Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Transcatheter Cardiac Valve Procedures

Policy #:11.02.25f

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

TRANSCATHETER AORTIC VALVE REPLACEMENT

MEDICALLY NECESSARY
Transcatheter Aortic Valve Replacement (TAVR)

Transcatheter aortic valve replacement (TAVR) for aortic stenosis, using an US Food and Drug Administration (FDA)-approved transcatheter heart valve system consistent with the device's FDA-labeled indication and intended purpose, is considered medically necessary and, therefore, covered when ALL of the following criteria are met:
  • The individual has aortic stenosis with a calcified aortic annulus, as defined by one or more of the following criteria:
    • An aortic valve area of less than or equal to 1 cm2
    • An aortic valve area index of less than or equal to 0.6 cm2
    • A mean aortic valve gradient greater than 40 mmHg
    • A jet velocity greater than 4.0 m/sec
  • The individual has New York Heart Association (NYHA) Classification II, III or IV symptoms.
  • The individual has left ventricular ejection fraction greater than 20 percent.
  • The individual is not an operable candidate for open surgery, as determined by at least two cardiovascular specialists (cardiologist and/or cardiac surgeon); or the individual is an operable candidate but is at intermediate or high risk for open surgery (i.e., Society of Thoracic Surgeons (STS) predicted operative score of 3 percent or greater) as determined by the Heart Team, including a cardiac surgeon. (The Heart Team is a cohesive, multi-disciplinary, team of medical professionals. The heart team concept embodies collaboration and dedication across medical specialties to offer optimal patient-centered care)
  • The procedure is being performed by a professional provider and at a facility that meets the recommendations for performing TAVR, as set forth in the Credentialing Recommendations for Heart Valve Replacement Procedure, established in collaboration with the following cardiovascular specialty societies: the American College of Cardiology Foundation (ACCF), the Society for Cardiovascular Angiography and Interventions (SCAI), the American Association for Thoracic Surgery (AATS), and the Society of Thoracic Surgeons (STS).

Transcatheter Aortic Valve Replacement (TAVR) for Degenerated Bio-prosthetic Valves ("Valve-In-Valve")

TAVR for repair of a degenerated bio-prosthetic valve ("valve-in-valve") using an FDA-approved transcatheter heart valve system consistent with the device's FDA-labeled indication and intended purpose, is considered medically necessary when ALL the of following criteria are met:
  • The individual has a failed (i.e., stenosed, insufficient, and/or combined) previous surgical bioprosthetic aortic valve
  • The individual has NYHA heart failure class II, III or IV symptoms
  • The individual has a left ventricular ejection fraction greater than 20 percent
  • The individual is not an operable candidate for open surgery, as judged by at least two cardiovascular specialists (cardiologist and/or cardiac surgeon); or the individual is an operable candidate but is at high risk for open surgery (i.e., STS predicted operative risk score of 8 percent or greater or have an expected mortality risk of 15 percent or greater for open surgery) as determined by the Heart Team, including a cardiac surgeon.
  • The procedure is being performed by a professional provider and at a facility that meets the recommendations for performing TAVR, as set forth in the Credentialing Recommendations for Heart Valve Replacement Procedure, established in collaboration with the following cardiovascular specialty societies: the ACCF, the SCAI, the AATS, and the STS.

EXPERIMENTAL/INVESTIGATIONAL
All other uses for TAVR are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed .

TRANSCATHETER PULMONARY VALVE (TPV) IMPLANTATION

MEDICALLY NECESSARY
Transcatheter pulmonary valve (TPV) implantation, using an FDA-approved transcatheter pulmonary valve system consistent with the device's FDA-labeled indication and intended purpose, is considered medically necessary and, therefore, covered when ALL of the following criteria are met:
  • The individual has had prior repair of congenital heart disease
    • Existence of a full (circumferential) right ventricular outflow tract (RVOT) conduit that was equal to or greater than 16 mm in diameter when originally implanted
  • The individual has a current dysfunctional right ventricular outflow tract (RVOT) conduit with one of the following clinical indications for intervention:
    • Moderate or greater pulmonary regurgitation
    • Pulmonary stenosis with a mean RVOT gradient 35 mmHg or greater
  • The individual is not good candidate for open surgery due to one or both of the following:
    • High risk for open surgery due to concomitant medical comoridities
    • Poor open surgical candidate due to multiple prior thoracotomies for open heart surgery
  • The procedure is being performed by a professional provider and at a facility that meets the recommendations for performing TPV implantation as set forth in the Credentialing Recommendations for Heart Valve Replacement Procedure, established in collaboration with the following cardiovascular specialty societies: the ACCF, the SCAI, the AATS, and the STS.

EXPERIMENTAL/INVESTIGATIONAL
All other uses for TPV implantation are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

TRANSCATHETER MITRAL VALVE REPLACEMENT (TMVR)

MEDICALLY NECESSARY
Transcatheter Mitral Valve Replacement

Transcatheter mitral valve repair (TMVR) for significant (MR ≥ 3+), symptomatic degenerative mitral regurgitation, using an FDA-approved transcatheter mitral valve system consistent with the device's FDA-labeled indication and intended purpose, is considered medically necessary and, therefore, covered when ALL of the following criteria are met:
  • Both a cardiothoracic surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease have independently examined the individual face-to-face and evaluated the individual’s suitability for mitral valve surgery and determination of prohibitive risk (i.e., STS predicted operative risk score of 12 percent or greater ; or presence of a logistic EuroSCORE of 20 percent or greater), and both professional providers have documented the rationale for their clinical judgment and the rationale is available to the Heart Team.
  • The individual, preoperatively and postoperatively, is under the care of a Heart Team. 
  • The procedure is being performed by a professional provider and at a facility that meets the recommendations for performing TMVR implantation as set forth in the Credentialing Recommendations for Heart Valve Replacement Procedure, established in collaboration with the following cardiovascular specialty societies: the ACCF, the SCAI, the AATS, and the STS.

Transcatheter Mitral Valve Replacement (TMVR) for Degenerated Bio-prosthetic Valves ("Valve-In-Valve")

TMVR for repair of a degenerated bio-prosthetic valve ("valve-in-valve") using an FDA-approved transcatheter heart valve system consistent with the device's FDA-labeled indication and intended purpose, is considered medically necessary when ALL the of following criteria are met:
  • The individual has a failed (i.e., stenosed, insufficient, and/or combined) previous surgical bioprosthetic mitral valve
  • The individual is not an operable candidate for open surgery, as judged by at least two cardiovascular specialists (cardiologist and/or cardiac surgeon); or the individual is an operable candidate but is at high risk for open surgery (i.e., STS predicted operative risk score of 8 percent or greater or have an expected mortality risk of 15 percent or greater for open surgery) as determined by the Heart Team, including a cardiac surgeon.
  • The procedure is being performed by a professional provider and at a facility that meets the recommendations for performing TMVR, as set forth in the Credentialing Recommendations for Heart Valve Replacement Procedure, established in collaboration with the following cardiovascular specialty societies: the ACCF, the SCAI, the AATS, and the STS.

EXPERIMENTAL/INVESTIGATIONAL
All other uses for TMVR are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

TRANSCATHETER TRICUSPID VALVE REPAIR (TVR)

EXPERIMENTAL/INVESTIGATIONAL
Transcatheter tricuspid valve repair (TVR) is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Guidelines

NEW YORK HEART ASSOCIATION CLASSIFICATION
    1. No symptoms and no limitation in ordinary physical activity, e.g., shortness of breath when walking, climbing stairs etc.
    2. Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.
    3. Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g., walking short distances (20–100 m). Comfortable only at rest.
    4. Severe limitations. Experiences symptoms even while at rest. Mostly bed bound individuals.

AMERICAN HEART ASSOCIATION/AMERICAN COLLEGE OF CARDIOLOGY

The American Heart Association/American College of Cardiology (AHA/ACC) defines the stages of vascular aortic stenosis in the 2014 practical guidelines for the management of patients with valvular heart disease. Each stage is defined by valve anatomy valve hemodynamics, the consequences of valve objection on the left ventricle, and vasculature, as well as by patient symptoms. Hemodynamic severity is best characterized by the transaortic maximum velocity (or mean pressure gradient) when the transaortic volume flow rate is normal. The definition of severe Aortic Stenosis (AS) is based on natural history studies of individuals with unoperated AS, which show that the prognosis is poor once there is a peak aortic valve velocity of greater than 4 m per second, corresponding to a mean aortic valve gradient greater than 40 mm Hg. In individuals with low forward flow, severe AS can be present with lower aortic valve velocities and lower aortic valve gradients. Thus, an aortic valve area should be calculated in these individuals. The prognosis of individuals with AS is poorer when the aortic valve area is less than or equal to 1.0 cm2, or an aortic valve area index of less than or equal to 0.6 cm2/m2.

SOCIETY OF THORACIC SURGEONS PREDICTED OPERATIVE RISK SCORE

The Society of Thoracic Surgeons (STS) predicts the risk of operative mortality and morbidity 30 days after surgery on the basis of an individual’s demographic and clinical variables, prior to surgery. This risk score is used to categorize the potential surgical candidate per risk percentage

The 24 variables used to determine this score are: age, sex, height, weight, diabetes, chronic lung/pulmonary disease, peripheral vascular disease, number of previous cardiac operations, previous CABG, previous valve surgery, renal failure, dialysis dependent renal failure, derum creatinine, hypertension, type of active endocarditis, cerebrovascular accident, timing of recent myocardial infarction, cardiogenic shock, New York Heart Association Classification, inotropic agents, pulmonary artery mean pressure, procedure status, intra-aortic balloon pump timing, mitral valve surgery.

EUROPEAN SYSTEM FOR CARDIAC OPERATIVE RISK EVALUATION EUROSCORE

The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is a method of calculating predictive operative mortality for individuals undergoing cardiac surgery. The logistic EuroScore predicts mortality according to the logistic regression equation. The variables used to determine this score are: individual related factors, cardiac related factors, and operation related factors.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, transcatheter aortic valve replacement (TAVR), TAVR for degenerated bio-prosthetic valves (valve-in-valve), transcatheter pulmonary valve (TPV) implantation, or transcatheter mitral valve replacement (TMVR) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

Services that are experimental/investigational (e.g., transcatheter tricuspid valve repair) are a benefit contract exclusion for all products of the Company. Therefore, they are not eligible for reimbursement consideration.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The Edwards SAPIEN Transcatheter Heart Valve System was approved by the FDA on November 2, 2011.Supplemental approvals for SAPIEN Transcatheter Heart Valve System have since been issued by the FDA.

The CoreValve Transcatheter Aortic Valve Replacement System was approved by the FDA on January 17, 2014. Supplemental approvals for CoreValve Transcatheter Aortic Valve Replacement System have since been issued by the FDA.

MitralClip Delivery System was approved by the FDA on October 24, 2013.

Melody® Transcatheter Pulmonary Valve (TPV) and the Ensemble® was approved by the FDA on January 27, 2015.

Description

There are four natural valves of the heart: the aortic, pulmonary, mitral, and tricuspid. They serve as one-way valves to direct the flow of blood to the lungs and aorta. The aortic valve closes off the lower left chamber that holds the oxygen-rich blood before it is pumped out to the body, and opens to allow blood to leave the heart from the left ventricle to the aorta and on to the body. The pulmonary valve closes off the lower right chamber (or right ventricle), and opens to allow blood to be pumped from the heart to the lungs (through the pulmonary artery) where it will receive oxygen. The mitral valve closes off the upper left chamber (or left atrium) collecting the oxygen-rich blood coming in from the lungs, and opens to allow blood to pass from the upper left side to the lower left side (or from the left atrium to the left ventricle). The tricuspid valve closes off the upper right chamber (or atrium) that holds blood coming in from the body and opens to allow blood to flow from the top right chamber to the lower right chamber (or from right atrium to right ventricle). The tricuspid valve prevents the back flow of blood from the ventricle to the atrium when blood is pumped out of the ventricle. Heart valves with congenital defects or those that become diseased can result in regurgitation, incompetence, insufficiency, or stenosis. Treatment of structural heart valve disorders may include surgical repair or replacement requiring open-heart surgery using cardiopulmonary bypass. Transcatheter cardiac valve procedures use catheter technology to access the heart and treat heart valve disorders without the need for open-heart surgery and cardiopulmonary bypass.

TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR)

Aortic stenosis is a narrowing of the aortic valve opening that causes an obstruction of the blood flow from the left ventricle into the ascending aorta. There are many conditions that may contribute to aortic stenosis, such as calcification of the aortic valve, rheumatic fever, and congenital anomalies.

When there is an elevated level of calcium traveling through the bloodstream, calcium deposits can occur, hardening the tissue and causing a narrowing, or stenosis, of the valve, which diminishes blood flow through the valve. This is referred to as calcification of a valve. Calcification risk factors include advanced age, male gender, smoking, hypertension (elevated blood pressure), and hyperlipidemia (an elevation of lipids or fats in the blood stream). When left untreated, severe aortic stenosis can result in heart failure and even sudden cardiac arrest.

Transcatheter aortic valve replacement (TAVR), also called transcatheter aortic valve implantation (TAVI), has been developed as an alternative treatment for individuals with severe aortic stenosis who are candidates at risk for open-heart-surgery or not surgery candidates at all. The procedure is performed percutaneously, most often through the transfemoral artery approach. It may also be performed through the subclavian artery approach and transapically using mediastinoscopy.

Currently, two transcatheter aortic valves have Food and Drug Administration (FDA) approval for the treatment of aortic stenosis. The Edwards SAPIEN balloon-expandable valve and the self-expanding Medtronic CoreValve™ Transcatheter Aortic Valve Replacement System (Medtronic Inc., Minneapolis, MN).

The Edwards SAPIEN™ Transcatheter Heart Valve System (Edwards LifeSciences, Irvine, CA) received original FDA approval in November 2011, via the transfemoral approach, for individuals with severe aortic stenosis who are not eligible for open heart procedures and have calcified aortic annulus (a fibrous ring in the wall of the root of the aorta), who are not candidates for open-heart procedures; who have been determined by a cardiac surgeon to be inoperable for open aortic valve replacement; and in whom comorbidities exist that would not preclude the expected benefit from correction of the aortic stenosis.

Since then, numerous FDA premarket approvals (PMA) have been granted for the Edwards SAPIEN™ (Edwards LifeSciences, Irvine, CA) with expanded indication for use. Approval was granted for both the transfemoral and transapical approaches. In 2012, indications for the transapical approach were expanded to include both inoperable individuals and individuals who are at high risk for open surgery. In June 2014, the next-generation SAPIEN™ XT Transcatheter Heart Valve (Model 9300TFX) was approved by the FDA for use with the NovaFlex+ delivery system. In June 2015, SAPIEN™3 Transcatheter Heart Valve (Model 9600TFX) was approved by the FDA for the treatment of severe aortic stenosis in individuals with symptomatic heart disease who are judged by a Heart Team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons [STS] operative risk score 8 percent or greater or at a 15 percent or greater risk of mortality at 30 days, and other clinical comorbidities unmeasured by the STS risk calculator). Compared to the previous-generation SAPIEN™ XT, the SAPIEN™3 can be inserted thru smaller iliofemoral arteries, has an improved delivery system that reportedly allows more accurate positioning, and contains a skirt to help prevent paravalvular leak. Additionally, in August 2016, The EDWARDS INTUITY Elite valve system received PMA supplemental approval (P150036) indicated for the replacement of diseased, damaged, or malfunctioning native or prosthetic aortic valves. This approval was based on the TRANSFORM clinical trial, in which participants were treated between September 26, 2012 and December 2, 2015 and included 889 individuals at 29 investigational sites. This device can be used as a treatment for aortic stenosis or stenosis-insufficiency of an aortic valve requiring a planned replacement as indicated in the preoperative evaluation, when a an individual is scheduled to undergo planned aortic valve replacement with or without concomitant coronary bypass surgery.

In August 2016, the FDA through a PMA supplement, approved an expanded indication for the SAPIEN™XT and SAPIEN™3 transcatheter heart valves for individuals with aortic valve stenosis who are at intermediate or greater risk (i.e., STS operative risk score 3 percent or greater at 30 days, and other clinical comorbidities unmeasured by the STS risk calculator) for death or complications associated with open-heart surgery. These devices were previously approved only in individuals at high or greater risk for death or complications during surgery.

In January 2014, FDA granted approval for the CoreValve™ Transcatheter Aortic Valve Replacement System (Medtronic, Inc., Minneapolis, MN, USA) for symptomatic heart disease due to severe native calcific aortic stenosis, who is at extreme high risk or who are not suitable for open surgery. In June 2014, the FDA expanded the indication for CoreValve™ to include individuals at high risk for open surgery. FDA labeling indicates that the device can be delivered via femoral, subclavian/axillary or ascending aortic access. In March 2015, the FDA expanded approval of the CoreValve™ system for "valve-in-valve" replacement to treat certain individuals who have previously had a tissue aortic valve replacement and are in need of a second one. The Medtronic Evolut R is the new generation of the CoreValve™ self-expanding family of valves. The valve has been re-engineered to be shorter, to provide a more consistent radial force within the recommended size range, and to allow recapture, repositioning, and redeployment prior to final release. The CoreValve™ Evolut R system was approved by FDA in June 2015 as a supplement to the original CoreValve approval from 2014. 

Given both the high-risk nature of procedures involving these catheter interventions and the availability of established alternative treatment options using traditional surgical approaches, several considerations are being recommended for institutions and professional providers planning to implement these new technologies, such as TAVR. Recommendations for performing TAVR were developed with the collaboration of cardiologists and cardiothoracic surgeons from the following specialty societies: the American College of Cardiology Foundation (ACCF), the Society for Cardiovascular Angiography and Interventions (SCAI), the American Association for Thoracic Surgery (AATS), and the Society of Thoracic Surgeons (STS). These recommendations were established to guarantee a successful TAVR program that ensures individual safety and demonstrates commitment to excellence by the institution and procedural volume requirements.

PEER-REVIEWED LITERATURE
Transcatheter Aortic Valve Replacement for Individuals with Aortic Stenosis Who Are Not Suitable Candidates for Open Surgery

There have been several case series of TAVR, the majority of which have included individuals who are considered high risk and inoperable for surgery. However, the selection of individuals for TAVR has been largely subjective: expert opinion of cardiac surgeons and/or cardiologists has been the main determining factor of individual suitability for the surgery. Consequently, it is difficult to clearly distinguish individuals who are high-risk operable candidates, and, therefore, some overlap may exist.

In 2010, the Agency for Healthcare Research and Quality (AHRQ) reviewed 84 case studies involving 2,375 individuals. Overall, TAVR was successful in 94 percent of individuals, and the aggregated 30-day survival rate was 89 percent across all studies. Adverse event rates were reported in larger case studies, with an estimated 30-day rate of major cardiovascular adverse events and stroke of eight percent.

The two largest studies included in the AHRQ review reported on 646 individuals treated with the Medtronic CoreValve™ and on 339 individuals treated with the Edwards SAPIEN™ valve. The CoreValve™ study by Piazza et al (2008) used an objective individual selection criteria that included: Logistic EuroScore of greater than or equal to 15 percent, 75 years of age or older, or 65 years of age or older with a condition (condition defined as: liver cirrhosis, pulmonary insufficiency, pulmonary hypertension, previous cardiac surgery, porcelain aorta, recurrent pulmonary emboli, right ventricular insufficiency, previous chest burns or radiation precluding open surgery, or body mass index (BMI) =18kg/m2)

Piazza et al (2008) reported a procedural success of 97 percent, a 30-day survival of 92 percent, and a 30-day combined rate of death, myocardial infarction (MI), or stroke of 9.3 percent. A study using Edwards SAPIEN™ valve by Rodes-Cabou et al (2010) included a subjective inclusion criteria (relying on the judgment of participating surgeons to determine eligibility for TAVR), and reported a procedural success rate of 93.3 percent, a 30-day mortality of 10.4 percent, and, at a median follow-up of eight months, a mortality rate of 22.1 percent.

A systematic review by Figulla et al (2011) included studies that enrolled symptomatic individuals with severe aortic stenosis, had a mean age of 75 years or older, reported on 10 or more individuals, and had a follow-up duration of 12 months or longer. A total of 12 studies met these criteria and were compared to a group of 11 studies that treated severe aortic stenosis with nonsurgical therapy. The procedural success in these studies ranged from 86 percent to 100 percent, and the 30-day mortality ranged from 5.3 percent to 23 percent. The combined mean survival rate at one year was 75.9 percent (95 percent confidence interval [CI]:73.3-78.4). This one-year survival rate compared favorably to medical therapy, which was estimated to be 62.4 percent (95 percent CI: 59.3-65.5).

A case series from on 697 individuals treated with the CoreValve™ reported a procedural success of 98.4 percent, and a 30-day mortality of 12.4 percent. Another large case series from Italy that included 663 individuals treated with the CoreValve™ device reported a procedural success of 98 percent and 15 percent mortality at one year. A study published by Gurvitch et al in 2010 reported on durability and longer clinical outcomes for up to three years. Seventy individuals who underwent TAVR and survived for greater than 30 days were included. Survival at one, two, and three years was 81 percent, 74 percent, and 61 percent, respectively. One individual (1.5 percent) required reoperation during this time period. The valve area decreased from 1.7 + 0.4 cm2 following the procedure to 1.4 +0.3 cm2 at three years. Aortic incompetence was trivial or mild in 84 percent of individuals and did not worsen over time.

The PARTNER (Placement of AoRtic TraNscathetER Valves) trial is a pivotal multicenter RCT of TAVR performed in the US, Canada, and Germany, using the Edwards SAPIEN™ heart-valve system. In 2010, Leon et al reported results of the cohort of individuals who were not candidates for open surgery. Individuals were considered not suitable for open surgery if they had a predicted probability of 50 percent or greater for death or a serious irreversible condition at 30 days post-surgery as determined by two surgeon investigators using clinical judgment and the Society of Thoracic Surgery (STS) risk score. The executive committee of the PARTNER trial reviewed all individual selection decisions and approved the classification of individuals as unsuitable for surgery. Of the total 3,105 individuals screened for aortic-valve surgery, 12 percent were included in the cohort of individuals deemed unsuitable for surgery. The primary outcome was death from any cause over the course of the trial (median follow-up 1.6 years); a co-primary endpoint was the composite of time to death from any cause or time to repeat hospitalization related to aortic stenosis or TAVR. Secondary endpoints were cardiovascular mortality, New York Heart Association (NYHA) functional class, the rate of hospitalization due to aortic stenosis or TAVR, the six minute walk test, valve performance as measured by echocardiography, and procedural complications (MI, stroke, acute kidney injury, vascular complications, and bleeding).

A total of 358 individuals were randomized to TAVR (performed via the transfemoral approach) or usual care. Standard therapy was determined by the treating clinicians, and included balloon valvuloplasty of the aortic valve in most cases (83.8 percent). A small number of individuals (6.7 percent) underwent open surgical valve replacement despite the high risk, and another 2.2 percent of individuals underwent TAVR at a center outside the US that was not participating in the trial. The mean age of enrolled individuals was 83.2 years, and there were some baseline imbalances in the individual population indicating that the standard therapy group may have had a higher severity of illness. Standardized scores of surgical risk were higher in the standard therapy group. The Logistic EuroSCORE in the standard therapy group compared to the TAVR group was (30.4+19.1 vs. 26.4+17.2, p=0.04) and the Society of Thoracic Surgery (STS) score was (12.1+6.1 vs. 11.2+5.8, p=0.14). Significantly more individuals in the standard therapy group had chronic obstructive pulmonary disease (COPD) (52.5 percent vs. 41.2 percent, p=0.04) and atrial fibrillation (48.8 percent vs. 32.9 percent, p=0.04), and there was a nonsignificant trend for more individuals in the standard therapy group having a lower ejection fraction (51.1 percent vs. 53.9 percent) and frailty, as determined by pre-specified criteria (28.0 percent vs. 18.15 percent).

At one-year follow-up, death from any cause was lower for the TAVR group (30.7 percent vs. 49.7 percent, p<0.001). This represents a 19 percent absolute risk reduction, a 38.2 percent relative risk reduction, and a number needed to treat of 5.3 to prevent one death over a one-year follow-up.

Cardiovascular death was lower in the TAVR group (19.6 percent vs. 44.1 percent, p<0.001). The composite of all-cause mortality and repeat hospitalization was reached by 42.5 percent of the individuals in the TAVR group compared with 70.4 percent in the standard therapy group. The percentage of individuals in NYHA Class I or II at one year was higher for the TAVR group (74.8 percent vs. 42.0 percent, p<0.001). The authors also reported a significant improvement in the six minute walk test for the TAVR group but not the standard group. Subgroup analysis did not report any significant differences in outcomes according to clinical and demographic factors.

Complication rates were higher in TAVR group: stroke or transient ischemic attack (TIA) at one year was more than twice as frequent for the TAVR group (10.6 percent vs. 5 percent, p=0.04). Major bleeding and vascular complications occurred in a substantial percent of individuals undergoing TAVR and were significantly higher than the standard therapy group (22.3 percent vs. 11.2 percent, p=0.007; and 32.4 percent vs. 7.3 percent, p=0.001, respectively).

In 2012, Quality of Life (QOL) outcomes were reported by Reynolds et al for the PARTNER trial. QOL were evaluated using the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score, the Medical Outcomes study short-form 12 (SF-12), and the EuroQol (EQ-5D). The exact number of participants who completed the QOL measurement was not clearly reported; however, estimates from the graphical representation show that 149-170 individuals in the TAVR group and 138-157 individuals in the medical therapy group completed baseline QOL measurements. At the follow-up time points of 30 days, 6 months, and 12 months, the change in the QOL score was greater for the TAVR group. At 30 days, the mean difference in the KCCQ was 13.3 points (95 percent CI: 7.6-19.0 p<0.001). This mean difference increased at six months to 20.8 points (95 percent CI: 14.7-27.0, p<0.001) and 26.0 points (95 percent CI: 18.7-33.3, p<0.001) at 12 months. Similar patterns were also seen in SF-12 and EQ-5D measurements.

The two-year outcomes of the PARTNER trial reported mortality at 43.3 percent in TAVR group compared to 68.0 percent in the medical therapy group (Hazard ratio 0.58, 95 percent CI: 0.36-0.92, p=0.02). Cardiovascular mortality and rate of hospitalization were also lower in the TAVR group compared to standard therapy (31.0 percent vs. 62.4 percent, p<0.001) and (35.0 percent vs. 72.5 percent, p<0.001), respectively. Detailed mortality outcomes comparing both arms of the PARTNER trial were published by Svensson et al in 2014. The PARTNER B RCT compared open surgical repair with TAVR in prohibitive open surgical risk individuals, and the PARTNER A RCT compared open surgical repair with TAVR in high surgical risk individuals. For the 258 individuals who were considered inoperable and enrolled in the PARTNER B RCT, 237 had died at last follow-up. Those randomized to standard therapy exhibited an early peak in mortality that was higher than those randomized to TAVR and prolonged beyond six months. Compared with standard therapy, the lifetime benefit added by transfemoral TAVR was 0.50 years [90 percent CI, 0.30,0.67].

The PARTNER B trial reported a large decrease in all-cause mortality and cardiovascular mortality at one year for TAVR compared to standard therapy. The large decrease in mortality and improved QOL was also reported for the TAVR group at two-year follow-up. Baseline group differences between the TAVR group and the standard therapy group were present, indicating that the TAVR group may have been healthier. While these differences are unlikely to account for the degree of mortality benefit reported, they may have resulted in an overestimation of the mortality benefit. The TAVR group also reported increased stroke risk, as well as substantial increase in vascular complication and major bleeding. Overall generalizability of this study is also uncertain because individual selection was primarily determined by the judgment of the cardiovascular surgeons and/or cardiologists.

Transcatheter Aortic Valve Replacement for Individuals with Aortic Stenosis Who Are High-Risk Candidates for Open Surgery

The PARTNER trial reported results on individuals who were high-risk for open surgery, but still suitable candidates in June 2011. The inclusion and exclusion criteria were generally the same as for the prior cohort, except that these candidates were classified as high-risk for surgery rather than unsuitable for surgery. A predicted perioperative mortality of 15 percent or greater as determined by a cardiac surgeon and cardiologist was determined to be a high-risk individual. An STS score of 10 or greater was included as a guide for high-risk status, but an STS score threshold was not a required criterion for enrollment. Of the total 3,105 individuals screened for aortic valve surgery, 22.5 percent of these were included in the cohort of individuals deemed high-risk for surgery.

The primary hypothesis was that TAVR was non-inferior to open aortic valve replacement (AVR), using a one-sided non-inferiority boundary of 7.5 percent absolute difference in mortality at one year. A total of 699 individuals were randomized to TAVR or usual care. TAVR was performed under general anesthesia using the transfemoral approach if possible (n=492), and through transapical approach (n=207) if the transfemoral approach was not possible. The comparison groups underwent open AVR. The primary outcome was death from any cause at one-year follow-up and the secondary powered endpoint was non-inferiority at one-year for the individuals undergoing TAVR by the transfemoral approach. Secondary endpoints were cardiovascular mortality, NYHA function class, re-hospitalizations, the six minute walk test, valve performance as measured by echocardiography, and procedural complications (MI, stroke, acute kidney injury, vascular complications, and bleeding). The mean age of enrolled individuals was 83.6 years in the TAVR group and 84.5 years in the open AVR group. Other baseline demographics and clinical characteristics were generally well-balanced, except for a trend toward an increased percentage of individuals in the TAVR group with a creatinine level >2.0 (11.1 percent vs. 7.0 percent, p=0.06).

At one-year follow-up, death from any cause was 24.2 percent for the TAVR group compared to 26.8 percent for the open AVR group (p=0.44 for difference between groups). The upper limit of the 95 percent confidence interval (CI) for the difference between groups was a 3.0 percent excess mortality in the TAVR group, which was well within the non-inferiority boundary of 7.5 percent. Thus the criterion of non-inferiority was met, with a p value of 0.001. Results were similar for the subgroup of individuals who underwent TAVR by the transfemoral approach with 22.2 percent mortality in the TAVR group compared with 26.4 percent mortality in the open AVR group (p=0.002 for non inferiority). The secondary outcomes of cardiovascular mortality (14.3 percent vs. 13.0 percent, p=0.63) and rehospitalization (18.2 percent vs. 15.5 percent, p=0.38) were not significantly different for the TAVR versus open AVR groups. The percent of individuals in NYHA Class I or II was similar between groups at one year, as was the improvement in the six minute walk test. On subgroup analysis, there was a significant effect of gender with women deriving greater benefit than men (p=0.045), and a significant effect for prior coronary artery bypass graft (CABG) with individuals who had not had prior CABG deriving greater benefit in the TAVR group.

Significant differences were observed between groups for certain complications. Stroke or TIA at one year was higher for the TAVR group compared to the open AVR group (8.3 percent vs. 4.3 percent, respectively, p=0.04). Vascular complications were higher in TAVR group than open AVR group (18 percent vs. 4.8 percent respectively, p=0.01), as were major vascular complications (11.3 percent vs. 3.5 percent, p=0.01). Major bleeding, however, was more common in the open AVR group than the TAVR group (25.7 percent vs. 14.7 percent, respectively, p=0.01).

Of the 699 individuals in the trial, 628 completed baseline QOL measures. Overall, individuals in both the TAVR and the open AVR groups demonstrated significant improvements in all QOL measures over the 12 months following treatment. Although the TAVR group reported superior improvement at one month on the KCCQ (mean difference 9.9, 95 percent CI: 4.9-14.9, p<0.001), this difference was no longer present at six months or 12 months. A similar pattern of results was also reported for the SF-12 and EQ-5D measures. Overall, for high-risk individuals who were eligible for open surgical AVR, there were no differences observed between TAVR and open AVR in terms of mortality at one year and most major secondary outcomes. The non-inferiority boundaries for this trial included an upper limit of 7.5 percent absolute increase in mortality, but in actuality the reported mortality for the TAVR group was lower than for the open AVR group. QOL was also similar at one year between the TAVR and AVR groups. Stroke or TIA were more common in the TAVR group. Other secondary outcomes were similar between groups, except for higher rates of vascular complications in the TAVR group and higher rates of major bleeding in the open surgery group. Generalizability of results is a concern because participant selection relied largely on the judgment of participating surgeons and cardiologists.

In 2012, the FDA broadened indications for TAVR to include individuals who are at high risk for surgery, as defined by an STS risk score of 8 percent or greater, or judged by a Heart Team to have an operative mortality of 15 percent or greater for open surgery. The US CoreValve High Risk Study by Adams et al (2014) was a RCT comparing open surgical aortic valve replacement with TAVR using a self-expanding transcatheter valve prosthesis (CoreValve device) in individuals who had severe aortic stenosis and were considered at risk of death during surgery. A total of 795 individuals were randomized in a 1:1 ratio to TAVR with self-expanding transcatheter valve (TAVR group) to open surgical aortic-valve replacement (surgical group). For the study’s primary end point, the rate of death from any cause at one year, was lower in TAVR group than in open surgical group (14.2 percent vs 19.1 percent; absolute risk reduction, 4.9; upper boundary of the 95 percent confidence interval, −0.4; P<0.001 for noninferiority; P=0.04 for superiority). At 30 days, major vascular complications occurred in 5.9 percent of the TAVR group compared with 1.7 percent of the open surgical group (p=0.003). Permanent pacemaker implantation was also significantly higher in the TAVR group as compared to the open surgical group (19.8 percent to 7.1 percent (p<0.001) respectively).

Transcatheter Aortic Valve Replacement for Individuals with Aortic Stenosis Who Are Intermediate Risk Candidates for Open Surgery

In recent years, advancements in transcatheter valve systems and improved operator experience have led to increased use of TAVR in intermediate risk individuals. Previously, only observational studies had examined this technique in low and intermediate risk individuals warranting further investigations into its efficacy in this group.

PARTNER 2 is an umbrella trial for several arms and comparators. In the PARTNER 2A trial, Leon et al (2016) evaluated TAVR and open surgical AVR in a multicenter, RCT involving 2032 individuals with intermediate risk (i.e., predicted risk of surgical mortality three percent or greater at 30 days, based on the STS risk score and other clinical comorbidities unmeasured by the STS risk calculator) for open surgery and severe aortic stenosis, with the mean age of 82 years. Individuals were assessed for TAVR access before randomization, with 76.3 percent suitable for transfemoral placement and 23.7 percent required transthoracic placement (transapical or transaortic access). Individuals were then randomized to TAVR using the SAPIEN XT valve system versus open surgical AVR, and were followed for two years. The primary end point was death from any cause or disabling stroke at two years. The hypothesis was that TAVR would not be inferior to open surgical AVR. The rate of death from any cause or disabling stroke was similar in the TAVR group and the open surgical AVR group (P=0.001 for noninferiority). At two years, the Kaplan–Meier event rates were 19.3 percent in the TAVR group and 21.1 percent in the open surgical AVR group (hazard ratio in the TAVR group, 0.89; 95 percent confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95 percent CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic access cohort, outcomes were similar in the two groups. The authors report that TAVR resulted in larger aortic-valve areas than did open surgical AVR and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. This trial proposes to support previous findings that major clinical outcomes with TAVR appear similar to open surgical AVR, and may turn out to actually reduce mortality and morbidity in individuals in whom transfemoral approach can be used or in individuals with high risk of major bleeding.

In a second study, Thourani et al (2016) conclude that TAVR with SAPIEN 3 was both noninferior and superior to surgical valve replacement at one year in a propensity score analysis of 1,077 intermediate-risk individuals for the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation (pooled weighted proportion difference: 9.2 percent; P< 0.0001 for both). The propensity score analysis compared one year results of this study with those from the surgical arm of PARTNER 2A. The propensity score analysis included 963 individuals treated with SAPIEN 3 TAVR and 747 with surgical valve replacement. Furthermore, the 30 day mortality was 80 percent lower than the STS predicted risk. The authors conclude that TAVR with SAPIEN 3 in intermediate-risk individuals with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at one year. The propensity score analysis indicates a significant superiority for the composite outcome with TAVR compared with surgery, suggesting that TAVR may be the preferred treatment alternative in intermediate-risk individuals.

Although five-year data from randomized trials indicate no evidence for premature structural valve deterioration, long-term durability of bioprosthetic transcatheter valves has not been firmly established and needs additional longer term follow-up data.

Transcatheter Aortic Valve Replacement for Individuals with Aortic Stenosis Who Are Low Risk Candidates for Open Surgery

Since, the approval of transcatheter valve replacement systems for individuals who are immediate risk candidates for open surgery in August, 2016, there has been an increase in clinical trials for individuals who are low risk candidates. Currently, there are two manufactures (Medtronic CoreValve (Minneapolis, MN) and Edwards LifeSciences SAPIEN 3 (Irvine, CA)) who are conducting clinical trials to demonstrate safety and effectiveness of transcatheter aortic valve replacement in low risk individuals. The earliest expected completion date is the second half of 2018.

The Nordic Aortic Valve Intervention Trial (NOTION) was the first to include all risk population (high, immediate, low surgical risk individuals) (n=280) and compared individuals with either transcatheter (TAVR) or surgical aortic valve replacement (SAVR) implants in a 1:1 ratio. All participants had severe aortic stenosis. The trials primarily evaluated death from any cause, stroke, or myocardial infraction (MI) at one year. The composite rate of death from any cause, stroke, and MI were not significantly different amongst the two groups (13.1% versus 16.3%, in TAVR and SAVR, respectively; p=0.43 for superiority). Post-procedure, the TAVR group had lower rates of major or life- threatening bleeds compared to the surgical arm (11.3% versus 20.9%, p= 0.03). NOTION was the first randomized trial to include low or immediate risk individuals; the trial failed to distinguish the variance of severity of risk amongst the participants.

The clinical trials are on-going and no device has received approval from the FDA; safety and effectiveness has not been established in the low risk population.

Transcatheter Aortic Valve Replacement (TAVR) for Individuals with Degenerated Bio-prosthetic Valves ("Valve-In-Valve") Who Are at a High or Greater Risk Candidates for Open Surgery

Bioprosthetic valves have limited durability; the best current valves can be expected to degenerate within 10 to 20 years, resulting in stenosis or regurgitation.

TAVR is also used for the treatment of failed surgical bioprosthetic valves in the aortic position. Indications include bioprosthetic valve stenosis, regurgitation, or a combination of the two, in individuals who are at a high or greater risk for open surgical valve replacement. In March 2015 and October 2015 respectively, FDA expanded the indication for the CoreValve system and SAPIEN XT transcatheter heart valve to include treatment of a failed surgical bioprosthesis (transcatheter aortic valve-in-surgical aortic valve [TAV-in-SAV] or "valve-in-valve").

The evidence comprises case series, the largest includes 459 individuals, and systematic reviews of the available case series. Relevant outcomes are overall survival, symptoms, morbid events, and treatment related morality and morbidity. These series have reported high rates of technical success of valve implantation, but also have reported high rates of short-term complications. At one year postprocedure, reported mortality rates are often high, but high proportions of individuals have improvement in heart failure related symptoms.

TRANSCATHETER PULMONARY VALVE (TPV) IMPLANTATION

Congenital heart disease, including tetralogy of Fallot, pulmonary atresia, and transposition of the great arteries, is generally treated by surgical repair at an early age. This involves reconstruction of the right ventricular outflow tract (RVOT) and pulmonary valve by means of a surgical homograft or a bovine derived valved conduit. These repairs are prone to development of pulmonary stenosis or regurgitation over long periods of follow-up. Because individuals with surgically corrected congenital heart disease repair are living longer into adulthood, RVOT dysfunction following initial repair has become more common. Calcification of the RVOT conduit can lead to pulmonary stenosis, while aneurysmal dilatation can result in pulmonary regurgitation.

Right ventricular outflow tract (RVOT) dysfunction can lead to decreased exercise tolerance, potentially fatal arrhythmias, and/or irreversible right ventricular dysfunction. Interventions for RVOT dysfunction often require repeat open heart surgery, resulting in numerous open heart procedures for individuals who live into adulthood. Treatment options for pulmonary stenosis are open surgery with valve replacement, balloon dilatation, or percutaneous stenting. Interventions for pulmonary regurgitation are primarily surgical, either reconstruction of the RVOT conduit or replacement of the pulmonary valve through open surgery.

Transcatheter pulmonary valve (TPV) implantation offers a potentially less invasive treatment option for individuals with prior surgery for congenital heart disease and RVOT dysfunction. It is possible that the use of less invasive valve replacement techniques can spare individuals from multiple repeat open heart procedures over long periods of follow-up.

The TPV and the valve delivery system are used together for percutaneous replacement of a dysfunctional pulmonary valve. For example, the Melody® valve consists of a section of bovine jugular vein with an intact native venous valve. The valve and surrounding tissue is sutured within a platinum-iridium stent scaffolding. The transcatheter delivery system consists of a balloon-in-balloon catheter with a retractable sheath and distal cup into which the valve is placed. The procedure is performed on the beating heart without use of cardiopulmonary bypass. The valve is first crimped to fit into the delivery system. It is introduced through the femoral vein and advanced into the right side of the heart and put into place at the site of the pulmonary valve. The inner balloon is inflated to open the artificial valve, and then the outer balloon is inflated to position the valve into place.

PEER-REVIEWED LITERATURE
In January 2010, the Melody® Transcatheter Pulmonary Valve (TPV) and the Ensemble® Transcatheter Valve Delivery System (Medtronic, Minneapolis, MN) were approved by the FDA under the Humanitarian Device Exemption (HDE) Program. Approval was for use as an adjunct to surgery in the management of pediatric and adult individuals with the following clinical conditions:
  • Existence of a full (circumferential) right ventricular outflow tract (RVOT) conduit that was 16 mm or greater in diameter when originally implanted
  • Dysfunctional RVOT conduits with clinical indication for intervention
  • Moderate-to-severe regurgitation or stenosis (mean RVOT gradient 35 mm Hg or greater )

In January 2015, approval of the Melody® Transcatheter Pulmonary Valve (TPV) and the Ensemble® Transcatheter Valve Delivery System was amended to a premarket approval (PMA) because FDA determined that the device represents a breakthrough technology. The PMA was based, in part, on two prospective clinical studies, the Melody® TPV Long-term Follow-up Post Approval Study (PAS) and the Melody® TPV New Enrollment PAS.

The US Melody® TPV trial was a multicenter, prospective uncontrolled trial designed to assess the safety, procedural success, and short-term effectiveness of the Melody® TPV. It was the pivotal trial on which FDA approval of the Melody® valve was based. The investigators planned to follow 150 individuals over a five-year period. Eligibility criteria included a dysfunctional RVOT conduit or a dysfunctional bioprosthetic pulmonary valve, plus evidence of heart failure. For individuals with New York Heart Association (NYHA) class I heart failure, a Doppler mean gradient of 40 mm Hg or greater or severe pulmonary regurgitation was required, and for individuals with NYHA class II to IV heart failure, a mean gradient of 35 mm Hg or greater or moderate pulmonary regurgitation was required. These inclusion criteria generally were indications for pulmonary valve replacement. The primary outcomes were defined as procedural success, adverse events (AEs) from the procedure, and effectiveness, as measured by the proportion of individuals with acceptable valve function at six months.

Armstrong et al (2014) published one-year follow-up results of the Melody® TPV Long-term Follow-up PAS, a prospective study designed to evaluate the short-term hemodynamic changes following device implantation. PAS enrolled 120 individuals, 101 of whom underwent attempted TPV implantation. Subject selection was based on the criteria used in an IDE cohort trial, but did not include the age and weight (30 kg or greater) limitations. Procedure related significant AEs occurred in 16 individuals (13.3 percent of total cohort; 15.8 percent of those who had an attempted TPV implantation), the most common of which was a confined conduit tear. Procedural success occurred in 99 subjects (98 percent of those with an attempted TPV implantation). At one-year follow-up, the proportion of individuals in NYHA class I heart failure increased from 35 percent at baseline to 89 percent. Of the 99 individuals implanted for at least 24 hours, 87 had acceptable TPV hemodynamic function confirmed at six months (96.7 percent of those with evaluable echocardiographic data, 87.9 percent of entire cohort) and 82 had acceptable TPV hemodynamic function at one year (94.3 percent of those with evaluable echocardiographic data, 82.8 percent of the entire cohort). Following the procedural period, serious device related AEs occurred in eight percent, most commonly endocarditis.

Trial results have been published in other reports including Cheatham et al (2015) reported on outcomes up to seven years following TPV implantation for the 148 individuals who received and were discharged with a TPV in the US Melody® TPV trial (of 171 individuals enrolled). Of the 171 individuals enrolled, 167 underwent catheterization, 150 had a Melody® valve implanted, and 148 of those survived to discharge with the Melody® valve in place. On echocardiogram at discharge, pulmonary regurgitation was absent/trivial or mild in 140 individuals and five individuals, respectively, which represented a significant improvement from baseline. Over a median follow-up of 4.5 years (range, 0.4-7.0 years), four deaths occurred. During the follow-up period, 32 individuals required a reintervention on RVOT, 25 of which were TPV reinterventions. A total of 11 individuals required Melody® valve explantation. Among the 113 individuals who were alive and free from reintervention at a median of 4.5 years postimplantation, the most recent RVOT gradient was unchanged from early after valve implantation. Functional outcomes generally improved during the study: before TPV implantation, 14 percent of individuals were in NYHA class I and 17 percent were in class III or IV. At every postimplantation annual evaluation, at least 74 percent of individuals were in class I and no more than one-two percent were in class III or IV.

In 2015, Gillespie et al evaluated results of TPV implantation after a Ross procedure (i.e., the individual's diseased aortic valve is replaced with his or her own pulmonary valve) in a retrospective review of pooled findings from the US. Melody® TPV trial and PAS and an additional European registry, the manufacturer sponsored Melody® TPV Post-Market Surveillance Study conducted in Canada and Europe (NCT00688571). In the pooled sample (total N=358 individuals), 67 (19 percent) had a prior Ross procedure. A Melody® valve was successfully implanted in 56 (84 percent) of 67 Ross individuals who underwent catheterization with intent for TPV implantation. Six (nine percent) individuals had symptomatic coronary artery compression after TPV implantation or did not undergo implantation due to the risk of compression. Right ventricular hemodynamics generally improved after TPV implantation, but RVOT reinterventions were required in 12 of 55 individuals discharged from the implant hospitalization with the Melody® valve in place.

In February 2016, the SAPIEN™ XT Transcatheter Heart Valve (THV) (Pulmonic) (Edwards LifeSciences, Irvine, CA), composed of a stainless steel frame with bovine pericardial tissue leaflets, available in 23, 26, and 29 mm sizes, was approved by FDA through the PMA process for use in individuals with a dysfunctional, non-compliant RVOT conduit with a clinical indication for intervention and pulmonary regurgitation, moderate or greater and/or mean RVOT gradient 35mmHg or greater. The COMPASSION (COngenital Multicenter trial of Pulmonic vAlve regurgitation Studying the SAPIEN InterventIONal THV) trial was conducted using the SAPIEN THV, Edwards’ first generation THV, which is no longer available for distribution. There were no clinical data collected on SAPIEN XT, Edwards’ second generation THV, in the COMPASSION trial. However, there is extensive clinical evidence on Edwards SAPIEN XT THVs in the aortic position from the PARTNER 1 and 2 trials.

In summary, the evidence for the use of TPV implantation consists of a prospective, interventional, noncomparative pivotal study, a prospective, non-randomized study on which the device’s FDA approval was based, along with a postapproval registry study and a number of additional case series. Overall, the evidence suggests that TPV implantation is associated with high rates of short-term technical success and improvements in heart failure related symptoms and hemodynamic parameters. Studies with follow-up extending to a maximum of seven years postprocedure have suggested that the functional and hemodynamic improvements are durable, with 20 percent to 30 percent requiring reintervention on the pulmonary valve.

TRANSCATHETER MITRAL VALVE REPLACEMENT (TMVR)

Mitral regurgitation (MR) is the second most common valvular heart disease which can result from a heterogeneous set of disease processes that may affect one or more parts of the mitral valve complex. Mitral regurgitation is a common valvular heart disease that can result from either a primary structural abnormality of the mitral valve complex or a dilated left ventricle due to ischemic or dilated cardiomyopathy, which leads to secondary dilation of an anatomically normal mitral valve.

Mitral regurgitation is classified into degenerative and functional mitral valve disease. In degenerative mitral valve regurgitation, disease results from primary structural abnormality of the mitral valve complex. Common cause of degenerative mitral regurgitation (DMR) include MV prolapse syndrome with subsequent myxomatous degeneration, rheumatic heart disease, coronary artery disease, infective endocarditis and collagen vascular disease.

In the function mitral regurgitation, the primary abnormality is dilated ventricle due to ischemic or dilated cardiomyopathy, which leads to secondary dilation of an anatomically normal mitral valve. The severity of MR is classified into mild, moderate, and severe disease on the basis of echocardiographic and/or angiographic findings (1+, 2+ and 3-4+ angiographic grade respectively).

In individuals with multiple comorbidities, surgical therapy may be underutilized. To address the unmet need for less invasive mitral valve repair, transcatheter approaches have been presented as a potential alternative to surgical therapy for MR, particularly among individuals who face prohibitively high surgical risks due to their age and comorbidities.

The MitraClip® Clip Delivery System (Abbott Vascular Menolo Park, CA) consists of implant catheters and the MitraClip device. The device, which is percutaneously deployed, is a permanent implant that attaches to the mitral valve leaflets as a treatment for reducing MR with the intended outcomes to improve recovery of the heart from overwork, improve function and potentially halt the progression of heart failure. The procedure is performed under general anesthesia via echocardiographic and fluoroscopic guidance. The heart beats normally during the procedure, and heart-lung bypass support is generally not required. The MitralClip Delivery System received FDA approval through the premarket approval process in October 24, 2013. The device received approval for treatment of significant symptomatic mitral regurgitation (MR >3+) due to primary abnormality of the mitral apparatus (DMR) in individuals who have been determined to be at prohibitive risk for mitral valve surgery by a Heart Team.

PEER-REVIEWED LITERATURE
The MitralClip® Delivery System received FDA approval through the premarket approval process in October 14, 2013. The device received approval for treatment of significant symptomatic mitral regurgitation (MR >3+) due to primary abnormality of the mitral apparatus (DMR) in individuals who have been determined to be at prohibitive risk for mitral valve surgery by a Heart Team.

The evidence for the use of MitralClip® in individuals with severe symptomatic DMR who are considered at prohibitive risk for open surgery includes single-arm cohort studies. No RCTs have been published evaluating MitraClip in prohibitive surgical risk populations. The reported results from Endovascular Valve Edge-to-Edge Repair Study (EVEREST) II high risk registry (HRR) and Real World Expanded Multicenter Study of the MitraClip® System (REALISM) registry subset of prohibitive risk DMR individuals served as a basis for the FDA premarket approval. The EVEREST II studies included individuals from the EVEREST I feasibility study, EVEREST II RCT, the EVEREST II single arm HRR, and the REALISM Continued Access Protocol (CAP) registry that included high risk and non-high risk enrollment. From 2003-2012, 544 individuals with ≥ 3+ DMR were prospectively enrolled in EVEREST I, EVEREST II RCT, EVEREST II HRR registry and the REALISM CAP registry. Of these 544 individuals, 141 were chosen. The charts for these 141 individuals were retrospectively reviewed by a multidisciplinary team that included two experienced mitral valve surgeons and one experienced mitral valve cardiologist for what the authors defined as prohibitive risk. The team also included echocardiographers to assess MR severity. From this group of 141 individuals, 127 met the definition of prohibitive risk and had at least one-year follow-up.

This cohort included 25 individuals from EVEREST II HRR, 98 from the REALISM CAP registry and four other individuals. This cohort of individuals had a mean age of 82 years, 87 percent New York Heart Association (NYHA) functional class III/IV, with STS score of 13.2 ± 7.3 percent. Comorbidities included congestive heart failure (125/127), coronary artery disease (95/125), cerebrovascular disease history (24/127), chronic obstructive pulmonary disease (40/127), and diabetes (38/127). Adverse events were adjudicated by an independent Clinical Events Committee.

In individuals who received the device, either one (44.1 percent) or two (51.2 percent) clips were implanted. Six individuals did not receive a device, with four of these failures due to technical reasons and the remaining two having complications during the procedure that included tamponade and hemodynamic instability. Despite being determined to be at prohibitive risk for surgery three individuals did have open surgery, with two of the three alive at one year. Adverse events at one year included 30 deaths (23.6 percent) as well as stroke (2.4 percent), renal failure (3.9 percent), bleeding complication (15.7 percent), vascular complication (7.1 percent), and gastrointestinal complication requiring surgery (2.4 percent). Most surviving individuals (82.9 percent) at one year had MR ≤ 2+ and were in NYHA functional class I or II. One-year survival appeared to be better for individuals who had 1+ or 2+ MR at discharge versus those who had 3+ or 4+. Short Form-36 health survey scores improved and the authors reported that hospitalizations were reduced in individuals whose MR was reduced.

The authors stated that the data were limited in that it was not completely from a randomized trial, due to not having a control arm to randomize to (as medical therapy lacks a treatment role in DMR, and surgical options are not standard in prohibitive surgical risk individuals). Because the cohort was retrospectively identified, all analyses were post-hoc.

The authors concluded that MitraClip therapy is safe in individuals with severe, primary DMR for whom a Heart Team has determined that mitral valve surgery is associated with a prohibitive risk/benefit ratio. Transcatheter reduction of DMR in these individuals provides significant benefits including improvements in symptoms and functional status, a decrease in hospitalizations, and favorable left ventricular remodeling at one year.

The MitralClip was identified in a Class I recall, the most serious type of recall by the FDA in February, 2016. The manufacture received reports of cases where the Clip Delivery System could not be detached from the Clip due to a malfunction of the device. These cases resulted in open heart surgery to retrieve the delivery system. The manufacture recalled the MitraClip Delivery System to provide updated instructions and training for health care providers who use the device. Per the FDA Code of Regulation Title 21, " A recall will be terminated when the Food and Drug Administration determines that all reasonable efforts have been made to remove or correct the product in accordance with the recall strategy, and when it is reasonable to assume that the product subject to the recall has been removed and proper disposition or correction has been made commensurate with the degree of hazard of the recalled product." The FDA terminated the recall status on May 12, 2016 after safety concerns were alleviated and they communicated to continue the usage of the device based on the previous indication of use.

Transcatheter Mitral Valve Replacement (TMVR) for Individuals with Degenerated Bio-prosthetic Valves ("Valve-In-Valve") Who Are at a High or Greater Risk Candidates for Open Surgery

Bioprosthetic, or tissue, valves can expect to last 10-20 years. For a young person with a tissue valve replacement, the need for additional surgery or another valve replacement later in life is highly likely. As the clinical utility of transcather mitral valve replacement procedure increases it can be expected that the need to replace degenerative valves will also increase in the future. Until recently, there was no approved device for mitral valve replacement for individuals with degenerative bio-prosthetic valves in the mitral position.

In June 2017, the FDA approved an expanded indication for the Sapien 3 Transcatheter Heart Valve (THV) for individuals with symptomatic heart disease due to failure of a previously placed bioprosthetic aortic or mitral valve whose risk of death or severe complications from repeat surgery is high or greater. An analysis of the real-world off-label use data captured in the Society of Thoracic Surgeons (STS) /American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry was performed to support the approval. The registry reported on mortality rates on date of discharge, and 30-day follow-up. 314 cases of individuals who had undergone aortic valve-in-valve procedures and 311 cases who had undergone mitral valve-in-valve procedures, of which only 70 individuals utilized the SAPIEN 3 device. Registry data showed that more than 93 percent of individuals (n=40) who underwent and had 30-day follow-up information in the mitral valve-in-valve procedures with SAPIEN 3 experienced clinically meaningful improvement in their heart failure symptoms 30-days post procedure, demonstrated by their New York Heart Association (NYHA) Classifications. The individuals in the SAPIEN 3 cohort also acknowledged an increase in quality of life according to the Kansas City Cardiomyopathy Questionnaire (KCCQ) (scale 0-100), more than doubling from the date of discharge to the 30-day follow-up. In either of the valve-in-valve procedures, the recipients observed mortality rates were substantially lower than the expected mortality rate for revision surgery.

The Sapien 3 THV was previously approved for individuals whose own native aortic valves become narrowed by aortic stenosis. The FDA stated the Sapien 3 THV should only be used in persons who are at high or greater risk of death or serious complications from traditional open-heart surgery to replace the failed surgical tissue valve, as determined by their heart team composed of a cardiologist and surgeon. As part of the approval, the manufacturer will participate in the STS/ACC Transcatheter Valve Therapy Registry to ensure FDA surveillance for the device over the next five years.
The registry results were limited by the timing of introduction of new devices. The registry reported on data available for the SAPIEN 3 between June 23, 2015 through June 15, 2016, which created few participants utilizing this newly approved device. Follow-up data is was sparse, as 25 percent of the SAPIEN 3 cohort failed to complete the 30-day follow-up visit; limiting analysis to 48/70 individuals.

At present, the evidence comprises of several case studies and a few case series exist focusing on the use of mitral valve replacement with degenerated bio-prosthetic valve. The largest case series available outside of the registry involved 11 individuals.

TRANSCATHETER TRICUSPID VALVE REPAIR

Few individuals undergo isolated tricuspid valve surgery, which remains associated with high in-hospital mortality rates. Individuals with severe tricuspid regurgitation are often managed medically for years before tricuspid valve repair or replacement. Studies are in progress on the possibility of treating tricuspid valves with transcatheter approaches similar to those used for mitral valve disease with either a clip on the valve leaflets or an annular remodeling device.  

The first-in-human case, reported by Schofer et al in March 2015, suggests that percutaneous transcatheter tricuspid repair may provide hemodynamic improvements in some individuals.  Transcatheter tricuspid valve repair could be proposed as an effective treatment for high surgical risk individuals who are non-responsive to optimal medical therapy. However, transcatheter tricuspid valve repair is in preclinical or early feasibility studies and is not available for general clinical use. Prospective registries with higher numbers of subjects and longer follow-up are needed to better evaluate the safety and efficacy of transcatheter tricuspid valve repair.
References


Adams DH, Popma JJ, Reardon MJ, et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014;370(19):1790-1798.

Agency for Healthcare Research and Quality (AHRQ). Percutaneous heart valve replacement. [AHRQ Web site]. August 2010. Available at: http://www.ncbi.nlm.nih.gov/books/NBK47033/. Accessed April 03, 2018.

Alozie A, Paranskaya L, Westphal B, et al. Clinical outcomes of conventional surgery versus MitraClip(R) therapy for moderate to severe symptomatic mitral valve regurgitation in the elderly population: an institutional experience. BMC Cardiovasc Disord. 2017;17(1):85.

American College of Cardiology (ACC). ACC News Story. New Statement Recommends tPVR as Less Invasive Option For RVOT Dysfunction in CHD Patients. [ACC Web site]. 03/24.2015. Available at: http://www.acc.org/latest-in-cardiology/articles/2015/03/24/13/16/new-statement-recommends-tpvr-as-less-invasive-option-for-rvot-dysfunction-in-chd-patients. Accessed April 03, 2018.

Armstrong AK, Balzer DT, Cabalka AK, et al. One-year follow-up of the Melody transcatheter pulmonary valve multicenter post-approval study. JACC Cardiovasc Interv. 2014;7(11):1254-1262.

Arora S, Misenheimer JA, Jones W, et al. Transcatheter versus surgical aortic valve replacement in intermediate risk patients: a meta-analysis. Cardiovasc Diagn Ther. 2016; 6(3): 241–249.

Baker, CM, & Reardon, MJ. The CoreValve US Pivotal Trial. Semin Thoracic Surg. 2014;26(3): 179-186.

Brecker SJ, Gaasch WH, Aldea GS, et al. Transcatheter aortic valve replacement: indications. [UpToDate Web site]. 06/02/2017. Available at: http://www.uptodate.com/contents/transcatheter-aortic-valve-replacement-indications. Accessed April 03, 2018.

Bonow RO, Carabello BA, Kanu C 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. Circulation. 2006;114(5):e84-231.

Borik S, Crean A, Horlick E, et al. Percutaneous pulmonary valve implantation: 5 years of follow-up: does age influence outcomes? Circ Cardiovasc Interv. 2015;8(2):e001745.

Boudjemline Y, Malekzadeh-Milani S, Patel M, et al. Predictors and outcomes of right ventricular outflow tract conduit rupture during percutaneous pulmonary valve implantation: a multicentre study. EuroIntervention.2016;11(9):1053-1062.

Bouleti C, Juliard JM, Himbert D, et al. Tricuspid valve and percutaneous approach: No longer the forgotten valve! Arch Cardiovasc Dis. 2016; 109(1):55-56.

Centers for Medicare & Medicaid Services (CMS). Decision Memo for Transcatheter Mitral Valve Repair (TMVR) (CAG-00438N). [CMS Web site]. 08/07/2014, Available at:https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=273. Accessed April 03, 2018.

Centers for Medicare & Medicaid Services (CMS). National Coverage Analysis (NCA) for Transcatheter Aortic Valve Replacement (TAVR) (CAG-00430N).Decision memo. [CMS Web site]. 05/01/2012. Available at:
https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=257&ver=4&NcaName=Transcatheter+Aortic+Valve+Replacement+(TAVR)&bc=ACAAAAAACAAAAA%3d%3d&. Accessed April 03, 2018.

Centers for Medicare & Medicaid Services (CMS). National Coverage Determination (NCD). Transcatheter Aortic Valve Replacement (TAVR). 20.32. [CMS Web site]. 05/01/2012. Available at:
https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=355&ncdver=1&NCAId=257&ver=4&NcaName=Transcatheter+Aortic+Valve+Replacement+(TAVR)&bc=ACAAAAAACAAAAA%3D%3D&. Accessed April 03, 2018.

Centers for Medicare & Medicaid Services (CMS). National Coverage Determination (NCD). Transcatheter Mitral Valve Repair (TMVR). 20.33 [CMS Web site]. 08/07/2014. Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=363&ncdver=1&bc=AgAAQAAAAAAAAA%3D%3D&. Accessed April 03, 2018.

Cheatham JP, Hellenbrand WE, Zahn EM, et al. Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary valve replacement in the US Melody valve investigational device exemption trial. Circulation.2015;131(22):1960-1970.

Clinical Trials.gov. Edwards cardioband tricuspid valve reconstruction early feasibility study. [Clinical Trials.gov Web site]. 12/27/2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03382457. Accessed April 03, 2018.

Coeytaux RR, Williams JW, Jr., Gray RN, et al. Percutaneous heart valve replacement for aortic stenosis: state of the evidence. Ann Intern Med. 2010; 153(5):314-324.

Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.

Dalton K. First-in-human transcatheter tricuspid repair feasible but questions remain. [Transcatheter Cardiovascular Therapeutics (TCT) MD Web site]. 12/06/2015. Available at: https://www.tctmd.com/news/first-human-transcatheter-tricuspid-repair-feasible-questions-remain. Accessed April 03, 2018.

Dewey, Todd M, et al. Reliability of risk algorithms in predicting early and late operative outcomes in high-risk patients undergoing aortic valve replacement. Discussion. J Thorac Cardiovasc Surg. 2008;135(1):180-187.

Dvir D, Webb J, Brecker S, et al. Transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: results from the Global Valve-in-Valve Registry. Circulation. 2012;126(19):2335-2344.

Eggebrecht H, Schafer U, Treede H, et al. Valve-in-valve transcatheter aortic valve implantation for degenerated bioprosthetic heart valves. J Am Coll Cardiol Intv. 2011;4(11):1218-1227.

Ewe SH, Delgado V, Ng AC, et al. Outcomes after transcatheter aortic valve implantation: transfemoral versus transapical approach. Ann Thorac Surg. 2011; 92(4):1244-1251.

Fanning JP, Wesley AJ, Walters DL, et al. Neurological injury in intermediate-risk transcatheter aortic valve implantation. J Am Heart Assoc. 2016;5(11).

Feldman T, Kar S, Elmariah S, et al. Randomized comparison of percutaneous repair and surgery for mitral regurgitation 5-year results of EVEREST II. J Am Coll Cardiol. 2015;66(25):2844-2854. 

Figulla L, Neumann A, Figulla HR, et al. Transcatheter aortic valve implantation: evidence on safety and efficacy compared with medical therapy. A systematic review of current literature. Clin Res Cardiol. 2011; 100(4):265-276.

Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation. 2005; 111(24):3316-3326.

Genereux P, Kodali SK, Green Pm et al. Incidence and effect of acute kidney injury after transcatheter aortic valve replacement using the New Valve Academic Research Consortium Criteria. Am J Cardiol. 2012;111(1):100-105.

Gilard M, Eltchaninoff H, Donzeau-Gouge P, et al. Late outcomes of transcatheter aortic valve replacement in high-risk patients: The FRANCE-2 Registry. J Am Coll Cardiol. 2016;68(15):1637-1647.

Gillespie MJ, McElhinney DB, Kreutzer J, et al. Transcatheter pulmonary valve replacement for right ventricular outflow tract conduit dysfunction after the Ross procedure. Ann Thorac Surg.2015;100(3):996-1003.

Gurvitch R, Wood DA, Tay EL, et al. Transcatheter aortic valve implantation: durability of clinical and hemodynamic outcomes beyond 3 years in a large patient cohort. Circulation. 2010; 122(13):1319-1327.

Hijazi ZM, Ruiz CE, Zahn E, et al. SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement, Part III: Pulmonic valve. J Am Coll Cardiol. 2015;65(23):2556-2563.

Holmes  DR, Mack  MJ, Kaul S, et al. 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement. J Am Coll Cardiol.2012;59(13):1200-1254.

Holmes DR, Jr., Mack MJ. Transcatheter valve therapy: a professional society overview from the American College of Cardiology Foundation and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011; 58(4):445-455.

Khawaja MZ, Thomas M, Joshi A, et al. The effects of VARC-defined acute kidney injury after transcatheter aortic valve implantation (TAVI) using the Edwards bioprosthesis. EuroIntervention. 2012;8(5):563-570.

Kondur A, Briasoulis A, Palla M, et al. Meta-Analysis of transcatheter aortic valve replacement versus surgical aortic valve replacement in patients with severe aortic valve stenosis. Am J Cardiol. 2016;117(2):252-257.

Kumbhani DJ. US Melody transpulmonary valve trial - US Melody TPV trial. [American College of Cardiology Web site]. 08/02/2010. Available at: http://www.acc.org/latest-in-cardiology/clinical-trials/2010/08/03/15/54/melody-transpulmonary-valve-trial?w_nav=LC. Accessed April 03, 2018.

Latib A, Agricola E, Pozzoli A, et al. First-in-man implantation of a tricuspid annular remodeling device for functional tricuspid regurgitation. JACC Cardiovasc Interv. 2015; 8(13):211-214.

Latib A, Ielasi A, Montorfano M et al. Transcatheter valve-in-valve implantation with the Edwards SAPIEN in patients with bioprosthetic heart valve failure: the Milan experience. EuroIntervention. 2012; 7(11):1275-1284.

Latib AMaisano FBertoldi L, et al. Transcatheter vs surgical aortic valve replacement in intermediate-surgical-risk patients with aortic stenosis: a propensity score-matched case-control study. Am Heart J. 2012;164(6):910-917.

Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010; 363(17):1597-1607.

Leon MD, Simth CR, Mack MJ et al. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med.2016;374(17):1609-1620.

Lieberman EB, Bashore TM, Hermiller JB, et al. Balloon aortic valvuloplasty in adults: failure of procedure to improve long-term survival. J Am Coll Cardiol. 1995; 26(6):1522-1528.

Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374(17):1609-1620.

Lindroos M, Kupari M, Heikkila J, et al. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol. 1993; 21(5):1220-1225.

Linke A, Woitek F, Merx MW et al. Valve-in-Valve Implantation of Medtronic CoreValve Prosthesis in Patients with Failing Bioprosthetic Aortic Valves. Circ Cardiovasc Interv. 2012; 5(5):689-697.

Ludman PF, Moat N, de Belder MA, et al. Transcatheter aortic valve implantation in the United Kingdom: temporal trends, predictors of outcome, and 6-year follow-up: a report from the UK Transcatheter Aortic Valve Implantation (TAVI) Registry, 2007 to 2012. Circulation. 2015;131(13):1181-1190.

Lung B, Cachier A, Baron G, et al. Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Eur Heart J. 2005; 26(24):2714-20.

Mack MJ, Leon MB, Smith CR, et al. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015;385(9986):2477-2484.

Makkar RR, Fontana GP, Jilaihawi H, et al. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. 2012; 366(18):1696-1704.

Mauri L, Foster E, Glower DD, et al. 4-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J Am Coll Cardiol. 2013;62(4):317-328.

McElhinney DB, Cabalka AK, Aboulhosn JA, et al. Transcatheter tricuspid valve-in-valve implantation for the treatment of dysfunctional surgical bioprosthetic valves: an international multicenter registry study. Circulation.2016;133(16):1582-1593.

McElhinney DB, Hellenbrand WE, Zahn EM, et al. Short- and medium-term outcomes after transcatheter pulmonary valve placement in the expanded multicenter US Melody valve trial. Circulation. 2010;122(5):507-516.

Malekzadeh-Milani S, Ladouceur M, Patel M, et al. Incidence and predictors of Melody(R) valve endocarditis: a prospective study. Arch Cardiovasc Dis.2015;108(2):97-106.

Maxwell YL. SAPIEN 3 superior to surgery among intermediate-risk patients in observational trial. [Transcatheter Cardiovascular Therapeutics (TCT) MD Web site]. 04/03/2016. Available at: http://www.tctmd.com/show.aspx?id=134646. Accessed April 03, 2018.

Minha S, Torguson R, Waksman R. Overview of the 2013 Food and Drug Administration circulatory system devices panel meeting on the MitraClip Delivery System. Circulation. 2013;128(8):864-868.

Moat NE, Ludman P, de Belder MA, et al. Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: The U.K. TAVR (United Kingdom Transcatheter Aortic Valve Implantation) Registry. J Am Coll Cardiol. 2011; 58(20):2130-2138.

National Institutes of Health. Clinical trials: Medtronic transcatheter aortic valve replacement in low risk patients (NCT02701283). [Clinical Trials Web site]. 4/24/2017. Updated 03/21/2018. Available at: http://clinicaltrials.gov/ct2/show/NCT02701283. Assessed April 03, 2018.

National Institutes of Health. Clinical trials: The Nordic aortic valve intervention trial (NOTION) (NCT01057173). [Clinical Trials Web site]. 5/18/2017. Available at:http://clinicaltrials.gov/ct2/show/NCT01057173. Accessed April 03, 2018.

National Institutes of Health. Clinical trials: The PARTNER 3 trial. The safety and effectiveness of the SAPIEN 3 transcatheter heart valve in low risk patients with aortic stenosis (P3) (NCT02675114). [Clinical Trials Web Site]. 7/26/2017. Update 03/23/2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02675114. Assessed April 03, 2018.

Nishimura, RA, Otto, CM, Bonow RO, 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 Cadiovasc Surg. 2014;148(1): e1-132.

O’Neill WW, O’Neill BP. Transcatheter tricuspid valve intervention: the next frontier. J Am Coll Cardiol. 2015;65:1196-1198.

Otto CM, Gaasch WH, Yeon SB. Management and prognosis of tricuspid regurgitation. 01/10/2018. UpToDate. [UpToDate Web site]. https://www.uptodate.com/contents/management-and-prognosis-of-tricuspid-regurgitation?source=search_result&search=Management%20and%20prognosis%20of%20tricuspid%20regurgitation.&selectedTitle=1~150. Accessed April 03, 2018.

Piazza N, Grube E, Gerckens U, et al. Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) CoreValve ReValving System: results from the multicentre, expanded evaluation registry 1-year following CE mark approval. EuroIntervention. 2008; 4(2):242-249.

Piazza N, Kalesan B, van Mieghem N, et al. A 3-center comparison of 1-year mortality outcomes between transcatheter aortic valve implantation and surgical aortic valve replacement on the basis of propensity score matching among intermediate-risk surgical patients. JACC Cardiovasc Interv. 2013;6(5):443-451.

Penn Medicine. News Release. Penn researchers find similar outcomes for patients with severe aortic stenosis who undergo transcatheter aortic valve replacement or surgery. [University of Pennsylvania Health System Web site]. 04/04/2016. Available at:
http://www.uphs.upenn.edu/news/News_Releases/2016/04/herrmann/. Accessed April 03, 2018.

Reynolds MR, Magnuson EA, Lei Y, et al. Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis. Circulation. 2011; 124(18):1964-1972.

Reynolds MR, Magnuson EA, Wang K, et al. Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results from the PARTNER (Placement of AoRTic TraNscathetER Valve) Trial (Cohort A). J Am Coll Cardiol. 2012; 60(6):548-558.

Rodes-Cabau J, Webb JG, Cheung A, et al. Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience. J Am Coll Cardiol. 2010; 55(11):1080-1090.

Schofer J, Bijuklic K, Tiburtius C, et al. First-in-human transcatheter tricuspid valve repair in a patient with severely regurgitant tricuspid valve. J Am Coll Cardiol.2015;65:1190-1195.

Schymik G, Heimeshoff MBramlage P, et al. A comparison of transcatheter aortic valve implantation and surgical aortic valve replacement in 1,141 patients with severe symptomatic aortic stenosis and less than high risk. Catheter Cardiovasc Interv. 2015;86(4):738-744.

Siemieniuk RA, Agoritsas T, Manja V, et al. Transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at low and intermediate risk: systematic review and meta-analysis. BMJ. 2016;354:i5130.

Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011; 364(23):2187-2198.

Society of Thoracic Surgeons (STS). Leading Cardiovascular Organizations Release Credentialing Recommendations for Heart Valve Replacement Procedure. [STS website]. 03/01/2012. Available at: https://www.sts.org/media/news-release-archive/leading-cardiovascular-organizations-release-credentialing-recommendations-heart-valve-replacement. Accessed April 03, 2018.

Society of Thoracic Surgeons. Short-term risk calculators. Available at:
http://riskcalc.sts.org/STSWebRiskCalc273/About%20the%20STS%20Risk%20Calculator%20v2.73.pdf. Accessed April 03, 2018.

Society of Thoracic Surgeons. STS Adult Cardiac Surgery Database Risk Model Variables – Data Version 2.73. 2016. Available at: http://www.sts.org/quality-research-patient-safety/quality/risk-calculator-and-models. Accessed April 03, 2018.

Søndergaard, L, Steinbrüchel, DA, Ihlemann, N, et al. Two-year outcomes in patients with severe aortic valve stenosis randomized to transcatheter versus surgical aortic valve replacement: the all-comers Nordic aortic valve intervention randomized clinical trial. Circ Cardiovasc Interv. 2016;9(6) :e003665.

Sorajja P, Mack M, Vemulapalli S, et al. Initial experience with commercial transcatheter mitral valve repair in the United States. J Am Coll Cardiol. 2016;67(10):1129-1140.

Svensson LG, Blackstone EHRajeswaran J, et al. Comprehensive analysis of mortality among patients undergoing TAVR: results of the PARTNER trial. J Am Coll Cardiol. 2014;64(2):158-168.

Takagi H, Ando T, Umemoto T. A review of comparative studies of MitraClip versus surgical repair for mitral regurgitation. Int J Cardiol. 2017;228:289-294.

Tamburino C, Barbanti M, D'Errigo P, et al. 1-year outcomes after transfemoral transcatheter or surgical aortic valve replacement: results from the Italian OBSERVANT Study. J Am Coll Cardiol. 2015;66(7):804-812.

Tamburino C, Capodanno D, Ramondo A, et al. Incidence and predictors of early and late mortality after transcatheter aortic valve implantation in 663 patients with severe aortic stenosis. Circulation. 2011; 123(3):299-308.

Thomas M, Schymik G, Walther T, et al. One-year outcomes of cohort 1 in the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry: the European registry of transcatheter aortic valve implantation using the Edwards SAPIEN valve. Circulation. 2011; 124(4):425-433.

Toggweiler S, Wood DA, Rodes-Cabau J, et al. Transcatheter valve-in-valve implantation for failed balloon-expandable transcatheter aortic valves. JACC Cardiovasc Interv. 2012; 5(5):571-577.

Tommaso CL, Fullerton DA, Feldman T, et al. SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement. Part II. Mitral valve. J Am Coll Cardiol. 2014;64(14):1515-1526.

Thourani VH, Kodali S, Makkar RR, et al. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: A propensity score analysis. [American College of Cardiology Web site]. 04/03/2016. Available at: http://www.acc.org/latest-in-cardiology/journal-scans/2016/04/03/10/48/transcatheter-aortic-valve-replacement-versus-surgical-valve-acc-2016. Accessed April 03, 2018.

Transcatheter Mitral Valve Repair (MitraClip) for Treating Degenerative Mitral Regurgitation in Patients at High/Prohibitive Surgical Risk. Plymouth Meeting (PA): ECRI Institute; 2016 July 20. (Emerging technology report). Also available:https://www.ecri.org/components/Target/Pages/30096.aspx. Assessed April 03, 2018.

US Food and Drug Administration (FDA). FDA expands use of Sapien 3 artificial heart valves for high risk patients. FDA News Release. [FDA Web site]. 06/05/2017. Available at:
http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm561924.htm. Assessed April 03, 2018.

US Food and Drug Administration (FDA). Summary of Safety and Effectiveness for the
Edwards SAPIEN 3 Transcatheter Heart Valve (PMA P140031/S028). [FDA Web site]. 06/05/2017. Available at:
https://www.accessdata.fda.gov/cdrh_docs/pdf14/P140031S028b.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. [FDA Web site]. Code of Federal Regulations. 04/01/2017. Available at:
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=7.55. Assessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. [FDA Web site]. Class 1 Devise Recall MitralClip Clip Delivery System. 05/12/2016. Available at:
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm?id=143617. Assessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Edwards SAPIEN 3™. Summary of safety and effectiveness. [FDA Web site]. 08/18/2016. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf14/P140031S010b.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Edwards SAPIEN™ XT Transcatheter Heart Valve. Summary of safety and effectiveness. [FDA Web site]. 08/18/2016. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf13/P130009S057b.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Edwards SAPIEN 3™ Transcatheter Heart Valve with the Edwards Commander Delivery System. Instructions for use. [FDA Web site]. August 2016. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf14/P140031S010d.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Edwards SAPIEN XT Transcatheter Heart Valve with the NovaFlex+ Delivery System Instructions for use- pulmonic. [FDA Web site]. February 2016. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf13/p130009s037d.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. MitralClip Delivery System. Premarket Approval. [FDA Web site]. 10/24/2013. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf10/P100009A.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Melody™ Transcatheter Pulmonary Valve. Summary of safety and effectiveness. [FDA Web site]. 01/27/2015. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf14/p140017b.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Melody™ Transcatheter Pulmonary Valve. Premarket approval letter. [FDA Web site]. 01/27/2015. Available at:https://www.accessdata.fda.gov/cdrh_docs/pdf14/P140017a.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Medtronic CoreValve™ System . Premarket approval letter. [FDA Web site]. 01/17/2014. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf13/P130021a.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Medtronic CoreValve System. 2014. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf13/p130021c.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Edwards SAPIEN™ Trancather Heart valve. 510(k) summary. [FDA Web site]. 11/02/2011. Available at:http://www.accessdata.fda.gov/cdrh_docs/pdf10/p100041a.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. Edwards SAPIEN™ XT Transcatheter Heart Valve with the Ascendra+ Delivery System. Instructions for use. [FDA Web site]. August 2016. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf13/P130009S057d.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). FDA approves expanded indication for two transcatheter heart valves for patients at intermediate risk for death or complications associated with open-heart surgery. FDA News Release. [FDA Web site]. 08/18/2016. Available online at:.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm517281.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Accessed April 03, 2018.

US Food and Drug Administration. Summary of Safety and Effectiveness for the Edwards SAPIEN Transcatheter Heart Valve (PMA P11021). [FDA Web site]. 06/13/2012. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf11/P110021b.pdf. April 03, 2018.

US Food and Drug Administration (FDA). Summary of Safety and Effectiveness for the
Edwards SAPIEN XT™ Transcatheter Heart Valve (PMA P130009/S037). [FDA Web site]. 02/29/2016. Available at:
https://www.accessdata.fda.gov/cdrh_docs/pdf13/P130009S037b.pdf. Accessed April 03, 2018.

US Food and Drug Administration (FDA). FDA Summary of Safety and Effectiveness for the EDWARDS UNTITY Elite Valve System. (PMA 150036). [FDA Web site]. 08/12/2016.
Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf15/p150036b.pdf. Assessed April 03, 2018.

Van Dijck I, Budts W, Cools B, et al. Infective endocarditis of a transcatheter pulmonary valve in comparison with surgical implants. Heart.2015;101(10):788-793.

Van Mieghem NM, Tchetche D, Chieffo A, et al. Incidence, predictors, and implications of access site complications with transfemoral transcatheter aortic valve implantation. Am J Cardiol. 2012; 110(9):1361-1367.

Villablanca P, Briceño D, Makkiya M, et al. Long-term outcomes of transcatheter versus surgical aortic valve replacement for severe aortic stenosis: a meta-analysis and meta-regression: PROSPERO 2016:CRD42016036772. PROSPERO International prospective register of systematic reviews 2016; https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016036772. Accessed April 03, 2018.

Villablanca PA, Mathew V, Thourani VH, et al. A meta-analysis and meta-regression of long-term outcomes of transcatheter versus surgical aortic valve replacement for severe aortic stenosis. Int J Cardiol. 2016;225:234-243.

Webb JG, Doshi D, Mack MJ, et al. A randomized evaluation of the SAPIEN XT transcatheter heart valve system in patients with aortic stenosis who are not candidates for surgery. JACC Cardiovasc Interv. 2015;8(14):1797-1806.

Zahn R, Gerckens U, Grube E, et al. Transcatheter aortic valve implantation: first results from a multi-centre real-world registry. Eur Heart J. 2011; 32(2):198-204.

Zhou Y, Wang Y, Wu Y, et al. Transcatheter versus surgical aortic valve replacement in low to intermediate risk patients: A meta-analysis of randomized and observational studies. Int J Cardiol. 2016;228:723-728.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

MEDICALLY NECESSARY

0345T, 33361, 33362, 33363, 33364, 33365, 33366, 33367, 33368, 33369, 33418, 33419, 33477

THE FOLLOWING CODE IS USED TO REPORT TRANSCATHETER MITRAL VALVE REPLACEMENT (TMVR) OF DEGENERATED BIO-PROSTHETIC VALVES ("VALVE-IN-VALVE")
33999


EXPERIMENTAL/INVESTIGATIONAL

THE FOLLOWING CODE IS USED TO REPORT TRANSCATHETER TRICUSPID VALVE REPAIR
33999


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

I06.0 Rheumatic aortic stenosis

I06.2 Rheumatic aortic stenosis with insufficiency

I34.0 Nonrheumatic mitral (valve) insufficiency

I35.0 Nonrheumatic aortic (valve) stenosis

I35.2 Nonrheumatic aortic (valve) stenosis with insufficiency

Q22.4 Congenital tricuspid stenosis

Q22.8 Other congenital malformations of tricuspid valve

Q22.9 Congenital malformation of tricuspid valve, unspecified

Q23.0 Congenital stenosis of aortic valve

Q23.1 Congenital insufficiency of aortic valve

Q23.2 Congenital mitral stenosis

Q23.3 Congenital mitral insufficiency

T82.01XA Breakdown (mechanical) of heart valve prosthesis, initial encounter

T82.01XD Breakdown (mechanical) of heart valve prosthesis, subsequent encounter

T82.01XS Breakdown (mechanical) of heart valve prosthesis, sequela

T82.02XA Displacement of heart valve prosthesis, initial encounter

T82.02XD Displacement of heart valve prosthesis, subsequent encounter

T82.02XS Displacement of heart valve prosthesis, sequela

T82.03XA Leakage of heart valve prosthesis, initial encounter

T82.03XD Leakage of heart valve prosthesis, subsequent encounter

T82.03XS Leakage of heart valve prosthesis, sequela

T82.09XA Other mechanical complication of heart valve prosthesis, initial encounter

T82.09XD Other mechanical complication of heart valve prosthesis, subsequent encounter

T82.09XS Other mechanical complication of heart valve prosthesis, sequela

T82.221A Breakdown (mechanical) of biological heart valve graft, initial encounter

T82.221D Breakdown (mechanical) of biological heart valve graft, subsequent encounter

T82.221S Breakdown (mechanical) of biological heart valve graft, sequela

T82.222A Displacement of biological heart valve graft, initial encounter

T82.222D Displacement of biological heart valve graft, subsequent encounter

T82.222S Displacement of biological heart valve graft, sequela

T82.223A Leakage of biological heart valve graft, initial encounter

T82.223D Leakage of biological heart valve graft, subsequent encounter

T82.223S Leakage of biological heart valve graft, sequela

T82.228A Other mechanical complication of biological heart valve graft, initial encounter

T82.228D Other mechanical complication of biological heart valve graft, subsequent encounter

T82.228S Other mechanical complication of biological heart valve graft, sequela

T82.827A Fibrosis of cardiac prosthetic devices, implants and grafts, initial encounter

T82.827D Fibrosis of cardiac prosthetic devices, implants and grafts, subsequent encounter

T82.827S Fibrosis of cardiac prosthetic devices, implants and grafts, sequela

T82.857A Stenosis of cardiac prosthetic devices, implants and grafts, initial encounter

T82.857D Stenosis of cardiac prosthetic devices, implants and grafts, subsequent encounter

T82.857S Stenosis of cardiac prosthetic devices, implants and grafts, sequela

Z87.74 Personal history of (corrected) congenital malformations of heart and circulatory system

Z95.2 Presence of prosthetic heart valve

Z95.3 Presence of xenogenic heart valve

Z95.4 Presence of other heart-valve replacement

THE FOLLOWING CODES ARE CONSIDERED MEDICALLY NECESSARY WHEN REPORTED WITH PROCEDURE CODE 33477

I37.0 Nonrheumatic pulmonary valve stenosis

I37.1 Nonrheumatic pulmonary valve insufficiency

I37.2 Nonrheumatic pulmonary valve stenosis with insufficiency

I37.8 Other nonrheumatic pulmonary valve disorders

I37.9 Nonrheumatic pulmonary valve disorder, unspecified

Q20.5 Discordant atrioventricular connection

Q21.3 Tetralogy of Fallot

Q22.0 Pulmonary valve atresia

Q22.1 Congenital pulmonary valve stenosis

Q22.2 Congenital pulmonary valve insufficiency

Q22.3 Other congenital malformations of pulmonary valve



HCPCS Level II Code Number(s)

N/A


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions from 11.02.25f:
05/09/2018The policy has been reviewed and reissued to communicate the Company’s continuing position on Transcatheter Aortic-Valve Replacement (TAVR) and Transcatheter Mitral Valve Repair (TMVR).


Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date: 09/15/2017
Version Issued Date: 09/15/2017
Version Reissued Date: 05/09/2018

Connect with Us        


© 2017 Independence Blue Cross.
Independence Blue Cross is an independent licensee of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.