Changes in serum uric acid levels and cardiovascular events: a meta-analysis.

BACKGROUND AND AIMS: The association between serum uric acid (SUA) levels and cardiovascular (CV) risk or all-cause death has been repeatedly reported. However, it has not been assessed whether reduction of SUA levels is associated with reduced CV risk. The aim of the current study was to evaluate the relationship between changes of SUA levels and CV events as well as all-cause death. METHODS AND RESULTS: Randomised trials reporting SUA at baseline and at the end of follow-up and clinical end-points (all-cause death, myocardial infarction (MI), stroke, heart failure (HF) and CV death) were included in the study. Meta-regression analysis was performed to test the relationship between SUA changes and clinical end-points. Eleven trials enrolling 21,373 participants followed up for 2.02 ± 1.76 years and reporting 4533 events were included. In meta-regression analysis, no relationship between SUA changes from baseline to end of follow-up and the composite outcome including CV death, stroke, MI and HF was found (change in Tau(2) (t) = -0.64; p Tau (p) = 0.541). Similarly, no relationship was found between SUA changes and single components of the composite outcome (MI: t = -0.83; p = 0.493; stroke: t = 0.46; p = 0.667; HF: t = 2.44; p = 0.162; CV death: t = -0.54; p = 0.614) and all-cause death (t = -0.72; p = 0.496). Results were confirmed by sensitivity analysis. No heterogeneity among studies or publication bias was detected. CONCLUSIONS: Changes in SUA levels observed during pharmacologic treatments do not predict the risk of all-cause death or CV events. As SUA levels are associated with increased CV risk, additional studies with direct xanthine-oxidase inhibitors are requested.

Restless legs syndrome in a group of patients with Alzheimer's disease.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterized by the urge to move the legs associated with peculiar unpleasant sensations during periods of rest and inactivity that are relieved by movement. A few studies analyzed RLS in neurodegenerative diseases such as Alzheimer's Disease (AD). The aim of our study was to assess the prevalence and the clinical characteristics of RLS in a cohort of AD patients. METHODS: Three hundred and thirty-nine subjects with a diagnosis of AD were recruited. Cognitive, functional, and neuropsychiatric measures were collected at baseline and six-monthly for a 2-years follow-up RESULTS: Fourteen subjects met the RLS criteria. RLS subjects were more frequently male (p:0,006) and younger than AD subject without RLS (p:0,029). MMSE, ADL and IADL were not significantly different. NPI total scores did not differ significantly, however, AD patients with RLS were found to be more apathetic (p:0,001) than AD subjects without RLS. CONCLUSION: RLS prevalence in our AD cohort was estimated to be about 4%. RLS appeared to be associated with neuropsychiatric symptoms such as apathy. RLS and apathy might share a common pathophysiological basis represented by a dysfunction of the central dopaminergic system.

Diagnostic accuracy of low-dose dobutamine echocardiography in predicting post-revascularisation recovery of function in patients with chronic coronary artery disease: relationship to thallium-201 uptake.

It is known that contractile reserve may be blunted if perfusion and coronary flow reserve are reduced. Thus, it is conceivable that the predictive accuracy of dobutamine echocardiography may differ according to perfusion tracer uptake. The aim of this study was therefore to assess the relationship between the level of thallium-201 uptake and the accuracy of dobutamine echocardiography in identifying reversible dysfunction. Sixty-nine patients (age 59+/-8 years, ejection fraction 40%+/-11%) with chronic coronary artery disease scheduled for coronary revascularisation were studied. All patients underwent rest 201Tl single-photon emission tomography and two-dimensional echocardiography at rest and during low-dose dobutamine infusion on the same day before revascularisation and repeated echocardiography at least 30 days thereafter. At follow-up, recovery of function was observed in 49% of 339 dysfunctional segments. The percentage of segments with post-revascularisation recovery of function and the percentage with contractile reserve increased in parallel with 201Tl uptake both in the total group of segments (chi2=35.5, P<0.0001 and chi2=35.9, P<0.0001, respectively) and among the 183 akinetic segments (chi2=44.4, P<0.0001 and chi2=14.6, P<0.05, respectively). The dysfunctional segments were divided into three groups according to 201Tl uptake: (a) uptake <65%, (b) uptake between 65% and 79%, (c) uptake >80%. The positive predictive value increased significantly with the level of 201Tl uptake, and was suboptimal (46%) in akinetic segments with severely reduced 201Tl uptake. The negative predictive value decreased significantly with 201Tl uptake, and it was less than suboptimal (29%) in akinetic segments with normal tracer uptake. Sensitivity was lower in the subset of akinetic segments (42%-63%) than in all dyssynergic segments (63%-76%), whereas specificity was very high in akinetic segments (80%-84%). It is concluded that the accuracy of low-dose dobutamine echocardiography in predicting reversibility of regional dysfunction varies considerably according to 201Tl uptake at rest and to the severity of regional dysfunction.

Low dose dobutamine echocardiography for predicting functional recovery after coronary revascularisation.

OBJECTIVE: To evaluate the effects of chronic coronary occlusion on the accuracy of low dose dobutamine echocardiography in predicting recovery of dysfunctional myocardium after revascularisation. DESIGN: Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 53 consecutive patients with >/= 70% stenosis of the left anterior descending coronary artery (LAD) and regional ventricular dysfunction (group 1, non-occluded LAD; group 2, occluded LAD) who underwent dobutamine echocardiography. INTERVENTIONS: 26 patients underwent coronary artery bypass grafting and 27 had percutaneous transluminal coronary angioplasty. MAIN OUTCOME MEASURES: Baseline studies before revascularisation included cross sectional echocardiography at rest and during dobutamine infusion (5-10 microgram), and coronary angiography. The dobutamine study was performed mean (SD) 35 (28) days before revascularisation. Echocardiography at rest was repeated 90 (48) days after revascularisation. RESULTS: Of 296 dysfunctional segments, 63 in group 1 (43%; 63/146) and 69 in group 2 (46%; 69/150) (NS) improved at follow up. Mean (SD) regional wall motion score index decreased from 1.97 (0.48) (95% confidence interval (CI) 1.01 to 2.93) before revascularisation to 1.74 (0.52) (95% CI 0.70 to 2.78) at follow up in group 1 (p = 0.001), and from 2.12 (0.41) (95% CI 1.30 to 2.98) to 1.88 (0.36) (95% CI 1.16 to 2.60) in group 2 (p = 0.0006). In group 1, sensitivity (87% v 52%; p < 0.0001), negative predictive value (88% v 65%; p = 0.001), and accuracy (77% v 64%; p = 0.01) were all significantly higher than in group 2, despite the angiographic evidence of collaterals in patients with occluded vessels. CONCLUSIONS: Dobutamine echocardiography shows reduced sensitivity in predicting recovery of dysfunctional myocardium supplied by totally occluded vessels. Thus caution should be used in selecting such patients for revascularisation on the basis of a viability assessment made in this way.

Prediction of improvement in global left ventricular function in patients with chronic coronary artery disease and impaired left ventricular function: rest thallium-201 SPET versus low-dose dobutamine echocardiography.

Accurate assessment of myocardial viability permits selection of patients who would benefit from myocardial revascularization. Currently, rest-redistribution thallium-201 scintigraphy and low-dose dobutamine echocardiography are among the most used techniques for the identification of viable myocardium. Thirty-one consecutive patients (all men, mean age 60 +/- 8 years) with chronic coronary artery disease and reduced left ventricular ejection fraction (31% +/- 7%) were studied. Rest 201Tl single-photon emission tomography (SPET), low-dose dobutamine echocardiography and radionuclide angiography were performed before revascularization. Radionuclide angiography and echocardiography were repeated after revascularization. An a/dyskinetic segment was considered viable on 201Tl SPET when tracer uptake was >65%, while improvement on low-dose dobutamine echocardiography was considered a marker of viability. Increase in global ejection fraction was considered significant at > or = 5%. In identifying viable segments, rest 201Tl SPET showed higher sensitivity than low-dose dobutamine echocardiography (72% vs 53%, P<0.05), while specificity was not significantly different (86% vs 88%). In 17 patients, global ejection fraction increased > or = 5% (group 1) while in 14 it did not (group 2). A higher number of a/dyskinetic segments were viable on 201Tl SPET in group 1 than in group 2 (2.6 +/- 1.9 vs 0.6 +/- 1.2, P < 0.005), while no significant differences were observed on low-dose dobutamine echocardiography (1.7 +/- 1.6 vs 1.1 +/- 1.6). A significant correlation was found between the number of a/dyskinetic segments viable on 201Tl SPET and post-revascularization changes in ejection fraction (r = 0.52, P < 0.05), but such a correlation was not observed for low-dose dobutamine echocardiography. Using as the cut-off the presence of at least one viable a/dyskinetic segment, rest 201Tl SPET had a higher sensitivity (82% vs 53%, P = 0.07) and showed a trend towards higher accuracy and specificity (77% vs 58%, and 71% vs 64%, respectively) as compared with low-dose dobutamine echocardiography. In conclusion, these findings suggest that when severely reduced global function is present, rest 201Tl SPET evaluation of viability is more accurate than low-dose dobutamine echocardiography for the identification of patients who will benefit most from revascularization.

Identification of viable myocardium in patients with chronic coronary artery disease using rest-redistribution thallium-201 tomography: optimal image analysis.

UNLABELLED: With the widely used 50% threshold, sensitivity is high, but specificity is low in detecting viable myocardium on 201Tl SPECT. In this study, we sought to identify the best threshold for semiquantitative 201Tl analysis. METHODS: Rest-redistribution 201Tl SPECT was performed in 46 patients with chronic coronary artery disease before and after myocardial revascularization. Regional function was evaluated by two-dimensional echocardiography before and after myocardial revascularization using a 3-point scale (1 = normal, 2 = hypokinetic, 3 = a/dyskinetic). Myocardial segments with abnormal systolic function were defined as viable if the systolic function score decreased > or = 1 after myocardial revascularization. A second group of 12 patients with chronic coronary artery disease constituted the validation population. Sensitivity-specificity curves, as well as receiver operating characteristic curves, for rest and redistribution mages were generated by varying the 201Tl uptake threshold. RESULTS: A 65% threshold uptake using resting images was found to be the best for detecting a/dyskinetic segments that improve after myocardial revascularization from those that do not improve. Sensitivity was lower with a 65% threshold (75%) than with a 50% threshold (90%, p < 0.05), but specificity was higher (76% versus 26%, p < 0.05) resulting in better accuracy (76% versus 57%, p < 0.05) and positive predictive value (77% versus 55%), while the negative predictive value was not different (69% versus 75%, p not significant). The area under the receiver operating characteristic curve was significantly (p < 005) larger for rest (0.80 +/- 0.05) as opposed to redistribution (0.72 +/- 0.05) images. Similar results were obtained in a subgroup of patients with low ejection fraction. Significant correlations between the percentage of revascularized viable segments and both the change in ejection fraction and in postrevascularization ejection fraction were found. When these findings were applied in the validation group, a gain in specificity, accuracy and positive predictive value was obtained with the 65% threshold compared with the 50% threshold. CONCLUSION: This study demonstrated that analysis of resting images and use of the 65% 201Tl uptake threshold is preferable for separating viable from not viable dyssynergic myocardial segments in patients with chronic coronary artery disease.

Combined evaluation of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the identification of viable myocardium in patients with chronic coronary artery disease.

The purpose of this study was to evaluate whether combined evaluation by discriminant analysis of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the accuracy in identifying viable myocardium in patients with chronic coronary artery disease. Rest-redistribution 201Tl has high sensitivity but low specificity in identifying viable myocardium, while the opposite is true for low-dose dobutamine echocardiography. Forty-six patients underwent low-dose dobutamine echocardiography and rest-redistribution 201Tl tomography on the same day. Rest echocardiography was repeated at least 30 days (mean 40+/-20) after myocardial revascularization. Discriminant analysis was applied to the results of 201Tl tomography and dobutamine echocardiography to classify a/dyskinetic segments as viable or non-viable. In 92 a/dyskinetic segments that were revascularized, rest-redistribution 201Tl tomography yielded an accuracy of 75%, while the accuracy of dobutamine echocardiography was 70% (P<0.05). When discriminant analysis was used, the combined evaluation gave an accuracy of 83% (P<0.05 vs both tests). These findings demonstrate that low-dose dobutamine echocardiography and 201Tl imaging are useful and complementary techniques for identifying viable myocardium in patients with chronic coronary artery disease. Combined evaluation by discriminant analysis significantly improves accuracy, although the cost-effectiveness of such an approach remains to be determined.

Effects of myocardial revascularization on regional thallium-201 uptake and systolic function in regions with reverse redistribution on tomographic thallium-201 imaging at rest in patients with chronic coronary artery disease.

OBJECTIVES: There is growing evidence that myocardial segments with reverse redistribution are viable in patients with chronic coronary artery disease. The aim of this study was to assess the effects of myocardial revascularization on systolic function and thallium-201 uptake in such segments. METHODS: Rest-redistribution thallium-201 tomography before and after myocardial revascularization was performed in 47 patients with chronic coronary artery disease. Regional function was evaluated by two-dimensional echocardiography before and after revascularization according to a 3-point scale (1 = normal, 2 = hypokinetic, 3 = a/dyskinetic). Improvement of dysfunctional segments was defined when systolic function score decreased > or =1 after revascularization. Reverse redistribution was defined as >8% decrease in relative thallium-201 uptake between rest and redistribution images. RESULTS: Reverse redistribution was found in 27 (57%) of 47 patients, corresponding to 60 (11%) of 564 myocardial segments. Of such segments, 24 (40%) had normal systolic function, 19 (32%) were hypokinetic, and 17 (28%) were a/dyskinetic. Thirty-six segments underwent myocardial revascularization, and reverse redistribution was no longer present in 86% of them subsequent to the procedure. Of 26 dyssynergic segments with reverse redistribution subjected to revascularization, 18 (69%) improved at follow-up. CONCLUSIONS: The findings of the present study indicate that reverse redistribution is a reversible phenomenon and is often associated with improvement of systolic function following revascularization in patients with chronic coronary artery disease.

Assessment of myocardial viability in patients with chronic coronary artery disease. Rest-4-hour-24-hour 201Tl tomography versus dobutamine echocardiography.

BACKGROUND: To date, late redistribution after resting 201Tl injection has not been evaluated. In addition, the concordance between resting 201Tl imaging and dobutamine echocardiography in identifying viable myocardium has not been assessed. METHODS AND RESULTS: Forty patients with coronary artery disease underwent rest-4-hour-24-hour 201Tl tomography and dobutamine echocardiography (5 to 10 micrograms.kg-1.min-1). Late redistribution occurred in 46 (21%) of 219 persistent defects at 4 hours. Systolic function and contractile reserve were similar among persistent defects at 4 hours with and without late redistribution. Contractile reserve was more frequent in segments with normal 201Tl uptake (59%), completely reversible defects (53%), or mild to moderate defects at 4 hours (56%) compared with severe defects (14%; P < .02 versus all). Of 105 hypokinetic segments, 99 (94%) were viable by 201Tl, and 88 (84%) showed contractile reserve. In contrast, of 155 akinetic segments, 119 (77%) were viable by 201Tl, but only 34 (22%) had contractile reserve. Concordance between 201Tl and dobutamine was 82% in hypokinetic segments but 43% in akinetic segments. In 109 revascularized segments, positive accuracy for functional recovery was 72% for 201Tl and 92% for dobutamine, whereas negative accuracy was 100% and 65%, respectively. Sensitivity was 100% for 201Tl and 79% for dobutamine. CONCLUSIONS: Late redistribution occurs in one fifth of persistent defects at 4 hours, and it does not correlate to systolic function or contractile reserve. Dobutamine and 201Tl yield concordant information in the majority of hypokinetic segments, whereas concordance is low in akinetic segments. Dobutamine demonstrates higher positive accuracy and sensitivity in predicting recovery of dysfunctional myocardium, whereas 201Tl shows higher negative predictive accuracy but reduced positive accuracy.

Inotropic stimulation by dobutamine increases left ventricular regional function at the expense of metabolism in hibernating myocardium.

The mechanism by which dobutamine increases the contraction of chronically dysfunctional myocardium and its effects on metabolism are still unknown. The aim of this study was to assess regional myocardial metabolism at rest and during an intracoronary dobutamine infusion in patients with hibernating myocardium. Eleven asymptomatic patients with single proximal stenosis of the left anterior descending coronary artery and persistent left ventricular dysfunction at rest (undergoing percutaneous transluminal coronary angioplasty [PTCA]) were studied prospectively. Regional left ventricular function was assessed by two-dimensional (2D) echocardiography and regional perfusion by thallium-201 single-proton-emission computed tomography. Great cardiac vein and aortic blood samples were obtained for measurements of lactate and plasma free fatty acid (FFA) concentrations. Inotropic challenge, obtained by using intracoronary dobutamine infusion, increases regional left ventricular function. However, the arteriovenous AV lactate difference was 0.206 = 0.070 mmol/L at rest, and it decreased to 0.018 = 0.069 mmol/L (p < 0.05 vs baseline) and 0.066 = 0.068 mmol/L (p < 0.05 vs baseline) at 4 and 10 minutes of dobutamine infusion, respectively. Thus the hibernating myocardium does not produce lactate at rest. However, when regional contraction is stimulated, dobutamine-induced inotropic challenge may cause a perfusion-contraction mismatch with an activation of anaerobic glycolysis.

Dobutamine echocardiography predicts improvement of hypoperfused dysfunctional myocardium after revascularization in patients with coronary artery disease.

BACKGROUND: In patients with coronary artery disease, dysfunctional hypoperfused myocardium at rest may represent either necrotic or viable hibernating myocardium. The accuracy of inotropic stimulation in identifying hypoperfused, reversibly dysfunctional myocardium has not been extensively investigated. METHODS AND RESULTS: Eighteen patients with stable chronic coronary artery disease underwent, while off drugs, quantitative 201Tl single-photon emission computed tomography after rest injection (2 to 3 mCi), two-dimensional echocardiography at rest and during dobutamine (5 to 10 micrograms/kg per minute i.v.), and radionuclide angiography. Single-photon emission computed tomography and echocardiography at rest were repeated 34 +/- 10 days after coronary revascularization, and radionuclide angiography was repeated 45 +/- 13 days after revascularization. Resting hypoperfusion was defined as 201Tl uptake < 80% of maximal activity. Systolic function was scored from 1 (normal) to 4 (dyskinesia), and functional improvement was defined as a score change > 1 grade. Of 79 dysfunctional hypoperfused segments, 48 (61%) improved function after revascularization. In 42 (88%) of these latter segments, function had improved during dobutamine. Conversely, systolic function after revascularization did not improve in 31 segments, and in 27 (87%), it had not improved during dobutamine. Functional improvement after revascularization was observed in 42 (91%) of 46 segments manifesting an improvement during dobutamine as opposed to 6 (18%) of 33 segments that did not improve during dobutamine. Resting 201Tl uptake (% of maximal activity) before revascularization (65 +/- 9%) significantly increased at follow-up in segments where function improved (70 +/- 12%, P < .005), whereas it did not change significantly in segments with unchanged systolic function after revascularization (from 57 +/- 13% to 60 +/- 17%, P = NS). In 10 patients with prerevascularization ejection fraction < 45%, left ventricular ejection fraction significantly increased from 36 +/- 7% before revascularization to 42 +/- 7% at follow-up (P < .05). CONCLUSIONS: Inotropic stimulation using dobutamine echocardiography identifies hypoperfused reversibly dysfunctional myocardium. Functional improvement during dobutamine is highly predictive of improvement after revascularization.

[Coronary angioplasty for the recovery of myocardial function after acute myocardial infarction: mid- and long-term results]. / Angioplastica coronarica per il recupero della funzione miocardica post-IMA: risultati a medio e lungo termine.

Sixty-three patients with previous myocardial infarction and documented hypoperfused reversibly dysfunctional myocardium after 201thallium tomography and/or echo-dobutamine were candidates to coronary angioplasty. Patients were enrolled at four hospitals (Naples, Milan, Pisa and Varese) and evaluated by different study protocols, while endpoint (presence of myocardial viability and efficacy of coronary angioplasty to improve dysfunctional myocardium) was similar. Sixty-two patients underwent successful angioplasty, and early evaluation (between 1 and 3 months after procedure) showed the ability of either 201thallium tomography and/or dobutamine echocardiography, to identify hypoperfused reversibly dysfunctional myocardium. Ten patients underwent late (after 8 +/- 2 months) evaluation of both wall motion and myocardial perfusion showing a sustained improvement in 25/32 hypoakinetic myocardial segments. Our data confirm the efficacy of revascularization of hypoperfused dysfunctional myocardial segments by coronary angioplasty. Further studies are warranted to obtain a better patient stratification and to evaluate the long-term results.