Clinical and Echocardiographic Impact of Tafazzin Variants on Dilated Cardiomyopathy Phenotype in Left Ventricular Non-Compaction Patients in Early Infancy.

BACKGROUND: Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood. Methods and Results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar. CONCLUSIONS: This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.

Stent migration after right ventricular outflow tract stenting in the severe cyanotic Tetralogy of Fallot case.

We report our experience with a stent migration after right ventricle outflow tract stenting and converted to patent ductus arteriosus stenting in Tetralogy of Fallot (TOF) with severe infundibular stenosis. Finally, the patient achieved to TOF repair, and the migrated stent was removed without any complication.

Phototherapy with blue and green mixed-light is as effective against unconjugated jaundice as blue light and reduces oxidative stress in the Gunn rat model.

OBJECTIVE: Phototherapy using blue light-emitting diodes (LED) is effective against neonatal jaundice. However, green light phototherapy also reduces unconjugated jaundice. We aimed to determine whether mixed blue and green light can relieve jaundice with minimal oxidative stress as effectively as either blue or green light alone in a rat model. METHODS: Gunn rats were exposed to phototherapy with blue (420-520 nm), filtered blue (FB; 440-520 nm without<440-nm wavelengths, FB50 (half the irradiance of filtered blue), mixed (filtered 50% blue and 50% green), and green (490-590 nm) LED irradiation for 24h. The effects of phototherapy are expressed as ratios of serum total (TB) and unbound (UB) bilirubin before and after exposure to each LED. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured by HPLC before and after exposure to each LED to determine photo-oxidative stress. RESULTS: Values < 1.00 indicate effective phototherapy. The ratios of TB and UB were decreased to 0.85, 0.89, 1.07, 0.90, and 1.04, and 0.85, 0.94, 0.93, 0.89, and 1.09 after exposure to blue, filtered blue, FB50, and filtered blue mixed with green LED, respectively. In contrast, urinary 8-OHdG increased to 2.03, 1.25, 0.96, 1.36, 1.31, and 1.23 after exposure to blue, filtered blue, FB50, mixed, green LED, and control, indicating side-effects (> 1.00), respectively. CONCLUSIONS: Blue plus green phototherapy is as effective as blue phototherapy and it attenuates irradiation-induced oxidative stress. PRACTICE IMPLICATIONS: Combined blue and green spectra might be effective against neonatal hyperbilirubinemia.

Correlations between global clotting function tests, duration of operation, and postoperative chest tube drainage in pediatric cardiac surgery.

BACKGROUND: Systemic coagulation disorders after cardiac surgery represent serious postoperative complications. There have been few reports, however, identifying preoperative coagulation tests that predict postoperative bleeding. The aim of the present study was to investigate the relationship between postoperative hemorrhage and coagulation parameters determined by global coagulation assays, to define potential predictive markers. METHODS: Twenty-one pediatric patients were enrolled. Blood samples were collected before and 24 h after cardiac surgery. Laboratory investigations included platelet count, hematocrit, classical coagulation tests [prothrombin time, activated partial thromboplastin time, thrombin-antithrombin complex (TAT)], rotation thromboelastometry (ROTEM), and the thrombin generation test (TGT). The duration of the surgical procedure was recorded. Chest tube drainage was monitored for 24 h after operation as an index of postoperative hemorrhage. RESULTS: Comparisons between preoperative and postoperative results indicated that TAT increased significantly after operation, whereas ROTEM parameters did not show a hypercoagulable pattern. Preoperative endogenous thrombin potential (ETP) measured in the TGT and clot formation time (CFT) in the ROTEM correlated with chest tube drainage. The classical coagulation tests were not informative. Postoperatively, peak height and ETP in TGT, all ROTEM parameters, and duration of surgery were correlated with chest tube drainage. Duration of surgery was correlated with postoperative ROTEM parameters but not with TGT. Postoperative maximum clot firmness and AUC were correlated with platelet count decrease ratio. CONCLUSIONS: The preoperative CFT and ETP provide useful indices for predicting postoperative chest tube drainage volume. In addition, the duration of surgery also correlated with chest tube drainage and affected ROTEM parameters.

Electrocardiographic and clinical characteristics of idiopathic restrictive cardiomyopathy in children.

BACKGROUND: Idiopathic restrictive cardiomyopathy (RCM) is not a single disease and is rare. METHODS AND RESULTS: The clinical features and clinical course of 12 pediatric patients with RCM seen between 1978 and 2005 were retrospectively analyzed. The age at diagnosis ranged from 4 months to 12 years (median 4 years). The age of 7 patients diagnosed because of an abnormal electrocardiogram (ECG) ranged from 4 to 12 years. Three infants less than 2 years old presented with cardiomegaly. Obliquely elevated ST-T segments and the late peak T waves on 12-lead ECG were present in 8 patients (67%). Three patients with ST depression during exercise had no perfusion defects on radioisotope myocardial perfusion imaging. Two patients underwent orthotopic heart transplantation. Of the remaining 10 patients, 7 have died: 4 died suddenly and 3 died of right heart failure. Three patients with a hypertrophic left ventricular wall had a prolonged survival. The probability of survival at 1, 2 and 3 years was 78%, 52% and 26%, respectively. CONCLUSIONS: Obliquely elevated ST-T segments and the late peak T wave on ECG are characteristic, and reflect the restrictive physiology, which may indicate abnormalities of repolarization of ventricular muscle. The mode of death was either heart failure from pulmonary hypertension or sudden death from presumed ventricular arrhythmia.

Respiratory inhibition after crying in infants.

BACKGROUND: Among full-term neonates, the authors discovered infants who showed respiratory inhibition after crying which involved a marked decrease in SpO2. The infants were found to present increased echogenicity or a cyst in a cranial region termed the ganglionic eminence, or to have a subependymal cyst. The authors prospectively examined the relationship between respiratory inhibition after crying and these changes to examine the prevention and treatment of the episode. METHODS: The authors conducted cranial ultrasonography to screen 381 full-term neonates who showed no abnormalities at birth and whose parents requested ultrasonographic screening of the head, followed by polygraphy of infants who showed increased echogenicity or a cyst in ganglionic eminence, or had a subependymal cyst. The authors similarly conducted polygraphy for 50 neonates without cranial ultrasound abnormalities; the former constituted the control group. Respiratory inhibition was defined to be central apnea immediately after crying with a decrease in SpO2 to <60%. RESULTS: Among 381 neonates examined, 104 showed cranial ultrasound abnormalities; 60 of the 104 neonates indicated respiratory inhibition after crying. Oxygenation failed to improve the episode in 17 neonates with severe respiratory inhibition. However, theophylline alleviated the episode, and SpO2 no longer decreased to <60%. Theophylline was discontinued successfully by 6 months after birth, while 50 neonates in the control group showed no respiratory inhibition after crying. CONCLUSION: Respiratory inhibition after crying which involved a marked decrease in SpO2 was observed in full-term neonates who showed no abnormalities after birth. These neonates could be screened by cranial ultrasonography.

Change in plasma volume during peak exercise in patients with cyanotic congenital heart disease after definitive operation.

OBJECTIVES: To evaluate changes in plasma volume (deltaPV) during exercise in patients with single ventricular physiology with cyanosis; post-Fontan patients; and in patients after right ventricular outflow tract reconstruction (RVOTR). BACKGROUND: Compensatory mechanisms which regulate body fluid volumes operate in heart failure patients to maintain blood pressure. A better understanding of this pathophysiological process, especially during exercise, should help manage and follow such patients. METHODS: Twenty-six CHD patients (14+/-4 years), including 5 cyanotic patients, 12 after the Fontan operation, 9 after RVOTR, and 13 controls (14+/-5 years), performed a treadmill exercise test. DeltaPV from rest to peak was calculated and compared with changes in cardiovascular responses, plasma total protein (TP), norepinephrine (NE), osmolality (Osm), and blood lactate concentration (La). RESULTS: DeltaPV was smaller in CHD patients than in controls (Cyanotic: -5.9%, Fontan: -10.0%, RVOTR: -11.4%, CONTROLS: -14.5%, p<0.001). In all subjects, peak heart rate, systolic blood pressure and oxygen uptake correlated inversely with deltaPV (p<0.05 to 0.005). DeltaPV correlated inversely with changes in TP, NE, and La (p<0.005 for all), but not with the change in Osm. In CHD patients, the deltaPV correlated only with the NE increase (p<0.01). CONCLUSIONS: DeltaPV is smaller in CHD patients than in controls, especially in cyanotic patients. The smaller increases in cardiovascular responses during exercise and La are associated with the small deltaPV. These mechanisms may help to maintain cardiac output and increased sympathetic nervous activity may be beneficial to ensure sufficient perfusion pressure against deltaPV during exercise.

Estimation of PaCO2 during exercise in children and postoperative pediatric patients with congenital heart disease.

We evaluated how Paco(2) and respiratory variables relate during and after exercise and derived a new noninvasive estimation of Paco(2) in children and postoperative patients with congenital heart disease. We randomly selected 8 subjects from each of three categorized groups from our previous studies: 15 control subjects (8 to 21 years old), 16 Fontan procedure patients (9 to 22 years old), and 13 patients after right ventricular outflow tract reconstruction (RVOTR) [7 to 21 years old], and used their respiratory variables during exercise testing to estimate Paco(2) (study 1). In a stepwise multiple regression analysis, end-tidal carbon dioxide tension (Petco(2)), age, ventilatory equivalent for carbon dioxide (minute ventilation [Ve]/carbon dioxide production [Vco(2)]), and gas exchange ratio (R) were major determinants of Paco(2) in control subjects: Paco(2) = 12.0 + 0.54 Petco(2) + 0.15 Ve/Vco(2) - 3.6 R + 0.22 age (r = 0.86). In addition to Petco(2) and Ve/Vco(2), arterial oxygen saturation and tidal volume were additional major determinants for Fontan procedure and RVOTR patients, respectively. We derived equations to predict the Paco(2) (r = 0.92 for Fontan procedure and r = 0.74 for RVOTR). These equations were applied to the remaining study subjects to estimate Paco(2) (study 2). Estimated values correlated with the measured Paco(2) (r = 0.71 to 0.86), and the mean differences for the control subjects, Fontan procedure, and RVOTR patients were - 0.1, - 0.1, and - 1.0, with limits of agreement of +/- 3.3, +/- 4.4, and +/- 3.1, respectively. Although estimated Paco(2) based on the Jones equation correlated with the measured Paco(2) in all groups, their slopes were significantly flatter than ours. Paco(2) throughout exercise testing may be estimated in control children and postoperative pediatric patients. The Jones equation should be applied with great care in pediatric subjects.

Post-exercise heart rate, blood pressure and oxygen uptake dynamics in pediatric patients with Fontan circulation Comparison with patients after right ventricular outflow tract reconstruction.

BACKGROUND: Post-exercise heart rate (HR) and oxygen uptake (V O(2)) recover more slowly in patients with the Fontan circulation, but little is known about the determinants of the delayed recovery. PURPOSE: To evaluate the post-exercise cardiovascular dynamics and clinical profiles in these patients. METHODS AND RESULTS: We studied 51 Fontan patients (14+/-4 years) (atriopulmonary connection, APC = 18 and total cavopulmonary connection, TCPC = 33) and compared the results with 34 patients after right ventricular outflow tract reconstruction (RVOTR) with identical exercise capacity and arterial baroreflex sensitivity (BRS) (15+/-4 years) and with 26 controls (14+/-4 years). There were no differences in post-exercise HR or VO2 declines between the Fontan and RVOTR groups. Although the systolic blood pressure (SBP) decline was delayed in the RVOTR group (p < 0.01), its early decline in the Fontan group was rapid and equivalent to that in controls. In Fontan patients, BRS had a great impact on early HR decline (p < 0.05) and early VO2 decline was determined by peak VO2, age and cardiac index (p < 0.05-0.001). TCPC and lower BRS were the main determinants of the slower SBP decline (p < 0.05). In another study of repeated paired exercise tests before and after Fontan operation, post-exercise SBP decline became greater after the operation (p < 0.07). CONCLUSIONS: In the Fontan group, post-exercise HR and VO2 declines are markedly delayed and are determined by cardiac vagal nervous activity, exercise capacity and age, respectively. Despite identical impaired hemodynamics and exercise capacity, post-exercise SBP decline is greater in the Fontan group, especially after APC, than in the RVOTR patients.

Negative chronotropic response to low-dose atropine is associated with parasympathetic nerve-mediated cardiovascular response in postoperative patients with congenital heart disease.

OBJECTIVES: To investigate the negative chronotropic response (NCR) to low-dose atropine in postoperative patients with congenital heart disease (CHD). BACKGROUND: Low-dose atropine causes a NCR through the central nervous system muscarinic receptor and is attenuated in adult heart failure patients. It has never been evaluated in CHD patients. METHODS: NCR corrected for basal heart rate (HR) (minimal HR/basal HR=cNCR) was determined after low-dose atropine (3 microg/kg) administration in 124 postoperative CHD patients (97 biventricular repair and 27 Fontan patients) and 11 controls and was compared with the cardiac autonomic nervous and functional status. RESULTS: The cNCR in simple CHD (post atrial or ventricular septal defect closure), complex biventricular CHD, and Fontan patients were 0.92+/-0.04, 0.94+/-0.04 and 0.96+/-0.04, respectively, and higher than in controls (0.87+/-0.03, p<0.001). In the complex CHD patients, higher cNCR was mainly associated with the lower pharmacologically determined cardiac parasympathetic nervous tone (PST), HR variability, high atrial natriuretic peptide, and lower right ventricular ejection fraction (p<0.0001). In Fontan patients, the lower beta sensitivity of the sinus node and the PST mainly determined the higher cNCR (p<0.01) and the cNCR did not correlate with either hemodynamics or exercise capacity. CONCLUSIONS: NCR is attenuated in proportion to the impaired cardiac parasympathetic nervous system and hemodynamics in postoperative complex biventricular CHD patients. In addition to PST, beta sensitivity of the sinus node significantly influences the NCR in Fontan patients.