Human herpes virus 6 in archival cardiac tissues from children with idiopathic dilated cardiomyopathy or congenital heart disease.

OBJECTIVE: To explore the possible role of human herpes virus 6 (HHV-6) in cardiac disorders in childhood in a retrospective study on archival specimens of explanted hearts. METHODS: 16 children (median age at transplantation 11.0 years) with idiopathic dilated cardiomyopathy (DCM) and 19 children (median age at transplantation 1.0 year) with congenital heart disease (CHD), previously found to be negative for other cardiotropic viruses such as enteroviruses, adenovirus, parvovirus B19, cytomegalovirus and Epstein-Barr virus, were tested for HHV-6 by quantitative real-time PCR and by genotyping. In addition, HHV-7/8 infection was investigated by qualitative PCR. RESULTS: HHV-6 B variant was detected in 11 of 35 samples (31.4%) with a mean viral load of 3.1 x 102 copies/microg of DNA. When assessed by heart disorder, the prevalence was different in the two groups (43.7% in DCM and 21% in CHD) while the mean viral loads were similar. In a logistic multivariate analysis HHV-6 was independently associated with DCM, taking CHD as reference and adjusting for age (best estimate: OR = 6.94; 95% CI 1.00 to 49.85; p = 0.05). CONCLUSIONS: Although the clinical significance of the results is unknown, HHV-6 B genome is frequently detected in explanted hearts from children with DCM and to a lesser extent with CHD, thus adding evidence for HHV-6 cardiac involvement.

Complete follow-up echocardiograms are needed to detect stenosis of normally connecting pulmonary veins.

Reimbursement for limited echocardiograms focusing on known pathology rather than complete studies has recently received widespread attention. Few data are available to determine if these limited examinations provide enough information to adequately evaluate many forms of congenital heart disease. Stenosis of normally connecting pulmonary veins is a congenital or acquired cardiac anomaly that is difficult to diagnose clinically and may be detectable only by echocardiography. To evaluate the yield of complete versus limited echocardiograms for detecting the presence and development of stenosis in pulmonary veins with anatomically normal connections, the cardiology database was searched for all patients with this diagnosis presenting between June 1990 and January 2000. Charts were reviewed for demographic data, associated defects, surgeries, and outcomes. Angiograms and echocardiograms were reviewed for location and severity of pulmonary vein stenosis. A pulsed-wave Doppler signal of > 1.6 mm/sec with loss of phasic flow was used to define stenosis. Eighteen patients were identified and ranged in age at first evaluation from 1 day to 17 years (median 15 days). All 18 patients had associated cardiac anomalies, and 4 (22%) of 18 had Trisomy 21. Pulmonary vein stenosis was detected on the initial evaluation in 5 patients, detected 8 +/- 5 months after the initial echocardiogram in 11 patients, and missed by echocardiography in 2 patients who were diagnosed by cardiac catheterization. The initial echocardiograms were complete, with pulsed-Doppler sampling of all four pulmonary veins in 17 of 18 patients. Of the 12 patients who had echocardiographic evidence of late stenosis, 10 had 17 limited interim studies prior to eventually having a complete diagnostic follow-up study. Of the two patients in whom the diagnosis was missed by echocardiography, one initial study was technically inadequate (17-year-old) and one had only limited interim studies after the initial echocardiogram. Of the 9 patients in whom repair of the pulmonary vein stenosis was attempted, 3 had no residual obstruction and 6 had progressive stenosis (three deaths). Of the remaining nine patients who had no intervention for their pulmonary venous stenosis, four have died from progressive pulmonary hypertension. Stenosis of normally connecting pulmonary veins is an uncommon lesion that has a significant impact on clinical outcome. The stenoses might be undetectable on limited echocardiograms that focus on evaluating only specified pathology. Complete follow-up examinations might be warranted to diagnose this lesion. This may be an important consideration when formulating reimbursement policies.

Evidence for early vessel involvement in the dysfunctional myocardium of Takayasu's arteritis.

A 15-year-old girl presented with persistent fevers, night sweats, leukocytosis, an elevated erythrocyte sedimentation rate, and a 13-pound weight loss over 2 months. Duplex Doppler scans, computed tomographic scan, and magnetic resonance imaging studies were suggestive of Takayasu's arteritis. Left ventricular dysfunction occurred during the episode of active disease, and an endomyocardial biopsy demonstrated increased HLA-DR (human leukocyte antigen-DR) on the endothelium and evidence of immune complex deposition in the walls of small vessels. One year later, after treatment with corticosteroids and resolution of clinical symptoms, repeat endomyocardial biopsy revealed focal interstitial fibrosis and persistent immune complex deposition. These results indicate that the inflammatory, vasculitic process affecting the large vessels in Takayasu's arteritis may also involve the endomyocardium and its small vessels resulting in ventricular dysfunction.

A prospective analysis of the immunogenicity of cryopreserved nonvalved allografts used in pediatric heart surgery.

BACKGROUND: The purpose of this study was to prospectively determine the immunogenicity of nonvalved allograft tissue used to repair congenital heart defects. METHODS AND RESULTS: We prospectively analyzed the immune response of 11 children, 1.4 months to 10 years of age, who required nonvalved allografts to alleviate stenosis during repair of congenital heart defects. In 7 patients, pulmonary arterial grafts were used; in 3 patients, monocusp pulmonary artery grafts were used; and in 1 patient, a section of glutaraldehyde-preserved allograft pericardium was used. We measured the level of HLA panel-reactive antibody (PRA) before surgery, 1 week after, 1 month after, and 3 months after surgery. PRA was determined by the antiglobulin technique and flow cytometry. HLA class I and class II antibodies measured by either technique were negligible before and 1 week after surgery. Nine of 11 patients (82%) exhibited a significant immune response at 1 month after surgery that further increased at 3 months. The measured PRA for class I antibodies with the antiglobulin technique increased to 43+/-36% at 1 month and to 69+/-38% at 3 months after surgery. Flow cytometry class I PRA measurements were similar. Class II PRA increased to 26+/-34% at 1 month and to 41+/-36% at 3 months. Age negatively correlated with the degree of elevation of PRA, but neither allograft area nor the area indexed to patient body surface area correlated with PRA. CONCLUSIONS: Cryopreserved nonvalved allografts induce a strong HLA antibody response in the majority of children.

Class I and class II anti-HLA antibodies after implantation of cryopreserved allograft material in pediatric patients.

OBJECTIVES: Very little is known regarding the immune response to cryopreserved allograft valves and patch material used in the surgical repair of congenital heart defects. METHODS: We prospectively measured the frequency of panel reactive antibodies directed against HLA class I (HLA-A, B, and C) and class II (HLA-DR/DQ) alloantigens in 24 children receiving cryopreserved allografts. We compared them with results in 11 previously reported control patients. Sixteen of the study patients underwent placement of a valved conduit (11 pulmonic, 5 aortic) between the right ventricle and pulmonary arteries, 6 underwent patch angioplasty of stenotic vessels with cryopreserved pulmonary artery, and 2 underwent placement of a pulmonary monocusp patch. Study patients had panel reactive antibodies measured before, 1 month, 3 months, and 1 year after the operation. RESULTS: With allograft implantation, panel reactive antibodies increased from 1.9% +/- 5% before the operation to 62% +/- 33% at 31 +/- 8 days after the operation, 92% +/- 15% at 3.3 +/- 0.6 months after the operation, and 85% +/- 18% at 1.1 +/- 0.2 years after the operation. The control group showed no change in panel reactive antibodies, with a level of 1.6% +/- 1% before the operation, 3.2% +/- 1% 28 +/- 5 days after the operation, and 1.7% +/- 1% 2.7 +/- 0.3 months after the operation. Class II antibodies (anti-HLA-DR/DQ) rose to 49% +/- 35% at 30 +/- 8 days and 70% +/- 26% at 3.3 +/- 0.6 months after the operation. CONCLUSIONS: Cryopreserved allograft material induces a marked response that involves both class I and class II anti-HLA antibodies within 3 months after operation in children. This alloantibody response may represent a form of "rejection," may have implications for those who require subsequent cardiac transplantation, and may play a role in early allograft failure.

Pulmonary vein stenosis with normal connection: associated cardiac abnormalities and variable outcome.

BACKGROUND: Pulmonary vein (PV) stenosis with anatomically normal connection is considered rare, unresponsive to treatment, progressive, and usually fatal. METHODS: We reviewed the records of 13 children with this diagnosis at our center since 1990. RESULTS: The number of stenosed PVs ranged from all PVs (n = 5); three PVs (n = 1); two PVs (n = 5); and one PV (n = 2). All patients had associated congenital cardiac abnormalities. Operation on PV stenosis was attempted in 7 patients (54%), 2 of whom have done well and 5 of whom have not. Two patients underwent heart transplantation for inoperable associated cardiac lesions. Significantly more patients with three or four stenosed PVs died (83%) compared with patients with one or two stenosed PVs (0%). CONCLUSIONS: (1) Pulmonary vein stenosis with anatomically normal connection is associated with other congenital cardiac abnormalities, (2) presentation and outcome are contingent on the number of stenosed PVs, (3) surgical palliation may be helpful in some patients, and (4) heart transplantation for inoperable associated cardiac abnormalities may be an option in patients with only one or two stenosed PVs.