Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The Computerized Index of Medieval Medical Images (IMMI) : Challenges and solutions

Infusino M. H., Layne Sara Shatford, Viole O’Neill Ynez. The Computerized Index of Medieval Medical Images (IMMI) : Challenges and solutions. In: Le médiéviste et l'ordinateur, N°26-27, Automne 1992 - printemps 1993 1992. Traitements informatiques et iconographie. pp. 11-13

J Wave, QRS Slurring and ST Elevation in Athletes with Cardiac Arrest in the Absence of Heart Disease : Marker of Risk, or Innocent Bystander?

Background-QRS-ST changes in the inferior and lateral ECG leads are frequently observed in athletes. Recent studies have suggested a potential arrhythmogenic significance of these findings in the general population. The aim of our study was to investigate whether QRS-ST changes are markers of cardiac arrest (CA) of unexplained cause or sudden death in athletes. Methods and Results-In 21 athletes (mean age 27 years; 5 women) with cardiac arrest or sudden death the ECG recorded before or immediately after the clinical event was compared with the ECG of 365 healthy athletes eligible for competitive sport activity. We measured the height of the J wave and ST elevation and searched for the presence of QRS slurring in the terminal portion of QRS. QRS slurring in any lead was present in 28.6% of cases and in 7.6% of control athletes (P=0.006). A J wave and/or QRS slurring without ST elevation in the inferior (II III and aVF) and lateral leads (V4 to V6) were more frequently recorded in cases than in control athletes (28.6% versus 7.9% P=0.007). Among those with cardiac arrest arrhythmia recurrences did not differ between the subgroups with and without J wave or QRS slurring during a median 36-month follow-up of sport discontinuation. Conclusions-J wave and/or QRS slurring was found more frequently among athletes with cardiac arrest/sudden death than in control athletes. Nevertheless, the presence of this ECG pattern appears not to confer a higher risk for recurrent malignant ventricular arrhythmias

Prevention of long-lasting atrial fibrillation through antitachycardia pacing in DDDR pacemakers

Objective: The MINERVA trial showed that in pacemaker patients with atrial fibrillation (AF) history, DDDRP pacing combining three algorithms – (a) atrial antitachycardia pacing with Reactive ATP enabled, (b) atrial preventive pacing and (c) managed ventricular pacing (MVP)—may effectively delay progression to persistent/permanent AF compared with standard DDDR pacing. We performed a comparative non-randomised evaluation to evaluate if Reactive ATP can be the main driver of persistent/permanent AF reduction independently on preventive pacing. Methods: Thirty-one centres included consecutive dual-chamber pacemaker patients with AF history. Reactive ATP was programmed in all patients while preventive atrial pacing was not enabled. These patients were compared with the three groups of MINERVA randomised trial (Control DDDR, MVP, and DDDRP). The main endpoint was the incidence of AF longer than 7 consecutive days. Results: A total of 146 patients (73 years old, 54% male) were included and followed for a median observation period of 31 months. The 2-year incidence of AF > 7 days was 12% in the Reactive ATP group, very similar to that found in the DDDRP arm of the MINERVA trial (13.8%, P =.732) and significantly lower than AF incidence found in the MINERVA Control DDDR arm (25.8%, P =.012) and in the MINERVA MVP arm (25.9%, P =.025). Conclusions: In a real-world population of dual-chamber pacemaker patients with AF history, the use of Reactive ATP is associated with a low incidence of persistent AF, highlighting that the positive results of the MINERVA trial were related to the effectiveness of Reactive ATP rather than to preventive pacing

Myval versus alternative balloon- and self-expandable transcatheter heart valves: A central core lab analysis of conduction disturbances

Background: Several studies have compared surface electrocardiographic changes following different self-expandable (SE) (Evolut (Medtronic, USA); Acurate (Boston Scientific, USA); Portico (Abbott, USA); and Allegra (NVT, Germany)) and balloon-expandable (BE) Sapien-3 (Edwards Lifesciences, USA) transcatheter heart valves. We aimed to compare these prosthesis with the novel Myval BE prosthesis (Meril Life, India). Methods: Academic European registry of consecutive patients with severe aortic stenosis who received any of the 6 aforementioned valves. Baseline, post-procedural, and discharge 12‑leads electrocardiograms (ECG) were centrally analyzed and compared. Results: A total of 1131 patients were included: 135 Myval (11.9%), 290 Sapien-3 (25.6%), 298 Evolut (26.3%), 180 Acurate (15.9%), 125 Portico (11.1%), and 103 Allegra (9.1%). There were no baseline differences in intraventricular conduction disturbances rate. Compared to the novel BE Myval, there were similar procedural and in-hospital outcomes. Similar rates of early new permanent pacemaker implant (PPI) were observed amongst Myval (7.4%), Sapien-3 (13.4%), and Acurate (9.1%), but Evolut, Portico, and Allegra presented significantly higher rates (18.5%, p = 0.003; 29.5% p < 0.001 and 22%, p = 0.001, respectively). Central analysis of ECGs, unraveled significant prolongation of the PR segment with Evolut, Portico and Allegra whereas Evolut, Acurate, and Portico showed significant QRS widening compared to Myval. However, at discharge no differences in PR segment duration were observed while, Evolut, and Portico– but not Acurate, Allegra or Sapien-3 – still presented significant widening of QRS segment compared to Myval. Conclusions: After blinded central ECG analysis, the novel Myval balloon-expandable prosthesis was associated with a low rate of early conduction disturbances