The aim of this study was to assess the possibility of increasing the sensitivity of dipyridamole-echocardiography testing (DET:2-D echo monitoring during dipyridamole infusion) by combining this procedure with handgrip testing. Dipyridamole-handgrip test (DHT) was therefore performed in 24 patients with rest/effort angina, negative DET, and negative handgrip-echo (without dipyridamole pretreatment). DHT consisted of 4.5 min of sustained 25% maximum grip strength, started 4 min after the end of dipyridamole infusion (0.56 mg/kg for 4 min). Interpretable studies were obtained in all patients. Of the 24 patients tested (10 without and 14 with significant coronary artery disease, CAD), only one CAD patient had a positive DHT, which indicates an increased sensitivity of 7% versus DET alone. In conclusion, DHT is feasible in all patients and--if compared to DET--has the same specificity. However, in spite of the theoretical premises, it provides only a modest step up in sensitivity

Alessandro Distante

Antonio L'Abbate

Eugenio Picano

Fabio Lattanzi

Michele Masini

English

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Clin. Cardiol. 10, 37-39 (1987) Does the Combination with Handgrip Increase the Sensitivity of Dipyridamole-Echocardiography Test? E. PICANO, M.D. ,  F. LATTANZI, M.D., M. MASINI, M.D., A .  DISTANTE, M.D., A. L’ABBATE. M.D. C.N.R. Institute of Clinical Physiology, University of Pisa, Pisa, Italy Summary: The aim of this study was to assess the pos- sibility of increasing the sensitivity of dipyridamole- echocardiography testing (DET:2-D echo monitoring dur- ing dipyridamole infusion) by combining this procedure with handgrip testing. Dipyridamole-handgrip test (DHT) was therefore performed in 24 patients with redeffort an- gina, negative DET, and negative handgrip-echo (without dipyridamole pretreatment). DHT consisted of 4.5 min of sustained 25 % maximum grip strength, started 4 min after the end of dipyridamole infusion (0.56 mg/kg for 4 min). Interpretable studies were obtained in all patients. Of the 24 patients tested (10 without and 14 with signifi- cant coronary artery disease, CAD), only one CAD pa- tient had a positive DHT, which indicates an increased sensitivity of 7% versus DET alone. In conclusion, DHT is feasible in all patients and-if compared to DET-has the same specificity. However, in spite of the theoretical premises, it provides only a modest step up in sensitivity. Key words: coronary heart disease, handgrip exercise, dipyridamole test, angina pectoris Introduction In previous studies we showed that dipyridamole- echocardiography testing (DET: two-dimensional echocardiographic and 12-lead ECG monitoring during dipyridamole infusion at a dosage of 0.56 mg/kg over 4 min) may offer useful information in patients with angi- Dr. Eugenio Picano is recipient of the A.R.MED. research fel- lowship for ultrasonic diagnosis of atherosclerosis. Address for reprints: Eugenio Picano, M.D. Istituto di Fisiologia Clinica del CNR Via P. Savi 8 56100 Pisa, Italy Received: February 11, 1986 Accepted: June 7 .  1986 na pectoris (Picano et al . ,  1985, 1986, in press a, b). In comparison with exercise stress test (EST), DET has some advantages, since: It is more specific (being grounded on a mechanical rather than electrical marker of ischemia) It locates with accuracy the site of apparent ischemia, dif- ferently from exercise-induced ST-segment depression It may unmask the elusive entity of “electrocardiographi- cally silent” myocardial ischemia (that is, anginal pa- tients with either nondiagnostic or negative EST (Picano et al., 1986) It evaluates the coronary reserve, eliminating the uncer- tainties of variable coronary tone, which modulates the response to EST (Picano et al., in press a,b) An important limitation of DET is a lower sensitivity than EST (56 vs. 62% in a group of 66 patients with ef- fort angina pectoris) (Picano et al., 1985); (62 vs. 80% in 62 patients with angina at rest), (Picano et al., in press b). It has been proposed that the sensitivity of thallium- 20 1 (201T1) dipyridamole scintigraphy might be augment- ed by the combination of isometric exercise (handgrip) (Brown et al . ,  1981). This may not be necessarily true for DET, since this latter test requires myocardial ische- mia as a diagnostic end-point, while thallium-201 dipyridamole does not (Gould, 1978; Gould et al., 1978). The aim of the present study was therefore to assess whether the sensitivity of DET might be increased by com- bination with handgrip. Materials and Methods Selection of Patients Twenty-four patients with angina at rest and/or on ef- fort were enrolled in the study. All patients had performed a DET, which was negative for ischemia (no transient asynergy of contraction developed after the dipyridamole infusion). On the following day, all patients performed a handgrip-echo test, and one hour later, a dipyridamole- handgrip test (DHT). 38 Clin. Cardiol. Vol. 10, January 1987 Handgrip-Echo Test Each patient performed 4.5 min of sustained isometric handgrip exercise at 25% of a predetermined maximum grip strength. Twelve-lead ECG tracings and blood pres- sure, by a cuff sphygmomanometer, were recorded every minute. Two-dimensional echocardiographic monitoring was continuously performed during the test (Mitamura et al., 1981). After this effort the patient was allowed to rest and hemodynamic parameters quickly returned to control values. Dipyridamole-Handgrip Test DHT was carried out performing a handgrip (with the same modalities previously described) 4 min after the end of the dipyridamole infusion (at the usual dose of 0.56/mg kg over 4 min). Twelve-lead ECG and blood pressure, by cuff sphygmomanometer, were taken every minute. Echocardiographic Examination and Data Analysis For all these tests (DET, handgrip, DHT), the detec- tion of a new asynergy of contraction was taken as the only criterion of positivity. Two-dimensional echocardi- ograms were continuously recorded during each of the described tests. A commercially available wide-angle phased-array imaging system (Hewlett Packard Model 77020, 3.5 and 5.0 MHz transducers) was used. In the baseline studies all standard echocardiographic views (parasternal and subxyphoid long and short axis, apical four chamber and two chamber) were obtained when possible. During the test any new area of abnormal wall motion was identified on multiple views by rapidly moving the ultrasound transducer through various positions. Having established an optimal position for the observation of ab- normal wall motion, the transducer was held stationary throughout the remainder of the study and the recovery period. The videotapes were analyzed by two independent ob- servers. When there was disagreement about the result (positivity vs. negativity), a third observer reviewed the study and the subsequent majority judgment was binding. None of the three observers has access to angiographic findings before their interpretation. Segmental anatomy and wall motion were assessed in a qualitative manner as previously reported (Distante et al . ,  1984). The wall mo- tion was graded as: hyperkinetic, normal, hypokinetic, akinetic, and dyskinetic. Hemodynamic differences after handgrip-echo and DHT were tested for significance by the Student’s paired t-test. Angiographic Study All patients underwent selective coronary arteriography , using either the Judkins or the Sones technique. Multiple views of each vessel were filmed. A vessel was consi- dered to have significant obstruction if its diameter was narrowed by 70% or more. Results Of the 24 patients, 10 had absent and 14 had signifi- cant coronary artery disease: 8 had single-, 6 had double-, no one had triple-vessel disease. Interpretable echocardiograms were obtained in all pa- tients from both handgrip-echo test and DHT. No patient had a positive handgrip-echo test (and neither angina nor ECG changes). Only one patient had a posi- tive DHT (this patient had septa1 akinesia; coronary an- giography showed 90% left anterior descending artery dis- ease): this means an increase in sensitivity of 1/14, that is 7 % versus DET alone. This patient had also mild chest pain and diagnositic (>O. 15 mV) ST-segment depression, more obvious in lead V4, during DHT. Anginal pain was elicited by DHT in another 2 patients (1 had significant coronary artery disease), while diagnostic ST-segment depression occurred in one other patient with significant coronary artery disease. Hemodynamic findings after handgrip-echo and DHT are reported in Table 1. No com- plications of any kind occurred after DHT. Discussion DHT slightly increases the sensitivity of DET alone, with no loss in feasibility and specificity (which remained loo%), and no apparent increase in risk. From a theoretical point of view, handgrip could pro- voke ischemia-when superimposed on dipyridamole infusion-through at least two different mechanisms: an increase in myocardial oxygen demand or a decrease in supply (Brown et al., 1984b). As previously shown by Brown e? al. ,  (1981), dipyridamole does not block the hemodynamic response of handgrip. The peak rate- pressure product (an established index of cardiac work (Gobel et al., 1978) achieved after DHT was significant- ly higher than after DET alone. As far as the blood sup- ply, it has been documented that dipyridamole causes a slight to mild reduction in coronary arterial vasomotor tone, but it does not prevent the coronary constrictor ef- fects of handgrip (Brown et al. ,  1981). In the presence of increased flow, the handgrip-induced increase in epicardial coronary stenoses might detrimentally potenti- ate the increase in dynamic coronary stenosis (Brown et al . ,  1984a). In fact, for any given degree of stenosis, in- creasing rates of flow (as those induced by dipyridamole) markedly raise the transtenotic gradient present in resting conditions. Finally, the increase in left ventricular end- diastolic pressure induced by handgrip might reduce per- fusion (by increasing extravascular resistances) and in- crease the oxygen demand (increasing the wall stress). E. Picano et al: Handgrip dipyridamole-echocardiography test 39 TABLE I Hemodynamic findings Basal HG DIP DIP + HG Patients without CAD (n= 10) Heart rate (beatshin) Systolic pressure (mmHg) Diastolic pressure (mmHg) RPP ( x  1/100) (beatshin X mmHg) Patients with CAD (n = 14) Heart rate (beatshin) Systolic pressure (mmHg) Diastolic pressure (mmHg) RPP ( x  1/100) (beatshin X mmHg) 7 2 f 6  137f14 85f11 99f I6 69f5  135f18 82f 12 95k18 90f 12" 101 f8"  1795 16' 162f26' 87 f6' 181 f20' 98f 11" 162 f 3  1' 88 f 22" I31 fI8" 82f10 117f45 81 f 10' 126f 15" 79f10 105i-23 98f 19" 165f33' lOOf 15" 171 f42' 98f 14' 175f16' 95f 15" 172f37' a = p < 0.05. b=p<O.Ol. Abbreviutians: CAD =coronary artery disease; DIP =dipyridamole test; HG = handgrip test; RPP= rate pressure product. Nevertheless, the ischemic effects of such combined ac- tion was modest: we had only 1 DHT-positive patient out of the 14 tested patients with coronary artery disease. To explain this rather disappointing result, it must be consi- dered that the increased aortic pressure-induced by handgrip-might well balance the increased severity of the stenosis, ultimately even enhancing the poststenotic per- fusion pressure. As a consequence, myocardial regions relatively underperfused may result, which are not neces- sarily ischemic. This fact can potentiate the diagnostic sen- sitivity of thallium-201 dipyridamole test, whose positiv- ity is based on the detection of differences of  perfusion but whose diagnostic end-point is not myocardial ische- mia (Brown et a f . ,  1984a; Gould et al . ,  1978). On the contrary, DET sensitivity is only slightly increased by the association of handgrip, since this test-being grounded on a mechanical marker-does require myocardial ische- mia to be positive. In conclusion, DHT is feasible in all patients and-if compared to DET alone-has the same specificity. However, in spite of the theoretical premises, it provides only a modest step up in sensitivity. Other, more effec- tive ways to increase the sensitivity of the test are needed (Picano et af., 1985b). References Brown BG, Bolson EL, Dodge HT: Dynamic mechanisms in hu- man coronary stenosis. Circulation 70, 917 (1984a) Brown BG, Lee AB, Bolson EL, Dodge HT: Reflex constriction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exer- cise. Circulation 70, 18 (1984b) Brown BG, Josephson MA, Petersen RB, Pierce CD, Wong M, Hecht HS, Bolson E, Dodge HT: Intravenous dipyridamole combined with isometric handgrip for near maximal acute in- crease in coronary flow in patients with coronary artery dis- ease. Am J Cardiol 48, 1077 (1981) Distante A, Rovai D, Picano E, Moscarelli E, Morales MA, Palom- bo C, L'Abbate A: Transient changes in left ventricular mechanics during attacks of Prinzmetal's angina: A two- dimensional echocardiographic study. Am Hearr J 108, 440 ( 1984) Gobel FL, Nordstrom LA, Nelson RR, Jorgensen CR, Wang Y: The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 57, 549 (1978) Gould KL: Non invasive assessment of coronary stenoses by my- ocardial imaging during pharmacologic coronary vasodilata- tion. I. Physiologic basis and experimental validation. Am J Curdiol 41, 267 (1978) Gould KL, Westcott RJ, Albro PC, Hamilton GW: Non invasive assessment of coronary stenoses by myocardial imaging dur- ing pharmacologic coronary vasodilatation. II. Clinical metho- dology and feasibility. Am J Cardiol41, 279 (1978) Mitamura H, Ogawa S ,  Hori S ,  Yamazaki H, Handa S ,  Nakamura Y: Two dimensional echocardiographic analysis of wall mo- tion abnormalities during handgrip exercise in patients with coronary artery disease. Am J Cardiol48, 711 (1981) Picano E, Masini M, Lattanzi F, Distante A, L'Abbate A: Role of Dipyridamole-echocardiography test in electmardiographi- cally silent effort myocardial ischemia. Am J Cardiol58, 235 (1986) Picano E, Masini M, Distante A, Simonetti I, Lattanzi F, Marzilli M, L'Abbate A: Dipyridamole-echocardiography test in pa- tients with exercise-induced ST segment elevation. Am J Curdi- 01 57, 765 (1986) Picano E, Morales MA, Distante A, Lattanzi F, Moscarelli E, Masi- ni M, L'Abbate A: Dipyridamole-echocadiography test in an- gina at rest: Non invasive assessment of coronary stenosis un- derlying spasm. Am Heart J 1 11, 688 (1986) Picano E, Lattanzi F, Masini, M, Distante A, L'Abbate A: High dose dipyridamole-echocardiography test in effort angina pec- tons. J Am Coll Cardiol 8, (1986) (in press) Picano E, Distante A, Masini M, Morales MA, Lattanzi F, L'Ab- bate A: Dipyridamole echocardiography test in effort angina pectoris. Am J Cardiol 56, 452 (1985) 

Does the combination with handgrip increase the sensitivity of dipyridamole-echocardiography test?

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Does the combination with handgrip increase the sensitivity of dipyridamole-echocardiography test?

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