The haemodynamic response to myocardial ischaemia in ambulant patients with variant angina.

The haemodynamic response to myocardial ischaemia in patients with variant angina during ambulatory activity is unknown. Ambulatory pulmonary artery pressure monitoring with a transducer tipped catheter and simultaneous frequency modulated electrocardiograms was used to assess changes in left ventricular function in five male patients (mean age 51.8 years) during variant angina; four patients had coronary artery stenosis and one had normal coronary arteries. Two hundred and seventy hours of ambulatory recordings were analysed. Twenty episodes (12 painful, 8 silent) of ST segment change greater than 1 mm occurred. Episodes tended to occur more frequently in the early morning hours. Six episodes of painful ST elevation were associated with a rise in pulmonary artery diastolic pressure. In the remaining episodes ST segment elevation was of shorter duration and there was no rise in pulmonary artery diastolic pressure. Pain was usually a late feature. Silent ST segment elevation occurred at rest and pulmonary artery diastolic pressure increased in all but one episode. Silent exertional ST segment depression was associated with a greater increase in pulmonary artery diastolic pressure than that seen during ST segment elevation. ST segment depression preceded or followed ST segment elevation in two episodes. The onset of ST segment elevation nearly always preceded the onset of a rise in pulmonary artery diastolic pressure. Ergometrine maleate provocation produced a rise in pulmonary artery diastolic pressure in three patients. In one there was no response to 1000 micrograms but spontaneous episodes of ST segment elevation were recorded during ambulatory monitoring. Treadmill exercise resulted in both ST segment elevation and depression with a similar haemodynamic response during both types of electrocardiographic change. When there is important coronary artery disease in two or more vessels ST segment changes may occur in different territories during treadmill exercise and during spontaneous episodes. Ambulatory pulmonary artery diastolic pressure monitoring is a useful technique for the investigation of variant angina.     

Silent myocardial ischemia in patients with variant angina

Twenty-four hour ambulatory electrocardiographic recording was performed in 56 patients with variant angina admitted to the coronary care unit in order to evaluate the incidence and pathophysiology of silent episodes of ST elevation. Of 696 episodes of ST elevation of more than 0.1 mV identified during a recording period of 141 days, 531 (76%) episodes were completely silent. The incidence of silent episodes increased as the number of total ischemic episodes per day increased. Silent ST elevation revealed a significantly shorter duration and a lower intensity than symptomatic ST elevation. However, there were wide overlaps in the duration and intensity of ST elevation between silent and symptomatic episodes. In some patients, silent and symptomatic episodes of similar duration and intensity were observed. Arrhythmias during ischemic episodes such as premature ventricular contractions, ventricular tachycardia, high grade atrioventricular block, and sinus arrest were observed in 32 of 56 patients, 57% of cases and 9% of the total episodes. Arrhythmias were more common during symptomatic episodes (29%) than during silent ones (9%, p less than 0.01), but serious arrhythmias such as ventricular tachycardia, high grade atrioventricular block and sinus arrest occurred even during silent episodes. In both silent and symptomatic episodes, the duration and intensity of ST elevation were significantly lower in ischemic episodes with arrhythmias than in those without arrhythmias. These results suggest that 1) the majority of ischemic events are silent in patients with variant angina; 2) the severity of ischemia seems to be an important factor as the cause of anginal pain, but additional factors may be involved; 3) arrhythmias were more common during sympatomatic than silent episodes.     

The contribution of ventricular tachy arrhythmias to the genesis of cardiac pain during transient myocardial ischaemia in patients with variant angina

The 24-h ambulatory electrocardiograms of 15 patients with bothvariant angina and ischaemia-related arrhythmias were analyzedto correlate cardiac pain with the following variables: site,type, duration and magnitude of ECG changes, presence and typeof arrhythmias and time of occurrence of ischaemic attacks duringthe 24-h. Apart from sublingual nitrate therapy, Holter monitoringwas performed in the Coronary Care Unit (CCU), in the drugfreestate in all patients. During a total of 79 days of monitoring,patients had 1385 ischaemic episodes, of which only 30% werepainful. The site of ischaemia did not predict the occurrenceof pain. Pain was more frequently associated with ST-segmentelevation, longer ischaemic duration, increased time to peakECG change, and greater ST-segment shift and arrhythmias. Whenthe 259 attacks in association with ventricular arrhythmiaswere compared to the arrhythmia-free episodes, they were morefrequently painful for the same duration and magnitude of ECGischaemic changes. Furthermore, the complexity of arrhythmiasincreased the probability of cardiac pain. Most ischaemic episodesoccurred at night and a decrease in the frequency of painfulepisodes (apart from those associated with arrhythmias) wasapparent. Thus, in addition to electrocardiographic severityand duration of ischaemia, the presence of ventricular arrhythmiasand the time of occurrence seem to influence pain perceptionduring ischaemia.     

Once daily felodipine in preventing ergonovine-induced myocardial ischaemia in Prinzmetal's variant angina

The efficacy of extended-release felodipine in preventing ergonovine-inducedmyocardial ischaemia was assessed in 14 patients (12 male, twofemale, aged 56±7 years) with Prinzmetal's variant angina.Four of the patients had normal coronary arteries, eight hadone-vessel and two had two-vessel disease. The ergonovine testwas performed once in basal conditions and twice 5 days afterbeginning the oral administration of felodipine 20 mg o.d.,4 and 24 h after the last administration. During a continuous6-lead ECG recording, ergonovine was injected at doses of 25,50, 100, 200, and 400 µg at 5 min intervals. Blood samplesfor felodipine plasma concentrations were drawn at the timeof the tests. The basal ergonovine test was positive in all 14 patients (sevenwith anterior and seven with inferior ST segment elevation >0•1m V) at a mean ergonovine dose of 162±138 µg. Thetest was repeated 4 h after the last felodipine administrationand was negative in 13 patients (93%), but 24 h after the lastdrug administration, eight patients (57%) had a positive testresponse (five with anterior, three with inferior ST segmentelevation) at a higher ergonovine dose than at baseline (150vs 97 µg, P=0•042). The only dtfferences betweenpatients with a negative and a positive test were the mean valuesof the left ventricular end-diastolic pressure (9•3 vs14•9 mmHg, P=0•002) and the ergonovine doses usedin the baseline tests (250 vs 97 µg, P=0•034). Themean felodipine plasma level 4 h after dosing was 18•0±12•2nmol. l^–1; 24 h post-dosing plasma concentrations weregenerally very low (<3 nmol. l^–1 in eight cases). Noacute side effects were observed during the trial. In conclusion, extended-release felodipine, given once daily,appears to be highly effective in preventing ergonovine-inducedischaemia in patients with Prinzmetal's variant angina, maintaininggood efficacy even 24 h post-dosing.     

Effect of benazepril on myocardial ischaemia in patients with chronic stable angina pectoris

The anti-ischaemic properties of benazepril, a non-sulfhydrylinhibitor of angiotensin-converting enzyme, were assessed in20 patients with chronic stable angina pectoris, by repeatedexercise tests and repeated 72-h ambulatory electrocardio-graphicmonitoring. The study was a double-blind, placebo-controlledcross-over; 11 patients received benazepril 10 mg b.i.d. andnine received 20 mg b.i.d. All patients had a positive treadmillstress test and at least three ischaemic episodes during 24h of ambulatory electrocardiographic monitoring. Benazepril at a dose of 10 mg b.i.d. did not improve the exerciseduration, the time taken to reach 1 mm ST depression. Similarfindings were observed during treatment with 20 mg b.i.d. Benazeprilat a dose of 10 mg b.i.d. was ineffective in improving ischaemicparameters during daily activities. However, among the ninepatients who received 20 mg b.i.d. the number of ischaemic episodeswas reduced from 142 to 103, and the total duration of ischaemiawas reduced from 1099 to 531 min. The number of weekly anginalattacks was reduced from 58 to 33, and the weekly sublingualnitroglycerin tablets consumption was reduced from 31 to 14.When the two doses (10 mg and 20 mg) were combined (N = 20),the number of ischaemic episodes was reduced from 314 to 260(P= 0.074), and the duration of ischaemia was reduced from 3453to 2514 min (P = 0.072).     

Lack of indication of myocardial cell damage after myocardial ischaemia in patients with severe stable angina.

To evaluate myocardial cell damage in relation to spontaneous and exercise-induced ischaemia, release of myoglobin, creatine kinase (CK) and its isoenzyme MB (CK-MB) into the serum was estimated in 10 patients with severe stable angina. All patients had a positive exercise test, significant stenosis of one or more of the main coronary arteries and more than five ischaemic attacks per week. ST-segment monitoring was performed for 36 h. During the last 24 h of that period (period A) serial blood samples were analysed for myoglobin, CK and CK-MB using sensitive assays. Three days later (period B) the patients performed an exercise test at 0815 h, with ST-segment monitoring and blood sampling carried out as described for period A. During period A, 47 ischaemic episodes (100% silent) with a total duration of 599 min were noted in four patients. Forty-seven ischaemic episodes (94% silent) with a total duration of 804 min, were observed in seven patients during period B. Release of myoglobin, CK, and CK-MB did not increase in relation either to spontaneous or exercise-induced ischaemia. Thus even frequent and prolonged episodes of transient myocardial ischaemia (symptomatic or asymptomatic) in patients with severe stable angina pectoris does not seem to cause irreversible myocardial damage.     

Acute heavy alcohol intake increases silent myocardial ischaemia in patients with stable angina pectoris.

OBJECTIVE: To evaluate the effect of acute alcohol ingestion on myocardial ischaemia in patients with coronary heart disease and stable angina. DESIGN: Randomised crossover study using fruit juice with and without ethanol. SETTING: Division of cardiology in a university hospital. PATIENTS: 20 patients with stable exertional angina and > or = 50% luminal diameter narrowing of at least one major coronary artery. INTERVENTIONS: Each patient was studied on two separate days, once after administration of 1.25 g of ethanol per kilogram of body weight diluted to 15% in juice, and once after an equivalent volume of juice; both tests were in the evening and lasted 90 minutes. The patients were scheduled to have 8 periods of walking for 10 min according to a time table. An ambulatory electrocardiogram and the occurrence of anginal attacks were recorded and blood pressure and blood ethanol concentration were measured until the next morning. RESULTS: The blood ethanol concentration (mean (SD)) rose to 28.8 mmol/l (1.3 (0.4)/1000). Alcohol raised the systolic blood pressure from 132 (16) to 141 (14) mm Hg (P < 0.05 compared with juice). The mean heart rate increased from 57 (7) to 64 (8) beats/min (P < 0.05) for 13 hours after ethanol ingestion compared with juice. The total duration of ischaemia during the ethanol test was 3.5 (median, range 0-80) min, compared with 0 (range 0-67) min for the juice test (P < 0.05). The difference resulted mainly from more silent ischaemia after ethanol ingestion (2.3 (0-80) v 0 (0-67) min; P < 0.05). The ST segment depression time integral increased during the ethanol test (4.4 (0-170) mm x min) relative to that during the juice test (0 (0-103) mm x min; P < 0.01) and especially during the following 13 hours after alcohol (3.5 (0-123) mm x min) compared with juice (0 (0-67) mm x min; P < 0.005). There were no changes in the number, duration, or ST segment depression time integral of the episodes of symptomatic angina, indicating that ethanol augmented the appearance of silent ischaemia. CONCLUSIONS: Acute heavy ethanol drinking aggravates myocardial ischaemia in patients with stable angina pectoris.     

Reflex cardiovascular response to acute myocardial ischaemia

The usual cardiovascular response to acute myocardial ischaemia is either pressor, characterised by tachycardia and hypertension or depressor, manifested by bradycardia, hypotension and systemic vasodilatation. We studied the incidence of ectopic arrhythmias, the changes in heart rate, in left ventricular pressure and dP/dt and the changes in plasma level of free fatty acids. Acute anterior ischaemia increased the heart rate, left ventricular dP/dtmax and plasma level of free fatty acids and developed frequent ventricular ectopic arrhythmias. Previous injection of propranolol prevented the elevation of plasma free fatty acids. Acute inferior ischaemia produced a slight decrease in heart rate, no change in plasma level of free fatty acids and a significant decrease in left ventricular dP/dtmax. The experimental model allowed us to study the response to acute myocardial ischaemia in conscious dogs; the results obtained point to a preferential location of the pressor and depressor receptors respectively to the anterior and inferior surfaces of the left ventricle.     

Detection, frequency and clinical significance of silent myocardial ischaemia in patients with chronic stable angina

Forty-two patients (mean age 50 years) with chronic stable angina pectoris were subjected to exercise treadmill testing, coronary arteriography and left ventricular cineangiography. Twenty-one of these patients also underwent Holter monitoring for 24 hours. On exercise treadmill testing, angina was the endpoint in 24 (57%), while 18 (43%) developed significant ST segment depression without symptoms. Holter monitoring in 27 patients revealed a total of 248 episodes of myocardial ischaemia of which 210 (84%) were asymptomatic. ST segment depression at 80 mS from J point varied from 1 to 4 mm, and the average duration of ischaemic episodes during Holter monitoring was 9 minutes (range 30 seconds to 1 hour). Heart rate during the ischaemic episodes varied between 65-85 beats/minute. Coronary angiography revealed triple vessel disease in 22 (52%) and double vessel and single vessel involvement in 10 (24%) each. Left ventricular ejection fraction was less than 50% in only 3 (7%) patients. Thus silent myocardial ischaemia is detected frequently in patients with angina pectoris. It occurs during routine daily activity, and on exercise. Heart rate at which silent myocardial ischaemia occurs is much less during daily activity as compared to exercise induced ischaemia. All patients who were detected to have silent myocardial ischaemia had significant coronary artery disease. These findings are of prognostic and therapeutic value.     

女性变异型心绞痛患者的临床特点

目的探讨变异型心绞痛中女性患者的临床特点及冠状动脉造影表现。方法回顾性分析185例接受冠状动脉造影的变异型心绞痛患者的临床资料,比较女性与男性在危险因素、临床表现、冠状动脉造影等方面的异同点。结果变异型心绞痛患者中女性所占比例较低(13.0%),与男性患者相比,吸烟者比例较少(12.5%VS81.4%,P0.001),冠心病家族史比例较高(33.3%VS11.2%,P0.01),其它危险因素与男性相比无明显差异,女性患者更易发生室颤(12.5%VS2.5%,P0.05)。结论国内变异型心绞痛患者中女性吸烟者比例低于男性,冠心病家族史及室颤发生率高于男性,其它临床表现及冠状动脉造影特点与男性相似。     

Left ventricular performance and related haemodynamic changes in Prinzmetal's variant angina pectoris

Attacks of Prinzmetal's variant form of angina pectoris are spontaneous, recur cyclically, and present unequivocal electrocardiographic alterations: they are ideal for a detailed haemodynamic study.Four patients with this form of angina were investigated. In each of them episodes occurred of electrocardiographic abnormalities either accompanied or unaccompanied by pain. During the same session, the cardiogram, heart rate, arterial pressure, and right atrial pressure were continuously recorded during periods ranging from 5 to 7 hours in each patient. Cardiac output was measured at selected times. Left ventricular ejection time, isovolumic contraction time, mean rate of isovolumic pressure development, and mean systolic ejection rate were also determined.In the 38 recorded anginal episodes, no circulatory change preceded the cardiographic modifications. From the onset of the electrocardiographic abnormalities to the beginning of their reversion, the following circulatory events were observed: (1) obvious reduction of cardiac output; (2) arterial hypotension; (3) lengthening of isovolumic contraction time and mean rate of isovolumic pressure development; (5) reduction of mean systolic ejection rate. It is concluded: (1) that no circulatory factor interfering with work or oxygen consumption of the heart is responsible for eliciting these anginal episodes; (2) that conspicuous left ventricular impairment occurs during the increasing and steady period of the electrocardiographic abnormalities.As the electrocardiogram started reverting to the pre-attack aspect, cardiac performance rapidly improved and, after a ;supernormal' phase, returned in about 2 minutes to basal levels. It is possible that this phase is dependent on a temporary sympathetic compensatory mechanism.No significant qualitative differences were detected between the circulatory pattern of various anginal episodes. The difference was mainly quantitative and the magnitude of the haemodynamic changes correlated well with the degree of the electrocardiographic abnormalities. Pain, when present, seemed just a concomitant symptom not significantly interfering with the circulatory changes associated with the episodes of this form of angina pectoris.     

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.     

Time-related decrease in sensitivity to ergonovine in patients with variant angina

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.     

Ischaemic threshold and haemodynamic changes during angina at rest in patients with unstable angina

To examine whether increases in heart rate might be a commontrigger of angina at rest, changes in heart rate, blood pressureand rate-pressure product during pain were compared with theischaemic threshold (heart rate with ST segment shift >=1 mm), determined by atrial pacing, in 272 patients with unstableangina. During an average of 5.9±5.2 episodes of angina,heart rate was comparable to control values (77.0±14.5vs 75.2±11.5, beats. min^–1, ns) and significantlylower than the ischaemic threshold (147.9±22.9, P <0.00001).The rate-pressure product was also lower (955±183 vs2033±369, x 10, P <0.00001). Heart rate during restangina was lower than the ischaemic threshold even when we consideredonly patients with ST depression during pain (n: 71, 81.4±16.0 vs 132.8±21.4, P<0.00001), those with three-vesseldisease (n: 43, 79.9±15.9 vs 136.9±22.0, P <0.00001), or those with a low ischaemic threshold (= <130beats. min, n: 78, 77.0±14.9 vs 118.3±10.7, P<0.00001).In 154 patients in whom a second pacing test was performed theresponse was reproducible in 137 cases (89%). Thus, heart rate barely changes during angina at rest in patientswith unstable angina and is consistently much lower than theischaemic threshold. These findings support the concept thatincreases in heart rate are an unlikely trigger of ischaemiaat rest, even in patients with markedly reduced coronary reserve.     

Left ventricular performance and related haemodynamic changes in Prinzmetal's variant angina pectoris

Attacks of Prinzmetal's variant form of angina pectoris are spontaneous, recur cyclically, and present unequivocal electrocardiographic alterations: they are ideal for a detailed haemodynamic study.     

Comparison of plasma serotonin levels in patients with variant angina pectoris versus healed myocardial infarction

Patients with variant angina pectoris showed greater serotonin plasma levels than did control subjects and patients with healed myocardial infarction. The levels also tended to be greater in those with >1 episode/month than in those with fewer episodes. Moreover, patients with variant angina pectoris also had greater levels of nitrite and nitrate plasma levels than did control subjects or patients with healed myocardial infarction, partly, perhaps, as a compensatory mechanism.     

Circulating T-lymphocyte activation in patients with variant angina

BACKGROUND: Both experimental and pathological studies suggest that immune response and inflammation may play an important role in the pathogenesis of coronary spasm. DESIGN: To elucidate the role of systemic immune and inflammatory responses in the pathogenesis of coronary spasm, we studied circulating T-lymphocyte activation in variant angina patients (VAPs), stable effort angina patients (EAPs) and in control participants. METHODS: Twenty documented VAPs, 13 EAPs and 20 control participants were studied. To evaluate T-lymphocyte activation, T-lymphocyte surface antigen expression, including CD3, CD4, CD8 and HLA-DR, was measured by two-colour flow cytometric analysis. Serum-soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were also measured by enzyme-linked immunosorbent assay. We restudied 10 of the VAPs to investigate the relationship between the disease activity of variant angina and T-lymphocyte activation. RESULTS: The percentage of CD3+/DR+ T-lymphocytes in VAPs (14.8%) was significantly higher than in EAPs (10.7%, P < 0.05) and control participants (9.7%, P < 0.005); however, levels of sIL-2R were the same among the three groups. Levels of CRP were within normal range in all VAPs. The percentage of CD8+/DR+ T-lymphocytes was significantly higher in VAPs (9.5%, P < 0.005) than in EAPs (5.5%) and control participants (5.9%), whereas the percentage of CD4+/DR+ T-lymphocytes was similar among the three groups. The percentage of activated T-lymphocytes in VAPs was unchanged during the follow-up period (mean intervals, 10 months). CONCLUSIONS: These results indicate that the chronic activation of T-lymphocytes, especially CD8+ T-lymphocytes, may be involved in the pathogenesis of coronary spasm.     

Rebound myocardial ischaemia following abrupt interruption of intravenous nitroglycerin infusion in patients with unstable angina at rest

Isolated observations prompted a prospective study of the possible occurrence of myocardial ischaemia following abrupt discontinuation of intravenous infusion of nitroglycerin in 46 consecutive patients with unstable angina. In 26 (55%, group 1), but not the remainder (45%, group 2), cessation of nitroglycerin produced in 10.3 +/- 5.8 (mean +/- SD) minutes ECG changes comparable with those of spontaneous angina without significant changes in heart rate and blood pressure. Reproducible results were observed in 18/20 patients in whom the test was repeated. In four patients with two positive tests, a third test failed to elicit ischaemia 15 min after sublingual administration of 5 mg isosorbide dinitrate. An ergonovine test performed in four other patients with a positive test produced similar ECG changes. Thus, acute interruption of intravenous nitroglycerin infusion in patients with unstable angina is often associated with acute myocardial ischaemia. The lack of preceding changes in heart rate and blood pressure and the similarities with the spontaneous episodes and with those produced by ergonovine, strongly suggest a rebound coronary vasoconstrictive phenomenon as the underlying mechanism.     

Potential deleterious haemodynamic effects of glyceryl trinitrate on myocardial ischaemia in man

The potential adverse effects of glyceryl trinitrate on myocardial ischaemia were studied using low and high dose infusions in 10 patients with coronary heart disease. Cardiac venous flow was measured by the thermodilution technique and blood was sampled for metabolic studies. Angina pectoris was provoked by atrial pacing before drug infusion and the same heart rate was regained with low and high doses of glyceryl trinitrate. Both doses reduced myocardial ischaemia equally. The low dose of glyceryl trinitrate reduced mean systolic aortic pressure from 145(23) to 128(23) mm Hg and the high dose further to 103(9) mm Hg. Myocardial oxygen uptake decreased owing to a combined reduction in preload and afterload with the low dose and was substantially more reduced with the high dose owing to a further afterload reduction. Transmural perfusion gradient did not change with the low dose of glyceryl trinitrate but fell significantly with the high dose. This fall in myocardial perfusion probably accounts for the lack of further reduction in ischaemia with the high dose. Thus the adverse effects of glyceryl trinitrate infusion are small and do not increase myocardial ischaemia.