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.

Normalization of ventricular repolarization with flecainide in long QT syndrome patients with SCN5A:DeltaKPQ mutation.

BACKGROUND: The Long QT Syndrome (LQTS) is a genetic channelopathy with life-threatening implications. The LQT3 form of this disease is caused by mutations of the SCN5A sodium-channel gene. A specific mutation, SCN5A:DeltaKPQ, is associated with repetitive reopenings of the sodium channel and prolonged inward current. This dominant inward current is manifest on the electrocardiogram as QT prolongation. Flecainide is a potent blocker of the open sodium channel. METHODS AND RESULTS: The effect of flecainide on the duration of the QT-interval and the T-wave morphology was systematically evaluated in five male patients age 2-64 years having the SCN5A:DeltaKPQ mutation. After baseline electrocardiograms were obtained, low-dose oral flecainide was administered for 48 hours. Serial electrocardiograms and blood flecainide levels were obtained during flecainide therapy. The QTc interval decreased on average by 104 ms, from a baseline value of 565 +/- 60 ms to 461 +/- 23 ms (P < 0.04) at a mean flecainide level of 0.28 +/- 0.08 mg/L, with shortening of the QTonset interval (P < 0.003) and normalization of T-wave morphology. The effects of flecainide were compared with oral mexiletine in two patients, with flecainide showing greater QTc shortening and more complete normalization of repolarization. No adverse side effects or proarrhythmia were observed with flecainide in this study. CONCLUSION: Low-dose, oral flecainide consistently shortened the QTc interval and normalized the repolarization T-wave pattern in five LQT3 patients with SCN5A:DeltaKPQ mutation. This preliminary study indicates that low-dose flecainide is a promising therapeutic agent for LQTS patients with the SCN5A:DeltaKPQ sodium channel mutation.

Is arrhythmia detection by automatic external defibrillator accurate for children?: sensitivity and specificity of an automatic external defibrillator algorithm in 696 pediatric arrhythmias.

BACKGROUND: Use of automatic external defibrillators (AEDs) in children aged <8 years is not recommended. The purpose of this study was to develop an ECG database of shockable and nonshockable rhythms from a broad age range of pediatric patients and to test the accuracy of the Agilent Heartstream FR2 Patient Analysis System for sensitivity and specificity. METHODS AND RESULTS: Children aged

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).

Accurate recognition and effective treatment of ventricular fibrillation by automated external defibrillators in adolescents.

OBJECTIVES: To evaluate the accuracy and efficacy of automated external defibrillators (AEDs) in patients <16 years old. BACKGROUND: AEDs are standard therapy in out-of-hospital resuscitation of adults and have led to higher success rates. Their use in children and adolescents has never been evaluated, despite recommendations from the American Heart Association that they be used in children >8 years of age. METHODS: This was a retrospective cohort study of children <16 years old who underwent out-of-hospital cardiac resuscitation and on whom an AED was used during the resuscitation. The setting was rural and urban prehospital emergency medical systems. Patients were identified by review of a database of cardiac arrests maintained by a large surveillance program of these services. RESULTS: AEDs were used to assess cardiac rhythm in 18 patients with a mean age of 12.1 +/- 3.7 years. The cardiac rhythms were analyzed 67 times and included ventricular fibrillation (25), asystole/pulseless electrical activity (32), sinus bradycardia (6), and sinus tachycardia (4). The AEDs recognized all nonshockable rhythms accurately and advised no shock. Ventricular fibrillation was recognized accurately in 22 (88%) of 25 episodes and advised or administered a shock 22 times. Sensitivity and specificity for accurate rhythm analysis were 88% and 100%, respectively. One patient with a nonshockable rhythm survived, whereas 3 of 9 patients with ventricular fibrillation survived. CONCLUSIONS: These data furnish evidence that AEDs provide accurate rhythm detection and shock delivery to children and young adolescents. AED use is potentially as effective for children as it is for adults.

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.

A multimodal approach to functional dysphagia.

Functional dysphagia in children has historically been treated using a cognitive behavioral approach. The case of a 7-year-old boy treated using a successful multimodal approach, including behavioral, family, and play therapy with alprazolam augmentation, is reported. The patient showed minimal response to early interventions but rapidly improved with the prescription of alprazolam before meals.

Pediatric defibrillation: current flow is improved by using "adult" electrode paddles.

OBJECTIVE: Current flow, the major determinant of defibrillation success, depends on delivered energy and transthoracic impedance. Previous experimental data suggest that transthoracic impedance is higher using "pediatric" electrode paddles compared to the larger "adult" electrode paddles. There are few data from actual shocks to support the experimental studies. The purpose of this study was to measure transthoracic impedance during actual shock delivery and to determine the optimal electrode paddle size for pediatric defibrillation and cardioversion. METHODS: We prospectively evaluated all shocks of < or = 20 joules given to pediatric patients at the University of Iowa from 1988 to 1992. Data collected included energy selected by the operator, energy delivered by the defibrillator, peak current flow and transthoracic impedance. Data were analyzed by unpaired t test and linear regression. RESULTS: Fifty-five shocks were delivered to 20 patients, age newborn to 8 years. Thirty-seven shocks were given with "pediatric" electrode paddles (surface area 21 cm2) and 18 with "adult" electrode paddles (surface area 83 cm2). Selected energy correlated well with delivered energy (r = .98, P < .0001). Delivered energy using "pediatric" electrodes did not differ from that delivered with "adult" electrodes (8.0 +/- 0.9 joules vs 10.5 +/- 1.2 joules P > .1). However transthoracic impedance was significantly higher with "pediatric" electrodes (78.1 +/- 4.4 ohms vs 54.6 +/- 2.7 ohms P < .0008), resulting in lower peak current flow through "pediatric" electrode paddles (6.2 +/- 0.5 amps vs 8.7 +/- 0.5 amps P < .002). There was no correlation between joules/kg and peak current flow (r = .26, P > .05). CONCLUSION: Use of "pediatric" electrode paddles results in higher transthoracic impedance and thus lower peak current flow. In pediatric defibrillation, larger "adult" electrode paddles should be used as soon as chest size permits (approximately 10 kg). Lower transthoracic impedance results in higher current flow that facilitates cardioversion and defibrillation.

Differential growth of neonatal WKY and SHR ventricular myocytes within sympathetic co-cultures.

Sympathetic innervation is known to increase heart size in the immature animal, yet the mechanism for this growth remains to be established. This comparative study stereologically quantified the volume of cultured neonatal ventricular myocytes with and without in vitro sympathetic innervation to isolate the mechanisms regulating cardiac growth. Since ventricular myocyte size at birth differs between the spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto (WKY), we questioned whether SHR myocytes respond differently than WKY myocytes to innervation. Four groups of ventricular myocytes from each strain were compared: myocytes grown alone, myocytes innervated by cultured sympathetic neurons, innervated myocytes exposed to adrenoceptor blockade, and non-innervated myocytes in co-culture dishes. Volumes for the myocyte, nucleus, cytoplasm, mitochondria, sarcomeres and other cellular organelles were assessed within each population and between populations. Relative volumes were determined for the mitochondria, sarcomeres, and other cellular components within the cytoplasm. Innervated WKY myocytes were 38% larger than control myocytes (P < 0.0004). This growth was not blocked by adrenoceptor blockade (P = 0.89 vs. innervated) and was present in the non-innervated myocytes distant from the neurons in the co-cultures (P = 0.39 vs. innervated). SHR myocytes were 36% larger than WKY myocytes (P < 0.009) but did not increase with innervation (P = 0.48). SHR myocyte size was also unaffected by adrenoceptor blockade (P = 0.39) or presence of the neurons in the culture dish (P = 0.53). Neonatal WKY ventricular myocyte growth can be provoked in vitro by sympathetic innervation via regulatory mechanisms independent of neuroeffector transmission or anatomic contact, whereas volume of neonatal SHR myocytes is unaltered by sympathetic coculture. These findings are significant for understanding normal as well as aberrant cardiomyocyte growth.