Images in cardiovascular medicine. The blue man: amiodarone-induced skin discoloration.
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Amiodarone↗
Biomedical subjects
Christophe A Wyss
Publications and source records attributed to Christophe A Wyss.
Caffeine decreases exercise-induced myocardial flow reserve.
OBJECTIVES: We studied the acute effect of caffeine on myocardial blood flow (MBF) at rest and exercise in healthy volunteers at normoxia and during acute exposure to simulated altitude. BACKGROUND: Caffeine is a widely consumed stimulant, although its cardiovascular safety remains controversial and its effect on MBF is unknown. METHODS: 15O-labeled H2O and positron emission tomography (PET) were used to measure regional MBF at rest and immediately after supine bicycle exercise in healthy volunteers at normoxia (n = 10; mean workload, 175 W; 98% predicted; mean age, 27 +/- 6 years) as well as during hypoxia, simulating an altitude of 4,500 m by inhalation of a mixture of 12.5% oxygen (n = 8; 148 W; 78% predicted; mean age, 29 +/- 4 years). Measurements were repeated 50 min after oral ingestion of caffeine (200 mg). Myocardial flow reserve (MFR) was calculated as the ratio of hyperemic to resting MBF. RESULTS: Resting MBF was not affected by caffeine at normoxia (1.05 +/- 0.36 ml/min/g vs. 1.17 +/- 0.27 ml/min/g; p = NS), although it was significantly increased at hypoxia (1.71 +/- 0.41 ml/min/g vs. 2.22 +/- 0.49 ml/min/g; p < 0.001). By contrast, exercise-induced hyperemic MBF decreased significantly at normoxia (2.51 +/- 0.58 ml/min/g vs. 2.15 +/- 0.47 ml/min/g; p < 0.05) and hypoxia (5.15 +/- 0.79 ml/min/g vs. 3.98 +/- 0.83 ml/min/g; p < 0.005 vs. baseline; p < 0.005 vs. normoxia). The MFR decreased by 22% at normoxia (2.53 +/- 0.69 to 1.90 +/- 0.49; p < 0.01) and by 39% at hypoxia (3.13 +/- 0.60 to 1.87 +/- 0.45, p < 0.005; p < 0.05 vs. normoxia). CONCLUSIONS: In healthy volunteers, a caffeine dose corresponding to two cups of coffee (200 mg) significantly decreased exercise-induced MFR at normoxia and was even more pronounced during exposure to altitude.
Adult↗
Platelet inhibition in percutaneous coronary interventions.
Mechanical disruption of atherosclerotic plaques at the time of percutaneous coronary intervention (PCI) is a potent stimulus for arterial thrombosis. Since platelets play a crucial role in the cascade of clot formation, platelet inhibition is an essential step for successful PCI. Aspirin remains the cornerstone of any antithrombotic regimen in the interventional setting. The addition of a thienopyridine is mandatory following stenting to prevent thrombosis of the device. Whenever possible, patients undergoing PCI should be pretreated with clopidogrel and the drug should be continued for up to 1 year. Glycoprotein IIb/IIIa antagonists should be administered in high-risk patients, such as those with acute coronary syndromes, diabetes, or complex coronary anatomy.
Angioplasty, Balloon, Coronary↗
Integrated PET/CT for the assessment of coronary artery disease: a feasibility study.
UNLABELLED: An accurate, noninvasive technique for the diagnosis of coronary artery disease (CAD) should provide complementary information on coronary anatomy and pathophysiologic lesion severity. We present, what is to our knowledge, the first clinical evaluation of integrated PET/CT for combined acquisition of coronary anatomy and perfusion. METHODS: On an integrated PET/CT scanner, contrast-enhanced CT angiography (CTA) and rest/adenosine-stress myocardial perfusion scanning with (13)N-ammonia were performed on 25 patients with CAD documented by coronary angiography. Contrast-enhanced CTA was performed with retrospective electrocardiography gating after injection of 150 mL of intravenous contrast medium. Decisions on whether to treat with revascularization (anatomic lesion plus ischemia) or conservatively (no lesion or no ischemia) based on PET/CT were compared with those based on PET plus coronary angiography. RESULTS: Of the 100 coronary artery segments (left main, left anterior descending, left circumflex, and right in 25 patients), 7 (in 5 patients) were considered impossible to evaluate by CT because of rapid vessel movement but were correctly categorized by PET alone. In the remaining 93 segments, the sensitivity and specificity of PET/CT versus PET plus coronary angiography were 90% and 98%, respectively. Positive and negative predictive values were 82% and 99%, and accuracy was 97%. CONCLUSION: The data of this preliminary study suggest that PET/CT allows accurate noninvasive clinical decision making about CAD. Because of its high negative predictive value, PET/CT may play an important role in noninvasive selection of CAD patients for revascularization. Integration of higher-performance multislice spiral CT scanners into PET/CT hybrids will accelerate the clinical implementation of this technique.
Adult↗
Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia.
PURPOSE: Tetrahydrobiopterin (BH4) is an essential co-factor for the synthesis of nitric oxide (NO), and BH4 deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH4 deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia. METHODS: Myocardial blood flow (MBF; ml min(-1) g(-1)) was measured at rest, during adenosine-induced (140 microg kg(-1) min(-1) over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using 15O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH4 (10 mg kg(-1) body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress. RESULTS: BH4 increased exercise-induced hyperaemia in controls (2.96+/-0.58 vs 3.41+/-0.73 ml min(-1) g(-1), p<0.05) and hypercholesterolaemic subjects (2.47+/-0.78 vs 2.70+/-0.72 ml min(-1) g(-1), p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52+/-1.10 vs 4.85+/-0.45 ml min(-1) g(-1), p=NS) or hypercholesterolaemic subjects (4.86+/-1.18 vs 4.53+/-0.93 ml min(-1) g(-1), p=NS). Flow reserve utilisation remained unchanged in controls (70+/-17% vs 71+/-19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53+/-15% vs 66+/-14%, p<0.05). CONCLUSION: BH4 restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH4 deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemia.
Adult↗
CT attenuation correction for myocardial perfusion quantification using a PET/CT hybrid scanner.
UNLABELLED: In routine PET, a 10- to 20-min transmission scan with a rotating (68)Ge source is commonly obtained for attenuation correction (AC). AC is time-consuming using this procedure and could considerably be shortened by instead using a rapid CT scan. Our aim was to evaluate the feasibility of CT AC in quantitative myocardial perfusion PET using a hybrid PET/CT scanner. METHODS: (13)N-labeled NH(3) and PET were used to measure myocardial blood flow (MBF) (mL/min/g) at rest and during standard adenosine stress. In group 1 (n = 7), CT scans (0.5 s) of the heart area with different tube currents (10, 40, 80, and 120 mA) were compared with a standard (68)Ge transmission (20 min) and with no AC. In group 2 (n = 3), the repeatability of 8 consecutive CT scans at a tube current of 10 mA was assessed. In group 3 (n = 4), emission was preceded and followed by 3 CT scans (10 mA) and 1 (68)Ge scan for each patient. For reconstruction, filtered backprojection (FBP) was compared with iterative reconstruction (IT). RESULTS: For group 1, no significant difference in mean MBF for resting and hyperemic scans was found when emission reconstructed with (68)Ge AC was compared with emission reconstructed with CT AC at any of the different tube currents. Only emission without any correction differed significantly from (68)Ge AC. For group 2, repeated measurements revealed a coefficient of variance ranging from 2% to 5% and from 2% to 6% at rest and at stress, respectively. For group 3, similar reproducibility coefficients (RC) for MBF were obtained when (68)Ge AC(FBP) was compared with (68)Ge AC(IT) (RC = 0.218) and when CT AC(FBP) was compared with CT AC(IT) (RC = 0.227). Even better reproducibility (lower RC) was found when (68)Ge AC(FBP) was compared with CT AC(FBP) (RC = 0.130) and when (68)Ge AC(IT) was compared with CT AC(IT) (RC = 0.146). CONCLUSION: Our study shows that for the assessment of qualitative and quantitative MBF with a hybrid PET/CT scanner, the use of CT AC (with a tube current of 10 mA) instead of (68)Ge AC provides accurate results.
Algorithms↗
Gated (99m)Tc-tetrofosmin SPECT for discriminating infarct from artifact in fixed myocardial perfusion defects.
UNLABELLED: Soft-tissue attenuation artifacts generally appear as fixed perfusion-scan defects. Gated (99m)Tc-tetrofosmin SPECT may help differentiate myocardial infarction (MI) from artifacts, as fixed defects with decreased function (wall motion and thickening) probably represent MI, whereas attenuation artifacts represent preserved function. METHODS: Ungated stress and gated rest (99m)Tc-tetrofosmin SPECT was performed on 153 consecutive patients referred for evaluation of coronary artery disease. From stress and summed gated rest images, 107 patients (70%) were identified with isolated fixed defects. The function of the defects was assessed semiquantitatively from gated stress images. The findings were correlated with clinical (history or electrocardiographic Q waves) evidence of MI. RESULTS: Of 62 patients with fixed defects and clinical MI, 60 (97%) had an abnormal defect function. Of 45 patients with no clinical MI, 16 (36%) had decreased function of the defect, possibly indicating silent MI. In 29 of the 45 patients (64%) with no clinical MI, defect function was normal. Because most (90%) fixed defects with normal systolic function occurred in men with inferior fixed defects (87%) or women with anterior fixed defects (3%), these were most likely attenuation artifacts. By reclassifying the condition of patients with fixed defects and normal function as normal, patients with unexplained fixed defects (no clinical MI) decreased from 29% to 10%. CONCLUSION: Gating adds considerable value to (99m)Tc-tetrofosmin SPECT myocardial perfusion imaging in characterizing fixed defects and potentially improves test specificity.
Adenosine↗
Beta-adrenergic blockade and myocardial perfusion in coronary artery disease: differential effects in stenotic versus remote myocardial segments.
UNLABELLED: Beta-adrenergic blocking agents are widely used in coronary artery disease (CAD), although their impact on myocardial blood flow (MBF) and coronary flow reserve (CFR) remains unclear. We studied the effect of long-term beta-blocker treatment (carvedilol or metoprolol) on coronary microcirculation in CAD patients using PET. METHODS: Regional and global resting and adenosine-induced hyperemic MBF and CFR were measured with 13N-ammonia and PET in 36 CAD patients before and after 12 wk of oral therapy with either carvedilol, 50 mg/d, or metoprolol, 100 mg/d. RESULTS: Beta-blockade decreased global resting MBF in proportion to cardiac work (from 0.86 +/- 0.20 to 0.77 +/- 0.14 mL/min/g, P < 0.05) without affecting global hyperemic flow. Hyperemic MBF was significantly lower in stenosis-dependent segments than in remote segments (1.76 +/- 0.64 vs. 2.04 +/- 0.67 mL/min/g, P < 0.05) at baseline but was comparable in both after treatment (2.02 +/- 0.68 vs. 1.90 +/- 0.78 mL/min/g, P = not statistically significant [NS]), resulting in a significant CFR increase in stenotic segments (+15%, P < 0.05) but not in remote segments (+9%, P = NS). CONCLUSION: The beneficial effect of beta-adrenergic blockade can be explained by the reduction in oxygen consumption (= decreased demand) but also by a modest improvement in vasodilator capacity (= increased supply). The improvement in CFR is found predominantly in stenosis-dependent rather than remote segments.
Adrenergic beta-Antagonists↗
Influence of altitude exposure on coronary flow reserve.
BACKGROUND: Although no data exist on the effect of altitude exposure on coronary flow reserve (CFR), patients with coronary artery disease (CAD) are advised not to exceed moderate altitudes of approximately 2500 m above sea level. We studied the influence of altitude on myocardial blood flow (MBF) in controls and CAD patients. METHODS AND RESULTS: In 10 healthy controls and 8 patients with CAD, MBF was measured by positron emission tomography and 15O-labeled water at rest, during adenosine stress, and after supine bicycle exercise. This protocol was repeated during inhalation of a hypoxic gas mixture corresponding to an altitude of 4500 m (controls) and 2500 m (CAD). Workload was targeted to comparable heart rate-blood pressure products at normoxia and hypoxia. Resting MBF increased significantly in controls at 4500 m (+24%, P<0.01) and in CAD patients at 2500 m (+24%, P<0.05). Altitude had no influence on adenosine-induced hyperemia and CFR. Exercise-induced hyperemia increased significantly in controls (+38%, P<0.01) at 4500 m (despite a reduction in workload, -28%, P<0.0001) but not in CAD patients at 2500 m (moderate decrease in workload, -11%, P<0.05). Exercise-induced reserve was preserved in controls (+10%, P=NS) but decreased in CAD patients (-18%, P<0.005). CONCLUSIONS: At 2500 m altitude, there is a significant decrease in exercise-induced reserve in CAD patients, indicating that compensatory mechanisms might be exhausted even at moderate altitudes, whereas healthy controls have preserved reserve up to 4500 m. Thus, patients with CAD and impaired CFR should be cautious when performing physical exercise even at moderate altitude.
Adult↗
Bicycle exercise stress in PET for assessment of coronary flow reserve: repeatability and comparison with adenosine stress.
UNLABELLED: PET allows absolute measurements of myocardial blood flow (MBF). The aim of the present study was to evaluate the feasibility and repeatability of supine bicycle exercise stress, compared with standard adenosine stress, in PET. METHODS: In 11 healthy volunteers, MBF was assessed at rest, during adenosine-induced (140 microg/kg/min over 7 min) hyperemia, and immediately after supine bicycle exercise (mean workload, 130 W, which is 70% of the predicted value) using PET and (15)O-H(2)O. The assessment was then repeated after 20 min. Coronary flow reserve (CFR) was calculated as hyperemic/resting MBF for adenosine stress and exercise stress. Repeatability was evaluated according to the method of Bland and Altman. RESULTS: No significant differences were found between the paired resting MBF (1.22 +/- 0.16 vs. 1.26 +/- 0.21 mL/min/g; mean difference, 3% +/- 11%) and the hyperemic MBF with adenosine stress (5.13 +/- 0.74 vs. 4.97 +/- 1.05; mean difference, -4% +/- 14%) or exercise stress (2.35 +/- 0.66 vs. 2.25 +/- 0.61; mean difference, -4% +/- 19%). CFR was reproducible with adenosine stress (4.23 +/- 0.62 vs. 4.05 +/- 1.06, P = not statistically significant; mean difference, -5% +/- 19%) and exercise stress (1.91 +/- 0.46 vs. 1.80 +/- 0.44, P = not statistically significant; mean difference, -5% +/- 15%). Repeatability coefficients for MBF were 0.26 (rest), 1.34 (adenosine stress), and 0.82 (exercise stress) mL/min/g. CONCLUSION: Assessment of CFR with (15)O-H(2)O and PET using bicycle exercise in the PET scanner is feasible and at least as repeatable as using adenosine stress.
Adenosine↗
Isolated ventricular noncompaction is associated with coronary microcirculatory dysfunction.
OBJECTIVES: We sought to analyze whether a microcirculatory dysfunction might be associated with isolated ventricular noncompaction (IVNC). BACKGROUND: In IVNC, which is a cardiomyopathy thus far "unclassified" by the World Health Organization, heart failure and sudden cardiac death are common findings, but the pathophysiologic mechanisms are unknown. METHODS: In 12 patients with IVNC and 14 control subjects, quantitative evaluation of regional myocardial perfusion (myocardial blood flow [MBF]) and coronary flow reserve (CFR, hyperemic/baseline MBF) was performed using positron emission tomography and (13)N-ammonia. The left ventricular myocardium was divided into nine segments, and the two-dimensional echocardiogram in each patient with IVNC was compared with CFR in each segment. Noncompaction was defined as a two-layered structure with excessive trabeculation. RESULTS: The CFR in control subjects averaged 4.2+/-0.9, providing a cut-off value > or =2.5, but it was 2.1+/-0.8 in patients with IVNC. A perfusion scan defect was found in 14 of 24 segments with noncompaction, although no defect was found in 76 of 84 normal segments (overall agreement 83%, p < 0.0001 by the chi-square test). In 16 of 21 segments with noncompaction, a decreased CFR was found; but a decreased CFR was also found in 36 of 60 segments without noncompaction (p = NS). In 45 of the 57 segments with wall motion abnormalities, CFR was decreased, but it was preserved in 17 of the 24 segments with normal wall motion (agreement 77%, p < 0.0001). CONCLUSIONS: In patients with IVNC, a decreased CFR is not confined to noncompacted segments, but extends to most segments with wall motion abnormalities. Thus, coronary microcirculatory dysfunction is associated with IVNC.
Adult↗