R. Daniel Murray

Cardioversion guided by transesophageal echocardiography: The ACUTE Pilot Study : A Randomized, controlled trial

A trial fibrillation is characterized by a lack of organized electrical and mechanical atrial activity that results in an irregular heartbeat and increased risks for congestive heart failure, thromboembolism, and death [1-3]. Since 1962, direct-current cardioversion has been used to restore sinus rhythm in patients with atrial fibrillation [4]. However, successful cardioversion, with the sudden resumption of sinus rhythm, is itself associated with an increased risk for embolic stroke, which can result when thrombi in the left atrial appendage are dislodged [5-12]. Transesophageal echocardiography (TEE) is an excellent method with which to detect thrombi in the left atrial appendage [13-19]. Its use has therefore been proposed as a way to allow cardioversion to be done earlier and more safely than would be possible with conventional therapy, which consists of a total of 7 weeks of treatment with warfarin [14-23]. Recent studies [15-19] indicate that TEE-guided cardioversion with short-term anticoagulation therapy may have several advantages over the conventional approach. These advantages include a decreased risk for embolism, which results from the avoidance of cardioversion in patients who have thrombi in the left atrial appendage [15]; a decreased risk for bleeding, which occurs because anticoagulation therapy can be briefer [19]; greater initial conversion to and long-term maintenance of sinus rhythm, which result from doing cardioversion earlier [18, 19]; and greater cost-effectiveness, which results from the decreased incidence of embolic stroke [17]. The ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) Pilot Study was a multicenter, randomized clinical trial designed to compare TEE-guided cardioversion with conventional management of cardioversion in patients with atrial fibrillation who have cardioversion [19]. The study had two objectives: to assess the general feasibility of a TEE-guided approach to cardioversion and to determine the general safety of the TEE-guided approach by comparing its clinical outcome with those of conventional management. Methods Patient Selection Patients who were candidates for electrical cardioversion were eligible for inclusion if they had atrial fibrillation, or atrial flutter with a history of atrial fibrillation, lasting longer than 2 days. Patients were excluded if they had received anticoagulant therapy for more than 7 days, had required urgent cardioversion as a result of hemodynamic instability, had had a cardioembolic event within the previous month, had contraindications to TEE or warfarin, were women with childbearing potential in whom pregnancy could not be excluded, were unable to give informed consent, or were unable to return for a follow-up visit. Our study protocol was approved by the institutional review boards at all clinical sites, and all patients provided written informed consent in advance. Study Protocol Patients who met the inclusion criteria were randomly assigned to receive either a conventional or a TEE-guided approach to cardioversion. Randomization was done using presealed, opaque envelopes that were computer generated and distributed to each clinical site (Figure 1). Random assignments were stratified by site and were generated in blocks of six. Figure 1. The ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) study protocol. The conventional approach to cardioversion was that recommended by the American College of Chest Physicians: 3 weeks of therapeutic warfarin therapy, then cardioversion, then 4 weeks of warfarin therapy, and then a follow-up examination at the end of the 4 weeks [23]. Prothrombin times were monitored regularly, and the target international normalized ratio (INR) was 2 to 3. If assigned to the TEE group, patients began receiving anticoagulation therapy at their initial visit. The goal was to have patients therapeutically anticoagulated (therapeutic anticoagulation was defined as a partial thromboplastin time 1.5 to 2.5 times control values or an INR of 2.0 to 3.0) at the time of and after the planned cardioversion, for a total of 4 weeks of therapy. The initial choice of antithrombotic agent was determined by whether the patient was an inpatient or an outpatient at the time of randomization: Heparin was used for inpatients; warfarin was administered to outpatients. Transesophageal echocardiography, with subsequent cardioversion within 24 hours, was then scheduled as soon as stable therapeutic anticoagulation was assured. For example, if a patient was hospitalized and intravenous heparin therapy was administered, TEE was done as soon as a stable therapeutic partial thromboplastin time could be documented (for 24 to 36 hours); subsequent cardioversion was done if the presence of a thrombus was excluded. A 4- to 5-day overlap of warfarin therapy and intravenous heparin therapy was often necessary to maintain adequate anticoagulation after cardioversion. If the patient was to be managed as an outpatient, warfarin therapy was initiated on the day of study enrollment, and TEE and subsequent possible cardioversion were scheduled for at least 5 to 7 days later. Again, cardioversion was done when the patient was therapeutically anticoagulated, and all patients received maintenance therapy with warfarin for 4 weeks after cardioversion [15]. In the TEE group, cardioversion was done immediately after or within 24 hours of TEE because of the potential for thrombus formation in the period between TEE and cardioversion. If thrombi were detected in the left or right atrial appendages or atrial cavities, cardioversion was postponed and the patient received warfarin therapy for 4 weeks. After 4 weeks, TEE was repeated and, if no thrombus was detected, cardioversion was done. If a thrombus was still present, another 4-week course of warfarin therapy was administered and cardioversion was not done [15]. Clinical Outcomes Our feasibility outcomes were frequency of cardioversion, frequency of cardioversion occurring as scheduled, time to cardioversion, and time to sinus rhythm. Our clinical safety outcomes were clinically apparent ischemic stroke, transient ischemic attack, systemic embolization, deaths related to cardioversion or episodes of bleeding, and detected episodes of clinical hemodynamic instability (worsening congestive heart failure or hypotension) that rendered the patient unable to complete the protocol. Other outcome variables were the prevalence of thrombi, the number of patients without thrombi who had early cardioversion, and the immediate and follow-up rhythms after cardioversion. These outcomes were assessed for as long as 4 weeks after cardioversion but for no longer than 8 weeks after randomization. In the patients who did not have cardioversion and who spontaneously reverted to sinus rhythm, the variables were assessed at 4 weeks after spontaneous reversion. Study Organization and Procedures The administrative organization of the pilot study is described in the Appendix. Echocardiographic Examination Conventional transthoracic echocardiography was done in both study groups using commercially available equipment. In the TEE group, TEE was done according to standard techniques using phased-array biplane or multiplane transducers [24-26]. Complete transesophageal echocardiographic examination was done, and special attention was paid to imaging the left and right atria and left and right atrial appendages to assess the presence or absence of thrombi and spontaneous echo contrast. Echocardiographic Data Analysis Two-dimensional directed M-mode transthoracic echocardiography was used to derive the left ventricular septal and posterior wall thicknesses and the end-diastolic, end-systolic, and left atrial dimensions. Ejection fraction was calculated using standard techniques [27, 28]. The maximal left atrial and right atrial areas were planimetered on-line, and the severity of mitral regurgitation was qualitatively graded from 0 to 4+ by using color-flow mapping [29]. A thrombus was considered to be present if a mass detected in the appendage or body of the atrium appeared to be distinct from the underlying endocardium, was not caused by pectinate muscles, and was detected in more than one imaging plane. The presence or absence of spontaneous echo contrast was analyzed and defined as dynamic intracavitary echoes with a characteristic swirling pattern distinct from artifact. The degree of spontaneous echo contrast was categorized independently as absent, mild, or severe [30, 31]. Quality Control Measures Standard definitions of echocardiographic measurements were available to all of the clinical centers as part of a pilot operations manual. Echocardiograms at each clinical center were interpreted locally by a single physician who was highly experienced in echocardiography. Videotapes that showed the results of the first five echocardiographic examinations and all videotapes that showed thrombi were forwarded from the clinical centers to a central laboratory and overread by three experienced reviewers for consensus [19]. Electrical Cardioversion Cardioversion was done by using the standard method of Lown and associates [4] with an initial energy of at least 40 J for atrial flutter and 200 J for atrial fibrillation. Statistical Analysis Summaries of clinical, echocardiographic, and outcome data are expressed as means or frequencies with 95% CIs. Data that were not normally distributed were log-transformed and presented as geometric means. Outcomes were compared for the TEE and conventional therapy groups, for patients with and without thrombus (in the TEE group only), and for patients in the TEE and conventional therapy groups who had cardioversion. These analyses were done using the t-test for independent groups for continuous variables and the Fisher exact test for categorical variables. StatXact (Cytel Software, Cambridge, Massachusetts) was used to compute binary CIs; SAS softwar

Comparison of New Doppler Echocardiographic Methods to Differentiate Constrictive Pericardial Heart Disease and Restrictive Cardiomyopathy

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.

Role of Transesophageal Echocardiography-Guided Cardioversion of Patients With Atrial Fibrillation

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 patients 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.

Left and right atrial transport function after the maze procedure for atrial fibrillation: An echocardiographic Doppler follow-up study

OBJECTIVES We evaluated atrial transport function after the Maze procedure in long-term follow-up and compared left and right atrial function in Maze patients with that of healthy age-matched controls using echo Doppler techniques. BACKGROUND The Maze procedure is designed to eliminate atrial fibrillation, restore normal sinus rhythm, and preserve atrial contraction. Initial data indicate that atrial transport function is restored in most patients undergoing the Maze procedure. The long-term echo Doppler evaluation of patients after the Maze procedure has not been well described. METHODS We performed pulsed-wave Doppler and two-dimensional echocardiographic studies on 31 patients (24 men, mean age 53.8 years) who underwent the Maze procedure and who had a follow-up study greater than 3 months (mean 16.5 months) after the procedure. Measurements included peak left ventricular and right ventricular inflow A-wave velocity, maximum and minimum left atrial and right atrial areas, and fractional area change of the left and right atria. Results were compared with those obtained from 15 age-matched control subjects (11 men, mean age 53.8 years). RESULTS Twenty-two patients (71%) had left atrial function shown by the presence of left ventricular inflow A-wave, and 25 patients (81%) had right atrial function shown by the presence of right ventricular inflow A-wave on Doppler echocardiography. The left ventricular inflow A-wave velocity was significantly lower than that of age-matched controls (37.5 +/- 15.5 versus 61.0 +/- 13.9 cm/sec; p < 0.001), whereas the right ventricular inflow A-wave velocity did not significantly differ between patients and control subjects (35.4 +/- 9.9 versus 35.3 +/- 4.9 cm/sec; p = Not significant). Although left and right atrial areas decreased significantly after the procedure, there was no significant change in the fractional area change which was smaller in Maze patients than control individuals. CONCLUSIONS (1) In long-term follow-up of 16.5 months after the Maze procedure, left atrial systolic function was preserved in 71% of our patients and right atrial systolic function was preserved in 81%; (2) the left ventricular inflow peak A-wave velocity after Maze is considerably less than that in age-matched controls; and (3) left and right atrial sizes decreased after the procedure with no change in the fractional area change. These findings suggest that the Maze procedure is effective in restoring atrial function in the majority of patients; however, restored function is less than in control individuals.

Effects of age and physiologic variables on right ventricular filling dynamics in normal subjects

The reference values for right ventricular (RV) filling of normal persons and the effects of physiologic variables in a large series have not been described. The objective of this study was to characterize superior vena cava, hepatic vein, and RV inflow Doppler measurements in a large normal reference group to reflect the aging process, gender, heart rate, and effects of respiration. We prospectively performed pulsed-wave Doppler echocardiography of the superior vena cava, hepatic vein, and RV inflow during inspiration, expiration, and apnea in 115 healthy volunteers (62 women and 53 men) ranging in age from 21 to 84 years (mean +/- SEM 48 +/- 17). For analysis, the study subjects were classified by age into 2 groups: those < 50 years of age (group 1; n = 60) and those > or = 50 years of age (group 2; n = 55). Multiregression models were used to assess the influence of age, gender, and heart rate on Doppler variables. There were important differences in superior vena cava and RV inflow between the 2 groups. Group 2 had a greater superior vena cava peak atrial flow velocity (16 +/- 3 vs 13 +/- 3 cm/s), flow integrals (1.5 +/- 0.4 vs 1.1 +/- 0.3 cm), and reverse flow as a percentage of forward flow (17 +/- 6% vs 14 +/- 6%) than group 1. In group 2, peak RV inflow early filling velocity (41 +/- 8 vs 51 +/- 7 cm/s) and ratio of early filling-to-atrial filling (1.3 +/- 0.4 vs 2 +/- 0.5) were lower than that of group 1. Likewise, peak atrial filling velocity was higher (33 +/- 8 vs 27 +/- 8 cm/s) and deceleration time was longer (198 +/- 23 vs 188 +/- 22 ms) in group 2. The superior vena cava and hepatic vein peak forward flow velocities were significantly higher during inspiration than during expiration and apnea. Similarly, RV inflow velocities were significantly higher during inspiration than in expiration and apnea. Multiregression analysis showed that age, gender, and heart rate had important effects on Doppler variables. Thus, this study demonstrates the effects of aging and normal physiologic variable flow velocities in the superior vena cava, hepatic veins, and RV inflow in a large series of normal subjects.

Integrated backscatter for quantification of left atrial spontaneous echo contrast

OBJECTIVES This study was designed to develop a quantitative method of spontaneous echo contrast (SEC) assessment using integrated backscatter and to compare integrated backscatter SEC measurement with independent qualitative grades of SEC and clinical and echocardiographic predictors of thromboembolism. BACKGROUND Left atrial SEC refers to dynamic swirling smokelike echoes that are associated with low flow states and embolic events and have been graded qualitatively as mild or severe. METHODS We performed transesophageal echocardiography in 43 patients and acquired digital integrated backscatter image sequences of the interatrial septum to internally calibrate the left ventricular cavity and left atrial cavity under different gain settings. Patients were independently assessed as having no, mild or severe SEC. We compared intensity of integrated backscatter in the left atrial cavity relative to that in the left ventricular as well as to the independently assessed qualitative grades of SEC. Fourier analysis characterized the temporal variability of SEC. The integrated backscatter was compared with clinical and echocardiographic predictors of thromboembolism. RESULTS The left atrial cavity integrated backscatter intensity of the mild SEC subgroup was 4.7 dB higher than that from the left ventricular cavity, and the left atrial intensity of the severe SEC subgroup was 12.5 dB higher than that from the left ventricular cavity. The left atrial cavity integrated backscatter intensity correlated well with the qualitative grade. Fourier transforms of SEC integrated backscatter sequences revealed a characteristic dominant low frequency/high amplitude spectrum, distinctive from no SEC. There was a close relationship between integrated backscatter values and atrial fibrillation, left atrial size, left atrial appendage flow velocities and thrombus. CONCLUSIONS Integrated backscatter provides an objective quantitative measure of SEC that correlates well with qualitative grade and is closely associated with clinical and echocardiographic predictors of thromboembolism. The relationship between integrated backscatter measures and cardioembolic risk will be defined in future multicenter studies.

Difference in the respiratory variation between pulmonary venous and mitral inflow doppler velocities in patients with constrictive pericarditis with and without atrial fibrillation

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.

Does rapid volume loading during transesophageal echocardiography differentiate constrictive pericarditis from restrictive cardiomyopathy

Background: Respiratory variation of the pulmonary venous (PV) peak flow velocities can be used to distinguish constrictive pericarditis (constriction) from restrictive cardiomyopathy (restriction). Rapid volume expansion has been used successfully to enhance diastolic pressure equalization in occult constriction. The effect of volume on the respiratory variation in constriction has not been studied previously. This study assessed the utility of volume in enhancing the PV respiratory variation of constriction to further separate it from restriction. Methods: The study population consisted of 15 patients referred to the echocardiography laboratory for further evaluation of clinically suspected diastolic dysfunction. Pulsed‐Doppler transesophageal echocardiography (TEE) of the left or right upper pulmonary vein and mitral inflow was performed with respiratory monitoring before and after infusion of 1 liter of normal saline over 5 to 10 minutes. The classification of patients as constriction (n = 8) or restriction (n = 7) was confirmed independently by cardiac catheterization or surgery. Peak velocities of the PV systolic and diastolic waves and the mitral inflow E were measured during inspiration and expiration. A mean of 3–6 respiratory cycles was obtained for each value before and after volume loading. The percent change from expiration to inspiration (%E) was calculated using the formula %E = expiration ‐ inspiration / expiration. Results: At baseline, patients with constrictive pericarditis can be separated reliably from those with restrictive cardiomyopathy based on a higher systolic/diastolic ratio and greater respiratory variation of their PV diastolic flow velocity. There were no complications in any patient due to volume expansion. Although the change from baseline to volume expansion was not statistically significant in either constriction or restriction, the %E of the PV diastolic wave became significantly higher in constriction than in restriction (P < 0.05). Conclusions: Rapid volume expansion is relatively safe during TEE and can be used for further separation of constrictive pericarditis from restrictive cardiomyopathy by significantly enhancing the respiratory variation of the PV diastolic flow velocity in constrictive pericarditis.

Role of transesophageal echocardiography in assessing diastolic dysfunction in a large clinical practice: a 9-year experience.

BACKGROUND Two-dimensional transthoracic echocardiography with respiratory monitoring has been used to characterize diseases that impair diastolic function. Transesophageal echocardiography (TEE) has emerged as a complementary technique to evaluate patients with these diseases. The purpose of this study was to evaluate in a large clinical practice the utility of TEE with respiratory monitoring for classification of patients with diastolic dysfunction. METHODS Over a 9-year period TEE was used to examine 192 patients referred to an echocardiography laboratory for additional evaluation of abnormal diastolic function. We performed pulsed-wave Doppler TEE of the left ventricular inflow and pulmonary veins and respiratory monitoring to categorize patients as showing restrictive physiologic features, constriction with or without effusion, mixed constriction and restriction, abnormal relaxation, pseudonormalization, large pericardial effusion or tamponade, or normal diastolic function. RESULTS Patients with diastolic dysfunction underwent 3% of the total number of transesophageal studies conducted during the study period. Among the 192 patients referred for TEE, abnormal diastolic function was found in 181 (94%); 11 (6%) had normal diastolic function. Seventy-one (39%) of the 181 patients had restrictive physiologic features. Constrictive pericarditis was found in 54 (30%) of the patients and was confirmed for all 31 patients who underwent pericardiectomy. Mixed constriction and restriction was present in 21 (12%) of the patients. The other 35 patients (19%) had abnormal relaxation, pseudonormalization, or large pericardial effusion or tamponade. The cause of diastolic dysfunction was idiopathic for 32% of the patients, previous cardiac operation for 26%, cardiac amyloidosis for 23%, radiation therapy for 11%, and hypertension or advanced ischemic heart disease for 8%. CONCLUSION Two-dimensional and Doppler TEE with respiratory monitoring is useful in categorizing patients with impaired diastolic function, primarily into those with restrictive physiologic features or constrictive pericarditis.

Experimental and numerically modeled effects of altered loading conditions on pulmonary venous flow and left atrial pressure in patients with mitral regurgitation

Pulmonary venous flow measured by pulsed-wave Doppler transesophageal echocardiography reflects the effects of mitral regurgitation on left atrial pressure contour. To assess the relationship between pulmonary venous flow and left atrial pressure in patients with mitral regurgitation under altered loading conditions, we studied 25 patients with 3+ or 4+ mitral regurgitation and a control group by measuring pulmonary venous flow with transesophageal echocardiography and left atrial pressures after administering saline solution (n = 6), nitroglycerin (n = 6), phenylephrine (n = 6), or nitroprusside (n = 7). After administration, the left atrial pressure v wave increased in the group given phenylephrine, concomitant with an increased diastolic flow. In contrast, the left atrial pressure v wave decreased in the group given nitroglycerin, concomitant with a decreased diastolic flow. Changes in diastolic flow were closely related to changes in the left atrial pressure v wave under all loading conditions (r = 0.91; p < 0.0001). Numeric modeling of left atrial pressure and pulmonary venous diastolic flow corroborated the experimental findings. We conclude that changes in pulmonary venous diastolic flow are closely related to changes in the left atrial pressure v wave in mitral regurgitation, under altered loading conditions.