Torsades de pointes associated with voriconazole use.

We describe 2 patients who developed prolonged QTc interval on electrocardiogram while being treated with voriconazole. The first patient had undergone induction chemotherapy for acute myelogenous leukemia, and her course had been complicated by invasive aspergillosis and an acute cardiomyopathy. She developed torsades de pointes 3 weeks after starting voriconazole therapy. She was re-challenged with voriconazole without recurrent QTc prolongation or cardiac dysfunction. The second patient had a significantly prolonged QTc interval while on voriconazole therapy. We recommend careful monitoring for QTc prolongation and arrhythmia in patients who are receiving voriconazole, particularly those who have significant electrolyte disturbances, are on concomitant QT prolonging medications, have heart failure such as from a dilated cardiomyopathy, or have recently received anthracycline-based chemotherapy. The potential for synergistic cardiotoxicity must be carefully considered.

Temporal arteritis in a patient with eosinophilia.

We present the case of a 69-year-old man with fever of unknown origin, headache, elevated sedimentation rate and peripheral eosinophilia. A biopsy of the temporal artery revealed transmural inflammation with eosinophilia. Therapy with corticosteroids resulted in resolution of the fever, headache, and eosinophilia, as well as normalization of the sedimentation rate. There have been only rare cases of eosinophilia associated with temporal arteritis. All of these cases were seen in patients with either juvenile temporal arteritis, acquired immunodeficiency syndrome, or Buerger's disease. This is the only case, to our knowledge, of eosinophilic temporal arteritis without association with any of these conditions. Our patient underwent extensive diagnostic studies and therapeutic trials en route to a long delayed correct diagnosis. The presence of eosinophilia should not deter physicians from considering a temporal artery biopsy in patients presenting with symptoms suggestive of temporal arteritis.

99mTc-tetrofosmin assessment of myocardial perfusion and viability in canine models of coronary occlusion and reperfusion.

UNLABELLED: The goal of this study was to determine whether 99mTc-tetrofosmin can assess regional flow heterogeneity when injected during sustained coronary artery occlusion and to estimate the degree of myocardial salvage and viability during coronary reperfusion. METHODS: In protocol 1, 99mTc-tetrofosmin, 201 TI and microspheres were injected during total left anterior descending (LAD) coronary artery occlusion in five anesthetized open-chested dogs. Protocol 2 dogs underwent LAD occlusion for either 60 min (n = 7) or 180 min (n = 6) followed by 105 min of reperfusion. 99mTc-tetrofosmin (10 mCi), 201TI (1 mCi) and microspheres were injected 90 min after reflow. In both protocols, myocardial 99mTc-tetrofosmin and 201TI activities were quantified from regions of interest on ex vivo images and by in vitro well counting. RESULTS: In protocol 1, there was a linear relationship between 201TI (r = 0.96) and 99mTc-tetrofosmin (r 0.92) activities and microsphere flow during the occlusion. In protocol 2, the LAD/left circumflex (LCx) defect count ratios for 99mTc-tetrofosmin and 201TI from images of myocardial slices were comparable in dogs undergoing either 1 or 3 h of LAD occlusion and 105 min of reperfusion. Similarly, the LAD/LCx in vitro count ratios were comparable between 201TI and 99mTc-tetrofosmin in 1 and 3 h occluded dogs, and significantly lower than the reperfusion flow when these tracers were injected. Uptake of both tracers was depressed to a greater extent in areas of severe ischemic damage. CONCLUSION: These data suggest that administration of 99mTc-tetrofosmin during coronary occlusion accurately delineates the flow heterogeneity. When given after reperfusion, 99mTc-tetrofosmin uptake was significantly reduced in reperfused, infarcted areas and was reflective of viability and the degree of myocardial salvage in addition to reperfusion flow. These experimental studies validate the clinical use of 99mTc-tetrofosmin for assessing persistent coronary artery occlusion, and infarct size and myocardial viability after reperfusion.

Predicting adverse outcome with exercise SPECT technetium-99m sestamibi imaging in patients with suspected or known coronary artery disease.

The goal of this study was to determine the ability of exercise single-photon emission computed tomographic (SPECT) technetium-99m (Tc-99m) sestamibi imaging to predict adverse events in a population with a comparable distribution of men (n = 114) and women (n = 115). Consecutive patients referred for evaluation of chest pain syndrome, known coronary artery disease, or residual ischemia after acute myocardial infarction underwent imaging using a single-headed SPECT camera. Clinical readings were reviewed and scored by independent observers as normal or abnormal. Follow-up, defined as time from scanning until an event, late revascularization, or patient response averaged 19.2 +/- 5.2 months and was 90% complete (229 of 255 patients). Cardiac death and nonfatal infarction were corroborated by chart review or physician contact. Patients were excluded from analysis if a revascularization procedure was performed within 1 month of imaging. There were 172 patients with normal scans (67%) and 83 with abnormal scans (33%). Of the patients in whom followup was obtained, 2 of 155 with normal scans (0.8%/year) and 6 of 74 with abnormal scans (5.4%/year) had cardiac events. Statistical analysis using the Kaplan-Meier survival curves suggests a significant difference in event-free survival between normal and abnormal scans. Patients with abnormal scans portended a worse outcome (chi-square = 8.04, p <0.005). Thus, exercise SPECT Tc-99m sestamibi scintigraphy is useful for prognostication in a mixed population of patients with suspected or known coronary artery disease in which women comprised 50% of the patient cohort.

Pharmacological stress thallium scintigraphy with 2-cyclohexylmethylidenehydrazinoadenosine (WRC-0470). A novel, short-acting adenosine A2A receptor agonist.

BACKGROUND: Pharmacological stress imaging with adenosine or dipyridamole is associated with a high incidence of side effects, including hypotension, chest pain, AV conduction abnormalities, and bronchospasm. Although the desired coronary vasodilatory response is mediated primarily by the adenosine A2A receptors, these side effects result from stimulation of the A1, A2B, or A3 adenosine receptors. We hypothesized that a selective adenosine A2A receptor agonist would induce coronary vasodilatation appropriate for pharmacological stress imaging, without evoking adenosine receptor-mediated side effects. METHODS AND RESULTS: Infusions of a potent and selective A2A adenosine receptor agonist, WRC-0470 (0.1 to 3 micrograms kg-1. min-1 for 10 minutes), to five open-chest dogs produced dose-related left anterior descending (LAD) and left circumflex (LCx) coronary artery vasodilatation without altering mean arterial pressure, heart rate, left atrial pressure, or left ventricular dP/dt. In the same dogs, adenosine (300 micrograms . kg-1. min-1 for 4 minutes) produced coronary vasodilatation that was limited by significant hypotension. To determine the utility of WRC-0470 for pharmacological stress imaging, the hemodynamic responses to WRC-0470 (0.6 microgram.kg-1.min-1 for 10 minutes) and adenosine (250 micrograms.kg-1.min-1 for 4 minutes) were compared in dogs with critical LAD stenoses. 201T1 was injected at the peak WRC-0470 stress response. WRC-0470 increased LCx flow nearly fivefold but did not significantly lower mean arterial pressure. Anteroseptal defects were readily apparent in slice images from all dogs. The mean defect ratio (LAD/LCx) was 0.59 +/- 0.06. CONCLUSIONS: The potent A2A-selective adenosine receptor agonist WRC-0470 is a short-acting coronary vasodilator with potential utility for pharmacological stress perfusion imaging.

Comparison between thallium-201 and technetium-99m-tetrofosmin uptake with sustained low flow and profound systolic dysfunction.

UNLABELLED: Technetium-99m-tetrofosmin uptake was compared to that of 201Tl in the setting of low flow and systolic dysfunction. METHODS: In nine open-chested dogs, a severe left anterior descending (LAD) coronary artery stenosis resulted in a 54.3% mean flow reduction and decreased left ventricular thickening from 21% +/- 1% to -3 +/- 2%. After 30 min, 37 MBq (1 mCi) of 201Tl and microspheres were injected and initial and 2-hr redistribution images acquired. Two hours later, 370 MBq (10 mCi) of 99mTc-tetrofosmin and microspheres were injected and an image was obtained. LAD: left circumflex (LCX) count ratios for both tracers and flows were calculated by well counting postmortem, and 201Tl and 99mTc-tetrofosmin defect magnitudes were determined by quantitative image analysis. RESULTS: LAD:LCx flow ratios were similar during 201Tl and 99mTc-tetrofosmin injections (0.48 +/- 0.04 versus 0.49 +/- 0.05, p = n.s.). Final 201Tl activity (0.66 +/- 0.04) was significantly higher than 99mTc-tetrofosmin (0.55 +/- 0.05; p < 0.05). LAD/LCx 99mTc-tetrofosmin image defect count ratio was similar to 201Tl defect count ratio on the initial rest 201Tl scan (0.57 +/- 0.03 versus 0.56 +/- 0.02, p = ns), but significantly less than 201Tl defect count ratio at 2 hr (0.57 +/- 0.03 versus 0.65 +/- 0.02, p < 0.05). CONCLUSION: In a low-flow model with profound systolic dysfunction, myocardial 99mTc-tetrofosmin uptake ( > 50%) reflective of viability was observed in the asynergic zone perfused by the stenotic LAD.