Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study.

OBJECTIVE: To investigate long-term safety and efficacy after intracoronary injection of autologous mononuclear bone marrow cells (mBMCs) in acute myocardial infarction (AMI). DESIGN: Randomised, controlled trial. SETTING: Two university hospitals in Oslo, Norway. PATIENTS: Patients from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study were re-assessed 3 years after inclusion. INTERVENTIONS: 100 patients with anterior wall ST-elevation myocardial infarction treated with acute percutaneous coronary intervention (PCI) were randomised to receive intracoronary injection of mBMCs (n = 50) or not (n = 50). MAIN OUTCOME MEASURES: Change in left ventricular (LV) ejection fraction (primary). Change in exercise capacity (peak VO(2)) and quality of life (secondary). Infarct size (additional aim), and safety. RESULTS: The rates of adverse clinical events in the groups were low and equal. There were no significant differences between groups in change of global LV systolic function by echocardiography or magnetic resonance imaging (MRI) during the follow-up. On exercise testing, the mBMC-treated patients had larger improvement in exercise time from 2-3 weeks to 3 years (1.5 minutes vs 0.6 minutes, p = 0.05), but the change in peak oxygen consumption did not differ (3.0 ml/kg/min vs 3.1 ml/kg/min, p = 0.75). CONCLUSION: The results indicate that intracoronary mBMC treatment in AMI is safe in the long term. A small improvement in exercise time in the mBMC group was found, but no other effects of treatment could be identified 3 years after cell therapy.

Late medical complications and fatigue in Hodgkin's disease survivors.

PURPOSE: Long-term medical complications, such as cardiac, pulmonary, and thyroid dysfunction, are frequent among Hodgkin's disease survivors (HDSs). Chronic fatigue is also highly prevalent among HDSs. Few studies have explored possible etiologic explanations for fatigue. The aim of this study was to explore whether late cardiac, pulmonary, and thyroid complications after curative treatment for Hodgkin's disease (HD) may explain the high level of fatigue among HDSs. PATIENTS AND METHODS: Four-hundred fifty-nine patients treated for HD at the Norwegian Radium Hospital from 1971 to 1991 were included in a cross-sectional, follow-up study of subjective health status. Fatigue (physical [PF] and mental), was measured by the Fatigue Questionnaire. A subcohort of the HDSs (116 patients) treated from 1980 to 1988 were included in a separate study in which long-term cardiac, pulmonary, and thyroid complications were assessed. All patients had received radiotherapy, and 63 patients had received additional chemotherapy. The present study comprised 92 patients (mean age, 37 years; range, 23 to 56 years) who participated in both studies. RESULTS: HDSs with pulmonary dysfunction were more fatigued than HDSs with normal pulmonary function (PF 10.9 v 8.9; P <.05). Gas transfer impairment was the most prevalent pulmonary dysfunction, and three times as many patients with gas transfer impairment reported chronic fatigue (duration, 6 months or longer), compared with patients without pulmonary dysfunction (48% v 17%, P <.01). No associations were found between cardiac sequelae or hypothyroidism and fatigue. CONCLUSION: Pulmonary dysfunction is associated with fatigue in HDSs. Cardiac sequelae was not associated with fatigue in HDSs. We question the absence of an association between thyroid complications and fatigue.

Myocardial laser revascularization in the year 2000 as seen by a Norwegian specialist panel. The process of evaluating and implementing new methods in clinical practice.

OBJECTIVE: In Norway "Transmyocardial laser revascularization" as a routine method was prohibited by the Ministry of Health in 1995 due to lacking evidence of treatment effect and concerns about procedural morbidity and mortality. In 1999 Norwegian health authorities asked for a re-evaluation of the method based on a systematic review of literature. METHODS: Medline and Embase were searched and a total of 267 articles were identified. Publications were classified by an expert panel according to type of study and importance for the project. RESULTS: Based on the literature review the panel concluded that heart laser treatment does not have a life-saving effect, nor does it improve myocardial function. However, the method has a considerable short-term symptomatic effect, the mechanism of which is not understood. Neoangiogenesis, denervation and placebo may play a role. Based on the report the Norwegian health authorities recommended use of this method be restricted to scientific trials only. CONCLUSIONS: Based on a systematic literature review it was concluded that the only documented effect of heart laser treatment is symptom relief, the mechanism for which is unclear. It could partly or totally be a placebo effect. A conflict of interest may arise when new technologies are to be implemented in health care. The communication between professionals evaluating scientific results and decision makers is challenging. Quality assurance of this process may be obtained by use of expert panels working under the auspices of an official institution.

Effects of transmyocardial revascularization on myocardial perfusion and systolic function assessed by nuclear and magnetic resonance imaging methods.

OBJECTIVE: There is no obvious explanation, except placebo, to the symptomatic effect of transmyocardial laser revascularization (TMR) in patients with refractory angina. Whether TMR improves myocardial perfusion or relieves symptoms without altering cardiac function is not clarified. METHODS: One hundred patients with refractory angina were randomized 1:1 to TMR (CO2 laser) and medical treatment, or medical treatment alone. Technetium 99m (99mTc)-tetrofosmin myocardial perfusion tomography (SPECT), quantitative myocardial perfusion gated SPECT (QGSPECT), technetium 99m (99mTc) multiple gated acquisition radionuclide ventriculografi (MUGA) and cine-magnetic resonance imaging (cine-MRI) were performed at baseline and after 3 and 12 months. RESULTS: Following TMR, a slight reduction in left ventricular ejection fraction (LVEF) (p < 0.05) was observed (MUGA and QGSPECT) compared to baseline. Inclusion of incomplete studies (QGSPECT) revealed a significant reduction in LVEF and increase in left ventricular end-diastolic volume (LVEDV) (p < 0.05) compared to a control group. Otherwise, no between-group comparisons showed statistically significant differences. CONCLUSION: TMR did not improve myocardial perfusion, but led to a reduction in LVEF and increase in LVEDV, however not significantly different from the control group.

Interaction between chemokines and oxidative stress: possible pathogenic role in acute coronary syndromes.

OBJECTIVES: We sought to study the relationships between chemokines and oxidative stress in acute coronary syndrome. BACKGROUND: In view of existing knowledge on the participation of leukocytes and oxidative stress in the pathogenesis of acute coronary syndrome, we hypothesized that chemokines may play a role in recruiting and activating leukocytes in this disorder. METHODS: The levels of chemokines and oxidative stress were studied in 38 patients with stable and 38 with unstable angina and in 20 controls. In separate in vitro experiments the effect of chemokines on reactive oxygen species in monocytes and the effect of antioxidants on chemokine levels in these cells were also studied. RESULTS: 1) Angina patients had raised serum levels of chemokines in both cross-sectional and longitudinal testing, with particularly high levels of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory peptide (MIP)-1-alpha in unstable disease. 2) T cells, and particularly monocytes, seem to contribute to the raised IL-8, MCP-1 and MIP-1-alpha levels in unstable angina. 3) Concomitantly, and significantly correlated with MCP-1 and IL-8 levels, stable and particularly unstable angina patients had decreased plasma levels of antioxidants and increased lipid peroxidation, suggesting enhanced oxidative stress. 4) Monocyte chemoattractant protein-1 enhanced the generation of O2- in monocytes from unstable angina patients, and the antioxidant glutathione-monoethyl ester suppressed the production of IL-8 and MCP-1 in these cells. CONCLUSIONS: Our findings suggest an interaction between chemokines and oxidative stress in unstable angina. This interaction may represent a vicious circle involved in the pathogenesis of acute coronary syndromes.

Myocardial performance after transmyocardial revascularization with CO(2)laser. A dobutamine stress echocardiographic study.

AIMS: Transmyocardial laser revascularization is a treatment for patients with severe angina pectoris not eligible for conventional revascularization. The effects on myocardial function and reversible ischaemia have not been clarified. METHODS AND RESULTS: One hundred patients with refractory angina not eligible for conventional revascularization were randomized 1:1 to receive continued optimal medical treatment or transmyocardial revascularization with CO(2)laser in addition to medical treatment. Dobutamine stress echocardiography examinations were performed at baseline and at 3 and 12 months after randomization. The effects of transmyocardial revascularization on myocardial function and reversible ischaemia were assessed by visual interpretation of cineloops at rest and during stress in a 16-segment model. After transmyocardial revascularization resting left ventricular wall motion abnormalities increased (P<0.01), whereas wall motion during dobutamine stimulation remained unchanged. The number of probably non-viable segments increased (P<0.01) with a corresponding decrease in the number of ischaemic segments. Fewer patients had the dobutamine infusion discontinued because of chest pain after transmyocardial revascularization with laser, but the chest pain threshold did not increase significantly. CONCLUSION: Following transmyocardial revascularization, resting wall motion abnormalities worsened, wall motion abnormalities during dobutamine stimulation remained unchanged and the number of probably non-viable segments increased.

Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris. Clinical results from the Norwegian randomized trial.

OBJECTIVES: The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris. BACKGROUND: Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published. METHODS: One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2. RESULTS: Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.) CONCLUSIONS: Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.

Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES).

OBJECTIVES: Our intent was to investigate the effect of the dihydropyridine calcium channel blocker amlodipine on restenosis and clinical outcome in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Amlodipine has sustained vasodilatory effects and relieves coronary spasm, which may reduce luminal loss and clinical complications after PTCA. METHODS: In a prospective, double-blind design, 635 patients were randomized to 10 mg of amlodipine or placebo. Pretreatment with the study drug started two weeks before PTCA and continued until four months after PTCA. The primary angiographic end point was loss in minimal lumen diameter (MLD) from post-PTCA to follow-up, as assessed by quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary artery bypass graft surgery and repeat PTCA (major adverse clinical events). RESULTS: Angioplasty was performed in 585 patients (92.1%); 91 patients (15.6%) had coronary stents implanted. Follow-up angiography suitable for QCA analysis was done in 236 patients in the amlodipine group and 215 patients in the placebo group (per-protocol group). The mean loss in MLD was 0.30 +/- 0.45 mm in the amlodipine group versus 0.29 +/- 0.49 mm in the placebo group (p = 0.84). The need for repeat PTCA was significantly lower in the amlodipine versus the placebo group (10 [3.1%] vs. 23 patients [7.3%], p = 0.02, relative risk ratio [RR]: 0.45, 95% confidence interval [CI]: 0.22 to 0.91), and the composite incidence of clinical events (30 [9.4%] vs. 46 patients (14.5%), p = 0.049, RR: 0.65, CI: 0.43 to 0.99) within the four months follow-up period (intention-to-treat analysis). CONCLUSIONS: Amlodipine therapy starting two weeks before PTCA did not reduce luminal loss, but the incidence of repeat PTCA and the composite major adverse clinical events were significantly reduced during the four-month follow-up period after PTCA with amlodipine as compared with placebo.

Physiologic response to gain and loss in coronary minimal luminal diameter in patients treated with coronary angioplasty: prediction of restenosis on the basis of exercise capacity.

BACKGROUND: The effect of percutaneous transluminal coronary angioplasty (PTCA) on physiologic measurements has previously been shown, but the relation between physiologic response and degree of change in coronary luminal diameter is not known. We studied the relation between exercise capacity and minimal luminal diameter before and after PTCA. We also explored the usefulness of measurement of attenuation in exercise capacity after PTCA to predict the likelihood of restenosis. METHODS: Bicycle exercise testing was performed 2 weeks before and 2 and 20 weeks after PTCA in 395 consecutively enrolled patients. Angiograms obtained before and after PTCA and 20 weeks afterward were analyzed by quantitative coronary angiography. Restenosis was defined as both angiographic (>/=50% diameter stenosis at follow-up angiography) and clinical (target-vessel revascularization), after successful PTCA. Exercise capacity was defined as the cumulative work performed divided by body weight (watt x minutes x kilograms(-1)). RESULTS: Exercise capacity increased 43% (P <.0001) from before PTCA to 2 weeks after PTCA (early increase) and decreased 4% (P =.01) from 2 to 20 weeks after PTCA (late decrease). The gain in minimal luminal diameter (Minimal luminal diameter after - Minimal luminal diameter before) was 0.92 +/- 0.46 mm. The loss in minimal luminal diameter (Minimal luminal diameter after PTCA - Minimal luminal diameter at follow-up examination) was 0.27 +/- 0.42 mm. Exercise capacity and minimal luminal diameter measured before PTCA were positively correlated (coefficient 3.3; R = 0.12; P =.01). Gain in minimal luminal diameter correlated with the early increase in exercise capacity (coefficient -3.8; R = 0.23; P <.0001). Loss in minimal luminal diameter correlated with the late decrease in exercise capacity (coefficient 3.3; R = 0.20; P <.0001). Multivariate logistic regression analysis revealed that the late decrease in exercise capacity was independently predictive of both angiographically (odds ratio 1.13; P <.0001) and clinically (odds ratio 1.12; P <.0001) defined restenosis. CONCLUSIONS: The results demonstrated a linear relation between the severity of coronary stenosis and exercise capacity measured before PTCA. The degree of coronary luminal enlargement achieved with angioplasty and the luminal reduction that occurred between PTCA and follow-up evaluation correlated with increases and decreases in exercise capacity. Attenuation in exercise capacity was found to be a strong predictor of restenosis.

Luminal loss and restenosis after coronary angioplasty. The role of lipoproteins and lipids.

AIMS: Lipoproteins and lipids, especially lipoprotein(a), have been studied as risk factors for restenosis after coronary angioplasty with conflicting results. We investigated the association between serum levels of lipoprotein(a) apolipoprotein A-1, apolipoprotein B-100, total-cholesterol, high density lipoprotein-cholesterol, triglycerides, and coronary luminal loss and restenosis after angioplasty. METHODS: The lipoproteins and lipids were measured in 305 consecutive patients who underwent successful angioplasty and reangiography 20+/-3 weeks after angioplasty. Single-vessel dilatation was performed in 251 patients. Luminal loss was defined as minimal luminal diameter post-angioplasty minus minimal luminal diameter at follow-up, divided by the interpolated reference diameter of the vessel. Restenosis was defined according to three dichotomous categorical criteria: (1) >50% diameter stenosis at follow-up (2) loss of >50% of the gain achieved by angioplasty, (3) the need for target vessel revascularization. RESULTS: There was no significant association between the serum levels of lipoproteins and lipids and luminal loss. Univariate analysis did not show any significant difference in the serum levels of any of the lipoproteins and lipids between the restenosis and no-restenosis groups. Multivariate analysis revealed that only the angiographic variables (luminal gain and post-angioplasty minimal luminal diameter) were associated with luminal loss and restenosis after angioplasty. CONCLUSION: Lipoproteins and lipids were neither associated with luminal loss nor independent risk factors for restenosis after angioplasty.

Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina. Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes.

BACKGROUND: The CD40 ligand (CD40L) on activated T cells and platelets may be activating matrix metalloproteinases, inducing procoagulant activity, and be involved in the pathogenesis of acute coronary syndromes by promoting plaque rupture in atheroma. METHODS AND RESULTS: To study the role of CD40L-CD40 interaction in coronary disease, we analyzed levels of soluble (s) and membrane-bound CD40L in the peripheral blood from 29 patients with stable angina, 26 with unstable angina, and 19 controls. Our main findings follow. (1) Patients with unstable angina had significantly raised serum levels of sCD40L when compared with patients with stable angina and controls. (2) Platelets could release large amounts of sCD40L when stimulated ex vivo with the thrombin receptor-agonist peptide SFLLRN in both patients and controls. (3) Platelets in patients with unstable angina were characterized ex vivo by decreased intracellular levels and decreased SFLLRN-stimulated release of sCD40L, which may possibly represent a higher percentage of degranulated platelets in these patients. (4) T cells in patients with unstable angina had enhanced surface expression of CD40L and increased release of sCD40L on anti-CD3/anti-CD28 stimulation in vitro when compared with patients with stable angina and controls. (5) Recombinant CD40L and serum from patients with unstable angina who had high sCD40L levels induced enhanced release of monocyte chemoattractant peptide-1 from mononuclear cells, a CC-chemokine involved in the pathogenesis of atherosclerosis. CONCLUSIONS: This first demonstration of enhanced levels of soluble and membrane-bound forms of CD40L in angina patients, with particularly high levels in patients with unstable angina, suggests that CD40L-CD40 interaction may play a pathogenic role in both the long-term atherosclerotic process and in the triggering and propagation of acute coronary syndromes.

[Late complications after treatment of Hodgkin's disease]. / Senkomplikasjoner etter behandling for Hodgkins sykdom.

Treatment of Hodgkin's disease involves chemotherapy and radiation. Both modalities may cause cardiac, pulmonary and thyroid side-effects. In a cross-sectional study, we aimed to assess the occurrence and severity of such complications. From 1980 to 1989, 129 Norwegian patients (< 50 years old) had curative treatment for Hodgkin's disease 116 (90%) of them participated in the study (follow-up period 5-13 years). Methods included lung function tests, chest X-rays, bicycle exercise tests, echocardiography and thyroid function tests. Nearly 30% of the patients reported dyspnoea on exertion and had associated reductions in lung function. Evidence of fibrosis occurred in 68%, but was associated with reduced lung function in only 12%. Pathological left-sided heart valve regurgitations were detected in 24% of the patients, pericardial thickening in 15%, and coronary artery disease in 5%. Biochemical hypothyreosis was found in 67% of the patients. We conclude that cardiac, pulmonary and thyroid dysfunctions are frequent long-term side-effects after treatment for Hodgkin's disease. We recommend annual screening of thyroid function and echocardiographic examination in patients who have received standard mantle field radiotherapy without cardiac shielding. Lung function testing should be done in individuals who require further radiation, chemotherapy or thoracic surgery.

[Current use of beta-blockers in coronary artery disease]. / Aktuell bruk av beta-blokkere ved koronar hjertesykdom.

This article presents the results of a retrospective analysis of the use of beta-blockers and current dosing of these agents in patients with coronary artery disease. While 70 to 78% of patients admitted to Norwegian university hospitals during 1990-1997 for angiographic evaluation of chest pain used beta-blockers, only 43-60% of patients with stable coronary artery disease enrolled in the 4S study in Norway received such treatment. High risk groups such as diabetics and patients with peripheral artery disease were less likely to receive beta-blockers during the early period, but were not treated differentially compared to low risk patients during recent years. Only 15% of patients with congestive heart failure received oral beta-blockers, and only 10.5% intravenous beta-blockade during acute myocardial infarction. The dosing of the most common beta-blockers were low, approximately 50% of doses shown to improve survival after acute myocardial infarction.

Effect of percutaneous transluminal coronary angioplasty on exercise in patients with and without previous myocardial infarction.

Improvement in exercise capacity is an important clinical effect of percutaneous transluminal coronary angioplasty (PTCA), and was assessed in patients with and without previous myocardial infarction (MI) undergoing PTCA. We prospectively followed patients with exercise testing before and 2 weeks after angioplasty in 415 patients, 170 (41%) of whom had a previous MI. A third exercise test was performed 20 +/- 2 weeks after PTCA in 403 patients. From left ventricular angiography obtained before PTCA, regional dyskinesia was classified into anterior or posterior locations. Both patients with and without previous MI had a significant increase in exercise capacity from before to 2 and 20 weeks after PTCA (previous MI: 31.9% and 29.3%; no MI: 50.7% and 38.2%; p <0.0001 [analysis of variance]). In patients with MI and anterior dyskinesia, in whom lesions on the left anterior descending artery were dilated or posterior dyskinesia in whom lesions on the right coronary artery were dilated, exercise capacity increased significantly from before to 2 and 20 weeks after PTCA (left anterior descending artery: 53.1% and 39.7%, p <0.0001; right coronary artery: 16.9% and 27.6%, p = 0.01 [analysis of variance]). Multivariate regression analysis revealed that male sex, no previous MI, and dilation of left anterior descending artery were significantly associated with increased exercise capacity after angioplasty adjusted for age and smoking habits, whereas left ventricular ejection fraction and end-diastolic pressure were not associated with increased exercise capacity.

Governmental steering of highly specialized medical services.

In Norway, highly specialized medicine has been under governmental steering since 1991. The Social and Health Department decides at which hospitals certain medical functions should be offered. In the field of cardiovascular medicine this has been experienced as mainly positive. The quality of the work has improved, and cooperation between hospitals has been stimulated.

Attenuated physical exercise capacity in smokers compared with non-smokers after coronary angioplasty despite similar luminal diameters.

AIMS: To study the impact of smoking on the change in exercise capacity in patients treated with coronary angioplasty. METHODS: Three hundred and sixty-eight men below 70 years of age eligible for percutaneous transluminal coronary angioplasty without previous coronary interventions were consecutively enrolled. Of the 334 patients (90.8%) who completed the study 77 (23.1%) were current smokers. Exercise tests were performed before percutaneous transluminal coronary angioplasty, 2 and 19 +/- 2.4 weeks after percutaneous transluminal coronary angioplasty. Coronary angiography was done in 333 patients (99.7%) (at mean 19 +/- 2.4 weeks). The angiograms were analysed quantitatively. RESULTS: There were no differences in the clinical and angiographic characteristics among the groups except for age. The non-smokers were older than the smokers (55.7 vs 52.4 years (P = 0.001)). Exercise capacity was equal before percutaneous transluminal coronary angioplasty in both groups (17.6 vs 16.5 W x min-1 x kg-1). Non-smokers had a significantly higher increase in exercise capacity than smokers from baseline to 2 weeks after percutaneous transluminal coronary angioplasty (mean difference 4.3 W x min-1 x kg-1 (95% CI: 2.3 to 6.2; P < 0.001)), and from baseline to 19 weeks after percutaneous transluminal coronary angioplasty (mean difference 3.9 W x min-1 x kg-1 (95% CI: 1.6 to 6.2; P < 0.001). CONCLUSION: A clinical benefit from percutaneous transluminal coronary angioplasty was seen in both groups as judged from exercise testing. Smokers had a substantially lower increase in exercise capacity than non-smokers, indicating an attenuated benefit from percutaneous transluminal coronary angioplasty among smokers.

Effect of bolus injection versus continuous infusion of furosemide on diuresis and neurohormonal activation in patients with severe congestive heart failure.

Previous studies have demonstrated that continuous infusion of furosemide results in increased diuresis and natriuresis compared with bolus administration of the drug in patients with severe heart failure. We reasoned that continuous infusion of furosemide caused less activation of neurohumoral mechanisms, since other studies have shown that bolus administration of furosemide may activate this system. We therefore tested the hypothesis that continuous administration of furosemide would increase water and sodium excretion due to less activation of neurohormones. Eight patients with severe heart failure were studied during continuous infusion over 24 h and bolus injections of furosemide twice daily in a randomized cross-over study. Bolus administration of furosemide increased diuresis and natriuresis significantly in the first 4 h after administration compared with continuous administration, but this was later reversed, resulting in similar 24 h total output. The neurohormones measured at baseline were all markedly elevated. Neither regimens of furosemide caused any further significant changes in neurohumoral response except that pro-ANF decreased more during the first 8 h after bolus administration compared to continuous infusion. This study has demonstrated that bolus administration of furosemide in conventional doses is equally effective as continuous intravenous infusion in patients with severe heart failure. This may be due to maximal neurohormonal activation in severe heart failure (NYHA III-IV) which could not be further activated by bolus administration.

Post-transplant hyperlipidaemia: low-dose lovastatin lowers atherogenic lipids without plasma accumulation of lovastatin.

OBJECTIVES: The purpose of the present study was twofold. First, to determine the frequency of hyperlipidaemia after heart transplantation (Tx) in relation to values obtained before Tx. Secondly, to examine the effect of low-dose lovastatin on possible antiatherogenic mechanisms and test the hypothesis that the side-effects are dose-dependent. SUBJECTS AND DESIGN: Retrospective study of the frequency of hyperlipidaemia disturbances in heart transplant patients. In addition, in a prospective study, the safety and efficacy of incremental low doses of lovastatin up to 20 mg day-1 were studied, with measurements of its plasma concentration in 24 cyclosporin A treated heart (n = 14) and kidney (n = 10) recipients with total cholesterol > 7.5 mmol L-1. RESULTS: Cholesterol increased markedly after heart transplantation from a pretransplant value of 5.3 (5.0,5.6) mmol L-1 to 6.7 (6.4,7.0) mmol L-1 after 1 year and then remained constant, but this increase was largely due to a 'normalization' since cholesterol decreased significantly during increasing heart failure before transplantation. Treatment with lovastatin decreased total cholesterol by 19% (P < 0.001), primarily by an effect on LDL cholesterol. HDL cholesterol increased by 15% (P < 0.05), whereas triglycerides remained unchanged. Lovastatin also caused a significant reduction in apolipoprotein B of 16%, and lipid peroxidation of 40%, whereas apolipoprotein A-I, fibrinogen, and glycerol were unchanged. Plasma concentration of lovastatin was significantly higher in transplant recipients compared with controls, but there was no accumulation during incremental dosing of lovastatin. The drug was well tolerated without significant symptoms or evidence of myopathy. CONCLUSIONS: Hyperlipidaemia is common after cardiac transplantation. Treatment with low dose lovastatin is well tolerated and has a favourable effect on atherogenic lipids.

[Restenosis and arterial remodelling after coronary angioplasty]. / Restenose og arteriell remodellering etter koronar angioplastikk.

Restenosis after coronary angioplasty (PTCA) is a complex process and is still the major problem, despite improvements in equipment and technique. Thrombus formation and intimal hyperplasia have been considered to be the main causes of the development of restenosis after primary successful angioplasty. As yet, pharmacological trials to prevent restenosis have failed to prevent it, despite the fact that the therapy has been aimed at reducing thrombus formation and intimal hyperplasia. Several new angioplasty devices have been developed. Series of observations and a few controlled trials have demonstrated restenosis rates similar to those obtained with conventional balloon angioplasty, except in the case of stent implantation, which appears to be promising. Intravascular ultrasound studies have provided new insight and a more complete understanding of the process leading to restenosis. Vascular remodeling is now considered as an important pathogenetic factor. It consists of a change in the cross-sectional vessel area and may involve an actual constriction of the artery. This may lead to lumen-narrowing and finally restenosis with minimal neointimal formation. In this review we summarise the literature on the restenosis process and the current status of the clinical trials aimed at preventing restenosis.

Increased risk of heart valve regurgitation after mediastinal radiation for Hodgkin's disease: an echocardiographic study.

OBJECTIVE: To assess by echocardiography the occurrence and degree of late cardiac sequelae after treatment for Hodgkin's disease by radiation and chemotherapy. PATIENTS AND METHODS: In Norway from 1980 to 1988, 129 patients < 50 years old with Hodgkin's disease had curative treatment with mediastinal radiation, with or without chemotherapy. 116 (90%) of these patients (mean (SD) age 37 (7) years, 67 males) were examined by echocardiography 5-13 years after treatment. 40 healthy individuals (mean (SD) age 40 (11), 20 males) were examined as controls. All those examined were in regular sinus rhythm. RESULTS: Grade > 1 (scale 0-3) aortic and/or mitral valvar regurgitation was found in 24% of the patients (15% aortic, 7% mitral, and 2% aortic+mitral), affecting 46% of the females v 16% of the males (P < 0.001). Female gender was a significant risk factor for aortic and mitral regurgitation (odds ratio 4.7, 95% confidence interval 2.0 to 11.2), whereas age, period of follow up, radiation dose, and chemotherapy were not. Thickened pericardium was diagnosed in 15% of the patients. No risk factors were identified. No cases of pericardial thickening or valvar regurgitation grade > 1 were recorded in the control group. Mean values for measured and calculated indices of systolic and diastolic function were within the normal range for patients and controls. The patients had reduced E/A ratio compared with the healthy controls (E/A 1.1 v 2.0, P < 0.001). CONCLUSIONS: Abnormal left sided valvar regurgitation was detected in one fourth of the patients, affecting the aortic valve in more than half of the cases. Females had an increased risk of valvar regurgitation. Echocardiographic screening after high-dose mediastinal radiation is recommended.