Introduction and objectives: Transcatheter aortic valve implantation (TAVI) is an increasingly used procedure to treat severe aortic stenosis (AS) that should be monitored in the real-world routine clinical practice. We assessed TAVI outcomes (SAPIEN 3) in terms of the patient’s health-related quality of life (HRQoL), clinical endpoints, and resource utilization considering a valid risk score.
Methods: This was an observational prospective study including all consecutive patients with severe AS treated with TAVI (Edwards SAPIEN 3, transfemoral access) conducted during the calendar year of 2018. A systematic assessment of the patients’ HRQoL (EQ-5D-5L, the 36-item Short Form Health Survey, and the Kansas City Cardiomyopathy Questionnaire), clinical endpoints, and resource utilization (length of stay at the hospital/intensive care unit setting) was implemented. Assessment was scheduled before the procedure (baseline), at discharge, and 1, 6, and 12 months after implantation. Multivariate regression models were applied to test outcomes while controlling the patients’ risk (eg, Society of Thoracic Surgeons risk score).
Results: A total of 76 patients (50% female) with a mean age of 82.05 ± 4.76 years, and 55% with intermediate-high risk were included. The rates of successful impantation and cardiac death were 97.37% and 2.63%, respectively, at 1 year. Significant reductions in mean and maximum gradients were achieved and maintained at follow-up. The mean length of stay at the hospital (5.2 6 ± 4.05) and intensive care unit setting (0.22 ± 0.64) was short. Significant improvements (all adjusted P < .05) were detected in the Kansas City Cardiomyopathy Questionnaire overall summary scores, EQ-5D-5L, and the 36-item Short Form (physical component summary).
Conclusions: This research highlights how positive clinical outcomes translated into significant improvements in relation to the patients’ HRQoL. Use of resources —generally low— was based on the Society of Thoracic Surgeons risk score. (SARU Study; code: 2017-01, Murcia, Spain).
Keywords: Aortic valve stenosis. Quality of life. Health resources. Length of stay. Clinical endpoint. Burden of illness.
Introducción y objetivos: El uso del implante percutáneo de válvula aórtica (TAVI, transcatheter aortic valve implantation) está aumentando en el tratamiento de la estenosis aórtica grave. Por ello, el uso de TAVI en la vida real debe monitorizarse. Evaluamos los resultados del TAVI en términos de calidad de vida relacionada con la salud (CVRS), resultados clínicos y uso de recursos teniendo en cuenta un marcador de riesgo válido.
Métodos: Estudio observacional prospectivo incluyendo todos los pacientes consecutivos con estenosis aórtica grave tratados con TAVI (Edwards SAPIEN 3, acceso transfemoral) en 2018. Se evaluaron de forma sistemática la CVRS (EQ-5D-5L, Short Form-36 Health Survey, Kansas City Cardiomyopathy Questionnaire), los resultados clínicos y el uso de recursos (estancia en planta/unidad de cuidados intensivos). La evaluación se hizo antes de la intervención (basal), al alta y después de 1,6 y 12 meses del implante. Se aplicaron modelos de regresión multivariante para evaluar los resultados mientras se controlaba el riesgo del paciente (por ejemplo, escala de riesgo de la Society of Thoracic Surgeons).
Resultados: Se inc luyó a 76 pacientes (el 50% mujeres), con una edad media de 82,05 ± 4,76, y el 55% con riesgo intermedio-alto. Hubo un 97,37% de éxito del implante y la tasa de muerte de causa cardiovascular fue del 2,63% al año. Se consiguieron reducciones significativas en los gradientes medios y máximos, y se mantuvieron durante las visitas de seguimiento. Las estancias medias en planta (5,26 ± 4,05 días) y en la unidad de cuidados intensivos (0,22 ± 0,64 días) fueron bajas. Se detectaron mejoras significativas (todo ajustado p < 0,05) en el Kansas City Cardiomyopathy Questionnaire (puntuaciones generales), el EQ-5D-5L y el Short Form-36 (componente físico).
Conclusiones: Esta investigación destaca resultados clínicos positivos que se traducen en mejoras significativas en términos de calidad de vida de los pacientes. El uso de recursos, que fue en general bajo, también fue dependiente de la escala de riesgo de la Society of Thoracic Surgeons. (Estudio SARU, código: 2017-01, Murcia, España).
Palabras clave: Estenosis valvular aórtica. Calidad de vida. Recursos sanitarios. Estancia. Resultado clínico. Carga de la enfermedad.
AS: Aortic stenosis. HRQoL: Health-related quality of life. HRU: Healthcare resource utilization. KCCQ: Kansas City Cardiomyopathy Questionnaire. STS: Society of Thoracic Surgeons. TAVI: transcatheter aortic valve implantation.
Aortic stenosis (AS) is the most common cause of valvular heart disease1 with an estimated prevalence of 3%-5% in people ≥ 65 years to 7.4% in people > 85 years.2,3 Severe AS is the leading cause of valvular surgery among adults. AS typically has a variable but long latent period (asymptomatic) followed by a rapid progression stage after symptom onset (eg, dyspnea, angina or syncope), and has a poor prognosis if aortic valve replacement is not performed in a timely manner.4,5
Although open heart surgery has been the gold standard treatment for many years, aortic valve procedures have progressively become less invasive. Transcatheter aortic valve implantation (TAVI) has become the treatment of choice for inoperable patients with symptomatic, severe AS,6 and a valid alternative for high- and intermediate-surgical risk patients with improved clinical results regarding survival and functional capacity.7,8 Similarly, with new evidence from recent clinical trials, the indication for TAVI was extended to low-risk patients.9,10
According to current clinical guidelines,11 the multidisciplinary decision regarding procedures to solve AS requires an individualized and appropriate assessment of the candidates to optimize the benefits achieved in these patients (eg, regarding survival and symptom amelioration). To this end, significant factors impact the patients’ surgical risk (eg, surgeon-specific risk-adjusted composite according to the Society of Thoracic Surgeons [STS] score), the patient’s quality-adjusted life expectancy, baseline characteristics like frailty (eg, ≥ 2 score in the Katz scale), modifiable risk factors, and comorbidities (eg, chronic obstructive pulmonary disease, pulmonary hypertension, liver disease, previous stroke, anemia, and other systemic conditions). In Europe, recent guidelines recommend TAVI for patients > 75 years. Also, that all patients with AS between 70 and 75 years should be referred for TAVI assessment regardless of their surgical risk.12
Due to the wider indication for TAVI and the ageing demographic factor seen in Western countries,3 TAVI is increasingly used in the routine clinical practice across Europe. This underscores the importance of monitoring TAVI outcomes, particularly among elderly patients to better characterize performance in the real-world practice.
Therefore, our objective was to prospectively assess TAVI (SAPIEN 3, Edwards Lifesciences, United States) outcomes regarding the patient’s health-related quality of life (HRQoL), and the clinical outcomes considering their surgical risk. Also, as secondary endpoint, a description of healthcare resource utilization adjusted for surgical risk (STS score) was intended.
This was a prospective, observational study of all consecutive patients with severe, symptomatic AS treated with elective TAVI via transfemoral access with SAPIEN 3 at the regional Hospital Universitario Virgen de la Arrixaca, a tertiary hospital and a regional referral center for cardiothoracic surgery and interventional cardiology located in Murcia, Spain. Patients received TAVI regardless of the study as part of the routine clinical practice. The recruitment stage was during the calendar year of 2018. In this study we present the observed results from the systematic djustent conducted 1 year after TAVI.
According to the ESC/EACTS guidelines,6 implantation decision was made by the heart team and all procedures followed the recommendations established by the manufacturer’s SAPIEN 3 valve instructions for use. All patients were followed for, at least, 12 months after TAVI and systematically assessed according to the hospital clinical protocol. Written patient information was provided to each participant, and the patient’s consent on data collection was signed before being included in the study that was conducted in full compliance with the recommendations guiding biomedical research in human subjects adopted by the 18th World Medical Assembly, Helsinki, Finland back in 1964. The study protocol was approved by the assigned ethics Committee (Murcia, SARU Study; code: 2017-01. Effective date, 02/06/2017).
Clinical assessment was conducted at baseline (preoperative), post-intervention (perioperative), and 30 days, 6 months, and 1 year after the procedure. The main objective clinical variables included echocardiographic measurements (eg, paravalvular and total aortic regurgitation, left ventricular ejection fraction, mean and maximum aortic valve gradient, effective orifice area), and major clinical events automatically available in the medical records (eg, all-cause and cardiovascular mortality, stroke, bleeding complications, myocardial infarction, new-onset atrial fibrillation, major vascular complications, permanent pacemaker implantation, rehospitalization and acute kidney injury). In addition, the patients’ New York Heart Association (NYHA) functional class IV was systematically registered. The patients’ risk profile was characterized based on the STS risk score which was validated for the in-hospital and 30-day mortality rates following surgical aortic valve replacement.13 Additionally, postoperative complications were defined based on a modified version of the Valve Academic Research Consortium criteria,14 and this score was routinely applied based on the clinical protocols of our referral hospital.
Finally, length of stay (LOS)–at the hospital and the intensive care unit (ICU) settings–associated with the TAVI procedure was automatically registered for each patient based on hospital medical records and described as a secondary endpoint in this research.
Measurement of patient’s health-related quality of life
A comprehensive assessment was implemented by combining a patient-reported disease-specific tool that has a higher ability to capture changes in the patient’s health status during the observation period, and 2 generic tools to establish comparisons with findings from other procedures or diseases and with the Spanish normal population. Patients’ health-related quality of life was evaluated at baseline and during per protocol medical visits for health management (6 months and 1 year after TAVI).
The Kansas City Cardiomyopathy Questionnaire (KCCQ)15 is a 23-item self-administered disease-specific questionnaire originally developed for patients with heart failure to monitor their reported symptoms and evaluate how and to what extent their heart failure impacts their quality of life (QoL) within a 2-week recall period. The KCCQ includes 6 distinct domains (physical function, symptoms, symptom stability, social limitation, self-efficacy, and quality of life) added to 2 summary scores: the clinical summary score (CSS) and the overall summary score (OSS). Summary scores can be transformed into 0–100 scales with higher scores being indicative of better levels of wellbeing to facilitate score interpretation. This tool has been recently revised and qualified for its use in heart failure by the United States Food and Drug Administration16 with minimal clinically important differences defined as 5-point changes in summary scales.17 Also, the KCCQ has a sound psychometrical performance when measuring functional status and HRQoL in patients with severe, symptomatic AS.18
Generic tools to measure health-related quality of life
The EQ-5D-519—a patient-reported measure—includes a descriptive system and the EQ visual analogue scale (EQ-5D-5L VAS). The former includes 5 different domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses to the EQ-5D-5L descriptive system were assigned preference-based (utility) weights from the Spanish population. The EQ-5D-5L VAS reflects the patient’s self-rated health on a vertical visual analogue scale (from 0, ‘the worst health you can imagine’ up to 100, ‘the best health you can imagine’).20,21
The Medical Outcomes Study Short Form-36 (SF-36)22 is one of the most widely used and evaluated generic HRQoL questionnaires. It includes 8 dimensions and 2 summary scores (physical component summary [PCS] and mental component summary [MCS]). In this study we used a standardization of summary scores based on age and gender using the Spanish population normative data.23
First, an exploratory analysis was performed to characterise the analytic cohort presented in this manuscript. Descriptive statistics were used for continuous variables (eg, mean, standard error of measurement) and frequency tables or proportions for discrete variables. McNemar’s test for dependent samples was used to compare NYHA health states at follow-up. Regarding the objective of this study, multivariate models (linear general models with repeated measures at different time points —baseline, 6M, and 12M— as intra-subject factors) were computed to better assess the potential benefits of both regarding clinical endpoints and the patients’ HRQoL at follow-up (baseline, 6M, and 12M) while considering the patients’ comorbidities and risk profile at baseline. To this end, the STS predicted risk of mortality score was included because it is a weighted index of the patients’ risk robustly estimated using a Bayesian hierarchical model for both mortality and major complication events. This model considers 24 meaningful preoperative variables like age, sex, body surface area, atrial fibrillation, chronic heart failure, NYHA functional classification, chronic obstructive pulmonary disease, diabetes mellitus, need for insulin use, arterial hypertension, previous cardiac surgeries, concomitant mitral stenosis, unstable angina, previous percutaneous coronary intervention, and other variables. Based on the estimated STS score, patients were classified into 3 risk groups: high (≥ 8%), intermediate (≥ 4%), and low mortality risk (< 4%).13 Importantly, this score was also considered in the secondary endpoint associated with the description of the LOS (at both the hospital and ICU settings) related to TAVI procedures.
Regarding the size of the sample required to conduct the adjusted analyses described above, the estimated minimal sample size was set at 60 TAVI patients to compare within and between subject differences at 3 different time points of evaluation, effect size (f) was 0.25, statistical power (1-β), 0.9, and risk of type-I error (1-α), 0.95 assuming a weak correlation among repeated measures (0.3).
The software statistical package SPSS 27.0 for Windows (IBM Corp., United States) and the R software (The R Project for Statistical Computing, Institute for Statistics and Mathematics, Austria) were used for analysis.
A total of 76 consecutive patients, 50% female, with a mean age of 82.05 ± 4.76 years underwent elective TAVI during the study period comprising the analytical cohort. STS (surgical risk) score was 5.4 ± 3.41 while 42.5%, 43.8%, and 13.7% of the cases were classified as low-, intermediate-, and high-risk patients, respectively. A complete description of comorbidities is shown on Table 1. Previous coronary artery bypass graft was reported in 1 patient. A total of 6 cases (7.9%) were valve-in-valve procedures, and in 71 cases (93.4%) vascular access was via right femoral artery. Only 1 patient required general anaesthesia before TAVI (table 1 of the supplementary data). The patients’ functional status (NYHA classification) at baseline was remarkably impaired in most cases with 61.84%, and 19.74% of the patients having NYHA functional class III and IV, respectively.
COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; DM, diabetes mellitus; TIA, transient ischemic attack.
Successful implantation was achieved in 74 cases (97.37%), and 2 patients (2.63%) died within the first 30 days after the procedure (both cardiovascular causes). In this period, the observed rates of major complications or rehospitalizations were low (Table 2), and permanent pacemaker implantation was required for 5 patients. One year after TAVI, no additional cardiovascular deaths were reported. However, 7 patients died of other causes (Table 2). We should mention that the sample mortality rate was similar to that of a comparable general population (figure 1 of the supplementary data). According to echocardiographic measurements, significant benefits in mean and maximum gradients, and aortic regurgitation were achieved and maintained at follow-up (figure 2 of the supplementary data). Notably, among survivors, 78.4% of patients had a NYHA functional class I-II at 1 month, a benefit that was maintained at 1 year with 77.3% of patients in these functional levels.
|Cardiovascular death (30d)||2||2.63|
|Major bleeding (30d)||4||5.26|
|All-cause rehospitalization (30d)||4||5.26|
|Permanent pacemaker implantation (30d)||5||6.60|
|CV rehospitalization (30d)||2||2.63|
|All deaths (1y*)||9||11.84|
|All cardiovascular deaths (1y)||2||2.63|
* All deaths reported a 1 year: Multiple myeloma: n = 1; sepsis (respiratory tract infection): n = 1; sepsis (renal disease): n = 1; pulmonary disease: n = 1; hepatocellular carcinoma: n = 1; stroke: n = 1; cardiac tamponade: n = 1 (cardiovascular death within 30d); thyroid cancer: n = 1; sudden cardiac death: n = 1 (cardiovascular death within 30d).
The patients’ HRQoL across the observational period according to STS risk score at baseline is shown on figure 1. In both summary scores of the KCCQ (OSS and CSS), statistically and clinically significant improvements after TAVI were seen. In OSS cases, the mean differences reported between baseline and 6 months ranged between 18.94 points (low risk) and 29.97 points (intermediate risk) indicative of a meaningful benefit (all P < .001). Similarly, the mean differences regarding the CSS ranged between 13.03 points and 27.3 points (low and intermediate, respectively). In addition, in both scales the observed benefit was maintained at follow-up with no differences being reported at 6 months and 1 year (P > .8 in both summary scales). Remarkably, these improvements were repeated across the 3 risk groups (figure 2).
Regarding generic questionnaires, a positive impact was also seen in EQ-5D-5L VAS scores and the SF-36 Physical Component Summary, postoperatively, in all patients (P < .006 and P < .004, respectively). However, the size of detected differences was smaller considering the respective scales. No statistically significant differences were seen in the mental component summary (P = .395). In addition, values in all groups were comparable to normative population based on age and sex since baseline (mean—95% confidence interval [95%CI]—at baseline: 47.44, 44.70, and 50.18; 6 months: 49.77, 47.36, and 52.17; and 1 year: 48.64, 46.04, and 50.83-; P = .52). Finally, EQ-5D-5L index values were fairly similar across all time points with a slight increase observed at 6 months (P = .054 compared to baseline) and a mild drop at 1 year, not reaching statistical significance compared to baseline values (mean—95%CI—at baseline: 0.77, 0.71, and 0.83; 6 months: 0.80, 0.75, and 0.85; and1 year: 0.74, 0.68, and 0.80; P = .499).
Secondary endpoint: description of the procedure-related length of stay
Mean LOS at the hospital setting was limited with a mean stay of 5.26 days (± 4.05), and only 10 patients (13.2%) required intensive care, 5 of whom (6.6% of the overall sample) remained at the ICU setting ≤ 1 day, 3 (3.9%) for 2 days, and 2 (2.6%) for 3 days. In figure 3, the ICU and hospital stays are shown based on the patients’ baseline risk (very low in all subgroups).
Ideally, severe, and symptomatic AS should be treated with a valve implanted via minimally invasive procedures while securing minimal perioperative and long-term risks, optimizing hemodynamic response, avoiding patients’ dependency on lifelong anticoagulation therapy, and maximizing their ability to do activities of daily living, and wellbeing. Insights from clinical trials indicate that the management of AS is moving in this direction.7,9 However it is still important to evaluate each innovation in real practice. This study provides new evidence on the performance of TAVI in elderly patients—mean age > 80 years—under real-world practice through a systematic prospective assessment of clinical outcomes, LOS, and patients’ reported outcomes 1 year after the procedure.
In our study, a noticeable positive clinical effect of TAVI was seen in all STS subgroups. Mean and maximum aortic gradients along with valve regurgitation improved significantly after the procedure, and major complications were kept at very reasonable rates. These outcomes were very similar to those recently published on SAPIEN 3.24 Also, regarding the NYHA scale, the percentage of patients with satisfactory functional status increased immediately after the procedure and was maintained at 1 year among survivors.
Importantly, these clinical benefits translated into meaningful improvements in the patients’ HRQoL. Particularly, the OSS of the KCCQ showed a mean change from baseline from 18.9 points in low-risk patients up to near 30 points in intermediate risk 6 months after treatment). Also, this benefit was preserved at 1 year with ranges between 21.9 points in low risk to 26.7 points in intermediate risk. These increments reported in the KCCQ were clearly over the minimal clinically important differences described in the medical literature for this tool.17 Actually, these results are especially important considering than a 10 points drop in KCCQ OSS scores turned out to be a prognostic factor for patients with AS associated with 34% more chances of dying at 12 months.18 Therefore, the HRQoL of older patients who survived 1 year improved significantly. Our results are similar to those from a former research that studied clinical outcomes from TAVI in clinical trials and registries including the SAPIEN 3. For instance, Baron et al.24—according to data from the SAPIEN 3 intermediate-risk registry—found changes at 1 year from TAVI in OS of 23.1 points (21.8-24.9; P > .001) among intermediate-risk patients. Their cohort had similar baseline characteristics and underwent TAVI with the same device (they did, however, include transfemoral and transapical access). In our study, we saw that this enhanced self-perceived health is also maintained in elderly patients classified as low- and high-risk patients.
Regarding generic tools, a positive trend was also detected in the EQ-5D-5L VAS and the PCS of the SF-36 (a summary component more focused on the overall functional performance of patients) with significant differences at 6 months and 1 year. We should mention that no differences were found at follow-up regarding the mental component summary. Also, the patients’ mental health was slightly lower compared to that reported in their reference population since baseline. Similarly, regarding the estimated utilities from the EQ-5D-5L, a global positive trend was seen at 6 months from baseline and a slight drop after 1 year. Nevertheless, all changes detected with this tool were minimal. This finding was surprising considering the great benefit demonstrated with both the OSS and the CSS of the KCCQ. However, as the EQ-5D-5L captures health-related quality of life more globally together with the mean age of the patients included, the slight decline seen could reflect general deterioration of health accumulated over the 1-year observational period (mean age of the sample > 80 years).
Furthermore, consistent with recent experiences in centers of excellence regarding TAVI in Italy, the Netherlands, and the UK, where authors tested novel standardized clinical care pathways to optimize the process with early discharge while reducing complications and LOS,25 we saw a very limited hospital stay with only 13% of patients requiring ICU admission (6.5% of the patients needed 3 days at the ICU). In our center, following an individualized protocol for candidates eligible for TAVI, we saw very high-quality outcomes in elderly patients while minimizing the procedure-related LOS.
Inherently to the nature of this observational study, our findings are subject to a few limitations. First, our findings come from the experience of a single center in a tertiary referral hospital very familiar with the procedure so the extrapolation of these results might be affected by the experience of the heart team. Importantly, sample size, especially in the high-risk group, was limited and subject to high dispersion of values and missing data at follow-up. Therefore, further research with a larger number of patients stratified by risk should confirm our findings. Despite this limitation, we should mention that our results observed in the intermediate-risk group are similar to those reported with larger samples allowing for extensive propensity score cohort adjustment.24
Also, in this analysis, we decided to use the STS score as a measure of patient-risk characterization because, even when we acknowledge that this was originally developed for surgical aortic valve replacement, it is a valid prognostic measure of mortality and occurrence of major complications in TAVI making up a comprehensive assessment of the patients’ health status.13,26 However, as it has been described in recent research,27,28 it would also be helpful to include a measure of frailty to complete thedjusttments. Unfortunately, this information was not routinely collected through a standard form as part of the standard clinical management when this study was conducted. Nevertheless, we should mention that in our center, the heart team involved in the decision-making process regarding the individualized management of the patients’ clinical condition, always considers frailty as a key parameter to better adjust the provision of care. Also, precisely due to this preoperative assessment most patients classified as low risk by the STS score (42.5%) were treated with TAVI instead of open surgery. Hence, frailty is a core aspect of this process, always among other important factors like patient preference, history of chest radiation, previous coronary artery bypass graft or porcelain aorta, and others. Although through the comprehensive analysis of clinical and patient-reported outcomes a consistent and positive tendency in outcomes has been shown, we should mention that our results come from a cohort of patients treated in 2018. Consequently, it would be interesting to conduct a new study in multiple centers to obtain data to compare the evolution of the current clinical practice outcomes to those from 2018. Therefore, further research is warranted to continue this monitorization of outcomes in larger samples of patients.
In conclusion, this research provides clinical and patient-reported evidence on the performance of TAVI in elderly patients with clinical benefits maintained 1 year after the intervention. Furthermore, the short hospital stay observed provides exploratory insights into the benefits of standardized protocols created to manage low- to high-risk patients safely and efficiently.
Edwards Lifesciences provided funds for the analysis of this study that was conducted and interpreted independently by clinicians and methodological experts.
E. Pinar, J. García de Lara, J. Hurtado, B. Martí-Sánchez, G. Leithold, and J. Cuervo were involved in the study idea and design, and in the analysis of the study data. All authors were involved in the interpretation of the results and in the critical revision of the paper regarding its intellectual content and agree on the final version of the manuscript to be published.
CONFLICTS OF INTEREST
J. Cuervo, who works for Axentiva Solutions, disclosed that Axentiva Solutions has received financial support in the form of consultancy payments from Edwards Lifesciences towards the design and analysis of the study, and for medical writing support. B. Martí-Sánchez, and P. González work for Edwards Lifesciences. E. Pinar, J. García de Lara, J. Hurtado, M. Robles, G. Leithold, and K. Rand declared no conflicts of interest whatsoever.
WHAT IS KNOWN ABOUT THE TOPIC?
- Severe AS is the leading cause of valvular surgery among adults.
- TAVI has become the treatment of choice for inoperable patients with symptomatic, severe AS, and a valid alternative for patients at high- and intermediate-surgical risk with improved clinical results regarding survival and functional capacity.
- There are factors that influence TAVI results like surgical risk, patient’s life expectancy, baseline characteristics, modifiable risk factors, and comorbidities.
WHAT DOES THIS STUDY ADD?
- Through a comprehensive assessment including clinical, functional, and quality of life variables, this study shows a positive performance of TAVI in elderly patients at follow up.
- Improvement in mean and maximum aortic gradients, and valve regurgitation.
- Higher percentage of patients with a satisfactory functional status according to the NYHA scale after the intervention.
- Clinical benefits also translated into HRQoL improvements, and effect that was seen among all risk groups.
- Overall, in this consecutive sample of patients, the TAVI-related LOS (hospital) was short.
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24. Baron SJ, Thourani VH, Kodali S, et al. Effect of SAPIEN 3 Transcatheter Valve Implantation on Health Status in Patients With Severe Aortic Stenosis at Intermediate Surgical Risk: Results From the PARTNER S3i Trial. JACC Cardiovasc Interv. 2018;11:1188-1198.
25. Barbanti M, van Mourik MS, Spence MS, et al. Optimising patient discharge management after transfemoral transcatheter aortic valve implantation: the multicentre European FAST-TAVI trial. EuroIntervention. 2019;15:147-154.
26. Hemmann K, Sirotina M, De Rosa S, et al. The STS score is the strongest predictor of long-term survival following transcatheter aortic valve implantation, whereas access route (transapical versus transfemoral) has no predictive value beyond the periprocedural phase. Interact Cardiovasc Thorac Surg. 2013;17:359-364.
27. Green P, Arnold S V, Cohen DJ, et al. Relation of frailty to outcomes after transcatheter aortic valve replacement (from the PARTNER trial). Am J Cardiol. 2015;116:264-269.
28. Goudzwaard JA, de Ronde-Tillmans MJAG, El Faquir N, et al. The Erasmus Frailty Score is associated with delirium and 1-year mortality after Transcatheter Aortic Valve Implantation in older patients. The TAVI Care & Cure program. Int J Cardiol. 2019;276:48-52.
* Corresponding author.
Email address: firstname.lastname@example.org (E. Pinar Bermúdez).
Introduction and objectives: Advances made in transcatheter aortic valve implantation (TAVI) valvular technology have resulted in better outcomes and fewer complications compared with older generations. We studied the rate and determinants of paravalvular leak (PVL) using Evolut PRO vs SAPIEN 3 valves as well as other perioperative and in-hospital outcomes.
Methods: A total of 110 consecutive patients with severe aortic stenosis scheduled for transfemoral TAVI were randomly selected to receive the SAPIEN 3 (N = 59) or the Evolut PRO valve (N = 51). Annular dimensions were determined++ by transesophageal echocardiography guided balloon sizing. The following postoperative and in-hospital endpoints were assessed: PVL, conduction defects, valve embolization, need for a second valve, annular rupture, stroke, vascular complications, acute kidney injury, and in-hospital mortality. We also studied the possible anatomical determinants of PVL.
Results: There were no relevant baseline differences between the 2 groups regarding clinical and echocardiographic characteristics. In-hospital complications were comparable between both valves apart from a significantly higher rate of immediate postoperative PVL and at discharge (≥ grade II) between the Evolut PRO and the SAPIEN 3 valves (19.6% vs 6.8%) and (5.9% vs 1.7%), respectively. Of the anatomical variables described, the left ventricular outflow tract/ascending aorta angle, aortic angulation, and calcification had a significant impact on PVL in the Evolut PRO valves. The left ventricular outflow tract/ascending aorta angle revealed a negative correlation with implantation depth in the Evolut PRO valves but not in the SAPIEN 3 ones.
Conclusions: Both valves demonstrated favorable comparable outcomes except for a significantly higher rate of PVL in patients implanted with Evolut PRO valves.
Keywords: Aortic stenosis. Transcatheter aortic valve implantation. TAVI. SAPIEN 3. Evolut PRO.
Introducción y objetivos: Los avances en la tecnología de implante percutáneo de válvula aórtica (TAVI) han dado lugar a mejores resultados y menos complicaciones en comparación con las generaciones anteriores. Se estudió la incidencia y los determinantes de las fugas paravalvulares (FPV) con las válvulas Evolut PRO y SAPIEN 3, así como otros resultados periprocedimiento y hospitalarios.
Métodos: Se seleccionó aleatoriamente a 110 pacientes consecutivos con estenosis aórtica grave programados para TAVI transfemoral para recibir una válvula SAPIEN 3 (n = 59) o una Evolut PRO (n = 51). Las dimensiones anulares se determinaron mediante el dimensionamiento del balón guiado por ecocardiografía transesofágica. Tras el procedimiento y durante la hospitalización, se evaluaron los siguientes objetivos: FPV, defectos de conducción, embolización de la válvula, necesidad de una segunda válvula, rotura anular, accidente vascular cerebral, complicaciones vasculares, daño renal agudo y mortalidad intrahospitalaria. También se estudiaron los posibles determinantes anatómicos de la FPV.
Resultados: No hubo diferencias basales relevantes entre los 2 grupos en cuanto a las características clínicas y ecocardiográficas. Las complicaciones intrahospitalarias fueron comparables entre ambos tipos de válvulas, excepto una incidencia significativamente mayor de FPV (de grado II o superior) inmediata tras el procedimiento y al alta con las válvulas Evolut PRO en comparación con las SAPIEN 3 (19,6 frente a 6,8% y 5,9 frente a 1,7%, respectivamente). De las variables anatómicas, el ángulo entre el tracto de salida del ventrículo izquierdo y la aorta ascendente, la angulación aórtica y la calcificación tuvieron un impacto significativo en la FPV en las válvulas Evolut PRO. El ángulo entre el tracto de salida del ventrículo izquierdo y la aorta ascendente tuvo una correlación negativa con la profundidad de implantación en las válvulas Evolut PRO, pero no en las válvulas SAPIEN 3.
Conclusiones: Ambas válvulas demostraron resultados favorables comparables, excepto por una incidencia significativamente mayor de FPV en los pacientes con válvulas Evolut PRO.
Palabras clave: Estenosis aórtica. Implante percutáneo de válvula aórtica. TAVI. SAPIEN 3. Evolut PRO.
AbbreviationsAS: aortic stenosis. PVL: paravalvular leak. TAVI: transcatheter aortic valve implantation. VARC: Valve Academic Research Consortium.
Over the past decade, the self-expandable CoreValve (Medtronic Ltd, United States) and the balloon-expandable SAPIEN valve (Edwards Lifesciences Ltd, United States) were the valves most commonly used for transcatheter aortic valve implantation (TAVI).1
There are few studies comparing Evolut PRO (Medtronic Ldt, United States) vs SAPIEN 3 (Edwards Lifesciences Ltd, United States), like the SMART trial for small aortic annuli2 and the ALSTER-TAVI all-comers registry.3 However, comparative randomized clinical trials are lacking. Therefore, we designed the present randomized study to provide a head-to-head comparison between these 2 valves regarding procedural data and in-hospital outcomes especially paravalvular leak (PVL). Although the transcatheter heart valves used in this trial are not the latest generation valves of the CoreValve and SAPIEN families (currently, the Evolut-Pro plus and the SAPIEN Ultra), this is the first randomized clinical trial to compare a self-expanding valve with an outer skirt to a balloon expandable valve (with an outer skirt too).
A total of 110 consecutive patients with severe symptomatic aortic stenosis eligible for TAVI were randomly assigned to receive the Evolut PRO valve (51 patients) or the SAPIEN 3 valve (59 patients) at Duisburg Heart Center, Duisburg, Germany, from December 2019 through May 2020. All patients undergoing TAVI for severe aortic stenosis with the SAPIEN 3 and the Evolut PRO via femoral access were included. Patients who underwent TAVI with other valve types like transapically implanted aortic valves, bicuspid aortic valves, and valve-in-surgical-bioprosthesis implantation were excluded. All procedures were performed after obtaining the patients’ written informed consent and in compliance with the national research committee ethical standards.
TAVIs were performed under local anesthesia and conscious sedation. Femoral cutdown was used in all the patients. Annular dimensions were obtained by transesophageal echocardiography-guided balloon sizing during the procedure. With this technique we were able to measure annuli with transesophageal echocardiography and then choose a balloon equal to annular size. Balloon inflation during rapid pacing and aortic angiography were performed with 3 different possibilities in mind a) the balloon completely fills the annulus with no para-balloon leak or waisting indicative that annular size equals the balloon size; b) para-balloon leak is indicative that the annulus is 1 mm to 2 mm larger than balloon size; c) balloon waisting is indicative that the annulus is 1 mm to 2 mm smaller than balloon size.4 Valve type (SAPIEN 3 or Evolut PRO) was randomly selected (using simple randomization method; Monday cases for Evolut and Thursday cases for SAPIEN). Valve size was based on the annular dimensions as suggested by the manufacturers. Based on annular diameter and the diameter of the valve finally selected, a so-called cover index was calculated.5
Our primary endpoints were PVL, in-hospital mortality, and the rate of permanent pacemaker implantation (PPI). The study secondary endpoints were valve embolization, need for a second valve, aortic rupture or dissection, stroke or transient ischemic attack, major vascular complications, and acute kidney injury. Endpoints were defined according to the Valve Academic Research Consortium-2 (VARC-2) definitions.6
Immediate PVL was semi-quantitatively assessed using Seller’s criteria 7: 0/4 (absent); 1/4 (mild); 2/4 (moderate); 3/4 (moderate-to-severe); and 4/4 (severe).7 Transvalvular pressure gradients were obtained invasively using the pullback method. Aortic regurgitation index (AR index) was calculated.8
In case of significant PVL ≥ grade II, if needed, balloon postdilatation using the VACS III or NUCLEUS balloon (NuMED, United States) or else implantation of second valve was used. TTE was performed at discharge to quantify PVL according to the main VARC-2 criteria.9
Assessment of anatomical factors possibly associated with PVL
The following measurements were supported by Philips software (Philips Medical, The Netherlands): the left ventricular outflow tract/ascending aorta (LVOT/AAo) angle was defined as the angle between the axis of the first 4 cm of the ascending aorta (contact surface with the upper part of the prosthesis), and the LVOT axis (the valve landing zone) indicated by a line perpendicular to the plane of the aortic valve annulus).10
Aortic angulation (AA) angle was defined as the angle between the horizontal plane and the plane of aortic annulus.11 We categorized it into < 48° and ≥ 48°.12
Both angles were measured in the optimal fluoroscopic deployment position with all 3 coronary cusps in the same plane (figure 1). Valve implantation depth was assessed in the deployment position on the fluoroscopy from the native aortic annular margin on the side of both the non-coronary cusp (NCC) and left coronary cusp to the proximal edge of the deployed valve on the corresponding side13 (figure 2). Aortic root calcification was fluoroscopically assessed as inexistent, mild (small, isolated calcification spots), moderate (multiple large calcification spots) or severe (extensive calcification).13 Presence or absence of LVOT and mitral annular calcification were also noted.
Data was collected and analyzed using the SPSS (Statistical Software Package for the Social Sciences, version 20, IBM, and Armonk, United States). Continuous data was expressed as mean ± SD or median (range). Nominal data was expressed as frequency (percentage). For the comparison of nominal and continuous data, the chi-square test and the Student’s t test were used, respectively. Pearson correlation was used to assess the correlation between implantation depth with LVOT and AA angles based on the type of valve. The level of confidence was kept at 95% and hence, P values < .05 were considered statistically significant. Univariable logistic regression analysis was performed for predictors of significant PVL. ROC analysis was performed for the optimum cut-off value of the LVOT/AAo angle for the outcome of significant PVL.
Regarding sample size, assuming a 1:1 ratio in treatment assignments and an estimated rate of a composite primary endpoint (PVL, in-hospital mortality and rate of pacemaker implantation) of 8% in each study group, we estimated that a total of 52 patients were required in each group for the study to reach an 80% statistical power % at a 1-sided alpha level of 0.05
A total of 110 consecutive patients with severe symptomatic aortic stenosis eligible for TAVI were randomly assigned to receive the Evolut PRO (51 patients) or the SAPIEN 3 valve (59 patients). There was no crossover between both study arms. Baseline clinical characteristics were comparable between both types of valves apart from a significantly higher body mass index among SAPIEN 3 patients and a significantly high baseline right bundle branch block in the SAPIEN group (table 1).
|Type of valve||P|
|Evolut PRO (N = 51)||SAPIEN 3 (N = 59)|
|Age (years)||82.6 ± 6.4||81.2 ± 5.8||.22|
|Body mass index (kg/m2)||26.4± 4.7||28.7 ± 4.7||.01a|
|Body surface area (m2)||1.9 ± 0.4||1.9 ± 0.2||.08|
|Peripheral artery disease||11.8||6.8||.28|
|Ischemic heart disease||62.0||45.8||.06|
|Previous revascularization (PCI/CABG)||41.2||37.3||.53|
|Previous history of stroke||5.9||5.1||.58|
|Chronic chest disease||9.8||23.7||.31|
|STS score||3.8 ± 2.6||3.5 ± 2.2||.51|
|STS class (%)||.65|
|Low (< 4%)||58.8||66.1|
|Intermediate (4% to 8%)||35.3||27.1|
|High (> 8%)||5.9||6.8|
|Total preoperative conduction defects||19.6||22.0||.47|
Unless otherwise indicated, data are expressed as no. (%). Preoperative conduction defects included atrioventricular block, intraventricular conduction delay, left anterior hemiblock, left bundle branch block, and RBBB. CABG, coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; OSAS, obstructive sleep apnea syndrome; PCI, percutaneous coronary intervention; RBBB, right bundle branch block; STS, Society of Thoracic Surgery risk score.
Echocardiographic and fluoroscopic findings
The baseline echocardiographic and fluoroscopic findings of both groups were comparable (table 2).
|Type of valve||P|
|Evolut PRO (N = 51)||SAPIEN 3 (N = 59)|
|Mean PG (mmHg)||42.3 ± 7.7||42.8 ± 9.9||.78|
|Maximum PG (mmHg)||68.5 ± 10.5||67.3 ± 12.0||.56|
|Aortic valve area (mm)||0.9 ± 0.7||0.9 ± 0.2||.46|
|Ejection fraction (%)|
|Class of ejection fraction||48.4 ± 11.7||50.9 ± 11.7||.25 |
|Preserved (> 50%)||62.7||67.8|
|Mildly impaired (40% to 50%)||17.6||15.3|
|Moderately impaired (30% to 40%)||9.8||11.9|
|Severely impaired (< 30%)||9.8||5.1|
|Flow gradient (%)|
|Aortic measurements (by TEE)|
|Aortic valve area (mm)||0.7 ± 0.1||0.7 ± 0.2||.22|
|Annulus (mm)||23.8 ± 2.1||24.5 ± 1.9||.07|
|LVOT (mm)||21.1 ± 2.1||21.6 ± 2.4||.26|
|Sinus of Valsalva (mm)||30.7 ± 3.6||31.2 ± 3.8||.45|
|Sinotubular junction (mm)||25.9 ± 3.1||26.4 ± 3.5||.37|
|Ascending aorta (mm)||33.3 ± 5.9||33.7 ± 4.6||.68|
|Distance of STJ/LVOT (mm)||20.1 ± 10.5||19.4 ±3.2||.62|
|Aortic root calcification (%)|
|Mitral annular calcification||15.7||18.6||.44|
|LVOT/AAo angle (°)||13.7 ± 5.1||13.9 ± 5.2||.84|
|AAo angle (°)||46.5 ± 9.4||47.5 ± 12.1||.62|
AAo, ascending aorta; Ao, aorta; EF, ejection fraction; HFHG, high flow-high gradient; LFLG, low flow-low gradient; LVOT, left ventricular outflow tract; PG, pressure gradient; STJ, sinotubular junction; TEE, transesophageal echocardiography.
Procedural data in relation to the type of valve used
There were few differences in procedural data related to valve design and sheath size as shown on table 3.
|Type of valve||P|
|Evolut PRO (N = 51)||SAPIEN 3 (N = 59)|
|Annulus by TEE (mm)||23.8 ± 2.1||24.5 ± 1.9||.07|
|Balloon size (mm)||22.5 ± 1.9||22.6 ± 1.9||.63|
|Balloon sizing (mm)||23.4 ± 1.7||23.6 ± 1.9||.44|
|Valve size (%)|
|Sheath size (Fr)||16.0||14.5 ± 0.9||< .001|
|Sheath outer diameter (mm)||7.3 ± 0.1||6.2 ± 0.3||< .001|
|Femoral artery diameter (mm)||7.9 ±1.1||8.2 ± 0.9||.20|
|Sheath femoral artery ratio||0.9 ± 0.1||0.8 ± 0.1||< .001|
|Cover index (%)|
|TEE||16.4 ± 5.6||5.2 ± 4.2||< .001|
|Balloon||18.3± 3.3||8.9 ± 3.3||< .001|
|Valve mean pressure gradient||9.8||12.2||.01|
|AR index (%)||28.4 ± 7.8||30.7 ± 7.4||.11|
|Implantation depth (mm)|
|LCC||5.8 ± 2.3||4.2 ± 1.7||< .001|
|NCC||6.3 ± 2.5||5.27 ± 1.7||.01|
|Amount of contrast (mL)||145.5 ± 48.8||128.6 ± 33.2||.03|
|Radiation (mGy)||4944.4 ± 2294.8||4557.8 ± 3133.9||.46|
AR, aortic regurgitation; LCC, left coronary cusp; NCC, non-coronary cusp; TEE, transesophageal echocardiography.
Outcomes in association with the type of valve used
There was a significant difference in PVL (both immediate and at hospital discharge) and consequently more balloon postdilatation in the Evolute compared to the SAPIEN 3 group. The use of significantly larger amounts of contrast with the Evolut PRO valves may explain the increased number of acute kidney injury described in this group compared to the SAPIEN valve group. Results were favorable to the SAPIEN 3 valve regarding the endpoints of stroke or in-hospital mortality. However, no statistically significant differences were reported. The rates of device success (absence of a significant PVL (≥ grade II) at hospital discharge, need for second valve implantation, valve embolization, the performance of the prosthetic heart valve, and mortality) were 86% and 98% with the Evolut PRO and SAPIEN 3 valves, respectively; P = .01 (table 4).
|Type of valve||P value|
|Evolut PRO (N = 51)||SAPIEN 3 (N = 59)|
|No/trace||19 (37.3)||46 (78)|
|Grade I||22 (43.1)||9 (15.2)|
|≥ grade II||10 (19.6)||4 (6.8)|
|Balloon postdilatation||8 (15.7)||3 (5.1)||.35|
|PVL at discharge||.01|
|No/trace||26 (50.9)||49 (83.1)|
|Grade I||22 (43.1)||9 (15.3)|
|Grade II||2 (3.9)||1 (1.7)|
|Grade III||1 (2)||0|
|Overall new-onset conduction defects||9 (17.6)||10 (16.9)||.56|
|New-onset LBBB||4 (7.8)||4 (6.7)||.40|
|Postoperative pacemaker implantation||4 (7.8)||3 (5.1)||.25|
|Major vascular complications||2 (3.9)||2 (3.4)|
|Minor vascular complications||4 (7.9)||3 (5.1)|
|Acute kidney injury*||3 (5.9)||2 (3.4)||.28|
|Valve embolization||1 (2)||0||.46|
|Need for second valve||2 (3.9)||0||.30|
|In-hospital mortality rate||2 (3.9)||0||.30|
Data are expressed as no. (%). PVL, paravalvular leak.
Impact of anatomical factors on PVL
Calcification and the LVOT/AAo angle had a greater impact on PVL in the Evolut PRO compared to the SAPIEN 3 valve. The LVOT/AAo angle was categorized based on the receiver operating characteristic (ROC)-derived cut-off value for the endpoint of significant PVL ≥ grade II: cut-off value = 11º, 80% sensitivity, and 35.8% specificity, area under the curve (0.57; 95% confidence interval, 0.474-0.666; P = .37.) On the other hand, the AA angle did not seem to be very relevant to PVL within the groups (table 5).
|Evolut PRO valve (N = 51)||SAPIEN 3 Valve (N = 59)||Pa||Pb||Pc|
|< Mild PVL||≥ Mild PVL||< Mild PVL||≥ Mild PVL|
|Mitral annular calcification||0.0||15.7||15.3||3.4||.001||.2||.035|
|AAo angle (%)||.78||.34|
LVOT, left ventricular outflow tract; AAo, ascending aorta.
Table 6 shows the univariate analysis of predictors of ≥ grade II PVL immediately after the procedure. As demonstrated, moderate and severe valvular calcification, LVOT calcification, and the LVOT/AAo angle contribute to PVL significantly.
|Severe calcification||35.000 (3.138-390.431)||.004|
|LVOT calcification||10.921 (3.208-37.174)||< .001|
|LVOT/AAo angle||1.047 (0.940-1.165)||.003|
|Valve type (Evolut PRO)||2.750 (0.872-8.669)||.084|
|TEE cover index||1.099 (1.018-1.188)||.016|
|Cover index by balloon sizing||1.108 (1.001-1.226)||.049|
|LCC implantation depth||1.199 (0.953-1.510)||.122|
|RCC implantation depth||1.167 (0.914-1.489)||.215|
P value was significant if < .05. 95%IC, 95% confidence interval; AA, aortic angulation; AAo, ascending aorta; AR, aortic regurgitation; LCC, left coronary cusp; LVOT, left ventricular outflow tract; PVL, paravalvular leak; RCC, right coronary cusp; TEE, transesophageal echocardiography.
Impact of LVOT/AAo and AA angles on implantation depth
There was a significant negative correlation between the implantation depth of the Evolut PRO valve at the NCC and LVOT/AAo angles (r = -0.38; P = .01). There was no such correlation with the SAPIEN 3 valve (table 7).
|Type of valve|
|Evolut PRO||SAPIEN 3|
|LVOT/AAo angle (°)||-0.23 (0.09)||-0.38 (0.01)||0.09 (0.46)||0.16 (0.21)|
|AAo angle (°)||0.13 (0.33)||0.06 (0.65)||0.02 (0.87)||0.06 (0.61)|
r indicates strength of correlation and P value indicates significance of correlation. P value was significant if < .05. AAo, ascending aorta; LCC, left coronary cusp; LVOT, left ventricular outflow tract; NCC, non-coronary cusp.
In this study 2 important findings were made. First, implantation of the Evolut PRO valve was associated with a higher risk of significant PVL compared to the SAPIEN 3 valve. Secondly, the rate of PPI was equal in both groups. Otherwise, both types of valves yielded similar outcomes.
Reducing PVL is an important challenge regarding TAVI as it is associated with worse outcomes especially with the current use of these devices in lower-risk patients.14
A randomized comparison between the CoreValve and SAPIEN XT valves in the CHOICE trial revealed a lower rate of moderate-to-severe PVL in the SAPIEN XT group.15 In the SOLVE-TAVI trial, the non-inferiority of 2 devices (SAPIEN 3 and Evolut R) was reported in terms of their primary efficacy composite endpoint (death, stroke, paravalvular regurgitation, and new pacemaker implantation).16 Currently, the SAPIEN 3 Ultra and Evolut PRO+ have been developed with early favorable outcomes.17
In our study, relevant PVL (≥ grade II) was more common in patients who received the Evolut PRO compared to the SAPIEN 3 valve (9.6% vs 6.8%, respectively). Enríquez-Rodríguez et al. reported a lower rate (2.5%) of moderate to severe PVL with the SAPIEN 3 valves possibly due to the presence of an external sealing cuff.18
Obviously, anatomical factors are important for the occurrence of PVL. We observed that larger LVOT/AAo angles were associated with a higher rate of PVL, particularly with the Evolut PRO valve. Sherif et al. demonstrated that the risk of PVL increases with larger LVOT/AAo angles.10 We also observed that the LVOT/AAo angle affects implantation depth in association with the NCC with the Evolut PRO, but not with the SAPIEN 3 valves. It is quite conceivable that implantation depth impacts the rate of PVL.
Sherif et al. were the first ones to report on the association between increased AA angles and postoperative PVL with self-expanding valves.10 A subsequent retrospective study conducted by Abramowitz et al. described a higher rate of complications (eg, postoperative PVL in patients with horizontal aortas (defined by an AA ≥ 48º as seen on the cardiac CT scan) who received self-expanding valves.11 We observed that AA angles impacted PVL in patients who received Evolut PRO valves even if these angles were < 48º with no significant differences in the rate of PVL for AA angles < 48º or ≥ 48º.
In this study we also observed 6 patients with AA angles ≤ 30º (3 patients with Evolut PRO and 3 patients with SAPIEN 3). All of them were free of PVL immediately after valve deployment. One could speculate that AA angles ≤ 30º are the best for Evolut PRO valve implantation, but the small size of the sample prevents us from drawing any definitive conclusions.
In our study, the rates of device success determined by the absence of a significant PVL (≥ grade II) at hospital discharge, need for a second valve, valve embolization, the performance of the prosthetic heart valve, and the mortality rate according to VARC definition9 were 86% and 98% with the Evolut PRO and SAPIEN 3 valve, respectively. Similarly, Li et. al found a high device success rate for both the SAPIEN 3 and the Evolut R valve (94% and 96%, respectively).19
We found similar rates of postoperative conduction defects and PPI for both Evolut PRO and SAPIEN 3 valve types (7.8% and 5.1%, respectively). Popma et al.20 and Vlastra et al.21 reported lower rates of PPI with new generation balloon expandable valves compared to new-generation self-expanding valves. The comparable rates of conduction defects and PPI with either valve in our study was probably due to the lower implantation depth of Evolut PRO valves.
Li et al. reported higher rates of postdilatation of up to 30% with the Evolut R compared to the SAPIEN 3 valve.19 This was not seen in our study (15.7% and 5.1%, respectively; P = .35). This was probably so thanks to the proper positioning of the Evolut PRO valve and routine predilatation in all our cases.
In this study, in-hospital mortality was similar in both valve groups. Li et al. also reported that mortality was not associated with the type of valve implanted.19 The CHOICE trial also showed a comparable mortality rate with the use of older-generation valves (CoreValve and SAPIEN XT).15
The rates of stroke were similar for both the Evolut PRO and the SAPIEN 3 valve and lower compared to those seen with older generation devices.15,19,22,23 The operators’ experience and improved delivery systems are likely to account for the reduced risk of thromboembolic complications.
Regardless of the type of valve used, acute kidney injury seemed to be slightly more common in our study (5.9% and 3.5% for the Evolut PRO and the SAPIEN 3, respectively) than previously reported. Husser et al.24 noted a rate of 2.7% in SAPIEN 3 valves while Kodali et al.25 reported rates of 1.7%. However, large multicenter studies usually have stricter inclusion criteria so the baseline kidney function of the patients included was better.19
Despite increased sheath/femoral artery ratios with the Evolut PRO valve, the rate of bleeding or vascular complications was similar compared to the SAPIEN 3 valve. Similar results were reported by Li et al.19 and Panchal et al.26
This was a single-center study with a small sample size and limited statistical power. As routine computed tomography scan was not part of our study, specific information on the anatomy of the aortic root was not available and no adjustment was performed based on the annular dimensions or degree/distribution of aortic annular calcification. Also, angiography-based measurements of the LVOT/AAo and AA angles may be inaccurate. However, this may have helped exclude selection bias as some operators are reluctant to use self-expanding valves in view of heavy calcifications or severe angulation.
Follow-up was limited to the length of stay (average 1 week). However, this seems reasonable since we focused on procedural aspects. Furthermore, in comparable studies, in-hospital outcome and 30-day follow-up results were quite similar.
This randomized study demonstrated comparable procedural and in-hospital outcomes for the Evolut PRO and SAPIEN 3 valves except for a significantly higher rate of PVL associated with the Evolut PRO valves. The PVL reported was associated with the LVOT/AAo angle in Evolut PRO group, which also impacted negatively the implantation depth of this type of valve.
Idea and design: H. M. Elnaggar, M. S. Mahmoud, W. Schoels, and Y. T. Kishk. Administrative support: W. Schoels, M. Kullmer, and M. Dia. Provision of study materials or patients: M. S. Mahmoud, M. Algowhary, and H. M. Elnaggar. Data collection and assembly: M. S. Mahmoud, M. Kullmer, and M. Dia. Data analysis and interpretation: M. S. Mahmoud, Y. T. Kishk, M. Algowhary, and H. M. Elnaggar. Manuscript drafting and final approval: all authors.
CONFLICTS OF INTEREST
WHAT IS KNOWN ABOUT THE TOPIC?
- Self-expanding (Evolut platform) and balloon-expandable (SAPIEN series) valves are the most commonly used TAVI devices.
- Outcomes between both types of valves are similar with a relative increase of PVL and conduction defects in the Evolut type.
- Also, there are some anatomical challenges when deploying self-expanding valves such as severe aortic angulation (horizontal aorta).
- There is no prospective randomized clinical trials comparing Evolut PRO (self-expanding valve with external skirt) to SAPIEN 3 valves.
WHAT DOES THIS STUDY ADD?
- This is considered the first prospective randomized clinical trial that compared the Evolut PRO valve (self-expanding valve with external skirt) to the SAPIEN 3 valve.
- This study demonstrated comparable favorable outcomes between both types of valves apart from a significantly higher PVL in the Evolut PRO group.
- Also, in our study, LVOT/AAo and AA angulation had an impact on PVL in the Evolut PRO group compared to the SAPIEN 3 group. However, AA angulation had no impact on PVL within the groups.
- The LVOT/AAo angle was negatively associated with implantation depth in the case of the Evolut PRO valve with no effect on SAPIEN 3 valves whatsoever, which may have impacted the development of PVL in the Evolut PRO group.
1. Athappan G, Patvardhan E, Tuzcu EM, et al. Incidence, predictors, and outcomes of aortic regurgitation after transcatheter aortic valve replacement: meta-analysis and systematic review of literature. J Am Coll Cardiol. 2013;61:1585-1595.
2. Herrmann HC, Abdel-Wahab M, Attizzani GF, et al, Rationale and design of the SMall Annuli Randomized to Evolut or SAPIEN Trial (SMART Trial). Am Heart J. 2022;243:92-102.
3. Paitazoglou C, Meincke F, Thorsten Hanke M, et al. The ALSTER-TAVI All-Comers Registry: Procedural and 1-Year Clinical Outcomes of Balloon-Expandable vs Self-Expanding Contemporary TAVI Valves. J Invasive Cardiol. 2021;33:E356-E364.
4. Mahmoud MS, Kishk YT, Algowhary M, et al. Balloon Sizing for Transcatheter Aortic Valve Implantation Using 3 rd Generation Valves, Does It Still Work? Int Med J. 2021;28:604-609.
5. Détaint D, Lepage L, Himbert D, et al. Determinants of significant paravalvular regurgitation after transcatheter aortic valve implantation: impact of device and annulus discongruence. JACC Cardiovasc Interv. 2009;2:821-827.
6. Wang J, Yu W, Jin Q, et al. Risk factors for post-TAVI bleeding according to the VARC-2 bleeding definition and effect of the bleeding on short-term mortality: a meta-analysis. Can J Cardiol. 2017;33:525-534.
7. Sellers RD, Levy MJ, Amplatz K, Lillehei CW. Left retrograde cardioangiography in acquired cardiac disease: Technic, indications and interpretations in 700 cases. Am J Cardiol. 1964;14:437-447.
8. Sinning JM, Hammerstingl C, Vasa-Nicotera M, et al. Aortic regurgitation index defines severity of peri-prosthetic regurgitation and predicts outcome in patients after transcatheter aortic valve implantation. J Am Col Cardiol. 2012;59:1134-1141.
9. Kappetein AP, Head SJ, Généreux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Thorac Cardiovasc Surg. 2013;145:6-23.
10. Sherif MA, Abdel-Wahab M, Stöcker B, et al. Anatomic and procedural predictors of paravalvular aortic regurgitation after implantation of the Medtronic CoreValve bioprosthesis. J Am Col Cardiol. 2010;56:1623-1629.
11. Abramowitz Y, Maeno Y, Chakravarty T, et al., Aortic angulation attenuates procedural success following self-expandable but not balloon-expandable TAVR. JACC Cardiovasc Imaging. 2016;9:964-972.
12. Di Stefano D, Colombo A, Mangieri A, et al. Impact of horizontal aorta on procedural and clinical outcomes in second-generation transcatheter aortic valve implantation. EuroIntervention. 2019;15:e749-e756.
13. Mostafa AE, Richardt G, and Abdel-Wahab M. Clinical utility of a predictive model for paravalvular aortic regurgitation after transcatheter aortic valve implantation with a self-expandable prosthesis. Egypt Heart J. 2017;69:253-259.
14. Reardon MJ, Van Mieghem NM, Popma JJ, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2017;376:1321-1331.
15. Abdel-Wahab M, Mehilli J, Frerker C, et al. Comparison of balloon-expandable vs self-expandable valves in patients undergoing transcatheter aortic valve replacement: the CHOICE randomized clinical trial. JAMA Cardiol. 2014;311:1503-1514.
16. Webb J, Wood D, Sathananthan J, Landes U. Balloon-expandable or self-expandable transcatheter heart valves. Which are best? Eur Heart J. 2020;41:1900-1902.
17. Jiang T, Hasan SM, Faluk M, Patel J. Evolution of Transcatheter Aortic Valve Replacement| Review of Literature. Curr Probl Cardiol. 2021;46:100600.
18. Enríquez-Rodríguez E, Amat-Santos IJ Jiménez-Quevedo P, et al. Comparison of the hemodynamic performance of the balloon-expandable SAPIEN 3 versus self-expandable Evolut R transcatheter valve: a case-matched study. Rev Esp Cardiol. 2018;71:735-742.
19. Li Y-M, Tsauo J-Y, Liao Y-B, Zhao Z-G, Chen M. Comparison of Third Generation Balloon-Expandable Edwards Sapien 3 Versus Self-Expandable Evolut R in Transcatheter Aortic Valve Implantation: A Meta-Analysis. Ann Palliat Med. 2020;9:700-708.
20. Popma JJ, Reardon MJ, Khabbaz K, et al. Early clinical outcomes after transcatheter aortic valve replacement using a novel self-expanding bioprosthesis in patients with severe aortic stenosis who are suboptimal for surgery: results of the Evolut R US study. JACC Cardiovasc Interv. 2017;10:268-275.
21. Vlastra W, Chandrasekhar J, Muñoz-Garcia AJ, et al. Comparison of balloon-expandable vs. self-expandable valves in patients undergoing transfemoral transcatheter aortic valve implantation: from the CENTER-collaboration. Eur Heart J. 2019;40:456-465.
22. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364:2187-2198.
23. Adams DH, Popma JJ, Reardon MJ, et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014;370:1790-1798.
24. Husser O, Kim WK, et al. Multicenter comparison of novel self-expanding versus balloon-expandable transcatheter heart valves. JACC Cardiovasc Interv. 2017;10:2078-2087.
25. Kodali S, Thourani VH, White J, et al. Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis. Eur Heart J. 2016;37:2252-2262.
26. Panchal HB, Barry N, Bhatheja S, Albalbissi K, Mukherjee D, Paul T. Mortality and major adverse cardiovascular events after transcatheter aortic valve replacement using Edwards valve versus CoreValve: A meta-analysis. Cardiovasc Revasc Med. 2016;17:24-33.
* Corresponding author. E-mail address: email@example.com (M.S. Mahmoud).
Introduction and objectives: Transcatheter aortic valve implantation (TAVI) was first introduced in 2007 as an alternative to open heart surgery to treat patients with severe symptomatic aortic stenosis (sSAS) with various indication expansions since that date. Recently, the PARTNER 3 study (Placement of aortic transcatheter valve) demonstrated clinical benefits with TAVI with the SAPIEN 3 valve vs surgical aortic valve replacement (SAVR) in selected low surgical mortality risk patients. We reviewed data from the PARTNER 3 and economic data from Spain to assess the cost-effectiveness ratio of TAVI vs SAVR in patients with sSAS and low surgical mortality risk.
Methods: A 2-stage model was used to estimate direct healthcare costs and health-related quality of life data regarding TAVI with the SAPIEN 3 valve and SAVR. Early adverse events associated with TAVI from the PARTNER 3 were fed into a Markov model that captured longer-term outcomes after TAVI or SAVR.
Results: TAVI with SAPIEN 3 improved quality-adjusted life years per patient (+ 1.00) with an increase in costs vs SAVR (€6971 per patient). This meant an incremental cost-effectiveness ratio/quality-adjusted life year of €6952 per patient. The results were robust with TAVI with the SAPIEN 3 valve remaining cost-effective across several sensitivity analyses.
Conclusions: TAVI with the SAPIEN 3 valve is cost effective compared to SAVR in patients with sSAS and low surgical mortality risk. These findings can inform policymakers to facilitate policy development in Spain on intervention selection in this patient population.
Keywords: Spain. Transcatheter aortic valve replacement. Heart procedures and surgeries. Prosthetic heart valve. Surgical aortic valve replacement. Cost-benefit analysis. Aortic stenosis. Low-risk.
Introducción y objetivos: El implante percutáneo de válvula aórtica (TAVI) se introdujo en 2007 como una alternativa a la cirugía a corazón abierto para tratar a pacientes con estenosis aórtica grave sintomática, y desde entonces han aumentado las indicaciones autorizadas. Recientemente, el Placement of Aortic Transcatheter Valve Study (PARTNER) 3 ha demostrado beneficios clínicos con el TAVI con la válvula SAPIEN 3 frente al reemplazo quirúrgico de válvula aórtica (RVAo) en pacientes seleccionados con bajo riesgo de mortalidad quirúrgica. Utilizando los datos del PARTNER 3 junto con datos económicos de España, se evaluó la relación coste-efectividad del TAVI en comparación con el RVAo en pacientes con estenosis aórtica grave sintomática con bajo riesgo de mortalidad quirúrgica.
Métodos: Se utilizó un modelo en dos etapas para estimar los costes directos sanitarios y los datos de calidad de vida relacionados con la salud para TAVI con la válvula SAPIEN 3 y RVAo. Los eventos adversos tempranos relacionados con TAVI del PARTNER 3 se incluyeron en un modelo de Markov, que capturó los resultados a más largo plazo tras TAVI o RVAo.
Resultados: El TAVI con SAPIEN 3 mejoró los años de vida ajustados por calidad por paciente (+1,00), con un aumento en el coste frente al RVAo de 6.971 € por paciente. Esto representó una ratio coste-efectividad incremental por año de vida ganado ajustado por calidad de 6.952€ por paciente. Los resultados fueron robustos en los diversos análisis de sensibilidad realizados, en los que el TAVI con SAPIEN 3 se mantiene como una opción coste-efectiva.
Conclusiones: El TAVI con SAPIEN 3 es coste-efectivo en comparación con el RVAo en pacientes con estenosis aórtica grave sintomática con bajo riesgo de mortalidad quirúrgica. Estos resultados pueden informar a los decisores políticos en España para facilitar el desarrollo de políticas sobre la selección de opciones terapéuticas en esta población de pacientes.
Palabras clave: España. Implante percutáneo de válvula aórtica. Cirugía cardiaca. Prótesis valvular cardiaca. Reemplazo quirúrgico de válvula aórtica. Análisis coste-beneficio. Análisis coste-efectividad. Estenosis aórtica. Bajo riesgo.
Abbreviations ICER: incremental cost-effectiveness ratio. QALYs: quality-adjusted life years. SAVR: surgical aortic valve replacement. sSAS: severe symptomatic aortic stenosis. TAVI: transcatheter aortic valve implantation.
Aortic stenosis affects nearly 3% of adults aged > 65 years.1 It often has an initial asymptomatic latent period, but as the disease becomes worse, signs of heart failure, angina, or syncope become evident.1,2 Aortic valve replacement is recommended for most symptomatic patients with echocardiographic evidence of significant aortic stenosis as well as for some asymptomatic patients.1,2
Since the first transcatheter aortic valve implantation (TAVI) was used as a treatment option for severe symptomatic aortic stenosis (sSAS) almost 20 years ago, clinical trial evidence has further increased and continued to validate its use.3 In 2013, TAVI became the treatment of choice for inoperable patients with sSAS, and high surgical mortality risk patients. More recently, this treatment choice has expanded to include patients of intermediate/low surgical mortality risk.4,5
The very recent Placement of aortic transcatheter valve study (PARTNER 3) is among the growing body of robust clinical trial evidence. This is a pivotal, multicenter, randomized, and controlled study in patients with sSAS of low surgical mortality risk.6,7 In PARTNER 3, treatment outcomes with surgical aortic valve replacement (SAVR) were compared to TAVI with the SAPIEN 3 transcatheter heart valve via transfemoral access.6,7 Compared to SAVR, TAVI with the SAPIEN 3 valve reduced the composite endpoint of death, stroke or rehospitalization after 1 and 2 years.6,7 In view of these positive clinical developments, the European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines now recommend SAVR in younger, low-risk patients, while TAVI is now the treatment of choice in older patients. Also, it can be considered in all other patients with sSAS following careful evaluation of individual clinical, anatomical, and procedural characteristics by the heart team.5
There are no treatment guidelines specific to Spain describing the use of TAVI, but the Spanish Society of Cardiology, as a member of the ESC, endorses the ESC guidelines, and healthcare professionals in Spain follow these ESC guidelines.5 Irrespective of these guidelines, TAVI adoption in Spain remains low compared to other European countries. Despite a higher level of infrastructure available,8 defined as the number of TAVI centres available per million population, there is still significant variability among regions regarding TAVI implantation rates in Spain.9 In 2021, nearly 5000 patients benefited from this transformative minimally invasive technology in Spain. In a recent publication,10 the annual number of TAVI candidates for Spain was estimated at 15 783 patients including low-risk patients. Considering this together with the increasingly evident clinical benefits of TAVI in patients with sSAS, it is important to evaluate the cost-effectiveness ratio of using TAVI vs SAVR for the low surgical risk sSAS patient group for whom TAVI is now advised in recent guidelines.5 Furthermore, compared to SAVR, transfemoral TAVI with the SAPIEN 3 valve has proven cost-effective in the high-and-intermediate-risk population in Spain.11 This further accentuates the need for evidence on the cost-effectiveness ratio of TAVI with the SAPIEN 3 valve in the low surgical risk population of patients with sSAS in Spain. Therefore, the objective of this article is to review the PARTNER 3 data and the economic data from Spain to assess the cost-effectiveness ratio of using TAVI vs SAVR in patients with sSAS and low surgical mortality risk.
A cost-utility analysis was developed using methodology validated for the French12 and Italian13 population to estimate changes in both direct healthcare costs and health-related quality of life with the use of TAVI with the SAPIEN 3 valve compared to SAVR in patients with sSAS and low surgical mortality risk (Society of Thoracic Surgeons < 4%) from the perspective of the Spanish National Health System. Costs were measured in 2021 euros and benefits in quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference in costs between the 2 treatment groups by the difference in QALYs. Consistent with previous studies,11,14 an incremental cost-effectiveness ratio of < €30 000 per QALY gained was used as the willingness-to-pay (WTP) threshold of acceptable cost-effectiveness.
Details of the 2-stage model structure have been previously described for the French population.12 In brief, early adverse events associated with TAVI were first captured using the 30-day early adverse events dataset from the PARTNER 3 study6 in a decision tree (figure 1A); subsequently, these data were fed into a Markov model that included 4 distinct health states (‘alive and well’, ‘treated atrial fibrillation [AF]’, ‘disabling stroke’, and ‘dead’) to capture longer-term outcomes of patients after TAVI or SAVR (figure 1B). The model was considered appropriate for the Spanish setting by all authors based on their clinical and health-economic expertise.
Reproduced from Gilard M, et al. Value Health 202112 under the terms of the creative commons licence.44 AE, adverse event; AF, atrial fibrillation; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation.
Given that sSAS requires life-long valve replacement, a lifetime timespan of 50 years was selected for the cost-utility analysis with a discounting factor per year of 3% applied for both future costs and benefits following the recommendations set for Spain.15 This timespan was chosen to reflect all potential consequences to individuals with sSAS over their lifetime. Healthcare costs and health-related quality of life was measured using QALYs.
The model was informed by the PARTNER 3 study population, which excluded patients with clinical frailty, bicuspid aortic valves or other anatomical features that increased the risk of complications associated with either surgery or TAVI. In the PARTNER 3, 1000 patients were enrolled, 503 of whom were randomized to TAVI and 497 to SAVR, with ‘as treated’ groups of 496 and 454 patients, respectively.6 The primary endpoint was a composite of all-cause mortality, stroke or rehospitalization 1 year after the procedure.
Probabilities of clinical events used in the model (table 1 of the supplementary data) were based on a decision tree that captured all early adverse events experienced up to 30 days after the procedure as reported in the PARTNER 3. Monthly transition probabilities among the Markov model health states were estimated. Regarding the transition from ‘alive and well’ to ‘treated AF’, data from the PARTNER 3 on new-onset treated AF between 30 days and 1 year were used.6 Other literature sources provided a more realistic estimate of the remaining 2 transitions due to the scarcity of these events reported in the PARTNER 3. Burden of stroke data in Spain (Stroke Alliance for Europe)16 were used for the transition from ‘alive and well’ to ‘disabling stroke’, and data from a systematic review/meta-analysis involving 104 eligible cohort studies were used for the transition from ‘treated AF’ to ‘disabling stroke’.17 Myocardial infarction, transient ischemic attack, and severe or life-threatening bleeding were captured as intercurrent events between 30 days and 1 year from PARTNER 3 data.6 Other relevant events like rehospitalization rates using data from the PARTNER 3,6 and reintervention rates due to valve deterioration (data up to 2 years from the PARTNER 3)6,7 and from 3 years onwards from a study on 20-year outcomes of pericardial aortic tissue valve bioprosthesis18 were also considered (table 1 of the supplementary data). In the base case, the same reintervention rate was used for both the TAVI and SAVR arms; this simplifying assumption allowed better use of the available data. In scenario #1, higher reintervention rates were assumed for TAVI with the SAPIEN 3 valve compared to SAVR based on data from the PARTNER 2 at 5 years19 while in scenario #2, an increased risk of stroke was assumed, which was consistent with the PARTNER 3 outcomes.
|Summary results||TAVI with SAPIEN 3||SAVR||Incremental|
|Cost per patient||€ 39 052||€ 32 081||€ 6971|
|Life year gained (undiscounted)||14.08||13.22||0.86|
|Median survival (years)||16.50||14.50||2.00|
|QALYs per patient||8.66||7.66||1.00|
|Incremental cost effectiveness ratio (ICER)||€ 6952|
|Incremental net monetary benefit (NMB)||€ 23 111|
|Incremental net health benefit (NHB)||0.77|
|Acute phase cost (first hospitalization and rehabilitation)|
|Index hospitalization||€ 24 781||€ 13 779||€ 11 003|
|Rehabilitation||€ 114||€ 461||-€ 347|
|Pacemaker implantation||€ 506||€ 311||€ 195|
|Acute phase costs||€ 25 401||€ 14 550||€ 10 656|
|Additional costs at 1 year|
|MI||€ 181||€ 92||€ 89|
|Pacemaker implantation complication costs||€ 38||€ 23||€ 15|
|Hospitalization costs||€ 212||€ 316||-€ 104|
|Reintervention costs||€ 117||€ 147||-€ 30|
|Alive and well health state costs||€ 1 258||€ 844||€ 415|
|Treated AF health state costs||€ 48||€ 376||-€ 328|
|Disabling stroke costs||€ 11||€ 221||-€ 210|
|Death costs||€ 0||€ 0||€ 0|
|Overall cost at 1 year||€ 27 267||€ 16 570||€ 10 698|
|Additional lifetime costs|
|Pacemaker implantation complication costs||€ 433||€ 251||€ 182|
|Hospitalization costs||€ 374||€ 353||€ 21|
|Reintervention costs||€ 4464||€ 4941||-€ 477|
|Alive & well health state costs||€ 4120||€ 2590||€ 1530|
|Treated AF health state costs||€ 970||€ 3963||-€ 2993|
|Disabling stroke costs||€ 1424||€ 3414||-€ 1990|
|Additional lifetime costs||€ 11 785||€ 15 512||-€ 3727|
|Total lifetime costs||€ 39 052||€ 32 081||€ 6971|
AF, atrial fibrillation; MI, myocardial infarction; QALY, quality-adjusted life-year.
There were 2 options regarding survival extrapolation. In option #1, transition probabilities were taken from the literature (relative risk of death with AF of 1.517; and relative risk of death with disabling stroke of 2.0520). In option #2, parametric survival fitting was performed based on Kaplan-Meier data from the PARTNER 3. A total of 3 parametric distributions were used (Weibull, Exponential, Gompertz) and adjusted to the survival of the overall Spanish population. Therefore, in the base case, survival estimates were based on transition probabilities due to immaturity of survival data from the trial. Annual mortality risk for ‘alive and well’, and other relative risks for other health states are shown on table 2 of the supplementary data. Option #2 (parametric survival analysis) was explored using alternative hazard ratios (HR) in scenario #3: HR, 0.75 from the PARTNER 3 at 2 years adjusted to Spanish population overall mortality. An additional scenario #4 removed any survival benefit with the SAPIEN 3 valve (HR, 1).
There were 2 options for determining utility decrement: option #1 used utility decrements by health state from the literature adjusted by age and Spanish population standards.21 This was the preferred option because there were very few corresponding events in the PARTNER 3, and estimates from the literature were deemed realistic. The age and population standards adjusted utility decrements were 0.16 for AF22 and 0.42 for disabling stroke.23 Option #2 used treatment options from the PARTNER 3 and was explored within scenario #5. The utility decrement for option #2 was individually extracted from the PARTNER 3 at baseline, after 30 days, 6 months and 1 year, and then converted to Spanish health utilities.24
Costs associated with TAVI and SAVR (procedure, complications, and long-term) are shown on table 3 of the supplementary data. Base case procedure cost information was drawn from the SERGAS.25 We should mention that the SERGAS fee includes market valve and ancillary material price. Also, personnel costs were additionally estimated on a per hour price basis for different professionals. Costs corresponding to complications and health states were drawn from the literature and diagnosis-related groups (DRG). The breakdown of TAVI and SAVR procedure costs are shown on table 4 of the supplementary data. The micro-cost elements are informed from the study conducted by Bayón et al.26 and updated to reflect current TAVI practice in Spanish low-risk patients with sSAS. As costs vary depending on the Spanish region at stake, 3 additional scenarios: 6A, 6B, and 6C were explored using cost information adjusted to reflect current clinical practice in Murcia, Huelva, and Basque regions. Furthermore, a scenario #7 was included to account for early adverse events costs at 30 days.
Key outputs of the model were the overall per-patient costs and QALYs in each arm and ICER.
To evaluate uncertainty, 1-way deterministic sensitivity analyses were performed by varying inputs using confidence intervals and ranges from the literature when available, and plausible ranges when data were unavailable (table 5 of the supplementary data). Multiple parameters were changed and the impact on the results explored. Overall parameter uncertainty was addressed using a probabilistic sensitivity analysis (PSA) (table 6 of the supplementary data). Several scenario analyses were conducted to explore the impact of major structural assumptions as shown on table 7 of the supplementary data. All analyses were performed using Microsoft Excel (Microsoft Corporation, United States).
TAVI with SAPIEN 3 improved QALYs per patient (+ 1.0) with higher costs compared to SAVR of approximately €6971 per patient. This represented an ICER of €6952 per QALY, which is lower compared to the WTP threshold of €30 000/QALY that is commonly referenced in the Spanish setting. Base case results over a 50-year timespan are shown on table 1. Further examination of the breakdown of costs for TAVI vs SAVR revealed that although initial procedural costs in the model were higher with TAVI, costs associated with ‘disabling stroke’ and ‘treated AF’ were somehow lower (table 1, and figure 1 of the supplementary data).
Deterministic sensitivity analyses
Univariate sensitivity analyses are displayed in the Tornado diagram (figure 2). SAPIEN 3 TAVI remained cost-effective regardless of any plausible changes to individual model parameters (note: the 20 parameters with the greatest influence on the model are shown on the diagram). The model was most sensitive to age, SAVR procedural costs, and risk of disabling stroke at 30 days with TAVI.
Probabilistic sensitivity analysis
The results of the PSA confirm the results of the base case analysis. At the conventional WTP threshold of €30 000/QALY, TAVI with SAPIEN 3 remains cost-effective compared to SAVR in 100% of the simulations run in the model (figure 3A). In addition, the cost-effectiveness acceptability curve indicates that SAPIEN 3 TAVI has a 99.9% probability of treatment being cost-effective with a €30 000/QALY WTP threshold (figure 3B). PSA assumptions are shown on table 5 of the supplementary data.
A series of different scenario analyses were conducted to assess the impact of changing various assumptions on the results of the model and the model robustness. TAVI with the SAPIEN 3 valve remains cost-effective compared to SAVR across most of the tested scenarios (table 6 of the supplementary data) including those with different timespans (10, 15, 20, and 30 years). The results from the scenario analyses demonstrate the comparative robustness of the model reported.
This analysis suggests that TAVI with the SAPIEN 3 vavle is likely to be a cost-effective valve replacement option for patients with sSAS and low surgical mortality risk in Spain. TAVI with the SAPIEN 3 valve showed an improvement in QALYs (+ 1.0) associated with slightly increased costs compared to SAVR (approximately €6971 per patient). The ICER benefits for TAVI with the SAPIEN 3 shown in this model represent a highly cost-effective intervention (ICER/QALY €6 952) in the Spanish system with a WTP threshold of €30 000/QALY. Uncertainty was assessed using various sensitivity analyses, and the results appeared robust.
The findings of the current study are supported by other cost-effectiveness studies that show that TAVI with SAPIEN 3 is either dominant or cost-effective in patients of low risk surgical mortality risk.27-31 The Spanish findings are also consistent with cost-effectiveness analyses of TAVI with SAPIEN 3 vs SAVR in France12 and Italy13 using the same model structure.
The current analysis is important because TAVI provides patients with a minimally invasive treatment option and a lower risk of complications and/or rehospitalization plus improved recovery rates and quality of life gains. From a provider perspective, TAVI also brings efficiencies by limiting healthcare resource use, reducing postoperative complications, and shortening hospital stays (including Intensive care unit [ICU] beds).32 Shortening the hospital stay allows more patients to be treated in the same hospital, an important element for a health system in high demand and with long waiting lists. These efficiencies also lead to a reduced risk of infections and contamination,33 which was much welcomed during the recent COVID-19 pandemic. Finally, TAVI reduces the recovery period to normal activity that may not be accounted for in this analysis. Indirect benefits like volunteering, grandchild support or less caregiving support most likely would increase even further the overall benefits of this technology.34
The results of this analysis could also enable greater access to TAVI for Spanish patients with sSAS. Recent studies demonstrate the efficacy and safety profile of transfemoral TAVI in Spain.9 This together with the recent European guidelines suggests that the number of TAVIs will increase, thus rendering many low surgical risk patients with sSAS eligible for TAVI. Moreover, with time, TAVI will likely become simplified even further with shorter admission times;35 this should lead to lower TAVI costs in the future. In this regard, the results of this study could inform policy makers on the management of patients with sSAS in Spain.
This study comes with certain limitations. The first pertains to certain model inputs and assumptions made. In this model, hospitalization data were based on 1- and 2-year data from the PARTNER 3 study with the assumption that this rate remained constant over the model timespan after 2 years. The impact of this assumption is unknown because individuals from both treatment arms in the model remained at risk of hospitalization. The rate of reinterventions was assumed to remain constant after 22 years; the impact of this assumption on modelled outcomes was deemed minimal based on the expectation that nearly 11% of patients would still be alive in the model after this point in time with limited need for reintervention. Despite of this, uncertainty on the longer-term durability of the TAVI device and subsequent reintervention rates in younger patients cannot be disregarded. Disutilities were not included for any intercurrent events because you can run the risk of counting them twice with the health state utilities being applied to patients in the ‘treated AF’ and ‘disabling stroke’ states. This was a conservative assumption because, apart from pacemaker complications, the rates of intercurrent events are generally lower for TAVI with SAPIEN 3 compared to SAVR.6
A second limitation of this study is the generalizability of the results. Conclusions cannot be generalised to the overall population with aortic stenosis because, among others, patients with unfavourable coronary anatomy were excluded from the PARTNER 3 study. Moreover, caution should be observed when trying to generalize any findings from this model to populations outside Spain.
Finally, we should mention that procedural costs across different regions of Spain are heterogenous. In this study, we use publicly available cost data from a region in Spain and our approach is conservative as we additionally account for current practice. We also conducted multiple scenario analyses with other available cost data sets.
Data from the PARTNER 3 suggested that the use of TAVI with the SAPIEN 3 valve was more favorable, on the clinical level, compared to SAVR in patients with sSAS and low surgical mortality risk. The results of this cost-effectiveness model indicate that, in Spain, TAVI could provide a cost-effective option over SAVR for this population with an estimated ICER/QALY value well below the national threshold. The model appeared to be robust with uncertainty assessed by various sensitivity analyses. The results of this cost-effectiveness analysis can support policy makers and healthcare budget holders to optimize the management of Spanish patients with sSAS.
Edwards Lifesciences SA, Switzerland provided funding for the economic assessment and was involved in the analysis as well as in the drafting of this manuscript.
J.M. Vázquez participated in economic data mining, model validation, and manuscript review. E Pinar in economic data mining, and model validation. J. Zamorano participated in data mining, and model validation. J. Burgos participated in data mining and model validation. J. Díaz participated in data mining, and model validation. B. García del Blanco participated in data mining, and model validation. A. Sarmah in data collection and analysis, result preparation, and manuscript drafting and review. P. Candolfi participated in cost analysis and manuscript drafting. J Shore was involved in model development and manuscript review. M. Green participated in model development, and manuscript drafting.
CONFLICTS OF INTEREST
J.M. Vázquez Rodríguez declared department research or training grants from Edwards Lifesciences, Medtronic, and Boston Scientific, and personal advisory fees from Medtronic, and Boston Scientific. J.L. Zamorano declared research grants from Abbott, and Medtronic to the Institution, and speaker fees from Edwards Lifesciences, Bayer, Novo Nordisk, and Daiichi Sankyo. J. Moreu Burgos declared having received fees from Biosensors, Boston Scientific, Cardiva, Edwards Lifesciences, and Medtronic. A. Sarmah declared to be an employee of Edwards Lifesciences and hold stock options. P. Candolfi declared to be an employee of Edwards Lifesciences and hold stock option. J. Shore declared consultancy fees to the employer for developing the economic model. M. Green declared consultancy fees to the employer for developing the economic model. E. Pinar, J.F. Díaz-Fernández, and B. García del Blanco declared no conflicts of interest whatsoever.
Writing support was provided by Zenith Healthcare Communications Ltd (Chester, United Kingdom), and funded by Edwards Lifesciences.
WHAT IS KNOWN ABOUT THE TOPIC?
- Recent clinical trial evidence confirms the clinical benefits of TAVI with the SAPIEN 3 valve for a low surgical risk population compared to SAVR. Furthermore, following favorable recent updates in the American and European guidelines, TAVI can now be considered as a treatment option in low surgical risk patients with sSAS. Regarding the economic evidence, however, TAVI with the SAPIEN 3 valve has proven cost-effective compared to SAVR only in high and intermediate risk patients with sSAS in Spain.
WHAT DOES THIS STUDY ADD?
- Data from the PARTNER 3 suggested that the use of TAVI with the SAPIEN 3 valve was more clinically favorable compared to SAVR in patients with sSAS and low surgical mortality risk. The results of this robust, cost-effectiveness analysis indicate that, in Spain, TAVI could provide a cost-effective option over SAVR for this population with an estimated ICER/QALY value well below the national threshold. Data from the PARTNER 3 together with data from this cost-effectiveness analysis can support policy makers and healthcare budget holders to optimize the management of Spanish patients with sSAS.
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* Corresponding author.
E-mail address: firstname.lastname@example.org (A. Sarmah).
@jmvazrod; @CorazonHuvr; @pepp183; @PascalCandolfi; @CIBER_CV
Introduction and objectives: Transcatheter aortic valve implantation (TAVI) has become the treatment of choice for the management of symptomatic severe aortic stenosis. As it happens with all procedures, the safety and effectiveness of TAVI must be monitored. To this end, we assessed the data available from the Spanish National Health Service from 2014 through 2017.
Methods: The study included patients aged > 50 years treated with TAVI and registered in the Activity Registry of Specialized Health Care from 2014 through 2017 from public and private hospitals in compliance with the National Health System. Multivariate logistic regression analyses were performed to identify factors associated with mortality and complications, and negative binomial models for the mean hospital length of stay (LoS). Standardized rates were used to discriminate both the effectiveness and safety among regions with higher and lower levels of implementation of the technique using the national median as the threshold, (37 implants x 105 habitants) in the 4-year period.
Results: A total of 5454 TAVIs were analyzed. The in-hospital mortality rate dropped from 4.89% in 2014 to 2.7% in 2017. The LoS decreased from 13.1 days in 2014 to 11.3 days in 2017. No differences in mortality were observed among the regions. However, the LoS of regions with a high volume of implants was significantly lower (OR, 0.88; 95%CI, 0.86-0.91; P < .01), as well as the risk of infections (OR, 0.54; 95%CI, 0.32-0.9; P = .02), and pacemaker implantation (OR, 0.77; 95%CI, 0.65-0.91; P < .01).
Conclusions: The use of TAVI in Spain is safe and has grown progressively with improved outcomes regarding morbidity and mortality. Differences among regions have been highlighted regarding patient access to TAVI. This heterogeneity was not associated with mortality but with differences in the morbidity rates.
Keywords: Aortic Stenosis. Surgical aortic valve replacement. Valvular heart disease. Activity Registry of Specialized Health Care. Transcatheter aortic valve implantation. TAVI.
Introducción y objetivos: El implante percutáneo de válvula aórtica (TAVI) se ha consolidado como tratamiento de la estenosis aórtica grave. Como toda intervención, su seguridad y su efectividad deben monitorizarse en condiciones de práctica real. Para ello, se han analizado los datos del Sistema Nacional de Salud disponibles entre los años 2014 y 2017.
Métodos: Se evaluaron todos los pacientes mayores de 50 años con TAVI por vía transfemoral incluidos en el Registro de Actividad de Atención Especializada entre 2014 y 2017 procedentes de centros públicos o concertados. Se hicieron análisis de regresión logísticos para evaluar los factores asociados con la mortalidad y las complicaciones, y modelos binomiales negativos para la estancia media hospitalaria. Se usaron tasas estandarizadas para ajustar diferencias en las variables de efectividad y seguridad entre las diferentes comunidades autónomas, de acuerdo con el alto y bajo volumen de implantación de la técnica, considerando como referencia la mediana nacional (37 implantes por 105 habitantes) durante el periodo de tiempo analizado.
Resultados: En total se analizaron 5.454 casos de TAVI. La mortalidad intrahospitalaria pasó del 4,89% en 2014 al 2,7% en 2017. La estancia media hospitalaria descendió de 13,1 días en 2014 a 11,3 en 2017. A pesar de no observar diferencias en la mortalidad entre comunidades autónomas, aquellas con mayor volumen de implantes tuvieron una menor estancia media hospitalaria (OR = 0,88; IC95%, 0,86-0,91; p < 0,01), menor riesgo de infecciones (OR = 0,54; IC95%, 0,32-0,9; p = 0,02) y menor necesidad de marcapasos permanente (OR = 0,77; IC95%, 0,65-0,91; p < 0,01).
Conclusiones: El uso de TAVI crece progresivamente en España con resultados cada vez mejores respecto al éxito del implante y la morbimortalidad perioperatoria. La variabilidad interregional en las tasas de implante no se relaciona con la mortalidad observada, pero sí con la morbilidad y la estancia hospitalaria.
Palabras clave: Estenosis aórtica. Reemplazo de la válvula aórtica. Registro de Actividad de Atención Especializada. Enfermedad de las válvulas cardiacas. Implante percutáneo de válvula aórtica. TAVI.
Abbreviations LoS: length of stay. PPI: permanent pacemaker implantation. RAE-CMBD: Activity Registry of Specialized Health Care. TAVI: transcatheter aortic valve implantation.
Aortic stenosis is the most common acquired valvular heart disease whose prevalence is around 3% in the population ≥ 65 years up to 7.4% in older ages (≥ 85 years).1 It is also the leading cause of valvular surgery in the adult population.2 Age and sex are among the risk factors (higher incidence rate in men).3,4 After symptom onset, mortality rate is high (up to 50%) during the following years.5,6 Due to the continuing growth of the elderly population in our country,7 a significant burden of disease associated with aortic stenosis is expected8 with the corresponding challenge that this poses to the healthcare system.
Until 14-15 years ago the only therapeutic option was surgical aortic valve replacement. In patients considered inoperable due to their age or comorbidities, the therapeutic alternative was only aimed at symptom control. Transcatheter aortic valve implantation (TAVI) created a new option of therapeutic opportunity for inoperable or high-risk patients at the beginning followed by intermediate-risk patients, and eventually for low-risk patients.9-13 Despite this, the rate of treatment with TAVI in Spain is significantly lower compared to other European countries.14 Although there are numerous reports and registries in Europe on the clinical results of TAVI, the evidence available in Spain on the local results from public ownership sources is scarce although 10 years have already gone by since the first TAVI was performed back in April 2007.14
This study presents the current evidence on the real-world clinical practice available in our country on the use of TAVI including a description of the profile of cases treated, the results obtained in terms of mortality, complications, and length of stay (LoS). Also, the main factors associated are analyzed from the perspective of the Spanish National Health System using the Activity Registry of Specialized Health Care (RAE-CMBD) as the main source of information.
Minimum Data Set
This study is based on information included in the RAE-CMBD of the Spanish Ministry of Health, Consumer Affairs, and Social Welfare. It provides detailed information on the demographic characteristics of hospitalized patients, administrative variables, and clinical variables associated with the diagnoses and procedures of both the patient and type of healthcare received. The diagnoses and procedures registered are coded according to the International Classification of Diseases, Ninth Revision – Clinical Modification (ICM-9-CM) for 2014-2015, and the International Classification of Diseases, Tenth Revision – Clinical Modification (ICM-10-CM) for 2016-2017 that is more specific with diagnoses.
This analysis included all episodes registered from 2014 through 2017 of patients > 50 years of age hospitalized in centers of public or public-private partnership after performing the following procedures: “Endovascular replacement of aortic valve” (ICM-9-CM code: 35.05), and “Replacement of aortic valve with zooplastic tissue, percutaneous approach” (ICM-10-CM code: 02RF38Z). Cases treated with extracorporeal circulation were excluded (ICM-9-CM code: 39.61, and ICM-10-CM code: 5A1221Z) for considering that TAVI does not need this technique, which would, therefore, be a coding mistake of the episode. Similarly, episodes of rehospitalization were excluded to complete the patient’s recovery.
The safety analysis included all complications coded in chapter 17 of ICM-9-CM, and in particular, with codes from category 996: “Complications peculiar to certain specified procedures” including complications not classified under other concepts, and in the use of artificial substitutes involving internal device implantation, among others. On the other hand, in the most recent ICM-10-CM classification, this type of complications can be found under category T82 “Complications of cardiac and vascular prosthetic devices, implants, and grafts”. Also, due to their potential association with TAVI and great interest from the clinical standpoint events such as acute kidney injury, acute myocardial infarction, aortic dissection, stroke, sepsis, and permanent pacemaker implantation (PPI) were considered as well.
A descriptive analysis of the study variables was conducted. Continuous variables were expressed as means and standard deviations. The categorical ones as absolute and relative frequencies. The differences between 2 independent groups were compared using the Student t test or the U Mann-Whitney-Wilcoxon test based on their distribution (parametric or nonparametric, respectively). The chi-square test or Fisher’s exact test were used with the categorical variables. Multivariate models were implemented to identify factors associated with the risk of in-hospital mortality, significant complications (logistic regression), and LoS (negative binomial regression). Demographic and clinical variables were examined as explanatory variables: age, sex, rate of implantation in the autonomous community where the procedure was performed, complications, and level of severity of each case based on the RAE-CMBD classification (stratified depending on the characteristics of each patient, diagnoses, and procedures) and categorized into a 4-level scale:15,16 mild, moderate, major or extreme according to the severity-adjusted Diagnosis Related Groups (DRG).
To analyze the possible differences among autonomous communities in the volume of TAVIs performed, the rates of implantation standardized per 100 000 inhabitants (×105) were estimated. The seasonal population of each region in the period adjusted by age group (50-74, 75-84, ≥ 85), and sex was taken as the reference point.17 Discrimination between high- and low-volume regions was made by categorizing the rates of implantation. Rates above the national average during the study period were considered high-volume regions (37 procedures × 105 inhabitants). Differences in the baseline characteristics of patients treated in high- and low-volume autonomous communities were taken into consideration during the adjustment of multivariate models.
The independent variables of all logistic regression and negative binomial models were reviewed by clinical experts to guarantee their clinical sense and then selected in such a way that the resulting model would minimize the Akaike information criterion.18 Once the best model was determined in each case, the odds ratios (OR) and their 95% confidence intervals (95%CI) were estimated to determine whether a certain factor was associated with a higher risk (OR > 1) in the presence of a given result and then compare the size of several factors.
Regarding the multivariate analysis of complications, when the number of cases registered was low and statistical power of contrast was limited, all major complications were grouped following the clinical criterion once again. This is how factors associated with the risk of bleeding and accidental puncture or laceration (ICM-9-CM: 998.11, and 998.2 | ICM-10-CM: I97.4, I97.6, and I97.5*), acute myocardial infarction (ICM-9-CM: 410.*1 | ICM-10-CM: I21*), PPI (ICM-9-CM: 37.8 | ICM-10-CM: 5A1223Z), sepsis, and infections (ICM-9-CM: 995.91, 995.92, and 998.5 | ICM-10-CM: T81.4XXA, and A41*); acute kidney injury (ICM-9-CM: 584 | ICM-10-CM: N17*); and stroke (ICM-9-CM: 997.02, 434, and 435 | ICM-10-CM: I97.8*0, I66, I63.3, I63.4, I63.5, G45*, and I67.82) were identified and assessed.
All statistical contrasts were bilateral, and differences with P values > .05 were considered statistically significant. Statistical analysis was conducted using the statistical software package R (version 3.6.1).
A total of 5454 cases with transcatheter aortic valve implantation via transfemoral access were accounted for: 763 cases reported in 2014, 1171 in 2015, 1477 in 2016, and 2043 back in 2017. Implantation was more common in women (52.2%), mostly in patients between 81 and 85 years of age, both men (37%) and women (44%). Mean age was 81.12 ± 6.43 years during the entire period. Overall, the most common diagnoses that triggered the patients’ hospitalization were aortic valve disease (79.7%, ICM-9-CM, and ICM-10-CM codes: 424.1, and I35, respectively) followed by mitral valve regurgitation, and rheumatic stenosis (3.1%, ICM-9-CM, and ICM-10-CM codes: 396.2, and T82.0*XA, respectively), and congestive heart failure (2.9%, ICM-9-CM, and ICM-10-CM codes: 428.0, and I08.0, respectively).
Rates of transfemoral TAVI, mortality, and hospital stay
The number of TAVIs performed remained variable across the years, and grew gradually with significant increases reported between 2014 and 2017 both in the number of centers where this procedure was conducted and in the overall number of TAVIs performed. Therefore, the national implantation rate (× 105 inhabitants) doubled, and the mean during the study period was 33 procedures × 105 inhabitants (table 1).
|Overall IR for the 2014-2017 period||Hospital stay||Mortality|
|Adjusted||2014||2015||2016||2017||Overall for the study period||Rate reported during the study period|
|Autonomous community||TAVI (n)||Seasonal population||Est (x 105 inhabitants)||95%CI LL||95%CI UL||LoS||SD||LoS||SD||LoS||SD||LoS||SD||LoS||SD|
95%CI, 95% confidence interval; IR, implantation rate; LL, lower limit; LoS, length of stay (days); SD, standard deviation; TAVI, transcatheter aortic valve implantation; UL, upper limit.
* Due to the peculiarities described in the rendering of the service in these regions, the implantation rate could take a detour with respect to the routine clinical practice in these regions.
The highest mortality rates are due to the negative results reported within the first years (eg, in autonomous community #3, the mortality rate in 2014 was 16.7% but dropped to 3.3% in 2017; in autonomous community #4, the rate in 2014 was 25% but dropped to 7.4% in 2017; in autonomous community #11, the rate in 2014 was 14.3% but dropped to 6.7% in 2017). In all cases, a clearly positive tendency towards a lower procedural mortality rate was reported.
The overall mortality rate during the entire period was 3.6% with an obvious decrease from 2014 (4.8%) through 2017 (2.7%) despite the fact that the severity profile assigned to the patients remained constant across the 4 years studied (in 70% of the patients the severity-adjusted DRG score was extreme).
Regarding the length of hospital stay associated with the procedure, the LoS reported in 2014 was 13.1 ± 12.5 days dropping gradually down to 11.3 ± 10.6 days in 2017 with great variability among the different autonomous communities (table 1). When extreme cases were eliminated (defined as cases with stays > 2 standard deviations with respect to the mean), the mean national hospital stay was 8.9 ± 4.69 days, and differences among autonomous communities were reduced from 6.07 ± 4.8 to 11.35 ± 4.31 days; see table 1.
Complications associated with TAVI
Table 2 describes the complications associated with TAVI. Same as it happened with mortality, a gradual reduction in the rate of the most significant complications was reported from 2014 through 2017. The need for PPI was 12.2%, also with great variability of this complication among the different autonomous communities.
|Mechanical heart valve prosthesis complication||218||4||996.02||56||7.3||47||4||T82.0* XA||49||3.3||66||3.2|
|Other complication of heart valve implantation||143||2.6||996.71||13||1.7||27||2.3||T82.8*7A, T82.9XXA||39||2.6||64||3.1|
|Dissection of aorta||15||0.3||441||2||0.3||3||0.3||I71.0*||3||0.2||7||0.3|
|Bleeding or iatrogenic stroke||40||0.7||997.02||4||0.5||9||0.8||I97.8*0||11||0.7||16||0.8|
|Cerebral artery occlusion||46||0.8||434||8||1||11||0.9||I66, I63.3, I63.4, I63.5||11||0.7||16||0.8|
|Transient cerebral ischemia||27||0.5||435||3||0.4||6||0.5||G45*, I67.82||9||0.6||9||0.4|
|Acute myocardial infarction||87||1.6||410.*1||14||1.8||14||1.2||I21*||25||1.7||34||1.7|
|Permanent pacemaker implantation||663||12.2||37.8||146||19.1||149||12.7||5A1223Z||155||10.5||213||10.4|
|Acute kidney injury||441||8.1||584||74||9.7||90||7.7||N17*||119||8.1||158||7.7|
|Postoperative shock||55||1||998||10||1.3||14||1.2||T81.1* XA||16||1.1||15||0.7|
|Bleeding complicating the procedure||314||5.8||998.11||54||7.1||63||5.4||I97.4*, I97.6*||90||6.1||107||5.2|
|Accidental puncture or laceration during the procedure||156||2.9||998.2||31||4.1||45||3.8||I97.5*||36||2.4||44||2.2|
|Infection following a procedure||45||0.8||998.5||11||1.4||13||1.1||T81.4XXA||12||0.8||9||0.4|
TAVI transcatheter aortic valve implantation. Codes (ICM-10-CM), T82.0
* XA, Other mechanical complication of heart valve prosthesis (initial encounter); T82.8*7A, Other specified complications of cardiac and vascular prosthetic devices, implants and grafts (initial encounter); T82.9XXA, Unspecified complication of cardiac and vascular prosthetic device, implant and graft (initial encounter); I71.0*, Dissection of aorta; I97.8*0, Intraoperative and postprocedural complications and disorders of circulatory system (cardiac surgery); I66, Occlusion and stenosis of cerebral arteries; I63.3, Cerebral infarction due to thrombosis of cerebral arteries; I63.4, Cerebral infarction due to embolism of cerebral arteries; I63.5, Cerebral infarction due to unspecified occlusion or stenosis of cerebral arteries; G45, Transient cerebral ischemic attacks and related syndromes; I67.82, Cerebral ischemia; I21, Acute myocardial infarction; 5A1223Z, Performance of cardiac pacing; N17, Acute kidney failure; T81.1*XA, Shock during or resulting from a procedure (initial encounter); I97.4*, Intraoperative hemorrhage and hematoma of a circulatory system organ or structure complicating a procedure; I97.6*, Postprocedural hemorrhage and hematoma of a circulatory system organ or structure following a procedure; I97.5*, Accidental puncture and laceration of a circulatory system organ or structure during a procedure; T81.4XXA, Infection following a procedure, initial encounter; A41, Sepsis.
Factors associated with mortality risk, hospital stay, and complications associated with TAVI
Table 3 describes the profile of cases treated, and the results of the procedures performed in high- and low-volume regions. High-volume autonomous communities treated older patients (80.47 vs 81.91, P < .001) with a rate of extreme risk that was slightly lower (70.3% in low-volume autonomous communities vs 67.1% in high-volume autonomous communities; P = .013). In these autonomous communities, it was reported that the population treated had a lower rate of comorbidities such as diabetes, arterial hypertension, heart failure, chronic obstructive pulmonary disease or smoking (table 3).
|Low-volume (N = 3002)||High-volume (N = 2452)||P|
|Characteristics of the patient|
|Age; mean (SD)||80.47||6.48||81.91||6.29||< .001*|
|Age group; n (%)|
|Sex (% women), n (%)||1520||50.6||1327||54.1||.011*|
|Level of severity, n (%)|
|Diabetes mellitus; n (%)||1059||35.3||706||28.8||< .001*|
|Hypercholesterolemia; n (%)||1365||45.5||1070||43.6||.185|
|Obesity; n (%)||381||12.7||273||11.1||.085|
|Arterial hypertension; n (%)||1742||58.0||1234||50.3||< .001*|
|Atrial fibrillation; n (%)||1037||34.5||904||36.9||.079|
|Heart failure; n (%)||611||20.4||357||14.6||< .001*|
|COPD; n (%)||330||11.0||207||8.4||.002*|
|Chronic kidney injury; n (%)||634||21.1||482||19.7||.194*|
|Smoking; n (%)||450||15.0||283||11.5||< .001*|
|Use of anticoagulants; n (%)||511||17.0||485||19.8||.01*|
|Death; n (%)||113||3.8||81||3.3||.401|
|Hospital stay (days); mean (SD)||12.72||11.82||10.85||11.08||< .001*|
|Puncture/laceration; n (%)||89||3.0||67||2.7||.667|
|Hemorrhage complicating the procedure; n (%)||156||5.2||158||6.4||.056|
|AMI; n (%)||56||1.9||31||1.3||.098|
|Permanent pacemaker implantation; n (%)||400||13.3||263||10.7||.004*|
|Sepsis and infectious events; n (%)||47||1.6||21||0.9||.026|
|Acute kidney injury; n (%)||215||7.2||226||9.2||.007|
|Stroke; n (%)||54||1.8||41||1.7||.801|
AMI, acute myocardial infarction; COPD, chronic obstructive pulmonary disease; SD, standard deviation.
* Statistically significant differences between high- and low-income autonomous communities.
High-volume of implants defined as regions with implantation rates > national mean of 37 procedures × 105 inhabitants. Level of severity according to the RAE-CMBD case classification.
Procedural results also varied between high- and low-volume autonomous communities: in high-volume regions, the duration of the LoS was shorter and the risk of certain complications like need for PPI, sepsis or infections was lower too. However, these regions reported a higher risk of acute kidney injury in the bivariate analysis (table 3).
Due to these differences, age, sex, and the level of severity of each case were included in the programmed multivariate models to adjust the analyses of the explanatory variables associated with the in-hospital mortality rate. Figure 1 shows that aortic dissection (OR, 20.58; 95%CI, 6.27-62.40; P < .01), and postoperative shock (OR, 18.16; 95%CI, 9.43-35.16; P < .01) were significantly associated with the postoperative mortality rate. The explanatory weight of other complications like acute myocardial infarction, acute kidney injury, cerebral artery occlusion or heart complications was significantly lower. Mortality differences between high- and low-risk autonomous communities did not reach statistical significance in the overall period studied (figure 1).
On the other hand, the higher severity of the cases, and the appearance of some complications contributed to a significant increase in the duration of the LoS (figure 1). The level of severity was also the factor that kept a stronger correlation with the occurrence of complications such as bleeding and accidental puncture or laceration, acute myocardial infarction, PPI, acute kidney injury, and stroke (figure 2). In high-volume autonomous communities, the risk of sepsis or infections and need for PPI was significantly lower compared to low-volume autonomous communities (OR, 0.77; 95%CI, 0.65-0.91; P < .01, and OR, 0.54; 95%CI, 0.32-0.9; P = .02, respectively). Finally, we should mention that high-volume autonomous communities also had a significantly shorter LoS that was 12% shorter compared to low-volume autonomous communities (OR, 0.88; 95%CI, 0.86-0.91; P < .01) as shown on figure 1.
Our study main finding was that transcatheter aortic valve implantation via transfemoral access is safe and effective in Spain. Secondly, with the growing number of procedures performed each year and the experience gained, the rates of non-lethal complications, and mortality (2.7% over the last year studied) have reduced gradually.
It is undeniable that TAVI is a safe and effective procedure according to the scientific evidence available from clinical trials,12,13,19 and meta-analyses.20,21 That is why its indication has probably widened from inoperable high-risk patients to intermediate and low-risk patients. This study includes evidence from sources from the Spanish Ministry of Health, Consumer Affairs, and Social Welfare including data from the real-world routine clinical practice in our country.
In Spain, data from the National Registry of Activities in Interventional Cardiology of the Spanish Society of Cardiology Working Group on Hemodynamics and Interventional Cardiology22 and from RAE-CMBD show a considerable increase in the number of cases treated in the 2014-2017 period22 in all autonomous communities. Even so, in our country, the rate of TAVI is still significantly lower compared to other countries.14 We should mention the ongoing improvement reported in the rates of mortality (56.25% reduction in the study period), non-lethal complications, and LoS despite the high rates (around 70%) of cases reported of extreme severity according to the codification of cases in the RAE-CMBD.
Unlike previous studies that showed a worse prognosis in men after implantation data do not show any significant differences based on sex.23 Indeed, the factors that seem to be associated with a higher mortality rate are postoperative shock, sepsis, aortic dissection, and myocardial infarction. In this case, the patient’s risk ratio and the volume of implantation are clearly associated with a different mortality rate, which may have to do with the fact that more experience has been gained with this procedure in the entire country. Consistent with this, data from the CMBD have shown a better mortality rate after conventional surgical aortic valve replacement of 3.3% in 2017 (3.6% in patients between 70 and 80 years of age, and 4.3% in patients > 80 years of age).24
The rate of PPI found was similar to the one reported by other authors in our country.22 In this case, coding the severity of the cases treated was actually associated with a higher risk. The need for PPI after TAVI has been associated, above all, with the type of valve used (this need is greater with self-expanding valves).25 In our analysis, it is impossible to distinguish the type of valve used because this information is not on the data provided by the RAE-CMBD. Both the need for postoperative PPI and the appearance of infectious processes and sepsis after the procedure were inversely associated with a higher number of procedures being performed. This association between the volume of procedures performed and fewer complications has already been described in different settings such as after coronary revascularization26 or after conventional surgical aortic valve replacement,24 among others.
Added to its clinical benefits, TAVI has consolidated as a cost-effective alternative to conventional surgical aortic valve replacement. The fact that the procedural results of TAVI have become safer and more effective gradually with lower mortality and morbidity rates and shorter LOSs is probably associated with the experience gained by the surgeons, the volume of procedures performed, and the technical and technological advances made.24
The growing elderly population in our country and the growing number of indications are the reason why the number of TAVI-eligible patients has been growing.1,11 In this sense, it is important to add new evidence to contribute to the assessment of the health outcomes of these procedures27 to guarantee homogeneous quality services in our National Health System. Also, to provide assessment mechanisms to the strategic lines defined in cardiovascular health28 since TAVI has consolidated a cost-effective option compared to conventional surgical aortic valve replacement.29,30
The use of an administrative database to obtain information has obvious pros and cons. On the one hand, it allows us to draw a great deal of information from the national census thanks to the obligatory nature of this registry. Also one of its strengths is the high data standardization.27 However, the administrative nature of the RAE-CMBD whose clinical variables are based on the discharge summary, the thoroughness of coding, and the possible inconsistencies among centers when implementing the codes can impact the accuracy of the results. However, since the period analyzed is a 4-year period, we could say that there are no substantial changes in coding capable of impacting the results significantly. Still, we should mention that the specific codes of complications of ICM-9-CM may not include all the complications that can occur during TAVI. Despite of this, all major clinical complications for the analysis of procedural results were studied. On the other hand, the analysis conducted took into consideration data from the RAE-CMBD until 2017, the most recent ones collected to this date. Also, it would be good to analyze data collected over the last years to see how results evolved. We should expect these results to be even better given the increased number of TAVIs performed, the surgeons’ greater experience, and the improved technology available. This should be analyzed by future studies.
Added to this, we should mention that the information collected in this analysis comes from procedures registered in public or public centers with shared activity. Therefore, discrepancies can be found with the data published by the National Registry of Activities in Interventional Cardiology of the Spanish Society of Cardiology Working Group on Hemodynamics and Interventional Cardiology in absolute terms.22 Still, both sources barely differ in the percentage of cases seen that require PPI (overall difference of 2% in 2016, and 0.1% in 2017 being the data from the Registry of the Spanish Society of Cardiology Working Group on Hemodynamics and Interventional Cardiology) greater.
One of the last limitations of this study is that only the episode that triggered the implantation was analyzed, and no long-term results were obtained, which would provide quality information to assess the extent and cost of healthcare. However, the results from this study are interesting to the extent that they provide key information on aspects to go deeper in the generation of arguments for quality healthcare management.
TAVI is a safe and effective procedure whose implantation rate is on the rise. Still, there is a huge variability between different autonomous communities and hospitals in Spain. This procedure is mostly performed in patients > 75 years of age with low morbidity and mortality rates that can be compared absolutely to those of conventional surgery. Rates have been going down over the 4 years studied (2014-2017) with gradual reductions in the postoperative LoS, especially in autonomous communities with higher implantation rates.
This study has been funded by Edwards Lifesciences S.L.
M. Álvarez-Bartolomé, and J. Cuervo conducted both the validation and statistical management of data. All authors contributed to the study design, conducted the critical review of the manuscript, and gave their final approval. Also, they take full responsibility in all aspects of the study by guaranteeing its integrity and accuracy.
CONFLICT OF INTERESTS
B. Martí-Sánchez is a member of Edwards Lifesciences S.L., the sponsor of this study. J. Cuervo is a member of Axentiva Solutions and received fees for his scientific consulting work for Edwards Lifesciences S.L.
WHAT IS KNOWN ABOUT THE TOPIC?
- The rate of TAVI via transfemoral access is significantly lower in Spain compared to other European countries. Also, even though a decade has passed since the first implantation was performed, there is still scarce evidence on the use and results of this procedure in our country.
WHAT DOES THIS STUDY ADD?
- The study provides solid and precise information on the safety, effectiveness, and results of the use of TAVI in the Spanish population.
- There is inter-territory variability in the use of TAVI. Still, the results show low mortality and morbidity rates and a gradual reduction of the mean hospital stay in the study period.
- The rate of complications and mortality seems to go down as more and more TAVIs are performed.
- Higher implantation rates were associated with shorter hospital stays, and a lower risk of permanent pacemaker implantation and infections during the hospital stay.
1. Ferreira-González I, Pinar-Sopena J, Ribera A, et al. Prevalence of calcific aortic valve disease in the elderly and associated risk factors:A population-based study in a Mediterranean area. Eur J Preventive Cardiol. 2013;20:1022-1030.
2. Salinas P, Moreno R, Calvo L, et al. Seguimiento a largo plazo tras implante percutáneo de válvula aórtica por estenosis aórtica grave. Rev Esp Cardiol. 2016;69:37-44.
3. Izquierdo-Gómez MM, Hernández-Betancor I, García-Niebla J, Marí-López B, Laynez-Cerdeña I, Lacalzada-Almeida J. Valve Calcification in Aortic Stenosis:Etiology and Diagnostic Imaging Techniques. BioMed Research International. 2017;5178:1-12.
4. Stewart BF, Siscovick D, Lind BK, et al. Clinical Factors Associated With Calcific Aortic Valve Disease fn1fn1This study was supported in part by Contracts NO1-HC85079 through HC-850086 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. J Am Coll Cardiol. 1997;29:630-634.
5. Ramaraj R, Sorrell VL. Degenerative aortic stenosis. BMJ (Clinical research ed). 2008;336:550-555.
6. Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of Aortic-Valve Sclerosis with Cardiovascular Mortality and Morbidity in the Elderly. N Engl J Med. 1999;341:142-147.
7. INE. Nota de prensa 20 de octubre de 2016. Proyecciones de Población 2016-2066. 2016;2066. Available online:https://www.ine.es/prensa/np994.pdf. Accessed 29 June 2020.
8. Thaden JJ, Nkomo VT, Enriquez-Sarano M. The Global Burden of Aortic Stenosis. Prog Cardiovasc Dis. 2014;56:565-571.
9. Leon MB, Smith CR, Mack M, et al. Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery. N Engl J Med. 2010;363:1597-1607.
10. Duncan A, Ludman P, Banya W, et al. Long-term outcomes after transcatheter aortic valve replacement in high-risk patients with severe aortic stenosis:the U.K. Transcatheter Aortic Valve Implantation Registry. JACC Cardiovasc Interv. 2015;8:645-653.
11. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2017;38:2739-2791.
12. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients. N Engl J Med. 2019;380:1695-1705.
13. Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. 2019;380:1706-1715.
14. Biagioni C, Tirado-Conte G, Nombela-Franco L, et al. Situación actual del implante transcatéter de válvula aórtica en España. Rev Esp Cardiol. 2017;70(Supl1):6-8.
15. Ministerio de Sanidad, Consumo y Bienestar Social. Grupos Relacionados de Diagnóstico APR-GRD V32. Norma Estatal 2017.;2019. Available online https://www.mscbs.gob.es/estadEstudios/estadisticas/docs/CMBD/Nota_difus_Norma_Estatal_2017.pdf. Accessed 3 Jul 2020
16. Subdirección General de Información Sanitaria e Innovación. Ministerio Sanidad, Servicios Sociales e Igualdad. Norma Estatal RAE-CMBD 2016 –Nota Informativa.;2018. Available online http://pestadistico.inteligenciadegestion.msssi.es/. Accessed 29 Jun 2020
17. Instituto Nacional de Estadística. Tablas de Mortalidad Por Año, Comunidades y Ciudades Autónomas, Sexo, Edad y Funciones. Available online https://www.ine.es/jaxiT3/Tabla.htm?t=27154&L=0. Accessed 29 Jun 2020.
18. Calcagno V, de Mazancourt C. glmulti:An R Package for Easy Automated Model Selection with (Generalized) Linear Models. J Statistical Software. 2010;34:1-29.
19. Castrodeza J, Amat-Santos IJ, Blanco M, et al. Propensity score matched comparison of transcatheter aortic valve implantation versus conventional surgery in intermediate and low risk aortic stenosis patients:A hint of real-world. Cardiol J. 2016;23:541-551.
20. Sardar P, Kundu A, Chatterjee S, et al. Transcatheter versus surgical aortic valve replacement in intermediate-risk patients:Evidence from a meta-analysis. Catheter Cardiovasc Interv. 2017;90:504-515.
21. Khan SU, Lone AN, Saleem MA, Kaluski E. Transcatheter vs surgical aortic-valve replacement in low- to intermediate-surgical-risk candidates:A meta-analysis and systematic review. Clin Cardiol. 2017;40:974-981.
22. Sección de Hemodinámica y Cardiología Intervencionista. Sociedad Española de Cardiología. Registro Nacional de Actividad En Cardiología Intervencionista 2017.;2018. Available online https://www.hemodinamica.com/wp-content/uploads/2018/11/PRESENTACIO%CC%81N-DEFINITIVA-REGISTRO-2017.pdf Accessed 27 Jun 2020.
23. European Society of Cardiology. Women less likely to die after TAVI than men. Published online 2013. Available online https://www.escardio.org/The-ESC/Press-Office/Press-releases/Women-less-likely-to-die-after-TAVI-than-men. Accessed 29 Jun 2020.
24. Carnero-Alcázar M, Maroto-Castellanos LC, Hernández-Vaquero D, et al. Isolated aortic valve replacement in Spain:national trends in risks, valve types, and mortality from 1998 to 2017. Rev Esp Cardiol. 2021;74:700-707.
25. Deharo P, Bisson A, Herbert J, et al. Impact of Sapien 3 Balloon-Expandable Versus Evolut R Self-Expandable Transcatheter Aortic Valve Implantation in Patients With Aortic Stenosis:Data From a Nationwide Analysis. Circulation. 2020;141:260-268.
26. Goicolea Ruigómez FJ, Elola FJ, Durante-López A, Fernández Pérez C, Bernal JL, Macaya C. Coronary artery bypass grafting in Spain. Influence of procedural volume on outcomes. Rev Esp Cardiol. 2020;73:488-494.
27. Íñiguez Romo A, Bertomeu Martínez V, Rodríguez Padial L, et al. The RECALCAR Project. Healthcare in the Cardiology Units of the Spanish National Health System, 2011 to 2014. Rev Esp Cardiol. 2017;70:567-575.
28. Ministerio de Sanidad. El Ministerio de Sanidad traslada a las CCAA el borrador de la Estrategia en Salud Cardiovascular del SNS. Available online https://www.mscbs.gob.es/gabinete/notasPrensa.do?id=4993. Accessed 20 Oct 2020.
29. Ribera A, Slof J, Andrea R, et al. Transfemoral transcatheter aortic valve replacement compared with surgical replacement in patients with severe aortic stenosis and comparable risk:Cost–utility and its determinants. International J Cardiol. 2015;182:321-328.
30. Baron SJ, Wang K, House JA, et al. Cost-Effectiveness of Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Intermediate Risk. Circulation. 2019;139:877-888.
* Corresponding author: Servicio de Cardiología, Hospital Álvaro Cunqueiro, Estrada Clara Campoamor 341, 36213 Vigo, Pontevedra, Spain.
E-mail address: Andres.Iniguez.Romo@sergas.es (A. Iñiguez-Romo).
Introduction and objectives: Vascular complications remain a potential problem after transcatheter aortic valve implantation (TAVI). Although suture-based vascular closure devices are most often used for vascular closure purposes, alternative plug-based vascular closure devices like the MANTA (Essential Medical Inc., United States) stand as a bail-out option for patients with failed suture-based closure devices. Since knowing the exact vessel depth is essential to use this device correctly before inserting the large introducer, we aimed to validate 2 different measurement techniques including preoperative multidetector computer tomography (MDCT) plus an alternative technique with the Angio-Seal device (Terumo Medical Corporation, United States) compared to a vendor specific measuring tool.
Methods: In patients eligible for TAVI, the depth of the femoral artery was measured preoperatively using MDCT, and then perioperatively with the Angio-Seal device. Both measurements were associated with the actual depth after puncture using the vendor-specific tool of the MANTA device.
Results: In a total of 168 patients treated with transfemoral TAVI, the depth of the vessel was measured both pre and perioperatively. The measurements obtained from the preoperative MDCT revealed the existence of a moderate correlation compared to the preoperative measurements obtained (r = 0.64; P < .001). Measurements obtained with the Angio-Seal device revealed a high correlation with the measuring tool included (r = 0.99; P < .001). Overall, 10 patients required the bail-out option with the MANTA device due to failed suture-based vascular closure devices.
Conclusions: In case of a failed suture-based vascular closure device after TAVI, the plug-based MANTA device can be used as a bail-out strategy. However, the measurement of the vessel depth obtained from preoperative MDCTs is not accurate enough for safe MANTA insertions. Measurements with the Angio-Seal device before inserting the large TAVI sheath stand as a simple solution to obtain exact measurements facilitating the use of the bail-out MANTA in case of failed suture-based closure vascular devices after TAVI.
Keywords: TAVI. Transfemoral. Access site complication. Vascular closure.
Introducción y objetivos: Entre las potenciales complicaciones del implante percutáneo de válvula aórtica (TAVI) se encuentran las complicaciones vasculares. Los dispositivos de sutura son los más utilizados para el cierre vascular, pero algunos sistemas de cierre con colágeno (MANTA, Essential Medical Inc., Estados Unidos) ofrecen una solución de rescate cuando los de sutura fallan. Para la correcta implantación de este dispositivo es necesario conocer la profundidad exacta de la arteria femoral antes de la inserción del introductor del TAVI. El objetivo de este estudio fue validar 2 técnicas diferentes de medida, la tomografía computarizada con multidetector (TCMD) y una técnica alternativa que emplea el dispositivo Angio-Seal (Terumo Medical Corporation, Estados Unidos), en comparación con el sistema específico de medida del dispositivo MANTA.
Métodos: En pacientes que recibieron TAVI, se midió la profundidad de la arteria femoral mediante TCMD antes y durante el procedimiento con un dispositivo Angio-Seal. Ambas medidas se correlacionaron con la real obtenida tras la punción mediante el medidor del dispositivo MANTA.
Resultados: En 168 pacientes a quienes se realizó TAVI transfemoral, se midió la profundidad de la arteria femoral antes y durante el procedimiento. La medida con TCMD previa al procedimiento mostró una correlación moderada con las medidas durante el procedimiento (r = 0,64; p < 0,001). La medida con el dispositivo Angio-Seal mostró una alta correlación con la herramienta de medición (r = 0,99; p < 0,001). En total, 10 pacientes necesitaron rescate con dispositivo MANTA por fracaso de los dispositivos de sutura.
Conclusiones: En caso de fracaso de los dispositivos de sutura tras TAVI, el dispositivo de tapón de colágeno MANTA puede actuar como técnica de rescate. Sin embargo, la medida antes del procedimiento obtenida con TCMD no es precisa para implantar correctamente el dispositivo MANTA. La medición con un dispositivo Angio-Seal antes de la inserción del introductor del TAVI puede ser una solución sencilla para conocer las medidas con exactitud y para la inserción de rescate de un dispositivo MANTA, cuando fracasan los dispositivos de cierre por sutura.
Palabras clave: TAVI. Transfemoral. Complicaciones en punto de acceso. Cierre vascular.
Abbreviations MDCT: multidetector computer tomography. TAVI: transcatheter aortic valve implantation.
Despite growing experience and the development of new closure devices, the rates of vascular complications after transcatheter aortic valve implantation (TAVI) remain high (between 5% and 18%).1-6 Recently, a new collagen plug-based device was recently introduced. Favorable results have been reported regarding the rate of vascular complications associated with this new collagen plug-based MANTA vascular closure device (Essential Medical Inc., United States) compared to suture-based devices.7-9 However, due to several potential disadvantages (including major bleeding events with rates that go from 1% to 16%), limited data on future vessel accessibility, and significantly higher costs, the routine use of the new device has been put into question compared to suture-based devices.7,10,11 Since puncture sites can safely be closed using suture-based devices, the new generation of plug-based systems may, therefore, be a valuable alternative as a bail-out strategy in case of failed suture-based devices.
However, one drawback of the MANTA system as a bail-out device is that it requires to know exactly the distance between the skin incision and the vessel for safe deployment and functionality purposes before inserting the large introducer sheath. Unfortunately, the vendor-specific measuring tool is not wrapped separately. Therefore, we aimed to validate 2 alternative measuring techniques including the preoperative multidetector computer tomography (MDCT), and the Angio-Seal device before inserting the large introducer sheath to get significant information of the depth of the vessel without having to unwrap the device.
Patient and procedural characteristics
Patients agreed to the data retrospective anonymized analysis. A total of 168 consecutive patients with severe aortic stenosis scheduled for TAVI were included. All patients were evaluated by interdisciplinary heart teams. As a standard procedure all patients received MDCT to plan TAVI. All procedures were performed under local anesthesia. In all the cases both femoral arteries were used. One side for the TAVI sheath and the other for the pigtail catheter for the angiography plus a 7-Fr arterial line for hemodynamic monitoring. Routine closure follows with a Proglide closure device and a 6-Fr Angio-Seal device for the TAVI side plus a 6-Fr Angio-Seal for the contralateral side.
Measuring the depth of the vessel
Preoperatively, the depth of the vessel was measured using preoperative MDCT. The depth of the vessel was measured on a split screen using the Picture Archiving and Communication System imaging modality. In all the patients the measurements were obtained perpendicularly at skin level towards the femoral artery at mid-femoral head level (figure 1).
Perioperatively, measurements were obtained using the introducer sheath of a 6-Fr Angio-Seal device as follows. The introducer sheath reaches the vessel when bleeding through the indicator channel of the introducer sheath starts (figure 2A). In this position the letter or dot on the outside of the introducer sheath is noted and translated into distance using the schematic representation shown on figure 2B and table 1. According to the instructions for use of the MANTA vascular closure device, 1 cm had to be added. Then, the deployment depth of the MANTA device was noticed.12
Following these precautionary measures, 1 suture-based Proglide closure device was inserted and TAVI was performed as usual.
|Angio-Seal||Vessel depth (cm)|
During closure, operators aimed for systolic blood pressures < 160 mmHg. Heparin, and protamine were used at the operator’s discretion. The delivery sheath was removed with a standard on-site wire while the access site was closed using the prepared Proglide system plus an additional 6-Fr Angio-Seal device. If the prepared suture-based system ruptures or in the presence of remaining severe bleeding following the insertion of the 8-Fr Angio-Seal introducer sheath, the introducer of the Angio-Seal was removed without implanting the plug, a MANTA vascular closure device was inserted, and then released based on the predefined vessel depth. The wire was removed after the final angiography to identify all possible access site-related complications. The contralateral side was closed using a 6-Fr Angio-Seal device.
A 300 mg clopidogrel loading dose was administered postoperatively, but not in patients already on clopidogrel. In patients on oral anticoagulants, therapy was interrupted prior to the procedure. All operators were familiar with all the vascular closure devices used.
Postoperative follow up
All patients received compression bandage at the puncture site for 6 hours and were monitored on an intermediate care unit for, at least, 24 hours. All the medical attention provided to the puncture site due to residual bleeding, and all postoperative imaging such as MDCT scan or duplex sonography were documented until hospital discharge.
The categorical variables were expressed as counts (percentages) while the continuous variables were expressed as median [interquartile range]. The correlation between measurements was estimated using Spearman’s rank correlation coefficient.
The data supporting this study findings are available from the corresponding author upon reasonable request.
A total of 168 patients treated with transfemoral TAVI were included. Patients were typical TAVI patients. The patients’ baseline characteristics are shown on table 2.
|Clinical characteristics||N = 168|
|Age (years)||83 [79.3-86.0]|
|Gender (male) (%)||66 (39.0%)|
|Body mass index (kg/m2)||26.9 [24.2-30.5]|
|NYHA ≥ III (%)||144 (85.2)|
|Logistic EuroSCORE I (%)||16.8 [12.2-22.8]|
|Arterial hypertension (%)||152 (89.9%)|
|Coronary artery disease (%)||113 (66.8%)|
|s/p PCI (%)||62 (36.6%)|
|s/p CABG (%)||17 (10.1)|
|Atrial fibrillation (%)||67 (39.6)|
|Pulmonary hypertension (%)||12 (7.1%)|
|Diabetes mellitus (%)||59 (34.9%)|
|Peripheral artery disease (%)||29 (17.1%)|
|COPD (%)||34 (20.1%)|
|s/p stroke (%)||17 (10.1%)|
CABG, coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; PCI, percutaneous coronary intervention; NYHA, New York Heart Association; s/p, status post.
Measurements from preoperative MDCTs were obtained from all patients revealing a moderate correlation compared to perioperative measurements obtained using the vendor-specific MANTA mea- suring tool (r = 0.64; P < .001; figure 3).+
Measurements using the Angio-Seal device were also successfully obtained from all patients revealing a high correlation with the vendor-specific MANTA measuring tool (r=0.99; P < .001).
Successful vascular closure was achieved in 158 cases using as a standard closure including the suture-based Proglide and the 6-Fr Angio-Seal device. The bail-out MANTA device was required in 10 patients (5.9%) due to Proglide suture rupture (n = 5) or remaining severe bleeding after insertion of the Angio-Seal introducer sheath (n = 5). The MANTA closure device was successfully inserted thanks to the measurements obtained with the Angio-Seal device before large sheath insertion. A total of 40 patients (23%) needed medical attention on the puncture site including prolonged pressure bandage or CT scan or duplex sonography. A total of 7 patients (4.1%) required postoperative surgery at the puncture site. One patient already carried a previous MANTA bail-out device that eventually led to a complete vascular occlusion due to known arterial occlusive disease. A total of 4 patients suffered a pseudoaneurysm after the routine use of the Proglide and the Angio-Seal that could not be treated by thrombin injection.
Although the rate of access site-related vascular complications after TAVI has decreased over the last few years, these complications are still associated with higher mortality and morbidity rates.2,3,6,13 In this context, suture-based closure devices such as the Prostar or the Proglide are safe and effective widely used tools.14 Although the use of the Prostar is associated with a lower risk of vascular stenosis, the use of the Proglide device has led to lower rates of adverse events such as device malfunction or residual bleeding.2,13,15,16 However, both systems rely on a similar suture-based technique that demands careful preparation before the large delivery sheath can be inserted. The safe use of these closure devices after the insertion of large delivery sheaths is not possible anymore. Therefore, in case of closure device failure and severe bleeding, covered stent implantation using the cross-over technique or surgery to achieve hemostasis may be the only option left. Although the implantation of a covered stent graft is an effective treatment option for bleeding control, implanting covered stents using the cross-over technique can be challenging. Also, the external iliac and common femoral arteries are exposed to flexion of the hip joint, which may be associated with higher stent compression and fractures.17-19 Additionally, the costs of covered stents are high.
Surgery should be spared as the last resort option only as it often needs to be performed under general anesthesia and the loss of blood is high until the surgical cut-down is prepared. Furthermore, wound infection or lymphatic fistulae may occur, thus delaying the patient’s mobilization after TAVI, which may be associated with pneumonia or thrombosis.
Recently, a new plug-based closure device, the MANTA vascular closure device, has entered the clinical arena, and proved its efficacy and safety profile after TAVI. The first reports show rapid hemostasis and low rates of complications after implantation of the MANTA device, even lower compared to the Prostar and the Proglide vascular closure devices.9 In contrast with this, a recently published randomized clinical trial showed similar results regarding access site bleedings compared to the Proglide system. However, while suture-based closure required additional closure devices more often like the Proglide or the Angio-Seal, the MANTA closure device numerically required complex maneuvers more often like covered stents or surgical bail-out strategies. The reason behind this may be the crossing of the wire through the toggle, which cannot be re-accessed using additional devices like the Angio-Seal or the Proglide.20
The considerably higher costs involved, 4 times more expensive compared to the Proglide, the unknown influence on the femoral artery wall, and re-access after device implantation have delayed the quick market penetration of this device as well as its routine use.
However, when using the MANTA vascular closure device, it is of utmost importance to measure the distance between the skin and the vessel accurately to ensure the precise placement of the anchor. During a scheduled MANTA procedure, this measurement is routinely obtained before the insertion of the large delivery sheath using a dedicated 8-Fr device that comes together with the MANTA device in the sterile package. This measurement may be cumbersome and yield inaccurate values if performed after the large sheath has been inserted given the degree of device-related bleeding. Therefore, we evaluated 2 different techniques to obtain this important data before the insertion of a large introducer device without having to unwrap the device to be prepared for a potential bail-out use. Compared with previous data we proved that a moderate correlation exists in the measurements obtained from preoperative MDCT only that were not good enough to allow the use of the MANTA device safely.21 An inaccurate release of the system could lead to malapposition with persistent major bleeding especially in small or heavily calcified vessels or even to the vessel total occlusion. This inaccuracy may be explained by a smaller angle in the direction of the stitches compared to the perpendicular measurements obtained on the MDCT or to a different distribution or position of a skin flap in very obese patients during the MDCT and the procedure.
In contrast, the measurements obtained with the Angio-Seal device followed by an imaging-based predefinition of the corresponding MANTA implantation depth kept a close association with the measurements of the MANTA device. With this information, the femoral artery can be safely closed after a failed Proglide system. Unsolvable failed suture-based device with an additional Angio-Seal or Proglide due to severe bleeding or suture rupture occurred in 5.9% of the patients. Bail-out with MANTA insertion was successful in all patients. Only 1 patient required surgery due to a complete vascular occlusion (Thrombolysis in Myocardial Infarction grade-0 flow) associated with the MANTA device. In retrospect, a prior MDCT had revealed a very small vessel diameter and wall calcification at the puncture site. In these patients, a surgical cut-down would have been the access of choice.
The method presented here is also helpful in other clinical settings without prior MDCT in which large bore sheath are used such as delayed closures after emergency extracorporeal membrane oxygenation or Impella device placement (Abiomed Inc., United States). In these cases, a wire can be inserted through the arterial cannula or Impella CP introducer, and late vascular closure can then be safely achieved using a MANTA vascular closure device. To avoid the unpacking of the sterile device before the simple measuring method the use of an Angio-Seal is cost-effective, not time consuming, and provides information for future reference in case it is needed.
The lack of randomization, and the small number of patients are obvious limitations of this study that should be taken into consideration when analyzing the data presented here.
Compared to MDCT measurements, the routine measurement of vessel depth using the Angio-Seal device stands as a simple option to obtain exact values to allow the bail-out use of the MANTA device in cases of failed suture-based closure device after TAVI. This method can also be used effectively in cases of delayed vascular closures of late explantations of the Impella device or emergency cannulations for venoarterial extracorporeal membrane oxygenation.
J. Blumenstein, T. Maruskin, O. Husser, and H. Möllmann contributed to the design, analysis, and writing of this manuscript. D. Sötemann, C. Eckel, C. Grothusen, G. Dohmen, C. Tesche, and H. Al.Terki contributed to both the writing and supervision of the manuscript.
CONFLICTS OF INTEREST
Neither one of the authors have made any disclosures regarding this manuscript, and they have all met all the requirements defined by the International Committee of Medical Journal Editors regarding the criteria for authorship of scientific articles.
WHAT IS KNOWN ABOUT THE TOPIC?
- Vascular closure can often be performed safely using suture-based devices after TAVI. However, suture ruptures or insufficient closures can directly lead to major vascular complications. In cases like this, closure can be performed using a different plug-based device (Manta Device). However, one drawback of this device is that it requires to know exactly the distance between the skin incision and the vessel for safe deployment and functionality purposes before inserting a large introducer sheath.
WHAT DOES THIS STUDY ADD?
- This study proved that preoperative MDCT obtained inappropriate measurements of the vessel depth. However, a new measuring technique can be established using an Angio-Seal device before inserting the large introducer sheath. In case of failed suture-based closures, the exact depth of the vessel should be known to be able to use a Manta device for bail-out closures. In addition, this technique can also be effectively in case of delayed vascular closures of late explantations of Impella devices or in cases of emergency cannulations for venoarterial extracorporeal membrane oxygenation.
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* Corresponding author: Department of Internal Medicine I, St.-Johannes-Hospital. Johannesstraße 9-13, 44139 Dortmund, Germany.
E-mail address: email@example.com (J. Blumenstein).
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