The CoreValve US Pivotal Trial

doi:10.1053/j.semtcvs.2014.10.001

Seminars in Thoracic and Cardiovascular Surgery

Volume 26, Issue 3, Autumn 2014, Pages 179-186

https://doi.org/10.1053/j.semtcvs.2014.10.001 Get rights and content

Transcatheter aortic valve replacement (TAVR) has been developed as a less-invasive approach to address patients at high risk to extreme risk for surgical aortic valve replacement. The CoreValve US trial enrolled patients with symptomatic severe aortic stenosis into 2 separate cohorts: an extreme-risk cohort and a high-risk cohort. The study of transfemoral TAVR using the CoreValve system in extreme-risk patients achieved its primary end point of all-cause mortality or stroke at 1 year. This was achieved with a low stroke rate and low paravalvular leak rate that improved with time. The CoreValve high-risk trial is the only randomized trial of TAVR vs surgical aortic valve replacement to show superior survival of TAVR. This was achieved with a numerically lower rate of major stroke and statistically superior changes in aortic valve function from baseline to 1 year.

Introduction

In developed countries without significant rheumatic heart disease, degenerative aortic stenosis (AS) is the most prevalent valve disease requiring treatment and increases as the population ages.¹ Open surgical aortic valve replacement (sAVR) has until recently been the only treatment option available shown to relieve symptoms and prolong life.² Unfortunately, studies have shown that up to half of patients that meet guideline criteria for sAVR based on symptomatic severe AS do not receive sAVR because they or their physicians consider them noncandidates based on age, frailty, comorbidity, and other issues.³ Unfortunately, these patients who are denied treatment have a very poor prognosis with a mortality of approximately 50% at 1 year.⁴ Transcatheter aortic valve replacement (TAVR) has been developed as a less-invasive approach to address patients at the high end of the risk scale. Three valves are commercially available in the United States (US) as Food and Drug Administration (FDA)–approved therapy for symptomatic severe AS based on their US investigational device exemption trials. They are the balloon-expandable SAPIEN and SAPIEN XT (Edwards Lifesciences, Irvine, CA) and the self-expanding CoreValve System (Medtronic, Inc., Minneapolis, MN). This article discusses the CoreValve US investigational device exception trial (CoreValve trial) and its outcomes as well as the future direction for the CoreValve platform.

Section snippets

Trial Design

The CoreValve US trial enrolled patients with symptomatic severe AS into 2 separate cohorts—an extreme-risk cohort and a high-risk cohort.5, 6 The extreme-risk cohort study of the trial was a multi-institution, prospective, nonrandomized study. Patients who were treated via iliofemoral access were evaluated against an objective performance goal (OPG) for all-cause mortality or stroke at 1 year for noninferiority. Noniliofemoral access was allowed and evaluated as a separate nested registry. The

Risk Evaluation

All patients were evaluated by their local heart team that needed to include at least 1 interventional cardiologist and at least 2 experienced cardiac valve surgeons. If approved by the local team, the cases were all reviewed on a national videoconference by the national screening committee (NSC) that included at least 1 interventional cardiologist and 2 cardiac valve surgeons for final approval for the trial. The NSC membership remained constant throughout the trial to provide consistency. The

Definition of AS

Severe AS was defined as an aortic valve area ≤0.8 cm² or aortic valve index ≤0.5 cm²/m² and either a mean aortic valve gradient greater than 40 mm Hg or a peak aortic valve velocity greater than 4.0 m/s, at rest or with a dobutamine stress if the left ventricular ejection fraction was less than 50%. All patients had to have at least New York Heart Association (NYHA) functional Class II symptoms.

Anatomy Evaluation

Access was specified as femoral first with subclavian or direct aortic (DA) access allowed if femoral access was not feasible or safe. For femoral placement of the 18-F sheath, the minimal diameter of the iliofemoral system had to be greater than 6 mm if noncalcified and greater than 7 mm if calcified over a 270° area of the artery. Technical aspects of noniliofemoral alternative access have been previously published.⁷

The CoreValve device size was chosen using annular perimeter derived diameter

Study Device Procedure

The CoreValve system consists of 3 components: the transcatheter heart valve (THV), the delivery catheter system, and the compression loading device. The THV is a self-expanding nitinol frame with a porcine trileaflet pericardial valve attached (Fig. 2). The valve has 3 distinct zones: the sealing skirt that includes the first 12 mm of the valve with high radial force, the supra valvular valve itself in a constrained portion with high hoop strength, and a distal flared outflow with low radial

Extreme-Risk Cohort

The extreme-risk cohort was originally designed to look like the Placement of Aortic Transcatheter Valves Cohort B (PARTNER B) inoperable arm of the SAPIEN valve trial.⁴ The PARTNER B trial randomized patients between TAVR and best medical therapy. The survival was highly positive for TAVR although stroke was more common in the TAVR arm in this trial. With this highly positive survival advantage of TAVR, randomization against medical therapy was no longer considered ethical for the CoreValve

Echocardiographic Findings

Serial echocardiograms at postprocedure, discharge, 1 month, 6 months, and 1 year were evaluated by the core laboratory. The mean aortic valve gradient was reduced from 47.3 ± 14.6 mm Hg at baseline to 8.9 ± 4.1 mm Hg (Δ39.8 ± 14.8 mm Hg, P < 0.0001 for paired echocardiograms), and the effective orifice area (EOA) was significantly increased from 0.7 ± 0.2 cm² to 1.9 ± 0.5 cm² at 1-year follow-up (Δ1.2 ± 0.6 mm Hg, P < 0.0001 for paired echocardiograms). The left ventricular ejection fraction was 54.5 ±

Conclusion Extreme Risk

The study of transfemoral TAVR using the CoreValve system in extreme-risk patients easily achieved its primary end point of all-cause mortality or stroke at 1 year. This was achieved with a low stroke rate and low PVL rate that improved with time. The CoreValve THV system is safe and effective in patients at prohibitive risk for surgery, providing a significant and sustained improvement in EOA, mean gradient, and clinical functional class. This led to FDA approval of the CoreValve System for

Extreme-Risk Noniliofemoral Alternative Access Nested Registry

Unlike the PARTNER B trial that did not allow nonfemoral access, the CoreValve extreme-risk trial allowed a nontested nested registry for noniliofemoral alternative access patients. This group has been untested, and no adequate comparator group exists prohibiting a prespecified OPG. Subclavian and DA access approaches were allowed in this trial cohort. The primary end point was all-cause mortality or stroke at 1 year. The purpose was to test the safety and effectiveness of the CoreValve system

High-Risk Trial

The high-risk cohort of the trial is a multi-institutional, prospective, randomized trial of TAVR with the CoreValve system vs sAVR in patients at high risk. It is a noninferiority trial that included prespecified hierarchical superiority testing. The primary end point was all-cause mortality at 1 year. Secondary end points of change in gradient from baseline to 1 year (noninferior), change in EOA from baseline to 1 year (noninferior), change in NYHA class from baseline to 1 year (noninferior),

High-Risk Conclusion

The CoreValve high-risk trial is the only randomized trial of TAVR vs sAVR to show superior survival of TAVR. This was achieved with a numerically lower rate of major stroke and statistically superior changes in EOA and mean gradient from baseline to 1 year. This led to FDA approval for CoreValve in the high-risk patient population with symptomatic severe AS.

Future Direction

TAVR has been broadly accepted for extreme-risk and high-risk patients with symptomatic severe AS, and the CoreValve device is commercially approved for both these indications. Controversy still exists as we move down the risk scale to the intermediate risk-groups owing to the lack of evidence in this population where sAVR is still considered the gold standard treatment.¹⁷ The CoreValve Surgical Replacement and Transcatheter Aortic Valve Implantation randomized trial is currently enrolling

Final Conclusion

In this multiarmed, fully monitored, interventional, safety and efficacy trial, the CoreValve system for TAVR has shown improved survival over an OPG in extreme-risk patients. In high-risk patients, the trial has shown for the first time, superior survival with TAVR compared with sAVR, in a randomized trial. This was also achieved with a numerically smaller rate of major stroke at 1 month and 1 year in the TAVR group. The Surgical Replacement and Transcatheter Aortic Valve Implantation trial

References (17)

B.A. Carabello et al.
Aortic stenosis
Lancet
(2009)
R.O. Bonow et al.
ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons
J Am Coll Cardiol
(2006)
B. Ramlawi et al.
Direct aortic and subclavian access for transcatheter aortic valve replacement: Decision making and technique
J Thorac Cardiovasc Surg
(2014)
A. Agarwal et al.
Results of repeat balloon valvuloplasty for treatment of aortic stenosis in patients aged 59 to 104 years
Am J Cardiol
(2005)
A.C. To et al.
Balloon aortic valvuloplasty in adults—A 10-year review of Auckland׳s experience
Heart Lung Circ
(2008)
S.R. Kapadia et al.
Characterization and outcome of patients with severe symptomatic aortic stenosis referred for percutaneous aortic valve replacement
J Thorac Cardiovasc Surg
(2009)
R.A. Nishimura et al.
2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
J Thorac Cardiovasc Surg
(2014)
B. Iung et al.
Decision-making in elderly patients with severe aortic stenosis: Why are so many denied surgery?
Eur Heart J
(2005)

There are more references available in the full text version of this article.

Cited by (35)

Depth of implantation in relation to membranous septum as a predictor of conduction disturbances after transcatheter aortic valve implantation
2024, Indian Pacing and Electrophysiology Journal
Conduction disturbances remain one of the most common complications occurring post TAVI. We aim to determine the predictors of cardiac conduction disturbances after Transcatheter Aortic Valve Implantation (TAVI) and propose a relevant predictive model.
We included 70 consecutive patients with severe symptomatic AS who underwent TAVI using the self-expanding valve Evolut R or the balloon expandable Sapien XT valve. All patients were subjected to electrocardiographic evaluation pre- and post-TAVI and at 30 days. Clinical, echocardiographic, CT-derived, and procedural parameters were collected and analyzed.
Conduction disturbances affected 28 patients (40%): 16 patients (22.9 %) developed Left Bundle Branch Block (LBBB), 7 patients (10%) experienced transient Complete Heart Block (CHB), and 5 patients (7.1%) experienced permanent CHB requiring Permanent Pacemaker Implantation (PPI). We classified predictors into preprocedural and procedural predictors. Multivariate logistic regression analysis of pre-procedural predictors showed that the presence of basal septal calcification is the most powerful independent predictor (OR: 28.63, 95% CI: 4.59–178.68, p < 0.001). Multivariate logistic regression analysis for pre and post procedural predictors showed that the relationship between depth of implantation at the septum and membranous septum expressed in percentage (sDIMS) with cut-off >70.42% is the most powerful independent procedural predictor (OR: 1.11, 95% CI: 1.03–1.2, p 0.006).
Conduction disturbances remain a common complication of TAVI. Presence of basal septal calcification is a non-modifiable risk factor that increase patient propensity of development such complication after TAVI. A depth of implantation exceeding 70% of the membranous septal length has been found to strongly predict conduction disturbances post TAVI. sDIMS can be used in planning the depth of implantation to reduce incidence of conduction disturbances post TAVI.
Systolic Heart Failure is Associated with Higher Mortality Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Nationwide Analysis
2023, Current Problems in Cardiology
Heart failure (HF) is prevalent among patients with aortic stenosis and presents a poor prognosis. In order to better portray outcomes for HF patients undergoing transcatheter aortic valve replacement (TAVR), we evaluated clinical outcomes in patients with systolic vs diastolic heart failure who underwent TAVR in a large nationwide database. We searched the National Inpatient Sample (NIS) for hospitalized adult patients who underwent TAVR with coexisting history of systolic (SHF) or diastolic heart failure (DHF) as a secondary diagnosis using the ICD-10 codes. The primary outcome was in-hospital mortality, with secondary outcomes of cardiac arrest (CA), cardiogenic shock (CS), respiratory failure (RF), Non-ST elevation myocardial infarction (NSTEMI), acute kidney injury (AKI), use of cardiac and respiratory assist device, and health care utilization defined as length of stay, average hospital cost (AHC) and patient charge (APC). Both univariate and multivariate logistic, generalized linear, and Poisson regression analyses were used to evaluate and test the outcomes. A P-value of <0.05 was significant. A total of 106,815 patients were admitted to acute care hospitals for TAVR, and 73% had a secondary diagnosis of heart failure (41% had SHF and 59% DHF). SHF group were older (mean age of 78.9 years [SD ± 8.9] vs 79.9 years [SD ± 8.3]) with more males (61.8% vs 48.2%) and white predominant (whites [85.9% vs 87.9%]). Compared to DHF, SHF had higher inpatient mortality (1.75% vs 1.14%, P = 0.003), CA (1.31% vs 0.81%, P = 0.01), NSTEMI (2.52% vs 1.0%, P = 0.001), RF (10.87% vs 8.01%, P = 0.001), and CS (3.94% vs 1.14%, P = 0.001). In addition, SHF had greater LOS (5.1 days vs. .3.9, P = 0.0001) & AHC ($52,901 vs $48,070, P = 0.0001). HF is common among patients admitted for TAVR. SHF had worse CV outcomes, greater use of hospital resources, and higher acute care hospital mortality compared to those with DHF.
Left Main Protection During Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve
2022, Journal of the Society for Cardiovascular Angiography and Interventions
Coronary obstruction during transcatheter aortic valve replacement (TAVR) is a rare, yet life-threatening, complication. The routine use of left main (LM) protection with or without stent placement in high-risk patients remains controversial. The aim of this study was to evaluate the outcomes of LM protection during TAVR and identify anatomic factors associated with need for stent placement.
We retrospectively reviewed all TAVR cases (native and valve-in-valve) performed in our institution between 2014 and 2019 and identified patients who underwent LM protection with a coronary wire, balloon, and/or stent during the procedure. We compared the pre-TAVR computed tomography aortic root characteristics, procedural data, short-, and long-term outcomes among the patients who eventually received an LM stent and those who did not.
Among 1925 TAVR patients, 41 (2.1%) underwent LM protection, and 10 of them (25%) had eventually a stent placed in the LM for threatened obstruction after valve deployment. In the native TAVR group (n = 35), 8 patients underwent LM stenting. A larger TAVR prosthesis, larger annular circumference (83.8 vs 76.1 mm; P = .038), lower ratio of sinotubular junction diameter to prosthesis size (1.02 vs 1.11; P = .032), and longer left coronary cusp (15.1 vs 13.9 mm; P = .18) were associated with higher incidence of LM stenting. In the valve-in-valve TAVR group (n = 6), 5 patients had a valve-to-coronary distance of less than 4 mm, and 2 of them received an LM stent. Both stent and nonstent groups had excellent outcomes with no major adverse cardiovascular events or coronary obstruction at 30 days. After a median follow-up of 351 days, 4 patients died (9.7%) (1 in the stent and 3 in the nonstent group), without any cases of late coronary obstruction or percutaneous coronary intervention in either group.
LM protection with a coronary guidewire, balloon, or stent is a safe and effective method of coronary protection during TAVR in appropriately selected high-risk patients. Annular circumference, prosthesis size, left coronary cusp length, LM ostial height, and ratio of sinotubular junction to prosthesis size are important predictors of stent deployment.
Transcatheter Aortic Valve Replacement with a Self-Expanding Prosthesis
2021, Interventional Cardiology Clinics
Citation Excerpt :
In 2014, the CoreValve US Pivotal Trial became the first of many trials investigating the safety and efficacy of SEVs in aortic valve replacement (Table 1). In the extreme risk cohort, TAVR with SEV was compared to medical therapy in inoperable patients and showed a marked survival benefit in patients treated with TAVR.8 Subsequently, TAVR with SEV was compared to SAVR in high-risk patients.
Bioengineered percutaneous heart valves for transcatheter aortic valve replacement: a comparative evaluation of decellularised bovine and porcine pericardia
2021, Materials Science and Engineering C
Glutaraldehyde-treated, surgical bioprosthetic heart valves undergo structural degeneration within 10–15 years of implantation. Analogous preliminary results were disclosed for percutaneous heart valves (PHVs) realized with similarly-treated tissues. To improve long-term performance, decellularised scaffolds can be proposed as alternative fabricating biomaterials. The aim of this study was to evaluate whether bovine and porcine decellularised pericardia could be utilised to manufacture bioengineered percutaneous heart valves (bioPHVs) with adequate hydrodynamic performance and leaflet resistance to crimping damage.
BioPHVs were fabricated by mounting acellular pericardia onto commercial stents. Independently from the pericardial species used for valve fabrication, bioPHVs satisfied the minimum hydrodynamic performance criteria set by ISO 5840-3 standards and were able to withstand a large spectrum of cardiac output conditions, also during extreme backpressure, without severe regurgitation, especially in the case of the porcine group. No macroscopic or microscopic leaflet damage was detected following bioPHV crimping.
Bovine and porcine decellularized pericardia are both suitable alternatives to glutaraldehyde-treated tissues. Between the two types of pericardial species tested, the porcine tissue scaffold might be preferable to fabricate advanced PHV replacements for long-term performance.
Current percutaneous heart valve replacements are formulated with glutaraldehyde-treated animal tissues, prone to structural degeneration. In order to improve long-term performance, bovine and porcine decellularised pericardia were utilised to manufacture bioengineered replacements, which demonstrated adequate hydrodynamic behaviour and resistance to crimping without leaflet architectural alteration.
Unilateral Access Is Safe and Facilitates Peripheral Bailout During Transfemoral-Approach Transcatheter Aortic Valve Replacement
2019, JACC: Cardiovascular Interventions
The aim of this study was to compare the rate and trend of vascular complications when placing a second arterial sheath in the contralateral femoral artery during transcatheter aortic valve replacement (TAVR) unilaterally versus bilaterally.
Vascular complications occur in approximately 5% to 8% of TAVR procedures. Many operators place a second arterial sheath in the contralateral femoral artery to perform aortic root angiography. The authors surmised that placing the second sheath ipsilateral and distal to the delivery sheath would be an easier option with similar safety.
The Cleveland Clinic Aortic Valve Center TAVR database was accessed, and data for patients undergoing transfemoral TAVR (TF-TAVR) from January 2014 to December 2017 were analyzed retrospectively. The primary outcome was the rate of peripheral vascular complications.
A total of 1,208 patients who underwent TF-TAVR were included in this study. One thousand seven patients (83.36%) underwent bilateral femoral access, and 201 patients (16.64%) underwent TF-TAVR using a unilateral femoral approach. Over the study duration, use of the unilateral access approach trended upward significantly, reaching 43.7% of total cases in 2017. A gradual decline in access site–related vascular complications was observed, from 13.7% in 2014 to 7.4% in 2017. After propensity-score matching, peripheral vascular complications were similar between bilateral access and unilateral access (10.8% vs. 8.6%) (p = 0.543).
There was a significant decline in vascular complications from 2014 to 2017. Unilateral-access TF-TAVR provided similar safety compared with bilateral-access TF-TAVR and is a more accessible approach for managing access site–related complications and possibly achieving better patient satisfaction.

View all citing articles on Scopus

: The CoreValve US Pivotal Study was funded by Medtronic, Inc., Minneapolis, Minnesota. Dr. Reardon reports receiving consulting fees from Medtronic. Dr. Barker reports receiving consulting and lecture fees from Medtronic, Boston Scientific, and Abbott Vascular.

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News and ViewsThe CoreValve US Pivotal Trial

Introduction

Section snippets

Trial Design

Risk Evaluation

Definition of AS

Anatomy Evaluation

Study Device Procedure

Extreme-Risk Cohort

Echocardiographic Findings

Conclusion Extreme Risk

Extreme-Risk Noniliofemoral Alternative Access Nested Registry

High-Risk Trial

High-Risk Conclusion

Future Direction

Final Conclusion

Lancet

J Am Coll Cardiol

J Thorac Cardiovasc Surg

Am J Cardiol

Heart Lung Circ

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Decision-making in elderly patients with severe aortic stenosis: Why are so many denied surgery?

Eur Heart J

News and Views
The CoreValve US Pivotal Trial