Safety, feasibility, and diagnostic accuracy of accelerated high-dose dipyridamole stress echocardiography

doi:10.1016/S0002-9149(00)01424-7

The American Journal of Cardiology

Volume 87, Issue 5, 1 March 2001, Pages 520-524

https://doi.org/10.1016/S0002-9149(00)01424-7 Get rights and content

Abstract

Protocols for dipyridamole stress testing have evolved in the last 16 years in the neverending quest of optimal diagnostic accuracy and user friendliness. Higher dipyridamole dose in a shorter infusion time provides higher sensitivity, but concern over safety is still controversial. An accelerated high-dose (0.84 mg/kg in 6 minutes without atropine) dipyridamole stress test was performed on 1,295 patients in 2 echocardiographic laboratories: Institute of Clinical Physiology of Pisa and Niguarda Hospital of Milan. During testing, there were no deaths and no patients had ventricular fibrillation. Major adverse reactions occurred in 3 cases (1 every 431 studies): 1 myocardial infarction, 1 brief cardiac asystole, and 1 transient ischemic attack. Overall feasibility was 97%. In 66 patients with normal function at rest who were evaluated off therapy, with coronary angiography performed independently of test results, the accelerated high-dose protocol showed a sensitivity of 85% (confidence interval [CI] 73% to 92%) and a specificity of 93% (CI 83% to 97%) for angiographically assessed coronary artery disease (quantitatively assessed diameter reduction ≥50%). Diagnostic accuracy of the accelerated high dose was 89% (CI 79% to 95%). Thus, accelerated high-dose dipyridamole stress echocardiography was reasonably safe and well tolerated. This protocol is especially appealing for its excellent diagnostic accuracy coupled with the short imaging time and no need for drug cocktails.

Section snippets

Patient population

Between April 1997 and April 1999, 1,295 nonconsecutive in-hospital patients or outpatients referred to the echocardiographic laboratory for evaluation of chest pain, or patients with known coronary artery disease, or both, were enrolled in the study. Exclusion criteria were congestive heart failure, unstable angina, or documented cardiomyopathy. Patients with second- or third-degree atrioventricular block or with sick sinus syndrome and severe asthmatic or chronic obstructive pulmonary disease

Feasibility and safety

The feasibility and safety analysis was performed on the total population of 1,295 patients, whereas the evaluation of diagnostic accuracy was evaluated in the subset of 216 patient with independently acquired angiographic information. The total laboratory time (from patient arrival to written report) was around 30 minutes.

Hemodynamic variables

Heart rate, systolic and diastolic blood pressure, and rate-pressure products both at baseline and at peak stress are presented in Table 1.

Stress tolerability

Echocardiographic studies were

Discussion

Accelerated high-dose dipyridamole is a highly feasible, reasonably well tolerated and accurate test in patients with known or suspected coronary artery disease. Its main advantage over the currently accepted version of high-dose testing is that it reduces imaging and laboratory time by almost 50%, with obvious favorable impact on logistics and costs.

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Cited by (48)

Prognostic Value of Heart Rate Reserve in Patients with Permanent Atrial Fibrillation during Dipyridamole Stress Echocardiography
2020, American Journal of Cardiology
Citation Excerpt :
Transthoracic SE studies were performed with commercially available ultrasound machines depending on the possibilities and the equipment available in each period. High-dose dipyridamole (up to 0.84 mg/kg over 10 minutes up to 200212 and over 6 minutes thereafter) SE was performed according to well-established protocols.2 Wall motion score index (WMSI) was derived by dividing the sum of individual segment scores by the number of interpretable segments in a 17-segment model of the left ventricle.2,3
In patients in sinus rhythm, a blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (SE) is a prognostically unfavorable sign of cardiac autonomic dysfunction.
In this study we sought to assess the prognostic meaning of HRR in patients with permanent atrial fibrillation (AF). The study population was made by 301 patients (176 men, age 73 ± 8 years) with suspected (n = 200) or known (n = 101) coronary artery disease and permanent AF who underwent high-dose dipyridamole SE. HRR was calculated on an average of 5 consecutive beats as the peak/rest ratio of HR from 12-lead EKG. During a median follow-up time of 77 months (first quartile 44, third quartile 115 months), 111 (37%) patients died. Receiver operating characteristics analysis identified HRR ≤1.17 as the best predictor of mortality. At multivariable analysis, HRR ≤1.17 (HR 1.75, 95% CI 1.17 to 2.62; p = 0.006) independently predicted mortality together with age (HR 1.09, 95% CI 1.06 to 1.13; p <0.0001), rest wall motion score index (HR 1.69, 95% CI 1.01 to 2.83; p = 0.04), and systemic hypertension (HR 1.76, 95% CI 1.06 to 3.00; p = 0.04). The annual mortality was 5.1% in the overall population, 7.0% in the 140 (46%) patients with abnormal HRR and 3.5% in the 161 (54%) patients with normal HRR. The 8-year mortality was 48% in patients with abnormal HRR and 18% in those with normal HRR (p <0.0001). In conclusion, patients with suspected or known coronary artery disease with permanent AF with a blunted HRR have an increased mortality. HRR outweighs inducible ischemia for prediction of survival. The assessment of HRR should become an integral part of dipyridamole SE reading also in AF.
Prognostic value of heart rate reserve is additive to coronary flow velocity reserve during dipyridamole stress echocardiography
2020, Archives of Cardiovascular Diseases
During dipyridamole stress echocardiography (SE), a blunted heart rate reserve (HRR) is a prognostically unfavourable sign of cardiac autonomic dysfunction.
To assess the prognostic meaning of HRR and coronary flow velocity reserve (CFVR).
The study group comprised 2149 patients (1236 men; mean age 66 ± 12 years) with suspected (n = 1280) or known (n = 869) coronary artery disease and without inducible regional wall motion abnormalities (RWMA) during dipyridamole SE (0.84 mg/kg in 6 min). We assessed CFVR of the left anterior descending artery with pulsed-wave Doppler as the ratio between hyperaemic peak and basal peak diastolic flow velocities (abnormal value ≤ 2.0). HRR was calculated as the peak/resting ratio of heart rate from a 12-lead electrocardiogram (abnormal value ≤ 1.22). All patients were followed up.
CFVR and HRR were abnormal in 520 (24%) and 670 (31%) patients, respectively. There was a positive linear correlation between CFVR and HRR (r = 0.30; P < 0.0001). During a median follow-up of 22 months (1st quartile 12 months, 3rd quartile 35 months), 75 (6%) patients died. The annual mortality was 1.6% in the overall population, 0.5% in the 1224 (57%) patients with normal CFVR and HRR, 1.7% in the 405 (19%) patients with abnormal HRR only, 3.6% in the 255 (12%) patients with abnormal CFVR only, and 6.2% in the 265 (12%) patients with abnormal CFVR and HRR.
HRR is weakly related to CFVR, and a blunted HRR usefully complements RWMA and CFVR for prediction of outcome with dipyridamole SE. The patient without inducible RWMA is still at intermediate risk, but the risk is low with concomitant preserved CFVR, and very low with concomitant normal HRR.
Pendant une échographie sous Dipyridamole, une altération de la réponse en fréquence cardiaque est un signe de mauvais pronostic, signant la dysfonction du système nerveux autonome.
Évaluer la valeur pronostique de la réponse altérée en fréquence cardiaque et de la réserve de flux coronaire en échocardiographie Doppler sous Dipyridamole.
Cette étude a inclus 2 149 patients (1 236 hommes, âge moyen 66 ± 12 ans) ayant une maladie coronaire suspectée (n = 1 280) ou connue et sans asynergie segmentaire lors de l’échographie sous Dipyridamole (0,84 mg/kg/en 6 minutes). La réserve coronaire a été évaluée en Doppler pulsé de l’artère ventriculaire antérieure comme un rapport des vélocités au pic en phase hyperhémique, versus état basal, une valeur normale étant définie comme un rapport ≤ 2. La réponse altérée en fréquence cardiaque a été calculée comme le rapport pic/repos de fréquence cardiaque à partir d’un ECG 12 dérivations et la valeur anormale a été définie comme un rapport ≤ 1,22. Tous les patients ont été suivis.
La réserve coronaire et la réponse altérée en fréquence cardiaque était anormale chez 524 (24 %) et 670 (31 %) patients respectivement. Nous avons observé une corrélation linéaire positive entre ces deux paramètres (r = 0,30, p < 0,0001). Pendant un suivi médian de 22 mois (1^er quartile 12 mois, 3^e quartile 35 mois), 65 patients (6 %) sont décédés. La mortalité annuelle est de 1,6 % dans la population globale, 0,5 % parmi les 1 224 patients ayant une réserve anormale (57 %), 1,7 % parmi les 405 patients ayant une altération de la réponse en fréquence cardiaque, 19 %, 3,6 % parmi les 225 patients ayant une réserve coronaire anormale isolément 12 %) et 6,2 % parmi les 265 patients ayant à la fois une anomalie de la réserve coronaire et de la réponse en fréquence cardiaque sous Dipyridamole (12 %).
La réponse altérée en fréquence cardiaque est faiblement liée à la réserve de flux coronaire et une réponse altérée en réponse cardiaque complète les informations pronostiques liées à l’asynergie segmentaire ou à l réserve de flux coronaire lors d’une échographie sous Dipyridamole. Les patients ayant une asynergie segmentaire lors de cet examen sont à risque intermédiaire mais le risque est faible en cas de préservation du flux coornair et ce risque est particulièrement faible lorsque la réponse en fréquence cardiaque lors de ce test est normale.
Age- and Gender-Specific Prognostic Cutoff Values of Coronary Flow Velocity Reserve in Vasodilator Stress Echocardiography
2019, Journal of the American Society of Echocardiography
Coronary flow velocity reserve (CFVR) of the left anterior descending artery is useful for risk stratification during stress echocardiography (SE) as an add-on to regional wall motion abnormalities (RWMA). We sought to provide sex- and age-specific prognostic cutoff values for CFVR.
A total of 5,577 patients (2,284 women; 110 age ≥ 85 years) who underwent dipyridamole SE with evaluation of RWMA and CFVR were enrolled in a multicenter prospective SE registry. Death and myocardial infarction were the clinical end points.
During 20 months' median follow-up, 649 events (236 deaths, 413 infarctions) occurred: 288 in women and 38 in patients ≥85 years. At receiver operating characteristics analysis, the best prognostic cutoff value for CFVR was similar for men (2.03) and women (2.02) and consistent across all age strata (<45 years: 2.03; 45-54 years: 2.04; 45-64 years: 2.03; 65-74 and 75-84 years: 2.0) except for patients >85 years, who showed 1.90 as the optimal value. Independent predictors of mortality or myocardial infarction were RWMA (hazard ratio [HR] = 5.42), reduced CFVR (HR = 3.26), resting ejection fraction (HR = 0.98), smoking habit (HR = 1.41), age (HR = 1.02), and prior percutaneous coronary intervention (HR = 1.20) in patients age <85 years; and RWMA (HR = 5.42), smoking habit (HR = 3.24), and resting ejection fraction (HR = 0.97) in those age ≥85 years. CFVR added a prognostic contribution over clinical parameters, resting ejection fraction, and stress-induced RWMA in all age and sex groups except men >85 years.
A sex-independent value of CFVR ≤2.0 provides the optimal prognostication across all age groups, except for those ≥85 years in whom a cutoff ≤1.90 is needed. Risk stratification is more effective for all age groups when CFVR is combined with RWMA.
Usefulness of Blunted Heart Rate Reserve as an Imaging-Independent Prognostic Predictor During Dipyridamole Stress Echocardiography
2019, American Journal of Cardiology
Citation Excerpt :
This finding has been consistently observed with adenosine,9 dipyridamole,10 and A2A receptor adenosine agonist regadenoson.26 The present study is the first one with echocardiography, which is different from perfusion scintigraphy (SPECT) since ischemia is the required end point, and is the first one with the high dose, which is the standard for echocardiography imaging.5,6 Association of chronotropic incompetence with events was present also in patients on β blockers,27 as previously reported with exercise28 and dipyridamole perfusion imaging stress.11
A blunted heart rate (HR) response during dipyridamole myocardial perfusion imaging has been associated with a poor outcome. To assess the value of HR response in patients who underwent high-dose dipyridamole stress echocardiography (SE), we retrospectively selected a sample of 3,059 patients (none with pacemakers or atrial fibrillation; mean age 66 ± 11 years). All underwent high-dose (0.84 mg/kg) dipyridamole SE for evaluation of known or suspected coronary artery disease and/or heart failure in 2 laboratories of Pisa-IFC and Lucca. HR (with 12-lead ECG) was obtained each minute and recorded at rest and peak stress. HR reserve (HRR) was calculated as the peak/rest HR ratio. All patients were followed up. Patients were randomly divided into the modeling and validation group of equal size. During a median follow-up time of 1,004 days, 321 hard events occurred: 231 deaths and 90 nonfatal myocardial infarctions. HRR ≤ 1.22 identified by receiver operating characteristic analysis in the modeling group was an independent predictor of infarction-free survival in the modeling (hazard ratio 1.83, 95% confidence interval [CI] 1.30 to 2.60, p = 0.001), in the validation (hazard ratio 1.47, 95% CI 1.08 to 2.01, p = 0.02), and in the overall group (hazard ratio 1.60, 95% CI 1.27 to 2.02, p <0.0001), either off- or on-β blockers. Five-year event rate increased from 8% to 24 % from the highest (≥1.41) to the lowest (≤1.14) HRR quartile. In conclusion, blunted HRR is a useful nonimaging predictor of adverse events during high-dose dipyridamole SE, independent of inducible ischemia, and beta-blocker therapy.
LDL apheresis improves coronary flow reserve on the left anterior descending artery in patients with familial hypercholesterolemia and chronic ischemic heart disease
2017, Atherosclerosis Supplements
LDL apheresis (LA) influences the microcirculation, endothelial function and cardiovascular homeostasis. The aim of our study was to analyze temporal variations of coronary flow reserve (CFR) on the left anterior descending artery, obtained during dipyridamole stress echocardiography (DSE), in patients with severe familial hypercholesterolemia on LA (LA group) or not (not LA group) and ischemic heart disease (IHD).
The LA group consisted in 10 patients (mean age 65 ± 7 years, male 70%) with Familial Hypercholesterolemia and chronic IHD on maximally tolerated lipid lowering therapy and chronic LA treatment (median 7 years, interquartile range 6–14 years). Hyperlipoproteinemia (a) was also present in 6/10 subjects. LA was performed biweekly by dextran-sulfate or heparin-induced LDL precipitation technique. IHD was diagnosed at a mean age of 44 ± 8 years.
The control group was matched for age, sex and follow-up period.
CFR was calculated as the ratio between blood diastolic velocity sampled at peak stress with dipyridamole and baseline diastolic velocity (normal value > 2.0). No relevant comorbidities were present.
During a median follow-up of 27 months (interquartile range 23–50 months), a significant increase in CFR (from 1.86 ± 0.47 to 2.25 ± 0.35; p < 0.001) was observed in LA group. During this period, no patients modified their anti-ischemic therapy and no cardiovascular events were reported. In the control group, during the study time (24 months – interquartile range 14–57 months) no significant variation in CFR was observed (from 2.08 ± 0.39 to 1.92 ± 0.26; p 0.283).
Myocardial blood perfusion, measured as CFR by dipyridamole stress echocardiography-is increased in patients with severe familial hypercholesterolemia chronically treated with LA.
DSE might be a reliable tool to monitor the therapeutic effect of lipid lowering therapy.
Accelerated dobutamine stress testing: Feasibility and safety in patients with moderate aortic stenosis
2015, Egyptian Heart Journal
A continuous infusion of a single high dose of dobutamine was suggested as a simple protocol of dobutamine stress echocardiography (DSE). The present study explores the feasibility and safety of an accelerated DSE protocol in patients with calcific moderate valvular aortic stenosis undergoing DSE for evaluation of suspected coronary artery disease.
Eligible patients (n = 100) were prospectively enrolled. They were randomly assigned to undergo either the accelerated (group A, 50 patients) or the conventional protocol (group B, 50 patients). Group A received a continuous infusion of 40 μg/kg/min ± 1–2 mg atropine. Patients were monitored for adverse drug effects. Test duration was recorded. Patients with positive stress results underwent coronary angiography (CA).
Mean age of the study cohort was 62.29 ± 9.8 years, 62 (62%) being males. Mean pressure gradient across the aortic valve was recorded (group A: 32.2 mmHg and group B: 31.16 mmHg, P < 0.05). Group B showed a longer mean test duration (17.9 ± 2.3 vs. 8.9 ± 1.9 min, P < 0.001) and higher mean weight-adjusted cumulative dobutamine dose (385 ± 115 vs. 350 ± 110.24 μg/kg, P < 0.05). The two groups received a similar total dose of atropine. Group A patients showed significantly lower incidence of extra-systoles, non-sustained ventricular tachycardia and severe hypotension (P < 0.05). CA results yielded almost similar diagnostic outcomes in both groups.
In patients with calcific moderate aortic stenosis undergoing DSE; adopting the described accelerated protocol is associated with shorter test duration, lower weight-adjusted cumulative dobutamine dose for target heart rate achievement and fewer adverse effects, while maintaining a comparable diagnostic value.

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Coronary artery diseaseSafety, feasibility, and diagnostic accuracy of accelerated high-dose dipyridamole stress echocardiography

Abstract

Section snippets

Patient population

Feasibility and safety

Hemodynamic variables

Stress tolerability

Discussion

Am J Cardiol

J Am Coll Cardiol

Am Soc Echocardiogr

J Am Coll Cardiol

J Nucl Cardiol

Enhanced sensitivity for detection of coronary artery disease by addiction of atropine to dipyridamole echocardiography

Eur Heart J

Circulation

Pharmacological stress echocardiography in the diagnosis of coronary artery disease and myocardial ischemiaa comparison between dobutamine and dipyridamole

Eur Heart J

Dipyridamole and dobutamine-atropine stress echocardiography in the diagnosis of coronary artery diseasecomparison with exercise stress test, analysis of agreement and impact of antianginal treatment

Chest

Accelerated high-dose dipyridamole stress-echo, the busy cardiologist’s stress test

Eur Heart J

Dipyridamole-echocardiography testthe historical background and the physiologic basis

Eur Heart J

Coronary artery disease
Safety, feasibility, and diagnostic accuracy of accelerated high-dose dipyridamole stress echocardiography