Renal sympathetic denervation in patients with vasospastic angina

Background. Sympathetic overactivity has been linked to vasospastic angina (VSA), although the exact pathophysiology of VSA is poorly understood. The purpose of this study is to assess if renal sympathetic denervation (RDN) reduces cardiac sympathetic nerve activity with a subsequent beneficial effect on angina relief in patients with refractory VSA. Methods and results. Cardiac sympathetic nerve activity was assessed prior to procedure and at 6 months post-procedure using iodine-123 labeled meta-iodobenzylguanidine ( 123I-MIBG) imaging. The Seattle Angina questionnaire (SAQ) was used to assess the degree to which the disease impacts quality of life. No significant change was observed in early HMR (pre-RDN: 2.74 [2.10 to 3.21] vs 6 months post-RDN: 2.57 [2.20 to 3.00]; P = 0.76), and late HMR (pre-RDN: 2.56 [2.18 to 3.20] vs 6 months post-RDN: 2.36 [2.13 to 3.22]; P = 0.22). Additionally, no change was seen in WR (P = 0.22). SAQ results revealed significant improvements in perceived physical limitation, angina frequency, and quality of life at 6 months (P < 0.05 for all). Conclusion. RDN resulted in improvements in angina class and quality of life at 6 months in patients with refractory VSA. RDN, however, did not result in significant changes in cardiac sympathetic nerve activity as measured using 123I-MIBG. The latter observation should be considered with caution given the small sample size of this study. Larger studies are needed to assess this further

Is quantitative analysis superior to visual analysis of planar thallium 201 myocardial exercise scintigraphy in the evaluation of coronary artery disease? - Analysis of a prospective clinical study

Quantitative analysis of myocardial exercise scintigraphy has been previously reported to be superior to visual image interpretation for detection of the presence and extent of coronary artery disease. Computer analysis of perfusion defects and washout rate of thallium 201 was performed on scintigrams from a group of 131 consecutive patients (prospective group), using criteria defined from a previous group of 72 patients (initial group), and compared with visual interpretation of scintigrams for detection and evaluation of coronary artery disease. The sensitivity of the quantitative technique with regard to overall detection of coronary artery disease was not significantly different from the visual method (69% and 74%, respectively), whereas the specificity was higher (86% and 68%). Quantitative analysis did not increase the sensitivity of thallium imaging over the visual method in the left anterior descending artery (46% vs 65%) and the right coronary artery (51% vs 72%) but did increase sensitivity in the left circumflex artery (75% vs 47%). Whereas in the initial group quantitative analysis resulted in a better identification of multivessel disease (sensitivity 81 % vs 57%), in the prospective group sensitivity decreased (54% vs 67%) without significant loss of specificity. The initial group had a 40% incidence of three-vessel disease and the prospective group, 22% (P < 0.05). One-vessel disease was higher in the prospective group (32% vs 11%, P < 0.05). Thus, assessing the quantitative technique in a larger prospective patient population, there was no improvement of detection of the presence and extent of coronary artery disease when compared with visual interpretation

Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma

Background: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3'-deoxy-3'L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods: This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response.

Thallium-201 scintigraphy after dipyridamole infusion with low-level exercise. III Clinical significance and additional diagnostic value of ST segment depression and angina pectoris during the test

Intravenous dipyridamole thallium testing is a useful alternative procedure for assessing coronary artery disease (CAD) in patients who are unable to perform maximal exercise tests. Ischaemic ST segment depression and angina pectoris are frequently observed during the test, in particular when exercise is added to dipyridamole infusion. To establish the clinical significance and additional diagnostic value of these markers of ischaemia during dipyridamole low-level exercise testing (DXT) 57 patients with CAD (group A), 21 patients with normal or near-normal coronary arteries at coronary arteriography (group B), and 20 healthy subjects with low likelihood of CAD (group C) were studied. During DXT ischaemic ST segment depression was observed in 28 patients (47%) of group A and in two patients (10%) of group B. Angina pectoris was experienced by 35 patients (61%) of group A and by five patients (24%) of group B. The positive predictive value of both ST depression and angina pectoris was high (88 and 93%, respectively), but the negative predictive values were low (42 and 40%, respectively). Combining ST segment analysis with the findings of thallium imaging significantly increased the diagnostic accuracy of the test. ST segment depression, angina pectoris, and thallium abnormalities were highly specific findings if the study population consisted of asymptomatic subjects with a low likelihood of CAD (group C). Sensitivity for the detection of the presence of CAD increased with the extent of CAD for all parameters studied. Thus, ST depression and angina pectoris, alone or in combination, during DXT have little diagnostic significance, although sensitivity is increased in patients with triple-vessel CAD.(ABSTRACT TRUNCATED AT 250 WORDS