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.

Exploration of time sequential, patient specific 3D heart unlocks clinical understanding

Abstract Objectives The purpose was to create a time sequential three-dimensional virtual reality model, also referred to as a four-dimensional model, to explore its possible benefit and clinical applications. We hypothesized that this novel solution allows for the visuospatial benefits of the 3D model and the dynamic benefits of other existing imaging modalities. Background We have seen how 3D models hold great value in medical decision making by eliminating the variable visuospatial skills of practitioners. They have proved especially invaluable concerning the correction of congenital heart defects and have altered the course of many surgeries. There are, however, limitations to three-dimensional models. The static models only show what the heart looks like in one snapshot of its cycle and do not allow for an understanding of the physiological and dynamic processes. Methods This solution segments a 3D heart derived from a 2D image stack, times the 18 phases of a cardiac cycle and creates a 4D model that can be manipulated in space and time through the use of virtual reality. Results We believe the 4D heart provides a unique understanding of in situ cardiac anatomy not possible with other imaging techniques. Our expanding case series of clinician experiences and their immediate recognition of the potency of this technique is highly encouraging and reveals the future of functional and dynamic 4D representations of anatomy. Conclusions The 4D heart improved our understanding around complex 3D relationships over time. We propose time and effort dedicated to 4D cardiac imaging analysis of dynamic cardiac pathologies such as hypertrophic obstructive cardiomyopathy or a pre-op Rastelli repair with a narrow outflow tract could offer tremendous insight into the medical decision-making process

SMI Life Goals: Description of a randomized trial of a Collaborative Care Model to improve outcomes for persons with serious mental illness

Background Persons with serious mental illnesses (SMI) are more likely to die earlier than the general population, primarily due to increased medical burden, particularly from cardiovascular disease (CVD). Life Goals Collaborative Care (LG-CC) is designed to improve health outcomes in SMI through self-management, care management, and provider support. This single-blind randomized controlled effectiveness study will determine whether patients with SMI receiving LG-CC compared to usual care (UC) experience improved physical health in 12 months. Methods Patients diagnosed with SMI and at least one CVD risk factor receiving care at a VA mental health clinic were randomized to LG-CC or UC. LG-CC included five self-management sessions covering mental health symptom management reinforced through healthy behavior change; care coordination and health monitoring via a registry, and provider feedback. The primary outcome is change in physical health-related quality of life score (VR-12) from baseline to 12 months. Secondary outcomes include changes in mental health-related quality of life, CVD risk factors (blood pressure, BMI), and physical activity from baseline to 12 months later. Results Out of 304 enrolled, 139 were randomized to LG-CC and 145 to UC. Among patients completing baseline assessments (N=284); the mean age was 55.2 (SD=10.9; range 28-75 years), 15.6% were women, the majority (62%) were diagnosed with depression, and the majority (63%) were diagnosed with hypertension or were overweight (BMI mean±SD=33.3±6.3). Baseline VR-12 physical health component score was below population norms (50.0±SD=10) at 33.4±11.0. Conclusions Findings from this trial may inform initiatives to improve physical health for SMI patient populations.Psycholog