- Email: [email protected]
Transesophageal echocardiography complications associated with interventional cardiology procedures
Journal Pre-proof Transesophageal echocardiography complications associated with interventional cardiology procedures
Afonso B. Freitas-Ferraz, Josep Rodés-Cabau, Lucía Junquera Vega, Jonathan Beaudoin, Kim O'Connor, Pierre Yves Turgeon, Jean-Michel Paradis, Alfredo Ferreira-Neto, Lluis Asmarats, Jean Champagne, Gilles O'Hara, Mathieu Bernier PII:
S0002-8703(19)30339-4
DOI:
https://doi.org/10.1016/j.ahj.2019.11.018
Reference:
YMHJ 6028
To appear in:
American Heart Journal
Received date:
12 July 2019
Accepted date:
22 November 2019
Please cite this article as: A.B. Freitas-Ferraz, J. Rodés-Cabau, L.J. Vega, et al., Transesophageal echocardiography complications associated with interventional cardiology procedures, American Heart Journal(2019), https://doi.org/10.1016/ j.ahj.2019.11.018
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2019 Published by Elsevier.
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Title: Transesophageal Echocardiography Complications Associated with Interventional Cardiology Procedures.
Afonso B. Freitas-Ferraza MD, Josep Rodés-Cabaua MD, Lucía Junquera Vegaa MD, Jonathan Beaudoina MD, Kim O´Connora MD, Pierre Yves Turgeona MD, Jean-Michel Paradisa MD,
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Mathieu Berniera MD.
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Alfredo Ferreira-Netoa MD, Lluis Asmaratsa MD, Jean Champagnea MD, Gilles O´Haraa MD,
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a- Department of Cardiology, Quebec Heart and Lung Institute, Laval University, Quebec
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City, Canada
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Short title: TEE related complications in interventional cardiology
Address for correspondence: Mathieu Bernier, MD
Quebec Heart Lung Institute, Laval University 2725 chemin Ste-Foy. G1V4G5, Quebec City, Quebec, Canada Phone: Tel: (+1)65687711-5106 Fax: 656-4675
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E-mail: [email protected]
ABSTRACT
Background: Although there have been several reports documenting complications related with transesophageal echocardiography (TEE) manipulation following cardiac surgery, there is no data regarding the safety of TEE used to guide catheter-based interventions. The aim of this
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study was to determine the prevalence, types and risk factors of complications associated with procedures requiring active TEE guidance.
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Methods: This study included 1249 consecutive patients undergoing either transcatheter aortic
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valve implantation (TAVI), Mitraclip, left atrial appendage occlusion (LAAO) or paravalvular leak closure (PVLC). Patients were divided into two cohorts based on the degree of probe
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manipulation required to guide the procedure and the risk of developing a TEE-related complication: low-risk (TAVI, n=1037) and high-risk (Mitraclip, LAAO and PVLC, n=212).
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Patients were further analyzed according to the occurrence of major and minor TEE-related complications.
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Results: The overall incidence of TEE-related complications was 0.9% in the TAVI group and 6.1% in the rest of the cohort (p<0.001). Patients in the high-risk cohort had also a higher
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incidence of major-complications (2.8% vs 0.6%, p=0.008), and factors associated with an increased risk were being underweight, having a prior history of gastrointestinal bleeding and the
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use of chronic steroids/immunosuppressive medications. Procedural time under TEEmanipulation was longer in patients exhibiting complications and was an independent predictor of major complications (OR=1.13, 95%CI:1.01-1.25, for each 10 min increments in imaging time). Patients undergoing Mitraclip had the longest median time under TEE-manipulation (297 min) and a risk of developing a major-complication that was 10.64 times higher than the rest of the cohort (95%CI 3.30-34.29, p<0.001).
Conclusion: The prevalence of TEE-related complications associated with interventional procedures is higher than previously reported. Undergoing a prolonged procedure, particularly in the setting of Mitraclip, was the main factor linked to TEE-related complications.
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Keywords: transesophageal echocardiography complications, transcatheter aortic valve implantation, TAVI, Mitraclip, edge-to-edge mitral valve repair, left atrial appendage occlusion, paravalvular leak closure.
ABBREVIATIONS LIST
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E2E-MVR: Edge-to-edge mitral valve repair
LAAO: Left atrial appendage occlusion PVLC: Paravalvular leak closure
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TEE: Transesophageal echocardiography
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TAVI: Transcatheter aortic valve implantation
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GIB: gastro-intestinal bleeding
TEE-RC: Transesophageal echocardiography related complications
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TU-TEE: Time under transesophageal echocardiography
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UGIB: Upper gastro-intestinal bleeding
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INTRODUCTION The use and indications of transesophageal echocardiography (TEE) have expanded
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exponentially since its first reported use in 1971 to measure flow in the aortic arch.1 Nowadays,
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TEE has become not only a diagnostic tool with widespread utilization, but also an invaluable
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monitoring adjunct for operative and percutaneous procedures. Particularly, in the field of transcatheter based interventions, it provides crucial real-time information to help guide and
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assess procedural results.2 Even though TEE is considered to have a good safety profile with
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overall rates of TEE-related morbidity ranging from 0.2 to 1.2%,3, 4 severe complications, some
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of which can be life-threatening, have been reported.4-8 The majority of the available data regarding complications associated with TEE procedural guidance stems from studies performed
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during the course of cardiac surgery.3-9 In contrast with the operating room TEE sequence, in
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which image acquisition generally lasts short periods of time at predefined moments (e.g. baseline, post cardio pulmonary bypass and chest closed), TEE used to guide catheter-based procedures entails constant probe manipulation while the procedure is performed. Consequently, the incidence of TEE related complications reported in the literature may not be extrapolated to the ever-expanding scenarios of interventional cardiology. The aim of this study was to determine the incidence and types of TEE complications related to procedures requiring active TEE guidance as well as identifying possible risk factors associated with these complications.
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METHODS Patient population
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We retrospectively analyzed a cohort of 1251 consecutive adult patients undergoing cardiac
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interventional procedures with an intraoperative-TEE, between May 2007 and August 2018, at
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the Quebec Heart and Lung Institute. Out of those patients, 1037 underwent transcatheter aortic
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valve implantation (TAVI) and the remaining 214 patients underwent either a transcatheter edgeto-edge mitral valve repair (E2E-MVR), a percutaneous left atrial appendage occlusion (LAAO)
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or a mitral/aortic paravalvular leak closure (PVLC). Of these 214 patients, 2 were excluded after
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intraprocedural TEE identified an unfavorable anatomy to LAAO, which led to aborting the procedure shortly after probe placement. Hence, the final population consisted of 1249 patients.
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All medical records were carefully reviewed to retrieve detailed demographic information,
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preoperative medication, procedural data from operative and anesthesiologist log sheets and progress notes. After full review of the patient chart, complications were classified as being TEE related if the type of injury was suggestive of being caused by the probe and no other cause was evident. Echocardiographic study All intraprocedural TEE examinations performed to guide E2E-MVR, LAAO and PVLO were done by 1 of 3 experienced cardiologists after the induction of general anesthesia and endotracheal intubation. For TAVI procedures, TEE was performed by anesthesiologists.
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Following adequate lubrication, the probe was blindly inserted with the help of a jaw-thrust maneuver and a mouth guard was inserted. A multiplane adult TEE probe from Philips iE33 (X72t) was used from the start of the study until April 2017, and from GE Vivid E9 (6VT-D) and Phillips EPIQ 7 (X8-2t) henceforth. As per standard practice to prevent overheating, the image was frozen when the probe was not being used and the lowest output intensity needed to achieve a good image quality was adjusted in each patient.
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Definitions
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Transesophageal echocardiography related complications (TEE-RC) were classified as minor or
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major. Major complications were defined as having one or more of the following: TEE-RC
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resulting in hemodynamic compromise warranting pressors and/or inotropes or mechanical support; 2) a TEE-RC resulting in an upper gastro-intestinal bleeding (UGIB) requiring
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transfusion; 3) persistent dysphagia/odynophagia or UGIB requiring a diagnostic imaging
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technique that reveals a TEE-RC likely responsible for the clinical presentation; and 4) the need
classified as minors.
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for a therapeutic endoscopic or surgical intervention to treat a TEE-RC. All other events were
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Early presentation was arbitrarily defined as occurring in the first 24 hours after TEE and late presentation was defined as occurring after 24 hours. Dysphagia and odynophagia likely associated to TEE were categorized into mild and moderate/severe. Moderate to severe dysphagia/odynophagia was defined as symptoms persisting more than 24h, requiring a specific diagnostic or therapeutic intervention or if it triggered further consultations after hospital discharge. Patients were diagnosed with mild dysphagia/odynophagia if they did not meet any of the above criteria.
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Time under transesophageal echocardiography (TU-TEE) was defined as the time interval from probe insertion until its removal at the end of the procedure. Frailty was defined by a slow gait speed (≥6 seconds) performance in the 5-meter walking test.10 Patients were categorized into two groups: patients with and without TEE-RC. The first group was then further subdivided into patients exhibiting major and minor complications. Patients undergoing TAVI were considered a low-risk group and analyzed separately from the rest of the
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cohort since TEE does not play a central role in guiding the procedure and, therefore,
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manipulation of the probe in the esophagus is not as important as in other structural
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interventions.
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Follow-up
Follow-up was performed retrospectively through review of medical records and phone contacts
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routinely made to patients after discharge as part of a standardized in-hospital protocol following
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structural interventional procedures. Information regarding possible complications and hospital
Statistical analysis
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readmissions was carefully reviewed to identify late-presenting complications related to TEE.
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Categorical variables were expressed as a number (percentage) and continuous variables as mean (standard deviation) or median (interquartile range [IQR]: 25-75th percentile) according to their distribution. Assessment of normality for continuous data was performed using the ShapiroWilks test. Comparison of qualitative variables was performed with the X 2 or Fisher exact test. Quantitative variables with a normal distribution were analyzed with a 1-way analysis of variance and quantitative variables with a non-normal distribution with a Kruskal-Wallis test. Post-hoc comparisons were performed with the parametric Tukey test or the non-parametric Kruskal-Wallis, as appropriate. A logistic regression was performed to determine independent
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predictors of TEE-RC. Those variables from the univariable analysis with a p value <0.05 were entered into a multivariable regression analysis Due to a low event per variable ratio, the logistic regression model was penalized using the Firth bias correction. 11 Receiver-operating characteristic (ROC) analysis was performed to assess the value of TU-TEE to predict TEE-RC. Optimal threshold values for ROC curve was determined according to the Youden index and the balance between sensitivity and specificity. Analyses were performed
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using STATA (version 14.2; StataCorp LLC, College Station, Tx, USA).
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No extramural funding was used to support this work. The authors are solely responsible for the
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design and conduct of this study, all study analyses, the drafting and editing of the paper and its
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final contents.
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RESULTS
Patient population and procedural characteristics
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Baseline clinical demographics and procedural characteristics of the study population are
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summarized in Table 1. Compared to the high-risk cohort, patients in the TAVI group were older (81 vs 75 years-old, p<0.01), had a lower weight (72 vs 76 kg, p<0.01) and were more frequently treated with acetylsalicylic acid (78% vs 59%, p<0.01). A prior history of bleeding, cerebral vascular accident (CVA)/transient ischemic attack (TIA) and atrial fibrillation/flutter was more frequent in the high-risk cohort, 61% vs 1% (p<0.01), 28% vs 17% (p<0.01) and 85 vs 32% (p<0.01), respectively. These patients were also more frequently under anticoagulant therapy (45% vs 24%, p<0.01) and were considered more frail (60 vs 38%, p<0.01) compared with the TAVI group.
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The overall median procedural time was 74 minutes, and PVLC patients had the longest TU-TEE time (155 minutes), followed by E2E-MVR (127 minutes), LAAO (73 minutes) and TAVI (72 minutes). Patients presenting with TEE-related complications A detailed summary of individual cases presenting with complications are listed in Table 2. The overall incidence of TEE-RC was 6.1 % and 0.9% in the high-risk cohort and in the TAVI
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TEE-RC (0.6%) and 3 with minor complications (0.3%).
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group, respectively (p<0.01) (Figure 1). In patients undergoing TAVI, 6 presented with a major
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In the high-risk cohort, 7 patients presented with a TEE-RC that was categorized as major
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(3.3%) and 6 as minor (2.8%). In this group, major complications included 1 case of esophageal
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perforation (0.5%), 3 cases of esophageal lacerations (1.4%), 2 cases of esophageal hematoma (0.9%) and 1 case of UGIB requiring blood transfusion (0.5%).
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A high proportion of major complications had an early presentation (67%). Patients presenting with a major TEE-related event following E2E-MVR, LAAO and PVLC had an increased
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median hospital length of stay duration compared to those with minor/no complications (5 [2-10]
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vs. 1 [1-2] days, p=0.02). Contrarily, no differences were found regarding hospitalization length in patients presenting with a major TEE-related complication after TAVI (12 [6-26] vs. 7 [5-10], p=0.06). There were no deaths related to a TEE complication in our cohort. High-risk cohort (E2E-MVR, LAAO, PVLC): When patients’ demographics were analyzed according to TEE-RC (Table 2), those presenting with a major complication had a significant lower weight and BMI, as well as a higher frequency of prior GIB. Additionally, we observed a higher prevalence of chronic corticosteroids and immunosuppressive medication use in patients presenting with a major complication. The
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remaining baseline characteristics, including antiplatelet and anticoagulant therapy, were well balanced between the two groups. Low-risk cohort (TAVI): There were no significant differences in baseline characteristics between TAVI patients presenting with major and minor complications (Table 3). Procedural characteristics:
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Procedural characteristics according to TEE-related complications are listed in Table 4.
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Imaging TU-TEE median was significantly longer in patients exhibiting major and minor
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complications compared to the rest of the cohort: 102 [88-281] min vs. 98 [59-113] min vs 74
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[60-97] min, respectively (p= 0.006). TU-TEE was also found to be an independent predictor of major complications: OR=1.13 (95%CI:1.01-1.25) for each 10 min increments (Table 5). The
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longest median TU-TEE, 297 min [192-324], was observed in patients exhibiting a major
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complication following E2E-MVR. The highest rate of major complications was also found in patients undergoing E2E-MVR (0.521 per 1000 patient-minutes), followed by PVLC (0.263 per
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1000 patient-minutes), LAAO (0.188 per 1000 patient-minutes) and TAVI (0.061 per 1000
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patients/min). Patients belonging to the high-risk cohort, compared to the TAVI group, had a higher incidence of major (2.8% vs 0.6%, p= 0.008) and minor TEE-RC (3.3% vs 0.3%, p<0.001) (Figure 1), as well as a higher median procedural time that was longest in patients presenting with major complications (143 min vs 90 min, p= 0.08). In this group of patients, a cutoff point of 143 minutes was the best predictor of major complications (area under ROC curve = 0.71, with a sensibility of 57% and specificity of 81%). Finally, the relative risk (RR) of presenting with a major TEE-RC was 9.47 (95%CI:3.01-29.81, p<0.01) in patients treated with E2E-MVR compared to the rest of the population (including
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TAVI). Moreover, patients undergoing TAVI, compared to the high-risk cohort, had an 82% risk reduction in developing a TEE-RC (RR: 0.18, 95%CI: 0.06-0.52, p< 0.01). Follow-up Clinical follow-up at 30 days was achieved in 1230 patients (98.6%). Only two patients consulted for dysphagia that persisted for more than 1 week after hospital discharge, both pertaining to the high-risk group. Out of those 2 patients, only 1 was readmitted with a late
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presenting complication in the form of a proximal esophageal hematoma.
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DISCUSSION
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As far as we know, this is the first study that looked into the prevalence and types of TEE complications associated with cardiac interventional procedures.
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The main findings of the study can be summarized as follows: 1) In patients requiring active
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TEE guidance, the overall prevalence of TEE-RC was noticeably higher compared to TAVI and to what has been previously reported in the literature, 2) In these patients, having a low weight,
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prior GIB and those taking chronic corticosteroids and immunosuppressive drugs were at an
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increased risk for complications and 3) the main procedural factors associated with major complications were a prolonged TU-TEE and undergoing E2E-MVR. Prevalence and timing of TEE-related complications Previous studies focusing in patients undergoing cardiac surgery have reported overall rates of TEE related morbidity ranging from 0.2 to 1.4% (Figure 2).3, 4, 6, 9 Similarly, we observed an incidence of overall complications of 0.9% in patients undergoing TAVI procedures. However, contrary to the previous reports, patients undergoing E2E-MVR, LAAO and PVLC had a substantially higher prevalence of overall and major TEE-RC of 6.1 and 3.3%, respectively. A
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likely explanation for this finding is that, in contrast with the use of TEE in a “conventional” intraoperative and TAVI setting, where image acquisition typically lasts short periods of time, TEE used to guide interventional procedures require constant probe manipulation through-out the course of the intervention. Several mechanisms for TEE associated injury have been recognized, such as forced manipulation of improperly placed probes, significant anteflexion of the probe tip for long periods (pressure-related) and thermal injury, especially in the setting of
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patients with severe atherosclerosis.8
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We observed that the majority of complications had an early presentation, nevertheless, in case
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nº 2, the diagnosis of proximal esophageal hematoma was made after discharge, at the 11th day
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post-procedure. Our findings are consistent with previous reports showing that even though the majority of complications are identified within the first week, some cases may be recognized up
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to several weeks later.4, 9
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we did not found any gastric TEE-RC
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Finally, and contrary to previous studies,3-6,
complications in the high-risk cohort. The most likely explanation is that the deep transgastric
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view, in which the probe is anteflexed and in close contact with the gastric wall, is seldom used
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for guidance during cardiac structural interventions and, if used, it is only for short periods of time. However, we did observe a high number of esophageal complications, ranging from esophageal lacerations/hematomas to one case of perforation. Factors associated with an increased risk of complications in the high-risk cohort: Patient related factors: A low weight, a prior history of GIB and the use of chronic corticosteroids and immunosuppressive medication were significantly associated with an increased risk of complications.
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It has been previously speculated that a small stature and the use of chronic steroids may be correlated with an increased risk of major gastrointestinal complications related to the TEE examination.12-14 It is well known that immunosuppressant drugs can potentially cause mucosal injury and ulceration,15, 16 which in turn may lead to an anatomical substrate that predisposes to the development of mechanical complications secondary to probe manipulation. A recent study evaluating TEE associated complications in patients undergoing cardiac surgery
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has also identified a low BMI as a risk factor.9 As suggested by the authors, larger patients may
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accommodate better the relatively large probe. In fact, in the pediatric population, TEE-RC are 18
Also, being
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clearly correlated to the size of the probe in relation to the patient weight.17,
underweight may be a marker of frailty, which has been linked to an increased risk of
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postoperative complications and in-hospital mortality.19 In the subgroup of patients undergoing
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E2E-MVR, all patients presenting with a major complication were considered frail, as opposed
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to none of the patients who had minor complications. Finally, a prior history of GIB may denote susceptible patients at increased risk for further
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gastrointestinal complications. It is reasonable to think that in some of those patients the
studied.
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condition responsible for the first bleeding episode may have contributed to the event being
Procedure related factors: Compared to patients who had an uneventful procedure, TU-TEE was significantly longer in those presenting with minor and major complications, and was the only independent predictor of major complications. Patients undergoing E2E-MVR who exhibited a major complication had the longest median TU-TEE and the highest incidence rate of complications. Edge-to-edge mitral valve repair is a complex technique that strongly relies on TEE guidance. Even though we
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routinely use real time 3D-TEE to guide the procedure, which has been associated with a reduction in procedural time by 28%,20 the intervention may occasionally still take up more than 5h in complex cases. Nonetheless, new technologies such as real time 3D-TEE and echocardiographic-fluoroscopic fusion imaging have shown to increase procedural success rate and lead to safer and faster transcatheter-based interventions.21-24 As an adjunct to 2D-TEE, the implementation of these new technologies may potentially reduce TEE-RC by decreasing
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procedural times.
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Limitations
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This report consists of an observational single center study with a retrospective analysis and a
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small number of patients in the high-risk cohort. Data regarding TEE-complications were recorded without an event adjudication committee and was subject to limitations including
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reporting bias and missing data. However, we carefully reviewed each medical chart individually
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to try to identify possible complications related to the TEE examination. It is also possible that some complications may have gone undiagnosed since they may have been self-limiting or not
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severe enough to trigger a note in the medical chart. Also, we cannot exclude that complications
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such as dysphagia or odynophagia were related to the endotracheal intubation. Finally, we are not able to completely rule out that the higher incidence of TEE-RC may be, in part, operator or institution specific. However, our center has one of the largest clinical volume in tertiary cardiology in Canada, with approximately 2280 TEE exams having been performed during the past year. Also, in the herein study, we found a higher prevalence of major TEE-RC in the second half of the cohort compared to the first half (data not shown), which makes it less likely that operator experience was the main factor associated with the higher complication rate and may instead reflect an increase in undertaking interventional procedures on higher risk patients.
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Conclusion The results of this study suggest that TEE-RC associated with interventional procedures requiring active TEE are relatively frequent. Undergoing prolonged procedures, especially in the setting of transcatheter mitral valve repair, seems to confer the highest risk of developing complications. ACKNOWLEDGMENTS:
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Dr. Afonso B. Freitas-Ferraz is supported by a research grant from the Quebec Heart & Lung
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Institute Fondation. Drs. Lucía Junquera and Lluis Asmarats were supported by a research grant
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from the Fundación Alfonso Martín Escudero (Madrid, Spain). Dr. Josep Rodés-Cabau holds the
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Canadian Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions. Dr. Jonathan Beaudoin holds research grants from the
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Heart and Stroke Foundation of Canada and Canadian Institutes for Health Research.
FUNDING:
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or not-for-profit sectors.
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This research did not receive any specific grant from funding agencies in the public, commercial,
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REFERENCES:
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1. Side CD, Gosling RG. Non-surgical assessment of cardiac function. Nature. 1971;232(5309):335-336. 2. Flachskampf FA, Wouters PF, Edvardsen T, et al. Recommendations for transoesophageal echocardiography: EACVI update 2014. Eur Heart J Cardiovasc Imaging. 2014;15(4):353-365. 3. Kallmeyer IJ, Collard CD, Fox JA, et al. The safety of intraoperative transesophageal echocardiography: a case series of 7200 cardiac surgical patients. Anesth Analg. 2001;92(5):1126-1130. 4. Lennon MJ, Gibbs NM, Weightman WM, et al. Transesophageal echocardiographyrelated gastrointestinal complications in cardiac surgical patients. J Cardiothorac Vasc Anesth. 2005;19(2):141-145. 5. Piercy M, McNicol L, Dinh DT, et al. Major complications related to the use of transesophageal echocardiography in cardiac surgery. J Cardiothorac Vasc Anesth. 2009;23(1):62-65. 6. Huang CH, Lu CW, Lin TY, et al. Complications of intraoperative transesophageal echocardiography in adult cardiac surgical patients - experience of two institutions in Taiwan. J Formos Med Assoc. 2007;106(1):92-95. 7. Sainathan S, Andaz S. A systematic review of transesophageal echocardiography-induced esophageal perforation. Echocardiography. 2013;30(8):977-983. 8. Hilberath JN, Oakes DA, Shernan SK, et al. Safety of transesophageal echocardiography. J Am Soc Echocardiogr. 2010;23(11):1115-1127; quiz 1220-1111. 9. Purza R, Ghosh S, Walker C, et al. Transesophageal Echocardiography Complications in Adult Cardiac Surgery: A Retrospective Cohort Study. Ann Thorac Surg. 2017;103(3):795-802. 10. Afilalo J, Eisenberg MJ, Morin JF, et al. Gait speed as an incremental predictor of mortality and major morbidity in elderly patients undergoing cardiac surgery. J Am Coll Cardiol. 2010;56(20):1668-1676. 11. Firth D. Bias Reduction of Maximum Likelihood Estimates. Biometrika. 1993;80(1):2738. 12. Min JK, Spencer KT, Furlong KT, et al. Clinical features of complications from transesophageal echocardiography: a single-center case series of 10,000 consecutive examinations. J Am Soc Echocardiogr. 2005;18(9):925-929. 13. Brinkman WT, Shanewise JS, Clements SD, et al. Transesophageal echocardiography: not an innocuous procedure. Ann Thorac Surg. 2001;72(5):1725-1726.
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Jo
ur
na
lP
re
-p
ro
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14. Lecharny JB, Philip I, Depoix JP. Oesophagotracheal perforation after intraoperative transoesphageal echocardiography in cardiac surgery. Br J Anaesth. 2002;88(4):592-594. 15. Aggarwal V, Williams MD, Beath SV. Gastrointestinal problems in the immunosuppressed patient. Arch Dis Child. 1998;78(1):5-8. 16. Tomizawa M, Shinozaki F, Hasegawa R, et al. Immunosuppressive agents are associated with peptic ulcer bleeding. Exp Ther Med. 2017;13(5):1927-1931. 17. Kohr LM, Dargan M, Hague A, et al. The incidence of dysphagia in pediatric patients after open heart procedures with transesophageal echocardiography. Ann Thorac Surg. 2003;76(5):1450-1456. 18. Stevenson JG. Incidence of complications in pediatric transesophageal echocardiography: experience in 1650 cases. J Am Soc Echocardiogr. 1999;12(6):527-532. 19. Lee DH, Buth KJ, Martin BJ, et al. Frail patients are at increased risk for mortality and prolonged institutional care after cardiac surgery. Circulation. 2010;121(8):973-978. 20. Biner S, Perk G, Kar S, et al. Utility of combined two-dimensional and three-dimensional transesophageal imaging for catheter-based mitral valve clip repair of mitral regurgitation. J Am Soc Echocardiogr. 2011;24(6):611-617. 21. Balzer J, Zeus T, Veulemans V, et al. Hybrid Imaging in the Catheter Laboratory: Realtime Fusion of Echocardiography and Fluoroscopy During Percutaneous Structural Heart Disease Interventions. Interventional cardiology (London, England). 2016;11(1):59-64. 22. Biaggi P, Fernandez-Golfín C, Hahn R, et al. Hybrid Imaging During Transcatheter Structural Heart Interventions. Curr Cardiovasc Imaging Rep. 2015;8(9):33. 23. Nucifora G, Faletra FF, Regoli F, et al. Evaluation of the left atrial appendage with realtime 3-dimensional transesophageal echocardiography: implications for catheter-based left atrial appendage closure. Circ Cardiovasc Imaging. 2011;4(5):514-523. 24. Altiok E, Becker M, Hamada S, et al. Real-time 3D TEE allows optimized guidance of percutaneous edge-to-edge repair of the mitral valve. JACC Cardiovasc Imaging. 2010;3(11):1196-1198.
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FIGURE LEGENDS
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Figure 1. Incidence of TEE-related complications according to procedure type.
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E2E-MVR: edge-to-edge mitral valve repair. LAAO: left atrial appendage occlusion. PVLC:
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paravalvular leak closure. TAVI: transcatheter aortic valve implantation. TEE: transesophageal
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echocardiography.
Figure 2. Overall comparison of TEE-related complications among studies.
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TEE: transesophageal echocardiography.
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TAVI: transcatheter aortic valve implantation
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Table 1. Baseline clinical demographics and procedural characteristics of the final study
Overall population (n=1249)
TAVI (n=1037)
High-risk cohort (n= 212)
P value
81 [75-85]
75 [68-80]
<0.01
80 [74-85]
Female Weight, kg
550 (44.0) 73 [61-84]
478 (46.1) 72 [61-84]
72 (34.0) 76 [64-89]
<0.01 <0.01
BMI, Kg/m2
26.7 [23.5-30.5]
26.6 [23.4-30.5]
27.3 [23.9-31.1]
0.12
Frailty*
418/1093 1075 (38.2)
384 /1018 (37.7)
34/57 (59.7)
0.001
1069 (85.6)
889 (85.7)
180 (84.9)
0.78
Diabetes mellitus Dyslipidemia
454 (36.4) 969 (77.6)
376 (36.3) 825 (79.6)
78 (36.8) 144 (67.9)
0.88 <0.01
Smokers
318 (25.5)
273 (26.3)
45 (21.2)
0.12
COPD Previous CAD
314 (25.1) 820 (65.7)
288 (27.8) 690 (66.5)
26 (12.3) 130 (61.3)
0.41 0.13
Chronic kidney disease (GFR < 60) Previous open-heart surgery Heart failure LVEF
665 (53.2)
555 (53.5)
110 (51.9)
0.76
500 (40.0)
404 (39.0)
96 (45.3)
0.09
616 (49.3) 60 [45-60]
527 (50.8) 60 [45-60]
89 (42.0) 55 [40-60]
0.02 <0.01
CVA/TIA
232 (18.6)
173 (16.7)
59 (27.8)
<0.01
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Comorbidities Hypertension
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Baseline characteristics Age, years
na
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ro
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population.
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136 (10.9) 70 (5.6)
7 (0.7) 2 (0.2)
129 (60.8) 68 (32.4)
<0.01 <0.01
Prior AF/Flutter
512 (41.0)
332 (32.0)
180 (84.9)
<0.01
Previous Treatment ASA
937 (75.0)
811 (78.8)
126 (59.4)
<0.01
Clopidogrel
360 (28.8)
346 (33.4)
14 (6.6)
<0.01
Double antiplatelet therapy Anticoagulant therapy
308 (24.7)
301 (29.0)
7 (3.3)
<0.01
350 (28.0)
249 (24.0)
101 (47.6)
<0.01
Warfarin DOACs Chronic steroids
294 (23.9) 54 (4.3) 39 (3.1)
238 (23.0) 10 (1.0) 31 (3.0)
56 (26.4) 44 (20.8) 8 (3.8)
0.33 <0.01 0.52
13 (1.0)
8 (0.8)
5 (2.4)
0.05
115 [103-130]
115 [103-131]
117 [106-130]
0.94
58 [49-65]
60 [58-70]
0.02
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Procedural characteristics SAP
re
Immunosupressors
of
Prior bleeding Previous GI bleeding
58 [50-66]
MAP
76.7 [69.0-86.7]
76.7 [68.3-86.3]
80.8 [73.3-88.2]
0.13
74 [60-97]
72 [60-90]
92 [65-132]
<0.01
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DAP TU-TEE guidance, min
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Values are mean SD, median and interquartile range or n (%). AF: atrial fibrillation; ASA: acetylsalicylic acid; BMI: body mass index; CABG: coronary artery by-pass graft. CAD: coronary artery disease. COPD: chronic obstructive pulmonary disease; CVA: cerebrovascular accident; DAP: diastolic arterial pressure; DOACs: Direct oral anticoagulants; GI: gastrointestinal; LVEF: left ventricular ejection fraction; MAP: mean arterial pressure; SAP: systolic arterial pressure; TAVI: transcatheter aortic valve implantation. TU-TEE: Time under transesophageal echocardiography; TIA: transient ischemic attack. * Frailty: only available in patients undergoing TAVI or edge-to-edge mitral valve repair.
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Table 2. Baseline clinical characteristics according to TEE-related complications in patients
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requiring active TEE guidance.
No (n=199)
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Baseline characteristics
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TEE-related complications Minor (n=6)
Major (n=7)
P value
79.5 [65-82]
79.0 [68-85]
0.28
75 [68-80]
Female
66 (33.2)
3 (50.0)
3 (42.9)
0.61
Weight, kg
77 [65-89]
66.5 [61-77]
59 [49-83]†
0.05
27.4 [24.2-31.1]
22.7 [20.7-27.3]
30/52 (57.7)
0/6 (0)
4/4 (100)
0.14
168 (84.4)
5 (83.3)
7 (100)
0.52
78 (39.2)
2 (33.3)
1 (14.3)
0.12
136 (70.5)
2 (33.3)
6 (85.7)
0.04
69 (34.7)
1 (16.7)
2 (28.6)
0.40
50 (25.1)
1 (16.7)
1 (14.3)
0.11
120 (60.3)
4 (66.7)
6 (85.7)
0.38
106 (53.3)
1 (16.7)
3 (42.9)
0.20
91 (45.7)
1 (16.7)
4 (57.1)
0.30
Heart failure
83 (41.7)
2 (33.3)
4 (57.1)
0.92
LVEF
55 [40-60]
52 [45-60]
60 [55-60]
0.45
CVA/TIA
53 (26.6)
3 (50.0)
3 (42.9)
0.30
Prior bleeding
118 (59.3)
6 (100)
5 (71.4)
0.12
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re
Age, years
BMI, Kg/m2
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Frailtyx Comorbidities
Dyslipidemia Smokers COPD
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Diabetes mellitus
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Hypertension
Previous CAD Chronic kidney disease (GFR < 60) Previous open-heart surgery
22.2 [19.1-32.8]†
0.06
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60 (30.2)
3 (50.0)
5 (71.4)†
0.01
169 (84.9)
6 (100)
5 (71.4)
0.36
117 (58.8)
3 (50.0)
6 (85.7)
0.30
Clopidogrel
13 (6.5)
0 (0)
1 (14.3)
0.60
Double antiplatelet therapy
6 (3.0)
0 (0)
1 (14.3)
0.36
93 (46.7)
3 (50.0)
5 (71.4)
0.46
Warfarine
51 (25.1)
1 (16.7)
4 (57.1)
0.16
DOACs
41 (20.6)
2 (33.3)
1 (14.4)
0.74
Bisphosphonates
8 (4.0)
0 (0)
(0)
1.00
Chronic steroids
6 (3.0)
0 (0)
2 (28.6)†‡
0.04
Immunosuppressors
2 (1.0)
0 (0)
3 (42.9)† ‡
<0.01
Hospital length of stay
1 [1-2]
1 [1]
5 [2-10]
0.03
Prior GI bleeding Prior AF/Flutter
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Anticoagulant therapy
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ASA
of
Previous Treatment
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ur
na
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re
Values are mean SD, median and interquartile range or n (%). AF: atrial fibrillation; ASA: acetylsalicylic acid; BMI: body mass index; CABG: coronary artery by-pass graft. CAD: coronary artery disease. COPD: chronic obstructive pulmonary disease; CVA: cerebrovascular accident; DOACs: Direct oral anticoagulants; GI: gastrointestinal; LVEF: left ventricular ejection fraction; TEE: Transesophageal echocardiography; TIA: transient ischemic attack. * Frailty: only available in patients undergoing TAVI or edge-to-edge mitral valve repair. †: p< 0.05 versus no complication. ‡: p < 0.05 versus minor complication.
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Table 3. Baseline clinical characteristics according to TEE-related complications in TAVI patients.
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TEE-related complications
Baseline characteristics
Minor (n=3)
Major (n=6)
P value
81 [71-84]
85 [83-86]
0.19
2 (66.7)
1 (16.7)
0.06
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No (n=1028)
81 [75-85]
Female
475 (46.2)
Weight, kg
72 [61-84]
92 [82-130]
74 [70-77]
0.09
BMI, Kg/m2
26.6 [23.4-30.5]
35.9 [25.3-54.1]
27.0 [21.8-30.1]
0.25
379 (37.6)
2 (66.7)
3 (50)
0.49
884 (86.0)
3 (100.0)
3 (50.0)
0.09
373 (36.3)
2 (66.7)
1 (16.7)
0.29
820 (79.8)
3 (100.0)
3 (50.0)
0.20
269 (26.2)
1 (33.3)
3 (50.0)
0.33
283 (27.5)
3 (100.0)
2 (33.3)
0.04
686 (66.7)
0 (0.0)
4 (66.7)
0.07
550 (53.5)
1 (33.3)
4 (66.7)
0.70
401 (39.0)
0 (0.0)
3 (50.0)
0.43
Heart failure
523 (50.9)
1 (33.3)
3 (50.0)
0.88
LVEF
60 [45-60]
60 [60-60]
50 [45-60]
0.44
CVA/TIA
173 (16.8)
0 (0.0)
0 (0.0)
0.77
6 (0.6)
0 (0.0)
1 (16.7)
0.06
2 (0.2)
0 (0.0)
0 (0.0)
1.00
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re
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Age, years
Frailty*
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Comorbidities Hypertension
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Diabetes mellitus Smokers COPD Previous CAD
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Dyslipidemia
Chronic kidney disease (GFR < 60) Previous open heart surgery
Prior bleeding Prior GI bleeding
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328 (32.0)
1 (33.3)
3 (50.0)
0.63
ASA
803 (78.1)
3 (100.0)
5 (83.3)
1.00
Clopidogrel
343 (33.4)
1 (33.3)
2 (33.3)
1.00
Double antiplatelet therapy
298 (29.0)
1 (33.3)
2 (33.3)
1.00
Anticoagulant therapy
245 (23.8)
0 (0.0)
3 (50.0)
0.27
235 (22.9)
0 (0.0)
3 (50.0)
0.39
10 (0.1)
0 (0.0)
0 (0.0)
1.00
Chronic steroids
30 (2.9)
0 (0.0)
1 (16.7)
0.24
Immunosuppressors
8 (0.8)
0 (0.0)
0 (0.0)
1.00
Hospital length of stay
7 [5-10]
7 [6-8]
12 [6-26]
0.16
DOACs
ro
Warfarine
of
Previous Treatment
Jo
ur
na
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re
-p
Values are mean SD, median and interquartile range or n (%). AF: atrial fibrillation; ASA: acetylsalicylic acid; BMI: body mass index; CABG: coronary artery by-pass graft. CAD: coronary artery disease. COPD: chronic obstructive pulmonary disease; CVA: cerebrovascular accident; DOACs: Direct oral anticoagulants; GI: gastrointestinal; LVEF: left ventricular ejection fraction; TEE: Transesophageal echocardiography; TIA: transient ischemic attack. * Frailty: only available in patients undergoing TAVI or E2E-MVR.
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Table 4. TEE-related complications according to procedure type.
Procedure type High-risk TAVI cohort (n=1037) (n=212) TEE related complication
13 (6.1)
9 (0.9)
- Minor complication
7 (3.3)
3 (0.3)
- Major complication
6 (2.8)
6 (0.6)
Procedure TU-TEE (min)
92 [65-132]
- Minor complication
107 [95-129]
- Major complication
143 [88-313]
P value
e
o r p
r P
<0.01
High-risk cohort
E2E-MVR (n=56)
LAAO (n=131)
PVLC (n=25)
4 (7.1)*
8 (6.1)*
1 (4.0)
6 (4.6) 2 (1.5) ‡
0 (0.0)
†
†
<0.01
0 (0.0)
<0.01
4 (7.1)
72 [60-90]
rn
<0.01
127 [96-168]*†
73 [56-99]
155 [95-181]*†
75 [47-113]
0.30
-
107 [95-129]
-
90 [77-98]
0.08
297 [192-324]*†
70 [51-88]
143†
u o
J
f o
l a
1 (4.0)
Values are mean SD, median and interquartile range or n (%). E2E-MVR: edge-to-edge mitral valve repair. LAAO: left atrial appendage occlusion. PVLC:
paravalvular leak closure. TAVI: transcatheter aortic valve implantation. TEE: transesophageal echocardiography. TU-TEE: Time under transesophageal echocardiography. *: p<0.05 vs. TAVI; †: p<0.05 vs. LAAO; ‡: p<0.05 vs. E2E-MVR
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Table 5. Predictors of major TEE-RC in the overall-cohort. Univariable model OR (95% CI)
p value
1.06 (0.98-1.15) 0.98 (0.95-1.01) 0.93 (0.83-1.05)
0.13 0.27 0.24
1.39 (0.76-2.53) 1.74 (0.48-6.37) 1.20 (0.40-3.59) 0.99 (0.95-1.04) 1.31 (0.36-4.82)) 7.29 (2.41-22.03) 12.86 (3.9741.61)
0.28 0.40 0.74 0.88 0.68 <0.01 <0.01
Multivariable model OR (95% CI)
p value
ro
-p
0.12 -
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5.06 (0.64-39.96) -
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0.45 0.65 0.89
4.18 (1.36-12.87)
0.01
2.95 (0.84-10.30)
0.09
9.99 (2.64-37.86) 22.29 (4.37113.78)
<0.01 <0.01
3.03 (0.35-26.50) 9.11 (0.95-87.34)
0.32 0.07
<0.01 <0.01
0.87 (0.11-6.91) 1.13 (1.01-1.25)
0.90 0.03
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Procedural characteristics TAVI procedures TU-TEE guidance, min*
1.79 (0.39-8.14) 0.74 (0.20-2.72) 0.91 (0.25-3.35)
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Age, years Weight, kg BMI, Kg/m2 Comorbidities Smokers Previous CAD Heart failure LVEF CVA/TIA Prior bleeding Previous GI bleeding† Previous Treatment ASA Clopidogrel Double antiplatelet therapy Anticoagulant therapy Chronic steroids Immunosupressors
of
Clinical variables
0.17 (0.06-0.51) 1.17 (1.09-1.26)
BMI: body mass index; CAD: coronary artery disease. CVA: cerebrovascular accident; TAVI: transcatheter aortic valve implantation. TU-TEE: Time under transesophageal echocardiography; TIA: transient ischemic attack. * for each 10 min † increments in imaging time. Variable excluded from the multivariable analysis due to collinearity.
Figure 1
Figure 2
Afonso B. Freitas-Ferraz, Josep Rodés-Cabau, Lucía Junquera Vega, Jonathan Beaudoin, Kim O'Connor, Pierre Yves Turgeon, Jean-Michel Paradis, Alfredo Ferreira-Neto, Lluis Asmarats, Jean Champagne, Gilles O'Hara, Mathieu Bernier PII:
S0002-8703(19)30339-4
DOI:
https://doi.org/10.1016/j.ahj.2019.11.018
Reference:
YMHJ 6028
To appear in:
American Heart Journal
Received date:
12 July 2019
Accepted date:
22 November 2019
Please cite this article as: A.B. Freitas-Ferraz, J. Rodés-Cabau, L.J. Vega, et al., Transesophageal echocardiography complications associated with interventional cardiology procedures, American Heart Journal(2019), https://doi.org/10.1016/ j.ahj.2019.11.018
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2019 Published by Elsevier.
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Title: Transesophageal Echocardiography Complications Associated with Interventional Cardiology Procedures.
Afonso B. Freitas-Ferraza MD, Josep Rodés-Cabaua MD, Lucía Junquera Vegaa MD, Jonathan Beaudoina MD, Kim O´Connora MD, Pierre Yves Turgeona MD, Jean-Michel Paradisa MD,
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Mathieu Berniera MD.
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Alfredo Ferreira-Netoa MD, Lluis Asmaratsa MD, Jean Champagnea MD, Gilles O´Haraa MD,
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a- Department of Cardiology, Quebec Heart and Lung Institute, Laval University, Quebec
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City, Canada
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Short title: TEE related complications in interventional cardiology
Address for correspondence: Mathieu Bernier, MD
Quebec Heart Lung Institute, Laval University 2725 chemin Ste-Foy. G1V4G5, Quebec City, Quebec, Canada Phone: Tel: (+1)65687711-5106 Fax: 656-4675
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E-mail: [email protected]
ABSTRACT
Background: Although there have been several reports documenting complications related with transesophageal echocardiography (TEE) manipulation following cardiac surgery, there is no data regarding the safety of TEE used to guide catheter-based interventions. The aim of this
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study was to determine the prevalence, types and risk factors of complications associated with procedures requiring active TEE guidance.
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Methods: This study included 1249 consecutive patients undergoing either transcatheter aortic
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valve implantation (TAVI), Mitraclip, left atrial appendage occlusion (LAAO) or paravalvular leak closure (PVLC). Patients were divided into two cohorts based on the degree of probe
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manipulation required to guide the procedure and the risk of developing a TEE-related complication: low-risk (TAVI, n=1037) and high-risk (Mitraclip, LAAO and PVLC, n=212).
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Patients were further analyzed according to the occurrence of major and minor TEE-related complications.
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Results: The overall incidence of TEE-related complications was 0.9% in the TAVI group and 6.1% in the rest of the cohort (p<0.001). Patients in the high-risk cohort had also a higher
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incidence of major-complications (2.8% vs 0.6%, p=0.008), and factors associated with an increased risk were being underweight, having a prior history of gastrointestinal bleeding and the
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use of chronic steroids/immunosuppressive medications. Procedural time under TEEmanipulation was longer in patients exhibiting complications and was an independent predictor of major complications (OR=1.13, 95%CI:1.01-1.25, for each 10 min increments in imaging time). Patients undergoing Mitraclip had the longest median time under TEE-manipulation (297 min) and a risk of developing a major-complication that was 10.64 times higher than the rest of the cohort (95%CI 3.30-34.29, p<0.001).
Conclusion: The prevalence of TEE-related complications associated with interventional procedures is higher than previously reported. Undergoing a prolonged procedure, particularly in the setting of Mitraclip, was the main factor linked to TEE-related complications.
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Keywords: transesophageal echocardiography complications, transcatheter aortic valve implantation, TAVI, Mitraclip, edge-to-edge mitral valve repair, left atrial appendage occlusion, paravalvular leak closure.
ABBREVIATIONS LIST
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E2E-MVR: Edge-to-edge mitral valve repair
LAAO: Left atrial appendage occlusion PVLC: Paravalvular leak closure
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TEE: Transesophageal echocardiography
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TAVI: Transcatheter aortic valve implantation
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GIB: gastro-intestinal bleeding
TEE-RC: Transesophageal echocardiography related complications
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TU-TEE: Time under transesophageal echocardiography
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UGIB: Upper gastro-intestinal bleeding
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INTRODUCTION The use and indications of transesophageal echocardiography (TEE) have expanded
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exponentially since its first reported use in 1971 to measure flow in the aortic arch.1 Nowadays,
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TEE has become not only a diagnostic tool with widespread utilization, but also an invaluable
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monitoring adjunct for operative and percutaneous procedures. Particularly, in the field of transcatheter based interventions, it provides crucial real-time information to help guide and
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assess procedural results.2 Even though TEE is considered to have a good safety profile with
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overall rates of TEE-related morbidity ranging from 0.2 to 1.2%,3, 4 severe complications, some
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of which can be life-threatening, have been reported.4-8 The majority of the available data regarding complications associated with TEE procedural guidance stems from studies performed
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during the course of cardiac surgery.3-9 In contrast with the operating room TEE sequence, in
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which image acquisition generally lasts short periods of time at predefined moments (e.g. baseline, post cardio pulmonary bypass and chest closed), TEE used to guide catheter-based procedures entails constant probe manipulation while the procedure is performed. Consequently, the incidence of TEE related complications reported in the literature may not be extrapolated to the ever-expanding scenarios of interventional cardiology. The aim of this study was to determine the incidence and types of TEE complications related to procedures requiring active TEE guidance as well as identifying possible risk factors associated with these complications.
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METHODS Patient population
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We retrospectively analyzed a cohort of 1251 consecutive adult patients undergoing cardiac
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interventional procedures with an intraoperative-TEE, between May 2007 and August 2018, at
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the Quebec Heart and Lung Institute. Out of those patients, 1037 underwent transcatheter aortic
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valve implantation (TAVI) and the remaining 214 patients underwent either a transcatheter edgeto-edge mitral valve repair (E2E-MVR), a percutaneous left atrial appendage occlusion (LAAO)
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or a mitral/aortic paravalvular leak closure (PVLC). Of these 214 patients, 2 were excluded after
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intraprocedural TEE identified an unfavorable anatomy to LAAO, which led to aborting the procedure shortly after probe placement. Hence, the final population consisted of 1249 patients.
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All medical records were carefully reviewed to retrieve detailed demographic information,
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preoperative medication, procedural data from operative and anesthesiologist log sheets and progress notes. After full review of the patient chart, complications were classified as being TEE related if the type of injury was suggestive of being caused by the probe and no other cause was evident. Echocardiographic study All intraprocedural TEE examinations performed to guide E2E-MVR, LAAO and PVLO were done by 1 of 3 experienced cardiologists after the induction of general anesthesia and endotracheal intubation. For TAVI procedures, TEE was performed by anesthesiologists.
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Following adequate lubrication, the probe was blindly inserted with the help of a jaw-thrust maneuver and a mouth guard was inserted. A multiplane adult TEE probe from Philips iE33 (X72t) was used from the start of the study until April 2017, and from GE Vivid E9 (6VT-D) and Phillips EPIQ 7 (X8-2t) henceforth. As per standard practice to prevent overheating, the image was frozen when the probe was not being used and the lowest output intensity needed to achieve a good image quality was adjusted in each patient.
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Definitions
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Transesophageal echocardiography related complications (TEE-RC) were classified as minor or
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major. Major complications were defined as having one or more of the following: TEE-RC
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resulting in hemodynamic compromise warranting pressors and/or inotropes or mechanical support; 2) a TEE-RC resulting in an upper gastro-intestinal bleeding (UGIB) requiring
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transfusion; 3) persistent dysphagia/odynophagia or UGIB requiring a diagnostic imaging
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technique that reveals a TEE-RC likely responsible for the clinical presentation; and 4) the need
classified as minors.
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for a therapeutic endoscopic or surgical intervention to treat a TEE-RC. All other events were
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Early presentation was arbitrarily defined as occurring in the first 24 hours after TEE and late presentation was defined as occurring after 24 hours. Dysphagia and odynophagia likely associated to TEE were categorized into mild and moderate/severe. Moderate to severe dysphagia/odynophagia was defined as symptoms persisting more than 24h, requiring a specific diagnostic or therapeutic intervention or if it triggered further consultations after hospital discharge. Patients were diagnosed with mild dysphagia/odynophagia if they did not meet any of the above criteria.
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Time under transesophageal echocardiography (TU-TEE) was defined as the time interval from probe insertion until its removal at the end of the procedure. Frailty was defined by a slow gait speed (≥6 seconds) performance in the 5-meter walking test.10 Patients were categorized into two groups: patients with and without TEE-RC. The first group was then further subdivided into patients exhibiting major and minor complications. Patients undergoing TAVI were considered a low-risk group and analyzed separately from the rest of the
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cohort since TEE does not play a central role in guiding the procedure and, therefore,
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manipulation of the probe in the esophagus is not as important as in other structural
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interventions.
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Follow-up
Follow-up was performed retrospectively through review of medical records and phone contacts
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routinely made to patients after discharge as part of a standardized in-hospital protocol following
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structural interventional procedures. Information regarding possible complications and hospital
Statistical analysis
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readmissions was carefully reviewed to identify late-presenting complications related to TEE.
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Categorical variables were expressed as a number (percentage) and continuous variables as mean (standard deviation) or median (interquartile range [IQR]: 25-75th percentile) according to their distribution. Assessment of normality for continuous data was performed using the ShapiroWilks test. Comparison of qualitative variables was performed with the X 2 or Fisher exact test. Quantitative variables with a normal distribution were analyzed with a 1-way analysis of variance and quantitative variables with a non-normal distribution with a Kruskal-Wallis test. Post-hoc comparisons were performed with the parametric Tukey test or the non-parametric Kruskal-Wallis, as appropriate. A logistic regression was performed to determine independent
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predictors of TEE-RC. Those variables from the univariable analysis with a p value <0.05 were entered into a multivariable regression analysis Due to a low event per variable ratio, the logistic regression model was penalized using the Firth bias correction. 11 Receiver-operating characteristic (ROC) analysis was performed to assess the value of TU-TEE to predict TEE-RC. Optimal threshold values for ROC curve was determined according to the Youden index and the balance between sensitivity and specificity. Analyses were performed
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using STATA (version 14.2; StataCorp LLC, College Station, Tx, USA).
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No extramural funding was used to support this work. The authors are solely responsible for the
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design and conduct of this study, all study analyses, the drafting and editing of the paper and its
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final contents.
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RESULTS
Patient population and procedural characteristics
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Baseline clinical demographics and procedural characteristics of the study population are
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summarized in Table 1. Compared to the high-risk cohort, patients in the TAVI group were older (81 vs 75 years-old, p<0.01), had a lower weight (72 vs 76 kg, p<0.01) and were more frequently treated with acetylsalicylic acid (78% vs 59%, p<0.01). A prior history of bleeding, cerebral vascular accident (CVA)/transient ischemic attack (TIA) and atrial fibrillation/flutter was more frequent in the high-risk cohort, 61% vs 1% (p<0.01), 28% vs 17% (p<0.01) and 85 vs 32% (p<0.01), respectively. These patients were also more frequently under anticoagulant therapy (45% vs 24%, p<0.01) and were considered more frail (60 vs 38%, p<0.01) compared with the TAVI group.
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The overall median procedural time was 74 minutes, and PVLC patients had the longest TU-TEE time (155 minutes), followed by E2E-MVR (127 minutes), LAAO (73 minutes) and TAVI (72 minutes). Patients presenting with TEE-related complications A detailed summary of individual cases presenting with complications are listed in Table 2. The overall incidence of TEE-RC was 6.1 % and 0.9% in the high-risk cohort and in the TAVI
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TEE-RC (0.6%) and 3 with minor complications (0.3%).
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group, respectively (p<0.01) (Figure 1). In patients undergoing TAVI, 6 presented with a major
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In the high-risk cohort, 7 patients presented with a TEE-RC that was categorized as major
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(3.3%) and 6 as minor (2.8%). In this group, major complications included 1 case of esophageal
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perforation (0.5%), 3 cases of esophageal lacerations (1.4%), 2 cases of esophageal hematoma (0.9%) and 1 case of UGIB requiring blood transfusion (0.5%).
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A high proportion of major complications had an early presentation (67%). Patients presenting with a major TEE-related event following E2E-MVR, LAAO and PVLC had an increased
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median hospital length of stay duration compared to those with minor/no complications (5 [2-10]
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vs. 1 [1-2] days, p=0.02). Contrarily, no differences were found regarding hospitalization length in patients presenting with a major TEE-related complication after TAVI (12 [6-26] vs. 7 [5-10], p=0.06). There were no deaths related to a TEE complication in our cohort. High-risk cohort (E2E-MVR, LAAO, PVLC): When patients’ demographics were analyzed according to TEE-RC (Table 2), those presenting with a major complication had a significant lower weight and BMI, as well as a higher frequency of prior GIB. Additionally, we observed a higher prevalence of chronic corticosteroids and immunosuppressive medication use in patients presenting with a major complication. The
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remaining baseline characteristics, including antiplatelet and anticoagulant therapy, were well balanced between the two groups. Low-risk cohort (TAVI): There were no significant differences in baseline characteristics between TAVI patients presenting with major and minor complications (Table 3). Procedural characteristics:
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Procedural characteristics according to TEE-related complications are listed in Table 4.
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Imaging TU-TEE median was significantly longer in patients exhibiting major and minor
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complications compared to the rest of the cohort: 102 [88-281] min vs. 98 [59-113] min vs 74
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[60-97] min, respectively (p= 0.006). TU-TEE was also found to be an independent predictor of major complications: OR=1.13 (95%CI:1.01-1.25) for each 10 min increments (Table 5). The
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longest median TU-TEE, 297 min [192-324], was observed in patients exhibiting a major
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complication following E2E-MVR. The highest rate of major complications was also found in patients undergoing E2E-MVR (0.521 per 1000 patient-minutes), followed by PVLC (0.263 per
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1000 patient-minutes), LAAO (0.188 per 1000 patient-minutes) and TAVI (0.061 per 1000
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patients/min). Patients belonging to the high-risk cohort, compared to the TAVI group, had a higher incidence of major (2.8% vs 0.6%, p= 0.008) and minor TEE-RC (3.3% vs 0.3%, p<0.001) (Figure 1), as well as a higher median procedural time that was longest in patients presenting with major complications (143 min vs 90 min, p= 0.08). In this group of patients, a cutoff point of 143 minutes was the best predictor of major complications (area under ROC curve = 0.71, with a sensibility of 57% and specificity of 81%). Finally, the relative risk (RR) of presenting with a major TEE-RC was 9.47 (95%CI:3.01-29.81, p<0.01) in patients treated with E2E-MVR compared to the rest of the population (including
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TAVI). Moreover, patients undergoing TAVI, compared to the high-risk cohort, had an 82% risk reduction in developing a TEE-RC (RR: 0.18, 95%CI: 0.06-0.52, p< 0.01). Follow-up Clinical follow-up at 30 days was achieved in 1230 patients (98.6%). Only two patients consulted for dysphagia that persisted for more than 1 week after hospital discharge, both pertaining to the high-risk group. Out of those 2 patients, only 1 was readmitted with a late
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presenting complication in the form of a proximal esophageal hematoma.
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DISCUSSION
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As far as we know, this is the first study that looked into the prevalence and types of TEE complications associated with cardiac interventional procedures.
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The main findings of the study can be summarized as follows: 1) In patients requiring active
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TEE guidance, the overall prevalence of TEE-RC was noticeably higher compared to TAVI and to what has been previously reported in the literature, 2) In these patients, having a low weight,
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prior GIB and those taking chronic corticosteroids and immunosuppressive drugs were at an
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increased risk for complications and 3) the main procedural factors associated with major complications were a prolonged TU-TEE and undergoing E2E-MVR. Prevalence and timing of TEE-related complications Previous studies focusing in patients undergoing cardiac surgery have reported overall rates of TEE related morbidity ranging from 0.2 to 1.4% (Figure 2).3, 4, 6, 9 Similarly, we observed an incidence of overall complications of 0.9% in patients undergoing TAVI procedures. However, contrary to the previous reports, patients undergoing E2E-MVR, LAAO and PVLC had a substantially higher prevalence of overall and major TEE-RC of 6.1 and 3.3%, respectively. A
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likely explanation for this finding is that, in contrast with the use of TEE in a “conventional” intraoperative and TAVI setting, where image acquisition typically lasts short periods of time, TEE used to guide interventional procedures require constant probe manipulation through-out the course of the intervention. Several mechanisms for TEE associated injury have been recognized, such as forced manipulation of improperly placed probes, significant anteflexion of the probe tip for long periods (pressure-related) and thermal injury, especially in the setting of
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patients with severe atherosclerosis.8
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We observed that the majority of complications had an early presentation, nevertheless, in case
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nº 2, the diagnosis of proximal esophageal hematoma was made after discharge, at the 11th day
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post-procedure. Our findings are consistent with previous reports showing that even though the majority of complications are identified within the first week, some cases may be recognized up
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to several weeks later.4, 9
9
we did not found any gastric TEE-RC
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Finally, and contrary to previous studies,3-6,
complications in the high-risk cohort. The most likely explanation is that the deep transgastric
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view, in which the probe is anteflexed and in close contact with the gastric wall, is seldom used
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for guidance during cardiac structural interventions and, if used, it is only for short periods of time. However, we did observe a high number of esophageal complications, ranging from esophageal lacerations/hematomas to one case of perforation. Factors associated with an increased risk of complications in the high-risk cohort: Patient related factors: A low weight, a prior history of GIB and the use of chronic corticosteroids and immunosuppressive medication were significantly associated with an increased risk of complications.
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It has been previously speculated that a small stature and the use of chronic steroids may be correlated with an increased risk of major gastrointestinal complications related to the TEE examination.12-14 It is well known that immunosuppressant drugs can potentially cause mucosal injury and ulceration,15, 16 which in turn may lead to an anatomical substrate that predisposes to the development of mechanical complications secondary to probe manipulation. A recent study evaluating TEE associated complications in patients undergoing cardiac surgery
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has also identified a low BMI as a risk factor.9 As suggested by the authors, larger patients may
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accommodate better the relatively large probe. In fact, in the pediatric population, TEE-RC are 18
Also, being
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clearly correlated to the size of the probe in relation to the patient weight.17,
underweight may be a marker of frailty, which has been linked to an increased risk of
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postoperative complications and in-hospital mortality.19 In the subgroup of patients undergoing
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E2E-MVR, all patients presenting with a major complication were considered frail, as opposed
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to none of the patients who had minor complications. Finally, a prior history of GIB may denote susceptible patients at increased risk for further
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gastrointestinal complications. It is reasonable to think that in some of those patients the
studied.
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condition responsible for the first bleeding episode may have contributed to the event being
Procedure related factors: Compared to patients who had an uneventful procedure, TU-TEE was significantly longer in those presenting with minor and major complications, and was the only independent predictor of major complications. Patients undergoing E2E-MVR who exhibited a major complication had the longest median TU-TEE and the highest incidence rate of complications. Edge-to-edge mitral valve repair is a complex technique that strongly relies on TEE guidance. Even though we
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routinely use real time 3D-TEE to guide the procedure, which has been associated with a reduction in procedural time by 28%,20 the intervention may occasionally still take up more than 5h in complex cases. Nonetheless, new technologies such as real time 3D-TEE and echocardiographic-fluoroscopic fusion imaging have shown to increase procedural success rate and lead to safer and faster transcatheter-based interventions.21-24 As an adjunct to 2D-TEE, the implementation of these new technologies may potentially reduce TEE-RC by decreasing
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procedural times.
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Limitations
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This report consists of an observational single center study with a retrospective analysis and a
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small number of patients in the high-risk cohort. Data regarding TEE-complications were recorded without an event adjudication committee and was subject to limitations including
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reporting bias and missing data. However, we carefully reviewed each medical chart individually
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to try to identify possible complications related to the TEE examination. It is also possible that some complications may have gone undiagnosed since they may have been self-limiting or not
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severe enough to trigger a note in the medical chart. Also, we cannot exclude that complications
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such as dysphagia or odynophagia were related to the endotracheal intubation. Finally, we are not able to completely rule out that the higher incidence of TEE-RC may be, in part, operator or institution specific. However, our center has one of the largest clinical volume in tertiary cardiology in Canada, with approximately 2280 TEE exams having been performed during the past year. Also, in the herein study, we found a higher prevalence of major TEE-RC in the second half of the cohort compared to the first half (data not shown), which makes it less likely that operator experience was the main factor associated with the higher complication rate and may instead reflect an increase in undertaking interventional procedures on higher risk patients.
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Conclusion The results of this study suggest that TEE-RC associated with interventional procedures requiring active TEE are relatively frequent. Undergoing prolonged procedures, especially in the setting of transcatheter mitral valve repair, seems to confer the highest risk of developing complications. ACKNOWLEDGMENTS:
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Dr. Afonso B. Freitas-Ferraz is supported by a research grant from the Quebec Heart & Lung
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Institute Fondation. Drs. Lucía Junquera and Lluis Asmarats were supported by a research grant
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from the Fundación Alfonso Martín Escudero (Madrid, Spain). Dr. Josep Rodés-Cabau holds the
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Canadian Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions. Dr. Jonathan Beaudoin holds research grants from the
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Heart and Stroke Foundation of Canada and Canadian Institutes for Health Research.
FUNDING:
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or not-for-profit sectors.
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This research did not receive any specific grant from funding agencies in the public, commercial,
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REFERENCES:
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1. Side CD, Gosling RG. Non-surgical assessment of cardiac function. Nature. 1971;232(5309):335-336. 2. Flachskampf FA, Wouters PF, Edvardsen T, et al. Recommendations for transoesophageal echocardiography: EACVI update 2014. Eur Heart J Cardiovasc Imaging. 2014;15(4):353-365. 3. Kallmeyer IJ, Collard CD, Fox JA, et al. The safety of intraoperative transesophageal echocardiography: a case series of 7200 cardiac surgical patients. Anesth Analg. 2001;92(5):1126-1130. 4. Lennon MJ, Gibbs NM, Weightman WM, et al. Transesophageal echocardiographyrelated gastrointestinal complications in cardiac surgical patients. J Cardiothorac Vasc Anesth. 2005;19(2):141-145. 5. Piercy M, McNicol L, Dinh DT, et al. Major complications related to the use of transesophageal echocardiography in cardiac surgery. J Cardiothorac Vasc Anesth. 2009;23(1):62-65. 6. Huang CH, Lu CW, Lin TY, et al. Complications of intraoperative transesophageal echocardiography in adult cardiac surgical patients - experience of two institutions in Taiwan. J Formos Med Assoc. 2007;106(1):92-95. 7. Sainathan S, Andaz S. A systematic review of transesophageal echocardiography-induced esophageal perforation. Echocardiography. 2013;30(8):977-983. 8. Hilberath JN, Oakes DA, Shernan SK, et al. Safety of transesophageal echocardiography. J Am Soc Echocardiogr. 2010;23(11):1115-1127; quiz 1220-1111. 9. Purza R, Ghosh S, Walker C, et al. Transesophageal Echocardiography Complications in Adult Cardiac Surgery: A Retrospective Cohort Study. Ann Thorac Surg. 2017;103(3):795-802. 10. Afilalo J, Eisenberg MJ, Morin JF, et al. Gait speed as an incremental predictor of mortality and major morbidity in elderly patients undergoing cardiac surgery. J Am Coll Cardiol. 2010;56(20):1668-1676. 11. Firth D. Bias Reduction of Maximum Likelihood Estimates. Biometrika. 1993;80(1):2738. 12. Min JK, Spencer KT, Furlong KT, et al. Clinical features of complications from transesophageal echocardiography: a single-center case series of 10,000 consecutive examinations. J Am Soc Echocardiogr. 2005;18(9):925-929. 13. Brinkman WT, Shanewise JS, Clements SD, et al. Transesophageal echocardiography: not an innocuous procedure. Ann Thorac Surg. 2001;72(5):1725-1726.
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14. Lecharny JB, Philip I, Depoix JP. Oesophagotracheal perforation after intraoperative transoesphageal echocardiography in cardiac surgery. Br J Anaesth. 2002;88(4):592-594. 15. Aggarwal V, Williams MD, Beath SV. Gastrointestinal problems in the immunosuppressed patient. Arch Dis Child. 1998;78(1):5-8. 16. Tomizawa M, Shinozaki F, Hasegawa R, et al. Immunosuppressive agents are associated with peptic ulcer bleeding. Exp Ther Med. 2017;13(5):1927-1931. 17. Kohr LM, Dargan M, Hague A, et al. The incidence of dysphagia in pediatric patients after open heart procedures with transesophageal echocardiography. Ann Thorac Surg. 2003;76(5):1450-1456. 18. Stevenson JG. Incidence of complications in pediatric transesophageal echocardiography: experience in 1650 cases. J Am Soc Echocardiogr. 1999;12(6):527-532. 19. Lee DH, Buth KJ, Martin BJ, et al. Frail patients are at increased risk for mortality and prolonged institutional care after cardiac surgery. Circulation. 2010;121(8):973-978. 20. Biner S, Perk G, Kar S, et al. Utility of combined two-dimensional and three-dimensional transesophageal imaging for catheter-based mitral valve clip repair of mitral regurgitation. J Am Soc Echocardiogr. 2011;24(6):611-617. 21. Balzer J, Zeus T, Veulemans V, et al. Hybrid Imaging in the Catheter Laboratory: Realtime Fusion of Echocardiography and Fluoroscopy During Percutaneous Structural Heart Disease Interventions. Interventional cardiology (London, England). 2016;11(1):59-64. 22. Biaggi P, Fernandez-Golfín C, Hahn R, et al. Hybrid Imaging During Transcatheter Structural Heart Interventions. Curr Cardiovasc Imaging Rep. 2015;8(9):33. 23. Nucifora G, Faletra FF, Regoli F, et al. Evaluation of the left atrial appendage with realtime 3-dimensional transesophageal echocardiography: implications for catheter-based left atrial appendage closure. Circ Cardiovasc Imaging. 2011;4(5):514-523. 24. Altiok E, Becker M, Hamada S, et al. Real-time 3D TEE allows optimized guidance of percutaneous edge-to-edge repair of the mitral valve. JACC Cardiovasc Imaging. 2010;3(11):1196-1198.
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FIGURE LEGENDS
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Figure 1. Incidence of TEE-related complications according to procedure type.
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E2E-MVR: edge-to-edge mitral valve repair. LAAO: left atrial appendage occlusion. PVLC:
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paravalvular leak closure. TAVI: transcatheter aortic valve implantation. TEE: transesophageal
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echocardiography.
Figure 2. Overall comparison of TEE-related complications among studies.
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TEE: transesophageal echocardiography.
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TAVI: transcatheter aortic valve implantation
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Table 1. Baseline clinical demographics and procedural characteristics of the final study
Overall population (n=1249)
TAVI (n=1037)
High-risk cohort (n= 212)
P value
81 [75-85]
75 [68-80]
<0.01
80 [74-85]
Female Weight, kg
550 (44.0) 73 [61-84]
478 (46.1) 72 [61-84]
72 (34.0) 76 [64-89]
<0.01 <0.01
BMI, Kg/m2
26.7 [23.5-30.5]
26.6 [23.4-30.5]
27.3 [23.9-31.1]
0.12
Frailty*
418/1093 1075 (38.2)
384 /1018 (37.7)
34/57 (59.7)
0.001
1069 (85.6)
889 (85.7)
180 (84.9)
0.78
Diabetes mellitus Dyslipidemia
454 (36.4) 969 (77.6)
376 (36.3) 825 (79.6)
78 (36.8) 144 (67.9)
0.88 <0.01
Smokers
318 (25.5)
273 (26.3)
45 (21.2)
0.12
COPD Previous CAD
314 (25.1) 820 (65.7)
288 (27.8) 690 (66.5)
26 (12.3) 130 (61.3)
0.41 0.13
Chronic kidney disease (GFR < 60) Previous open-heart surgery Heart failure LVEF
665 (53.2)
555 (53.5)
110 (51.9)
0.76
500 (40.0)
404 (39.0)
96 (45.3)
0.09
616 (49.3) 60 [45-60]
527 (50.8) 60 [45-60]
89 (42.0) 55 [40-60]
0.02 <0.01
CVA/TIA
232 (18.6)
173 (16.7)
59 (27.8)
<0.01
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Comorbidities Hypertension
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Baseline characteristics Age, years
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population.
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136 (10.9) 70 (5.6)
7 (0.7) 2 (0.2)
129 (60.8) 68 (32.4)
<0.01 <0.01
Prior AF/Flutter
512 (41.0)
332 (32.0)
180 (84.9)
<0.01
Previous Treatment ASA
937 (75.0)
811 (78.8)
126 (59.4)
<0.01
Clopidogrel
360 (28.8)
346 (33.4)
14 (6.6)
<0.01
Double antiplatelet therapy Anticoagulant therapy
308 (24.7)
301 (29.0)
7 (3.3)
<0.01
350 (28.0)
249 (24.0)
101 (47.6)
<0.01
Warfarin DOACs Chronic steroids
294 (23.9) 54 (4.3) 39 (3.1)
238 (23.0) 10 (1.0) 31 (3.0)
56 (26.4) 44 (20.8) 8 (3.8)
0.33 <0.01 0.52
13 (1.0)
8 (0.8)
5 (2.4)
0.05
115 [103-130]
115 [103-131]
117 [106-130]
0.94
58 [49-65]
60 [58-70]
0.02
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Procedural characteristics SAP
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Immunosupressors
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Prior bleeding Previous GI bleeding
58 [50-66]
MAP
76.7 [69.0-86.7]
76.7 [68.3-86.3]
80.8 [73.3-88.2]
0.13
74 [60-97]
72 [60-90]
92 [65-132]
<0.01
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DAP TU-TEE guidance, min
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Values are mean SD, median and interquartile range or n (%). AF: atrial fibrillation; ASA: acetylsalicylic acid; BMI: body mass index; CABG: coronary artery by-pass graft. CAD: coronary artery disease. COPD: chronic obstructive pulmonary disease; CVA: cerebrovascular accident; DAP: diastolic arterial pressure; DOACs: Direct oral anticoagulants; GI: gastrointestinal; LVEF: left ventricular ejection fraction; MAP: mean arterial pressure; SAP: systolic arterial pressure; TAVI: transcatheter aortic valve implantation. TU-TEE: Time under transesophageal echocardiography; TIA: transient ischemic attack. * Frailty: only available in patients undergoing TAVI or edge-to-edge mitral valve repair.
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Table 2. Baseline clinical characteristics according to TEE-related complications in patients
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requiring active TEE guidance.
No (n=199)
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Baseline characteristics
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TEE-related complications Minor (n=6)
Major (n=7)
P value
79.5 [65-82]
79.0 [68-85]
0.28
75 [68-80]
Female
66 (33.2)
3 (50.0)
3 (42.9)
0.61
Weight, kg
77 [65-89]
66.5 [61-77]
59 [49-83]†
0.05
27.4 [24.2-31.1]
22.7 [20.7-27.3]
30/52 (57.7)
0/6 (0)
4/4 (100)
0.14
168 (84.4)
5 (83.3)
7 (100)
0.52
78 (39.2)
2 (33.3)
1 (14.3)
0.12
136 (70.5)
2 (33.3)
6 (85.7)
0.04
69 (34.7)
1 (16.7)
2 (28.6)
0.40
50 (25.1)
1 (16.7)
1 (14.3)
0.11
120 (60.3)
4 (66.7)
6 (85.7)
0.38
106 (53.3)
1 (16.7)
3 (42.9)
0.20
91 (45.7)
1 (16.7)
4 (57.1)
0.30
Heart failure
83 (41.7)
2 (33.3)
4 (57.1)
0.92
LVEF
55 [40-60]
52 [45-60]
60 [55-60]
0.45
CVA/TIA
53 (26.6)
3 (50.0)
3 (42.9)
0.30
Prior bleeding
118 (59.3)
6 (100)
5 (71.4)
0.12
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Age, years
BMI, Kg/m2
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Frailtyx Comorbidities
Dyslipidemia Smokers COPD
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Diabetes mellitus
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Hypertension
Previous CAD Chronic kidney disease (GFR < 60) Previous open-heart surgery
22.2 [19.1-32.8]†
0.06
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60 (30.2)
3 (50.0)
5 (71.4)†
0.01
169 (84.9)
6 (100)
5 (71.4)
0.36
117 (58.8)
3 (50.0)
6 (85.7)
0.30
Clopidogrel
13 (6.5)
0 (0)
1 (14.3)
0.60
Double antiplatelet therapy
6 (3.0)
0 (0)
1 (14.3)
0.36
93 (46.7)
3 (50.0)
5 (71.4)
0.46
Warfarine
51 (25.1)
1 (16.7)
4 (57.1)
0.16
DOACs
41 (20.6)
2 (33.3)
1 (14.4)
0.74
Bisphosphonates
8 (4.0)
0 (0)
(0)
1.00
Chronic steroids
6 (3.0)
0 (0)
2 (28.6)†‡
0.04
Immunosuppressors
2 (1.0)
0 (0)
3 (42.9)† ‡
<0.01
Hospital length of stay
1 [1-2]
1 [1]
5 [2-10]
0.03
Prior GI bleeding Prior AF/Flutter
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Anticoagulant therapy
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ASA
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Previous Treatment
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Values are mean SD, median and interquartile range or n (%). AF: atrial fibrillation; ASA: acetylsalicylic acid; BMI: body mass index; CABG: coronary artery by-pass graft. CAD: coronary artery disease. COPD: chronic obstructive pulmonary disease; CVA: cerebrovascular accident; DOACs: Direct oral anticoagulants; GI: gastrointestinal; LVEF: left ventricular ejection fraction; TEE: Transesophageal echocardiography; TIA: transient ischemic attack. * Frailty: only available in patients undergoing TAVI or edge-to-edge mitral valve repair. †: p< 0.05 versus no complication. ‡: p < 0.05 versus minor complication.
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Table 3. Baseline clinical characteristics according to TEE-related complications in TAVI patients.
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TEE-related complications
Baseline characteristics
Minor (n=3)
Major (n=6)
P value
81 [71-84]
85 [83-86]
0.19
2 (66.7)
1 (16.7)
0.06
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No (n=1028)
81 [75-85]
Female
475 (46.2)
Weight, kg
72 [61-84]
92 [82-130]
74 [70-77]
0.09
BMI, Kg/m2
26.6 [23.4-30.5]
35.9 [25.3-54.1]
27.0 [21.8-30.1]
0.25
379 (37.6)
2 (66.7)
3 (50)
0.49
884 (86.0)
3 (100.0)
3 (50.0)
0.09
373 (36.3)
2 (66.7)
1 (16.7)
0.29
820 (79.8)
3 (100.0)
3 (50.0)
0.20
269 (26.2)
1 (33.3)
3 (50.0)
0.33
283 (27.5)
3 (100.0)
2 (33.3)
0.04
686 (66.7)
0 (0.0)
4 (66.7)
0.07
550 (53.5)
1 (33.3)
4 (66.7)
0.70
401 (39.0)
0 (0.0)
3 (50.0)
0.43
Heart failure
523 (50.9)
1 (33.3)
3 (50.0)
0.88
LVEF
60 [45-60]
60 [60-60]
50 [45-60]
0.44
CVA/TIA
173 (16.8)
0 (0.0)
0 (0.0)
0.77
6 (0.6)
0 (0.0)
1 (16.7)
0.06
2 (0.2)
0 (0.0)
0 (0.0)
1.00
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Age, years
Frailty*
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Comorbidities Hypertension
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Diabetes mellitus Smokers COPD Previous CAD
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Dyslipidemia
Chronic kidney disease (GFR < 60) Previous open heart surgery
Prior bleeding Prior GI bleeding
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328 (32.0)
1 (33.3)
3 (50.0)
0.63
ASA
803 (78.1)
3 (100.0)
5 (83.3)
1.00
Clopidogrel
343 (33.4)
1 (33.3)
2 (33.3)
1.00
Double antiplatelet therapy
298 (29.0)
1 (33.3)
2 (33.3)
1.00
Anticoagulant therapy
245 (23.8)
0 (0.0)
3 (50.0)
0.27
235 (22.9)
0 (0.0)
3 (50.0)
0.39
10 (0.1)
0 (0.0)
0 (0.0)
1.00
Chronic steroids
30 (2.9)
0 (0.0)
1 (16.7)
0.24
Immunosuppressors
8 (0.8)
0 (0.0)
0 (0.0)
1.00
Hospital length of stay
7 [5-10]
7 [6-8]
12 [6-26]
0.16
DOACs
ro
Warfarine
of
Previous Treatment
Jo
ur
na
lP
re
-p
Values are mean SD, median and interquartile range or n (%). AF: atrial fibrillation; ASA: acetylsalicylic acid; BMI: body mass index; CABG: coronary artery by-pass graft. CAD: coronary artery disease. COPD: chronic obstructive pulmonary disease; CVA: cerebrovascular accident; DOACs: Direct oral anticoagulants; GI: gastrointestinal; LVEF: left ventricular ejection fraction; TEE: Transesophageal echocardiography; TIA: transient ischemic attack. * Frailty: only available in patients undergoing TAVI or E2E-MVR.
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Table 4. TEE-related complications according to procedure type.
Procedure type High-risk TAVI cohort (n=1037) (n=212) TEE related complication
13 (6.1)
9 (0.9)
- Minor complication
7 (3.3)
3 (0.3)
- Major complication
6 (2.8)
6 (0.6)
Procedure TU-TEE (min)
92 [65-132]
- Minor complication
107 [95-129]
- Major complication
143 [88-313]
P value
e
o r p
r P
<0.01
High-risk cohort
E2E-MVR (n=56)
LAAO (n=131)
PVLC (n=25)
4 (7.1)*
8 (6.1)*
1 (4.0)
6 (4.6) 2 (1.5) ‡
0 (0.0)
†
†
<0.01
0 (0.0)
<0.01
4 (7.1)
72 [60-90]
rn
<0.01
127 [96-168]*†
73 [56-99]
155 [95-181]*†
75 [47-113]
0.30
-
107 [95-129]
-
90 [77-98]
0.08
297 [192-324]*†
70 [51-88]
143†
u o
J
f o
l a
1 (4.0)
Values are mean SD, median and interquartile range or n (%). E2E-MVR: edge-to-edge mitral valve repair. LAAO: left atrial appendage occlusion. PVLC:
paravalvular leak closure. TAVI: transcatheter aortic valve implantation. TEE: transesophageal echocardiography. TU-TEE: Time under transesophageal echocardiography. *: p<0.05 vs. TAVI; †: p<0.05 vs. LAAO; ‡: p<0.05 vs. E2E-MVR
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Table 5. Predictors of major TEE-RC in the overall-cohort. Univariable model OR (95% CI)
p value
1.06 (0.98-1.15) 0.98 (0.95-1.01) 0.93 (0.83-1.05)
0.13 0.27 0.24
1.39 (0.76-2.53) 1.74 (0.48-6.37) 1.20 (0.40-3.59) 0.99 (0.95-1.04) 1.31 (0.36-4.82)) 7.29 (2.41-22.03) 12.86 (3.9741.61)
0.28 0.40 0.74 0.88 0.68 <0.01 <0.01
Multivariable model OR (95% CI)
p value
ro
-p
0.12 -
re
5.06 (0.64-39.96) -
na
lP
0.45 0.65 0.89
4.18 (1.36-12.87)
0.01
2.95 (0.84-10.30)
0.09
9.99 (2.64-37.86) 22.29 (4.37113.78)
<0.01 <0.01
3.03 (0.35-26.50) 9.11 (0.95-87.34)
0.32 0.07
<0.01 <0.01
0.87 (0.11-6.91) 1.13 (1.01-1.25)
0.90 0.03
Jo
Procedural characteristics TAVI procedures TU-TEE guidance, min*
1.79 (0.39-8.14) 0.74 (0.20-2.72) 0.91 (0.25-3.35)
ur
Age, years Weight, kg BMI, Kg/m2 Comorbidities Smokers Previous CAD Heart failure LVEF CVA/TIA Prior bleeding Previous GI bleeding† Previous Treatment ASA Clopidogrel Double antiplatelet therapy Anticoagulant therapy Chronic steroids Immunosupressors
of
Clinical variables
0.17 (0.06-0.51) 1.17 (1.09-1.26)
BMI: body mass index; CAD: coronary artery disease. CVA: cerebrovascular accident; TAVI: transcatheter aortic valve implantation. TU-TEE: Time under transesophageal echocardiography; TIA: transient ischemic attack. * for each 10 min † increments in imaging time. Variable excluded from the multivariable analysis due to collinearity.
Figure 1
Figure 2