A New Natural Antioxidant Mixture Protects against Oxidative and DNA Damage in Endothelial Cell Exposed to Low-Dose Irradiation.

Exposure to ionizing radiation during diagnostic procedures increases systemic oxidative stress and predisposes to higher risk of cancer and cardiovascular disease development. Many studies indicated that antioxidants protect against radiation-induced damage and have high efficacy and lack of toxicity in preventing radiation exposure damages. The purpose of this study was to investigate the in vitro protective effect of a new antioxidant mixture, named RiduROS, on oxidative stress generation and DNA double-strand breaks (DSBs) induced by low doses of X-rays in endothelial cells. Human umbilical vein endothelial cells (HUVEC) were treated with RiduROS mixture 24 h before a single exposure to X-rays at an absorbed dose of 0.25 Gy. The production of reactive oxygen species (ROS) was evaluated by fluorescent dye staining and nitric oxide (NO) by the Griess reaction, and DSBs were evaluated as number of γ-H2AX foci. We demonstrated that antioxidant mixture reduced oxidative stress induced by low dose of X-ray irradiation and that RiduROS pretreatment is more effective in protecting against radiation-induced oxidative stress than single antioxidants. Moreover, RiduROS mixture is able to reduce γ-H2AX foci formation after low-dose X-ray exposure. The texted mixture of antioxidants significantly reduced oxidative stress and γ-H2AX foci formation in endothelial cells exposed to low-dose irradiation. These results suggest that RiduROS could have a role as an effective radioprotectant against low-dose damaging effects.

Reproductive effects of low-to-moderate medical radiation exposure.

Medical radiation from x-rays and nuclear medicine is the largest man-made source of radiation exposure in Western countries, accounting for a mean effective dose of 3.0 mSv per capita per year, comparable to the radiologic risk of 150 chest x-rays, and in many cases gonads fall in the imaging field, with > 20 millions examinations per year in US being abdominal and pelvic CT, and > 0.5 million barium enema. Of the over 7 million workers exposed to medical radiation, special attention has been paid to those working in the interventional cardiology and radiology labs, with high and increasing professional exposures, two-to three times higher than diagnostic radiologists. Thus, adverse effects of radiation exposure are well worth of the scientific community's interest. Aims of this review are: 1) to assess gonad dose to patients undergoing diagnostic testing or interventional fluoroscopy therapy and in professionally exposed interventional fluoroscopists; and 2) to evaluate the evidence linking radiation exposure in the low-to-moderate range (besides the radiotherapy high dose range) to adverse reproductive effects. In patients, the gonad radiation exposure can reach 5 mSv for a lower limb angiography, 20 mSv for a CT pelvis and hips, and 36 (in females) to 90 mSv (for males) for a lower gastrointestinal series. For interventional cardiologists, the gonad dose (below lead apron) is in the same order of magnitude of the shielded thyroid dose, with a median of 50 to 100 microSievert per cine-angiography procedure. The dose can be ten-fold higher for a complex interventional procedure. This leads to a cumulative exposure in the 0.5-1 Sv range over a professional lifetime of 30 years. At present, the epidemiological approach provided inconclusive results, inadequate for a robust evidence-based advice to exposed subjects, since large groups followed-up for decades would be required to detect a small increase in risk. A molecular epidemiology approach and/or the use of integrated biomarkers of reproductive health (e.h., reproductive hormone balance, sperm quality, sperm DNA damage) might be more fruitful in future research focused in the low-to-moderate dose range (< 1000 mSv) of greatest interest for diagnostic and professional exposures.

Cognitive, psychological and psychiatric effects of ionizing radiation exposure.

Radiation exposure leads to an increased risk for cancer and, possibly, additional ill-defined non-cancer risk, including atherosclerotic, cardiovascular, cerebro-vascular and neurodegenerative effects. Studies of brain irradiation in animals and humans provide evidence of apoptosis, neuro-inflammation, loss of oligo-dendrocytes precursors and myelin sheaths, and irreversible damage to the neural stem compartment with long-term impairment of adult neurogenesis. With the present paper we aim to present a comprehensive review on brain effects of radiation exposure, with a special focus on its impact on cognitive processes and psychological functions, as well as on their possible role in the pathophysiology of different psychiatric disorders.

Radioprotection (un)awareness in cardiologists, and how to improve it.

In 2010 the International Atomic Energy Agency launched the "3 A's campaign": Audit, Appropriateness and Awareness for radiological justification, which is an effective tool for cancer prevention. Cardiologists prescribe the majority of radiological testing, but their awareness of doses and risks of ionizing cardiac imaging test is low. To assess radioprotection awareness of prescribing and practicing physicians (mainly cardiologists) before and after a radioprotection course. We held a 1-day 6-h primer of radioprotection for a limited number (20-35) of physicians. The course offered 8 continuing education credits from the Italian Health Ministry and was held 9 times over 3 years. We had 425 attendees, but full data sets (with complete questionnaires) were available for 403 physicians (55% women, age 45 ± 6 years), including 55% cardiologists, 40% general practitioners, 5% others (mainly cardiology fellows). For each attendee, a radiological awareness score was obtained before and after the course, with a survey containing 10 multiple-choice questions (5 answers) on radioprotection basics (doses of common examinations in multiples of chest x-rays; associated cancer risk, etc.). Each answer was scored from 0 ("don't know"), 1 ("strongly disagree") to 4 ("strongly agree"). The radiological awareness score of the 403 attendees improved from 31 ± 3 (before) to 37 ± 2 (after training, P < 0.001 vs. pre-training). As an example, before training, 25% of attendees believed that radiation-induced cancer risk disappears after 6 months (10% of respondents), 12 months (8%) or 5 years (7%), whereas 75% (becoming 98% after training) correctly estimated that radiological damage is cumulative over one's lifetime. Awareness of radiological doses and risks, albeit essential for risk-benefit assessment of radiological testing, is suboptimal among cardiologists, but can dramatically improve with a limited teaching effort through targeted training.

Cumulative patient effective dose in cardiology.

Medical radiation from X-rays and nuclear medicine is the largest non-natural (man-made) source of radiation exposure in Western countries. The aim of this study was to assess the individual cumulative effective dose in patients admitted to our cardiology ward. We collected a cumulative radiological history from a structured questionnaire and access to hospital records in 50 consecutive adult patients (36 males; age, 66.7+/-10.8 years) admitted to the Institute of Clinical Physiology in Pisa. The cumulative effective dose was assessed as an indicator of stochastic risk of cancer. We derived the effective dose for each individual examination from the Medical Imaging Guidelines of the European Commission (2001). On average, each patient underwent a median of 36 examinations (interquartile range, 23-46). The median cumulative effective dose was 60.6 mSv. Three types of procedures were responsible for approximately 86% of the total collective effective dose: (i) arteriography and interventional cardiology (12% of examinations, 48% of average dose per patient); (ii) nuclear medicine (5% of examinations, 21% of average dose per patient); and (iii) CT (4% of examinations, 17% of average dose per patient). The median estimated extra risk of cancer was approximately 1 in 200 exposed subjects. In conclusion, the average contemporary cardiological patient is exposed to a significant cumulative effective dose from diagnostic and therapeutic interventions. It is important to log cumulative dose for each patient at the time of each examination. Every effort should be made to justify the indications and to optimize the doses.

Radiation dose exposure during cardiac and peripheral arteries catheterisation.

BACKGROUND: Ionising radiation carries an oncogenic risk which is linearly related to the dose. An estimation of the effective dose can be obtained from the measurements of the dose-area product (DAP), which is a measure of stochastic risk and a potential quality indicator. AIM: To assess radiation exposure of patients in a large volume cardiac cath-lab. METHODS: A retrospective analysis of adult cardiac and peripheral percutaneous procedures (April to December 2004) was carried out to determine the DAP and estimated risk of malignancy. We identified 6 groups: Group 1 (n=100, coronary angiography and ventriculography); Group 2 (n=50, carotid stenting); Group 3 (n=50, aortography+coronary angiography+ventriculography); Group 4 (n=100, inferior extremities angiography+predilatation and stenting); Group 5 (n=100, coronary angiography+ventriculography+direct coronary stenting); Group 6 (n=100, coronary angiography+ventriculography+coronary predilation and stenting). Dose-area product meter attached on the X-ray unit was used for the estimation of the radiation dose received by the patient during the procedures. RESULTS: DAP values (mean+/-S.D.) ranged from 41+/-30 Gy cm2 in Group 1 (lowest) to 118+/-89 Gy cm2 in Group 6 (highest). Within each group, individual radiation exposure varies substantially: from 11 to 200 Gy cm2 in Group 1, and from 30 to 733 Gy cm2 in Group 6 patients. Average exposure in a Group 6 patient corresponds to a risk of mortality from a malignancy of about 1 in 1000. CONCLUSION: The radiation dose varies substantially across different types of procedures and up to tenfold within the same procedure. The enhanced knowledge of radiation dose might help the cardiologist to implement radiation sparing procedures eventually minimizing patient and operator radiation hazards in invasive cardiology.

Blunted increase in plasma adenosine levels following dipyridamole stress in dilated cardiomyopathy patients.

BACKGROUND: Heart failure is characterized by chronically increased adenosine levels, which are thought to express a protective anti-heart failure activation of the adenosinergic system. The aim of the study was to assess whether the activation of adenosinergic system in idiopathic dilated cardiomyopathy (IDC) can be mirrored by a blunted increase in plasma adenosine concentration following dipyridamole stress, which accumulates endogenous adenosine. METHODS: Two groups were studied: IDC patients (n = 19, seven women, mean age 60 +/- 12 years) with angiographically confirmed normal coronary arteries and left ventricular ejection fraction <35%; and normal controls (n = 15, six women, mean age 68 +/- 5 years). Plasma adenosine was assessed by high-performance liquid chromatography methods in blood samples from peripheral vein at baseline and 12 min after dipyridamole infusion (0.84 mg kg-1 in 10 min). RESULTS: At baseline, IDC patients showed higher plasma adenosine levels than controls (276 +/- 27 nM L-1 vs. 208 +/- 48 nM L-1, P < 0.001). Following dipyridamole, IDC patients showed lower plasma adenosine levels than controls (322 +/- 56 nM L-1 vs. 732 +/- 250 nM L-1, P < 0.001). The dipyridamole-induced percentage increase in plasma adenosine over baseline was 17% in IDC and 251% in controls (P < 0.001). By individual patient analysis, 18 IDC patients exceeded (over the upper limit) the 95% confidence limits for normal plasma adenosine levels at baseline, and all 19 exceeded (below the lower limit) the 95% confidence limits for postdipyridamole plasma adenosine levels found in normal subjects. CONCLUSION: Patients with IDC have abnormally high baseline adenosine levels and--even more strikingly--blunted plasma adenosine increase following dipyridamole infusion. This is consistent with a chronic activation of the adenosinergic system present in IDC, which can be measured noninvasively in the clinical theatre.

Dipyridamole in chronic stable angina pectoris; a randomized, double blind, placebo-controlled, parallel group study.

BACKGROUND: Oral dipyridamole induces accumulation of endogenous adenosine, which in a hypoxic milieu exerts experimentally an angiogenic effect on coronary collateral circulation. A meta-analysis of 13 randomized placebo-controlled trials published between 1960 and 1992 showed evidence of benefit for dipyridamole in the treatment of angina pectoris, especially with longer duration of treatment. Aim To assess the efficacy and safety of dipyridamole in the treatment of patients with chronic stable angina in a large scale, international, randomized, placebo-controlled, parallel group study. METHODS: Four hundred patients with chronic stable angina pectoris and a positive treadmill exercise test were randomized to receive either modified release dipyridamole (200 mg b.i.d. p.o., n=198) or corresponding placebo (n=202), for 24 weeks as an add-on to conventional antianginal therapy and for 4 additional weeks as monotherapy--the latter after withdrawal of standard treatment with calcium antagonists and/or beta-blockers and/or long-acting (prophylactic) nitrates. RESULTS: Of the 198 patients randomized to dipyridamole, 134 completed the add-on and only 12 the monotherapy phase. Of the 202 patients randomized to placebo, 162 reached the add-on and only 12 the monotherapy phase. Serious adverse events occurred in 15 patients with dipyridamole and in 12 with placebo (7.6% vs 6.0, P=0.52). Increase over the baseline treadmill exercise test was similar in the treatment groups at each stage of the trial for all the main efficacy parameters: total treadmill exercise test duration; time to first anginal pain (except for a -13 s difference in favour of placebo at week 24;P=0.040); time to ST segment depression >0.1 mVolt (except for a +21 s difference in favour of dipyridamole at week 8;P=0.024; this latter difference was totally attributable to patients with lower exercise tolerance--Bruce stage II at study entry). CONCLUSION: In patients with chronic stable angina treated with regular antianginal background medication, the use of oral dipyridamole is safe and well tolerated. Antianginal and antiischaemic efficacy, as assessed by exercise testing, is comparable to placebo, except for a beneficial effect on time to ischaemia after 2 months, totally attributable to patients with lower exercise tolerance at study entry.

[Evaluation of the safety of stress echocardiography in Spain and Portugal]. / Evaluación de la seguridad de la ecocardiografía de estrés en España y Portugal.

UNLABELLED: INTRODUCTION. There are few studies that evaluate the safety of stress echocardiography with discordant results. They are done in well-trained centers with highly selected populations leading to selection bias. OBJECTIVE: To assess the safety of the different modalities of stress echocardiography in Spain and Portugal. METHOD: Severe complications were retrospectively analyzed during the stress echocardiography performed in 29 hospitals in Portugal and Spain, from the beginning of their activity to September, 1999. In this period 22,105 stress echocardiograms were performed: 10,975 exercise echos, 2,969 low dose dobutamine echos, 6,832 high dose dobutamine echocardiograms, 1,276 dypiridamole echocardiograms, 41 paced echocardiograms and 12 with adenosine. A complication was defined as severe when it was life-threatening or led to hospital admission. RESULTS: We registered 26 complications, one death, 3 ventricular fibrillations, 10 sustained ventricular tachycardias, 2 complete atrioventricular blocks, 6 acute myocardial infarctions, 2 ruptures of the free wall or ventricular septal defects, 1 transient ischemic attack and 1 severe symptomatic hypotension. We had one severe complication for every 2,743 exercise stress, 1 every 1,231 dypiridamole, 1 every 325 high dose dobutamine without any complications with low dose dobutamine stress. We found a relationship between experience in dobutamine stress echocardiography and the frequency of complications. Three complications appeared once the test was finished. CONCLUSIONS: The stress echocardiography is a safe technique, but not harmless. The exercise stress echo is the safest of all the modalties of stress echocardiography. There is a relation between experience and the number of complications.

Diagnosis of myocardial ischemia in hypertensive patients.

Arterial hypertension can provoke a reduction in coronary flow reserve through several mechanisms that are not mutually exclusive (i.e. epicardial coronary artery disease (CAD), left ventricular hypertrophy and structural and/or functional microvascular disease). These different targets of arterial hypertension should be explored with different diagnostic markers. In fact, stress-induced wall motion abnormalities are highly specific for angiographically assessed epicardial CAD, whereas ST segment depression and/or myocardial perfusion abnormalities are frequently found with angiographically normal coronary arteries associated with left ventricular hypertrophy and/or microvascular disease. Exercise-electrocardiography stress test can be used to screen patients with negative maximal test due to its excellent negative predictive value, which is high and comparable in normotensives and hypertensives. When exercise-electrocardiography stress test is positive (or uninterpretable or ambiguous), an imaging stress-echo test is warranted for a reliable identification of significant, prognostically malignant epicardial CAD in view of an ischemia-guided revascularization.

Effect of coronary bypass and cardiac valve surgery on systemic endothelial function.

Seventeen patients scheduled for a cardiac procedure necessitating cardiopulmonary bypass underwent serial perioperative assessment of brachial artery flow-mediated dilation. Patients who underwent coronary bypass surgery had a sustained systemic endothelial dysfunction in the perioperative period, whereas those undergoing cardiac valve surgery experienced transient postoperative systemic endothelial dysfunction.

Antioxidant effect of oral dipyridamole during cerebral hypoperfusion with human carotid endarterectomy.

We sought to test the hypothesis of an antioxidant effect of dipyridamole in vivo in a model of cerebral hypoperfusion. Twenty-one patients (65+/-10 years, 11 men) undergoing carotid endarterectomy were allocated in two groups (group 1, 10 with dipyridamole, 200 mg p.o., 3-4 h before surgery; group II, 11 with placebo) in a double-blind placebo-controlled randomized design. Blood was sampled from ipsilateral jugular bulb, and plasma vitamin E content was assayed before, after 15 and 30 min of clamp, and 2 and 10 min after declamping. In 12 of them, lipoperoxides were assayed. Vitamin E plasma content decreased significantly in group II (rest, 3.71+/-0.22 mmol/mol of cholesterol, 100%) after clamp (91.5% of rest, p < 0.01) and remained unchanged during declamping (90.9% of rest, p < 0.01), but did not change in group I (rest, 3.5+/-0.44 mmol/mol of cholesterol, 100%) during clamping (99.9% of rest; p = NS) and after declamping (97.6% of rest; p = NS). Lipoperoxide concentration did not change in group I (rest, 302+/-8 a.u.; clamp, 296+/-13 a.u.; p = NS vs. rest; declamp, 304+/-8 a.u.; p = NS vs. rest), and increased significantly in group II (rest, 313+/-5 a.u.; clamp, 352+/-9 a.u.; p < 0.01 vs. rest; declamp, 343+/-6 a.u.; p < 0.05 vs. rest). Cerebral oxidative stress associated with human carotid endarterectomy can be attenuated by pretreatment with oral dipyridamole.

Increase in plasma adenosine during brain ischemia in man: a study during transient ischemic attacks, and stroke.

Adenosine is a "retaliatory metabolite" which accumulates during experimental brain ischemia and has vasodilatory and putative neuroprotective effects. The aim of this study was to assess whether human cerebral ischemia and necrosis-evaluated in the clinical models of transient ischemic attack (TIA) and stroke, respectively-acutely raise plasma adenosine levels. We studied 20 patients: 10 with TIA and 10 with stroke. In all, blood was serially sampled for assessment of plasma adenosine by an high-performance liquid chromatography method. Sampling occurred on peripheral blood during TIA and stroke upon admission, and serially thereafter every day up to 7 days and every other day up to 20 days. We found that in TIA and stroke patients, peripheral adenosine levels were increased to a similar extent upon admission (TIA = 264 +/- 53 vs. stroke = 257 +/- 60 nM, p = ns), peaked on the day 2 for TIA (300 +/- 60) and on day 3 for stroke (289 +/- 43) patients, and steadily decreased towards the normal range, reached by all TIA patients by day 5 and by stroke patients by day 15. Stroke and TIA are associated with a rapid increase in circulating plasma adenosine concentration in man, detectable in peripheral vein. The adenosine surge likely mirrors an increased production from the ischemic brain, and it lasts days (for TIA) and weeks (for stroke) after the acute event.

Low-dose dipyridamole infusion acutely increases exercise capacity in angina pectoris: a double-blind, placebo controlled crossover stress echocardiographic study.

OBJECTIVES: The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND: Adenosine is a recognized mediator of ischemic preconditioning in experimental settings. METHODS: Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design. RESULTS: In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs. dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01). CONCLUSIONS: Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity A1 myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals.

Perioperative prognostic value of dipyridamole echocardiography in vascular surgery: A large-scale multicenter study in 509 patients. EPIC (Echo Persantine International Cooperative) Study Group.

BACKGROUND: Patients undergoing major vascular surgery are at a relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for perioperative risk stratification. The aim of the current study was to evaluate the value of dipyridamole echocardiography test (up to 0.84 mg/kg over 10 minutes) in predicting cardiac events in a large-scale, multicenter, prospective, observational study design. METHODS AND RESULTS: Five hundred nine patients (mean age 66+/-10 years) were studied before vascular surgery by dipyridamole stress echocardiography in 11 different centers. All patients underwent preoperative clinical risk assessment according to the American Heart Association guidelines. No major complications occurred during dipyridamole stress echocardiography. Technically adequate images were obtained in all patients; however, in 4 patients only the low dipyridamole dose (0.56 mg/kg over 4 minutes) was given for limiting side effects. Eighty-eight (17.3%) had a positive test. Perioperative events occurred in 31 (6.1%) patients: 6 deaths, 11 myocardial infarctions, and 14 episodes of unstable angina. Sensitivity and specificity of dipyridamole stress echocardiography for predicting spontaneous cardiac events were 81% and 87%, respectively, with a positive predictive value of 28% and negative predictive value of 99%. By multivariate analysis, the difference between wall motion score index at rest and peak stress (Deltawall motion score index), test positivity, and ST-segment depression during dipyridamole infusion were independent predictors of any perioperative cardiac event. CONCLUSIONS: Dipyridamole stress echocardiography is safe and well tolerated in patients undergoing major vascular surgery and provides an effective preoperative screening test for the risk stratification of these patients, mainly because of the extremely high negative predictive value, which is a potent predictor of complication-free procedure.

Comparison of combination of dipyridamole and dobutamine during echocardiography with thallium scintigraphy with thallium scintigraphy to improve viability detection.

The aim of this study was to investigate the relation between radioisotopic and echocardiographic markers of myocardial viability and their correlation with functional recovery after coronary revascularization. Myocardial viability can be detected by techniques exploring various aspects of cell physiology: thallium-201 scintigraphy and dobutamine and dipyridamole echocardiography focus on cell membrane integrity, beta-1 and adrenoceptor, and A2-adenosine receptor-mediated inotropic response, respectively. Fifty-seven patients (mean age 60+/-8 years) with previous myocardial infarction (>3 months), angiographically assessed coronary artery disease, and resting regional dysfunction underwent rest-redistribution 201-thallium scintigraphy and low-dose pharmacologic stress echo with dobutamine (up to 10 microg/kg/min), very low dose regimen of dipyridamole (0.28 mg/kg over 4 minutes), and combined dipyridamole-dobutamine. Criteria for viability in a 13-segment model for both techniques were percent peak activity in redistribution images >55% for thallium-201 and a decrease in wall motion score >1 grade (1 [normal] to 4 [dyskinetic]) for stress echo. Thirty patients underwent coronary revascularization (bypass surgery in 8, angioplasty in 22) and were followed up at 4 weeks from intervention with a resting echocardiogram. The rate of agreement between thallium-201 and stress echo was 63% for dipyridamole, 66% for dobutamine, and 74% for combined dipyridamole-dobutamine (p <0.05 vs dipyridamole and dobutamine). In the 30 patients who underwent revascularization, a regional resting dyssynergy was observed in 225 segments, assuming that postrevascularization functional recovery (which occurred in 126 segments) was the gold standard; combined dipyridamole-dobutamine showed a higher sensitivity (90% confidence interval [CI] 85% to 95%) than thallium-201, dobutamine, or dipyridamole (87%, CI 81% to 92%; 82%, CI 76% to 89%; and 82%, CI 76% to 89%, respectively). Specificity was lower for viability recognition with thallium-201 (61%, CI 51% to 71%) than with dobutamine (93%, CI 88% to 98%), dipyridamole (95%, CI 91% to 99%), and combined dipyridamole-dobutamine (92%; CI 87% to 97%). Combined adrenergic and adenosinergic stimulation recruits an inotropic reserve in a significant proportion of segments with preserved thallium uptake that were nonresponders after either dipyridamole or dobutamine. When functional recovery after successful revascularization is considered as the postoperative gold standard, thallium has a higher sensitivity than dipyridamole or dobutamine; this sensitivity gap is filled with combined dipyridamole-dobutamine. The specificity of all forms of pharmacologic stress echo is better than thallium-201.

Relative role of coronary stenosis severity and morphology in determining pharmacologic stress echo positivity.

Angiographically assessed plaque morphology, not only plaque severity, may affect myocardial vulnerability to ischemia during stress testing. The aim of this study was to evaluate directly, in a head-to-head comparison, the relation between coronary stenosis severity and morphology and pharmacologic stress echo response. From our inpatients echo databank, we selected 68 patients (62 men, mean age 57 +/- 9 years) who had undergone high-dose dipyridamole and high-dose dobutamine-atropine echocardiography, performed within 1 week and in random order, before coronary angiography that showed significant coronary artery disease by selection. There were altogether 121 vessels with visually assessed stenosis >50% in 68 patients. Thirty-three had complex-type and 56 simple-type lesions (according to the Ambrose classification), whereas 32 vessels were occluded. During dobutamine echocardiography there were 51 dyssynergic regions of the left ventricle fed by different coronary arteries in 50 patients and dipyridamole stress was able to induce ischemia in 45 separate regions in 44 patients. The overall agreement between the 2 tests in recognizing ischemia was 76%. Induced ischemia was associated with greater quantitatively assessed stenosis severity for both dipyridamole (positive, 70 +/- 12% vs negative, 63 +/- 12% area reduction; p <0.05) and dobutamine (positive, 68 +/- 12% vs negative, 63 +/- 12% area reduction; p <0.05). The simple-type stenosis was more frequently identified with dobutamine (46%) versus dipyridamole (21%, [p <0.01]), whereas the complex-type stenosis was associated with a trend toward more frequent positivity of dipyridamole (55%) versus dobutamine (36%), p = 0.13. Adenosinergic stress positivity is affected not only by plaque severity, but also by plaque morphology, whereas adrenergic stress positivity is affected by plaque severity, not by plaque morphology.

Value of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease: a report from the Echo-Persantine and Echo-Dobutamine International Cooperative Studies.

OBJECTIVES: This study sought to verify the effectiveness of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease. BACKGROUND: Noninvasive prognostic assessment of single-vessel disease is an unresolved issue to date. METHODS: The study evaluated prospectively collected data from 754 patients with angiographic single-vessel disease who underwent either dipyridamole (n = 576) or dobutamine (n = 178) stress echocardiography. Invasive treatment (coronary revascularization within 3 months of stress testing) was performed in 260 patients and medical treatment in 494. RESULTS: Echocardiographic positivity was observed in 421 patients (56%). Patients treated invasively had a higher incidence of stress test positivity (69% vs. 49%, p < 0.001) and left anterior descending coronary artery involvement (60% vs. 46%, p < 0.001) than patients maintained with medical therapy. During a mean follow-up of 37 months, 54 hard cardiac events occurred (14 deaths, 40 nonfatal infarctions): 37 in medically and 17 in invasively treated patients (7.5% vs. 6.5%, p = NS). On Cox analysis, a positive result on stress testing was the only independent prognostic predictor in medically treated patients (relative risk 2.92, 95% confidence interval 1.29 to 6.59). The 4-year infarction-free survival rate was higher for a negative than a positive stress test result in medically (93.9% vs. 87.3%, p = 0.009) but not invasively treated patients (92.7% vs. 97.1%, p = 0.545). Moreover, a significantly higher 4-year infarction-free survival rate was found in invasively versus medically treated patients with a positive (p = 0.012), but not in those with a negative, stress test result (p = 0.853). CONCLUSIONS: Pharmacologic stress echocardiography is effective in risk stratification of single-vessel disease and can accurately discriminate patients in whom coronary revascularization can have the maximal beneficial effect. These findings have a potential favorable impact on the cost-effectiveness of invasive procedures.