Comparative study to assess the efficacy and adverse effects of amlodipine and nifedipine retard in patients with stable exertional angina and hypertension

The purpose of the study was to compare the antianginal and hypotensive efficacy and tolerability of 8 weeks of treatment with amlodipine taken once daily and nifedipine taken twice daily in patients with stable exertional angina pectoris and mild-to-moderate hypertension. Following a 2-week placebo run-in-period 13 patients were randomized to receive amlodipine (5 to 10 mg once daily) and 8 patients to receive nifedipine (20 or 40 mg twice daily) in an 8-week treatment phase. Antianginal efficacy was assessed with angina diares, investigators, and patients global evaluations and with treadmill exercise test during placebo run-in-period and after 8 weeks of the therapy. Amlodipine significantly reduced both weekly anginal attacks and consumption of glyceryl trinitrate tablets. This effect was more pronounced compared to efficacy of nifedipine. Exercise tolerance was also improved more markedly after amlodipine than after nifedipine treatment. Amlodipine treatment resulted in significant increase in total exercise time, increase the exercise time to angina onset, increase time to ST segment depression, decrease in ST segment depression, decrease in total duration of ST segment depression and decrease in duration of pain. In patients treated with nifedipine only favourable effect was significant decrease in total duration of ST segment depression, without significant changes of other examined parameters. Both drugs decreased blood pressure with no significant change in heart rate. No serious adverse events occurred in any patients during therapy with amlodipine as well as with nifedipine. The results of the study demonstrate that amlodipine has markedly better anti-anginal efficacy than nifedipine with respect to the most of the parameters examined. However both drugs showed comparable antihypertensive action and both were well tolerated by angina patients. The good anti-anginal and hypotensive efficacy and safety of amiodipine with once daily dosage regimen makes this drug an excellent choice of treatment for hypertensive patients with severe coronary artery disease.     

Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm

BACKGROUND: Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. METHODS AND RESULTS: In the Angina Prognosis Study in Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double-blind treatment with metoprolol or verapamil. Various measures of fibrinolytic function were studied in 631 (of 809) patients. During a median follow-up time of 3.2 years (2132 patient-years), 32 patients suffered a CV death, 21 had a nonfatal myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen activator inhibitor (PAI-1) activity at test, and TPA responses to exercise were determined at baseline and after 1 month's treatment and were related to subsequent fatal and nonfatal CV events. Univariate Cox regression analysis revealed that elevated levels of TPA-ag at rest (P < .05), high PAI-1 activity (P < .05), and low TPA-ag responses to exercise (P < .05) were associated with increased risk of subsequent CV death. After adjustment for baseline risk factors, TPA-ag independently predicted CV death or MI. In addition, PAI-1 activity independently predicted CV death or MI in male patients. Verapamil treatment was associated with a 10% decrease of TPA-ag levels and metoprolol treatment with a 2% increase (P < .001 for treatment difference). CONCLUSIONS: Plasma TPA-ag levels at rest, and among male patients PAI-1 activity as well, independently predict subsequent CV death or MI in patients with stable angina pectoris.     

Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study

BACKGROUND: Spinal cord stimulation is known to be a successful treatment for chronic intractable angina pectoris. Its effect may be anti-ischemic. It is uncertain if the clinical effect is partly caused by a placebo effect of surgery for implantation of a stimulator. In this study, clinical efficacy is investigated, together with a possible placebo effect. METHODS AND RESULTS: Efficacy of spinal cord stimulation as a treatment for chronic intractable angina pectoris was studied for 6 weeks in 13 treated patients and 12 control patients with chronic angina. Assessments were exercise capacity and ischemia, daily frequency of anginal attacks and nitrate tablet consumption, and quality of life (perceived quality of life and pain). Compared with control, exercise duration (P =.03) and time to angina (P =.01) increased; anginal attacks and sublingual nitrate consumption (P =.01) and ischemic episodes on 48-hour electrocardiogram (P =.04) decreased. ST-segment depression on the exercise electrocardiogram decreased at comparable workload (P =.01). Anginal attacks and consumption of sublingual nitrates decreased (P =.01), perceived quality of life increased (P =.03), and pain decreased (P =.01). CONCLUSIONS: Spinal cord stimulation is effective in chronic intractable angina pectoris, and its effect is exerted through anti-ischemic action. Efficacy is unlikely to be explained as a placebo effect from surgery.     

The electrocardiogram during physical stress and Holter monitoring in the detection of asymptomatic myocardial infarct

INTRODUCTION: In patients with myocardial infarction acute myocardial ischaemia could be manifested by characteristic ischaemic symptoms or noncharacteristic symptoms such as cardiac insufficiency or heart rhythm disturbances. Sometimes myocardial ischaemia is not followed by any symptom. This condition is known as asymptomatic myocardial ischaemia. Asymptomatic myocardial ischaemia usually could be detected by treadmill exercise tolerance test or 24-hour Holter ECG monitoring. PATIENTS AND METHODS: We analyzed a group of 58 patients suffering from myocardial infarction with ST segment depression during the treadmill exercise tolerance test. All patients were on Holter 24-hour ECG monitoring. As a criterion of myocardial ischaemia during Holter monitoring ST segment depression of 1 mm and more, lasting 1 minute and more, and 0.08" of J point was accepted. RESULTS: During the treadmill exercise tolerance test segment depression was not followed by any symptom in 18 (31%) patients. There were no differences in the number of patients with hypertension in the group with symptoms and the group without symptoms. Diabetes mellitus was more frequent in the group with asymptomatic myocardial ischaemia. The average values of maximum ST segment depression and heart rates during treadmill tests were not statistically significant in both groups (with and without symptoms). During daily activities myocardial ischaemia was found in 30 (51%) patients by a 24-hour Holter ECG monitoring. We observed 198 episodes of myocardial ischaemia of which 138 (69.1%) were asymtomatic. The amplitude of ST segment depression and duration of these changes were significantly greater in the group with symptomatic episodes than in the group with asymptomatic episodes of myocardial ischaemia. DISCUSSION: Asymptomatic myocardial ischaemia is an often appearance in patients with myocardial ischaemia. Almost in 25% of persons in whom sudden death occurred obstructive changes in coronary arteries during the autopsy were found. Asymptomatic myocardial ischaemia could be found even an a "completely healthy person" without any complaints. Asymptomatic myocardial ischaemia is usually detected in a "completely healthy person" by casual diagnosis, in patients with stable and non stable angina pectoris, in patients with stenosis of the coronary arteries proved by angiography, and in patients after myocardial infarction. Some authors considered that treadmill exercise tolerance testing is less reliable to discover asymptomatic myocardial ischaemia comparing to the continuous 24-hour Holter ECG monitoring. It is know that in patients with diabetes mellitus neuropathy precedes the onset of symptomatic myocardial ischaemia. Asymptomatic myocardial ischaemia has the same predictive value for prognosis of the disease as symptomatic myocardial ischaemia. In some patients "anginal alarm system" is defective, and perception and conduction of pain sensations are disturbed. CONCLUSION: 1. In 31% of patients who suffered from myocardial infarction with ST segment depression during the treadmill testing asymptomatic myocardial ischaemia was found. 2. By Holter monitoring ischaemia ST segment depression during the exertion is observed in 52% of patients. Most of ischaemic episodes were asymptomatic. 3. The amplitude of ST segment depression is significantly greater and duration of depression is significantly longer in symptomatic episodes of myocardial ischaemia comparing to asymptomatic myocardial ischaemia obtained by Holter ECG monitoring.     

Hemodynamic action of captopril in coronary patients with heart failure tolerant to nitroglycerin

BACKGROUND: At present there is little dispute that clinical tolerance of organic nitrates occurs during long-term treatment of patients with stable angina pectoris and congestive heart failure. HYPOTHESIS: Captopril exerts a favorable hemodynamic effect in coronary patients with heart failure who are clinically tolerant to nitroglycerin. METHODS: Development of nitrate tolerance was observed during intravenous nitroglycerin treatment (10 mg/h) in 16 of 19 patients (7 women, 12 men; mean age 56 +/- 8 years) with coronary heart disease [stenosis > or = 75%, New York Heart Association (NYHA) classes II-III). The criterion applied was a loss of efficacy of at least 50% with regard to mean pulmonary capillary wedge pressure compared with the maximum effect of nitrate. The effect of captopril (50 mg p.o.) was determined in a blank test. Captopril (50 mg p.o.) was administered again at the stage of clinically manifest nitrate tolerance. RESULTS: Compared with the effect of captopril alone, significantly more pronounced reductions in mean pulmonary capillary wedge pressure (33% compared with 27%) and in mean pulmonary arterial pressure (36% compared with 17%) and significantly greater increases in cardiac index (14% compared with 7%) and stroke work index (34% compared with 18%) (p < 0.05 in each case; Wilcoxon test for linked random samples) were measured. Maintaining nitroglycerin infusion, the effect of captopril (at least 90% of the maximum effect) lasted for 123 +/- 24 min. The baseline values (at least 75% decline in the effect of captopril) were only reached after 369 +/- 34 min. CONCLUSION: The results document a favorable hemodynamic effect of captopril in nitrate tolerance which is significantly better than that of captopril alone.     

Effect of a standardized meal on the threshold of exercise-induced myocardial ischemia in patients with stable angina

OBJECTIVES: This study was undertaken to determine the effect of a standardized meal on the ischemic threshold and exercise capacity in a series of 20 patients with stable angina, exercise-induced ischemia and reversible exercise-induced perfusion defects. BACKGROUND: It is generally accepted that exercise tolerance in patients with angina is reduced after a meal. However, studies that have addressed this phenomenon have yielded results that are contradictory and inconclusive. METHODS: Two exercise tests using the Bruce protocol with technetium-99m (99mTc)-sestamibi were performed on consecutive days in a randomized order. One test was performed in the fasting state and the other 30 min after a 1,000-calorie meal. RESULTS: In the postprandial state, exercise time to ischemia was reduced by 20% from 248 +/- 93 s to 197 +/- 87 s (p = 0.0007), time to angina by 15% from 340 +/- 82 s to 287 +/- 94 s (p = 0.002) and exercise tolerance by 9% from 376 +/- 65 s to 344 +/- 86 s (p = 0.002). Rate-pressure products at these exercise test end points were not significantly different in the fasting and postprandial tests, and the quantitative 99mTc-sestamibi ischemia score was unchanged. CONCLUSIONS: In patients with stable angina, a 1,000-calorie meal significantly reduced time to ischemia, time to angina and exercise tolerance because of a more rapid increase in myocardial oxygen demand with exercise. The extent and severity of exercise-induced ischemia were unchanged.     

Conservative therapy of angina pectoris using nifedipine (Adalat)

35 patients with angina pectoris or previous myocardial infarction were treated for the period of 6 weeks with a new calcium-antagonist (4-2'-Nitrophenyl-2,6-Dimethyl 1,4-dihydro-pyridin-3,5-dicarbon acid dimethylester) Adalat. The attacks of angina pectoris decreased by 75 percent, the need for nitroglycerin decreased by 84 percent. Examination at rest and under exercise before and during the treatment with Adalat showed when registered by electrocardiogram and by the mean pulmonary-capillary pressure a better tolerance under exercise during treatment as well as a decrease of the PCPm in rest and under exercise after 6 week-therapy with Adalat. No improvement during the period of treatment was seen in 2 patients, who suffered from a severe diffuse type of coronary artery disease.     

Effects of amlodipine and isosorbide dinitrate on exercise-induced and ambulatory ischemia in patients with chronic stable angina pectoris

This study was designed to compare once-daily administration of 5-10 mg amlodipine with two daily doses of 40 mg sustained-release isosorbide dinitrate in 59 patients with stable angina using a randomized, double-blind, crossover study design. Anginal episodes, nitroglycerin consumption, and possible adverse events were recorded in a diary. A maximal symptom-limited bicycle exercise test and 48-hour ambulatory ECG monitoring were performed at baseline and at the end of each 5-week period of therapy. Exercise time, time to angina, time to ST depression, and maximal ST depression were measured during exercise. During ambulatory monitoring, the number of ischemic episodes and the duration per hour of ST depression were assessed. Amlodipine significantly reduced anginal episodes (P < 0.001) when compared with isosorbide dinitrate. Furthermore, amlodipine prolonged time to ST depression (P < 0.001) and time to angina (P < 0.05) when compared with isosorbide dinitrate. The number and duration of ischemic episodes during ambulatory monitoring were significantly reduced with amlodipine when compared with baseline values (P < 0.05), whereas no differences were found between isosorbide dinitrate and baseline. Adverse events were reported more frequently with isosorbide dinitrate than with amlodipine (P < 0.02). Amlodipine appears to be more effective and tolerable than sustained-release isosorbide dinitrate as monotherapy for chronic stable angina.     

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Circulating blood volume, cardiac index, heart rate, and ejection rate were measured in patients with angina pectoris. The controls and the patients were divided in sub-groups of those under 45 and over 45 years of age. The investigation was carried out using the isotope method. A significant difference was observed in the value of intravascular blood volume at rest between the controls and patients with ischaemic heart disease unrelated to anginal attack. The blood volume was 5.6 litre in the control group and 6.4 litre in patients with ischaemic heart disease. Exercise tests produced further increases during attack in the blood volume of angina patients. A significant increase of blood volume after moderate exercise was also observed in patients under 45 with ischaemic heart disease but without angina. It is suggested that the increase of intravascular blood volume plays a part in the pathogenesis of angina pectoris.     

Effect of extended-release isosorbide mononitrate one hour after dosing in patients with stable angina pectoris. IMDUR Study Group

The effect of extended-release isosorbide mononitrate (ER-ISMN) on exercise tolerance 1 hour after dosing was compared with that of placebo in a multicenter, randomized, double-blind study of 151 patients with stable effort-induced angina. During a 9- to 24-day placebo run-in, patients underwent Bruce protocol baseline exercise tolerance tests, after which they received ER-ISMN or placebo for 5 days. ER-ISMN patients took 60 mg each morning for the first 4 days and 120 mg on the morning of the fifth day. One hour after dosing, ER-ISMN patients had a significantly greater increase in total exercise time (days 1 to 4: 5 +/- 53 seconds; day 5: 53 +/- 58 seconds) than the placebo-treated patients (days 1 to 4: 14 +/- 37 seconds; day 5: 21 +/- 48) (p <0.001). The times to development of angina and 1-mm ST-segment depression were significantly longer in the ER-ISMN group than in the placebo group. The difference between the groups in mean time to onset of angina was 34 seconds after the 60-mg dose (p = 0.004) and 49 seconds after the 120-mg dose (p <0.001). The mean time to development of a 1-mm ST-segment depression was 51 and 61 seconds longer after the 60-mg and 120-mg ER-ISMN doses, respectively, than after placebo (p <0.001). Treatment-related adverse events were reported in 37% (28 of 75) and 7% (5 of 76) of patients in the ER-ISMN and placebo groups, respectively. As expected, headache was more frequent in the ER-ISMN group than in the placebo group (28% and 1%, respectively). The effects of ER-ISMN (60 mg and 120 mg) are clinically evident 1 hour after dosing, resulting in better exercise tolerance in patients with angina pectoris.     

Short-term effects of captopril on exercise tolerance in patients with chronic stable angina pectoris and normal left ventricular function

A double-blind, placebo-controlled, crossover study was carried out to evaluate the short-term effects of captopril on exercise tolerance in 18 normotensive patients with chronic stable angina pectoris and normal left ventricular function. Captopril 25 mg (or placebo) was given twice, i.e. in the evening (10 p.m.) and the following morning (8 a.m.), prior to a maximal symptom-limited bicycle exercise test (11 a.m.). Captopril reduced the systolic and diastolic blood pressures at rest (p < 0.01) without causing any reflex tachycardia. The time to onset of S-T depression was prolonged (p < 0.05), and the maximal S-T depression was reduced (p < 0.02). No differences were found between captopril and placebo in total exercise duration or time to onset of angina. The effects of captopril on exercise-induced ischemia were demonstrated most clearly in patients who responded with a greater than 10 mm Hg fall in the resting systolic blood pressure. In conclusion, this study suggests that captopril has anti-ischemic properties, which may be of importance in the treatment of patients with chronic stable angina and normal left ventricular function. These beneficial effects probably relate to a reduction in afterload and myocardial wall stress and therefore a reduction in myocardial oxygen demand.     

Glia increase degeneration of hippocampal neurons through release of tumor necrosis factor-alpha

A multicenter, randomized, double-blind, crossover, placebo-controlled study was conducted in 90 isosorbide dinitrate responders showing stable angina to compare the efficacy of molsidomine retard, 8 mg b.i.d., with that of molsidomine, 4 mg t.i.d., for 6 weeks. Total work performance (workload x min) was significantly improved, compared with baseline and placebo until 8 and 12 h after molsidomine and molsidomine retard administration, respectively. ST-segment depression decreased significantly under the two treatments at 60 W as well as at maximal exercise. The rate-pressure product (heart rate x systolic blood pressure) decreased and increased significantly at submaximal and maximal exercise level, respectively. All these effects remained significant after 6-week treatment, with only the ST segment showing a nonsignificant tendency to improvement at maximal work. The frequency of anginal attacks and of sublingual nitroderivative-tablets consumption decreased significantly with molsidomine, 4 mg, and molsidomine retard, 8 mg. However, overall results showed that the latter form reduces myocardial ischemia more efficiently at submaximal exercise level, has a more prolonged effect on exercise tolerance, and maintains it at a somewhat higher level after 6-week treatment.     

Do parental convict cichlids of different sizes value the same brood number equally?

OBJECTIVES: We sought to determine endothelium-dependent vasodilator function in the brachial artery of patients with microvascular angina pectoris. BACKGROUND: Previous studies suggest the presence of endothelial dysfunction of the coronary microcirculation in patients with microvascular angina pectoris. It is not known whether endothelial dysfunction in these patients is a generalized process or whether it is confined to the coronary microcirculation only. METHODS: In 11 women (mean [+/-SD] age 60.1 +/- 7.8 years) with microvascular angina (anginal pain, normal epicardial coronary arteries, positive exercise stress test), endothelium-dependent vasodilation was assessed in the brachial artery by measuring the change in brachial artery diameter in response to hyperemic flow. Results were compared with 11 age- and gender-matched patients with known three-vessel coronary artery disease and 11 age- and gender-matched healthy control subjects. In all subjects, the intima-media thickness (IMT) of the common carotid artery was also measured. RESULTS: Flow-mediated dilation (FMD) was comparable in patients with microvascular angina and coronary artery disease (1.9 +/- 2.5% vs. 3.3 +/- 3.3%, p = NS) but was significantly lower in patients with microvascular angina than in healthy control subjects (1.9 +/- 2.5% vs. 7.9 +/- 3%, p < 0.05). IMT was significantly lower in patients with microvascular angina than in those with coronary artery disease (0.64 +/- 0.08 vs. 1.0 +/- 0.28 mm, p < 0.05) and was comparable between patients with microvascular angina pectoris and healthy control subjects (0.64 +/- 0.08 vs. 0.56 +/- 0.14 mm, p = NS). IMT > or = 0.8 mm was observed in 1 of 11 patients with microvascular angina, 1 of 11 control subjects and 10 of 11 patients with coronary artery disease. CONCLUSIONS: These findings suggest that endothelial dysfunction in microvascular angina is a generalized process that also involves the peripheral conduit arteries and is similar to that observed in atherosclerotic disease. IMT could be helpful in discriminating patients with microvascular angina and atherosclerotic coronary artery disease.     

Long-term (10-year) outcome in patients with unstable angina pectoris treated by coronary balloon angioplasty

OBJECTIVES: We sought to examine completed 10-year survival and event-free survival in patients with stable and unstable angina pectoris treated by coronary balloon angioplasty. BACKGROUND: Patients with unstable angina are at increased risk for recurrent acute coronary events. METHODS: The study included 208 consecutive patients (133 with stable and 75 with unstable angina pectoris) undergoing angioplasty from 1984 to 1986. The balloon crossed the lesion in 185 patients (121 with stable and 64 with unstable angina pectoris). Angioplasty was performed in patients with unstable angina pectoris 12+/-15 days (median 8) after symptom onset. Patients with unstable angina pectoris were classified retrospectively into Braunwald class I (n=3), class II (n=20), class III (n=28), class B (n=52) and class C (n=12). Follow-up data were obtained from hospital charts, telephone interview and official death certificates where applicable. The study had >80% power to detect a clinically significant 20% difference in survival and a 20% difference in event-free survival between the stable and unstable patient groups. RESULTS: Despite similar baseline characteristics, early (40-day) mortality was slightly higher in patients with unstable angina (4.7% [3 of 64 patients] vs. 0.8% [1 of 121 patients], p=NS). Long-term outcome was not different, because survival curves were parallel thereafter (10-year survival was 83% for those with stable and 77% for those with unstable angina, p=NS). Survival free of myocardial infarction or coronary artery bypass graft surgery at 10 years was 53% in patients with stable and 47% in patients with unstable angina (p=NS), and survival free of infarction, bypass surgery or repeat angioplasty was 32% for both groups at 10 years. In patients with Braunwald class III unstable angina, 10-year survival was 80%, as compared with 85% in other patients with unstable angina, due to the early hazard (p=NS). Survival and event-free survival were similar in patients who had had a recent myocardial infarction (Braunwald class C) and in patients with acute electrocardiographic changes. Repeat hospital admissions were not more frequent in patients with unstable angina (3.1+/-3.5 vs. 3.0+/-2.6, p=NS). CONCLUSIONS: Ten-year survival and event-free survival were similar in patients with stable and unstable angina pectoris treated by coronary balloon angioplasty, with no evidence of an increased rate of recurrent cardiovascular events in the unstable group.     

Effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls

The effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls were investigated. Platelet function was studied at rest, and during mental stress (colour word test), or after exercise (bicycle ergometry), in 113 angina patients (21 on aspirin) and 50 matched controls. Platelet function was assessed by filtragometry ex vivo (reflecting platelet aggregability), by measuring platelet secretion (beta-thromboglobulin and platelet factor 4 levels in plasma), and by Born aggregometry in vitro. At rest, platelet function did not differ between patients and controls. Exercise increased platelet aggregability and secretion similarly in both groups. Aspirin did not attenuate the platelet activating effect of exercise despite inhibition at rest. Mental stress increased heart rate, blood pressure and plasma catecholamines, but platelet responses were highly variable. However, mental stress tended to shorten filtragometry readings in patients but not in controls (P < 0.05 between the groups); plasma beta-thromboglobulin showed a similar difference between patients and controls (P < 0.05 between the groups; aspirin-treated patients included). Physical exercise activates platelets in patients with stable angina pectoris and healthy controls. Aspirin is not an effective inhibitor of exercise-induced platelet aggregation. Platelet responses to mental stress are variable, but more pronounced in angina patients.     

The role of transcription factors in circadian gene expression

The pool of controlled clinical studies on mibefradil, a new selective T-type calcium channel blocker, for the treatment of chronic stable angina pectoris was analysed to determine the effects in subgroups of patients defined by age, gender, body weight and common co-existing conditions. Total exercise tolerance test duration increased similarity in all subgroups, both at 50 mg (range 8.9-17.3%; n = 383) and 100 mg mibefradil (range 23.6-30.8%; n = 235). The increases in time to onset of angina and 1 mm ST-segment depression were similarly comparable. Safety and tolerability was similar to placebo for subgroups at 50 mg, but the incidence of adverse events was slightly higher in females, older, and lower weight patients at the 100 mg dose, particularly in reported leg oedema (7.9% in females vs 1.0% in males and 5.1% in older vs 0% in younger patients). Mibefradil proved a safe, well tolerated, and effective antianginal agent that can be used regardless of demographic factors or of frequently coexisting clinical conditions.     

Influence of combination therapy (isosorbide dinitrate and molsidomine) on the incidence of angina pectoris in patients with coronary heart disease

Angina pectoris in patients with severe 3-vessel-disease refractory to treatment is a challenge for the treating physician. We have therefore tested the treatment efficacy of isosorbide dinitrate combined with molidomine on the frequency of angina pectoris in patients with symptoms refractory to treatment. PATIENTS AND METHODS: 15 patients with severe coronary heart disease were included in the study. The protocol included a 2-weeks stabilisation phase, followed by a 4-weeks treatment phase with 100 mg isosorbide dinitrate in the morning as well as 8 mg slow-release molsidomine at 6 p.m. RESULTS: Initially all of the 15 patients reported about daily angina pectoris attacks. After 4 weeks of treatment 4 out of 15 patients became free of symptoms. From the other 11 patients 6 reported an improvement, 5 an unchanged frequency of attacks. DISCUSSION: Combination treatment with isosorbide dinitrate with molsidomine in a slow-release form (in the nitrate free interval) showed a distinct improvement in patients with angina pectoris refractory to treatment with reduction of complaints. The effect of the combination is possibly based on a prolonged vasodilatation of the stenosed vessels and a prolonged reduction of filling pressure (reduction of preload).     

Paradigms and expectations: the nature of research and diagnostics

OBJECTIVES: Our purpose was to evaluate the long-term benefit of myocardial viability assessment for stratifying risk and selecting patients with low ejection fraction for coronary artery bypass grafting and to determine the relation between the severity of anginal symptoms, the amount of ischemic myocardium, and clinical outcome. METHODS: We studied 93 consecutive patients with severe coronary artery disease and low ejection fraction (median, 25%) who underwent positron emission tomography to delineate the extent of perfusion-metabolism mismatch (reflecting hibernating myocardium) for potential myocardial revascularization. Median follow-up was 4 years (range, 0 to 6.2 years). RESULTS: Fifty patients received medical therapy, and 43 patients underwent bypass grafting. In Cox survival models, heart failure class, prior myocardial infarction, and positron emission tomographic mismatch were the best predictors of survival. Patients with positron emission tomographic mismatch receiving bypass grafting had improved 4-year survival compared with those on medical therapy (75% versus 30%; P =.007) and a significant improvement in angina and heart failure symptoms. In patients without positron emission tomographic mismatch, bypass grafting tended to improve survival and symptoms only in those patients with severe angina (100% versus 60%; P =.085), whereas no survival advantage was apparent in patients with minimal or no anginal symptoms (63% versus 52%; P =.462). CONCLUSIONS: Patients with low ejection fraction and evidence of viable myocardium by positron emission tomography have improved survival and symptoms with coronary bypass grafting compared with medical therapy. In patients without evidence of viability, survival and symptom improvement with bypass grafting are apparent only among those patients with severe angina.     

Effects of sublingual nitroglycerin on the gas exchange response to exercise in stable angina pectoris

To quantitate changes in gas exchange variables that occur after administration of sublingual nitroglycerin in patients with stable angina pectoris, a randomized double-blind 2-period crossover study was performed with continuous expired gas exchange analysis and progressive exercise using individualized ramp treadmill protocols. Significant reductions in minute ventilation and respiratory rate were observed at 5 minutes of exercise during nitroglycerin therapy. Gas exchange variables i.e., minute ventilation, carbon dioxide production and oxygen uptake were significantly increased at the onset of angina after nitroglycerin administration. When techniques for optimizing the assessment of cardiopulmonary function were used, significant improvements in gas exchange variables were demonstrated in stable angina pectoris after administration of sublingual nitroglycerin.     

1998 Annual Meeting of the Society of Orthopedics and Athletic Traumatology (GOTS)

BACKGROUND: Elevation of acute phase proteins [C-reactive protein (CRP) and serum amyloid type A (SAA)] has been demonstrated in unstable angina with an adverse clinical prognosis. HYPOTHESIS: The study was undertaken to determine the effect of angioplasty on the levels of SAA and the correlation with postangioplasty restenosis. METHODS: In a university-affiliated tertiary medical center, a prospective case study was undertaken in 55 patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) of a single coronary lesion for angina pectoris. Three groups of patients were clinically characterized according to Braunwald's classification of anginal syndrome: Group A: class III; Group B: class I; Group C: stable angina. Serum amyloid type A was measured by an ELISA method before PTCA and after 24 h, 1, and 3 months. Patients were followed clinically for 12 months. A thallium stress perfusion scan was performed 3 months after PTCA and coronary angiography was repeated in patients with an abnormal thallium perfusion scan. RESULTS: Serum amyloid type A levels > 100 micrograms/ml could identify Group A patients with a high sensitivity and specificity (r = 0.85 and 0.86, respectively). Of the patients studied, 75% increased their SAA level 24 h after angioplasty. An increase of SAA by > 100% was associated with an increased risk of restenosis, with a relative risk of 6.4 (p < 0.05). CONCLUSION: Increased levels of SAA characterize patients with unstable angina pectoris with a high specificity and sensitivity. Levels of SAA that increase > 100% 24 h after angioplasty may serve as a marker of restenosis.