Exercise-induced distal atrioventricular block

Three patients with 1:1 atrioventricular (AV) conduction at rest developed fixed 2:1 or 3:1 AV block during treadmill exercise testing. Electrophysiologic study documented block distal to the AV node in all three patients, and suggested that the exercise-induced block occurred because of increased atrial rate and abnormal refractoriness of the His-Purkinje conduction system. The findings in these three patients suggest that high grade AV block appearing during exercise reflects conduction disease of the His-Purkinje system rather than of the AV node, even in the absence of bundle branch block. Patients with this diagnosis should be considered for permanent cardiac pacing.     

Efficacy of verapamil in exercise-induced ventricular tachycardia

The antiarrhythmic efficacy of verapamil was determined by serial treadmill testing in 16 patients with reproducible exercise-induced ventricular tachycardia (VT). Twelve of the 16 patients responded to verapamil, 0.2 mg/kg intravenously; in 8 of these 12 responders, an oral verapamil regimen of 160 to 320 mg given every 8 hours also prevented exercise-induced VT. Plasma verapamil concentration was significantly higher in the responders than in the nonresponders to intravenous verapamil, but levels were similar in responders and nonresponders to oral therapy. The 8 responders to the oral drug were followed up while receiving verapamil therapy for 6 to 22 months (mean 15), and exercise-induced VT did not recur in any patient. Five of the 8 responders also had concomitant spontaneous VT unrelated to exercise which verapamil suppressed initially as well: 4 remained free of spontaneous VT, while 1 patient had recurrence of spontaneous VT. Thus, in patients with exercise-induced VT, verapamil is a promising alternative therapy to beta-adrenergic blocking agents. The effectiveness of verapamil is consistent with a mechanism of arrhythmogenesis involving calcium channels.     

Clinical characteristics of ventricular tachycardia and ventricular fibrillation in exercise stress testing

OBJECTIVES: Ventricular tachycardia (VT) and ventricular fibrillation (Vf) induced in exercise stress testing should be treated urgently, although the occurrence of arrhythmia is rare. The conditions for the onset of arrhythmia and the clinical characteristics of VT and Vf patients in exercise stress testing were studied. METHODS: Fifty-nine patients (mean age 54 +/- 17 years, 41 males, 18 females) with VT (succession of 3 or more ventricular premature beats) or Vf induced in exercise stress testing were selected from 7,594 patients with consecutive treadmill stress testing in our hospital from January 1993 to February 1998. RESULTS: The incidence of exercise-induced VT or Vf was 0.8%, and there were no fatal accidents in all tests. Among the 59 patients with exercise-induced VT or Vf, 52 patients had non-sustained VT, 5 had sustained VT, and 2 had Vf. Of the 59 patients, 23 had rhythm or conduction disturbances, 14 had coronary artery disease, 13 had cardiomyopathy, and 9 had valvular heart disease. The VT or Vf incidence in coronary artery disease was 0.2%, and in valvular heart disease was 10.8%. VT or Vf occurred at over 80% of maximum heart rate exercise intensity in 40 patients, including 4 with sustained VT and 2 with Vf, of the 59 patients. Also, in 9 VT patients including the 4 sustained VT patients, VT occurred in the exercise recovery period within 2 min after the exercise. Although VT disappeared spontaneously in 52 non-sustained VT and 3 sustained VT patients, intravenous injection of lidocaine was needed in 2 sustained VT patients and direct current defibrillator was needed in 2 Vf patients. Furthermore, only one non-cardiac death was observed in the follow-up period of average 42 months. CONCLUSIONS: Our results showed clinical characteristics and incidence of VT or Vf similar to past reports. Furthermore, all sustained VT and Vf patients, who should be treated urgently, had a past history of ventricular premature beats or VT. Our data suggest that VT and Vf could occur during the recovery period, especially in patients with documented ventricular tachyarrhythmias when the stress intensity has reached the critical level in the exercise tolerance test.     

Incidence, pathophysiology and prognosis of exercise-induced sustained ventricular tachycardia associated with healed myocardial infarction.

Of 150 consecutive patients with sustained monomorphic ventricular tachycardia (VT) (n = 116) or ventricular fibrillation (VF) (n = 34) late after acute myocardial infarction, 17 had reproduction of their sustained monomorphic VT during exercise testing. Data from these patients (group I) were compared with data from patients without exercise-induced VT (group II). No statistical difference was found between groups I and II with relation to age, sex, number of vessels with greater than 70% stenosis, left ventricular ejection fraction, number of previous myocardial infarctions, inducibility during programmed stimulation and total mortality during follow-up. In group I, only 1 patient (6%) developed ST depression during exercise compared with 47 patients (35%) in group II (p less than 0.01). After a 34-month mean follow-up, 6 patients in group I (35%) and 18 patients in group II (13%) died suddenly (p = 0.02). It is concluded that sustained monomorphic VT is reproduced during exercise in only 11% of patients with spontaneous late sustained monomorphic VT or VF. Electrocardiographic findings do not support ischemia as a triggering mechanism of exercise-induced sustained monomorphic VT. Patients with exercise-induced sustained monomorphic VT have a high incidence of sudden death.     

Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia

BACKGROUND: The mainstay of therapy for catecholaminergic polymorphic ventricular tachycardia (CPVT) is maximal doses of beta-blockers. However, although beta-blockers prevent exercise-induced ventricular tachycardia (VT), most patients continue to have ventricular ectopy during exercise, and some studies report high mortality rates despite beta-blockade. OBJECTIVE: The purpose of this study was to investigate whether combining a calcium channel blocker with beta-blockers would prevent ventricular arrhythmias during exercise better than beta-blockers alone since the mutations causing CPVT lead to intracellular calcium overload. METHODS: Five patients with CPVT and one with polymorphic VT (PVT) and hypertrophic cardiomyopathy who had exercise-induced ventricular ectopy despite beta-blocker therapy were studied. Symptom-limited exercise was first performed during maximal beta-blocker therapy and repeated after addition of oral verapamil. RESULTS: When comparing exercise during beta-blockers with exercise during beta-blockers + verapamil, exercise-induced arrhythmias were reduced: (1) Three patients had nonsustained VT on beta-blockers, and none of them had VT on combination therapy. (2) The number of ventricular ectopics during the whole exercise test went down from 78 +/- 59 beats to 6 +/- 8 beats; the ratio of ventricular ectopic to sinus beats during the 10-second period recorded at the time of the worst ventricular arrhythmia went down from 0.9 +/- 0.4 to 0.2 +/- 0.2. One patient with recurrent spontaneous VT leading to multiple shocks from her implanted cardioverter-defibrillator (ICD) despite maximal beta-blocker therapy (14 ICD shocks over 6 months while on beta-blockers) has remained free of arrhythmias (for 7 months) since the addition of verapamil therapy. CONCLUSIONS: This preliminary evidence suggests that beta-blockers and calcium blockers could be better than beta-blockers alone for preventing exercise-induced arrhythmias in CPVT.     

Positive treadmill stress tests post myocardial infarction in patients with single-vessel coronary disease

To investigate the possibility that patients with single-vessel coronary artery disease (CAD) and recent myocardial infarction (MI) can have ST segment depression on post infarction treadmill testing due to ischemia, we studied 16 such patients who underwent cardiac catheterization and exercise testing after MI. Of the 11 patients with ST segment depression on treadmill testing, 10 failed to increase their ejection fraction and nine had a focal worsening of wall motion during exercise radionuclide ventriculography. Seven of these 11 patients had hypokinesis or normokinesis in the suspected area of infarction. In contrast, four of the five patients without ST segment depression on treadmill stress testing had an increase in ejection fraction with stress which was significantly greater than that seen in patients with ST depression (7.2% vs 0%, p less than 0.05). Short-term follow-up (1.1 years) revealed continued post infarction angina in 10 of the 11 patients with positive treadmill stress tests. Four of these patients underwent either percutaneous transluminal angioplasty or surgery. We conclude that positive post infarction treadmill tests due to exercise-induced ischemia may occur in patients with single-vessel CAD and may be associated with continued angina that requires surgical intervention.     

Efficacy and safety of oral nadolol for exercise-induced ventricular arrhythmias

Sixty-four patients with reproducible exercise-induced ventricular arrhythmias were enrolled in an open-label, multicenter study to assess the efficacy and safety of oral nadolol therapy. There were 53 men and 11 women ranging in age from 19 to 75 years (mean 53.9). The severity of arrhythmias varied from frequent ventricular premature beats to nonsustained and sustained ventricular tachycardias. Using serial treadmill exercise tests, patients underwent dose titration for 1 month and were followed up for 3 to 6 months. Depending on drug tolerance and response to treadmill exercise testing, the single daily required dose of oral nadolol ranged from 20 to 240 mg (average 66). Twenty-three (36%) of the patients experienced a total of 30 adverse effects of nadolol therapy; however, only 9 (14%) patients had to be withdrawn from the study. The adverse effects observed were those commonly associated with beta-adrenergic blocking agents, and all were dose-dependent and reversible. At the last patient visit, the severity of exercise-induced ventricular arrhythmias was significantly decreased compared with pretreatment in 36 (75%) of 48 evaluable patients. Eighteen (38%) of the patients demonstrated total suppression of arrhythmias. This was accompanied by significant increases from pretreatment in both the mean duration of symptom-limited exercise (+1.02 +/- 0.41 minutes, p less than 0.05) and the mean time of exercise required for arrhythmia induction (+1.80 +/- 0.66 minutes, p less than 0.01), a significant decrease from pretreatment in the mean peak exercise double-product (-4,775, p less than 0.001) and a decrease in the incidence of exercise-induced ST-segment depression (-33%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Naloxone and asymptomatic ischemia: failure to induce angina during exercise testing

Endorphins and endorphin receptors are believed to modulate pain perception. To investigate whether naloxone, a specific antagonist, could initiate anginal pain during exercise-induced myocardial ischemia in asymptomatic patients with angiographically defined coronary artery disease, a single-blind trial was conducted in 10 men with prior positive exercise electrocardiograms. Multistage treadmill exercise tests were performed twice within a week. On the second test, patients received naloxone, 2 mg intravenously, by a syringe infusion pump. Exercise was terminated because of fatigue in 6 patients and completion of the protocol in 4. No patient reported chest pain during exercise. Naloxone did not significantly alter exercise duration, heart rate, blood pressure and ST-segment changes compared with control testing. It is concluded that endorphins do not play a significant role in the recognition of anginal pain in patients who have asymptomatic exercise-induced ischemia.     

Maximal exercise stress testing in evaluation of arrhythmias in children: results and reproducibility.

To assess reproducibility in evaluating arrhythmias in children, two maximal treadmill exercise tests using the Bruce protocol were performed an average of 3.1 months apart in 19 children aged 5 to 16 years (mean 11) with chronic idiopathic ventricular (Group 1) and supraventrlcular (Group II) arrhythmias. The performance of each child during the two tests was not statistically different with regard to maximal heart rate achieved or duration of exertion; all but one child achieved expected maximal heart rates. in Group I, eight of nine children with ventricular premature complexes at rest showed suppression of the arrythmia during exercise at similar heart rates on both tests. In one child, ventricular premature complexes were not diminished in either test. One child with accelerated idioventricular rhythm and one with ventricular parasystole had reproducible arrhythmia suppression during exercise. One child with known episodes of ventricular tachycardia had this arrhythmia induced by exercise on both tests. In Group II, five children with supraventricular or junctional premature complexes at rest showed reproducible arrhythmia suppression on exercise, but one unexpectedly manifested ventricular premature complexes and one manifested runs of ectopic atrial rhythm during both exercise periods. Two children with severe sinus bradycardia achieved expected maximal heart rates. One unexpectedly manifested reproducible supraventricular premature complexes after exercise.Comparison of results of exercise testing with ambulatory electrocardiographic monitoring showed that in four patients testing uncovered arrhythmias not evident on monitoring, whereas in one patient severe sinus bradycardia occurred only during monitoring. These results indicate that maximal treadmill exercise for evaluation of arrhythmias can be performed in children using standard methodology and can yield important data reproducibly.     

氟卡胺对运动心电图和血流动力学的作用

采用随机、双盲、交叉和安慰剂对照研究观察氟卡胺对24例阵发性房性心律失常.无明显器质性心脏病患者运动心电图、运动血压和心率-收缩压乘积的影响.结果发现.与安慰剂比较,氟卡胺不改变静态心率,但显著减低运动时窦性心率,显著减低运动时心率 收缩压乘积;明显延长QRS间期,并表现为频率依赖性;明显缩短运动时J-Tc时问     

Prevalence and prognosis of exercise-induced nonsustained ventricular tachycardia in apparently healthy volunteers

Although exercise-induced ventricular tachycardia (VT), whether sustained or nonsustained, is usually associated with significant organic heart disease, its prevalence, associated characteristics and prognostic significance in an asymptomatic, unreferred community-dwelling population are unknown. Therefore, the prevalence of VT associated with maximal treadmill exercise was assessed in 597 male and 325 female volunteers, aged 21 to 96 years (mean +/- standard deviation 54 +/- 16), from the Baltimore Longitudinal Study on Aging who were without apparent heart disease. Ten subjects, 7 men and 3 women, with exercise-induced VT were identified, representing 1.1% of those tested; only 1 was younger than 65 years. All episodes of VT were asymptomatic and nonsustained. In 9 of 10 subjects, VT developed at or near peak exercise. The longest run of VT was 6 beats; multiple runs of VT were present in 4 subjects. Two subjects had exercise-induced ST-segment depression, but subsequent exercise thallium scintigraphic results were negative in each. Compared with a group of age- and sex-matched control subjects, those with asymptomatic, nonsustained VT displayed no difference in exercise duration, maximal heart rate, or the prevalence of coronary risk factors or exercise-induced ischemia as measured by electrocardiography and thallium scintigraphy. Over a mean follow-up period of 2 years, no subject has developed symptoms of heart disease or experienced syncope or sudden death. Thus, exercise-induced VT in apparently healthy subjects occurs almost exclusively in the elderly, is limited to short, asymptomatic runs of 3 to 6 beats usually near peak exercise, and does not portend increased cardiovascular morbidity or mortality rates over a 2-year period of observation.     

Diltiazem and propranolol combination for the treatment of chronic stable angina pectoris

To examine the benefits and risks of combined diltiazem and propranolol therapy, 23 patients who had completed a double-blind placebo-controlled cross-over comparison between diltiazem and propranolol and who continued to develop angina despite treatment were studied. The patients received the previous dose of diltiazem (180 or 360 mg/day) combined with propranolol 120 mg daily for 4 weeks and if they still developed angina on exercise testing, they went on to propranolol 240 mg daily for a further 4 weeks. Efficacy and safety were evaluated by computer-assisted maximal treadmill tests, ambulatory heart rate monitoring, and resting systolic time intervals at the end of each 4-week treatment period. Low-dose combination therapy abolished treadmill angina in 6 patients, but 2 patients had to be withdrawn. The high-dose combination abolished treadmill angina in 5 of 15 patients. The exercise time and 1-mm ST depression time increased with each increment of combination therapy in patients on both doses of diltiazem. The resting, maximal, and ambulatory heart rates progressively decreased with each increment of combined therapy. Left ventricular function, as evaluated clinically and by the systolic time intervals, was not impaired, but severe sinus bradycardia (heart rate less than 40 beats/min) appeared in 3 patients. Two died during 6 months of follow-up. Only 11 of the 23 patients completed 6 months of combined therapy without an adverse reaction. Although combined diltiazem and propranolol therapy relieved angina and increased exercise tolerance in patients refractory to single drug therapy, it should be used with caution in such patients, since bradycardia can pose serious problems.     

Effect of direct, reflex and exercise-provoked increases in sympathetic tone on idiopathic ventricular tachycardia.

Exercise treadmill testing and direct enhancement of sympathetic influence with agents such as isoproterenol are often used to reproduce ventricular tachycardia (VT). The cardiac effects of, and arrhythmia responses to, graded exercise, isoproterenol infusion and lower body negative pressure (the latter 2 with and without atrial and ventricular stimulation) were studied in 11 patients with idiopathic VT. During maximal exercise, substantial increases in heart rate and blood pressure occurred, but only 2 of 9 exercised patients had VT (during recovery in both). During programmed stimulation alone, VT was initiated in 6 patients. During maximum levels of lower body negative pressure (-60 cm of water in most), mean systolic blood pressure decreased by 10 mm Hg, heart rate increased by 15 beats/min, and ventricular refractory period decreased by 10 ms. In 4 patients VT occurred spontaneously during lower body negative pressure; in 2, lower body negative pressure was the only intervention producing VT. During isoproterenol infusion VT occurred spontaneously in 2 patients; both had VT initiated during other interventions. Lower body negative pressure and isoproterenol increased VT rate, but did not prolong it. It is concluded that there is significant variability in arrhythmia responses to sympathetic augmentation, suggesting that additional covariables such as parasympathetic input and ventricular volume may also have a role in arrhythmia occurrence.     

Prevalence and reproducibility of exercise-induced ventricular arrhythmias during maximal exercise testing in normal men.

The occurrence of ventricular arrhythmias at rest or during ordinary daily activities has been implicated as a risk factor for future coronary-related events and sudden death. However, the clerical significance of exercise-induced ventricular arrhythmias remains uncertain. To assess the prevalence and reproducibility of such arrhythmias, two serial maximal treadmill exercise tests were performed in a study population of 543 male Indian State policemen at an average interval of 2.9 years. Four hundred sixty-two subjects were clinically free of evidence of cardiovascular disease, and 81 had evidence of definite or suspected cardiovascular disease. The prevalence of exercise-induced ventricular arrhythmias during the first test was 30% in men aged 25 to 34 years, 32% in those aged 35 to 44 years and 36% in those aged 45 to 54 years. The prevalence rate in these age groups with repeat testing was 36, 38 and 42%, respectively. These differences were not statistically significant. The group with definite or suspected cardiovascular disease had a greater prevalence of exercise-induced ventricular arrhythmias than normal subjects during both tests but the prevalence rate with repeat testing remained constant. The occurrence of exercise-induced ventricular arrhythmias was reproducible in individual subjects during the second test in 55% of 25 to 34 year olds, 58% of 35 to 44 year olds and 62% of 45 to 54 year olds. Thus, individual reproducibility in two consecutive tests was only slightly greater than reproducibility by chance alone. The group with known or suspected cardiovascular disease demonstrated a trend toward greater reproducibility with repeat testing. Exercise-induced ventricular arrhythmias were not reproducible by type or complexity. The marked variability of exercise-induced ventricular arrhythmias during repeat maximal exercise testing in a clinically normal population appears to negate the usefulness of this finding during a single test as a marker of future cardiovascular disease. Nevertheless, subjects whose arrhythmias were reproducible may form a group destined to manifest clinical cardiovascular disease in long-term follow-up studies.     

Exercise testing early after myocardial infarction: Predictive value for subsequent unstable angina and death

Recently, modified treadmill exercise testing before hospital discharge has been reported to be safe in patients after uncomplicated myocardial infarction. Accordingly, the frequency of treadmill exercise-induced abnormalities and their prognostic value were evaluated in 130 patients with uncomplicated myocardlal infarction. Seventy-eight patients (60 percent) had one or more treadmill exercise-induced abnormalities; 42 had S-T segment depression, 35 had angina and 17 had an inadequate blood pressure response. During the mean follow-up period of 11 months, 27 patients experienced unstable angina, 12 had a recurrent myocardlal infarction and 10 died of cardiac causes. Compared with patients with no exercise-induced abnormality, patients with S-T segment depression, angina pectoris or an inadequate blood pressure response had a significantly greater (p < 0.001) incidence of all cardiac events during the follow-up period. Furthermore, unstable angina pectoris was significantly more frequent (p <0.005) in patients with S-T segment depression or angina pectoris. Finally, when the patients with ischemic treadmill abnormalities were combined with the patients exhibiting an inadequate blood pressure response, they had a statistically greater (p < 0.005) incidence of cardiac death than that of patients with no treadmill abnormalities. Therefore, these three abnormalities during modified treadmill exercise testing before hospital discharge identify patients with uncomplicated myocardial infarction who are at risk for a future cardiac event.     

Exercise-induced silent myocardial ischemia and future cardiac events in healthy, sedentary, middle-aged and older men.

OBJECTIVES: Before men older than age 45 participate in vigorous exercise programs, the American Heart Association and the American College of Sports Medicine recommend they undergo a screening maximal exercise treadmill test. We examined the predictive value for subsequent cardiac events of exercise-induced silent myocardial ischemia (SI) during the exercise treadmill test in healthy, sedentary, obese, middle-aged and older men recruited for research studies. DESIGN: A cohort study with 7 years of follow-up. SETTING: Out-patient research at a tertiary hospital. PARTICIPANTS: 170 healthy, sedentary, obese, middle-aged and older (ages 45-79 years) men with no prior history of coronary artery disease (CAD) recruited for research studies. MEASUREMENTS: Cardiac risk factors, exercise-induced SI (ST segment depression on the electrocardiogram during a maximal exercise treadmill test), maximal aerobic capacity (VO2max), and 7- year follow-up data on incident CAD. RESULTS: At baseline, 37 of the men (22%) had exercise-induced SI on their treadmill tests. Seven-year follow-up data was obtained in 97% of the patients. In the interim, 31 men had cardiac endpoints (sudden cardiac death, myocardial infarction, angioplasty, coronary artery bypass graft surgery, angina), and four had noncardiac deaths. Seventeen of the 37 men (46%) with exercise-induced SI on their baseline exercise tests had cardiac endpoints compared with 14 of 133 (11%) men with normal exercise tests (P < .001). Compared with the men with no cardiac endpoints, the men with subsequent cardiac endpoints were older (63 +/- 1 vs 58 +/- 1 years, mean +/- SEM, P < .001) and had a lower maximal aerobic capacity (VO2max) (24 +/- 1 vs 29 +/- 1 mL/kg/min, P < .001). In Cox proportional hazards analysis, exercise-induced SI and a low VO2max were independent predictors of subsequent cardiac endpoints. CONCLUSION: In a healthy population of obese, sedentary, middle-aged and older men, exercise-induced SI and low VO2max were predictors of incident CAD. This suggests that exercise treadmill testing is beneficial in assessing risk for future cardiac events in obese, sedentary individuals.     

Diagnostic usefulness of graded exercise testing in pediatric supraventricular tachycardia

BACKGROUND:

Episodic symptoms, often reported during exertion, complicate the assessment of suspected supraventricular tachycardia (SVT).

OBJECTIVE:

To examine the diagnostic sensitivity of graded exercise testing in young patients with documented SVT or ventricular pre-excitation.

METHODS:

A single-centre retrospective review identified 53 patients (5.1 to 17.5 years of age) with structurally normal hearts who had undergone 65 graded treadmill exercise tests in the setting of either documented SVT with normal resting electrocardiograms (n=30) or ventricular pre-excitation (n=23). Twenty-five patients (13 pre-excited and 12 nonpre-excited) had exercise-related symptoms. SVT induction during exercise testing was assessed in relation to pre-excitation and the patient’s history of exercise-induced symptoms.

RESULTS:

SVT was induced during six of the 65 exercise tests performed in three of 53 patients (overall sensitivity 5.7%). All three patients had a history of exercise-induced symptoms, and two had ventricular pre-excitation. SVT was induced in 12% of patients with exercise-related symptoms. No other rhythm disturbances occurred during exercise testing.

CONCLUSION:

The diagnostic yield of graded exercise testing in patients with suspected SVT is limited, even among those with exercise-related symptoms.     

Increased exercise tolerance after nitroglycerin oral spray: a new and effective therapeutic modality in angina pectoris

The prophylactic antianginal efficacy of nitroglycerin (NTG) oral spray was assessed in 20 patients with angiographically documented coronary disease and stable angina pectoris. The evaluation was by a randomized crossover trial involving treadmill exercise testing. On study day 1, a control treadmill exercise test was performed, followed 30 minutes later by a second exercise test 2 minutes after administration of either placebo (group A, 10 patients) or NTG spray 0.8 mg (group B, 10 patients). One week later, on study day 2, the patients again underwent control treadmill exercise testing followed by a second exercise test after either NTG spray (group A) or placebo (group B). NTG spray delayed the onset of anginal pain during exercise by a mean of 100 +/- 64 seconds (p less than 0.001) in 13 patients and prevented pain entirely in seven. Placebo did not significantly delay the appearance of angina and prevented chest pain in only one patient. NTG spray increased treadmill exercise duration by 31% before the onset of angina (p less than 0.001); placebo did not significantly alter the duration of exercise. NTG spray abolished in six patients and delayed in 14 patients the onset of exercise-induced ST-segment depression of 1 mm (p less than 0.001). Patients achieved a higher heart rate at peak exercise with NTG spray, and yet the maximal exercise-induced ST-segment depression of 2.1 +/- 1.0 mm during the control study declined to 1.3 +/- 0.9 mm on NTG spray (p less than 0.001). Placebo had no effect on exercise ST-segment depression. These data indicate that the oral NTG spray is an effective prophylactic for exercise-induced angina.