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State of Transcatheter Aortic Valve Implantation in Spain Versus Europe and Non-European Countries
Abstract: Background. Transcatheter aortic valve implantation (TAVI) is now the standard treatment for severe aortic stenosis in high-risk symptomatic patients, and its indications are expanding to lower-risk patients. Objectives. The objective of this study was to analyze the state of TAVI in Spain vs other European and non-European countries. Methods. Using an online questionnaire, we analyzed the routine practice of 250 TAVI centers worldwide. The questionnaire included 59 questions on patient selection, technical aspects of the procedure, and postprocedural management. The centers were divided into Spain (n = 41), rest of Europe (n = 105), and rest of the world (n = 104). Results. The cumulative number of procedures (74; range, 40-122) and those performed in the last year (16.5; range, 15-29.5) in Spain, were significantly lower than the rest of Europe (P<.01) and the rest of the world (P<.01). The patient risk profile was higher, with an under-use of functional tests compared to the rest of the world. While the use of computed tomography to analyze the aortic annulus was lower in Spain (P<.001), general anesthesia and transesophageal echocardiography were more frequently used in Spain than in the rest of Europe (P<.001 for both). Dual-antiplatelet therapy is the most common post-TAVI antithrombotic therapy in the absence of an indication for anticoagulation, although its duration is longer in Spain (6 months) compared to European centers (3 months). Conclusions. Routine TAVI practice in Spain differed in some key aspects of preprocedural, intraprocedural, and postprocedural management. Future studies will help to unify strategies and assess their impact on clinical results.
J INVASIVE CARDIOL 2018;30(8):301-309.
Key words: TAVI, TAVR, aortic valve disease, transcatheter valve implantation, Spain, Europe, Survey
The emergence of transcatheter aortic valve implantation (TAVI) for the treatment of aortic stenosis is one of the greatest revolutions in the field of interventional cardiology. Currently, TAVI has established itself as the optimal treatment for severe aortic stenosis in inoperable or high-risk symptomatic patients.1,2 Following the results of recent randomized trials demonstrating the non-inferiority of TAVI3-5 and even superiority of transfemoral access over surgical valve replacement in intermediate-risk patients,6 expansion to lower-risk patients has begun. However, despite the significant advances, this technique remains in a relatively early stage, and there are some controversial aspects where there is no consensus or clearly established evidence.
Despite the annual increase in TAVI implants in Spain (1324, 1586, and 2026 in 2014, 2015, and 2016, respectively),7 the use of this technique is low compared to the rest of Europe. The European average is 83 implants per million inhabitants, with 227 in Germany and 137 in France, compared to 42 implants per million inhabitants in Spain. To obtain an overview of the TAVI practice, a global survey was designed. The Worldwide TAVI experience survey (Written) allowed us to evaluate three fundamental aspects: pre-TAVI patient selection and assessment; technical aspects of the procedure; and postprocedural management.8 The objective of this substudy was to analyze the state of TAVI in Spain in relation to the other centers in Europe and the world.
Methods
This survey was designed with the purpose of analyzing the characteristics of TAVI worldwide. The survey was developed on an online platform (www.cardiogroup.org/TAVI/) and included 59 questions.8 The questionnaire evaluates aspects of contemporary practice: (1) general characteristics of the TAVI program; (2) patient selection; (3) preimplant preparation, eg, imaging tests, pharmacological treatment; (4) characteristics of the technique and imaging during the procedure; (5) postimplant management; and (6) clinical follow-up.
During a 6-month period (March 2015 to September 2015), centers with a TAVI program were invited to participate, including at least one expert from each country or region of the world. Participation in the survey was promoted through emails to TAVI operators and was advertised by interventional cardiology societies (www.TCTMD.com, www.hemodinamica.com). There were no restrictions on the number of procedures performed per year by each center, the date of initiation of the TAVI program, or type of hospital. The overall results were previously published.8 For this substudy, the centers were divided into three groups – centers in Spain, centers in the rest of Europe, and centers in the rest of the world – and comparative analyses were performed.
Statistic analysis. Categorical variables are presented as numbers and percentages and continuous variables as mean and standard deviation or median and interquartile range (25th-75th percentiles), according to their distribution. The normal distribution was evaluated with the Shapiro-Wilks test. Qualitative variables were compared with the Chi-square test or Fisher’s exact test, the qualitative variables with normal distribution using Student’s T-test, and the non-normal with the Wilcoxon test. A P-value <.05 was considered significant. Analyses were performed using the statistical package Stata 14.0 (StatCorp).
Results
A total of 296 questionnaires were received from the website, and 46 (15.5%) were excluded (32 empty questionnaires, 12 incomplete questionnaires, and 2 duplicates). Finally 250 centers were included, of which 41 (16.4%) were Spanish, 105 (42.0%) were from the rest of Europe, and 104 (41.6%) were from countries outside Europe (49% from the United States). The names, cities, and countries of the participating centers are shown in Supplemental Table S1 (see end of Results section). In Spain, the number of implants per center, cumulative number of implants, and implants in the last year were significantly lower than in European centers and the rest of the world (Table 1).
Preprocedure evaluation. The mean number of monthly heart team meetings in Spain, Europe, and the rest of the world were similar (3.1 ± 2.3 vs 4.5 ± 4.9 [P=.09] vs 3.0 ± 1.8 [P=.80], respectively). The heart team comprised mainly interventional cardiologists (Spain, 97.5%; Europe, 99.1%; rest of the world, 99.0%) and cardiac surgeons (Spain, 95.0%; Europe, 99.1%; rest of the world, 97.0%). Inclusion of anesthesiologists, internists, or geriatricians was significantly lower in Spain than in Europe (anesthesiologists, 20.0% vs 53.3% [P<.001]; internists or geriatricians, 5.0% vs 17.4% [P=.058]). The use of surgical risk scores was similar in Spain vs the rest of Europe (61.0% and 53.7% of Spanish centers used the logistic EuroSCORE and STS score, compared to 52.4% and 54.3% of European centers [P=.35 and P=.95, respectively]). However, STS score was more widespread in the rest of the world (96.2%; P<.001), with EuroSCOREs less commonly used (22.1%; P<.001). The percentage of patients with surgical contraindications was significantly higher in Spain than in Europe and the world, while high-risk, intermediate-risk, and low-risk patients were more frequent in centers outside Spain (Figure 1). Fragility scores and 6-minute walk tests were more widespread outside Spain (Figure 2). Preprocedural cardiac computed tomography aortic annulus assessment was performed less frequently in Spain than in Europe or the rest of the world, with a transesophageal echocardiogram (TEE) rate of almost 27% in Spanish centers. There were no differences in pretreatment with antiplatelet agents, antibiotic prophylaxis, or the timing of revascularization in patients with significant coronary disease.
Periprocedural management. Tables 2 and 3 show the technical characteristics of the implant, approaches and vascular closure, type of anesthesia, and use of preimplantation valvuloplasty. With the transfemoral approach, the use of general anesthesia was significantly higher in Spanish (100% [IQR, 60%-100%]) and non-European institutions (100% [IQR, 50%-100%]) compared to Europe (25% [IQR, 5%-93%]; P<.001) (Figure 3A). Furthermore, the routine use of TEE during the procedure was significantly higher in Spain and the rest of the world compared to Europe (61.0% vs 65.4% vs 19.6%, respectively) (Figure 3B). Embolic protection devices were used selectively in 17.7% of cases in Europe and 14.4% of cases in the rest of the world, whereas they were not used in Spanish centers at the time of the survey. Finally, the immediate assessment of post-TAVI aortic regurgitation (AR) was similar at all centers, using aortography and hemodynamic evaluation. In cases of discrepancy, TEE was used less often in European centers than in Spanish centers or in the rest of the world (Table 2).
Postprocedural management. Post-TAVI management is shown in Table 4. There were no differences in the duration of telemetry monitoring or use of temporary pacing wires in Spain vs the non-Spanish centers. In patients who developed a complete left bundle-branch block, additional investigations were uncommon in Spanish centers, both with expandable balloon valves (10.7%) and with self-expanding valves (8.0%). Centers in Europe and the rest of the world had higher rates of direct pacemaker implantation. Antiplatelet therapy at hospital discharge was assessed according to the need for anticoagulation for other causes (Figure 4). Without an indication for anticoagulation, the most frequent antithrombotic treatment in Spain and in non-European centers was dual-antiplatelet therapy (DAPT) for 6 months, while 3 months of DAPT was more common in Europe (P=.04). In patients with indications for anticoagulation, 42.1% of the Spanish centers did not add any antiplatelet therapy (compared to 17.9% of non-Europeans) and 57.9% combined anticoagulation and antiplatelet therapy. Although triple therapy was uncommon (10.5%) in Spanish centers, the rate was higher than the other groups.
Supplemental Table 1
Discussion
The results of this survey on the real-world implantation of TAVI showed differences in key aspects between Spanish centers and the rest of Europe and the world. The main findings were: (1) the number of TAVIs per center is significantly lower in Spain with a higher risk profile; (2) the use of 6-minute walk tests and fragility scores is significantly lower than in non-Spanish centers; (3) the general anesthesia strategy and the TEE-guided procedure remain most common in Spain; and (4) there is significant variability in the type and duration of post-TAVI antithrombotic therapy at a global level, with Spanish centers maintaining DAPT for longer than European centers.
Preprocedure evaluation. Disparate use of different technologies in Europe has been previously described.9-12 Spanish centers have a significantly lower annual volume and cumulative experience than the rest of Europe, which could be explained by several factors. First, the number of annual TAVI implants per million population is significantly lower compared to the European average.12 Second, the relative number of TAVI centers is considerably higher than in the majority of European countries. In 2016, there were 66 centers (17% without on-site surgery) performing this procedure, for a total national volume of 2026 TAVI procedures (mean of 31 procedures/center).7 For example, some regions in Spain with a catchment area of 6 million people had 10 public centers performing TAVI. In contrast, in France, a total of 4293 TAVIs were performed in 2015 in 48 centers (mean of 89 procedures/center).13 Thus, this relatively low number of procedures/center with their own learning curves could preclude the rapid development of TAVI across Spain and other countries with similar geographical TAVI distribution and economic factors. Third, the economy and health policies, such as health-care funding and TAVI reimbursement, are also critical factors in determining this low TAVI penetration. In Spain, healthcare is primarily funded by taxation and TAVI costs come from the hospital budget with no additional reimbursement; this has been previously related to a lower adoption of novel health technologies.12
Preprocedural assessment and patient selection are key determinants for obtaining good results. In this regard, clinical practice guidelines14 recommend the formation of a multidisciplinary heart team, which allows the discussion of the indication, type of approach, and potential risks of aortic valve implantation based on the results of randomized trials1-6 and recommendations of the Valve Academic Research Consortium-2.15 This survey shows that heart teams in Spanish centers are comprised of mostly clinical cardiologists, interventional cardiologists, and cardiac surgeons. Compared to non-Spanish centers, relatively few other specialists participate in heart team discussions. Internists, geriatricians, and anesthesiologists are fundamental for risk assessment in complex cases. Moreover, their participation and input in the clinical decision-making process could confer a direct and easier way to refer patients for TAVI, as well as ensure that the referral physicians have a more detailed knowledge of TAVI techniques, advantages, and complications.
The TAVI patient profile continues to be mostly high risk in Spain, which is a different scenario than the rest of Europe and the world, where the percentage of intermediate-risk or low-risk patients is significantly higher. Potential explanations for this situation could be economic restrictions that limit the number of valves implanted in addition to the relatively high number of centers performing TAVI. Also, the low participation of cardiac surgeons in TAVI programs may represent another point of resistance for TAVI penetration. These factors may cause a selection bias toward higher-risk patients as well as explain why the technique is in an earlier stage in Spain compared to other European centers. Although classic surgical scores provide information on the individual risk of each patient, they have many limitations in the adequate evaluation of these risks. In an attempt to avoid poor functional outcomes and predict those patients who will benefit least from the intervention, the preprocedural functional assessment and quality of life of patients have become increasingly relevant.16 High-risk patients undergoing TAVI in Spain would likely benefit greatly from preprocedural functional evaluations in order to avoid futile procedures, yet these tests are used less frequently in Spain. Fewer clinical resources dedicated to this aspect of the procedure and less involvement in research protocols may partly explain the under-use of these tests in Spain. Computed tomography has an undisputed role as the most important imaging tool in preprocedure assessment for both aortic annulus evaluation and assessment of the remainder of the vasculature.17 Despite this, it is noteworthy that in Spain, computed tomography imaging is less prevalent compared to the rest of Europe or the world. This may be due to increased confidence with the older technique (TEE), logistical issues in carrying out the study, such as accessibility and waiting time for the test, or reduced participation of radiologists and/or imaging cardiologists in the decision-making process.
Periprocedural management. The use of the femoral approach as the predominant access site, at least when technically possible, appears to be widely accepted. The reduced profile of the delivery systems and better clinical results compared to other access sites18,19 have increased transfemoral use and it is currently used in 90% of patients undergoing TAVI. In this regard, the natural evolution of the technique is to adopt a less invasive approach,20 and the use of general anesthesia and TEE guidance is compared with sedation and local anesthesia. There is a lack of consensus regarding the type of anesthesia, with significant variability between centers. The conventional approach with general anesthesia and TEE guidance was the most common approach in Spain (65% of the centers in all the procedures). This probably relates to the lower experience level at individual centers and treatment of higher-risk patients with increased risks of complications, where it may be felt that potential complications would be resolved quicker in already anesthetized patients under TEE guidance. However, several studies have demonstrated the feasibility of the minimalist approach21,22 with similar results. This approach allows early hospital discharge with a low rate of rehospitalizations at 30 days in selected patients.23 Physicians training in the minimalist approach at experienced centers may help to expand this approach to other centers less familiar with it. In addition, standardization of the technique as a routine practice and inclusion of a specific anesthesia team in TAVI procedures could help to implement the minimalist approach.
Residual greater than mild AR is associated with an increase in long-term mortality, and although its incidence has decreased with the new generations of valves, it continues to be more than observed with surgery.6 Postprocedure quantification of AR remains a challenge. The combination of imaging and hemodynamic evaluation techniques is likely the most appropriate approach in patients with significant residual AR. TEE is the investigation that provides the most information about the origin and severity of AR. However, systematic use of TEE can compromise the minimalist approach, with one option being to have it available in case of complications or if a more accurate assessment of AR is required. Post-TAVI stroke remains a relatively frequent complication (~3%-4%), with important prognostic implications.24 In order to prevent early stroke and silent emboli during implantation, embolic protection devices have been developed. Randomized studies have shown a reduction in the number and volume of new cerebral lesions, with insufficient power to determine an impact in clinical events, although recent meta-analyses would indicate some benefit in the combined reduction of stroke and mortality.25 However, the use of embolic protection devices was confined to selected cases of high stroke risk in non-Spanish centers and there was no experience in Spain. The prevention of stroke continues to be complex and multifactorial;26 therefore, future studies focused on the technical aspects of the procedure, as well as the subsequent antithrombotic treatment, should demonstrate their effectiveness in reducing this serious complication.
Postprocedure management and follow-up. Other aspects that are increasingly important with the expansion of TAVI to lower-risk patients include the occurrence of arrhythmias and conduction disorders. To date, there are no clear guidelines for the treatment of these conditions. In this survey, the duration of post-TAVI telemetry and temporary pacemaker is highly variable depending on the type of valve and from center to center, both European and in the rest of the world. The occurrence of atrial arrhythmias and atrioventricular block has important clinical implications, and therefore continuous monitoring during hospitalization (or at least during the first 72 hours) is recommended.15 Despite this, the results of this survey show that up to 22.5% and 35% of Spanish centers discontinue monitoring in the first 24 hours and 48 hours, respectively. The optimal removal of the temporary pacemaker is not clearly defined, and jugular access may be optimal for early mobilization, especially with self-expanding valves in which immediate withdrawal seems to be less frequent. Finally, the development of a new left bundle-branch block is a complication that may have different prognostic implications, such as a higher rate of sudden death, a need for definitive pacemaker implantation, or a negative impact on ejection fraction.27,28 According to our survey, 90% of Spanish centers take a conservative approach to this complication, not employing additional measures (electrophysiological studies or implantation of devices). Although no strategy has been prospectively validated, when a more conservative strategy is adopted, these patients should probably have more intensive clinical and electrocardiographic follow-up. Future studies, such as the implantation of a loop recorder (NCT02153307), will provide more evidence on the evolution and management of these patients.
Postprocedure antithrombotic therapy (type and duration) is one of the areas in which there are currently several ongoing studies. This survey seems to indicate that Spanish centers adopted a more aggressive antithrombotic treatment with a longer duration of DAPT in patients without atrial fibrillation, probably reflecting the treatment empirically recommended earlier in the TAVI era. In the absence of definitive evidence, the potential benefit of single-antiplatelet therapy in terms of bleeding complications vs DAPT after TAVI was recently reported in the ARTE trial29 and has to be confirmed in larger ongoing randomized trials (NCT02247128). In contrast, and supported by previous trials in surgical valves, there are other clinical trials (NCT02556203; NCT02664649) adopting a more aggressive antithrombotic therapy strategy, prescribing anticoagulation during the first 3 months. In patients with atrial fibrillation, the results are even more disparate, with half of the centers opting for anticoagulation alone and the other half adding an antiplatelet agent (aspirin or clopidogrel) to anticoagulation. Several ongoing studies will help determine the best therapeutic option.
Study limitations. This is a voluntary observational study; therefore, data were not audited. However, given the extensive participation, the data can be considered representative of normal real-world practices. This survey was carried out in a specific timeframe, and given the rapid evolution of TAVI techniques and the advances in scientific evidence, its results should be put into perspective in the timeframe in which it was performed.
Conclusion
This survey provided extensive data on standard TAVI practice in Spain compared to Europe and non-European countries. This allowed us to identify differences in some key aspects of preprocedural, periprocedural, and postprocedural management, which could help interventionists adopt new approaches. Primarily, this study showed that the implant rate in Spain was lower than in other centers; however, the Spanish patient population has a higher risk profile. In regard to preprocedural management, the participation of non-cardiologists in the heart team and the use of functional tests occurred significantly less frequently than in non-Spanish centers. In addition, Spanish centers continued to employ general anesthesia and a TEE-guided strategy, while the minimalist approach had more prominence in Europe. Differences observed in the postprocedure management of conduction disorders and antithrombotic therapy highlight the need for future studies to help determine optimal management and improve outcomes. The identification of differences in TAVI practice is relevant to generate discussion and initiatives to develop new approaches with better outcomes, principally through further clinical and experimental studies. Moreover, regional differences in TAVI diffusion are likely to be related to economic, political, regulatory, and cultural circumstances. These results could be of interest to health-care professionals, regulatory authorities, and health-care payers in Spain and similar countries in order to improve resource allocation and to promote program development that guarantees optimal physician training, adequate number of TAVI procedures/center, and continuous improvement of all aspects related to preprocedural, periprocedural, and postprocedural management.
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*Authors contributed equally to this work.
From the 1Instituto Cardiovascular, Hospital Clínico Universitario San Carlos, Madrid, España; 2Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada; 3Unified Interventional Cardiology Unit, San Luigi Gonzaga Orbassano University Hospital, Rivoli infermi Hospital, Turin, Italy; 4Columbia University Medical Center, NewYork-Presbyterian Hospital, the Cardiovascular Research Foundation, NY, New York; 5Cardiology Department, Charles Nicolle Hospital, University of Rouen, Rouen, France; 6The Heart Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 7Heart Insitute (InCor), São Paulo University Medical School (USP), São Paulo, Brazil; 8Ferrarotto Hospital, University of Catania, Italy; 9University Heart Center, Hospital Zurich, Zurich, Switzerland; 10Thoraxcenter, Erasmus Medical Center, Rotterdam, Netherlands; 11St. Antonius Hospital, Nieuwegein, Netherlands; 12Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, España; 13University of Turin – Città della Salute e della Scienza Hospital, Turin, Italy; 14King’s College Hospital, London, United Kingdom; 15Clinica Alemana, Santiago, Chile; 16West China Hospital, Sichuan University, China.
Funding: Fundación de Cardiología from Cardiovascular Institute, Hospital Clínico San Carlos, provided funding for the electronic web platform.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rodés-Cabau and Dr Wendler report consultant income from Edwards Lifesciences; grant support from Edwards Lifesciences and St. Jude Medical. Dr Nazif and Dr Leon report consultant income from Edwards Lifesciences. Dr Nietlispach reports consultant income from Edwards Lifesciences, Medtronic, and St. Jude Medical. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted May 27, 2018 and accepted June 8, 2018.
Address for correspondence: Luis Nombela-Franco, MD, PhD, Cardiovascular Institute, Hospital Universitario Clínico San Carlos, IdISSC, C/Prof Martin Lagos s/n 28040 Madrid, Spain. Email: luisnombela@yahoo.com
