Background: Patients with mixed physiology of constriction and restriction have been reported, but their long-term survival has not been well documented. Methods: Study subjects consisted of 38 patients (57 ± 14 yrs, 8 female, 30 male) who were diagnosed as having mixed physiology based on echocardiography, MRI (or CT), cardiac catheterization, endomyocardial biopsy and/or surgical findings. We evaluated their echocardiographic, clinical features and calculated Kaplan-Meier survival curve to compare with that in patients with pure constriction. Results: Prior radiation therapy was the most frequent (50%) cause of mixed physiology followed by coronary artery bypass graft without prior radiation and heart transplantation. The respiratory variation of peak early diastolic transmitral flow velocity was 10.7% in patients with sinus rhythm, 18.1% in patients with atrial arrhythmia. Pericardial thickening was localized in 29 patients. All-cause 5-year mortality was 40 % and unrelated to age, etiology, left ventricular systolic function and therapeutic course. There was a significant difference between the survival rates in patients with mixed physiology and in 133 patients with pure constriction (Figure). Conclusions: Because of the high mortality in mixed disease, discrimination of this entity from pure constriction is important. Echocardiography is helpful noninvasive technique in diagnosis and understanding the physiology of the patients with mixed constriction and restriction.

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. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:222-226)

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).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.The ADEPT (Assessment of Doppler Echocardiography for Prognosis and Therapy) trial enrolled 192 subjects with chronic systolic HF (left ventricular ejection fraction [LVEF] <or=35%). The RA volume was calculated by Simpson's method using single-plane RA area and indexed to body surface area (RAVI). RV systolic function was graded as normal, mild, mild-moderate, moderate, moderately severe, or severe dysfunction.In our study cohort, the mean RAVI was 28 +/- 15 ml/m(2), and increased with worsening RV systolic dysfunction, LVEF, and LV diastolic dysfunction (Spearman's r = 0.61, r = 0.26, and r = 0.51, respectively; p < 0.001 for all). RAVI correlated modestly with echocardiographic estimates of RV diastolic dysfunction, including tricuspid early/late velocities ratio (Spearman's r = 0.34, p < 0.0001), hepatic vein systolic/diastolic ratio (Spearman's r = -0.26, p < 0.001) but not tricuspid early/tricuspid annular early velocities ratio (E/Ea) (Spearman's r = 0.12, p = 0.11). Increasing tertiles of RAVI were predictive of death, transplant, and/or HF hospitalization (log-rank p = 0.0002) and remained an independent predictor of adverse clinical events after adjusting for age, B-type natriuretic peptide, LV ejection fraction, RV systolic dysfunction, and tricuspid E/Ea ratio (hazard ratio: 2.00, 95% confidence interval: 1.15 to 3.58, p = 0.013).In patients with chronic systolic HF, RAVI is a determinant of right-sided systolic dysfunction. This quantitative and reproducible echocardiographic marker provides independent risk prediction of long-term adverse clinical events.

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 6 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 <= 9.7 cm/s on TTE best identified the group of patients with severe SEC, sludge, or thrombus. An anterior S velocity <= 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. (J Am Soc Echocardiogr 2009; 22: 1165-72.)

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 Optisono. LAA-SEC was qualitatively graded by a btindedreader 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.

The ACUTE II study demonstrated that transesophageal echocardiographically guided cardioversion with enoxaparin in patients with atrial fibrillation was associated with shorter initial hospital stay, more normal sinus rhythm at 5 weeks, and no significant differences in stroke, bleeding, or death compared with unfractionated heparin (UFH). The present study evaluated resource use and costs in enoxaparin (n = 76) and UFH (n = 79) during 5-week follow-up. Resources included initial and subsequent hospitalizations, study drugs, outpatient services, and emergency room visits. Two costing approaches were employed for the hospitalization costing. The first approach was based on the UB-92 formulation of hospital bill and diagnosis-related group. The second approach was based on UB-92 and imputation using multivariable linear regression. Costs for outpatient and emergency room visits were determined from the Medicare fee schedule. Sensitivity analysis was performed to assess the robustness of the results. A bootstrap resample approach was used to obtain the confidence interval (CI) for the cost differences. Costs of initial and subsequent hospitalizations, outpatient procedures, and emergency room visits were lower in the enoxaparin group. Average total costs remained significantly lower for the enoxaparin group for the 2 costing approaches ($5,800 vs $8,167, difference $2,367, 95% CI 855 to 4,388, for the first approach; $7,942 vs $10,076, difference $2,134, 95% CI 437 to 4,207, for the second approach). Sensitivity analysis showed that cost differences between strategies are robust to variation of drug costs. In conclusion, the use of enoxaparin as a bridging therapy is a cost-saving strategy (similar clinical outcomes and lower costs) for atrial fibrillation. (c) 2008 Elsevier Inc. All rights reserved.

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) 11 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.

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.

Introduction: Atrial fibrillation (AF) represents a cardiovascular syndrome which can lead to embolic stroke. Several AF clinical trials have shown a decrease risk of stroke with anticoagulation using warfarin. Currently, there are two approaches for anticoagulation in AF patients. For outpatients, warfarin is used with an INR goal 2.0–3.0. For inpatients requiring cardioversion, unfractionated heparin (UFH, IV) is used as a bridge to therapeutic warfarin. More recently, anticoagulation with a low molecular weight heparin, enoxaparin, has been reported to give a more predictable anticoagulant response than UFH in TEEguided cardioversion. The present study compares the markers of inflammation and thrombin generation in patients included in the ACUTE II study.

AIMSTo 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 RESULTSThe 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).CONCLUSIONIn 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.

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 mates) 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. (c) 2006 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.

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.

The ACUTE II Study compared low molecular weight heparin (LMWH) to unfractionated heparin (UFH) in patients with atrial fibrillation (AF) >2 days’ duration, undergoing TEE guided cardioversion over...

Background: Increased oxidative stress and endothelial dysfunction are commonly observed in patients with chronic heart failure. The relationship between myeloperoxidase (MPO) to severity and long-term prognosis in chronic heart failure (HF) patients with systolic and diastolic dysfunction has not been reported. Methods: We evaluated plasma MPO levels (CardioMPO, PrognostiX) in 140 patients with chronic systolic HF (LV ejection fraction [LVEF] <35%) with varying degrees of diastolic dysfunction. We examined the relationship between plasma MPO levels to echocardiographic indices of systolic and diastolic dysfunction, and long-term clinical outcomes (death, cardiac transplantation, or HF hospitalization). Results: Increasing quartiles of plasma MPO levels correspond to increasing likelihood of more advanced cardiac dysfunction (LVEF<25%, restrictive diastolic stage, RV systolic dysfunction). Within the whole cohort, MPO levels were predictive of incident mortality, HF hospitalization or cardiac transplantation (OR (95% CI) = 1.44 (1.09 - 1.93)). Plasma MPO remained to be a significant predictor of mortality, HF hospitalization or cardiac transplantation following adjustment for age, LVEF, diastolic stage, NYHA class, and even plasma BNP level (see Figure; +/− denotes above/below median plasma levels). Conclusion: In patients with chronic systolic heart failure, increased plasma MPO levels are both associated with more advanced indices of systolic and diastolic dysfunction and an independent predictor of increased risk for clinical events.