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Clinical Outcome and Cost Analysis of Sutureless Versus Transcatheter Aortic Valve Implantation With Propensity Score Matching Analysis
Clinical Outcome and Cost Analysis of Sutureless Versus Transcatheter Aortic Valve Implantation With Propensity Score Matching Analysis Giuseppe Santarpino, MDa,*, Steffen Pfeiffer, MDa, Jürgen Jessl, MDb, Angelo Dell’Aquila, MDc, Ferdinand Vogt, MDa, Che von Wardenburg, MDa, Johannes Schwab, MDb, Joachim Sirch, MDa, Matthias Pauschinger, MDb, and Theodor Fischlein, MDa Surgical sutureless and interventional transcatheter aortic valve prostheses are nowadays extensively adopted in high-risk elderly patients. An explorative analysis was carried out to compare the clinical outcome and costs associated to these approaches. Since 2010, a total of 626 patients were distributed between transcatheter aortic valve implantation (TAVI; n [ 364) and sutureless (n [ 262) groups. Patients of both groups were not comparable for clinical and surgical characteristics, but many patients were in a “gray zone”; therefore, a retrospective propensity score analysis was possible and performed. For the matched pair samples, postoperative, follow-up clinical data, and costs data were obtained. In-hospital death occurred in 5 patients in sutureless group and 3 patients in TAVI group (p [ 0.36). Blood transfusions were higher in sutureless group (2.1 – 2.3 vs 0.4 – 1.0 U). TAVI group had a shorter intensive care unit and hospital stay (2.2 – 2.7 vs 3.2 – 3.5 days, p [ 0.037; 12 – 6 vs 14 – 6 days, p [ 0.017). No differences in postoperative neurologic (p [ 0.361), renal (p [ 0.106), or respiratory (p [ 0.391) complications were observed between groups. At follow-up (24.5 – 13.8 months), 1 patient in sutureless group and 7 patients in TAVI group died (p [ 0.032). Paravalvular leakage occurred more frequently in patients in TAVI group (35 [34%] vs 7 [6.9%]; p <0.001) with an impact on follow-up survival rate. The costs associated to the 2 procedures are similar when the cost of the device was excluded (p [ 0.217). When included, the sutureless approach resulted a cost saving (V22,451 vs V33,877, p <0.001). In conclusion, the patients in the “gray zone” record a satisfying clinical outcome after sutureless surgery and TAVI. Patients in the sutureless group endure more hospital complications, but TAVI entails a higher follow-up mortality. On the costs aspects, TAVI technologies are more expensive, and it reflects on higher overall hospital costs. Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;-:-e-) Transcatheter aortic valve implantation (TAVI) has emerged as an alternative treatment to conventional surgery for patients of advanced age who are deemed inoperable.1,2 However, studies comparing TAVI with conventional surgical aortic valve replacement (AVR) in elderly patients showed that isolated advanced age per se should not be considered an indication for TAVI.3 In addition, the use of new sutureless aortic bioprostheses that allow shorter cardiopulmonary bypass (CPB) and cross-clamp times4 has proved to be associated with good outcome in
Departments of aCardiac Surgery and bCardiology, Cardiovascular Center, Klinikum Nürnberg, Paracelsus Medical University, Nuremberg, Germany; and cDepartment of Cardiac Surgery, University of Münster, Münster, Germany. Manuscript received July 1, 2015; revised manuscript received and accepted August 25, 2015. Funding: The work was supported by a grant from Sorin Group, Saluggia, Italy. See page 6 for disclosure information. *Corresponding author: Tel: 0049 0911 398 5441; fax: 0049 0911 398 5443. E-mail address: [email protected] (G. Santarpino). 0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.08.043
octogenarians.5 All these findings together suggest that recently developed surgical and interventional techniques may also be adopted in high-risk elderly patients. This issue has a significant economic relevance for health care systems, given the high costs of the new devices and the limited life expectancy of this patient population. The aim of this observational study was to evaluate the clinical outcome and the associated costs of sutureless AVR versus TAVI in patients with aortic stenosis using propensity score matching analysis to generate 2 homogeneous groups with respect to preoperative surgical risk. Methods We collected data of all patients with a diagnosis of severe aortic valve stenosis and an indication for surgery in our center since 2010. Two specific programs were initiated in our institution at the same time: the first program was developed in collaboration between cardiologists and cardiac surgeons for the use of TAVI (Sapien, Sapien XT, and Sapien 3; Edwards Lifesciences Inc., Irvine, California; CoreValve; Medtronic, Minneapolis, Minnesota; Acurate TA; Symetis SA, Ecublens, Switzerland), whereas the www.ajconline.org
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Table 1 Preoperative characteristics of the study population Variable Age (years) Logistic EuroSCORE Height (cm) Weight (kg) LVEF (%) NYHA class Pulmonary hypertension class* Hypertension Male gender Pacemaker Redo Poor mobility Peripheral arterial disease Diabetes Diabetes managed with insulin therapy CCS class 4 ACS <90 days COPD Renal insufficiency† Associated procedure CABG Surgical approach Full sternotomy Partial sternotomy Right thoracotomy Transapical Transfemoral Transaortic Prosthesis size (mm) Cross-clamp time (min) CPB time (min)
Table 2 Preoperative characteristics of the matched groups
Sutureless (n ¼262)
TAVI (n ¼364)
P value
Variable
785 1311 16610 7715 599 2.80.5 0.50.7
826 2617 16513 7416 5414 3.10.4 0.80.9
<0.001 <0.001 0.36 0.009 <0.001 <0.001 0.001
Age (years) Logistic EuroSCORE Height (cm) Weight (kg) LVEF (%) NYHA class Pulmonary hypertension class* Hypertension Male gender Pacemaker Redo Poor mobility Peripheral arterial disease Diabetes Diabetes managed with insulin therapy CCS class 4 ACS <90 days COPD Renal insufficiency†
228 122 9 24 48 61 76 17
(87%) (47%) (3.4%) (9%) (18%) (23%) (29%) (6.5%)
339 158 12 81 75 98 143 64
(93%) (43%) (3.3%) (22%) (21%) (27%) (39%) (18%)
0.01 0.24 1 <0.001 0.3 0.18 0.002 <0.001
3 3 43 48 88 67
(1.1%) (1.1%) (16%) (18%) (34%) (76%)
90 4 105 171 1 1
(25%) (1.1%) (29%) (47%) (0.2%) (0.2%)
<0.001 0.59 <0.001 <0.001 <0.001
94 (36%) 159 (61%) 9 (3.4%)
241.6 4418 7326
158 (43%) 205 (56%) 1 (0.2%) 252.2
Data are expressed as mean standard deviation or numbers (%). ACS ¼ acute coronary syndrome; CABG ¼ coronary artery bypass grafting; CCS ¼ Canadian Cardiovascular Society; COPD ¼ chronic obstructive pulmonary disease; CPB ¼ cardiopulmonary bypass; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association. * 0: 30 mm Hg; 1: 31 to 55 mm Hg; 2: >55 mm Hg. † K/DOQI stage >2.
second program involved the use of the Perceval sutureless bioprosthesis (Sorin Group, Saluggia, Italy). Every week, during an interdepartmental conference, we evaluated all patients with severe aortic valve stenosis referred to our center from peripheral hospitals, private practices, or our emergency department, considering co-morbidities and surgical risk to determine the best therapy. In all patients aged >65 years with an indication for isolated AVR considered candidates for surgery (irrespective of EuroSCORE), a low frailty score (evaluated by clinical inspection and other factors not included in the EuroSCORE or Society of Thoracic Surgeons scoring system) and compatible echocardiographic findings, a Perceval sutureless valve was implanted. An informed consent for the use of personal data and follow-up contact was also signed by all patients. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in
Sutureless (n¼102)
TAVI (n¼102)
P value
804 1714 1659 7615 589 3.00.4 0.60.8
797 1811 16610 7616 5414 3.00.5 0.60.8
0.27 0.86 0.75 0.79 0.09 0.88 0.86
88 42 6 13 14 27 40 15
(86%) (41%) (6.5%) (13%) (14%) (26%) (39%) (15%)
94 44 6 14 15 16 37 13
(92%) (43%) (6.5%) (14%) (15%) (16%) (36%) (13%)
0.13 0.44 1 0.50 0.50 0.08 0.56 0.46
2 1 22 34
(2%) (1%) (22%) (33%)
4 1 24 33
(4%) (1%) (23%) (32%)
0.34 1 0.43 0.66
Data are expressed as mean standard deviation or numbers (%). ACS ¼ acute coronary syndrome; CCS ¼ Canadian Cardiovascular Society; COPD ¼ chronic obstructive pulmonary disease; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association. * 0: 30 mm Hg; 1: 31 to 55 mm Hg; 2: >55 mm Hg. † K/DOQI stage >2.
a priori approval by the institution’s Human Research Committee. All patients with frailty factors judged at very high surgical risk with or without a logistic EuroSCORE >20% underwent a TAVI. The transfemoral approach was considered as the first-line strategy, leaving the transapical approach in case of inadequate vascular access. After 5 years of extensive experience with both procedures, a total of 626 patients were operated on, distributed between the TAVI and sutureless groups (n ¼ 364 and n ¼ 262, respectively). Patients of both groups were not comparable for clinical and surgical characteristics, but many patients were “similar”; therefore, a retrospective propensity score analysis was possible and performed. For the matched pair samples, postoperative and follow-up clinical data were obtained. Prosthetic valve function was evaluated with transthoracic echocardiography. The presence of paravalvular regurgitation was defined according to current guidelines as none or trace, mild, moderate, or severe.6 All echocardiographic examinations were performed by echocardiographers of our cardiology department. The Perceval implantation technique has been described previously.7 General anesthesia with endotracheal intubation was used in both groups. Our heart team prefers this technique because it allows performance of intraoperative transesophageal echocardiography. In patients who underwent TAVI by the transfemoral and transapical route, the endotracheal tube was removed immediately after the procedure if appropriate, and these patients were discharged to an
Valvular Heart Disease/Sutureless AVR Versus TAVI: Cost Analysis
Figure 1. Follow-up survival rate (KaplaneMeier). Sutureless aortic valve replacement versus transcatheter aortic valve implantation (TAVI), overall population.
intermediate care unit. In the surgical group, patients were extubated in the intensive care unit (ICU). Transfemoral procedures were performed through a minimally invasive direct vascular access: the access site was chosen according to computed tomographic findings, size of the common femoral artery, amount of calcification of the vessel and iliac arteries, and tortuosity. Before all TAVI procedures, the cardiac apex and intended optimal coaxial alignment were localized by transthoracic echocardiography. The surgical technique for positioning and deploying the Sapien XT valve prosthesis, our main TAVI prosthesis used in 92% of our TAVI population, has been well described and standardized for both the transapical and transfemoral approaches.8,9 In-hospital preprocedural and postprocedural resource use data were retrospectively collected from electronic patient records. Hospital financial department provided the associated costs identified according to the German diagnostic related group matrix. The costs analysis was performed according to 10 cost centers, including normal ward, ICU, dialysis unit, operating room, anesthesia, cardiac diagnostic therapy, endoscopic diagnostics, radiology, laboratory, and other diagnostics, and the 3 main cost element groups of labor, material, and infrastructure. Costs were subsequently aggregated and reported according to three main categories: (1) operating room, including anesthesia; (2) hospital stay, including ICU and cardiac surgical ward; (3) diagnostic, radiology, and laboratory, including cardiac diagnostic therapy, endoscopic diagnostics, radiology, laboratory, and other diagnostics. A mean cost of the device was calculated from the observations included in this data set, starting from 2009 to 2013. TAVI mean cost is threefold compared with Perceval mean cost, and this is in line with the figures reported by Biancari et al10 where the device cost difference between TAVI and Perceval was even higher. Categorical variables were summarized as frequencies (%), and continuous variables were summarized as mean SD. Normal distribution of data was assessed with the ShapiroeWilk test. Continuous variables were compared by
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paired Student t-test and categorical variables by chi-square test. A propensity score matching (1:1) was performed to control selection bias as a result of nonrandom assignment to the groups. The propensity score was defined as the probability of receiving TAVI. This was estimated by means of a multivariate regression analysis. Twenty-two patient characteristics and major preoperative risk factors were entered into the model. The p value of the HosmereLemeshow test was 0.014, and c-statistic for the fitted logistic regression model was 0.867 (p <0.001), indicating that model fitting was excellent. Pairs were generated with the 5:1 digit-matching approach. Finally, postoperative outcomes of the resulting 102 matched pairs of both groups (TAVI and sutureless AVR) with the same propensity score were compared, including in-hospital and valve-related complications and survival rate. Cumulative survival curves were computed according to the KaplaneMeier method. Survival curves and freedom from valve-related complications were compared with a Cox proportional hazards model stratified for the matched pairs. A cost comparison between patients treated with Perceval and TAVI on mean and SD were provided. A conditional logistic test was run to detect a statistical significant difference in costs between the 2 cohorts. Results Preoperative characteristics of the whole study population and of the matched groups are reported in Tables 1 and 2, respectively. Intraoperative complications occurred in both groups (4 patients [3.9%] in the sutureless group vs 3 patients [2.9%] in the TAVI group; p ¼ 0.5). In particular, in the sutureless group, 1 patient required removal of the prosthetic valve, performed using the “X-movement” technique11 with subsequent reimplantation; 1 patient with previous coronary revascularization experienced vein graft damage requiring suture repair; 1 patient developed severe paravalvular leakage with annular rupture requiring removal of the sutureless bioprosthesis followed by implantation of a stented valve; and 1 patient, operated on through a right lateral minithoracotomy, required conversion to longitudinal sternotomy due to right ventricular damage and ventricular fibrillation not amenable to cardioversion. In the TAVI group, 1 patient experienced aortic injury during manipulation of the guidewire requiring a thoracotomy to control bleeding; 1 patient experienced valve migration into the left ventricle requiring CPB and conventional AVR through partial sternotomy; and 1 patient with refractory ventricular fibrillation required prolonged cardiopulmonary resuscitation and circulatory support using CPB. The rate of pacemaker implantation was similar between groups (10 patients [10%] in the sutureless group vs 9 patients [9.4%] in the TAVI group; p ¼ 0.588). Conversely, the need for blood transfusion was significantly higher in the sutureless group than that in the TAVI group (2.1 2.3 vs 0.4 1.0 U). Patients who underwent TAVI had a significantly shorter ICU and hospital stay than patients who underwent sutureless AVR (ICU: 2.2 2.7 vs 3.2 3.5 days, p ¼ 0.037; hospital: 12 6 vs 14 6 days, p ¼ 0.017).
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Figure 2. Follow-up survival rate (Kaplan-Meier). Sutureless aortic valve replacement versus transcatheter aortic valve implantation (TAVI), with and without paravalvular insufficiency.
Table 3 Mean costs (Euro) per patient at discharge for Sutureless and TAVI Variable mean (SD) OR costs including anaesthesia Hospital stay costs including ICU Diagnostics* Total costs - excluding the device Mean cost of the device (min; max) Total costs - including the device
Sutureless (n¼102)
TAVI (n¼102)
P value
5,076 1,399 9,188 9,590 1,883 1,887 16,148 11,704 6,303 (3,600 - 7,214) 22,451 11,704
4,312 1,362 5,714 4,055 4,137 3,128 14,164 6,148 18,712 (17,050 - 22,015) 32,877 6,148
0.004 0.009 <0.001 0.217 <0.001
* Diagnostics includes radiology laboratory, cardiac diagnostic therapy, endoscopic diagnostics, and other diagnostics.
No differences in postoperative neurologic (sutureless vs TAVI: 3 [2.9%] vs 5 [4.9%] patients; p ¼ 0.361), renal (5 [4.9%] vs 1 [1.0%] patients; p ¼ 0.106), or respiratory (6 [5.9%] vs 8 [7.8%] patients; p ¼ 0.391) complications were observed between groups. Postoperative delirium developed more frequently in patients from the sutureless group (10 [9.8%] vs 2 [2.0%] patients; p ¼ 0.017), whereas major vascular complications occurred more frequently in patients from the TAVI group (5 [4.9%] vs 0 [0%] patients; p ¼ 0.03). In-hospital death occurred in 5 and 3 patients of the sutureless and TAVI groups, respectively (p ¼ 0.36). At follow-up (sutureless vs TAVI: 26 13 vs 23 14 months; p ¼ 0.205), 1 patient of the sutureless group and 7 patients of the TAVI group died (p ¼ 0.032). Overall survival rate of the whole study population was 96% (sutureless vs TAVI: 99 vs 93%; Figure 1). Paravalvular leakage (at least 1/4þ) occurred more frequently in patients from the TAVI group (35 [34%] vs 7 [7%] patients; p <0.001) with an impact on follow-up survival rate (Figure 2). Outcomes regarding the costs associated to the 2 procedures at discharge showed similar costs for patients treated with Perceval compared with those with TAVI when the cost of the device was excluded (p ¼ 0.217, Table 3). More precisely, no statistical significant difference in costs for the 2 procedures was detected: although patients treated with Perceval showed statistically significant higher costs in hospital stay (p ¼ 0.009, Table 3), this was offset by
statistically significant higher cost for patients treated with TAVI in diagnostics compared with patients treated with Perceval, and this is because of the nature of TAVI procedure requiring more diagnostic tests (p <0.001, Table 3). When the cost of the device was included, Perceval resulted as a cost-saving treatment compared with TAVI with a total cost per patient at discharge of V22,451 compared with V33,877, with a net saving of 34%. Discussion The possibility of performing rapid procedures with shorter CPB and cross-clamp times has proved beneficial to patient outcome.12 In this regard, sutureless aortic valve prostheses, by enabling shorter procedural times, have been shown to be associated with clinical advantages and cost savings.3,13 However, this holds true for nonehigh-risk and nonfrail patients, in whom TAVI remains an established treatment option with well-recognized benefits, especially in those who cannot undergo surgery.1 Notwithstanding this, there is a large proportion of patients who fall in the “gray zone,” for whom the indication to TAVI or surgical AVR depends on both individual characteristics and implanting center. The clinical results obtained so far do not greatly diverge from expectations, in that both procedures performed by experienced operators were associated with intraoperative complications of such magnitude that did not preclude successful completion of the intervention. A higher
Valvular Heart Disease/Sutureless AVR Versus TAVI: Cost Analysis
rate of blood transfusions and postoperative delirium was recorded in patients who underwent sutureless AVR. However, this finding is not surprising given the surgical approach, often also performed in redo patients, and the need for CPB compared with TAVI procedures. Patients who underwent TAVI showed a higher rate of vascular complications (n ¼ 5 [4.9%], 3 hematomas requiring surgical evacuation and 2 lymphatic fistulas requiring revision surgery). If we consider that all complications developed in patients operated on by way of the transfemoral approach, the occurrence rate is quite low if compared with that of other patient cohorts, as seen in the Placement of Aortic Transcatheter Valves (PARTNER) trial in which vascular complications were recorded in more than 1/4 of patients treated with transfemoral TAVI.14 Although no significant differences in postoperative complications were observed between groups, a longer ICU and hospital stay was reported in patients who underwent sutureless AVR despite the use of a minimally invasive approach in most cases, the shorter procedural time associated with the use of sutureless valves, and delayed extubation in ICU. With regard to the latter, in contrast, patients in TAVI group are usually extubated immediately after the procedure in the operating room and discharged to an intermediate care unit. In any case, it is known that our average hospital stay in both groups, to our institutional policy, health insurance, and prudential, is longer than that presented by other centers. The costs analysis regarding the 2 procedures confirms those outcomes: even excluding device costs, patients treated with Perceval present similar total costs at discharge mainly driven by longer hospital stay and ICU compared with TAVI, offset by higher diagnostic costs for patients with TAVI. The rate of pacemaker implantation seems encouraging, being approximately 10% in both groups. This finding is of particular relevance given that in other case series, conduction disturbances requiring permanent pacemaker implantation have been reported in 1/3 of patients after TAVI, although data strongly vary according to the type of aortic prosthesis implanted.15 As for the sutureless group, although our findings are consistent with previous studies, the advanced age of our population in combination with technical measures may have accounted for the recorded rate of pacemaker implantation. Follow-up data are noteworthy. TAVI procedures are associated with a higher rate of paravalvular leak16 compared with sutureless AVR, as also confirmed in the present study. In addition, paravalvular leak is associated with increased mortality.16 Our follow-up period for clinical outcomes is associated to 1 year, whereas costs are associated up to hospital discharge only. Because of this time lag between clinical outcomes and costs, a costs analysis was carried out instead of a cost-effectiveness analysis. This cannot prevent to notice that costs associated to patients treated with Perceval are significantly lower compared with patients treated with TAVI, and in the meanwhile, longer term clinical outcomes showed lower mortality for patients treated with Perceval compared with patients in TAVI group presenting paravalvular leak. This outcome agrees with other studies such as that by Biancari et al,10 which reported a mortality rate for the matched analysis equal to 6.9% for TAVI and 1.4% for
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Perceval: this outcome is probably driven by a significantly different rate of mild-to-severe paravalvular leak for TAVI compared with Perceval, 14.1% for TAVI group versus 0.3% for Perceval cohort.10 Even if not in the condition to fullfledged cost-effectiveness analysis, for the reasons laid previously around different time horizons for costs and effectiveness, a beneficial cost-effectiveness profile in favor of Perceval could be reasonably expected: this may be one of the outcomes of future studies that we are being planning in our institution. In a preliminary study from our group that compared sutureless AVR with TAVI,17 a significant difference in the mortality rate at follow-up was observed between patients with and without paravalvular leak in the TAVI group. In addition, by comparing the survival rate in the sutureless group with that of patients with no paravalvular leak in the TAVI group, no significant differences were evidenced,17 according with the described big TAVI trials.1,2 Our preliminary results based on 37 matched pairs with a mean follow-up of 12 months are reinforced by the present findings obtained in 102 matched pairs with a mean followup of 2 years (Figure 2). However, whether paravalvular regurgitation is the key determinant of this survival mechanism remains to be clearly established, but this issue may provide targets for further studies and the development of new TAVI prostheses that, by minimizing the risk of paravalvular leak (e.g., Lotus or Sapien 3), may achieve comparable if not better results than those reported with surgical AVR. The most appropriate therapeutic strategy in patients with aortic valve stenosis is still a matter of debate. Besides anatomic features, a number of other factors should be taken into consideration, including frailty and cost-effectiveness of the procedure.18 In a review published in 2003, long before the introduction of TAVI, Bramstedt19 concluded that AVR devices are cost-effective and there is no ethical justification for denying AVR to clinically suitable elderly candidates. In view of the favorable results in terms of both quality of life and long-term outcome, surgical AVR should not be denied to elderly patients solely on the basis of their “chronologic age” without considering their true “biologic age”.20 With increasing surgical risk, a higher postoperative complication rate and increased hospital costs have been documented.21 In a previous experience, we demonstrated that shorter procedural times are associated with a reduction in postoperative complications and hospital costs.13 However, costs of the devices used were not included, and this represented an important limitation of our study. As a matter of fact, the high costs of the new devices have driven cost-effectiveness studies, in particular after the introduction of TAVI into clinical practice. This issue is extremely complex, with inherent ethical concerns and legal implications surrounding sponsorship.22 In assessing the cost-effectiveness of TAVI in Belgium,23 the authors concluded that TAVI should be restricted to patients who are inoperable because of anatomic prohibitive conditions. These findings strongly contrast with the cost-effectiveness data from the PARTNER trial, showing lower costs in patients treated with TAVI because of reduced hospitalization rates.24,25 The lack of univocal results suggests that the debate is still ongoing and, to the best of our knowledge, our study is the first to compare sutureless implantable valves with TAVI prostheses.
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A limitation of the study is in the nonprospective randomized design. Although the propensity score matching balances of randomization, our study need a prospective confirm. Moreover, we analyzed in the TAVI group both trans-apical and trans-femoral, although we know these are 2 different populations.26 An analysis with 2 separate groups for trans-apical and trans-femoral is planned. In conclusion, the patients in the “gray zone” record a satisfying clinical outcome after sutureless surgery and TAVI. Patients in the sutureless group endure more hospital complications, but, on the other hand, TAVI, due to paravalvular leakage with the actual used technology, entails a higher follow-up mortality. On the costs aspects, TAVI technologies are more expensive, and it reflects on higher overall hospital costs.
7. 8. 9. 10.
Disclosures Dr. Fischlein is consultant for Sorin Group. 11. 1. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597e1607. 2. Popma JJ, Adams DH, Reardon MJ, Yakubov SJ, Kleiman NS, Heimansohn D, Hermiller J Jr, Hughes GC, Harrison JK, Coselli J, Diez J, Kafi A, Schreiber T, Gleason TG, Conte J, Buchbinder M, Deeb GM, Carabello B, Serruys PW, Chenoweth S, Oh JK; CoreValve United States Clinical Investigators. Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J Am Coll Cardiol 2014;63:1972e1981. 3. Strauch JT, Scherner M, Haldenwang PL, Madershahian N, Pfister R, Kuhn EW, Liakopoulos OJ, Wippermann J, Wahlers T. Transapical minimally invasive aortic valve implantation and conventional aortic valve replacement in octogenarians. Thorac Cardiovasc Surg 2012;60: 335e342. 4. Santarpino G, Pfeiffer S, Concistré G, Grossmann I, Hinzmann M, Fischlein T. The Perceval S aortic valve has the potential of shortening surgical time: does it also result in improved outcome? Ann Thorac Surg 2013;96:77e81. 5. Santarpino G, Pfeiffer S, Vogt F, Hinzmann M, Concistrè G, Fischlein T. Advanced age per se should not be an exclusion criterion for minimally invasive aortic valve replacement. J Heart Valve Dis 2013;22:455e459. 6. Zoghbi WA, Chambers JB, Dumesnil JG, Foster E, Gottdiener JS, Grayburn PA, Khandheria BK, Levine RA, Marx GR, Miller FA Jr, Nakatani S, Quiñones MA, Rakowski H, Rodriguez LL, Swaminathan M, Waggoner AD, Weissman NJ, Zabalgoitia M; American Society of Echocardiography’s Guidelines and Standards Committee; Task Force on Prosthetic Valves; American College of Cardiology Cardiovascular Imaging Committee; Cardiac Imaging Committee of the American Heart Association; European Association of Echocardiography; European Society of Cardiology; Japanese Society of Echocardiography; Canadian Society of Echocardiography; American College of Cardiology Foundation; American Heart Association; European Association of Echocardiography; European Society of Cardiology; Japanese Society of Echocardiography; Canadian Society of Echocardiography. Recommendations for evaluation of prosthetic valves with echocardiography and Doppler ultrasound: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Task Force on Prosthetic Valves, developed in conjunction with the American College of Cardiology Cardiovascular Imaging Committee, Cardiac Imaging Committee of the American Heart Association, the European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of
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18. 19. 20. 21.
22. 23.
Echocardiography and the Canadian Society of echocardiography, endorsed by the American College of Cardiology Foundation, American Heart Association, European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography, and Canadian Society of Echocardiography. J Am Soc Echocardiogr 2009;22: 975e1014. Santarpino G, Pfeiffer S, Concistre G, Fischlein T. Perceval S aortic valve implantation in mini-invasive surgery: the simple sutureless solution. Interact Cardiovasc Thorac Surg 2012;15:357e360. Walther T, Möllmann H, van Linden A, Kempfert J. Transcatheter aortic valve implantation transapical: step by step. Semin Thorac Cardiovasc Surg 2011;23:55e61. Willson A, Toggweiler S, Webb JG. Transfemoral aortic valve replacement with the SAPIEN XT valve: step-by-step. Semin Thorac Cardiovasc Surg 2011;23:51e54. Biancari F, Barbanti M, Santarpino G, Deste W, Tamburino C, Gulino S, Immè S, Di Simone E, Todaro D, Pollari F, Fischlein T, Kasama K, Meuris B, Dalén M, Sartipy U, Svenarud P, Lahtinen J, Heikkinen J, Juvonen T, Gatti G, Pappalardo A, Mignosa C, Rubino AS. Immediate outcome after sutureless versus transcatheter aortic valve replacement. Heart Vessels 2015. [Epub ahead of print], http://dx.doi.org/10.1007/ s00380-014-0623-3. Santarpino G, Pfeiffer S, Concistre G, Fischlein T. A supra-annular malposition of the Perceval S sutureless aortic valve: the “X-movement” removal technique and subsequent reimplantation. Interact Cardiovasc Thorac Surg 2012;15:280e281. Chalmers J, Pullan M, Mediratta N, Poullis M. A need for speed? Bypass time and outcomes after isolated aortic valve replacement surgery. Interact Cardiovasc Thorac Surg 2014;19:21e26. Pollari F, Santarpino G, Dell’Aquila AM, Gazdag L, Alnahas H, Vogt F, Pfeiffer S, Fischlein T. Better short-term outcome by using sutureless valves: a propensity-matched score analysis. Ann Thorac Surg 2014;98:611e616. Généreux P, Webb JG, Svensson LG, Kodali SK, Satler LF, Fearon WF, Davidson CJ, Eisenhauer AC, Makkar RR, Bergman GW, Babaliaros V, Bavaria JE, Velazquez OC, Williams MR, Hueter I, Xu K, Leon MB; PARTNER Trial Investigators. Vascular complications after transcatheter aortic valve replacement: insights from the PARTNER (Placement of AoRTic TraNscathetER Valve) trial. J Am Coll Cardiol 2012;60:1043e1052. Roten L, Wenaweser P, Delacrétaz E, Hellige G, Stortecky S, Tanner H, Pilgrim T, Kadner A, Eberle B, Zwahlen M, Carrel T, Meier B, Windecker S. Incidence and predictors of atrioventricular conduction impairment after transcatheter aortic valve implantation. Am J Cardiol 2010;106:1473e1480. Kodali SK, Williams MR, Smith CR, Svensson LG, Webb JG, Makkar RR, Fontana GP, Dewey TM, Thourani VH, Pichard AD, Fischbein M, Szeto WY, Lim S, Greason KL, Teirstein PS, Malaisrie SC, Douglas PS, Hahn RT, Whisenant B, Zajarias A, Wang D, Akin JJ, Anderson WN, Leon MB; PARTNER Trial Investigators. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med 2012;366:1686e1695. Santarpino G, Pfeiffer S, Jessl J, Dell’Aquila AM, Pollari F, Pauschinger M, Fischlein T. Sutureless replacement versus transcatheter valve implantation in aortic valve stenosis: a propensitymatched analysis of 2 strategies in high-risk patients. J Thorac Cardiovasc Surg 2014;147:561e567. Gallo M, Gerosa G. Multiparameter approach to evaluate elderly patients undergoing aortic valve replacement. J Thorac Cardiovasc Surg 2014;148:1749e1751. Bramstedt KA. Aortic valve replacement in the elderly: frequently indicated yet frequently denied. Gerontology 2003;49:46e49. Seco M, Edelman JJ, Forrest P, Ng M, Wilson MK, Fraser J, Bannon PG, Vallely MP. Geriatric cardiac surgery: chronology vs. biology. Heart Lung Circ 2014;23:794e801. Osnabrugge RL, Speir AM, Head SJ, Fonner CE, Fonner E Jr, Ailawadi G, Kappetein AP, Rich JB. Costs for surgical aortic valve replacement according to preoperative risk categories. Ann Thorac Surg 2013;96:500e506. Neyt M, Van Brabandt H. TAVI: reveal the truth, the whole truth, and nothing but the truth. J Med Econ 2013;16:581e585. Neyt M, Van Brabandt H, Devriese S, Van De Sande S. A cost-utility analysis of transcatheter aortic valve implantation in Belgium: focusing
Valvular Heart Disease/Sutureless AVR Versus TAVI: Cost Analysis on a well-defined and identifiable population. BMJ Open 2012;2: e001032. 24. Reynolds MR, Magnuson EA, Wang K, Lei Y, Vilain K, Walczak J, Kodali SK, Lasala JM, O’Neill WW, Davidson CJ, Smith CR, Leon MB, Cohen DJ; PARTNER Investigators. Cost-effectiveness of transcatheter aortic valve replacement compared with standard care among inoperable patients with severe aortic stenosis: results from the placement of aortic transcatheter valves (PARTNER) trial (Cohort B). Circulation 2012;125:1102e1109. 25. Reynolds MR, Magnuson EA, Lei Y, Wang K, Vilain K, Li H, Walczak J, Pinto DS, Thourani VH, Svensson LG, Mack MJ, Miller DC, Satler LE, Bavaria J, Smith CR, Leon MB, Cohen DJ;
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PARTNER Investigators. Cost-effectiveness of transcatheter aortic valve replacement compared with surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results of the PARTNER (Placement of Aortic Transcatheter Valves) trial (Cohort A). J Am Coll Cardiol 2012;60:2683e2692. 26. Blackstone EH, Suri RM, Rajeswaran J, Babaliaros V, Douglas PS, Fearon WF, Miller DC, Hahn RT, Kapadia S, Kirtane AJ, Kodali SK, Mack M, Szeto WY, Thourani VH, Tuzcu EM, Williams MR, Akin JJ, Leon MB, Svensson LG. Propensity-matched comparisons of clinical outcomes after transapical or transfemoral transcatheter aortic valve replacement. A placement of aortic transcatheter valves (PARTNER)-I trial Substudy. Circulation 2015;131:1989e2000.
Departments of aCardiac Surgery and bCardiology, Cardiovascular Center, Klinikum Nürnberg, Paracelsus Medical University, Nuremberg, Germany; and cDepartment of Cardiac Surgery, University of Münster, Münster, Germany. Manuscript received July 1, 2015; revised manuscript received and accepted August 25, 2015. Funding: The work was supported by a grant from Sorin Group, Saluggia, Italy. See page 6 for disclosure information. *Corresponding author: Tel: 0049 0911 398 5441; fax: 0049 0911 398 5443. E-mail address: [email protected] (G. Santarpino). 0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.08.043
octogenarians.5 All these findings together suggest that recently developed surgical and interventional techniques may also be adopted in high-risk elderly patients. This issue has a significant economic relevance for health care systems, given the high costs of the new devices and the limited life expectancy of this patient population. The aim of this observational study was to evaluate the clinical outcome and the associated costs of sutureless AVR versus TAVI in patients with aortic stenosis using propensity score matching analysis to generate 2 homogeneous groups with respect to preoperative surgical risk. Methods We collected data of all patients with a diagnosis of severe aortic valve stenosis and an indication for surgery in our center since 2010. Two specific programs were initiated in our institution at the same time: the first program was developed in collaboration between cardiologists and cardiac surgeons for the use of TAVI (Sapien, Sapien XT, and Sapien 3; Edwards Lifesciences Inc., Irvine, California; CoreValve; Medtronic, Minneapolis, Minnesota; Acurate TA; Symetis SA, Ecublens, Switzerland), whereas the www.ajconline.org
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Table 1 Preoperative characteristics of the study population Variable Age (years) Logistic EuroSCORE Height (cm) Weight (kg) LVEF (%) NYHA class Pulmonary hypertension class* Hypertension Male gender Pacemaker Redo Poor mobility Peripheral arterial disease Diabetes Diabetes managed with insulin therapy CCS class 4 ACS <90 days COPD Renal insufficiency† Associated procedure CABG Surgical approach Full sternotomy Partial sternotomy Right thoracotomy Transapical Transfemoral Transaortic Prosthesis size (mm) Cross-clamp time (min) CPB time (min)
Table 2 Preoperative characteristics of the matched groups
Sutureless (n ¼262)
TAVI (n ¼364)
P value
Variable
785 1311 16610 7715 599 2.80.5 0.50.7
826 2617 16513 7416 5414 3.10.4 0.80.9
<0.001 <0.001 0.36 0.009 <0.001 <0.001 0.001
Age (years) Logistic EuroSCORE Height (cm) Weight (kg) LVEF (%) NYHA class Pulmonary hypertension class* Hypertension Male gender Pacemaker Redo Poor mobility Peripheral arterial disease Diabetes Diabetes managed with insulin therapy CCS class 4 ACS <90 days COPD Renal insufficiency†
228 122 9 24 48 61 76 17
(87%) (47%) (3.4%) (9%) (18%) (23%) (29%) (6.5%)
339 158 12 81 75 98 143 64
(93%) (43%) (3.3%) (22%) (21%) (27%) (39%) (18%)
0.01 0.24 1 <0.001 0.3 0.18 0.002 <0.001
3 3 43 48 88 67
(1.1%) (1.1%) (16%) (18%) (34%) (76%)
90 4 105 171 1 1
(25%) (1.1%) (29%) (47%) (0.2%) (0.2%)
<0.001 0.59 <0.001 <0.001 <0.001
94 (36%) 159 (61%) 9 (3.4%)
241.6 4418 7326
158 (43%) 205 (56%) 1 (0.2%) 252.2
Data are expressed as mean standard deviation or numbers (%). ACS ¼ acute coronary syndrome; CABG ¼ coronary artery bypass grafting; CCS ¼ Canadian Cardiovascular Society; COPD ¼ chronic obstructive pulmonary disease; CPB ¼ cardiopulmonary bypass; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association. * 0: 30 mm Hg; 1: 31 to 55 mm Hg; 2: >55 mm Hg. † K/DOQI stage >2.
second program involved the use of the Perceval sutureless bioprosthesis (Sorin Group, Saluggia, Italy). Every week, during an interdepartmental conference, we evaluated all patients with severe aortic valve stenosis referred to our center from peripheral hospitals, private practices, or our emergency department, considering co-morbidities and surgical risk to determine the best therapy. In all patients aged >65 years with an indication for isolated AVR considered candidates for surgery (irrespective of EuroSCORE), a low frailty score (evaluated by clinical inspection and other factors not included in the EuroSCORE or Society of Thoracic Surgeons scoring system) and compatible echocardiographic findings, a Perceval sutureless valve was implanted. An informed consent for the use of personal data and follow-up contact was also signed by all patients. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in
Sutureless (n¼102)
TAVI (n¼102)
P value
804 1714 1659 7615 589 3.00.4 0.60.8
797 1811 16610 7616 5414 3.00.5 0.60.8
0.27 0.86 0.75 0.79 0.09 0.88 0.86
88 42 6 13 14 27 40 15
(86%) (41%) (6.5%) (13%) (14%) (26%) (39%) (15%)
94 44 6 14 15 16 37 13
(92%) (43%) (6.5%) (14%) (15%) (16%) (36%) (13%)
0.13 0.44 1 0.50 0.50 0.08 0.56 0.46
2 1 22 34
(2%) (1%) (22%) (33%)
4 1 24 33
(4%) (1%) (23%) (32%)
0.34 1 0.43 0.66
Data are expressed as mean standard deviation or numbers (%). ACS ¼ acute coronary syndrome; CCS ¼ Canadian Cardiovascular Society; COPD ¼ chronic obstructive pulmonary disease; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association. * 0: 30 mm Hg; 1: 31 to 55 mm Hg; 2: >55 mm Hg. † K/DOQI stage >2.
a priori approval by the institution’s Human Research Committee. All patients with frailty factors judged at very high surgical risk with or without a logistic EuroSCORE >20% underwent a TAVI. The transfemoral approach was considered as the first-line strategy, leaving the transapical approach in case of inadequate vascular access. After 5 years of extensive experience with both procedures, a total of 626 patients were operated on, distributed between the TAVI and sutureless groups (n ¼ 364 and n ¼ 262, respectively). Patients of both groups were not comparable for clinical and surgical characteristics, but many patients were “similar”; therefore, a retrospective propensity score analysis was possible and performed. For the matched pair samples, postoperative and follow-up clinical data were obtained. Prosthetic valve function was evaluated with transthoracic echocardiography. The presence of paravalvular regurgitation was defined according to current guidelines as none or trace, mild, moderate, or severe.6 All echocardiographic examinations were performed by echocardiographers of our cardiology department. The Perceval implantation technique has been described previously.7 General anesthesia with endotracheal intubation was used in both groups. Our heart team prefers this technique because it allows performance of intraoperative transesophageal echocardiography. In patients who underwent TAVI by the transfemoral and transapical route, the endotracheal tube was removed immediately after the procedure if appropriate, and these patients were discharged to an
Valvular Heart Disease/Sutureless AVR Versus TAVI: Cost Analysis
Figure 1. Follow-up survival rate (KaplaneMeier). Sutureless aortic valve replacement versus transcatheter aortic valve implantation (TAVI), overall population.
intermediate care unit. In the surgical group, patients were extubated in the intensive care unit (ICU). Transfemoral procedures were performed through a minimally invasive direct vascular access: the access site was chosen according to computed tomographic findings, size of the common femoral artery, amount of calcification of the vessel and iliac arteries, and tortuosity. Before all TAVI procedures, the cardiac apex and intended optimal coaxial alignment were localized by transthoracic echocardiography. The surgical technique for positioning and deploying the Sapien XT valve prosthesis, our main TAVI prosthesis used in 92% of our TAVI population, has been well described and standardized for both the transapical and transfemoral approaches.8,9 In-hospital preprocedural and postprocedural resource use data were retrospectively collected from electronic patient records. Hospital financial department provided the associated costs identified according to the German diagnostic related group matrix. The costs analysis was performed according to 10 cost centers, including normal ward, ICU, dialysis unit, operating room, anesthesia, cardiac diagnostic therapy, endoscopic diagnostics, radiology, laboratory, and other diagnostics, and the 3 main cost element groups of labor, material, and infrastructure. Costs were subsequently aggregated and reported according to three main categories: (1) operating room, including anesthesia; (2) hospital stay, including ICU and cardiac surgical ward; (3) diagnostic, radiology, and laboratory, including cardiac diagnostic therapy, endoscopic diagnostics, radiology, laboratory, and other diagnostics. A mean cost of the device was calculated from the observations included in this data set, starting from 2009 to 2013. TAVI mean cost is threefold compared with Perceval mean cost, and this is in line with the figures reported by Biancari et al10 where the device cost difference between TAVI and Perceval was even higher. Categorical variables were summarized as frequencies (%), and continuous variables were summarized as mean SD. Normal distribution of data was assessed with the ShapiroeWilk test. Continuous variables were compared by
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paired Student t-test and categorical variables by chi-square test. A propensity score matching (1:1) was performed to control selection bias as a result of nonrandom assignment to the groups. The propensity score was defined as the probability of receiving TAVI. This was estimated by means of a multivariate regression analysis. Twenty-two patient characteristics and major preoperative risk factors were entered into the model. The p value of the HosmereLemeshow test was 0.014, and c-statistic for the fitted logistic regression model was 0.867 (p <0.001), indicating that model fitting was excellent. Pairs were generated with the 5:1 digit-matching approach. Finally, postoperative outcomes of the resulting 102 matched pairs of both groups (TAVI and sutureless AVR) with the same propensity score were compared, including in-hospital and valve-related complications and survival rate. Cumulative survival curves were computed according to the KaplaneMeier method. Survival curves and freedom from valve-related complications were compared with a Cox proportional hazards model stratified for the matched pairs. A cost comparison between patients treated with Perceval and TAVI on mean and SD were provided. A conditional logistic test was run to detect a statistical significant difference in costs between the 2 cohorts. Results Preoperative characteristics of the whole study population and of the matched groups are reported in Tables 1 and 2, respectively. Intraoperative complications occurred in both groups (4 patients [3.9%] in the sutureless group vs 3 patients [2.9%] in the TAVI group; p ¼ 0.5). In particular, in the sutureless group, 1 patient required removal of the prosthetic valve, performed using the “X-movement” technique11 with subsequent reimplantation; 1 patient with previous coronary revascularization experienced vein graft damage requiring suture repair; 1 patient developed severe paravalvular leakage with annular rupture requiring removal of the sutureless bioprosthesis followed by implantation of a stented valve; and 1 patient, operated on through a right lateral minithoracotomy, required conversion to longitudinal sternotomy due to right ventricular damage and ventricular fibrillation not amenable to cardioversion. In the TAVI group, 1 patient experienced aortic injury during manipulation of the guidewire requiring a thoracotomy to control bleeding; 1 patient experienced valve migration into the left ventricle requiring CPB and conventional AVR through partial sternotomy; and 1 patient with refractory ventricular fibrillation required prolonged cardiopulmonary resuscitation and circulatory support using CPB. The rate of pacemaker implantation was similar between groups (10 patients [10%] in the sutureless group vs 9 patients [9.4%] in the TAVI group; p ¼ 0.588). Conversely, the need for blood transfusion was significantly higher in the sutureless group than that in the TAVI group (2.1 2.3 vs 0.4 1.0 U). Patients who underwent TAVI had a significantly shorter ICU and hospital stay than patients who underwent sutureless AVR (ICU: 2.2 2.7 vs 3.2 3.5 days, p ¼ 0.037; hospital: 12 6 vs 14 6 days, p ¼ 0.017).
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Figure 2. Follow-up survival rate (Kaplan-Meier). Sutureless aortic valve replacement versus transcatheter aortic valve implantation (TAVI), with and without paravalvular insufficiency.
Table 3 Mean costs (Euro) per patient at discharge for Sutureless and TAVI Variable mean (SD) OR costs including anaesthesia Hospital stay costs including ICU Diagnostics* Total costs - excluding the device Mean cost of the device (min; max) Total costs - including the device
Sutureless (n¼102)
TAVI (n¼102)
P value
5,076 1,399 9,188 9,590 1,883 1,887 16,148 11,704 6,303 (3,600 - 7,214) 22,451 11,704
4,312 1,362 5,714 4,055 4,137 3,128 14,164 6,148 18,712 (17,050 - 22,015) 32,877 6,148
0.004 0.009 <0.001 0.217 <0.001
* Diagnostics includes radiology laboratory, cardiac diagnostic therapy, endoscopic diagnostics, and other diagnostics.
No differences in postoperative neurologic (sutureless vs TAVI: 3 [2.9%] vs 5 [4.9%] patients; p ¼ 0.361), renal (5 [4.9%] vs 1 [1.0%] patients; p ¼ 0.106), or respiratory (6 [5.9%] vs 8 [7.8%] patients; p ¼ 0.391) complications were observed between groups. Postoperative delirium developed more frequently in patients from the sutureless group (10 [9.8%] vs 2 [2.0%] patients; p ¼ 0.017), whereas major vascular complications occurred more frequently in patients from the TAVI group (5 [4.9%] vs 0 [0%] patients; p ¼ 0.03). In-hospital death occurred in 5 and 3 patients of the sutureless and TAVI groups, respectively (p ¼ 0.36). At follow-up (sutureless vs TAVI: 26 13 vs 23 14 months; p ¼ 0.205), 1 patient of the sutureless group and 7 patients of the TAVI group died (p ¼ 0.032). Overall survival rate of the whole study population was 96% (sutureless vs TAVI: 99 vs 93%; Figure 1). Paravalvular leakage (at least 1/4þ) occurred more frequently in patients from the TAVI group (35 [34%] vs 7 [7%] patients; p <0.001) with an impact on follow-up survival rate (Figure 2). Outcomes regarding the costs associated to the 2 procedures at discharge showed similar costs for patients treated with Perceval compared with those with TAVI when the cost of the device was excluded (p ¼ 0.217, Table 3). More precisely, no statistical significant difference in costs for the 2 procedures was detected: although patients treated with Perceval showed statistically significant higher costs in hospital stay (p ¼ 0.009, Table 3), this was offset by
statistically significant higher cost for patients treated with TAVI in diagnostics compared with patients treated with Perceval, and this is because of the nature of TAVI procedure requiring more diagnostic tests (p <0.001, Table 3). When the cost of the device was included, Perceval resulted as a cost-saving treatment compared with TAVI with a total cost per patient at discharge of V22,451 compared with V33,877, with a net saving of 34%. Discussion The possibility of performing rapid procedures with shorter CPB and cross-clamp times has proved beneficial to patient outcome.12 In this regard, sutureless aortic valve prostheses, by enabling shorter procedural times, have been shown to be associated with clinical advantages and cost savings.3,13 However, this holds true for nonehigh-risk and nonfrail patients, in whom TAVI remains an established treatment option with well-recognized benefits, especially in those who cannot undergo surgery.1 Notwithstanding this, there is a large proportion of patients who fall in the “gray zone,” for whom the indication to TAVI or surgical AVR depends on both individual characteristics and implanting center. The clinical results obtained so far do not greatly diverge from expectations, in that both procedures performed by experienced operators were associated with intraoperative complications of such magnitude that did not preclude successful completion of the intervention. A higher
Valvular Heart Disease/Sutureless AVR Versus TAVI: Cost Analysis
rate of blood transfusions and postoperative delirium was recorded in patients who underwent sutureless AVR. However, this finding is not surprising given the surgical approach, often also performed in redo patients, and the need for CPB compared with TAVI procedures. Patients who underwent TAVI showed a higher rate of vascular complications (n ¼ 5 [4.9%], 3 hematomas requiring surgical evacuation and 2 lymphatic fistulas requiring revision surgery). If we consider that all complications developed in patients operated on by way of the transfemoral approach, the occurrence rate is quite low if compared with that of other patient cohorts, as seen in the Placement of Aortic Transcatheter Valves (PARTNER) trial in which vascular complications were recorded in more than 1/4 of patients treated with transfemoral TAVI.14 Although no significant differences in postoperative complications were observed between groups, a longer ICU and hospital stay was reported in patients who underwent sutureless AVR despite the use of a minimally invasive approach in most cases, the shorter procedural time associated with the use of sutureless valves, and delayed extubation in ICU. With regard to the latter, in contrast, patients in TAVI group are usually extubated immediately after the procedure in the operating room and discharged to an intermediate care unit. In any case, it is known that our average hospital stay in both groups, to our institutional policy, health insurance, and prudential, is longer than that presented by other centers. The costs analysis regarding the 2 procedures confirms those outcomes: even excluding device costs, patients treated with Perceval present similar total costs at discharge mainly driven by longer hospital stay and ICU compared with TAVI, offset by higher diagnostic costs for patients with TAVI. The rate of pacemaker implantation seems encouraging, being approximately 10% in both groups. This finding is of particular relevance given that in other case series, conduction disturbances requiring permanent pacemaker implantation have been reported in 1/3 of patients after TAVI, although data strongly vary according to the type of aortic prosthesis implanted.15 As for the sutureless group, although our findings are consistent with previous studies, the advanced age of our population in combination with technical measures may have accounted for the recorded rate of pacemaker implantation. Follow-up data are noteworthy. TAVI procedures are associated with a higher rate of paravalvular leak16 compared with sutureless AVR, as also confirmed in the present study. In addition, paravalvular leak is associated with increased mortality.16 Our follow-up period for clinical outcomes is associated to 1 year, whereas costs are associated up to hospital discharge only. Because of this time lag between clinical outcomes and costs, a costs analysis was carried out instead of a cost-effectiveness analysis. This cannot prevent to notice that costs associated to patients treated with Perceval are significantly lower compared with patients treated with TAVI, and in the meanwhile, longer term clinical outcomes showed lower mortality for patients treated with Perceval compared with patients in TAVI group presenting paravalvular leak. This outcome agrees with other studies such as that by Biancari et al,10 which reported a mortality rate for the matched analysis equal to 6.9% for TAVI and 1.4% for
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Perceval: this outcome is probably driven by a significantly different rate of mild-to-severe paravalvular leak for TAVI compared with Perceval, 14.1% for TAVI group versus 0.3% for Perceval cohort.10 Even if not in the condition to fullfledged cost-effectiveness analysis, for the reasons laid previously around different time horizons for costs and effectiveness, a beneficial cost-effectiveness profile in favor of Perceval could be reasonably expected: this may be one of the outcomes of future studies that we are being planning in our institution. In a preliminary study from our group that compared sutureless AVR with TAVI,17 a significant difference in the mortality rate at follow-up was observed between patients with and without paravalvular leak in the TAVI group. In addition, by comparing the survival rate in the sutureless group with that of patients with no paravalvular leak in the TAVI group, no significant differences were evidenced,17 according with the described big TAVI trials.1,2 Our preliminary results based on 37 matched pairs with a mean follow-up of 12 months are reinforced by the present findings obtained in 102 matched pairs with a mean followup of 2 years (Figure 2). However, whether paravalvular regurgitation is the key determinant of this survival mechanism remains to be clearly established, but this issue may provide targets for further studies and the development of new TAVI prostheses that, by minimizing the risk of paravalvular leak (e.g., Lotus or Sapien 3), may achieve comparable if not better results than those reported with surgical AVR. The most appropriate therapeutic strategy in patients with aortic valve stenosis is still a matter of debate. Besides anatomic features, a number of other factors should be taken into consideration, including frailty and cost-effectiveness of the procedure.18 In a review published in 2003, long before the introduction of TAVI, Bramstedt19 concluded that AVR devices are cost-effective and there is no ethical justification for denying AVR to clinically suitable elderly candidates. In view of the favorable results in terms of both quality of life and long-term outcome, surgical AVR should not be denied to elderly patients solely on the basis of their “chronologic age” without considering their true “biologic age”.20 With increasing surgical risk, a higher postoperative complication rate and increased hospital costs have been documented.21 In a previous experience, we demonstrated that shorter procedural times are associated with a reduction in postoperative complications and hospital costs.13 However, costs of the devices used were not included, and this represented an important limitation of our study. As a matter of fact, the high costs of the new devices have driven cost-effectiveness studies, in particular after the introduction of TAVI into clinical practice. This issue is extremely complex, with inherent ethical concerns and legal implications surrounding sponsorship.22 In assessing the cost-effectiveness of TAVI in Belgium,23 the authors concluded that TAVI should be restricted to patients who are inoperable because of anatomic prohibitive conditions. These findings strongly contrast with the cost-effectiveness data from the PARTNER trial, showing lower costs in patients treated with TAVI because of reduced hospitalization rates.24,25 The lack of univocal results suggests that the debate is still ongoing and, to the best of our knowledge, our study is the first to compare sutureless implantable valves with TAVI prostheses.
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A limitation of the study is in the nonprospective randomized design. Although the propensity score matching balances of randomization, our study need a prospective confirm. Moreover, we analyzed in the TAVI group both trans-apical and trans-femoral, although we know these are 2 different populations.26 An analysis with 2 separate groups for trans-apical and trans-femoral is planned. In conclusion, the patients in the “gray zone” record a satisfying clinical outcome after sutureless surgery and TAVI. Patients in the sutureless group endure more hospital complications, but, on the other hand, TAVI, due to paravalvular leakage with the actual used technology, entails a higher follow-up mortality. On the costs aspects, TAVI technologies are more expensive, and it reflects on higher overall hospital costs.
7. 8. 9. 10.
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