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Medical research on persantine
Int J Cardiol. 2008 Jun 24;
Sharman JE, Moir S, Kostner KM, Haluska B, Marwick TH
BACKGROUND: Patients with coronary slow flow (CSF) present with a syndrome (often recurrent) of resting angina with no significant coronary stenoses. The nature of myocardial blood flow (MBF), MBF reserve and systemic arterial characteristics may contribute to symptoms in these patients but this has not been examined previously. This study sought to measure MBF, arterial stiffness and wave reflection in patients with CSF and controls. METHODS: Ten patients with angiographically proven CSF and 20 controls underwent dipyridamole-exercise stress myocardial contrast echocardiography and arterial waveform analysis. MBF was quantified off-line from 10 mid and apical segments with calculation of myocardial blood volume (A), red cell velocity (beta) and their product, MBF, at rest and post-stress. MBF reserve was calculated as the ratio of peak stress to resting MBF. Central arterial pressure waveforms were derived by radial tonometry, with arterial wave reflection expressed by augmentation index. Arterial stiffness was determined by aortic and brachial pulse wave velocities. RESULTS: There was no significant difference between CSF and control groups in mean resting beta (0.56+/-0.24 versus 0.59+/-0.26), A (7.9+/-1.4 versus 7.9+/-5.2), MBF (4.3+/-1.8 versus 4.4+/-3.6), MBF reserve (3.7+/-2.0 versus 4.0+/-2.0), augmentation index (26+/-12 versus 23+/-9%), aortic (7.4+/-1.8 versus 7.4+/-1.5 m/s) or brachial (8.0+/-0.8 versus 8.1+/-1.3) pulse wave velocity (p>0.4 for all). Similarly, there were no significant haemodynamic differences between groups after exercise (p>0.2 for all). CONCLUSIONS: MBF, large artery stiffness and arterial wave reflection characteristics are normal in CSF patients between their acute episodes.
Antiplatelet agents for secondary prevention of stroke.
Curr Treat Options Cardiovasc Med. 2008 Jun; 10(3): 223-8
Bernstein RA
Patients with recent ischemic stroke or transient ischemic attack (TIA) face a high risk of recurrent stroke as well as an increased risk of myocardial infarction and sudden cardiac death. In the absence of a clearly established indication for long-term anticoagulation, such as atrial fibrillation, antiplatelet agents are the antithrombotic drugs of choice for preventing recurrent vascular events. For many years, aspirin (ASA) has been the first-line therapy for patients at high risk of vascular ischemic events. Two large clinical trials have established the superiority of the combination of ASA and extended-release dipyridamole (ASA/ERDP) over ASA alone in patients with recent noncardioembolic ischemic stroke or TIA. Clopidogrel, another antiplatelet agent, is a reasonable alternative to ASA, but its superiority to ASA in patients with a history of stroke has not been as clearly established. The combination of ASA and clopidogrel, which is effective in patients with acute coronary syndrome, has not been shown to be either effective or safe, compared with either agent alone, in stroke patients, although there may be some benefit to this combination in patients with acute TIA. The results from a large randomized trial comparing ASA/ERDP with clopidogrel, anticipated soon, will further assist clinicians in choosing among available antiplatelet agents.
Eur J Echocardiogr. 2008 Jul; 9(4): 415-37
Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, Voigt JU, Zamorano JL,
Stress echocardiography is the combination of 2D echocardiography with a physical, pharmacological or electrical stress. The diagnostic end point for the detection of myocardial ischemia is the induction of a transient worsening in regional function during stress. Stress echocardiography provides similar diagnostic and prognostic accuracy as radionuclide stress perfusion imaging, but at a substantially lower cost, without environmental impact, and with no biohazards for the patient and the physician. Among different stresses of comparable diagnostic and prognostic accuracy, semisupine exercise is the most used, dobutamine the best test for viability, and dipyridamole the safest and simplest pharmacological stress and the most suitable for combined wall motion coronary flow reserve assessment. The additional clinical benefit of myocardial perfusion contrast echocardiography and myocardial velocity imaging has been inconsistent to date, whereas the potential of adding - coronary flow reserve evaluation of left anterior descending coronary artery by transthoracic Doppler echocardiography adds another potentially important dimension to stress echocardiography. New emerging fields of application taking advantage from the versatility of the technique are Doppler stress echo in valvular heart disease and in dilated cardiomyopathy. In spite of its dependence upon operator's training, stress echocardiography is today the best (most cost-effective and risk-effective) possible imaging choice to achieve the still elusive target of sustainable cardiac imaging in the field of noninvasive diagnosis of coronary artery disease.
Head to head comparison of 2D vs real time 3D dipyridamole stress echocardiography.
Cardiovasc Ultrasound. 2008 Jun 20; 6(1): 31
Varnero S, Santagata P, Pratali L, Basso M, Gandolfo A, Bellotti P
ABSTRACT: Real-time three-dimensional (RT-3D) echocardiography has entered the clinical practice but true incremental value over standard two-dimensional echocardiography (2D) remains uncertain in stress echo. The aim of the present study is to establish the additional value of RT-3D stress echo over standard 2D stress echocardiography. We evaluated 23 consecutive patients (age = 6510 years, 16 men) referred for dipyridamole stress echocardiography with Sonos 7500 (Philips Medical Systems, Palo, Alto, CA ) equipped with a phased - array 1.6-2.5 MHz probe with second harmonic capability for 2D imaging and a 2-4 MHz matrix-phased array transducer producing 60 x 70 volumetric pyramidal data containing the entire left ventricle for RT-3D imaging. In all patients, images were digitally stored in 2D and 3D for baseline and peak stress with a delay between acquisitions of less than 60 seconds. Wall motion analysis were interpreted on-line for 2D and off-line for RT-3D by joint reading of two observers. Segmental image quality was scored from 1=excellent to 5=uninterpretable. Interpretable images were obtained in all patients. Acquisition time for 2D images was 67 21 sec while it was 40 22 sec for RT-3D (p=0.5). Wall motion analysis time was 0.67 21 min for 2D and 13 7 min for 3D (p=0.0001). Segmental image quality score was 1.4 0.5 for 2D and 2.6 0.7 for 3D (p=0.0001). Positive ischemic exams were found in 5/23 patients. 2D and RT-3D agreed in three of these five positive exams while they both independently score a positive exam. Overall stress result (positive vs negative) concordance was 91 % (Kappa=0.80) between 2D and RT-3D. During dipyridamole stress echocardiography RT-3D imaging is highly feasible and shows high concordance with standard 2D stress echo. 2D images take longer to acquire and RT-3D more time-consuming to analyze. At present, there is no clear clinical advantage justifying routine RT-3D stress echocardiography.
Ren Fail. 2008; 30(4): 357-62
Katerinis I, Nguyen QV, Magnin JL, Descombes E
BACKGROUND: The prevalence and significance of higher than normal cardiac troponin I (cTnI) levels in asymptomatic chronic hemodialysis (HD) patients remains a source of discussion. The aim of the present study was to evaluate the prevalence of higher than normal cTnI levels in asymptomatic HD patients, as determined by the last generation of immunoassay, and to perform further cardiological investigations in those patients with persistently elevated cTnI levels. METHODS: All chronic HD patients in our center who had exhibited no symptoms of coronary artery disease (CAD) during the previous four weeks were screened. cTnI levels were determined before dialysis in all patients using the last generation AccuTnI assay (UniCel DxI 800, Beckman Coulter). The cTnI levels of those patients with elevated cTnI at the screening evaluation were then measured monthly for six months. We were thus able to identify a group of patients with persistently elevated cTnI levels (> 3 consecutive months) who subsequently underwent cardiac echography and dipyridamole-exercise (D-E) thallium testing. If stress myocardial ischemia was detected, a coronary angiography was then performed. RESULTS: Fifty patients (32 males) were included: mean age 62.8 +/- 13.6 years, 20 (40%) with a history of CAD, and 21 (42%) diabetic. At the initial screening, the mean cTnI concentration was 0.05 +/- 0.06 microg/L and the cTnI levels were higher than normal (> 0.09 microg/L) in six patients (12%). In the follow-up, the cTnI normalized immediately in two patients but remained persistently elevated (range, 0.10-0.48 microg/L) in four (8%). These four patients (all males, one diabetic) had a mean age of 70.2 +/- 6.6 years, and all had heart failure with a history of severe CAD with previous myocardial infarction (n = 4), coronary stenting (n = 3), and/or bypass (n = 2). D-E thallium imaging showed reversible myocardial ischemia in all. The stress ischemia involved one to four cardiac segments and was slight to moderate in three patients and severe in the diabetic patient. A coronary angiogram was performed in all patients, and showed lesions of variable severity: severe three-vessel CAD with severe systolic dysfunction in two patients (including the diabetic), and non-critical/peripheral coronary stenosis in the other two. CONCLUSIONS: Among the asymptomatic HD patients in our center, we identified four (8%) with persistently elevated cTnI levels, as determined using the last generation AccuTnI assay. All of them had a history of severe CAD with heart failure and exhibited reversible myocardial ischemia upon D-E thallium imaging; coronary angiography revealed coronary lesions of variable severity. Overall, our data indicate that persistent low-grade cTnI elevation occurs in HD patients having longstanding severe cardiac disease, but, from our data, it is difficult to reach a conclusion as to the best clinical approach for this group of patients.
Cardiovasc Ultrasound. 2008 Jun 19; 6(1): 30
Picano E, Molinaro S, Pasanisi E
ABSTRACT: BACKGROUND: Recent American Heart Association /American College of Cardiology guidelines state that "dobutamine stress echo has substantially higher sensitivity than vasodilator stress echo for detection of coronary artery stenosis" while the European Society of Cardiology guidelines and the European Association of Echocardiography recommendations conclude that "the two tests have very similar applications". Who is right? Aim: To evaluate the diagnostic accuracy of dobutamine versus dipyridamole stress echocardiography through an evidence-based approach. METHODS: From PubMed search, we identified all papers with coronary angiographic verification and head-to-head comparison of dobutamine stress echo (40 mcg/kg/min +/- atropine) versus dipyridamole stress echo performed with state-of-the art protocols (either 0.84 mg/kg in 10' plus atropine, or 0.84 mg/kg in 6' without atropine). A total of 5 papers have been found. Pooled weight meta- analysis was performed . RESULTS: the 5 analyzed papers recruited 435 patients, 299 with and 136 without angiographically assessed coronary artery disease (quantitatively assessed stenosis > 50%). Dipyridamole and dobutamine showed similar accuracy (87%, 95 % confidence intervals, CI, 83-90, vs. 84%, CI , 80-88, p=0.48), sensitivity (85%, CI 80-89, vs. 86%, CI 78-91, p=0.81) and specificity (89%, CI 82-94 vs. 86%, CI 75-89, p= 0.15). CONCLUSIONS: When state-of-the art protocols are considered, dipyridamole and dobutamine stress echo have similar accuracy, specificity and - most importantly - sensitivity for detection of CAD. European recommendations concluding that "dobutamine and vasodilators (at appropriately high doses) are equally potent ischemic stressors for inducing wall motion abnormalities in presence of a critical coronary artery stenosis" are evidence-based.
Regadenoson in the detection of coronary artery disease.
Vasc Health Risk Manag. 2008; 4(2): 337-40
Buhr C, Gössl M, Erbel R, Eggebrecht H
Myocardial perfusion studies use either physical exercise or pharmacologic vasodilator stress to induce maximum myocardial hyperemia. Adenosine and dipyridamole are the most commonly used agents to induce coronary arterial vasodilation for myocardial perfusion imaging. Both cause frequent undesirable side-effects. Because of its ultrashort half-life, adenosine must be administered by constant intravenous infusion during the examination. A key feature of an ideal A2A agonist for myocardial perfusion imaging studies would be an optimal level and duration of hyperemic response. Drugs with a longer half-time and more selective A2A adenosine receptor agonism, such as regadenoson, should theoretically result in a similar degree of coronary vasodilation with fewer or less severe side-effects than non-selective, ultrashort-lasting adenosine receptor stimulation. The available preclinical and clinical data suggest that regadenoson is a highly subtype-selective, potent, low-affinity A2A adenosine receptor agonist that holds promise for future use as a coronary vasodilator in myocardial perfusion imaging studies. Infusion of regadenoson achieves maximum coronary hyperemia that is equivalent to adenosine. After a single bolus infusion over 10 s, hyperemia is maintained significantly longer (approximately 2-5 min) than with adenosine, which should facilitate radionuclide distribution for myocardial perfusion imaging studies. In comparison with the clinically competitive A2A adenosine receptor agonist binodenoson, regadenoson has a several-fold shorter duration of action, although the magnitude of hyperemic response is comparable between the two. The more rapid termination of action of regadenoson points to an advantage of enhanced control for the clinical application. Regadenoson selectively causes vasodilation of the coronary circulation, whereas effects on systemic blood pressure are only mild. The clinical adverse effect profile of regadenoson appears to be favorable, particularly with respect to dreaded atrioventricular conduction disturbances and bronchospasm.
J Nucl Med. 2008 Jun 13;
Sotgia B, Sciagrà R, Olivotto I, Casolo G, Rega L, Betti I, Pupi A, Camici PG, Cecchi F
To clarify the spatial relationship between coronary microvascular dysfunction and myocardial fibrosis in hypertrophic cardiomyopathy (HCM), we compared the measurement of hyperemic myocardial blood flow (hMBF) by PET with the extent of delayed contrast enhancement (DCE) detected by MRI. METHODS: In 34 patients with HCM, PET was performed using (13)N-labeled ammonia during hyperemia induced by intravenous dipyridamole. DCE and systolic thickening were assessed by MRI. Left ventricular myocardial segments were classified as with DCE, either transmural (DCE-T) or nontransmural (DCE-NT), and without DCE, either contiguous to DCE segments (NoDCE-C) or remote from them (NoDCE-R). RESULTS: In the group with DCE, hMBF was significantly lower than in the group without DCE (1.81 +/- 0.94 vs. 2.13 +/- 1.11 mL/min/g; P < 0.001). DCE-T segments had lower hMBF than did DCE-NT segments (1.43 +/- 0.52 vs. 1.91 +/- 1 mL/min/g, P < 0.001). Similarly, NoDCE-C segments had lower hMBF than did NoDCE-R (1.98 +/- 1.10 vs. 2.29 +/- 1.10 mL/min/g, P < 0.01) and had no significant difference from DCE-NT segments. Severe coronary microvascular dysfunction (hMBF in the lowest tertile of all segments) was more prevalent among NoDCE-C than NoDCE-R segments (33% vs. 24%, P < 0.05). Systolic thickening was inversely correlated with percentage transmurality of DCE (Spearman rho = -0.37, P < 0.0001) and directly correlated with hMBF (Spearman rho = 0.20, P < 0.0001). CONCLUSION: In myocardial segments exhibiting DCE, hMBF is reduced. DCE extent is inversely correlated and hMBF directly correlated with systolic thickening. In segments without DCE but contiguous to DCE areas, hMBF is significantly lower than in those remote from DCE and is similar to the value obtained in nontransmural DCE segments. These results suggest that increasing degrees of coronary microvascular dysfunction might play a causative role for myocardial fibrosis in HCM.
Atherosclerosis. 2008 May 4;
Bozbas H, Pirat B, Demirtas S, Simşek V, Yildirir A, Sade E, Sayin B, Sezer S, Karakayali H, Muderrisoglu H
BACKGROUND: Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. METHODS: Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. RESULTS: The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CONCLUSIONS: CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.
J Neurol Neurosurg Psychiatry. 2008 Jun 5;
Pha H, Lj G, Pmw BM, Hc D, B GC, Fm Y, A A
OBJECTIVES: The aim of this meta-analysis was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D. DATA SOURCES: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on the comparison of A+D versus ASA were excluded. Review METHODS: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification. RESULTS: A total of 7,612 patients (5 trials) were included in the analyses, 3,800 allocated to A+D and 3,812 to ASA alone. The trial-adjusted hazard ratio for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval 0.72-0.92). Hazard ratios did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke, HR 0.78 (95% CI 0.68 - 0.90). CONCLUSION: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischemic stroke of presumed arterial origin in the secondary prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk.