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Biomedical subjects

K Swedberg

Publications and source records attributed to K Swedberg.

At least 37 records · Page 2Linked to original sources
PubMed2001

Practical recommendations for the use of ACE inhibitors, beta-blockers and spironolactone in heart failure: putting guidelines into practice.

Surveys of prescribing in both hospitals and primary care have shown delays in translating improved survival data from clinical trials into clinical practice thereby denying patients the benefits of proven treatments, such as the angiotensin converting enzyme inhibitors. This may be due to unfamiliarity with clinical guidelines and concerns about adverse events. Recent trials have shown that substantial improvements in survival are associated with spironolactone and beta-blocker therapy. In order to accelerate the uptake of these treatments, and to ensure that all eligible patients should receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of heart failure. The objective of these recommendations is to provide practical guidance for non-specialists in order to support the implementation of evidenced-based therapy for heart failure. These practical recommendations are meant to supplement rather than replace existing guidelines.

Adrenergic beta-Antagonists↗
PubMed2001

Pharmacodynamic models for the cardiovascular effects of moxonidine in patients with congestive heart failure.

AIMS: To assess the pharmacodynamics of moxonidine in patients with functional NYHA Class II-III congestive heart failure (CHF). METHODS: A parallel population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed to assess the effect of moxonidine (0.1, 0.2, 0.3 mg twice daily) and placebo treatment on plasma noradrenaline (NA) levels, standing systolic blood pressure (SBP), and heart rate (HR) over 12 weeks in 97 patients with CHF using a parallel group design with dose escalation. A sequential analysis was also developed, where the relative changes in NA concentration were related to both SBP and HR. RESULTS: In the parallel PD analysis, an effect delay was shown for all three end points (NA, SBP, and HR). An inhibitory Emax model was used to characterize the concentration-effect relationships. For SBP and HR, the EC50 value increased over time. For NA, there was a positive baseline drift over the 12 weeks; this was interpreted as disease progression. Moxonidine delayed this increase by 9.8 weeks. For SBP, there was a circadian pattern at baseline. In the sequential PD analysis, the relationship between the drug response (NA) and SBP or HR was best described by an inhibitory Emax model. No effect delays between the response and effects were found. CONCLUSIONS: Effects of moxonidine on NA, SBP, and HR could be quantified by an effect compartment model in the presence of disease progression and circadian variations. Disease progression, as judged by increasing NA levels with time, was delayed by moxonidine. A direct relationship was found between NA and SBP/HR.

Adult↗
PubMed2001

Hemodynamic profiles of advanced heart failure: association with clinical characteristics and long-term outcomes.

BACKGROUND: Classifying patients with advanced congestive heart failure (CHF) by baseline measures of congestion and perfusion has been used to estimate hemodynamic status and to select and titrate therapy. We describe clinical characteristics of 4 hemodynamic profiles-wet/cold, wet/warm, dry/cold, and dry/warm-in patients with advanced CHF and assess relations between symptoms, physical signs, and outcomes with each profile. METHODS AND RESULTS: We retrospectively assessed baseline symptoms, physical-examination variables, and 1-year outcomes of 440 patients in a randomized trial. With univariable and multivariable logistic regression, we examined relations of physical-examination variables to hemodynamic profiles. We also assessed the rates of death and death or readmission by profile. Severity of CHF symptoms did not predict the wet-versus-dry profile or cold-versus-warm status, despite significant differences in hemodynamics among groups. Of the physical-examination variables, only a lower proportional pulse pressure was a significant multivariable predictor of the wet category. Among wet patients (n = 348), this same variable was the only significant multivariable predictor of the cold category. For dry patients (n = 92), the cold category was predicted in multivariable analysis by supine heart rate and hepatomegaly. Survival was similar among profiles: wet/cold, 54.2% (n = 91); wet/warm, 58.3% (n = 105); dry/cold, 78.9% (n = 15); and dry/warm, 67.1%, P =.13 (n = 49). Event-free survival also was similar among profiles: wet/cold, 22.0% (n = 37); wet/warm, 29.4% (n = 53); dry/cold, 42.1% (n = 8); and dry/warm, 31.5%, P =.44 (n = 23). CONCLUSIONS: The patient's history and physical examination alone may lead to inaccurate estimation of hemodynamic status and thus suboptimal management for patients with advanced CHF.

Aged↗
PubMed2001

ST variability during the first 4 hours of acute myocardial infarction predicts 1-year mortality.

BACKGROUND: Early and complete myocardial reperfusion is the goal when treating a patient with acute myocardial infarction. To achieve this in each individual, an on-line, accurate, easily handled and preferably noninvasive technique to monitor flow alterations is needed. Recurrent ST-segment elevation has been shown to reflect cyclic disturbances in perfusion. METHODS: We have retrospectively analyzed ST variability in 102 patients with acute myocardial infarction randomized to 100 mg of rt-Pa or placebo. Patients were monitored for 24 hours using vectorcardiography. RESULTS: Patients alive at one year (86%) had significantly less ST variability during the first four hours: 4.3 versus 7.1 episodes, P = 0.007. Patients having six or more ST episodes showed a 31.3% one-year mortality as compared to no mortality in patients having no ST variability. Furthermore ST variability was reduced by fibrinolysis. CONCLUSION: Early ST variability detectable in real time is associated with worse outcome.

Algorithms↗
PubMed2000

Gene therapy enhances the antiproliferative effect of radiation in intimal hyperplasia.

BACKGROUND: Although ionizing radiation (IR) has been demonstrated to attenuate vessel wall restenosis and intimal hyperplasia (IH), dose-related mural injury and atrophy are possible deleterious side effects. We tested the hypothesis that a radiosensitizing strategy may improve IR-induced inhibition of in vivo vascular smooth muscle cells (VSMCs) without influencing apoptotic cell death. METHODS: In 28 New Zealand White rabbits, the right common carotid artery (CCA) was injured and subjected to low-flow conditions to promote IH. The CCA was transfected with an adenoviral vector incorporating the cytosine deaminase (CD) gene (1 x 10(9) PFU/ml). 5-Fluorocytosine (5-FC), a prodrug that is converted to the radiosensitizing agent 5-fluorouracil (5-FU) by CD, was thereafter administered intravenously. The CCA was exposed to 5 Gy IR at 24 h. Intimal/medial (I/M) area and thickness ratios were determined in the harvested CCAs at 14 days. VSMC proliferative and apoptotic indices were assessed with immunohistochemistry. RESULTS: A 50% reduction in I/M area was found in rabbits treated with IR and IR + CD/5-FC (0.19 +/- 0.03 and 0.18 +/- 0.02) when compared with untreated controls (UC) (0.37 +/- 0.06) (P = 0.005). This finding was substantiated by attenuation of I/M thickness in the IR groups [0.47 +/- 0.13 (IR), 0.41 +/- 0.11 (IR + CD/5-FC), 0.61 +/- 0.17 (UC)] (P = 0.007). The number of proliferating VSMCs was notably smaller when IR was combined with CD/5-FC (4.17 +/- 1.16 vs 2.97 +/- 1.09 log transformed cells/mm(2), P < 0.07). Apoptosis was similar in all groups. CONCLUSIONS: Both IR alone and IR combined with a radiosensitizing agent are effective in attenuating experimental IH. However, combination therapy is synergistic and achieves greater inhibition of VSMC proliferation and may involve selective killing of radioresistant S-phase VSMCs. IR + CD/5-FC represents a novel therapeutic strategy that offers potential for long-term control of IH.

Animals↗
PubMed2000

Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors.

BACKGROUND: Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. METHODS: Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). RESULTS: The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). CONCLUSIONS: Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.

Aged↗
PubMed2000

Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group.

OBJECTIVES: We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA). BACKGROUND: Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI. METHODS: This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0-36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial). RESULTS: Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use. CONCLUSIONS: Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.

Aged↗
PubMed2000

The effects of moxonidine, a novel imidazoline, on plasma norepinephrine in patients with congestive heart failure. Moxonidine Investigators.

OBJECTIVE: To evaluate the dose response relationship of moxonidine on plasma concentration of norepinephrine during acute and chronic administration in patients with congestive heart failure (CHF). BACKGROUND: Sympathetic activation is increased in heart failure. Moxonidine is an imidazoline ligand acting on the central nervous system (CNS) receptors to decrease sympathetic activation. METHODS: Ninety-seven patients with heart failure and New York Heart Association class II-III symptoms and ejection fraction <40% were randomized to placebo or one of three target doses of moxonidine, 0.1, 0.2 or 0.3 mg administered twice daily. An initial dose of moxonidine 0.1 mg twice a day (b.i.d.) was followed by weekly increments of 0.1 mg b.i.d. until target dose. The second and third study days occurred after four weeks (at target dose) and after 12 weeks, respectively. At each study day, repeated blood samples were drawn. RESULTS: There was a significant dose-related decrease of systolic blood pressure across all three study days. Heart rate decreased significantly on study day 3 in a dose-related manner. The acute 2 h decrease in plasma norepinephrine in response to all three doses of moxonidine was significantly different compared with placebo after four and 12 weeks. There was a significant linear relation between dose and plasma norepinephrine after four and 12 weeks in both 2 h peak and the time averaged effect (>8 h). The number of adverse events was similar in the moxonidine and placebo groups. CONCLUSIONS: The increased sympathetic activation in CHF can be reduced by moxonidine through CNS inhibition.

Administration, Oral↗
PubMed2000

Implantable left ventricular assist systems (LVAS): recent results. A report from a series of meetings sponsored by the Study Group on Advanced Heart Failure of the Working Group on Heart Failure.

Implantable left ventricular assist systems (LVAS) consist of implantable pumps with small control consoles and power sources that can be worn externally. These systems provide far greater patient mobility and independence than external pumps with bulky control consoles. Patients with implantable LVAS can be discharged from hospital and are able to return to work and resume active sports. Most patients have received these systems as a bridge to heart transplantation. Clinical status and quality of life improve dramatically after device implantation and survival on support (60-70% after approx. 100 days of support) is acceptable compared with transplant candidates on medical therapy. Patient selection and adverse events, primarily bleeding, thromboembolism and infection, are important issues with LVAS. In the future, long-term support and bridging to myocardial recovery may become important indications for LVAS.

Adolescent↗
PubMed2000

The Euro Heart Failure Survey of the EUROHEART survey programme. A survey on the quality of care among patients with heart failure in Europe. The Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The Medicines Evaluation Group Centre for Health Economics University of York.

BACKGROUND: The EUROHEART programme is a rolling programme of cardiovascular surveys among the member nations of the European Society of Cardiology (ESC). These surveys will provide information on the nature of cardiovascular disease and its management. This manuscript describes a survey into the nature and management of heart failure. AIMS: The EuroHeart Failure survey aims to describe the quality of hospital care, diagnostic and therapeutic, for patients with suspected or confirmed heart failure in ESC member countries. Patients will be interviewed subsequent to hospital discharge to assess their understanding of their condition, side effects from and their compliance with therapy and their satisfaction with the management for heart failure. The quality of management will be judged against the recommendations contained in the ESC guidelines on diagnosis and treatment of heart failure. Outcome will be further assessed by repeat interviews in 6-12 months time. A further survey of heart failure in 2001/2002 is also planned. METHODS: A prospective survey of all deaths and discharges from medical (cardiology, internal medicine and geriatric medicine) and cardiac surgical wards to identify patients with heart failure, suspected or confirmed. Approximately 70 hospital clusters, comprising two to six hospitals in each cluster, in 24 member countries of the ESC are conducting the study. At the time of writing, approximately 30000 deaths and discharges have been screened and approximately 4000 patients have been enrolled. CONCLUSIONS: The EuroHeart Survey will allow actual practice to be compared to ESC guidelines on the diagnosis and treatment of heart failure. The surveys and guidelines should prove mutually informative. The main EuroHeart Failure project will be completed by late 2000. However, new centres volunteering to participate in the study (contact corresponding author) may be accepted providing they have the necessary research personnel and provided funding can be agreed for statistical support and administration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Comparison of QT dispersion during atrial fibrillation and sinus rhythm in the same patients, at normal and prolonged ventricular repolarization.

AIMS: Drug-induced increase in QT dispersion has been associated with increased risk of ventricular proarrhythmia. The aim of the present study was to compare QT dispersion during atrial fibrillation and sinus rhythm in the same patients at normal and prolonged ventricular repolarization. METHODS AND RESULTS: Sixty-one patients who had had chronic atrial fibrillation for 8 +/- 14 months received a 6 h infusion of the Ikr-blocker almokalant, the first 90 min of which are used for this analysis. The following day, after conversion to sinus rhythm, by almokalant (n = 19) or direct current cardioversion (n=42), an identical 90 min infusion was administered. Prior to infusion, there was no difference in precordial QT dispersion between atrial fibrillation and sinus rhythm (29 +/- 12 vs 36 +/- 17 ms, P=ns). During infusion, at prolonged repolarization, the increase in QT dispersion was greater during sinus rhythm than during atrial fibrillation (58 +/- 49 vs 30 +/- 15 ms, P=0.0011, after 30 min infusion). No correlation was found between QT dispersion and the QT or RR interval. CONCLUSION: QT dispersion during atrial fibrillation does not differ from QT dispersion during sinus rhythm during normal repolarization. while measurement of QT dispersion during prolonged repolarization, induced by an Ikr-blocker, yielded larger values during sinus rhythm than during atrial fibrillation.

Action Potentials↗