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Regardless of the disease under study, the FWHM technique for LGE quantification gives LGE volume mean results similar to manual quantification and is statistically the most reproducible, reducing required sample sizes by up to one-half.

Objectives ⁄ methods: This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3-81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond-Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or b-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC). Results: In patients with baseline LIC ‡7 mg Fe ⁄ g dry weight, deferasirox initiated at 20 or 30 mg ⁄ kg ⁄ d produced statistically significant decreases in LIC (P < 0.001); these decreases were greatest in MDS and least in DBA. As chelation efficiency and iron excretion did not differ significantly between disease groups, the differences in LIC changes are consistent with mean transfusional iron intake (least in MDS: 0.28 ± 0.14 mg ⁄ kg ⁄ d; greatest in DBA: 0.4 ± 0.11 mg ⁄ kg ⁄ d). Overall, LIC changes were dependent on dose (P < 0.001) and transfusional iron intake (P < 0.01), but not statistically different between disease groups. Changes in serum ferritin and LIC were correlated irrespective of disease group (r = 0.59), supporting the potential use of serum ferritin for monitoring deferasirox therapy. Deferasirox had a safety profile compatible with long-term use. There were no disease-specific safety ⁄ tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases. Conclusions: Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias. There were no disease-specific adverse events. Once differences in transfusional iron intake are accounted for, dose-dependent changes in LIC or serum ferritin are similar in MDS and other disease groups.

IntroductionPhiladelphia chromosome-positive (Ph ϩ ) acute lymphoblastic leukemia (ALL) occurs in 25% to 30% of adults and in approximately 4% of children with ALL, [1][2][3][4][5][6] and is associated with a very poor prognosis. The reported incidence in the elderly (Ͼ 60 years) seems even higher, 7 with more unfavorable results and a median survival of less than one year. 8,9 In the last few years, studies aimed at testing the activity of different associations of imatinib and chemotherapy as frontline treatment for Ph ϩ patients with ALL have been carried out, both for younger adults 10-13 and for elderly patients. [14][15][16] The question of whether a chemotherapy-free treatment, based only on imatinib plus steroids, could effectively control the disease by inducing durable hematologic and/or molecular responses, is still open. This report summarizes our results on a total of 30 elderly Ph ϩ patients with ALL who received imatinib plus steroids in induction and imatinib in consolidation until relapse or death. Patients, materials, and methods PatientsPatients were treated according to the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol, which had been approved by the internal review board and by the ethics committee of the trial coordinating center, as well as by the local ethics committee of each participating institution. Patients with a diagnosis of ALL who were older than 60 years of age were eligible for this study if they carried either the Ph chromosome or the BCR-ABL molecular translocation. Written informed consent was obtained from each patient in accordance with the Declaration of Helsinki. BCR-ABL diagnosis and monitoringAll molecular examinations at diagnosis and during the follow-up were performed in the same reference GIMEMA laboratory. 17 Total RNA was extracted from bone marrow (BM) cells. cDNA synthesis and reverse transcriptasepolymerase chain reaction (RT-PCR) specific for the BCR-ABL transcripts encoding either the p190 Bcr-Abl or the p210 Bcr-Abl proteins were performed using the standardized BIOMED-1 protocol. 18 Quantitative real-time PCR (Q-RT-PCR) analysis of minimal residual disease was carried out using the methods standardized within a Europe Union concerted action program. 19 ABL was used as the control gene and the BCR-ABL values were expressed as a percentage of the ABL transcript levels of ABL. Study design and therapyPatients were assigned to receive a 7-day steroid pretreatment (prednisone, at increasing doses from 10 to 40 mg/m 2 per day) followed by induction treatment with imatinib at the fixed dose of 800 mg/d, associated to steroids (prednisone by mouth at the dose of 40 mg/m 2 per day) from day 1 to day 45. Response evaluation was carried out at day 45. Assessments of BM aspirates, including molecular biology evaluation, were planned after the response evaluation, at the second, fourth, and sixth month from complete remission (CR), and/or at the time of possible relapse. For personal use only. on May 12, 2018. by guest www.bloodjournal....

Myocardial ECV, assessed non-invasively in the septum with equilibrium contrast cardiovascular magnetic resonance, shows gender differences in normal individuals and disease-specific variability. Therefore, ECV shows early potential to be a useful biomarker in health and disease.

In distinction to prior perceptions, LV mass index was normal in about 20% of patients with definite HCM phenotype. Therefore, increased LV mass is not a requirement for establishing the clinical diagnosis of HCM. The LV mass correlated weakly with maximal wall thickness, and proved more sensitive in predicting outcome.

Background-The prognostic significance of syncope has not been investigated systematically in hypertrophic cardiomyopathy, and treatment strategies have been based largely on intuition and experience. Methods and Results-We assessed the relationship between syncope and sudden death in 1511 consecutive patients with hypertrophic cardiomyopathy. Unexplained (nϭ153) or neurally mediated (nϭ52) syncope occurred in 205 patients (14%). Over a 5.6Ϯ5.2-year follow-up, 74 patients died suddenly. Relative risk of sudden death was 1.78 (95% confidence interval 0.88 to 3.51, Pϭ0.08) in patients with unexplained syncope and 0.91 (95% confidence interval 0.00 to 3.83, Pϭ1.0) in those with neurally mediated syncope compared with patients without syncope. In multivariable analysis, the temporal proximity of unexplained syncope to initial patient evaluation was independently associated with risk of sudden death (Pϭ0.006). Patients with unexplained syncope within 6 months before the initial evaluation showed a 5-fold increase in risk compared with patients without syncope (adjusted hazard ratio 4.89, 95% confidence interval 2.19 to 10.94), a relationship that was maintained throughout all age groups (Ͻ18, 18 to 39, and Ն40 years). Older patients (Ն40 years of age) with remote episodes of syncope (Ͼ5 years before initial evaluation) did not show an increased risk of sudden death (adjusted hazard ratio 0.38, 95% confidence interval 0.05 to 2.74). Conclusions-In the present large cohort of patients with hypertrophic cardiomyopathy, unexplained syncope was a risk factor for sudden death. Patients with syncopal events that occurred in close temporal proximity to the initial evaluation showed a substantially higher risk of sudden death than patients without syncope. Older patients with remote syncopal events did not show an increased risk.

Background-With recognition of disease-causing genes in arrhythmogenic right ventricular cardiomyopathy, mutation analysis is being applied. Methods and Results-The role of genotyping in familial assessment for arrhythmogenic right ventricular cardiomyopathy was investigated, including the prevalence of mutations in known causal genes, the penetrance and expressivity in genotyped families, and the utility of the 2010 Task Force criteria in clinical diagnosis. Clinical and molecular genetic evaluation was performed in 210 first-degree and 45 second-degree relatives from 100 families. In 51 families, the proband was deceased. The living probands had a high prevalence of ECG abnormalities (89%) and ventricular arrhythmia (78%) and evidence of more severe disease than relatives. Definite or probable causal mutations were found in 58% of families and 73% of living probands, of whom 28% had an additional desmosomal variant (ie, mutation or polymorphism). Ninety-three relatives had a causal mutation; 33% fulfilled the 2010 criteria, whereas only 19% satisfied the 1994 version (Pϭ0.03). An additional desmosomal gene variant was found in 10% and was associated with a 5-fold increased risk of developing penetrant disease (odds ratio, 4.7; 95% confidence interval, 1.1 to 20.4; Pϭ0.04). 3 Estimates of penetrance have been confined to single-gene studies. With the identification of disease-causing genes, the familial basis of ARVC is increasingly recognized, and the clinical identification of the relatives at risk has become central to management. This study evaluated a large cohort of families with ARVC to investigate the prevalence of mutations in known causal genes, the penetrance and disease expression in both probands and relatives, and the utility of 2010 diagnostic criteria in familial diagnosis. Conclusions-Arrhythmogenic Editorial see p 2661 Clinical Perspective on p 2709 Methods Study SampleThe Heart Hospital, University College London Hospitals (London, UK) is a national referral center for the diagnosis and management of inherited cardiac diseases. Specialist weekly clinics operate for each of inherited cardiomyopathies (hypertrophic, dilated, arrhythmogenic right ventricular). The families were drawn from referrals to the ARVC, inherited arrhythmia, and victims of sudden death clinics. Diagnosis was considered definite when 2 major, or 1 major and 2 minor criteria, or 4 minor criteria from different categories, were fulfilled. Diagnosis was considered borderline when 1 major and 1 minor or 3 minor criteria from different categories were fulfilled. 5 Evidence of disease expression in relatives was defined by the presence of a borderline (incomplete disease expression) or definite diagnosis. All first-degree relatives and second-degree relatives from families in whom a disease-causing mutation was found were invited for prospective evaluation. Clinical EvaluationClinical evaluation included 12-lead ECG, signal-averaged ECG, transthoracic echocardiography, symptom-limited exercise test, and 24-hour ambulatory ECG...