temic ventricular dysfunction is a significant medical problem for children and represents the reason for at least 50% of pediatric referrals for heart transplantation. 1 To date, there have been no large randomized controlled trials of any medication in children and adolescents with chronic heart failure. Treatment recommendations in children and adolescents with heart failure are extrapolated from the results of clinical trials conducted in adults, which may be problematic. 2 Although multiple studies in adults have demonstrated beneficial effects of ␤-blockers on left ventricular function, symptoms, and survival, [3][4][5][6][7] little isFor editorial comment see p 1214.

SummaryBackgroundStents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.MethodsThe International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.FindingsThe trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197).InterpretationCompletion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

The limited number of prospective randomised studies on STP does not allow strong recommendations to be given. Although STP most often is perceived as benign, it can coexist with or progress to DVT, and even give rise to PE. It is also associated with hypercoagulability and malignancy.

Objective To describe the clinical course and outcome of 10 patients with Kawasaki disease (KD) treated with a calcineurin inhibitor after failing to respond to multiple therapies. Study design Demographic and clinical data were prospectively collected using standardized case report forms. T-cell phenotypes were determined by flow cytometry, and KD risk alleles in ITPKC (rs28493229), CASP3 (rs72689236), and FCGR2A (rs1801274) were genotyped. Results Intravenous followed by oral therapy with cyclosporine (CSA) or oral tacrolimus was well tolerated and resulted in defervescence and resolution of inflammation in all 10 patients. There were no serious adverse events, and a standardized treatment protocol was developed based on our experiences with this patient population. Analysis of T-cell phenotype by flow cytometry in 2 subjects showed a decrease in circulating activated CD8+ and CD4+ T effector memory cells after treatment with CSA. However, suppression of regulatory T-cells was not seen, suggesting targeting of specific, proinflammatory T-cell compartments by CSA. Conclusion Treatment of refractory KD with a calcineurin inhibitor appears to be a safe and effective approach that achieves rapid control of inflammation associated with clinical improvement.

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Doxorubicin is a highly effective cancer chemotherapeutic agent that produces a dose-dependent cardiomyopathy that limits its clinical usefulness. Clinical and animal studies ofmorphological changes during the early stages of doxorubicin-induced cardiomyopathy have suggested that the sarcoplasmic reticulum, the intracellular membrane system responsible for myoplasmic calcium regulation in adult mammalian heart, may be the early target of doxorubicin. To detect changes in the calcium pump protein or the calcium release channel (ryanodine receptor) of the sarcoplasmic reticulum during chronic doxorubicin treatment, rabbits were treated with intravenous doxorubicin (1 mg/kg) twice weekly for 12 to 18 doses. Pair-fed controls received intravenous normal saline. The severity ofcardiomyopathy was scored by light and electron microscopy of left ventricular papillary muscles. Developed tension was measured in isolated atrial strips. In subcellular fractions from heart, I3Hjryanodine binding was decreased in doxorubicin-treated rabbits (0.33±0.03 pmol/mg) compared with control rabbits (0.66±0.02 pmol/mg, P < 0.0001). The magnitude of the decrease in I3Hjryanodine binding correlated with both the severity of the cardiomyopathy graded by pathology score (light and electron microscopy) and the decrease in developed tension in isolated atrial strips. B. for [3Hlryanodine binding and the amount of immunoreactive ryanodine receptor by Western blot analysis using sequence-specific antibody were both decreased, consistent with a decrease in the amount of calcium release channel of sarcoplasmic reticulum in doxorubicin-treated rabbits. In contrast, there was no decrease in the amount or the activity of the calcium pump protein of the sarcoplasmic reticulum in doxorubicin-treated rabbits. Doxorubicin treatment did not decrease [3H I ryanodine binding or the amount ofimmunoreactive calcium release channel of sarcoplasmic reticulum in skeletal muscle. Since the sarcoplasmic reticulum regulates muscle contraction by the cyclic uptake and release of a large internal calcium pool, altered function of the calcium release channel could lead to the abnormalities ofcontraction and relaxation observed in the doxorubicin cardiomyopathy. (J. Clin.A portion of this paper has been presented in abstract form ( 1991.Biophys. J. 59: lOla).

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EMB is widely utilized for graft surveillance after HTx; however, there is significant variation in the frequency of surveillance EMB use during the first year post-HTx. The aim of this study was to assess changes in the utilization of surveillance EMB over time among member institutions of PHTS. A survey of PHTS centers assessing the frequency of surveillance EMB use during the first year post-HTx was conducted in 2006. The same survey was repeated in 2014 to assess changes in practice over time. The number of EMB in infants ranged from 0 to 9 and in adolescents 0 to 16. The number of EMB decreased or remained unchanged in the majority of centers. Fewer EMB are performed in infants compared to adolescents and this practice did not change over time. There was a significant decrease in surveillance EMB use in adolescents (p = 0.012). International centers perform significantly fewer EMB in adolescents when compared to centers within the United States (p = 0.006). There continues to be significant variation in the utilization of surveillance EMB, with a shift toward less reliance on EMB for adolescents in the current era. Further research is necessary to determine the optimal frequency of invasive monitoring that reduces costs without compromising outcomes.