[Chronic heart failure--suggestion to a management program]. / Kronisk hjertesvikt--forslag til handlingsprogram.

In 1994, a Norwegian programme for diagnosis and treatment of chronic heart failure was published. Recently the American College of Cardiology, the American Heart Association and the Task Force on Heart Failure of the European Society of Cardiology have published similar guidelines. In this article, the Working Group on Heart Failure of the Norwegian Society of Cardiology presents an updated programme for evaluation and management of patients with chronic heart failure.

[Calcium channel blockers in heart failure]. / Kalsiumkanalblokkarar ved hjartesvikt.

Patients with heart failure are particularly susceptible to the negative effects of calcium channel blockers because the failing heart demonstrates a defect in the delivery of calcium to the contractile proteins, and an attenuation of the normal sympathetic reflexes. Currently these drugs have no place in the treatment of heart failure caused by systolic dysfunction of the left ventricle. Calcium channel blockers should probably not be described for patients with coronary artery disease and left ventricular dysfunction. When the patient needs additional treatment for angina and beta-blockers or nitrates have not given satisfactory results, it may be appropriate to prescribe amlodipine or felodipine.

[Treatment of heart failure with beta-blockaders]. / Betablokkerbehandling av hjertesviktpasienter.

Since 1975 several studies have indicated that treatment with beta-adrenergic blocking drugs has a positive effect on prognosis in patients with left ventricular dysfunction. After myocardial infarction, treatment with timolol and propranolol improves prognosis in patients with symptoms of cardiomegaly and heart failure. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol improves the left ventricular ejection fraction and symptoms of heart failure, and may have a positive effect on prognosis. Recent studies of patients with chronic congestive heart failure also indicate that carvedilol has a positive effect on mortality and morbidity. The authors review some relevant studies, to stimulate the use of beta-adrenergic blocking drugs to treat certain types of heart failure.

Felodipine in addition to beta-adrenergic blockade for angina pectoris. a multicentre, randomized, placebo-controlled trial.

The additional efficacy, duration of action and tolerability of felodipine were evaluated in patients with stable angina pectoris and a positive stress test who were already receiving therapy with a beta-adrenergic blocker. One hundred and twenty-eight patients were randomized to double-blind treatment with 5-10 mg felodipine once daily or matching placebo, and were evaluated by serial exercise testing during 12 weeks of treatment. Felodipine at 4 h significantly increased exercise duration assessed after 4 weeks of treatment (increase 34 +/- 65 s vs 18 +/- 71 s in placebo-treated patients; 95% confidence interval 1.01-1.11; P = 0.01), and after 12 weeks of treatment (increase 39 +/- 103 s vs 3 +/- 72 s; 95% confidence interval 1.01-1.16; P = 0.02). The time until onset of exercise-induced anginal pain and time until 1 mm ST depression assessed after 4 weeks of treatment also increased significantly with felodipine compared to placebo. No statistically significant changes in exercise test parameters evaluated 24 h after medication were observed. The addition of felodipine once daily demonstrated a sustained improvement in exercise duration in patients symptomatic despite treatment with a beta-blocker evaluated 4 h after drug intake. At 24 h post dose, no statistically significant effect was observed. Felodipine is well tolerated with a low incidence of side-effects and no adverse effect on quality of life.

[Chronic left heart ventricle failure and inotropic stimulation]. / Kronisk venstre ventrikkel-svikt og inotrop stimulering.

Congestive left heart failure can be treated using three main strategies: change preload to optimize the Frank-Starling relationship, decrease after-load to reduce external work and increase cardiac contractility by inotropic stimulation. The third option is reviewed in this article, which discusses the pharmacological and clinical effects of different inotropic drugs as known in 1994. It is concluded that digitalis should be considered apart from other inotropic drugs. Even when in sinus rhythm, digitalis seems reasonable as an adjuvans to after-load reduction and diuretics. Chronic use of other inotropic drugs for congestive left heart failure is not recommended.

Functional capacity in healthy volunteers before and following beta-blockade with controlled-release metoprolol.

The effects of the beta 1-selective beta-adrenergic blocker metoprolol on physiological responses, exercise capacity and gas exchange parameters were measured in healthy men using different graded bicycle exercise protocols on separate days before and following administration of 200 mg controlled-release metoprolol. Eleven men performed in randomised order maximal cardiopulmonary exercise testing on 50-W/6-min stage, 50-W/3-min stage and ramp (15-W/min-1) protocols. Peak heart rate and peak heart rate-blood pressure products were similar on all exercise protocols, and were significantly reduced by metoprolol. Submaximal and peak oxygen consumption were similar before and following beta-adrenoceptor blockade. Depending on the exercise protocol applied, an insignificant decrease of 4-10% in maximal cumulated exercise capacity (work-rate x time integral) was observed following administration of metoprolol. It is concluded that in healthy men evaluated with different exercise protocols the beta 1-selective controlled-release beta-adrenoceptor blocker metoprolol does not influence exercise capacity despite a marked reduction of heart rate and rate-pressure product.

[Chronic heart failure. A management program. Proposal for diagnosis and treatment]. / Kronisk hjertesvikt. Handlingsprogram. Forslag til undersøkelser og behandling.

An expert meeting on the treatment of heart failure was organized by the Swedish Medical Products Agency in 1992. There were four participants from Norway. Two of these (AW, JK), in cooperation with a group of cardiologists with a special interest in heart failure, present in this article a modified Norwegian programme for treatment of chronic heart failure. When evaluating risk for patients with chronic heart failure, it is necessary to take into account both symptoms and left ventricular systolic function determined by ejection fraction. Specific recommendations are made for treatment of asymptomatic patients with left ventricular dysfunction and for symptomatic patients with mild, moderate and severe heart failure.

Importance of the exercise programme for the assessment of functional capacity after myocardial infarction.

To evaluate the effect of different bicycle exercise programmes on estimates of functional capacity in cardiac patients, the cumulated exercise capacity, physiologic and gas exchange responses were measured in eleven men 5-10 weeks after an acute myocardial infarction. The patients were not limited by angina and all were treated with a beta-blocker. On separate days and in randomized order the patients performed symptom-limited cardiopulmonary exercise testing on 50 W/3 min stage, 50 W/6 min stage and continuous 'ramp' (15 W per min) programmes. Submaximal and peak oxygen consumption, peak heart rate, rate pressure product, workload and minute ventilation were independent of the various exercise programmes, but exercise time and maximal cumulated exercise capacity (workload x time integral) were significantly higher on the 50 W/6 min stage (50.3 +/- 20.0 kJ) and ramp (41.1 +/- 16.4 kJ) programmes compared to the 50 W/3 min stage programme (32.8 +/- 11.9 kJ). The variation of exercise time and cumulated work capacity, but not oxygen consumption between different exercise programmes has to be considered when estimating functional capacity early after acute myocardial infarction.

Prognostic importance of predischarge exercise capacity for long-term mortality and non-fatal myocardial infarction in patients admitted for suspected acute myocardial infarction and treated with metoprolol.

To evaluate the influence of acute beta-blockade on the ability of predischarge exercise test data to predict long-term prognosis in patients admitted for suspected acute myocardial infarction, patients randomized at hospital admission to intravenous metoprolol or placebo were studied. Among 190 patients discharged alive, total 4-year mortality was 20.5% (n = 39); (33 cardiac deaths, 6 non-cardiac deaths). Non-fatal infarction rate was 6.8% (n = 13). Multiple logistic regression analysis revealed that total mortality and non-fatal infarctions were independently predicted by (a) inability to perform predischarge stress testing (event-free survival for patients exercise tested 79.5% vs 56.9% for patients not eligible for testing; relative risk (RR) 1.40, 95% confidence interval (CI) 1.10-1.78; P = 0.01), and (b) low predischarge exercise capacity (RR 1.44, CI 1.08-1.93; P = 0.034). ST segment shift > or = 1 mm did not predict mortality or reinfarction. Administration of metoprolol in the acute phase did not influence the predictive value of these parametres. It is concluded that assessment of exercise capacity at early exercise testing yields independent information for later death and myocardial infarctions, and that beta-blockade with metoprolol does not influence the predictive value of early exercise testing.

Increased occurrence of exercise-induced silent ischemia after treatment with aspirin in patients admitted for suspected acute myocardial infarction.

Patients admitted for suspected acute myocardial infarction within 6 hours (mean 3 hours 42 minutes) after onset of symptoms were randomised to double-blind treatment with low-dose oral aspirin or placebo. Early exercise ischemic responses, exercise capacity and resting left ventricular ejection fraction (radionuclide ventriculography) were estimated in 77 survivors 2-4 weeks later. Exercise performance and ejection fraction in patients with confirmed acute myocardial infarction were equal in the two groups. During exercise, patients treated with aspirin had significantly more silent ischemia (ST depression without chest pain) compared to placebo (28% versus 6%; P = 0.015). The occurrence of positive exercise tests (chest pain or ST-segment depression), however, was similar in the two groups. The results indicate that the administration of aspirin early after acute myocardial infarction increases the occurrence of silent ischemia but has no effect on left ventricular function.

Effect of metoprolol on early exercise-induced ST-segment changes and ventricular arrhythmias in patients with suspected acute myocardial infarction.

One-hundred and ninety-seven consecutive patients admitted for suspected acute myocardial infarction were randomized to double-blind treatment with intravenous followed by oral metoprolol or matching placebo within 24 hours (mean 6.9 hours) after onset of symptoms. A symptom-limited exercise test was performed 15 days after admission in 132 patients (70 patients receiving metoprolol; 62 placebo). Patients treated with metoprolol had a lower observed frequency of exercise-induced ST-segment elevation (11.4% vs. 22.6%; P less than 0.05) and less ventricular arrhythmias (7.1% vs. 19.4%; P less than 0.05) on the predischarge exercise test compared to placebo-treated patients; however, ST-segment depressions were equally distributed to the two treatment groups. Mean exercise capacity was the same in the two groups. Early administration of metoprolol to patients with suspected acute myocardial infarction reduces early exercise-induced parameters related to a bad prognosis and may therefore improve the long-term prognosis without reducing physical performance.

Predicting return to work after acute myocardial infarction. Significance of clinical data, exercise test variables and beta-blocker therapy.

Among 66 full-time employed men surviving an acute myocardial infarction (AMI) and participating in the Norwegian postinfarction study with timolol, 50 (75.7%) resumed their previous work within 12 months, and 16 (24.3%) retired. Stepwise logistic regression analysis of clinical data and of results from an exercise test 3 months post AMI revealed the following factors of independent predictive value for enhanced return to work: previous labor characterized as light or moderately heavy (p = 0.001), low age at the time of infarction (p = 0.001), timolol treatment (p = 0.009), ability to stop smoking post AMI (p = 0.006), and a high exercise capacity on the exercise test (p = 0.016). It is concluded that the clinical history and an exercise test 3 months after AMI can identify patients who are more likely to resume work, and that post-AMI beta-blocker treatment with timolol and ability to stop smoking are predictive of an enhanced return to work.

Tolerability and antiarrhythmic efficacy of disopyramide compared to lignocaine in selected patients with suspected acute myocardial infarction.

In a randomized open study with intravenous lignocaine and disopyramide in patients with suspected acute myocardial infarction and ventricular premature contractions the occurrence of cardiac events, adverse reactions, withdrawals and arrhythmias were compared. Of the total 68 patients included in the study, 33 were randomized to disopyramide and 35 to lignocaine treatment. The treatment was given for 24 hours or until withdrawal due to occurrence of serious cardiac events or side-effects possibly related to the drugs. Sustained ventricular tachycardia occurred in one patient in each treatment group. 15 per cent of the patients treated with disopyramide and 14 per cent of the patients treated with lignocaine were withdrawn because of adverse reactions. Withdrawals due to depressed left ventricular function and sinoatrial and atrioventricular conduction disturbances were not different in the two treatment groups. However, more patients treated with lignocaine had supraventricular arrhythmias compared to disopyramide. Significantly more patients treated with disopyramide obtained complete abolition of premature ventricular contractions on Holter recordings compared to lignocaine treatment (P less than 0.001). The results indicate that disopyramide and lignocaine can be used alternatively in the treatment of ventricular arrhythmias in patients with suspected acute myocardial infarction.

Effect of smoking habits and timolol treatment on mortality and reinfarction in patients surviving acute myocardial infarction.

The Norwegian Multicenter Group Study noted the effect of smoking habits before and after myocardial infarction and their relation to mortality and reinfarction rate after treatment with timolol in patients surviving acute myocardial infarction. The mean follow up period was 17.3 (range 12-33) months. No relation was found between initial smoking habits and risk category after infarction or between initial smoking habits and later outcome. At the time of their first infarct smokers were seven years younger than non-smokers. One moth after infarction nearly 60% of the smokers had stopped smoking completely. A significantly lower incidence of early cardiac death and lower total mortality was found in patients treated with timolol in both those who continued smoking and in the combined non-smoking groups and a significantly lower reinfarction rate among non-smokers. Cessation of smoking alone was associated with a reduced reinfarction rate by 45% but a non-significant reduction in mortality by 26%. It is concluded that treatment with timolol and cessation of smoking have an additive effect in reducing mortality and reinfarction rate after myocardial infarction.

Comparative efficacy of oral sotalol and procainamide in patients with chronic ventricular arrhythmias: a multicenter study.

In an open, randomized, crossover study, the efficacy of sotalol and procainamide was compared in 33 patients with frequent, chronic premature ventricular contractions (PVCs). A 75% reduction in PVCs/24 hours (two 24-hour recordings) was arbitrarily considered to constitute an adequate therapeutic effect. Sotalol was started at a dose of 160 mg once daily for 1 week, followed by a 24-hour recording. In the absence of any therapeutic effect, the same procedure was repeated with 320 mg, 480 mg, and 640 mg daily. Procainamide, 1 gm three times/day, was given or, if plasma concentrations were insufficient, 1.5 gm three times/day for 1 week. PVC control was obtained in 22 (67%) patients on sotalol, including all 12 with ischemic heart disease. Procainamide was successful in 13 (39%) patients. Effects on the number of attacks of ventricular tachycardia were achieved by both drugs in those patients where PVCs were reduced by at least 75%. Sotalol caused side effects in five patients, who therefore could not accept planned increases in dosage. Side effects were noted by 12 patients with procainamide. Nine patients responded to both drugs, seven to neither. Thirteen responded to sotalol only and four to procainamide only. We conclude that sotalol is a useful alternative to procainamide in controlling chronic PVCs, especially in patients with ischemic heart disease.

Changes in heart size during long-term timolol treatment after myocardial infarction.

The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.

Long-term effect of beta-blockade with timolol on maximal work capacity following myocardial infarction.

In a double-blind, randomized, placebo controlled trial 74 patients surviving a myocardial infarction (MI) were stress tested three and twelve months following MI. Thirty-eight patients received the beta blocking agent timolol and 36 patients received placebo. There was no significant difference in the mean total exercise capacity of the two groups. Most of the patients treated with timolol discontinued the exercise test because of exhaustion, but the placebo treated patients usually stopped the test because of chest pain, exhaustion or a fall in blood pressure. Patients treated with timolol had significantly less increase in heart rate, systolic blood pressure and rate-pressure product during exercise compared to placebo. We conclude that beta-blockade with timolol after MI does not affect work capacity, but timolol-treated patients perform the same work with a lower rate-pressure product.

Timolol-related reduction in mortality and reinfarction in patients ages 65-75 years surviving acute myocardial infarction. Prepared for the Norwegian Multicentre Study Group.

Long-term treatment with timolol in patients ages 65--75 years who survived myocardial infarction was related to a significant reduction, compared with placebo, in overall mortality (p less than 0.05), total cardiac death (p less than 0.01), sudden death (p less than 0.05) and reinfarction (p less than 0.01). The analyses were based on 732 patients (384 taking placebo and 348 timolol) from a cohort of 1884 patients in the Norwegian multicenter timolol study. The dosage of timolol was 10 mg twice daily and the patients were followed for 12--33 months (mean 17 months). There were 83 deaths in the placebo group and 52 deaths in the timolol group, a reduction of 35.5%. There were 69 initial reinfarctions in the placebo group and 38 in the timolol group, a reduction of 39.2%. There was no difference in the reduction of mortality and reinfarction between patients 65--75 years of age and patients less than 65 years of age. The incidence of side effects, the number of withdrawals and the reasons for withdrawal were similar in older and younger patients. We conclude that age should not be a decision-making factor concerning timolol therapy in postinfarct patients.