The Prevalence of and Predisposing Factors for Late Atrial Arrhythmias after Transcatheter Closure of Secundum Atrial Septal Defects in Children.

BACKGROUND: A 24 h Holter study in children after transcatheter secundum ASD (ASD II) closure was conducted to detect the prevalence of defects and/or device-related late atrial arrhythmias (LAAs). ASD II closure with an Amplatzer septal occluder (ASO) is an established procedure. Little is known about LAAs after device implantation. METHODS: The eligible participants were children who had undergone ASO implantation, with a follow-up of ≥5 years, as well as one pre- and at least one post-procedural Holter ECG. RESULTS: In total, 161 patients (mean age: 6.2 ± 4.3 years), with a mean follow-up of 12.9 ± 3.1 years (range 5-19), were included. A median of four Holter ECGs per patient were available. LAAs occurred before intervention in four patients (2.5%), and it was peri-interventional in four patients (2.5%), sustained in three patients (1.9%), and developed in three patients (1.9%). In patients with pre- and peri-interventional LAAs, the Qp/Qs ratio was higher (6.4 ± 3.9 vs. non-AA: 2.0 ± 1.1 (p = 0.002)) and the IAS/ASO ratio was lower (1.18 ± 0.27 vs. non-AA: 1.7 ± 0.4 (p < 0.001)). The patients with LAAs differed from those without LAAs in their Qp/Qs (6.8 ± 3.5 vs. 2.0 ± 1.3; p < 0.0001) and IAS/ASO ratios (1.14 ± 0.19 vs. 1.73 ± 0.45; p < 0.001). The patients with LAAs had a Qp/Qs ratio ≥2.94:1, and those who developed LAAs had an IAS/ASO ratio <1.15. CONCLUSIONS: LAAs occurred in 1.9% of patients and were sustained in another 1.9% of patients but persisted in those with large shunt defects and large occluders in relation to the atrial septal length. The predisposing factors for LAAs after ASD closure were a high Qp/Qs ratio, pre-existing atrial arrhythmias, and a low IAS/ASO ratio.

Impact of Pectus Excavatum on Cardiopulmonary Function.

BACKGROUND: Pectus excavatum is classified using the Haller Index (HI) or the Correction Index. However, no correlation between the HI and CI and cardiopulmonary impairment has been described in detail. METHODS: This prospective cohort study included 99 otherwise healthy patients with pectus excavatum who underwent cardiopulmonary exercise testing and magnetic resonance imaging at inspiration and expiration to correlate cardiopulmonary function with the grade of thoracic dysmorphia. RESULTS: Probands with an HI exceeding 3.25 had first an increase in heart rate at anaerobic threshold (from 148.0 ± 16.0 beats/min to 155.9 ± 15.0 beats/min, p = 0.036), with an HI of more than 3.6 a reduction in oxygen pulse at anaerobic threshold (from 10.7 ± 2.6 mL/beat to 9.3 ± 2.9 mL/beat, p = 0.017), with an HI exceeding 3.8 a reduction of maximum oxygen pulse (from 13.9 ± 3.4 mL/beat to 11.9 ± 3.7 mL/beat, p = 0.010), and with an HI of exceeding 4.0 a decline in maximum oxygen uptake (from 43.7 ± 6.5 mL · kg-1 · min-1 to 40.4 ± 7.4 mL · kg-1 · min-1, p = 0.025). The CI of more 27% reflects cardiopulmonary changes earlier than the corresponding HI exceeding 3.25 (p = 0.01 for maximum oxygen pulse; p = 0.017 for oxygen pulse at anaerobic threshold; p = 0.015 for heart rate at anaerobic threshold). CONCLUSIONS: The inspiratory HI and CI reflect the effect of pectus excavatum on cardiopulmonary function. The cardiopulmonary system reacts first with an increase in heart rate at anaerobic threshold, followed by a decrease in stroke volume at anaerobic threshold and maximum stroke volume. Increased severity of the deformity then leads to a decrease in cardiac output.

Management of Life-Threatening Tracheal Stenosis and Tracheomalacia in Patients with Mucopolysaccharidoses.

Several different lysosomal storage diseases, mainly mucopolysaccharidosis (MPS) type I, II, and VI, are complicated by severe obstruction of the upper airways, tracheobronchial malacia, and/or stenosis of the lower airways. Although enzyme replacement therapies (ERTs) are available, the impact of these on tracheobronchial alterations has not been reported. By extending the life expectancy of MPS patients with ERTs, airway problems may become more prevalent at advanced ages. These airway abnormalities can result in severe, potentially fatal, difficulties during anesthetic procedures. Usually, upper airway obstruction is treated by tracheostomy. However, with lower airway malacia and/or stenosis, there are no procedures available to date to address these difficulties. We report the first cases using a new technique of tracheal stenting in patients with MPS type VI (Maroteaux-Lamy syndrome) and type II (Hunter syndrome) who had almost complete tracheal occlusion and total airway collapse. An updated literature review is also reported.

Heart and Cardiovascular Involvement in Patients with Mucopolysaccharidosis Type IVA (Morquio-A Syndrome).

BACKGROUND: Mucopolysaccharidosis (MPS) IVA is a rare lysosomal storage disorder with multiple skeletal and non-skeletal abnormalities requiring multiple surgical interventions. It is well known that patients with MPS IVA suffer from tachycardia, but cardiac and hemodynamic alterations have not been reported to date. We investigated the cardiovascular and hemodynamic alterations in patients with MPS IVA and developed a possible patho-mechanism for cardiovascular deterioration during anesthesia. MATERIAL AND METHODS: In this observational study, serial cardiac examinations were performed in 54 patients with MPS IVA who were followed at the Children's Hospital of the Mainz Medical University (Mainz, Germany) between 1991 and 2014 (follow-up 1-24 years; median 5.8 years). Results were compared with data from a large central European cohort of more than 2000 healthy infants and children. RESULTS: None of the patients had arterial hypertension, but 4% had evidence of increased pulmonary artery pressure. Patients developed aortic root extension up to 6.9 standard deviations above normal. Left-sided valve leaflet thickening occurred in 26 patients (five with valve disease). Patients had lower left ventricular dimensions (z: -1.02±0.1), lower stroke volumes (z: -2.3±0.17), lower left ventricular mass (z: -1.5±0.21), but higher wall thickness (z: +0.8±0.16), and higher work index (z: +2.5±0.2) compared to healthy control subjects. Cardiac output was preserved by an increase in heart rate of 21%. Sixty % of patients showed impaired diastolic filling; heart rate (99.0±1.8 vs. 92.0±2.1 bpm), age (18.0±1.8 vs. 14.2±1 years), and cardiothoracic ratio (61.6±3.6% vs. 55±4.2%) of these patients were higher compared to those with normal filling. CONCLUSIONS: The results of this study suggest an age-progressive disproportion of the intra-thoracic organs of patients with MPS IVA, which is accompanied by aortic root extension and thickened left ventricles, with reduced stroke volumes, impaired diastolic filling patterns, and increased heart rates.

Transcatheter Closure of Atrial Septal Defects using the GORE(®) Septal Occluder in Children Less Than 10 kg of Body Weight.

The GORE(®) Septal Occluder (GSO) is a well-evaluated device for interventional ASD closure with closure rates comparable to the Amplatzer(®) Septal Occluder (ASO), but there are no published reports of its use in small children weighing less than 10 kg. This may be due to the necessity of a large-sized introducing sheath of at least 10 Fr and therefore the assumed risk of complications in vascular access. The GSO is an alternative option for interventional ASD closure in children weighing less than 10 kg. Fourteen infants and children with a median body weight 8900 g (range 6350-9650 g) underwent successful ASD closure using the GSO. The closure was performed under fluoroscopic and transthoracic echocardiographic guidance. Postprocedure, the vessels passed by the occluder and delivery catheter were examined by duplex sonography. The median ASD diameter was 11 mm (5-17 mm), and the median GSO size was 22.5 mm (15-30 mm), whereas the median ASO left disc size that would have been recommended was 25 mm (17-31 mm). All ASDs were successfully closed. During a median follow-up of 1.57 years (range 0.5-4.2), no complications like erosion, embolization, arrhythmias, or vascular injuries occurred. Although using a 10-Fr introducer sheath, no vascular complications were detected. Our data suggest that the small usable size as well as the soft and flexible design of the device allows successful use of the GSO in young children.

Mucopolysaccharidosis VI: cardiac involvement and the impact of enzyme replacement therapy.

OBJECTIVE: To describe cardiac abnormalities in patients with mucopolysaccharidosis (MPS) VI and to evaluate the impact of enzyme replacement therapy (ERT) on cardiac structure and function. METHODS: Data from electrocardiographic and echocardiographic evaluations were retrospectively collected from patients with MPS VI who are followed up at the Children's Hospital of Mainz. RESULTS: The study included 44 (16 male and 28 female) patients. At baseline, valvular regurgitation (mainly aortic and mitral) and left ventricular (LV) volume overload were present in over half of patients. Other common cardiac manifestations were sinus tachycardia, LV hypertrophy, concentric LV remodelling, and pulmonary hypertension. One patient had left atrial dilation and one had congestive heart failure. Interventricular septal wall thickness and LV posterior wall thickness were above normal in most patients. Twenty five patients had a pre-ERT and at least one follow-up visit after ERT start. Mean follow-up after ERT start was 5.6 (SD 2.3) years. Despite the late onset (mean age 14.6 years) of treatment, ERT appeared to improve or arrest the progression of LV remodelling and LV hypertrophy and suspend the progression of cardiac valve disease. CONCLUSIONS: MPS VI is associated with an array of cardiac manifestations. ERT appears to have some impact on cardiac structure and function when started late in life, but may have better long-term results when started during early infancy.

Onset and progression of the Anderson-Fabry disease related cardiomyopathy.

BACKGROUND: Cardiac involvement is responsible for substantial morbidity and mortality in Anderson-Fabry disease (AFD). We sought to document its onset and progression in a population of male and female AFD patients. METHODS: We performed a cross sectional echocardiographic study of a cohort of 177 male and female AFD patients with subsequent longitudinal follow-up of 76 patients (38 males and 38 females; mean follow-up 4.5 years) who did not receive enzyme replacement therapy. RESULTS: In this population, aged 3.3 to 70.8 years, a strong correlation between age and left ventricular mass indexed (LVMi, g/m(2.7)) was found in both males and females (P<0.0001 for both). At the initial examination 48.6% of the male patients and 36.4% of the female patients were classified as having left ventricular hypertrophy (LVH). The cumulative prevalence of LVH peaked at age 40 years in males and 60 years in females. In patients with longitudinal follow-up, LVMi increased by 4.07+/-1.03 g/m(2.7) per year in males and by 2.31+/-0.81 g/m(2.7) in females (P<0.01, Wilcoxon rank sum). In patients with LVH at baseline, the median progression rate was 5.52 g/m(2.7) per year in males and by 1.80 g/m(2.7) in females (P=0.12). CONCLUSION: AFD is associated with high prevalence of LVH in both genders. However, the age of onset is delayed in females and progression rate slower.

Cardiac manifestations of Anderson-Fabry disease in children and adolescents.

AIM: Fabry disease (Fabry) is a rare X-linked disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A. The progressive accumulation of the major substrate, globotriaosylceramide, leads to renal dysfunction and hypertrophic cardiomyopathy, which are reported to become apparent in the third decade. This study was performed to determine if signs of cardiac manifestations of Fabry are seen in younger Fabry patients. METHODS: Twenty children and adolescents of 75th percentile of that in healthy controls. After a mean 26-month follow-up, 12 out of 14 patients (85.7%) showed a mean increase of 7.5+/-3.2 g/m(2.7) in LVM/h(2.7). Heart rate variability (HRV) analyses revealed that male, but not female, Fabry patients had significantly reduced HRV, reflecting a reduction in parasympathetic stimulation of the heart (p<0.05). CONCLUSION: Cardiac involvement in children with Fabry is frequent and may progress even at young age.

Cardiac manifestations of Anderson-Fabry disease in heterozygous females.

OBJECTIVES: We sought to define the prevalence of cardiac involvement in female patients with Anderson-Fabry disease (AFD). BACKGROUND: Anderson-Fabry disease is a rare inborn X-linked lysosomal storage disorder. Globotriaosylceramide (Gb(3)), the major substrate of the deficient alpha-galactosidase A enzyme, accumulates progressively in vulnerable cells, including the cardiovascular system. It has been believed that heterozygous females have less cardiac involvement than hemizygous males with AFD. METHODS: We performed two-dimensional echocardiographic examinations of female patients heterozygous for AFD. RESULTS: Since 1997, a total of 55 female patients (mean age, 39.6 years; range, 6.1 to 70.8 years) with proven AFD have been investigated prospectively at our hospital. Of these, 13 (23.6%) had normal left ventricular (LV) geometry and LV mass (LVM). Seven patients (12.7%) had concentric remodeling, 29 patients (52.7%) concentric LV hypertrophy (LVH), and 6 patients (10.9%) eccentric LVH (2 with subaortic pressure gradients). There was a strong correlation between age and the severity of LVH (r(2) = 0.905; p < 0.0001), and all patients older than 45 years had LVH. With increasing LVM, there was a significant age-independent decrease in systolic and diastolic LV function. Mild thickening of the aortic valve leaflets was present in 25.5% of patients, with the same percentage demonstrating mild thickening of the mitral valve leaflets. Mild mitral valve prolapse was documented in 10.9% of patients. CONCLUSIONS: Cardiac involvement, with LVH and structural valve abnormalities, is very common and worsens with age in females who are heterozygous for AFD, and they should therefore be considered candidates for enzyme replacement therapy.

The heart in Anderson Fabry disease.

Anderson Fabry disease is a life threatening, X-linked inborn metabolic defect of the lysosomal enzyme áalpha-galactosidase A. The deficiency of alpha-galactosidase A leads to a progressive accumulation of globotriaosylceramide (Gb(3)), the major glycosphingolipid substrate of the enzyme, within vulnerable cells, tissues, and organs, including the cardiovascular system. Cardiac involvement is frequent and patients with cardiac affection develop progressive hypertrophic infiltrative cardiomyopathy, valvular abnormalities, arrhythmias, and conduction abnormalities and may develop coronary heart disease. Hemizygous male patients have no detectable alpha-galactosidase A activity, while affected heterozygous females may have normal level of alpha-galactosidase A activity. Death occurs in male patients at 45 to 50 years, about 15 to 20 years earlier than in female patients due to a vicious circle from chronic renal insufficiency, arterial hypertension, atherosclerotic lesions and cerebrovascular hemorrhage or insults, and cardiomyopathy. Cardiac involvement in hetero- and hemizygotes will be discussed as well as the influence of enzyme replacement of alpha-galactosidase A.