Biomedical subjects

F Waagstein

Publications and source records attributed to F Waagstein.

At least 37 records · Page 2Linked to original sources

PubMed2000

Induction of cardiomyopathy in severe combined immunodeficiency mice by transfer of lymphocytes from patients with idiopathic dilated cardiomyopathy.

Growing evidence suggests that autoimmune mechanisms play an important role in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). The aim of the study was to evaluate the effects of transfer of lymphocytes from patients with DCM into severe combined immunodeficiency (SCID) mice on the heart structure and function. Thirty CB-17 SCID (6-8 weeks old) mice were used and divided into 3 groups (n = 10). Mice were injected intraperitoneally with up to 25 x 10(6) peripheral blood lymphocytes (PBL) from either patients with DCM which contain human autoantibodies against cardiac beta1-adrenergic receptors and M2-muscarinic receptors (DCM group) or PBL from healthy controls (control-H group). Ten mice did not receive any injections and were used as baseline controls (control-N group). Echocardiography and morphological studies were performed seventy five days after the transfer. Results showed that in DCM group, left ventricle dimensions (LVD) in diastole were increased (4.2 +/- 0.1mm) as compared to both control-H group (3.8 +/- 0.1mm) and control-N group (3.6 +/- 0.1 mm) (p < 0.01). Further, there was a trend for increased LVD in systole. Fractional shortening was not different between groups. Histological evaluation revealed accumulation of human lymphocytes in the capillaries and scarce infiltration of the lymphocytes in the hearts from DCM group. Diffuse fibrosis was significant increased in DCM mice as compared to mice receiving PBL from normal subjects (2.2 +/- 0.3% vs. 0.8 +/- 0.1%, p < 0.01). In conclusion, transfer of the PBL from the patients with DCM was able to induce early stage of heart dilatation in SCID mice. These data provide for the first time the direct evidence supporting that the autoimmune mechanism is important in the pathogenesis of human DCM.

Animals↗

PubMed1999

Potential risk of beta-blockade withdrawal in congestive heart failure due to abrupt autonomic changes.

Beta-Blockers reduce mortality in patients with congestive heart failure and a proposed mechanism has been changes of autonomic tone. Heart rate variability is a non-invasive tool to estimate cardiac autonomic tone. The aim was to study changes of heart rate variability in patients with congestive heart failure on placebo, on the beta1-selective antagonist metoprolol or 24 h after metoprolol withdrawal. Forty-five patients with congestive heart failure were studied with Holter recordings. Heart rate variability measurements were performed before, after 6-12 months of treatment with 150 mg metoprolol/placebo, or 24 h after discontinued metoprolol. After treatment, patients on beta-blockade had a significantly longer mean RR interval and changes of heart rate variability, suggesting elevated vagal tone. Patients monitored in the rebound phase of beta-blocker withdrawal had a significant vagal reduction to the level of the placebo group. There was also a nonsignificant trend towards increased sympathetic tone (LF/HF over 24 h), compared with the beta-blockade group. Heart rate variability indicates an elevated vagal tone during treatment with metoprolol but beta-blockade withdrawal shifts the autonomic balance towards lower vagal and higher sympathetic tone within 24 h. These results could imply a potential risk when abruptly discontinuing beta-blockade medication in these patients.

Adolescent↗

PubMed1999

Bioenergetic, functional and morphological consequences of postinfarct cardiac remodeling in the rat.

Despite recent advances in the treatment, severe chronic heart failure (CHF) remains a syndrome associated with high mortality. Therefore, the search for new agents to improve both patient symptoms and survival, as well as the pursuit for detailed knowledge about pathophysiology of the failing heart, will continue to depend on relevant animal models. Large acute myocardial infarction (MI) initiates complex changes in the geometrical, structural, and biochemical architecture of both infarcted and non-infarcted regions of ventricular myocardium, which can profoundly affect left ventricular function and prognosis. In this paper we present a new model for non-invasive cardiac (31)P MRS in the rat. Volume-selective (31)P magnetic resonance spectroscopy and echocardiography were used for evaluation of myocardial energy metabolism, cardiac morphology and function in rats 3 days and 3 weeks after induction of large MI. The phosphocreatine:adenosine triphosphate (PCr:ATP) ratio was decreased in rats with MI comparing with controls both at 3 days (1.6+/-0.06 vs 2.7+/-0.04; mean+/-s.e.m. P<0.0001) and 3 weeks (1.6+/-0.07 v 2.7+/-0.02 P<0.0001) postinfarct. The results from the study demonstrate that postinfarct cardiac remodeling is a rapid process of changes not only in cardiac geometry, structure and function but also in myocardial energy metabolism after large transmural MI in the rat.

Adenosine Triphosphate↗

PubMed1999

High and low pulmonary vascular resistance in heart transplant candidates. A 5-year follow-up after heart transplantation shows continuous reduction in resistance and no difference in complication rate.

BACKGROUND: In heart transplantation candidates, high pulmonary vascular resistance has been found to decrease promptly after heart transplantation without any further reduction during follow-up. Pulmonary hypertension has been described as associated with an increased peri- and postoperative complication rate and mortality. This study describes the evolution of pulmonary vascular resistance and the outcome for patients during 5 years following heart transplantation. METHODS AND RESULTS: Haemodynamic data, complication rate and mortality have been analysed during 5-year follow-up in all patients (n = 80) who were heart transplanted at Sahlgrenska University Hospital from 1988 through 1990. We found a significant and continuous reduction in pulmonary vascular resistance both in patients with a pre-operative high (> 3 Wood Units; n = 36), but reversible on nitroprusside, and pre-operative low (< or = 3 Wood Units; n = 44) pulmonary vascular resistance. A multivariate analysis showed that a pre-operative high mean pulmonary artery and low mean pulmonary capillary wedge pressure predicted the decline in pulmonary vascular resistance during 5 years after heart transplantation. The need for a postoperative assist device, complication rate, and early and late mortality were independent of the pre-operative level of pulmonary vascular resistance. CONCLUSIONS: A continuous reduction in pulmonary vascular resistance during 5 years following heart transplantation was found in patients with both high, but reversible, and low pre-operative resistance levels. The outcome and survival were independent of the pre-operative pulmonary vascular resistance level.

Adolescent↗

PubMed1999

Heart rate dependency of cardiac performance in heart failure patients treated with metoprolol.

AIMS: To investigate whether a low heart rate is necessary to maintain improvement in myocardial function after long-term treatment with a beta-blocker in patients with heart failure. METHODS AND RESULTS: Forty-eight patients with congestive heart failure were investigated: 30 patients with dilated cardiomyopathy participating in a placebo-controlled trial (15 on placebo, 15 on metoprolol), and 18 patients treated by metoprolol in an open protocol. Investigations of spontaneous heart rate and of matched paced heart rates were performed at baseline and after 3, 6 and 12 months of follow-up by radionuclide angiography. There were significant signs of improvement in systolic indices of the spontaneous heart rate in the metoprolol-treated group (peak ejection rate: 0.98 to 1.32 end-diastolic volume.s-1, P = 0.015) as compared to placebo (1.14 to 1.19 end-diastolic volume.s-1, not significant). Similar effects were observed during the matched paced heart rate (peak ejection rate: metoprolol 0.91 to 1.38 end-diastolic volume.s-1, P = 0.037; placebo 1.22 to 1.12 end-diastolic volume.s-1, not significant). No effects were observed in the early peak filling rate. Left ventricular volumes decreased during metoprolol treatment, both for the spontaneous heart rate and during matched pacing. CONCLUSIONS: These data imply that beta-blocker treatment improves the force-frequency relationship of myocardial performance. A lower heart rate is not necessary to maintain cardiac function on a short-term basis, once myocardial recovery has occurred.

Adrenergic beta-Antagonists↗

PubMed1999

Graft coronary artery disease is strongly related to the aetiology of heart failure and cellular rejections.

AIMS: To identify risk factors for the development of coronary artery disease after heart transplantation. METHODS AND RESULTS: In consecutive heart transplanted patients, who underwent coronary angiography at the first year follow-up, the aetiology of heart failure in 113 was ischaemic heart disease or dilated cardiomyopathy. Development of clinically significant graft coronary artery disease was analysed vs recipient and donor pre- and post-transplantation variables. At 1, 5 and 9 years follow-up, coronary artery disease had developed in 4%, 16%, and 20% of the included patients, respectively. Among patients with ischaemic heart disease as the aetiology of heart failure, 38% developed graft coronary artery disease, while the corresponding figure for patients with dilated cardiomyopathy was 9% (P<0.001) during 9 years of follow-up. In multivariate regression analysis, the aetiology of ischaemic heart disease and the number of cellular rejections were independent predictors of developing graft coronary artery disease, with risk ratios of 5.8, (95% confidence interval of 2.2-14.8 (P=0.0003)) and 3.3, (95% confidence interval of 1.7-6.5 (P=0.0004)), respectively. Classical risk factors for coronary artery disease did not influence the development of graft coronary artery disease. CONCLUSIONS: Ischaemic heart disease as the aetiology of heart failure and the number of cellular rejections were powerful independent predictors of development of graft coronary artery disease following heart transplantation. The low incidence of graft coronary artery disease among patients with dilated cardiomyopathy implies that coronary angiography after heart transplantation can be made on a more selective basis.

Adolescent↗

PubMed1999

Hypertonic saline without or with dextran-70 in the treatment of experimental acute myocardial ischemia and reperfusion.

OBJECTIVE: To evaluate the effects of treatment with hypertonic saline without (HS) or with dextran (HSD) on cardiac function and myocardial damage during reperfusion after acute myocardial ischemia. DESIGN: A prospective, randomized, controlled study. SETTING: Animal laboratory at a university medical center. SUBJECTS: Three-month-old male, crossbred (Swedish landrace, Yorkshire, and Hampshire) pigs. INTERVENTIONS: The pigs were anesthetized and catheterized. A mid-sternal thoracotomy was performed, the pericardial sac was opened, and the left anterior descending artery was dissected free and occluded for 45 mins. A 10-min treatment period with 4 mL/kg HS (7.5%), HSD (7.5%/6%), or normal saline (0.9%) was started 5 mins before reperfusion. After a reperfusion period of 240 mins, biopsies from the ischemic area were taken. Thereafter, the hearts were excised and subjected to a staining procedure (triphenyltetrazoliumchloride and Evan's blue), and the left ventricle was sliced for assessment of the size of the infarcted area and the area at risk. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics and myocardial performance were monitored before, during, and for 240 mins after 45 mins of acute left anterior descending artery occlusion. Alterations in blood chemistry and serum levels of markers of myocardial damage were repeatedly analyzed during the experimental procedure. Biopsies from the injured myocardium were analyzed for adenosine triphosphate, adenosine 5'-diphosphate, adenosine monophosphate, creatine phosphate, lactate, and glucose. Infarct sizes and areas at risk were planimetrically quantified. HS was not found to enhance, but rather to depress, cardiac performance at reperfusion, whereas HSD improved hemodynamics and myocardial contractility. HS or HSD administration was not found to increase the ischemia-induced myocardial damage. CONCLUSIONS: The administration of HSD but not HS will improve hemodynamics and myocardial performance during reperfusion after 45 mins of myocardial ischemia. The documented myocardial ischemic injury was not affected by any of the fluid therapies. Therefore, the present data do not support previously suggested detrimental effects of HS on myocardial ischemic injury.

Analysis of Variance↗

PubMed1999

Glucose turnover and adipose tissue lipolysis are insulin-resistant in healthy relatives of type 2 diabetes patients: is cellular insulin resistance a secondary phenomenon?

To elucidate potential mechanisms for insulin resistance occurring early in the development of type 2 diabetes, we studied 10 young healthy individuals, each with two first-degree relatives with type 2 diabetes, and 10 control subjects without known type 2 diabetic relatives. They were pairwise matched for age (35 +/- 1 vs. 35 +/- 1 years), BMI (23.6 +/- 0.6 vs. 23.1 +/- 0.4 kg/m2), and sex (four men, six women). Glucose turnover was assessed during a euglycemic clamp at two insulin levels (low approximately 20 mU/l; high approximately 90 mU/l), and abdominal subcutaneous adipose tissue (SAT) lipolysis and blood flow were concomitantly studied with microdialysis and 133Xe clearance. HbA1c was higher in patients with type 2 diabetic relatives than in control subjects (4.8 +/- 0.1 vs. 4.5 +/- 0.1%, P < 0.02), but fasting glucose, insulin, and C-peptide levels were similar. During the clamp, the insulin sensitivity index for glucose disposal was lower (P < 0.03) in relatives than in control subjects (low 12.0 +/- 1.6 vs. 18.1 +/- 1.4; high 9.4 +/- 0.8 vs. 12.9 +/- 0.6 [100 x mg x l x kg(-1) x mU(-1) x min(-1)]). This difference was partially attributed to slightly higher clamp insulin levels in the relatives (P < 0.03), suggesting an impaired rate for insulin clearance. SAT lipolysis measured as in situ glycerol release did not differ under basal conditions (2.0 +/- 0.2 vs. 2.1 +/- 0.2 micromol x kg(-1) x min(-1)), but the suppression during the insulin infusion was less marked in relatives than in control subjects (glycerol release: low 0.92 +/- 0.09 vs. 0.68 +/- 0.16; high 0.71 +/- 0.10 vs. 0.34 +/- 0.10 micromol x kg(-1) x min(-1); P < 0.03). Plasma nonesterified fatty acids also tended to be higher in relatives than in control subjects during the insulin infusion (NS). In contrast, in vitro experiments with isolated subcutaneous adipocytes displayed similar effects of insulin in relatives and control subjects with respect to both glucose uptake and antilipolysis. In conclusion, insulin action in vivo on both lipolysis and glucose uptake is impaired early in the development of type 2 diabetes. Since this impairment was not found in isolated adipocytes, it may be suggested that neural or hormonal perturbations precede cellular insulin resistance in type 2 diabetes.

Adipocytes↗

PubMed1998

Myocardial turnover of endogenous opioids and calcitonin-gene-related peptide in the human heart and the effects of spinal cord stimulation on pacing-induced angina pectoris.

Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe coronary artery disease. In the present study, 14 patients were subjected to right-sided atrial catheterization and atrial pacing. The patients were paced to angina during a control session and during spinal cord stimulation. Myocardial extraction of beta-endorphin (BE) during control pacing (8 +/- 22%) changed to release at the maximum pacing rate during treatment (-21 +/- 47%, a negative value representing release). Furthermore, the results indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene-related peptide. In addition, it is implied that SCS may induce myocardial release of BE which could explain the beneficial effects in myocardial ischemia.

Aged↗

PubMed1997

Effect of metoprolol on the prognosis for patients with suspected acute myocardial infarction and indirect signs of congestive heart failure (a subgroup analysis of the Göteborg Metoprolol Trial).

The aim of this study is to describe the impact of early treatment with metoprolol on prognosis during 1 year of follow-up in patients with suspected acute myocardial infarction (AMI) and indirect signs of congestive heart failure (CHF). Patients aged 40-74 years who presented within 48 hours of onset of symptoms raising suspicion of AMI were assessed for inclusion. All patients participated in the Göteborg Metoprolol Trial and had indirect indices of CHF according to various clinical criteria. As soon as possible after hospital admission, patients received either placebo or metoprolol (15 mg) divided into 3 intravenous injections, then oral treatment, 200 mg daily for 3 months. Thereafter, most patients in both treatment groups received metoprolol in an open manner. Among the 1,395 randomized patients, 262 (19%) had signs of mild-to-moderate CHF before randomization. Of these, 131 were randomized to metoprolol and 131 to placebo. During the first 3 months, mortality was 10% among patients randomized to metoprolol versus 19% among patients randomized to placebo (p = 0.036). The corresponding figures for the first year were 14% and 27%, respectively (p = 0.0099). Patients randomized to placebo who showed signs of CHF had a 1-year mortality rate of 28% compared with 10% among patients without such signs (p <0.001). The results suggest that early treatment with metoprolol markedly reduces mortality in patients having suspected AMI and signs of CHF.

Adrenergic beta-Antagonists↗

PubMed1997

Efficacy of beta blockers in idiopathic dilated cardiomyopathy and ischemic cardiomyopathy.

Despite the well-documented benefits of beta blockade in a variety of cardiovascular conditions, the value of beta blockade in congestive heart failure (CHF) is still in question. The concept of neurohormonal blockade in heart failure has, however, brought beta blockade into focus. There is experimental evidence for the value of blocking sympathetic activation in CHF, and increased sympathetic activation may be an etiologic factor for development of CHF. Clinical studies have shown that long-term beta blockade improves both systolic and diastolic function. The effects on exercise tolerance and quality of life seem to differ between beta1-selective and nonselective beta blockers in favor of the beta1-selective blockers. To date, results of all trials reveal a consistent pattern of decreased cardiovascular morbidity. In one trial of metoprolol, fewer heart transplantations were required; such a reduction may have a great impact on healthcare costs associated with heart failure. Improved long-term survival found by one study must be confirmed in additional trials: 3 such survival trials (with metoprolol, bisoprolol, and bucindolol) are now in progress.

Adrenergic beta-Antagonists↗

PubMed1997

Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover.

AIMS: Spinal cord stimulation has been used in the treatment of intractable angina pectoris since the beginning of the 1980s. This study was designed to investigate whether the documented anti-ischaemic effects of spinal cord stimulation are mediated through a decrease in sympathetic activity. METHODS AND RESULTS: Ten patients with a spinal cord stimulator implanted as anti-anginal treatment were included in the study. Atrial pacing until the patient experienced moderate angina was performed and after 50 min rest the procedure was repeated during spinal cord stimulation. Total body and cardiac norepinephrine spillover was calculated and the former was found to have increased during pacing (47%, P = 0.02). When spinal cord stimulation was applied, total body norepinephrine spillover decreased at a comparable pacing rate (18%, P = 0.02). Cardiac norepinephrine spillover was not affected during the procedure. CONCLUSION: The results of this study indicate that the anti-ischaemic effect of spinal cord stimulation is not due to reduced cardiac sympathetic activity. However, spinal cord stimulation decreases overall sympathetic activity which may benefit the heart, possibly by reducing oxygen demand.

Aged↗

PubMed1997

The role of beta-blockers in left ventricular dysfunction and heart failure.

It was first reported by our group in 1975 that heart failure due to idiopathic dilated cardiomyopathy (IDC) could be improved by long term treatment with a beta-blocker, starting at a low dose and continuing with a stepwise up-titration. Since then, many studies have been performed in patients with heart failure of various aetiologies and the beneficial effects of long term beta-blockade have been confirmed. About 3000 patients have been included in randomised studies in which beta-blockade, given for more than 2 months, mostly elicited significant improvements in functional class, exercise capacity, cardiac function, quality of life and/or morbidity. When started at a very low dose (one-tenth to one-twentieth of the doses generally used in angina or hypertension), the treatment is well tolerated in most patients. In these studies, various types of beta-blockers were used, including beta1-selective blockers and nonselective blockers with additional properties (vasodilator and antioxidative) such as metoprolol, bisoprolol, bucindolol and carvedilol. Several large studies have also reported benefits on mortality and morbidity. In the Metoprolol in Dilated Cardiomyopathy (MDC) trial, metoprolol treatment in patients with IDC resulted in a 34% reduction of the primary combined endpoint, total number of deaths and need for cardiac transplantation. In the Cardiac Insufficiency Bisoprolol Study (CIBIS), in patients with idiopathic as well as ischaemic cardiomyopathy, there was a nonsignificant 20% reduction in mortality. In the US carvedilol studies (n = 1094), also in patients with ischaemic and idiopathic cardiomyopathy, carvedilol reduced mortality by 65%, which was highly significant. A nonsignificant reduction in mortality was observed in the Australia-New Zealand (ANZ) Heart Failure Study with carvedilol. In all these studies there was a reduction in hospitalisations, with all drugs being generally well tolerated. It can thus be concluded that the beneficial effects of beta-blockers on cardiac function and morbidity have been documented in a large number of studies in selected groups of patients. The treatment has been accepted in some countries by the regulatory authorities. Larger, placebo-controlled studies are needed to convincingly demonstrate a reduction in total mortality as observed in the pooling of the 4 US carvedilol studies. Such studies are in progress for various beta-blockers, which may lead to acceptance of their routine clinical use in patients with congestive heart failure.

Adrenergic beta-Antagonists↗

PubMed1996

Changes in early and late diastolic filling patterns induced by long-term adrenergic beta-blockade in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: beta-Blockers have been used in patients with idiopathic dilated cardiomyopathy to improve cardiac performance and theoretically would be beneficial to diastolic function. However, there are few reports on changes in diastolic function during chronic pharmacological treatment of congestive heart failure. METHODS AND RESULTS: The present study was a substudy in the international Metoprolol in Dilated Cardiomyopathy Trial. Transmitral Doppler echocardiography was used to evaluate diastolic function in 77 patients randomly assigned to placebo (n = 37) or metoprolol (n = 40). The patients were treated for 12 months. Changes in Doppler flow variables in the metoprolol group implied a less restrictive filling pattern, expressed as an increase in E-wave deceleration time (placebo, 185 +/- 126 to 181 +/- 64 ms; metoprolol, 152 +/- 63 to 216 +/- 78 ms; P = .01, placebo versus metoprolol). Maximal increase in deceleration time had occurred by 3 months, whereas systolic recovery was achieved gradually and maximal effect was seen by 12 months of treatment. Although deceleration time was correlated to heart rate at baseline, changes in deceleration time were not significantly correlated to changes in heart rate during treatment. CONCLUSIONS: During the first 3 months of treatment, maximal effects on diastolic variables were reached, whereas the most prominent effect on systolic function was seen late in the study. It is suggested that effects on diastolic filling account for subsequent later myocardial systolic recovery. The E-wave deceleration time, which in recent studies has been shown to be a powerful predictor of survival, was significantly improved in the metoprolol-treated patients.

Adrenergic beta-Antagonists↗

PubMed1996

Quality of life on treatment with metoprolol in dilated cardiomyopathy: results from the MDC trial. Metoprolol in Dilated Cardiomyopathy trial.

Quality of life in heart failure patients is receiving increased attention as a reflection of a treatment's potential secondary benefit of general well-being and daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was conducted as a large, multicenter trial to establish the effects of metoprolol on mortality and need for heart transplantation in patients with symptomatic idiopathic cardiomyopathy. It was found that metoprolol was well tolerated, improved symptoms and cardiac function, and prevented clinical deterioration in patients with symptomatic idiopathic dilated cardiomyopathy. Quality of life was evaluated as a secondary endpoint in 345 out of 383 randomized patients using a disease-specific questionnaire, the Quality of Life in Heart Failure Questionnaire, depicting physical activity, somatic symptoms, emotions, and life satisfaction. In a comparison of patients treated with metoprolol or placebo, patients treated with metoprolol noted a significantly more favorable response than those treated with placebo in terms of the overall treatment evaluation (p < 0.05). Additionally, an analysis of the changes from baseline to 18 months, using 95% confidence intervals, revealed that patients treated with metoprolol showed a significant improvement from baseline to 18 months in life satisfaction, physical activity, and the total score, while patients treated with placebo did not change at all. The improvement in quality of life was supported by the correlations with improvement in traditional clinical parameters.

Adrenergic beta-Antagonists↗

PubMed1996

Cardiac nuclear hormone receptor mRNA in heart failure in man.

Eight donor hearts and six explanted hearts due to dilated cardiomyopathy, normal skeletal muscle and liver were analysed. Glucocorticoid receptor (GR) and thyroid hormone receptor (T3R) isoforms beta 1, beta 2, alpha 1 and alpha 2 mRNA abundance were determined by solution hybridization. Both GR and T3R receptor mRNA isoforms were lower in the myocardium as compared to skeletal muscle and in particular to liver. GR mRNA abundance was higher than that of any T3R isoform while the sum of ligand-binding isoforms (beta 1, beta 2 and alpha 1) were similar in the myocardium and in skeletal muscle as opposed to the liver where GR mRNA was higher. GR mRNA abundance was similar in right and left ventricles from donor hearts and in cardiomyopathy. T3R beta 1 showed higher levels in the right ventricle with higher levels in cardiomyopathy as compared to donor heart. T3R isoform alpha 1 and especially the alpha 1/alpha 2 ratio were lower in left ventricle in cardiomyopathy compared to donor hearts. In conclusion, GR and T3R isoforms mRNA abundance are low in the human myocardium. In the failing myocardium GR and T3R beta 2 and alpha 2 show no signs of reactivity while T3R beta 1 and alpha 1 mRNA adapt.

Adolescent↗

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↗

PubMed1995

Idiopathic dilated cardiomyopathy among Swedish patients with congestive heart failure.

Idiopathic dilated cardiomyopathy (IDCM) is an exclusion diagnosis. Although it is a prognostically important entity and a common indication for cardiac transplantation, the incidence and age distribution of idiopathic IDCM in a well-defined population today is unknown. The present study intended to estimate the proportion of IDCM among congestive heart failure (CHF) patients, and to evaluate its prognostic implications. The records of all 16-65-year-old patients hospitalized for CHF or IDCM during a 6-year period (n = 2711) were evaluated in a defined region of Western Sweden (1.05 million inhabitants 16-65 years of age). Twenty-two percent (584/2711) of these records contained no plausible cause of CHF or IDCM, and among living patients an obvious aetiology was lacking in 27% (411/1516). These 411 patients were subsequently offered a diagnostic investigation including echocardiography, and were compared to a randomly selected healthy control group (n = 103). Of 411 patients, 293 accepted the investigation and 286 had acceptable echocardiographic recordings, indicating left ventricular dilatation and systolic dysfunction in 30%. From the hospital records, 170 patients were identified as new cases of IDCM during the 6-year period. Adding another 34 cases revealed by our diagnostic procedures yielded an age-gender standardized incidence rate of 29.2 cases per 10(6) persons/year. The incidence of IDCM increased considerably with age, although in younger patients its relative contribution to heart failure was greater. The incidence of IDCM was higher in the urban compared to the rural parts of the region 21 vs 32/10(6); P = 0.013). The estimated prevalence was 131/10(6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗