Evaluation of Effectiveness and Safety of Transcatheter Mitral Valve Repair Under Moderate Conscious Sedation

Ismail Ates, MD1; Sercan Okutucu, MD2; Gulcan Kose, MD1; Drew Hinson, MD3; Konstantinos Marmagkiolis, MD4; Cezar Iliescu, MD5; Mehmet Cilingiroglu, MD1,5

Ismail Ates, MD1; Sercan Okutucu, MD2; Gulcan Kose, MD1; Drew Hinson, MD3; Konstantinos Marmagkiolis, MD4; Cezar Iliescu, MD5; Mehmet Cilingiroglu, MD1,5

Abstract: Background. Transcatheter mitral valve repair (TMVR) using the MitraClip system (Abbott Vascular) has become a world-wide, well-established therapeutic alternative to symptomatic patients with severe mitral regurgitation (MR) and prohibitive surgical risk. Currently, TMVRs are performed under general anesthesia. Herein, we aimed to present the effectiveness and safety of TMVR under moderate conscious sedation (MCS). Methods. A total of 102 patients with severe MR (49 primary MRs and 53 secondary MRs) who underwent TMVR with MCS between December 2018 and December 2019 were included. We prospectively evaluated clinical and procedural outcomes using medical records of these patients. Results. Among all the patients, the mean age was 81.6 ± 3.5 years, 60 (59%) were women, and 72.7% had coronary artery disease. The mean left ventricular ejection fraction was 47.9 ± 12.7%, while the MR grade was 3+ in 18.2% of the patients and 4+ in 81.8%. A mean of 1.2 ± 0.4 clips (range, 1-2 clips) were implanted per patient. Postprocedural MR grade was 1+ or lower in 64 patients (63.6%) and 2+ in 38 patients (36.4%). Procedural duration, clip implant time, and fluoroscopy times were 60 ± 10.5 minutes, 19.5 ± 8.0 minutes, and 10.1  ±  2.1 minutes, respectively. The median required dosage of propofol was 140 mg (interquartile range, 84-156 mg). No complications arose from MCS. There was no need for conversion to general anesthesia in any of these patients during the procedure. Conclusions. TMVR can be performed safely and effectively under moderate conscious sedation. Applying moderate conscious sedation may simplify the TMVR procedure and reduce procedural time and costs, while increasing overall patient satisfaction. 

J INVASIVE CARDIOL 2020;32(6):206-210.

Key words: anesthesia, conscious sedation, MitraClip, mitral repair, transcatheter


Mitral regurgitation (MR) remains a common valvular disease worldwide and it increases with age. The MitraClip (Abbott Vascular) is a transcatheter mitral valve repair (TMVR) device that has been successfully used in high-risk surgical patients.1,2 MitraClip reduces the severity of MR by percutaneous approximation of the anterior and posterior mitral valve leaflets, leading to a double-orifice valve similar to the Alfieri stitch technique.3-5 Since its Conformité Européene (CE) mark approval in 2008, United States Food and Drug Administration (FDA) approval in 2013, and the results of the COAPT trial in 2018,6 the overall implantation volume has significantly increased, making MitraClip the leading percutaneous device for selected high surgical risk patients with severe MR.

Most TMVR procedures have been traditionally performed under general anesthesia (GA), whereas other percutaneous interventional approaches to treat valve diseases, such as transcatheter aortic valve replacement, are increasingly performed under moderate conscious sedation (MCS) — the so-called “monitored anesthesia care” (MAC) — or deep sedation (DS).7,8 Transesophageal echocardiography (TEE) is an essential imaging technique to guide TMVR, and the main reason for GA requirement.9-11 GA is easily and rapidly administered, with the advantages of complete airway control, patient immobility, operator comfort, analgesia, amnesia, and ability to breath-hold.10,12 However, GA increases the overall procedure complexity, time, costs, and possible major complications.9,12 Furthermore, GA is associated with a mortality risk of 0.03 deaths per 1000 patients.13 There is scarce knowledge about the feasibility and safety of MCS in TMVR procedures and no reported experience in the United States.9,10,14 Herein, we aim to present the effectiveness, procedural characteristics, and safety of TMVR under MCS.

Methods

Study population and preprocedural evaluation. A total of 102 patients with severe MR (49 with primary MR and 53 with secondary MR) who underwent TMVR with MAC between December 2018 and December 2019 were studied prospectively. We evaluated clinical and procedural outcomes using medical records. Before the TMVR procedure, each patient was assessed and judged unsuitable for a surgical approach by an interdisciplinary heart team of cardiologists, cardiothoracic surgeons, and cardiac anesthesiologists. Decisions were based on Society of Thoracic Surgeons (STS) score. MV surgery was deemed unsuitable if STS score for the risk of death within 30 days after mitral valve replacement was 8% or higher or in the presence of poor prognostic features that were not included in the STS score (frailty, cancer, autoimmune conditions, etc). All patients gave informed consent to undergo the procedure, and the authors have conformed to institutional guidelines for the study.

Preprocedural evaluation standards consisted of transthoracic echocardiography and TEE to determine the grade and etiology of the MR, the left ventricular ejection fraction (LVEF), effective regurgitant orifice area (EROA), and the anatomy of the MV and MR jet locations. Primary MR, defined as the pathology of ≥1 of the components of the valve (leaflets, chordae tendineae, papillary muscles, annulus), causes valve incompetence with systolic regurgitation of blood from the left ventricle to the left atrium. Secondary MR was defined as MR due to primary left ventricular dysfunction with normal mitral valve leaflets and chordae. In addition to clinical assessment, a full laboratory work-up and electrocardiography were obtained.

TMVR procedure. The MitraClip procedure was performed under MCS (or MAC) in all patients with fluoroscopic and TEE guidance. Left atrial pressure was invasively measured and recorded before and after MitraClip implantation in all patients. The selection of the type of device (NTR or XTR) and number of clips was left at the discretion of the interventionist upon preprocedural review of the MV morphology and width of the MR jet. Procedural time, clip implant time, and fluoroscopy time were calculated. Procedural time was defined as the time from the insertion to the removal of the steerable guiding catheter. Clip implant time was defined as the time from transseptal puncture to the clip delivery. Procedural success was defined as at least 2 grade reductions in MR jet.

Conscious sedation protocol. MCS (or MAC) is a drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation.15,16 DS is a drug-induced depression of consciousness during which patients cannot be easily aroused, but respond purposefully following repeated or painful stimulation. The ability to independently maintain ventilatory function may be impaired in DS.15,17 

All patients are seen and screened for best mode of anesthesia and airway protection by both structural heart disease interventionist as well as anesthesiologist on the day of the procedure. The Mallampati score was obtained during the physical examination of each patient. The score was assessed by asking the patient to open his or her mouth as wide as possible, while protruding the tongue as far as possible. The patient was instructed to not emit sounds during the assessment. A standard I to IV grading system was used: class I = soft palate and entire uvula visible; class II = soft palate and portion of uvula visible; class III = soft palate visible (may include base of uvula); and class IV = soft palate not visible.18 Patients with class IV scores were not deemed to be suitable for TMVR under MCS. 

All equipment needed for intubation (laryngoscope including a working battery/light, endotracheal tube of the appropriate sizes, stylet), oropharyngeal airway, suction, medications, and reversal agents (flumazenil, naloxone) were supplied. Etomidate was readily available in case of emergent intubation. A certified registered nurse anesthetist (CRNA) and a nurse were available during the entire procedure. The CRNA and nurse were experienced with patient communication and sedative medication administration during TEE and/or catheterization laboratory procedures. Essentially, the procedure was guided by TEE and fluoroscopy. All patients fasted for at least 8 hours before the procedure. All patients were treated with preoperative glycopyrrolate and acetaminophen. Local anesthesia of the groin prior to access was performed with prilocaine. Midazolam was administered for anxiolysis/sedation in some cases. Topical anesthetic spray was applied up to 6 puffs before TEE. After an initial bolus of propofol, TEE was inserted via the face mask (Figure 1). 

Propofol infusion was maintained throughout the TMVR. Arterial blood pressure and oxygen saturation were continuously monitored. The MCS protocol for TMVR is summarized in Table 1.

Statistical analysis. This was a prospective, descriptive study and statistical analyses were performed using SPSS 23 for Windows (SPSS). Distribution of data was assessed by using a one-sample Kolmogorov-Smirnov test. Data are presented as mean ± standard deviation for normally distributed continuous variables, median with interquartile range (IQR) for skew-distributed continuous variables, and frequencies for categorical variables. 

Results

All 102 patients (49 with primary severe MR and 53 with secondary severe MR) underwent TMVR under MCS, with an acute procedural success rate of 100%. Mean age was 81.6 ± 3.5 years, 60 (59.0%) were women, and 72.7% had coronary artery disease. The mean left ventricular ejection fraction was 47.9 ± 12.7%. MR grade was 3+ in 18.2% and 4+ in 81.8% of the patients. Baseline clinical and demographic features of the study population are presented in Table 2.

A mean of 1.2 ± 0.4 clips were implanted per patient (range, 1-2 clips). Postprocedural MR grade was 1+ or lower in 64 patients (63.6%) and 2+ in 38 patients (36.4%). Procedural duration, clip implant time, and fluoroscopic time were 60  ± 10.5 minutes, 19.5 ± 8.0 minutes, and 10.1 ± 2.1 minutes, respectively. The median required dosage of propofol was 140 mg (IQR, 84-156 mg). No complications arose from MCS. There was no need for conversion from MCS to GA in any of the patients during the procedure. Procedural data, outcomes, and complications are shown in Table 3.

Discussion 

Technological advances within the last decade have made TMVR increasingly feasible and safe in clinical practice.1,9 TMVR in patients with severe MR has successfully reduced mortality, patient symptoms, and disease morbidity, improved quality of life, and facilitated reverse LV remodeling. Recent randomized controlled trials on MitraClip use in secondary MR have reinvigorated interest in this disease.6,19 TMVR with the MitraClip system requires comprehensive TEE guidance throughout the MitraClip procedure to achieve exact positioning of the clip.11,20,21 Thus, TMVR procedures are commonly performed under GA because of the prolonged TEE duration.9,10,22 Furthermore, breath-holding and ventilation maneuvers can facilitate TMVR in patients with challenging MV anatomies.23 However, GA is associated with disadvantages, including perioperative hypotension, catecholamine induced cardiotoxicity, oropharyngeal and tracheal injury, pneumonia, difficulty in weaning, risk of ancillary procedures (eg, radial line placement), more challenging esophageal intubation for TEE, higher likelihood of oropharyngeal or esophageal injury, cost and interruption of work-flow, delay in identification of serious problems, and neurological complications.12,24 It has been demonstrated that perioperative hypotension and duration of anesthesia (deep hypnotic time) are predictors for complications and prolonged hospital stay.25

Recent studies revealed that DS might be an alternative to GA in TMVR.9,10 Horn et al9 investigated whether the MitraClip procedure could be performed safely using DS without GA. They analyzed 232 MitraClip procedures (76 procedures with GA, 156 procedures with DS). The primary combined safety endpoint was defined as the occurrence of major adverse cardiac and cerebrovascular events, conversion to surgery, major vascular complications, or pneumonia, and did not differ between the GA and DS groups. Intraprocedural conversion to GA was required in 2% of the patients in the DS group. There were no differences in procedural success rates or clinical outcomes between the groups at 3-month follow-up. Catheterization laboratory prep time and intensive care unit stay were shorter in the DS group than in the GA group.9 

In another study, Patzelt et al10 compared patients undergoing TMVR with GA or DS. They observed that propofol and norepinephrine doses were significantly lower in the DS group, while procedure time, fluoroscopy time, and dose area product were significantly higher in the GA group. There was no significant difference between the GA and DS groups with respect to overall bleeding complications, postinterventional pneumonia, or C-reactive protein levels. Significantly fewer patients with DS needed a postinterventional stay in the intensive care unit. Importantly, there was no significant difference between DS and GA regarding intra-hospital or 6-month mortality.10 

To the best of our knowledge, this is the first study to date in United States to compare CS with GA in TMVR patients. In contrast to other TMVR studies, our study applied MCS, which is a lighter sedation than DS. We structured a well-designed and easily applicable MCS protocol for TMVR. Our data reveal that MCS for TMVR is safe and feasible. No disadvantages with respect to procedural outcome or complications were observed. Although fluoroscopy time is similar in our study with the results of Patzelt et al,10 procedural duration time was significantly shorter than the previous two reports (Figure 2).9,10 In our cost analysis, we were able to save about $6,875.00 per patient undergoing MitraClip procedure, as these patients were extubated right in the cardiac catheterization laboratory instead of in the postanesthesia care unit and went directly to regular telemetry unit for observation. 

Study limitations. Our study had a limited number of patients. We did not compare results with GA or DS. We addressed only the MitraClip system, and our findings in patients with MCS cannot necessarily be transferred to other TMVR systems. Finally, sedation is a continuum and it is not always possible to predict how an individual patient will respond. Hence, practitioners intending to produce a given level of sedation should be able to rescue patients whose level of sedation becomes deeper than initially intended. Individuals administering MCS should be able to rescue patients who enter a state of DS, while those administering DS should be able to rescue patients who enter a state of GA.

Conclusion

TMVR can be performed safely and effectively under MCS. Applying MCS may simplify the TMVR procedure while resulting in shorter procedural times, increased patient satisfaction, and overall procedural cost reductions. A structural heart disease team approach that includes the anesthesiology specialists should be applied, with the focus on the patient. This will lead to increased patient comfort, reduced cost, reduced morbidity, and more streamlined patient flow in the cardiac catheterization laboratory. Further large-scale, randomized controlled studies are needed to confirm these initial findings regarding MCS for TMVR. 


From 1Bahcesehir University, School of Medicine, Istanbul, Turkey; 2Memorial Ankara Hospital, Department of Cardiology, Ankara, Turkey; 3Arkansas Heart Hospital, Little Rock, Arkansas; 4HCA Northside Hospital, St. Petersburg, Florida; and 5UT Houston, MD Anderson Cancer Center, Houston, Texas.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted January 1, 2020, final version accepted January 14, 2020.

Address for correspondence: Mehmet Cilingiroglu, MD, FSCAI, FACC, FESC, FAHA, Professor of Medicine and Biomedical Engineering, 11800 Carmel Creek Road, San Diego, CA 92130. Email: cilingiroglumehmet@gmail.com

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