Identification and management of fetal isolated right-sided aortic arch in an unselected population.

OBJECTIVE: Inclusion of the three vessels and trachea view in the routine assessment of the fetal heart at the 18-20-week morphology scan improves recognition of a right-sided aortic arch (RAA). We report our experience of RAA diagnosed in an unselected population of pregnant women attending for a routine morphology scan. METHODS: The obstetric imaging databases of two ultrasound centers were reviewed retrospectively to identify all routine fetal morphology scans performed at 18-22 weeks' gestation between January 2011 and December 2014. A review of postnatal charts was conducted to ascertain findings at birth, neonatal complications and the anatomical findings at any neonatal echocardiographic or surgical procedure. Parents of older infants were contacted by phone to assess their wellbeing and identify any respiratory or feeding difficulties. RESULTS: In the 48-month study period, 43 083 routine anomaly scans were performed. Twenty-three cases of isolated RAA were identified, a prevalence of 0.05%. Nineteen (83%) cases of isolated RAA had a left-sided arterial duct and four (17%) had a right-sided duct. Postnatal follow-up data were obtained in all cases. The prevalence of a symptomatic vascular ring due to a double aortic arch was 13% (3/23). One (4%) case was diagnosed with DiGeorge syndrome. CONCLUSIONS: RAA can be identified easily on a routine fetal anomaly scan, however the prevalence of RAA is low in an unselected population. Antenatally diagnosed cases should be referred for detailed fetal echocardiography and the patient should be made aware of the association with DiGeorge syndrome and the symptoms associated with a vascular ring. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Multiple antibodies targeting tumor-specific mutations redirect immune cells to inhibit tumor growth and increase survival in experimental animal models.

BACKGROUND: T cell therapy for cancer involves genetic introduction of a target-binding feature into autologous T cells, ex vivo expansion and single large bolus administration back to the patient. These reprogrammed T cells can be highly effective in killing cells, but tumor heterogeneity results in regrowth of cells that do not sufficiently express the single antigen being targeted. We describe a cell-based therapy that simultaneously targets multiple tumor-specific antigens. METHODS: High-affinity polyclonal rabbit antibodies were generated against nine different surface-related tumor-specific mutations on B16F10 cells. Unsorted splenic effector cells from syngeneic mice were incubated with a cocktail of the nine anti-B16F10 antibodies. These 'armed' effector cells were used to treat mice previously inoculated with B16F10 melanoma cells. RESULTS: The cocktail of nine antibodies resulted in dense homogeneous binding to histological sections of B16F10 cells. Five treatments with the armed effector cells and PD1 inhibition inhibited tumor growth and improved survival. Shortening the interval of the five treatments from every three days to every day increased survival. Arming effector cells with the four antibodies showing best binding to B16F10 cells even further increased survival. CONCLUSIONS: This study demonstrates that ex vivo arming a mixed population of immune effector cells with antibodies targeting multiple tumor-specific mutated proteins in conjunction with PD1 inhibition delayed tumor growth and prolonged survival in mice inoculated with an aggressive melanoma. A remarkably low total antibody dose of less than 5 µg was sufficient to accomplish tumor inhibition. Scaling up to clinical level may be feasible.

Noninvasive estimation of the left ventricular pressure waveform throughout ejection in young patients with aortic stenosis.

Validation of a totally noninvasive method for estimating instantaneous left ventricular pressure and constructing a pressure waveform throughout ejection in patients with aortic stenosis is reported. In 20 patients (aged 8.75 +/- 10 years) with congenital aortic stenosis (measured peak left ventricular pressure 120 to 260 mm Hg; transvalvular gradient 18 to 165 mm Hg), transaortic valve continuous wave Doppler ultrasound, indirect carotid pulse tracing, peripheral blood pressure and measured left ventricular pressure were recorded simultaneously at cardiac catheterization. Data were entered into a microcomputer using a digitizing tablet and the instantaneous Doppler gradient was calculated and added to instantaneous aortic pressure, derived from the time-corrected and calibrated carotid pulse tracing, to estimate instantaneous left ventricular pressure. Estimated left ventricular pressure waveforms reproduced measured left ventricular pressure closely. The mean error at peak left ventricular pressure was 0.2 +/- 4.8 mm Hg (r = 0.98, p = 0.001). The average error throughout ejection was 0.9 +/- 5.1 mm Hg. The error of estimated pressure was not related to age or the severity of aortic stenosis. The Doppler peak instantaneous gradient was observed to correlate closely (r = 0.97, p = 0.001) with peak to peak gradient. With this technique, the left ventricular pressure waveform throughout ejection can be accurately estimated noninvasively in patients with aortic stenosis. This methodology enables determination of mean, total and instantaneous systolic left ventricular pressure.

Evaluation of a staged treatment protocol for rapid automatic junctional tachycardia after operation for congenital heart disease.

OBJECTIVES: This study sought to 1) develop an efficient treatment protocol for postoperative automatic junctional tachycardia (JT) using conventional drugs and techniques, and 2) identify clinical features associated with this disorder by analyzing a large study group. BACKGROUND: Postoperative JT is a transient arrhythmia that may be fatal after operation for congenital cardiac defects. Its precise cause is unknown. A variety of palliative treatments have evolved, but because of a low incidence of JT, large studies of the most efficient therapeutic sequence are lacking. METHODS: A protocol for rapid JT (>170 beats/min) was adopted in 1986, and was tested in 71 children between 1986 and 1994. Staged therapy involved 1) a reduction of catecholamines; 2) correction of fever; 3) atrial pacing to restore synchrony; 4) digoxin; 5) phenytoin or propranolol or verapamil; 6) procainamide or hypothermia; and 7) combined procainamide and hypothermia. Effective therapy was defined as a sustained reduction of JT rate <170 beats/min within 2 h. Clinical profiles of the study group were contrasted with all patients without JT from this same era to identify features associated with JT. RESULTS: Of the multiple treatment stages, only correction of fever and combined procainamide and hypothermia appeared to be efficacious. By refining the protocol to eliminate nonproductive stages, the time to JT control was significantly shortened for the last 30 patients. Treatment was ultimately successful in 70 of 71 children. Postoperative JT was strongly associated with young age, transient atrioventricular block and operations involving ventricular septal defect closure. CONCLUSIONS: A staged approach to therapy, with emphasis on combined hypothermia and procainamide in difficult cases, appears to be an effective management strategy for postoperative JT. These results may also serve as comparison data for evaluation of newer and promising JT options, such as intravenous amiodarone. Trauma to conduction tissue may play a central role in the etiology of this disorder.

Echocardiographic assessment of aortic root dimensions in normal children based on measurement of a new ratio of aortic size independent of growth.

Two-dimensional echocardiography is commonly used as a method of monitoring aortic root dimensions in children with connective tissue disease. Measurements are usually standardized to body surface area (BSA) to account for growth. However, there are several theoretical and practical disadvantages to adopting this approach, and there has been little investigation of alternative methods of standardization. This study of 48 normal children and adolescents (age range 2 weeks to 23 years) was performed to determine the relation of 2-dimensional echocardiographic aortic root dimensions to indexes of body size and growth, and to examine a simple means of internally standardizing aortic root measurements to create an index of aortic root size independent of growth. Maximal diameters in the parasternal long-axis view were recorded at 4 levels: annulus, sinuses of Valsalva (SOV), supraaortic ridge (SAR), and ascending aorta (AAO). Ratios of aortic root size were created by internally standardizing aortic root diameters to aortic annular size. All diameters correlated closely with age, height, weight, and BSA (all r > 0.87). Linear regression in each case showed a significant positive slope (all p < 0.0001). The best predictor of aortic dimensions was height, with r values of 0.93 for annulus, SOV, and AAO, and 0.95 for SAR. Ratios of SOV/annulus, SAR/annulus, and AAO/annulus remained constant, with no correlation with age or any growth parameters. Mean values and 95% confidence limits were: SOV/annulus 1.37 (1.18-1.56); SAR/annulus 1.11 (0.95-1.28); and AAO/annulus 1.16 (0.97-1.35). Standardization to height, or the use of internally standardized aortic root ratios, provides a simple and accurate alternative to standardization to BSA for assessing aortic root dimensions in normal growing children.

Effect of isolated right ventricular outflow obstruction on left ventricular function in infants.

Resting left ventricular (LV) function was evaluated in 29 infants with isolated right ventricular (RV) outflow obstruction. Age-corrected cardiac index was significantly inversely correlated with the degree of obstruction (r = 0.59, p = 0.0001). Right ventricular hypertension resulted in septal displacement and altered LV geometry. The magnitude of RV outflow obstruction related closely to the degree of LV distortion. Septal displacement toward the LV free wall was associated with lower values for cardiac index, indexed LV end-diastolic volume, ejection fraction, ratio of early to atrial LV diastolic inflow and with a higher RV ejection fraction. The LV end-diastolic volume index and the ratio of early to atrial LV diastolic inflow correlated with the degree of obstruction and amount of septal displacement. Four infants evaluated during the development of supravalvar pulmonary stenosis demonstrated decreasing cardiac index during development of obstruction and significant increase in cardiac index after surgical relief. These findings indicate that significant RV outflow obstruction in infants is associated with a reversible alteration in LV function related to abnormal LV geometry and impaired LV diastolic filling.

Echo Doppler assessment of cardiac output and its relation to growth in normal infants.

In a study of 38 normal infants, serial measurements of systemic (n = 169) and pulmonary (n = 143) blood flow were undertaken from the ages of 2 weeks to 12 months by 2-dimensional, M-mode and pulsed Doppler echocardiography. Cardiac output changed linearly (cardiac output = 0.3 X height -0.99 liter/min), and cardiac index was validated as a means for standardizing cardiac output in infants younger than 10 to 13 months of age. Infants younger than 2 months had lower cardiac indexes and stroke volume indexes (2.6 +/- 0.7 liters/min/m2 and 19 +/- 5 ml/m2, respectively) compared with those aged 12 months (3.2 +/- 0.7 liter/min/m2 and 25 +/- 5 ml/m2, respectively). Changes in cardiac output in individual infants over time suggest nonmorphometric modulating factors for cardiovascular function.

Minimally invasive management of transposition of the great arteries in the newborn period.

This study reports on a predominantly noninvasive management program for neonatal transposition of the great arteries [TGA] incorporating balloon atrial septostomy [BAS] under echocardiographic control. BAS was performed in 25 consecutive patients presenting with TGA between April 1988 and April 1990. Structural and coronary anatomy was evaluated echocardiographically with angiographic supplementation only when additional data were required. This information was correlated, where possible, with direct anatomic findings and subsequent course. BAS was performed through the umbilicus in 17 patients (85% of patients in whom this approach was attempted). Thirteen patients did not require ventilation during BAS. There were minimal complications and satisfactory septostomies in all cases. Coronary anatomy was correctly predicted in all patients where anatomic correlation was available. Without invasive investigation 9 patients underwent neonatal arterial switch procedures and 2 underwent palliative procedures. BAS under echocardiographic control proved safe, effective, minimally traumatic and mostly possible via the umbilical vein. The umbilical vein, where patent, permitted rapid safe access for BAS. Echocardiographic diagnosis of the coronary artery, and structural and functional anatomy was reliable and allowed minimally invasive preoperative management in many patients.

Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13--implications for cytogenetics and molecular biology.

We report on a female with a interstitial deletion of 10p13 and a phenotype similar to that seen with the 22q deletion syndromes (DiGeorge/velo-cardio-facial). She had a posterior cleft palate, perimembranous ventricular septal defect, dyscoordinate swallowing, T-cell subset abnormalities, small ears, maxillary and mandibular hypoplasia, broad nasal bridge, deficient alae nasi, contractures of fingers and developmental delay. This could indicate homology of some developmental genes at 22q and 10p so that patients with the velocardiofacial phenotype who do not prove to be deleted on 22q are candidates for a 10p deletion.

Primary left ventricular rhabdomyosarcoma in a child: noninvasive assessment and successful resection of a rare tumor.

Rhabdomyosarcoma of the heart is a rare tumor, especially in childhood and particularly in the left ventricle. A primary tumor of this type was successfully resected after echocardiographic assessment alone in a young girl exposed prenatally to diphenylhydantoin. The patient is well and free of recurrence 2 1/2 years later.

Simplified single patch technique for the repair of atrioventricular septal defect.

OBJECTIVE: Because of the complexity of traditional 1- and 2-patch techniques for the repair of complete atrioventricular septal defect, we modified our repair technique to avoid the use of any ventricular septal patch material. We report our prospective experience with this simplified 1-patch technique. METHOD: Forty-seven consecutive patients between May 1995 and August 1998 underwent repair with the use of this technique without modification. Repair was done in all patients by direct suturing of the common atrioventricular valve leaflets to the crest of the ventricular septum. No division of valve leaflets was necessary. A single pericardial patch was used to close the defect in the atrial septal component. Follow-up included electrocardiography and echocardiographic assessment of ventricular function, atrioventricular valve function, and adequacy of the left ventricular outflow tract. RESULTS: There were 2 deaths (4%), only 1 cardiac related, in the series. There were 17 male patients and 30 female patients. Mean age at repair was 5.6 months (median, 3.4 months). Associated lesions were repaired in 19 patients (40%). Mean follow-up was 1.85 years (median, 1.9 years). There was no heart block. There were no significant residual ventricular septal defects detected and no left ventricular outflow tract obstruction seen on echocardiography in any patient to date. Mitral valve status after operation was assessed as no incompetence in 13 patients (28%), minimal in 19 patients (40%), mild in 12 patients (26%), and moderate in 3 patients (6%). CONCLUSION: The repair of complete atrioventricular septal defect by direct suturing of the atrioventricular valve leaflets to the crest of the ventricular septum with a single-patch technique greatly simplifies the repair and does not lead to left ventricular outflow tract obstruction nor interfere with valve function.

Internal mammary artery grafting in a neonate for coronary hypoperfusion after arterial switch.

Coronary hypoperfusion may occur after the arterial switch operation, especially when coronary anatomy is complicated. We report successful use of the left internal mammary artery graft for a neonate with coronary hypoperfusion after the arterial switch operation for transposition of great arteries with intramural left coronary artery. Internal mammary arteriography showed a patent graft 19 months after operation.

Salvage of infected truncus repair using rifampicin-impregnated gelatin-sealed graft.

An infant suffered sternal infection and ventricular septal patch dehiscence after a truncus arteriosus repair. Successful reoperation used rifampicin-impregnated gelatin-sealed Dacron to repair the recurrent ventricular septal defect and replace the contaminated conduit. This was an effective solution to a potentially lethal surgical complication.

Pulmonary hypertension--a new manifestation of mitochondrial disease.

Mitochondrial respiratory chain (RC) abnormalities in children can present as multiorgan disease, including liver failure, usually within the first year of life. Cardiorespiratory complications have previously been described in association with RC defects; however, to our knowledge no cases of pulmonary hypertension have been described. We discuss two patients with proven mitochondrial RC liver disease who developed severe pulmonary hypertension, one subsequent to cadaveric orthotopic liver transplantation, the second in the neonatal period. It is our contention that pulmonary hypertension should now be included as another potential manifestation of paediatric mitochondrial disease.

Congenital complete heart block in patients without anatomic cardiac defects.

Forty-three patients with congenital complete heart block and an otherwise structurally normal heart were reviewed in an effort to better define the profile of an anatomically homogenous group and to identify factors that may predict the need for pacing. Fourteen patients (32%) developed "symptoms" during follow-up, including two with out-of-hospital cardiac arrest. Heart rate on electrocardiogram or Holter monitor did not clearly distinguish this subgroup. The presence of alternate "risk factors," such as atrial enlargement seen on electrocardiogram, cardiomegaly seen on x-ray film, or prolonged QT interval were independent predictors of symptoms and poor outcome (p less than 0.05). Ventricular ectopy determined on Holter monitoring was also common among the symptomatic group, although this finding was inconsistent. Prophylactic pacing is indicated in select patients with congenital complete heart block and otherwise normal anatomy. Surveillance for rick factors beyond rate criteria alone may refine this selection process.