Effects of regional systolic asynchrony on left ventricular global diastolic function in patients with coronary artery disease

AbstractPatients with coronary artery disease often have impaired left ventricular diastolic filling despite normal global systolic function. The influence of regional systolic asynchrony on diastolic function was assessed by radionuclide angiography in 60 patients with coronary artery disease and normal ejection fraction at rest: group 1 (n = 30) with normal wall motion at rest and group 2 (n = 30) with abnormal wall motion. Data were compared with those obtained from 19 normal volunteers.Age, heart rate, ejection fraction and echocardiographic enddiastolic dimension did not differ among the three groups. Peak filling rate in group 1 and group 2 was similar (2.5 ± 0.5 and 2.3 ± 0.6 end-diastolic counts/s, respectively) and significantly lower than that in the normal subjects (2.8 ± 0.7 end-diastolic counts/s; p < 0.01 vs. group 2, p < 0.05 vs. group 1). Time to peak filling rate was prolonged in group 2 (184 ± 27 ms) compared with that in normal subjects (162 ± 19 ms; p < 0.01) and group 1 (172 ± 15 ms; p < 0.05). Left ventricular end-diastolic pressure was significantly higher in group 2 than in group 1 (14 ± 7 vs. 10 ± 5 mm Hg, respectively; p < 0.05).Asynchrony was assessed by sector analysis of the radionuclide left ventricular region of interest. Diastolic asynchrony was similar in the two patient groups (30 ± 23 ms in group 2, 26 ± 16 ms in group 1) and was higher in both groups than in the normal subjects (16 ± 8 ms; p < 0.61). However, systolic asynchrony was higher in group 2 (32 ± 15 ms) than in both group 1 (14 ± 6 ms; p < 0.01) and the normal group (9 ± 6 ms; p < 0.01). In the total group of patients with coronary artery disease, systolic asynchrony correlated with global time to peak filling rate (r = 0.53; p < 0.001). This correlation became stronger when only group 2 was considered (r = 9.62; p < 0.001). Moreover, in group 2 systolic asynchrony correlated with the duration of the isovolumetric relaxation period (r = 0.58; p < 0.001) and the isovolumetric relaxation period, in turn, correlated with global time to peak filling rate (r = 0.72; p < 0.001).Thus, left ventricular systolic asynchrony affects both the relaxation and filling phases of diastole, thereby contributing to the impairment of diastolic function commonly observed in patients with coronary artery disease

Myocardial thickness by gated PET and SPECT variability and bias

Proceedings of the 40th annual meeting of the Society of Nuclear Medicine, Toronto, Ontario, Canada, June 8-11, 1993Publicad

Comparison of Methods to Reduce Myocardial 18F-FDG Uptake in Mice: Calcium Channel Blockers versus High-Fat Diets

Besides its application in oncology, 18F-FDG PET-CT imaging is also useful in the diagnosis of certain lung infections, inflammatory diseases, and atherosclerotic plaques. Myocardial uptake of 18F-FDG may hamper visualization of the lesions caused by these diseases. Two approaches have been proposed for reducing myocardial uptake in preclinical studies, namely, calcium channel blockers (verapamil) and high-fat diets such as commercial ketogenic diets and sunflower seed diets. The objective of this study was to compare the efficacy of these approaches in reducing myocardial uptake of 18F-FDG in mice.This research was funded in part by the Innovative Medicines Initiative Joint Undertaking under grant agreement nu115337 (www.imi.europa.eu), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution, and from the Spanish MICINN (CEN-20101014) and the RIC-RETIC network, Spanish MINECO (RD12/0042/0057). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Publicad

Measurement of myocardial wall thickening from PET/SPECT images: comparison of two methods

Purpose: We compared two methods for measuring myocardial wall thickening from nuclear medicine perfusion scans. The first method uses the percent change in peak activity, and the second method models a profile measured across the myocardium. Method: Mathematical simulations of the myocardium were used. In addition, images with PET or SPECT resolution were created from real MR images. Known amounts of noise were then added. Results: The percent peak thickening (%PT) is nonlinear with true percent thickening, especially for PET resolutions [7 mm full width at half-maximum (FWHM)]. For the peak method, low levels of noise (10%) introduced an error of 8%PT for PET and of 16%PT for SPECT. Additional smoothing reduced these errors. For the fitted model, at 10% noise, the error in thickening was large: 2.3 mm for PET and 7.8 mm for SPECT. Conclusion: The fitted model works well only with good resolution and low noise (e.g., 7 mm FWHM and 10%). The peak method is also sensitive to noise, especially for poorer resolutions. Additional smoothing gives more reliable results for the peak method but not the fitted method. The peak method is therefore the more generally reliable, but even this method may only allow classification of myocardial thickening into broad categories.Publicad

Comparative effects of verapamil and nitroprusside on left ventricular function in patients with hypertension

AbstractThe effects of verapamil were compared with those of nitroprusside at matched mean arterial pressures and heart rates in 10 symptomatic hypertensive patients during cardiac catheterization. Simultaneous radionuclide angiography and micromanometer pressure measurements were obtained to assess left ventricular pressure-volume relations. Compared with control conditions, verapamil increased left ventricular end-diastolic volume index from 57 ± 16 to 70 ± 28 ml/m2 (p = 0.05) without a significant increase in left ventricular end-diastolic pressure (from 10 ± 4 to 13 ± 6 mm Hg). Despite a downward and rightward shift in the end-systolic pressure-volume relation indicating negative inotropic effects, ejection fraction did not decrease significantly (from 52 ± 9% to 46 ± 9%); cardiac index and stroke volume index remained unchanged. The change in stroke volume index with verapamil was directly related to the magnitude of change in end-diastolic volume index (r = 0.82, p < 0.005), suggesting that the increase in enddiastolic volume did not arise purely from negative inotropic effects. Systemic vascular resistance index decreased from 42 ± 8 to 34 ± 7 mm Hg-min-m2/liter (p < 0.05).In contrast, nitroprusside decreased left ventricular end-diastolic volume index from 57 ± 16 to 41 ± 10 ml/m2 (p < 0.05), cardiac index from 3.2 ± 0.7 to 2.8 ± 0.6 liters/min per m2 (p < 0.05) and stroke volume index from 28 ± 6 to 24 ± 5 ml/m2 (p < 0.01), with no change in systemic vascular resistance index (40 ± 10 mm Hg·min·m2). The end-systolic pressure-volume relation shifted downward and leftward in all patients, stemming from altered left ventricular loading.Thus, in equihypotensive doses, verapamil and nitroprusside have markedly different effects on left ventricular function. The peripheral vasodilation and apparent improvement in left ventricular filling during verapamil balanced the negative inotropic effects, resulting in maintenance of stroke volume and cardiac index. The primary hypotensive effect of verapamil was a decrease in systemic vascular resistance, whereas that of nitroprusside was a decrease in cardiac index stemming from reduced left ventricular preload

Metabolic evidence of viable myocardium in regions with reduced wall thickness and absent wall thickening in patients with chronic ischemic left ventricular dysfunction

AbstractReduced end-diastolic wall thickness with absent systolic wall thickening has been reported to represent nonviable myocardium in patients with chronic coronary artery disease. To assess whether reduced regional end-diastolic wall thickness and absent wall thickening accurately identify nonviable myocardium, 25 patients with ischemic left ventricular dysfunction (ejection fraction at rest 27 ± 10%) underwent positron emission tomography with oxygen-15-labeled water and 18fluorodeoxyglucose to assess metabolic activity and spin-echo gated nuclear magnetic resonance imaging to measure regional end-diastolic wall thickness and wall thickening. The presence of metabolic activity was defined as 18fluorodeoxyglucose uptake (corrected for partial volume) >50% of that in normal regions.Of 355 myocardial regions evaluated, 266 were hypokinetic or normokinetic at rest and 89 were akinetic (that is, absent wall thickening). 18Fluorodeoxglucose uptake was observed in 97% of the hypokinetic and normokinetic regions and in 74% of the akinetic regions. End-diastolic wall thickness was greater in akinetic regions with than in those without 18fluorodeoxyglucose uptake (11 ± 4 vs. 7 ± 3 nun, p < 0.01). The highest values for sensitivity and specificity of end-diastolic wall thickness in predicting the absence of metabolic activity in akinetic regions were 74% and 79%, respectively, and corresponded to an end-diastolic threshold of 8 mm. However, the positive predictive accuracy was only 55% and did not improve for other end-diastolic wall thickness values. In all myocardial regions, there was only a weak correlation between 18fluorodeoxyglucose activity and either end-diastolic wall thickness (r = 0.17) or wall thickening (r = 0.32).Thus, metabolic activity is present in many regions with reduced end-diastolic wall thickness and absent wall thickening. These data indicate that assessment of regional anatomy and function may be inaccurate in distinguishing asynergic but viable myocardium from nonviable myocardium

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma