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PubMed1994

Pharmacologic stress testing: experience with dipyridamole, adenosine, and dobutamine.

The use of pharmacologic stress testing for detecting and assessing ischemic heart disease (IHD) is reviewed. Methods of diagnosing IHD are designed to emulate conditions that increase myocardial oxygen demand in order to identify areas of ischemia and atherosclerotic lesions and to evaluate their functional or anatomical importance. Diagnostic methods can be divided into functional assessment with stress testing and anatomical assessment with coronary angiography. Physical stressors, such as exercise or atrial pacing, or pharmacologic stressors, such as vasodilators or beta-adrenergic-receptor agonists, can be used in stress testing. Electrocardiography, thallium planar scintigraphy, echocardiography, and other techniques are used to evaluate the response to stress testing. Unlike exercise stress testing, pharmacologic testing does not require physical exertion. Adenosine, dipyridamole, and dobutamine are the principal agents used in pharmacologic stress testing. Adenosine and dipyridamole mediate coronary artery vasodilation. Adenosine, a direct agonist, has a rapid onset and short duration of action. Dipyridamole, the only agent with approved labeling for use in stress testing, inhibits adenosine indirectly. Dobutamine increases cardiac output and heart rate as well as promoting coronary artery vasodilation. Clinical trials show that all three drugs can be used safely and effectively in patients after acute myocardial infarction or before vascular surgery and in individuals with risk factors for or symptoms of IHD. The sensitivity and specificity of pharmacologic stress testing for detecting IHD are at least as high as those of exercise testing. Minor adverse effects, including chest pain, headache, and facial flushing, are common, but major adverse effects are rare. Pharmacologic stress testing can be used in patients who cannot undergo exercise testing and offers a noninvasive alternative to coronary angiography.

Adenosine↗
PubMed1994

Computer-assisted evaluation of dipyridamole thallium-201 SPECT in patients with aortic stenosis.

UNLABELLED: Dipyridamole SPECT detects significant coronary artery disease (CAD) in patients without aortic stenosis. This study was done to establish normal 201Tl distribution limits in patients with aortic stenosis and to apply these normal limits to patients with aortic stenosis and angiographically significant CAD (> or = 75% area reduction). METHODS: Fifty-two patients (mean age 68 yr; mean valve area 0.67 cm2) were examined with 201Tl SPECT after dipyridamole infusion (0.56 mg/kg during 4 min). After tomographic reconstruction, basal, mid-ventricular and apical short-axis slices were selected. The highest activity in each six-degree segment was normalized to the maximal activity of each slice. RESULTS: Significant CAD was found in 24 patients. Five patients without CAD, but with localized hypokinesia or left bundle-branch block, were excluded from the reference group which finally consisted of 16 patients. Sensitivity for CAD was 88% when the lowest relative activity in each segment was used as the lower limit of normal. With -2 s.d. and -2.5 s.d. curves the sensitivity was 83% and 75%, respectively. Gender-specific limits were not used. Nonsignificant CAD was found in seven patients (< 75% stenoses). CONCLUSIONS: This study presents the normal distribution of 201Tl uptake for patients with aortic stenosis, using dipyridamole SPECT. The range method had the highest sensitivity for detection of significant CAD.

Adult↗
PubMed1993

[Determination of myocardial risk on basis of the outcome of previous myocardial infarcts. Advantages of myocardial tomoscintigraphy using thallium with dipyridamole].

Exercise stress test, 24-hour-ambulatory electrocardiographic monitoring and myocardial perfusion 201-Thallium single photon emission computerized tomography (SPECT) with dipyridamole pharmacological stress probably have different sensitivities and specificities for the identification of residual ischemia after an acute myocardial infarction. Their clinical value is still a matter of debate. To comparatively evaluate various non-invasive methods, we studied 63 patients with previous myocardial infarction consecutively referred to our Nuclear Medicine Department to undergo myocardial dipyridamole (0.56 mg/kg) Thallium SPECT, by comparing scintigraphic results with those of the exercise stress test and Holter monitoring. In basal conditions, heart rate was 67 +/- 14 beats per minute; systolic and diastolic arterial pressures were 139 +/- 24 and 86 +/- 12 mmHg, respectively. Following intravenous dipyridamole, heart rate rose to 84 +/- 15 beats per minute (p < 0.0001), while systolic and diastolic pressures dropped to 133 +/- 26 and 79 +/- 13 mmHg, respectively (p < 0.0001; p < 0.0001). In only one patient with a non-Q wave myocardial infarction we did not observe any myocardial perfusion defect. Of 62 patients with stress perfusion defects, 53 (85.5%) showed reversible defects and 9 (14.5%) persistent defects. Of 53 patients with reversible defects, 29 (55%) showed defects at the infarct site, 6 (11%) had defects outside the infarct site and 18 (34%) had defects at as well as outside the infarct site. Forty-two patients were examined by both exercise stress test and myocardial SPECT imaging: SPECT demonstrated reversible perfusion defects in 34 (81%) of them, whereas exercise stress test showed evidence of residual ischemia in 24 (57%) (p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Doppler echocardiography under dipyridamole after thrombolyzed early myocardial infarction. Comparison with coronarographic data].

The reliability and safety of Doppler echocardiography with dipyridamole (0.84 mg/kg in 10 min) were evaluated in 63 patients an average of 7 days after a thrombolysed early lateral infarct and 24 hours before follow-up coronary arteriography. The aims of the test were the detection of tight stenoses (diameter reduced by more than 75%) affecting the artery responsible for the infarct as well as the other coronary vessels, using the vasodilator action of dipyridamole. The echocardiographic manifestation of induced coronary steal consisted of transitory asynergism in the territory of the artery involved. Clinical tolerability of the test was good. The brief onset of anginal pain was nevertheless seen in 6 patients. Analysis of the zone corresponding to the necrosed area was possible in only 43 cases. Sensitivity of the test for detection of a post-infarction residual stenosis was 64% (39-89) and specificity 90% (79-100). Study of other territories was possible in 59 cases. Sensitivity of the test for the diagnosis of multiple vessel disease was 70% (42-98) and specificity 94% (88-100). In the population as a whole, Doppler study of variations in anterograde mitral flow revealed a sensitivity of 40% (27-53) and specificity of 87% (78-96). Variations in sub-aortic flow were analysed only in the final 27 patients, with a sensitivity and specificity of 100%. The specificity of dipyridamole echocardiography after infarction is good, both for the detection of residual stenosis and that of multiple vessel disease, the chief limiting factor being the impossibility of analysis of the infarcted region in the presence of initial akinesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Thallium-201 myocardial perfusion imaging after aortocoronary bypass in patients treated with sulodexide or ASA-dipyridamole].

The aim of this investigation was to compare the preventive effect of sulodexide, a glycosaminoglycan drug, tested versus ASA-dipyridamole association, on the occlusion of venous aortocoronary bypass. A group A of 23 patients, for a total of 22 anastomosis with internal mammary artery and 46 venous bypass, was treated with sulodexide 500 USL/day. A group B of 18 patients for a total of 19 anastomosis with internal mammary artery and 33 venous bypass, was treated with ASA-dipyridamole 300 mg + 400 mg/day. Three and 9 months after surgery, all patients underwent thallium-201 myocardial perfusion imaging, associated with ergometric test. At the first control after 3 months, reversible perfusion defect in one or more myocardial segments was observed in 8 patients of group A and 3 patients of group B (2 A patients and 1 B patient in non revascularized myocardial segments); after 9 months, reversible perfusion defects were observed in 4 A patients and in 4 B patients. After 3 months, non reversible perfusion defect imaging in non infarcted myocardial segments was observed in 2 A patients and in 1 B patient; after 9 months, in 1 patient of both groups. This research shows higher incidence, at first control after 3 months, of ischemic reversible perfusion defects in patients treated with sulodexide, with an evident improvement in some patients recontrolled after 9 months. At the last control after 9 months, the scintigraphic findings showed similar evidence of perfusion defects in both groups treated with sulodexide or ASA-dipyridamole, with concordant angiographic findings (78.6%). Our preliminary results are encouraging and suggest further widespread studies on sulodexide therapy.

Arterial Occlusive Diseases↗
PubMed1993

Dipyridamole-thallium stress testing: a local community hospital experience.

Clinical data on the first 100 patients who underwent dipyridamole-thallium stress testing in our hospital were reviewed in order to re-evaluate safety guidelines and diagnostic utility in patients with coronary artery disease. Forty patients developed symptoms, including three major ones. One patient had significant bronchospasm, and two others developed significant hypotension with near syncope. The rest had nonspecific chest, shoulder, arm or throat pain, dyspnea, nausea, vomiting, and paresthesia. Most symptoms occurred within the first 10 minutes of dipyridamole infusion. Twenty-eight patients required treatment with intravenous (IV) aminophylline. Of the remaining 60 patients, 30 became hypotensive but remained asymptomatic. Fourteen of 20 patients who underwent coronary angiography had coronary disease. Thirteen were correctly identified by thallium imaging, and only one was identified by electrocardiogram (EKG). Six patients' angiographies showed no evidence of coronary disease. Five of these patients developed perfusion abnormalities during thallium scintigraphy. These results suggest that dipyridamole is a relatively safe drug for pharmacologic stress testing even though the incidence of side effects is relatively high. The high incidence of thallium perfusion abnormalities in patients without coronary disease probably reflects bias in patient selection for coronary angiography, resulting in a relatively small sample of catheterized patients. However, this requires further investigation.

Aged↗
PubMed1993

[Is there a specific response of the ECG R-wave amplitude to exercise-induced myocardial ischemia? Exercise test and dipyridamole test].

Changes in electrocardiogram R-wave amplitude are often noted during treadmill stress testing. The two main reasons for this phenomenon discussed in the literature are left ventricular dimension changes and myocardial ischemia. To evaluate the relation between myocardial ischemia and electrocardiogram R-wave amplitude changes, we investigated in a retrospective study the data of 99 patients (20 females/79 males) with clinical signs of coronary artery disease. All patients had undergone exercise ECG and dipyridamole test. Electrocardiogram R-wave amplitude changes and ST-segment alterations were measured before, during and after provocation by bicycle stress test and intravenous dipyridamole. In neither test was there a specific reaction of R-wave amplitude to myocardial ischemia. During myocardial ischemia there were patients with an increase as well as a decrease R-wave amplitude. There was no significant correlation between the reaction of the R-wave amplitude in the exercise ECG when compared with the Dipyridamole test. Quantitative analysis showed a reduction of R-wave amplitude during maximum provocation in both tests, which was statistically significant in almost every subgroup of patients. In both tests the ST-segment depression was statistically significant in all groups, but there was no significant correlation between the reaction of R-wave amplitude and the ST-segment depression. In conclusion, there is no specific reaction of R-wave amplitude to myocardial ischemia. It is very unlikely, that the often noted changes in R-wave amplitude during stress testing are caused by ischemic episodes of the myocardium. Other mechanisms must be sought to explain the observed R-wave alterations.

Adult↗
PubMed1996

[Heart arrest during dipyridamole scintigraphy: report of 3 cases].

Potentially life threatening rythm disturbances, such as third degree A-V block and sinus arrest without "escape rythm", represent infrequent and unexpected events during dipyridamole thallium scintigraphy. We report three cases of cardiac arrest requiring resuscitation maneuvers after dipyridamole infusion during myocardial thallium scan. On the basis of these clinical observations we suggest that a trained cardiologist and resuscitation kit should be available in nuclear lab. Moreover elderly patients may require careful screening for preexisting conduction defects and sick sinus syndrome. When dipyridamole infusion provokes severe bradyarrhythmias not related to myocardial ischemia, a transesophageal electrophysiological study should always be performed.

Aged↗
PubMed1997

European stroke prevention study 2: dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.

In 1988, an optimal antiplatelet regimen for secondary stroke prevention remained to be defined. We undertook a randomised, placebo-controlled, double-blind trial to investigate the safely and efficacy of low-dose acetylsalicylic acid (ASA), modified-release dipyridamole, and the two agents in combination. Patients with prior stroke or transient ischaemic attack (TIA) were randomised to treatment with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. We concluded that dipyridamole, in a modified-release form, at a dose of 200 mg b.d. and ASA 25 mg b.d., have been shown to be equally effective in the secondary prevention of ischaemic stroke and TIA; that when co-prescribed, the protective effects are additive, the combination being significantly more effective than each agent prescribed singly; and that low-dose ASA does not eliminate the propensity for induced bleeding.

Aged↗
PubMed1998

Dipyridamole stress echocardiography and exercise testing for risk stratification after uncomplicated myocardial infarction.

BACKGROUND: Risk stratification for subsequent cardiac events after an acute infarction can be obtained by exercise testing or dipyridamole stress echocardiography. It remains to be determined whether these modalities are equivalent and provide incremental information on top of clinical evaluation. The aim of our study was to compare the prognostic information obtained early after an acute uncomplicated myocardial infarction of high dose dipyridamole coupled with echocardiography (stress echo) or maximal symptom-limited exercise testing. METHODS AND RESULTS: Ninety patients underwent dipyridamole stress echo and exercise testing at a mean +/- SD of 9 +/- 4 days after admission for acute uncomplicated first myocardial infarction. All patients were prospectively followed for 22 +/- 16 months. There were 9 hard events (3 cardiac deaths and 6 acute myocardial infarctions) and 12 soft events due to post MI angina (6 angioplasty and 6 bypass surgery procedures). Univariate predictor of hard events was rest-stress wall motion score index variation (p = 0.009); univariate predictors of all events (hard + soft) were: positive exercise testing (p = 0.001), positive stress echo (p = 0.001), rest-stress wall motion score index variation (p = 0.002), extent of ischemia at echo (p = 0.008). Multivariate analysis by Cox selected a non-Q wave infarction and rest-stress wall motion score index variation as predictors of death or reinfarction (overall chi-square for the model 12.2, p = 0.0022). CONCLUSIONS: Stress echo is superior to ergometric variables for predicting events after uncomplicated myocardial infarction.

Aged↗
PubMed2006

The action of dipyridamole to prevent thrombosis: practical implications for the treatment and prevention of stroke.

Aggrenox (Boehringer Ingelheim, Ingelheim, Germany), a novel combination of low-dose aspirin with dipyridamole, represents a safe and promising combination alternative for mild but sustained platelet inhibition, and reduction of both arterial and venous thrombi occurrences. In a large, well-controlled randomized trial (ESPS-2 ) evaluating antiplatelet agents for stroke prevention, Aggrenox was twice as effective as monotherapy with either aspirin or dipyridamole. There is an increasing body of evidence that a delicate strategy with Aggrenox provides modest inhibition of platelet activity, especially in a chronic, long-term setting. Mild platelet inhibition beyond conventional aggregation may represent a substantial advantage over aggressive antiplatelet regimens for the treatment, and especially for secondary prevention, of cerebrovascular ischemic events. Although there is no doubt that the concept of inhibiting platelets is vital for the treatment of vascular ischemic disease in general and ischemic stroke and transient ischemic attack (TIA) in particular, the optimal degree of such inhibition still remains an unsolved mystery. It seems that the concepts of "the more, the better" and "one size fits all" may no longer be valid for ideal antiplatelet protection in such high-risk populations. Without routine individual laboratory assessment of platelet function, mild regimens have the advantage of being more suitable for the majority of patients and will contribute substantially to the success of dipyridamole. Conversely, if we can determine baseline platelet status and intelligently apply therapy based on platelet activity in each particular patient, clinical outcomes may be better. Avoiding excessive bleeding risks after aggressive strategies in patients with normal or already decreased platelet function, but targeting those who exhibit activated platelets, may improve risk stratification and save lives. Therefore, Aggrenox should be considered a drug of choice to prevent the second stroke. Eliminating, or at least minimizing, the most frequent side effect, namely transitory headaches at the beginning of therapy with Aggrenox, will benefit patients and increase the use of this agent. Should the PRoFESS (Prevention Regimen For Effectively avoiding Second Strokes) trial show an advantage in event reduction with Aggrenox over clopidogrel, the increase will be especially dramatic. In short, based on current evidence most guidelines include Aggrenox as a first-line option for secondary prevention of ischemic stroke or TIA, and some recent versions suggest it may be preferable in other clinical scenarios.

Journal Article↗
PubMed1986

Effects of dipyridamole, nifedipine, verapamil, hydralazine and propranolol on the formation of prostacyclin and thromboxane in a coupled system of platelets and aorta.

The effects of some vasodilatory (dipyridamole, nifedipine, verapamil) and antihypertensive (hydralazine, propranolol) drugs on the metabolism of exogenous arachidonic acid (AA), and on the production of thromboxane from endogenous AA stores were examined. In a coupled system of platelets and rat aorta, dipyridamole (100 microM), nifedipine (300 microM) and hydralazine (250 microM) potentiated the formation of 6-keto-F1 alpha from exogenous AA. Hydralazine in this system reduced the formation of TxB2. At higher concentrations the drugs (dipyridamole 500 microM; hydralazine 1 mM, verapamil 2mM; propranolol 2mM) were effective in reducing the formation of TxB2. Moreover, the drugs at lower concentrations produced reduced amounts of TxB2 in clotting blood. A dose-dependent inhibition of platelet aggregation induced by ADP, epinephrine, collagen and arachidonate was observed with these drugs. The results demonstrate that some of the beneficial effects of the drugs in the cardiovascular system can be explained on the basis of their effects on platelet aggregation and on AA metabolism.

Animals↗
PubMed2001

The prognostic value of myocardial viability recognized by low dose dipyridamole echocardiography in patients with chronic ischaemic left ventricular dysfunction.

AIMS: The aim of this study was to assess the prognostic value of myocardial viability recognized as a contractile response to vasodilator stimulation in patients with left ventricular dysfunction in a large scale, prospective, multicentre, observational study. METHODS AND RESULTS: Three hundred and seven patients (mean age 60 +/- 10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction and severe left ventricular dysfunction (ejection fraction <35%; mean ejection fraction: 28 +/- 7%) were enrolled in the study. Each patient underwent low dose dipyridamole echo (0.28 mg x kg(-1) in 4 min). Myocardial viability was identified as an improvement of >0.20 in the wall motion score index. By selection, all patients were followed up for a median of 36 months. One-hundred and twenty-four were revascularized either by coronary artery bypass grafting (n=83) or coronary angioplasty (n=41). The only end-point analysed was cardiac death. In the revascularized group, cardiac death occurred in one of the 41 patients with and in 16 of the 83 patients without a viable myocardium (2.4% vs 19.3%, P<0.01). Outcome, as estimated by Kaplan-Meier survival, was better for patients with, compared to patients without, a viable myocardium, who underwent coronary revascularization (97.6 vs 77.4%, P=0.01). Using a Cox proportional hazards model, the presence of myocardial viability was shown to exert a protective effect on survival (chi-square 4.6, hazard ratio 0.1, 95% CI 0.01-0.8, P<0.03). The survival rate in medically treated patients was lower than in revascularized patients irrespective of the presence of a viable myocardium (79.7% vs 86.2, P=ns). CONCLUSION: In severe left ventricular ischaemic dysfunction, myocardial viability, as assessed by low dose dipyridamole echo, is associated with improved survival in revascularized patients.

Aged↗
PubMed1982

Aspirin and dipyridamole inhibit endothelial healing.

Aspirin and dipyridamole have been used to treat the thromboembolic complications of atherosclerosis. We studied the effects of these drugs on the rate of endothelial healing after a standard de-endothelializing injury of the thoracic aorta. Twenty-five rabbits received 13.5 mg/kg/day of aspirin and 15 mg/kg/day of dipyridamole one week before injury and for the period of endothelial regrowth. There were 25 control animals. Mean serum aspirin salicylate levels were 12 micrograms/dL at the time of injury and 15 micrograms/dL at death. Areas of endothelial regrowth were measured by Evans blue dye at 1, 4, 7 and 14 days after injury. The percentage of endothelial regrowth was measured by computer-assisted morphometry. Antiplatelet treatment retarded endothelial regrowth by 66% at four days, 22% at seven days, and 28% at 14 days. Antiplatelet drugs must be used cautiously, as re-endothelialization of injured arteries is retarded.

Animals↗
PubMed1993

Dipyridamole thallium imaging in patients being considered for vascular procedures.

We routinely performed intravenous dipyridamole thallium imaging and resting radionuclide ventriculography on 190 patients being considered for elective vascular procedures. Patients with thallium redistribution underwent coronary arteriography. Patients in group 1 (n = 78) had clinical evidence of coronary artery disease, and patients in group 2 (n = 112) had no history or electrocardiographic evidence of coronary artery disease. The frequency of thallium redistribution was not significantly different in the two groups (45% in group 1 and 46% in group 2). Coronary arteriography identified severe three-vessel or left main disease in eight patients (10%) in group 1 and 16 patients (14%) in group 2. Selection of patients for dipyridamole thallium imaging prior to vascular reconstruction should be based on whether or not documentation of the extent of coronary artery disease would influence therapy rather than on clinical indicators of coronary disease.

Aged↗
PubMed1987

Short-term reproducibility of dipyridamole-echocardiography test.

The aim of this study was to assess the short-term reproducibility of dipyridamole-echocardiography test (DET) consisting of two-dimensional echo monitoring during dipyridamole infusion (up to 0.84 mg/kg in 10 min). The diagnostic end-point of the test is the detection of new onset or worsening regional asynergy. A group of 87 patients with rest and/or effort angina performed two DETS on two consecutive days. All 60 patients with a positive DET had a positive repeat test, and the 27 negative DETs were also negative on the following day. The timing of the asynergy was also very similar between the two tests, both in patients with angina on effort (r = .93, p less than 0.01) and at rest (r = .92, p less than 0.01). In conclusion, DET has a very high short-term reproducibility regarding the presence and timing of asynergy.

Angina Pectoris↗
PubMed1988

Thallium-201 scintigraphy perfusion defect with dipyridamole in a patient with a myocardial bridge.

A patient with myocardial bridging and a thallium-201 scintigraphy perfusion defect after the administration of intravenous dipyridamole is presented. The same patient had a normal perfusion study on exercise stress testing. The effects of coronary vasodilators and dipyridamole on coronary artery flow patterns in patients with myocardial bridging are discussed. We suggest that coronary vasodilators may induce perfusion defects in patients with myocardial bridging and should be avoided in such patients.

Adult↗
PubMed1990

Dipyridamole thallium imaging may not be a reliable screening test for coronary artery disease in patients undergoing vascular surgery.

Dipyridamole thallium imaging has been proposed for cardiac risk stratification in patients undergoing peripheral vascular surgery. The purpose of this study was to define the benefit of this investigation in routine preoperative evaluation of these patients. The outcome of 86 patients undergoing vascular surgery procedures was examined in light of preoperative clinical assessment and dipyridamole SPECT thallium imaging (DST). Fifty-one patients (59%) were considered at high risk on clinical grounds, and 22 patients (26%) had perfusion defects. Ten patients suffered a perioperative coronary event, including unstable angina, myocardial infarction, or cardiac death. Seven of the patients with such events were among the 51 clinically high-risk subjects (14%). Three perioperative events occurred in the group of 19 patients with positive DST images who underwent surgery (16%), but the DST test failed to identify 7 patients who suffered coronary events. The frequency of abnormal thallium imaging was similar to the prevalence of angiographically significant coronary disease reported previously at this center, but considerably less than the rate of abnormal thallium imaging in past studies of vascular surgery patients. The application of the test to a low to moderate risk population is probably responsible for its lower predictive accuracy for coronary events. DST is not an ideal routine noninvasive technique for risk stratification in patients undergoing vascular surgery.

Aged↗