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Biomedical subjects

K Swedberg

Publications and source records attributed to K Swedberg.

At least 91 records · Page 5Linked to original sources
PubMed1996

What is the ideal study design for evaluation of treatment for heart failure? Insights from trials assessing the effect of ACE inhibitors on exercise capacity.

There is a wealth of evidence that angiotensin converting enzyme (ACE) inhibitors improve symptoms, morbidity and mortality in patients with heart failure. In this context the use of ACE inhibitors could be considered a tool with which to assess the effect of trial design and methodology on the ability to detect improvement in symptoms and exercise performance. Thirty-five published, double-blind, randomized placebo-controlled trials, involving a total of 3411 patients, which compared the effect of ACE inhibitors and placebo on exercise capacity in patients with symptomatic chronic heart failure were identified. Studies were examined in relation to whether they used cross-over or parallel group study design, study size, use of treadmill vs bicycle exercise test, year of publication, patient entry criteria, duration of follow-up and the particular ACE inhibitor used. Exercise duration improved in 23 of the studies, while symptoms improved in 25 of the 33 studies which evaluated this. In the majority of the trials (27 of 33) there was concordance between the effect on symptoms and on exercise capacity. There were six trials which showed discrepant results. Study size, duration of follow-up and method of exercise testing used were found to be major factors affecting the outcome. Trials using treadmill exercise tests were more likely to be positive than those using bicycle ergometry. All nine trials with study size more than 50, follow-up of 3-6 months and using treadmill exercise tests showed improved exercise capacity as well as symptoms. These findings may be useful in designing future trials for evaluating treatment for heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Beta-blocking agents in heart failure. Should they be used and how?

Experience accumulated from several large trials strongly suggests that beta-blockers should be used for the management of chronic heart failure[87]. It is appropriate to add beta-blockade to conventional therapy such as diuretics, ACE inhibitors and digoxin, as this was the approach used in the major trials. It is appropriate to treat patients with mild, moderate and, when stable, severe chronic heart failure. The benefits obtained include improvements in left ventricular function, reductions in symptoms and morbidity, improvement of quality of life, and delay of clinical progression, reflected in a reduced need for cardiac transplantation and, probably, a reduction in mortality. beta-blockers are much better tolerated, when used appropriately in selected patients, than was previously supposed. To confirm the improvement in survival recently reported with carvedilol, further prospective trials using different beta-blockers are warranted. No major comparative trials have been carried out between beta-blockers in chronic heart failure, therefore it is not known whether the differences between them are clinically significant. The optimal dose of beta-blocker and the effect in patient groups excluded from or poorly represented in the clinical trials (e.g. elderly patients) have yet to be determined. Placebo-controlled mortality trials with bucindolol (BEST) and bisoprolol (CIBIS-II) are under way[89,90]. A large study of carvedilol versus metoprolol (COMET), added to conventional treatment, is planned.

Adrenergic beta-Antagonists↗
PubMed1996

Skeletal muscle changes in patients with chronic heart failure before and after treatment with enalapril.

To evaluate if enalapril treatment can influence skeletal muscle metabolism and histology we investigated 26 patients with congestive heart failure and 20 normal subjects. The patients were treated with enalapril for 3 months in addition to diuretics and digitalis. Biopsies from the lateral vastus muscle were taken before and after treatment. Citrate synthetase, 3-hydroxyacyl-CoA dehydrogenase and phosphorylase activities were significantly decreased in the patients compared with controls. The number of capillaries per fibre and the number of capillaries surrounding each fibre were significantly decreased among patients. After 3 months of enalapril treatment functional class improved significantly. The lactate dehydrogenase activity increased whereas the oxidative enzymes did not change significantly. The type I, II and II A fibre areas increased significantly after enalapril treatment. We conclude that patients with chronic heart failure have decreased activity of oxidative enzymes and of phosphorylase in skeletal muscle. They also have decreased capillarization in skeletal muscle. These changes were not influenced by enalapril treatment. The increase in muscle fibre area seen after enalapril treatment could be due to increased physical activity. The cause of increased muscle lactate dehydrogenase activity after enalapril treatment needs further investigation.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1996

Thrombin inhibition with inogatran for unstable angina pectoris: evidence for reactivated ischaemia after cessation of short-term treatment.

BACKGROUND: The acute coronary syndromes of unstable angina and non-Q-wave infarction are initiated by coronary plaque rupture and subsequent thrombus formation. Thrombin is central to this response as it activates platelets and the coagulation system. In an open design study we assessed the tolerability and safety of the low molecular weight thrombin inhibitor, inogatran, for unstable angina or non-Q-wave infarction. METHODS: Thirty-seven patients, treated within 72 h of symptoms, were allocated consecutively to groups to receive a 4 h infusion with one of three doses of inogatran. Thrombin generation and activity were measured with plasma markers at baseline, after the 4 h treatment period and 4 h later. Ischaemia was monitored using continuous vectorcardiography during the 4 h of treatment and during the subsequent 4 h after inogatran infusion had been stopped, to detect any increase in ischaemic events after the period of treatment. In addition, 12 patients received inogatran as an infusion for 72 h. RESULTS: Inogatran was tolerated well. There were no adverse haemodynamic effects or allergic reactions. Minor bleeding events were detected in 37% of the patients. The biochemical and vectorcardiographic findings indicated suppression of thrombin generation after the 4 h treatment period compared with baseline. During the first 4 h after inogatran treatment, thrombin activity and episodes of ischaemia were increased compared with during the treatment period. CONCLUSION: Inogatran was tolerated well and was safe, but its discontinuation was followed by a reactivation of thrombin activity and ischaemia. Whether this reactivation represented a rebound phenomenon, or merely resulted from the discontinuation of an effective therapy, cannot be established from the present study.

Adult↗
PubMed1996

Skeletal muscle metabolism during exercise in patients with chronic heart failure.

OBJECTIVE: To investigate the metabolic response of skeletal muscle to exercise in patients with chronic heart failure and determine its relation to central haemodynamic variables. SETTING: University hospital in Sweden. PARTICIPANTS: 16 patients in New York Heart Association class II-III and 10 healthy controls. MAIN OUTCOME MEASURES: Skeletal muscle biopsies were obtained from the quadriceps muscle at rest and at submaximal and maximal exercise. Right sided heart catheterisation was performed in eight patients. RESULTS: The patients had lower maximal oxygen consumption than the control group (13.2 (2.9) v 26.8 (4.4) ml/kg/min, P < 0.001). They had reduced activities of citrate synthetase (P < 0.05) and 3-hydroxyacyl-CoA dehydrogenase (P < 0.05) compared with the controls. At maximal exercise adenosine triphosphate (P < 0.05), creatine phosphate (P < 0.01), and glycogen (P < 0.01) were higher whereas glucose (P < 0.001) and lactate (P < 0.06) were lower in the patients than in the controls. Citrate synthetase correlated inversely with skeletal muscle lactate at submaximal exercise (r = -0.90, P < 0.003). No correlations between haemodynamic variables and skeletal muscle glycogen, glycolytic intermediates, and adenosine nucleotides during exercise were found. CONCLUSION: Neither skeletal muscle energy compounds nor lactate accumulation were limiting factors for exercise capacity in patients with chronic heart failure. The decreased activity of oxidative enzymes may have contributed to the earlier onset of anaerobic metabolism, but haemodynamic variables seemed to be of lesser importance for skeletal muscle metabolism during exercise.

Adenosine Triphosphate↗
PubMed1996

The role of neurohormonal activation in chronic heart failure and postmyocardial infarction.

Chronic heart failure is a disabling and lethal disorder with high incidence and prevalence in Western societies. Treatment with angiotensin-converting enzyme (ACE) inhibitors and heart transplantations diminish both mortality and morbidity, although both still remain high. Increased understanding of some of the pathophysiologic mechanisms involved in the development of left ventricular dysfunction and the transition from asymptomatic systolic dysfunction to symptomatic heart failure has opened gates to new dimensions for the treatment of this disorder. The initial event in the pathophysiologic process is damage to the myocardium, most frequently a myocardial infarction. Almost simultaneously, activation of different neurohormonal systems occurs. The renin-angiotensin system and sympathetic nervous system are activated. Increased concentrations of hormones with counteractive activity have also been found, such as ANP and BNP. Interestingly, prolonged neurohormonal activation seems to occur only in patients with large infarcts or in patients with poor systolic function of the left ventricle. Moreover, available data from an echocardiographic study indicates that in patients with high concentrations of neurohormones in plasma a week after their infarction, left ventricular dilatation and systolic dysfunction of the left ventricle are highly likely to develop during long-term follow-up. Several studies have showed that ACE inhibitors are efficacious in chronic heart failure and among patients with reduced ejection fraction after myocardial infarction. What these patients have in common is prolonged neurohormonal activation, which theoretically may be harmful to myocardial cell structure and function. ACE inhibitors reduce the breakdown of angiotensin I to angiotensin II and increase the concentration of circulating bradykinins and prostaglandins. Further modulation of neurohormonal activity might be beneficial. Therefore, future treatment of chronic heart failure or asymptomatic left ventricular dysfunction might include beta-adrenergic blockers, neutral endopeptidase inhibitors, ANP, BNP, angiotensin II receptor antagonists, and modulators of sympathetic activity.

Chronic Disease↗
PubMed1995

Dynamic on-line vectorcardiography improves and simplifies in-hospital ischemia monitoring of patients with unstable angina.

OBJECTIVES: This study sought to validate computerized vectorcardiography against the established technique of Holter electrocardiographic (ECG) monitoring and to compare the feasibility of the two methods for monitoring patients with unstable angina pectoris. BACKGROUND: Detection of myocardial ischemic episodes is an important objective in patients admitted to the hospital for unstable angina pectoris. Standard ECG monitoring may be sufficient for detection of symptomatic episodes but will often overlook silent ischemia. Holter ECG monitoring has a higher likelihood of discovering such episodes, but analysis is time-consuming, and the results are not available on-line. METHODS: We simultaneously monitored 53 consecutive patients with unstable angina, 46 of whom had technically adequate 24-h Holter ECGs and computerized vectorcardiograms. RESULTS: The Holter tapes had a mean (+/- SD) of 15.3 +/- 10.3 h of recording with both channels technically adequate for analysis compared with 23.7 +/- 1.77 h of vectorcardiographic recording that could be analyzed (p < 0.01). Of the 15 symptomatic episodes detected by Holter ECG monitoring, 13 were also detected with dynamic vectorcardiography. In contrast, eight patients had 18 episodes of chest pain, with simultaneous ST segment changes detected by dynamic vectorcardiography; only 9 of these episodes were also detected by Holter ECG monitoring. CONCLUSIONS: Monitoring of myocardial ischemia with dynamic vectorcardiography seems to be more efficient than Holter monitoring and may have a higher sensitivity. Computerized, continuous vectorcardiography has a complete real-time capacity, allowing monitoring over prolonged periods of time, and the results are immediately available without time-consuming analysis.

Adult↗
PubMed1995

Effects of 12 weeks of ramipril treatment on the quality of life in patients with moderate congestive heart failure: results of a placebo-controlled trial. Ramipril Study Group.

The assessment of quality of life (QoL) has become recognized as an important tool for evaluating heart failure therapy. The angiotensin-converting enzyme inhibitor ramipril (mean dose 8 mg) was evaluated in 223 patients with moderate chronic congestive heart failure at 24 centers in 4 Nordic countries following a randomized, double-blind, placebo-controlled, parallel group design. The follow-up period was 12 weeks. QoL was evaluated using a questionnaire with 47 items, including the disease-specific Severe Heart Failure Questionnaire, the Sleep Dysfunction Scale, and the Psychological General Well-Being Index. In both treatment groups the total score increased from baseline to 12 weeks for both the Severe Heart Failure Questionnaire and for the Psychological Well-Being Index, reflecting relief of symptoms and improved well-being. However, no significant differences between the placebo and ramipril groups could be detected. Only a trend toward improvement in sleep on ramipril compared with placebo therapy was observed. In conclusion, in this placebo-controlled trial no significant effects of 12-week ramipril treatment of QoL could be demonstrated in patients with moderate congestive heart failure.

Adult↗
PubMed1995

Skeletal muscle fiber composition and capillarization in patients with chronic heart failure: relation to exercise capacity and central hemodynamics.

Patients with chronic heart failure have structural and metabolic changes in skeletal muscle, which may be of importance for symptomatology. The origin of these changes are still unknown. The relationship between fiber composition and capillarization in skeletal muscle with exercise capacity and central hemodynamic variables was examined. Biopsies from the lateral vastus muscle were taken in 12 patients with chronic heart failure. Samples from eight normal subjects served as control samples. All patients underwent maximal exercise tests. Central hemodynamic variables were measured during exercise in five patients. The patients had a higher percentage of type II B fibers (P = .03) and fewer capillaries per fiber (P = .02) than the controls subjects. VO2 max correlated with the percentage of type I fibers, whereas the correlation with the type II A fibers was inverse. Cardiac index and pulmonary capillary wedge pressure at submaximal and maximal exercise were related to fiber type composition and relative fiber areas. Skeletal muscle fiber type composition and capillarization was changed in patients with chronic heart failure. These changes might influence exercise capacity. There were relationships between central hemodynamic variables and skeletal muscle changes. What the cause and effects were need further investigation.

Aged↗
PubMed1995

Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group.

Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 +/- 10 years, ejection fraction at rest was 22% +/- 10%, and maximal exercise tolerance was 91 +/- 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% +/- 12% versus 23% +/- 12% (NS), 25% +/- 13% versus 23% +/- 12% (P < .05), and 23% +/- 11% versus 22% +/- 11% (NS). Maximal exercise capacity increased from 94 +/- 31 W during the placebo period to 100 +/- 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 +/- 23 during the placebo period to 113 +/- 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.

Aged↗
PubMed1995

Atrial natriuretic peptide ANP(1-98) and ANP(99-126) in patients with severe chronic congestive heart failure: relation to echocardiographic measurements. A subgroup analysis from the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).

Studies in patients with moderate heart failure have shown a positive relation between atrial size and plasma atrial natriuretic peptide (ANP)(99-126) concentrations; however, the relation of the hormone level and left atrial size and left ventricular function in patients with severe chronic heart failure has not been determined. Fifty-three patients from the Cooperative North Scandinavian Enalapril Survival Study with severe chronic heart failure were evaluated with M-mode echocardiography and determination of plasma concentrations of ANP(99-126). In 35 patients, the plasma level of N-terminal ANP(1-98) was also measured. A significant negative relation was found between ANP(1-98), ANP(99-126), and left atrial diameter (r = -.28, P = .05 and r = -.41, P < .005, respectively). Plasma concentrations of both ANP(1-98) and ANP(99-126) were related to left ventricular systolic function as determined by the systolic time interval index (r = .4, P < .05 and r = .29, P < .05, respectively). A significant improvement of left ventricular systolic function was found in the enalapril group but not in the placebo group. After 6 weeks of therapy, no correlation was found between changes in left atrial size or systolic function or changes in either the ANP(1-98) or ANP(99-126) concentration. The results indicate that high ANP(1-98) or ANP(99-126) plasma concentration is determined by the depressed left ventricular function rather than increased left atrial size in patients with chronic severe heart failure. The findings suggest that the ANP release relation to atrial pressure/atrial size is distorted in severe heart failure.

Aged↗
PubMed1995

Neurohormonal activation and congestive heart failure: today's experience with ACE inhibitors and rationale for their use.

Treatment with angiotensin converting enzyme (ACE) inhibitors delays deterioration and improves survival in chronic congestive heart failure and left ventricular dysfunction. In two large placebo-controlled trials with survivors of acute myocardial infarction, but with left ventricular dysfunction, mortality was significantly lower in the ACE inhibitor arms, with risk reductions of 19% (with captopril) and 27% (with ramipril). A study of left ventricular dysfunction in more than 4000 patients resulted in significantly fewer myocardial infarctions among patients given enalapril than in those receiving placebo; the risk reduction was 24%. Knowledge of the degree of neurohormonal activation in patients with congestive heart failure (New York Heart Association [NYHA] Functional Class II-III) appears to be of major importance in determining the efficacy of ACE inhibition. Patients with plasma concentrations above normal show the greatest increase in survival when treated with ACE inhibitors compared to similarly treated patients with low or normal neurohormonal plasma levels as well as those treated with placebo or direct-acting vasodilators. In a study of 239 patients with NYHA Class IV heart failure, randomized to receive enalapril or placebo, mortality was significantly reduced in patients receiving enalapril who had plasma noradrenaline, adrenaline, angiotensin II, aldosterone, or atrial natriuretic peptide levels above median values. No significant differences in survival between groups were found in patients with hormone levels below the median. A study in 804 men with congestive heart failure who received either enalapril or hydralazine plus isosorbide dinitrate showed the greatest reduction in mortality after 2 years in enalapril treated patients with plasma noradrenaline levels > 900 pg.ml-1 or plasma renin levels > 16 ng.ml-1.h-1. These results indicate that the main rationale for ACE inhibition in chronic congestive heart failure, in left ventricular dysfunction, and after myocardial infarction is the modulation of prolonged neurohormonal activation. Knowledge of this effect may provide the means to forestall disease progression and thus offer long-term treatment benefits.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Prevention of congestive heart failure by ACE inhibition in patients with acute myocardial infarction.

Ischaemic heart disease is a major cause of chronic heart failure in Western societies. Despite some progress in the treatment of heart failure, it is still a disabling disorder with both high mortality and high morbidity. The incidence of chronic heart failure has increased over the past decade, probably as a result of the recent success in the management of patients with acute myocardial infarction. The importance of measures with potential capacity to prevent the development of symptomatic heart failure may be best illustrated by the fact that, among patients with left ventricular dysfunction, the prognosis is much worse in those with symptomatic failure than in those who are asymptomatic. Recently, the efficacy of angiotensin converting enzyme (ACE) inhibitors after myocardial infarction has been studied in a number of large placebo-controlled trials. These studies indicate that patients with symptomatic or asymptomatic left ventricular dysfunction after an acute myocardial infarction should receive long-term treatment with an ACE inhibitor and that such treatment may improve survival, reduce the incidence of overt heart failure and reduce the risk of reinfarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Neuroendocrine activation in relation to left ventricular function in chronic severe congestive heart failure: a subgroup analysis from the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).

Left ventricular (LV) function and plasma levels of cardiovascular hormones were examined in patients with severe chronic congestive heart failure (CHF), randomized to placebo or enalapril, in addition to conventional therapy. M-mode echocardiography and plasma hormone concentrations were available at baseline and after 6 weeks of treatment. There was a significant relationship between LV systolic function and levels of angiotensin-II and norepinephrine. Enalapril increased LV fractional shortening (FS%) (13.3 +/- 5.6 to 15.4 +/- 5.8, p < 0.05) and decreased the systolic time interval index (0.58 +/- 0.14 to 0.48 +/- 0.15, p < 0.05) concurrent with a significant decrease in angiotensin-converting enzyme activity and in aldosterone, angiotensin-II, and norepinephrine concentrations after 6 weeks. No changes were found in the placebo group. However, there was no direct relationship between the amount of change in neurohormones and improvement in LV function after 6 weeks. These findings indicate that in patients with severe chronic CHF, severe LV systolic dysfunction is associated with high plasma levels of angiotensin-II and norepinephrine, which can be favorably modified by enalapril. This may be of importance for prolonging life in severe heart failure. The lack of relationship between changes in individual hormones and systolic function suggests complex dynamic interaction. It is, therefore, not sufficient to predict changes in LV function by measuring changes in only one hormone.

Aldosterone↗
PubMed1994

ECG changes during myocardial ischemia. Differences between men and women.

Women have a higher short-term mortality in acute myocardial infarction (MI) compared with men. This may be partly explained by differences in risk factors such as age and diabetes. However, several reports have focused on the occurrence of a sex bias making women less likely to be subjected to angiography and revascularization as well as aggressive pharmacologic treatment of acute MI. The decision to initiate these procedures is often based on ischemic changes of the electrocardiogram. It was therefore investigated whether differences between men and women in magnitude of electrocardiographic changes during myocardial ischemia could explain some of the differences previously reported. A total of 178 patients with chest pain suggestive of MI (135 men and 43 women) included in a study of thrombolytics were monitored for 24 hours with continuous vectorcardiography. Also, 81 patients with stable angina pectoris undergoing elective angioplasty were monitored during the procedure. In patients admitted with suspicion of MI, the initial summated ST deviation was 178 +/- 146 microV for men as compared with 105 +/- 91 microV for women (P = .002). During angioplasty, men had significantly more pronounced maximum ST deviation during inflation of the balloon (235 +/- 165 vs 156 +/- 89 microV; P = .036). In conclusion, men have more pronounced ST changes than women during myocardial ischemia. When fixed magnitudes of ST deviation are required for initiating therapy such as thrombolytics, this will favor treatment of men. A sex-adjusted limit for administrating thrombolytic drugs may be warranted in the light of the above findings.

Angioplasty, Balloon, Coronary↗