Dipyridamole

We describe a case of prolonged sinus arrest resolved by external cardiac massage following intravenous infusion of dipyridamole, during a thallium myocardial perfusion test. The arrhythmia, presumably due to an acute drug adverse effect, had not been previously described (to our knowledge) as a complication of dipyridamole stress testing.

Dipyridamole stress testing is commonly accepted as an effective alternative to exercise stress in patients with suspected or proven coronary artery disease. On the whole, major side effects are rare,[1-5] even among subjects soon after infarction.[6] We present a case of syncope due to prolonged sinus arrest following intravenous infusion of dipyridamole.

CASE REPORT

This 47-year-old man had a history of resting chest pain with transient ST elevation followed by T-wave inversion ([V.sub.2]-[V.sub.6] ECG leads) since November 1991. Coronary angiography disclosed a 90 percent irregular stenosis of midleft anterior descending coronary artery. In February 1992, he underwent a percutaneous transluminal angioplasty followed by rotational atherectomy on this vessel. Symptoms disappeared after the procedure. A myocardial perfusion stress test was ordered 1 month later, while receiving metoprolol (150 mg/d) and aspirin (160 mg/d). The day of the test, resting blood pressure was 120/75 mm Hg, and basal heart rate was 55 beats per minute. While a right arm vein was being cannulated, the patient looked quiet and went on talking with physicians and the technician. Blood loss was minimal. About 10 min later, the standard dose of dipyridamole (0.56 mg/kg intravenously in 4 min) was infused while the patient was in the supine position. Blood pressure and ECG were continuously monitored, and they showed no significant changes during the infusion. Just before thallium injection, about 3 min after the end of dipyridamole infusion, he felt a sensation of warmth in the neck and suddenly collapsed. External cardiac massage restored a normal circulation in about 60 s. When awake, the patient denied any chest pain. The ECG during the episode (Fig 1) showed a progressive sinus bradycardia followed by a prolonged sinus arrest. Sinus rhythm resumed after a few junctional escape beats. Asystole lasted about 18 s. Intravenous aminophylline (240 mg) had been given shortly after the syncope. Routine blood chemistry studies gave normal results. A 24-h ECG monitoring in the intensive care unit showed no rhythm disturbance. The patient refused a formal study in the electrophysiology laboratory.

DISCUSSION

Dipyridamole infusion in man is known to cause a significant increase of coronary flow, with usually mild systemic hemodynamic changes, such as a reduction of aortic pressure and a reflex increase of heart rate.[7] As scintigraphic test protocol requires that the drug be infused in the supine position, and thallium infused in the sitting position, some hemodynamic postural adjustment might also occur. Finally, should profound myocardial ischemia develop as a consequence of pharmacologic challenge, one could eventually find a systemic arterial hypotension and an increasing pulmonary capillary pressure.

A direct effect of dipyridamole on sinus node, apart from the reflex increase of automaticity,[8] has not been described. The drug is supposed to act through release of endogenous adenosine.[9] As the latter is known to affect atrioventricular[9-12] and sinus node[12] function, a similar reaction to dipyridamole can be expected. However, a significant sinus node dysfunction is not reported in the largest series as a major side effect.[1-6,13] We could find only two similar case reports in the literature. In the first, sinus arrest developed in the context of acute transmural myocardial infarction.[14] In the second, a sinus node depression and a presumably nodal escape rhythm, without complete loss of consciousness, were reported in a patient with proximal right coronary artery occlusion and evidence of posterolateral ischemia on thallium scan.[15] In our patient, a reflex increase of vagal tone can be invoked to explain syncope and sinus arrest, though [beta]-blockade would, if ever, prevent a purely vagal, reflex-mediated syncope,[16] and no hemodynamic changes could be detected before abrupt sinus arrest. The arrhythmia described eventually appeared about 15 min after vein cannulation and 3 min after the end of sinus arrest in our patient was related to dipyridamole infusion.

REFERENCES

[1] Ranhosky A, Kempthorne-Rawson J. The safety of intravenous dipyridamole thallium myocardial perfusion imaging. Circulation 1990; 81:1205-09

[2] Homma S, Gilliland Y, Guiney TE, Strauss HW, Boucher CA. Safety of intravenous dipyridamole for stress testing with thallium imaging. Am J Cardiol 1987; 59:152-54

[3] Gerson MC, Moore EN, Ellis K. Systemic effects and safety of intravenous dipyridamole in elderly patients with suspected coronary artery disease. Am J Cardiol 1987; 60:1399-1401

[4] Lam JYT, Chaitman BR, Glaenzer M, Byers S, Fite J, Shay Y, et al. Safety and diagnostic accuracy of dipyridamole-thallium imaging in the elderly. J Am Coll Cardiol 1988; 11:585-89

[5] Lette J, Waters D, Lassonde J, Rene P, Picard M, Laurendeau F. Multivariate clinical models and quantitative dipyridamole thallium imaging to predict cardiac morbidity and death after vascular reconstruction. J Vasc Surg 1991; 14:160-69

[6] Pirelli S, Inglese E, Suppa M, Corrada E, Campolo L. Dipyridamole thallium-201 scintigraphy in the early postinfarction period: safety and accuracy in predicting the extent of coronary disease and future recurrence of angina in patients suffering from their first myocardial infarction. Eur Heart J 1988; 9:1324-31

[7] Gould KL, Westcott RJ, Albro PC, Hamilton GW. Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilatation: II. Clinical methodology and feasibility. Am J Cardiol 1978; 41:279-87

[8] Bubinski R, Markiewicz K, Cholewa M, Gorski L, Gawor Z, Kus W. Electrophysiologic effects of intravenous dipyridamole. Int J Cardiol 1989; 24:327-35

[9] Iskandrian AS. Single photon emission computed tomographic thallium imaging with adenosine, dipyridamole and exercise. Am Heart J 1991; 122:279-83

[10] Nguyen T, Heo J, Ogilby JD, Iskandrian AS. Single photon emission tomography with thallium-201 during adenosine-induced coronary hyperemia: correlation with coronary arteriography, exercise thallium and 2-D echo. J Am Coll Cardiol 1990; 16:1375-83

[11] Rossen JD, Quillen JE, Lopez AG, Stenberg RG, Talman CL, Winniford MD. Comparison of coronary vasodilation with intravenous dipyridamole and adenosine. J Am Coll Cardiol 1991; 18:485-91

[12] Coyne EP, Belvedere DA, Van de Streek PR, Weiland FL, Evans RB, Spaccavento LJ. Thallium-201 scintigraphy after intravenous infusion of adenosine compared with exercise testing in the diagnosis of coronary artery disease. J Am Coll Cardiol 1991; 17:1289-94

[13] Laarman GJ, Niemeyer MG, van der Wall EE, Verzijlbergen FJ, Go TL, Bruschke AV, et al. Dipyridamole thallium testing: noncardiac side effects, cardiac effects, electrocardiographic changes and hemodynamic changes after dipyridamole infusion with and without exercise. Int J Cardiol 1988; 20:231-38

[14] Blumenthal MS, McCauley CS. Cardiac arrest during dipyridamole imaging. Chest 1988; 93:1103-04

[15] Pennell DJ, Underwood SR, Ell PJ. Symptomatic bradycardia complicating the use of intravenous dipyridamole for thallium-201 myocardial perfusion imaging. Int J Cardiol 1990; 27:272-74

[16] Raviele A, Gasparini G, DePede F, Delise P, Bonso A, Piccolo E. Usefulness of head-up tilt in evaluating patients with syncope of unknown origin and negative electrophysiologic study. Am J Cardiol 1990; 65:1322-27

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