Frequency and significance of early postoperative silent myocardial ischemia in patients having peripheral vascular surgery

Coronary disease causes the majority of perioperative complications after peripheral vascular surgery. Twenty-four patients with stable coronary disease undergoing peripheral revascularization were studied using continuous electrocardiographic monitoring to determine the incidence of perioperative asymptomatic myocardial ischemia and its relation to postoperative clinical ischemic events. Patients were monitored preoperatively (17 +/- 1 hours), intraoperatively and postoperatively (29 +/- 2 hours) using 4-channel calibrated amplitude-modulated units. Fifteen patients (63%) had early postoperative silent ischemia; 3 also had preoperative silent ischemia and 5 intraoperative transient ischemia. Patients with and without silent ischemia had similar clinical characteristics, perioperative antianginal medications and postoperative episodes of hemodynamic instability. However, 8 of 15 patients (53%) with silent ischemia had postoperative clinical ischemic events (2 had myocardial infarction, 2 had new congestive heart failure and 4 had new rest angina), versus only 1 of 9 patients (11%) without silent ischemia who had angina (p less than 0.05). Early postoperative silent myocardial ischemia occurs frequently after vascular surgery and is associated with postoperative clinical ischemic events.     

Stress myocardial scintigraphy in coronary artery disease: its clinical significance]

To evaluate the clinical significance of asymptomatic ischemic heart disease, exercise electrocardiography and stress myocardial scintigraphy were performed. These were correlated with symptoms during exercise tests and histories of myocardial infarction (MI). The study subjects consisted of 70 patients with coronary artery disease, including 34 with MI, and 36 without MI but with angina pectoris. Stress tests were performed using bicycle ergometer under electrocardiographic monitoring throughout the test. Transient myocardial ischemia was confirmed by perfusion defects on thallium myocardial imaging demonstrated immediately after exercise, but not 3 hours after the stress test. Asymptomatic ST depression was observed in 18 of 34 patients with MI (53%) and in 21 of the 36 patients with angina (58%); however, transient myocardial perfusion defects were confirmed in 61% of the patients with MI (11 of 18 patients), but in only 33% of those with angina (7 of 21 patients). The difference was statistically significant (p less than 0.05). It was suggested that there are some differences in the clinical significance of asymptomatic ST depression between the patients with MI and those without MI but with angina pectoris.     

Diagnosis of chest pain with foregut symptoms in Chinese patients

AIM： To evaluate the diagnosis of chest pain with foregut symptoms in Chinese patients.
METHODS： Esophageal manometric studies, 24-h introesophageal pH monitoring and 24-h electrocardiograms （Holter electrocardiography） were performed in 61 patients with chest pain.
RESULTS： Thirty-nine patients were diagnosed with non-specific esophageal motility disorders （29 patients with abnormal gastroesophageal reflux and eight patients with myocardial ischemia）. Five patients had diffuse spasm of the esophagus plus abnormal gastroesophageal reflux （two patients had concomitant myocardial ischemia）, and one patient was diagnosed with nutcracker esophagus.
CONCLUSION： The esophageal manometric studies, 24-h intra-esophageal pH monitoring and Holter electrocardiography are significant for the differential diagnosis of chest pain, particularly in patients with foregut symptoms. In cases of esophageal motility disorders, pathological gastroesophageal reflux may be a major cause of chest pain with non-specific esophageal motility disorders. Spasm of the esophageal smooth muscle might affect the heart-coronary smooth muscle, leading to myocardial ischemia.     

Comparative effects of nitroglycerin, nifedipine and metoprolol on regional left ventricular function in patients with one-vessel coronary disease

To compare acute effects of nitroglycerin (0.8 mg sublingually), nifedipine (5 ng/kg/min i.v.) and metoprolol (0.15 mg/kg i.v.) on normal, ischemic and scarred myocardial segments in man, we performed simultaneous hemodynamic and radionuclide measurements of left ventricular functions. Sixteen patients with isolated left anterior descending (LAD) disease were studied at rest and during exercise. Nine patients had angina and exercise-induced ischemia (LAD stenosis) and seven patients had previous transmural myocardial infarction and no ischemic changes during thallium imaging (LAD occlusion). The effects of the drugs on regional ejection fraction of the involved anteroseptal region and the normal posterolateral area were compared. Global ejection fraction at rest did not change after nitroglycerin, increased after nifedipine and decreased after metoprolol. In patients with ischemia, the exercise ejection fraction improved after all drugs due to increased regional ejection fraction in ischemic segments: i.e., a regional antiischemic effect evidenced by improved regional function could be demonstrated with all three agents. Regional ejection fraction increased from 35.8 +/- 19.5% to 66.2 +/- 15.2% (+/- SD) after nitroglycerin (p less than 0.001), to 61.7 +/- 8.7% after nifedipine (p less than 0.001), and to 48.4 +/- 7.0% after metoprolol (p less than 0.01). In regions of myocardial scar, regional ejection fraction was not changed after any drug. In normal areas, regional ejection fraction remained unchanged after nitroglycerin and nifedipine, but decreased after metoprolol. Despite similar antiischemic effects of all three drugs, underlying hemodynamic mechanisms were quite different and may provide a rationale for combined forms of treatment. These results may help to select optimal drug combinations to improve myocardial performance in patients with chronic ischemic heart disease.     

三种无创检查方法诊断冠心病无症状心肌缺血的价值

本文以冠状动脉造影作为诊断冠心病的标准,对临床确诊为冠心病的患者进行运动心电图、运动~(201)铊心肌显像和动态心电图检查。结果证明:这三种方法诊断冠心病心肌缺血的敏感性在心绞痛组分别为85.9%、88.7%和58.4%,心肌梗塞组分别为77.2%、91.1%和53.4%,特异性分别为77%、90%和73%。检查中无症状心肌缺血发生率在心绞痛组分别为52.9%、56.3%和58.4%,心肌梗塞组分别为58.7%、75.3%和53.4%。表明这三种方法对诊断冠心病无症状心肌缺血有较高价值。     

Therapeutic effects of pindolol and nifedipine in patients with stable angina pectoris and asymptomatic resting ischemia.

A single blind randomized parallel study designed to assess the anti-anginal efficacy of pindolol and nifedipine was carried out in 42 ambulatory coronary patients with stable angina pectoris. Drug efficacy was assessed in terms of (a) pain, (b) frequency of anginal episodes, (c) nitroglycerin consumption, (d) exercise tolerance and (e) ST-segment changes. The effect of these drugs on asymptomatic resting myocardial ischemia was also assessed by means of 24-h dynamic electrocardiography (DCG). All patients were checked at weekly intervals. At the end of a 4-wk placebo period, the patients were randomly assigned either to the pindolol or nifedipine group. The treatment lasted for 45 days. During the placebo period, ischemic ECG changes and symptoms of coronary insufficiency were detected in all patients. Furthermore, 12 out of 42 patients had asymptomatic myocardial ischemia at rest. One patient from each group was dropped because of tolerance. At the end of the 45-day study, pindolol and nifedipine were equi-effective on spontaneous and effort-related angina. There were, however, some differences: increased tolerance to exercise appeared earlier with pindolol: the pindolol group showed a slightly reduced while the nifedipine group showed a slightly increased heart rate. Furthermore, nifedipine reduced or eliminated asymptomatic myocardial ischemia in 6 out of 7 patients while only 1 out of 5 improved in the pindolol group.     

Diagnostic and prognostic value of ambulatory ECG (Holter) monitoring in patients with coronary heart disease: a review

Silent ischemia, the most common expression of atherosclerotic heart disease, affects approximately 30–50% of patients during their activities of daily living. The present review provides a comprehensive and practical summary of current knowledge on perioperative myocardial ischemia through MEDLINE searches up to June 2005, using keywords including “silent ischemia,” “transient ischemia,” and “Holter monitoring.” Holter monitoring (i.e., continuous ambulatory ST-segment monitoring) is an effective tool for assessing the frequency and duration of silent transient myocardial ischemia, particularly in patients who are post-acute myocardial infarction (MI), those with acute coronary syndromes (ACS), and in patients in the acute post-operative period. Holter monitoring allows for further risk stratification of patients who have a positive exercise ECG by collecting long-term ECG data on ischemic and arrhythmic events while patients perform routine activities. Both the presence and increased duration of transient ischemia as detected by continuous ST-segment Holter monitoring are associated with increased rates of coronary events and mortality. Holter monitoring may aid in the identification of patients and subgroups of patients with ACS who may derive the greatest benefit from antiplatelet and antithrombotic therapy. Indeed, many ongoing and upcoming trials of pharmacotherapy include ischemia on Holter monitoring as an endpoint.     

Preoperative silent myocardial ischemia. Has it prognostic significance?

We studied the prognostic significance of preoperative silent myocardial ischemia in patients undergoing coronary artery bypass grafting (CABG). Nonfatal and fatal perioperative myocardial infarction were regarded as prognostically important endpoints. Ninety-five patients (9 women) with stable-effort angina pectoris were studied during their hospital stay in the surgery ward before CABG. Silent ischemia was detected using Holter monitoring; all patients had Holter monitoring 76 +/- 9 h before surgery using Marguette Laser Holter and Cardiodata Prodigy systems. Two-channel electrocardiographic recordings were used which included CM5 and a modified inferior lead. Effort was taken to avoid leads with pathological Q waves and resting ST segment abnormalities. The mean duration of the monitoring was 27.9 +/- 11.3 h. Three patients (3.2%) had angina pectoris during these observations, 1 of them with significant ST depression. Silent ST depression was found in 12 patients (12.6%). Twelve patients (12.6%) had perioperative myocardial infarction. Perioperative myocardial infarction was more common in patients with silent ischemia: 4/12 vs. 8/83; chi 2 = 4.48955, p = 0.0341. Our results suggest that Holter monitoring identifies a group of patients with a higher probability of perioperative myocardial infarction. In the future, it may be possible to study different methods to prevent this surgical complication.     

Coronary artery disease and upper abdominal surgery: impact of anesthesia on perioperative myocardial ischemia

BACKGROUND/AIMS: Some papers claim that epidural anesthesia and analgesia lowers the incidence of perioperative ischemic events and may have a favorable effect on perioperative cardiac morbidity and mortality. We studied the effect of epidural anesthesia and analgesia on perioperative myocardial ischemia, in a group of patients with known coronary artery disease, who underwent upper abdominal surgery. METHODOLOGY: Fifty patients with coronary artery disease scheduled for elective upper abdominal surgery, were randomized to two study groups: Group A (n = 25) received general anesthesia plus epidural anesthesia and analgesia, while group B (n = 25) received general anesthesia with postoperative i.v. analgesia. All patients had Holter ECG recording from 24 hours preoperatively until 48 hours postoperatively. RESULTS: Preoperatively, no significant differences in ischemic burden were observed between the two groups. Intraoperatively, significantly fewer patients in group A had ischemic episodes (8% vs. 36%, p < 0.05) and there was also a significant reduction in the number of ischemic episodes and in mean duration of ischemia per hour of monitoring. Similar findings were observed in the first 24 hours postoperatively but not later on, with 12% of patients in group A having ischemic episodes vs. 60% in group B (p < 0.01). Group A had significantly better pain control postoperatively. Only one third of ischemic episodes were related to hemodynamic abnormality, and most of them were clinically silent. No serious cardiac morbidity or mortality was observed during the period of monitoring. CONCLUSIONS: Epidural anesthesia and analgesia reduces intraoperative and early postoperative ischemia in patients with known coronary artery disease undergoing upper abdominal surgery.     

Perioperative myocardial infarction after coronary artery bypass surgery. Clinical significance and approach to risk stratification

The clinical significance of perioperative myocardial infarction (MI) after coronary artery bypass surgery is not known. Therefore, strategies for the risk stratification of these patients do not exist. This study was undertaken to define the effect of perioperative MI on prognosis after discharge from the hospital and to develop an approach to the risk stratification of these patients. Fifty-nine patients with and 115 patients without perioperative MI were observed for 30 months for the development of cardiac events (death, nonfatal MI, and admission to hospital for unstable angina or congestive heart failure). Patients with perioperative MI were significantly more likely than patients without to have a cardiac event (31% versus 12%, p less than 0.01) and multiple events (19% versus 1%, p less than 0.001). Cox regression analysis identified two independent predictors of cardiac events other than perioperative MI (relative risk, 2.7): inadequate revascularization (relative risk, 3.5) and depressed (less than 40%) postoperative ejection fraction (EF) (relative risk, 2.1). Event-free survival rate of patients with perioperative MI varied markedly depending on the number of other negative prognostic variables present. Patients with perioperative MI who were adequately revascularized and had a postoperative EF greater than 40% had an event-free survival rate similar to patients without a perioperative MI (92% versus 87%, p = NS). Patients with perioperative MI who were inadequately revascularized and had depressed postoperative EF had an event-free survival rate of 13% (p less than 0.001 versus all other subsets). Event-free survival rate was intermediate (68%) in patients with perioperative MI and with only one of the other two variables (p less than 0.001 versus other subsets). In conclusion, perioperative MI adversely affects prognosis. Patients can be stratified into low, high, and intermediate risk subsets based on a simple assessment of the adequacy of revascularization and a determination of residual left ventricular function.     

老年高血压左室肥厚患者的室性心律失常与心肌缺血

目的　了解老年原发性高血压左室肥厚患者的室性心律失常、心肌缺血的特点及两者的关系。方法　 90例老年 (≥ 6 0岁 )高血压患者经超声心动图测定左室质量指数 (LVMI) ,分为左室肥厚 (A组 )和非左室肥厚 (B组 )。经2 4h动态心电图测定 2 4h室性早搏总数 (VPCs)、Lown’s分级、ST段压低程度、持续时间及 2 4h发作次数。结果　A组室性心律失常的发生率明显增加 (P <0 .0 5 ) ,室性早搏 :75 %比 5 4% ,Lown’s 3～ 4级 :2 6 %比 4%。A组发作性ST段压低的发生率高 ,缺血持续时间长 (5 0 %比 15 % ,P <0 .0 5 )。所有缺血发作均为无症状性。室性心律失常与心肌缺血的昼夜节律变化基本相同。结论　无冠心病临床证据的老年原发性高血压左室肥厚患者的室性心律失常及心肌缺血的发生率增加 ,两者的昼夜节律变化基本相同     

Role of perceptive threshold in myocardial infarction patients without previous angina

The purpose of this study is to clarify the mechanism of sudden onset myocardial infarction (MI) without previous angina and the relationship of MI without previous angina to the mechanism of onset of postinfarction asymptomatic myocardial ischemia. The mean initial time of ischemic pain in the upper arm under the tourniquet test was significantly prolonged in the MI patients without previous angina, compared with that for the MI patients with previous angina and normal control subjects, although there are some overlapping cases (74 +/- 37 sec versus 52 +/- 20 sec (p less than 0.01), and versus 56 +/- 15 sec (p less than 0.05), respectively). The tolerance time for ischemic pain also was similarly prolonged. There was no significant difference between the groups of MI patients (with and without previous angina) with respect to age, frequency of complications of diabetes mellitus, severity of coronary artery lesions or site of MI. The incidence of post-infarction myocardial ischemia was 50% for the previous angina group and 39.5% for the group without previous angina, but the frequency of asymptomatic ischemia was significantly higher in patients without previous angina, at 66.7%, than in those with previous angina, 32.3% (p less than 0.05). These results suggest that there is a close relationship between the mechanism of MI with sudden onset and that of asymptomatic myocardial ischemia during the pre- and post-infarction periods in patients with low sensitivity to pain.     

Dobutamine stress thallium myocardial scintigraphy compared with two-dimensional echocardiography

To assess the relationships among wall motion abnormality, myocardial ischemia and ST change in patients with myocardial infarction (MI), dobutamine stress thallium (Tl) myocardial scintigraphy, and two-dimensional echocardiography (2DE) and electrocardiography were simultaneously performed. Sixteen patients with anterior MI who underwent 2DE and ECG were studied at baseline and during dobutamine infusion with incremental doses of two to 40 micrograms/kg/min. The stress endpoints were chest pain, significant ST changes, tachycardia (greater than or equal to 110/min), and complicated arrhythmias. At the maximal tolerable dose of dobutamine, Tl scintigraphy was completed, and then repeated again four hours later. Left ventricular wall motion was evaluated using superimposed wall tracings of the configuration on 2DE, and was expressed as regional % area changes. Myocardial ischemia was quantified by SPECT and measured as regional % Tl uptake. Dobutamine stress testing was well tolerated by all patients, and no complications occurred. Hemodynamic changes included: heart rate increased from 61 +/- 9 to 113 +/- 11 beats/min, left ventricular end-diastolic volume (2DE) decreased from 93 +/- 27 to 59 +/- 33 ml, and mean blood pressure and ejection fraction were unchanged. In 11 of the 16 patients, redistributions on planar and SPECT images were observed. Although redistributions were observed in the areas adjacent to infarcts in patients with significant ST elevation in V3, additional wall motion abnormalities were not observed. The shape of the ST elevation had no relation to myocardial ischemia. In some cases, wall motion abnormality can be improved in spite of ischemia. Thus, this new combined method is useful for evaluating the relationship between ischemia and wall motion dynamics.     

Effect of intravenous isosorbide dinitrate versus nitroglycerin on elevated pulmonary arterial wedge pressure during acute myocardial infarction

To compare the acute and sustained effect of intravenous isosorbide dinitrate to intravenous nitroglycerin in patients with acute myocardial infarction and elevated pulmonary artery wedge pressure, 111 patients were randomized and studied within 96 hours of admission to the coronary care unit. All patients had a pulmonary artery wedge pressure greater than or equal to 10 mm Hg and received either isosorbide dinitrate (74 patients) or nitroglycerin (37 patients) for 24 to 48 hours. Blood pressure, heart rate, pulmonary artery wedge pressure, cardiac output, medication dose in micrograms per minute and retitration episodes were compared at baseline and at 6, 12, 18 and 24 hours. Both drugs significantly (p less than 0.05) lowered pulmonary artery wedge pressure and blood pressure and increased cardiac output. Isosorbide dinitrate required fewer retitration episodes and less increases in dosage than nitroglycerin at 24 hours. In the patient with acute myocardial infarction complicated by high pulmonary artery wedge pressure who requires intravenous nitrates for 24 hours, isosorbide dinitrate may offer the benefit of a more stable hemodynamic effect.     

Silent myocardial ischemia as a potential link between lack of premonitoring symptoms and increased risk of cardiac arrest during physical stress

The risk of cardiac arrest is increased during strenuous physical exercise in patients with stable coronary artery disease (CAD). Because premonitoring symptoms are rarely observed, silent myocardial ischemia may represent the pathophysiological basis for the induction of malignant ventricular arrhythmias. Holter monitoring was, therefore, performed in 40 consecutive patients entering a randomized intervention trial on progression of CAD. In 20 of 21 participants (95%) in the intervention program greater than or equal to 1 episode of silent myocardial ischemia was observed during the initial training session. The mean duration of silent myocardial ischemia per patient was 25 +/- 13 min/hr of training session. During normal daily activity only 5 patients (24%) experienced greater than or equal to 1 episode of silent myocardial ischemia (p less than 0.001) yielding a mean duration of 0.6 +/- 1.3 minutes of silent myocardial ischemia/hr of ordinary activity per patient (p less than 0.001 vs training session). During a control period of 24 hours without exercise training the incidence (33%) and mean duration of silent myocardial ischemia (0.8 +/- 2.1 min/hr/patient) were similar to those during normal daily activity on the day of the training session. During the training session the occurrence of frequent or repetitive ventricular arrhythmias was related to 10 silent myocardial ischemia episodes detected in 5 patients. During normal daily activity in 1 patient only was the onset of malignant ventricular arrhythmias associated with silent myocardial ischemia (p less than 0.05). Conditions and results of the Holter studies in the control group patients were comparable to those of the patients in the intervention group on the day without physical exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of nitrates in acute myocardial infarction.

In patients with acute myocardial infarction, intravenous nitroglycerin lowers left ventricular filling pressure and systemic vascular resistance. At lower infusion rates (less than 50 micrograms/min) nitroglycerin is principally a venodilator, whereas at higher infusion rates more balanced venous and arterial dilating effects are seen. Patients with left ventricular failure demonstrate increased or maintained stroke volumes, whereas patients without failure show a decrease in stroke volume. All hemodynamic subgroups show a decrease in left ventricular filling pressures and a reduction in electrocardiographic evidence of regional myocardial ischemia. Longer-term infusions (24-48 hours) have been shown to result in myocardial preservation, as assessed by global and regional left ventricular function and laboratory indices of infarct size. Comparison of intravenous nitroglycerin and sodium nitroprusside reveals increased intercoronary collateral flow with nitroglycerin, in contrast to a decrease with nitroprusside, compatible with a "coronary steal." Short-term administration of intravenous nitroglycerin with or without chronic administration of long-acting nitrates have been found both to reduce short-term mortality and to have long-term beneficial effects on left ventricular remodeling in patients with anterior transmural infarctions. Current clinical practice would utilize intravenous nitroglycerin as initial therapy for patients receiving intravenous thrombolytic therapy and/or acute percutaneous transluminal coronary angioplasty within 4-6 hours of the onset of symptoms of acute myocardial infarction, in order to optimize intercoronary collateral flow until reperfusion can be accomplished. Patients reaching the hospital greater than 6 hours but less than 14 hours after symptom onset can still benefit from intravenous nitroglycerin for 24-48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cutaneous nitroglycerin patches on coronary artery diameter: issues concerning development of tolerance

The coronary dilative and systemic responses to graded doses of intracoronary nitroglycerin were studied in 53 patients undergoing diagnostic coronary arteriography, 43 of whom had received a cutaneous nitroglycerin patch. During coronary arteriography, graded doses of 50, 100 and 200 micrograms of intracoronary nitroglycerin were given 5 min apart. An arteriogram and hemodynamic measurements were obtained after each dose. In the control group (n = 10) cumulative intracoronary nitroglycerin doses of 50, 150 and 350 micrograms caused an increase in coronary diameter in the left anterior descending artery of 20 +/- 4%, 21 +/- 3% and 22 +/- 7%, respectively, and in the circumflex artery of 18 +/- 6%, 23 +/- 8% and 18 +/- 5% (p less than 0.01 versus values in untreated group). In Group 1 (15 patients given a 5 mg/24 h nitroglycerin patch 2 to 12 h before coronary arteriography), the same intracoronary nitroglycerin doses increased the left anterior descending artery diameter by 6 +/- 2%, 7 +/- 2% and 7 +/- 2%, respectively, and the circumflex artery diameter by 3 +/- 2%, 3 +/- 2% and 1 +/- 3%. All values were statistically different from control (p less than 0.05). An even more pronounced blunting (p less than 0.01) of the coronary dilative response was observed in Group 2 (14 patients given a 15 mg/24 h nitroglycerin patch 2 to 12 h before arteriography).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intracoronary nifedipine on coronary bloodflow and myocardial metabolism during pacing-induced ischemia

The effects of intracoronary nifedipine on coronary bloodflow, its regional distribution, myocardial oxygen consumption and lactate metabolism during pacing-induced angina were evaluated in 15 subjects. These responses were directly compared to 10 subjects who received an alcohol-based control solvent. Myocardial bloodflow was measured by thermodilution, with changes in regional coronary flow assessed using a dual radiolabelled (technetium-99m and indium-111) intracoronary microsphere technique and single photon emission tomography. Neither intracoronary nifedipine (100 micrograms) or the control solvent produced changes in systemic arterial pressure (nifedipine -2 mmHg and control +2 mmHg, both not significant). Intracoronary nifedipine markedly increased left ventricular end diastolic pressure (pre-nifedipine 13.0 mmHg versus post nifedipine 20.1, P less than 0.05), while increasing total coronary sinus bloodflow (pre-nifedipine 134 mL/min versus post nifedipine 189, P less than 0.05): Regional coronary bloodflow increased in all myocardial segments, regardless of the severity of coronary stenosis (64 to 132% baseline, all P less than 0.05). In addition, intracoronary nifedipine increased myocardial oxygen consumption (pre-nifedipine 12.3 mL/min versus post nifedipine 15.7, P less than 0.05), with a trend towards improved lactate extraction (pre-nifedipine 0.24 mg/mL versus post nifedipine 0.12, not significant). Although decreased ventricular afterload (left ventricular systolic wall stress) may contribute to nifedipine's antianginal properties, a primary increase in regional coronary bloodflow also appears to be an important factor in the alleviation of myocardial ischemia.     

Dissociation of exercise tolerance and total myocardial ischemic burden in chronic stable angina pectoris

Exercise treadmill tests and ambulatory monitoring were used in a double-blind, placebo-controlled, double-dummy crossover comparison of nifedipine (10 mg, 3 times daily) and transdermal nitroglycerin (15 mg). All patients (n = 20) had chronic stable angina with symptomatic and silent events. All patients had 3 episodes of angina/week and 3 episodes of ischemia/24 hr. The protocol was made up of 2 weeks of placebo followed by 2 weeks of active drug, then crossed over for 2 weeks of placebo followed by the other active drug. At the end of each 2-week period, patients had ambulatory monitoring and exercise treadmill testing. All ambulatory monitoring reports were read blind and entered into an independent data base. The results were the following: on transdermal nitroglycerin, the duration of ischemia decreased by 57% from 140 min/24 hr to 60 min/24 hr (p = 0.0054). The exercise time increased by 5.5% from 4.8 to 5.0 minutes (p = 0.16). With nifedipine, the duration of ischemia decreased by 22% from 175 min/24 hr to 137 min/24 hr (p = 0.16). The exercise tolerance time increased by 13% from 4.5 to 5.0 minutes (p = 0.0264). Nifedipine increased exercise time without altering total ischemic time, while transdermal nitroglycerin decreased total ischemic time without increasing exercise time. Thus, changes in exercise time do not necessarily predict changes in total ischemic time.     

The efficacy of the addition of nifedipine in patients with mixed angina compared to patients with classic exertional angina: a multicenter, randomized, double-blind, placebo-controlled clinical trial

Episodes of myocardial ischemia in patients with coronary artery disease may be due to transient increases in coronary vasomotor tone superimposed on a fixed atherosclerotic obstruction. The purpose of this study was to determine whether identification of the clinical pattern of angina could predict the therapeutic response to the addition of nifedipine to a regimen of beta blockers and/or long-acting nitrates. Seventy-two patients with stable exertional angina were divided into two groups: "classic exertional angina" (17 patients), defined as exertional angina with a stable threshold; and "mixed angina" (55 patients), defined as exertional angina provoked by a variable threshold and/or at least two episodes of rest angina within the 3 months prior to screening. Patients were studied with nifedipine and placebo in a 6-week, double-blind, crossover design that used serial anginal diaries, exercise treadmill tests, and 24-hour ambulatory ECG monitoring. In patients with mixed angina, nifedipine reduced the frequency of angina compared to that during placebo treatment (13.1 vs 9.9 episodes/3 weeks, p less than 0.01) and reduced nitroglycerin consumption (11.7 vs 7.5 tablets/3 weeks, p less than 0.05); while in patients with classic exertional angina, nifedipine had no symptomatic effect (7.9 vs 6.8 anginal episodes/3 weeks, NS; 6.4 vs 5.8 nitroglycerin tablets/3 weeks, NS). Patients in both groups experienced a significant decrease in the manifestations of ischemia during exercise testing. Patients with mixed angina experienced a reduction in the daily frequency of painful episodes of ST segment depression during nifedipine treatment compared to placebo (0.6 vs 0.2 episodes, p less than 0.05), but there was no effect on the frequency of episodes of silent ischemia (4.2 vs 3.4 episodes, NS). In patients with classic exertional angina, the addition of nifedipine had no effect on any measure of ambulatory ischemia. We conclude that patients with mixed angina are more likely to benefit symptomatically from the addition of nifedipine therapy than patients with classic exertional angina. The lack of a consistently preferential response to nifedipine in patients with mixed angina, however, suggests that episodic coronary vasoconstriction may not be the only mechanism responsible for ischemia in these patients, and/or that nifedipine may not necessarily provide additional therapeutic benefit beyond that conferred by a regimen of beta blockers and/or nitrates.