Usefulness of early exercise testing after non-Q-wave myocardial infarction in predicting prognosis.

The value of an early symptom-limited maximal exercise test in predicting coronary anatomy, left ventricular ejection fraction and hemodynamics was assessed prospectively in 64 patients after an acute non-Q-wave myocardial infarction (MI). Exercise tests and cardiac catheterization were performed at a median of 6 and 7 days, respectively, after non-Q MI. Forty-one percent of the patients had a negative exercise test response (no angina, less than 1 mm of ST depression and normal blood pressure responses). Twenty-five percent had a positive response (1 to 1.9 mm of ST depression or angina); 34% had a "strongly positive" exercise test response (at least 2 mm of ST depression or abnormal blood pressure responses). A negative response predicted the absence of 3-vessel disease (at least 70% stenosis) or critical stenoses (at least 90% stenosis) involving major coronary arteries (negative predictive accuracy 92%), whereas a strongly positive response predicted their presence (positive predictive value 77%, specificity 88%). Cardiac index and mean pulmonary artery wedge pressure did not vary significantly among the 3 exercise groups, whereas left ventricular ejection fraction was slightly higher in the exercise test group with a positive response (p less than 0.025). Thus, in patients who have had a non-Q MI, early exercise testing can be used to predict the extent and severity of coronary artery disease, and the decision to perform coronary angiography should be guided by the exercise test results.

Myocardial salvage with streptokinase combined with nitroglycerine and verapamil in acute myocardial infarction.

We tested the hypothesis that preservation of left ventricular function results from treatment with intravenous streptokinase given in the first 2 hours from onset of acute transmural myocardial infarction together with nitroglycerine and verapamil. Thirty-three consecutive patients with onset of pain less than 2 hours prior to admission, received intravenous streptokinase 1.5 x 10(6) units with intravenous nitroglycerine and verapamil; 23 concurrently admitted "control" patients with pain onset 2-4 hours received intravenous nitroglycerine and verapamil only. Radionuclide ventriculographic assessment at 2 days revealed a significantly greater left ventricular ejection fraction in the streptokinase-treated patients (54.5 +/- 2.8 vs 46.1 +/- 2.9; P less than 0.05), which persisted at 28-35 days (50.1 +/- 2.3 vs 41.2 +/- 2.9; P less than 0.05). Streptokinase-treated patients had a significantly increased incidence of ischaemic events in the 35 days following infarction, but a lower incidence of death, congestive cardiac failure and non-fatal ventricular tachycardia than control group patients. Infarct-related artery patency assessed at 3-5 days was 94% in streptokinase-treated patients. We conclude that early presentation and treatment with intravenous streptokinase, nitroglycerine and verapamil is associated with a high incidence of successful thrombolysis and significant preservation of left ventricular function. Nitroglycerine and verapamil may augment the efficacy of streptokinase in this group of patients.

Perhexiline maleate treatment for severe angina pectoris--correlations with pharmacokinetics.

Perhexiline maleate, which causes inhibition of myocardial fatty acid catabolism with a concomitant increase in glucose utilization, is particularly useful in the management of patients with severe angina pectoris. While perhexiline exerts no significant negative inotropic or dromotropic effects, its short- and long-term use has hitherto been restricted because of complex pharmacokinetics and the eventual development, in many patients, of hepatitis and peripheral neuropathy. Correlations between perhexiline dose, plasma drug concentrations, efficacy and development of toxicity were examined prospectively in 3 groups of patients. The first group (n = 29) were patients in whom perhexiline was added to previously prescribed anti-anginal medication for short-term (pre-surgical or post-myocardial infarction) control of angina pectoris. Over a mean treatment period of 18 +/- 2 (SEM) days, 13 patients experienced a marked reduction in frequency and severity of attacks. No adverse effects occurred. A second group of patients (n = 19) were treated chronically with 50-400 mg/day of perhexiline, dosage being adjusted to minimize symptoms. Over a mean treatment period of 8.8 +/- 1.7 months, 5 patients became asymptomatic, while 9 developed evidence of hepatitis or neurotoxicity, with concomitant plasma perhexiline concentrations of 720-2680 ng/ml. Subsequently, a further group of similar patients (n = 22) were treated for 12.4 +/- 2.6 months, perhexiline dosage being adjusted to maintain plasma perhexiline concentrations below 600 ng/ml. Nine patients became asymptomatic, while none developed adverse effects. It is concluded that perhexiline is useful both as a short-term adjunct to anti-anginal therapy and in the long-term management of patients unsuitable for coronary artery bypass grafting. The risk of long-term toxicity can be reduced markedly by maintenance of plasma drug concentrations below 600 ng/ml without significantly compromising anti-anginal efficacy.

High-performance liquid chromatographic assay of perhexiline maleate in plasma.

A sensitive assay is described for the calcium antagonist perhexiline maleate. Alkalinized plasma was extracted with nb-hexane, the organic phase was evaporated, and the residue was dansylated prior to analysis by reversed-phase high-performance liquid chromatography using a fluorescence detector. Perhexiline was resolved from its mono- and dihydroxylated metabolites, and the limit of sensitivity was 5 ng of perhexiline/ml. This limit represents approximately 100 times the sensitivity of the previously described GLC assay. Single-dose pharmacokinetic studies were performed with 150- and 300-mg oral doses of perhexiline maleate in five patients with severe angina pectoris and impaired left ventricular function. Peak plasma perhexiline levels occurred 3-6 hr after drug ingestion in four patients and after 12-18 hr in the fifth patient. The mean elimination half-life, measured 24 hr after drug ingestion, varied with plasma perhexiline concentration. It was 11.2 +/- 2.1 hr after the 150-mg dose and 19.1 +/- 2.8 hr after the 300-mg dose. The mean ratio of areas under the concentration-time curve for the 300-versus 150-mg doses ws 5.3:1, suggesting that hepatic metabolism of perhexiline may be saturable and that the bioavailability of perhexiline is dose dependent.

Maintenance of behaviour change in patients with coronary artery disease.

This paper comments upon patterns of behavioural change after acute cardiac illness and discusses determinants of longterm compliance with advice. The importance of comprehensive rehabilitation during convalescence is emphasised. Education, motivation and support of the patients are essential for the adoption of healthier lifestyles. Despite comprehensive rehabilitation, however, recidivism to former habits is common, particularly with smoking and physical inactivity. This is partly determined by premorbid social and personality characteristics of patients. Social and behavioural support at the workplace and within the community may well be of significant benefit in supporting patients to maintain their necessary health behaviour changes. Some of the evidence related to these issues is discussed and recommendations are made regarding future directions for patient support.

Early programmes of high and low intensity exercise and quality of life after acute myocardial infarction.

OBJECTIVE: To determine whether a group programme of light exercise could improve quality of life in patients after acute myocardial infarction to the same extent as a high intensity exercise training programme. SETTING: Australian teaching hospital. PATIENTS: 224 men from a consecutive series of 339 men under 70 admitted to a coronary care unit with transmural acute myocardial infarction. INTERVENTION: Patients were randomly allocated in hospital to a group programme lasting eight weeks of either high intensity exercise training or light exercise. MAIN OUTCOME MEASURES: Physical working capacity based on metabolic equivalents achieved from treadmill exercise tests at entry, after 11 weeks, and after one year. Quality of life based on self report scores of anxiety, depression, denial, and wellbeing and interview assessments of activities and psychosocial adjustment at entry, after four months, and after one year. RESULTS: The two groups were well matched at entry. At 11 weeks the mean results of treadmill testing were 10.7 (95% confidence interval 10.20 to 11.20) metabolic equivalents for exercise training and 9.7 (9.26 to 10.14) for light exercise (t = 2.85, df = 181, p = 0.005). Apart from this small temporary benefit in mean physical working capacity, there were no significant differences between groups. Improvement in occupational adjustment score from baseline to four months was greater after exercise training than after light exercise, but at one year repeated measures analysis of variance showed no significant effects of treatment or interaction between treatment and time point. CONCLUSION: The effects on quality of life of a low cost programme of light exercise are similar to those obtained from a high intensity exercise training programme.

Diuretics, beta blockers and vasodilators. Dosage in mild and moderate hypertension.

This paper presents experience with the treatment of mild to moderate hypertension by means of a thiazide diuretic (cyclopenthiazide), a small dose of a beta adrenergic blocking agent (oxprenolol) and progressively increasing doses of a vasodilator (hydrallazine). Satisfactory control of blood pressure was achieved in 38 of 41 cases without the production of distressing effects. This treatment regime was acceptable to patients and appears more promising than other currently available methods for blood pressure control.

Control of cardiac valve related hemolytic anemia by sulphinpyrazone.

Sulphinpyrazone has a beneficial effect in a patient with hemolytic anemia related to cardiac valve prostheses. It may also have a clinically significant role in the control of symptoms and may delay the need for surgery.

Effect of propranolol on exercise tolerance of patients with atrial fibrillation.

Six patients with atrial fibrillation who were taking digitalis were exercised before and after 30 mg. of propranolol twice daily. Though there was a lower pulse rate at rest and on exercise in all patients, three suffered deterioration of exercise tolerance. It is concluded that propranolol does not improve the exercise tolerance of patients with atrial fibrillation whose resting ventricular rate is controlled with digitalis.

Cardiac rehabilitation based on group light exercise and discussion. An Australian hospital model.

Patients with cardiac disease potentially have many physical, psychological, and social problems. With adequate rehabilitation, most patients can return to enjoyable, productive lives. If rehabilitation programs can be provided at relatively low cost, they can be introduced more widely. It is obviously important that low-cost programs should include most of the effective components of more sophisticated programs. The program presented here, based on group light exercise and discussion, is effective and inexpensive. Therefore, it provides a potential model for group cardiac rehabilitation in situations where cost-containment is an important consideration.

Stroke syndromes in young people.

PIP: All contributory factors to the unusual occurrence of stroke in young people were evaluated in patients under age 40 admitted to the Stroke Unit of the Austin Hospital in Melbourne, Australia. Over the August 1977 to December 1980 period there were 700 admissions. Of these 14 patients were under the age of 40. There were 7 males and 7 females whose ages ranged from 17-38 years. Each patient was screened for factors which might contribute to premature vascular disease including hypertension, diabetes, smoking, obesity, and hyperlipidemia. In addition, the following tests were performed to exclude an arteritic process: full blood examination; ESR; protein electrophoresis; syphilis serology; and the presence of antinuclear factor. Each of the 14 patients suffered cerebral infarction. A summary of each case is presented in a table. In 9 patients, infarction occurred in the carotid territory of supply. Large cortical infarcts with or without subcortical involvement occurred in cases 1-8, of whom 5 had major vessel occlusion demonstrated angiographically and another had stenosing and ulcerative atheromatous disease at the extracranial carotid bifurcation. In a further 4 patients, infarction occurred within the vertebrobasilar territory and was either confined to the brain stem, the occiptal cortex, or involved both. Angiograms were performed in 2 of these patients and showed irregular narrowing of the vertebral artery which was interpreted as spasm and segmentally narrowing of the basilar artery. The final patient had several ischemic events which included right sided amaurosis fugax, and left frontal, right parieto-occipital and left occipital infarctions. Angiography was normal. All patients survived the stroke and were able to go home. There may be an interrelationship between the pathological findings of Irey et al. (1978) and the effect oral contraceptives (OCs) has on migraine. This is relevant to Case 13. Sustained exposure to OCs may produce the pathological changes described (visible as segmental narrowing angiographically). In 2 patients cerebral infarction was caused by atheromatous or hypertensive occlusive vascular disease. In Case 3 an embolus occluded the middle cerebral artery. Infarction complicating migraine was diagnosed confidently in 4 patients on the basis of typical migrainous symptomatology in the past and accompanying the stroke. Of the 12 patients fully evaluated, there were no cases of polycythemia or thrombocytosis. There were no abnormalities of the clotting factors. Almost every patient had some form of emotional upset, and there were 7 who had significant psychiatric illness and emotional problems of extreme magnitide.^ieng

Effect of early programmes of high and low intensity exercise on physical performance after transmural acute myocardial infarction.

Does a programme of light exercise training after acute myocardial infarction produce the same improvement in treadmill performance as aerobic exercise training? Three hundred and eight men from a consecutive series of 479 men with transmural (Q wave) acute myocardial infarction, admitted to a single coronary care unit, were randomly allocated to eight weeks of group aerobic exercise training or group light exercise. Groups were well matched for all characteristics other than site of infarction, which did not significantly affect results. Mean (SD) physical working capacity (metabolic equivalents) determined by treadmill testing at the start of the study (in the third week after infarction) was 6.8 (2.2) v 6.7 (2.5) METs, at the end (in the eleventh week after infarction) 10.8 (2.3) v 9.9 (2.4) METs, and at 12 month review 10.8 (2.4) v 10.7 (1.9) METs for the exercise training group and the light exercise group respectively. The difference of 0.9 METs at the end of the study was the only significant difference between groups. There were no significant intergroup differences at any stage in resting and maximal heart rate, resting and maximal systolic blood pressure, or rate-pressure product. Apart from a small temporarily greater physical working capacity, the physical benefits of aerobic exercise training were equally well achieved by group light exercise.

Effects of captopril (SQ 14,225) in a patient with primary pulmonary hypertension.

In a 33-year-old patient with severe primary pulmonary hypertension, the acute administration of the angiotensin-converting-enzyme inhibitor captopril (SQ 14,225) induced a rise in cardiac output, and a fall in both pulmonary and systemic vascular resistance. Subsequent chronic oral administration of captopril induced only transient clinical improvement, and the patient died. Captopril may nevertheless be useful in the treatment of less advanced cases of this disease.

Comparative trial of mexiletine and lignocaine in the treatment of early ventricular tachyarrhythmias after acute myocardial infarction.

The antiarrhythmic effects of intravenously administered lignocaine and mexiletine were compared over a period of 48 hr in a randomized trial on 24 patients who developed ventricular tachyarrhythmias within 48 hr of the onset of acute myocardial infarction. Mexiletine was given as an initial bolus of 200 mg, followed by an infusion of 1 mg/min reduced to 0.5 mg/min after 1 hr. Lignocaine was given as a bolus of 100 mg, followed by an infusion of 3 mg/min reduced to 2 mg/min after 1 hr. Plasma levels of mexiletine, lignocaine, and monoethylglycinexylidide were monitored. The frequency of "complex" ventricular tachyarrhythmias was significantly lower in the mexiletine-treated group. This group of patients also had significantly fewer ventricular extrasystoles than those receiving lignocaine, the difference being most marked during the second 24 hr of treatment. Too few episodes of ventricular fibrillation occurred for statistical comment. The greater efficacy of mexiletine was not associated with increased drug toxicity.

Aggravation of myocardial ischaemia by nifedipine.

Three cases in which myocardial ischaemia was possibly precipitated by the administration of nifedipine are reported. It is suggested that the initial administration of nifedipine should be undertaken with caution in patients with unstable ischaemic heart disease.

Haemodynamic effects of a single low dose of prazosin in patients with chronic congestive cardiac failure correlations with pharmacokinetics.

The haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m. = 4.5 to 19.4, s.e.m. = 5.1 mmHg; P less than 0.001), mean arterial blood pressure (from 94.5, s.e.m. = 6.0 to 85.4, s.e.m. = 5.0 mmHg; P less than 0.01), and systemic vascular resistance (from 1690, s.e.m. = 360 to 1420, s.e.m. = 200 dyn. s/cm5; P less than 0.05) and a rise in cardiac index from 1.98 (s.e.m. = 0.07) to 2.28 (s.e.m. = 0.16) litres/min per m2 (P less than 0.05). There was a non-significant fall in heart rate. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m. = 1.4) ng/ml, occurring 2.1 (s.e.m. = 0.4) h after drug ingestion. The mean elimination half-life was 5.1 (s.e.m. = 0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half-life and area under the concentration-time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral dose of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initial doses.