Arterial spin labeled MRI detects clinically relevant increases in myocardial blood flow with vasodilatation

ObjectivesThis study sought to determine whether arterial spin labeled (ASL) cardiac magnetic resonance (CMR) is capable of detecting clinically relevant increases in regional myocardial blood flow (MBF) with vasodilator stress testing in human myocardium.BackgroundMeasurements of regional myocardial perfusion at rest and during vasodilatation are used to determine perfusion reserve, which indicates the presence and distribution of myocardial ischemia. ASL CMR is a perfusion imaging technique that does not require any contrast agents, and is therefore safe for use in patients with end-stage renal disease, and capable of repeated or continuous measurement.MethodsMyocardial ASL scans at rest and during adenosine infusion were incorporated into a routine CMR adenosine induced vasodilator stress protocol and was performed in 29 patients. Patients who were suspected of having ischemic heart disease based on first-pass imaging also underwent x-ray angiography. Myocardial ASL was performed using double-gated flow-sensitive alternating inversion recovery tagging and balanced steady-state free precession imaging at 3-T.ResultsSixteen patients were found to be normal and 13 patients were found to have visible perfusion defect based on first-pass CMR using intravenous gadolinium chelate. In the normal subjects, there was a statistically significant difference between MBF measured by ASL during adenosine infusion (3.67 ± 1.36 ml/g/min), compared to at rest (0.97 ± 0.64 ml/g/min), with p < 0.0001. There was also a statistically significant difference in perfusion reserve (MBFstress/MBFrest) between normal myocardial segments (3.18 ± 1.54) and the most ischemic segments in the patients with coronary artery disease identified by x-ray angiography (1.44 ± 0.97), with p = 0.0011.ConclusionsThis study indicates that myocardial ASL is capable of detecting clinically relevant increases in MBF with vasodilatation and has the potential to identify myocardial ischemia

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.

Cytokine and Chemokine Concentrations as Biomarkers of Feline Mycobacteriosis

Abstract Mycobacteriosis is an emerging zoonotic disease of domestic cats and timely, accurate diagnosis is currently challenging. To identify differential cytokine/chemokine concentrations in serum/plasma of cats, which could be diagnostic biomarkers of infection we analysed plasma/serum from 116 mycobacteria-infected cats, 16 healthy controls and six cats hospitalised for unrelated reasons was analysed using the Milliplex MAP Feline Cytokine Magnetic Bead multiplex assay. Three cytokines; sFAS, IL-13 and IL-4 were reduced while seven; GM-CSF, IL-2, PDGF-BB, IL-8, KC, RANTES and TNF-α were elevated in mycobacteria-infected cats compared to healthy controls. However, IL-8 and KC concentrations were not significantly different from cats hospitalised for other reasons. Elevations in TNF-α and PDGF-BB may have potential to identify M. bovis and M. microti infected cats specifically while GM-CSF, IL-2 and FLT3L were increased in MTBC infected cats. This study demonstrates potential use of feline tuberculosis as a spontaneously occurring model of this significant human disease. Cytokine profiling has clear diagnostic potential for mycobacteriosis of cats and could be used discriminate tuberculous from non-tuberculous disease to rapidly inform on zoonotic risk. Future work should focus on the in-field utility of these findings to establish diagnostic sensitivity and specificity of these markers