Is arrhythmogenicity related to the speed of reperfusion during thrombolysis for myocardial infarction?

The objective of this study was to relate the number of ventricular arrhythmias (VA) to the normalization time of the ST segment during thrombolysis for acute myocardial infarction. The 24 h Holter recordings, begun on start of intravenous thrombolytic therapy, and the 12-lead electrocardiograms of 41 patients with a patent infarct-related artery according to coronary angiography were analysed. The mean time from onset of chest pain to angiography was 30.5±3.1 h, ≥24 h in 59%. The normalization time of the ST segment, assessed by the time of decrease of ST segment elevation from start of Holter recording to normal or steady state was ≥60 min in 13 patients (group 1), 60 to 180 min in 15 patients (group 2) and > 180 min in 13 patients (group 3). The incidence of VA was similar in all groups, except for ventricular tachycardias (VT) >15 beats (group 1:69%, group 2:13%, group 3:15%, P=0.002) The frequency of accelerated idioventricular rhythms (AIVR), early AIVR (≤6 h) and of VT was significantly higher in group 1 than in group 3 with a 8-, 30- and 6- fold increase, respectively (back transformed mean). We conclude that the number of V As is related to the normalization time of the ST segment during reperfusion. This may suggest that faster reflow is more arrhythmogeni

S.4.1 N-terminal pro-brain natriuretic peptide levels predict incident pulmonary arterial hypertension in SSc

Introduction. Pulmonary arterial hypertension (PAH) is a major cause of mortality in SSc. NT-proBNP may be a useful biomarker of prevalent PAH but its role in screening for incident PAH has not been evaluated. Methods. Patients recruited into the Australian Scleroderma Cohort Study undergo annual echocardiography, pulmonary function tests (PFTs), 6-min walk test (6MWT) and have serum NT-proBNP measured (ElecsysproBNP II). The diagnosis of PAH is based on Dana point criteria at right heart catheterization (RHC). Patients with LV dysfunction or eGFR 36 mmHg, (ii) FVC/DLCO% >1.6 and no significant ILD, (iii) DLCO 189.2 pg/ml had a likelihood ratio of 26.4 for presence of PAH (c-statistic = 0.9; sensitivity 85%; specificity 97%). An NT-proBNP level 189.2 pg/ml and <82.9 pg/ml defining patients with a high and low likelihood of PAH, respectively. Further prospective studies are required in unselected patients in order to confirm these finding

Risk factors for death and the 3-year survival of patients with systemic sclerosis: the French ItinérAIR-Sclérodermie study

Objectives. This longitudinal study investigated survival, risk factors and causes of death in the multicentre ItinérAIR-Sclérodermie cohort of patients with SSc without severe pulmonary fibrosis or severe left heart disease at baseline

S.11.1 Influence of digital ulcer healing on disability and daily activity limitations in SSc

Objective. We previously showed that DU significantly increased global and hand disability with a significant impact on activities of daily living (ADLs) and work disability. This study aims to evaluate the impact of digital ulcer (DU) healing on disability and daily activity limitations in SSc. Methods. From January 2008 and June 2009, we prospectively evaluated 189 SSc patients for DU history, disability, employment and occupational status during meetings of the French SSc Patient Association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%)1. Among the 60 patients with at least one active DU at baseline (M0), 40 patients were followed longitudinally over 6 (3) months. These patients were evaluated for DU history, global and hand disability, health-related quality of life (HRQoL), daily activity limitation and employment status. Results. The median (IQR) age was 57.5 (43.5-68) years and the median (IQR) disease duration was 8.3 (3-16.5) years. Twenty-two (55%) patients had diffuse SSc and 34 (85%) were females. At baseline, a mean of 2.9 (2.8) DU per patient was reported. Thirty-three (82.5%) patients had ischaemic DU, 7 (17.5%) patients had >1 DU associated with calcinosis and 13 (32.5%) patients had mechanical DU. Thirteen (32.5%) patients had >4 DU at baseline. Among the 40 patients, 16 (40%) patients showed complete ulcer healing. In these patients with DU, the presence of calcinosis was associated with a lower probability of healing (P = 0.03). Comparison between healed and no-healed DU patients showed an improvement of hand disability provided by an improvement of the Cochin Hand Function score (P = 0.05)) and a trend towards HAQ domain dressing and grooming (P = 0.06) between M0 and M6 (3) visit in healed patients but not in no-healed patients. Concerning HRQoL, there were no difference for Mental and Physical component Scores of SF-36 but significant improvement of Bodily Pain score (P = 0.04) and Physical Role score (P = 0.05) between M0 and M6 (3) visit in patients with healed DU. The absence of healing was associated with significantly decreased work productivity (P = 0.05), whereas the performance in ADL was not significantly decreased (P = 0.15). Patients who were on sick-leave and who received some help for household tasks at the time of active DU were more likely to heal. Conclusion. For the first time, we provide prospective data with evidence that DU healing is associated with an improvement in hand function. Sick leave was associated with better healing of D

Obinutuzumab versus Rituximab in young patients with advanced DLBCL, a PET-guided and randomized phase 3 study by LYSA.

Rituximab plus polychemotherapy is standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED trial compares obinutuzumab to rituximab. GAINED (NCT01659099) is an open-label, randomized phase 3 trial. Transplant-eligible patients (18-60yrs) with untreated aged-adjusted international prognostic index (aaIPI) ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab. Patients were stratified by aaIPI (1; 2-3) and chemotherapy regimen (ACVBP; CHOP). Consolidation treatment was determined according to response assessed by centrally reviewed interim semi-quantitative PET. Responders after cycle 2 and 4 (PET2-/PET4-) received planned immuno-chemotherapy consolidation. Responders only after cycle 4 (PET2+/4-) received highdose methotrexate plus transplantation. The primary objective was an 8% improvement (HR=0.73; 80% power; alpha risk 2.5%; one-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. Events included death, progression, PET 2 or 4 positivity, modification of planned treatment. From September 20, 2012, 670 patients were enrolled (obinutuzumab n=336; rituximab n=334). 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP and 324 (48.4%) received ACVBP. Median follow-up was 38.7 months. The 2-year EFS were similar in obinutuzumab and rituximab groups (59.8% vs 56.6%; p=0.123; HR=0.88). The 2-year PFS in the whole cohort was 83.1% (95%CI 80–85.8). PET2-/4- and PET2+/4- had similar 2-year PFS and OS (89.9% vs 83.9%) and 94.8% vs 92.8%). The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in untreated aaIPI≥1 DLBCL transplant-eligible patients

Bosentan for the treatment of pulmonary arterial hypertension associated with congenital heart defects

Bosentan is an effective first-line therapy in New York Heart Association (NYHA) III patients with idiopathic pulmonary arterial hypertension (PAH). Pre-clinical data support the rationale for the potential benefit of bosentan in PAH associated with congenital heart disease (CHD)

Caractéristiques et suivi prospectif sur deux ans des enfants atteints d'hypertension artérielle pulmonaire

BACKGROUND: Limited data are available describing paediatric pulmonary arterial hypertension. AIMS: To characterize the epidemiology, management and impact on quality of life and outcome of paediatric pulmonary arterial hypertension, excluding persistent pulmonary hypertension of the newborn and pulmonary arterial hypertension caused by congenital heart disease. METHODS: In this multicentre study, children with pulmonary arterial hypertension were included and followed prospectively for two years at 21 referral centres in France. WHO functional class, 6-minute walk distance and quality of life (CHQ-PF50 questionnaire) were evaluated. RESULTS: Fifty children were included with a mean age of 8.9 +/- 5.4 years from May 2005 until June 2006. The estimated prevalence for pulmonary arterial hypertension was 3.7 cases/million. Patients had idiopathic pulmonary arterial hypertension (60%), familial pulmonary arterial hypertension (10%), pulmonary arterial hypertension associated with, but not caused by, congenital heart disease (24%), pulmonary arterial hypertension associated with connective tissue disease (4%) or portal hypertension (2%). During follow-up, the combination of pulmonary arterial hypertension-specific therapies was increasingly prescribed (44% patients versus 22% at inclusion). Patients remained stable regarding clinical status, 6-minute walk distance and quality of life. Survival estimates after one and two years were 86% (95% CI 76, 96) and 82% (95% CI 71, 93), respectively. CONCLUSIONS: In children, idiopathic/familial pulmonary arterial hypertension accounts for the majority of cases. A specific pulmonary arterial hypertension group in conjunction with congenital heart disease can be identified that resembles patients with idiopathic pulmonary arterial hypertension. Combined pulmonary arterial hypertension-specific therapies may have contributed to disease stability and favourable survival