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Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG)., Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction., Findings: In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001)., Interpretation: (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease., Funding: Chief Scientist Office Scotland and British Heart Foundation., (Copyright © 2014 Joshi et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

Background: Coronary atherosclerotic-plaque thrombosis is a key event in the pathogenesis of unstable angina and myocardial infarction. Although plaque rupture or fissuring frequently occurs in atherosclerosis, only a small proportion of ruptured plaques develop thromboses., Methods: Tissue-factor antigen and activity were measured in atherectomy samples from 50 consecutive patients with coronary artery disease (stable angina n = 19, unstable angina n = 24, and myocardial infarction n = 7)., Findings: Median tissue-factor antigen and activity concentrations were significantly higher in plaques from patients with unstable angina and myocardial infarction than in those from patients with stable angina (antigen: 66.1 pg/mg [interquartile range 43.8-82.5] vs 32.4 pg/mg [9.8-43.4], p = 0.0001; activity: 0.22 mU/mg [0.17-0.41] vs 0.13 mU/mg [0.05-0.16], p = 0.0004)., Interpretation: Tissue-factor, an initiator of the coagulation cascade, may account for the different thrombotic responses to the rupture of human coronary atherosclerotic plaques.

Patients with microvascular angina (syndrome X) may be insulin resistant. We designed a study to establish whether this is the case. 11 patients with microvascular angina were compared with 9 matched subjects with noncardiac chest pain. Patients and controls were evaluated by coronary sinus catheterisation, and by isotopic measurement of glucose turnover, indirect calorimetry, and forearm technique during a 3 h baseline period after overnight fast and during a 2 h hyperinsulinaemic euglycaemic clamp. Pace-induced increase in coronary sinus blood flow was less in patients than in controls, whereas forearm blood flow did not differ between groups. Baseline measures of glucose metabolism were normal. During the clamp, glucose production and lipolysis were equally suppressed in both groups. Mean (SE) total insulin-induced glucose uptake was significantly impaired in patients compared with controls (3.9 [0.7] vs 6.4 [0.7] mg/kg per min; p < 0.01), and insulin-stimulated glucose uptake in the forearm was significantly reduced in patients (0.88 [0.10] vs 1.6 [0.30] mmol/L; p < 0.001). Reduced oxidative and nonoxidative metabolism accounted for the defect in overall glucose uptake in patients. No correlation between changes in coronary sinus blood flow and total body glucose uptake was seen. We found that microvascular angina was associated with substantial insulin resistance. Whether this relation is causal or coincidental is as yet unsettled.

The development and pathophysiology of myocardial ischaemia is a dynamic process in which increased myocardial oxygen demand or decreased coronary blood flow are not the sole determinants. Both these factors are inappropriately altered before, during, or after the onset of ischaemia, and a vicious cycle ensues. Drug therapy should be aimed at not only preventing the development of myocardial ischaemia but also at reversing the abnormal hormonal, metabolic, and haemodynamic effects.

The warm-up phenomenon, in which the second of two successive exercise tests manifests less ischaemia than the first, was studied to find out whether it results from decreased myocardial oxygen consumption or from increased coronary-artery blood-flow during the second test. Patients performed an initial exercise test, then continued to exercise for 30 minutes after which they rested for 20 minutes. They then repeated the exercise test with a work load and duration identical to the first. 21 (95%) of 22 patients tested with a bicycle and 9 (75%) of 12 patients tested by a modified two-step test had less electrocardiographic evidence of ischaemia on the second test than on the first. Rate-pressure products at peak exercise suggested that the lessened ischaemia was not due to decreased mnyocardial oxygen consumption. Rather, the warm-up phenomenon seemed to result from increased coronary flow. It can be evoked in most patients who have an ischaemic response to exercise.

8 patients with exertional angina pectoris were treated for 3 months with a low-fat, low-calorie diet. Serum cholesterol was reduced by 28% and body-weight by 7.9 kg on average. The effect of the dietary intervention was assessed by a heart metabolic study during pacing-induced tachycardia. After dietary treatment coronary sinus blood-flow and myocardial oxygen consumption were considerably reduced, but pacing time before angina developed increased. Other improvements were a reduction in lactate release during pacing, a reduction in citrate release during recovery, a reduction in alanine output during rest and recovery, and a lower uptake of glutamate. The results suggest a beneficial effect of low-fat, low-calorie dietary treatment on myocardial energy metabolism in patients with exertional angina pectoris.