Diagnosis of important fixed coronary stenosis in patients with variant angina by exercise tests after treatment with calcium antagonists.

A 12 lead electrocardiogram was recorded during treadmill exercise in 57 patients with variant angina in whom coronary angiography was performed. Thirty six patients performed exercise tests with and without calcium antagonists, and 21 performed them only with calcium antagonists. In 55 patients calcium antagonists had prevented spontaneous attacks of variant angina for more than two days before the test. The other two patients were given a single dose of diltiazem (90 mg) two hours before the test. Exercise testing without calcium antagonists induced ST segment elevation with chest pain in nine patients, ST segment depression in 10 (nine with chest pain), and no important shift of the ST segment in 17. Five patients had severe coronary stenosis (greater than or equal to 75%) and all of them showed positive response. Thirty one patients had no important coronary stenosis and 14 of them showed positive response. The sensitivity of the exercise test in detecting a coronary stenosis greater than or equal to 75% was 100% without calcium antagonists but the specificity was low (55%). When the exercise test was done in patients taking calcium antagonists, only two (specificity 96%) of 48 patients without severe coronary stenosis showed positive response (elevation of ST segment in one and depression in another) whereas all nine patients with severe coronary stenosis had a positive response (depression of ST segment in six and elevation in three (sensitivity 100%). It is concluded that exercise testing with calcium antagonists may be a useful method for detecting severe coronary stenosis in patients with variant angina.     

Spontaneous remission of variant angina documented by Holter monitoring and ergonovine testing in patients treated with calcium antagonists

Twenty-four patients with Prinzmetal's variant angina showing a favorable initial response to calcium antagonist treatment were studied to assess the evolution of the disease and the frequency and time course of spontaneous remission. At 3, 6 and 12 months from the acute phase, patients underwent in-hospital control studies, with 48-hour Holter monitoring and ergonovine testing carried out during treatment and after its interruption. During calcium antagonist therapy complete protection from spontaneous attacks was documented in 22 of 24 patients at 3 months, in 19 of 21 at 6 months and in all 21 at 12 months; ergonovine test results were negative in 16 of 23 patients at 3 months, in 16 of 20 at 6 months and in all 20 studied at 12 months. After stopping treatment spontaneous attacks did not reappear in 7 of 24 patients (29%), 14 of 21 (66%) and 16 of 21 (76%) at 3, 6 and 12 months respectively, while the ergonovine test response remained negative in 6 of 21 (28%), 7 of 18 (39%) and 13 of 20 (65%) of the patients controlled at 3, 6 and 12 months. Thus, complete remission of angina documented by both Holter recording and ergonovine testing occurred in 5 of 24 patients (21%) at 3 months, in 7 of 21 (33%) at 6 months and in 12 of 21 (57%) at 12 months. Patients with remission of angina had a shorter duration of symptoms and more often showed normal or not critically diseased coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nocturnal angina in patients with fixed coronary stenosis. Increased coronary vasoconstrictive sensitivity with independence of pacing ischaemic threshold

Atrial pacing and ergonovine tests were performed in 18 consecutivepatients with unstable angina at rest and significant coronaryartery stenosis ( 90% in one vessel in 16 patients). 13 ofthem also had exertional angina. 14 patients presented at leastone positive response (1.0 mm ST-segment shift) to pacing, witha heart rate (144±11 vs 75±13 beats min^–1,P<0.001) and double product (195±26 vs 108±32x 10^–2 P<0.001) significantly higher than during anginaat rest. In the ten patients who presented nocturnal angina,the incidence of positive response to pacing and the pacingischaemic threshold, tested on three different days, were similarto those seen in the remaining patients. In contrast, the ergonovinetest was positive in all patients with nocturnal angina (100%),who required a low dose (0.28±0.2 mg), but it was positivein only four (50%) of those without nocturnal angina, who neededa higher dose (0.55±0.12 mg, P<0.005). Therefore, in patients with severe coronary stenosis and exertionalangina, spontaneous episodes, including nocturnal angina, arenot related to increases in heart rate. The increased coronaryvasoconstrictive sensitivity found in these patients, particularlythose with nocturnal angina, was not dependent on the statusof the coronary reserve, which strongly suggests that changesin coronary tone, focal or diffuse, are involved in the mechanismsof these ischaemic events.     

A comparative study of eccentric and concentric coronary stenosis vasomotion in patients with prinzmetal's variant angina and patients with stable angina pectoris

Background and hypothesis: In patients with stable angina pectoris, eccentric stenoses have a greater potential for dynamic changes of caliber in response to vasoactive stimuli than concentric lesions. It is not known whether in patients with coronary artery spasm the degree of coronary vasoconstriction differs in eccentric versus concentric stenoses. Therefore, we examined the relationship between coronary stenosis morphology and the vasomotor response to vasoactive stimuli in patients with variant angina. Methods: Computerized quantitative angiography was used to measure minimum luminal diameter of eccentric and concentric stenoses before and after the administration of ergonovine and isosorbide dinitrate in 22 patients with Prinzmetal's variant angina and in 20 patients with chronic stable angina. Results: In patients with variant angina, mean stenosis diameter reduction with ergonovine was -0.85 ± 0.38 and -1.12 ±0.69 mm in eccentric and concentric stenoses, respectively (p = NS). Isosorbide dinitrate promptly relieved spasm in all patients and increased the diameter of eccentric stenoses by 0.26 ± 0.34 mm and that of concentric stenoses by 0.24 ± 0.32 mm (p = NS). In patients with chronic stable angina, mean diameter reduction with ergonovine was -0.23 ±0.12 and -0.12 ± 0.10 mm for eccentric and concentric stenoses, respectively (p < 0.05). Isosorbide dinitrate increased coronary diameter by 10% from baseline in 70% of eccentric and 38% of concentric stenoses (p < 0.01). Conclusion: In patients with variant angina pectoris, eccentric and concentric spastic stenoses react similarly in response to vasoactive stimuli. In patients with chronic stable angina, eccentric stenoses are more likely to show vasomotor responses than concentric stenoses.     

Ischemic preconditioning detected by treadmill exercise tests in patients with stable angina

The aim of this study was to explore the ischemic preconditioning (IP) phenomenon in patients with chronic stable angina (SA) by using treadmill exercise tests (TETs). Twenty-nine patients with SA were divided into 2 groups: group A (n = 15) and group B (n = 14). There was no difference between the 2 groups in both clinical characteristics and extent of coronary stenosis. Group A was subjected to 2 TETs at a 10-minute interval, but group B had a 60-minute interval according to Bruce protocol. The occurrence and time of chest pain, maximal value, duration of ST segment depression, and arrhythmias that occurred during TETs were analyzed for differences in the 2 tests in the 2 groups. In group A, 9 patients (60.0%) complained of chest pain in the first test, whereas only 4 (26.7%) did in the second test (p < 0.01); The time of occurrence of chest pain during exercise was 1.88 +/- 0.2 min in the first test, 2.3 +/- 0.4 min in the second test (p < 0.05); The maximal value of ST segment depression decreased from 0.21 +/- 0.09 mV in the first test to 0.14 +/- 0.05 mV in the second (p < 0.01); the duration of ST segment depression decreased from 7.12 +/- 0.9 min in the first test to 4.42 +/- 0.3 min in the second (p < 0.01). The incidence of arrhythmia decreased from 40.0% in the first test to 13.3% in the second (p < 0.05). However, no significant difference was observed in the multiple parameters, mentioned above, in group B. In conclusion, the first ischemic event could induce the IP phenomenon and protect the heart from more serious damage at a 10-minute interval. However, this effect disappeared when the second test was done at a 60-minute interval.     

Resting angina with fixed coronary artery stenosis: nocturnal decline in ischemic threshold

Atrial pacing was performed in 16 patients with angina at rest and significant coronary artery stenosis (greater than 70%) over 2 consecutive days in the morning (10 A.M. to 1 P.M.), in the afternoon (4 to 7 P.M.), and at night (12 midnight to 3 A.M.) to assess possible circadian variations of their ischemic threshold. Overall, the incidence of resting angina was highest at night. All pacing results were positive (greater than or equal to 1.0 mm ST segment shift) and tended to be reproducible in nine patients, whereas some or all were negative in seven. Among all positive results, ischemic thresholds at night were significantly lower than those in the morning and in the afternoon (125 +/- 3 vs 138 +/- 3 and 139 +/- 2 beats/min, mean +/- SEM; p less than .005). In nine patients, 19 pacing tests produced ST segment elevation, of which 13 were performed at night (68%). We conclude that patients with resting angina and severe coronary stenosis often exhibit a nocturnal decline in their ischemic threshold, which seems to facilitate development of transmural ischemia during atrial pacing.     

Provocation of coronary spasm by dopamine in patients with active variant angina pectoris

The effects of dopamine on arteries are different depending on the dose, route of administration, and receptor population. Its administration can cause vasodilation by stimulation of dopaminergic receptors, vasoconstriction by stimulation of alpha-adrenergic and serotonergic receptors, and even spasm of cerebral arteries when given intracisternally in dogs. The ability of dopamine to provoke coronary spasm was assessed in 18 patients with active vasospastic angina in whom this amine was infused at rates of 5, 10, and 15 micrograms/kg/min for periods of 5 min each. The 12-lead electrocardiogram and blood pressure (cuff) were monitored throughout the whole test. In nine patients dopamine caused angina and ischemic electrocardiographic changes suggestive of coronary spasm: ST segment elevation in six patients and ST segment depression in the absence of important coronary stenoses in the remaining three. Infusion of dopamine was repeated during coronary angiography in three patients with positive test results: this provoked occlusive coronary spasm with ST segment elevation in two patients and nonocclusive spasm with ST segment depression in the remainder. In conclusion, infusion of dopamine provokes coronary spasm in a sizeable proportion of patients with active vasospastic angina. Its administration may be detrimental in patients susceptible to coronary spasm, such as those with acute myocardial infarction.     

Role of percutaneous transluminal coronary angioplasty in patients with variant angina and coexistent coronary stenosis refractory to maximal medical therapy

Percutaneous transluminal coronary angioplasty (PTCA) was performed with initial success in 7 patients with variant angina and significant (greater than 60%) coronary stenosis. The mean degree of stenosis was reduced from 77 +/- 12% to 29 +/- 15% and the mean systolic pressure gradient from 78 +/- 18 to 25 +/- 9 mmHg. Apart from a reversible spasm in one patient, PTCA was free of acute complications. Despite long-term treatment with nifedipine, nitrates, and warfarin (patients 1 to 5) or aspirin (patients 6 and 7) restenoses occurred in 4 of 7 patients. An aortocoronary bypass was necessary in 2 patients, 3 respectively 6 weeks after PTCA because of tighter restenoses than before PTCA. Another patient underwent successful repeat angioplasty after 6 weeks and remained improved. During a mean follow-up observation of 21 months (6 to 30 months), 4 patients were asymptomatic, even without medication. In one of these patients, the follow-up angiography (6 months after PTCA) demonstrated a restenosis. These results suggest that PTCA demonstrated a restenosis. These results suggest that PTCA can be performed without a higher risk of acute complications in patients with variant angina. Although the recurrence rate is high in these patients, sustained clinical improvement was achieved in a substantial percentage of patients in our study.     

Comparative results of coronary intervention in patients with variant angina versus those with non-variant angina

Coronary angioplasty is reported to be feasible and safe in patients with coronary spasm and fixed stenosis. However, the long-term results are not positive. We compared the results of coronary angioplasty in 20 patients with variant angina versus 17 patients with non-variant angina among 231 consecutive patients with vasospastic angina. Coronary angioplasty was performed successfully in all 37 patients without any complications. Stenting for coronary dissection or recoil was performed in 8 patients, directional coronary atherectomy was selected for ostial lesion of left anterior descending coronary artery stenosis in 2 patients, and standard balloon angioplasty was performed in 27 patients. There were no clinical differences between the two groups. The restensois rate in patients with variant angina was similar to that in patients with non-variant angina (30% vs 29%, ns). There was no relationship between the provoked spasm and restenosis. During the follow-up period, no major complications were observed in patients with variant angina or those with non-variant angina. In conclusion, full medication with calcium channel antagonists and isosorbide dinitrate, and treatment by coronary angioplasty including the use of new devices, were useful treatments for patients with coronary vasospasm and significant organic stenosis. There was no difference concerning the results of coronary intervention between the patients with variant angina and those with non-variant angina.     

Protection from digoxin-induced coronary vasoconstriction in patients with coronary artery disease by calcium antagonists

Intravenous digoxin induces constriction of normal and stenotic coronary arteries in patients with coronary artery disease, which may lead to ischemic complications. We found that pretreatment with oral nisoldipine and intracoronary nitroglycerin neutralizes this digoxin-induced effect.     

Results of coronary transluminal angioplasty following Prinzmetal's angina or fixed stenosis with associated spasm

Transluminal coronary angioplasty (TCA) was carried out in 130 patients (109 men and 21 women) with an average age of 51 years (range 20 to 76 years) between April 1980 and December 1982. The most commonly affected artery was the LAD (100). All patients were on heparin, coronary vasodilators and calcium antagonists before the procedure, and on calcium antagonists and platelet antiaggregant drugs after TCA. The material and methods used were those described by Gruntzig. In this population, we identified a group of patients, Group I, with fixed stenosis and associated coronary spasm--either Prinzmetal angina (13 cases, 6 of which had both ST-T elevation and other ECG changes) or spontaneous spasm with a variable degree of stenosis (2 cases). The stenosis remained greater than or equal to 70% in all cases after intracoronary injection of nitrate derivatives. There were no differences between this group and that of fixed stenosis (Group II) with respect to age and type of diseased vessel (although the right coronary artery was more commonly involved in cases of spasm). The overall primary success rate was 72.8% (14/15--93%--in Group I, and 85/121--70.2%--in Group II: no statistically significant difference). The angiographic relapse rate at 6 months was significantly higher in Group I (8/12: 67%) than in Group II (15/63: 23.8%) p less than 0.02. When "redilatation" with stable success is taken into consideration the difference is not significant (33% and 22.2% respectively). The relapses may be dissociated in Group I (2 cases with recurrent spastic angina and normal angiography).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise-induced angina provoked by aspirin administration in patients with variant angina

The effects of aspirin (4.0 g/day) given orally to eight patients with variant angina were observed. An exercise stress test performed in the morning was positive in two of seven patients during placebo administration, whereas a test performed in the afternoon at the same exercise work load resulted in negative findings. During aspirin administration, the afternoon exercise test repeatedly provoked anginal attacks associated with electrocardiographic changes (S-T segment elevation in five and S-T depression in two). Rate-pressure product at the end of the exercise test during aspirin administration was significantly lower than that during placebo administration (p <0.01). During aspirin administration, the frequency of angina increased markedly, and the attacks occurred not only during the night or early morning but also in the daytime in six of the eight patients. Our observations suggest that aspirin, in this large dose, reduces the capacity for exercise and provokes exercise-induced coronary arterial spasm in patients with variant angina.     

Persistent coronary artery spasm documented by follow-up coronary angiography in patients with symptomatic remission of variant angina

For patients with variant angina it is very important to start medical therapy using calcium-channel blockers. However, the decision of physicians regarding whether to decrease the dose of the drug or discontinue it is controversial. We investigated whether the nature of spasm is remissive and whether the termination of medications is safe. The subjects studied were included in the Vasospastic Angina in Catholic Medical Center Registry from March 2001 to December 2009. We analyzed 37 patients (62 lesions) with variant angina, diagnosed using coronary angiography (CAG) and he acetylcholine provocation test, without any organic coronary stenosis, whose symptoms were well controlled after medication. The follow-up CAG with provocation test was performed at a median interval of 44 months. The characteristics of spasm were analyzed on each pair of CAGs. The study group consisted of 23 men (62.2 %) and 14 women (37.8 %) with a mean age of 59 ± 11.1 years. The follow-up CAG with provocation test showed that the characteristics of the spasmodic nature were consistent with the first test in all patients. Although the patients with variant angina had no chest pain after medical treatment, the spasmodic nature of coronary arteries still remained. We may decrease the drug dosage after carefully checking the patient’s symptoms but recommend not discontinuing therapy, even if the patient is asymptomatic.     

Circadian variation of exercise capacity in patients with Prinzmetal's variant angina: role of exercise-induced coronary arterial spasm.

Thirteen patients with Prinzmetal's variant angina performed treadmill exercise tests in the early morning and in the afternoon of the same day. The attacks with ST elevation were induced repeatedly in all 13 patients in the early morning, but in only two patients in the afternoon. Propranolol did not suppress the exercise-induced attacks in all 13 patients. Diltiazem suppressed the attacks in all 13 patients and phentolamine in eight of the nine patients. Coronary arteriograms demonstrated that spasm occluding completely or almost completely the large coronary artery supplying the area of myocardium showing ST elevation appeared during the attacks and disappeared along with the attacks after nitroglycerin administration in all four patients in whom the attacks were induced by arm exercise in the catheterization laboratory. We conclude that there is circadian variation of exercise capacity in patients with Prinzmetal's variant angina caused by coronary arterial spasm induced by exercise in the early morning but not in the afternoon.     

Elevated coronary calcium scores are associated with higher residual platelet aggregation after clopidogrel treatment in patients with stable angina pectoris

High coronary calcium scores are known to be associated with elevated all-cause mortality. Moreover, low response to clopidogrel influences cardiovascular outcome after coronary stent placement. We sought to evaluate whether elevated calcium scores measured by cardiac computed tomography are associated with a higher residual platelet aggregation (RPA) after treatment with clopidogrel. Thus, in 62 patients coronary calcium scoring was measured prior to stent implantation. RPA was assessed by ADP (20 micromol/L)-induced aggregometry at least 6 h after administration of a loading dose of 600 mg clopidogrel. We found a significant correlation between ASE and RPA (r2 = 0.135, p = 0.0033, slope 7.809 +/- 2.549). Patients within the first quartile of ASE had significantly lower RPA after administration of clopidogrel than other patients (p < 0.05). Establishing a threshold of 200 ASE responsiveness to clopidogrel could be predicted with a positive predictive value of 80% and a specificity of 91%. In conclusion, we could demonstrate that patients with a low coronary plaque burden are more likely to have low RPA. Coronary calcium scoring might help to identify low responders to clopidogrel prior to stent placement and aggregometry.     

Nocturnal angina: precipitating factors in patients with coronary artery disease and those with variant angina

Factors precipitating nocturnal myocardial ischaemia were investigated in 10 patients with frequent daytime and nocturnal angina pectoris. Eight patients had fixed obstructive coronary artery disease or a low exercise threshold or both before the onset of ischaemia. Two patients had variant angina with normal coronary arteries and negative exercise tests. During sleep the electrocardiogram, electroencephalogram, electro-oculogram, electromyogram, chest wall movements, nasal airflow, and oxygen saturation were continuously measured. Forty two episodes of transient ST segment depression were recorded in the eight patients with coronary artery disease and 26 episodes of ST segment depression and elevation in the two patients with variant angina and normal coronary arteries. All episodes of ST segment depression in the former group of patients were preceded by an increase in heart rate as a result of arousal and lightening of sleep, bodily movements, rapid eye movement sleep, or sleep apnoea (one episode). In contrast, in the variant angina group no increase in heart rate, arousal, or apnoea preceded 23 of the 26 episodes of ST segment change. Thus increase in myocardial oxygen demand was important in precipitating nocturnal angina in patients with coronary artery disease and reduced coronary reserve. In the patients with coronary spasm these factors did not often precede the onset of nocturnal myocardial ischaemia.     

Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina

The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm.