High resolution sonography in the evaluation of the peripheral nervous system in polyneuropathy--a review of the literature.

Clinical, laboratory and electrodiagnostic studies are the mainstay in the diagnosis of polyneuropathy. An accurate etiological diagnosis is of paramount importance to provide the appropriate treatment, prognosis and genetic counselling. High resolution sonography of the peripheral nervous system allows nerves to be readily visualized and to assess their morphology. Ultrasonography has brought pathophysiological insights and substantially added to diagnostic accuracy and treatment decisions amongst mononeuropathies. In this study the literature on its clinical application in polyneuropathy is reviewed. Several polyneuropathies have been studied by means of ultrasound: Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, multifocal motor neuropathy, paraneoplastic polyneuropathy, leprosy and diabetic neuropathy. The most prominent reported pathological changes were nerve enlargement, increased hypo-echogenicity and increased intraneural vascularization. Sonography revealed intriguingly different patterns of nerve enlargement between inflammatory neuropathies and axonal and inherited polyneuropathies. However, many studies concerned case reports or case series and showed methodological shortcomings. Further prospective studies with standardized protocols for nerve sonography and clinical and electrodiagnostic testing are needed to determine the role of nerve sonography in inherited and acquired polyneuropathies.

The diagnostic value of provocative clinical tests in ulnar neuropathy at the elbow is marginal.

BACKGROUND: Provocative clinical tests are often performed in the diagnosis of ulnar neuropathy at the elbow (UNE) although the evidence for the usefulness of these tests is limited. The aim of this study was to determine the diagnostic value of provocative clinical tests in the diagnosis of UNE in a relevant spectrum of patients and controls. METHODS: A prospective cohort study was performed in consecutive patients clinically suspected of having UNE. All patients underwent a neurological examination and four commonly used provocative clinical tests (Tinel's test, flexion compression test, palpating for local ulnar nerve tenderness and nerve thickening). Subsequently, in all patients a reference standard test comprising electrophysiological studies and neurosonography was independently assessed. RESULTS: 192 eligible patients completed the study protocol. UNE was diagnosed in 137 and an alternative diagnosis was made in 55 patients. The sensitivity, specificity, and positive and negative predictive values were as follows: Tinel's test 62%, 53%, 77% and 30%; flexion compression test 61%, 40%, 72% and 29%; palpating for nerve thickening 28%, 87%, 84% and 33%; and palpating for nerve tenderness 32%, 80%, 80% and 32%. Logistic regression and receiver operating characteristic curves showed that the added value of one or more provocative tests over routine clinical examination is minimal. CONCLUSION: The diagnostic value of provocative clinical tests in UNE is poor.

Correction: Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding single-nucleotide variants, copy number variants and structural variants, regions of kataegis and mutation signatures between IgHVmut and IgHVunmut subtypes. We demonstrate that one-quarter of non-coding mutations in regions of kataegis outside the Ig loci are located in genes relevant to CLL. We show that non-coding mutations in ATM may negatively impact on ATM expression and find non-coding and regulatory region mutations in TCL1A, and in IgHVunmut CLL in IKZF3, SAMHD1,PAX5 and BIRC3. Finally, we show that IgHVunmut CLL is dominated by coding mutations in driver genes and an aging signature, whereas IgHVmut CLL has a high incidence of promoter and enhancer mutations caused by aberrant activation-induced cytidine deaminase activity. Taken together, our data support the hypothesis that differences in clinical outcome and biological characteristics between the two subgroups might reflect differences in mutation distribution, incidence and distinct underlying mutagenic mechanisms.

Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.

This corrects the article DOI: 10.1038/leu.2017.177.

[Nitrous oxide-induced polyneuropathy]. / Lachgasgeïnduceerde polyneuropathie.

Nitrous oxide, laughing gas, is used as a party drug to achieve a euphoric effect. It has been gaining popularity in recent years and is considered a relatively innocent substance. Nitrous oxide is known to cause subacute degeneration of the spinal cord by inactivation of active vitamin B12. Vitamin B12 plays an essential role in the synthesis of myelin. Hence, vitamin B12 deficiency can lead to degeneration of the dorsal and lateral columns of the spinal cord. Polyneuropathy is a less known complication. We present a 17-year-old woman and a 19-year-old man with subacute axonal polyneuropathy caused by laughing gas abuse. Abstinence of laughing gas and treatment with intramuscular and oral vitamin B12 suppletion respectively have led to improvement of their symptoms. Our cases demonstrate a less-known but treatable complication of laughing gas.

[Reversible posterior leucoencephalopathy due to hypercalcaemia]. / Reversibele posterieure leuko-encefalopathie bij hypercalciëmie.

A 60-year-old woman presented with changes in behaviour, cognition, cortical blindness and headache. These symptoms were caused by a reversible posterior leucoencephalopathy syndrome due to hypercalcaemia caused by a multiple myeloma, type IgD wavelength. She was treated with isotonic saline and pamidronate; the serum calcium levels normalised and the radiological brain abnormalities disappeared as did the clinical neurological abnormalities. Hypercalcaemia probably affects cerebral perfusion and has direct neurotoxic effects which can lead to cerebral oedema. This case history illustrates a rare cause of a syndrome that can be easily treated and is completely reversible.

Effect of thyroid state on cytosolic free calcium in resting and electrically stimulated cardiac myocytes.

The effects of the thyroid state on the cytosolic free Ca2+ concentration, [Ca2+]i, of resting and K+-depolarized cardiomyocytes were studied using the fluorescent Ca2+ indicator fura2. The mean resting [Ca2+]i in euthyroid myocytes (89 +/- 8 nM) was not significantly different from that in hyperthyroid myocytes (100 +/- 14 nM). The resting O2-consumption rate was identical for both groups when expressed per mg protein, but a 35% higher value was observed in the hyperthyroid group when expressed per cell on account of the cellular hypertrophy induced by thyroid hormone. Potassium induced depolarization (50 mM [K+]0) raised the level of [Ca2+]i by 50% in both groups. When ATP-coupled respiration was blocked with oligomycin, the 50 mM K+-induced rise in [Ca2+]i was accompanied in both groups by a 40% rise in glycolytic activity as inferred from measurement of lactate production. Ca2+-fluorescence transients were recorded from electrically stimulated myocytes of euthyroid, hyperthyroid and hypothyroid rats. The time taken to reach peak fluorescence (TPL) and that to 50% decay of peak fluorescence (RL0.5) decreased in the direction hypothyroid----hyperthyroid, indicating an increase in Ca2+ fluxes in the same direction. Isoproterenol (1 microM) enhanced the peak Ca2+ fluorescence in electrically stimulated hypothyroid and euthyroid myocytes but not in hyperthyroid myocytes. Both the TPL and RL0.5 were decreased by isoproterenol in euthyroid, but more so in hypothyroid myocytes. None of these parameters were influenced by isoproterenol in the hyperthyroid group. We conclude that (1) thyroid hormone increases neither the O2-consumption rate nor the level of [Ca2+]i of resting cardiomyocytes and (2) the effects of the beta-receptor-agonist isoproterenol on Ca2+ transients of electrically stimulated myocytes, are inversely related to the documented changes in beta-receptor density in heart tissue occurring with alterations in the thyroid state.

Unrecognized pulmonary venous desaturation early after Norwood palliation confounds Gp:Gs assessment and compromises oxygen delivery.

BACKGROUND: Hemodynamic stability after Norwood palliation often requires manipulation of pulmonary vascular resistance to alter the pulmonary-to-systemic blood flow ratio (Qp:Qs). Qp:Qs is often estimated from arterial saturation (SaO2), a practice based on 2 untested assumptions: constant systemic arteriovenous O2 difference and normal pulmonary venous saturation. METHODS AND RESULTS: In 12 patients early (

Acute hemodynamic effects of increasing hemoglobin concentration in children with a right to left ventricular shunt and relative anemia.

The short-term effects of increasing hemoglobin concentration were evaluated at cardiac catheterization in seven children (aged 0.3 to 7.5 years) with a right to left ventricular shunt and relative anemia. Diagnoses were tetralogy of Fallot in six and L-transposition of the great vessels with ventricular septal defect and pulmonary stenosis in one. Before and 20 minutes after isovolumic partial exchange transfusion with 20 ml/kg packed red cells, the following variables were measured: hemoglobin, partial pressure of oxygen (PO2), oxygen consumption, oxygen saturation and pressure in the aorta, superior vena cava and right and left atria. After partial exchange transfusion, hemoglobin increased from 13.7 +/- 0.5 to 16.4 +/- 0.4 g/100 ml (p less than 0.001, mean +/- SEM). Aortic PO2 increased from 55.0 +/- 3.5 to 62.0 +/- 4.1 mm Hg (p less than 0.01) and aortic oxygen saturation increased from 84.3 +/- 2.3 to 90.9 +/- 1.3% (p less than 0.002). Effective pulmonary blood flow increased by 17% from 2.72 +/- 0.10 to 3.17 +/- 0.10 liters/min per m2 (p less than 0.01), and right to left shunt decreased by 59% from 1.44 +/- 0.29 to 0.59 +/- 0.10 liters/min per m2 (p less than 0.01). Systemic oxygen transport increased from 658 +/- 48 to 738 +/- 46 ml/min per m2 (p less than 0.002). After partial exchange transfusion, systemic vascular resistance increased from 15.9 +/- 1.1 to 20.0 +/- 1.4 units (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon valvuloplasty for critical aortic stenosis in the newborn: influence of new catheter technology.

Between 1986 and July 1990, balloon valvuloplasty was attempted in eight newborns (less than 28 days of age) with isolated critical aortic valve stenosis. Balloon valvuloplasty could not be successfully accomplished in any of the three infants presenting before 1989. Since March 1989, when improved catheter technology became available, all five neonates presenting with critical aortic stenosis were treated successfully by balloon valvuloplasty. A transumbilical approach was utilized in all four infants in whom umbilical artery access could be obtained. One newborn who was 25 days of age underwent transfemoral balloon valvuloplasty. Balloon valvuloplasty was immediately successful in all five newborns, as evidenced by a decrease in valve gradient and improvement in left ventricular function and cardiac output. Peak systolic gradient was reduced by 64% from 69 +/- 8 to 25 +/- 3 mm Hg (p = 0.005). Left ventricular systolic pressure decreased from 128 +/- 9 to 95 +/- 9 mm Hg (p = 0.02) and left ventricular end-diastolic pressure decreased from 20 +/- 2 to 11 +/- 1 mm Hg (p = 0.02). Moderate (2+) aortic regurgitation was documented in two infants after valvuloplasty. The time from first catheter insertion to valve dilation averaged 57 +/- 14 min (range 26 to 94) and the median length of the hospital stay was 4 days. With the use of recently available catheters, the transumbilical technique of balloon valvuloplasty can be performed quickly, safely and effectively in the newborn with critical aortic stenosis. It does not require general anesthesia, cardiopulmonary bypass or a left ventricular apical incision and it preserves the femoral arteries for future transcatheter intervention should significant aortic stenosis recur.

Balloon valvuloplasty for recurrent aortic stenosis after surgical valvotomy in childhood: immediate and follow-up studies.

The immediate and intermediate-term effects of balloon valvuloplasty were assessed at cardiac catheterization in nine children with recurrent stenosis after a previous surgical aortic valvotomy. At valvuloplasty the patients ranged in age from 0.35 to 16 years and had undergone surgical valvotomy 0.3 to 12.5 years previously. Balloon valvuloplasty immediately reduced the peak systolic aortic stenosis gradient by 53%, from 88 +/- 9 (mean +/- SEM) to 41 +/- 6 mm Hg (p = 0.004). The left ventricular systolic pressure was reduced from 189 +/- 8 to 157 +/- 8 mm Hg (p = 0.001) and the left ventricular end-diastolic pressure from 17 +/- 1 to 14 +/- 2 mm Hg (p = 0.025). The heart rate and cardiac index remained unchanged. Before valvuloplasty, one patient had 1 + and two patients had 2+ aortic insufficiency. In six of nine patients, balloon valvuloplasty caused no change in the degree of valvular insufficiency. Two patients had a 1 + increase (from 0 to 1 + insufficiency in both), and one patient with no insufficiency developed 2+ aortic insufficiency. Elective follow-up catheterization was performed 0.8 to 2.5 years (mean 1.5 +/- 0.2) after valvuloplasty. At follow-up, the peak aortic stenosis gradient remained significantly reduced from the gradient before valvuloplasty (37 +/- 5 versus 85 +/- 10 mm Hg, p = 0.002). The gradient had not changed significantly from that measured immediately after valvuloplasty (37 +/- 5 versus 38 +/- 5 mm Hg, p = 0.75). At follow-up, aortic insufficiency had decreased from that immediately after valvuloplasty in three patients and had increased in two.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermediate-term outcome after pulmonary balloon valvuloplasty: comparison with a matched surgical control group.

To assess late (4 to 5 years) gradient reduction after pulmonary balloon valvuloplasty in childhood, and to compare the effectiveness of valvuloplasty with that of surgical valvotomy, 20 valvuloplasty-treated children and their age- and gradient-matched surgical control patients underwent prospective, noninvasive evaluation. The average age at intervention was 4.3 +/- 1 years for the valvuloplasty group versus 4.7 +/- 0.8 years for the surgical control group (p = NS). Before intervention the peak systolic pulmonary stenosis gradient was 76 +/- 5 and 74 +/- 4.4 mm Hg for the valvuloplasty and surgery groups, respectively (p = NS). Late evaluation consisted of clinical examination, two-dimensional echocardiogram and Doppler study, 24-hour Holter monitoring, 12-lead electrocardiogram, exercise treadmill study and chest radiograph performed an average of 5.3 +/- 0.3 years after valvuloplasty and 11.7 +/- 0.5 years after surgery (p less than 0.01). The patients treated with balloon valvuloplasty had no evidence of restenosis; the residual pulmonary stenosis gradient at follow-up was 24 +/- 2.7 mm Hg (range 8 to 48) versus 35 +/- 3.6 mm Hg (range 19 to 70) immediately after valvuloplasty (p = NS). Comparison of the late residual gradients between treatment groups showed no hemodynamically significant difference (24 +/- 2.7 versus 16 +/- 1.5 mm Hg, balloon versus surgery; p less than 0.01). However, there was, a significant difference in the degree and severity of pulmonary valve insufficiency and ventricular ectopic activity between groups. In the balloon valvuloplasty group 11 patients had no pulmonary insufficiency, and the remaining 9 had mild insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid progression of aortic aneurysms after patch aortoplasty repair of coarctation of the aorta.

OBJECTIVES: This study was undertaken to evaluate the progression of aortic aneurysms after patch aortoplasty repair of coarctation of the aorta. BACKGROUND: Previous studies demonstrated a 5% to 25% incidence rate of repair site aneurysm 3 to 18 years after patch aortoplasty repair of coarctation. The natural history of aneurysmal progression in this disease entity has not previously been examined. METHODS: Twenty-nine patients were identified 5.6 +/- 1 years (mean +/- SE) postoperatively and classified into two groups: Group A, aneurysm (n = 7); Group B, no aneurysm (n = 22). The presence of an aneurysm was defined angiographically as a ratio of the repair site diameter to diaphragmatic aortic diameter (aortic ratio) greater than or equal to 1.5. A 23% prevalence (7 of 29) of aortic aneurysm was identified. One patient in Group A underwent semiemergency aneurysmectomy and two patients in Group B were lost to follow-up. The remaining 26 patients were reevaluated 3 to 5 years later by clinical examination and chest radiography. Aortograms were performed in all patients with suspected aneurysm formation or progression. RESULTS: Five of six patients in Group a demonstrated progressive aneurysmal dilation documented by an increase in aortic ratio from 1.64 +/- 0.06 to 2.04 +/- 0.2 (p = 0.03) and an increase in absolute aneurysm diameter from 2.5 +/- 0.3 to 3.6 +/- 0.5 cm (p = 0.006). Only 1 of 20 patients in Group B had evidence of new aneurysmal dilation (p less than 0.05 vs. Group A). Four patients in Group A have undergone elective aneurysmectomy, with equal distribution of true and pseudoaneurysms by pathologic examination. CONCLUSIONS: Aortic aneurysm formation is common after patch aortoplasty repair of coarctation of the aorta. The majority of patients with an aortic ratio greater than or equal to 1.5 will show significant progressive aneurysmal dilation within 3 to 5 years.

Determinants of successful balloon valvotomy in infants with critical pulmonary stenosis or membranous pulmonary atresia with intact ventricular septum.

OBJECTIVES: This study reviewed our experience with percutaneous balloon valvotomy in infants with critical pulmonary stenosis or membranous pulmonary atresia with intact ventricular septum and defined the anatomic and hemodynamic characteristics of infants in whom this procedure is successful and provides definitive therapy. BACKGROUND: Unlike children with valvular pulmonary stenosis, the follow-up of infants with critical pulmonary stenosis undergoing percutaneous balloon valvotomy is limited. METHODS: Between December 1987 and August 1992, percutaneous balloon valvotomy was attempted in 12 infants with critical pulmonary stenosis (n = 10) or pulmonary atresia with intact ventricular septum (n = 2). Two outcome groups were identified: Group A patients are acyanotic, have mild residual pulmonary stenosis and have not required operation; Group B patients have required operation. RESULTS: Of the 12 infants, 11 had a successful balloon valvotomy procedure. Group A patients (n = 7) have a residual gradient of 22 +/- 18.7 mm Hg (mean +/- SD) at follow-up of 3.2 years (range 1.2 to 5.0). In Group B (n = 5), operation was required for inability to cross the pulmonary valve (n = 1) or persistent severe hypoxemia for > or = 2 weeks after valvotomy (n = 4). Significant differences (p < or = 0.01) between the two groups (Group A vs. Group B) were identified in pulmonary valve annulus (Z value) 8.1 mm (-1.1) versus 5.5 mm (-3.4); tricuspid valve annulus (Z value) 14.0 mm (0.8) versus 8.8 mm (-1.8); right ventricular volume 65 versus 29 ml/m2; and Lewis index 10.9 versus 8.9. CONCLUSIONS: Percutaneous balloon valvotomy is effective and likely to provide definitive therapy in infants with critical pulmonary stenosis or membranous pulmonary atresia with intact ventricular septum who have a tricuspid valve annulus > 11 mm, pulmonary valve annulus > or = 7 mm and right ventricular volume > 30 ml/m2.

Sinus of Valsalva aneurysm complicating bacterial endocarditis in an infant: diagnosis with two-dimensional and Doppler echocardiography.

Sinus of Valsalva aneurysm is a rare complication of bacterial endocarditis in infancy and childhood. This report describes an infant with congenital aortic stenosis who developed bacterial endocarditis after abdominal surgery and placement of indwelling central venous catheters for long-term parenteral nutrition. Bacterial endocarditis in this infant was complicated by the development of an aneurysm of the left sinus of Valsalva. Surgical intervention was necessary because of gradual expansion of the aneurysm with compression of the adjacent right pulmonary artery and descending aorta. Two-dimensional and Doppler echocardiography proved useful for the initial diagnosis and serial follow-up of this unusual disorder and for its successful surgical management.

Hemodynamic and clinical effects of oral levodopa in children with congestive heart failure.

OBJECTIVES: This study was undertaken to evaluate the safety, efficacy and pharmacodynamic variables of oral levodopa in pediatric patients with congestive heart failure refractory to standard therapy. BACKGROUND: Therapeutic options for children with congestive cardiomyopathies are limited to digoxin, diuretic agents and angiotensin-converting enzyme inhibitors. Previous work in adults with congestive heart failure has shown a short-term effectiveness of levodopa and improvement of cardiac function. METHODS: Baseline two-dimensional and M-mode echocardiography, surface electrocardiography, Holter monitoring and exercise testing, when applicable, were performed. Levodopa was administered in a dose escalation scale from 8 mg/kg body weight per dose to 20 mg/kg per dose over 3 days with concomitant metoclopramide and pyridoxine. Catecholamine levels at initiation of the trial and throughout dose escalation were measured, with echocardiographic and electrocardiographic correlation. After 24-h drug washout, cardiac catheterization was performed both before and after administration of levodopa. RESULTS: Between February 1992 and December 1995, nine children (age 10 +/- 1.7 years, weight 27.8 +/- 4.3 kg) were enrolled in this study. At cardiac catheterization, serum dopamine levels rose from 108.5 +/- 59.2 pg/ml to 1,375.8 +/- 567.9 pg/ml (p = 0.03) at 100 +/- 14.8 min after levodopa administration without a significant change in serum norepinephrine or epinephrine levels. Paralleling these increases, there were significant changes in the cardiac index (1.7 +/- 0.3 to 3.2 +/- 0.7 liters/min per m2), stroke volume index (16.1 +/- 3.2 to 31.2 +/- 7.0 ml/m2 per min), oxygen consumption (138.6 +/- 24.4 to 188.3 +/- 30.8 ml/min per m2) and systemic vascular resistance (36.8 +/- 8 to 21.9 +/- 5.5 indexed Wood's units; all p < 0.01). There was a significant reversal of the daily fluid volume output/input ratio from 0.8 +/- 0.1 to 1.2 +/- 0.1 (p < 0.01). Levodopa administration was complicated by hypertension or tachycardia, or both, requiring a dose reduction in three patients, and by significant gastrointestinal distress in one. There was sustained symptomatic improvement a median of 19.5 months after drug initiation in seven of the patients. CONCLUSIONS: These preliminary data support the hemodynamic value of oral levodopa in the treatment of severe congestive heart failure in children.

Surgical repair is safe and effective after unsuccessful balloon angioplasty of native coarctation of the aorta.

Since 1985 balloon angioplasty, followed by surgical repair if angioplasty is unsuccessful, has been used as a treatment strategy for eligible children with discrete native coarctation of the aorta. Although balloon angioplasty has been successful in most patients, this strategy is appropriate only if surgery is safe and effective in children in whom angioplasty does not succeed. To address this issue, the surgical procedure and clinical outcome in 11 children who underwent surgery after unsuccessful balloon angioplasty (defined as a residual systolic gradient greater than 20 mm Hg in 10 and a saccular aneurysm in 1) were evaluated. Data for subjects were compared with data for a control group of seven children who had surgical repair of a discrete coarctation without prior angioplasty during the same time period. In the study group, balloon angioplasty was performed at 4.3 +/- 1.2 years of age, resulting in a balloon/isthmus ratio of 0.98 +/- 0.05 and decreasing mean peak systolic gradient from 54 +/- 3 to 27 +/- 2 mm Hg (p less than 0.001). Follow-up angiography (n = 7) or nuclear magnetic resonance imaging (n = 4) documented a discrete residual stenosis in 10 patients and a small saccular aneurysm in 1. Collateral circulation decreased in three patients. The subsequent surgical procedure and its outcome were similar in the study and control groups. Chylothorax was the only complication, occurring in one child from each group. No paraplegia or mortality occurred. Pathologic examination revealed irregular intimal surfaces with small flaps of intima in 5 of 10 resected specimens from the study group and in 2 of 6 from the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise-induced hypertension after repair of coarctation of the aorta: arm versus leg exercise.

The etiology of exercise-induced upper limb hypertension after repair of coarctation of the aorta is unknown. We hypothesized that blood flow across the coarctation repair site is a major determinant of such exercise-induced hypertension. Because arm ergometry should produce a smaller increase in descending aortic blood flow than treadmill exercise, we compared the changes in upper limb pressure and the coarctation gradient produced by each type of exercise at equivalent levels of heart rate and peak oxygen consumption in 28 children with repaired coarctation of the aorta. The children were classified into three groups: Group I, resting gradient less than 15 mm Hg and treadmill gradient less than 20 mm Hg; Group II, resting gradient less than 15 mm Hg and treadmill gradient greater than 20 mm Hg; and Group III, resting gradient greater than or equal to 15 mm Hg. Twelve children with no heart disease served as control subjects. All children were exercised to exhaustion with 45 minutes' rest between the two exercise protocols. There were no differences in maximal heart rate and oxygen consumption between the two types of exercise. In all groups, treadmill exercise produced a larger increase in arm systolic blood pressure and arm-leg gradient than did arm exercise. With treadmill exercise coarctation Groups II and III developed a greater rise in both arm-leg gradient and arm systolic pressure than was observed in the control subjects (p less than 0.05). However, with arm exercise, Group III developed a significantly greater rise in both arm pressure and arm-leg gradient (p less than 0.05) than was observed in the control subjects.

Intermediate-term results of Phase I Food and Drug Administration Trials of buttoned device occlusion of secundum atrial septal defects.

OBJECTIVES: This study was conducted to evaluate the intermediate-term results of the multi-institutional U.S. trial of the buttoned device for transcatheter closure of atrial septal defects (ASDs). BACKGROUND: The trial was conducted in three centers (University of Arizona, University of Michigan and University of Wisconsin) under a Food and Drug Administration (FDA)-approved clinical trial with investigational device exemption. Only short-term follow-up is known. METHODS: All 46 patients who had successful implantation of the device were prospectively followed up. Patients were evaluated at 1, 6 and 12 months after device occlusion and yearly thereafter. RESULTS: This cohort was followed up from 51 to 68 months (mean 60.8, median 62). Patient ages ranged from 1 to 62 years (median 4); weights ranged from 10 to 105 kg (median 18); and stretched ASD sizes were 14 +/- 4 mm (left to right shunts) and 10 +/- 3 mm (right to left shunts). Of the 46 patients, 45 (98%) had effective occlusion of their ASD, and 34 (74%) had complete ASD closure. The incidence of residual shunts decreased from 65% (30 of 46 patients) at 1 month after device placement to 27% (12 of 45 patients) at last follow-up. All residual shunts were quantitated as trivial. Only two patients (4%) required reintervention for significant residual defects. There were no cases of endocarditis or thromboembolism in 224 patient-years of follow-up. CONCLUSIONS: In up to 5.5 years of follow-up, the buttoned device provided effective closure in 98% of patients in whom the device was successfully implanted. The incidence of residual shunts decreased during follow-up, and no instances of endocarditis or thromboembolism were observed.