Clinical presentations of mitochondrial cardiomyopathies.

UNLABELLED: To determine the clinical manifestations and interfamilial variability of patients diagnosed with a mitochondrial cardiomyopathy, we reviewed the charts of 14 patients with cardiomyopathy out of 59 patients with mitochondrial disorders who attended the mitochondrial disease clinic at Wolfson Medical Center from 1996 to 2001. All patients underwent a metabolic evaluation including blood lactate, pyruvate, carnitine, and amino acids and urine organic acids. Respiratory chain enzymes were assessed in 10 patients. The mitochondrial DNA (mtDNA) was assessed for mutations. The age at presentation ranged between 6 months and 24 years. Six of the patients died, 5 from heart failure. The cardiomyopathy was hypertrophic in 10 and dilated in 4. Conduction and rhythm abnormalities were present in 6. Eleven patients had family members with mitochondrial disorders. All the patients had additional involvement of one or more systems. Seven patients exhibited a deficiency of a respiratory chain enzyme in the muscle. The MELAS mtDNA point mutation (3243) was found in one patient. Blood lactic acid levels were increased in 5. Brain MRI abnormalities were observed in 4. CONCLUSIONS: Mitochondrial dysfunction frequently affects the heart and may cause both hypertrophic and dilated cardiomyopathy. The cardiomyopathy is usually a part of a multisystem involvement and may rarely be isolated. The course may be stable for many years, but rapid deterioration may occur. Understanding the biochemical and genetic features of these diseases will enable us to comprehend the clinical heterogeneity of these disorders.

Inferior vena cava diameter: a useful method for estimation of fluid status in children on haemodialysis.

BACKGROUND: An accurate assessment of fluid status in haemodialysis patients presents a significant challenge especially in growing children. Clinical parameters of hydration are not always reliable, and invasive methods such as measurement of central venous pressure cannot be used routinely. We evaluated the usefulness of inferior vena cava diameter (IVCD) measured by echocardiography in the estimation of hydration in children on haemodialysis. METHODS: Fifteen haemodialysis patients (mean age 14 years) were evaluated. Clinical assessment included patients' symptoms, weight, blood pressure, heart rate, presence of oedema and vascular congestion, before and after dialysis session. Dry weight was assessed based on the above parameters. Fifty-two echocardiographic studies immediately prior and 30-60 min following dialysis were performed. The anteroposterior IVCD was measured 1.5 cm below the diaphragm in the hepatic segment in supine position during normal inspiration and expiration. IVCD was expressed per body surface area. RESULTS: Following haemodialysis mean IVCD (average of expiration and inspiration) decreased from 1.12+/-0.38 to 0.75+/-0.26 cm/m(2) (P<0.0001). Changes in IVCD were significantly correlated with alterations in body weight following dialysis (P<0.0001). The collapse index (per cent of change in IVCD in expiration vs inspiration) increased significantly after dialysis (P=0.035). IVCD clearly reflected alterations in fluid status. It did not vary significantly with changes in dry weight in a given patient. CONCLUSIONS: Our findings support the applicability of VCD measurement in the estimation of hydration status in paediatric haemodialysis patients. The combination of clinical parameters and measurement of IVCD may enable more accurate evaluation of hydration of children on haemodialysis.

Transcatheter closure of secundum atrial septal defects with the amplatzer septal occluder: early experience.

BACKGROUND: Secundum atrial septal defect is a common congenital heart defect that causes right heart volume overload and produces symptoms usually after the third decade of life. Treatment until the last few years has been open heart surgery. OBJECTIVES: To review our early experience with transcatheter closure of ASD2 using the Amplatzer septal occluder. METHODS: Between November 1999 and February 2000, 20 children and young adults with a median age of 9.1 years (4.2-35.1 years) were referred for transcatheter closure of ASD2. Diagnosis was established by transthoracic echocardiography. Implantation was performed under general anesthesia through the femoral vein with the guidance of transesophageal echocardiography and fluoroscopy. Femoral arterial puncture was performed for blood pressure monitoring during the procedure. The device size chosen was similar to the balloon-stretched diameter of the ASD2. RESULTS: Implantation was completed successfully in 18 patients. Two patients were referred for elective surgery: one had an unsuitable anatomy for transcatheter closure by TEE in the catheterization laboratory and the device could not be implanted properly, the other patient had a large multiperforated septal aneurysm that was retrieved. Mean ASD2 diameter by TTE and TEE was similar (13.9 +/- 3 mm, 13.4 +/- 3.5 mm) and mean stretched diameter was 18.3 +/- 4.3 mm. Mean Qp:Qs (pulmonary flow:systemic flow) was 2.2 +/- 0.6. Mean fluoroscopy time for the procedure was 14.8 +/- 4.8 minutes. The patients were discharged the day after the procedure. Four patients had a tiny leak immediately post-procedure, and none had a leak at one month follow-up. The only complication was a small pseudoaneurysm of the femoral artery in one patient, that resolved spontaneously. CONCLUSIONS: Transcatheter closure of ASD2 with the Amplatzer septal occluder is a safe and effective alternative to surgical closure. Long-term outcome has to be evaluated.

The risk for congenital heart defects in offspring of individuals with congenital heart defects.

BACKGROUND: Congenital heart defects (CHDs) occur in approximately 1% of all live births. Although most CHDs are of unknown etiology, a family history of CHDs is a known risk factor, and offspring of individuals with CHDs are at a higher risk of having CHDs. The aim of this study was to investigate the relative risk for CHDs to offspring of individuals with CHDs. METHODS: The prevalence rates of CHDs in offspring of 203 individuals with CHDs and 282 individuals without CHDs were investigated. The study participants completed a questionnaire that included information on medical and reproductive history, lifestyle indicators, and family history of CHDs and other congenital malformations. The prevalence rates of CHDs in offspring were calculated. RESULTS: The prevalence of CHDs was 3.1% (18/575) in offspring of individuals with CHDs and 1.3% (8/589) in offspring of individuals without CHDs. The adjusted odds ratio for CHDs to offspring of parents with CHDs was 1.73 (95% confidence interval [95% CI] 0.89-2.44, p=0.02). The estimated relative risk for offspring to females with CHD was higher than for males [2.3 (95% CI 1.1-4.7, p=0.03) versus 1.31 (95% CI 0.48-4.30, p=0.66), respectively]. There was no suggestion of association between CHDs and maternal smoking, alcohol consumption, and use of medication during pregnancy. CONCLUSIONS: Offspring of parents with CHDs are at a higher risk for CHDs compared with the general population. Couples where one member is affected with CHD should receive pre-conceptional or pre-natal genetic counseling and should be informed about the magnitude of the potential risk of CHDs to the offspring.

Anomalous origin of the left coronary artery from the pulmonary artery: diagnosis and postoperative follow up.

BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital malformation that presents a diagnostic challenge to the pediatrician and pediatric cardiologist. Although surgical repair is always indicated, the optimal technique has yet to be determined. OBJECTIVES: To review our experience with the diagnosis of children with ALCAPA and to assess short to midterm surgical results. METHODS: Between 1992 and 1998, 13 infants and children (2 months to 15 years) were treated for ALCAPA at our medical center. Eight were diagnosed during the first year of life; all were symptomatic and had severe dysfunction of the left ventricle. The five patients diagnosed at an older age had normal myocardial function. Diagnosis was established by echocardiography alone in seven patients; six required catheterization (one infant and all older patients). Surgery was performed in 12 patients to establish dual coronary artery system: 7 underwent the Takeuchi procedure and 5 had re-implantation of the anomalous left coronary artery. RESULTS: One infant died shortly after diagnosis before surgical repair was attempted, and one died postoperatively. Four patients required additional surgery: three for late complications of the Takeuchi procedure and one valve replacement for mitral insufficiency. Recent evaluation revealed good global left ventricle function in all patients except for one, who is still within the recovery phase and shows gradual improvement. However, most patients who presented with severe myocardial dysfunction upon diagnosis still display abnormal features such as echo-dense papillary muscles or evidence of small akinetic segments. In this group, early repair was associated with faster myocardial recovery. CONCLUSIONS: The diagnosis of ALCAPA remains a clinical challenge to the pediatrician and cardiologist. Diagnosis can be established echocardiographically, and early diagnosis and treatment may lead to faster myocardial recovery. The preferred surgical method appears to be re-implantation of the ALCA. The chance for good recovery of global ventricular function is high even in the sickest patients, nonetheless abnormal myocardial features can be identified even years after surgery.

The Ross operation: initial Israeli experience.

BACKGROUND: The need for aortic valve replacement in children and young adults poses a special problem to cardiologists and surgeons. Replacing the sick aortic valve with the patient's pulmonary valve as described by Ross has proven to be a good option in this special age group. OBJECTIVE: To review our initial experience in order to assess the short-term results. METHODS: From January 1996 to June 1999, 40 patients (age 8 months to 41 years) underwent aortic valve replacement with pulmonary autograft. Indications for surgery were congenital aortic valve disease in 30 patients, bacterial endocarditis in 5, rheumatic fever in 3, and complex left ventricular outflow tract obstruction in 3. Trans-esophageal echocardiography was performed preoperatively and post-bypass in all patients, and transthoracic echocardiography was done prior to discharge and on follow-up. RESULTS: There was no preoperative or late mortality. All patients remain in functional class I (New York Heart Association) and are free of complications and medication. None showed progression of autograft insufficiency or LVOT obstruction. Homograft insufficiency in the pulmonary position has progressed from mild to moderate in one patient, and three developed mild homograft stenosis. CONCLUSIONS: The Ross procedure can be performed with good results in the young population and is considered an elegant surgical alternative to prosthetic values and homografts.

Acute complications in the current era of therapeutic cardiac catheterization for congenital heart disease.

The acute complications of therapeutic cardiac catheterization for congenital heart disease as performed currently in a small unit were reviewed. In recent years, there has been a significant increase in the number of lesions thought amenable to catheter therapy. Only a few reports, however, have addressed the overall incidence of acute complications of therapeutic cardiac catheterization, all representing the experience of centres performing moderate-to-large numbers of procedures. A retrospective review was performed of 425 therapeutic catheter procedures performed at our institution between May 1993 and November 1997. Acute complications were retrieved from the database. This included all adverse events that were clinically recognized at the time of or within 2 weeks after the procedure and which, to the best of the authors' clinical judgement, were related to the catheterization and not part of the natural history of the child's illness. All patients were observed overnight following the procedure, and stayed in hospital if a complication developed. There were 49 acute complications (11.5%), of which 43 (10.1%) were deemed minor and 6 (1.4%) were considered major. The rate was low in patients with valvar pulmonary stenosis, including three neonates (3/45, 6.7%), for those undergoing angioplasty of native co-arctation (1/15, 6.7%) and pulmonary arteries (2/27, 7.4%); and for coil embolization of systemic to pulmonary collateral arteries (1/16, 6.3%). The rate was high in patients with valvar aortic stenosis, including 12 neonates (9/37, 24.3%), and for angioplasty of re-coarctation (4/23, 21.7%). There were more overall complications in neonates (25.6%) than in older patients (10.1%) (p < 0.01). Two patients died (0.5%), but no patient required emergency surgical intervention. In spite of the introduction of many new therapeutic modalities with greater intrinsic risk, and the fact that patients with more complex lesions and who are more acutely ill are being treated, the overall rate of complications remains relatively low. This probably reflects improvements in pericatheterization medical management, in selection of patients, in procedural techniques, and in the experience of operators.

Interventional catheterization decreases plasma levels of atrial natriuretic peptide (ANP) in children with congenital heart defects.

Atrial natriuretic peptide (ANP) is one of the cardiac peptides implicated in volume and sodium homeostasis. We investigated the effect of interventional catheterization on plasma levels of ANP, aldosterone, and cortisol in 28 children with various congenital heart defects (CHD). Patients were divided by age into two groups: group A--infants and children over 3 months of age (n = 22), and group B--newborns (n = 6). These were compared to age-matched control groups. In group A, interventions included pulmonic valvotomy (n = 8), aortic valvotomy (n = 4), balloon angioplasty of native coarctation of the aorta (n = 3), balloon dilatation of the mitral valve (n = 1), and Rashkind double umbrella closure of patent ductus arteriosus (n = 6). Group B interventions included pulmonic valvotomy (n = 3), aortic valvotomy (n = 1), and balloon atrial septosomy (n = 2). In group A, mean ANP levels were markedly higher than in age-matched controls (125.2+/-15.8 vs. 24.6+/-4.6 pg/ml) (P <0.0001), and decreased immediately after intervention (75.6+/-11.4 pg/ml, P <0.02), and more markedly on follow-up (42.9+/-5.0 pg/ml, P < 0.0001). In group B (newborns), mean basal plasma levels were high before and after intervention and were not different from age-matched controls (243+/-42.1 vs. 220.8+/-16.2 pg/ml). There was a significant decrease on follow-up measurement (62.1+/-12.7 pg/ml, P < 0.005). In both groups, plasma cortisol levels increased significantly immediately following catheterization (P < 0.02), and normalized on follow-up. Basal aldosterone levels were normal in group A and high in Group B (9.9+/-3.8 vs. 167.6+/-16.9 ng/dl) (P < 0.001). It is suggested that plasma ANP levels are increased in children with CHD, without overt heart failure, and decrease significantly following successful intervention. In newborns with CHD, the physiological high ANP levels obscure the effect of the CHD.

[Transcatheter closure of atrial septal defect].

Isolated secundum atrial septal defect is one of the most common congenital heart defects. Surgical closure is the treatment of choice but is associated with a chest scar, some morbidity and a relatively long recovery and the use of cardiopulmonary bypass. Transcatheter closure of secundum atrial septal defect is therefore an attractive approach. 3 children, aged 5-10 years, underwent successful transcatheter closure of moderate to large central atrial septal defects with the Cardioseal device. The procedures were performed under x-ray and transesophageal echocardiographic guidance. Our initial experience, and that of others, indicates that transcatheter occlusion of secundum atrial septal defects is safe and effective and can be an appropriate alternative in approximately 60% of patients.

Trends of childhood infective endocarditis in Israel with emphasis on children under 2 years of Age.

This study retrospectively analyzed the characteristics of infective endocarditis (IE) in children in light of recent advances in pediatric cardiology. We evaluated 25 consecutive patients with IE from 1980 to 1991 at a tertiary Children's Medical Center in Israel. The incidence of IE increased significantly over the second half of the study period, owing mainly to an increase in the number of patients less than 2 years old. Concomitantly, the causative microorganisms changed considerably, with a decrease in viridans streptococci, an increase in staphylococci and other uncommon causes of IE, and increased antibiotic resistance. Children under the age of 2 years, previously considered uncommon IE patients, accounted for 47% of the IE cases during the second half of the study period. The infection often (78%) appeared in children with complex congenital heart diseases, commonly after early palliative or definitive cardiac surgery. Infants who underwent systemic-to-pulmonary shunting, especially with implantation of foreign materials, were at highest risks. IE was more often hospital-acquired (56% versus 6%) and acute (56% versus 44%) in the younger children than in the older ones and often lacked the typical clinical presentation of the disease. In addition, uncommon causative organisms were noted more frequently (67% versus 13%; p = 0.009) in the younger group. The study shows a significant increase in IE in infants and young children with distinctive underlying conditions, clinical presentation, and microbiologic findings, all of which should be considered currently for the diagnosis and treatment of pediatric IE.

Midterm clinical impact versus procedural success of balloon angioplasty for pulmonary artery stenosis.

The objective of this study was to determine the procedural success rate of balloon angioplasty for branch pulmonary artery stenosis in terms of its clinical impact on the subsequent management of these patients. Most previous studies of balloon angioplasty have concentrated on the initial success rate (50-60%), complications (6-10%), recurrence rate ( approximately 15%), and technical issues. A favorable clinical impact was noted in only 35% of patients. Over a 3-year period (March 1990 to March 1993), 32 patients (17 boys, 15 girls) underwent 34 balloon angioplasty procedures. Their mean age at dilation was 7.6 +/- 4.3 years (range 1.1-19.0 years). Postoperative tetralogy of Fallot and tetralogy of Fallot with pulmonary atresia were the most frequent cardiac lesions (44%). The procedures were "technically" successful in 56% (19 of 34) of balloon dilations on the basis of at least two of the following criteria: an increase of >50% of the predilation diameter; an increase of >20% in the relative flow to the affected lung by radioisotope study; or a decrease in the systolic right ventricular/aortic pressure ratio from 85-100% to <60%. Twelve percent of the patients had transient complications (two deep vein thromboses, one unilateral pulmonary edema, and one pneumothorax). In 17 of 19 (89%) of the patients there was a favorable clinical impact on their subsequent care as based on one of the following criteria: resolution of the stenosis and avoidance of surgical intervention (n = 14); optimization of future surgical procedure (n = 3); reduction in right ventricular pressure to <60% of aortic pressure (n = 13). Five patients who had unsuccessful balloon angioplasty and one with initially successful balloon angioplasty later underwent endovascular stent placement, which also favorably influenced their clinical status. The success rate of balloon angioplasty for branch pulmonary artery stenosis, when measured by strict procedural criteria, is accompanied by a favorable clinical impact in more than 50% of patients. Hence this procedure should be the initial therapeutic modality in this setting despite the relatively high transient complication rate. The use of endovascular stents probably increases the favorable clinical impact.

Radiofrequency catheter ablation of ectopic atrial tachycardia.

Ectopic atrial tachycardia (EAT) is an uncommon type of supraventricular tachycardia. It is usually chronic, incessant and resistant to pharmacologic therapy. Radiofrequency catheter ablation, which has become one of the treatments of choice for the more common types of supraventricular tachycardia, has recently also been shown to be effective in EAT. Radiofrequency catheter ablation was attempted in three patients with incessant EAT. Two of the patients, aged 7 and 13 years, had signs of left ventricular dysfunction, and the EAT originated in the left atrium. The remaining patient, aged 72 years, had a right EAT with normal left ventricular function. Radiofrequency ablation was guided by endocardial atrial mapping to locate the site of earliest atrial activation. Ablation was successful in all three patients, with complete cure of the tachycardia for a follow-up period of 12 to 19 months. Radiofrequency catheter ablation of EAT is highly successful and should be considered as one of the treatments of choice for this arrhythmia.

Non-traditional risk factors for atherosclerosis in high risk children.

Non-traditional risk factors for atherosclerosis were examined in children whose fathers suffered from myocardial infarction up to age 48. Factors examined were hyperinsulinemia, insulin resistance, lipoprotein(a) [Lp(a)], fibrinogen, cardiovascular hyperreactivity, and autonomic nervous system dysfunction. Hyperinsulinemia was present in five cases (9%) and hypoinsulinemia in two. Insulin output following glucose load was significantly higher in obese children compared with controls. There was an increase in Lp(a) alone in 14 cases (24%) and with low density lipoprotein in 6 cases. Increased fibrinogen and positive correlation with insulin abnormality was present in 29% (76% females) (P >0.02). Cardiac hyperreactivity (increased systolic blood pressure) was present in 9% and increased blood pressure and pulse rate in 17%. Holter monitoring pattern was sympathetic in 39% and parasympathetic in 47% of cases. Thus a number of non-traditional risk factors were found to be higher than normal in a relatively large number of children at high risk for atherosclerosis, with 25 children having more than three risk factors.

Late death from aneurysm rupture following balloon angioplasty for branch pulmonary artery stenosis.

We report on a child with Williams syndrome who died from aneurysm rupture 2 weeks following balloon angioplasty for branch pulmonary artery stenosis.

Percutaneous closure of small patent ductus arteriosus: comparison of Rashkind double-umbrella device and occluding spring coils.

We compared our current practice of closing small patent ductus arteriosus (PDA) with coils with our previous experience of using double-umbrellas. Twelve patients underwent percutaneous closure of a small PDA with a coil. Selection criteria were a minimal diameter of < or = 2.5 mm and angiographic type A or E. The 12 most recent, non-consecutive patients who had undergone double-umbrella device closure of a PDA and would presently be considered suitable candidates for spring coil occlusion were retrospectively reviewed. The two groups were compared with regard to complications and immediate and midterm results. Eleven of the 12 attempted PDA occlusions using spring coils were successful. The mean follow-up period was 5.8 +/- 4.6 months. Color-Doppler echocardiograms have shown no residual leaks, no turbulence in the descending aorta, and no left pulmonary artery stenosis. All 12 attempted double-umbrella device placements were successful. The mean follow-up period was 16.2 +/- 5.8 months. Color-Doppler echocardiograms have shown trivial residual leaks in four patients and mild turbulent flow in the left pulmonary artery in one patient. There was no significant difference between the two groups in demographic and hemodynamic data. Although the mean follow-up time was significantly longer in the patients who underwent double-umbrella closure, there was significantly more color-Doppler echocardiographic evidence of residual flow (P < 0.03). Small PDA closure with coils is effective, resulting in less residual leaks compared with the double-umbrella device.

Surgical management of ventricular septal defect with aortic valve prolapse: clinical considerations and results.

Aortic valve prolapse is found in over 5% of children with ventricular septal defect (VSD). Although this association occurs mostly with doubly committed subarterial VSDs, in this study the predominant type of VSD was perimembranous. In order to determine the need and timing for surgery and whether the anatomical features of septal defect may influence clinical management and outcome in this lesion, we reviewed our experience with 28 consecutive patients, operated on for VSD with prolapsed aortic valve cusp, with or without aortic regurgitation. Twenty-two patients had a perimembranous VSD and six had doubly committed VSD. Aortic regurgitation was trivial or absent in nine patients, mild in ten and moderate to severe in nine. Associated cardiac anomalies were present in 18 patients, all having perimembranous VSD, and included right ventricular outflow tract (RVOT) obstruction (n = 6), discrete subaortic membrane (n = 4) or both (n = 8). None of these patients had more than moderate aortic regurgitation. The patients underwent surgical closure of the septal defect between the ages of 1.5 and 34 years of age (median = 7). Sixteen patients having mild or trivial aortic regurgitation underwent closure of the VSD only, and 12 patients underwent VSD closure with aortic valvuloplasty. Valvuloplasty was required more often in doubly committed VSDs (66%) and in the perimembranous type without associated anomalies (100%), and significantly less often in the presence of RVOT obstruction, subaortic membrane or both (22%). At follow-up (up to 5 years, mean 18 months), the grade of aortic regurgitation was unchanged in 11 and decreased in 5 patients undergoing closure of the VSD only.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful pregnancy in a woman with cyanotic congenital heart disease after a palliative pulmonary-systemic shunt. A case report.

A 20-year-old woman with cyanotic congenital heart disease composed of corrected transposition of the great vessels, severe pulmonic stenosis, atresia of the left pulmonary artery and a large ventricular septal defect, had a successful pregnancy following a pulmonary-systemic shunt (Blalock-Taussig). The hemoglobin decreased from 21 to 16 g/dL following the operation. The antepartum course was complicated by intrauterine growth retardation and pregnancy-induced hypertension. A normal fetal nonstress test and biophysical profile permitted continuation of the pregnancy until 38 weeks' gestation, with delivery of a healthy infant.

A prospective evaluation of pediatric patients with syncope.

Fifty-eight children with syncope were evaluated prospectively to determine the characteristics of syncope in the pediatric age group and the yield of various diagnostic tests. The age at first syncope ranged from 0.5 to 15 years. Twenty-five children presented after a single episode and 33 after multiple episodes. Ten had a history of breath-holding spells. Nineteen had a family history of syncope. A diagnosis was established in 53 patients (91%): vasodepressor (31), cardioinhibitory (13), tussive (3), hyperventilation (2), and mixed syncope (4). In five patients (9%), the cause remained unknown. The diagnosis was established from the history in 45 cases, by a positive oculocardiac reflex in 11, and by the head-up tilt test in four. We conclude that the cause of most cases of pediatric syncope is vasodepressor or cardioinhibitory and can be diagnosed by good history-taking. Costly evaluations are rarely necessary.

Coronary risk factors in children of parents with premature coronary artery disease.

In order to assess the value of family history of premature coronary artery disease as a criterion for coronary risk factor screening, a group of 53 children with such a family history was selected. We determined various coronary risk factors in these children in comparison to 33 controls. Statistically significant differences were observed in apoprotein concentrations but not in concentrations of lipids, lipoproteins or glucose, or in blood pressure or body mass index. The ratio between apoprotein B and apoprotein AI was the best discriminator between the two groups. The predictive value of family history is more reliable for detecting abnormal apoprotein ratio than for detection of hypercholesterolemia. We conclude that if abnormal apoprotein levels during childhood are found to be a valued predictor of premature coronary artery disease, then family history of premature coronary artery disease can be used to select children for determination and assessment of their coronary risk.