Background: Data are lacking on the utility of real-time three-dimensional (3D) echocardiography (RT3DE) in congenital abnormalities of the atrioventricular (AV) valves. The purpose of this study was to determine whether transthoracic RT3DE is superior to combined transthoracic echocardiography and two-dimensional (2D) transesophageal echocardiography in determining mechanisms and sites of AV valve regurgitation in congenital heart disease.Methods: Between January 2005 and November 2007, 48 consecutive patients were studied prior to AV valve repair (22 left AV valves and 26 tricuspid valves) using 2D transthoracic echocardiography, 2D transesophageal echocardiography, and transthoracic RT3DE. Ages ranged from 24 days to 30 years. The 2D data were reviewed by blinded observers, and the real-time 3D data by a separate observer. In all patients, surgical findings were documented by a surgical report, while in 40, video recordings were also available. Surgical findings were used as the reference standard for structural abnormalities; RT3DE was the reference standard for the site of AV valve regurgitation.Results: Compared with 2D echocardiography, RT3DE provided superior detail of the mural leaflet and anterior commissural abnormalities for the left AV valve. For the tricuspid valve, improved detection of leaflet abnormalities, prolapse of the anterior and posterior leaflets, and commissural pathology was observed by RT3DE. Apart from a central location, surgical saline testing correlated poorly with jet location on RT3DE.Conclusion: RT3DE provides complementary information as to the mechanisms and sites of AV valve failure in congenital heart disease. (J Am Soc Echocardiogr 2010;23:726-34.)

Interrupted aortic arch is a rare congenital cardiovascular anomaly with a wide spectrum of anatomical and clinical presentation. We report the case of a newborn presenting at 11 days of age with a type B-2 aortic arch interruption, a closed ductus arteriosus, and an unusual large collateral vessel arising from the ascending aorta proximal to the right carotid artery and joining an aberrant right subclavian arising from the descending aorta.

Objective: The purpose of this study was to determine whether Real-time three-dimensional echocardiography (RT3D) is superior to two-dimensional echocardiography (2D) in determining mechanisms and site(s) of atrioventricular valve (AV valve) regurgitation in congenital heart disease. Background: Data is lacking on the utility of RT3D echo in congenital abnormalities of the AV valves. Methods: Between May 2006 and April 2007, 35 cases were prospectively studied prior to AV valve repair (20 left and 15 right) by 2D transthoracic (2DTTE), 2D transesophageal (2DTEE) and RT3D (Philips matrix array X 3–1 and X 7–2). Thirty one had significant and 4 mild regurgitation. Ages ranged from 24 days to 30 years (mean 13.8 years), weight 2.2 to 42kg (mean 26.1Kg). The 2DTTE and TEE were reviewed by a blinded observer. The 3D data were analyzed by a separate observer. In 28 patients surgical findings and regurgitation from saline testing were recorded by digital video and later analyzed by an experienced cardiac surgeon. The remaining 7 had a detailed description of the valve morphology documented immediately after surgery. Surgical findings were used as the gold standard for the assessment of structural abnormalities, with RT3D for the evaluation of regurgitation. Results: See table for structural abnormalities. For both the left and right AV valve, saline testing provided a poorer correlation with RT3D color Doppler jet location, in particular for regurgitant jets from the commmissures (p < 0.01). Conclusion: Transthoracic RT3D provides new and superior information as to the mechanisms and site(s) of AV valve failure in congenital heart disease. Concordance between 2D TTE, 2D TEE and 3D TTE compared to surgical findings

Anion exchanger 1 (AE1; SLC4A1), the plasma membrane Cl(-)/HCO(3)(-) exchanger of erythrocytes, is also expressed in heart. The aim of this study was to assess the role of AE1 in heart function through study of AE1-null (AE1(-/-)) mice, which manifest severe hemolytic anemia resulting from erythrocyte fragility. Heart weight-to-body weight ratios were significantly higher in the AE1(-/-) mice than in wild-type (AE1(+/+)) littermates at both 1-3 days postnatal (3.01 +/- 0.38 vs. 1.45 +/- 0.04) and at 7 days postnatal (9.45 +/- 0.53 vs. 4.13 +/- 0.41), indicating that loss of AE1 led to cardiac hypertrophy. Heterozygous (AE1(+/-)) mice had no signs of cardiac hypertrophy. Morphology of the adult AE1(-/-) mutant heart revealed an increased left ventricular mass, accompanied by increased collagen deposition and fibrosis. M-mode echocardiography revealed dysfunction of the AE1(-/-) hearts, including dilated left ventricle end diastole and systole and expanded left ventricular mass compared with AE1(+/+) hearts. Expression of intracellular pH-regulatory mechanisms in the hypertrophic myocardium of neonate AE1(-/-) mutant mice was indistinguishable from AE1(+/-) and AE1(+/+) mice, as assessed by quantitative real-time RT-PCR. Confocal immunofluorescence revealed that, in normal mouse myocardium, AE1 is sarcolemmal, whereas AE3 and slc26a6 are found both at the sarcolemma and in internal membranes (T tubules and sarcoplasmic reticulum). These results indicate that AE1(-/-) mice, which suffer from severe hemolytic anemia and spherocytosis, display cardiac hypertrophy and impaired cardiac function, reminiscent of findings in patients with hereditary abnormalities of red blood cells. No essential role for AE1 in heart function was found.

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We examined two expression systems for studying the Na(+)/H(+) exchanger in the mammalian myocardium. Mammalian NHE1 with a hemagglutinin (HA) tag and was cloned behind the alpha myosin heavy chain promoter. Transgenic mice were made with wild type NHE1 protein or with a hyperactive NHE1 protein mutated at the calmodulin-binding domain. Three lines of transgenic mice were made of each cDNA with expression levels of each type varying from high to low. Higher levels and activity of the Na(+)/H(+) exchanger were associated with decreased long-term survival of mice, and with dilated or hypertrophic cardiomyopathy. The exogenous NHE1 protein was present in freshly made cardiomyocytes from transgenic mice, however, expression from the alpha myosin heavy chain promoter declined rapidly and little exogenous NHE1 was apparent on the fourth day after cardiomyocyte isolation. To express NHE1 protein in isolated cardiomyocytes, we transferred a mutated form of the protein into an adenoviral expression system. Infection of neonatal rat cardiomyocytes resulted in robust expression of the exogenous NHE1 protein. The mutant form of the NHE1 protein could be distinguished from the endogenous Na(+)/H(+) exchanger by its resistance to inhibition by amiloride analogs. Our results suggest that for in vivo studies on intact hearts and animals, expression in transgenic mice is an appropriate system, however for long-term studies on cardiomyocytes, this model is inappropriate due to waning expression from the alpha myosin heavy chain promoter. Therefore, infection by adenovirus is a superior system for long-term studies on cardiomyocytes in culture.

Phillipos, E; Escoredo, S; Robertson, M; Rigo, VEditor(s): Chang, Anthony C. MD, MBA, Editor Author Information

Congenital cardiac tumors are very rare and fibromas are the second most common type. Fibromas are benign tumors, but they have potentially serious complications. Their antenatal diagnosis is infrequently reported in the literature, and the management of these tumors is a source of controversy. We report the case of a rare form of right ventricular free wall fibroma. Antenatal diagnosis was made at 36 weeks of gestation, with subsequent successful resection at 2 weeks of age. A brief review of the literature focuses on the diagnostic approach and the clinical and surgical management of congenital cardiac fibromas.

BACKGROUND:Mediastinitis results in significant morbidity in pediatric cardiac patients. It is not clear whether delayed sternal closure is a risk factor for these infections. Management of mediastinitis remains controversial.METHODS:Cases of mediastinitis at the Stollery Children's Hospital from January 1, 1991, to June 30, 2004, were reviewed.RESULTS:There were 29 cases of mediastinitis in 2,675 open cardiac procedures for an overall incidence of 1.1%. Infection was diagnosed 5 to 27 days after the original surgical procedure (median, 10 days). The odds ratio for infection with delayed sternal closure versus primary sternal closure was 1.88 (95% confidence interval, 0.63 to 5.60). Signs at the onset of infection included fever (86%), incisional erythema (69%), purulent drainage from the incision or pacer wire sites (83%), and wound dehiscence (23%). Debridement was followed by primary sternal closure in all but three cases in which the sternum had not been closed before debridement and rotational muscle flaps were not used. Continuous irrigation systems were used only in the first 7 patients. One patient died of mediastinitis complicated by infective endocarditis, and 2 patients died of multiorgan failure.CONCLUSIONS:Delayed sternal closure was not a major risk factor for mediastinitis, especially if primary skin closure was used with delayed sternal closure. Excellent results were attained with debridement and primary closure of these infections.

Infectious complications of cancer treatment are potentially life threatening and remain a leading cause of morbidity and mortality in children diagnosed with cancer. There is substantial evidence to show that single bouts of exercise can produce relatively small but significant changes in the distribution and function of components of the immune system. To date, no study has examined the effects of acute exercise on neutrophils in patients with acute lymphoblastic leukemia (ALL) receiving maintenance therapy. PURPOSE To determine the effects of acute exercise on neutrophils in children receiving maintenance treatment for ALL compared to matched controls. METHODS Participants (n = 10; 4 ALL patients and 6 matched controls) were males between the ages of 7–18 years. On day 1, participants completed an incremental exercise test to exhaustion on a treadmill to determine peak aerobic fitness (VO2peak). On day 2, participants completed a 30-minute submaximal exercise test on a treadmill at 70% VO2peak with 4 blood sampling time points: pre exercise, post exercise, 1-hour post exercise and 2-hours post exercise. RESULTS Repeated measures analyses of variance demonstrated significant main effects for Time such that there was a significant increase in absolute neutrophil counts from pre exercise to post exercise [F (1,7) = 11.8; p=.011], a significant decrease from post exercise to 1-hour post exercise [F(1,7) = 5.9; p = .045], and a significant increase from 1-hour post exercise exercise to 2-hours post exercise [F(1,7) = 5.4; p = .052]. There were no main effects for Group and no Time by Group interactions (all ps >.100). The means and standard deviations for the ALL group were: pre exercise (M=3293; SD=1985), post exercise (M=4153; SD=2218), 1-hour post exercise (M=3199; SD=1274) and 2-hours post exercise (M=3498; SD=1358). The means and standard deviations for the control group were: pre exercise (M=2053; SD=898), post exercise (M=3022; SD=1294), 1-hour post exercise (M=2729; SD=1226) and 2-hours post exercise (M=3056; SD=1483). CONCLUSIONS This is the first study to investigate the effect of acute exercise on absolute neutrophil count in children with ALL receiving maintenance therapy. This pilot study demonstrates a similar neutrophil response in ALL patients as compared to matched controls with an increase following exercise. This finding may be of clinical importance for the ALL patient during periods of low immunity during maintenance treatment. At the least, it suggests that ALL patients on maintenance therapy do not have an adverse neutrophil response to an acute bout of30-minute moderate intencity exercice.

Calreticulin is a Ca2+ binding/storage chaperone resident protein of the endoplasmic reticulum. This protein plays a key role in the calreticulin/calnexin cycle and the quality control pathways in the endoplasmic reticulum. Calreticulin deficiency is lethal due to impaired cardiac development. However, over-expression of the protein in developing and postnatal heart leads to bradycardia, complete heart block and sudden death. Ultrastructural evidence indicates that the deficiency associated with the absence of calreticulin in the heart may be due to a defect in the development of the contractile apparatus and/or a defect in development of the conductive system as well as a metabolic abnormality. Collectively, we postulate that calreticulin and endoplasmic reticulum plays an important role in cardiac development and postnatal pathologies. (Mol Cell Biochem 263: 137–142, 2004)

Calreticulin is a Ca2+ binding chaperone resident in the lumen of endoplasmic reticulum. The protein is highly expressed in developing heart and down-regulated after birth. In mice, calreticulin deficiency is lethal due to impaired cardiac development. Overexpression of calreticulin in developing and postnatal heart leads to bradycardia, complete heart block and sudden death. This indicates that calreticulin plays an important role in the development of the cardiac conduction system and in the pathology of congential heart block. These findings may have important implications on the molecular understanding of congenital heart block and may prove to be a target for future therapies.

J Thorac Cardiovasc Surg 2001;122:180-1

The expression of calreticulin, a Ca(2+)-binding chaperone of the endoplasmic reticulum, is elevated in the embryonic heart, and because of impaired cardiac development, knockout of the Calreticulin gene is lethal during embryogenesis. The elevated expression is downregulated after birth. Here we have investigated the physiological consequences of continued high expression of calreticulin in the postnatal heart, by producing transgenic mice that overexpress the protein in the heart. These transgenic animals exhibit decreased systolic function and inward I(Ca,L), low levels of connexin43 and connexin40, sinus bradycardia, and prolonged atrioventricular (AV) node conduction followed by complete heart block and sudden death. We conclude that postnatal downregulation of calreticulin is essential in the development of the cardiac conductive system, in particular in the sinus and AV nodes, when an inward Ca(2+) current is required for activation. This work identifies a novel pathway of events, leading to complete heart block and sudden cardiac death, which involves high expression of calreticulin in the heart.

OBJECTIVE: To review our experience in managing infants with hypoplastic left heart syndrome (HLHS) and to establish a consistent approach in counseling families based on our experience and on review of medical literature. METHODS: Infants were divided into three group periods based on significant changes in the approach to treatment. After a diagnosis of HLHS was made, a multidisciplinary team met the family to discuss different management options: compassionate care, active treatment by heart transplantation, or Norwood staged surgery. RESULTS: Parents of 58 infants (58%) opted for compassionate care, and 41 (42%) opted for active treatment. Seven infants underwent heart transplantation and all remain alive. A total of 27 infants underwent Norwood stage I, and 19 (70%) survived. There was a significant increase in parental choice for active treatment over the three time periods. CONCLUSION: These results indicate that HLHS can no longer be regarded as a uniformly fatal congenital anomaly. However, due to uncertainty about long-term outcome, discussion with parents should be open, and compassionate care should be presented as a management option until long-term data are available.