[Dofetilide to patients with heart failure and left ventricular dysfunction]. / Dofetilid til patienter med hjerteinsufficiens og dårligt fungerende venstre ventrikel.

INTRODUCTION: Dofetilide, a new class III antiarrhythmic drug, was tested for its ability to reduce mortality and morbidity in patients with congestive heart failure and left ventricular dysfunction. METHODS: In 34 Danish centers, 1518 patients with NYHA class III or IV heart failure and wall motion index of the left ventricle < or = 1.2 (ejection fraction < or = 35%) were randomized to receive dofetilide or placebo in a double blind study. The dose of dofetilide was adjusted to renal function and the QT interval. Patients were monitored continuously with ekg during the first three days in the study. Minimum follow up was one year. RESULTS: Dofetilide did not affect mortality. Hospitalizations for worsening of heart failure were reduced significantly, hazard ratio 0.75 (0.63-0.89) Dofetilide effectively converted atrial fibrillation to sinus rhythm. After one year, 61% of patients with atrial fibrillation had converted on dofetilide and 33% on placebo (p < 0.001). DISCUSSION: Dofetilide can be used to convert atrial fibrillation to sinus rhythm and to maintain sinus rhythm in patients with congestive heart failure and left ventricular dysfunction. Dofetilide does not affect mortality.

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2.

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.

Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial.

BACKGROUND: Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS: In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS: No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION: In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.

Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.

BACKGROUND: Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death. METHODS: We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause. RESULTS: During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group. CONCLUSIONS: In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.

[Sotalol and torsades de pointes ventricular tachycardia]. / Sotalol og torsade de pointes ventrikøulaer takykardi.

Sotalol is together with amiodarone the most effective antiarrhythmic. Compared to class I antiarrhythmics it has less mortality. However, sotalol can, like class IA antiarrhythmics, release life-threatening attacks of torsade de pointes ventricular tachycardia (TdP-VT), as proarrhythmia or by overdosing. TdP-VT appears in 2% of all patients treated with sotalol. In patients treated for ventricular tachycardias TdP-VT appears in 4%. Some factors increase the incidence of TdP-VT: reduced left ventricular function, hypokalaemia, hypomagnesiaemia, bradycardia, extended QT-interval and daily doses exceeding 320 mg. We recommend increased attention to these predisposing factors so as to prevent TdP-VT. Pharmacologically induced TdP-VT may be misdiagnosed as "genuine" ventricular tachycardia. This often results in increased doses of sotalol, which worsen the TdP-VT. Sotalol is renally excreted and TdP-VT can appear in patients with reduced renal function where normal doses are used. QTC prolongation above 550 ms. or severe bradycardia indicates risk of TdP-VT and should result in end of treatment or dose-reduction. Six case-stories are presented.

[Prognosis of acute myocardial infarction after introduction of thrombolytic therapy]. / Prognosen ved akut myokardieinfarkt efter introduktion af trombolysebehandling.

The present study describes the use of intravenous thrombolytic therapy, the in-hospital and the long-term mortality in a cohort of 1881 consecutive patients with confirmed myocardial infarction. Thirty-two percent received thrombolytic therapy. Common reasons for not administering thrombolytic therapy were contraindications, diagnostic problems and late hospital admission. The total in-hospital mortality was 14% among patients treated with, and 27% among those treated without thrombolytic therapy (p < 0.001). The mortality among all patients after 48 months of follow-up was 50%. Advanced age, previous myocardial infarction and a higher Killip class on admission were independent predictors of an adverse outcome. In conclusion, in an unselected population with confirmed myocardial infarction the long-term prognosis continues to be dubious, despite the advances in coronary care including intravenous thrombolytic therapy.

Planar 201Tl scintigraphy in ischaemic heart disease: a critical re-evaluation of qualitative and quantitative data analysis.

The aims of the present study were to examine the observer agreement of qualitative (visual) and quantitative (computer-assisted) analysis of planar 201Tl imaging and to compare the diagnostic values of these methods in the detection of infarcted and exercise-induced ischaemic myocardium. The study population comprised of 119 patients (aged 24-77 years) referred consecutively for stress thallium scintigraphy for either diagnostic reasons (n = 42, 35%) or for further evaluation of known coronary artery disease (CAD) (n = 77, 65%). The interobserver agreement was low with the qualitative method and significantly higher with the quantitative method: Kappa-values 0.29-0.39 vs. 0.80-0.92, P < 0.00001. Sensitivity and specificity for the detection of previous Q-wave infarct was significantly higher with the quantitative method (94% and 94%) compared to the qualitative method (77% and 74%), P < 0.01. The corresponding predictive values of a positive and a negative test were 96% and 92% vs. 80% and 70% (P < 0.01). In 86 patients in whom coronary angiography was performed the two methods did not differ significantly regarding sensitivity, specificity and predictive values for the diagnosis of reversible ischaemia or rather CAD. However, when 22 patients with a maximal exercise heart rate < 80% of the predicted target heart rate were excluded the sensitivity was increased with both techniques and was significantly higher with the quantitative method. We conclude that qualitative image analysis has an unacceptably low reproducibility and that quantitative image analysis increases the diagnostic value of 201Tl scintigraphy considerably in both the detection of previous infarcts and, provided a sufficient exercise level is achieved, in the disclosure of reversible myocardial ischaemia.

[Influence of various therapeutic models on survival after prehospital cardiac arrest]. / Forskellige behandlingsmodellers indflydelse på overlevelse efter praehospitalt hjertestop.

We analyzed the outcome after prehospital cardiac arrest in a part of greater Copenhagen. Four different emergency medical systems were acting: a system providing basic life support only (group 1), a system providing basic life support and early defibrillation (group 2), a system providing basic life support followed by advanced cardiac life support (group 3), and a system providing basic life support and early defibrillation followed by advanced cardiac life support (group 4). Over a 2-year period 624 cases of cardiac arrest were reported, 34 were discharged from hospital. The survival to discharge from hospital and the one-year survival were significantly better in group 4. Our data reconfirm that early advanced cardiac life support improves survival rates for prehospital cardiac arrest.

[Atrial flutter with paroxysmal 1:1 atrioventricular conduction]. / Atrieflagren med paroksystisk 1:1 atrioventrikulaer overledning.

Three patients with "lone" paroxysmal atrial flutter complicated by paroxysms of 1:1 AV conduction are presented. One patient (42 years of age) had been misdiagnosed as an neurotic for 18 years. The mechanism, diagnosis and treatment of the condition are outlined. The most characteristic symptoms are dizzy spells and fainting. The recommended diagnostic procedures include long term ECG recording by telemetry or Holter, exercise-ECG and oesophageal-ECG.

Atrial fibrillation in the Wolff-Parkinson-White syndrome.

Atrial fibrillation in patients with Wolff-Parkinson-White (WPW) syndrome may lead to syncope, ventricular fibrillation, and sudden death. In a follow-up study of 241 patients with WPW syndrome in a relatively unselected population, 26 patients had documented atrial fibrillation (11%). These patients were followed up after 1-37 years (median 11 years; mean 15 years). During this period, 2 of 26 died suddenly. These 2 patients had the shortest RR interval during spontaneous atrial fibrillation (less than or equal to 220 msec), greater than or equal to 1 episodes of syncope, and a persistent delta wave in all available electrocardiograms. In comparison, sudden or tachycardia-related death was seen in 4 of the 241 patients. This difference is not statistically significant. Thus, atrial fibrillation of 26 patients with WPW syndrome was surprisingly well tolerated in our follow-up study with only 2 sudden deaths.

[Cardiac arrhythmias. Diagnosis and treatment]. / Kardiale arytmier. Diagnostik og behandling.

This review is a task force report prepared by a working group appointed by the Danish Society of International Medicine. The report gives guidelines for the pharmacological and non-pharmacological treatment of tachyarrhythmias and bradyarrhythmias and for the referral of patients to centers with electrophysiological experience.

[A randomized study of streptokinase and recombinant tissue plasminogen activator, with and without heparin, in patients with acute myocardial infarction. The results of GISSI-2/International tPA/SK Mortality Trial]. / Randomiseret undersøgelse af streptokinase og rekombinant vaevsplasminogenaktivator, med og uden heparin, hos patienter med akut myokardieinfarkt. Resultater of GISSI-2/International tPA/SK Mortality Trial.

A total of 20,981 patients in 14 countries with suspected myocardial infarction (AMI) admitted within six hours from onset of symptoms, were randomized to recombinant tissue plasminogen activator (tPA) (100 mg over 3 hours) or streptokinase (SK) (1.5 MU over one hour). Half of the patients were also randomly allocated to subcutaneous heparin (12,500 U twice daily). The hospital mortality was similar with SK and tPA (8.5% vs. 8.9%), and similar with and without heparin (85.5% vs. 8.9%). Likewise, no differences were found in the number of cardiac complications. More strokes occurred with tPA (1.3%) than with SK (0.9%), while more major bleeds were seen with SK (0.9%) than with tPA (0.6%). More major hemorrhages were also observed with heparin (1.0%) than without heparin (0.5%), whereas, heparin did not affect the incidence of stroke or reinfarction. Fewer allergic reactions were observed with tPA (0.2%) than with SK (1.7%). It is concluded that tPA and SK are equally effective and safe for use, and should be recommended for treatment in patients with an AMI of less than six hours duration.

Prevalence and significance of an abnormal exercise ECG in asymptomatic males. Outcome of thallium myocardial scintigraphy.

During a 3-year period 2500 asymptomatic male aviators were screened routinely for coronary artery disease by maximal bicycle exercise testing. In 55 cases (2.1%) the exercise ECG was abnormal (40 subjects exhibited ST depression, 14 ventricular ectopic activity and in one subject both abnormalities were observed). Further non-invasive studies (Thallium scintigraphy, echocardiography and ambulatory ECG monitoring for arrhythmias) identified nine out of the 55 aviators (16%, 95% CL = 7-26%) with an abnormal exercise test as having cardiac disease. We conclude that standard exercise ECG by itself is a poor predictor of coronary artery disease in asymptomatic subjects because of too many false-positives when the pre-test likelihood of disease is low. Therefore, exercise electrocardiography cannot be recommended as the single routine screening test for coronary artery disease in such individuals.

Management of Stokes-Adams syndrome.

Stokes-Adams attacks are related to paroxysmal or chronic atrioventricular (AV) block (50-60%), sinoatrial (SA) block (30-40%) or paroxysmal tachycardia or fibrillation (0-5%). In between attacks most patients present with sinus rhythm, a large part with widened QRS complex. A minor proportion of patients present with chronic AV block. ECG is very rarely normal. Diagnosis is based on ECG recording during fainting. In patients with sinus rhythm and bundle-branch block or AV block, ECG monitoring should be performed in hospital, since Stokes-Adams syndrome in these patients is a potentially life-threatening disease. In sick sinus syndrome where the suspected arrhythmia is not life-threatening, ambulatory ECG by Holter monitoring can be performed to establish the diagnosis. In cases where ECG monitoring leaves doubt, an electrophysiologic study including His bundle electrography and sinus node recovery time may support the diagnosis, although normal findings do not preclude the diagnosis. Pacemaker implantation should be performed in Stokes-Adams syndrome, as oral drug treatment is ineffective. The dual-chamber pacemaker presents the advantages of both physiological heart rate and AV synchrony, but has troublesome side effects. Most patients with tachycardia/bradycardia syndromes require supplementary anti-arrhythmic treatment, and in some patients additional long-term anticoagulation should be considered.

[Treatment of acute myocardial infarction--an elucidative report]. / Behandling af akut myokardieinfarkt--en klaringsrapport.

The present-day optimal treatment of patients with acute myocardial infarction (AMI) is reviewed. The prehospital phase should be as brief as possible. Emergency observation and treatment in hospital should be initiated without delay. Schematic stages for mobilization have been discarded and free mobilization is recommended. Routine acute intervention with thrombolysis is recommended for patients in whom symptoms have been present for 6-12 hours and treatment with Aspirin is recommended. Beta-blocking agents are recommended for patients with increased risk after discharge. Treatment of ventricular and supraventricular arrhythmias, block and cardiac failure are reviewed in detail. Patients without complications should be monitored for three to five days and may be discharged after seven to ten days. Exercise ECG should be carried out at discharge to assess the working capacity, ischaemia and subjective reaction. The importance of good patient information is emphasized. Cessation of smoking, control of lipids and blood pressure are important as secondary interventions. As far as possible, outpatient control should be offered after discharge. The criteria for referral to specialized cardiological departments are established both for emergency and elective referral. Patients under the age of 70 years with high risk for repeated AMI or death after discharge (with residual ischaemia) should possibly be referred for coronary arteriography.