Search

Background: Autonomic nervous discharge has been implicated in the pathogenesis of coronary artery spasm., Methods: Cardiac autonomic nervous activities were evaluated from the power of the low-frequency and the high-frequency spectral components of heart rate variability with Holter monitoring in 18 patients with nocturnal variant angina. Samples during the first 512 seconds of each 10-minute period from 60 minutes before to immediately before an anginal attack occurring during the night or at dawn (2:00 to 7:00 AM) were analyzed by fast Fourier transformation., Results: The R-R interval during the 10- to 0-minute period was significantly shorter than those during the other 10-minute periods. The coefficient of variance of the high-frequency component (0.15 to 0.40 Hz) (CVHF) from the 10- to 0-minute period was not significantly different from the other 10-minute periods. However, both the coefficient of variance of the low-frequency component (0.04 to 0.15 Hz) (CVLF) and the ratio of CVLF and CVHF (CVLF/CVHF) were significantly greater during the 10- to 0-minute period than those during the 30- to 20-minute period, respectively. A significant nighttime fluctuation in the spectral components of heart rate variability with a peak in the CVHF and a nadir in both the CVLF and CVLF/CVHF observed in the control group was blunted in the patients during the attack-free periods while they were medicated with calcium entry blockers., Conclusion: Sympathovagal imbalance, sympathetic activation without parasympathetic augmentation, enhanced in the early morning may play an important role in the genesis of coronary artery spasm in patients with nocturnal variant angina.

Insulin resistance has been demonstrated in patients with angina pectoris irrespective of detectable atherosclerosis at coronary angiograms. We compared insulin sensitivity, lipid profiles, and exercise capacity in 20 patients with syndrome X, 15 patients with variant angina, and 20 healthy controls to investigate whether the presentation of the insulin resistance syndrome differs between the two patient groups with disparate vascular abnormalities. All patients had angiographically normal coronary arteries. Maximal oxygen uptake (VO2 max) was determined at bicycle exercise testing. Insulin sensitivity (SI) was assessed by the minimal model analysis of the intravenous glucose tolerance test. Patients with variant angina had significantly lower VO2 max than controls (mean +/- SE, 25.6 +/- 1.5 vs 30.6 +/- 1.4 ml x kg-1 x min-1, p < 0.05), whereas VO2 max in patients with syndrome X was intermediate (27.1 +/- 1.3 ml x kg-1 x min-1). Compared with controls, patients with syndrome X and variant angina had reduced insulin sensitivity (controls, 1.47 +/- 0.16 10(-4) x min-1/per pmol/L vs syndrome X, 0.86 +/- 0.11 10(-4) x min-1 per pmol/L and variant angina, 0.96 +/- 0.15 x 10(-4) x min-1 per pmol/L; analysis of variance, p < 0.05). Only patients with syndrome X exhibited fasting hyperinsulinemia. Patients with syndrome X also had higher fasting concentrations of triglycerides and total cholesterol and lower concentrations of high-density lipoprotein cholesterol than controls. When adjusting SI for variances of VO2 max, differences in SI vanished between controls and patients with variant angina but not between controls and patients with syndrome X. Thus syndrome X and variant angina are both associated with insulin resistance, but lipid abnormalities are only prominent in patients with syndrome X. A variable expression in terms of concomitant disturbances of lipid profiles and disparate influences of physical capacity suggests different underlying mechanisms.

With the use of iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy, this study evaluated regional sympathetic nerve activity in vasospastic angina. Twenty male patients with left anterior descending coronary artery spasm and 18 male patients with normal coronary arteries as a control group were studied. All patients underwent quantitative 123I-MIBG scintigraphy and atropine stress 123I-MIBG scintigraphy. Both groups showed a similar heterogeneous 123I-MIBG uptake in the left ventricle. However, the regional washout rate in patients with coronary artery spasm was significantly reduced in all three territories compared with that in the control group. In vasospastic angina, the regional washout rate in the left anterior descending coronary artery territory was significantly reduced as compared with the other two regions. After intravenous injection of 1 mg atropine, the regional washout rate in the three regions significantly increased in both groups, but the regional differences between the two groups disappeared. The current study demonstrated that cardiac sympathetic nerve activity in vasospastic angina was suppressed, especially in the territory of the spasm-induced coronary artery, probably because of the enhanced parasympathetic nerve activity.

Exercise and hyperventilation tests are often used as the provocative tests for coronary artery spasm. To examine the distribution of myocardial blood flow during exercise-induced and hyperventilation-induced attacks of coronary spasm, thallium-201 myocardial scintigraphy was performed in 47 patients with variant angina. The extent and severity scores and severity index (severity score/extent score) of scintigraphic perfusion defect were calculated. In 32 patients, anginal attack associated with ST elevation on the electrocardiogram was induced by exercise; in 23 patients, the attack was induced by hyperventilation. In patients with either anterior or inferior wall ischemia, both the extent and severity scores and severity index in the scintigram were significantly greater in exercise-induced anginal attack than those in hyperventilation-induced attack. In patients with simultaneous anterior and inferior wall ischemia, they tended to be greater in exercise-induced attack. In eight patients in whom anginal attack was induced by both exercise and hyperventilation, these scores and index were significantly greater in exercise-induced attack than those in hyperventilation-induced attack. These data suggest that myocardial ischemia during exercise-induced attack is enhanced as compared with that during hyperventilation-induced attack. Thallium-201 scintigraphy combined with exercise testing seems to be more sensitive for detecting myocardial ischemia induced by coronary spasm.

The effects of beta-adrenoreceptor and calcium channel-blocking agents on the balance of myocardial oxygen supply and demand were studied in 15 patients (2 women and 13 men), aged 46 to 69 (mean 62) years, with variable-threshold angina. An exercise test was performed before therapy was begun, and 24-hour ambulatory ECG monitoring was performed after 1 week of long-acting nitrate therapy, in the third week after random assignment to either atenolol or diltiazem, and in the third week after crossover. All exercise tests were positive except in one patient taking diltiazem. The exercise time to 0.1 mV ST change was 4.2 +/- 1.7 minutes with no therapy, 5.1 +/- 1.6 minutes with nitrates, 6.6 +/- 0.8 minutes with diltiazem, and 6.5 +/- 2.1 minutes with atenolol. The rate-pressure product at 0.1 mV ST change was 20.9 +/- 4.6 with no therapy and 21.2 +/- 5.7 and 22 +/- 4.6 with nitrates and diltiazem, respectively, but fell to 15 +/- 3.9 beats.min.-1 mm Hg 10(-3) after atenolol (p < 0.01). There was no significant difference in the number of anginal attacks or in nitroglycerin consumption per week. The heart rate at the onset of ST-segment change during the exercise test and during ambulatory ECG monitoring was significantly lower during atenolol than during diltiazem treatment. Both atenolol and diltiazem were of similar efficacy in increasing nonischemic exercise duration in patients with variable-threshold angina and acted primarily by slowing the resting heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to assess the role of the autonomic nervous system in the pathogenesis of coronary artery spasm in patients with variant angina. We evaluated cardiac sympathetic and parasympathetic activity from the power (logarithmic scale) of the low-frequency (approximately 0.04 to 0.12 Hz) and the high-frequency (approximately 0.22 to 0.32 Hz) spectral components of heart rate variability with Holter monitoring in seven patients with nocturnal variant angina and in 11 healthy men who served as control subjects. None of the patients had organic coronary artery stenosis as determined by angiography. Low-frequency and high-frequency logarithmic values were calculated for each 5-minute period from 30 minutes before to immediately before each angina attack. The logarithmic low-frequency value during the 5-to-0-minute period was greater than the low-frequency values during most of the other periods (p < 0.05 - p < 0.01). The logarithmic high-frequency values during the 10-to-5-minute and 5-to-0-minute periods were greater than those during the 30-to-25-minute period (p < 0.05 and p < 0.01, respectively). These data indicate that parasympathetic activity increased during the 10 minutes before attacks of nocturnal variant angina, whereas sympathetic activity with vagal modulation increased during the 5 minutes before such attacks. The same pattern of changes in heart rate variability was found in the absence of ST-segment elevation in patients and in control subjects. So this phenomenon was not just associated with coronary spasm and variant angina. It is suggested that circadian variation in disease activity is also associated with spontaneous attacks.

Chronologic changes of coronary spasm were examined by repeated ergonovine provocation tests during angiography. A total of 322 patients who had variant angina without severe atherosclerosis demonstrated a positive response to the first test. Ninety of these patients had recurrent variant anginal symptoms after an angina-free period of 38 +/- 12 months (mean +/- SD). Of these 90 patients, 76 (84%) had symptoms or electrocardiographic (ECG) findings similar to those of the first test. The initial 9 of these 76 patients underwent a second provocation test and showed coronary responses analogous to those on the first test. Of the 90 patients, 14 (16%) had different symptoms or ECG findings from those elicited at the first episode. All 14 patients again had a positive response to a second ergonovine test and the following angiographic changes were observed in the three major vessels between the two tests. Of the 21 vessels that had spasm on the first test, eight vessels (19%) did not have spasm on the second test. Of the 21 vessels that did not demonstrate spasm on the first test, 10 (24%) demonstrated spasm on the second test. In the present study it is concluded that the majority of patients with recurrent angina seemed to have consistency in the location of coronary spasm, while in some patients the fluctuation of coronary spasm was confirmed by two ergonovine provocation tests.

The objective of this study was to determine if endothelium-dependent vasodilation is preserved in the spastic segment of the epicardial coronary artery. Segmental responses of the coronary artery to substance P were examined by the use of a quantitative angiographic technique in 21 patients with variant angina. Coronary diameter at the basal state did not differ between the spastic and the nonspastic segments (2.3 +/- 0.2 mm, 2.3 +/- 0.4 mm, p greater than 0.05). Changes in coronary diameter in response to substance P did not differ between segments with ergonovine-induced spasm and nonspastic segments. Maximal dilation averaged 27.1 +/- 9.5% in the spastic segment and 24.4 +/- 9.6% in the nonspastic segment (expressed as a percent increase over the value before drug administration). It appears that both the potential of the endothelium to release endothelium-dependent relaxing factor and the dilating response of the smooth muscle to endothelium-dependent relaxing factor are preserved, even in the spastic segment.

The interpretation of a diagnostic modality requires consideration of the entire distribution of potential responses in both the normal and diseases population to extract the maximum available information from the test. Accordingly, we developed a probabilistic format for interpretation of scintigraphic left ventricular ejection fraction (LVEF) in the diagnosis of coronary artery disease (CAD). This format is distinguished (1) by accurate assessment of CAD likelihood based upon age, sex, and symptom classification using a logistical regression model (mean r = 0.9991, mean SEE = 0.008) and (2) by consideration of LVEF as a continuous probabilistic variable which obeys beta frequency distribution. This format allows assessment of the probability of CAD in an individual patient, according to Bayes' theorem of conditional probability of disease, given combinations of LVEF at rest and/or with exercise, and thereby is designed to provide more information than conventional categorical classification of "normal" or "abnormal" test observations.

M-mode echocardiograms were recorded in 12 patients with Prinzmetal's angina during 29 episodes of transient myocardial ischemia at rest (18 spontaneous and 11 ergonovine-induced). At peak ST segment elevation a regional mechanical impairment was observed in the interventricular septum during 23 episodes of angina and in the posterior wall during six episodes. In the 18 spontaneous episodes the left ventricular ischemic wall, when compared to the basal state, was found to have a significant reduction in motion (-76.3 +/- 9.1%) (mean +/- SEM), in diastolic thickness (-11.7 +/- 2.5%), and in percent systolic thickening (-88.0 +/- 5.6%). Increase in left ventricular end-diastolic diameter (+13.1 +/- 2.1%) and decrease in percent fractional shortening (-38.1 +/- 3.7%) were also observed. When ST segment was back to the isoelectric line, a transient overshoot in regional left ventricular function was observed. In induced episodes statistically significant changes could be detected by M-mode echocardiography even before appearance of ST segment elevation and anginal pain. No significant difference was found in type or degree of mechanical impairment between induced and spontaneous episodes. Therefore, in patients with Prinzmetal's angina: (1) M-mode echocardiography allows detection of mechanical changes due to transient myocardial ischemia; and (2) mechanical impairment occurs earlier than clinical (pain) and electrocardiographic (ST segment elevation) signs of transmural ischemia.

The efficacy of isosorbide dinitrate (ISDN) in variant angina is enhanced by the addition of a calcium antagonist. A prospective double-blind, crossover trial of ISDN, 40 to 120 mg/day, and nifedipine, 40 to 120 mg/day, in 19 patients with variant angina and various degrees of coronary atherosclerosis showed that although both agents were equally effective in controlling angina of vasospastic origin, some patients responded better to one or the other drug. Such response could not be predicted by demographic factors, ECG changes, or degree of coronary atherosclerosis. Since quantitative angiography done in a similar group of patients showed that intracoronary nitroglycerin, 200 micrograms, was a more potent vasodilator than sublingual nifedipine, 10 mg (p less than 0.01), the calcium antagonists may have a different mechanism of preventing variant angina attacks and may act in an additive or synergistic fashion when administered in combination with long-acting nitrates. Such a combination will increase coronary blood flow, reduce ventricular volume and end-diastolic pressure, and reduce systemic arterial resistance. Coronary vasospasm may be directly prevented by a general inhibition of smooth muscle contraction by the calcium antagonist. Clinical studies suggest that combination therapy significantly improves the long-term prognosis of patients with variant angina and reduces the need for bypass surgery. Thus combining ISDN with a calcium antagonist is a rational and effective treatment for variant angina.

Flow impedance, probably of vasomotor origin, superimposed on severe coronary stenosis has been considered a trigger for the spontaneous component of angina occurring both on effort and at rest. To investigate more thoroughly this pathophysiologic aspect we evaluated (by means of quantitative coronary angiography) the acute vasomotor reaction to nifedipine (10 mg sublingually) of significant (greater than 50%) stenotic lesions in 22 patients with double-component angina. We also correlated this reaction with the clinical response (daily number of ischemic episodes evaluated by means of 48-hour Holter ambulatory monitoring) to treatment with nifedipine (20 mg four times a day); calcium channel blockade, in fact, is considered a specific remedy in cases of altered coronary vasomotility. Patients with Prinzmetal angina, who were known to have homogeneous coronary vasodilating reactions and favorable clinical responses to nifedipine, were studied by means of the same methods and served as the control group (14 patients). In double-component angina the residual lumen diameter of significant lesions was unchanged in two patients, enhanced in 10, and reduced in 10 after sublingual nifedipine; lumen variations from baseline values ranged from +1.29 to -1.56 mm. Acute changes in stenosis correlated closely with results obtained with oral treatment. In the group with Prinzmetal angina, coronary stenoses invariably responded with dilatation (the residual coronary lumen increased by an average of 69% of baseline); 100% of the patients in this group responded favorably to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

To facilitate the outpatient diagnosis of variant angina by documenting transient ST segment evaluation during chest pain, we studied the feasibility of transtelephonic ECG monitoring during angina episodes. Eight patients with known coronary artery spasm underwent simultaneous continuous ambulatory and transtelephonic ECG monitoring during a 24-hour period. Five patients (62%) had transient diagnostic ST segment shifts on both continuous ambulatory and transtelephonic monitoring. Another eight patients with coronary spasm underwent 24-hour continuous ambulatory monitoring and separate 14-day period of transtelephonic monitoring. The addition of this longer monitoring period provided diagnostic ST segment shifts in three patients. We conclude that transtelephonic monitoring in patients with suspected coronary artery spasm can provide important additional diagnostic information to continuous ambulatory monitoring, particularly in the patient with infrequent or predictable chest pain.

This study was performed (1) to assess the frequency of ventricular ectopic activity (ventricular bigeminy, couplets, or ventricular tachycardia) during spontaneous variant angina; (2) to assess the relation between ventricular ectopy and the severity and duration of ischemia; and (3) to evaluate the precise temporal relation between episodes of ischemia and ventricular ectopy. Fifteen ambulatory patients with variant angina (12 men, 3 women, aged 50 +/- 8 [mean +/- SD] years) had Holter monitoring for 24 hours/week for 10 months (total, 10,238 hours of monitoring), from which the following were measured during each episode of ST deviation (elevation or depression): duration of ST deviation (minutes), maximal ST deviation (millivolts), presence of ventricular ectopic activity, and timing of ventricular ectopy in relation to ST deviation. Of 645 episodes of ST deviation, 79 (12.2%) had associated ectopy, almost all of which occurred in three patients. The 79 episodes of ST deviation with ectopy lasted 4.6 +/- 3.3 minutes and averaged 0.16 +/- 0.12 mV, whereas the 566 episodes of ST deviation without ectopy lasted 4.7 +/- 6.1 minutes and averaged 0.17 +/- 0.11 mV (NS in comparison to the 79 episodes with ectopy). Of 489 episodes of ST elevation, 72 (14.7%) were accompanied by ventricular ectopy; of 156 episodes of ST depression, only seven (4.5%) had ectopy (chi 2 = 11.531, p less than 0.001). Of the 79 episodes of ventricular ectopy, almost all appeared during a period of increasing or maximal ST deviation, whereas only two appeared as ST deviation was resolving.(ABSTRACT TRUNCATED AT 250 WORDS)

Eighteen patients with variant angina, a positive ergonovine test, and a favorable response to calcium antagonists were studied by serial ergonovine tests and Holter monitoring to assess the long-term changes in response to ergonovine and the relationship with the spontaneous activity of the disease. The number of patients with a positive test decreased from 18 of 18 in the acute phase to 12 of 18 (66%) at 3 months, 10 of 17 (59%) at 6 months, and five of 17 (29%) at 12 months. The mean dose level of ergonovine associated with a positive response and the percentage of positive tests with ST segment depression increased progressively during follow-up. The results of the ergonovine test were well correlated with the spontaneous activity of the disease in 94%, 83%, 76%, and 71% of the patients at initial observation and at 3, 6 and 12 months, respectively. Thus in patients with variant angina and a favorable response to calcium antagonists, a time-related decrease in sensitivity to ergonovine develops during follow-up. In most patients the response to ergonovine is well correlated with the spontaneous activity of the disease; thus the ergonovine test may be a useful tool in the assessment of the natural evolution of vasospastic angina.

We studied the prevalence and clinical significance of transient U wave inversion in 43 patients with variant angina. Twenty-four patients (group A) had ST segment elevation in the anterolateral and 19 patients (group B) had this finding in the inferoposterior leads of the ECG during spontaneous angina. In none of these patients was U wave inversion present on the resting 12-lead ECG in the absence of anginal attack. During anginal attacks, U wave inversion developed in association with ST segment elevation in 16 patients (66.7%) of group A but in no patient of group B. To exclude the possibility that a transient rise of systolic blood pressure during angina caused U wave inversion, treadmill exercise testing was done in the 16 patients after the discontinuation of antianginal drugs. In 12 of the 16 patients, exercise testing did not produce angina or U wave inversion despite a marked elevation of systolic blood pressure. These results indicate that transient U wave inversion frequently develops with anterolateral ischemia but not with inferoposterior ischemia during attacks of variant angina. It is likely that transient U wave inversion was caused by myocardial ischemia but not by a rise of blood pressure during angina.

Tiapamil is a new calcium entry blocker. The ability of its intravenous form to prevent methylergometrine-induced coronary artery spasm was studied in 11 consecutive patients with angiographically documented vasospastic angina. The study was designed as a double-blind crossover trial of tiapamil vs placebo. Each patient received, in a randomized order, either tiapamil, as a 1.5 mg/kg intravenous bolus followed by a 50 micrograms/kg/min infusion lasting 3 hours, or a matched placebo. Immediately after the infusion, methylergometrine tests were performed with up to 0.4 mg of methylergometrine or until a positive ECG was recorded. Compared to the values obtained after placebo infusion, tiapamil significantly lowered systolic and diastolic blood pressure (respective pre- and posttiapamil values: 119.9 +/- 17.7 vs 142.1 +/- 25.5 mm Hg, p less than 0.01; and 72.0 +/- 9.1 vs 82.4 +/- 9.3 mm Hg, p less than 0.02); the drug exerted no significant effect on heart rate (63.9 +/- 13.3 vs 67.6 +/- 16.5 bpm, NS), PR interval (0.180 +/- 0.020 vs 0.177 +/- 0.017 sec NS), or QTc interval (404.4 +/- 16.5 vs 396.0 +/- 26.6 msec, NS). After placebo, 10 patients had positive methylergometrine tests following single doses ranging from 0.1 to 0.4 mg. The remaining patient developed ventricular bigeminy, which resolved immediately after administration of isosorbide dinitrate; his test was therefore considered negative in the evaluation of the results. In contrast, after tiapamil, eight patients had negative tests for doses of up to 0.4 mg methylergometrine, and three had positive tests for the same methylergometrine doses as after the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined segmental left coronary artery responses to nitroglycerin in 17 variant angina patients and in 34 nonvariant angina patients using a quantitative angiography technique. In those patients with left anterior descending vasospasm, there was a marked exaggeration in the degree of dilation to nitroglycerin in those segments which at other times were involved with spasm. This observation was consistent when these segments were compared to (1) other left coronary segments in the same patient, (2) the same left coronary segments in nonvariant angina patients, and (3) the same left coronary segments in patients with right coronary spasm. These data suggest that a localized disorder in coronary vasomotion is present in patients with coronary spasm that is not limited to constriction but also involves increased dilation in response to nitroglycerin.

Fifty-five ischemic attacks at rest with ST segment elevation were recorded by two-dimensional echocardiography (2DE) in 20 patients with Prinzmetal angina. Eighteen ischemic attacks were recorded starting from intravenous injection of ergonovine maleate while 37 spontaneous ischemic attacks were recorded from onset of either anginal pain or ECG changes or from the basal state. In each ischemic attack at least one of the following transient alterations was observed by 2DE during ST elevation: (1) Regional hypokinesia, akinesia, or dyskinesia; (2) "step sign," that is, a sharp demarcation between an akinetic or dyskinetic area and an adjacent normal or hypercontracting region; and (3) geometric changes in left ventricular shape, that is, globular appearance in diastole and hourglass silhouette in systole. Regional myocardial asynergy was detected earlier than onset of pain (which was not present in 21 [38%] ischemic episodes) or ST segment elevation on ECG, as documented in 40 ischemic episodes (16 induced and 24 spontaneous) in which echocardiographic monitoring was performed from basal state and carried on up to the appearance of ischemia. All described mechanical changes were fully reversible after pain subsided and ST segment was back to isoelectric, either spontaneously or with nitrates; furthermore, a contractile "rebound phenomenon" of the previously ischemic wall was observed in some episodes. In conclusion, these results outline a role for 2DE in detecting cardiac mechanical impairment due to transient myocardial ischemia with ST segment elevation in humans.

Responses of heart rate and blood pressure to transient myocardial ischemia were analyzed in patients with variant angina. Heart rate changes during ST segment elevation were examined by means of a Holter ECG monitoring system. All 27 ST segment elevations from 10 patients with anterior ischemia were accompanied by an increase in heart rate by 12 +/- 2 bpm (mean +/- SEM, p less than 0.001) at peak ST segment elevation. With inferior ischemia in nine patients, heart rate decreased significantly by 4 +/- 1 bpm (n = 28, p less than 0.001). However, 9 of these 28 ST segment elevations showed a biphasic response of heart rate, that is, an initial increase and subsequent decrease. Such heart rate changes were not different between ST segment elevations with and without chest pain. With chest pain systolic blood pressure rose in anterior ischemia by 42 +/- 5 mm Hg (n = 10, p less than 0.001) but fell in inferior ischemia by 22 +/- 8 mm Hg (n = 7, p less than 0.05). We conclude that a different cardiovascular reflex occurs in response to inferior versus anterior ischemia and it is independent of chest pain.

In summary, we have examined the response to arterial vasoconstriction in an in vitro coronary artery preparation. Without a preexisting stenosis, arterial vasoconstriction had minimal hemodynamic effects. Similarly, with a stenosis created by a circumferential snare, arterial vasoconstriction had minimal hemodynamic effects. In striking contrast, with a stenosis created by intraluminal obstruction, arterial vasoconstriction dramatically increased the hemodyamic severity of the stenosis. The use of an intraluminal obstruction provides a useful animal model for examining hemodynamics in coronary artery disease and had provided some insight into the effects of vasoconstriction on coronary artery hemodynamics. Obviously, this is an experimental study, and care must be taken in extrapolating these results to diseased human coronary arteries.

The present study is an angiographic demonstration of coronary artery spasm during both spontaneous and exercise-induced angina in three patients with variant angina. In each case, clinical, ECG, coronary angiographic, and left ventriculographic observations were made at rest, during spontaneous angina, and during exercise-induced angina. The character of chest pain was similar during spontaneous and exercise-induced episodes. ST segment elevation was present in the anterior ECG leads during both episodes. The left anterior descending coronary artery became partially or totally obstructed during both types of attacks. When coronary spasm was demonstrated during both types of attacks, left ventriculography disclosed akinetic or dyskinetic wall motion in the area supplied by the involved artery. In those patients with reproducible exercise-induced ST segment elevation and chest pain, thallium-201 scintigraphy showed areas of reversible anteroseptal hypoperfusion. Thus in selected patients exercise-induced attacks of angina were similar to spontaneous episodes.

The present study was performed to assess the efficacy of concomitant calcium antagonist/isosorbide dinitrate therapy in patients with frequent episodes of variant angina and to compare such combination therapy with isosorbide dinitrate alone. We enrolled nine such patients (six men and three women, aged 47 +/- 9 [mean +/- standard deviation] years) in a long-term comparison of (1) oral isosorbide dinitrate (117 +/- 63 mg per day) alone, (2) verapamil (453 +/- 75 mg per day) + isosorbide dinitrate (given in the same dose as stated above), and (3) nifedipine (71 +/- 14 mg per day) + isosorbide dinitrate (also given in the same dose as stated), each administered for 2 months. During isosorbide dinitrate therapy, these nine patients averaged 23.7 +/- 37.3 chest pains per week, consumed 24.4 +/- 47.4 sublingual nitroglycerin tablets per week, and demonstrated 46.5 +/- 43.2 episodes per week of transient ST segment deviations on calibrated two-channel Holter monitoring. During therapy with verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate, the frequency of angina and ST segment deviations was dramatically reduced (verapamil/isosorbide dinitrate, 3.9 +/- 3.6 chest pains per week and 3.5 +/- 2.6 ST segment deviations per week, p less than 0.05; nifedipine/isosorbide dinitrate, 3.1 +/- 4.0 chest pains per week and 5.5 +/- 6.6 ST segment deviations per week, p less than 0.05). In all respects, verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate were similar to one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymptomatic episodes of ST segment and/or T wave changes are often reported during Holter monitoring in patients with angina pectoris. However, the interpretation of such changes is debated relative to silent myocardial ischemia. We studied 11 patients admitted to the CCU because of frequent episodes of unstable anginal attacks who had undergone repeated periods of Holter monitoring, characterized by predominantly occurring asymptomatic episodes of ST segment and/or T wave changes associated with less frequent typical anginal attacks. In a total of 89 days of Holter monitoring, the patients evidenced 520 episodes of transient ECG changes including 180 of ST elevation, 73 of ST depression, and 267 of T wave alterations. Only 12% of episodes were symptomatic. Coronary injection during asymptomatic ST-T changes was performed in eight patients. In six it was possible to document spontaneous coronary spasm. In seven patients ergonovine administration induced anginal pain, ST-T changes, and coronary spasm. In all patients the anginal attacks completely disappeared with medical treatment and the asymptomatic episodes were abolished in six and reduced in four. Our findings support the hypothesis that in certain selected unstable anginal patients, transient asymptomatic ECG changes are caused by acute myocardial ischemia.

To test the hypothesis that intracoronary concentrations of thromboxane (Tx)A2 could influence the response to cold pressor test (CPT) in variant angina, great cardiac vein blood flow (by thermodilution) and the concentration of TxB2 (the stable metabolite of TxA2) in the great cardiac vein and aorta were measured under control conditions and during CPT in 14 patients with angina at rest associated with transient ST-segment elevation in the anterior leads. In seven patients pretreated with aspirin (intravenous administration of 3.6 mg/kg lysine salt of acetylsalicylic acid, corresponding to 2 mg/kg aspirin), TxB2 baseline concentrations were lower in both the great cardiac vein (47 +/- 19 vs 176 +/- 88 pg/ml; p less than 0.005) and the aorta (45 +/- 16 vs 109 +/- 56 pg/ml, p less than 0.02) than in seven patients who were not taking cyclooxygenase inhibitors. In the two groups, great cardiac vein flow and anterior region coronary resistance were similar under control conditions. During CPT anterior region coronary resistance increased in patients pretreated with aspirin (from 1.97 +/- 0.99 to 2.22 +/- 1.11 mm Hg/ml/min; p less than 0.02) and in patients without aspirin pretreatment (from 1.94 +/- 0.43 to 2.06 +/- 0.34 mm Hg/ml/min; p less than 0.05), and the difference between the two groups was not statistically significant. Therefore the vasoconstrictor response of coronary vessels to CPT in variant angina is not influenced by the intracoronary TxB2 concentrations and is not modified by aspirin pretreatment.

Kn patients with Prinzmetal's angina, episodes of transient T wave abnormalities (T abn) are often documented in addition to the typical episodes of ST segment elevation (ST). As the interpretation of these minor ECG changes is still uncertain, we investigated if transient T abn are associated with reversible ventricular asynergies, similar to episodes with ST. For this purpose an ECG lead and a two-dimensional echocardiographic projection, which showed clear-cut changes during previous episodes of ST, were simultaneously monitored in five patients with Prinzmetal's angina for a total of 13 hours and 20 minutes. In all patients, the 30 episodes of ST recorded were all accompanied by reversible ventricular asynergies. Furthermore, in four of these patients, 14 episodes of T abn (peaking, flattening, or the appearance of a diphasic T wave) were recorded. All T abn were associated with reversible asynergies, as detected by three independent observers. The mechanical impairment occurred in the same ventricular wall both during ST and during T abn. During T abn the degree of mechanical impairment appeared less severe (hypokinesia in 12 and akinesia in two episodes) than during ST (hypokinesia in one, akinesia in 25, and dyskinesia in four episodes) (p less than 0.001). The duration of asynergies was less during T abn (107 +/- 76 seconds) than during ST (169 +/- 83 seconds) (p less than 0.05). Chest pain was reported in 5 of 14 episodes of T abn (36%) and in 20 of 30 (66%) episodes of ST (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary angiography of both right and left coronary arteries, using the Sones technique, was performed during the attack of total spastic obstruction in 11 patients with clinically documented history of variant angina. None of the patients had more than 70% stenosis of organic atherosclerosis in any coronary artery and none had a history of myocardial infarction. Total spastic obstruction occurred spontaneously in 3 of 11 patients, and was provoked by ergonovine maleate in eight patients. Six patients had total spastic obstruction in the left anterior descending coronary artery, four patients had total obstruction in the right coronary artery, and one patient had total obstruction in the left anterior descending and right coronary arteries. In 7 of 11 patients, the coronary artery distal to the total spastic obstruction received collaterals from the nonspastic artery. The collaterals disappeared promptly when the spastic coronary artery was patent. These patients had ST segment elevation in the ECG during the attacks. In the remaining four patients, the spastic artery did not receive any collaterals from the nonspastic artery, associated with ST segment elevation during the attacks. These findings suggest that the brief, repetitive total occlusion of the coronary artery may stimulate the enlargement of collaterals. These collaterals may not always function to prevent the ischemia of the myocardium on the ECG.

Thirty-six patients with variant angina pectoris (VAP) were analyzed to investigate whether the mechanism underlying dysrhythmia is related to coronary occlusion or reperfusion. Fifteen of the 36 patients demonstrated dysrhythmias (42%). Twelve of 15 patients (80%) experienced dysrhythmia prior to the acme of ST-segment elevation (occlusive dysrhythmia), and those of tachyarrhythmia type were characterized by the presence of ventricular premature beats initially isolated, increasing in frequency, and preceding the more malignant forms of dysrhythmias, such as ventricular tachycardia or ventricular fibrillation. The occlusive dysrhythmias included ventricular dysrhythmia (ventricular premature beats, ventricular tachycardia, slow ventricular tachycardia, ventricular fibrillation) in eight patients and conduction abnormalities (second- and third-degree AV block, left posterior fascicular block) in four patients. Thirteen episodes of VAP were fully recorded electrocardiographically. The average time to onset of dysrhythmia, after the beginning of ST-segment elevation, was 4.94 minutes +/- 1.52. The duration of the episodes without dysrhythmia was 0.86 minute +/- 0.53. The "reperfusion dysrhythmia" occurred in three patients (20%) and was characterized by the appearance of isolated couplets of ventricular premature beats, ventricular tachycardia, or ventricular fibrillation without prodromal ectopic activity. The dysrhythmia occurred in one patient during the resolution of ST-segment elevation and in two patients within seconds of ST-segment normalization. We conclude that the occlusive related dysrhythmias are the most important mechanism in VAP. They are dependent on the duration of the ischemic episode.