Cost-Effectiveness Analysis of SAPIEN 3 Transcatheter Aortic Valve Implantation Procedure Compared With Surgery in Patients With Severe Aortic Stenosis at Low Risk of Surgical Mortality in France.

OBJECTIVES: The clinical and cost-saving benefits of transcatheter aortic valve implantation (TAVI) over surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis who are at high or intermediate risk of surgical mortality are supported by a growing evidence base. The PARTNER 3 trial (Placement of AoRTic TraNscathetER Valve Trial) demonstrated clinical benefits with SAPIEN 3 TAVI compared with SAVR in selected patients at low risk of surgical mortality. This study uses PARTNER 3 outcomes in combination with a French national hospital claim database to inform a cost-utility model and examine the cost implications of TAVI over SAVR in a low-risk population. METHODS: A 2-stage cost-utility analysis was developed to estimate changes in both direct healthcare costs and health-related quality of life using TAVI with SAPIEN 3 compared with SAVR. Early adverse events associated with TAVI were captured using the PARTNER 3 data set. These data fed into a Markov model that captured longer-term outcomes of patients, after TAVI or SAVR intervention. RESULTS: TAVI with SAPIEN 3 offers meaningful benefits over SAVR in providing both cost saving (€12 742 per patient) and generating greater quality-adjusted life-years (0.89 per patient). These results are robust with TAVI with SAPIEN 3 remaining dominant across several scenarios and deterministic and probabilistic sensitivity analyses. CONCLUSIONS: This model demonstrated that TAVI with SAPIEN 3 was dominant compared with SAVR in the treatment of patients with severe symptomatic aortic stenosis who are at low risk of surgical mortality. These findings should help policy makers in developing informed approaches to intervention selection for this patient population.

Percutaneous mitral valve repair in severe secondary mitral regurgitation: Analysis of index hospitalization and economic evaluation based on the MITRA-FR trial.

BACKGROUND: Percutaneous mitral valve repair (pMVR) is reimbursed in France for severe secondary mitral regurgitation (SMR), but French data regarding the hospitalization index stay are lacking. AIMS: Our objectives were to describe the index hospitalization stay and to evaluate the cost of hospital stay for pMVR used in SMR. METHODS: A secondary evaluation based on patients who were randomized to the intervention group of the MITRA-FR study was undertaken. The economic evaluation was conducted according to the French hospital perspective. Medical resource use was estimated using specific data collected from patients enrolled in the MITRA-FR study and non-specific data from national statistics. RESULTS: The population was represented by 144 patients who underwent pMVR at 33 French centres. There was a mean±standard deviation of 7.9±1.5 hospital staff during procedures. The mean procedure duration was 154±68 minutes and increased with the number of implanted clips. Median total length of stay was 8 days. The occurrence of a serious adverse event was not associated with an increased risk of admission to the critical care unit, but was associated with an increased length of stay. The mean total cost was 28,025±3424€, which includes 21,547€ for the cost of medical devices used during pMVR and 6478±3424€ for other costs. CONCLUSION: The cost of pMVR is substantial for patients with SMR, which advocates for further efforts to identify the patients with SMR who are likely to derive a clear clinical benefit from the procedure.

Dismal Outcomes and High Societal Burden of Mitral Valve Regurgitation in France in the Recent Era: A Nationwide Perspective.

Background Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population-based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level. Methods and Results In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In-hospital and 1-year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1-year mortality or all-cause readmission and 1-year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively. Conclusions At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390-615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.

Successful linkage of French large-scale national registry populations to national reimbursement data: Improved data completeness and minimized loss to follow-up.

BACKGROUND: Registries, a cornerstone of contemporary medicine, frequently suffer from incomplete documentation and losses to follow-up. By linking data to a single-payer national claims database, national registries may be enriched and the quality enhanced. AIMS: To explore the value of data from the French Système National des Données de Santé (SNDS) as a resource to enhance the quality of registries when combined with data from electronic case report forms, and to assess the power to minimize data gaps and losses to follow-up. METHODS: A probabilistic algorithm was developed to link and match records in the SNDS with patient data from the electronic case report forms of two registries on transcatheter aortic valve implantation: FRANCE-2 and FRANCE-TAVI. The algorithm created patient profiles from transcatheter aortic valve implantation procedures in the SNDS, matching them as closely as possible to the profiles in the registry databases. The objective was to achieve 90% linkage of the populations. The linked database was analysed for completeness and loss to follow-up. For validation, mortality curves for the linked registry cohorts were compared with those for the original populations. RESULTS: A total of 34,397 unique registries entries were identified, and 89.9% of patients in the SNDS could be linked. Rates of losses to follow-up over 2 years were 1.0% in the linked FRANCE-TAVI population compared with 40.3% based on electronic case report form documentation. For FRANCE-2, 3-year rates of losses to follow-up were 1.7% and 6.1%, respectively. Mortality curves for populations based on SNDS and electronic case report form data were practically superimposable. CONCLUSIONS: Linking data from a single-payer national claims database to national registries using a probabilistic approach is feasible and can close data gaps and practically abolish losses to follow-up in the registry population.

Assessment of Long-Term Structural Deterioration of Transcatheter Aortic Bioprosthetic Valves Using the New European Definition.

BACKGROUND: The durability of transcatheter aortic bioprosthetic valves is a crucial issue, but data are scarce, especially beyond 5 years of follow-up. We aimed to assess long-term (7 years) structural valve deterioration (SVD) and bioprosthetic valve failure of transcatheter aortic bioprosthetic valves. METHODS AND RESULTS: Consecutive patients with at least 5-year follow-up available undergoing transcatheter aortic valve implantation from April 2002 to December 2011 in 5 French centers were included. Incidence of SVD and bioprosthetic valve failure were defined according to newly standardized criteria of the European Association of Percutaneous Cardiovascular Interventions/European Society of Cardiology/European Association for Cardio-Thoracic Surgery and reported as cumulative incidence function to account for the competing risk of death. One thousand four hundred three consecutive patients were included with a mean age of 82.6±7.5 years and with a mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) of 21.3±7.5%. A balloon-expandable valve was used in 83.7% of cases. Survival rates were 83.5% (95% CI, 81.4%-85.5%) and 18.6% (95% CI, 15.3%-21.8%) at 1 and 7 years, respectively. Median duration of follow-up was 3.9 years. Bioprosthetic valve failure occurred in 19 patients with a 7-year cumulative incidence of 1.9% (95% CI, 1.4%-2.4%). SVD occurred in 49 patients (moderate, n=32; severe, n=17) with a 7-year cumulative incidence of moderate and severe SVD of 7.0% (95% CI, 5.6%-8.4%) and 4.2% (95% CI, 2.9%-5.5%), respectively. Five patients had aortic valve reintervention (1.0%; 95% CI, 0.4%-1.6%) including 1 case of surgical aortic valve replacement and 4 redo-transcatheter aortic valve implantation. The incidences of SVD and bioprosthetic valve failure were not significantly different between balloon and self-expandable prostheses. CONCLUSIONS: The long-term assessment of transcatheter aortic bioprosthetic valves durability is limited by the poor survival of our population beyond 5 years. Further studies are warranted, particularly in younger and lower-risk patients.

Clinical outcomes and direct costs after transcatheter aortic valve implantation in French centres: a longitudinal study of 1332 patients using a national database.

OBJECTIVES: To describe the clinical outcomes of patients undergoing transcatheter aortic valve implantation (TAVI) and to determine the direct costs before and after TAVI. METHODS: A nationwide longitudinal study using data extracted from the French Hospital Information System. SELECTION CRITERIA: all patients who underwent TAVI between 1 January 2010 and 31 December 2010. Period of follow-up: 12 months preceding TAVI to 36 months after. End-points: mortality, morbidity and total costs of acute and rehabilitation care from the perspective of the hospital. RESULTS: A total of 1332 patients (mean age: 82.0 ± 7.2 years; 50.2% men) were identified. The mean hospitalization length of stay was 13.5 ± 9.3 days. The intrahospital mortality from any cause was 7.9% during the index hospitalization, 8.8% at 30 days, 14.8% at 6 months, 18.4% at 1 year, 24.8% at 2 years and 32.3% at 3 years. The mean number of hospital stays per patient was 4.79 the year preceding TAVI and 4.11 the year after. The cumulated number of hospital stays at 2 and 3 years post-TAVI was 6.88 and 9.69, respectively. The mean hospitalization costs were 14 665€ the year preceding, 26 575€ for the index procedure and 12 308€ the year after TAVI. The cumulated hospitalization costs per patient at 3 years after TAVI were 22 110€ for acute hospitalizations and 5689€ for rehabilitation. CONCLUSIONS: Mortality at 3 years is consistent with other published studies. After TAVI, hospitalization stays in both acute and rehabilitation settings, and the associated costs do not appear to be reduced compared with the year preceding TAVI. The total cost for patients undergoing TAVI is substantial at 3 years.

Predictive factors of early mortality after transcatheter aortic valve implantation: individual risk assessment using a simple score.

OBJECTIVE: Decision making for intervention in symptomatic aortic stenosis should balance the risks of surgery and of transcatheter aortic valve implantation (TAVI). We identified the factors associated with early mortality after TAVI and aimed to develop and validate a simple risk score. METHODS: A population of 3833 consecutive patients was randomly split into two cohorts comprising 2552 and 1281 patients, used respectively to develop and validate a scoring system predicting 30-day or in-hospital mortality. RESULTS: TAVI was performed using the Edwards Sapien prosthesis in 2551 (66.8%) patients and the Medtronic Corevalve in 1270 (33.2%). Approach was transfemoral in 2801 (73.4%) patients, transapical in 678 (17.8%), subclavian in 219 (5.7%) and other in 117 (3.1%). Early mortality was 10.0% (382 patients). A multivariate logistic model identified the following predictive factors of early mortality: age ≥90 years, body mass index <30 Kg/m(2), New York Heart Association class IV, pulmonary hypertension, critical haemodynamic state, ≥2 pulmonary oedemas during the last year, respiratory insufficiency, dialysis and transapical or other (transaortic and transcarotid) approaches. A 21-point predictive score was derived. C-index was 0.67 for the score in the development cohort and 0.59 in the validation cohort. There was a good concordance between predicted and observed 30-day mortality rates in the development and validation cohorts. CONCLUSIONS: Early mortality after TAVI is mainly related to age, the severity of symptoms, comorbidities and transapical approach. A simple score can be used to predict early mortality after TAVI. The moderate discrimination is however a limitation for the accurate identification of high-risk patients.

Cost of transcatheter aortic valve implantation and factors associated with higher hospital stay cost in patients of the FRANCE (FRench Aortic National CoreValve and Edwards) registry.

BACKGROUND: Currently, several anatomical approaches and intervention sites can be used to perform transcatheter aortic valve implantations (TAVIs), often with no clinical indications for choosing one or another. While these choices can have an impact on resource consumption, no costing study is available in the European context to provide information on resource use and assist decision-making. AIMS: To provide comparative data on the cost of the TAVI procedure, depending on anatomical approach and intervention site used, from a hospital perspective, and to analyze factors associated with cost of hospital stay. METHODS: Multicentre national registry data were collected in 16 centres between January and October 2009. For 287 patients, a descriptive costing study and a multivariable analysis of hospital stay cost were performed. RESULTS: The mean cost of the TAVI procedure was €22,876 and the mean initial hospital stay cost was €35,164. The procedure cost, excluding valve cost, did not differ between anatomical approaches and was highest in the hybrid room and lowest in the catheterization laboratory. Factors associated with higher hospital stay cost were transapical approach, Society of Thoracic Surgeons score>10%, warfarin use at inclusion, complications during procedure and pacemaker implantation following valve implantation. CONCLUSIONS: If clinical considerations do not interfere, hospital staff may find it economically favorable to opt for the catheterization laboratory and against the hybrid room. The mean hospital stay cost is higher than the tariff paid in 2011, a difference that has grown since the change in tariff in 2012, representing an economic disincentive for the uptake of TAVI in France.

Comparison of semiquantitative and quantitative assessment of severity of aortic regurgitation: clinical implications.

BACKGROUND: Recent studies have emphasized the importance of quantitative assessment of the degree of aortic regurgitation (AR). However, semiquantitative methods have remained mainly used despite their unclear diagnostic value. The aim of this study was to define the sensitivity and specificity of semiquantitative methods compared with the proximal isovelocity surface area method as a reference for the diagnostic of severe AR. METHODS: The degree of AR was evaluated using the proximal isovelocity surface area method and four semiquantitative measurements (left ventricular cardiac output, pressure half-time, diastolic flow reversal, and vena contracta) in 224 patients with a wide range of AR severity. RESULTS: The mean effective regurgitant orifice area was 25 ± 14 mm(2) (range, 3-69 mm(2)), the mean regurgitant volume was 57 ± 31 mL (range, 9-183 mL), and 100 patients (44%) had severe AR (effective regurgitant orifice area ≥ 30 mm(2) or regurgitant volume ≥ 60 mL). Overall, semiquantitative methods had good specificity but poor sensitivity, except the vena contracta, which had good sensitivity and specificity. Sensitivity, specificity, and positive and negative predictive values of the recommended thresholds for severe AR of the four semiquantitative methods were 53%, 89%, 77%, and 73% for left ventricular cardiac output ≥ 10 L/min; 12%, 100%, 100%, and 52% for pressure half-time < 200 msec; 45%, 87%, 79%, and 60% for diastolic flow reversal ≥ 18 cm/sec; and 81%, 83%, 78%, and 85% for vena contracta ≥ 6 mm, respectively. CONCLUSIONS: For the assessment of AR severity, current thresholds appear specific but poorly sensitive, except for vena contracta, which provides good discriminative value. Semiquantitative methods should be integrated into the comprehensive evaluation of AR severity, but severe AR should not be excluded only on the basis of semiquantitative criteria. These results emphasize the need for the quantitative assessment of AR severity.

Echocardiographic right ventricular function assessment before and after successful percutaneous mitral commissurotomy.

BACKGROUND AND AIM OF THE STUDY: In patients with mitral stenosis (MS), previous studies have shown discordant results with regards to improvements in right ventricular (RV) function immediately after percutaneous mitral commissurotomy (PMC). Hence, the study aim was to evaluate the impact of PMC on RV function, by using Doppler-echocardiography. METHODS: A total of 41 patients with severe symptomatic MS, in sinus rhythm, who had been referred to the authors' institution for PMC, was prospectively enrolled. A group of 25 healthy age- and gender-matched subjects served as controls. Transthoracic echocardiography (TTE) was performed on the day before and at 24/48 h after PMC. The RV function was evaluated using the Tricuspid Annular Plane Excursion (TAPSE), the RV Tei index, and systolic myocardial velocities by Doppler tissue imaging peak isovolumic contraction (DTI(IVC)) and peak systolic (DTI(S)) at the lateral tricuspid annulus). RESULTS: All patients but three underwent a successful PMC. The mitral valve area (MVA) was significantly increased (1.8 +/- 0.3 versus 1.1 +/- 0.2 cm2, p <0.0001), while the mean gradient (5 +/- 2 versus 10 +/- 7 mmHg, p <0.0001) and systolic pulmonary artery pressure (40 +/- 10 versus 54 +/- 21 mmHg, p = 0.0002) were decreased. Compared to healthy controls, the RV dysfunction in MS patients was authenticated by the DTI(IVC) and the Tei index (8.4 +/- 3.0 versus 11.1 +/- 2.1 cm/s, p = 0.0002 and 0.33 +/- 0.10 versus 0.18 +/- 0.10 respectively, p <0.0001), but not by DTI(S) (12.9 +/- 3 versus 12.3 +/- 1.5 cm/s, p = 0.35) or TAPSE (24 +/- 5 versus 23 +/- 3 mm, p = 0.50). After PMC, no significant change regarding RV function was observed (TAPSE: 24 +/- 5 versus 24 +/- 5 mm, p = 0.54; Tei Index: 0.33 +/- 0.10 versus 0.36 +/- 0.12, p = 0.20; DTI(IVC): 8.4 +/- 3.0 versus 9.2 +/- 3.4 cm/s, p = 0.08 and DTI(S): 12.9 +/- 3.0 versus 13.0 +/- 3.4 cm/s, p = 0.54). CONCLUSION: The DTI(IVC) and Tei index appear to serve as the more sensitive indices of RV dysfunction in patients with MS. Immediately after a successful PMC, no significant change in Doppler echocardiographic parameters of RV function was observed. Whether late improvement in RV function can be observed, and the prognostic value of these parameters realized, deserve further investigation.

Multimodal assessment of the aortic annulus diameter: implications for transcatheter aortic valve implantation.

OBJECTIVES: We sought to compare 3 methods of measurements of the aortic annulus, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and multislice computed tomography (MSCT), and to evaluate their potential clinical impact on transcatheter aortic valve implantation (TAVI) strategy. BACKGROUND: Exact measurement of the aortic annulus is critical for a patient's selection and successful implantation. METHODS: Annulus diameter was measured using TTE, TEE, and MSCT in 45 consecutive patients with severe aortic stenosis referred for TAVI. The TAVI strategy (decision to implant and choice of the prosthesis' size) was based on manufacturer's recommendations (Edwards-Sapien prosthesis, Edwards Lifesciences, Inc., Irvine, California). RESULTS: Correlations between methods were good but the difference between MSCT and TTE (1.22 +/- 1.3 mm) or TEE (1.52 +/- 1.1 mm) was larger than the difference between TTE and TEE (0.6 +/- 0.8 mm; p = 0.03 and p < 0.0001, respectively). Regarding TAVI strategy, agreement between TTE and TEE overall was good (kappa = 0.68), but TAVI strategy would have been different in 8 patients (17%). Agreement between MSCT and TTE or TEE was only modest (kappa = 0.28 and 0.27), and a decision based on MSCT measurements would have modified the TAVI strategy in a large number of patients (40% to 42%). Implantation, performed in 34 patients (76%) based on TEE measurements, was successful in all but 1 patient with grade 3/4 regurgitation. CONCLUSIONS: In patients referred for TAVI, measurements of the aortic annulus using TTE, TEE, and MSCT were close but not identical, and the method used has important potential clinical implications on TAVI strategy. In the absence of a gold standard, a strategy based on TEE measurements provided good clinical results.

Understanding risk assessment in cardiac surgery patients.

Understanding the risk of surgery in valvular disease is of interest because aging of the population renders decision making more difficult and the magnitude of risk will influence not only the decision to intervene but also the choice of intervention and its timing. To assist clinicians in assessing the risk of cardiac surgery, multivariate risk scores are increasingly used to estimate operative mortality. Overall, the currently available scores, mostly U.S. Society of Thoracic Surgeons score and European System for Cardiac operative Risk Evaluation, achieve acceptable discrimination but suboptimal calibration in estimating the operative mortality of heart valve surgery. The intrinsic limitations of scoring systems highlight the fact that risk scores should be integrated into clinical judgment but should not be a substitute for it. A multidisciplinary approach involving cardiologists, cardiac surgeons, and anesthesiologists is required for this purpose, especially in high-risk patients.