaired cardiac autonomic nervous control after cardiac bypass surgery for congenital heart disease

We undertook a study to describe changes in heart rate variability (HRV) postoperatively in children undergoing cardiac bypass surgery for congenital heart disease (CHD). HRV was recorded for a 1-h period preoperatively and a 24-h period postoperatively in 20 children with CHD. We found a highly significant reduction in HRV in both time and frequency domain indices compared to preoperative values, which was sustained throughout the 24-h study period. There was a negative correlation between both time and frequency domain HRV measurements and length of cardiac bypass. HRV is reduced postoperatively and correlates with cardiac bypass time. Length of cardiac bypass time may be one mechanism whereby HRV is reduced following surgery.

Acute B-type natriuretic peptide response and early postoperative right ventricular physiology following tetralogy of Fallot's repair

B-type natriuretic peptide (BNP) response early after a tetralogy of Fallots repair remains unclear. BNP was measured pre- and post-operatively (immediately, day 1) in 18 children undergoing corrective repair with concurrent echocardiography (pre-, post-op day 1) to assess right ventricular (RV) systolic dysfunction, restrictive physiology, wall motion and pulmonary regurgitation (PR). In the first 24 h postoperatively, BNP rose acutely in all patients (mean 34.9 vs 144.4 vs 716.9 pg/ml at pre-op, days 0 and 1; P < 0.001). Immediate postoperative BNP correlated with preoperative haematocrit (rho = 0.52, P = 0.03) and inversely with preoperative oxygen saturation (rho = -0.63, P = 0.007). All patients showed reduced RV systolic function and abnormal wall motion with at least moderate PR in six patients (33.3%) and restrictive physiology in four (24%). Subsequent BNP expression (post-op day 1) correlated with a low RV fractional area change (rho = -0.51, P = 0.04), high oxygen extraction ratio (rho = 0.56, P = 0.02) and high central venous pressure (rho = 0.79, P < 0.001). The LV function and wall motion remained preserved in all patients. The mechanism of BNP expression is likely to be multi-factorial in the presence of a complex postoperative RV physiology in tetralogy of Fallot. An acute BNP response in the early postoperative period reflects an important physiological role and may be used as an adjunct biomarker to assess the RV function.

Myocardial expression of heat shock protein 70i protects early postoperative right ventricular function in cyanotic tetralogy of Fallot

BACKGROUND Right ventricular dysfunction occurs after tetralogy of Fallot repair and may relate to greater myocardial vulnerability to ischemia-reperfusion injury in cyanotic patients. The inducible form of heat shock protein 70 (HSP-70i), a molecular chaperone, is upregulated in response to cellular stress and limits myocardial injury against ischemia-reperfusion. We evaluated the myocardial expression of HSP-70i and its relation to right ventricular function and clinical outcome in patients with tetralogy of Fallot undergoing corrective surgery. METHODS Twenty patients with tetralogy of Fallot were studied: 10 cyanotic (group Cy) and 10 noncyanotic (group noCy). Western blot was used to quantify HSP-70i from resected right ventricular outflow tract myocardium at baseline and subsequent ischemic time. Biventricular function was quantified by tissue Doppler echocardiography and compared with that of 15 age-matched healthy children. Postoperative systemic perfusion was assessed by mixed venous oxygen saturation, oxygen extraction ratio, and lactate. RESULTS Group Cy had thicker septum (median 0.85 vs 0.66 cm; P = .01) and longer crossclamp time (median 100.0 vs 67.5 minutes; P = .004). There were no difference in HSP-70i between groups at baseline (4.12 vs 3.44 relative optical density; P = .45) or subsequent ischemic time. Preoperative biventricular systolic function was reduced in patients with tetralogy compared with controls with further postoperative right ventricular impairment. Group Cy had higher troponin-I levels (median 16.5 vs 11.1 ng/mL; P = .04) and inotrope scores (14.0 vs 6.5; P = .05) but no differences in ventricular function, mixed venous oxygen saturation, oxygen extraction ratio, and lactate between groups. In group Cy, baseline HSP-70i correlated with better postoperative right ventricular function (rho = 0.80; P = .009), mixed venous oxygen saturation (rho = 0.68; P = .04), and oxygen extraction ratio (rho = -0.71; P = .03). These relationships were absent in group noCy. CONCLUSIONS The association of HSP-70i expression with improved right ventricular function and systemic perfusion suggests an important cardioprotective effect of HSP-70i in cyanotic tetralogy of Fallot.

Computational modelling to optimize the hybrid configuration for hypoplastic left heart syndrome

OBJECTIVES Hybrid palliation for hypoplastic left heart syndrome (HLHS) is associated with mortality and late ventricular dysfunction. Increased ventricular workload and coronary perfusion limitation may be the important factors. Using mathematical modelling, this study investigated the effects of differing hybrid configurations on the demands on this single ventricle circulation. METHODS A multicompartmental Windkessel model of hybrid HLH-aortic atresia circulation was adopted, with a time-varying elastance representing ventricular functionality. The effects of diameter increases in bilateral pulmonary artery bandings (PABs) (+0.5, 2.5-4 mm) and ductal stent (+1, 4-10 mm) on cardiovascular haemodynamics, systemic oxygenation and ventricular energetics were assessed. RESULTS Simulations showed that an increase in PAB diameter of 2.5-4 mm resulted in an increased Q (0.61-2.66), and diastolic stent backflow (-0.2 to -0.78 l/min) with reduced systemic perfusion (0.82-0.77 l/min) and diastolic pressures (48.3-41.2 mmHg). Arterial and venous saturations increased, SaO2 (%) was 62-88 and SvO(2) 41-65. To maintain mean systemic pressures, substantial increases in cardiac output (1.3-2.8 l/min) and ventricular stroke work (576-1360 mmHg ml) were required. A decrease in the ductal stent diameter over the range 10-7 mm had a negligible haemodynamic effect: reduced systemic systolic pressure (77-72 mmHg) and increase in ventricular stroke work (781-790 mmHg ml). When the ductal diameter was restricted to <7 mm, it resulted in a significant reduced systemic flow and increased stroke work. Optimal hybrid configuration was defined at PAB 3 mm and ductal stent ≥7 mm. CONCLUSIONS In this model, increasing the PAB diameter, or a stent diameter <7 mm, substantially increased single ventricle workload and reduced systemic perfusion and diastolic pressure. This may compromise myocardial oxygen demand-supply, particularly in the setting of retrograde-dependent coronary perfusion.

Computational modelling of the hybrid procedure in hypoplastic left heart syndrome : a comparison of zero-dimensional and three-dimensional approach.

Previous studies have employed generic 3D-multiscale models to predict haemodynamic effects of the hybrid procedure in hypoplastic left heart syndrome. Patient-specific models, derived from image data, may allow a more clinically relevant model. However, such models require long computation times and employ internal pulmonary artery band [dint] dimension, which limits clinical application. Simpler, zero-dimensional models utilize external PAB diameters [dext] and provide rapid analysis, which may better guide intervention. This study compared 0-D and 3-D modelling from a single patient dataset and investigated the relationship dint versus dext and hemodynamic outputs of the two models. Optimum oxygen delivery defined at dint=2mm corresponded to dext=3.1 mm and 3.4 mm when models were matched for cardiac output or systemic pressure, respectively. 0-D and 3-D models when matched for PAB dimension produced close equivalence of hemodynamics and ventricular energetics. From this study we conclude that 0-D model can provide a valid alternative to 3D-multiscale in the hybrid-HLHS circulation.

Circumflex Retroesophageal Aorta Mimicking Aortic Interruption A Rare Cause of Aortic Obstruction in a Neonate

Critical obstruction of the aorta presenting in the neonate typically occurs with aortic interruption or coarctation, following ductus arteriosus closure. Circumflex retroesophageal aortic arch is a rare aortic arch anomaly in which a right aortic arch continues as a retroesophageal component and descends on the left of the spine. Obstruction within the arch can occur, usually identified incidentally in older children. We report a neonate with circumflex aorta with ventricular septal defect in which there was hypoplasia of the retroesophageal segment. The patient presented with cardiovascular collapse following duct closure mimicking aortic interruption. The case is presented, together with the surgical repair.