Safety of transoesophageal echocardiography during structural heart disease interventions under procedural sedation: a single-centre study

Abstract

Aims

The aim of this study was to determine the incidence of transoesophageal echocardiography (TOE)-related adverse events (AEs) during structural heart disease (SHD) interventions and to identify potential risk factors.

Methods and results

We retrospectively analysed 898 consecutive patients undergoing TOE-guided SHD interventions under procedural sedation. TOE-related AEs were classified as bleeding complications, mechanical lesions, conversion to general anaesthesia with intubation, and the occurrence of pneumonia. A follow-up was conducted up to 3 months after the intervention. TOE-related AEs were observed in 5.3% of the patients (n = 48). The highest rate of AEs was observed in the percutaneous mitral valve repair (PMVR) group with 8.2% (n = 32), whereas 4.8% (n = 11) of the patients in the left atrial appendage group and 1.8% (n = 5) in the patent foramen ovale/atrial septal defect group developed a TOE-related AE (P = 0.001). The most frequent AE was pneumonia with an incidence of 2.6% (n = 26) in the total cohort. Bleeding events occurred in 1.8% (n = 16) of the patients, mostly in the PMVR group with 2.1% (n = 8). In the multivariate regression analysis, we found a lower haemoglobin {odds ratio (OR) [95% confidence interval (CI)]: 8.82 (0.68–0.98) P = 0.025} and an obstructive sleep apnoea syndrome (OSAS) [OR (95% CI): 2.51 (1.08–5.84) P = 0.033] to be associated with AE. Furthermore, AEs were related to procedural time [OR (95% CI): 1.01 (1.0–1.01) P = 0.056] and oral anticoagulation [OR (95% CI): 1.97 (0.9–4.3) P = 0.076] with borderline significance in the multivariate regression analysis. No persistent damages were observed.

Conclusion

TOE-related AEs during SHD interventions are clinically relevant. It was highest in patients undergoing PMVR. A lower baseline haemoglobin level and an OSAS were found to be associated with the occurrence of a TOE-related AE.

Graphical Abstract

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Introduction

Structural heart disease (SHD) interventions include a wide range of interventions such as percutaneous mitral valve repair (PMVR), closure of patent foramen ovale (PFO) or atrial septal defects (ASDs), and left atrial appendage (LAA) closure. Growing evidence and technical progress have led to an increasing number of procedures, becoming an inherent part of daily cardiovascular care delivery. For many structural heart interventions, transoesophageal echocardiography (TOE) is essential to guide procedural steps and to perform a successful procedure. Although TOE has shown to be safe with a low complication rate ranging from 0.1% to 3% depending on the definition of complication,¹ periprocedural TOE can be challenging during complex procedures. As the setting differs from routinely performed TOEs for diagnostic reasons or during open heart surgery, associated complications may occur more often. The peri-interventional approach is characterized by a prolonged TOE time, patients’ supine position, which may hinder the image acquisition and increase the risk for aspiration, a difficult access to the patient due to the C-arm and the need for either procedural sedation (PS) or general anaesthesia (GA). Furthermore, patients referred to SHD interventions are often high-risk patients with various comorbidities what may have an impact on the incidence and type of complications. Until now, only Freitas-Ferraz et al.² reported adverse event (AE) rates for peri-interventional TOE in a GA setting. No analysis has been performed involving TOE-associated AEs in a PS setting. This analysis seems to be highly relevant as many centres perform TOE-guided interventions under PS, which is presumed to induce aspiration events as a completely secured airway management is lacking. We hypothesized that the incidence of TOE-associated AEs is high during SHD interventions.

Thus, the aim of this study was to assess the incidence of TOE-related AEs during SHD interventions performed under PS and to identify potential risk factors.

Methods

We retrospectively analysed 898 consecutive patients undergoing TOE-guided SHD interventions between November 2012 and December 2017 at our heart centre. All procedures were performed under PS, which has been described previously.^3,4 PS was performed by a cardiologist with intensive care experience of at least 6 months, of these patients, 279 patients underwent PFO/ASD closure, 229 patients received closure of LAA, and 390 underwent PMVR. A modified patient flow chart is provided in Figure 1. IRB approval was obtained for all SHD procedures (NCT02033811, NCT02608008, local ethic committee no. 5272R).

TOE was performed using a Philips EPIC 7 ultrasound system with an X7-2t probe (Philips Medical Systems Nederland BV) till November 2016. Afterwards, the Philips X8-2T TOE probe (Philips Medical Systems Nederland BV) was introduced in our clinical routine. All patients received 2–3 mg p.o. midazolam as a mild sedative 30 min prior to procedure. A bite protection was placed after local anaesthesia of the pharynx with lidocaine spray (1%). Catecholamines (norepinephrine at a dose of 5 mg/50 mL) and saline were available, if needed. Haemodynamic monitoring and measurements were obtained through a radial or femoral arterial catheter. A bolus of 0.5 mg/kg of 2% of propofol was administered. Half of the bolus was applied initially followed by a partial dose of the remaining amount within 5 min while monitoring haemodynamic and respiratory response as well as the depth of sedation according to the Richmond Agitation Sedation Score (RASS) score. If the aimed PS level was not achieved, we continued propofol 2% with a dosage of 1.5 mg/kg/h. Furthermore, 1 mg of Atropine was given to reduce secretions. After achieving a RASS of −2 to −3, the TOE probe was inserted with the help of a jaw-thrust manoeuvre. After the procedure, the patient was referred either to the normal ward or the intermediate care unit as soon as vital signs were stable, and the patient was adequately awake (RASS 0 to −1). A continuous monitoring of blood pressure, heart rate, and oxygen saturation were performed for at least 24 h. Patients receiving a PMVR were referred to the intermediate care, whereas patients undergoing closure of PFO/ASD or LAA closure were routinely monitored on the general ward.

Baseline patient characteristics were obtained as well as procedural data and in-hospital data. Laboratory results were obtained 1 day prior to the procedure. Procedure time was defined as time from local anaesthesia until final closure of femoral access site. Pre-existing oesophageal disorders were defined as oesophageal varices, reflux oesophagitis, candidal oesophagitis, and Mallory–Weiss syndrome. TOE-related complications were classified as (i) local bleeding complications (minor bleeding and major bleeding), (ii) mechanical injuries including lesions of teeth, oropharynx, vocal cords, larynx or oesophagus, dysphagia, dysphonia, and perioral hypaesthesia, and (iii) conversion to GA with intubation. Furthermore, (iv) the occurrence of pneumonia during the hospital stay was assessed and analysed as AE and (v) sepsis related to pneumonia. Pneumonia was defined as clinical presentation of pneumonia as symptoms of cough, shortness of breath, fever, and respiratory distress in combination with elevated laboratory markers of infection (C-reactive protein and white blood count) and signs of pneumonia in the chest X-ray (infiltrate) requiring antibiotics.

Dysphagia, dysphonia, and perioral hypoaesthesia were defined as persistent symptoms after 24 h and permanent if still present at discharge. Minor bleedings were any actionable sign of bleeding without meeting the criteria of a major bleeding. A major bleeding was defined as overt bleeding meeting at least one of the following criteria: (i) loss of ≥2 points of haemoglobin (g/dL), (ii) haemorrhage requiring transfusion, (iii) haemorrhage leading to intervention, or (iv) fatal bleeding.

A follow-up was conducted up to 3 months after the intervention, according to clinical standard operating procedure with the assessment of vital status, need for re-intervention, or re-hospitalization.

Statistical analysis was performed with SPSS (IBM, Inc.). Continuous variables are expressed as means ± standard deviation and compared using analysis of variance and Kruskal–Wallis test depending on variable distribution. Categorical variables were compared using χ² testing or Fisher’s exact test. A P-value <0.05 was considered statistically significant. A multivariate regression analysis was performed to identify potential associated factors for the occurrence TOE-related complications. Parameters with a P < 0.1 in the univariate analysis were included in the multivariate regression analysis.

Results

Baseline characteristics

Patients receiving PMVR or LAA closure were older than patients who underwent closure of PFO/ASD (PMVR vs. LAA vs. ASD/PFO: 75.7 years ± 9.6 vs. 76.0 years ± 7.5 vs. 52.2 years ± 14.7; P < 0.01) and presented with a higher logistic EuroSCORE (PMVR vs. LAA vs. PFO/ASD: 24.4% ± 18.4 vs.18.4% ± 15.6 vs. 5.9% ± 6.3; P < 0.01). Furthermore, the prevalence of other comorbidities was higher in both groups. Further details regarding baseline patient characteristics are shown in Table 1.

Procedural data

Procedure time was the longest in the PMVR repair group [128 ± 40.9 min (PMVR group) vs. 86 ± 25.8 min (LAA group) vs. 43 ± 19.7 min (PFO/ASD group); P < 0.01]. In-hospital mortality was low with 1.7% (n = 4) in the LAA group and 0.3% (n = 1) in the PMVR group; no deaths were observed in the PFO/ASD group (P = 0.018). Four patients died due to a cardiogenic shock (procedure-unrelated), whereas one patient died because of a pneumonic septic shock. Procedural data and in-hospital data are shown in Table 2.

Adverse events

TOE-related AEs were observed in 5.3% of the patients (n = 48). The highest rate of AEs was observed in the PMVR group with 8.2% (n = 32), whereas 4.8% (n = 11) of the patients in the LAA group and 1.8% (n = 5) in the PFO/ASD group developed a TOE-related AE (P = 0.001). The most frequent AE was aspiration pneumonia with an overall incidence of 2.6% (n = 26) in the total cohort. Divided by subgroups, pneumonia was most frequent in the PMVR group with 4.9% (n = 19) vs. 2.6% (n = 6) in the LAA group and 0.4% (n = 1) in the PFO/ASD group (P = 0.003). Bleeding events occurred in 1.8% (n = 16) of the patients, mostly in the PMVR group with 2.1% (n = 8) [LAA group: 2.6% (n = 6) vs. PFO/ASD group: 0.7% (n = 2); P = 0.236]. All TOE-related AEs according to procedure type are shown in Table 3. Figure 2/Graphical Abstract displays the incidence of AEs sorted by category (bleeding event, mechanical injury, and conversion to endotracheal intubation) and procedure type.

Characterization of patients with adverse events

Patients with a TOE-related AEs were older (73.8 ± 12.1 years vs. 68.2 ± 15.7 years; P = 0.015) and presented more often with an obstructive sleep apnoea syndrome (OSAS) (16.7% vs. 7.7%; P = 0.016) and anaemia (75.0% vs. 52.4%; P = 0.002). Procedure time was longer in these patients (118 ± 56.3 min vs. 89 ± 47.4 min; P < 0.001) and the total hospital stay (20 ± 21.7 days vs. 8 ± 9.7 days; P < 0.001). All data comparing patients with a TOE-related AE to patients without an AE are shown in Table 4.

Risk factors

Furthermore, we investigated potential risk factors which may trigger AEs independent of the type of procedure. The multivariate regression analysis revealed a lower haemoglobin {odds ratio (OR) [95% confidence interval (CI)]: 8.82 (0.68–0.98) P = 0.025} and an OSAS [OR (95% CI): 2.51 (1.08–5.84) P = 0.033] to be associated with the occurrence of an AE. A borderline significance was found for procedural time [OR (95% CI): 1.01 (1.0–1.01) P = 0.056] and oral anticoagulation [OR (95% CI): 1.97 (0.9–4.3) P = 0.076] (Table 5).

Follow-up

All patients were seen up to 3 months after the index procedure in our outpatient clinic according to clinical standard operating procedure. No persistent damages of the TOE-related AEs could be observed. Thirty-day mortality was 3.2% (n = 20) in the total cohort and higher in patients undergoing PMVR [3.8% (PMVR) vs. 2.2% (LAA) vs. 0.4% (PFO/ASD); P = 0.028]. Re-hospitalization was needed in 4.6% (n = 41) of the patients. Follow-up data are shown in Table 6.

Discussion

In many SHD interventions, TOE is essential for procedural success. Whether the continuous manipulation with the TOE probe is associated with AEs during these procedures if performed under PS is not known so far. The major findings of the current study are as follows: (i) in 5.3% of the patients TOE-related AE was observed during SHD intervention performed under PS. (ii) The highest incidence of AEs was observed in the PMVR group. (iii) A lower preprocedural haemoglobin and OSAS might be associated with the occurrence of AE.

TOE-related adverse events

TOE-related AEs have been reported recently with a complication rate of 6.1% in a high-risk cohort of patients undergoing either closure of LAA, paravalvular leakage, or PMVR under GA.² In our study, all procedures were performed under PS. A TOE-related AE occurred in 5.3% of the patients. Pneumonia was the most common TOE-related AE. Having said that the occurrence of pneumonia cannot only be related to TOE. As the procedure was performed under PS, pneumonia may be due to micro-aspiration during the intervention. It remains controversial whether pneumonia is related to TOE or more to the conduction of the procedure. However, previous studies comparing SHD interventions under PS with GA found no significant differences in the incidence of pneumonia.^3,5–7

Patients undergoing PMVR presented the highest rate of AEs with 8.2%. These patients are often characterized by frailty and multiple comorbidities. Therefore, they may be at higher risk to develop a complication. Interestingly, recent data confirmed this, demonstrating the highest incidence of complications as well as in their edge-to-edge PMVR group with 7.1%.² They found TOE-time to be association with a TOE-related major complication. As we reported the procedure time, we could not demonstrate this association though it seems to be reasonable that a longer time under TOE may trigger TOE-related AEs.

Further observed AEs, in our study, were bleeding events. Most frequent mechanical lesions, in our cohort, were oropharyngeal haematomas and dysphagia with both 0.6% in the total cohort, which were all recurrent during hospital stay. Previous studies have reported similar results with 0.3% of the patients presenting with dysphagia in the setting of cardiac surgery⁸ and occurrence of an oesophageal haematoma in 0.9% of the patients in a high-risk cohort undergoing either interventional closure of LAA, paravalvular leakage, or edge-to-edge PMVR.²

One aspect could be the aimed activated clotting time >250 that is required to avoid coagulation and thromboembolic events during SHD interventions. Bleeding events may therefore occur more often compared to routine diagnostic TOE in the echocardiography laboratory, which have been described below 1%.⁹ As the setting in the cardiac catheterization laboratory differs from the setting for routine diagnostic TOEs in the echocardiography laboratory, the performance can be challenging. The patient is in a supine position and the working conditions for the echocardiographer can be difficult with the rotating C-arm and anaesthesiologic equipment needed for the procedure. Besides the technical aspects, the procedure time and therefore the time under TOE probe manipulation is prolonged, as compared to diagnostic TOEs which may lead to a higher incidence of AEs as for example mechanical lesions. Freitas-Ferraz et al.¹⁰ performed an oesophagogastroduodenoscopy before and after SHD intervention in order to investigate TOE-related mechanical lesions. They found a new injury in 86% (n = 43 of 50) of patients, with complex lesions in 40% (n = 20 of 50) of the cases. As a risk factor, they identified a longer time under TOE and a poor image quality. These data underline that lesions caused by TOE during SHD interventions are frequent and physicians should be aware of potential complications resulting from TOE.

Risk factors associated with TOE-related AEs

In our study, we found a lower haemoglobin and the presence of an OSAS to be associated with TOE-related AEs, even in the subgroup of patients undergoing PMVR or LAA closure. Preprocedural haemoglobin level has been shown to be associated with a higher midterm mortality in many cardiac procedures such as TAVR and with a higher risk for major adverse cerebrovascular events in patients undergoing percutaneous coronary intervention.^11,12 Furthermore, anaemia was associated with an unfavourable outcome in patients with cardiovascular diseases including heart failure,¹³ acute coronary syndrome¹⁴ and recently, to affect survival negatively in patients undergoing PMVR.¹⁵ A lower baseline haemoglobin level may be a marker for a comorbid condition as it can be found in nearly one-third of the patients with heart failure,¹⁶ in patients with renal failure or nutritional deficiencies. Patients with complications were older and presented with a significantly reduced renal function and a higher prevalence of anaemia reflecting a worse baseline condition. These patients are at high risk to develop TOE-related complications and should be monitored closely.

Furthermore, we found an OSAS to be associated with a TOE-related AE. The underlaying cause may be a weaker pulmonary function at baseline which may result in higher risk for AEs, especially with regard to pneumonia. Often, these patients are accompanied by a short and thick neck, the anatomy may increase the risk of micro-aspiration and pneumonia and the manipulation of the probe in this difficult airway may increase the risk of mechanical injuries.

Though all observed TOE-related AEs were regredient during hospital stay and no persistent damages or new onset of TOE-related symptoms were observed during follow-up, patients with AEs had a longer in-hospital stay. We observed a large standard deviation regarding total length of stay in hospital, especially in patients undergoing closure of LAA and PMVR. As these patients are high-risk patients and presented with the highest incidence of AEs, clinical course seems to be influenced by an AE and therefore vary within this patient groups.

Allocating the mortality to each type of procedure, 30-day mortality was comparable to those reported from previously published studies: For PMVR, 30-day mortality in our study was 3.8% and has been described with 1% in the early EVEREST II trial¹⁷ to 3.4% in the ACCESS-EU study¹⁸ and 4.5% in the TRAMI registry.¹⁹ Patients undergoing closure of LAA presented with a 30-day mortality of 2.2%, which was higher than reported in the AMULET registry (0.6%).²⁰ Two factors are most likely responsible for this slightly elevated number. First, a learning curve might be reflected in this mortality rate as patients from the beginning of our LAA occluder programme were included in this study. Second, the cohort consisted of multimorbid patients, presenting with multiple comorbidities and a mean logistic EuroScore of 18%. One patient in the ASD/PFO group died after discharge within 30 days due to a combined cardiogenic and septic shock. This patient had a severely reduced ejection fraction and was re-admitted with a haemodynamic relevant rhythm disturbance.

Perspectives

Clinicians have to be aware of potential AEs which accompany peri-interventional TOE in SHD interventions. Other imaging tools such as intracardiac echocardiography might be helpful in selected patients as there is less need for sedation and no probe has to be placed in the oesophagus. Moreover, novel imaging approaches such as the application of real-time fusion imaging technology that combines echocardiographic and fluoroscopic images, facilitating anatomical spatial orientation during complex SHD procedures may increase safety. This technology may have an impact on procedural parameters by reducing total procedure time, the amount of contrast agent, and radiation exposure.^21–25

Limitations

The study has several limitations. Firstly, it was a retrospective single-centre study. Data were obtained throughout a time of 6 years and a certain learning curve affecting procedural workflow cannot be excluded though the team was highly experienced. Secondly, due to the retrospective design, the number of AEs might be underestimated. Some events might not be recorded as they were self-limiting or felt not to be worth of mentioning in the medical report. Thirdly, the definition of a TOE-related AE is not well defined yet. To our best knowledge, we therefore assessed and characterized all possible TOE-related AEs from our clinical perspective. Furthermore, we observed 67 events but 11 variables were entered into the multivariate analysis Thus, our multivariate analysis might be overfitted and results regarding potential associations between risk factors and TOE-related AEs should be interpreted with caution.

Conclusion

TOE-related AEs during SHD interventions are clinically relevant affecting 5.3% of the patients. It was highest in patients undergoing PMVR. A lower baseline haemoglobin level and an OSAS were found to be associated with the occurrence of a TOE-related AE. Furthermore, a borderline significance was found for procedural time and the presence of oral anticoagulation in the multivariate regression analysis.

Funding

This work was supported by the Forschungskommission of the Medical Faculty of the Heinrich-Heine-University Duesseldorf with funding for Clinician Scientist Track (No 2019-15 to SA).

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

References

Author notes