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Aims The DANish Acute Myocardial Infarction 2 (DANAMI-2) trial found that interhospital transport to primary percutaneous coronary intervention (pPCI) was superior to fibrinolysis at the local hospital in patients with ST-segment elevation myocardial infarction (STEMI) at 30 days. The present study investigates the 16-year cardiovascular outcomes. Methods and results We randomized 1572 STEMI patients to pPCI or fibrinolysis at 24 referral hospitals and 5 invasive centres in Denmark. Patients randomized to pPCI at referral hospitals were immediately transported to the nearest invasive centre. The main endpoint of the current study was a composite of death or rehospitalization for myocardial infarction (MI). Outcome information beyond 3 years was obtained through Danish health registries. After 16 years, pPCI-treated patients had a sustained lower rate of composite endpoint compared to patients treated with fibrinolysis in the overall cohort [58.7% vs. 62.3%; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76–0.98], and among patients transported for pPCI (58.7% vs. 64.1%; HR 0.82, 95% CI 0.71–0.96). No difference in all-cause mortality was found, but cardiac mortality was reduced by an absolute of 4.4% in favour of pPCI (18.3% vs. 22.7%; HR 0.78, 95% CI 0.63–0.98). pPCI postponed a main event with 12.3 months in average compared to fibrinolysis (95% CI 5.0–19.5). Conclusion The benefit of pPCI over fibrinolysis was maintained at 16-year follow-up. pPCI reduced the composite endpoint of death or rehospitalization for MI, reduced cardiac mortality, and delayed average time to a main event by approximately 1 year.

Aims: To examine the association between coronary artery calcium score (CACS) and risk of future atrial fibrillation (AF), and to estimate the predictive accuracy of CACS for AF development in patients undergoing non-contrast cardiac computed tomography (nCCT).Methods and results: We conducted a registry-based cohort study of 27 962 patients suspected of having coronary artery disease and without history of AF who were identified in the Western Denmark Heart Registry. The patients underwent nCCT between 2010 and 2015 and were followed until 2016 (median 2.9 years). CACSs were determined using nCCT. We used Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals (CI). A receiver operating characteristic (ROC) curve for AF was used to assess the predictive accuracy of CACS. Among the patients, 52% had a CACS of 0, 26% of 1-99, 13% of 100-399, 6% of 400-999, and 4% of ≥ 1000. AF occurred in 622 patients after nCCT, corresponding to an overall incidence rate of 7.5 (95% CI: 6.9-8.1) per 1000 person-years. After multivariable adjustment, the HRs (95% CIs) were (ref. CACS 0) CACS 1-99: 1.00 (0.80-1.25); CACS 100-399: 1.36 (1.06-1.74); CACS 400-999: 1.76 (1.33-2.35); and CACS ≥ 1000: 1.67 (1.20-2.34). An ROC curve showed an area under the curve of 0.68 (0.65-0.71) for the prediction of AF within one year after nCCT.Conclusion: A high CACS is associated with a high risk of subsequent AF development and may have potential to guide future follow-ups for AF detection after CACS measurement in order to identify AF patients earlier.

Aim: To explore the potential of small-area variation analysis as a tool for identifying unwarranted variation in oral anticoagulation (OAC) use and clinical outcomes in patients with atrial fibrillation (AF) and thereby identify locations with opportunity for improvement in AF care.Methods and results: Based on Danish health care registries, we conducted a nationwide historical cohort study including first-time AF patients with a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75, diabetes, thromboembolism, vascular disease, age 65-74, and sex category) score ≥ 2 between 2007 and 2014 (n = 94 482). For each administrative region and municipality, we assessed OAC initiation and persistence as well as the risk of ischaemic stroke, haemorrhagic stroke, and other major bleeding, respectively. In addition, potential temporal changes were examined for all outcomes. Initiation of OAC varied among regions from 49.5% to 62.4%. In patients initiating OAC, the proportion of patients still receiving OAC after 1 year varied from 73.9% to 79.3%. Oral anticoagulation use increased in all regions during the study period, particularly after 2010, but regional variation in OAC initiation persisted. Generally, the regions and municipalities with the highest initiation of OAC also had the highest OAC persistence. The risk of ischaemic stroke and other major bleeding was lower in these regions and municipalities. We found no significant difference between regions in risk of haemorrhagic stroke.Conclusion: Substantial geographical variation in OAC use and clinical outcomes occurs in Denmark demonstrating the potential of small-area variation analysis as a tool for identifying unwarranted variation in AF care and clinical outcomes. Our findings demonstrate the need for additional initiatives to ensure uniform high-quality care for AF patients.

AIMS: The DANPACE trial randomized patients with sick sinus syndrome (SSS) to single lead atrial (AAIR) or dual chamber (DDDR) pacemaker (PM). After 5 years follow-up, no difference in overall survival, stroke or heart failure (HF) was observed, whereas risk of atrial fibrillation (AF) and PM reoperation were increased in the AAIR group. The present study aimed to investigate very long term risk of death, AF hospitalization, stroke, HF and rate of change in pacing mode using national register-based data.METHODS AND RESULTS: The study population consisted of all 1384 patients included at Danish PM centres in the DANPACE trial randomized to AAIR (n = 696) or DDDR (n = 688). Long-term follow-up data was obtained from Danish national registers. Analysis was intention-to-treat.RESULTS: During mean follow-up of 8.9 years, 413 patients (59.3%) died in the AAIR-group compared to 367 (53.3%) in the DDDR-group (adjusted hazard ratio 1.03; 95% confidence interval 0.90-1.19; P = 0.65). We observed no difference in risk of AF hospitalization, stroke or HF. During extended follow-up, annual rate of pacing mode change to DDDR in the AAIR group was 4.5%, and higher than the 2.3% observed during trial conduct.CONCLUSION: This register-based long-term follow-up study indicates that there is no difference in mortality among patients with SSS randomized to AAIR or DDDR pacing, even with very long follow-up. Nor is there any difference in risk of AF hospitalization, stroke or HF. The higher rate of pacing mode-change to DDDR in the AAIR group suggests a different management of patients with an AAIR PM after the DANPACE trial.

Evidence of a causal link between atherosclerosis and cancer is sparse and conflicting. Therefore, we examined the association between extent of coronary atherosclerosis determined by coronary artery calcium score (CACS) and risk of cancer. We conducted a historical population-based cohort study of 28,549 cancer-free patients identified in the Western Denmark Heart Registry. All patients underwent cardiac computed tomography for measurement of CACS for suspected coronary artery disease. The outcome was an incident cancer diagnosis: total, tobacco-related, lung, prostate, breast, and colorectal. We used Cox proportional hazards regression analyses stratified by gender to estimate hazard ratios (HRs) for relations between CACS and cancer with 95% confidence intervals (95% CI). During follow-up, 455 men and 527 women had a cancer diagnosis. In a multivariable model (reference group: CACS 0), adjusted hazard ratios (95% confidence interval) for total cancer were as follows: CACS 1 to 99: 1.07 (0.83 to 1.39), CACS 100 to 399: 1.24 (0.94 to 1.63), CACS 400 to 999: 0.88 (0.62 to 1.25), CACS ≥1,000: 0.96 (0.66 to 1.41) in men; and CACS 1 to 99: 0.96 (0.77 to 1.19), CACS 100 to 399: 0.99 (0.75 to 1.31), CACS 400 to 999: 1.11 (0.76 to 1.62), and CACS ≥1,000: 1.16 (0.73 to 1.83) in women. We found no significant association between CACS and the specified outcomes for men or women, except for an increased risk of lung cancer among women with a high CACS. In conclusion, extent of coronary atherosclerosis determined by CACS was not associated with development of total, tobacco-related, lung, prostate, breast, or colorectal cancer. However, we did observe an association between CACS and risk of lung cancer in women.

Objective The risk of stroke in patients with atrial fibrillation (AF) can be assessed by use of the CHADS2 and the CHA2DS2-VASc score system. We hypothesised that these risk scores and their individual components could also be applied to patients paced for sick sinus syndrome (SSS) to evaluate risk of stroke and death. Design Prospective cohort study. Settings All Danish pacemaker centres and selected centres in the UK and Canada. Patients Risk factors were recorded prior to pacemaker implantation in 1415 patients with SSS participating in the Danish Multicenter Randomized Trial on Single Lead Atrial Pacing versus Dual Chamber Pacing in Sick Sinus Syndrome (Danpace) trial. Development of stroke was assessed at follow-up visits and by evaluation of patient charts. Mortality was assessed from the civil registration system. Interventions Patients were randomised to AAIR (N=707) or DDDR pacing (N=708). Main outcome measures Stroke and death during follow-up. Results Mean follow-up was 4.3±2.5 years. In the AAIR group 6.9% patients developed stroke versus 6.1% in the DDDR group (NS). There was a significant association between CHADS2 score and the development of stroke (HR 1.41; 95% CI 1.22 to 1.64, p

OBJECTIVE: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint of ablation was elimination of electrical activity inside pulmonary veins. We present the results of the 5-year follow-up.METHODS: This pre-specified 5-year follow-up included assessment of any AF and symptomatic AF burden by one 7-day Holter recording and quality of life (QoL) assessment, using SF-36 questionnaire physical and mental component scores. Analysis was intention-to-treat. Imputation was used to compensate for missing Holter data.RESULTS: 245 of 294 patients (83%) randomised to RFA (n=125) or AAD (n=120) attended the 5-year follow-up, 227 with Holter recording. Use of class I or III AAD was more frequent in AAD group (N=61 vs 13, pCONCLUSIONS: At 5 years, the occurrence and burden of any AF and symptomatic AF were significantly lower in the RFA group than in the AAD group. Improved QoL scores observed after 2 years persisted after 5 years without between-group differences.TRIAL REGISTRATION NUMBER: NCT00133211; Results.

Summary. Background: The risk factors associated with, and the incidence of systemic embolism in patients with atrial fibrillation (AF) are poorly understood. Objectives: We studied the association between AF and upper limb thromboembolectomy involving brachial, ulnar or radial artery in a national cohort study that included all individuals aged 40–99 years with incident AF. Methods: Data were retrieved from the Danish National Vascular Registry, the National Registry of Patients, the Danish Civil Registration System and Statistics Denmark. Results: In total, 131 476 patients (68 042 men and 63 434 women) with AF without previous thromboembolectomy in the upper limb were registered. In the study cohort, 130 men underwent upper limb thromboembolectomy over 220 890 person-years of observation, whilst 275 women underwent thromboembolectomy over 197 777 patient-years. The incidence per 100 000 person-years was 58.9 (95% CI, 49.2–69.8) for men and 139.1 (95% CI, 123.1–156.5) for women. The relative risk of thromboembolectomy among patients with AF compared to the background population was 7.5 (95% CI, 6.3–8.9) for men, and 9.3 (95% CI, 8.3–10.5) for women. Women with AF had a relative thromboembolectomy risk of 1.8 (95% CI, 1.5–2.3) compared to men with AF. Among patients with AF, history of hypertension (HR 2.2–2.9), myocardial infarction (HR 2.9–3.9), heart failure (HR 1.6–1.9) and stroke (HR 2.2–3.8) were significantly associated with increased risk of thromboembolectomy in both men and women. Conclusions: AF substantially increases the risk of upper limb thromboembolectomy. This risk is higher with increasing age, female gender, and associated with hypertension, myocardial infarction, heart failure and stroke.

Introduction: Chronic kidney disease (CKD) is a progressive disease leading to loss of glomerular filtration rate (ΔGFR, measured in ml/min/1.73 m2/year). ΔGFR is usually assumed to be constant, but the hyperfiltration theory suggests that it accelerates in severe uraemia. A retrospective analysis of estimated GFR (eGFR) calculated from the Modification of Diet in Renal Disease equation was performed to evaluate whether ΔGFR is constant or accelerating. Methods: 1,441 patients attending a nephrology clinic over a 21-year period, with an initial eGFR 2 and an observation period ≧2 years, were included. eGFR was calculated from all creatinine measurements. 420 patients developed end-stage renal disease (ESRD). First- and second-order polynomial regression analysis of eGFR against time was performed for each patient individually. Patients had accelerating uraemia progression if the second-order term coefficient was negative. Results: The initial eGFR was 30.8 ±15.1 ml/min/1.73 m2. The second-order coefficient was median –0.15 ml/min/1.73 m2/year2 (interquartile range –0.92, +0.34). Significantly more patients had an accelerating loss (62%, p < 0.001). Acceleration was mainly seen when eGFR was 2/year (male 1.67, female 1.22). ESRD patients lost 5.4 ± 5.4 ml/min/year/1.73 m2 during the last year before ESRD. Accelerating loss was seen for all diagnoses except polycystic disease. Diagnoses with higher ΔGFR were polycystic renal disease (3.3 ml/min/1.73 m2/year), hypertensive nephropathy (2.1 ml/min/1.73 m2/year) and diabetic nephropathy (2.6 ml/min/ 1.73 m2/year). There was no evidence of improvement in overall uraemia progression during the period of observation. Conclusions: Uraemia progression in CKD stages 3–5 is not linear, but shows an accelerating trend. This suggests that hyperfiltration mechanisms play a role in CKD progression. ESRD cannot thus be predicted from previous ΔGFR alone.

Udgivelsesdato: 2009-Jul AIMS: No large randomized multicentre trial has evaluated the efficacy of radiofrequency ablation (RFA) vs. anti-arrhythmic drug (AAD) therapy as a first-line treatment of paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation (MANTRA-PAF) trial is a randomized, controlled, parallel group, multicentre study designed to test whether catheter-based RFA is superior to optimized AAD therapy in suppressing relapse within 24 months of symptomatic and/or asymptomatic AF in patients with paroxysmal AF without prior AAD therapy. The primary endpoint is cumulative AF burden on repeated 7 days Holter monitoring. Secondary endpoints are: thromboembolic events, hospitalization due to arrhythmia, pro-arrhythmic events, procedure/treatment-related side effects, health economics, quality of life, and change in left ventricular function. Ten centres in Scandinavia and Germany are participating in the study. Enrolment was started in 2005 and as of November 2008, 260 patients have been enrolled into the study. It is expected that enrolment will end by March 2009, when 300 patients have been included. CONCLUSION: The MANTRA-PAF trial will determine whether catheter-based RFA is superior to optimized AAD therapy as a first-line treatment in suppressing long-term relapse of symptomatic and/or asymptomatic AF.

Udgivelsesdato: 2008-Dec 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.

Objectives: To evaluate clinical reinfarction during a 3-year follow-up after randomization to primary angioplasty versus fibrinolysis in anterior and non-anterior ST elevation myocardial infarction (STEMI). Methods: Clinical reinfarction was prospectively assessed by an endpoint committee blinded to the study treatment. Results: At 30 days, primary angioplasty compared with fibrinolysis reduced the reinfarction rate both in anterior STEMI patients (n = 823; 2.5 vs. 5.6%, p = 0.02) and in non-anterior STEMI patients (n = 743; 0.8 vs. 7.4%, p < 0.001). After 3 years, the reduction in reinfarction rate was no longer present in anterior STEMI patients (11.2 vs. 11.2%, p = 0.86), but persisted in non-anterior STEMI patients (5.2 vs. 13.5%, p < 0.001). Reinfarction after anterior STEMI carried a higher mortality than reinfarction after non-anterior STEMI (37.6 vs. 15.3%, p = 0.01). Independent predictors of death were: age [hazard ratio (HR) per 1-year increase in age = 1.08 (1.07–1.09)], clinical reinfarction [HR = 5.15 (3.57–7.43)], anterior index STEMI [HR = 1.65 (1.24–2.19)], and Killip class ≥2 [HR = 1.42 (1.01–2.00)]. The additional late reinfarctions after angioplasty for anterior STEMI were located within the angioplasty-treated target segment. Anterior STEMI patients had smaller mean target vessel diameter, which was associated with reinfarction. Conclusions: Clinical reinfarction is an independent predictor of death. The early superiority of primary angioplasty over fibrinolysis on reinfarction rate after anterior STEMI diminished during long-term follow-up.

Udgivelsesdato: 2008-Aug BACKGROUND: Primary angioplasty in patients with acute ST-elevation myocardial infarction has been shown to be superior to fibrinolysis. Whether elderly patients have the same long-term benefit from angioplasty, compared with fibrinolysis, as younger patients is unknown. METHODS: The effect of angioplasty versus fibrinolysis was investigated in 1,572 patients from the DANAMI-2 study across age groups. End points were total mortality and a composite end point of death, reinfarction, or disabling stroke. Follow-up was 3 years. RESULTS: Increasing age was associated with mortality (adjusted hazard ratio [HR] 2.45 per 10 year increment, 95% confidence interval [CI] 1.78-3.37, P < .0001) and a higher composite event rate (adjusted HR 1.51, CI 1.26-1.82, P < .0001). The long-term superiority of angioplasty over fibrinolysis on the combined outcome was independent of age: patients aged 75 years (HR 0.83, CI 0.59-1.17) (P = .006 for overall treatment effect and P = .5 for interaction between age and treatment). There was no long-term effect of angioplasty versus fibrinolysis on mortality and no interaction with age (P = .5 and P for interaction = .6). CONCLUSIONS: The long-term effect of primary angioplasty compared with fibrinolysis in patients with ST-elevation myocardial infarction is not affected by age.

OBJECTIVE: A previous randomised trial showed that structured, nurse-led atrial fibrillation (AF) care is superior to conventional AF care, although further research is needed to determine the outcomes of such care in a real-world setting. We compared the outcomes of patients in real-world, nurse-led, structured hospital AF clinics with the outcomes of a randomised trial of the efficacy of a nurse-led AF clinic, with respect to a composite outcome of cardiovascular-related hospitalisation and death.METHODS: All patients were referred to the AF nurse specialist by cardiologists. The AF nurse specialist provided patient education, risk-factor control and stimulated empowerment and compliance. During follow-up, treatment was adjusted according to clinical guidelines. Patient education was repeated, and compliance with medical treatment was controlled. The study size was powered as a non-inferiority study. Outcome measures were adjudicated by the same principles in both cohorts.RESULTS: A total of 596 patients from the real world and 356 patients from a clinical trial were included in this study. No significant difference between groups with respect to age, type of AF or CHA2DS2VASc score was found. The composite primary end point occurred with an incidence rate of 8.0 (95% CI 6.1 to 10.4) per 100 person-years in the real-world population and 8.3 (95% CI 6.3 to 10.9) per 100 person-years in the clinical trial, with a crude HR of 0.83 (95% CI 0.56 to 1.23).CONCLUSIONS: Structured, nurse-led, hospital-based AF care appears to be effective, and patient outcomes in an actual, hospital-based, structured AF care are as least as good as those in trial settings.

BACKGROUND: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) is a randomized trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drugs (AADs) as first-line treatment of paroxysmal atrial fibrillation (PAF). In order to eliminate the clouding effect of crossover we performed an on-treatment analysis of the data.METHODS AND RESULTS: Patients (n=294) were divided into three groups: those receiving only the assigned therapy (RFA and AAD groups) and those receiving both therapies (crossover group). The primary end points were AF burden in 7-day Holter recordings at 3, 6, 12, 18, and 24months and cumulative AF burden in all recordings. At 24months, AF burden was significantly lower in the RFA (n=110) than in the AAD (n=92) and the crossover (n=84) groups (90th percentile 1% vs. 10% vs. 16%, P=0.007), and more patients were free from any AF (89% vs. 73% vs. 74%, P=0.006). In the RFA, AAD and the crossover groups 63%, 59% and 21% (PCONCLUSIONS: In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy. Thus, it is reasonable to offer RFA as first-line treatment for highly symptomatic patients who accept the risks of the procedure and are aware of frequent need for reablation(s).

AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months.METHODS AND RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time.CONCLUSION: Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale.CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

The DANAMI-2 trial showed a 40% decrease in the composite end point with primary coronary angioplasty versus fibrinolysis. This result was primarily driven by a decrease in reinfarction, with no significant difference in mortality or stroke rates. The objective of this study was to determine the prognostic value of the sum ST-segment elevation (SigmaST) on baseline electrocardiography in patients who were randomized to receive primary coronary angioplasty versus fibrinolysis. In the DANAMI-2, 1,450 patients had baseline ST-segment deviation measurements and were assigned to quartiles according to SigmaST: 0 to 6.5, 7.0 to 9.5, 10.0 to 14.5, and 15.0 to 70.5 mm. The composite and component end-point rates at 30 days were determined for each quartile and chi-square for trend statistic was used to compare end-point rates across quartiles of SigmaST. The composite end point occurred more often with increasing SigmaST (p = 0.05). With regard to component end points, only mortality increased significantly with SigmaST (p = 0.03), whereas reinfarction and stroke rates did not. By multivariate analysis, only SigmaST and age were independent predictors of mortality. The relative benefit of primary coronary angioplasty was similar for all SigmaST quartiles. In conclusion, the magnitude of SigmaST correlates with increased mortality at 30 days, thus driving the composite end point rate. Regardless of SigmaST, patients had a lower composite end-point rate with primary coronary angioplasty than with fibrinolysis.

Aim: There are few data on seasonal variation in stroke and seasonal variation in mortality after stroke in patients with atrial fibrillation. We examined the seasonal pattern in stroke occurrence and the effect of the season on mortality after stroke in patients with a history of nonvalvular atrial fibrillation. Methods:We identified all individuals, aged 40–89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) in the 1980–2002 period and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used periodic regression models to estimate the peak-trough ratio stratified by sex, age and comorbid medical conditions. Seasonal effect on mortality after stroke was analyzed in a Cox proportional hazards model. Results: The relative incidence of stroke estimated as the ratio of the incidence in the month of the peak (January) to the incidence in the month of the trough (July) was 1.11 (95% confidence interval: 1.07–1.15). The relative incidence of stroke was similar for men and women, did not differ by age (stratified by age 75 years) and was essentially similar for comorbid conditions considered. There was no seasonal effect on mortality after stroke. Conclusions: The occurrence of stroke in patients with atrial fibrillation is modestly higher during the winter. Stroke-associated mortality does not vary by season.

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.

Background The incidence of diagnosed atrial fibrillation is increasing in the USA, England, Wales, Scotland and Denmark, and the mortality rate in patients with diagnosed atrial fibrillation has been reported to be declining in Scotland and Denmark. We undertook this study to examine recent trends in incidence and mortality in subjects with a hospital diagnosis of atrial fibrillation or flutter in Denmark from 1980 to 1999 by sex, 10-year age group and conditions of comorbidity. Methods We identified all individuals, aged 40–89 years, with an incident hospital diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients, and subjects were followed in the Danish Civil Registration System. We used multivariate Cox proportional hazard models to estimate trends in mortality. Results Atrial fibrillation or flutter was diagnosed in 131,728 subjects (68,660 men and 63,068 women), and the incidence of a hospital diagnosis of atrial fibrillation or flutter more than doubled during the study period. The hazard ratios for mortality adjusted for 10-year age group, conditions of comorbidity and mortality trend in the Danish population in the last 5-year period compared to the first 5-year period were 0.80 (95% confidence interval 0.78–0.82) in men, and 0.82 (95% confidence interval 0.80–0.84) in women. Conclusions The incidence of a hospital diagnosis of atrial fibrillation or flutter more than doubled, and the 10-year age group- and comorbidity- and general population-adjusted mortality decreased, equally, from the first to the last 5-year period by 20% in men and 18% in women.

For the treatment of myocardial infarction with ST-segment elevation, primary angioplasty is considered superior to fibrinolysis for patients who are admitted to hospitals with angioplasty facilities. Whether this benefit is maintained for patients who require transportation from a community hospital to a center where invasive treatment is available is uncertain.We randomly assigned 1572 patients with acute myocardial infarction to treatment with angioplasty or accelerated treatment with intravenous alteplase; 1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 invasive-treatment centers. The primary study end point was a composite of death, clinical evidence of reinfarction, or disabling stroke at 30 days.Among patients who underwent randomization at referral hospitals, the primary end point was reached in 8.5 percent of the patients in the angioplasty group, as compared with 14.2 percent of those in the fibrinolysis group (P=0.002). The results were similar among patients who were enrolled at invasive-treatment centers: 6.7 percent of the patients in the angioplasty group reached the primary end point, as compared with 12.3 percent in the fibrinolysis group (P=0.05). Among all patients, the better outcome after angioplasty was driven primarily by a reduction in the rate of reinfarction (1.6 percent in the angioplasty group vs. 6.3 percent in the fibrinolysis group, P0.001); no significant differences were observed in the rate of death (6.6 percent vs. 7.8 percent, P=0.35) or the rate of stroke (1.1 percent vs. 2.0 percent, P=0.15). Ninety-six percent of patients were transferred from referral hospitals to an invasive-treatment center within two hours.A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis, provided that the transfer takes two hours or less.

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.

Aim The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. Methods and results A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients. Conclusion Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).

Heart rate variability (HRV) has been demonstrated to be a risk factor after acute myocardial infarction (AMI). In the present study serial measurement of SDNN (standard deviation of the mean of qualified NN-interval) in short intervals was used to assess HRV changes after AMI, and determine the role of these as independent risk factors compared to clinical, arrhythmic, ischemic and anamnestic variables. Measurements from a normal healthy middle-aged male population were used as reference (n = 63).SDNN from a five-minute period during day and night-time, respectively, was examined in 103 patients 1 week (n = 54), 1 month (n = 72) and 12-16 months (n = 54) after infarction.Day SDNN did not change during one-and-a-half years after AMI, and was significantly reduced compared with healthy males. Night SDNN, low after 1 week, with recovery 1 month after AMI, was significantly reduced compared with healthy males early, but not late after AMI. Thus, the study indicated during day-time a continuous abnormal sympathetic preponderance in the course of 16 months after AMI, and during night-time a gradual recovery of parasympathetic preponderance beginning early after AMI.One week after AMI day-time SDNN of30 ms, and night-time SDNN of18 ms, ageor =60 years, and myocardial ischemia (Holter monitoring) were independent predictors of 9 years' mortality. One and 12-16 months after AMI reduced day and night-time SDNN had no prognostic implication.

The cyclin-dependent kinase inhibitor p27Kip1 is a negative cell cycle regulator linking extracellular growth-regulatory signals to the cell cycle machinery in G1. We investigated the pattern and prognostic value of p27Kip1 expression in a population-based group of 203 non-Hodgkin's lymphoma (NHL) patients. The expression of p27Kip1 was identified by immunohistochemistry and correlated with Ki-67 expression and clinical features. Correlation with outcome was determined using uni- and multivariate analysis stratified by clinical grade. Except for very aggressive NHL, there was a negative correlation between p27Kip1 and Ki-67 expression. Low expression of p27Kip1, defined as nuclear p27Kip1 expression in 40%) was associated with poor survival in indolent and aggressive lymphomas. Multivariate analysis using the proportional hazards model showed that only p27Kip1, and not Ki-67, maintained independent prognostic significance in indolent and aggressive lymphomas (relative risk = 2.0; P = 0.0095). The low cost and simplicity of this standard immunohistochemistry analysis makes p27Kip1 a promising and suitable prognostic marker in routine diagnostic laboratories in a standard diagnostic panel.

Background Recurrent nonfatal myocardial infarction (RNMI) is the most significant risk factor for later outcome after an index infarction. However, little is known about the prognosis after RNMIs that occur beyond the first year after the index infarction. Methods and Results In 3867 nonselected patients p = 0.12) or standardized mortality rates. Conclusions Late RNMIs have almost the same grave prognosis as do early RNMIs. (Am Heart J 1998;136:164-8.)

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.

Survival in 190 consecutive patients with congestive heart failure, discharged from a general hospital, was studied. Sixteen patients were in New York Heart Association (NYHA) class I, 87 in II, 83 in III and 4 in IV. Median left ventricular ejection fraction (LVEF) from radionuclide ventriculography was 0.30 (range 0.06-0.74). Two-year survival was 68%. Wall motion index was the only echocardiographic variable with significant, independent, prognostic information on survival. The 2-year survival in NYHA classes I and II was 90.7% for wall motion index ≧ 1.3, and 78.6% when

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.).

The prognosis, and clinical findings related to prognosis, were examined in a consecutive series of 190 patients under 76 years of age (mean 64 years) with congestive heart failure (CHF). The aetiology of CHF was ischaemic heart disease in 66%, hypertension in 11% and cardiomyopathy in 23%. The 2-year mortality was 32%. Median left ventricular ejection fraction (LVEF) was 0.30, range 0.06 to 0.74. Eight per cent were in New York Heart Association (NYHA) class I, 46% in II, 44% in III and 2% in IV. Multivariate analysis, excluding exercise test variables, revealed seven variables with independent, significant prognostic information, (hazard ratios for death in brackets): ln (natural logarithm) (LVEF) (3.19), NYHA class III+IV (2.72), plasma urea > 7.6 mmol.l-1 (2.22), serum creatinine > 121 mumol.l-1 (2.05), serum sodium 65 years (1.86). Multivariate analysis, including exercise testing, showed the following variables to contain independent, significant prognostic information: increase in heart rate during maximal exercise 121 mumol.l-1 (2.9), maximal exercise time 7.6 mmol.l-1 (1.9). In conclusion, patients with CHF have a high risk of death despite intensive medical treatment. LVEF is a strong predictor of mortality. Both NYHA class and exercise variables have strong independent prognostic information as regards mortality in combination with LVEF, but are mutually exclusive.

The purpose was to evaluate the 10-year mortality in patients with acute chest pain suspected of myocardial infarction with (AMI) and without (non-AMI) confirmed diagnosis and to determine risk factors from the medical history and the diagnosis at discharge. One-thousand eight-hundred and ninety-seven non-AMI patients and 1,401 patients with AMI consecutively admitted to 1 of 16 coronary care units participating in The Danish Verapamil Infarction Study were included. During follow-up, 630 deaths occurred among the non-AMI patients and 415 of these could be classified as cardiac deaths. Multivariate analysis identified the following risk factors containing independent prognostic information about mortality for non-AMI patients: age, previous AMI, sex, and diabetes. In patients with AMI the risk factors were: age, previous AMI, clinical heart failure, diabetes, and angina pectoris. By including the diagnosis at discharge for non-AMI patients in the Cox analysis, the prognostic significance was compared to the variables from the medical history. Only the diagnoses bronchopneumonia, musculoskeletal disorders and observatio sine indicatione therapiae added independent prognostic information. We conclude that non-AMI patients are at high risk for mortal events in the long term. High-risk patients can be identified from their medical history, whereas the diagnosis at discharge only adds limited prognostic information. All non-AMI patients should be carefully evaluated regarding coronary artery disease at the time of discharge in order to improve the risk stratification, treatment and prognosis.

Background: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18–60 years with two or more risk factors (stage III–IV, elevated lactate dehydrogenase levels, performance status 2–4). To our knowledge, this is the first study comparing these two regimens in this patient group.Methods: We obtained data for the period 2004–2009 from the Danish Lymphoma Database. One hundred and fifty-nine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety.Results: Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P = 0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P = 0.02).Conclusion: R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14.

Abstract 5074 Background: PTLD is a lymphoid proliferation that develops as a consequence of immunosuppression. It represents monoclonal B-cell, or rarely T-cell, proliferations, occurring in a setting of decreased T-cell immune surveillance. It has been shown that HLA-B mismatching is associated with increased risk of skin cancer in recipients of renal transplants. An association between skin cancer related to human papillomavirus and HLA-A11 has also been established in this group of patients. Bakker et al has shown that HLA-B mismatching is a risk marker of PTLD. More specifically, Subklewe et al found that HLA-B18 and HLA-B21 were associated with increased risk of PTLD, whereas mismatch at HLA-A03 and HLA-DR7 level reduced the risk of PTLD. We therefore hypothesized that mismatch of certain HLA alleles may be risk predictors of PTLD after renal transplantation. Methods: According to the national renal transplantation database of the Danish Society of Nephrology, 872 renal transplantations in 793 patients were performed at Aarhus University Hospital between 1990 and 2005. A total of 11 cases of PTLD were retrospectively identified through the National Danish Pathology database and individually reviewed by an experienced hematopathologist (KB). PTLD patients were investigated according to transplantation procedure, clinicopathological patient characteristics, type of lymphoma, outcome and HLA haplotype of both donor and recipient. Results: Univariate Cox regression analysis showed no positive correlation between risk of PTLD and number of HLA-B mismatches, or with HLA-A or HLA-DR mismatches. Conversely, we found a decreased risk with one/two HLA-B mismatches compared to no mismatches (p Conclusions: Our data suggest not only that the risk of developing PTLD is unaffected by an increasing number of HLA-B mismatches, but that a low number of such mismatches may even protect against PTLD developement. In our analysis, we found a moderate correlation between PTLD and HLA-B37, and a stronger one with HLA-DR6. The latter observation has never been previously reported. Further analyses with larger cohorts of renal transplant patients are needed to clarify the role of HLA antigens as risk markers for PTLD in order to establish whether a pre-emptive PTLD monitoring of renal transplant patients expressing certain haplotypes/haplotype mismatches is justified. Disclosures: No relevant conflicts of interest to declare.

Dr Fresco raises concerns regarding a secondary endpoint (all-cause mortality) in the subgroup analyses of DANAMI-2. We will try to elaborate on this issue, even though DANAMI-2 was never powered to perform such analyses. First, age is a strong predictor for mortality. In the referral hospital subgroup, there was a trend toward higher age in the fibrinolysis subgroup (median 64 versus 62 years, P =0.06), than in the group allocated to primary percutaneous coronary intervention (pPCI), and the opposite was found in the invasive hospital subgroup (median 62 versus …

Objectives We investigated the incidence of thrombo-embolectomy in upper-limb and prognosis with respect to arm amputation, stroke and death. Methods We performed a national cohort study of individuals, aged 40–99 years, and undergoing first-time thrombo-embolectomy in the brachial, ulnar or radial artery in Denmark from 1990 to 2002. The data were retrieved from the National Vascular Registry and from the National Registry of Patients and the Civil Registration System. Patients were followed until 2006 to ascertain the occurrence of amputation and stroke and until 2007 with respect to death. Results In total, 1377 incident cases of thrombo-embolectomy were registered, comprising 504 (36.6%) males with a mean age of 72.0 (standard deviation (SD) 12.4) years and 873 (63.4%) females with a mean age of 77.2 (SD 11.7) years. Incidence was 3.3 (95% confidence interval (CI): 3.1–3.7) for males and 5.2 (95% CI: 4.9–5.6) for females per 100000 person-years. After thrombo-embolectomy, upper-limb amputation was performed in 11 (incidence 2.2%; 95% CI: 1.2–3.4) males and 31 (3.6%; 95% CI: 2.5–4.9) females. Age- and sex-specific risk of stroke was 2–16 times higher, and risk of death 3–11 times higher, than in the general population. Conclusions Upper-limb thrombo-embolectomy is associated with an increased risk of limb amputation, stroke and death.

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.

ST-segment resolution has long been used as one of several clinical markers of response to reperfusion therapy. With the use of the DANish trial in Acute Myocardial Infarction-2 (DANAMI-2) database, this case-control study tests the hypothesis that incomplete ST-segment resolution (70%) will be predictive of the risk of reinfarction in the same myocardial region regardless of the reperfusion therapy employed.One hundred forty-nine (9.5%) patients with clinical reinfarction were matched to patients with no documented reinfarction ("no reinfarction"). With the use of the initial DANAMI-2 and reinfarction electrocardiograms, 80 patients were found to have reinfarction in the same myocardial region ("reinfarction"). "Reinfarction" and their matched "no-reinfarction" patients were included (n=160), and prereperfusion and postreperfusion ST segments were measured manually. Of all "reinfarction" patients, 66% (53 of 80) had incomplete ST-segment resolution [P=.13; odds ratio (OR)=1.69]. Stratified by the reperfusion strategy employed, this corresponded to 67% (35 of 52) being treated with fibrinolytics (P=.45; OR=1.33), suggesting that these patients were equally likely to reinfarct in the same myocardial region regardless of the degree of ST-segment resolution. In the primary percutaneous coronary intervention (pPCI) arm, 64% (18 of 28) of patients with reinfarction in the same myocardial region had incomplete ST-segment resolution (P=.10; OR=6.0). In the pPCI arm, the trend was that patients with incomplete ST-segment resolution were more likely to reinfarct in the same myocardial region than those with complete ST-segment resolution, but these findings did not reach statistical significance. No statistically significant difference was found in the association of reinfarction in the same myocardial region and ST-segment resolution between the two treatment arms (P=.11).The results from this study suggest that, although fibrinolytic-treated patients are more likely to reinfarct in the same myocardial region than pPCI-treated patients, there is no clear statistically significant association between ST-segment resolution and reinfarction in the same myocardial region. Trends in the data suggest that fibrinolytic-treated patients are equally likely to reinfarct in the same myocardial region regardless of the degree of ST-segment resolution. However, the trend in the pPCI population is such that incomplete ST-segment resolution is associated with a higher likelihood of reinfarction in the same myocardial region.

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, andor =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 timeor =5 hours (hazard ratio 2.36, 95% confidence interval 1.51 to 3.67, p0.001), 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 ofor =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, p0.001). 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 fraction40%, and greater 3-year survival in patients with ST-segment elevation myocardial infarction treated with pPCI.

Ljubica V Andersen1, Leif S Mortensen2, Jes S Lindholt3, Ole Faergeman4, Eskild W Henneberg3, Lars Frost51Department of Pharmacology, Odense University Hospital, Denmark; 2UNI-C, The Danish IT Centre for Education and Research, Aarhus, Denmark; 3Vascular Research Unit, Department of Vascular Surgery, Viborg Hospital, Denmark; 4Department of Cardiology and Internal Medicine, Aarhus University Hospital, Denmark; 5Department of Medicine, Silkeborg Hospital, DenmarkObjective: To evaluate completeness and positive predictive value of the Danish National Vascular Registry regarding registration of the surgical procedures: embolectomy of brachial, ulnar, or radial artery. Study design and settings: The study was based on first-time embolectomies in the brachial, ulnar, or radial artery performed in Denmark from January 1, 1990 to December 31, 2002. The data were primarily retrieved from the Danish National Vascular Registry and secondarily from the Danish National Registry of Patients. Medical records were retrieved using a standardized form.Results: In total, 1433 incident cases of first-time embolectomy were found in both registries. The positive predictive value of the registration was 97.5% (95% confidence interval [CI]; 96.4–98.4). The degree of completeness was 86.5% (95% CI; 84.3–88.5). For the registration period from 1990 till 1996 the degree of completeness was 78.2% (95% CI; 74.4–81.7), and from 1997 till 2002 it was 93.8% (95% CI; 91.6–95.7). Conclusion: The completeness and positive predictive value of registration of embolectomy in the upper limb in the Danish National Vascular Registry was 86.5% and 97.5%, respectively. This registry can be a valuable tool for epidemiological research and quality-monitoring. Keywords: positive predictive value, completeness, capture-recapture method, validity, embolectomy, registration.

The effect of nonsteroid anti-inflammatory drugs (NSAIDs) after acute myocardial infarction was studied in a retrospective study of 88 patients who were receiving regular NSAID treatment at randomization in the Danish Verapamil Infarction Trial II. There were no significant differences in mortality or major events between NSAID-treated patients versus controls (1,687); however, in a multivariate analysis a nonsignificant beneficial trend in favor of NSAIDs was observed.

Aim: We assessed the number of lost life years attributable to stroke among patients with a hospital diagnosis of nonvalvular atrial fibrillation. Methods: We identified all patients, aged 40–89 years, with an incident hospital diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients from calendar year 1980 to 2002, and no previous or concomitant diagnosis of stroke or heart valve disease. All patients were followed in the Danish National Registry of Patients for occurrence of an incident diagnosis of stroke of any type (ischemic and/or hemorrhagic) and in the Danish Civil Registration System for emigration or change in vital status. We used multivariate Cox regression analysis with stroke as a time dependent covariate to estimate excess mortality associated with incident stroke. The baseline hazard function for mortality was computed and used for modeling lost life years by sex, age, and time to incident stroke after diagnosis of atrial fibrillation, adjusted for conditions of comorbidity and calendar year of diagnosis of atrial fibrillation. Results: The mean loss of life years attributable to incident stroke within 20 years after a first diagnosis of atrial fibrillation was most frequently less than 5 years, but a mean of up to 10 years of lost life years was observed. The largest number of lost life years was observed in women, in younger patients, and in those who had a stroke early after the diagnosis of atrial fibrillation. The relative loss of life years was up to 90% of the estimated expected remaining lifetime without stroke within 20 years after the diagnosis of atrial fibrillation, and was highest in the elderly. Conclusion: Stroke causes a substantial loss of life years in patients with atrial fibrillation.

Aim: Guidelines for the clinical management of patients with atrial fibrillation suggest that treatment strategies for prescribing oral anticoagulant therapy should implicate change at age 60, 65 and 75 years. We examined if there is any threshold concerning risk of stroke by age. Methods: We identified 141,493 subjects, aged 40–89 years, with an incident hospital diagnosis of nonvalvular atrial fibrillation or flutter and no previous or concomitant diagnosis of stroke in the Danish National Registry of Patients from January 1, 1980, to December 31, 2002. The subjects were followed in the Danish National Registry of Patients for the occurrence of an incident diagnosis of stroke of any nature and in the Danish Civil Registration System for emigration and vital status. We examined the risk of stroke by age in men and women using Cox regression models, which included age categorized in intervals, linear splines of age with cut points at age 60 and 75 years, or at age 65 and 75 years. We also analyzed age as a continuous variable in linear and polynomial regression models. Results: During follow-up 15,964 incident strokes were reported to the Danish National Registry of Patients. The risk of stroke increased by increasing age at baseline. We did not find any evidence for a threshold concerning risk of stroke by age, and the best model fit was obtained in a third-order polynomial regression model. Conclusion: The risk of stroke increased gradually by increasing age, and we could not detect any threshold concerning risk of stroke by age.

Purpose To evaluate trend in mortality in stroke associated with atrial fibrillation, we examined mortality trend after stroke with atrial fibrillation by calendar year period (1980-1984, 1985-1989, 1990-1994, 1995-1999, and 2000-2002). We estimated trends separately for each sex in unadjusted analyses. We also adjusted for age, comorbid conditions, and general trend in mortality in the background population. Methods We identified all individuals, aged 40-89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used multivariate Cox proportional hazards regression analysis to estimate trend in mortality. Results Incident stroke with a previous or concomitant diagnosis of nonvalvular atrial fibrillation or flutter was diagnosed in 24,470 subjects (11,554 men and 12,916 women). During 34,405 years of observation, 9237 men died, and during 35,381 years of observation, 10,827 women died. The hazard ratio for mortality after stroke in the last 3-year period compared with the first 5-year period was .65 (95% confidence interval [CI], .61-.71) in men and .69 (95% CI, .64-.74) in women. Conclusions We observed a substantially better survival in men and women after stroke associated with atrial fibrillation or flutter in Denmark during the years 1980 to 2002. However, we could not control for changes in admission practice, diagnostic performance, or treatment.

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.

There are few data on seasonal variation in stroke and seasonal variation in mortality after stroke in patients with atrial fibrillation. We examined the seasonal pattern in stroke occurrence and the effect of the season on mortality after stroke in patients with a history of nonvalvular atrial fibrillation.We identified all individuals, aged 40-89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) in the 1980-2002 period and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used periodic regression models to estimate the peak-trough ratio stratified by sex, age and comorbid medical conditions. Seasonal effect on mortality after stroke was analyzed in a Cox proportional hazards model.The relative incidence of stroke estimated as the ratio of the incidence in the month of the peak (January) to the incidence in the month of the trough (July) was 1.11 (95% confidence interval: 1.07-1.15). The relative incidence of stroke was similar for men and women, did not differ by age (stratified by age 75 years) and was essentially similar for comorbid conditions considered. There was no seasonal effect on mortality after stroke.The occurrence of stroke in patients with atrial fibrillation is modestly higher during the winter. Stroke-associated mortality does not vary by season.

Objectives. To calculate the incidence and analyse and outcome after coronary artery bypass grafting (CABG) within the first year after randomisation of 1 572 patients with acute myocardial infarctions with ST-segment elevation (STEMI) to either percutaneous coronary intervention (PCI) or fibrinolysis. Design. The study includes 131 patients: 108 male and 23 female with a mean age 62 years. Results. The total 30-day mortality after CABG was 4.6% (7.5% in the PCI group and 2.6% in the fibrinolysis group). The 30-day mortality was 9.8% after CABG within the first 30-days and 1.3% after CABG within 31–365 days. The patients who were operated early had a reduced EF to 43% as compared to 50% in patients who were not operated or patients having CABG after 30-days (p = 0.002). Conclusion. CABG was performed within the first year after STEMI in 10% of patients randomised to fibrinolysis and in 6.7% of patients randomised to PCI. Patients having CABG within the first 30-days after treatment of STEMI had an increas...