Abstract: Objectives. The Evolut-R (Medtronic, Inc) is a transcatheter aortic valve implantation (TAVI) system that was built on the well-established foundation of Medtronic’s CoreValve device platform. Although already in extensive clinical utilization, it is unknown if the Evolut-R improves TAVI outcomes. Herein, we compared TAVI outcomes of the Evolut-R and CoreValve devices. Methods. A propensity score 1:1 matching was conducted on 358 Evolut-R patients (n = 75) and CoreValve patients (n = 283). Thirty-day outcomes were compared using Valve Academic Research Consortium (VARC)-2 criteria. A combined 30-day endpoint including all-cause death, stroke, major vascular complication, major bleeding, implantation failure, paravalvular leak (PVL) ≥ moderate, and new pacemaker implantation was also tested. Results. The final study group included 146 patients (73 Evolut-R; 73 CoreValve). Post matching, baseline characteristics were similar between the two groups. Mean patient age was 82 ± 6 years, mean STS score was 5.2 ± 3.8, 72% were female, and 17% were deemed frail. Implantation success reached 99% with Evolut-R and 94% with CoreValve (P=.10). Both groups had low periprocedural stroke/myocardial infarction/mortality rates and there was also no difference in 30-day vascular complications (P=.18), bleeding (P=.37), PVL (P=.24), and new pacemaker (P=.14). The combined outcome rate was 24% with Evolut-R and 37% with CoreValve (P=.10). Conclusion. This study indicates that the efficacy and safety of the self-expandable second-generation Evolut-R transcatheter valve is at least comparable with the first-generation CoreValve. The observed improved performance in correct positioning of a single valve and the numerically lower chance to suffer a combined TAVI endpoint needs further investigation.
J INVASIVE CARDIOL 2017;29(2):69-74.
Key words: transcatheter heart valve, THV, first-generation device, new-generation device, outcomes
Transcatheter aortic valve implantation (TAVI) offers significant benefits to a wide spectrum of patients who suffer from severe symptomatic aortic stenosis (AS).1-5 However, it is not free of complications; its main potential problems include paravalvular leak (PVL), vascular complications, and conduction abnormalities. Procedural success is not yet optimal, and periprocedural stroke and even death may occur. The CoreValve Evolut-R (Medtronic, Inc) transcatheter aortic valve is a second-generation device system that was built on the well-established foundation of the first-generation CoreValve platform. It is fortified with a smaller-caliber delivery system and a fully recapturable platform that could theoretically improve procedural results. Although already in extensive clinical use, it is not yet known if the Evolut-R improves TAVI outcomes.
Patients treated. At our tertiary institute at Rabin Medical Center in Israel, patients with severe symptomatic AS are referred to a dedicated consultation by a multidisciplinary heart team. Our screening policies to determine the most appropriate treatment strategy have been previously described6 and will be briefly summarized here. Severe AS is defined by echocardiography as a valvular orifice area <1.0 cm2 or <0.6 cm2/m2 and/or a mean transaortic valvular gradient >40 mm Hg and/or jet velocity >4.0 m/s. All patients go through a rigorous assessment process that includes history taking, physical examination, physical performance measures, cognitive assessments, laboratory tests, and calculation of both the European System for Cardiac Operative Risk Evaluation score II (EuroSCORE II) and Society of Thoracic Surgeons (STS) score. Frailty is assessed with the aid of objective performance measures: gait speed, body mass index, cognitive assessment, and serum albumin. Patients with an estimated life expectancy of <1 year or cognitive decline are referred for palliative medical treatment and/or balloon aortic valvuloplasty. All patients considered for valve replacement are assessed by angiography, and patients selected for TAVI undergo transesophageal echocardiography and computed tomography angiography as required. Patients who are candidates for valve replacement with an acceptable operative risk, defined as STS score <8% as verified by the heart team forum, are considered for surgical aortic valve replacement. However, prohibitive surgical risks such as fragility have also been taken into account. Patients with STS score >8% are evaluated individually and are often referred for TAVI. The heart team further discusses issues regarding access site, device size/type, etc, and the procedures are performed in our catheterization suites by interventional cardiologists.
Outcomes reporting. Clinical, procedural, and outcome information is prospectively collected for all patients, and all endpoint definitions are standardized according to the Valve Academic Research Consortium (VARC)-2 document.7 All patients are prospectively examined at 30 days, at 6 and 12 months, and yearly thereafter. Thirty-day outcomes were compared and reported according to VARC-2 definitions. Also, we tested a combined 30-day endpoint comprised of all-cause death, stroke, major vascular complication, major bleeding, implantation failure, PVL ≥ moderate and new permanent pacemaker [PPM] implantation after TAVI.
Propensity matching for comparison of Evolut-R vs CoreValve. For the purpose of this study, a propensity score match was used to identify a set of Evolut-R/CoreValve patient pairs who were matched based on a comprehensive set of clinical characteristics, so as to minimize the potential selection bias that may be associated with our observational study. The propensity score was derived by developing a logistic regression model that predicted the probability that a given patient would receive an Evolut-R valve on the basis of all clinical characteristics available in our registry. The device type was used as the dependent variable, while potential confounders were used as independent variables in the propensity model. The propensity score was used to match Evolut-R to CoreValve patients on a 1:1 basis so as to minimize the overall distance in propensity scores between the groups. The propensity score included the following variables: age, gender, STS score, EuroSCORE II, New York Heart Association (NYHA) functional class level, glomerular filtration rate (mL/min/1.73 m2), frailty, porcelain aorta, history of severe liver disease, chronic obstructive pulmonary disease, stroke, diabetes mellitus, atrial fibrillation, coronary artery bypass graft surgery, valvular surgery, percutaneous coronary intervention, myocardial infarction (MI), peripheral vascular disease, PPM, dyslipidemia, hypertension, smoking, and chest pain and/or syncope at presentation. For propensity score calculation, the issue of missing baseline covariates was addressed using near-neighbor analysis technique with an average of 3 to 5 similar patients before the propensity score model was finalized. The imputed missing data were not used for baseline characteristic comparisons. Pairs of Evolut-R and CoreValve patients were matched unless their estimated log-odds from the logistic regression model were greater than 0.5 standard deviations apart. Standardized differences in the prevalence of propensity model variables were then calculated. The propensity-matched pairs were then used to analyze differences in outcomes between the groups.
Statistical analysis. All data were registered in an electronic file. Continuous variables were expressed as mean ± standard deviation. Categorical data were summarized as percentages. Characteristics of patients were compared between groups using the t-test for continuous variables and the c2-test or Fisher’s exact test for dichotomous variables, as appropriate. The odds ratio (OR) and 95% confidence interval (CI) were calculated for the primary endpoint and for the risk of new PPM using logistic regression analysis. All P-values were two sided, and a P-value <.05 was considered statistically significant. Analyses were conducted with SPSS software, version 19.0 (SPSS) and SAS software, version 9.4 (SAS Institute).
A total of 535 consecutive patients underwent TAVI at our center between November 2008 and February 2016, of which 358 (67%) received self-expanding CoreValve (n = 283; 53%) or Evolut-R devices (n = 75; 14%). CoreValve deployment started in September 2009 and lasted until April 2015. Evolut-R deployment started in November 2014. Compared with the CoreValve, the Evolut-R TAVI patients had lower surgical risk as reflected by a lower STS score (Table 1). From these two cohorts, we were able to conduct a propensity-score pair match between 73 Evolut-R and 73 CoreValve patients, which constructed the present analysis. Post matching, baseline characteristics were similar between the two groups, with a non-significant trend toward slightly lower hemoglobin concentration and mean aortic valve gradient in the CoreValve group (Table 2). Mean patient age was 82 ± 6 years and mean STS score was 5.2 ± 3.8. Females comprised 72%, and 17% were assessed as extremely frail. Table 2 summarizes the baseline characteristics of the two matched groups.
Procedural outcomes. In both groups, most cases were performed under conscious sedation (86% Evolut-R vs 84% CoreValve; P=.62) and by transfemoral access route (99% Evolut-R vs 95% CoreValve; P=.36). Predilation of the native aortic valve was performed in 28% of the Evolut-R cases and 34% of the CoreValve cases (P=.44). Positioning of a single valve in the proper location was achieved in 99% of Evolut-R patients and 94% of CoreValve patients (P=.10). Postprocedural mean transaortic gradient was 7.3 ± 5.3 mm Hg in the Evolut-R group and 9.2 ± 7.2 mm Hg in the CoreValve group (P=.16). No difference in PVL was seen between the groups, and there were no patients with PVL ≥ moderate in either group (Figure 1).
Clinical outcomes. There were 3 cases (4%) of in-hospital death among the Evolut-R group and 1 case (1%) among the CoreValve group (P=.31). All deaths were cardiovascular in nature except 1 Evolut-R case. The 2 cardiovascular death cases in the Evolut-R group occurred in patients admitted in acute heart failure state and pulmonary edema that underwent urgent TAVI.8 Figure 2 illustrates some of the main procedural complications within each group. The rates of periprocedural stroke and MI were <1.5%, there was 1 coronary occlusion (in a CoreValve patient), and there were no instances of tamponade or annular rapture. In each group, major vascular complication was observed in 2 cases, and the rate of any vascular complications was 14% in the Evolut-R group and 20% in the CoreValve group (P=.18). At 30 days, a new PPM implantation was required in 8 Evolut-R patients (11%) and 13 CoreValve patients (18%; P=.14). When compared with Core-Valve, the OR was 0.55 (95% CI, 0.20-1.51) for a new PPM in the Evolut-R group (P=.24).
The rate of the 30-day combined endpoint of all-cause death, stroke, major vascular complication, major bleeding, implantation failure, PVL ≥ moderate, and new PPM was 24% in the Evolut-R group vs 37% in the CoreValve group (P=.10), with an OR of 0.54 (95% CI, 0.25-1.13) with an Evolut-R patient compared with a CoreValve patient (P=.10).
Symptom relief (expressed as NYHA functional class decrease) 30 days after TAVI was observed in the majority of the patients, with no apparent different between the Evolut-R and CoreValve groups (Figure 3).
The most cardinal TAVI data are based on two devices: the balloon-expandable Edwards prosthesis (Edwards Lifesciences) and the self-expanding Medtronic CoreValve (Medtronic).9-12 The Evolut-R second-generation valve was built on the well-established foundation of the CoreValve platform, engineered to improve TAVI efficacy/safety outcomes, fortified with lower delivery profile (14-16 Fr) to reduce vascular complications and alternative TAVI access necessity, enhanced frame geometry to enable better housing inside the aortic root, and a fully recapturable platform that allows movement of the valve to a new position during deployment, if needed. This valve is already in extensive clinical use and is more expensive than the first-generation device. However, it’s unknown if the Evolut-R provides a superior outcome. Although some data comparing first-generation and second-generation TAVI devices were recently published,13 to the best of our knowledge, no comparative evaluation of this device has been reported. Thus, we have compared TAVI outcomes between the first-generation and second-generation fundamental self-expanding valve, aiming to explore if this step in technology translates to short-term clinical outcome differences. We used propensity-score matching to minimize the potential bias that may be associated with each valve generation.
Our results support short-term efficacy and safety performance of the Evolut-R compare with the CoreValve, with no significant outcome differences found between the two devices. The Evolut-R was associated with a trend toward higher implantation success rate and numerically less chance to suffer the combined endpoint of all-cause death, stroke, major vascular complication, major bleeding, implantation failure, PVL ≥ moderate, and new PPM.
Some available data on the Evolut-R valve come from Manoharan et al,14 who reported the short-term, first-in-man results on 60 patients. Similar to our experience, the transfemoral access adherence and the implantation success rate were exceedingly high (achieved in 96% and 98% of the patients, respectively). It is probable that the novel edge of the delivery system (containing the folded valve), which is smaller and expandable, empowers these abilities because it facilitates more slender peripheral arterial transport, recapturing, and repositioning.
PVL is one of the relatively common complications after TAVI and also carries an adverse impact on patient survival.5,15 The recently reported Evolut-R postprocedural PVL rates16 were 70.5% (no/trace PVL), 26.4% (mild PVL), and 3.1% (moderate PVL). We also observed very similar low PVL rates. Moreover, all patients in our cohorts were within the ≤ moderate PVL range (Figure 1); nevertheless, no difference in PVL rate was found between the Evolut-R and CoreValve patient groups.
Likewise, the event rates of stroke, MI, major vascular complications, bleeding, and in-hospital mortality at 30 days were all small, and no differences were identified between the groups. While Ruparelia et al13 found a significant decrease in the rate of vascular complications between first-generation and second-generation devices, we did not. However, we were underpowered to demonstrate differences in major vascular complications, as there were only 2 such cases in each group. There were numerically fewer vascular complications in the Evolut R group (14%) vs the CoreValve group (20%), although this also was not statistically significant (P=.18).
In the early United States experience with the Evolut-R,16 the device was shown to be safe, with 1-month mortality rate of 2.5% and disabling stroke rate of 3.3%. Importantly, the use of the re-sheath feature was not associated with an increase in stroke rate. A recent systematic review on the safety of second-generation transcatheter aortic valves17 captured 24 reports on 1708 patients and 8 valve types. It did not, however, include the Evolut-R valve. In that study, the 30-day event rates of mortality, MI, stroke, major vascular complications, and PPM utilization were similar to ours. Additionally, it should be pointed out (as mentioned in the results section) that in our series, the 2 in-hospital cardiovascular deaths in the Evolut-R group occurred in patients in acute heart failure and followed urgent TAVI, which was shown to be a more complex and risky procedure but appears to offer generally favorable results among carefully selected patients.8
The most common TAVI complication is atrioventricular conduction block requiring PPM implantation.18 The incidence was reported to be 13.9% (95% CI, 10.6%-18.9%) in a meta-analysis on the overall first-generation valves and 13.5% (95% CI, 10.8%-16.9%) in a pooled analysis of the second-generation devices,17,19 which is similar. Specifically with the CoreValve, new PPM incidence was reported to be as high as 25% within the first-generation CoreValve11,12 and about 12% with the Evolut-R.14 In this line, we found a numerically lower chance to require a new PPM with the Evolut-R compared with the CoreValve, although it was not found to be statistically significant (OR, 0.55; 95% CI, 0.20-1.51; P=.24).
Study limitations. This was a single-center observational study with a relatively small patient population and short (30-day) follow-up. Moreover, the event rate of most of the adverse events was low, which may be partially explained by the relatively low STS risk score (mean score, 5.2 ± 3.8%) of the population studied. There was a lower STS score in the original Evolut-R population compared with the original CoreValve population, which was addressed with a propensity scoring as best as possible. Nevertheless, the sequential nature of CoreValve then Evolut-R experience may have affected the outcomes in ways that propensity matching may not fully address – namely, the incorporation of the overall TAVI learning curve from which the Evolut-R group may benefit, making it susceptible to selection bias despite the propensity matching we conducted. Lastly, the assessment of some outcomes, namely, the PVL and postimplantation transvalvular gradients, were not assessed by a core lab or in a blinded fashion.
This study supports the efficacy and safety of the self-expandable second-generation Evolut-R transcatheter valve compared with its archetype first-generation CoreValve. The affinity for superiority in correct positioning of a single valve and the numerically less chance to suffer any of the combined endpoints of all-cause death, stroke, major vascular complication, major bleeding, implantation failure, PVL ≥ moderate, and new PPM require further investigation in larger prospective studies with longer follow-up.
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From the Department of Cardiology, Institute of Interventional Cardiology, Rabin Medical Center, Petach Tikva and Tel Aviv University, Tel Aviv, Israel.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted July 26, 2016, provisional acceptance given August 31, 2016, final version accepted October 13, 2016.
Address for correspondence: Prof. Ran Kornowski, M.D, FACC, FESC, Chairman- Department of Cardiology, Beilinson Hospital- Rabin Medical Center, Jabotinski St. 39, Petah-Tikva, 39100, Israel. Email: firstname.lastname@example.org