Long-term survival after mitral valve replacement in children aged <5 years: a multi-institutional study.

BACKGROUND: Short- and long-term outcomes after prosthetic mitral valve replacement (MVR) in children aged <5 years are ill-defined and generally perceived as poor. The experience of the Pediatric Cardiac Care Consortium (45 centers, 1982 to 1999) was reviewed. METHODS AND RESULTS: MVR was performed 176 times on 139 patients. Median follow-up was 6.2 years (range 0 to 20 years, 96% complete). Age at initial MVR was 1.9+/-1.4 years. Complications after initial MVR included heart block requiring pacemaker (16%), endocarditis (6%), thrombosis (3%), and stroke (2%). Patient survival was as follows: 1 year, 79%; 5 years, 75%; and 10 years, 74%. The majority of deaths occurred early after initial MVR, with little late attrition despite repeat MVR and chronic anticoagulation. Among survivors, the 5-year freedom from reoperation was 81%. Age-adjusted multivariable predictors of death include the presence of complete atrioventricular canal (hazard ratio 4.76, 95% CI 1.59 to 14.30), Shone's syndrome (hazard ratio 3.68, 95% CI 1.14 to 11.89), and increased ratio of prosthetic valve size to patient weight (relative risk 1.77 per mm/kg increment, 95% CI 1.06 to 2.97). Age- and diagnosis-adjusted prosthetic size/weight ratios predicted a 1-year survival of 91% for size/weight ratio 2, 79% for size/weight ratio 3, 61% for size/weight ratio 4, and 37% for size/weight ratio 5. CONCLUSIONS: Early mortality after MVR can be predicted on the basis of diagnosis and the size/weight ratio. Late mortality is low. These data can assist in choosing between MVR and alternative palliative strategies.

A soluble neuronal factor alters contractile function of ventricular myocytes without effect on troponin T isoform expression.

OBJECTIVE: The purpose of this investigation was to establish a model system to facilitate identification of the sympathetic neuronal factor(s) that promotes improved contractility in neonatal cardiac myocytes. Conditioned medium from PC12 cells with sympathetic phenotype served as the source of the neuronal factor. METHODS: Contraction frequency, amplitude and velocity of cultured neonatal rat cardiac myocytes were measured by online video analysis. Interventions included in vitro sympathetic innervation, exposure to PC12 conditioned medium, neurotransmitters and antagonists. Metabolic activity was assayed by 2-deoxyglucose uptake. Troponin T isoform expression was analyzed by SDS-polyacrylamide gel electrophoresis. RESULTS: Medium conditioned by neuronal PC12 cells induced contractility changes similar to those induced by in vitro sympathetic innervation. These effects of PC12 conditioned medium and innervation were not suppressed by adrenergic or muscarinic antagonists nor reproduced by neuropeptide Y or somatostatin. Neuronal PC12 conditioned medium but not chromaffin PC12 conditioned medium, increased metabolic activity of the myocytes as detected by [3H]-2-deoxyglucose, indicating that the effect was specific to the neuronal PC12 cells. The in vitro switch of troponin T isoform expression was not altered by exposure to PC12 conditioned medium. CONCLUSIONS: Increased contractile function induced by sympathetic innervation is reproduced by PC12 conditioned medium, but neither is mediated by sympathetic or muscarinic neurotransmitters. Troponin T isoform expression is not related to the contractility changes. This model system will allow identification of the factor(s).

Complete heart block in association with graft-versus-host disease.

An infant who received haploidentical BM for severe combined immunodeficiency (SCID) developed acute, reversible complete heart block in association with an exacerbation of GVHD. Respiratory distress and myocardial dysfunction were also seen with this and previous GVHD exacerbations. The patient had not received chemotherapy or radiation prior to BMT. The complete heart block resolved after 1 week of intensive immunosuppression. The association of complete heart block with GVHD is important because the heart block is potentially reversible with prompt, aggressive control of the GVHD.

Common cardiovascular problems in the young: Part II. Hypertension, hypercholesterolemia and preparticipation screening of athletes.

Blood pressure should be measured during health maintenance visits in all children three years of age and older. Cholesterol levels should be obtained in children with a family history of hypercholesterolemia or premature coronary artery disease and in children with other risk factors, such as hypertension, smoking or obesity. Preparticipation screening for sports participation should include a detailed questionnaire regarding the athlete's personal or family history of syncope, sudden death or arrhythmia, as well as measurement of blood pressure, auscultation of the heart and evaluation of upper and lower extremity pulses.

Regulation of rat cardiac myocyte growth by a neuronal factor secreted by PC12 cells.

Sympathetic innervation of cardiac myocytes in vitro induces growth independent of anatomic contact between the neurons and myocytes and is not mediated by alpha- or beta-adrenergic receptor stimulation. To establish a model system that will allow purification and identification of the neuronal factor(s) responsible for mediating this regulation, we have initiated studies utilizing conditioned medium from the PC12 cell line. PC12 cells acquire a cholinergic sympathetic neuronal phenotype when exposed to nerve growth factor. Culture medium conditioned by neuronal PC12 cells, but not nonneuronal PC12 cells, induces growth in newborn rat cardiac myocytes as measured by surface area and [35S]methionine incorporation into protein and increases expression of atrionatriuretic peptide, a marker for myocyte hypertrophy. The magnitude of the growth response is dose-dependent and mimics the response to sympathetic innervation. The myocyte response to conditioned medium is not detectable after 24 h of exposure; maximal rate of protein synthesis is obtained within 48 h. Neuronally differentiated PC12 cell-conditioned medium stimulation of growth could not be mimicked by alpha- or beta-adrenergic agonists or muscarinic agonists, nor inhibited by alpha- or beta-adrenergic antagonists, nor by muscarinic antagonists. Neuropeptide Y and somatostatin, peptides known to be present in PC12 cells and sympathetic neurons, were also ineffective at reproducing the effect of neuronally differentiated PC12 cell-conditioned medium. These data indicate that neuronal cells release a soluble factor, different from neurotransmitter, which stimulates myocyte growth. They further identify the PC12 cell line as providing a convenient and abundant supply of this molecule, thus facilitating its further characterization.

Operative mortality and frequency of coexistent anomalies in interruption of the aortic arch.

Operative mortality for 262 infants with interruption of the aortic arch repaired from 1982 to June 1993 has remained constant at about 35%. Major coexistent cardiac malformations, type B interruption, or staged repair are risk factors for mortality.