Health status outcomes after cardioversion for atrial fibrillation: results from the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) II Trial.

BACKGROUND: Atrial fibrillation is the most common significant cardiac arrhythmia and substantially impacts the health status of patients. Enoxaparin has been shown to be a safe and effective alternative to unfractionated heparin for use with transesophageal echocardiography (TEE)-guided cardioversion, but the implications on health status remain unknown. The aim of the study was to compare the health status outcomes of patients who undergo TEE-guided cardioversion with enoxaparin or unfractionated heparin as anticoagulation bridging therapy. METHODS: The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) II multicenter trial randomized 155 patients to bridging therapy with either enoxaparin or unfractionated heparin. Of these, 118 were included in the health status substudy. Health status was assessed at baseline and 5 weeks using the RAND 36-item health survey (RAND-36), the Duke Activity Status Index (DASI), and the Health Utilities Index Mark 3 (HUI-3). RESULTS: There were no significant differences in the health status measures between the treatment groups. However, patients who remained in normal sinus rhythm at follow-up had absolute improvement in all measures of health status, whereas patients in atrial fibrillation at follow-up had an absolute decrease in the DASI, HUI-3, and 5 of 8 subscales of the RAND-36. These findings reached statistical significance in the HUI-3 and 3 of 8 subscales of the RAND-36. CONCLUSIONS: Health status outcomes in TEE-guided cardioversion do not significantly differ between anticoagulant bridging therapy with enoxaparin or unfractionated heparin. However, maintenance of sinus rhythm at 5 weeks was associated with an improvement in health status.

Comparison of anticoagulant and anti-inflammatory responses using enoxaparin versus unfractionated heparin for transesophageal echocardiography-guided cardioversion of atrial fibrillation.

The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) II study compared enoxaparin with unfractionated heparin (UFH) as bridging therapy in patients with atrial fibrillation >2 days in duration who underwent transesophageal echocardiography-guided cardioversion. In the present study, the anticoagulant and anti-inflammatory effects of enoxaparin and UFH were compared at prespecified time points. In a randomized substudy of 155 patients from 17 clinical sites, the anticoagulant activity of enoxaparin (n = 76) was compared with that of UFH (n = 79). Blood samples were drawn at enrollment, on day 2, and on day 4 in the 2 groups. Blood samples were evaluated for anticoagulant activity by measuring the activated partial thromboplastin time, anti-Xa, anti-IIa, and tissue factor pathway inhibitor levels. In addition, levels of coagulation activation (by thrombin antithrombin complex) and inflammation (by highly sensitive C-reactive protein) were measured. The results of this substudy showed that the anti-Xa levels in the 2 groups increased on day 2. Similar increases in anti-Xa were observed on day 4. The anti-Xa levels and tissue factor pathway inhibitor levels were higher in the enoxaparin group compared with the UFH group on days 2 and 4. However, as expected, the anti-IIa levels in the UFH group were higher. In addition, markers of coagulation activation and inflammation were increased in patients with atrial fibrillation. Treatment with enoxaparin significantly decreased thrombin antithrombin complex levels compared with treatment with UFH. Highly sensitive C-reactive protein levels were also decreased after treatment in the 2 groups. In conclusion, the ACUTE II study showed that the use of enoxaparin for bridging therapy in patients with atrial fibrillation who underwent transesophageal echocardiography-guided cardioversion resulted in a more predictable and stronger anticoagulant response than that observed with UFH. Markers of inflammation were also decreased in the 2 groups.

Contrast-enhanced tissue Doppler imaging of the left atrial appendage is a new quantitative measure of spontaneous echocardiographic contrast in atrial fibrillation.

AIMS: Although left atrial appendage spontaneous echo contrast (LAASEC) is a marker of increased thromboembolic risk in atrial fibrillation, it has previously only been evaluated qualitatively. We sought to determine if an intravenous contrast echocardiographic agent combined with tissue Doppler imaging (TDI) of the LAA could accurately quantify LAA-SEC in patients with atrial fibrillation. METHODS AND RESULTS: We prospectively identified 55 patients with persistent atrial arrhythmias (mean age 63+/-13 years) undergoing a transesophageal echocardiography (TEE), with LAA-SEC prior to direct current cardioversion. In addition to off-line calculation of backscatter index and shear rate, quantification of the velocity in a color TDI region of interest was performed in the LAA cavity following a 0.5-mL intravenous bolus of Optison. LAA-SEC was qualitatively graded by a blindedreader as mild (n = 29) or severe (n = 26), and was compared off-line to TEE-derived quantitative variables. Compared to patients with mild LAA-SEC, those with severe LAA-SEC had significantly decreased LAA emptying velocity, LAA TDI mean velocities and shear rate. Over the whole group, the mean maximal velocity of the LAA using TDI correlated with LAA emptying velocity (r = 0.59; P < 0.0001), shear rate (r = 0.55; P < 0.0001) and LAA area (r = 0.34; P = 0.014). Severe LAA-SEC was found with 72% sensitivity and 82% specificity if TDI mean velocity was <6.13 cm/s. On logistic regression analysis, LAA-TDI was the only predictor of qualitative LAA-SEC grade. CONCLUSION: Contrast-enhanced TDI is an original new tool that provides a quantification of the mean velocity of LAA-SEC that might improve our decision making in patients with atrial fibrillation.

Efficacy of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation at 6 months: a randomized controlled trial.

BACKGROUND: Electrical cardioversion in patients with atrial fibrillation (AF) is associated with an increased risk of stroke. We compared a transesophageal echocardiography (TEE)-guided strategy with a conventional strategy in patients with AF > 2 days' duration undergoing electrical cardioversion over a 6-month follow-up. METHODS: The ACUTE study was a multicenter, randomized, clinical trial, with 1222 patients. Six-month follow-up was available in 1034 patients (85%), 525 in the TEE group and 509 in the conventional group. The primary composite end points were cerebrovascular accident, transient ischemic attack, and peripheral embolism at 6 months, which was a prespecified time point. Secondary end points were hemorrhage, mortality, and sinus rhythm. RESULTS: At 6 months, there was no difference in composite embolic events between the TEE group and the conventional group (10 [2%] vs 4 [0.8%]; risk ratio (RR) 2.47, 95% CI 0.78-7.88; P = .11). However, the hemorrhagic rate was significantly lower in the TEE group (23 [4.4%] vs 38 [7.5%]; RR 0.58, 96% CI 0.35-0.97; P = .04). There was no difference between the 2 treatment groups in all-cause mortality (21 [4%] vs 14 [2.8%]; RR 1.48, 95% CI 0.76-2.92; P = .25) and in the occurrence of normal sinus rhythm between the 2 groups (305 [62.2%] vs 280 [58.1%]; P = .51). Sinus rhythm at 6 months was more common in the TEE-guided group, in those patients who had direct current cardioversion (238 [62.5%] vs 151 [53.9%]; P = .03). CONCLUSION: The TEE-guided strategy may be considered a clinically effective alternative to a conventional anticoagulation strategy for patients with AF of > 2 days' duration undergoing electrical cardioversion over a 6-month period.

Spontaneous conversion of patients with atrial fibrillation scheduled for electrical cardioversion: an ACUTE trial ancillary study.

OBJECTIVES: This study was designed to determine the characteristics and outcomes of spontaneous conversion (SC) to sinus rhythm (SR) in patients with atrial fibrillation (AF) of more than two days. BACKGROUND: The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) multicenter study was a prospective trial in which transesophageal echocardiography (TEE)-guided treatment was compared with conventional anticoagulation treatment for the management of patients with AF >2 days undergoing direct current cardioversion (DCC). In an ancillary analysis, we evaluated the baseline and outcome data in patients who underwent SC to SR before scheduled DCC. METHODS: We identified 1,041 patients for this analysis after excluding patients on pre-existing antiarrhythmic agents. Patients with SC in the TEE-guided and conventional groups were first compared then pooled and compared with non-spontaneous conversion (No-SC) patients. RESULTS: Overall, 167 of 1,041 (16%) patients underwent SC, with twice as many in the conventional compared with the TEE-guided group (110/523 [21%] vs. 57/518 [11%]; p < 0.001). When compared with No-SC patients, a higher proportion of SC patients maintained SR at eight weeks (87.2% vs. 48.9%, p < 0.001), without statistically significant differences in bleeding, thromboembolism or mortality. Multivariate predictors of SC were shorter duration of AF, New York Heart Association (NYHA) functional class 1 or 2, smaller left atrial size, and absence of left atrial spontaneous echo contrast. CONCLUSIONS: Spontaneous conversion was associated with shorter duration of AF, lower NYHA class, smaller left atrial size, and absence of left atrial spontaneous echo contrast. There was a better SR outcome in the SR group, but no differences in the other clinical end points. The conventional treatment strategy allowed greater opportunity for SC. In the absence of favorable predictors of SC, the TEE-guided approach should be considered.

Economic analysis of a transesophageal echocardiography-guided approach to cardioversion of patients with atrial fibrillation: the ACUTE economic data at eight weeks.

OBJECTIVES: The aim of this study was to compare the relative cost of a transesophageal echocardiography (TEE)-guided strategy versus conventional strategy for patients with atrial fibrillation (AF) >2 days duration undergoing electrical cardioversion over an eight-week period. BACKGROUND: The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) trial found no difference in embolic rates between the two approaches. However, the TEE-guided strategy had a shorter time to cardioversion and a lower rate of composite bleeding. While similar clinical efficacy was concluded, the relative cost of these two strategies has not been explored. METHODS: Two economic approaches were employed in the ACUTE trial. The first approach was based on hospital charge data from complete hospital Universal Billing Code of 1992 forms, a detailed hospital charge questionnaire, or imputation. Regression analysis was used to investigate the added cost of adverse events. The second economic approach involved the development of an independent analytic model simulating treatment and actual ACUTE outcome costs as a validation of clinically derived data. Sensitivity analysis was performed on the analytic model to investigate the potential range in cost differences between the strategies. RESULTS: A total of 833 of the 1,222 patients were enrolled from 53 U.S. sites; TEE-guided (n = 420) and conventional (n = 413). At eight-week follow-up, total mean costs did not significantly differ between the two groups, respectively (6,508 dollars vs. 6,239 dollars; difference of 269 dollars; p = 0.50). Cumulative costs were 24% higher in the conventional group, primarily due to increased incidence of bleeding and hospital costs associated with bleeding. A separate analytic model showed that treatment costs were higher for the TEE-guided strategy, but outcome costs were higher for the conventional strategy. Sensitivity analysis of the analytic model illustrated that varying the incidence and cost of major bleeding and the cost of TEE had the greatest impact on cost differences between the two groups. CONCLUSIONS: In patients with AF >2 days duration undergoing electrical cardioversion, the TEE-guided group showed little difference in patient costs compared with the conventional group. The TEE strategy had higher initial treatment costs but lower outcome-associated costs. Cumulative costs were 24% higher in the conventional group, primarily due to bleeding. The TEE-guided strategy is an economically feasible approach compared with the conventional strategy.

Impact of cardioversion strategy on functional capacity in patients with atrial fibrillation: the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study.

BACKGROUND: The ACUTE Trial studied a transesophageal echocardiography (TEE)-guided strategy compared with a conventional strategy for management of patients with atrial fibrillation undergoing direct current cardioversion. The primary aim was to determine if patient functional capacity, measured by the Duke Activity Status Index (DASI), would differ between treatment strategies. METHODS: The DASI was self-administered at study enrollment and at 8-week follow-up in 1074 (88%) of 1222 total patients. Clinical outcomes associated with enrollment DASI scores and change in follow-up DASI scores were reviewed. RESULTS: There was no difference between the TEE-guided (n = 544) and conventional treatment (n = 530) groups for mean baseline and 8-week DASI scores, adjusting for baseline; however, patients who improved their DASI score were more likely to be in the TEE-guided group (P = .03). Pooled group data showed that the higher the enrollment DASI score, the more it tended to be positively related to maintenance of sinus rhythm (P = .06) at 8 weeks. The lower the enrollment DASI score, the more it was predictive of death (P = .03) and bleeding (P = .01) within 8 weeks. Patients with congestive heart failure (CHF) at enrollment showed greater improvement in DASI scores at 8 weeks compared with patients without CHF (DASI Delta 45.9% vs 31.6%, P < .001). CONCLUSIONS: There was no difference in DASI scores between treatment groups. However, TEE-guided treatment was a predictor of improved DASI at follow-up, and subgroup analysis showed that patients with CHF did show improvement in functional capacity with cardioversion.

Utility of transesophageal echocardiography in identification of thrombogenic milieu in patients with atrial fibrillation (an ACUTE ancillary study).

The ACUTE trial randomly assigned patients who had atrial fibrillation (AF) of >2 days' duration to a transesophageal echocardiographically guided or a conventional strategy before cardioversion. In the 571 patients who underwent transesophageal echocardiography (TEE) in the ACUTE trial, we assessed the relative predictive value of baseline data derived by history, transthoracic echocardiography, and TEE for prediction of thrombus and adjudicated embolism (thromboembolism) as a composite end point. TEE was performed at 70 centers in 571 patients, 549 in the transesophageal echocardiographically guided group and 22 crossovers in the conventional group. Six patients (1.1%) who had embolism and 79 (13.8%) who had thrombi were identified in this group. Thrombus was completely resolved in 76.5% of patients who had repeat transesophageal echocardiographic procedures after 31.7 +/- 7.5 days of anticoagulation. For patients who had embolic events, none had a transesophageal echocardiographically identified thrombus; 5 of 6 (83.3%) had >/=1 transesophageal echocardiographic risk factors (including spontaneous echocardiographic contrast, aortic atheroma, patent foramen ovale, atrial septal aneurysm, mitral valve strands), and 4 of 6 (66.66%) had subtherapeutic anticoagulation or no anticoagulation. Clinical, transthoracic echocardiographic, and transesophageal echocardiographic risk factors contributed significantly to the prediction of composite thrombus/embolism. However, transesophageal echocardiographic thromboembolic risk factors were the strongest predictors of thromboembolism and provided statistically significant incremental value (chi-square 38.0, p <0.001) for identification of risk. Thus, in addition to thrombus identification, TEE has significant incremental value in the identification of patients who had high thromboembolic risk. In conclusion, this study supports the role of TEE and anticoagulation monitoring in patients who have atrial fibrillation and is useful for identifying thromboembolic risk factors.

Bleeding complications in patients with atrial fibrillation undergoing cardioversion randomized to transesophageal echocardiographically guided and conventional anticoagulation therapies.

In a multicenter randomized trial, we studied a transesophageal echocardiography (TEE) guided strategy with short-term anticoagulation compared with a conventional strategy for patients with atrial fibrillation >2 days' duration and undergoing cardioversion. Composite major and minor bleeding was a predetermined secondary end point of the study. The objective of the study was to assess the incidence, location, and predictors of bleeding in the 2 treatment groups. A total of 1,222 patients were assigned to a TEE guided or conventional strategy and followed over 8 weeks. We present data on major and minor adjudicated bleeding complications for the 2 study groups during the 8-week study period. Composite major and minor bleeding complications occurred in 51 of 1,222 patients (4.2%) and were significantly lower in the TEE guided group compared with the conventional group (2.9 vs 5.5%, p = 0.025). The TEE group had fewer cancellations of cardioversion as a result of bleeding (0% vs 0.7%, p = 0.003). Major (n = 14) and minor (n = 38) bleeding complications were predominantly gastrointestinal (71.4% and 31.6%, respectively) and were associated with warfarin use. Predictors of bleeding included patient age, conventional group assignment, inpatient status, and functional status. Thus, composite major and minor bleeding complications occurred in 4.2% of the 1,222 patients and were significantly lower in the TEE guided group compared with the conventional group. Treatment variables affecting length of anticoagulant therapy in the conventional arm combined with advancing age and functional status are important concerns in patients who undergo cardioversion of atrial fibrillation.

Relation of C-reactive protein correlates with risk of thromboembolism in patients with atrial fibrillation.

The relation between C-reactive protein, an inflammatory marker, and thromboembolic risk factors was investigated in 104 patients with atrial fibrillation and found that patients with transesophageal echocardiography identified thromboembolic risk factors had greater C-reactive protein levels than those without (1.00 vs 0.302 mg/dl). C-reactive protein also correlated with clinical stroke risk factors. Increased C-reactive protein levels were also independently associated with transesophageal echocardiographic thromboembolic risk factors.

Role of CHADS2 score in evaluation of thromboembolic risk and mortality in patients with atrial fibrillation undergoing direct current cardioversion (from the ACUTE Trial Substudy).

The CHADS(2) (congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke or transient ischemic attack [2 points]) scoring scheme has been found to be a good predictor of stroke risk in patients with nonvalvular atrial fibrillation (AF). However, the value of the CHADS(2) scoring system in the risk stratification of patients with AF who undergo direct-current cardioversion has not yet been specifically investigated. In this study, a subgroup of 541 patients from the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study who had AF for >48 hours and planned to undergo transesophageal echocardiography before direct-current cardioversion were enrolled. Each patient had a CHADS(2) score calculated. Of the patients with CHADS(2) scores of 0, 14 (10%) were found to have left atrial appendage thrombi on transesophageal echocardiography. After 6 months of follow up, patients with CHADS(2) scores of 3 to 6 showed a significantly higher mortality rate in comparison with patients with lower CHADS(2) scores (4.3% vs 0.5%, p = 0.004), despite their similar prevalence of left atrial appendage thrombus and stroke (thrombus: 13.4% vs 11.6%, p = 0.60; stroke: 0% vs 0.3%, p = 0.70). In conclusion, the CHADS(2) scoring system may be useful for predicting short-term mortality risk in patients with AF receiving elective direct-current cardioversion. However, in the preprocedural risk assessment of these patients, the CHADS(2) scoring system is not reliable in predicting risk for left atrial appendage thrombus formation, especially in patients with low CHADS(2) scores.

Right atrial volume index in chronic systolic heart failure and prognosis.

OBJECTIVES: The aim of this study was to determine the relationship between right atrial volume index (RAVI) and right ventricular (RV) systolic and diastolic function, as well as long-term prognosis in patients with chronic systolic heart failure (HF). BACKGROUND: RV dysfunction is associated with poor prognosis in patients with HF, although echocardiographic assessment of RV systolic and diastolic dysfunction is challenging. The ability to visualize the RA allows a quantitative, highly reproducible assessment of the RA volume that can be indexed to body surface area. METHODS: The ADEPT (Assessment of Doppler Echocardiography for Prognosis and Therapy) trial enrolled 192 subjects with chronic systolic HF (left ventricular ejection fraction [LVEF]

Comprehensive left atrial appendage optimization of thrombus using surface echocardiography: the CLOTS multicenter pilot trial.

BACKGROUND: The aim of this study was to determine the ability to identify thrombus within the left atrial appendage (LAA) in the setting of atrial fibrillation (AF) using transthoracic echocardiography (TTE). In AF, the structure and function of the LAA has historically been evaluated using transesophageal echocardiography (TEE). The role of TTE remains undefined. METHODS: The Comprehensive Left Atrial Appendage Optimization of Thrombus (CLOTS) multicenter study enrolled 118 patients (85 men; mean age, 67 +/- 13 years) with AF of >2 days in duration undergoing clinically indicated TEE. On TEE, the LAA was evaluated for mild spontaneous echo contrast (SEC), severe SEC, sludge, or thrombus. Doppler Tissue imaging (DTI) peak S-wave and E-wave velocities of the LAA walls (anterior, posterior, and apical) were acquired on TTE. Transthoracic echocardiographic harmonic imaging (with and without intravenous contrast) was examined to determine its ability to identify LAA SEC, sludge, or thrombus. RESULTS: Among the 118 patients, TEE identified 6 (5%) with LAA sludge and 2 (2%) with LAA thrombi. Both LAA thrombi were identified on TTE using harmonic imaging with contrast. Anterior, posterior, and apical LAA wall DTI velocities on TTE varied significantly among the 3 groups examined (no SEC, mild SEC, severe SEC, sludge or thrombus). An apical E velocity < or = 9.7 cm/s on TTE best identified the group of patients with severe SEC, sludge, or thrombus. An anterior S velocity < or = 5.2 cm/s on TTE best identified the group of patients with sludge or thrombus. CONCLUSIONS: The CLOTS multicenter pilot trial determined that TTE is useful in the detection of thrombus using harmonic imaging combined with intravenous contrast (Optison; GE Healthcare, Milwaukee, WI). Additionally, LAA wall DTI velocities on TTE are useful in determining the severity of LAA SEC and detecting sludge or thrombus.

Clinical features of mixed physiology of constriction and restriction: echocardiographic characteristics and clinical outcome.

AIMS: An entity of patients with mixed physiology of constriction and restriction has been reported, however, the characteristics of these patients have not been well documented. We evaluated the clinical features and the outcome of these patients. METHODS AND RESULTS: Study subjects consisted of 38 patients (57+/-14 years, 8 females, 30 males) who were diagnosed as having mixed physiology based on transthoracic and/or transesophageal echocardiography, MRI (or CT), cardiac catheterization, endomyocardial biopsy and/or surgical findings. Prior radiation therapy was the most frequent (50%) cause of mixed physiology followed by coronary artery bypass graft without prior radiation (24%) and heart transplantation (8%). The respiratory variation of peak early diastolic transmitral flow velocity by pulsed Doppler transesophageal echocardiography was 10.7% in patients with sinus rhythm and 18.1% in patients with atrial arrhythmia. Pericardial thickening was noted adjacent to the right-sided chambers in 19 patients, left-sided chambers in 10 patients, or both in 9 patients. All-cause 5-year mortality was 40% and unrelated to age, etiology, left ventricular systolic function and therapeutic course. There was a statistically significant difference (p<0.01) between the survival rates in patients with mixed physiology and in patients with pure constriction (n=125). CONCLUSIONS: Due to the high mortality in this disease, discrimination of the entity from the patients with pure constriction is mandatory. Transthoracic and transesophageal echocardiography are helpful noninvasive techniques in the diagnosis and the understanding of the physiology of patients with mixed constriction and restriction.

The use of enoxaparin compared with unfractionated heparin for short-term antithrombotic therapy in atrial fibrillation patients undergoing transoesophageal echocardiography-guided cardioversion: assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II randomized multicentre study.

AIMS: To compare the feasibility and safety of transoesophageal echocardiograpy-guided cardioversion (CV) with enoxaparin and unfractionated heparin (UFH) in patients with atrial fibrillation (AF). METHODS AND RESULTS: The Assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II pilot trial compared the safety and efficacy of enoxaparin with UFH in 155 patients with AF who were scheduled for transoesophageal echocardiography (TEE)-guided CV. Safety outcomes over a 5-week period were ischaemic stroke, major or minor bleeding, and death. Efficacy outcomes were length of stay (LOS) and return to normal sinus rhythm (NSR). Of the 76 patients assigned to the enoxaparin group, 72 (94.7%) had a transoesophageal echocardiogram and 63 (82.9%) had early CV, of which 59 (93.7%) were successful. Of the 79 UFH patients, 66 (83.5%) had a transoesophageal echocardiogram and 58 (73.4%) had early CV, of which 54 (98.2%) were successful. There were no significant differences in embolic events, bleeding, or deaths between groups. The enoxaparin group had shorter median LOS compared with the UFH group [3(2-4) vs. 4(3-5)] days; P<0.0001). There was also more NSR at 5 weeks in the enoxaparin group (76 vs. 57%; P=0.013). CONCLUSION: In the ACUTE II trial, there were no differences in safety outcomes between the two strategies. However, the enoxaparin group had a shorter LOS. Thus, the TEE-guided enoxaparin strategy may be considered a safe and effective alternative strategy for AF. The shorter LOS may translate to lower costs using the enoxaparin TEE-guided approach.