Current Advances in Vasodilator Pharmacological Stress Perfusion Imaging

doi:10.1053/j.semnuclmed.2008.12.003

Seminars in Nuclear Medicine

Volume 39, Issue 3, May 2009, Pages 204-209

https://doi.org/10.1053/j.semnuclmed.2008.12.003 Get rights and content

More than 7 million stress perfusion studies are performed in the United States annually, 44% with pharmacological vasodilator stress agents. Both adenosine and dipyridamole are nonselective coronary vasodilators that are commonly used for stress perfusion imaging. These agents are safe and provide an effective means to diagnose coronary artery disease. A newer agent, regadenoson, is an adenosine receptor agonist that is selective for coronary vasodilation. Regadenoson is noninferior to adenosine for the detection of ischemia and is better tolerated by patients. Recent trials such as INSPIRE (Adenosine Sestamibi Post-Infarction Evaluation) and the COURAGE (Results from Clinical Outcomes Utilizing Revascularization and Aggressive Guideline-driven Drug Evaluation) Nuclear Imaging Substudy have established clearly that noninvasive risk stratification with vasodilator testing is an important and appropriate step in guiding medical therapy and invasive coronary intervention.

Section snippets

Basic Principles of Pharmacological Stress Perfusion Imaging

Adenosine is infused at the rate of a 140 μg/kg/min for 6 minutes, although an abbreviated 4-minute protocol has been found to be comparable with the standard 6-minute infusion.² Intravenously administered adenosine is promptly cleared from the circulation by cellular uptake, predominately by erythrocytes and vascular endothelial cells. Once inside the cell, adenosine is quickly metabolized either via phosphorylation by adenosine kinase to adenosine monophosphate or via deamination by adenosine

New Vasodilator Stress Agents

Although adenosine and dipyridamole are the most commonly used agents for vasodilator myocardial perfusion imaging, they have a significant disadvantage of nonselective stimulation of all 4 subtypes of adenosine receptors (Table 1). Activation of receptors other than those responsible for vasodilation leads to undesirable minor and major side-effects and results in need to carefully screen and monitor vasodilator stress patients. A newer group of agents in various stages of development has

Conclusion

Vasodilator stress perfusion imaging is safe and effective in identifying prognostically significant coronary artery disease. Newer agents allow better tolerance, ease of administration, and improved side-effect profile. Recent trials have firmly established a pivotal role of vasodilator stress perfusion imaging in risk stratification and therapeutic guidance of patients with stable coronary artery disease.

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Cited by (20)

How to assess nonresponsiveness to vasodilator stress
2024, Journal of Nuclear Cardiology
Myocardial perfusion imaging (MPI) is a powerful tool for the functional assessment of ischemia in patients with suspected or known coronary artery disease (CAD). Given that the diagnostic accuracy and prognostic value of MPI and post-test management are highly dependent on achieving an adequate stress vasodilatory response, it is critical to identify those who may not have adequately responded to vasodilator pharmacological stress agents such as adenosine, dipyridamole, and regadenoson. Caffeine, a potent inhibitor of the adenosine receptor, is a compound that can affect vasodilatory hemodynamics, result in false negative studies, and potentially alter management in cases of inaccurate test results. Vasodilator non-responsiveness can be suspected by examining hemodynamics, quantitative positron emission tomography (PET) metrics such as myocardial flow reserve (MFR), and splenic response to stress. Quantitative MFR values of 1–1.2 should raise suspicion for nonresponsiveness in the setting of normal perfusion, along with the absence of a splenic switch off. Newer metrics, such as splenic response ratio, can be used to aid in the identification of potential nonresponders to pharmacologic vasodilators.
The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated <sup>82</sup>Rb PET myocardial perfusion imaging
2013, Journal of Nuclear Cardiology
Gated rubidium-82 (⁸²Rb) positron emission tomography (PET) imaging studies are acquired both at rest and during pharmacologic stress. Stress-induced ischemic left ventricular dysfunction (LVD) can produce a significant decrease in left ventricular ejection fraction (LVEF) from rest to stress. We determined the prevalence on PET of stress LVD with reduced ejection fraction (EF) and its association with absolute global and regional coronary flow reserve (CFR), and with relative perfusion defect summed difference score (SDS).
We studied 205 patients with known or suspected coronary disease (120 M, 75 F, age 69 ± 13 years) who had clinically indicated rest/regadenoson stress ⁸²Rb PET/CT studies. Data were acquired in dynamic gated list mode. Global and 17-segment regional CFR values were computed from first-pass flow data using a 2-compartment model and factor analysis applied to auto-generated time-activity curves. Rest and stress LVEF and SDS were quantified from gated equilibrium myocardial perfusion tomograms using Emory Cardiac Toolbox software. LVD was defined as a change in LVEF of ≤−5% from rest to stress. A subgroup of 109 patients also had coronary angiography. Stress LVD developed in 32 patients (16%), with mean EF change of −10 ± 5%, vs +6 ± 7% for patients without LVD (P < .0001). EF was similar at rest in patients with and without stress LVD (57 ± 18% vs 56 ± 16%, P = .63), but lower during stress for patients with LVD (47 ± 20% vs 61 ± 16%, P = .0001). CFR was significantly lower in patients with LVD (1.61 ± 0.67 vs 2.21 ± 1.03, Wilcoxon P = .002), and correlated significantly with change in EF (r = 0.35, P < .0001), but not with SDS (r = −0.13, P = .07). The single variable most strongly associated with high risk of CAD (i.e., left main stenosis ≥50%, LAD % stenosis ≥70%, and/or 3-vessel disease) was stress EF (χ² = 17.3, P < .0001). There was a higher prevalence of patients with territorial CFR values ≤1.0, consistent with coronary steal, in the LVD group than in the non-LVD group (39% vs 12%, P = .001).
LVD developed in 16% of patients undergoing ⁸²Rb PET myocardial perfusion imaging, and was associated with multivessel coronary artery disease. There was a significant relationship between LVD and coronary blood flow during stress, with LVD corresponding to a low CFR. Territorial CFR ≤1.0 was more common in patients with LVD than those without, suggesting that coronary steal is an important pathophysiologic mechanism contributing to pharmacologic stress-induced LVD.
Factors influencing non-cardiac side effects of dipyridamole when used for myocardial perfusion stress testing
2012, Journal of Medical Imaging and Radiation Sciences
Citation Excerpt :
The time required at the clinic to obtain a large sample size would be prohibitive. New pharmacological stress agents such as regadenoson claim to perform as well as dipyridamole with fewer side effects [8, 29–31]. Once this product is available in Canada, a similar study could investigate factors that influence side effects caused by this new agent.
This study evaluates whether patient demographic information can be used to predict the non-cardiac side effects experienced during myocardial perfusion imaging (MPI) procedures using dipyridamole.
Heart disease is a major cause of death in the industrialized world. MPI of coronary blood flow using radiopharmaceuticals is frequently used to assess coronary artery disease. Pharmacological methods can be used to increase coronary blood flow with vasodilators such as dipyridamole or adenosine, or inotropic and chronotropic agents such as dobutamine or arbutamine. The side effects of these agents are recognized, but little is known about the factors that influence their frequency and severity.
One hundred and nineteen patients scheduled for myocardial perfusion pharmacological stress testing using dipyridamole participated in the study. Patient demographic data, which included age, sex, body mass index (BMI), diabetic status, smoker status, and daily aspirin usage, were collected before the start of the procedure. Patients underwent a 1-day rest and stress MPI procedure. The radiopharmaceuticals used were ^99mTc-Myoview or ²⁰¹Tl. The pharmacological stress procedure used dipyridamole injections based on body weight. Aminophylline was injected at the end of the stress session. Gated single photon emission computed tomography was performed for both rest and stress images. Once the patients completed the procedure, they were given a questionnaire that asked them to report the severity of any side effects experienced from the dipyridamole. Specific data types determined the statistical test best suited for analysis. The Chi-square test was used to evaluate the nominal scale data (sex, diabetic status, aspirin usage, and smoker status), Mann-Whitney test was used to compare nominal scale data and ordinal scale data (side effect severity), Student’s t-test r was used for ratio scale data (age, BMI, and percent of population), and multiple linear regression and multiple logistic regression tests were used to evaluate multiple variables.
A total of 119 patients were surveyed (58 male, 61 female). The average age was 67.7 years (10.7 year standard deviation). There were no statistically significant differences in the male and female demographics except for daily aspirin usage (more common with males). Headaches were the most common side effect (50% of all patients), followed by dizziness (26%), flushing (24%), chest pain (19%), and nausea (18%). Correlations were found between patients experiencing no side effects with age (r = −0.607) and sex (P = .034); headaches with age (r = −0.706) and BMI (r = 0.464); chest pain with diabetic status (P = .017); dizziness with diabetic status (P = .039); and nausea with age (r = −0.612).
Side effects of dipyridamole are generally known, but the factors influencing incidence and severity are not. This study has shown that patient demographic information normally gathered before MPI procedures can help determine the frequency and severity of some side effects. Providing more accurate information to a patient on the possible side effects could help reduce patient anxiety and improve patient cooperation.
Cette étude évalue si les renseignements démographiques sur les patients peuvent être utilisés pour prédire les effets secondaires non cardiaques susceptibles de survenir durant les procédures d’imagerie par perfusion myocardique (IMP) à l’aide de dipyridamole.
La maladie cardiaque est une cause de décès importante dans le monde industrialisé. L’IMP de la circulation sanguine coronaire à l’aide de produits radiopharmaceutiques est souvent utilisée pour évaluer la coronopathie. Des méthodes pharmacologiques peuvent être utilisées pour augmenter le flux sanguin coronaire avec des vasodilatateurs comme le dipyridamole ou l’adénosine, ou des agents inotropiques et chronotropiques comme la dobutamine ou l’arbutamine. Les effets secondaires de ces agents sont connus mais on sait peu de choses sur les facteurs qui influencent leur fréquence et leur gravité.
Cent dix-neuf patients en attente d’un examen par perfusion myocardique sous stress pharmacologique au dipyridamole ont participé à l’étude. Les données démographiques des patients, incluant l’âge, le sexe, l’IMC, le statut diabétique, le statut de fumeur et l’usage quotidien de l’aspirine ont été recueillies avant le début des procédures. Les patients ont subi un examen d’IMP sous stress après un repos d’une journée. Les produits radiopharmaceutiques utilisés étaient le 99mTc-Myoview ou le 201Tl. La procédure de stress pharmacologique utilisait des injections de dipyridamole selon le poids corporel. Une injection d’aminophylline a été faite à la fin de la séance de stress. La TEM synchronisée a été utilisée pour l’image au repos et sous stress. Une fois la procédure terminée, les patients ont été invités à remplir un questionnaire qui leur demandait de décrire la gravité des effets secondaires ressentis, le cas échéant, du fait du dipyridamole.
Les types de données spécifiques ont déterminé les tests statistiques les mieux adaptés à l’analyse. Le test du chi carré a été utilisé pour évaluer les données d’échelle nominale (sexe, état diabétique, usage de l’AAS et usage du tabac); le test de Mann Whitney a été utilisé pour comparer les données d’échelle nominale et les données d’échelle ordinale (gravité des effets secondaires), le test de Student a été utilisé pour les données d’échelle de rapport (âge, IMC et pourcentage de la population) et des tests de régression linéaire et de régression logistique multiple ont été utilisés pour évaluer les variables multiples.
Au total, 119 patients ont été évalués (58 hommes et 61 femmes). L’âge moyen était de 67,7 ans (écart-type : 10,7 ans). Il n’y avait pas de différences statistiquement significatives entre les données démographiques des hommes et des femmes, sauf pour l’utilisation quotidienne de l’aspirine (plus fréquente chez les hommes). Les maux de têtes sont les effets secondaires les plus fréquents (50 % de tous les patients), suivis des étourdissements 26 %), des bouffées de chaleur (24 %), des douleurs thoraciques (19 %) et des nausées (18 %). Une corrélation a été établie entre les patients qui n’ont ressenti aucun effet secondaire et l’âge (r = −0,607) et le sexe (p = 0,034); entre les maux de tête et l’âge (r = −0,706) et l’IMC (r = 0,464); entre les douleurs thoraciques et le diabète (p = 0,017); entre les étourdissements et le diabète (p = 0,039); et entre la nausée et l’âge (r = −0,612).
Les effets secondaires du dipyridamole sont généralement bien connus, mais les facteurs qui en influencent l’incidence et la gravité ne le sont pas. Cette étude démontre que les données démographiques des patients qui sont habituellement recueillies avant une procédure d’IMP peuvent aider à déterminer la fréquence et la gravité de certains effets secondaires. Le fait de fournir aux patients une information plus précise sur les effets secondaires possibles pourrait contribuer à diminuer l’anxiété chez les patients et améliorer leur coopération.
Correlation Between Dipyridamole-Induced Electrocardiogram Arrhythmia and Risk Stratification in Myocardial Perfusion SPECT Imaging
2022, Iranian Heart Journal
Regadenoson versus dipyridamole: Evaluation of stress myocardial blood flow response on a CZT-SPECT camera
2022, Journal of Nuclear Cardiology
Chapter 9: Field Discoveries (Case Reports)
2022, RSC Drug Discovery Series

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Current Advances in Vasodilator Pharmacological Stress Perfusion Imaging

Section snippets

Basic Principles of Pharmacological Stress Perfusion Imaging

New Vasodilator Stress Agents

Conclusion

J Nucl Cardiol

J Nucl Cardiol

J Nucl Cardiol

J Nucl Cardiol

J Nucl Cardiol

Am J Cardiol

JACC Cardiovascular Imaging

J Am Coll Cardiol

J Am Coll Cardiol