Mycobacterium abscessus in cystic fibrosis lung transplant recipients: report of 2 cases and risk for recurrence.

Mycobacterium abscessus is increasingly recognized as an important pathogen in some individuals with advancing lung disease related to cystic fibrosis (CF). Because of its resistance to antimicrobial agents and virulence, its presence in the lungs of potential lung transplant recipients can be problematic. We present 2 cases of individuals with CF in whom M. abscessus was present in the preoperative sputum cultures. The organism manifested different degrees of invasiveness in the 2 cases after transplantation with different outcomes, suggesting an approach to future candidates for lung transplantation that may be of clinical significance to their physicians and surgeons.

Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1. This study sought to analyse KCNJ2 in patients with familial ATS and to determine the functional characteristics of the mutated gene. METHODS AND RESULTS: We screened a family with inherited ATS for the mutation in KCNJ2, using direct DNA sequencing. A missense mutation (T75R) of Kir2.1, located in the highly conserved cytoplasmic N-terminal domain, was identified in three affected members of this family. Using the Xenopus oocyte expression system and whole cell voltage clamp analyses, we found that the T75R mutant was non-functional and possessed a strong dominant negative effect when co-expressed with the same amount of wild type Kir2.1. Transgenic (Tg) mice expressing the mutated form of Kir2.1 in the heart had prolonged QTc intervals compared with mice expressing the wild type protein. Ventricular tachyarrhythmias were observed in 5 of 14 T75R-Tg mice compared with 1 of 7 Wt-Tg and none of 6 non-transgenic littermates. In three of five T75R-Tg mice with ventricular tachycardia, their ECG disclosed bidirectional tachycardia as in our proband. CONCLUSIONS: The in vitro studies revealed that the T75R mutant of Kir2.1 had a strong dominant negative effect in the Xenopus oocyte expression system. It still preserved the ability to co-assemble and traffic to the cell membrane in mammalian cells. For in vivo studies, the T75R-Tg mice had bidirectional ventricular tachycardia after induction and longer QT intervals.

Sudden death and cardiovascular collapse in children with restrictive cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is rare in children, and the prognosis is poor. In the present study, we evaluated all pediatric patients with RCM who were at our institution during a 31-year period to determine the clinical outcome and cause of death. Those who sustained sudden, unanticipated cardiac arrests were evaluated for risk factors that are predictive of sudden death. METHODS AND RESULTS: Eighteen consecutive patients were reviewed. Presentation, clinical course, laboratory data, and histopathological evidence of ischemia were compared between patients with and without sudden death events. The results demonstrated that patients who were at risk for sudden death were girls with chest pain, syncope, or both at presentation and without congestive heart failure. Although not statistically significant for sudden death, Holter monitor evidence of ischemia predicted death within months. Histopathological evidence of acute or chronic ischemia was found in the majority of patients, with acute ischemia more common among those who sustained sudden death events. CONCLUSIONS: All children with RCM are at risk for ischemia-related complications and death, and some are at risk of sudden death. In the present study, patients at risk of sudden death appeared well and had no evidence of ongoing heart failure but often had signs or symptoms of ischemia characterized by chest pain, syncope, or both. ECGs and Holter monitors may be useful screening tools. The use of beta-blockade, the placement of an implantable cardioverter-defibrillator, and preferential status 1A or B listing for cardiac transplantation are proposed for pediatric patients with RCM and evidence of ongoing ischemia.

Persistence of ventricular arrhythmia after resolution of occult myocarditis in children and young adults.

OBJECTIVES: We sought to examine whether resolution of occult myocarditis in children with associated ventricular arrhythmia correlated with the presence of arrhythmia at late follow-up. BACKGROUND: Complex ventricular arrhythmias have been documented in children with myocarditis. Therapy is aimed at controlling the arrhythmia and any associated ventricular dysfunction. However, no reported studies have documented whether resolution of myocarditis in children is associated with resolution of the associated arrhythmias. METHODS: We performed a retrospective analysis of 12 patients (mean age 12 years) with myocarditis. Ambulatory electrocardiographic (Holter) monitors were reviewed for ventricular arrhythmias at presentation and follow-up. Patients were assigned to Group I if they received corticosteroids in addition to any antiarrhythmic agents and to Group II if they did not receive steroids. Follow-up endomyocardial biopsy was performed in some patients, and results were analyzed in relation to the presence of arrhythmias at follow-up. RESULTS: Eleven patients had ventricular tachycardia, and one had multiform couplets. Corticosteroids were given to seven patients (Group I). Follow-up biopsy was performed in seven patients (six received steroids), with resolution of inflammation in all; four of the seven still had ventricular arrhythmias but with improved control. Of the five patients without follow-up biopsy, three had persistent arrhythmia. Absence of inflammation at follow-up biopsy did not correlate with loss of ventricular arrhythmias, and there was no difference between Group I and II patients with respect to resolution of arrhythmia (Fisher exact test, p = 0.70, power 11%). CONCLUSIONS: Complex ventricular arrhythmias persist after apparent resolution of occult myocarditis in children. Although these arrhythmias are easier to control after such resolution, the patients may require long-term antiarrhythmic therapy.

Incessant ventricular tachycardia in infants: myocardial hamartomas and surgical cure.

Infants with incessant ventricular tachycardia (occurring greater than 10% of the day) have generally been described in pathologic studies. This report describes 21 patients with incessant ventricular tachycardia present greater than 90% of the day and night; the age at diagnosis ranged from birth to 30 months (mean 10.5 months). The most common clinical presentation was cardiac arrest (11 patients, in 5 after digitalis for presumed supraventricular tachycardia); another 6 patients had congestive heart failure and 4 were asymptomatic. Three patients had coexisting Wolff-Parkinson-White syndrome. The rate of incessant ventricular tachycardia ranged from 167 to 440 (mean 260 beats/min) and the QRS duration from 0.06 to 0.11 second. The most common electrocardiographic (ECG) pattern (10 of 21) was right bundle branch block with left axis deviation, but other right and left bundle branch block patterns were observed. Conventional and investigational antiarrhythmic agents (nine patients received amiodarone) failed to eliminate incessant ventricular tachycardia in all. Electrophysiologic studies localized incessant ventricular tachycardia to the left ventricle in 17 (to the apex in 2, the free wall in 9 and the septum in 6) and to the right ventricular septum in 4. No structural abnormalities were found on the echocardiogram or angiocardiogram. All 21 patients had surgery at an age of 3.5 to 31 months (mean 16). In 15 a tumor was found: 13 myocardial hamartomas (9 discrete, 4 diffuse throughout both ventricles) and 2 rhabdomyomas (1 multiple). Myocarditis was found in one patient (the oldest). In four, only myocardial fibrosis was found; results of one biopsy were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

The detection of viral genomes by polymerase chain reaction in the myocardium of pediatric patients with advanced HIV disease.

OBJECTIVES: The aim of this study was to investigate the frequency of viral nucleic acid detection in the myocardium of human immunodeficiency virus (HIV)-infected children to determine whether an association exists with the development of heart disease. BACKGROUND: As improved medical interventions increase the life expectancy of HIV-infected patients, increased incidences of myocarditis and dilated cardiomyopathy (DCM) are becoming more apparent, even in patients without clinical symptoms. METHODS: Myocardial samples were obtained from the postmortem hearts of 32 HIV-infected children and from 32 age-matched controls consisting of patients with structural congenital heart disease and no myocardial inflammation and no cardiac or systemic viral infection. The hearts were examined histologically and analyzed for the presence of viral sequences by polymerase chain reaction (PCR) or reverse transcription-PCR. RESULTS: Myocarditis was detected histologically in 11 of the 32 HIV-infected patients, and borderline myocarditis was diagnosed in another 13 cases. Infiltrates were confined to the epicardium in two additional hearts. Virus sequences were detected by PCR in 11 of these 26 cases (42.3%); adenovirus in 6, CMV in 3 and both adenovirus and CMV in 2. Two cases without infiltrates were also positive for adenovirus: one had congestive heart failure (CHF) and the other adenoviral pneumonia. No other viruses were detected by PCR, including HIV proviral DNA. All control samples were negative for all viruses tested. CONCLUSIONS: These data suggest that the presence of viral nucleic acid in the myocardium is common in HIV-infected children, and may relate to the development of myocarditis, DCM or CHF and may contribute to the rapid progression of HIV disease.

Late ventricular arrhythmia and sudden death following direct-current catheter ablation of the atrioventricular junction.

Early reports of direct-current catheter ablation (DCCA) of the atrioventricular (AV) junction for resistant AV tachycardias documented efficacy of DCCA with little morbidity. Nine patients underwent DCCA at our institution 4 to 9 years ago: 3 patients had DCCA in the coronary sinus for permanent junctional reciprocating tachycardia, 2 patients had His ablation, 2 had coronary sinus and His ablation for permanent junctional reciprocating tachycardia, and 2 had DCCA for congenital tachycardia, and 2 had DCCA for congenital junctional ectopic tachycardia. Shocks (total 1 to 5) ranged from 12.5 to 400 J. Five patients had pacemaker implant at the time of DCCA. During follow-up, 3 patients developed clinical ventricular tachycardia: all 3 had DCCA of the His bundle. One asymptomatic patient with ventricular tachycardia, who had DCCA of the bundle of His, died suddenly 6 years later with ventricular fibrillation. Autopsy revealed 2 ventricular scars: 1 extending from the AV junction and 1 in the outflow tract. No patient with DCCA limited to the coronary sinus developed ventricular tachycardia. DCCA of the His bundle can result in late ventricular arrhythmias, possibly a result of extension of the DCCA lesion into the ventricle. These late findings should be considered in evaluating the safety and efficacy and follow-up for patients undergoing radiofrequency ablation.

Premature closure of the foramen ovale associated with aortic stenosis, left ventricular dilation with thrombus, and early mortality.

Premature foramen ovale (FO) closure has been postulated as a cause of hypoplastic left heart syndrome. We suggest that premature FO closure is also associated with left ventricular (LV) dilation and LV thrombus formation, and that FO closure in patients with aortic stenosis and LV dilation is a secondary event that occurs later in gestation than that seen with the hypoplastic left heart.

Coronary arteries in transposition of the great arteries.

The topic of coronary arteries in transposition of the great arteries (TGA) is complex and confusing despite having been the subject of several recently published reports. One hundred thirty-three autopsy specimens of uncomplicated TGA were studied, with special attention to methodologic issues in anatomic description and classification. Uncomplicated TGA was defined as congenital anomaly involving origin of the aorta from the right ventricle and of the pulmonary artery from the left ventricle. Three types of transposition were recognized ("anterior aorta," "side-by-side," and "posterior aorta") depending on the aortopulmonary relations, which were intrinsically defined by the relation of the valvular orifices of the great arteries with respect to the atrioventricular orifices. The frequency of distribution of individual coronary patterns differs substantially in the first 2 types of TGA. As in normal hearts, coronary arteries in TGA tend to originate from the facing sinuses (adjacent to the pulmonary valve); in TGA, however, variations in further distal anatomy are much more frequent. It is suggested that individual coronary patterns be described in terms of number of ostia, exact ostial location within or outside the aortic sinuses, and proximal course and distribution. The use of strict, simplified classifications of coronary patterns is discouraging because of the relevance of each individual anatomic parameter to clinical aims. Because of the aortopulmonary switch repair for TGA, this study emphasizes the surgical implications of the different coronary features.

Usefulness of routine surveillance biopsies in children more than one year after orthotopic heart transplantation.

This retrospective study examines the usefulness of routine biopsies following the first year after transplant. This study found that routine biopsies detect few episodes of rejection in the first year after transplant and were less useful than nonroutine biopsies.

Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error.

Among 38 hearts from autopsies in which lymphocytic myocarditis contributed to death, 10 endomyocardial specimens from the apical septal aspect of each ventricle (760 specimens) and 6 slices of ventricular myocardium (228 slices) were evaluated for myocarditis by the Dallas criteria. For each case, the number of positive biopsy samples correlated well with the mean lymphocyte counts in biopsy tissues (P less than 0.0001) and the mean number of inflammatory foci per square centimeter in myocardial slices (P less than 0.001). Right ventricular biopsy specimens, however, were positive in only 63% of the 38 cases and 17% of the 380 specimens. Similarly, left ventricular biopsy tissues were positive in only 55% of the cases and 20% of the specimens. Sampling error was somewhat more prevalent among the 11 cases with isolated myocarditis than in the 27 with myocarditis and other illnesses. Even when 10 biopsy specimens per ventricle were evaluated, the frequency of false-negative results was 45% for the left and 37% for the right ventricle. Although myocarditis was noted in 68% of the 38 septal slices, it involved the subendocardium of the right ventricle (from which biopsy specimens are usually obtained) in only 24%. Because of the mild and focal nature of the inflammatory infiltrates and involvement of regions inaccessible to the bioptome, sampling error contributes appreciably to false-negative results in endomyocardial biopsy tissue from patients with myocarditis. Thus, when myocarditis is evaluated by biopsy alone, only positive findings are considered diagnostic.

Long-term follow-up of arrhythmias in pediatric orthotopic heart transplant recipients: incidence and correlation with rejection.

BACKGROUND: Arrhythmias in adult orthotopic heart transplant (OHT) recipients are common and have been used as predictors of rejection. Because of the paucity of information in pediatric OHT recipients, the purpose of this study was to determine the incidence and correlation of arrhythmias with rejection or with coronary artery disease (CAD) in children. METHODS: We retrospectively reviewed the records, electrocardiograms (ECGs), and 24-hour ambulatory ECGs of patients who underwent OHT from January 1984 to December 1999. We excluded arrhythmias occurring in the first 2 weeks after OHT. RESULTS: Sixty-nine patients underwent OHT, received triple-immunosuppression therapy, were discharged home, and have been followed for a mean of 4.7 years (0.3-13 years). Each patient had an average of 10 ECGs and three 24-hour ECGs. Twenty-six patients had 33 arrhythmias: sinus bradycardia (n = 9), atrial tachycardia (n = 9), ventricular tachycardia (n = 3), and Wenckebach periodicity (n = 6). Sinus bradycardia was treated with theophylline in 8 patients, and 2 required pacemakers. Atrial tachycardias (atrial flutter in 4 patients and atrial ectopic tachycardia in 5) were treated with digoxin, propranolol, or procainamide. Ventricular tachycardia was treated with mexiletine, lidocaine, and amiodarone. There were 65 episodes of rejection, 20 of which were moderate/severe (> or =3B). Only Wenckebach was associated with the presence of either rejection or CAD (p < 0.05). CONCLUSIONS: We noted clinically significant arrhythmias in 38% of the pediatric OHT recipients. Sinus bradycardia, atrial tachyarrhythmias, and ventricular tachycardia occurred with the same frequency. Only new-onset Wenckebach periodicity was noted in the presence of either CAD or rejection. No arrhythmia was of negative predictive value for rejection or CAD. From this data, we suggest that new-onset Wenckebach prompt evaluation for rejection or CAD.

Update on pediatric heart transplantation. Long-term complications.

Despite evolution to "higher-order" immunosuppressive agents that better control cell-mediated allograft rejection and, therefore, short- and intermediate-term survival, allograft vasculopathy and PTLD remain factors that limit extended graft survival. While improved basic science "bench" techniques have enabled investigation of their pathogenesis at the subcellular and molecular levels, each scientific advance leads the way to the next horizon of complex questions. Only through a more complete understanding of the etiology and pathophysiology of these processes will we be able to design strategies to combat these complications.

Severe supravalvar aortic stenosis in familial homozygous hypercholesterolemia.

Familial homozygous hypercholesterolemia is a rare disease with diverse clinical presentations. Patients often present with cutaneous xanthomas, particularly in the Achilles' tendon. They may have significant cardiovascular involvement, including premature atherosclerotic coronary artery disease and valvar and supravalvar aortic stenosis. Standard therapy includes diet modulation, pharmacotherapy, and lipid apheresis. Rarely, patients require surgical intervention for coronary artery bypass grafting and/or relief of the aortic stenosis. We present the case of a patient with severe progressive supravalvar aortic stenosis that ultimately required surgical resection despite aggressive medical therapy.

Pulmonary venous stenosis as an associated manifestation of left-sided obstructive lesions in an infant with partial atrioventricular canal defect.

Patients with partial atrioventricular canal defect (PAVC) who present with congestive heart failure within the first year of life are usually found to have associated left-sided obstructive lesions. We present a case of a child with PAVC who subsequently developed progressive pulmonary venous stenosis as a manifestation of her disease.

Pathologic features of myocardial hamartomas causing childhood tachyarrhythmias.

We have observed in 11 infants, aged 2 years or less, a distinct clinicopathologic lesion responsible for tachyarrhythmias that were fatal in 96% (25/26) of previously reported cases. Nine of the 11 patients, who underwent electrophysiologic mapping and surgical excision of the lesion, have survived, with follow-up periods ranging from 1 month to 6 years. The morphologic findings in these 11 patients and in the 26 cases cited in the literature are reviewed. Pathogenic considerations have included viral-induced lesion, cardiomyopathy, neoplasm, and developmental disorder of Purkinje cells. We believe this lesion to be a myocardial hamartoma. Supportive evidence includes prevalence in infants, tumorlike growth pattern without mitotic figures, and association of other developmental abnormalities. Through electrophysiologic mapping, this myocardial hamartoma is potentially accessible to surgical excision and long-term cure.

Developmental differences in canine cardiac surgical scars.

Sudden death and arrhythmias are significant problems in patients with various types of repaired congenital heart disease and have been associated with increasing time after and older age at surgery. Arrhythmias have been mapped clinically to areas of surgical scars in some patients, leading to the hypothesis that scar morphology changes with age. This study compared the morphology and histology of right ventriculotomy scars or right atriotomy scars in newborn (2 to 3 weeks), young (5 to 8 weeks), and older (> or = 6 months) dogs at postmortem examination 5 months postoperatively. Atriotomy lengths increased significantly compared with the initial incision in the newborn (6.0 mm +/- 0.1 to 15.2 mm +/- 5.8; p < 0.05) and young (6.8 mm +/- 0.9 to 19.6 mm +/- 4.8; p < 0.01) groups but were similar in the older group (35.5 mm +/- 11.7 to 27.0 mm +/- 2.5). Ventriculotomy scars grew 110 +/- 69% in the newborn group and 126 +/- 71% in the young group but shrank 31 +/- 6% of the original length in the older group (young vs older; p < 0.05). This increase in the atriotomy and ventriculotomy scars in the young group and the decrease in the older group resulted in scars of similar length; only those scars in the newborn group remained significantly shorter than scars in the older group (p < 0.05). Atriotomy and ventriculotomy scars in the older group had more bone or cartilage (p < 0.05) but less dystrophic calcification (p < 0.05) than those scars in the younger groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Subclavian steal syndrome in anomalous connection of the left subclavian artery to the pulmonary artery in d-transposition of the great arteries.

Several reports have documented the occurrence of an isolated left subclavian artery in association with both tetralogy of Fallot and double-outlet right ventricle. In certain cases a congenital subclavian or pulmonary artery steal syndrome exists in which the left subclavian artery is connected to the main pulmonary artery via a ductus arteriosus. We describe a subclavian steal syndrome secondary to anomalous origin of the left subclavian artery from the pulmonary artery in d-transposition of the great arteries in a patient with Spondylocostal dysostosis (SCD). Cardiac anomalies are rare in SCD and this constellation of findings have not previously been described.

Rett syndrome: analysis of deaths in the British survey.

The mortality rate in Rett syndrome is 1.2% per annum, 48% of deaths occurring in debilitated people, 13% from natural causes, 13% with prior severe seizures and 26% sudden and unexpected. Respiratory dysrhythmias were usually present. Neuropathology confirmed reductions in cortical dendrites and in one case immaturity of cardiac conducting tissues.