Mårten Rosenqvist

Defibrillator Implantation Early after Myocardial Infarction

BACKGROUND The rate of death, including sudden cardiac death, is highest early after a myocardial infarction. Yet current guidelines do not recommend the use of an implantable cardioverter-defibrillator (ICD) within 40 days after a myocardial infarction for the prevention of sudden cardiac death. We tested the hypothesis that patients at increased risk who are treated early with an ICD will live longer than those who receive optimal medical therapy alone. METHODS This randomized, prospective, open-label, investigator-initiated, multicenter trial registered 62,944 unselected patients with myocardial infarction. Of this total, 898 patients were enrolled 5 to 31 days after the event if they met certain clinical criteria: a reduced left ventricular ejection fraction (< or = 40%) and a heart rate of 90 or more beats per minute on the first available electrocardiogram (ECG) (criterion 1: 602 patients), nonsustained ventricular tachycardia (> or = 150 beats per minute) during Holter monitoring (criterion 2: 208 patients), or both criteria (88 patients). Of the 898 patients, 445 were randomly assigned to treatment with an ICD and 453 to medical therapy alone. RESULTS During a mean follow-up of 37 months, 233 patients died: 116 patients in the ICD group and 117 patients in the control group. Overall mortality was not reduced in the ICD group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.35; P=0.78). There were fewer sudden cardiac deaths in the ICD group than in the control group (27 vs. 60; hazard ratio, 0.55; 95% CI, 0.31 to 1.00; P=0.049), but the number of nonsudden cardiac deaths was higher (68 vs. 39; hazard ratio, 1.92; 95% CI, 1.29 to 2.84; P=0.001). Hazard ratios were similar among the three groups of patients categorized according to the enrollment criteria they met (criterion 1, criterion 2, or both). CONCLUSIONS Prophylactic ICD therapy did not reduce overall mortality among patients with acute myocardial infarction and clinical features that placed them at increased risk. (ClinicalTrials.gov number, NCT00157768.)

Net Clinical Benefit of Warfarin in Patients With Atrial Fibrillation A Report From the Swedish Atrial Fibrillation Cohort Study

Background— Known risk factors for bleeding during anticoagulant treatment are largely the same as those predicting thromboembolic events in patients with atrial fibrillation (AF). Our objective was to investigate how to maximize the likelihood of avoiding both stroke and bleeding. Methods and Results— All 182 678 subjects with atrial fibrillation in the Swedish Hospital Discharge Register were studied for an average of 1.5 years (260 000 patient-years at risk). Patients were stratified according to risk scores with the use of historic International Classification of Disease diagnostic codes in the register. Information about medication was obtained from the Swedish Drug Registry. Our primary end point was net benefit defined as number of avoided ischemic strokes with anticoagulation minus the number of excess intracranial bleedings with a weight of 1.5 to compensate for the generally more severe outcome with intracranial bleedings. The adjusted net clinical benefit favored anticoagulation for almost all atrial fibrillation patients. The exceptions were patients at very low risk of ischemic stroke with a CHA2DS2-VASc score of 0 and moderately elevated bleeding risk (−1.7%/y). The results were broadly similar with CHADS2, except for patients with very low embolic risk; the CHA2DS2-VASc was able to identify those patients (n=6205, 3.9% of all patients) who had no net clinical benefit or even some disadvantage from anticoagulant treatment. Conclusions— In almost all patients with atrial fibrillation, the risk of ischemic stroke without anticoagulant treatment is higher than the risk of intracranial bleeding with anticoagulant treatment. Analysis of the net benefit indicates that more patients may benefit from anticoagulant treatment. # CLINICAL PERSPECTIVE {#article-title-39}Background— Known risk factors for bleeding during anticoagulant treatment are largely the same as those predicting thromboembolic events in patients with atrial fibrillation (AF). Our objective was to investigate how to maximize the likelihood of avoiding both stroke and bleeding. Methods and Results— All 182 678 subjects with atrial fibrillation in the Swedish Hospital Discharge Register were studied for an average of 1.5 years (260 000 patient-years at risk). Patients were stratified according to risk scores with the use of historic International Classification of Disease diagnostic codes in the register. Information about medication was obtained from the Swedish Drug Registry. Our primary end point was net benefit defined as number of avoided ischemic strokes with anticoagulation minus the number of excess intracranial bleedings with a weight of 1.5 to compensate for the generally more severe outcome with intracranial bleedings. The adjusted net clinical benefit favored anticoagulation for almost all atrial fibrillation patients. The exceptions were patients at very low risk of ischemic stroke with a CHA2DS2-VASc score of 0 and moderately elevated bleeding risk (−1.7%/y). The results were broadly similar with CHADS2, except for patients with very low embolic risk; the CHA2DS2-VASc was able to identify those patients (n=6205, 3.9% of all patients) who had no net clinical benefit or even some disadvantage from anticoagulant treatment. Conclusions— In almost all patients with atrial fibrillation, the risk of ischemic stroke without anticoagulant treatment is higher than the risk of intracranial bleeding with anticoagulant treatment. Analysis of the net benefit indicates that more patients may benefit from anticoagulant treatment.

Stroke in paroxysmal atrial fibrillation: report from the Stockholm Cohort of Atrial Fibrillation

AIMS Knowledge about stroke risk in paroxysmal atrial fibrillation (PxAF) is limited. Although current guideline recommendations advocate the same treatment as in permanent atrial fibrillation (PermAF), most patients with PxAF do not receive prophylactic anticoagulation. The aim of this study is to investigate whether there are differences in stroke risk between PxAF and PermAF. METHODS AND RESULTS All patients with PxAF (n = 855) and PermAF (n = 1126) treated for atrial fibrillation (AF) during 2002 at one of Scandinavias largest hospitals were followed-up for 3.6 years regarding incidence of stroke. Information about type of AF, comorbidity, medication, and clinical events during follow-up was acquired from medical records and the National Register of Hospital Discharges. The incidence of ischaemic stroke was similar in PxAF and PermAF (26 vs. 29 events/1000 patient years). The multivariable-adjusted hazard ratio (HR) for ischaemic stroke in PxAF compared with PermAF was 1.07 (95% CI 0.71-1.61) in subjects without prior stroke. The corresponding HR for any stroke, ischaemic or haemorrhagic, was 0.89 (95% CI 0.61-1.30). Compared with the general population, ischaemic stroke was twice as common as expected in PxAF after standardization for age and sex (standardized incidence ratio 2.12, 95% CI 1.52-2.71). PxAF patients who took warfarin had approximately half as many ischaemic strokes as those who did not take warfarin (HR 0.44, 95% CI 0.30-0.65). CONCLUSION Ischaemic stroke is about as common in PxAF as in PermAF, and about twice as common as in the general population. Yet, PxAF patients do not receive protective anticoagulant treatment as often as patients with PermAF do. It is therefore important to increase the use of anticoagulants among PxAF patients in accordance with current guideline recommendations.

Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves

OBJECTIVES Cell-specific antibodies were used to identify immunocompetent cells in a comparison of valves from patients who had symptomatic tricuspid aortic stenosis with subjects who had no evidence of valvular heart disease. BACKGROUND Nonrheumatic valvular aortic stenosis is the most common valvular heart disease among adults. The biologic processes involved in the development of this disease are poorly understood. METHODS Tricuspid stenotic aortic valves were obtained from 19 patients undergoing surgery for nonrheumatic valvular aortic stenosis, and 10 control valves were collected at autopsy. The valves were fixed in formaldehyde, cryosectioned and stained with antibodies against fibroblasts, endothelial cells, macrophages, T lymphocytes and interleukin-2 receptors. A subset of valves were also analyzed with antibodies against T-helper cells and cytotoxic T cells. RESULTS Stenotic valves were characterized by a basal accumulation of calcium deposits and a cell-rich subendothelial thickening. The immunohistologic analysis indicated that the cells in the subendothelial connective tissue were fibroblasts. T lymphocytes appeared to be the most common cell type in the vicinity of the calcium deposits and were also found close to the endothelial lining of the valves. T-helper cells were more frequent than cytotoxic T cells. Expression of interleukin-2 receptors occurred at the same location as T lymphocytes. Control valves lacked subendothelial thickening and contained only few cells reacting with antibodies against lymphocytes and macrophages. CONCLUSIONS The presence of activated T lymphocytes in tricuspid stenotic valves suggests that immunologic mechanisms may be involved in the etiology of nonrheumatic aortic stenosis.

Early Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest

BACKGROUND Three million people in Sweden are trained in cardiopulmonary resuscitation (CPR). Whether this training increases the frequency of bystander CPR or the survival rate among persons who have out-of-hospital cardiac arrests has been questioned. METHODS We analyzed a total of 30,381 out-of-hospital cardiac arrests witnessed in Sweden from January 1, 1990, through December 31, 2011, to determine whether CPR was performed before the arrival of emergency medical services (EMS) and whether early CPR was correlated with survival. RESULTS CPR was performed before the arrival of EMS in 15,512 cases (51.1%) and was not performed before the arrival of EMS in 14,869 cases (48.9%). The 30-day survival rate was 10.5% when CPR was performed before EMS arrival versus 4.0% when CPR was not performed before EMS arrival (P<0.001). When adjustment was made for a propensity score (which included the variables of age, sex, location of cardiac arrest, cause of cardiac arrest, initial cardiac rhythm, EMS response time, time from collapse to call for EMS, and year of event), CPR before the arrival of EMS was associated with an increased 30-day survival rate (odds ratio, 2.15; 95% confidence interval, 1.88 to 2.45). When the time to defibrillation in patients who were found to be in ventricular fibrillation was included in the propensity score, the results were similar. The positive correlation between early CPR and survival rate remained stable over the course of the study period. An association was also observed between the time from collapse to the start of CPR and the 30-day survival rate. CONCLUSIONS CPR performed before EMS arrival was associated with a 30-day survival rate after an out-of-hospital cardiac arrest that was more than twice as high as that associated with no CPR before EMS arrival. (Funded by the Laerdal Foundation for Acute Medicine and others.).

Anticoagulation control in Sweden: reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry AuriculA

AIMS In anticoagulation treatment with warfarin, the risk of thrombo-embolic events must be weighed against the risk of bleeding. Time in therapeutic range (TTR) is an important tool to assess the quality of anticoagulation treatment, and has been shown to correlate with less bleeding and thrombo-embolic complications. AuriculA, the Swedish national quality registry for atrial fibrillation and anticoagulation, is used for follow-up and dosage control of warfarin. This is the first report of TTR in AuriculA and, in a subgroup of two centres, bleeding and thrombo-embolic complications during 2008. METHODS AND RESULTS Prothrombin complex (International normalized ratio) values from 18 391 patients in 67 different centres were analysed. The mean (SD) age was 70 (12) years. The main indications for warfarin treatment were: atrial fibrillation (64%), venous thromboembolism (19%), and heart valve dysfunction (13%). Time in therapeutic range for all patients was 76.2%. The mean weekly dose of warfarin decreased with age and TTR increased with age. In 4273 patients from two centres in AuriculA, the frequency of major bleedings and venous/arterial thrombo-embolism were 2.6 and 1.7% and for atrial fibrillation, 2.6 and 1.4%, per treatment year, respectively. A correlation between age and the risk of major bleeding (P< 0.001), but not thrombo-embolic complications (P= 0.147), was seen. CONCLUSION Compared with prospective randomized trials of warfarin treatment, TTR in the AuriculA population was higher. Complications were low, probably due to the organization of anticoagulation treatment in Sweden. Use of the AuriculA dosing programme could have contributed to the results by keeping dosing regimens consistent over all centres.

Compression-Only CPR or Standard CPR in Out-of-Hospital Cardiac Arrest

BACKGROUND Emergency medical dispatchers give instructions on how to perform cardiopulmonary resuscitation (CPR) over the telephone to callers requesting help for a patient with suspected cardiac arrest, before the arrival of emergency medical services (EMS) personnel. A previous study indicated that instructions to perform CPR consisting of only chest compression result in a treatment efficacy that is similar or even superior to that associated with instructions given to perform standard CPR, which consists of both compression and ventilation. That study, however, was not powered to assess a possible difference in survival. The aim of this prospective, randomized study was to evaluate the possible superiority of compression-only CPR over standard CPR with respect to survival. METHODS Patients with suspected, witnessed, out-of-hospital cardiac arrest were randomly assigned to undergo either compression-only CPR or standard CPR. The primary end point was 30-day survival. RESULTS Data for the primary analysis were collected from February 2005 through January 2009 for a total of 1276 patients. Of these, 620 patients had been assigned to receive compression-only CPR and 656 patients had been assigned to receive standard CPR. The rate of 30-day survival was similar in the two groups: 8.7% (54 of 620 patients) in the group receiving compression-only CPR and 7.0% (46 of 656 patients) in the group receiving standard CPR (absolute difference for compression-only vs. standard CPR, 1.7 percentage points; 95% confidence interval, -1.2 to 4.6; P=0.29). CONCLUSIONS This prospective, randomized study showed no significant difference with respect to survival at 30 days between instructions given by an emergency medical dispatcher, before the arrival of EMS personnel, for compression-only CPR and instructions for standard CPR in patients with suspected, witnessed, out-of-hospital cardiac arrest. (Funded by the Swedish Heart–Lung Foundation and others; Karolinska Clinical Trial Registration number, CT20080012.)

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial

BACKGROUND In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. METHODS Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. FINDINGS Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. INTERPRETATION The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. FUNDING Bristol-Myers Squibb and Pfizer.

Assessment of female sex as a risk factor in atrial fibrillation in Sweden: nationwide retrospective cohort study.

Objective To determine whether women with atrial fibrillation have a higher risk of stroke than men. Design Nationwide retrospective cohort study. Setting Patients with a diagnosis of atrial fibrillation in the Swedish hospital discharge register between 1 July 2005 and 31 December 2008. Information about drug treatment taken from the Swedish drug register. Participants 100 802 patients with atrial fibrillation at any Swedish hospital or hospital affiliated outpatient clinic with a total follow-up of 139 504 years at risk (median 1.2 years). We excluded patients with warfarin at baseline, mitral stenosis, previous valvular surgery, or who died within 14 days from baseline. Main outcome measure Incidence of ischaemic stroke. Results Ischaemic strokes were more common in women than in men (6.2% v 4.2% per year, P<0.0001). The univariable hazard ratio for women compared with men was 1.47 (95% confidence 1.40 to 1.54), indicating a 47% higher incidence of ischaemic stroke in women than in men. Stratification according to the CHADS2 scheme showed increased stroke rates for women in all strata. After multivariable adjustment for 35 cofactors for stroke, an increased risk of stroke in women remained (1.18, 1.12 to 1.24). Among patients with “lone atrial fibrillation” (age <65 years and no vascular disease), the annual stroke rate tended to be higher in women than in men, although this difference was not significant (0.7% v 0.5%, P=0.09). When low risk patients with CHADS2 scores of 0-1 were stratified according to their CHA2DS2-VASc scores, women did not have higher stroke incidence than men at CHA2DS2-VASc scores of 2 or less. Conclusion Women with atrial fibrillation have a moderately increased risk of stroke compared with men, and thus, female sex should be considered when making decisions about anticoagulation treatment. However, women younger than 65 years and without other risk factors have a low risk for stroke, and do not need anticoagulant treatment.

The Effect of Ventricular Activation Sequence on Cardiac Performance During Pacing

The aim of this study was to evaluate the importance of a normal ventricular activation pattern for cardiac performance. In nine mongrel clogs, atrial pacing was compared to AV synchronous pacing at three different A V delays (150, 100, and 60 nis). In six dogs, proximal septal AV synchronous pacing was compared to apical A V synchronous pacing at three different A V delays. AV synchronous pacing was performed after RF induced complete heart block. Hemodynarnics were evaluated by assessment of positive and negative dP/dt, cardiac output, and left ventricular and pulmonary pressures. Atrial pacing was superior to AV synchronous pacing with respect to positive and negative dP/dt and cardiac output. This difference was present at all AV delays. Proximal septal pacing was associated with a higher positive and negative dP/dl compared to apical pacing at all AV delays. Left ventricular activation time was significantly shorter during proximal septal pacing than during apical pacing (88 ± 4 vs 115 ± 4 ms, P < 0.001). We conclude that atrial and proximal septal pacing improves cardiac function and shortens the ventricular activation time compared to apical AV synchronous pacing independent of the AV interval.