i(

SMAS

R2

Paec

REPO

RT

SPECIAL REPORT FROM THE SOCIETY OF THORACIC SURGEONS

Transcatheter Valve Therapy: A ProfessionalSociety Overview from the American Collegeof Cardiology Foundation and The Societyof Thoracic SurgeonsWriting Committee Members: David R. Holmes, Jr, MD, FACC, ACCF President,

Michael J. Mack, MD, FACC, STS President

Preamble

The evolution of transcatheter valve therapy raises im-portant questions for practitioners, patients, and govern-ment agencies on the appropriate treatment strategy forpatients who could be eligible for this procedure. TheAmerican College of Cardiology Foundation (ACCF) andThe Society for Thoracic Surgeons (STS) joined togetherto write this paper to set the stage for a series ofdocuments, to be joined by other professional societies,to address the issues critical to successful integration ofthis new procedure into medical practice in the UnitedStates. Final review and approval of the document wasprovided by the ACCF Board of Trustees and the STSBoard of Directors. The ACCF and STS believe thisdocument will be helpful to frame the discussion of keyissues and questions for consideration as this new tech-nology unfolds. Our organizations remain committed toproviding guidance on key clinical issues.

1. Introduction

Transformational technology is defined as one that whenintroduced radically changes markets, creates whollynew markets, or could even eliminate existing marketsfor older technology (1). The field of medicine is repletewith examples of such therapies that have radicallyaltered the treatment of disease, including sterile tech-

This document is approved by The Society of Thoracic Surgeons (STS)Board of Directors and the American College of Cardiology Foundation(ACCF) Board of Trustees. This article is co-published in The Annals ofThoracic Surgery and the Journal of the American College of Cardiology ands available via CTSNet (http://ats.ctsnetjournals.org), Science Directhttp://www.sciencedirect.com/science) and www.acc.org.

TS requests that this document be cited as follows: Holmes DR Jr, MackJ. Transcatheter valve therapy: a professional society overview from themerican College of Cardiology Foundation and The Society of Thoracicurgeons. Ann Thorac Surg 2011;92:380-9.

eprints are available from Elsevier Inc, Reprint Department, FAX:12-633-3820; e-mail: reprints@elsevier.com.

ermissions: Multiple copies, modification, alteration, enhancement,nd/or distribution of this document are not permitted without the

xpress permission of STS. Please contact healthpermissions@elsevier.om.

© 2011 by The Society of Thoracic Surgeons andthe American College of Cardiology FoundationPublished by Elsevier Inc

niques in surgery, vaccines to cure polio, penicillin andsulfa drugs for infectious diseases, and cortisone. Thesetherapies have each been developed in concert by phy-sicians, scientists, and industry partners.

Catheter-based therapies present new and potentiallytransformational technology for valvular and structuralheart disease (2). The associated issues are complex, withmultiple stakeholders: first and foremost, the patientsreceiving this therapy, but also including clinicians, in-ventors, industry, regulatory agencies, government andprivate payers, and professional societies. The purpose ofthis document is to capture all the core elements propor-tionally with the overarching goal of aligning the inter-ests of all expert physicians including cardiologists; pro-ceduralists; heart valve, heart failure, and imagingspecialists; and imaging experts with other relevantstakeholders (regulators, payers, professional societies)in delivering the best possible patient-centered care. Therole of societies is to realize this goal through ongoingdevelopment of expert consensus statements, guidelines,credentialing criteria, and training paradigms, therebyensuring responsible diffusion of this technology.

1.1. Components of New Valve TechnologyIntroductionSeveral issues emerge with the introduction of this newtechnology.

1. How will this technology be regulated and bywhom?

2. Will the technology be available in all centers by allphysicians or only in selected regional centers; ifthe latter, how will those centers be selected?

3. How will training of physicians and centers beaccomplished? What will the training paradigms beand what experience is necessary for credentialingto be deemed proficient? Will the training be thesame for cardiologists and surgeons?

4. Will clinical databases be linked to administrativedatabases facilitating long-term outcome assess-ment, comparative effectiveness research, and cost-

See Appendix for disclosures regarding authors finan-cial relationships with industry.

Ann Thorac Surg 2011;92:380–9 • 0003-4975/$36.00doi:10.1016/j.athoracsur.2011.05.067

EtarsctpvproG

TI

381Ann Thorac Surg HOLMES, JR AND MACK2011;92:380–9 TRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW

REP

OR

T

effectiveness analysis? Will data collection berequired using standardized definitions in harmo-nized national clinical and administrative data-bases and registries, and if so, from where will theresources come to accomplish this? Can these stan-dardized registries be used worldwide?

5. What will be the rational diffusion of the newtechnology to other patient groups not originallystudied in randomized clinical trials?

6. How will this new technology be reimbursed? Howwill patient cohorts be identified that will benefitthe most and provide the most cost-effective andclinically effective treatment?

These complexities are compounded by the multipleconstituents involved—patients, competing physiciansand practice centers, payers, and industry—each ofwhich may have different goals. The intent of this docu-ment is to provide a platform of issues to be solvedand provide some direction as to how this may beaccomplished.

2. Heart Valve Surgery and Transcatheter ValveTherapy

Traditional aortic and mitral surgery has been the main-stay of treatment for valvular heart disease; prior tosurgical techniques for valve replacement and repair,there were no effective therapies for patients with severedisease. In selected patients at experienced centers withexpert surgeons, the results have generally been excel-lent with improved morbidity and mortality comparedwith medical therapy but at a cost of significant invasive-ness and recovery time for the patient. Since the intro-duction of minimally invasive and catheter-based thera-pies, patients have wanted less invasive options for alltypes of medical procedures including general surgical,orthopedic, spine, and urologic operations with the goalof decreasing morbidity and mortality and shorteningrecovery time (3).

Other issues with traditional aortic and mitral valvesurgery include the fact that patients may not even beoffered operation; in multiple series from different cen-ters and in different countries, up to 40% of patients withsevere aortic stenosis are treated medically (4–6). Someof these patients may be too sick because of associatedmedical comorbidities, and some may be considered tooold to be offered surgery. Finally, some who may benefitthe most from an operation may decline surgery eventhough they develop irreversible damage from the valvelesion that could have been treated.

These factors have led to the continuous developmentof less invasive strategies in an attempt to preserve thewell-documented, long-term efficacy of standard proce-dures with lower mortality, lower morbidity, and lessinvasiveness. Such an improved risk-benefit ratio would

result in a therapy that could be applied to more patients, b

as well as earlier in the course of their specific diseaseprocess. A critical question is whether there is a changein the risk-benefit ratio with these new therapies that iskey to the multiple stakeholders—most importantly, pa-tients and their families.

For these less invasive approaches to work and to beintroduced in a rational, balanced, and least disruptivemanner, a number of critical elements must be broughttogether (Table 1). Successful implementation of theseprinciples and practices will, in our opinion, maximizethe chances for the successful introduction of this newtechnology and treatment paradigms, ensuring greatestpatient benefit.

2.1. The Professional Multidisciplinary Heart TeamThe concept of a multidisciplinary professional heartteam has received increasing interest, beginning partic-ularly with the SYNTAX (SYNTAX Study: TAXUS Drug-

luting Stent Versus Coronary Artery Bypass Surgery forhe Treatment of Narrowed Arteries) trial of patients withdvanced coronary artery disease (7). Following angiog-aphy, the interventional cardiologist and cardiovascularurgeon reviewed the angiographic films together in theontext of the clinical setting. If the patient was deemedo be an acceptable candidate for either procedure, bothhysician and surgeon—ideally together—would inter-iew both patient and family to formulate an optimallan. This “heart team” concept has been endorsed andecommended in the recent European Society of Cardi-logy/European Association for Cardio-Thoracic Surgeryuidelines on Myocardial Revascularization and should

able 1. Necessary Components for the Successfulntroduction of Transcatheter Heart Valve Therapy

1. Specialized heart centers with experienced multidisciplinaryphysicians and paramedical personnel

2. The professional multidisciplinary heart teama. Primary cardiologistsb. Cardiac surgeonsc. Interventional cardiologistsd. Echocardiographers and imaging specialistse. Heart failure specialists

3. Proper procedure and facilitiesa. Modified conventional cardiac laboratoryb. Hybrid operating room

4. Development of and participation in clinical databases andregistries to evaluate practice patterns, treatment outcomes,and comparative effectiveness

5. Scientific literature—knowledge of and evaluation ofevidence-based medical literature concerning patientselection, procedural performance, and complicationmanagement

6. Specific standardized protocols for management strategies,procedural performance, problem solving, and complicationmanagement

7. Appropriate ongoing personnel training

ecome the standard of care (8).

n

2ewoi

sfiAC(tdvAotw

smrltaast

hmfvcaaoev

382 HOLMES, JR AND MACK Ann Thorac SurgTRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW 2011;92:380–9

REPO

RT

This heart team concept has been extended to valvularheart disease. In PARTNER (Placement of AoRTic TraNs-cathetER Valve Trial), the pivotal U.S. trial of a newdevice for transcatheter aortic valve replacement (TAVR),patients are routinely evaluated by “partners” of cardi-ologists and surgeons together to determine patient eli-gibility and optimal treatment strategy (9). This requirespre-procedural evaluation in valvular heart disease clin-ics, multidisciplinary team conferences, and joint perfor-mance of the procedure, as well as postoperative care.This same heart team principle has also proven to beextremely successful in centers participating in the U.S.pivotal trial of the first catheter-based approach for thetreatment of mitral valve disease, EVEREST II (PivotalStudy of a Percutaneous Mitral Valve Repair System)(10). Such a heart team will be even more critical as theissues with structural heart disease become more com-plex, as the treatment expands to more centers, and asnew technology is applied outside of the constraints ofrandomized clinical trials. The success of this team con-cept has been demonstrated in heart transplant centersin which patient treatment decisions and care are man-aged by heart failure cardiologists, transplant and ven-tricular assist device surgeons, experts in immunosup-pression, as well as specialists in echocardiography andin anesthesia; all collaborate as a multidisciplinary team.Key members of the multidisciplinary team for structuralheart valve disease management include primary cardi-ologists, interventional cardiologists, cardiac surgeons,noninvasive and heart failure cardiologists, echocardiog-raphers and cardiac imaging specialists, cardiac anesthe-siologists, nurse practitioners, physician assistants, re-search coordinators, administrators, dietary andrehabilitation specialists, and social workers. Each com-ponent will need to develop and implement specificprotocols depending on the individual patient and spe-cific technical procedure.

2.1.1. THE ROLE OF THE PRIMARY CARDIOLOGIST. Typically, pa-tients who are candidates for these procedures have beenseen longitudinally in the course of their disease byprimary cardiologists who have a unique perspective ofpatient and family dynamics. These physicians coordi-nate care, ensure complete evaluation, order and evalu-ate diagnostic studies, implement medical care, andensure involvement of patients and families in the deci-sion-making process. These primary cardiologists alsoresume care of the patient after the procedure and needto be cognizant of the follow-up needs and protocols;accordingly, these individuals are an essential compo-nent of the heart team to enhance patient-centered care.Primary cardiologists in concert with the surgeons andinterventional cardiology teams will be central in apply-ing scoring systems to evaluate risk-benefit profiles inthis diverse group of patients (11,12). The patient’s valuesand goals need to be central in benefit-risk assessmentand treatment decisions.

2.1.2. IMAGING SPECIALISTS. Mandatory imaging modalities

ecessary for a structural heart disease program include m

- and 3-dimensional transthoracic and transesophagealchocardiography, vascular computerized tomographyith 3-dimensional reconstruction, cardiac magnetic res-nance imaging, diffusion-weighted magnetic resonance

maging of the brain, and transcranial Doppler imaging.Echocardiography will be critical, with collection of

tandardized definition sets. Such data will be best de-ned by large-scale registries such as the STS Nationaldult Cardiac Database and the American College ofardiology-National Cardiovascular Data Registry

ACC-NCDR). The Valve Academic Research Consor-ium (VARC) Consensus Report, which established stan-ardized endpoint definitions for transcatheter aorticalve therapy, is the first step in this direction (13). Themerican Society of Echocardiography (ASE) has devel-ped specific definitions of severity of valvular lesionshat could benefit from transcatheter valve therapy thatill need to be incorporated in registry reporting (14,15).An important screening component involves 3-dimen-

ional reconstruction of the aortoiliac vasculature usingultislice computerized tomography (MSCT). The cur-

ent aortic transvalvular device delivery sheaths arearge, ranging from 18- to 24-Fr in diameter. Althoughhey are becoming smaller in diameter, access remainsn issue. Accordingly, it is essential to identify absoluterterial diameters and specific abnormalities such asevere calcification or tortuosity of the aortoiliac vascularree that may dictate an alternative access route.

2.1.3. HEART FAILURE SPECIALISTS. An increasing number ofpatients with advanced valvular heart disease have acomponent of left ventricular dysfunction. For patientswith aortic stenosis, left ventricular dysfunction mayrender the assessment of the severity of the aortic steno-sis difficult, thus complicating decision making about theneed for or performance of a procedure. In addition,heart failure specialists will need to help assess thepotential for reversibility of left ventricular dysfunctionfollowing TAVR. This will also be of particular impor-tance for the treatment of mitral valve disease. Identifi-cation of appropriate patients with mitral insufficiencyand heart failure who may benefit from a catheter-basedapproach is best accomplished by consultation with heartfailure specialists.

2.2. Specialized Experienced Facilities2.2.1. REGIONAL HEART CENTERS. The concept of regional

eart centers will be extremely important. Because of theyriad of specialists, imaging equipment, procedural

acilities, and support infrastructure necessary to build aalve center, it is unlikely that accessibility to new trans-atheter valve technology will be universal and immedi-te. In the United States, many cardiac surgical centersnd catheterization laboratories have a very low volumef structural heart disease cases. In these centers, forxample in patients with mitral regurgitation, mitralalve replacement is more frequently performed than is

itral valve repair, which is the preferred strategy (16).

hsrp2pliwsc

trfadeodwlttatmrs2“rphcapcaXvtinmandr“

tnmsecettbtndbttle

s

383Ann Thorac Surg HOLMES, JR AND MACK2011;92:380–9 TRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW

REP

OR

T

Outcomes for patients undergoing surgery for valvularheart disease have clearly been demonstrated to berelated to center procedural volume (17). In England,Centers of Excellence with specific volume criteria fortreatment of mitral valve disease have been proposed bythe National Institutes for Health and Clinical Excellence(NICE) (18). The complexities of the management ofvalvular heart disease will require the infrastructureavailable only in regional referral centers with apprecia-ble patient volume in valvular heart disease. The devel-opment of specialized regional centers will be controver-sial; a tenet of modern cardiovascular practice has beenthat each hospital that has experienced personnel shouldbe able to do any and all indicated procedures. However,in the case of percutaneous valve repair/replacement, thespecialized expertise, experience, imaging equipment,and facilities that will be required to optimize outcomesare not available in all programs. The analogy to regionaltransplant referral centers is apropos. Although access tocare should not be as limited as it is with cardiactransplantation, patient populations will not be bestserved being treated in multiple institutions with rela-tively low volumes in the same geographic region. Itmust be remembered that the initial results of the firstrandomized trial of TAVR were achieved by a heart teamof experienced surgeons and structural interventionalcardiologists working together in high-volume tertiarycare centers. We believe that the criteria for regulatoryapproval and reimbursement by the appropriate federalagencies should initially be based on similar criteria interms of expertise and high valve procedure volumes innew, approved centers.

In order for this approach of specialized regionalcenters to be implemented, detailed lists of facilities andpersonnel experience in addition to pre- and post-procedural care protocols, as well as complication man-agement strategies, must be developed and then imple-mented. An analogy to this approach may be the NewYork State Department of Health program for perfor-mance of primary percutaneous coronary interventioncenters without onsite surgery that has set up specificrequirements with physician oversight, periodic review,and feedback (19). Key to this program, all data must usestandardized forms and be sent to a central data registryfor reporting. A similar national central data repositoryneeds to be constructed for valve therapy.2.2.2. PROCEDURE SETTING: MODIFIED CATHETERIZATION LABORA-

TORY AND HYBRID OPERATING ROOM. Two major approachesave been developed, both with specific advantages andpecific proponents. The core tenet of both is that supe-ior imaging is mandatory. In addition, sterility is ofaramount importance..2.2.1. Modified Conventional Cardiac Laboratory. This ap-roach can utilize a conventional cardiac catheterization

aboratory with some modifications. A specific drawbacks the size of the conventional catheterization room,hich is typically 600 square feet. Such a room can

upport conventional angiography and percutaneous

oronary intervention. In addition, for treatment of some r

ypes of structural heart disease, these conventionalooms can also be used as such for closure of a patentoramen ovale, a paravalvular leak, and a left atrialppendage occlusion, although for each of these proce-ures, the rooms typically need to have biplane imagingquipment and be integrated with real-time echocardi-graphy procedural guidance. A modified room of thisesign can also be used for hybrid surgical procedureshere the left internal mammary artery is placed to the

eft anterior descending, and the remaining stenoses arereated percutaneously. For transcatheter valve therapy,he room needs to be large enough to accommodatenesthesia equipment, echocardiography machines, in-ra-aortic balloon pumps, and cardiopulmonary bypass

achines. If a conventional cardiac catheterization labo-atory is to be used, adaptation to meet surgical sterilitytandards including airflow exchanges is essential..2.2.2. Hybrid Operating Room. Another type of surgicalhybrid” room has attracted great interest. These areooms that are focused on newer procedures such asercutaneous aortic and pulmonary valve implantation,ybrid percutaneous/surgical coronary and valve/oronary procedures, and some composite hybrid aorticrch and descending thoracic and abdominal aortic ap-roaches with aortic stent grafts. These rooms are typi-ally larger (800 to 900 square feet) than hybrid coronaryngiographic rooms. Catheterization laboratory–quality-ray imaging is a requisite but is supplemented by aariety of alternative imaging modalities, particularlyransesophageal echocardiography and 3-dimensionalntravascular ultrasound images. In addition, other tech-ologies, such as rotational angiography, computed to-ography (CT), or at the very least, real-time interactive

ccess to magnetic resonance imaging and CT images,eed to be available because these newer imaging mo-alities are expected to play a larger role in the field witheal-time 3-dimensional reconstruction of CT images androad-mapping” of important structures.An important, yet unresolved issue is the location of

hese new-generation hybrid rooms. Placement of theew hybrid rooms in an operating room suite environ-ent affords accessibility to the operating suite infra-

tructure and personnel, whereas placement in the cath-terization laboratory provides wider availability toatheterization laboratory personnel and catheter-basedquipment. These are important issues because hybrideams may have very different skill sets if they come fromhe background of surgery, whereas a hybrid team with aackground of interventional cardiology may not have

he same skill set. Maintenance of separate teams mayot be efficient. Alternatively, cross-training 1 team mayilute the experience. Current procedural teams functionest with both disciplines involved and with both cathe-

erization laboratory and operating room personnel par-icipating. No matter where the procedural room isocated—catheterization laboratory or operating suites—qual access by both specialties is required.The location of patient care post-procedure is of con-

iderable importance. Coronary care units are very expe-

ienced with hemodynamic assessment but are not ac-

sa

384 HOLMES, JR AND MACK Ann Thorac SurgTRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW 2011;92:380–9

REPO

RT

customed to dealing with very large-bore catheter- andsheath-vessel access issues nor surgical incisions andchest drainage tubes. In addition, surgical units are mostaccustomed to dealing with the rapidly changing hemo-dynamics occurring after aortic valve replacement. Thispart of the field will continue to evolve as the technologybecomes smaller with percutaneous vascular access clo-sure devices. It will be important to centralize the imme-diate post-procedural care of these patients in 1 locationon a single clinical service at the individual center tomaximize expertise, team training, and the developmentof clinical protocols.

3. Scientific Literature

3.1. Results of Clinical TrialsA robust knowledge of the current scientific literature ismandatory to place this technology in perspective. Datafrom multiple single-center series, and national andcommercial registries are available for both transcatheteraortic and mitral procedures. Randomized clinical trialsrepresent the highest form of evidence-based medicineand form the backbone of regulatory approval and in-structions for use. The results of 1 pivotal trial of trans-catheter aortic valves and 1 of transcatheter mitral valveshave been published. A complete review of the increas-ingly large dataset is beyond the scope of this work, buta committee of the societies involved will subsequentlyconvene and publish an expert consensus statement in2011. Evaluation of some of the data from these 2 ran-domized trials is important as it affects the process ofdevelopment and implementation of these technologies.

The pivotal PARTNER trial has received a great deal ofinterest. Specific details about patient selection, protocolsused, endpoints, and statistical evaluation are crucial.

The PARTNER trial was basically 2 parallel trials thatenrolled the highest-risk patients ever seen in any car-diovascular trial by virtue of their age and severity ofcomorbid conditions: 1) PARTNER Cohort A, whichrandomized high-risk surgical patients to either tradi-tional aortic valve replacement or to TAVR by either atransfemoral or transapical approach; and 2) PARTNERCohort B in which patients who were inoperable wererandomized to either a TAVR by a transfemoral approachor to conventional medical therapy, which typically con-sisted of balloon aortic valvuloplasty. Screening requiredan evaluation by 2 experienced cardiac surgeons to agreeon the surgical risk using the STS Predicted Risk ofMortality score (20) and was rigorous, with approxi-mately one quarter to one third of screened patientssubsequently enrolled. The primary endpoint was deathfrom any cause at 1 year.

The results of PARTNER Cohort B have recently beenpublished (9) and included 358 patients deemed unsuit-able for conventional aortic valve replacement because ofpredicted probability of �50% mortality or at risk for aerious irreversible complication by 30 days. At 1 year,

ll-cause mortality with TAVR was 30.7% versus 50.7%

with medical therapy (hazard ratio: 0.55, 95% confidenceinterval: 0.40 to 0.74). Despite the marked improvementin survival and event-free survival, there were somesignificant safety hazards, particularly a higher incidenceof major strokes (5.0% versus 1.1%) as well as increasedmajor vascular complications (16.2% versus 1.1%) withTAVR, both of which may impact early and longer-termoutcome adversely. Longer-term outcomes will berequired.

These results were received enthusiastically; however,they have important implications. First, they can beapplied only in patients similar to those in the study (i.e.,those patients deemed to be inoperable). Second, theyare the result of treatment by very experienced operatorsworking as a heart team in a hybrid operating room orsimilar facility with a specific device and do not neces-sarily apply to other devices.

The preliminary results of the PARTNER Cohort A trialwere presented and, when published, will also haveimportant implications. The primary endpoint of the trialwas met, with TAVR found to be noninferior to aorticvalve replacement for all-cause mortality at 1 year (TAVRversus aortic valve replacement, 24.2% versus 26.8%,respectively, p�0.001 for noninferiority). Death at 30 dayswas lower than expected in both arms of the trial: TAVRmortality (3.4%) was the lowest reported in any series,despite an early generation device and limited previousoperator experience. Aortic valve replacement mortality(6.5%) was lower than the expected operative mortality(11.8%). Furthermore, both TAVR and aortic valve re-placement were associated with important but differentperi-procedural hazards: major strokes at 30 days (3.8%versus 2.1%, p�0.20) and 1 year (5.1% versus 2.4%,p�0.07), and major vascular complications were morefrequent with TAVR (11.0% versus 3.2%, p�0.001). Majorbleeding (9.3% versus 19.5%, p�0.001) and new onsetatrial fibrillation (8.6% versus 16.0%, p�0.001) were morefrequent with aortic valve replacement.

The trial investigators also concluded that “a multidis-ciplinary valve team approach benefits patients and isrecommended for all future valve centers.” These resultscannot be extrapolated to evaluate the outcome of thisprocedure in patients who are excellent candidates forconventional aortic valve replacement. For this to occur,more randomized controlled studies will need to beperformed.

The 30-day mortality in PARTNER Cohort A (3.4%) andPARTNER Cohort B (5.2%) is better than publishedEuropean registry mortality (8.5%) (21–23). This raisesquestions about the “generalizability” of these trial re-sults after commercialization in the United States. Re-sponsible diffusion of this technology with close moni-toring of outcomes after commercialization will be criticalto maintain these results. The incidence of neurologicevents (5.5% at 30 days, 8.3% at 1 year) and majorvascular complications (11%) that occur in patients un-dergoing TAVR also needs to be addressed. The role ofembolic protection, smaller delivery systems, and post-

procedure anticoagulation remains to be determined.

385Ann Thorac Surg HOLMES, JR AND MACK2011;92:380–9 TRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW

REP

OR

T

The other completed pivotal randomized trial is theEVEREST II trial of the MitraClip, which randomizedpatients with severe mitral regurgitation to surgery or acatheter-based approach. The MitraClip was used toperform an “Alfieri-type” approximation of the freeedges of the mitral leaflets for the treatment of eitherfunctional mitral regurgitation due to annular dilation orstructural mitral regurgitation due to mitral leaflet abnor-malities (10). Although less effective at reducing mitralregurgitation, percutaneous repair was associated withsuperior safety and comparable improvements in clinicaloutcomes at 12 months compared with mitral valvesurgery (10).

4. Technological Improvement

The field of percutaneous structural heart disease thera-pies continues to advance rapidly. There now are approx-imately 10 different companies involved in the develop-ment of TAVR and even a greater number of companiesinvolved with the development of transcatheter mitralapproaches. Although only a few of these technologieshave been subjected to randomized clinical trials, it isimportant to remember that each specific technologymay have unique complication patterns, such as thefrequency of stroke, vascular complications, and com-plete heart block, that may require different deploymentstrategies (24). Other issues will undoubtedly evolve asdevices—which can be recaptured and replaced—will bedeveloped and tested. But each device will have its ownunique safety and efficacy profile.

The situation is even more complex for the transcath-eter mitral valve approaches. Some of these will involveusing percutaneous technology to create the equivalentof an Alfieri stitch to treat structural mitral regurgitation.Others will involve manipulation of catheters to deliverenergy to shrink the mitral annulus or to deliver a varietyof bands to decrease the diameter, as well as otherapproaches that will be combined. Again, each of theseapproaches will have specific device deployment issuesand considerations. Some of these new technologies anddeployment approaches will be aimed at expandingeither the number or types of valves that can be treatedsuccessfully; some of these will make the procedureeasier. The number of new devices, however, will con-tribute to the growing complexity of the field.

5. Operator Training

Operator training is a crucial component for treatingstructural heart disease. A number of training programsare already training physicians involved in very complexstructural heart disease, but interventional cardiologistsand cardiac surgeons who are already in practice may nothave the time or the opportunity to train in these pro-grams. For physicians and surgeons in practice, there-fore, these issues will be much more problematic. Com-ponents of the training program may vary, for example,in the use of simulators or in vivo animal laboratory

experience. Construction of a training curriculum is es-

sential. Initial work in developing a curriculum hasrecently been set forth (25). In the past, with some newtechnology, for example, carotid stenting, the specificcompany involved with a particular proprietary deviceprepared the material to be mastered. It is our opinionthat this approach is not adequate; instead, the profes-sional societies should develop the materials, outline themetrics of evaluation, and then certify performance in thetraining module. How this interfaces with industry train-ing with specific devices as mandated by the U.S. Foodand Drug Administration approval process will need tobe determined. In addition, the costs of designing andimplementing the training programs need to be estab-lished. Combined committees of the ACCF and the STS,along with other societies, are currently being formed toaddress these issues.

The creation of clinical fellowships for training intranscatheter valves is also quite problematic at thecurrent time. Since there is not commercial approval forany aortic or mitral device in the United States, thepotential for training exists only in current trial centers.There are only 30 to 40 centers currently with experiencein transcatheter aortic valves and approximately 20 cen-ters with transcatheter mitral valves. The procedurevolume at each of these centers is currently limited by theconstraints of trial enrollment, and experience at thesenior staff level is limited, which further constrainsfellowship training. The most advantaged individuals fortranscatheter valve training are those who are currentlyfellows in programs that are trial centers. The training ofother individuals, especially those who have completedtheir fellowships and are currently in practice, is alsocurrently being addressed by our societies. The questionsbeing asked include: What is the requisite experience togain the necessary expertise to be proficient in theprocedures? What is the length of training necessary togain proficiency? Are 3-month fellowships sufficient, ordo they need to be 6 months or 1 year? How are thesefellowships to be funded? Is 1 common training pathwaysufficient for cardiologists and surgeons alike, or arethere different fellowships with some commonality?Should cardiologists and surgeons interested in beingtrained in valvular heart disease be trained as teams?

In our opinion, the professional societies should as-sume the leading role in establishing the minimal per-formance criteria and helping to build the infrastructurefor these fellowships. Abrogating the responsibility fortraining to commercial sponsors who have a regulatoryresponsibility for training in their devices is not sufficient.The establishment of these criteria is beyond the scope ofthis document; however, the appropriate committees inthe professional societies are currently establishing op-erator and institutional requirements for transcathetervalve performance.

6. Protocols for Care

Specialized heart centers, staffed by trained primary cardi-

ologists, interventional cardiologists, and cardiac surgeons,

386 HOLMES, JR AND MACK Ann Thorac SurgTRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW 2011;92:380–9

REPO

RT

should have specific protocols for care related to pre-procedure assessment and screening. These protocols op-timally should be implemented and executed jointly by themultidisciplinary heart team. These protocols will involvescreening for the presence, degree, and severity of comor-bidities; issues related to the aortic, mitral, or right ventric-ular outflow tract pathology that may affect outcome; anddetailed evaluation of the etiology, severity, and functionalimpairment of the specific lesion under consideration. Inthis process, there needs to be full exploration of the patientand family expectations. These protocols should then in-clude obligatory consultations with the heart team to iden-tify optimal strategies and then identify other proceduresthat may be required (e.g., the treatment of coronary ob-structive lesions prior to the placement of a percutaneousTAVR). Such protocols and procedures should be man-dated as a patient-care pathway. This will do much toprevent inappropriate use of these devices, as well asmisinterpretation of the data required for optimal deviceutilization.

7. Assessment of Outcomes

Both the STS and ACC maintain large clinical databasesthat collect and analyze outcomes of surgical and catheter-based procedures. These clinical databases, however, arecurrently limited by the lack of modules to adequatelycollect data on transcatheter valves and are further limitedto clinical follow-up for only 30 days after the procedure. Aninitial pilot project, ASCERT: the ACCF/STS Collaborationon the Comparative Effectiveness of RevascularizationStrategies, linking the 2 clinical databases to administrativedatabases including the Social Security Death Master File(SSDMF) and Centers for Medicare & Medicaid ServicesMedicare Provider and Analysis Review (MedPAR) data inpatients with coronary artery disease is currently underway (24,26). Another pilot project highlighting successfullinkage of the STS database to the SSDMF and reporting1-year survival after cardiac surgery was published in 2010(27). A similar linking of clinical and administrative data-bases to perform post-market surveillance, assess long-term patient-centered outcomes research, and performcomparative effectiveness research and cost effectivenessfor all patients with valvular heart disease is crucial. Thislinkage needs to involve shared modules to avoid duplicatedata entry. One model currently being utilized for trackingoutcomes of patients receiving left ventricular assist devic-es—the Interagency Registry for Mechanically AssistedCirculatory Support (INTERMACS) registry—should beconsidered for transcatheter valves (28). This is potentially ahuge undertaking for which financial support does notcurrently exist. However, construction of these linked out-come databases is critical to adequately assess the impact oftranscatheter valves on the clinical outcomes of patientswith valvular heart disease and can overcome the short-comings traditionally associated with registry outcomedata. It is important to also consider the use of commondata forms, definitions, and reporting processes in differentcountries. Initial discussions are under way to determine

the feasibility of linking various national registries together

to establish a truly global database. Transcatheter andsurgical valve therapy provide an optimal initial platform tofoster this linkage. This will facilitate evaluation and inter-pretation of the results of ongoing and future plannedstudies. It will additionally facilitate regulatory trials for theU.S. Food and Drug Administration by being able to betterutilize global data when considering new device trial sub-missions and will enhance payer understanding of the bestdecision making for application of these technologies. Thiswill require that the different international societies becomemore fully engaged and integrated.

8. Summary

Transcatheter valve therapy is a transformational technol-ogy with the potential to significantly impact the clinicalmanagement of patients with valvular heart disease in aless invasive manner. Although the initial experience ispositive, evidence exists from only 1 randomized clinicaltrial in patients with aortic stenosis and 1 in patients withmitral insufficiency. Adoption of these techniques to popu-lations beyond those studied in these randomized trials,therefore, is not appropriate at the current time. However,in view of the promising results obtained in these limitedpopulation subsets, conduct of further randomized trials inother patient groups is strongly encouraged.

In order to address the challenges ahead for the respon-sible diffusion of this innovative transformational technol-ogy, it is critical that the professional societies, industry,payers, and regulatory agencies work together. The leader-ship of the ACCF and STS in consultation with multipleleaders within the primary and interventional cardiologyand cardiac surgical communities, regulators, and payersmake the following recommendations (Table 2).

1. Establishment of regional centers of excellence forheart valve diseases. Criteria for centers perform-ing interventional therapy in valvular and struc-tural heart disease should be established, and theavailability of devices and reimbursement for thoseprocedures should be limited to those centersmeeting those criteria.

2. Formation of multidisciplinary heart teams withinthese centers led by primary cardiologists, cardiacsurgeons, and interventional cardiologists. Perfor-mance of isolated procedures without construction ofa dedicated valve therapy program to encompass all

Table 2. Critical Areas for Implementation

1. Development of multidisciplinary structural heart diseaseteams and institutions

2. Development of standardized protocols of care3. Engagement of multiple stakeholder societies in generating

procedural, credentialing, and training documents andspecific site standards

4. Standardized definitions, data reporting, and post-marketsurveillance strategies for outcome assessment

5. Robust strategy for comparative effectiveness studies

aspects of care including pre-procedural assessment

387Ann Thorac Surg HOLMES, JR AND MACK2011;92:380–9 TRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW

REP

OR

T

in common clinics, joint procedure performance, andcommon patient care pathways is not recommended.

3. Establishment of a national registry of valvular heartdisease to perform post-market surveillance, long-term outcome measurement, and comparative effec-tiveness research. This could be accomplished bylinking the ACC-NCDR and STS clinical databases tothe Social Security Death Masterfile and Centers forMedicare & Medicaid Services administrative data-bases in a national “research engine.” This will, ineffect, create a national registry of valvular heartdisease similar to those that exist in Great Britain andGermany. Funding for this initiative will be a concern,but it is our position that this linkage of databases is akey element of quality patient care, outcomes analy-sis, and comparative effectiveness.

4. Establishment of training and credentialing criteriafor practitioners in this field. Formation of criteriafor the formation of fellowship programs as well aspostgraduate training with appropriate experiencefor adequate patient care leading to guidelines forcredentialing is currently under way by multipleprofessional societies working together.

5. Interpretation of the current evidence by expertconsensus documents and appropriate use criteriais necessary and will be forthcoming.

The ACCF and STS are committed as professional soci-eties to work with the U.S. Food and Drug Administrationand the Centers for Medicare & Medicaid Services toaddress all issues that are crucial to the safe and efficaciousintroduction of transcatheter valve therapy into clinicalpractice. Forthcoming will be multisocietal guidelines fortraining and credentialing, an expert consensus document,and grant proposals for creation of a national registry. Thisis an exciting time with the introduction of new technologyand techniques to care for our patients with valvular heartdisease. With society leadership, multidisciplinary partner-ships, and cooperation, a reasoned, balanced introductionof this new therapy can be accomplished.

References

1. Christensen CM. The Innovator’s Dilemma: When NewTechnologies Cause Great Firms to Fail. Boston, MA: Har-vard Business School Press, 1997.

2. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous trans-catheter implantation of an aortic valve prosthesis for calcificaortic stenosis: first human case description. Circulation2002;106:3006–8.

3. Mihaljevic T, Cohn LH, Unic D, Aranki SF, Couper GS,Byrne JG. One thousand minimally invasive valve opera-tions: early and late results. Ann Surg 2004;240:529–34.

4. Iung B, Baron G, Butchart EG, et al. A prospective survey ofpatients with valvular heart disease in Europe: the EuroHeart Survey on Valvular Heart Disease. Eur Heart J 2003;24:1231–43.

5. Iung B, Cachier A, Baron G, et al. Decision-making in elderlypatients with severe aortic stenosis: why are so many deniedsurgery? Eur Heart J 2005;26:2714–20.

6. Pai RG, Kapoor N, Bansal RC, Varadarajan P. Malignantnatural history of asymptomatic severe aortic stenosis: ben-efit of aortic valve replacement. Ann Thorac Surg 2006;82:

2116–22.

7. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneouscoronary intervention versus coronary-artery bypass graft-ing for severe coronary artery disease. N Engl J Med 2009;360:961–72.

8. Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardialrevascularization: the Task Force on Myocardial Revascular-ization of the European Society of Cardiology (ESC) and theEuropean Association for Cardio-Thoracic Surgery (EACTS).Eur Heart J 2010;31:2501–55.

9. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannotundergo surgery. N Engl J Med 2010;363:1597–607.

10. Feldman T, Foster E, Glower DG, et al. Percutaneous repairor surgery for mitral regurgitation. N Engl J Med 2011;364:1395–406.

11. Dewey TM, Brown D, Ryan WH, Herbert MA, Prince SL,Mack MJ. Reliability of risk algorithms in predicting earlyand late operative outcomes in high-risk patients undergo-ing aortic valve replacement. J Thorac Cardiovasc Surg2008;135:180–7.

12. Wendt D, Osswald BR, Kayser K, et al. Society of ThoracicSurgeons score is superior to the EuroSCORE determiningmortality in high risk patients undergoing isolated aorticvalve replacement. Ann Thorac Surg 2009;88:468–74.

13. Leon MB, Piazza N, Nikolsky E, et al. Standardized endpointdefinitions for transcatheter aortic valve implantation clini-cal trials: a consensus report from the Valve AcademicResearch Consortium. J Am Coll Cardiol 2011;57:253–69.

14. Baumgartner H, Hung J, Bermejo J, et al. Echocardiographicassessment of valve stenosis: EAE/ASE recommendationsfor clinical practice. J Am Soc Echocardiogr 2009;22:1–23.

15. Zoghbi WA, Chambers JB, Dumesnil JG, et al. Recommen-dations for evaluation of prosthetic valves with echocardi-ography and Doppler ultrasound: a report from the Ameri-can Society of Echocardiography’s Guidelines andStandards Committee and the Task Force on ProstheticValves. J Am Soc Echocardiogr 2009;22:975–1014.

16. Bolling SF, Li S, O’Brien SM, Brennan JM, Prager RL,Gammie JS. Predictors of mitral valve repair: clinical andsurgeon factors. Ann Thorac Surg 2010;90:1904–11.

17. Birkmeyer JD, Stukel TA, Siewers AE, Goodney PP, Wenn-berg DE, Lucas FL. Surgeon volume and operative mortalityin the United States. N Engl J Med 2003;349:2117–27.

18. Bridgewater B, Hooper T, Munsch C, et al. Mitral repair bestpractice: proposed standards. Heart 2006;92:939–44.

19. Hannan EL, Zhong Y, Racz M, et al. Outcomes for patientswith ST-elevation myocardial infarction in hospitals withand without onsite coronary artery bypass graft surgery: theNew York State experience. Circ Cardiovasc Interv 2009;2:519–27.

20. O’Brien SM, Shahian DM, Filardo G, et al. The Society ofThoracic Surgeons 2008 cardiac surgery risk models: part2—isolated valve surgery. Ann Thorac Surg 2009;88:S23–42.

21. Thomas M, Schymik G, Walther T, et al. Thirty-day results ofthe SAPIEN aortic Bioprosthesis European Outcome(SOURCE) Registry: a European registry of transcatheteraortic valve implantation using the Edwards SAPIEN valve.Circulation 2010;122:62–9.

22. Eltchaninoff H, Prat A, Gilard M, et al. Transcatheter aorticvalve implantation: early results of the FRANCE (FRenchAortic National CoreValve and Edwards) registry. EurHeart J 2011;32:191–7.

23. Zahn R, Gerckens U, Grube E, et al. Transcatheter aorticvalve implantation: first results from a multi-centre real-world registry. Eur Heart J 2011;32:198–204.

24. Webb JG. TAVI in Canada and Europe: the changing spectrum ofmanagement of aortic stenosis—what it means for the UnitedStates. Presented at: the Society of Thoracic Surgeons 4th AnnualMeeting; January 31, 2011; San Diego, CA. Available at: http://www.sts.org/sites/default/files/documents/pdf/annmtg/2011AM/

STS47AM_MonJan31.pdf. Accessed May 13, 2011.

388 HOLMES, JR AND MACK Ann Thorac SurgTRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW 2011;92:380–9

REPO

RT

25. Ruiz CE, Feldman TE, Hijazi ZM, et al. Interventional fel-lowship in structural and congenital heart disease for adults.J Am Coll Cardiol Intv 2010;3:e1–15.

26. Weintraub WS, Edwards FH. Introducing ASCERT: the Amer-ican College of Cardiology-The Society of Thoracic Surgeons

Collaboration on the Comparative Effectiveness of Revascular-ization Strategies (abstr). J Am Coll Cardiol 2010;55:A129.E1207.

27. Jacobs JP, Edwards FH, Shahian DM, et al. Successful linkingof the Society of Thoracic Surgeons adult cardiac surgerydatabase to Centers for Medicare and Medicaid ServicesMedicare data. Ann Thorac Surg 2010;90:1150–6.

28. Interagency Registry for Mechanically Assisted Circulatory

Support. Available at: http://www.intermacs.org. AccessedApril 27, 2011.

389Ann Thorac Surg HOLMES, JR AND MACK2011;92:380–9 TRANSCATHETER VALVE THERAPY: ACCF/STS OVERVIEW

Appendix. Author Relationships With Industry and Other Entities (relevant)—Transcatheter ValveTherapy: A Professional Society Overview from the American College of Cardiology Foundation andThe Society of Thoracic Surgeons

CommitteeMember Employment Consultant

Speakers’Bureau

Ownership/Partnership/

PrincipalPersonalResearch

Institutional,Organizational, or

Other FinancialBenefit

ExpertWitness

David R.Holmes, Jr.

Mayo Clinic—Consultant,CardiovascularDiseases

None None None None None None

Michael Mack The Heart Hospital,Baylor Plano—Director

None None None ● Edwards Lifesciences* None None

* No financial benefit.

This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document.These relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the writing committee during the documentdevelopment process. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have asignificant interest in a business if the interest represents ownership of 5% or more of the voting stock or share of the business entity, or ownership of$10,000 or more of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross

income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in thistable are modest unless otherwise noted.

REP

OR

T