Transient left bundle branch block and left ventricular dysfunction in a patient with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome.

The NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome is a rare novel autoinflammatory disorder. Cardiac involvement has not been previously reported. We present a 12-year-old girl with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome who was diagnosed with severely impaired left ventricular function and complete left bundle branch block during an exacerbation of the disease. Cardiac dysfunction proved to be rapidly reversible after initiation of high-dose methylprednisolone.

Distribution of strain patterns in children with dilated cardiomyopathy.

OBJECTIVES: This study aimed to evaluate the predicting value of quantitative and qualitative dyssynchrony parameters as assessed by two-dimensional speckle tracking echocardiography (STE) on outcome in children with dilated cardiomyopathy (DCM). Furthermore, the reproducibility of these parameters was investigated. BACKGROUND: In previous studies in adults with heart failure, several dyssynchrony parameters have been shown to be a valuable predictor of clinical outcome. METHODS: This multicenter, prospective study included 75 children with DCM and 75 healthy age-matched controls. Using STE, quantitative (time to global peak strain and parameters describing intraventricular time differences) and qualitative dyssynchrony parameters (pattern analysis) of the apical four-chamber, three-chamber, two-chamber views, and the short axis of the left ventricle were assessed. Cox regression was used to identify risk factors for the primary endpoints of death or heart transplantation. Inter-observer and intra-observer variability were described. RESULTS: During a median of 21 months follow-up, 10 patients (13%) reached an endpoint. Although quantitative dyssynchrony measures were higher in patients as compared to controls, the inter-observer and intra-observer variability were high. Pattern analysis showed mainly reduced strain, instead of dyssynchronous patterns. CONCLUSIONS: In this study, quantitative dyssynchrony parameters were not reproducible, precluding their use in children. Qualitative pattern analysis showed predominantly reduced strain, suggesting that in children with DCM dyssynchrony may be a minor problem.

Six-Minute Walk Test as a Predictor for Outcome in Children with Dilated Cardiomyopathy and Chronic Stable Heart Failure.

Cardiopulmonary exercise testing is an important tool to predict prognosis in children and adults with heart failure. A much less sophisticated exercise test is the 6 min walk test, which has been shown an independent predictor for morbidity and mortality in adults with heart failure. Therefore, we hypothesized that the 6 min walk test could be predictive for outcome in children with dilated cardiomyopathy. We prospectively included 49 children with dilated cardiomyopathy ≥6 years who performed a 6 min walk test. Median age was 11.9 years (interquartile range [IQR] 7.4-15.1), median time after diagnosis was 3.6 years (IQR 0.6-7.4). The 6 min walk distance was transformed to a percentage of predicted, using age- and gender-specific norm values (6MWD%). For all patients, mean 6MWD% was 70 ± 21%. Median follow-up was 33 months (IQR 14-50). Ten patients reached the combined endpoint of death or heart transplantation. Using univariable Cox regression, a higher 6MWD% resulted in a lower risk of death or transplantation (hazard ratio 0.95 per percentage increase, p = 0.006). A receiver operating characteristic curve was generated to define the optimal threshold to identify patients at highest risk for an endpoint. Patients with a 6MWD% < 63% had a 2 year transplant-free survival of 73%, in contrast to a transplant-free survival of 92% in patients with a 6MWD% ≥ 63% (p = 0.003). In children with dilated cardiomyopathy, the 6 min walk test is a simple and feasible tool to identify children with a higher risk of death or heart transplantation.

Parent reports of health-related quality of life and heart failure severity score independently predict outcome in children with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy in children causes heart failure and has a poor prognosis. Health-related quality of life in this patient group is unknown. Moreover, results may provide detailed information of parents' sense of their child's functioning. We hypothesised that health-related quality of life, as rated by parents, and the paediatric heart failure score, as assessed by physicians, have both predictive value on outcome. Methods and results In this prospective study, health-related quality of life was assessed by parent reports: the Infant Toddler Quality of Life questionnaire (0-4 years) or Child Health Questionnaire-Parent Form 50 (4-18 years) at 3-6-month intervals. We included 90 children (median age 3.8 years, interquartile range (IQR) 0.9-12.3) whose parents completed 515 questionnaires. At the same visit, physicians completed the New York University Pediatric Heart Failure Index. Compared with Dutch normative data, quality of life was severely impaired at diagnosis (0-4 years: 7/10 subscales and 4-18 years: 8/11 subscales) and ⩾1 year after diagnosis (3/10 and 6/11 subscales). Older children were more impaired (p<0.05). After a median follow-up of 3 years (IQR 2-4), 15 patients underwent transplantation. Using multivariable time-dependent Cox regression, "physical functioning" subscale and the Heart Failure Index were independently predictive of the risk of death and heart transplantation (hazard ratio 1.24 per 10% decrease of predicted, 95% confidence interval (CI) 1.06-1.47 and hazard ratio 1.38 per unit, 95% CI 1.19-1.61, respectively). CONCLUSION: Physical impairment rated by parents and heart failure severity assessed by physicians independently predicted the risk of death or heart transplantation in children with dilated cardiomyopathy.

Prospective Evaluation of Sleep Apnea as Manifestation of Heart Failure in Children.

In adults with heart failure, central sleep apnea (CSA), often manifested as Cheyne-Stokes respiration, is common, and has been associated with adverse outcome. Heart failure in children is commonly caused by dilated cardiomyopathy (DCM). It is unknown whether children with heart failure secondary to DCM have CSA, and whether CSA is related to the severity of heart failure. In this prospective observational study, 37 patients (<18 year) with heart failure secondary to DCM were included. They underwent polysomnography, clinical and laboratory evaluation and echocardiographic assessment. After a median follow-up time of 2 years, eight patients underwent heart transplantation. CSA (apnea-hypopnea index [AHI] ≥1) was found in 19 % of the patients. AHI ranged from 1.2 to 4.5/h. The occurrence of CSA was not related to the severity of heart failure. Three older patients showed a breathing pattern mimicking Cheyne-Stokes respiration, two of whom required heart transplantation. CSA was found in 19 % of the children with heart failure secondary to DCM. No relation was found with the severity of heart failure. In a small subset of children with severe DCM, a pattern mimicking Cheyne-Stokes respiration was registered.

Clinical recognition of mid-aortic syndrome in children.

Mid-aortic syndrome is characterized by narrowing of the abdominal aorta, usually with the involvement of renal arteries and other visceral branches. The combination of the presence of an abdominal bruit, diminished or absent pulsations of the lower extremities, and a blood pressure discrepancy between upper and lower extremities is the classic triad associated with mid-aortic syndrome. However, it has a wide variety of clinical symptoms, and awareness of the variable presentation can lead to early diagnosis of the vascular anomaly. We report three cases presenting at three different stages of this disease, such as hydrops fetalis, refractory hypertension, and intracerebral bleeding. In conclusion, these cases highlight the importance of blood pressure measurements in all patients and accurate physical examination for early recognition of a mid-aortic syndrome.

Low agreement between cardiologists diagnosing left ventricular hypertrophy in children with end-stage renal disease.

BACKGROUND: Monitoring of the appearance of left ventricular hypertrophy (LVH) by echocardiography is currently recommended for in the management of children with End-stage renal disease (ESRD). In order to investigate the validity of this method in ESRD children, we assessed the intra- and inter-observer reproducibility of the diagnosis LVH. METHODS: Echocardiographic measurements in 92 children (0-18 years) with ESRD, made by original analysists, were reassessed offline, twice, by 3 independent observers. Smallest detectable changes (SDC) were calculated for continuous measurements of diastolic interventricular septum (IVSd), Left ventricle posterior wall thickness (LVPWd), Left ventricle end-diastolic diameter (LVEDd), and Left ventricle mass index (LVMI). Cohen's kappa was calculated to assess the reproducibility of LVH defined in two different ways. LVH(WT) was defined as Z-value of IVSd and/or LVPWd>2 and LVH(MI) was defined as LVMI> 103 g/m² for boys and >84 g/m² for girls. RESULTS: The intra-observer SDCs ranged from 1.6 to 1.7 mm, 2.0 to 2.6 mm and 17.7 to 30.5 g/m² for IVSd, LVPWd and LVMI, respectively. The inter-observer SDCs were 2.6 mm, 2.9 mm and 24.6 g/m² for IVSd, LVPWd and LVMI, respectively. Depending on the observer, the prevalence of LVH(WT) and LVH(MI) ranged from 2 to 30% and from 8 to 25%, respectively. Kappas ranged from 0.4 to 1.0 and from 0.1 to 0.5, for intra-and inter- observer reproducibility, respectively. CONCLUSIONS: Changes in diastolic wall thickness of less than 1.6 mm or LVMI less than 17.7 g/m² cannot be distinguished from measurement error in individual children, even when measured by the same observer. This limits the use of echocardiography to detect changes in wall thickness in children with ESRD in routine practice.

Exercise capacity in children with isolated congenital complete atrioventricular block: does pacing make a difference?

The management of patients with isolated congenital complete atrioventricular block (CCAVB) has changed during the last decades. The current policy is to pace the majority of patients based on a variety of criteria, among which is limited exercise capacity. Data regarding exercise capacity in this population stems from previous publications reporting small case series of unpaced patients. Therefore, we have investigated the exercise capacity of a group of contemporary children with CCAVB. Sixteen children (mean age 11.5 ± 4; seven boys, nine girls) with CCAVB were tested. In 13 patients, a median number of three pacemakers were implanted, whereas in three patients no pacemaker was given. All patients had an echocardiogram and completed a cardiopulmonary cycle exercise test. Exercise parameters were determined and compared with reference values obtained from healthy Dutch peers. The peak oxygen uptake/body mass was reduced to 34.4 ± 9.5 ml kg(-1) min(-1) (79 ± 24% of predicted) and the ventilatory threshold was reduced to 52 ± 17% of peak oxygen uptake (78 ± 21% of predicted), whereas the peak work load/body mass was 2.8 ± 0.6 W/kg (91 ± 24% of predicted), which was similar to controls. Importantly, 25% of the paced patients showed upper rate restriction by the pacemaker. In conclusion, children with CCAVB show a reduced peak oxygen uptake and ventilatory threshold, whereas they show normal peak work rates. This indicates that they generate more energy during exercise from anaerobic energy sources. Paced children with CCAVB do not perform better than unpaced children.

Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification.

BACKGROUND: This study aimed to describe the current practice and results of genetic evaluation in Dutch children with dilated cardiomyopathy and to evaluate genotype-phenotype correlations that may guide prognosis. METHODS: We performed a multicenter observational study in children diagnosed with dilated cardiomyopathy, from 2010 to 2017. RESULTS: One hundred forty-four children were included. Initial diagnostic categories were idiopathic dilated cardiomyopathy in 67 children (47%), myocarditis in 23 (16%), neuromuscular in 7 (5%), familial in 18 (13%), inborn error of metabolism in 4 (3%), malformation syndrome in 2 (1%), and "other" in 23 (16%). Median follow-up time was 2.1 years [IQR 1.0-4.3]. Hundred-seven patients (74%) underwent genetic testing. We found a likely pathogenic or pathogenic variant in 38 children (36%), most often in MYH7 (n = 8). In 1 patient initially diagnosed with myocarditis, a pathogenic LMNA variant was found. During the study, 39 patients (27%) reached study endpoint (SE: all-cause death or heart transplantation). Patients with a likely pathogenic or pathogenic variant were more likely to reach SE compared with those without (hazard ratio 2.8; 95% CI 1.3-5.8, P = 0.007), while transplant-free survival was significantly lower (P = 0.006). Clinical characteristics at diagnosis did not differ between the 2 groups. CONCLUSIONS: Genetic testing is a valuable tool for predicting prognosis in children with dilated cardiomyopathy, with carriers of a likely pathogenic or pathogenic variant having a worse prognosis overall. Genetic testing should be incorporated in clinical work-up of all children with dilated cardiomyopathy regardless of presumed disease pathogenesis.

Cardiac output measurement using an ultrasound dilution method: a validation study in ventilated piglets.

OBJECTIVE: To assess agreement between a new method of cardiac output monitoring, using ultrasound dilution technology and ultrasound transit time-based measurement of pulmonary blood flow in a piglet model. DESIGN: Prospective, experimental juvenile animal study. SETTING: Animal laboratory of a university hospital. SUBJECTS: Nine random-bred piglets. INTERVENTIONS: After the animals received general anesthesia, we placed intravascular arterial and central venous catheters with the tip positioned in the abdominal aorta and the right atrium, respectively. The catheters were connected to the ultrasound dilution cardiac output monitor. An ultrasound transit time perivascular flow probe was positioned around the common pulmonary artery and served as the standard reference measurement. Cardiac output was manipulated during the experiment by creating hemorrhagic hypotension. Ultrasound dilution cardiac output was measured intermittently with injection volumes of 0.5 mL/kg and 1.0 mL/kg of isotonic saline at body temperature. MEASUREMENTS AND MAIN RESULTS: Ultrasound dilution cardiac output (Q) measurement was compared with pulmonary blood flow (Q). Bias, defined as Q minus Q, was calculated for each measurement. Mean bias with standard deviation was calculated for measurements with volumes of injected saline, 0.5 mL/kg and 1.0 mL/kg, and compared using the Mann-Whitney U test. Mean bias (sd) between Q and Q was 0.040 (0.132) and 0.058 (0.136) L/min for measurement with 0.5 mL/kg and 1.0 mL/kg of isotonic saline, respectively (no statistically significant difference). CONCLUSIONS: Ultrasound dilution cardiac output measurement is reliable in piglets with the use of a small volume of a nontoxic indicator (isotonic saline).

Application of ultrasound dilution technology for cardiac output measurement: Cerebral and systemic hemodynamic consequences in a juvenile animal model.

OBJECTIVE: Analysis of cerebral and systemic hemodynamic consequences of ultrasound dilution cardiac output measurements. DESIGN: : Prospective, experimental piglet study. SETTING: Animal laboratory. SUBJECTS: Nine piglets. INTERVENTIONS: Ultrasound dilution cardiac output measurements were performed in ventilated, anesthetized piglets. Interventions that are required for ultrasound dilution cardiac output measurement were evaluated for its effect on cerebral and systemic circulation and oxygenation. MEASUREMENTS AND MAIN RESULTS: DeltacHbD and DeltactHb, representing changes in cerebral blood flow and cerebral blood volume, respectively, were measured with near infrared spectrophotometry. Pulmonary artery (Q) and left carotid artery (Q) blood flow were assessed with transit time flow probes. Starting and/or stopping blood flowing through the arteriovenous loop did not cause relevant hemodynamic changes. Fast injection of isotonic saline caused a biphasic change in DeltacHbD and DeltactHb. After injection of 0.5 mL/kg, the mean (sd) increase in DeltacHbD and DeltactHb was 0.175 (0.213) micromol/L and 0.122 (0.148) micromol/L, respectively, with a subsequent mean decrease of -0.191 (0.299) micromol/L and -0.312 (0.266) micromol/L. Injection of 1.0 mL/kg caused a mean increase in DeltacHbD and DeltactHb of 0.237 (0.203) micromol/L and 0.179 (0.162) followed by a mean decrease of -0.334 (0.407) micromol/L and -0.523 (0.335) micromol/L, respectively. Q and Q changed shortly with a mean increase of 5.9 (3.0) mL/kg/min and 0.23 (0.10) mL/kg/min after injection of 0.5 mL/kg and with 12.0 (4.2) mL/kg/min and 0.44 (0.18) mL/kg/min after injection of 1.0 mL/kg, respectively. The observed changes were more profound after an injection volume of 1.0 mL/kg compared with 0.5 mL/kg for DeltacHbD (p = .06), DeltactHb (p = .09), Q, and Q (p < .01). No relevant changes in mean arterial blood pressure or heart rate were detected in response to the indicator injection. CONCLUSIONS: Cardiac output measurement by ultrasound dilution does not cause clinically relevant changes in cerebral and systemic circulation and oxygenation in a piglet model.

Emotional and behavioral problems in children with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) in children is an important cause of severe heart failure and carries a poor prognosis. Adults with heart failure are at increased risk of anxiety and depression and such symptoms predict adverse clinical outcomes such as mortality. In children with DCM, studies examining these associations are scarce. AIMS: We studied whether in children with DCM: (1) the level of emotional and behavioral problems was increased as compared to normative data, and (2) depressive and anxiety problems were associated with the combined risk of death or cardiac transplantation. METHODS: To assess emotional and behavioral problems in children with DCM, parents of 68 children, aged 1.5-18 years (6.9±5.7 years), completed the Child Behavior Checklist. RESULTS: Compared to normative data, more young children (1.5-5 years) with DCM had somatic complaints (24.3% vs. 8.0%; p < .001), but fewer had externalizing problems (5.4% vs. 17.0%; p = .049). Overall internalizing problems did not reach significance. Compared to normative data, more older children (6-18 years) showed internalizing problems (38.7% vs. 17.0%; p = .001), including depressive (29.0% vs. 8.0%; p < .001) and anxiety problems (19.4% vs. 8.0%; p = .023), and somatic complaints (29.0% vs. 8.0%; p < .001). Anxiety and depressive problems, corrected for heart failure severity, did not predict the risk of death or cardiac transplantation. CONCLUSION: Children of 6 years and older showed more depressive and anxiety problems than the normative population. Moreover, in both age groups, somatic problems were common. No association with outcome could be demonstrated.

Furosemide in preterm infants treated with indomethacin for patent ductus arteriosus.

OBJECTIVE: To evaluate the effect of furosemide on renal function and water balance in preterm infants treated with indomethacin (3 x 0.2 mg/kg at 12-h intervals) for symptomatic patent ductus arteriosus. PATIENTS AND METHODS: We performed a retrospective multi-centre double cohort study in preterm infants <32 weeks of gestational age. Thirty-two infants treated with furosemide (1 mg/kg i.v.) before each indomethacin dose (furosemide group) were matched with 32 infants with indomethacin treatment alone (control-group). Renal effects (urine output, weight gain, serum creatinine, sodium concentration) were registered. RESULTS: The study groups were comparable for gestational age, birth weight and day of therapy. Pretreatment differences were observed for urine output, weight and serum sodium. However, no differences were noticed in day-to-day urine output change or weight gain between the groups. A significant increase in serum creatinine concentration (50% vs. control, 18%; p < 0.05) and a concomitant significant decrease in serum sodium (-9 vs. control, -3 mmoL/L; p < 0.05) in the furosemide group was observed 72-96 h after starting therapy. CONCLUSION: Furosemide before each indomethacin dose resulted in a significant increase in serum creatinine and hyponatremia, without increasing urine output.

Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.

Management of children with dilated cardiomyopathy in The Netherlands: Implications of a low early transplantation rate.

BACKGROUND: The policy for listing and transplant for children with dilated cardiomyopathy (DCM) in The Netherlands has been conservative because of low donor availability. The effects of this policy on outcome are reported. METHODS: This was a multicenter, nationwide study performed in 148 children with DCM. The primary outcome was death or heart transplant. RESULTS: Overall, 43 patients (29%) died or were transplanted. Within 1 year of diagnosis, 21 patients died, and only 4 underwent transplantation (3 on mechanical circulatory support). The 1-year survival was 85% (95% confidence interval [CI] = 79-91), and 5-year survival was 84% (95% CI = 78-90). Transplantation-free survival at 1 year was 82% (95% CI = 75-88) and at 5 years was 72% (95% CI = 64-80). Within 1 year of diagnosis, with death as the main end-point (21 of 25, 84%), intensive care unit admission (hazard ratio = 2.6, p = 0.05) and mechanical circulatory support (hazard ratio = 3.2, p = 0.03) were risk factors (multivariable Cox analysis); inotropic support was longer in patients reaching an end-point. At >1 year after diagnosis, with transplantation as the main end-point (15 of 18, 83%), age >6 years (hazard ratio = 6.1, p = 0.02) was a risk factor. There were 56 (38%) children who recovered, 50% within 1 year of diagnosis. Recovery was associated with younger age; was similar in patients with myocarditis (43%) and idiopathic disease (41%); and was similar in patients initially admitted to the intensive care unit, admitted to the ward, or treated as outpatients. CONCLUSIONS: The transplantation rate in our cohort in the first year was low, with 1-year and 5-year survival rates similar to other cohorts. Our results suggest that a conservative approach to list children for transplantation early after presentation may be justifiable except for patients with prolonged intensive care unit or mechanical circulatory support.

Nonmuscular involvement in merosin-negative congenital muscular dystrophy.

The spectrum of nonmuscular involvement in six children with merosin-negative congenital muscular dystrophy is described. In all children, biochemical, neuroradiologic, cardiac, and neurophysiologic studies were performed. Cerebral structures that were myelinated at gestation, including internal capsule, corpus callosum, brainstem, and cerebellar white matter, demonstrated no abnormalities, whereas the periventricular and subcortical white matter, which were myelinated in the first postnatal year, demonstrated signs of leukoencephalopathy. Cerebrospinal fluid analysis revealed an elevated albumin cerebrospinal fluid to serum ratio in the younger children. Electroencephalogram results were abnormal in the two elder children. One child suffered from congestive cardiomyopathy. The increase in nerve conduction velocity in these children over the years lagged behind those of healthy patients, pointing to a demyelinating neuropathy. We conclude that in merosin-negative congenital muscular dystrophy patients, nonmuscular involvement includes the central and peripheral nervous system and the heart. The pattern of myelination of the brain and nerve conduction slowing suggests a myelination arrest. Merosin deficiency can give rise to a congestive cardiomyopathy, which is of no clinical relevance in the majority of children.

Ductus arteriosus with left-to-right shunt during venoarterial extracorporeal membrane oxygenation: effects on cerebral oxygenation and hemodynamics.

OBJECTIVE: To investigate the effect on cerebral oxygenation and hemodynamics of a patent ductus arteriosus with left-to-right shunt during venoarterial extracorporeal membrane oxygenation in a lamb model. DESIGN: Prospective intervention study in animals. SETTING: Animal research laboratory of a university medical center. SUBJECTS: Six anesthetized newborn lambs with patent ductus arteriosus and left-to-right shunt, installed on venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: Six lambs of 140 days gestational age were prepared to keep the ductus arteriosus open by infiltration of the vessel wall with formaline 10%. The animals were installed on standard venoarterial extracorporeal membrane oxygenation. With a mechanical occluder, the ductus was closed. MEASUREMENTS AND MAIN RESULTS: Changes of mean arterial blood pressure and carotid artery blood flow were measured simultaneously. Using near infrared spectrophotometry, we calculated changes in cerebral concentration of oxyhemoglobin and deoxyhemoglobin (reflecting changes in cerebral oxygen supply) and total hemoglobin (reflecting changes in cerebral blood volume). Also, cerebral oxygen delivery before and after ductus closure was calculated. Before ductus closure there was a left-to-right shunt with a mean +/- SEM of 41 +/- 20% of total body blood flow. Closure of the ductus resulted in an immediate increase in mean arterial blood pressure and carotid artery blood flow. The concentration of oxyhemoglobin increased and the concentration of deoxyhemoglobin decreased, representing increased cerebral oxygen supply. The concentration of total hemoglobin was unchanged, representing unchanged cerebral blood volume. There was an increase in cerebral oxygen delivery. CONCLUSIONS: In this lamb model, a considerable left-to-right shunt over the ductus during venoarterial extracorporeal membrane oxygenation reduced cerebral circulation and oxygenation.

Serial plasma concentrations of atrial natriuretic peptide, plasma renin activity, aldosterone, and antidiuretic hormone in neonates on extracorporeal membrane oxygenation.

To obtain information on water and salt regulating hormones and volume homeostasis during neonatal extracorporeal membrane oxygenation (ECMO), serial determinations of atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), antidiuretic hormone (ADH), colloid-osmotic pressure (COP), osmolality (Osmol), and central venous pressure (CVP) before, during, and after neonatal ECMO in 10 neonates with meconium aspiration syndrome (MAS) were carried out. Mean gestational ages and birth weights were 41(+3) weeks (39(+6) - 42(+4)) and 4,063 gm (3,500-4700), respectively; mean age at start and duration of ECMO 29.3 (14-69) and 152.6 hr (92-267), respectively. Plasma ANP (mean +/- SD) was 67.8+/-69.1 pmol/L before, decreased to 33.3+/-22.1 (not significant) pmol/L during, and significantly increased to 274.6+/-131.8 pmol/L after ECMO (p < 0.05). ANP correlated positively with CVP (r = 0.63; p < 0.001). Pre-ECMO PRA, Aldo, and ADH were comparable to those described earlier in normal neonates, decreased during (p < 0.001 for Aldo; p < 0.05 for PRA and ADH) and either remained elevated (PRA, p < 0.001; Aldo, p < 0.05) or decreased (ADH) after ECMO. COP and Osmol remained unchanged. Neonatal ECMO for MAS is characterized by circulatory and osmotic equilibrium. It is suggested that circulating volume contracts during and expands after neonatal ECMO for MAS.

Persistent reduction in left ventricular strain using two-dimensional speckle-tracking echocardiography after balloon valvuloplasty in children with congenital valvular aortic stenosis.

BACKGROUND: The aim of this study was to investige serial changes of myocardial deformation using two-dimensional speckle-tracking echocardiographic (2DSTE) imaging in children undergoing balloon valvuloplasty for congenital valvular aortic stenosis (VAS). METHODS: Thirty-seven children with isolated congenital VAS were enrolled in this study prospectively. Patients underwent echocardiographic evaluation at three instances: before balloon valvuloplasty, 6 months after intervention, and 3 years after intervention. Longitudinal, circumferential, and radial peak systolic strain values were determined, as well as systolic strain rate and the time to peak global systolic strain. Linear mixed statistical models were used to assess changes in 2DSTE parameters after balloon intervention. Using one-way analysis of variance, 2DSTE results at 3-year follow-up were compared with 2DSTE measurements in 74 healthy age-matched children and 76 children with uncorrected VAS whose severity of stenosis corresponded to residual stenosis of study subjects at 3-year follow-up. RESULTS: Global peak strain and strain rate measurements in all three directions were decreased before intervention compared with healthy children. Global peak strain and strain rate measurements increased significantly (P < .001) several months after balloon valvuloplasty and continued to increase at 3-year follow-up. However, at 3-year follow-up, global peak strain and strain rate in the longitudinal and circumferential directions were significantly lower (P < .001) compared with both control groups. Measurements of time to peak global systolic strain were significantly shorter at early follow-up compared with measurements before intervention (P < .05). CONCLUSIONS: Shortly after balloon valvuloplasty for severe congenital VAS, there is an improvement in systolic myocardial deformation. However, 2DSTE parameters do not return to normal at 3-year follow-up. These abnormalities in systolic deformation cannot be fully attributed to residual stenosis or aortic regurgitation.