Low molecular weight heparin and non valvular atrial fibrillation

Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.     

Treatment failure of low molecular weight heparin bridging therapy before a cardiac surgery intervention in a patient with atrial fibrillation

From time to time, it may be necessary to interrupt oral anticoagulant therapy in preparation for surgical procedures. In high-risk patients or for longer periods, unfractionated or low-molecular-weight heparin bridging treatment has been reported safe. This case focuses attention on treatment failure of low molecular weight heparin bridging therapy in a patient with atrial fibrillation.     

Low molecular weight heparin versus unfractionated heparin for thromboprophylaxis in patients with acute atrial fibrillation: a randomized control trial

While long-term anticoagulation prevents ischemic stroke in high-risk patients with atrial fibrillation (AF), the optimal initial anti-thrombotic regime in acute AF is less well defined. We randomized 96 patients with new onset acute AF in an emergency admission ward to receive (1) once-daily preparation of low molecular weight heparin (LMWH), tinzaparin or (2) conventional intravenous unfractionated heparin (target APTT 50-70 s). 5 patients in unfractionated heparin group compared with no patients in LMWH group (0%, P = 0.04) developed ischemic stroke/transient ischemic attack during the first 48 h. An initial subcutaneous LMWH was safe and effective in ischemic stroke prevention in patients with acute AF.     

Low molecular weight heparin versus unfractionated heparin for thromboprophylaxis in patients with acute atrial fibrillation: A randomized control trial

While long-term anticoagulation prevents ischemic stroke in high-risk patients with atrial fibrillation (AF), the optimal initial anti-thrombotic regime in acute AF is less well defined. We randomized 96 patients with new onset acute AF in an emergency admission ward to receive (1) once-daily preparation of low molecular weight heparin (LMWH), tinzaparin or (2) conventional intravenous unfractionated heparin (target APTT 50–70 s). 5 patients in unfractionated heparin group compared with no patients in LMWH group (0%, P = 0.04) developed ischemic stroke/transient ischemic attack during the first 48 h. An initial subcutaneous LMWH was safe and effective in ischemic stroke prevention in patients with acute AF.     

Cardioversion of atrial fibrillation in the elderly

The purpose of this investigation was to define cardioversion success rates, frequency of complications of cardioversion, and current treatment practices in elderly patients (aged > 65 years) with atrial fibrillation (AF). The results were compared with those in younger patients (aged < 65 years). The investigation was a prospective multicenter observational study with 61 participating cardiology clinics. Consecutive patients in whom cardioversion of AF was planned had to be prospectively registered. Of 1,152 patients registered, 570 (49.5%) were < 65 years old (group 1) and 582 (50.5%) were ≥65 years (group 2). The overall success rate of cardioversion on an intention-to-treat basis was 76.1% in group 1 and 72.7% in group 2 (p = 0.18). In multivariate analysis, left atrial size and New York Heart Association functional class before cardioversion were identified as predictors of success (p < 0.001, respectively; P = 0.025). These clinical factors were not equally distributed between the age groups: Left atrial size was larger in the elderly than in younger patients (44.0 ± 6.4 mm vs 42.8 ± 6.4 mm; P = 0.006) and a New York Heart Association functional class ≥II was more prevalent in group 2 than in group 1 (48.6% vs 29.6%; p < 0.001). The overall complication rates were not significantly different between the 2 groups (4.2% in group 1 vs 5.3% in group 2; P = 0.37). The frequency of patients who were adequately anticoagulated for cardioversion was 56.9% in age group 1 and 39.6% in age group 2 (p < 0.001). In chronic AF the same trend for age-dependent underuse of anticoagulation was observed. Age itself was not a predictor of cardioversion success and did not predispose to higher complication rates. Therefore, cardioversion should be considered in older patients with the same criteria and emphasis as in younger patients. Anticoagulation and antithrombotic medication is underused for cardioversion and in treating chronic AF, especially in elderly patients.     

Feasibility of home self-administration of low molecular weight heparin by patients with atrial fibrillation recurrence. A new approach to thromboembolic prophyllaxis

We checked the feasibility of self-screening for atrial fibrillation (AF) by instructed patients pts and prompt home self-administration of an initial dose of low-molecular weight heparin (LMWH) prior to seeking medical attention. INVESTIGATED GROUP AND METHODS: Pts with persistent AF and low risk of systemic embolisation qualified to elective cardioversion (CV) were the subjects of our interest. All pts were trained to identify AF by palpation of the radial pulse and to self-inject LMWH in case of arrhythmia recurrence. 232 pts (mean age 59.8 +/- 8.6 years) who maintained sinus rhythm (SR) during 4 weeks following successful cardioversion (CV) and correctly recognized AF recurrence and those without episodes of AF were equipped with nadroparine after acenocoumarol discontinuation. Thromboembolic prophylaxis was continued with antiplatelets agents or those no additional risk factors of systemic embolisation were left without medical therapy. RESULTS: 191 pts had AF recurrence during the mean 2.6 +/- 1.7 years observation period, 172 of them correctly identified AF episode, including 162 who performed LMWH injections at home. 7 pts, who had performed LMWH injections, presented with SR on arrival to hospital, 6 pts had AF1.2 out of 21 pts who failed to identify their AF episodes and 1 pt of those who correctly detected the AF recurrence but failed to perform LMWH self-injection suffered from ischemic stroke (sensitivity 96.1%, specificity 60.4%). No side effects of domiciliary LMWH self-injection were found. CONCLUSION: When properly trained, the majority of pts can accurately diagnose AF recurrence and self-inject initial dose of LMWH, what is feasible and may represent an attractive anti-thromboembolic strategy.     

Cardioversion of persistent atrial fibrillation by a combination of atrial specific and non-specific class III drugs in the goat

OBJECTIVE: In electrically remodeled atria the effect of blockers of the delayed rectifier K+ current I(Kr) on repolarization is reduced, whereas the efficacy of 'early' class III drugs (I(Kur)/I(to)/I(Kach) blockers) is enhanced. We evaluated the electrophysiological and antifibrillatory effects of AVE0118, dofetilide, and ibutilide (alone and in combination) on persistent atrial fibrillation (AF) in the goat. METHODS AND RESULTS: The effects of separate and combined administration of AVE0118, dofetilide, and ibutilide were determined before and after 48 h of AF. AVE0118 alone markedly prolonged the atrial refractory period (400 ms cycle length) (AERP(400)) before and after 48 h of AF. The prolongation of AERP(400) by dofetilide and ibutilide, respectively, was reduced by AF from 22+/-2 to 7+/-2 ms (p<0.01) and 25+/-5 to 5+/-2 ms (p=0.01). Pre-treatment with AVE0118 restored the prolongation of AERP(400) by dofetilide or ibutilide (to 20+/-3 and 30+/-6 ms; p<0.01). This effect was atrial specific since the QT-interval was not changed. The antifibrillatory action was evaluated in 10 goats that were in persistent AF for 57+/-7 days. Dofetilide (20 mug/kg/h) or ibutilide (4 mg/h) alone restored sinus rhythm in only 20% of the animals. AVE0118 (1, 3 and 10 mg/kg/h) [corrected] terminated AF in 11, 30, and 60%, respectively. Additional infusion of I(Kr) blockers caused an additional number of cardioversions, resulting in a final cardioversion rate of 56, 80, and 100%, respectively. AVE0118 alone prolonged the AF cycle length (AFCL) while the conduction velocity during AF (CV(AF)) remained unchanged (70+/-1 vs. 68+/-2 cm/s; p=0.3). Addition of dofetilide or ibutilide caused a synergistic increase in AFCL and a slight increase in CV(AF) to 74+/-1 cm/s (p<0.001). The length of the reentrant trajectories increased from 7.6+/-0.3 (control) to 11.6+/-0.5 cm after AVE0118 alone (p<0.001) and 14.8+/-0.8 cm after addition of dofetilide or ibutilide (p<0.001). CONCLUSIONS: In electrically remodeled atria, blockade of I(Kur)/I(to)/I(KAch) restored the class III action of I(Kr) blockers. Persistent AF could be effectively cardioverted by infusion of a combination of AVE0118 and dofetilide or ibutilide. This antifibrillatory action was associated with an almost twofold lengthening of the intra-atrial pathways for reentry.     

Clinical characteristics of patients with persistent atrial fibrillation referred for cardioversion: Spanish Cardioversion Registry (REVERSE)

The objectives were to investigate the treatment and clinical characteristics of patients referred for cardioversion in Spain and to compare them with those reported in the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) and RACE (RAte Control versus Electrical cardioversion) studies. The prospective study involved 1515 consecutive patients with persistent atrial fibrillation who were referred for cardioversion at 96 Spanish hospitals. Half of the patients were being treated with Vaughan-Williams group-I or -III antiarrhythmic drugs. The most frequently used approach to anticoagulation was to administer dicoumarins 34 weeks before and after cardioversion. Our patients were younger than those in the AFFIRM and RACE studies. Compared with AFFIRM patients, our patients had a lower prevalence of previous embolism, ischemic heart disease, hypertension, diabetes, and systolic dysfunction. Compared with RACE patients, our patients had a lower prevalence of ischemic heart disease and previous embolism, but a slightly higher prevalence of hypertension and diabetes. We conclude that patients referred for cardioversion in Spain clearly had a lower cardiovascular risk profile than those in the AFFIRM study, and appeared to have a lower risk profile than those in the RACE study.     

电复律治疗风湿性心脏病瓣膜置换术后持续性心房颤动的疗效观察

目的探讨电复律治疗风湿性心脏病瓣膜置换术后伴左房明显增大的持续性心房颤动的疗效。方法将164例风湿性心脏病瓣膜置换术后持续性心房颤动的患者（左房内径均〉50mm）随机分为3组：胺碘酮组20例;胺碘酮＋雷米普利组76例;胺碘酮＋厄贝沙坦组68例。所有患者在经静脉应用胺碘酮后,房颤如未转复,则行电复律治疗。复律成功者胺碘酮改为口服200mg／d,联合雷米普利及厄贝沙坦组同时口服雷米普利5mg／d、厄贝沙坦150mg／d,3～6个月后停用。结果即时成功率92．7％（152／164例）。平均随访（1．8±0．4）年,128例（78．0％）保持窦性心律。联合雷米普利组窦律维持率为86．8％（66／76例）,联合厄贝沙坦组窦律维持率为75．0%（51／68例）无统计学差异,单独口服胺碘酮组55．0%（11／20例）维持窦性心律,与联合雷米普利组、厄贝沙坦组比较,有显著差异。末次随访,胺碘酮组左房内径较复律前明显增加[（60．5±3．8）mm vs（57．7±4．5）mm;P=0．04];联合雷米普利组[（58．2±4．3）mm vs（57．3±5．8）mm,P=0．283和联合厄贝沙坦组[（57．2．±5．5）mm vs（56．4±4．9）mm,P=0．373前后对照无显著差异。三组患者心功能均改善,两两比较无显著差异。结论对于房颤时间长,左房增大的患者只要正确掌握电复律的指征及方法,并予以辅助药物维持治疗,电复律的成功率较高,转复后维持率亦高,并能改善患者心功能。胺碘酮联合雷米普利或厄贝沙坦能延缓左房增大,提高窦律维持率。     

Embolic events in patients with atrial fibrillation and effective anticoagulation: value of transesophageal echocardiography to guide direct-current cardioversion. Final results of the Ludwigshafen Observational Cardioversion Study

OBJECTIVES: The primary objective was to evaluate the usefulness of transesophageal echocardiography (TEE)-guided cardioversion to prevent thromboembolic complications in patients with atrial fibrillation (AF) and effective anticoagulation (International Normalized Ratio of 2 or 3) at least three weeks before cardioversion. BACKGROUND: Transesophageal echocardiography has been proposed as a method of screening patients for left atrial thrombi before direct-current cardioversion of AF. The usefulness of TEE as a screening tool has always been evaluated in patients without long-term anticoagulation before cardioversion. METHODS: This prospective, single-center, observational study, performed on an intention-to-cardiovert basis, comprised 1,076 consecutive, unselected patients with AF. The initial two years were designed to be the control phase, during which the conventional approach was used. After that, cardioversion guided by TEE was performed in consecutive patients. RESULTS: The prevalence of left atrial thrombi was 7.7% in patients with persistent AF and effective anticoagulation. During the first four weeks after electrical cardioversion, six thromboembolic complications were observed in patients in whom the TEE-guided approach was employed (6 [0.8%] of 719 patients), compared with three thromboembolic complications in patients in whom the conventional approach was used (3 [0.8%] of 357 patients). None of the patients in whom electrical cardioversion was not performed experienced an embolic event. CONCLUSIONS: There were no differences in the rate of embolic events between the two treatment groups. In patients with AF and effective anticoagulation, TEE-guided electrical cardioversion does not reduce the embolic risk. However, TEE revealed left atrial thrombi in 7.7% of patients with AF and effective anticoagulation, before direct-current cardioversion.     

Internal low energy atrial cardioversion: efficacy and safety in older patients with chronic persistent atrial fibrillation

BACKGROUND: Low-energy internal atrial cardioversion is a relatively new technique based on delivery of intracardiac shocks through transvenous catheters placed into the atria or the vessels. OBJECTIVE: The aim of this study was to assess in older and younger patients with chronic persistent atrial fibrillation (AF) the efficacy and safety of transvenous low-energy internal atrial cardioversion performed without routine administration of sedatives or anesthetics. DESIGN: A prospective longitudinal study. SETTING: A cardiological university hospital. PARTICIPANTS: 82 patients, divided into older (> or = 60 years) (n = 49) and younger (n = 33) subjects. MEASUREMENTS: Atrial defibrillation threshold for internal cardioversion, measured as leading edge voltage (V) and delivered energy (J) of effective shocks, percentage of patients maintaining sinus rhythm at short-term (within 3 days) and at long-term follow-up. METHODS: Patients with chronic persistent AF, treated with oral anticoagulants for at least 3 to 4 weeks, were admitted to hospital. Following a clinical work-up, patients were subjected to low-energy internal atrial cardioversion with shock delivery according to a step-up protocol. RESULTS: Internal cardioversion was effective in restoring sinus rhythm in 90% (44/49) of the older patients and in 94% (31/33) of the younger patients. Shocks were effective at a mean energy between 6 and 8 joules (range 0.9-23) and administration of sedatives or anesthetics was required during the procedure in 22% (11/49) of older and in 48% (16/33) of younger patients (P = .026 at chi-square). No major complications occurred during the procedure. Pharmacological prophylaxis of AF recurrences was instituted immediately following the procedure. During inhospital stay and during the follow-up (mean 12 +/- 9 months for older patients and 15 +/- 10 months for younger patients), AF recurred in 39% (17/44) of older patients and in 16% (5/31) of younger subjects (P = .064 at chi-square). CONCLUSIONS: Internal low energy cardioversion is a very effective procedure for restoring sinus rhythm in patients with AF; it can be performed in older patients, and administration of sedatives or anesthetics can be avoided or minimized in a substantial proportion of subjects. Recurrences of AF in the long term tend to be higher in older subjects and intensive prophylaxis with antiarrhythmic drugs is required.     

Treatment of left intraventricular thrombosis with low molecular weight heparin

Following the discovery of a left intra ventricular thrombus (LIVT), the classical approach consists of treatment with non-fractionated heparin (NFH) followed by oral anticoagulants. The use of NFH for this indication has only been evaluated in one open, non randomised study of 23 patients with no control group. Low molecular weight heparins (LMWH) have not been the object of any study although they are routinely used by certain teams. The objective of this study was to evaluate the feasibility of the use of LMWH in the treatment of left intra ventricular thrombus. This was an open, non randomised prospective study. All patients having a newly diagnosed LIVT between September 2000 and September 2002 were treated with enoxaparine (100 IU/kg twice daily) for an average duration of 13 days; replacement with fluindione was started on the fifth day. The progression of the LIVT was followed using twice weekly transthoracic echocardiography for 3 weeks. RESULTS: 19 LIVT were discovered in 2 years (13 complicating an anterior infarct and 6 with a dilated cardiomyopathy). The average area was between 2.64 +/- 0.41 cm2 and 0.43 +/- 0.21 cm2 (p < 0.0001). Thirteen out of 19 thrombi disappeared with treatment (68.5%). There was no thrombocytopenia or haemorrhage. One transient ischaemic attack was noted. CONCLUSION: This preliminary work shows that LMWH are well tolerated and effective to make a thrombus disappear or to reduce its size.     

Determination of low molecular weight heparin in clinical laboratory

The applicability was investigated of automated spectrophotometric heparin assays and three clotting assays for determination of two low molecular weight (LMW) heparin fractions: Org 10172 and DxN10 and two infractionated commercially available heparins. The relative activity of the two commercially available heparins was similar in the anti-Xa assay, in the anti-IIa assay and in 3 clotting assays. The LMW heparins showed markedly different relative activity in all 5 assays. The activities of those heparin preparations relative to the standard heparin were compared in the 5 assays, but standardization against a standard heparin preparation appeared impossible. Methods of heparin determination can be used to monitor treatment with a heparin preparation only if the same preparation is used as a reference substance.