Author + information
- Received October 23, 2017
- Revision received December 14, 2017
- Accepted December 19, 2017
- Published online March 19, 2018.
- Oliver Husser, MD, PhDa,∗ (, )
- Buntaro Fujita, MDb,
- Christian Hengstenberg, MDa,c,d,
- Christian Frerker, MDe,
- Andreas Beckmann, MDf,
- Helge Möllmann, MDg,
- Thomas Walther, MDh,
- Raffi Bekeredjian, MDi,
- Michael Böhm, MDj,
- Costanza Pellegrini, MDa,
- Sabine Bleiziffer, MDk,l,
- Rüdiger Lange, MDk,l,
- Friedrich Mohr, MDm,
- Christian W. Hamm, MDn,o,
- Timm Bauer, MDn,
- Stephan Ensminger, MDb,
- on behalf of the GARY Executive Board
- aKlinik für Herz-und Kreislauferkrankungen, Deutsches Herzzentrum München, Technical University Munich, Munich, Germany
- bDepartment for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Ruhr-University Bochum, Bad Oeynhausen, Germany
- cDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
- dDeutsches Zentrum für Herz- und Kreislauf-Forschung e.V. (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
- eDepartment of Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany
- fDeutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie, Berlin, Germany
- gDepartment of Cardiology, St. Johannes Hospital, Dortmund, Germany
- hDepartment of Cardiac Surgery, Kerckhoff Heart Center, Bad Nauheim, Germany
- iCenter for Internal Medicine, Heidelberg University Hospital, Heidelberg, Germany
- jKlinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
- kKlinik für Herz- und Gefäßchirurgie, Deutsches Herzzentrum München, Technical University Munich, Munich, Germany
- lInsure (Institute for Translational Cardiac Surgery), Department of Cardiovascular Surgery, German Heart Center Munich, Technische Universität München, Munich, Germany
- mLeipzig Heart Center, University of Leipzig, Leipzig, Germany
- nDepartment of Medical Clinic I, University of Giessen, Giessen, Germany
- oDepartment of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany
- ↵∗Address for correspondence:
PD Dr. med. Oliver Husser, Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technische Universität München, Lazarettstrasse 36, 80636 Munich, Germany.
Objectives The aims of this study were to report on the use of local anesthesia or conscious sedation (LACS) and general anesthesia in transcatheter aortic valve replacement and to analyze the impact on outcome.
Background Transcatheter aortic valve replacement can be performed in LACS or general anesthesia. Potential benefits of LACS, such as faster procedures and shorter hospital stays, need to be balanced with safety.
Methods A total of 16,543 patients from the German Aortic Valve Registry from 2011 to 2014 were analyzed, and propensity-matched analyses were performed to correct for potential selection bias.
Results LACS was used in 49% of patients (8,121 of 16,543). In hospital, LACS was associated with lower rates of low-output syndrome, respiratory failure, delirium, cardiopulmonary resuscitation, and death. There was no difference in paravalvular leakage (II+) between LACS and general anesthesia in the entire population (5% vs. 4.8%; p = 0.76) or in the matched population (3.9% vs. 4.9%, p = 0.13). The risk for prolonged intensive care unit stay (≥3 days) was significantly reduced with LACS (odds ratio: 0.82; 95% confidence interval [CI]: 0.73 to 0.92; p = 0.001). Thirty-day mortality was lower with LACS in the entire population (3.5% vs. 4.9%; hazard ratio [HR]: 0.72; 95% CI: 0.60 to 0.86; p < 0.001) and in the matched population (2.8% vs. 4.6%; HR: 0.6; 95% CI: 0.45 to 0.8; p < 0.001). However, no differences in 1-year mortality between both groups in the entire population (16.5% vs. 16.9%; HR: 0.93; 95% CI: 0.85 to 1.02; p = 0.140) and in the propensity-matched population (14.1% vs. 15.5%; HR: 0.90; 95% CI: 0.78 to 1.03; p = 0.130) were observed.
Conclusions Use of LACS in transcatheter aortic valve replacement is safe, with fewer post-procedural complications and lower early mortality, suggesting its broad application.
Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of severe symptomatic aortic valve stenosis and has recently been shown to be noninferior to conventional surgery in intermediate-risk patients (1). As a consequence, there is a considerable increment in TAVR procedures, with a projected annual case number of about 17,000 in Europe (2). Additionally, increasing operator and heart team experience, refinement of transcatheter heart valves (THVs), introducers, and delivery systems, and economic considerations have fostered interest in a simplification of the TAVR procedure.
In this regard, the possibility to perform TAVR only in local anesthesia or conscious sedation (LACS) instead of general anesthesia (GA) appears appealing. Compared with GA, LACS may be associated with logistic benefits of shorter procedure times and shorter intensive care unit (ICU) and in-hospital stays (3–5). However, these potential benefits need to be carefully weighed against patient safety, as increased risk for paravalvular leakage (PVL) and need for permanent pacemaker implantations (PPI) has been observed with LACS (5,6).
In the absence of randomized controlled data, registries offer an opportunity to investigate the value of each anesthesiologic strategy in TAVR. Therefore, we analyzed the use of each anesthesiologic strategy in a large population from the GARY (German Aortic Valve Registry), reporting and assessing the influence of LACS versus GA on early and midterm mortality. Apart from conventional multivariate adjustment, the impact of LACS versus GA was analyzed in a propensity-matched subset of patients to correct for an inherent selection bias and baseline differences.
The GARY is a nonprofit nationwide registry inaugurated in July 2010 by the German Society of Cardiology and the German Society of Thoracic and Cardiovascular Surgery. The aim of GARY is to collect data on a real-world and all-comer basis for short- and long-term outcomes and to provide information on current practices of treatment in patients undergoing the complete spectrum of interventional and surgical aortic valve interventions in Germany. The protocol of GARY has been previously described in detail (7). The responsible societies and the BQS Institute are independent organizations by virtue of their constitution both from legal and scientific points of view. GARY receives financial support in form of unrestricted grants from medical device companies (Edwards Lifesciences, Medtronic, Symetis, JenaValve Technology, Liva-Nova, St. Jude Medical, and Direct Flow Medical), the German Heart Foundation, the German Society of Cardiology, and the German Society of Thoracic and Cardiovascular Surgery, none of which have access to data or any influence on publications.
Study population and endpoints
All patients undergoing elective or urgent transfemoral TAVR in Germany from 2011 to 2014 were included in this analysis. Not included in the analysis were patients undergoing surgical aortic valve replacement, TAVR using nontransfemoral access treatment, or in an emergency or ultima-ratio setting. In total, 16,543 patients were analyzed and divided into 2 groups according to the primary anesthesiologic strategy used during the procedure (LACS, n = 8,121; GA, n = 8,422). Baseline parameters, procedural characteristics, and in-hospital outcomes were analyzed according to LACS versus GA. Endpoints of the present study were 30-day and 1-year mortality. Patients were followed during the first year after TAVR, and survival status was determined through direct telephone contact. Thirty-day survival status was available for all patients, and 1-year follow-up was complete for >97% of patients. Event-free patients were censored at last contact alive.
Continuous variables are expressed as mean ± SD or median (interquartile range) and were compared using the Student t test or the Mann-Whitney U test, respectively. Discrete variables were compared using the chi-square test.
The association of LACS versus GA with time to 30-day and 1-year mortality was assessed using Cox proportional hazard models. Hazard ratios (HRs) with their respective 95% confidence intervals (CIs) were computed. To test the independent influence of LACS on both outcomes, conventional multivariate adjustment for variables yielding p values <0.100 in univariate analyses was performed. Because of a likely influence of a learning curve or team experience on outcome, the year of treatment was included as a covariate. Additionally, to account for center experience, centers were categorized in quintiles according to cases performed per year.
To correct for potential selection bias in the use of anesthesiologic strategy, 2 approaches were used. First, a propensity score for the probability to undergo TAVR in LACS was calculated using multivariate regression analysis including variables associated with LACS in univariate analysis. This propensity score was included into the multivariate models. Second, 2 matched cohorts were created by means of propensity matching using R version 3.2.3 (R Foundation for Statistical Computing, Vienna, Austria) and the package MatchIt (8). In short, 1-to-1 nearest neighbor matching was used to identify 1 control patient treated with GA for each patient treated with LACS. To improve matching quality, the caliper was set at 0.0001, resulting in 2,624 matched cases per group. Baseline characteristics showing significant association with LACS and with 30-day mortality as well as the type of THV were included in the matching algorithm. Online Figure 1 summarizes the study flow and variables used for propensity matching.
All analyses were performed in the entire as well as in the propensity-matched population. A 2-sided p value of <0.05 was considered to indicate statistical significance for all analyses. SPSS version 19.0 (IBM, Armonk, New York) and R were used for analyses.
Temporal evolution, proportion of TAVR in LACS, and influence of center experience
In total, 16,543 patients were analyzed. The median age was 81 years, 56% were women, and the median Society of Thoracic Surgeons score was 4.8%. Overall, LACS was used as the primary anesthesiologic strategy in 49% of cases (8,121 of 16,543). From 2011 to 2013, the proportion of procedures performed in LACS decreased with increasing number of procedures and then remained stable at 46% (p for trend <0.001) (Figure 1A). There was an inverse relationship in the use of LACS with center experience, with 66% of patients undergoing TAVR in LACS at high-volume centers (>358 procedures per year) and 38% in the 2 lowest quintiles of center experience (p for trend <0.001) (Figure 1B).
Predictors of LACS and propensity matching
Table 1 shows the baseline characteristics of the entire patient population and according to LACS and GA. Independent predictors to undergo TAVR in LACS were younger age, lower Society of Thoracic Surgeons score and American Society of Anesthesiologists (ASA) class, presence of a permanent pacemaker, pulmonary hypertension, lower mean transaortic gradient, and year of procedure and increasing center experience (see Online Table 1 for complete results of multivariate analysis). Propensity matching resulted in 2 cohorts of 2,624 patients per anesthesiologic strategy. Online Figures 2A and 2B show the distribution of the propensity scores before and after matching, and differences in baseline characteristics between LACS versus GA disappeared after matching (Table 1).
Procedural results and complications
Procedural characteristics and in-hospital complications according to LACS versus GA are depicted in Table 2 for the entire and matched populations. The majority of cases was performed in an elective setting (85%). Balloon-expandable THVs were less frequently used with LACS in the entire population (40% vs. 63%; p < 0.001), but matching resulted in an equal distribution (55% vs. 54%; p = 0.450).
Overall, procedural success was achieved in 97.6%. Comparing LACS with GA in both the entire and the matched populations, procedural duration and fluoroscopy time were significantly shorter, conversion to sternotomy and bleeding complications were less frequent, and the rate of vascular complications was higher. After matching, the rate of device embolization and malposition was lower with LACS, and a difference in need for new pacemaker implantation observed in the entire population disappeared. There was no difference in PVL II+ between both groups in the entire (5% vs. 4.8%; p = 0.76) or in the matched population (3.9% vs. 4.9%; p = 0.13).
Post-procedural course was less complicated with LACS compared with GA. This was the case for both the entire and the matched population with a lower incidence of low-output syndrome, respiratory failure, post-operative delirium, cardiopulmonary resuscitation, and in-hospital death.
Duration of ICU and hospital stay was not different between both anesthesiologic strategies in the entire population analysis (Figure 2A). However, in the matched population analysis (Figure 2B), LACS was significantly associated with shorter ICU stays (higher proportion of cases with ≤1 day [38% vs. 34%, p = 0.003] and lower proportion of cases with ≥4 days [19% vs. 22%; p = 0.001]). The risk for prolonged ICU stay (≥3 days) was significantly reduced with LACS (odds ratio: 0.82; 95% CI: 0.73 to 0.92; p = 0.001).
30-day and 1-year mortality
Overall, 30-day and 1-year mortality was 4.2% (695 of 16,543) and 16.7% (2,761 of 16,543), respectively. Baseline characteristics associated with both outcomes were used for adjustment in the multivariate analysis (Online Tables 2 and 3). Figures 3A, 3B, and 4 show the rates and risk for mortality. Thirty-day mortality was significantly lower in patients undergoing TAVR in LACS compared with GA in both the entire (3.5% vs. 4.9%, p < 0.001) and the matched (2.8% vs. 4.6%; HR: 0.60; 95% CI: 0.45 to 0.80; p < 0.001) analysis. The unadjusted risk for 30-day mortality was significantly lower with LACS (HR: 0.71; 95% CI: 0.61 to 0.83; p < 0.001), an effect that persisted after multivariate and propensity score adjustment (odds ratio: 0.72; 95% CI: 0.60 to 0.86; p < 0.001). The mortality benefit observed at 30 days did not translate into a significant difference in 1-year mortality in the entire population (16.5% vs. 16.9%, p = 0.380; adjusted HR: 0.93; 95% CI: 0.85 to 1.02; p = 0.140) or in the propensity-matched population (14.1% vs. 15.5%; HR: 0.90; 95% CI: 0.78 to 1.03; p = 0.130) (Figures 3A, 3B, and 4).
Subgroup analyses of the differential effect of LACS versus GA on 30-day (Figure 5) and 1-year (Figure 6) mortality in the entire and matched populations were performed. When performing TAVR in LACS, a trend toward lower risk for 30-day mortality was observed in patients of older age, lower ASA class (<4), and pulmonary hypertension. No significant interaction for the effect of LACS versus GA on 30-day mortality was observed in case of conversion to sternotomy. For 1-year mortality, LACS was associated with a significant reduction in women and in patients with pulmonary hypertension (matched population only).
The use of LACS and GA during TAVR was analyzed in a large national registry. The results can be summarized as follows. First, almost one-half of TAVR procedures were performed in LACS, primarily at high-volume centers. Second, LACS was associated with faster procedure times, fewer procedural complications, and a more favorable post-procedural course. Third, 30-day mortality was lower with LACS, an effect that persisted after multivariate adjustment and propensity matching. This benefit appeared more pronounced in female patients and those with older age, lower ASA class, and pulmonary hypertension. Fourth, despite this risk reduction, 1-year survival did not differ, except for female patients.
Available data on LACS versus GA in TAVR
The number of TAVR procedures performed in LACS is rising (9). Increasing operator experience, reduction of device profiles, and use of percutaneous arterial closure systems led some groups to exclusively use LACS (10). Several studies (3,5,11–20) and a recent meta-analysis (6) investigated the impact of LACS versus GA in TAVR providing data on more than 5,000 patients to date. There are, however, several issues that may hamper the relevance and the scope of the available data. First, the majority of these studies were conducted in the early years of TAVR, and only 3 studies were conducted after 2012 (16,19,20). Thus, these reports may rather reflect the learning curve of the performing teams when switching from GA to LACS with increasing experience. Second, sample sizes of these previous studies were comparatively small, with only 4 studies including more than 250 patients (5,15,17,18). Third, only 3 studies addressed inherent patient selection bias using adequate statistical methods such as propensity matching (5,18,19). Therefore, the present study significantly adds to the body of evidence by including more than 16,000 patients up to 2014 and using propensity matching to address potential selection bias and the influence of a learning curve.
LACS versus GA: pros and cons
The implementation of LACS indicated an increased experience of the heart team performing the procedure and is often driven by potential benefits. These benefits include the possibility for periprocedural neurological assessment, less vasopressor use (12,19), shorter procedure times (12,14–16,19), and shorter ICU stays with earlier ambulation. Consistent with this observation, we detected a clear benefit of LACS, with faster procedures and a less complicated peri- and post-procedural course, persisting even after propensity matching. Especially encouraging is the observation of a significantly lower rate of low-output or psychological syndromes, which was reduced by almost 50% with LACS in the propensity-matched population. This overall less complicated post-procedural course may result in a significant reduction in health care expenses, as already suggested by a recent study (16). However, regarding the length of ICU and in-hospital stay, results of previous studies have not been univocal. Although some observed a reduction of the length of stay (3,12–16), others failed to show statistically significant differences (11,17–19,21) or even reported longer stays after TAVR in LACS (5,20). The present study shows that after propensity matching, LACS was associated with shorter ICU stays and a reduced risk for prolonged ICU stay. When looking to the overall in-hospital stay, these benefits were not observed. The median length of stay was 9 days in the present study. There are several factors that need to be taken into consideration when interpreting this observation. First, the study population includes patients treated between 2011 and 2014 and therefore may not entirely be comparable with contemporary patients referred for TAVR. Second, in Germany, if the actual length of stay falls below the diagnosis-related group–determined average length of stay, this difference is deducted from the total revenues obtained from a case, offering little stimulus to fall below the average length of stay. However, significantly shorter ICU stays with LACS observed in the present study support the notion of possible shorter hospital stays with LACS. In this regard, LACS is not inferior to GA, and future studies focusing on possible economic benefits of LACS with earlier discharge are warranted. These potential economic and logistic benefits of LACS in TAVR need to be well balanced by a similar safety profile compared with GA. Although most studies have shown similar procedural success rates with both strategies (5,12,14,16), one showed lower rates with LACS (15). The possible advantages of GA include less unrest of the patient and the additional option for respiratory hold and for minimal movement during implantation of the prosthesis. Indeed, unexpected patient movement (22) may have played a role in the observation of a higher permanent pacemaker rate due to misplacement of the THV (15,18) or a higher rate of major vascular complications (18) using LACS. The present study calls these findings into question. In the univariate analysis we found a significantly higher rate of PPI in the LACS group, after adjustment of THV type, we found no higher PPI rate in the matched population. Self-expanding THVs were more frequently used in patients undergoing LACS and are a known factor for PPI after TAVR. Therefore, our data indicate that the anesthesiologic strategy does not influence PPI rate, and rates of device malposition and embolization were even lower with LACS. However, our data confirm higher rates of vascular complications with LACS, indicating a potential influence of patient movement on the safety of vascular access and closure.
The integration of periprocedural imaging in form of transesophageal echocardiography to early recognize procedural complications as well as to evaluate the presence and degree of PVL (23) has been discussed as a potential argument in favor of GA. Indeed, the absence of intraprocedural transesophageal echocardiography may be the putative mechanism behind a higher incidence of PVL observed with LACS in several studies (5,18) and in a recent meta-analysis (6). Contrarily, in the present study we found no differences in PVL between the 2 anesthesiologic strategies, arguing against the need for routine transesophageal echocardiography during the procedure and against a higher incidence of PVL with LACS.
Finally, with respect to mortality, all studies consistently have shown comparable results for LACS versus GA in 30-day and long-term mortality. However, as most studies were performed in small populations or did not correct for baseline differences by propensity matching, potential mortality differences might have been overlooked. In the 2 largest observational studies to date, the Sentinel European TAVR Pilot Registry and the FRANCE-2 (French Aortic National CoreValve and Edwards-2) Registry (5,15), no difference regarding outcomes between LACS and GA were observed. In a propensity-matched analysis of 490 patients from the ADVANCE study, no difference in safety outcomes up to 2 years with LACS over GA was reported (18). In the present study, we observed a clear benefit of LACS in terms of 30-day mortality in the entire population of more than 16,000 patients. This benefit remained present even after rigorous correction for potential selection bias by means of conventional multivariate adjustment and propensity matching. Still, consistent with other studies (5,15,16,18), this early benefit did not translate into an advantage in 1-year survival.
Patient selection for LACS and GA
Analyzing data of more than 16,000 patients treated with TAVR in Germany during a time period of 4 years allowed us to further analyze the benefit of each anesthesiologic strategy in important subgroups of patients. Consistent to the entire population analysis, subgroup analyses also showed early mortality benefit with LACS but no midterm advantage in most subgroups. This observation likely reflects the high comorbidity burden in TAVR patients. However, it must be highlighted that benefits of LACS were more pronounced in women and patients of older age, lower ASA class and with pulmonary hypertension. Especially women derived benefit to undergo TAVR in LACS, with a significant decrease in risk for 1-year mortality. These findings, though necessitating confirmation in other studies, may guide further improvements in TAVR outcomes and guide the use of LACS.
Although propensity matching is an accepted approach to reduce selection bias in observational studies (24), we cannot exclude the influence of residual bias on our results. There is a wide range of anesthesiologic regimes that may be used in LACS or GA for TAVR with a potential influence on procedural outcome, and the present study does not account for these. In addition, conversion from LACS to GA is not routinely documented in GARY, but when excluding patients with conversion to sternotomy, the results remained unchanged (data not shown) and support the conclusions of our study. Finally, as the present study includes patients undergoing TAVR from 2011 to 2014, the impact of LACS on outcome as well as cost-effectiveness in contemporary cohorts, which include a higher proportion of lower risk patients, is a pending issue that will need to be addressed in the future, ideally in form of randomized comparisons.
The present study underlines the safety and efficacy of LACS in TAVR, with a less complicated post-procedural course and lower early mortality, and confirms logistic benefits justifying the broad application by experienced teams. Further randomized studies are warranted to determine the true value of LACS versus GA in TAVR.
WHAT IS KNOWN? TAVR can be performed in LACS or under GA. Potential benefits of LACS in the context of faster procedures and shorter hospital stays need to be evaluated with care.
WHAT IS NEW? In a large population of 16,543 patients included in the GARY the use and impact of LACS versus GA in TAVR were analyzed. LACS was associated with reduced post-procedural complications and lower early mortality, suggesting that its broader application in TAVR is safe.
WHAT IS NEXT? Additional randomized studies are warranted to further elucidate the value of LACS versus GA in TAVR.
This work was supported by unrestricted grants from medical device companies (Edwards Lifesciences, Medtronic, Symetis, JenaValve Technology, Liva-Nova, St. Jude Medical, and Direct Flow Medical), the German Heart Foundation, the German Society of Cardiology, and the German Society of Thoracic and Cardiovascular Surgery. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- American Society of Anesthesiologists
- confidence interval
- general anesthesia
- hazard ratio
- intensive care unit
- local anesthesia or conscious sedation
- paravalvular leakage
- permanent pacemaker implantation
- transcatheter aortic valve replacement
- transcatheter heart valve
- Received October 23, 2017.
- Revision received December 14, 2017.
- Accepted December 19, 2017.
- 2018 American College of Cardiology Foundation
- O’Sullivan K.E.,
- Bracken-Clarke D.,
- Segurado R.,
- et al.
- Oguri A.,
- Yamamoto M.,
- Mouillet G.,
- et al.
- Maas E.H.A.,
- Pieters B.M.A.,
- Van de Velde M.,
- Rex S.
- King G.,
- Imai K.,
- Stuart E.A.
- Durand E.,
- Borz B.,
- Godin M.,
- et al.
- Dehédin B.,
- Guinot P.-G.,
- Ibrahim H.,
- et al.
- Attizzani G.F.,
- Alkhalil A.,
- Padaliya B.,
- et al.
- D’Errigo P.,
- Ranucci M.,
- Covello R.D.,
- et al.
- Brecker S.J.D.,
- Bleiziffer S.,
- Bosmans J.,
- et al.
- Miles L.F.,
- Joshi K.R.,
- Ogilvie E.H.,
- et al.
- Hahn R.T.,
- Little S.H.,
- Monaghan M.J.,
- et al.
- Elze M.C.,
- Gregson J.,
- Baber U.,
- et al.