Leif Spange Mortensen

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.

BACKGROUND There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).

A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome

AIMS In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any difference between single-lead atrial pacing (AAIR) and dual-chamber pacing (DDDR). METHODS AND RESULTS We randomly assigned 1415 patients referred for first pacemaker implantation to AAIR (n = 707) or DDDR (n = 708) pacing and followed them for a mean of 5.4 ± 2.6 years. The primary outcome was death from any cause. Secondary outcomes included paroxysmal and chronic atrial fibrillation, stroke, heart failure, and need for pacemaker reoperation. In the AAIR group, 209 patients (29.6%) died during follow-up vs. 193 patients (27.3%) in the DDDR group, hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.88-1.29, P = 0.53. Paroxysmal atrial fibrillation was observed in 201 patients (28.4%) in the AAIR group vs. 163 patients (23.0%) in the DDDR group, HR 1.27, 95% CI 1.03-1.56, P = 0.024. A total of 240 patients underwent one or more pacemaker reoperations during follow-up, 156 (22.1%) in the AAIR group vs. 84 (11.9%) in the DDDR group (HR 1.99, 95% CI 1.53-2.59, P < 0.001). The incidence of chronic atrial fibrillation, stroke, and heart failure did not differ between treatment groups. CONCLUSION In patients with sick sinus syndrome, there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing. AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation. These findings support the routine use of DDDR pacing in these patients. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00236158.

Simple Risk Stratification at Admission to Identify Patients With Reduced Mortality From Primary Angioplasty

Background—Randomized trials comparing fibrinolysis with primary angioplasty for acute ST-elevation myocardial infarction have demonstrated a beneficial effect of primary angioplasty on the combined end point of death, reinfarction, and disabling stroke but not on all-cause death. Identifying a patient group with reduced mortality from an invasive strategy would be important for early triage. The Thrombolysis in Myocardial Infarction (TIMI) risk score is a simple validated integer score that makes it possible to identify high-risk patients on admission to hospital. We hypothesized that a high-risk group might have a reduced mortality with an invasive strategy. Methods and Results—We classified 1527 patients from the Danish Multicenter Randomized Study on Fibrinolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2) trial with information for all variables necessary for calculating the TIMI risk score as low risk (TIMI risk score, 0 to 4) or high risk (TIMI risk score ≥5) and investigated the effect of primary angioplasty versus fibrinolysis on mortality and morbidity in the 2 groups. Follow-up was 3 years. We classified 1134 patients as low risk and 393 as high risk. There was a significant interaction between risk status and effect of primary angioplasty (P=0.008). In the low-risk group, there was no difference in mortality (primary angioplasty, 8.0%; fibrinolysis, 5.6%; P=0.11); in the high-risk group, there was a significant reduction in mortality with primary angioplasty (25.3% versus 36.2%; P=0.02). Conclusions—Risk stratification at admission based on the TIMI risk score identifies a group of high-risk patients who have a significantly reduced mortality with an invasive strategy of primary angioplasty.

Danish multicenter randomized study on fibrinolytic therapy versus acute coronary angioplasty in acute myocardial infarction: rationale and design of the danish trial in acute myocardial infarction-2 (DANAMI-2)

BACKGROUND Randomized trials have indicated that primary coronary angioplasty performed in patients admitted directly to highly-experienced angioplasty centers offers certain advantages over intravenous fibrinolytic therapy. However, the large majority of patients with acute myocardial infarction are submitted to hospitals without a catheterization laboratory. This means that additional transportation will be necessary for many patients if a strategy of acute coronary angioplasty is to be introduced as routine treatment. The delay of treatment caused by transportation might negate (part of) the benefits of primary angioplasty compared to fibrinolytic therapy given immediately at the local hospital. STUDY DESIGN The DANish trial in Acute Myocardial Infarction-2 (DANAMI-2) is the first large-scale study to clarify, in a whole community, which of the 2 treatment strategies is best. A total of 1900 patients with ST-elevation myocardial infarction are to be randomized: 800 patients will be admitted to invasive hospitals and 1100 patients will be admitted to referral hospitals. Half of the 1100 patients admitted to referral hospitals will immediately be transferred to an invasive center to be treated with primary angioplasty. IMPLICATIONS If acute transfer from a local hospital to an angioplasty center is the superior strategy, primary angioplasty should be offered to all patients as routine treatment on a community basis.

Cardiac Event Rates After Acute Myocardial Infarction in Patients Treated With Verapamil and Trandolapril Versus Trandolapril Alone

Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), but mortality may be as high as 10% to 15% after 1 year. Verapamil prevents cardiac events after an AMI in patients without CHF. We hypothesized that in postinfarct patients with CHF already prescribed diuretics and an ACE inhibitor, additional treatment with verapamil may reduce cardiac event rate. In this multicenter, double-blind study, patients with CHF receiving diuretic treatment were consecutively randomized to treatment with trandolapril 1 mg/day for 1 month and 2 mg/day the following 2 months (n = 49), or to trandolapril as mentioned plus verapamil 240 mg/day for 1 month and 360 mg/day for 2 months (n = 51). Trial medication started 3 to 10 days after AMI. All patients were followed for 3 months. End points in the trandolapril/trandolapril-verapamil groups were death 1/1, reinfarction 7/1, unstable angina 9/3, and readmission for CHF 6/2. The 3-month first cardiac event rate was 35% in trandolapril-treated patients and 14% in trandolapril-verapamil-treated patients (hazard ratio 0.35, 95% confidence interval 0.15 to 0.85, p = 0.015). These data suggest that verapamil reduces cardiac event rates in post-AMI patients with CHF when added to an ACE inhibitor and a diuretic.

Primary Angioplasty Versus Fibrinolysis in Acute Myocardial Infarction Long-Term Follow-Up in the Danish Acute Myocardial Infarction 2 Trial

Background— The Danish Acute Myocardial Infarction 2 (DANAMI-2) study found that primary angioplasty (primary percutaneous coronary intervention [pPCI]) compared with fibrinolysis reduced 30-day adverse events in patients with ST-segment elevation myocardial infarction. The present study investigated whether the benefit of pPCI was maintained at a long-term follow-up. Methods and Results— We randomly assigned 1572 patients with ST-segment elevation myocardial infarction—1129 patients at referral hospitals and 443 patients at invasive hospitals—to pPCI or fibrinolysis. Median time from randomization to arrival in the catheterization laboratory for patients admitted to referral hospitals was 67 minutes, with 96% of patients arriving in the catheterization laboratory within 120 minutes. The primary study end point was a composite of death or reinfarction. Median follow-up time was 7.8 years. For the primary end point, 8-year cumulative incidence (1-Kaplan–Meier) was 34.8% in the pPCI group and 41.3% in the fibrinolysis group (hazard ratio, 0.78; 95% confidence interval, 0.66 to 0.92). Reinfarction rates were reduced in the pPCI group (11.7% versus 18.5%; hazard ratio, 0.60; 95% confidence interval, 0.46 to 0.77). Among patients randomized at referral hospitals, pPCI reduced reinfarction (13% versus 18.5%; hazard ratio, 0.66; 95% confidence interval, 0.49 to 0.89) and mortality (26.7% versus 33.3%; hazard ratio, 0.78; 95% confidence interval, 0.63 to 0.97). Conclusions— The benefit of pPCI over fibrinolysis was maintained at a long-term follow-up. pPCI reduced the risk of reinfarction in the overall cohort and reduced reinfarction and mortality among patients randomized at referral hospitals. This result reinforces that pPCI should be offered to ST-segment elevation myocardial infarction patients when interhospital transport to an invasive hospital can be completed within 120 minutes.

Warfarin for the prevention of systemic embolism in patients with non-valvular atrial fibrillation: a meta-analysis

Background: Warfarin for stroke prevention in patients with atrial fibrillation (AF) is well documented. However, it has not been examined in the prevention of systemic embolism. Objectives: To evaluate the efficacy of warfarin in preventing systemic embolism (embolism to limbs or viscera) in patients with AF. Methods and results: A combined Medline, Embase, Cochrane Library and SveMed+ search were made. Fifteen studies were included. Warfarin was better than antiplatelet agents for preventing systemic embolism with a 50% reduction of risk (odds ratio (OR) = 0.50, 95% CI 0.33 to 0.75) without increasing the risk of major bleeding (OR = 1.07; 95% CI 0.85 to 1.34). Warfarin compared with placebo resulted in a risk reduction of 71% (OR = 0.29; 95% CI 0.08 to 1.07) with higher risk of major bleeding with warfarin (OR = 3.01; 95% CI 1.31 to 6.92). Results of a comparison of warfarin with low-dose warfarin (OR = 1.52; 95% CI 0.40 to 5.81) or low-dose warfarin with aspirin (OR = 1.00; 95% CI 0.17 to 5.81) were inconclusive. Conclusions: Warfarin not only reduces the risk of stroke but is also better than placebo and antiplatelet agents in prevention of systemic embolism in patients with non-valvular AF. Warfarin increases the risk of major bleeding compared with placebo but not compared with antiplatelet agents.

Trends in Risk of Stroke in Patients with a Hospital Diagnosis of Nonvalvular Atrial Fibrillation: National Cohort Study in Denmark, 1980–2002

Aim: We examined trends in incidence of stroke of any nature (ischemic and/or hemorrhagic) in subjects with a hospital diagnosis of nonvalvular atrial fibrillation or flutter in Denmark from 1980 to 2002 by sex, age and conditions of comorbidity. Methods: We identified all individuals, aged 40–89 years, with an incident hospital diagnosis of atrial fibrillation or flutter and no history of stroke or heart valve disease in the Danish National Registry of Patients, and subjects were followed in the Danish National Registry of Patients for occurrence of an incident diagnosis of stroke of any nature (ischemic and/or hemorrhagic) and in the Danish Civil Registration System (emigration and vital status). We used multivariate Cox proportional hazard regression analysis to estimate trends in incidence of stroke. Results: Nonvalvular atrial fibrillation or flutter was diagnosed in 141,493 subjects (75,126 men and 66,367 women), and during follow-up 15,964 subjects had an incident diagnosis of stroke. The hazard ratios for stroke in the last 3-year period compared to the first 5-year period, adjusted for 10-year age group, conditions of comorbidity, and general stroke trend in the Danish population were 0.78 (95% CI 0.70–0.86) in men, and 0.80 (95% CI 0.72–0.88) in women. The reduction in risk of stroke by calendar year was most prominent in patients aged 40–74 years. Conclusion: We observed a modest decrease in risk of stroke in subject with atrial fibrillation in Denmark during calendar years 1980–2002. However, we could not control for any changes in diagnostic performance, admission practice, and medical management of patients with atrial fibrillation.

Atrial fibrillation in patients with sick sinus syndrome: the association with PQ-interval and percentage of ventricular pacing

AIMS In the recently published DANPACE trial, incidence of atrial fibrillation (AF) was significantly higher with single-lead atrial (AAIR) pacing than with dual-chamber (DDDR) pacing. The present analysis aimed to evaluate the importance of baseline PQ-interval and percentage of ventricular pacing (VP) on AF. METHODS AND RESULTS We analysed data on AF during follow-up in 1415 patients included in the DANPACE trial. In a subgroup of 650 patients with DDDR pacemaker, we studied whether %VP, baseline PQ-interval, and programmed atrio-ventricular interval (AVI) was associated with AF burden measured as time in mode-switch (MS) detected by the pacemaker. In the entire DANPACE study population, the incidence of AF was significantly higher in patients with baseline PQ-interval >180 ms (P< 0.001). Among 650 patients with DDDR pacemaker, telemetry data were available for 1.337 ± 786 days, %VP was 66 ± 33%, AF was detected at planned follow-up in 160 patients (24.6%), MS occurred in 422 patients (64.9%), and AF burden was marginally higher with baseline PQ-interval >180 ms (P= 0.028). No significant association was detected between %VP and %MS (Spearmans ρ 0.056, P= 0.154). %MS was not different between minimal-paced programmed AVI ≤ 100 and >100 ms (median value), respectively (P= 0.60). CONCLUSIONS The present study indicates that a longer baseline PQ-interval is associated with an increased risk of AF in patients with sick sinus syndrome. Atrial fibrillation burden is not associated with the percentage of VP or the length of the programmed AVI.

Time to treatment and three-year mortality after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction-a DANish Trial in Acute Myocardial Infarction-2 (DANAMI-2) substudy.

In patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (pPCI), early reperfusion is believed to improve left ventricular systolic function and reduce mortality; however, long-term (>1 year) data are sparse. In the DANish Trial in Acute Myocardial Infarction-2 (DANAMI-2) study, 686 patients with ST-segment elevation myocardial infarction were treated with pPCI. Long-term mortality was obtained during 3 years of follow-up. We classified the patients according to the symptom-to-balloon time (<3, 3 to 5, and > or =5 hours). The groups were compared using a Cox proportional hazards regression model adjusted for confounding factors. The left ventricular systolic ejection fraction was estimated by echocardiography before discharge. Coronary flow was evaluated using the Thrombolysis In Myocardial Infarction score. Mortality did not differ between the 2 earliest symptom-to-balloon groups, and they were therefore combined into 1 group in the analysis of survival. Mortality was significantly increased for patients with a symptom-to-balloon time > or =5 hours (hazard ratio 2.36, 95% confidence interval 1.51 to 3.67, p <0.001), a difference that remained significant after controlling for confounding factors (adjusted hazard ratio 2.44, 95% confidence interval 1.31 to 4.54, p = 0.007). The symptom-to-balloon time was inversely associated with a left ventricular systolic ejection fraction of < or =40% (19.7% vs 22.8% vs 33.1%, p = 0.036), with the latter a major predictor of 3-year mortality in this cohort (hazard ratio 6.02, 95% confidence interval 3.68 to 9.85, p <0.001). A shorter symptom-to-balloon time was associated with greater rates of Thrombolysis In Myocardial Infarction 3 flow after pPCI (86.5% vs 80.9% vs 75.7%, p = 0.002). In conclusion, a shorter symptom-to-balloon time was associated with improved coronary flow, an increased likelihood of subsequent left ventricular systolic ejection fraction >40%, and greater 3-year survival in patients with ST-segment elevation myocardial infarction treated with pPCI.