Exercise-Induced Angina with Intermittent ST-Segment Elevation

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1 CASE REPORT Exercise-Induced Angina with Intermittent ST-Segment Elevation Takayuki Inomata, Yutaka Igarashi*, Katsuya Ebe, Tsuneo Nagai and Akira Shibata* A 59-year-old man was admitted for evaluation of mild exertional angina in the morning. During graded treadmill exercise stress testing, the patient had reproducibly intermittent chest pains associated with ST-segment elevations in leads II, III and avf. A baseline coronary angiogram showeda coronary narrowing of90%in the middle segment of the right coronary artery. The coronary narrowing was immediately resolved by an intracoronary injection of nitroglycerin. This was a very rare case of variant angina with intermittent ST-segmentelevations and chest pains which were reproducibly demonstrated during exercise and the recovery phase of treadmill testing. (Internal Medicine 34: , 1995) Key words: coronary vasospasm, cyclic flow variation Introduction Coronary vasospasmis widely recognized as a cause of rest angina (1). Although variant angina predominantly occurs at rest in the morning period, it has been demonstrated that coronary spasm can be induced by exercise (2-4). Here we present a patient in whomintermittent chest pains and STsegment elevations reproducibly occurred during exercise and the recovery phase of treadmill testing. Case Report A 59-year-old manwas admitted to our hospital because of the recent onset of chest pain only during mild exercise in the morning. The patient had a history of smoking 80 cigarettes per day for 40 years. Blood pressure was 138/90 mmhgand heart rate was 72 beats/min. Other physical examinations revealed no pathological findings. Fasting blood sugar and lipids were normal. Other laboratory examinations, rest electrocardiogram (ECG), chest X-ray, and two-dimensional echocardiogram were also normal. A treadmill exercise test using Bruce protocol was performed without any antianginal medication in the morning (Fig. 1A, Fig. 2). At 1.5 min of the exercise, chest pain and ECG changes developed: ST-segmentelevation in leads II, III and avf (Fig. 1A: #1) and simultaneous ST-segment depression in leads V2_6 (Fig. 1A: #2). The chest pain spontaneously disappeared one minute later and the ST changes returned to baseline. The exercise stress testing was still continued, and then the chest pain recurred 2 minutes later. ECGdemonstrated STsegment depression in leads II, III and avf (Fig. 1A: #4) followed by ST-segment elevation (Fig. 1A: #5) with concomitant ST-segment depression in leads V2_6 (Fig. 1A: #3). The exercise was stopped because of the second chest pain. The chest pain and ST-segment changes were augmented for less than oneminuteeven after stopping exercise but then spontaneously disappeared. Ten days later, we again performed exercise stress testing to examine the reproducibility of this phenomenon after withdrawal of all antianginal drugs, and a similar pattern of ST-segmentchanges and chest pain were observed (Fig. IB). Right and left cardiac catheterization showedno abnormal findings. Left ventriculogram showed normal left ventricular wall motion and global ejection fraction was 73%. A baseline coronary angiogram disclosed 90%coronary narrowing in the middle segment of the right coronary artery (Fig. 3A). This narrowing was, however, immediately relieved by an intracoronary injection of nitroglycerin (Fig. 3B). Coronary arteriogram after administration of nitroglycerin revealed organic stenosis of 30% assessed by a digital caliper. Coronary spasm provocation was not performed because a baseline coronary angiogram showed severe coronary narrowing. There were no collateral vessels arising from the left coronary artery (Fig. 3C). Neither chest pain nor ECGchanges appeared during From the Division of Cardiology, Nagaoka Red-Cross Hospital, Nagaoka and *the First Department of Internal Medicine, Niigata University School of Medicine, Niigata Received for publication October 3, 1994; Accepted for publication February 27, 1995 Reprint requests should be addressed to Dr. Takayuki Inomata, the First Department of Internal Medicine, Niigata University School of Medicine, Asahimachi-Dori, Niigata

2 Inomata et al A B bpm HEART RATE bpm, HEART RATE 190 -j H I - I 130 ] 1301 ioo i /^~~^~~~\s^ 10 \ /~^~-'~"""~V~n^a, 70{ 70f I I, X1OO DOUBLE PRODUCT xl00 DOUBLE PRODUCT I 240] à"*à"à"à"% f *à"à" 80>* mv avf STL LEVEL mv avr STL LEyEL -4" 0.4- #1 t # ' # mv V5 STL LEVEL mv V5 STL LEVEL -4 " " 0.2 \ ~QALi k -" min mm chestpain 1 1 I å t stopped exercise stopped exercise Figure 1. Trendgrams of exercise stress electrocardiogram. Each trendgram demonstrated heart rate, pressure-rate product, and ST-segment levels in leads avf and V5, respectively. A: On admission. The first chest pain appeared with ST-segment elevation in leads II, III and avf (#1) and simultaneous ST-segment depression in leads V2--6 (#2)«About 2 minutes later, the second chest pain was observed with ST-segment depression in leads II, III and avf (#4) followed by ST-segment elevation (#5) with concomitant ST-segment depression in leads \2-6 (#3)«B: Ten days after test A. I coronary angiography. After treatment with diltiazem 90 mg t.i.d. and nitrendipine 10 mg b.i.d., no chest symptoms were observed and exercise 598 stress testing did not show any ST-segment changes or chest pain up to stage III of the Bruce protocol: heartrate 1 38 beat/min and blood pressure 148/70 mmhg.

3 Intermittent ST Changes during Exercise at rest ex.1'50" 4'00" post. 0'32" at rest ex.1'50" 4'00" post. 0'32"!»^#^^ ^mi ^gfc Vi ^^^ ^^,^^" 31 ii ^fefe ^g #jg ^fe Vz z$^^ =SE^S:^g^ avr 2TVH3St ^ly^ty" ^tv^ ^kt^i^ jl/v" r- IJV- ^j\7^~7: J;A-J~a~=Ju^^ ~^W^ 7T-1-- ::-- -~r-- y5 5^Q^E^pd^ d^x g^p Figure 2. Electrocardiograms during the exercise stress test on admission. Discussion In vasospastic angina, angina pectoris with ST-segment elevation is frequently induced during exercise stress testing, especially in the morning (2-4). Yasue et al (2) reported that anginal attacks with ST-segmentelevation were induced in all 1 3 patients during exercise stress testing in the morning. There have been, however, only a few reports on exercise-induced intermittent ST-segment elevation in vasospastic angina (5, 6). Basal coronary tone in variant angina is augmented (7), and Table 1. Comparison of Clinical Findings among Previously Reported Patients with Intermittent Exercise-Induced ST Segment Elevation Timing of ST segment Type of angina pectoris elevation during exercise Coronary artery Site of Age Sex stress testing Site of ST disease coronary elevation (%DS) spasm Rest angina Mild Early Peak Recovery exertional stage stage stage Sato et al (5) 64 Male (+) (+) (+) (+) (+) II, III, avf Middle RCA (90%) Middle RCA Middle CX (75%) Distal RCA (40%) Scardi et al (6) 64 Male (+) (-) (+) (-) (+) II, III, avf Distal LAD (60%) unknown Middle LAD (65%) Present case 59 Male (-) (+) (+) (-) (+) II, III, avf Middle RCA (30%) Middle RCA CX: circumflex coronary artery, LAD:left anterior descending coronary artery, RCA:right coronary artery, %DS:percent diameter stenosis. 599

4 Inomata et al circadian variation of exercise capacity has also been shown (2). In the present case, baseline coronary angiograms showed Figure 3. Coronaryangiograms. A: Baselineangiogram demonstrated 90%stenosis (arrowheads) in the middle segment of the right coronary artery. B: After intracoronary administration of nitroglycerin, the lesion was reduced to 30% stenosis (arrowheads). C: Baseline angiogram in the left coronary artery showed no significant stenosis. a high basal tone and severe coronary narrowing in the right coronary artery. Exercise-induced changes on humoral factors or on the autonomicnervoussystemmayhave an impact on the coronary tone and result in ST-segmentelevation and chest pain (8). Cyclic flow variations have been observed in a canine model with endothelial damage and coronary constriction (9, 10), and recently in humanswith severe coronary stenosis before and after coronary angioplasty (1 1). In 2 of 3 patients with cyclic flow variations, coronary spasm was shown in an adjacent area just distal to the dilated segment immediately after balloon angioplasty (1 1). Cyclic flow variations maybe associated with platelet aggregation (10) or increased coronary tone caused by the release of vasoactive substances or sympathetic stimulation (9, 12). In the present case, severe coronary narrowing was suggested to be induced by exercise, and it is possible that cyclic flow variations may occur during exercise stress testing. However, it is unknownwhether cyclic flow variations caused by platelet aggregation and the subsequent release of vasoactive substances contribute to the intermittent ST-segment elevation. The effect of antiplatelet agents on the intermittent ST-segment elevation should be examined. Comparisons of the clinical findings of three patients with exercise-induced intermittent ST-segmentelevation are summarized in Table 1. All patients had rest angina and/or mild exertional angina in the morning. The first episode of STsegment elevation developed during an early stage of exercise, and ST-segment elevation was also observed during the recovery stage or just after stopping exercise in all patients. These findings show that intermittent ST-segmentelevation maynot be associated with the intensity of exercise. In the present case, augmentation of chest pain and STchanges after exercise may result from relative predominance of the parasympathetic nervous system. All patients had ST-segment elevation in leads II, III, and avf, and in two cases coronary spasmwas demonstrated in the right coronary artery. It is of interest whether intermittent ST-segment elevation during exercise is likely to occur only in the right coronary artery. Further examinations will be needed to confirm this. It was reported that both STsegment elevation and depression could be shown in coronary vasospasm by the degree of the coronary flow (13). In the present case it was found in the stress test that ST depression was consistently followed by ST elevation in lead avf as shown in the trendgram (Fig. 1A, #4->#5). This finding might result from myocardial ischemia by gradually advancing vasospasm. Wereported a rare case of angina with intermittent STsegment elevation during exercise and the recovery phase of treadmill testing. To provide insight into the potential mechanism of intermittent ST-segment elevation during exercise stress, it will be necessary to investigate more cases as well as the efficacy of blockade of vasoactive substances. References 1) Maseri A, Severi S, Nes MD, et al. "Variant" angina: One aspect ofa 600

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