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Biomedical subjects

Lars Køber

Publications and source records attributed to Lars Køber.

72 records · Page 4Linked to original sources
PubMed2003

The prognostic value of QTc interval and QT dispersion following myocardial infarction in patients treated with or without dofetilide.

BACKGROUND: Acute myocardial infarction (MI) is associated with an increased risk of death, with a 1-year mortality close to 10% in patients discharged from hospital alive. During the first year following MI, close to 50% of deaths are assumed to be due to arrhythmic events. HYPOTHESIS: The study was undertaken to determine the interaction between dofetilide treatment and pretreatment QTc interval and QT dispersion regarding mortality in patients with left ventricular (LV) dysfunction and a recent MI. METHODS: The study population consisted of 894 patients with a recent MI and LV systolic dysfunction, who were randomized to receive dofetilide or placebo. The study was a substudy of the Danish Investigations of Arrhythmia and Mortality on Dofetilide-MI (DIAMOND-MI). RESULTS: During a minimum of 1-year follow-up, 261 (29%) patients died. Baseline QTc interval did not hold any prognostic value on mortality for placebo-treated patients. When pretreatment QTc interval was <429 ms, dofetilide resulted in a 45% reduction of mortality (hazard ratio 0.55, 95% confidence limits 0.34-0.88, p<0.02) compared with placebo. When QTc interval was >429 ms, dofetilide did not influence mortality significantly. This study revealed no statistically significant relation between QT dispersion, dofetilide treatment, and mortality. CONCLUSION: In patients with a recent MI, LV dysfunction, and a short baseline QTc interval, dofetilide is associated with significant survival benefit. This benefit is not seen with a longer QTc interval. QT dispersion is not a risk factor in this population.

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PubMed2003

The angiotensin converting enzyme inhibitor trandolapril has neutral effect on exercise tolerance or functional class in patients with myocardial infarction and reduced left ventricular systolic function.

AIMS: To study the effect of angiotensin-converting enzyme (ACE) inhibitor trandolapril on exercise tolerance time (ETT) and New York Heart Association (NYHA) classification in patients with reduced left ventricular systolic dysfunction (LVSD) after acute myocardial infarction (AMI). METHODS AND RESULTS: The TRAndolapril Cardiac Evaluation (TRACE) was a randomized controlled study designed to evaluate the effect of trandolapril on mortality in 1749 consecutive Danish patients with LVSD after AMI. NYHA class was recorded every 3 months in all patients. In a prospective sub-study, 254 patients underwent exercise tolerance tests at 1, 3 and 12 months. The two treatment arms showed equal improvement in NYHA class both in the entire and exclusively symptomatic population over 4 years of follow-up (P=ns). ETT increased equally in both treatment arms at 1, 3, 12 months (P=ns). A mean of 12mg/day of furosemide was spared in trandolapril arm (P=0.001). CONCLUSIONS: Trandolapril had a mild diuretic-sparing effect. These results emphasis the importance of explaining to patients that ACE inhibitors provide protection against death and hospitalisation for heart failure but do not have any significant effect upon symptoms.

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PubMed2003

Long-term survival in patients hospitalized with congestive heart failure: relation to preserved and reduced left ventricular systolic function.

AIMS: The purpose of this study was to evaluate the influence of left ventricular systolic function on the survival in a large consecutive cohort of patients hospitalized with congestive heart failure and to determine how left ventricular systolic function interacts with co-morbid conditions in terms of prognosis. METHODS AND RESULTS: Analysis of survival data from 5491 patients admitted for new or worsening heart failure to 34 departments of cardiology or internal medicine in Denmark from 1993-1996 was carried out. A standardized echocardiogram was available for 95% of the patients, and left ventricular systolic function was estimated using wall motion index score. Follow-up time was 5-8 years. Patients with preserved systolic function were older, more frequently female, and had less evidence of ischemia than patients with systolic dysfunction. After 1 year, 24% of the patients had died. Low wall motion index was a potent independent predictor of death (risk ratio for one unit increase, 0.60 (0.56-0.64)), and was of greater prognostic significance in younger patients and patients with a history of myocardial ischemia. However, even in patients with preserved systolic function, mortality was high (1 year mortality, 19%). CONCLUSION: In hospitalized heart failure patients, particularly in younger patients with ischemic heart disease, mortality risk is inversely related to left ventricular systolic function.

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PubMed2003

Congestive heart failure with preserved left ventricular systolic function after acute myocardial infarction: clinical and prognostic implications.

AIMS: To characterise the prevalence, in-hospital complications, management, and long-term outcome of patients with congestive heart failure but preserved left ventricular systolic function after acute myocardial infarction. METHODS: 3166 consecutive patients screened for entry in the Bucindolol Evaluation in Acute Myocardial Infarction Trial with definite acute myocardial infarction and echocardiographic assessment of left ventricular systolic function were included between 1998 and 1999 in this prospective observational study. Main outcome measures were occurrences of in-hospital complications and all cause mortality. RESULTS: Congestive heart failure was seen during hospitalisation in 1464 patients (46%), 717 patients had preserved left ventricular systolic function (wall motion index > or =1.3 corresponding to ejection fraction > or =0.40), and 732 patients had systolic dysfunction (wall motion index <1.3). One year mortality in patients with no heart failure, heart failure with preserved systolic function, and heart failure with systolic dysfunction were 6, 22 and 35%, P<0.0001. Unadjusted risk of death from all causes associated with heart failure and preserved systolic function was 3.3 (95% CI 2.8-4.0), and after adjustment for baseline characteristics and left ventricular systolic function in multivariate Cox proportional hazards analysis the risk was 2.1 (95% CI 1.7-2.6), P<0.0001. CONCLUSIONS: Congestive heart failure is frequently present in patients with preserved left ventricular systolic function, and is associated with increased risk of in-hospital complications and death following acute myocardial infarction.

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PubMed2003

Does conversion and prevention of atrial fibrillation enhance survival in patients with left ventricular dysfunction? Evidence from the Danish Investigations of Arrhythmia and Mortality ON Dofetilide/(DIAMOND) study.

BACKGROUND: Atrial fibrillation is a common arrhythmia in patients with left ventricular dysfunction associated with increased morbidity and mortality. The present study investigated the potential of dofetilide to restore and maintain sinus rhythm in patients with left ventricular dysfunction, which might reduce mortality and hospitalizations. METHODS AND RESULTS: In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies, 506 patients were in atrial fibrillation (AF) or atrial flutter (AFl) at baseline. Over the course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%) placebo-treated patients. In these patients, the probability of maintaining sinus rhythm for 1 year was 79% with dofetilide versus 42% with placebo ( P < 0.001). Dofetilide had no effect on all-cause mortality, but restoration and maintenance of sinusrhythm (independent of study treatment) was associated with a significant reduction in mortality (risk ratio [RR], 0.44; 95% CI, 0.30 to 0.64; P < 0.0001). In addition, dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P < or = 0.005) or congestive heart failure (RR, 0.69; 95% CI, 0.51 to 0.93; P < or = 0.02) rehospitalization. CONCLUSIONS: Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease. The present study suggests that restoration of sinus rhythm--on placebo or dofetilide--is associated with improved survival.

Anti-Arrhythmia Agents↗
PubMed2003

Prognostic importance of systolic and diastolic function after acute myocardial infarction.

BACKGROUND: Although risk stratification after acute myocardial infarction (AMI) often is focused on systolic left ventricular (LV) function, it appears that a more complete study of ventricular function including assessment of LV filling would be useful. Doppler echocardiography allows assessment of LV filling, and with the use of the Tei index (sum of isovolumic relaxation and contraction times divided by ejection time), a global estimate of ventricular function may be obtained. Therefore, the aim of this study was to determine the prognostic importance of LV systolic, diastolic, and overall LV function in a large consecutive population with AMI. METHODS: Echocardiography was performed within 6 days of AMI. LV systolic, diastolic, and global function was assessed by means of wall motion index (WMI), mitral flow pattern, and Tei index. The primary end point was all-cause death. RESULTS: Of 799 enrolled patients, 197 died during a median follow-up of 34 months. In a multivariate model including WMI and clinical parameters, WMI had important prognostic information. When mitral filling pattern and quartiles of Tei index were added to the model, restrictive filling (mitral deceleration time <140 ms) was associated with a risk ratio of 1.9 (95% CI 1.3-2.7, P <.0001, Tei index values of >0.68/0.56-0.68/0.46-0.55/<0.46 were associated with risks of 4.0 [2.1-6.9]/2.3 [1.5-3.9]/2.1 [1.2-3.6]/1.0, P <.001). In this model, WMI had no prognostic value (P =.18). CONCLUSIONS: Mitral deceleration time and the Tei index have independent and important prognostic value after AMI.

Adult↗
PubMed2003

Prehospital behaviour of patients admitted with acute coronary syndrome or witnessed cardiac arrest.

OBJECTIVE: To study prehospital behaviour of patients admitted with acute coronary syndrome or witnessed cardiac arrest. DESIGN: Structured interview of 250 consecutive patients with acute coronary syndrome and relatives of 48 patients with witnessed cardiac arrest. The following courses of action were studied: contact the emergency medical service (centre); contact the general practitioner from the emergency service or the general practitioner during working hours; self-transportation to the emergency department; or as the first action to call the emergency medical service. RESULTS: Forty-four per cent of the patients admitted with cardiac arrest expressed no prior symptoms. Two-thirds of patients with typical symptoms interpreted it as cardiac-still only half took action within 20 min. Fifty per cent of patients who called a physician were delayed by wrong advice or misinterpretation. One hundred and thirteen patients (45%) knew of thrombolytic therapy. Twenty-seven of 75 patients with knowledge of the benefit of prompt treatment with thrombolysis, acted in accordance with this awareness. CONCLUSION: Patients misinterpret symptoms of acute coronary syndrome and are misguided when calling for medical assistance. Perceiving jeopardy had positive influence on the behaviour. Awareness of therapeutic options influences the decision-making process.

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PubMed2003

Dofetilide: a new drug to control cardiac arrhythmia.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Mortality, and especially morbidity caused by AF, are major and growing health problems in the western world. AF is strongly associated with arterial hypertension, congestive heart failure, valvular heart disease, ischaemic heart disease, and with prevalence increasing with age. A variety of drugs have been used to terminate or prevent AF but, as many antiarrhythmic agents have the potential life-threatening pro-arrhythmia, safety problems remain. Dofetilide (Tikosyn, Pfizer), a new Vaughan Williams class III antiarrhythmic agent, has been developed and approved for the treatment of AF. In contrast to most antiarrhythmic agents, the development programme included two safety studies in high-risk patients. Dofetilide is effective and safe when an elaborate procedure for dosing is implemented. Along with amiodarone and betablockers, dofetilide is the only antiarrhythmic drug, which is recommended by guidelines for the treatment of AF in a wide range of patients.

Anti-Arrhythmia Agents↗
PubMed2003

Can antiarrhythmic drugs save lives in patients with congestive heart failure?

Although arrhythmic death is a common cause of death in patients with congestive heart failure (CHF), numerous trials involving prophylactic antiarrhythmic drug treatment have yielded few gains. To date, only beta-blockers have shown a distinct mortality-reducing effect and despite the antiarrythmic effect of gamma-blockers, results point towards causes other than the antiarrhythmic effect in obtaining this beneficial effect. Atrial fibrillation is an often-encountered arrhythmia in patients with CHF and recent trials have cast doubt on the present treatment strategy of persistently striving to obtain sinus rhythm. This paper outlines the results of the large clinical trials dealing with antiarrhythmic drug treatment in CHF patients with or without atrial fibrillation and certain subgroup analysis and future treatment possibilities are discussed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Fractal analysis of heart rate variability and mortality after an acute myocardial infarction.

The recently developed fractal analysis of heart rate (HR) variability has been suggested to provide prognostic information about patients with heart failure. This prospective multicenter study was designed to assess the prognostic significance of fractal and traditional HR variability parameters in a large, consecutive series of survivors of an acute myocardial infarction (AMI). A consecutive series of 697 patients were recruited to participate 2 to 7 days after an AMI in 3 Nordic university hospitals. The conventional time-domain and spectral parameters and the newer fractal scaling indexes of HR variability were analyzed from 24-hour RR interval recordings. During the mean follow-up of 18.4 +/- 6.5 months, 49 patients (7.0%) died. Of all the risk variables, a reduced short-term fractal scaling exponent (alpha(1) <0.65), measured by detrended fluctuation analysis, was the most powerful predictor of mortality (univariate relative risk 5.05, 95% confidence intervals [CI] 2.87 to 8.89, p <0.001). A low scaling exponent alpha(1) predicted death in the patients with and without depressed left ventricular function (p <0.001 and p <0.01, respectively). Several other HR variability parameters also predicted mortality in univariate analyses, but in a multivariate analysis after adjustments for clinical variables and left ventricular ejection fraction, alpha(1) was the most significant independent HR variability index that predicted subsequent mortality (relative risk 3.90, 95% CI 2.03 to 7.49, p <0.001). Short-term fractal scaling analysis of HR variability is a powerful predictor of mortality among patients surviving an acute myocardial infarction.

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PubMed2002

[Electrocardiographic Q wave is of no significance after myocardial infarction].

A Q wave has high specificity in identifying acute myocardial infarction and is associated with infarcts of a larger size. A considerable number of studies have addressed the prognostic value of the presence of a Q wave in the electrocardiogram before and after the introduction of thrombolytic therapy. Overall, these studies have demonstrated that a Q wave has slight, or even no, prognostic impact, especially in studies performed since the introduction of thrombolytic therapy. Some therapeutic choices have been suggested according to the presence or absence of Q waves. These suggestions depend basically on subgroup analysis with different results and hence have not documented that a Q wave has any value in therapeutic choices. A pathological Q wave has no significant prognostic value after a myocardial infarction and there is very doubtful documentation that a Q wave has any value for therapeutic choice.

Electrocardiography↗
PubMed2002

Effect of dofetilide on QT dispersion and the prognostic implications of changes in QT dispersion for patients with congestive heart failure.

AIMS: Drug-induced changes in QT dispersion may be a way of detecting harmful repolarisation abnormalities for patients receiving antiarrhythmic drugs affecting ventricular repolarisation. METHODS AND RESULTS: In 463 congestive heart failure (CHF) patients enrolled in the Danish Investigations Of Arrhythmia and Mortality On Dofetilide-CHF (DIAMOND-CHF) study, both pre-treatment and on-treatment day 2-6 QT dispersion was available from standard 12-lead ECGs. Patients were randomised in a double-blind manner to receive either placebo or dofetilide, a new class III antiarrhythmic drug. During a median follow-up of 19 months (minimum 1 year), 179 patients (39%) died (135 patients from cardiac causes). Changes in QT dispersion did not predict all-cause or cardiac mortality for patients treated with dofetilide in multivariate survival analysis (Risk ratio: 1.02, 95% confidence interval: 0.97-1.08, P>0.4). This finding was independent of pre-treatment QT dispersion. Dofetilide caused a small QT dispersion increment of 8 ms, not different from the changes seen in the placebo group (3 ms). CONCLUSION: For patients with CHF and reduced left ventricular systolic function, changes in QT dispersion following treatment with dofetilide do not predict all-cause or cardiac mortality. The dofetilide-induced QT dispersion changes are small and comparable to those seen in placebo treated patients.

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PubMed2002

The incomplete bucindolol evaluation in acute myocardial infarction Trial (BEAT).

UNLABELLED: The aim of this study was to evaluate the efficacy of adding the beta-blocker bucindolol to standard therapy shortly after a myocardial infarction in a high-risk population with reduced left ventricular function. METHODS: The study was planned to include 2000 patients with an enzyme confirmed myocardial infarction and severely reduced left ventricular function determined by echocardiography (corresponding to ejection fraction < or =0.35). The primary endpoint was all cause mortality and the secondary endpoints were time to first event of death, progression of heart failure or reinfarction-and the components. The study was closed early due to discontinuation of development of bucindolol by the manufacturer. Therefore, 170 patients were randomised to receive bucindolol and 173 to receive placebo. RESULTS: There were 27 deaths in the bucindolol group and 30 in the placebo group, hazard ratio of bucindolol 0.88 (95% confidence limits 0.5-1.5; P=0.6). There were 9/4 (bucindolol/placebo, P=0.16) heart failure events and 5/17 (P=0.01) reinfarctions in the bucindolol/placebo groups. CONCLUSION: Due to early closure it is unknown whether bucindolol changes mortality in high-risk post myocardial infarct patients when added to best medical therapy. The frequency of reinfarction was significantly reduced.

Adrenergic beta-Antagonists↗
PubMed2002

QTc interval in the assessment of cardiac risk.

In the United States alone 300,000-400,000 people die of sudden cardiac death every year. Much of this mortality is assumed to be caused by ventricular tachyarrhythmias. Prolonged QTc reflect cardiac repolarization prolongation and/or increased repolarization inhomogenity known to be associated with increased risk of arrhythmias. The paper gives a review of the possibilities to assess the risk of ventricular arrhythmia and/or cardiac death from QTc. Prolonged QTc may hold independent prognostic importance for mortality in common diseases as ischemic heart disease and diabetes mellitus where as the prognostic importance in heart failure and arterial hypertension is more uncertain. In more rare diseases as the inborn long QT syndrome the QT interval gives not only important hint to the diagnosis but the magnitude also provides information on prognosis. QTc has probably no independent prognostic importance in hypertrophic cardiomyopathy or in the arrhythmogenic right ventricular disease. The degree of QTc prolonging during treatment with QTc prolonging drugs is prognostic for the risk of ventricular arrhythmia in form of torsade de pointes and QTc prolonging drugs should probably not be prescribed for patients with a QTc greater than 460 ms and withdrawn if QTc exceeds 500 ms during treatment. Data from the DIAMOND study suggest that QTc can be used to point out those heart failure patients who will benefit from antiarrhythmic therapy.

Cardiovascular Diseases↗
PubMed2002

The immediate future for the medical treatment of atrial fibrillation.

Atrial fibrillation is the most commonly sustained cardiac arrhythmia and a common reason for mortality and morbidity. Atrial fibrillation causes disease for three reasons: i) the ventricular rate is often high, which leads to symptoms ranging from discomfort to life threatening heart failure; ii) the rhythm causes loss of atrioventricular synchrony, which reduces diastolic filling and may lead to heart failure; and iii) atrial contraction is lost leading to stagnant blood that again may lead to atrial thrombi and peripheral embolism. Thus, the treatment of atrial fibrillation is focused on the maintenance of sinus rhythm, rate control and prevention of embolism. For the maintenance of sinus rhythm, all drugs under current development are potassium channel blockers; the so-called class III anti-arrhythmic drugs. Those which have been further investigated appear to be valuable for maintenance of sinus rhythm but all carry a significant risk of pro-arrhythmia, in particular Torsade de Pointe ventricular tachycardia. Rate control has been a focus of treatment for many years and several very old drugs, including digoxin, are used for this. There is, to the author's knowledge, no current effort for evaluating new drugs for this indication. Prevention of embolism has for many years been obtained with vitamin K antagonists for which the clinical evidence is overwhelming. Previous attempts to replace vitamin K antagonists with aspirin have not been fruitful. A large number of newer anticoagulation regimes are in development, but to the author's knowledge only a single thrombin inhibitor is actively being developed for atrial fibrillation.

Journal Article↗
PubMed2002

A benefit-risk assessment of class III antiarrhythmic agents.

With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural heart disease, and class IV drugs are avoided in heart failure. Unfortunately, arrhythmias are a growing problem due to an increase in the incidence of atrial fibrillation and sudden death. The population is becoming older and more patients survive for a longer time period with congestive heart failure, which again increases the frequency of both supraventricular as well as ventricular arrhythmias. Class III antiarrhythmic drugs act by blocking repolarising currents and thereby prolong the effective refractory period of the myocardium. This is believed to facilitate termination of re-entry tachyarrhythmias. This class of drugs is developed for treatment of both supraventricular and ventricular arrhythmias. Amiodarone, sotalol, dofetilide, and ibutilide are examples of class III drugs that are currently available. Amiodarone and sotalol have other antiarrhythmic properties in addition to pure class III action, which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and secondary prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide suggest that patients with atrial fibrillation may have a mortality reduction with these drugs. However, this needs to be tested in a prospective trial. Similarly, subgroups that will benefit from prophylactic treatment with class III antiarrhythmic drugs may be found based on QT-intervals or - in the future - from genetic testing. Class III drugs are effective in converting atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines, amiodarone and dofetilide have their place as second-line therapy except for patients with heart failure where they are first line therapy being the only drugs where the safety has been documented for this group of high risk patients.

Action Potentials↗
PubMedDate not supplied

Prevalence, prognostic significance, and treatment of atrial fibrillation in congestive heart failure with particular reference to the DIAMOND-CHF study.

Atrial fibrillation is a growing health problem and the most common cardiac arrhythmia, affecting 5% of persons above the age of 65 years. The number of hospital discharges for atrial fibrillation has more than doubled in the past decade. It occurs very often in patients with congestive heart failure and the prevalence increases with the severity of the disease. These two conditions seem to be linked together, and congestive heart failure may either be the cause or the consequence of atrial fibrillation. The prognosis of atrial fibrillation is controversial, but studies indicate that atrial fibrillation is a risk factor in congestive heart failure patients. In the last 10-15 years, significant advances in the treatment of heart failure have improved survival, whereas effective management of atrial fibrillation in heart failure patients still awaits similar progress. Empirically, two strategies have evolved for treatment of atrial fibrillation: 1) rhythm control, which means conversion to sinus rhythm and maintenance of sinus rhythm; and 2) rate control, which means reduction of heart rate to an acceptable frequency. It is unknown whether one of these strategies is better than the other. In this review the authors discuss the prevalence, impact, and treatment of atrial fibrillation in heart failure patients.

Anti-Arrhythmia Agents↗