The safety of adenosine pharmacologic stress testing in patients with first-degree atrioventricular block in the presence and absence of atrioventricular blocking medications

The safety of adenosine pharmacologic stress testing in patients with first-degree atrioventricular block in the presence and absence of atrioventricular blocking medications G h a s s a n S. Alkoutami, MD, William C. Reeves, MD, a n d A s s a d M o v a h e d , MD

Background. Pharmacologic stress testing in conjunction with radionuclide myocardial perfusion imaging may be used in the diagnosis of coronary artery disease and risk assessment. Adenosine can cause atrioventricular nodal (AV) block during infusion. In this study, we evaluated whether patients with baseline first-degree AV block could safely undergo adenosine stress testing. Methods and Results. We evaluated the frequency of second- and third-degree AV block in patients with baseline first-degree AV block during adenosine stress testing, in the presence and absence of AV blocking medications (digitalis, ~-blockers, diltiazem, verapamil). Six hundred consecutive patients underwent pharmacologic stress myocardial perfusion imaging with adenosine infusion at 140 gg/kg/min for 6 minutes. A total of 43 patients (7.16%) had baseline firstdegree AV block (PR interval > 200 msec), and 557 patients had a baseline PR interval < 200 msec. Twenty-one of the 43 patients (48.8 %) had further prolongation of PR interval > 240 msec, compared with 58 of 557 patients (10.4%) in the control group (P < .0001). In 16 of the 43 patients (37.3 %), second-degree AV block developed, compared with 45 of 557 patients (8.0%) in the control group (P < .0001). In 6 o f the 43 patients (13.9 %), third-degree AV block developed, compared with 6 of 557 patients (1.0%) in the control group (P < .0001). All types of AV block were short duration and were not associated with any specific symptoms. None of these episodes required specific treatment. The presence of AV blocking medications (digitalis, [3-blockers, diltiazem, verapamil) did not increase the incidence of AV block during adenosine infusion. Conclusion. In patients with baseline PR interval of more than 200 msec, the frequency of second- and third-degree AV block during adenosine stress testing was significantly higher than in patients with a normal baseline PR interval. AV blocking medications did not increase the incidence of second- and third-degree AV block during adenosine stress testing. We conclude that it is safe to perform adenosine pharmacologic stress testing in patients with baseline PR prolongation. (J Nucl Cardiol 1999;6:495-7.) Key Words: AV blocking medications • adenosine stress testing • myocardial perfusion studies

Pharmacologic stress testing in conjunction with radionuclide myocardial perfusion studies constitutes roughly 30% of all stress tests performed for the detection of coronary artery disease and risk assessment. Ideal candidates are patients who either cannot exercise or can From the Section of Cardiology, Department of Internal Medicine, East Carolina University School of Medicine, Greenville, North Carolina. Received for publication March 13, 1998; revision accepted Dec 2, 1998. Reprint requests: Assad Movahed, MD, Section of Cardiology, Department of Medicine, East Carolina University School of Medicine, Greenville, NC 27858; [email protected]. Copyright © 1999 by the American Society of Nuclear Cardiology. 1071-3581/99/$8.00 + 0 4311196896

perform only limited exercise. 1,2 The stress agents can be divided into vasodilators (dipyridamole, adenosine, and adenosine triphosphate), which cause primary coronary vasodilation, and inotropes/chronotropes (dobutamine and arbutamine), which cause secondary vasodilation as a result of increase in myocardial oxygen demand. 3,4 Adenosine, when infused intravenously, has an ultrashort half-life, less than 10 seconds. 5,6 First degree atrioventricular nodal (AV) block occurs in about 10% of patients but is hemodynamically unimportant. Seconddegree AV block occurs in 4% and is well tolerated. Third-degree AV block occurs in < 1% and requires either a decreased rate of infusion or discontinuation of the drug. 7,8 In this study, we retrospectively evaluated the 495

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Alkoutarni,Reeves, and Movahed Safety of adenosine pharmacologic stress testing

Journal of Nuclear Cardiology September/October 1999

t2 ~

"5

6-

=E 4.

z

1st

AV'B

2nd AVB

3rd AVB

Figure 1. Effect of AV blocking medications (digitalis, [3-blockers,diltiazem, verapamil) on incidence of AV block.

Table 1. Patient characteristics Men

Women

Total

(n = 359)

(n = 2 4 1 )

(n = 6 0 0 )

30-90 280/0 160/0 42% 120/0 81 19

30-92 320/0 15.5% 43% 25% 202 43

val < 200 msec (control group). Patients with atrial fibrillation or flutter were excluded.

Adenosine Stress Protocol Age (yr) Previous MI DM Hypertension Previous CABG AVBM (n) Baseline PR > 200 msec

30-92 37% 15% 43% 31% 121 24

M/, Myocardial infarction; DIM, diabetes mellitus; CABG, coronary artery bypass grafting; AVBIM, atrioventricular blocking medications (digitalis, 13-blockers, diltiazem, verapamil).

safety and frequency of second- and third-degree AV block in patients with baseline first-degree AV block in the presence and absence of AV blocking medications (digitalis, I]-blockers, diltiazem, and verapamil).

Patients were instructed not to consume coffee or other caffeine-containing products for 24 hours before the test. Adenosine was infused at a rate of 140 gg/kg/min for a total of 6 minutes. Radionuclide tracer (thallium 201 or technetium 99m sestamibi) was injected at peak effect (the end of the third minute of adenosine infusion). A baseline electrocardiogram and arterial blood pressure were obtained on all patients, with continuous monitoring of electrocardiograms throughout the test and for 5 minutes after the infusion of the adenosine. The frequency of second- (Wenckebach AV block or 2 to 1 AV conduction) and third-degree AV block (high degree or complete AV block) with associated symptoms (dizziness, near syncope, or syncope) were recorded.

Statistical Methods METHODS

Study Population The study population included all patients referred to our institute for pharmacologic stress myocardial perfusion imaging who received adenosine as a stress agent between March 1995 and January 1997. We studied 600 consecutive patients whose ages varied from 30 to 92 years old. Three hundred fifty-nine were men, and 241 were women (Table 1). Fogy-three patients had baseline first-degree AV block (study group) with PR interval > 200 msec, and 557 patients had normal baseline PR inter-

The statistical analyses were carried out with STATXACT version 3 for Windows used. We used Fisher's exact tests.

RESULTS A total of 43 patients (7.16%) had baseline firstdegree AV block (PR interval > 200 msec). During adenosine infusion, in 21 of the 43 patients (48.8%), further prolongation of PR interval of more than 240 msec developed (9 patients received AV blocking medications) compared with in 58 of 557 patients in the control group (10.4%) in whom new first-degree AV block developed

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Table 2. The incidence of atrioventricular block with adenosine Baseline PP~ 2 0 0 m s e c (n -- 43)

Baseline PR < 2 0 0 m s e c (n = 557)

Pvalue

21 (48.8%) 16 (37.30/0) 6 (13.9%)

58 (10.4%) 45 (8.00/0) 6 (1.13%)

<.00131 <.0001 <.0001

Further prolongation of PR Second-degree AVB Third-degree AVB PR, PR interval; AVB, atrioventricular block.

(;(2 _- 145.8 with 3 degrees of fi'eedom and P < .0001). In 16 of the 43 patients (37.3%) in the study group, seconddegree AV block developed; 7 of the patients were receiving AV blocking medications, compared with 45 of 557 patients (8.0%) in the control group (%2 = 37.1, with 1 degree of freedom and P < .0001). In 6 of the 43 patients in the study group (13.9%), third-degree AV block developed (3 of the patients were receiving AV blocking medications) compared with 5 of 557 patients in the control group (1.0%) (Fig 1). This was highly significant ()~2 = 33.8, with 1 degree of freedom and P < .0001) (Table 2). All types of AV block in the study and control groups were of short duration and were not associated with any specific symptoms (significant hypotension, near syncope, or syncope). None of the patients in whom AV block developed required any specific treatment or discontinuation of the adenosine infusion. DISCUSSION

Previous large prospective studies established the overall safety of adenosine stress testing in conjunction with radionuclide myocardial perfusion imaging. Serious side effects such as death, myocardial infarction, or serious arrhythmias are extremely unusual. 4 In our patients with baseline first-degree AV block, the frequency of the second- and third-degree AV block during adenosine stress testing was 37.3% and 13.9%, compared with 8.0% and 1.0% in the control group, respectively. Our study showed that, although patients with baseline first-degree AV block had statistically significant higher incidence of second- and third-degree AV block compared with patients with no baseline first-degree AV block, these incidences were well tolerated and did not require specific treatments. Our study also showed that the concomitant use of AV blocking medications (digitalis, ~-blockers, diltiazem, verapamil) did not influence the incidence of any type of

AV block during adenosine infusion. These results confirm the results of many previous large-scale studies. 7,8 CONCLUSION

Adenosine pharmacologic stress testing in conjunction with radionuclide myocardial perfusion imaging can be performed safely in patients with first-degree AV block in the presence or absence of AV blocking medications (digitalis, ~-blockers, diltiazem, verapamil) for evaluation of coronary artery disease and risk assessment.

References 1. Belier GA, ed. Pharmacologic stress imaging in clinical nuclear cardiology. Philadelphia: WB Saunders, 1995:248-90. 2. Iskandrian AS, Heo J. Pharmacologic stress testing. In: Zaret BL, Beller GA, editors. Nuclear cardiology: state of the art and future directions. St. Louis: Mosby; 1992. p. 170-87. 3. Hays JT, Mahmarian JJ, Cochran AJ, Verani MS. Dobutamine thallium 201 single tomography for evaluating patients with suspected coronary artery disease unable to undergo exercise or vasodilator pharmacologic stress testing. J Am Coil Cardiol 1993;21:1583-90. 4. Kiat H, Iskandrian AS, Villegas BJ, et al. Arbutamine stress thallium 201 single photon emission computed tomography using a computerized closed-loop delivery system: multicenter trial for evaluation of safety and diagnosis accuracy. J Am Coll Cardiol 1995;26:1159-67. 5. Verani MS, et al. Diagnosis of coronary artery disease by controlled coronary vasodilation with adenosine and thallium-201 scintigraphy in patients unable to exercise. Circulation 1990;82:80-7. 6. Bellardinelli L, Linden J, Berne R. The cardiac effects of adenosine. Prog Cardiovasc Dis 1989;32:73-91. 7. Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging in 9,256 patients: results from the Adenoscan Multicenter Trial Registry. J Am Coll Cardiol 1994;23:384-9. 8. Iskandrian AS, Verani M, Heo J. Pharmacologic stress testing: Mechanism of action, hemodynamic responses, and results in detection of coronary artery disease. J Nucl Cardiol 1994;1:94-111.