Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes.

BACKGROUND: Infantile cardiomyopathy is a genetically heterogeneous disorder with significant morbidity and mortality. METHODS: This study aimed to identify the mutation present in four unrelated patients who presented as infants with isolated hypertrophic cardiomyopathy. RESULTS: In all four, a novel mitochondrial m.8528T-->C mutation was identified. This results in a change of the initiation codon in ATPase 6 to threonine and a concurrent change from a highly conserved hydrophobic amino acid, tryptophan, at position 55 of ATPase 8 to a highly basic arginine. To our knowledge, this is the first report of a mutation affecting both mitochondrial genome-encoded complex V subunit proteins. Testing of the relatives of one patient indicated that the mutation is heteroplasmic and correlated with disease. CONCLUSION: Mitochondrial genome sequencing should be considered in patients with infantile hypertrophic cardiomyopathy.

Pediatric restrictive cardiomyopathy associated with a mutation in beta-myosin heavy chain.

Most children do not have a known cause of cardiomyopathy which limits the potential for disease-specific therapies. Of the different phenotypic presentations of cardiomyopathy, the restrictive form carries the poorest prognosis and has the lowest rate of identification of etiology. We present the first description of a beta-myosin heavy chain gene mutation in an infant with restrictive cardiomyopathy requiring cardiac transplantation. As demonstrated by three-dimensional protein structure modeling, the missense mutation is in a highly conserved amino acid at the critical binding region for the essential light chain. This case emphasizes that mutations in sarcomeric proteins, which are known to cause hypertrophic cardiomyopathy in adults, may be associated with the development of restrictive physiology in childhood. Identification of the genetic basis of pediatric cardiomyopathy has important implications for management and genetic counseling.

Percutaneous closure of the small patent ductus arteriosus using occluding spring coils.

OBJECTIVES: This report summarizes our experience with the use of occluding spring coils to close the small patent ductus arteriosus. BACKGROUND: Several patent ductus arteriosus occluders (most notably the Rashkind device) have been developed and studied. Occluding spring coils have been used to close abnormal vessels and vascular connections. We previously reported the use of occluding spring coils to close the small patent ductus arteriosus in a small group of patients. This report describes our series of patients having patent ductus arteriosus closure with occluding spring coils. METHODS: Between June 1990 and June 1993, 30 patients underwent cardiac catheterization to have patent ductus arteriosus closure by occluding spring coils. Selection criteria were age > 6 months and narrowest patent ductus arteriosus internal dimension < or = 3.0 mm by color flow imaging. Definitive selection was based on review of aortograms performed at catheterization. A 5.2F coronary catheter was used to deliver one or two standard occluding spring coils. A loop was delivered in the main pulmonary artery, and the remainder of the coil was delivered across the patent ductus arteriosus and into the aortic diverticulum. Patent ductus arteriosus closure was confirmed by aortography or color flow imaging, or both. Follow-up after coil placement occurred at 6 weeks and 6 months and included two-view chest radiography, echocardiography and color flow imaging. RESULTS: Of the 30 patients, 29 had successful implantation by one (27 patients) or two (2 patients) occluding spring coils. Of these 29 patients, 19 had a clinically apparent and 10 had a silent patent ductus arteriosus. Average ductus minimal internal dimension was 1.7 mm (range 1.0 to 3.0). Complete closure of the ductus was confirmed in 27 patients by aortography or color flow imaging or both (in 24 within 4 h, in 2 after 6 weeks and in 1 after 6 months). Six weeks after implantation, two patients had a tiny residual patent ductus arteriosus noted on color flow imaging. One patient did not have successful implantation. This patient had a 3.2-mm ductus, and two coils migrated to the distal left pulmonary artery and could not be retrieved. There were no deaths or any significant complications noted during early or late follow-up in these patients. CONCLUSIONS: Occluding spring coils may have additional application in closing the small patent ductus arteriosus.

Percutaneous balloon angioplasty for native coarctation of the aorta.

Twenty-six children, aged 5 weeks to 14.7 years, underwent percutaneous balloon angioplasty for a discrete native coarctation of the aorta. The procedure reduced the systolic coarctation gradient acutely in all children. The mean systolic gradient decreased by 75%, from 48.6 +/- 2.4 before to 12.3 +/- 1.9 mm Hg after angioplasty (p less than 0.001). Long-term results were evaluated in 14 children by follow-up catheterization 12 to 26 months (mean 15.3) after angioplasty. At follow-up, the residual gradient averaged 11.7 +/- 3.7 mm Hg (range -5 to 36) and had not changed from that measured immediately after angioplasty (p = 0.64). Compared with preangioplasty values, the systolic pressure in the ascending aorta had improved substantially at follow-up (116.0 +/- 3.2 versus 143.9 +/- 3.1 mm Hg, p less than 0.001). On the basis of follow-up data, two groups of children were identified: Group 1 consisted of nine children with a good result, defined as a residual gradient less than 20 mm Hg and no aneurysm; Group 2 consisted of five children with a poor result, four with a residual gradient greater than 20 mm Hg (range 25 to 36) and one with an aneurysm at the dilation site. There was no statistical difference between the two groups in age at angioplasty, balloon size, ratio of balloon to isthmus diameters, follow-up duration, heart rate or cardiac output. However, of the four children with a residual gradient greater than 20 mm Hg, two were the youngest in the study, and in two the aorta was inadvertently dilated with a balloon 4 to 5 mm smaller than the isthmus diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Quinidine syncope in children.

Quinidine syncope and factors associated with it are well known among adult patients treated for cardiac arrhythmias. To define factors that may influence the occurrence of syncope in children taking quinidine, the clinical, anatomic, electrocardiographic, roentgenographic and pharmacologic data were compared in six patients with syncope (Group A) and 22 patients without syncope (Group B). There was a significant (chi-square = 10.2, p = 0.001) relation between heart disease and quinidine syncope: all six Group A (syncopal) patients had heart disease whereas 15 of the 22 Group B (non-syncopal) patients had no structural heart disease. In contrast, no significant difference was noted between Group A and Group B patients in mean age (11.4 versus 11.4 years), mean quinidine serum concentration (2.9 versus 2.3 micrograms/ml), mean corrected QT interval before quinidine (0.43 versus 0.40 second) or mean corrected QT interval during quinidine therapy (0.46 versus 0.46 second) or between those taking digitalis and those not. Two of the six Group A (syncopal) patients died during therapy, one 6 days after initiating therapy and one suddenly at home 6 months after beginning quinidine. Another two of the six Group A patients exhibited hypokalemia (both 2.9 mEq/liter) at the time of syncope, 2 weeks and 6 months, respectively, after initiation of quinidine therapy; both survived. Syncope occurred within 8 days of initiation of quinidine therapy in three of the six patients. Sustained ventricular tachycardia was observed during quinidine associated arrhythmia in three of six patients with syncope; nonsustained ventricular tachycardia or complex ventricular ectopic activity while on this therapy was observed before syncope in the other three patients in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Common pulmonary vein atresia: the role of extracorporeal membrane oxygenation.

Common pulmonary vein atresia is a rare form of cyanotic congenital heart disease in which the pulmonary veins join to form a blind confluence that does not communicate with the heart or the major systemic veins. Twenty-one cases have been reported since the lesion was first described in 1962; only two patients with this lesion have survived. Over a 4-year period, common pulmonary vein atresia was diagnosed in five newborns referred to the San Diego Regional Extracorporeal Membrane Oxygenation Program. All five improved dramatically as a result of venoarterial bypass. Congenital heart disease was diagnosed at autopsy in the initial case and by cardiac ultrasound and/or catheterization in the others. Surgical repair was attempted in three neonates; all three required continued extracorporeal membrane oxygenation support postoperatively because of pulmonary hypertension and severe pulmonary parenchymal disease. One infant died of respiratory insufficiency at 3 months of age. The other two survived and were discharged from the hospital. The diagnostic and therapeutic dilemmas posed by this lesion and the life-saving potential for extracorporeal membrane oxygenation in this rapidly fatal cardiac anomaly are the bases of this report.

Neurodevelopmental outcomes in children with Fontan repair of functional single ventricle.

OBJECTIVES: The purpose of this study was to assess the neurodevelopmental status of children after Fontan repair of functional single ventricle and to examine the relationship between cognitive function and selected patient characteristics. STUDY DESIGN: Neurodevelopmental tests including the Stanford-Binet Intelligence (IQ) scale and the Developmental Test of Visual Motor Integration (VMI) were administered to 32 children (26 months to 16 years of age) with complex single ventricle. The mean and distribution of IQ and VMI scores were compared with population norms. The relationship between test scores and patient characteristics was examined utilizing analysis of variance and correlational methods. RESULTS: The majority of children had intellectual function within the normal range (mean, 97.5 +/- 12.1). Below average VMI scores were found in 21.4% of children. There were no significant correlations between intellectual function or visual motor integration ability and preoperative oxygen saturation or age at Fontan. Children who had deep hypothermic circulatory arrest during a prior Norwood procedure tended to have a lower IQ score. CONCLUSIONS: Intellectual development in children with Fontan repair of complex heart defects is essentially within the normal range. Visual motor integration deficits may be more prevalent in these children. In our population, the duration and degree of preoperative hypoxemia had no apparent effect on cognitive function.

Atrial overdrive pacing for conversion of atrial flutter in children.

Twenty-three successive patients with 27 different episodes of sustained atrial flutter were treated with atrial pacing for conversion of the tachyarrhythmia; 15 patients with 16 episodes of atrial flutter underwent intracardiac right atrial pacing and eight patients with 11 episodes of atrial flutter were treated with transesophageal atrial pacing. Ten of sixteen episodes (63%) and eight of 11 episodes (73%) were successfully converted using intracardiac and transesophageal techniques, respectively. Mean flutter cycle length for all 27 episodes was 219 ms (mean heart rate 274 beats per minute); successful pacing conversion cycle length (n = 15) was 72% of the flutter cycle length. Hemodynamic, electrophysiologic, and roentgenographic data were not predictive of conversion by either technique. Induction of localized atrial fibrillation or failure to meet critical pacing criteria may explain pacing failures. Based on this experience, a trial of transesophageal atrial pacing for acute conversion of any episode of atrial flutter in children prior to direct current cardioversion is recommended.

Chronic verapamil therapy in pediatric and young adult patients with hypertrophic cardiomyopathy.

Oral verapamil, 5.2 +/- 1.1 mg/kg/day (range 2.8 to 7), was administered to 13 pediatric patients with hypertrophic cardiomyopathy for 13 +/- 6 months (range 2 to 20). The patients had significant symptomatic improvement on verapamil therapy. Murmur intensity diminished in 6 patients during therapy and left ventricular (LV) electromotive forces on the electrocardiogram diminished in 4, increased in 5 and did not change in 4. Exercise endurance increased from 8.4 +/- 3.9 to 10.9 +/- 2.8 minutes (p less than 0.01). Seven patients had ST-segment depression (0.38 +/- 0.28 mV) before verapamil therapy, which improved after verapamil therapy in 5 (0.24 +/- 0.17 mV, p less than 0.02). Of 4 patients with exercise-induced ventricular ectopic activity, 3 had diminution or abolishment of ectopy following verapamil. By echocardiography, the patients had an increase in LV end-diastolic dimension from 3.4 +/- 0.7 to 3.9 +/- 0.8 cm (p less than 0.01), with no significant change in shortening fraction (46.1 +/- 8.0% vs 44.6 +/- 8.0%). When adjusted for body size and age there was a significant decrease in LV septal thickness (from 106 +/- 70 to 45 +/- 52% of predicted normal values, p less than 0.05) and LV posterior wall thickness (from 40 +/- 45 to 5 +/- 26% of predicted normal values p = 0.05) after verapamil. Isovolumic relaxation time decreased from 69 +/- 26 to 42 +/- 19 ms after verapamil (p less than 0.01). Systolic anterior motion of the anterior mitral leaflet disappeared in 5 of 8 patients and midsystolic closure of the aortic valve was no longer present in 4 of 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of left ventricular ejection fraction in pediatric patients using the nuclear stethoscope.

Left ventricular (LV) ejection fraction (EF) was measured in 25 patients, aged 2 weeks to 20 years (mean 8.6 years), using a portable nonimaging scintillation stethoscope. Technically satisfactory studies were obtained in 23 patients. LVEF was validated by cineangiography in 19 patients and by standard gated blood pool scintigraphy in 4. EF measured by the nuclear stethoscope correlated well with values obtained by cineangiography or scintigraphy (r = 0.869, p less than 0.001) over a wide range of EF values (18 to 79%). In children younger than 5 years (n = 11), the correlation (r = 0.728, p less than 0.02) was less satisfactory than in those older than 5 years (r = 0.926; p less than 0.001). Although modifications in the instrument and further clinical trials with the stethoscope are needed before the device becomes clinically useful to pediatric cardiologists, our data indicate that the nuclear stethoscope can provide reliable assessment of LVEF in pediatric patients.

Effects of verapamil on left ventricular diastolic filling in children with hypertrophic cardiomyopathy.

The effects of oral verapamil on resting left ventricular (LV) diastolic filling were examined in 10 children and adolescents with hypertrophic cardiomyopathy. Measurements of diastolic filling were made from gated technetium-99m radionuclide angiograms with postbeat rejection of data outside a 5% RR-interval window. LV time-activity curves were generated and the rapid-filling phase fit with a 3 degrees polynomial to calculate the peak filling rate and the time from end-systole to the point of peak filling. All patients had a radionuclide angiogram performed before and after 0.25 to 3 years of oral verapamil therapy. Verapamil did not change the LV ejection fraction but increased the peak filling rate (3.24 +/- 0.15 to 4.62 +/- 1.05 end-diastolic volume/s,p less than 0.01) and reduced the time to peak filling (217 +/- 57 to 168 +/- 63 ms, p less than 0.01). An increase in exercise endurance as measured by exercise treadmill test and subjective symptomatic improvement were also seen after verapamil therapy. Thus, in children with hypertrophic cardiomyopathy, symptomatic improvement and LV diastolic filling parameters improved with long-term oral verapamil.

Correction of truncus arteriosus in the neonate using a nonvalved conduit.

Successful correction of truncus arteriosus in two neonates, both 4 days of age, is described. Nonvalved polytetrafluoroethylene (PTFE) conduits were used because of the small size of the infants. Both recovered from operation with no signs right ventricular failure and remain well. Catheterization data on one patient show satisfactory hemodynamics 1 year after operation with only residual branch pulmonary artery stenosis. These data suggest that a conduit valve is not essential in the correction of truncus arteriosus even in the neonate.

The bidirectional cavopulmonary shunt.

The bidirectional cavopulmonary shunt improves systemic arterial oxygen saturation without increasing ventricular work or pulmonary vascular resistance. Since 1983, 17 patients have undergone a cavopulmonary shunt procedure (five primary operations, 12 secondary operations). Diagnoses were single ventricle complex (n = 4), hypoplastic right heart syndrome (n = 10), and hypoplastic left ventricle (n = 3). Age at primary operation ranged from 3 1/2 to 30 months (median 6 months). Weight ranged from 3.5 to 9.7 kg. Age at secondary operation ranged from 10 months to 14 years (median 15 months). Seven cavopulmonary shunt operations were performed without cardiopulmonary bypass (six via thoracotomy and one via sternotomy) and 10, with cardiopulmonary bypass. All patients in the bypass group had additional procedures: takedown of modified Blalock-Taussig shunt, seven patients; revision of right ventricular outflow tract, four patients; reconstruction of pulmonary arteries, four patients; tricuspid valvuloplasty, one patient; and Damus procedure, one patient. There was one (1/17) operative death (Damus procedure). One patient required early revision. Follow-up ranges from 1 to 53 months (median 23 months). Twelve of 16 had a good to excellent late result, with a rise in mean arterial oxygen saturation from 69% to 83%. Three patients died late (4 to 53 months) (pulmonary vascular disease, pulmonary arteriovenous malformations, and pneumonia, one patient each). There was one late failure (converted to Glenn shunt). The cavopulmonary shunt is an excellent palliative procedure when right atrium-pulmonary artery connection (modified Fontan) must be deferred because of age, weight, or anatomic considerations. Five patients have undergone right atrium-pulmonary artery connection later. In addition, at the time of the modified Fontan operation, the cavopulmonary shunt approach may optimize the anatomic connection (eight additional patients).

Factors influencing perioperative morbidity during palliation of the univentricular heart.

BACKGROUND: The modified Fontan procedure has become the treatment of choice for patients born with a univentricular heart. Although the operative mortality has steadily decreased in recent years, the hospital stay is still prolonged in many patients due to fluid retention and pleural effusions. METHODS: We retrospectively analyzed subsets of patients undergoing the bidirectional cavopulmonary shunt (BDCPS) and modified Fontan procedure in an attempt to define factors influencing operative mortality and morbidity. RESULTS: Multivariate analysis of 64 patients undergoing BDCPS revealed that age 6 months or less, concomitant operation, mean pulmonary pressure of 15 mm Hg or less, and mean pulmonary artery ratio of 1.8:1 or less were not statistically significant indicators of risk. Abnormal pulmonary artery architecture was a significant predictor of early and late death (p < or = 0.01). Retrospective analysis of 71 patients undergoing the modified Fontan procedure revealed no significant relationship between duration of pleural effusions and age at operation, preoperative oxygen saturation, pulmonary artery pressure, ventricular end-diastolic pressure, or prior BDCPS: Patients with important aortopulmonary collateral vessels defined by angiography had prolonged pleural drainage. Selective use of the total extracardiac conduit and the fenestrated Fontan resulted in low overall mortality with no statistical differences between subsets of patients undergoing different modifications of the Fontan procedure. CONCLUSIONS: These data indicate that the operative risk for BDCPS or modified Fontan procedure is quite low if a procedure appropriate for the patient is selected. Abnormal pulmonary artery architecture is an important risk factor for death after the BDCPS: Aortopulmonary collateral vessels are associated with fluid retention and pleural effusions after a modified Fontan procedure. Important aortopulmonary collateral vessels should be occluded before or during the modified Fontan procedure.

The Damus-Fontan procedure.

The Damus-Kaye-Stansel operation is a useful technique for the treatment of complex cyanotic congenital heart disease when there is obstruction between the systemic ventricle and the aorta. Modifications of the technique include transection of the aorta and the pulmonary artery, anastomosis of the contiguous aortic and pulmonary walls, and connection of the distal aorta to the perimeter of the new bivalved proximal great artery. In addition, the bidirectional cavopulmonary shunt technique can be used with or without the Fontan procedure. Six patients underwent a Damus-Fontan operation, and all survived. Two patients underwent the Damus-cavopulmonary shunt (hemi-Fontan) procedure, and 1 survived. The postoperative status of the 7 survivors is good to excellent. Follow-up ranges from 2 months to 7 1/2 years.

Late reoperation for systemic atrioventricular valve regurgitation after repair of congenital heart defects.

Since 1979, 17 infants and children have undergone reoperation for systemic atrioventricular (AV) valve regurgitation 6 weeks to 7 years after repair of congenital heart defects. Prior operations were repair of incomplete or complete AV canal (14 patients), Mustard repair of complex transposition of the great arteries including ventricular septal defect closure (2 patients), or first-stage operation for hypoplastic left heart (1 patient). Age ranged from 6 months to 11 years. In 12 of the 17 patients (10, AV canal; 1, transposition; 1, hypoplastic left heart), valve reconstruction was possible. Operative techniques included a combination of septal cleft approximation, leaflet resection, commissural annuloplasty, or ring annuloplasty. There were no operative deaths, and there were no reoperations in the repair group. The condition of these patients has improved. Follow-up ranges from 1 month to 9 years (mean follow-up, 4.1 years). Five of the 17 patients (4, AV canal; 1, transposition) underwent valve replacement. There were no operative deaths. Follow-up ranges from 3 to 8 years. Three patients later underwent re-replacement of the prosthetic valve; there was 1 late death. The condition of all 4 survivors is improved. Substantial AV valve regurgitation can occur months or years after repair of congenital heart defects. A combination of reconstructive techniques may be useful in preserving native valve function and avoiding systemic AV valve replacement.

Cardiovascular disease in Down syndrome.

This article focuses on the clinical evaluation of children with cardiovascular diseases associated with Down syndrome. Recent advances in diagnosis and management are discussed and the medical or surgical approach to the patient with severe cardiovascular malformations is presented.

High-risk angioplasty. Coarctation of the aorta after Norwood Stage 1.

This report describes 2 patients with hypoplastic left heart syndrome who developed severe coarctations of the aorta after Norwood Stage I procedures and subsequently survived recurrent ventricular fibrillation during successful percutaneous angioplasty. Although ventricular fibrillation has not been associated with hypoplastic left heart syndrome, postoperative Norwood Stage I, or angioplasty of isolated coarctations of the aorta, we believe that the complex physiology of our patients created conditions that precipitated ventricular tachycardia and ventricular fibrillation. We strongly recommend that follow-up of infants with hypoplastic left heart syndrome after Norwood Stage I operations be meticulous; that even mild coarctation be treated aggressively, to avoid progression to high-risk situations; and that interventionalists be prepared to manage malignant ventricular dysrhythmias whenever postoperative Norwood Stage I patients undergo percutaneous angioplasty for coarctation of the aorta.

Steroid therapy and cardiac function in Duchenne muscular dystrophy.

Duchenne muscular dystrophy leads to progressive deterioration in skeletal and cardiac muscle function. Steroids prolong ambulation and improve respiratory muscle strength. The authors hypothesized that steroid treatment would stabilize cardiac muscle function. Echocardiograms performed from 1997 to 2004 for 111 subjects 21 years of age or younger with Duchenne muscular dystrophy were restrospectively reviewed. The medical record was reviewed for steroid treatment. Untreated and steroids-treated subjects did not differ in age, height, weight, body mass index, systolic and diastolic blood pressure, or left ventricular mass. The shortening fraction was lower in the untreated group. Of those treated, 29 received prednisone and 19 received deflazacort. There was no difference in the shortening fraction between the two treated subgroups. Treated subjects not receiving steroids still had a normal shortening fraction, which was no different from the shortening fraction of those still receiving treatment. As compared with the treated subjects, the untreated subjects 10 years of age or younger were 4.4 times more likely to have a shortening fraction less than< 28% (p = 0.03), and the untreated subjects older than 10 years were 15.2 times more likely to have a shortening fraction less than< 28% (p < 0.01). This retrospective study suggests that the progressive decline in cardiac function of patients with Duchenne muscular dystrophy can be altered by steroid treatment. The effect appears to be sustained beyond the duration of treatment and independent of steroid type.

Management of absent pulmonary valve syndrome with patent ductus arteriosus.

The etiology of absent pulmonary valve syndrome is unknown. Several theories have been advanced to explain the associated findings of a rudimentary pulmonary valve, ventricular septal defect, aneurysmal pulmonary arteries, and absence of the ductus arteriosus. The patient presented here would contradict these currently held theories. A review of the literature follows the case report.