Quantitative magnetic resonance perfusion imaging detects anatomic and physiologic coronary artery disease as measured by coronary angiography and fractional flow reserve.

OBJECTIVES: To evaluate the ability of quantitative perfusion cardiac magnetic resonance (CMR) to assess the hemodynamic significance of coronary artery disease (CAD) compared with well-established anatomic and physiologic techniques. BACKGROUND: Fractional flow reserve (FFR) is considered by many investigators to be a reliable stenosis-specific method to determine hemodynamically significant CAD. Quantitative perfusion CMR is a promising noninvasive approach to detect CAD but has yet to be validated against FFR. METHODS: This is a prospective study in patients with suspected CAD who underwent coronary angiography, FFR, and CMR assessments. The quantitative myocardial perfusion reserve (MPR) was calculated in 720 myocardial sectors (8 sectors/slice). The MPR was calculated from the ratio between stress and rest myocardial flow based on signal intensity time curves using deconvolution analysis. Stress was simulated with adenosine for both FFR and MPR. The MPR assessments were compared to FFR (n = 44 coronary segments) and quantitative coronary angiography (n = 108 segments) in the corresponding coronary territories. RESULTS: The MPR was 1.54 +/- 0.36 in segments with FFR < or =0.75 (n = 14) and 2.11 +/- 0.68 in those with FFR >0.75 (n = 30; p = 0.0054). An MPR cutoff of 2.04 was 92.9% (95% CI 77.9 to 100.0) sensitive and 56.7% (95% CI 32.8 to 80.6) specific in predicting a coronary segment with FFR < or =0.75. The MPR was 1.54 +/- 0.49 in coronary segments with > or =50% diameter stenosis (DS) (n = 47) and 2.13 +/- 0.80 in segments with <50% DS (n = 61; p < 0.001). An MPR cutoff of 2.04 was 85.1% (95% CI 71.1 to 99.2) sensitive and 49.2% (95% CI 33.6 to 64.8) specific in predicting CAD with > or =50% DS. CONCLUSIONS: Quantitative perfusion CMR is a safe noninvasive test that represents a stenosis-specific alternative to determine the hemodynamic significance of CAD.     

Symptoms of advanced heart failure—A case for radiofrequency catheter ablation?

A sixty-year-old man with previous history of coronary artery disease was admitted due to progressive worsening of dyspnoea at exertion (NYHA III functional class) and no angina. Coronary angiography confirmed occlusion of the right coronary artery which was naturally bypassed by homocollaterals with TIMI 3 flow to the peripheral branches. The lesion was not technically suitable for percutaneous angioplasty. The left coronary artery was without stenosis. On echocardiography, both the left ventricle and the left atrium were dilated and hemodynamically significant mitral regurgitation was present. Surface ECG showed a left bundle branch block with repeated runs of monomorphic ventricular ectopic beats (PVC). Radiofrequency catheter ablation of the focus in the posteroseptal region of the left ventricle underneath the mitral valve was performed using electroanatomical mapping system. After the procedure, mitral regurgitation decreased and reverse remodeling of the left ventricle and the left atrium occurred with concomitant significant clinical improvement of the patient. The authors discuss several treatment strategies: mitral valve repair surgery combined with revascularization, implantation of a biventricular ICD system or elimination of the focus of monomorphic VT runs by radiofrequency catheter ablation as a possible causal approach in the treatment of PVC-induced cardiomyopathy.     

Ten most notable family medicine research studies in Canada

Objective

To identify 10 noteworthy Canadian family medicine research studies that have affected practice in order to demonstrate the unique value that Canadian family medicine research offers.

Composition of the committee

Representatives from the Section of Researchers (SOR) and the Health Policy and Government Relations department of the College of Family Physicians of Canada developed a framework for inclusion and identified an initial list of articles. Members of the SOR Council and research directors from the 17 Canadian departments of family medicine reviewed the preliminary list and suggested additional studies.

Methods

The authors developed an initial list of studies carried out by Canadian family medicine researchers from those researchers who had received awards from the College of Family Physicians of Canada since 2002. Additional studies were proposed by members of the SOR Council and the university research directors. A total of 36 published articles were reviewed by the SOR authors, and an annotated short list of 16 articles was prepared. From that list, the other authors identified 7 noteworthy studies that were used to form the basis of advocacy materials. The SOR authors, along with 3 additional members of the SOR Executive, used an informal consensus process to select the final 3 articles to arrive at the top 10.

Report

The top 10 most noteworthy family medicine research studies are presented in this article and represent the unique contribution that Canadian family medicine research brings to health care in Canada. They have helped advance health care quality and improve care delivery, beneficially influencing health care practices, health care policy, and patient experiences.

Conclusion

This project has identified 10 classic Canadian family medicine research studies that continue to influence practice today. In addition to their usefulness as tools for teaching, advocating, and championing the contribution of research to modern family practice, these studies are important examples of the value of research to patient health in Canada and around the world.     

CXCL13 antibody for the treatment of autoimmune disorders

Background

Homeostatic B Cell-Attracting chemokine 1 (BCA-1) otherwise known as CXCL13 is constitutively expressed in secondary lymphoid organs by follicular dendritic cells (FDC) and macrophages. It is the only known ligand for the CXCR5 receptor, which is expressed on mature B cells, follicular helper T cells (Tfh), Th17 cells and regulatory T (Treg) cells. Aberrant expression of CXCL13 within ectopic germinal centers has been linked to the development of autoimmune disorders (e.g. Rheumatoid Arthritis, Multiple Sclerosis, Systemic Lupus Erythematosis). We, therefore, hypothesized that antibody-mediated disruption of the CXCL13 signaling pathway would interfere with the formation of ectopic lymphoid follicles in the target organs and inhibit autoimmune disease progression. This work describes pre-clinical development of human anti-CXCL13 antibody MAb 5261 and includes therapeutic efficacy data of its mouse counterpart in murine models of autoimmunity.

Results

We developed a human IgG1 monoclonal antibody, MAb 5261 that specifically binds to human, rodent and primate CXCL13 with an affinity of approximately 5 nM and is capable of neutralizing the activity of CXCL13 from these various species in in vitro functional assays. For in vivo studies we have engineered a chimeric antibody to contain the same human heavy and light chain variable genes along with mouse constant regions. Treatment with this antibody led to a reduction in the number of germinal centers in mice immunized with 4-Hydroxy-3-nitrophenylacetyl hapten conjugated to Keyhole Limpet Hemocyanin (NP-KLH) and, in adoptive transfer studies, interfered with the trafficking of B cells to the B cell areas of mouse spleen. Furthermore, this mouse anti-CXCL13 antibody demonstrated efficacy in a mouse model of Rheumatoid arthritis (Collagen-Induced Arthritis (CIA)) and Th17-mediated murine model of Multiple Sclerosis (passively-induced Experimental Autoimmune Encephalomyelitis (EAE)).

Conclusions

We developed a novel therapeutic antibody targeting CXCL13-mediated signaling pathway for the treatment of autoimmune disorders.