Oral Enoximone as an Alternative to Protracted Intravenous Medication in Severe Pediatric Myocardial Failure.

Phosphodiesterase 3 inhibitors have been used successfully in pediatric patients with acute or chronic myocardial dysfunction over the last two decades. Their protracted continuous intravenous administration is associated with risk of infectious and thromboembolic complications. Weaning intravenous medication and starting oral angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers can be challenging. We reviewed retrospectively hospital records of 48 patients receiving oral enoximone treatment in a single tertiary pediatric cardiac center between November 2005 and April 2014. Failure to wean from intravenous milrinone infusion and/or intolerance of ACE inhibitors and/or beta-blockers was indications for oral enoximone treatment. Age of the patients ranged between 0.5 and 191 months (median 7.5 months) at the time of starting enoximone treatment. There were 14 patients (29 %) with left ventricular dysfunction due to myocarditis or dilated cardiomyopathy and 34 patients (71 %) with myocardial dysfunction complicating congenital heart disease. Fifteen (44 %) of these 34 patients had left ventricular dysfunction, 13 (38 %) right ventricular dysfunction, and in 6 (18 %) both ventricles were failing. Duration of oral enoximone treatment was between 3 days and 34 months (median of 2.3 months). Myocardial functional recovery allowed for weaning of enoximone treatment in 15 patients (31 %) after 6 days-15 months (median 5 months). No adverse hemodynamic effects were noted. Blood stained gastric aspirates encountered in two patients resolved with concomitant milk administration. Based on our limited experience, oral enoximone is a well-tolerated and promising alternative to intravenous medication and/or other commonly used oral medications in selected pediatric patients with chronic heart failure.

Right Ventricular Pressure Overload and Pathophysiology of Growing Porcine Biomodel.

The primary objective was to create a clinically relevant model of right ventricular hypertension and to study right ventricular myocardial pathophysiology in growing organism. The secondary objective was to analyse the effect of oral enoximone (phosphodiesterase inhibitor) therapy on right ventricular haemodynamic parameters and myocardial changes in biomodel of right ventricular hypertension. The study included a total of 12 piglets of 42 days of age. Under general anaesthesia, pulmonary artery banding (PAB) was performed surgically to constrict the main pulmonary artery to about 70-80 % of its original dimension. The study presented two groups of animals labelled C (control animals with PAB; n = 8) and E (animals with PAB and oral administration of enoximone; n = 4). Direct pressure and echocardiographic measurements were taken during operation (time-1), and again at 40 days after surgery (time-2). The animals were killed, and tissue samples from the heart chambers were collected for quantitative morphological assessment. Statistical analysis was performed on all acquired data. At time-2, the median weight of animals doubled and the median systolic pressure gradient across the PAB increased (46.59 ± 15.87 mmHg vs. 20.29 ± 5.76 mmHg; p < 0.001). Changes in haemodynamic parameters were compatible with right ventricular diastolic dysfunction in all the animals. Apoptosis, tissue proliferation and fibrosis were identified in all the myocardial tissue samples. Right ventricular pressure overload leads to increased apoptosis of cardiac myocytes, proliferation and myocardial fibrosis. Our study did not show evidence of haemodynamic benefit or myocardial protective effect of oral enoximone treatment.

Mesenteric near-infrared spectroscopy and risk of gastrointestinal complications in infants undergoing surgery for congenital heart disease.

We hypothesised that lower mesenteric near-infrared spectroscopy values would be associated with a greater incidence of gastrointestinal complications in children weighing <10 kg who were recovering from cardiac surgery. We evaluated mesenteric near-infrared spectroscopy, central venous oxygen saturation, and arterial blood gases for 48 hours post-operatively. Enteral feeding intake, gastrointestinal complications, and markers of organ dysfunction were monitored for 7 days. A total of 50 children, with median age of 16.7 (3.2-31.6) weeks, were studied. On admission, the average mesenteric near-infrared spectroscopy value was 71±18%, and the systemic oxygen saturation was 93±7.5%. Lower admission mesenteric near-infrared spectroscopy correlated with longer time to establish enteral feeds (r=-0.58, p<0.01) and shorter duration of feeds at 7 days (r=0.48, p<0.01). Children with gastrointestinal complications had significantly lower admission mesenteric near-infrared spectroscopy (58±18% versus 73±17%, p=0.01) and higher mesenteric arteriovenous difference of oxygen at admission [39 (23-47) % versus 19 (4-27) %, p=0.02]. Based on multiple logistic regression, admission mesenteric near-infrared spectroscopy was independently associated with gastrointestinal complications (Odds ratio, 0.95; 95% confidence interval, 0.93-0.97; p=0.03). Admission mesenteric near-infrared spectroscopy showed an area under the receiver operating characteristic curve of 0.76 to identify children who developed gastrointestinal complications, with a suggested cut-off value of 72% (78% sensitivity, 68% specificity). In this pilot study, we conclude that admission mesenteric near-infrared spectroscopy is associated with gastrointestinal complications and enteral feeding tolerance in children after cardiac surgery.

Vascular histopathologic reaction to pulmonary artery banding in an in vivo growing porcine model.

Pulmonary artery banding (PAB) is used as a surgical palliation to reduce excessive pulmonary blood flow caused by congenital heart defects. Due to the lack of microscopic studies dealing with the tissue remodeling caused by contemporary PAB materials, this study aimed to assess histologic changes associated with PAB surgery by analyzing local tissue reaction to the presence of Gore-Tex strips fixed around the pulmonary artery. Gore-Tex strips were used for PAB in a growing porcine model. After 5 weeks, histologic samples with PAB (n = 5) were compared with healthy pulmonary arterial segments distal to the PAB or from a sham-treated animal (n = 1). Stereology was used to quantify the density of the vasa vasorum and the area fraction of elastin, smooth muscle actin, macrophages, and nervi vasorum within the pulmonary arterial wall. The null hypothesis stated that samples did not differ histopathologically from adjacent vascular segments or sham-treated samples. The PAB samples had a greater area fraction of macrophages, a lower amount of nervi vasorum, and a tendency toward decreased smooth muscle content compared with samples that had no PAB strips. There was no destruction of elastic membranes, no medionecrosis, no pronounced inflammatory infiltration or foreign body reaction, and no vasa vasorum deficiency after the PAB. All the histopathologic changes were limited to the banded vascular segment and did not affect distal parts of the pulmonary artery. The study results show the tissue reaction of palliative PAB and suggest that Gore-Tex strips used contemporarily for PAB do not cause severe local histologic damage to the banded segment of the pulmonary arterial wall after 5 weeks in a porcine PAB model.

Antibiotic surveillance on a paediatric intensive care unit: easy attainable strategy at low costs and resources.

BACKGROUND: Antibiotic surveillance is mandatory to optimise antibiotic therapy. Our objectives were to evaluate antibiotic use in our pediatric intensive care unit (PICU) and to implement a simple achievable intervention aimed at improving antibiotic therapy. METHOD: Prospective, 3 months surveillance of antibiotic use on PICU (phase I) and evaluation according to the CDC 12-step campaign with development of an attainable intervention. 3 months surveillance (phase II) after implementation of intervention with comparison of antibiotic use. RESULTS: Appropriate antibiotic use for culture-negative infection-like symptoms and targeted therapy for proven infections were the main areas for potential improvement. The intervention was a mandatory checklist requiring indication and recording likelihood of infection at start of antibiotic therapy and a review of the continuing need for therapy at 48 h and 5 days, reasons for continuation and possible target pathogen. The percentage of appropriate empiric antibiotic therapy courses for culture-negative infection-like symptoms increased from 18% (10/53) to 74% (42/57; p<0.0001), duration of therapy <3 days increased from 18% (10/53) to 35% (20/57; p=0.05) and correct targeting of pathogen increased from 58% (7/12) to 83% (20/24; p=0.21). CONCLUSIONS: Antibiotic surveillance using the CDC 12-step campaign can help to evaluate institutional antibiotic therapy. Development of an attainable intervention using a checklist can show improved antibiotic use with minimal expense.

Novel postoperative use of beta-blocking medication for infants with left ventricular outflow obstruction and diastolic myocardial dysfunction.

Severe left ventricular outflow obstruction often is associated with diastolic left ventricular myocardial dysfunction and tachycardia despite successful initial treatment. The authors have used esmolol to lower heart rate in this setting for successful weaning of patients from ventilation in postoperative recovery. Their limited experience supports the beneficial effect of continuous esmolol administration on infants with persistent tachycardia and severe left ventricular diastolic dysfunction in postoperative cardiac intensive care.

ß-blockers in postoperative myocardial diastolic dysfunction: not a panacea.

Successful treatment with heart rate lowering medication has been used to treat adults with chronic myocardial dysfunction of various aetiologies for a number of years. There has been recent evidence for the successful use of ß-receptor blocking medication in highly selected group of infants with diastolic myocardial dysfunction. This case series demonstrates that while the use of ß-receptor blockers in infants early following initial treatment of congenital left heart obstructive lesions appears promising and safe adjunct to more conventional management, the medium-term and long-term care of these patients remains as challenging as before.

Fetal warfarin syndrome.

A case of a baby born preterm with an antenatal diagnosis of aortic coarctation for which prostin was electively started at birth. The baby was found to be profoundly anaemic with no clear obstetric cause. Features consistent with antenatal intracerebral haemorrhage were noted on cranial ultrasonography in the context of severe coagulopathy, prompting investigations which confirmed fetal-maternal haemorrhage. It transpired that, following aortic and mitral valve replacements, the mother was anticoagulated with warfarin at conception, having misunderstood her cardiologist's advice that: 'you cannot get pregnant whilst on warfarin'. Following conversion to low molecular weight heparin, she suffered a stroke, thus warfarin was restarted, with an international normalised ratio of 3-4.7 during pregnancy. Following transfer to the paediatric intensive care unit, fetal warfarin syndrome was diagnosed. The coagulopathy and anaemia were corrected and aortic coarctation was excluded. The baby returned to the neonatal intensive care unit for ongoing care and was discharged home in good condition around his due date. At the present time, there is no clinically overt neurological deficit.

Use of surveillance criteria reduces interstage mortality after the Norwood operation for hypoplastic left heart syndrome.

OBJECTIVES: While hospital mortality after the Norwood operation for hypoplastic left heart syndrome (HLHS) has decreased steadily, interstage mortality until the superior cavopulmonary anastomosis (SCPA) remains a major concern. Our aim was to institute a home surveillance programme to decrease interstage mortality. METHODS: We enrolled 45 HLHS patients surviving the Norwood operation into our home surveillance programme and compared them with 97 patients treated before the initiation of the programme and with a third group of 20 patients not discharged between the first- and the second-stage operation. While still in hospital, parents were taught to record weight and fluid intake as well as oxygen saturations with the help of a vital sign monitor. During the last week of the hospital stay, the following criteria had to be met: oxygen saturation >75%, weight gain of at least 20-30 g in 3 days and a maximum weight loss of 30 g in a day. After discharge, these criteria had to be maintained at all times or the parents were supposed to call our hospital. Additionally, an experienced paediatric cardiologist from our centre called the parents at home once a week. RESULTS: Interstage mortality was reduced significantly from 12.4% (12/97) to 2.2% (1/45) (P = 0.042). The number of patients, who were not discharged before the SCPA, was significantly higher after the start of the home surveillance programme (12/57 vs. 8/105, P = 0.022). After discharge, 14 (31%) infants breached the surveillance criteria. Of these, one patient died and eight patients were operated earlier (SCPA, n = 6; shunt replacement, n = 2). The remaining five patients could be discharged home after observation. Children in the home surveillance programme were younger [102 (67-299) vs. 152 (77-1372) days, P = 0.001] and weighed less (5.09 ± 0.79 vs. 5.75 ± 1.22 kg, P = 0.001) at the SCPA compared with the remainder. Early survival after SCPA was not different. CONCLUSIONS: The home surveillance programme led to an important decrease in interstage mortality. The adherence to the surveillance criteria before discharge resulted in a larger number of patients receiving inpatient treatment until SCPA. Earlier SCPA in the surveillance group had no negative impact on early survival after SCPA.

Hypoplastic left heart syndrome: current considerations and expectations.

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients.

Changes of right ventricular function and longitudinal deformation in children with hypoplastic left heart syndrome before and after the Norwood operation.

BACKGROUND: The purpose of this study was to investigate changes in right ventricular (RV) function and deformation parameters before and at steady state after the Norwood operation in neonates with hypoplastic left heart syndrome. A further aim was to delineate factors that affected these changes. METHODS: On echocardiograms before and 21 days (range, 10-35 days) after the Norwood operation, the two-dimensional speckle-tracking parameters global and regional peak systolic longitudinal strain and strain rate were retrospectively compared in 33 patients with hypoplastic left heart syndrome. In addition, RV functional assessment included RV fractional area change and tricuspid annular plane systolic excursion. The associations between postoperative echocardiographic findings and preoperative or postoperative complications, prenatal diagnosis, postoperative heart rate, oxygen saturation, and medication use as well as cardiopulmonary bypass and aortic cross-clamp times were tested. RESULTS: Global strain (-18.3 ± 3.6% vs -16.8 ± 3.8%, P = .02) and global strain rate (-1.6 ± 0.3 vs -1.2 ± 0.3 sec(-1), P < .0001) decreased significantly. Regional strain decreased significantly in the apical and mid lateral segments, while regional strain rate decreased significantly in all but the basal septal segments. Tricuspid annular plane systolic excursion of the lateral annulus decreased significantly, while RV fractional area change remained the same. No significant associations were found between postoperative RV function and potential impact factors. CONCLUSIONS: Two-dimensional global and regional longitudinal strain and strain rate as well as tricuspid annular plane systolic excursion were reduced in patients with hypoplastic left heart syndrome after the Norwood operation. None of the examined preoperative and postoperative patient or surgical factors was found to explain this decrease.

Perioperative cerebral and somatic oxygenation in neonates with hypoplastic left heart syndrome or transposition of the great arteries.

OBJECTIVE: Significant depression in cerebral oxygen saturation has been observed in patients with hypoplastic left heart syndrome (HLHS) undergoing Norwood operations. We monitored cerebral oxygen saturation with near-infrared spectroscopy before and after this procedure. Patients with transposition of great arteries (TGA) before and after arterial switch operation were also studied to elucidate whether post-cardiopulmonary bypass (CPB) changes in cerebral oxygen saturation are related to CPB or hemodynamic alterations inherent in single-ventricle physiology. METHODS: We monitored 33 patients with HLHS and 20 with TGA 24 hours before and 48 hours after CPB. In addition to cerebral oxygen saturation, routine measurements of oxygen transport and delivery were performed. RESULTS: Preoperatively, cerebral oxygen saturation was higher in patients with HLHS than with TGA (61% ± 7% vs 56% ± 8%, P = .04). After CPB, cerebral oxygen saturation was markedly depressed in both groups but increased toward end of monitoring (HLHS vs TGA minimal value 42% ± 12% vs 54% ± 11%, P < .001, value 48 hours after CPB 62% ± 7% vs 80% ± 8%, P < .0001). Routine measures of oxygen delivery, such as arterial and central venous oxygen saturations, were similar at minimal cerebral oxygen saturation and 48 hours after CPB. CONCLUSIONS: Depression of cerebral oxygen saturation is prevalent among neonates with congenital heart disease regardless of whether univentricular or biventricular circulation is present, suggesting that cerebral desaturation is mainly induced by CPB's effect on cerebral blood flow. Routine measures of oxygen delivery fail to indicate cerebral desaturation.

Risk factors for adverse outcome after superior cavopulmonary anastomosis for hypoplastic left heart syndrome.

OBJECTIVE: Outcome of staged palliation for hypoplastic left heart syndrome (HLHS) has improved over the past decades. We sought to evaluate the outcome of the second palliative procedure, the superior cavopulmonary anastomosis (SCPA), in a single-centre cohort and to identify risk factors for adverse outcome. METHODS: Full data on all 119 HLHS patients who underwent SCPA in our centre between January 1996 and December 2007 were analysed. RESULTS: Early adverse outcome (death or cardiac transplant within 30 days after surgery or before hospital discharge) was 3.4%. Late adverse outcome (death or transplant after hospital discharge but before the next operative procedure) was 8.7%. Postoperative complications occurred in 30% of patients (n = 36), with transient arrhythmia (n = 11; 9%) and pulmonary artery stenosis or thrombosis (n = 10; 8%) being the most common. The presence of more than moderate tricuspid valve regurgitation after surgery proved to be a strong predictor of late adverse outcome (odds ratio (OR) 16.5 (4.4-62.6), P < 0.001). SCPA at less than 4 months of age did not increase the risk for adverse outcome (OR 1.2 (0.4-3.6), P = 0.78) but increased the risk for postoperative complications (OR 6.3 (2.3-14.9), P < 0.001). CONCLUSIONS: SCPA can nowadays be performed in HLHS patients with low mortality. However, more than moderate tricuspid valve regurgitation should be targeted at surgery as it is a risk factor for adverse outcome such as death or need for cardiac transplant. SCPA should ideally be performed in children older than 4 months to minimise the risk of postoperative complications.

The impact of afterload reduction on the early postoperative course after the Norwood operation - a 12-year single-centre experience.

OBJECTIVE: The objective of this study was to analyse the postoperative course and early outcome after the Norwood operation for patients with hypoplastic left heart syndrome. We particularly aimed to assess the impact of surgical and pharmacological modifications introduced. METHODS: Of 157 patients who underwent the Norwood operation between January 1996 and December 2007, postoperative intensive care data on haemodynamics, pharmacological support and ventilation were analysed from 146 patients (six patients died intra-operatively and data were incomplete in five). The cohort was divided into three groups depending on the surgical method and type of afterload reduction. Patients of group 1 (n=39, January 1996-December 1999) were operated with deep hypothermic circulatory arrest. In patients of group 2 (n=59, January 2000-June 2003) and group 3 (n=59, July 2003-December 2007) antegrade selective cerebral perfusion was used. Patients of groups 1 and 2 received sodium nitroprusside to reduce afterload; in group 3 phentolamine was used. RESULTS: There were no differences between the groups in terms of preoperative status and anatomy, except a higher incidence of prenatal diagnosis between groups 3 and 1. The duration and dosage of sodium nitroprusside administration were similar in groups 1 and 2. The median duration of afterload reduction was significantly longer in group 3 compared with both the other groups (72 h (range: 24-201 h) vs 48 h (range: 8-145 h) and 48 h (range: 4-173 h), respectively). The median ventilation times was shorter in group 2 compared with group 1 (61 h (range: 16-1191 h) vs 119 h (range: 26-648 h)). During the first 36 postoperative hours, the mean arterial blood pressure and coronary perfusion pressure were significantly lower in group 3 than in group 1 (50.7+/-4.8 and 28+/-3.7 mmHg vs 53.6+/-5.2 and 31.4+/-4.3 mmHg), but, in patients of group 3, the time period to consistently reach a mean arteriovenous oxygen difference below 5 ml dl(-1) was markedly shorter than in the other groups (group 3: 12h 4.90+/-1.97 ml dl(-1); group 1: 24h 4.53+/-2.25 ml dl(-1) and group 2: 24h 4.57+/-2.04 ml dl(-1)). Complication rates were similar between the groups. However, 30-day mortality decreased over the study period to an exponentially weighted moving average of 2.3%. CONCLUSION: Adamant afterload reduction improves systemic blood flow early after the Norwood operation and may have contributed to the reduction in early postoperative mortality achieved over 12 years.

Outcome of the Norwood operation in patients with hypoplastic left heart syndrome: a 12-year single-center survey.

OBJECTIVE: Recent advances in perioperative care have led to a decrease in mortality of children with hypoplastic left heart syndrome undergoing the Norwood operation. This study aimed to evaluate the outcome of the Norwood operation in a single center over 12 years and to identify clinical and anatomic risk factors for adverse early and longer term outcome. METHODS: Full data on all 157 patients treated between 1996 and 2007 were analyzed. RESULTS: Thirty-day mortality of the Norwood operation decreased from 21% in the first 3 years to 2.5% in the last 3 years. The estimated exponentially weighted moving average of early mortality after 157 Norwood operations was 2.3%. Risk factors were an aberrant right subclavian artery, the use and duration of circulatory arrest, and the duration of total support time. The anatomic subgroup mitral stenosis/aortic atresia and female gender tended to show an increased early mortality. In the group of patients who required postoperative cardiopulmonary resuscitation, the ascending aorta was significantly smaller than in the remainder (3.03 +/- 1.05 vs 3.63 +/- 1.41 mm). Interstage mortality was 15% until the initiation of a home surveillance program in 2005, which has zeroed it so far. It was significantly higher in the mitral stenosis/aortic atresia subgroup and tended to be higher in patients who required cardiopulmonary resuscitation after the Norwood operation. The best actuarial survival was observed in the mitral atresia/aortic atresia subgroup. CONCLUSION: The Norwood operation can now be performed with low mortality. Patients with mitral stenosis/aortic atresia still constitute the most challenging subgroup.

Exercise capacity of a contemporary cohort of children with hypoplastic left heart syndrome after staged palliation.

OBJECTIVE: Outcome of staged palliation for hypoplastic left heart syndrome has improved over the past decades. However, only little is known about the exercise capacity of children with palliated hypoplastic left heart syndrome where a systemic right ventricle supports the systemic circulation. The aim of the study was to assess exercise capacity in a contemporary cohort of children with hypoplastic left heart syndrome palliated in a single centre according to a uniform surgical strategy. METHODS: Standardised cardiopulmonary exercise testing on a treadmill was performed in 46 consecutive hypoplastic left heart patients (median age: 6.0 (4.1-11.4) years). All but one patient reached the anaerobic threshold. Exercise data were compared to normal values obtained with a similar exercise protocol in a large cohort of paediatric volunteers. RESULTS: Oxygen uptake at anaerobic threshold (26.9+/-6.0 ml kg(-1)min(-1); 74.5+/-18.2% of predicted) and maximal oxygen uptake (31.0+/-6.8 ml kg(-1)min(-1); 60.8+/-15.0% of predicted) were significantly reduced compared with controls (P<0.0001 for both). The limitation in exercise capacity was due to an impaired rise in heart rate (158+/-23 bpm; 79.7+/-11.5% of predicted; P<0.0001) and oxygen pulse (4.5+/-1.6 ml per beat; 85.5+/-22.0% of predicted; P<0.0001). Furthermore, respiration during exercise was inefficient with an elevated respiratory rate and reduced maximal tidal volume and minute ventilation at maximal exercise. CONCLUSIONS: The exercise capacity of children with hypoplastic left heart syndrome is markedly reduced. Limitations in heart rate increase and stroke volume augmentation are the major contributors to this. An abnormal ventilatory response to exercise also adds to their limitation in exercise tolerance. However, the degree of physical disability does not justify discouraging these patients from school and leisure sports.