Subtherapeutic anticoagulation: the bane of conventional anticoagulation for cardioversion of atrial fibrillation.
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Publications and source records attributed to A L Klein.
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Transesophageal echocardiography (TEE) has contributed to our understanding of the patho-physiology of the thromboembolic sequelae of atrial fibrillation. This imaging modality has demonstrated thrombus formation within the left atrial appendage, as well as allowing for assessment of dynamic indices of left atrial appendage function. Studies using TEE have introduced the concept of post conversion "stunning", suggesting an increased milieu for thrombus formation after restoration of sinus rhythm. The detailed assessment of the atrium allowed for by TEE gave rise to the concept of TEE guided cardioversion, bypassing the traditional practice of prolonged anticoagulation prior to cardioversion. The only randomized trial of this practice, the multicenter ACUTE trial, has demonstrated that this strategy is a safe one with less bleeding, and appears to be a strong alternative to the conventional approach. There is some suggestion that TEE may play a role in further risk stratification of patients with chronic atrial fibrillation, but more data is needed on this potential utility of TEE. Treatment strategies for atrial fibrillation are continuing to evolve, and TEE has played a role and will likely continue to play a role in this development.
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OBJECTIVES: The goal of this study was to evaluate the difference in the respiratory change from expiration to inspiration (%E) between pulsed Doppler mitral inflow (MV) and pulmonary venous flow (PV) velocities in patients with constrictive pericarditis (CP) and to describe the influence of atrial fibrillation (AF). BACKGROUND: The difference in %E between MV and PV velocities as well as the influence of AF on %E has not been well described. METHODS: Pulsed-wave Doppler transesophageal echocardiography (TEE) was performed with respiratory monitoring in 31 patients with CP and sinus rhythm (SR) and in 10 patients with CP and AF. The MV early (E) and late diastolic (A) velocities and their velocity time integral (VTI) as well as PV systolic (S) and diastolic (D) velocities and their VTI were measured. RESULTS: Regardless of the cardiac rhythm: 1) The MV-E velocity and E-VTI as well as PV-D velocity and D-VTI significantly decreased from expiration to inspiration; 2) the %E in PV-D velocity (27% in SR and 35% in AF) and D-VTI (38% in SR and 45% in AF) was significantly greater than that in MV-E velocity (18% in SR and 15% in AF) and E-VTI (21% in SR and 19% in AF), respectively; 3) the PV S/D and S/D-VTI significantly increased from expiration to inspiration. CONCLUSIONS: A significant respiratory variation was observed in both MV and PV velocities in CP, not only in patients with SR but also in those with AF. Moreover, the %E was greater in the PV velocities than it was in the MV velocities. Evaluation of the %E in the PV velocities using TEE can be a sensitive diagnostic strategy for evaluation of patients with CP, even in patients with AF.
BACKGROUND: The conventional treatment strategy for patients with atrial fibrillation who are to undergo electrical cardioversion is to prescribe warfarin for anticoagulation for three weeks before cardioversion. It has been proposed that if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after only a short period of anticoagulant therapy. METHODS: In a multicenter, randomized, prospective clinical trial, we enrolled 1222 patients with atrial fibrillation of more than two days' duration and assigned them to either treatment guided by the findings on transesophageal echocardiography or conventional treatment. The composite primary end point was cerebrovascular accident, transient ischemic attack, and peripheral embolism within eight weeks. Secondary end points were functional status, successful restoration and maintenance of sinus rhythm, hemorrhage, and death. RESULTS: There was no significant difference between the two treatment groups in the rate of embolic events (five embolic events among 619 patients in the transesophageal-echocardiography group [0.8 percent]) vs. three among 603 patients in the conventional-treatment group [0.5 percent], P=0.50). However, the rate of hemorrhagic events was significantly lower in the transesophageal-echocardiography group (18 events [2.9 percent] vs. 33 events [5.5 percent], P=0.03). Patients in the transesophageal-echocardiography group also had a shorter time to cardioversion (mean [+/-SD], 3.0+/-5.6 vs. 30.6+/-10.6 days, P<0.001) and a greater rate of successful restoration of sinus rhythm (440 patients [71.1 percent] vs. 393 patients [65.2 percent], P=0.03). At eight weeks, there were no significant differences between the two groups in the rates of death or maintenance of sinus rhythm or in functional status. CONCLUSIONS: The use of transesophageal echocardiography to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned.
Electrical cardioversion of patients with atrial fibrillation (AF) is frequently performed to relieve symptoms and improve cardiac performance. Patients undergoing cardioversion are treated conventionally with therapeutic anticoagulation for three weeks before and four weeks after cardioversion to decrease the risk of thromboembolism. A transesophageal echocardiography (TEE)-guided strategy has been proposed as an alternative that may lower stroke and bleeding events. Patients without atrial cavity thrombus or atrial appendage thrombus by TEE are cardioverted on achievement of therapeutic anticoagulation, whereas cardioversion is delayed in higher risk patients with thrombus. The aim of this review is to discuss the issues and controversies associated with the management of patients with AF undergoing cardioversion. We provide an overview of the TEE-guided and conventional anticoagulation strategies in light of the recently completed Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) clinical trial. The two management strategies comparably lower the patient's embolic risk when the guidelines are properly followed. The TEE-guided strategy with shorter term anticoagulation may lower the incidence of bleeding complications and safely expedite early cardioversion. The inherent advantages and disadvantages of both strategies are presented. The TEE-guided approach with short-term anticoagulation is considered to be a safe and clinically effective alternative to the conventional approach, and it is advocated in patients in whom earlier cardioversion would be clinically beneficial.
This study assesses how the newer modalities of tissue Doppler echocardiography and color M-mode flow propagation compare with respiratory variation of Doppler flow in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. We studied 30 patients referred for further evaluation of diastolic function who had a diagnosis of constrictive pericarditis or restrictive cardiomyopathy established by diagnostic tests, including clinical assessment, magnetic resonance imaging, cardiac catheterization, endomyocardial biopsy, and surgical findings. Nineteen patients had constrictive pericarditis and 11 had restrictive cardiomyopathy. We performed 2-dimensional transesophageal echocardiography combined with pulsed-wave Doppler of the pulmonary veins and mitral inflow with respiratory monitoring, tissue Doppler echocardiography of the lateral mitral annulus, and color M-mode flow propagation of left ventricular filling. Respiratory variation of the mitral inflow peak early (peak E) velocity of > or =10% predicted constrictive pericarditis with 84% sensitivity and 91% specificity and variation in the pulmonary venous peak diastolic (peak D) flow velocity of > or =18% distinguished constriction with 79% sensitivity and 91% specificity. Using tissue Doppler echocardiography, a peak early velocity of longitudinal expansion (peak Ea) of > or =8.0 cm/s differentiated patients with constriction from restriction with 89% sensitivity and 100% specificity. A slope of > or =100 cm/s for the first aliasing contour in color M-mode flow propagation predicted patients with constriction with 74% sensitivity and 91% specificity. Thus, the newer methods of tissue Doppler echocardiography and color M-mode flow propagation are equivalent and complimentary with Doppler respiratory variation in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. The additive role of the new methods needs to be established in difficult cases of constrictive pericarditis where respiratory variation may be absent or decreased.
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BACKGROUND: Previous studies have reported the clinical and echocardiographic findings of patients with left atrial spontaneous echo contrast (SEC) and thrombi. We sought to study these characteristics in patients with right atrial SEC and thrombi. METHODS: We reviewed 580 consecutive patients from the ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) Registry and found 79 patients (14%, aged 67 +/-13 years, 67 male) with transesophageal echocardiography (TEE) findings of right atrial SEC or thrombi (group 1). This group was compared with a control group of 75 consecutive patients (group 2) (aged 68 +/- 13 years, P = not significant; 49 male, P <.005) from the registry with no TEE findings of SEC or thrombi in the left or right atrium. RESULTS: Atrial fibrillation was present in 60 of 79 group 1 patients (76%). Five right atrial (6%) and 11 left atrial (14%) thrombi were identified. Both left ventricular ejection fraction (39% +/- 16% versus 47% +/- 14%; P =.0005) and presence of right ventricular dysfunction (n = 44 versus 18; P =.0001) differed significantly between groups 1 and 2, respectively. Right atrial area (24 +/- 6 cm(2) versus 22 +/- 6 cm(2); P = .02) was larger in patients in group 1. Left atrial SEC was present in 68 of 79 group 1 patients (86%). Patients with right atrial thrombi and right atrial SEC had a longer duration of arrhythmia (524 +/-812 days versus 147 +/-368 days, P <.05) than patients with right atrial SEC only. CONCLUSIONS: Right atrial SEC has a prevalence of 14% in patients with atrial arrhythmia who undergo TEE-guided cardioversion. Right atrial thrombi are a rare finding and were seen in fewer than 1% (5/580) of patients with atrial arrhythmia. Right atrial thrombi among patients on anticoagulation therapy were not associated with clinically significant pulmonary embolism.
An alternative clinical management strategy and cost analysis model is presented for patients with atrial fibrillation of >2 days' duration who may benefit from immediate cardioversion with self-administered low-molecular-weight heparin (enoxaparin) as a bridge antithrombotic therapy to warfarin, after a negative transesophageal echo-cardiography (TEE) screening for thrombus. Assuming no difference in stroke or bleeding rates, our cost minimization model shows that the TEE-guided enoxaparin treatment costs are $1353 lower per patient than an intravenous unfractionated heparin approach. Sensitivity analyses for stroke and bleeding reveal that the treatment-cost economic dominance of the TEE-guided enoxaparin approach may be enhanced by an expected improvement in clinical outcome.
The objective of this study was to determine whether Doppler echocardiography is useful in assessing the effects of pericardiectomy in patients with constrictive pericarditis by studying the postoperative change in the respiratory variation of mitral inflow and pulmonary venous Doppler flows. The study population consisted of 35 cases with surgically proven constrictive pericarditis. Thirty-five patients had preoperative Doppler echocardiography, whereas 4 patients died of non-cardiac causes and 1 patient had a heart transplant before follow-up. Postoperative studies were performed at a mean of 1081 +/- 84 days (range 120-2700 days) after pericardiectomy. The mean (+/- SD) respiratory variation changed after surgery from a baseline value of 17% +/- 14% to 8% +/- 8% for peak mitral E velocity (P <.01); from 25% +/- 18% to 7% +/- 13% (P <.001) for pulmonary venous (PV) peak diastolic flow velocity, and from 21% +/- 13% to 11% +/- 13% (P =.009) for PV peak systolic flow velocity. The 23 patients who became asymptomatic after surgery had a significantly lower mean mitral and PV respiratory variation than the 7 patients who were NYHA class II (4% +/- 4% and 6% +/- 4% vs 21% +/- 6% and 19% +/- 10%, respectively, P <.0001 for both). Pulsed Doppler echocardiographic assessment of respiratory variation is useful for evaluating the outcome of pericardiectomy.
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In this study, we sought evidence for an underlying atrial or ventricular myopathy in patients with paroxysmal lone atrial fibrillation using standard echocardiographic parameters in addition to Doppler tissue imaging of mitral annular motion. No impairment in atrial contractile function was found, but there was evidence for impaired diastolic function in these patients.
Transesophageal echocardiographic (TEE)-guided cardioversion of patients in atrial fibrillation (AF) of >2 days' duration is used as an alternative to conventional therapy. The purpose of this study was to investigate practice patterns employed for stroke prophylaxis in patients with AF who underwent cardioversion, and to determine the relative use of conventional and TEE-guided management strategies. We forwarded regionally stratified survey questionnaires to 947 clinical practices within the United States. The 10-question questionnaire queried demographic and clinical practice volumes and practices for managing patients with AF who underwent cardioversion. In addition, we used historical data to determine longitudinal use patterns of the TEE-guided approach for a large institution over 7 years. The 197 completed and returned surveys yielded a return rate of 20.8%. The TEE-guided approach was employed in approximately 12% of total cardioversions, but 75% of practices indicated that they employed transesophageal echocardiography only occasionally. The TEE-guided approach was associated with community size (r = 0.19; p<0.008), type of practice (r = 0.26; p = 0.001), total use of transesophageal echocardiography (r = 0.48; p<0.001), and volume of cardioversions (r = 0.28; p<0.001). Importantly, there was little consensus on the most appropriate clinical indications for TEE-guided cardioversions, and the proportions of TEE-guided cardioversion to total number of electrical cardioversions remained stable over 7 years. Practice volume and physician training may be the most important variables in the adoption of the TEE approach.
Transesophageal echocardiography has given new insight into the pathogenesis of the thromboembolic sequelae of AF and expanded the available therapeutic options. Studies to date indicate that TEE-guided cardioversion is a safe and reasonable approach when the clinical situation warrants prompt restoration of sinus rhythm. Whether widespread use of this strategy offers further benefit remains to be established, although there are theoretical advantages to such an approach. The potential for earlier cardioversion using a TEE-guided approach may facilitate the achievement and maintenance of sinus rhythm. In the long term, earlier restoration of sinus rhythm prevents adverse atrial remodeling, lowers embolic risk, and may improve cardiac performance and functional status. Thromboembolic sequelae (either cardioversion-related or as a result of chronic AF) remain the most devastating complications of AF. Every attempt to minimize this risk should be pursued aggressively. Information gathered from TEE has helped to elucidate the mechanisms responsible for postcardioversion embolism and has emphasized the importance of anticoagulation during and after the restoration of sinus rhythm. TEE also has the potential to further risk stratify patients with AF. Ultimately, a subset of patients may be identified who require more intense anticoagulation (i.e., those with dense SEC or thrombus, or persistent thrombus after prolonged anticoagulation) or in whom cardioversion may be deferred entirely. Likewise, TEE also may prove to be useful in identifying patients with a low-clinical risk profile who may be treated with aspirin alone and patients in whom warfarin may be superior. The results of the ACUTE study should help to further define the role of TEE in the management of patients with AF. Additional clinical studies are needed to address some of the issues that have been raised and to allow for optimal use of TEE in this patient population.
BACKGROUND: Patients with atrial fibrillation >2 days' duration for whom immediate cardioversion is desired or required are commonly hospitalized for 4 or more days of antithrombotic therapy with intravenous unfractionated heparin and commencement of oral warfarin. For these early cardioversion patients, self-administered low-molecular-weight heparin (enoxaparin sodium) as "bridge" therapy to warfarin may obviate the need for hospitalization and activated partial thromboplastin time monitoring and thus potentially lower costs and enhance utility. OBJECTIVE: To compare feasibility and safety of a transesophageal echocardiography (TEE)-guided enoxaparin strategy with those of a TEE-guided unfractionated heparin strategy in patients with atrial fibrillation of >2 days' duration undergoing early electrical or chemical cardioversion. DESIGN AND SETTING: This is a randomized, multicenter clinical trial at 11 hospitals in the United States. PATIENTS AND INTERVENTION: Two hundred patients with atrial fibrillation >2 days' duration requiring early chemical or electric cardioversion will be enrolled. TEE-guided intravenous unfractionated heparin bridge therapy will be compared with TEE-guided subcutaneous enoxaparin bridge therapy. OUTCOME MEASURES: Feasibility outcomes are time to hospital discharge, patient quality of life/utility, treatment costs, and sinus rhythm. Safety outcomes are ischemic stroke, transient ischemic attack, systemic embolization, major and minor bleeding, clinical hemodynamic instability, and cardiac and cardioversion-related death for a 5-week period from enrollment. CLINICAL IMPLICATIONS: The results of this pilot study will have important clinical and economic implications for the antithrombotic management of patients with atrial fibrillation undergoing TEE-guided cardioversion.
BACKGROUND: Transesophageal echocardiography (TEE) is the gold standard for evaluation of the left atrium and the left atrial appendage (LAA) for the presence of thrombi. Anticoagulation is conventionally used for patients with atrial fibrillation to prevent embolization of atrial thrombi. The mechanism of benefit and effectiveness of thrombi resolution with anticoagulation is not well defined. METHODS AND RESULTS: We used a TEE database of 9058 consecutive studies performed between January 1996 and November 1998 to identify all patients with thrombi reported in the left atrium and/or LAA. One hundred seventy-four patients with thrombi in the left atrial cavity (LAC) and LAA were identified (1.9% of transesophageal studies performed). The incidence of LAA thrombi was 6.6 times higher than LAC thrombi (151 vs 23, respectively). Almost all LAC thrombi were visualized on transthoracic echocardiography (90.5%). Mitral valve pathology was associated with LAC location of thrombi (P <.0001), whereas atrial fibrillation or flutter was present in most patients with LAA location of thrombi. Anticoagulation of 47 +/- 18 days was associated with thrombus resolution in 80.1% of the patients on follow-up TEE. Further anticoagulation resulted in limited additional benefit. CONCLUSIONS: LAC thrombi are rare and are usually associated with mitral valve pathology. Transthoracic echocardiography is effective in identifying these thrombi. LAA thrombi occur predominantly in patients with atrial fibrillation or flutter. Short-term anticoagulation achieves a high rate of resolution of LAA and LAC thrombi but does not obviate the need for follow-up TEE.
BACKGROUND: Spontaneous inspiration causes a characteristic decrease of the mitral valve (MV) and pulmonary venous (PV) flow velocities obtained by Doppler echocardiography in patients with constrictive pericarditis (CP). This has been explained by the decrement it causes in the intrathoracic pressure. Positive pressure ventilation (PPV) causes an increment of intrathoracic pressure with mechanical inspiration. Therefore the pattern of respiratory variation produced during PPV may differ from that seen during spontaneous breathing. OBJECTIVE: Our goal was to describe the effect of PPV on the pattern and magnitude of respiratory variation of MV and PV flow velocities in CP. METHODS: We performed intraoperative pulsed Doppler transesophageal echocardiography on 15 patients (13 men, mean age 52+/-15 years) with CP after general anesthesia and before sternotomy and pericardial stripping. The peak velocity and time-velocity integral (TVI) of the mitral inflow E and A waves and the PV systolic and diastolic waves were measured at onset of inspiration and expiration for 3 to 6 respiratory cycles. Respiratory phase was monitored with a heat-sensitive nasal thermistor. The percent change in Doppler flow velocities from mechanical inspiration (INS) to mechanical expiration (EXP) was calculated with the formula %change = INS - EXP / INS x 100. RESULTS: The peak velocity of the mitral inflow E wave was significantly higher during mechanical inspiration than expiration (57 +/-14.5 versus 47+/-13.9 cm/s, P<.001). This represented a percent change of 18%+/-7.9% from expiration to inspiration. The mean TVI of the mitral inflow E was also higher during mechanical inspiration than expiration (P = .02). The peak velocity of the PV D wave was higher during mechanical inspiration than expiration (39+/-17.8 versus 28+/-14.7 cm/s, P<.001). This represented a mean percent change of 28%+/-13.8%. The mean value of the TVI for the PV D wave was also significantly greater during mechanical inspiration than expiration (P <.05). CONCLUSIONS: Positive pressure ventilation reverses the pattern of respiratory variation of the MV and PV flow velocities in CP. The percent change in the peak velocities of the MV and PV flows produced by PPV is the same range reported in CP during spontaneous breathing.