Etanercept with IVIg for acute Kawasaki disease: a long-term follow-up on the EATAK trial.

BACKGROUND: The Etanercept as Adjunctive Treatment for Acute Kawasaki Disease, a phase-3 clinical trial, showed that etanercept reduced the prevalence of IVIg resistance in acute Kawasaki disease. In patients who presented with coronary artery involvement, it reduced the maximal size and short-term progression of coronary artery dilation. Following up with this patient group, we evaluated the potential long-term benefit of etanercept for coronary disease. METHODS: Patients were followed for at least 1 year after the trial. The size of dilated arteries (z-score ≥ 2.5) was measured at each follow-up visit. The z-score and size change from baseline were evaluated at each visit and compared between patients who received etanercept versus placebo at the initial trial. RESULTS: Forty patients who received etanercept (22) or placebo (18) in the Etanercept as Adjunctive Treatment for Acute Kawasaki Disease trial were included. All patients showed a persistent decrease in coronary artery size measurement: 23.3 versus 5.9% at the 6-month visit, 24 versus 13.1% at the 1-year visit, and 20.8 versus 19.3% at the ≥ 2-year visit for etanercept or placebo, respectively, with similar results for decrease in coronary artery z-scores. In a multivariate analysis, correcting for patients' growth, a greater size reduction for patients on the etanercept arm versus placebo was proved significant for the 6-month (p = 0.005) and the 1-year visits (p = 0.019) with a similar end outcome at the ≥ 2-year visit. DISCUSSION: Primary adjunctive therapy with etanercept for children with acute Kawasaki disease does not change the end outcome of coronary artery disease but may promote earlier resolution of artery dilation.

Etanercept With IVIg for Acute Kawasaki Disease: A Randomized Controlled Trial.

OBJECTIVES: Patients with Kawasaki disease can develop life-altering coronary arterial abnormalities, particularly in those resistant to intravenous immunoglobulin (IVIg) therapy. We tested the tumor necrosis factor α receptor antagonist etanercept for reducing both IVIg resistance and coronary artery (CA) disease progression. METHODS: In a double-blind multicenter trial, patients with Kawasaki disease received either etanercept (0.8 mg/kg; n = 100) or placebo (n = 101) subcutaneously starting immediately after IVIg infusion. IVIg resistance was the primary outcome with prespecified subgroup analyses according to age, sex, and race. Secondary outcomes included echocardiographic CA measures within subgroups defined by coronary dilation (z score >2.5) at baseline. We used generalized estimating equations to analyze z score change and a prespecified algorithm for change in absolute diameters. RESULTS: IVIg resistance occurred in 22% (placebo) and 13% (etanercept) of patients (P = .10). Etanercept reduced IVIg resistance in patients >1 year of age (P = .03). In the entire population, 46 (23%) had a coronary z score >2.5 at baseline. Etanercept reduced coronary z score change in those with and without baseline dilation (P = .04 and P = .001); no improvement occurred in the analogous placebo groups. Etanercept (n = 22) reduced dilation progression compared with placebo (n = 24) by algorithm in those with baseline dilation (P = .03). No difference in the safety profile occurred between etanercept and placebo. CONCLUSIONS: Etanercept showed no significant benefit in IVIg resistance in the entire population. However, preplanned analyses showed benefit in patients >1 year. Importantly, etanercept appeared to ameliorate CA dilation, particularly in patients with baseline abnormalities.

Imaging of early modification in cardiomyopathy: the doxorubicin-induced model.

Doxorubicin chemotherapy is effective and widely used to treat acute lymphoblastic leukemia. However, its effectiveness is hampered by a wide spectrum of dose-dependent cardiotoxicity including both morphological and functional changes, affecting primarily the myocardium. Non-invasive imaging techniques are used for the diagnosis and monitoring of these cardiotoxic effects. The purpose of this review is to summarize and compare the most common imaging techniques used in early detection and therapeutic monitoring of doxorubicin-induced cardiotoxicity and the suggested mechanisms of such side effects. Imaging techniques using echocardiography including conventional 2D and 3D echocardiography along with MRI sequences including Tagging, Cine, and quantitative MRI in detecting early myocardial damage are also reviewed. As there is a multitude of reported indices and imaging methods to assess particular functional alterations, we limit this review to the most relevant techniques based on their clinical application and their potential to early detection of doxorubicin-induced cardiotoxic effects.

Rejection of transplanted hearts in patients evaluated by the component analysis of multi-wavelength NAD(P)H fluorescence lifetime spectroscopy.

Rejection of transplanted hearts remains one of the principal reasons for death of paediatric patients, but an appropriate diagnostic tool for the mild rejection in early stages is still missing. Tissue autofluorescence (AF) is one of the most versatile non-invasive tools for mapping the metabolic state in living tissues. Increasing interest in the imaging and diagnosis of living cells and tissues based on their intrinsic fluorescence rather than fluorescence labelling is closely connected to the latest developments in high-performance spectroscopy and microscopy techniques. In this contribution, we investigate individual components in spectrally- and time-resolved NAD(P)H fluorescence, revealed by linear unmixing, responsible for increased fluorescence in patients presenting mild rejection of transplanted hearts. Application of such approach has the potential to improve the diagnostics of the cardiac transplant rejection by helping currently used histological analysis.

Therapeutic strategies in children with an isolated unilaterally absent proximal pulmonary artery.

Therapeutic strategies for isolated unilateral absence of a proximal pulmonary artery remain unclear. The natural history of the disease, or thrombosis of primary surgical anastomosis, leads to exclusion of the affected lung with increased risk of intrapulmonary bleeding, impaired quality of life, and shortened life expectancy. We herein describe our two-stage approach in a small series of patients starting with interventional catheterization followed by surgical anastomosis. Other medical interventions, such as anticoagulation and pulmonary vasodilatation, are key factors to successfully restore pulmonary circulation in this rare defect.

An infant with mucolipidosis-II and an atretic orifice of the left coronary artery.

A one-month-old boy, with type-II mucolipidosis, presented with congestive heart failure and elevated cardiac enzymes. The atretic nature of the orifice of the left coronary artery was revealed by retrograde flow on color Doppler and selective coronary angiography. Type-II mucolipidosis and atresia of the left coronary artery are rare. To the best of our knowledge, this is the first report of their combined occurence, suggesting a possible causal relationship.

Cardiovascular evaluation of fetal anemia due to alloimmunization.

OBJECTIVE: To evaluate the cardiovascular impact of fetal anemia. METHODS: We reviewed 53 echo-Doppler studies from 24 fetuses with anemia due to alloimmunization. RESULTS: There was no difference between the severe and nonsevere anemia for heart rate, cardiothoracic ratio, and contractility. There was an increased left ventricular dimension, peak velocities of the middle cerebral artery (MCA) and a decreased pulsatility index of the umbilical artery (UAPI) in the severe group. The combination of MCA and UAPI had a high sensitivity (86%), specificity (91%), positive (80%) and negative (94%) predictive value as well as positive predictive likelihood ratio (9.6) to detect severe anemia. CONCLUSION: Standard echocardiograhic parameters are not useful to correlate anemia. The combination of MCA and UAPI improves the accuracy to detect severe anemia.

Comparison of surgical and transcatheter treatment for native coarctation of the aorta in patients > or = 1 year old. The Quebec Native Coarctation of the Aorta study.

BACKGROUND: The objectives of this study were to compare, in the current era, the immediate results, complications, and midterm outcomes obtained by surgical repair versus transcatheter treatment of coarctation of the aorta (CoA). METHODS: The study was of retrospective nature and included 80 consecutive patients > or = 1 year old (mean age 12 +/- 10 years) treated for an isolated CoA in 4 university centers in Quebec between 1998 and 2004. Fifty patients underwent aortic angioplasty, with stent implantation in 19, and 30 had surgical repair. Immediate results, procedural complications, clinical events, and the incidence of aortic aneurysm at follow-up were compared between groups. RESULTS: There were no differences between the 2 groups in clinical baseline characteristics. Percentage reduction in peak systolic pressure gradient across the coarctation was similar between the 2 groups (angioplasty 72% +/- 23% vs surgery 75% +/- 18%, P = .55). Procedure-related complications occurred more frequently after surgical repair compared with angioplasty (50% vs 18%, P = .005), and median hospitalization time was longer in the surgical than in the angioplasty group (7 vs 1 day, P < .001). At 38 +/- 21 months' follow-up, no patient in the surgical group and 16 patients in the angioplasty group had at least 1 aortic reintervention (0% vs 32%, P < .0001). The presence of an aortic aneurysm was diagnosed more frequently in the angioplasty group compared with the surgical group (24% vs 0%, P = .01). CONCLUSION: Aortic angioplasty provided comparable immediate hemodynamic results to surgery, with reduced morbidity and hospitalization length for the treatment of CoA in patients > or = 1 year old. However, angioplasty was associated with a higher rate of reintervention and aneurysm formation at a mean follow-up of 3 years.

Reversible atrioventricular block associated with closure of atrial septal defects using the Amplatzer device.

OBJECTIVES: We sought to determine the incidence, nature, and predisposing factors of atrioventricular block (AVB) associated with closure of atrial septal defects (ASDs) using the Amplatzer septal occluder (ASO). BACKGROUND: In our institution, 162 patients underwent ASD closure using ASO between December 1997 and December 2001. This includes small children with large defects. METHODS: Electrocardiographic tracings during ASO implantation and at follow-up visits were reviewed. Anatomic characteristics and device size were assessed as potential risk factors for AVB. RESULTS: Ten patients (6.2%) presented with new-onset (n = 9) or aggravation of preexisting (n = 1) AVB. Atrioventricular block occurred during the procedure (n = 3) or was first noted one day to one week later (n = 7). Patients had first-degree (n = 4), second-degree Wenckebach (n = 4), or third-degree (n = 2) AVB, with no symptoms or hemodynamic compromise. First-degree AVB persisted in two patients at 12 and 33 months of follow-up, whereas most recovered normal AV conduction within one (n = 7) or six months (n = 1). A larger shunt (Qp/Qs ratio 2.8 +/- 0.9 vs. 2.1 +/- 0.8, p < 0.01) and device size (24 +/- 5 vs. 19 +/- 6 mm, p < 0.01) were the only determinant factors for AVB. A device size > or =19 mm was used in 90% (9 of 10) of patients who developed AVB, as compared with 49% of those without AVB (p < 0.02). CONCLUSIONS: Closure of ASDs using the large ASO can be associated with the development of AV block and mandate a closer follow-up. In our series, however, all AVBs resolved or improved spontaneously, with no recurrence at mid-term follow-up.

The use of the air leak test and corticosteroids in intubated children: a survey of pediatric critical care fellowship directors.

INTRODUCTION: Uncertainties exist regarding the value of the air leak test or use of steroids for preventing post-extubation stridor and extubation failure in children. OBJECTIVE: Determine the practice preferences of pediatric critical care physicians regarding the air leak test and administration of glucocorticosteroids to prevent airway edema. METHODS: A 14-question survey regarding the value of the air leak test, use of glucocorticosteroids, and management of airway edema in intubated children was sent to all North American pediatric critical care fellowship directors affiliated with medical school teaching hospitals. RESULTS: The response rate was 85% (58/68). Seventy-six percent (44/58) routinely check for air leak prior to extubation. The physicians who check for air leak were more likely to delay extubation in order to administer glucocorticosteroids (60% [26/43] vs 15% [2/13], p = 0.01). An air leak of >or= 30 cm H(2)O was more likely (than >or= 20 cm H(2)O) to result in delaying extubation (95% [35/37] vs 51% [19/37], p <0.001). Of the respondents who use steroids for airway edema prophylaxis, 73% (24/33) give steroids based on the air leak test. CONCLUSIONS: The majority of surveyed pediatric critical care fellowship program directors rely on the air leak test and use corticosteroids to prevent post-extubation stridor and extubation failure. At an air leak of >or= 30 cm H(2)O most of the surveyed physicians would delay extubation and initiate glucocorticosteroids.