Pending Policies - Surgery


Transcatheter Aortic-Valve Implantation for Aortic Stenosis

Number:SUR707.028

Effective Date:11-01-2018

Coverage:

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Transcatheter aortic valve replacement, with a U.S. Food and Drug Administration (FDA)-approved transcatheter heart valve system performed via an approach consistent with the device’s FDA-approved labeling may be considered medically necessary for patients with native valve aortic stenosis when all of the following conditions are present:

Severe aortic stenosis (see NOTE 1) with a calcified aortic annulus; AND

New York Heart Association (NYHA) heart failure Class II, III or IV symptoms; AND

Left ventricular ejection fraction >20%; AND

Patient is not an operable candidate for open surgery, as judged by at least two cardiovascular specialists (cardiologist and/or cardiac surgeon); or patient is an operable candidate but is at high or intermediate risk for open surgery (see NOTE 2).

Transcatheter aortic valve replacement with a transcatheter heart valve system approved for use for repair of a degenerated bioprosthetic valve may be considered medically necessary when all of the following conditions are present:

Failed (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve; AND

NYHA heart failure class II, III or IV symptoms; AND

Left ventricular ejection fraction greater than 20%; AND

Patient is not an operable candidate for open surgery, as judged by at least two cardiovascular specialists (cardiologist and/or cardiac surgeon); or patient is an operable candidate but is at high risk for open surgery (see NOTE 2).

Transcatheter aortic valve replacement is considered experimental, investigational and/or unproven for all other indications.

NOTE 1: For the use of the FDA approved SAPIEN or CoreValve device, severe aortic stenosis is defined by one or more of the following criteria:

An aortic valve area of less than or equal to 1 cm²; or

An aortic valve area index of less than or equal to 0.6 cm2/m2; or

A mean aortic valve gradient greater than or equal to 40 mm Hg; or

A peak aortic-jet velocity greater than or equal to 4.0 m/sec

NOTE 2: The FDA has provided the following guidance related to the risk for open surgery:

1. High risk:

A Society of Thoracic Surgeons predicted operative risk score of 8% or higher; or

An expected mortality risk of 15% or greater based on judgement of a heart team that includes an experienced cardiac surgeon and a cardiologist.

2. Extreme risk or inoperable:

An expected risk of operative mortality and/or serious irreversible morbidity of 50% or higher.

3. Intermediate risk:

Society of Thoracic Surgeons predicted operative risk score of 3% to 7%.

Description:

Transcatheter aortic valve implantation (TAVI; also known as transcatheter aortic valve replacement) is a potential treatment for patients with severe aortic stenosis. Many patients with aortic stenosis are elderly and/or have multiple medical comorbidities, thus indicating a high, often prohibitive, risk for surgery. This procedure is being evaluated as an alternative to open surgery, or surgical aortic valve replacement (SAVR), for high-risk patients with aortic stenosis and as an alternative to nonsurgical therapy for patients with a prohibitive risk for surgery.

Transcatheter aortic valve implantation (TAVI; also known as transcatheter aortic valve replacement) is a potential treatment for patients with severe aortic stenosis. Many patients with aortic stenosis are elderly and/or have multiple medical comorbidities, thus indicating a high, often prohibitive, risk for surgery. This procedure is being evaluated as an alternative to open surgery for high-risk patients with aortic stenosis and as an alternative to nonsurgical therapy for patients with a prohibitive risk for surgery.

Aortic Stenosis

Aortic stenosis is defined as narrowing of the aortic valve opening, resulting in obstruction of blood flow from the left ventricle into the ascending aorta. Progressive calcification of the aortic valve is the most common etiology in North America and Europe, while rheumatic fever is the most common etiology in developing countries. (1) Congenital abnormalities of the aortic valve, most commonly a bicuspid valve, increase the risk of aortic stenosis, but aortic stenosis can also occur in a normal aortic valve. Risk factors for calcification of a congenitally normal valve mirror those for atherosclerotic vascular disease, including advanced age, male gender, smoking, hypertension, and hyperlipidemia. (1) Thus, the pathogenesis of calcific aortic stenosis is thought to be similar to that of atherosclerosis, i.e, deposition of atherogenic lipids and infiltration of inflammatory cells, followed by progressive calcification.

The natural history of aortic stenosis involves a long asymptomatic period, with slowly progressive narrowing of the valve until the stenosis reaches the severe stage. At this time, symptoms of dyspnea, chest pain, and/or dizziness/syncope often occur, and the disorder progresses rapidly. Treatment of aortic stenosis is primarily surgical, involving replacement of the diseased valve with a bioprosthetic or mechanical valve by open heart surgery.

Disease Burden

Aortic stenosis is a relatively common disorder in elderly patients and is the most common acquired valve disorder in the United States. Approximately 2% to 4% of people older than 65 years of age have evidence of significant aortic stenosis, (1) increasing up to 8% of people by age 85 years. (2) In the Helsinki Aging Study (1993), a population-based study of 501 patients, ages 75 to 86 years, the prevalence of severe aortic stenosis by echocardiography was estimated to be 2.9%. (3) In the United States, more than 50,000 aortic valve replacements are performed annually due to severe aortic stenosis.

Aortic stenosis does not cause substantial morbidity or mortality when the disease is mild or moderate in severity. By the time it becomes severe, there is an untreated mortality rate of approximately 50% within 2 years. (4) Open surgical repair is an effective treatment for reversing aortic stenosis, and artificial valves have demonstrated good durability for up to 20 years. (4) However, these benefits are accompanied by perioperative mortality of approximately 3% to 4% and substantial morbidity, (4) both of which increase with advancing age.

Unmet Needs

Many patients with severe, symptomatic aortic stenosis are poor operative candidates. Approximately 30% of patients presenting with severe aortic stenosis do not undergo open surgery due to factors such as advanced age, advanced left ventricular dysfunction, or multiple medical comorbidities. (5) For patients who are not surgical candidates, medical therapy can partially alleviate the symptoms of aortic stenosis but does not affect the underlying disease progression. Percutaneous balloon valvuloplasty can be performed, but this procedure has less than optimal outcomes. (6) Balloon valvuloplasty can improve symptoms and increase flow across the stenotic valve but is associated with high rates of complications such as stroke, myocardial infarction, and aortic regurgitation. In addition, restenosis can occur rapidly, and there is no improvement in mortality. As a result, there is a large unmet need for less invasive treatments for aortic stenosis in patients at increased risk for open surgery.

Treatment

Transcatheter aortic valve implantation has been developed in response to this unmet need and was originally intended as an alternative for patients for whom surgery was not an option due to prohibitive surgical risk or for patients at high risk for open surgery. The procedure is performed percutaneously, most often through the transfemoral artery approach. It can also be done through the subclavian artery approach and transapically using mediastinoscopy. Balloon valvuloplasty is first performed to open up the stenotic area. This is followed by passage of a bioprosthetic artificial valve across the native aortic valve. The valve is initially compressed to allow passage across the native valve and is then expanded and secured to the underlying aortic valve annulus. The procedure is performed on the beating heart without cardiopulmonary bypass.

Regulatory Status

Two manufacturers have transcatheter aortic valve devices with U.S. Food and Drug Administration (FDA) approval. Regulatory status data for these devices are listed in Table 1.

Table 1. FDA-Approved Transcatheter Aortic Valve Device Systems

Device and Indication

Manufacturer

Date Cleared

PMA

Edwards SAPIEN Transcatheter Heart Valve System™

Severe native aortic valve stenosis determined to be inoperable for open aortic valve replacement (transfemoral approach)

Expanded to include high-risk aortic stenosis (transapical approach)

Expanded to include replacement of bioprosthetic valve in high risk for death or severe complications of repeat surgery

Expanded to include severe aortic stenosis with intermediate risk

Edwards Lifesciences

11/2011

10/2012

06/2017

08/2016

P100041

Edwards SAPIEN XT Transcatheter Heart Valve (model 9300TFX) and accessories

Severe native aortic valve stenosis at high or greater risk for open surgical therapy

Expanded to include failure of bioprosthetic valve in high or greater risk for open surgical therapy

Expanded to include severe aortic stenosis with intermediate surgical risk

07/2014

10/2015

08/2016

P130009

P130009/S034

Medtronic CoreValve System™

Severe native aortic stenosis at extreme risk or inoperable for open surgical therapy

Expanded to include high risk for open surgical therapy

Expanded to include intermediate risk for open surgical therapy

Medtronic CoreValve

01/2014

06/2016

07/2017

P130021

P130021/S002

P130021/S033

Medtronic CoreValve Evolut R System™

Design iteration for valve and accessories

Expanded to include intermediate risk for open surgical therapy

06/2015

07/2017

P130021/S014

P130021/S033

Medtronic CoreValve Evolut PRO System™

Design iteration for valve and accessories

Expanded to include intermediate risk for open surgical therapy

03/2017

07/2017

P130021/S029

P130021/S033

Table Key:

FDA: Food and Drug Administration; PMA: postmarket approval.

Other transcatheter aortic valve systems are under development. The following repositionable valves are under investigation:

Lotus™ Aortic Valve Replacement System (Boston Scientific) (7)

Portico™ Transcatheter Aortic Valve (St. Jude Medical)

JenaValve™ (JenaValve Technology, designed for transapical placement)

Several embolic protection devices, which are designed to collect embolic debris distal to the transcatheter aortic valve implantation apparatus and to prevent ischemic stroke, are under investigation. No devices have FDA approval for use in the United States. Examples include the TriGuard (Keystone Heart) and the Sentinel Cerebral Protection System (Claret Medical).

Rationale:

This medical policy was created in 2011 and has been updated regularly with searches of the MEDLINE database. The most recent literature search was performed through July 2018.

Net Health Outcome

Broadly defined, health outcomes are length of life, quality of life, and ability to function - including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

The literature evaluating transcatheter aortic valve implantation (TAVI) has reported on 4 potential populations: 1) patients who are not surgical candidates, 2) patients who are at high risk for surgery but still considered to be surgical candidate, 3) patients who at intermediate-risk for surgery, and 4) patients who are at low- risk for surgery.

TAVI Outcomes in Patients at Prohibitive Risk for Open Surgery

Systematic Reviews

Systematic reviews assessing whether TAVI improves outcomes for patients who are not suitable candidates for open surgery consist of summaries of case series. An Agency for Healthcare Research and Quality (AHRQ)?sponsored systematic review in 2010 evaluated 84 publications (total n =2375 patients). (2) Implantation was successful in 94% of patients overall, with higher success rates reported in more recent publications. The aggregate 30-day survival was 89% across all studies. Adverse event (AE) rates were reported in the larger case series, with an estimated 30-day rate of major cardiovascular AEs and stroke of 8%.

A second systematic review was published in 2011 by Figulla et al. (8) It included studies that enrolled symptomatic patients with severe aortic stenosis who had a mean age of 75 years or older, reported on 10 or more patients, and had a follow-up duration of 12 months or more. Twelve studies met these criteria and were compared with a group of 11 studies that treated severe aortic stenosis with nonsurgical therapy. The procedural success in these studies ranged from 86% to 100%, and the 30-day mortality ranged from 5.3% to 23%. The combined mean survival rate at 1 year was 75.9% (95% confidence interval [CI], 73.3% to 78.4%). This 1-year survival rate compared favorably with medical therapy, which was estimated to be 62.4% (95% CI, 59.3% to 65.5%).

Randomized Controlled Trials

SAPIEN and SAPIEN XT

The PARTNER trial was a pivotal multicenter RCT of TAVI performed in the United States, Canada, and Germany, using the SAPIEN system. Leon et al. (2010) reported on trial results for patients with severe aortic stenosis who were not candidates for open surgery, referred to as the PARTNER B trial. (9) To be classified as unsuitable for open surgery, patients had to have a predicted probability of 50% or higher for death or a serious irreversible condition at 30 days postsurgery. This probability was determined by 2 surgeon investigators using clinical judgment and the Society of Thoracic Surgery (STS) Risk Score. The executive committee of the PARTNER trial reviewed all patient selection decisions and approved the classification of patients as unsuitable for surgery. A total of 3105 patients were screened for aortic valve surgery, and 12% of them were included in the cohort of patients deemed unsuitable for surgery.

A total of 358 patients were randomized to TAVI or usual care. TAVI was performed by the transfemoral approach under general anesthesia. Standard therapy was determined by treating clinicians. In most cases (83.8%), standard treatment included balloon valvuloplasty of the aortic valve. A small number of patients (6.7%) underwent open surgical valve replacement, despite the high risk, and another 2.2% of patients underwent TAVI at a center outside the United States not participating in the trial. The primary outcome was death from any cause during the trial (median follow-up, 1.6 years). A coprimary end point was the composite of time to death from any cause or time to repeat hospitalization related to aortic stenosis or TAVI. Secondary end points were cardiovascular mortality, New York Heart Association (NYHA) functional class, the rates of hospitalizations due to aortic stenosis or TAVI, the 6-minute walk test (6MWT), valve performance as measured by echocardiography, and procedural complications (e.g., myocardial infarction [MI], stroke, acute kidney injury [AKI], vascular complications, bleeding).

The mean age of enrolled patients was 83.2 years. Some baseline imbalances in the patient population indicated that the standard therapy group might have had a higher severity of illness. Standardized scores of surgical risks were higher in the standard therapy group. The logistic EuroSCORE was significantly higher in the standard therapy group (30.4) than in the TAVI group (26.4; p=0.04), and the STS score was numerically higher but was not statistically significant (12.1 vs 11.2, respectively; p=0.14). Significantly more patients in the standard therapy group had chronic obstructive pulmonary disease (52.5% vs 41.3%, p=0.04) and atrial fibrillation (48.8% vs 32.9%, p=0.04), and there was a nonsignificant trend for more patients in the standard therapy group having a lower ejection fraction (51.1% vs 53.9%) and frailty, as determined by prespecified criteria (28.0% vs 18.1%), all respectively.

Death from any cause at 1 year after enrollment was lower for the TAVI group (30.7% vs 49.7%, p<0.001). This represents a 19% absolute risk reduction, a 38.2% relative risk (RR) reduction, and a number needed to treat of 5.3 to prevent 1 death over a 1-year follow-up. Most secondary outcomes also favored the TAVI group. Cardiovascular death was lower in the TAVI group (19.6% vs 44.1%, p<0.001). The composite of all-cause mortality and repeat hospitalizations was reached by 42.5% of the patients in the TAVI group compared with 70.4% in the standard therapy group. Symptoms and functional status were also superior in the TAVI group. The percentage of patients in NYHA class I or II at 1 year was higher for the TAVI group (74.8% vs 42.0%, p<0.001), and there was a significant improvement in the 6MWT for the TAVI group but not for the standard therapy group (between-group comparisons not reported). Subgroup analysis did not report any significant differences in outcomes according to clinical and demographic factors.

Complication rates were higher for the TAVI group. Stroke or transient ischemic attack (TIA) at 1 year was more than twice as frequent for the TAVI group (10.6% vs 4.5%, p=0.04). Major bleeding and vascular complications occurred in a substantial percentage of patients undergoing TAVI (22.3% vs 11.2%, p=0.007) and were significantly higher than in the standard therapy group (32.4% vs 7.3%, p<0.001).

Quality of life (QOL) outcomes from this trial were reported by Reynolds et al. (2011). (10) QOL outcomes were evaluated using the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score, the 12-Item Short-Form Health Survey (SF-12), and the EuroQoL (EQ-5D). The number of participants who completed the QOL measures was not clearly reported; estimates from graphical representation show that between 149 and 170 patients in the TAVI group and 138 and 157 patients in the medical therapy group completed baseline QOL measures. At follow-up time points of 30 days, 6 months, and 12 months, change in the QOL scores was greater for the TAVI group. At 30 days, the mean difference in the KCCQ score was 13.3 points (95% CI, 7.6 to 19.0; p<0.001). This mean difference increased at later time points to 20.8 points (95% CI, 14.7 to 27.0; p<0.001) at 6 months and to 26.0 points (95% CI, 18.7 to 33.3; p<0.001) at 12 months. Changes in the SF-12 and EQ-5D measures showed similar patterns.

Two-year outcomes were reported from the PARTNER trial by Makkar et al. (2012). (11) Mortality at 2 years was 43.3% in the TAVI group compared with 68.0% in the medical therapy group (hazard ratio [HR], 0.58; 95% CI, 0.36 to 0.92; p=0.02). Cardiovascular mortality was also lower with TAVI (31.0%) than with medical therapy (62.4%; p<0.001). The rate of hospitalization over the 2-year period was lower with TAVI (35.0%) than with medical therapy (72.5%; p<0.001).

Svensson et al. (2014) reported detailed mortality outcomes for both arms of the PARTNER trial: the PARTNER B RCT (previously described), which compared surgical repair with TAVI in prohibitive surgical risk patients, and the PARTNER A RCT, which compared surgical repair with TAVI in high surgical risk patients (described next). (12) For the 358 patients considered inoperable and enrolled in the PARTNER B RCT, at last follow-up, 237 patients had died. Those randomized to standard therapy exhibited an early peak in mortality that was higher than those randomized to TAVI, and that persisted beyond 6 months. Compared with standard therapy, the estimated net lifetime benefit added by transfemoral TAVI was 0.50 years (90% CI, 0.30 to 0.67).

Kapadia et al. (2014) reported on 3-year outcomes for 358 prohibitive-risk patients randomized to standard therapy or TAVI in the PARTNER trial, along with all outcomes (early and long term) for randomized inoperable PARTNER patients, including 91 subjects in the randomized PARTNER continued-access study. (13) Analysis of the pooled randomized patients was anticipated in the study protocol. At the 3-year follow-up for the pivotal trial subjects, all-cause mortality was 54.1% in the TAVI group and 80.9% in the standard therapy group (HR=0.53; 95% CI, 0.41 to 0.68; p<0.001). The incidence of stroke was higher in the TAVI group (15.7%) than in the standard therapy group at 3 years (5.5%; HR=3.81; 95% CI, 1.26 to 6.26; p=0.012). However, at 3 years, the incidence of the composite of death or stroke was significantly lower in the TAVI group (57.4% vs 80.9%; HR=0.60; 95% CI, 0.46 to 0.77; p<0.001). Survivors at 3 years who had undergone TAVI were more likely to have NYHA class I or II symptoms than those who had received standard therapy. In the pooled sample, at the 2- and 3-year follow-ups, mortality was lower for patients who had undergone TAVI than in those who had standard therapy (2 years: 44.8% vs 64.3%; 3 years: 54.9% vs 78.0%; all p<0.001).

Webb et al. (2015) reported on a multicenter RCT comparing a newer-generation SAPIEN XT system with the original SAPIEN system in 560 patients with severe, symptomatic aortic stenosis considered at prohibitive risk for open surgery. (14) The trial used a noninferiority design; for its primary end point, a composite of all-cause mortality, major stroke, and rehospitalization at 1 year in the intention-to-treat population, the RR between the SAPIEN and SAPIEN XT groups was 0.99 (p<0.002), which met the criteria for noninferiority.

Case Series and Cohort Studies

Many case series of TAVI have been published in the last 10 years, most of which have included patients not candidates for open surgery. However, the selection process for TAVI has largely been subjective, with the expert opinion of the surgeons and/or cardiologists as the main factor determining suitability for open surgery. As a result, there may be overlap in these series with patients who are surgical candidates, but the distinction cannot be gleaned easily from the reported studies.

Some of the larger and/or prospective case series are discussed next. Included are the series reporting on the pivotal trials leading to devices’ approvals (ie, Popma et al. [2014] (15) and Reardon et al. [2014] (16)) or on postapproval registries (ie, Mack et al. [2013] (17)).

CoreValve Extreme Risk Study

Popma et al. (2014) published results of the CoreValve Extreme Risk Study pivotal trial, which was designed to evaluate the CoreValve self-expanding valve among patients with severe aortic stenosis who were considered to be at extreme risk (NYHA class ≥II) for surgical aortic valve replacement (AVR). (15) A patient was judged to be at extreme risk if 2 cardiac surgeons and 1 interventional cardiologist at the clinical site estimated a 50% or greater risk for mortality or irreversible morbidity at 30 days with surgical repair. The study’s primary end point was the 12-month rate of all-cause mortality or major stroke in the “attempted implant” population. This population included all patients who underwent a documented valve implant via an iliofemoral approach. The study defined an objective performance goal of 43% for all-cause mortality or major stroke at 12 months postprocedure. This goal was based on 2 sources: 1) a weighted meta-analysis of 7 balloon aortic valvuloplasty studies, which yielded a rate of 12-month all-cause mortality or major stroke of 42.7% (95% CI, 34.0% to 51.4%); and 2) an adjusted estimate based on the lower 95% confidence bound of 43% in the standard therapy arm of inoperable patients in the PARTNER trial.

Four hundred eighty-nine patients were included in the attempted implant analysis population of 506 patients recruited (11 of whom exited the study before treatment, 6 of whom did not complete the procedure with iliofemoral access). The Kaplan-Meier estimate of the primary end point (all-cause mortality or major stroke) was 26.0% (upper bound of 95% CI, 29.9%), which was lower than the prespecified performance goal of 43% (p<0.001). The rate of all-cause mortality at 1 year following enrollment was 24.3%, while the rate of major stroke at 12 months was 4.3%. These rates are comparable or better than those seen in the TAVI arm of the PARTNER pivotal trial, although patients in the PARTNER pivotal trial had a higher baseline STS score (12.1% in the PARTNER trial vs 10.3% in the CoreValve Extreme Risk trial).

Two-year results from the CoreValve study were reported by Yakubov et al. (2015). (18) The Kaplan-Meier estimate of all-cause mortality or major stroke was 38.0% (upper bound of 95% CI, 42.6%). The incremental rates between years 1 and 2 were 12.3% for all-cause mortality, 7.9% for cardiovascular mortality, and 0.8% for stroke. Baron et al. (2017) reported on 3-year results of the QOL data. The QOL improvements following TAVR were largely sustained through 3 years with clinically meaningful (≥10 point) improvements in the KCCQ overall summary score at 3 years observed in greater than 83.0%. (19)

Osnabrugge et al. (2015) reported on health status outcomes for the 471 patients who underwent TAVI via the transfemoral approach. (20) On average, general and disease-specific QOL scores both showed substantial improvements after TAVI. However, 39% of patients had a poor outcome at 6 months (22% death, 16% very poor QOL, 1.4% QOL declined).

Reardon et al. (2014) reported on outcomes for the group of patients enrolled in the CoreValve study who received the device through an approach other than the iliofemoral. (16) Inclusion criteria and procedures were the same as for the primary CoreValve Extreme Risk Trial. One hundred fifty patients with prohibitive iliofemoral anatomy were included and received the CoreValve device through an open surgical approach via the subclavian artery (n=70) or a direct aortic approach via a median hemisternotomy or right thoracotomy (n=80). Included patients were elderly (mean age, 81.3 years) and significantly symptomatic, with 92% of subjects having NYHA class III or IV heart disease. At 30 days postprocedure, 23 (15.3%) patients met the primary end point of all-cause mortality or major stroke; of the 23 patients, 17 (11.3%) died, and 11 (7.5%) experienced a major stroke. At 12 months postprocedure, 59 (39.4%) patients met the primary end point; of those, 54 (36%) died, and 13 (9.1%) experienced a major stroke. The 30-day mortality of 11.3% was higher than that reported in the studies of TAVI using a transfemoral or an iliofemoral approach (PARTNER B RCT and the CoreValve Extreme Risk Pivotal Trial) but similar to the 30-day mortality reported by the patients treated with a transapical approach (PARTNER A trial).

Postapproval Registries

Mack et al. (2013) reported on outcomes after TAVI from 224 hospitals participating in the Edwards SAPIEN device post Food and Drug Administration (FDA) approval registry. (17) From November 2011 to May 2013, the registry included 7710 patients who underwent TAVI placement, of whom 1559 (20%) patients were considered inoperable and 6151 (80%) were considered high risk but operable. Of those considered inoperable, 1139 underwent device placement via transfemoral access, while 420 underwent device placement via nontransfemoral access. In-hospital mortality was 5.4% and 7.1% for the inoperable patients who underwent TAVI via transfemoral and nontransfemoral access, respectively. Thirty-day clinical outcomes were reported for 694 inoperable patients; of those, 30-day mortality was 6.7% and 12.6% for patients who underwent TAVI via transfemoral and nontransfemoral access, respectively.

Additional Case Series

The prospective nonrandomized ADVANCE study had central adjudication of end points and adverse events to evaluate the CoreValve implants in individuals with severe symptomatic aortic stenosis who were considered inoperable or at higher risk for surgical AVR (SAVR). (21) The study enrolled 1015 patients, of whom 996 were implanted, most (88.4%) by the iliofemoral approach, with 9.5% and 2.1% by the subclavian and direct aortic approaches, respectively. For the study’s primary end point of major adverse cardiac and cerebrovascular events (MACCE; a composite of all-cause mortality, MI, stroke, or reintervention), rates were 8.0% (95% CI, 6.3% to 9.7%) at 30 days and 21.2% (95% CI, 18.4% to 24.1%) at 12 months. The all-cause mortality rate was 4.5% (95% CI, 3.2% to 5.8%) at 30 days and 17.9% (95% CI, 15.2% to 20.5%) at 12 months. Overall, strokes occurred in 3.0% (95% CI, 2.0% to 4.1%) at 30 days and in 4.5% (95% CI, 2.9% to 6.1%) at 12 months. A new permanent pacemaker was implanted in 26.3% (95% CI, 23.5% to 29.1%) and in 29.2% (95% CI, 25.6% to 32.7%) of patients at 30-day and 12-month follow-ups, respectively. Patients were grouped into 3 categories of surgical risk based on logistic EuroSCORE values (≤10%, >10% but ≤20%, and >20%). Thirty-day survival did not differ significantly across risk groups, but 12-month rates of MACCE, all-cause mortality, cardiovascular mortality, and death from any cause or major stroke were higher for higher surgical risk patients.

The 2 largest series included in the Agency for Healthcare Research and Quality review (2) (described previously) reported on 646 patients treated with the CoreValve (22) and 339 patients treated with the SAPIEN valve. (23) The CoreValve study by Piazza et al. (2008) was notable in that it used more objective patient selection criteria than is common in this literature. Their criteria for eligibility included: 1) logistic EuroSCORE of 15% or higher, 2) age of 75 or older, or 3) age of 65 or older with 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 of 18 kg/m2 or less. Procedural success was 97%, and 30-day survival was 92%. The 30-day combined rate of death, MI, or stroke was 9.3%. The Canadian study by Rodes-Cabau et al. (2010) used SAPIEN valve. This study had subjective inclusion criteria, relying on the judgment of the participating surgeons to determine eligibility for TAVI. The procedural success rate was 93.3%, and the 30-day mortality was 10.4%. The authors also reported a mortality rate of 22.1% at a median follow-up of 8 months.

Additional series have described experiences with TAVI in European centers. Zahn et al. (2011), in a large case series from Germany, reported on 697 patients treated with the CoreValve system. (24) Procedural success was 98.4%, and 30-day mortality was 12.4%. Another large case series (2011) from Italy included 663 patients treated with the CoreValve device. (25) Procedural success was 98%, and mortality at 1 year was 15%.

Section Summary: TAVI Outcomes in Patients at Prohibitive Risk for Open Surgery

Numerous case series have demonstrated the feasibility and short-term efficacy for TAVI in patients who are not surgical candidates. In the PARTNER B trial, there was a large decrease in all-cause mortality and cardiovascular mortality at 1 year for TAVI compared with standard therapy. Subsequent publications from this same trial reported that the mortality benefit was maintained at 2 years and that QOL was improved for the TAVI group. Baseline between-group differences were present, indicating that the TAVI 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 CoreValve Extreme Risk Study pivotal trial also demonstrated mortality rates much lower than the prespecified performance goal and comparable or better than those seen in the TAVI arm of the PARTNER pivotal trial.

The benefit in mortality was accompanied by an increased stroke risk as well as substantial increases in vascular complications and major bleeding. There is also uncertainty concerning the generalizability of these results, because patient selection was primarily determined by the cardiovascular surgeons and/or cardiologists. It is not known whether this type of decision making is reliable across the range of practicing clinicians.

TAVI Outcomes in Patients at High Risk for Open Surgery

Systematic Reviews

A meta-analysis of 4 RCTs was published by Panoulas et al. (2018) to determine whether sex differences had any impact on mortality rates for TAVI and SAVR. (26) The 4 RCTs comprised of 3758 patients (2052 men, 1706 women); all patients had severe aortic stenosis. The study revealed that among women undergoing TAVI, a significantly lower mortality rate was found than in women undergoing SAVR at the 1-year mark; in fact, women undergoing TAVI were found to have a 31% lower mortality rate than women undergoing SAVR, again at the 1-year mark (odds ratio [OR], 0.68; 95% CI, 0.50 to 0.94). There was no statistical difference in mortality in men undergoing TAVR vs men undergoing SAVR.

Villablanca et al. (2016) reported on a meta-analysis and meta-regression of long-term outcomes (>1 year) of TAVI compared with SAVR for severe aortic stenosis. (27) Trial methods were described in the meta-analysis protocol, which was registered with PROSPERO. (28) The review was limited to studies comparing TAVI with surgical repair, with subgroup analyses for high- and intermediate-risk patients. Overall, 4 RCTs (n=3806 patients) and 46 observational studies (n=40,441 patients) were included, with a median follow-up of 21.4 months. Two of the RCTs were conducted in high-risk patients, and are described in detail below (PARTNER 1 [Mack et al., 2015] (29) and CoreValve High Risk Trial [Reardon et al., 2015](30)). Results from the subgroup analyses focused on high-risk patients are shown in Table 2.

Table 2. TAVI vs Surgical Repair in High-Risk Patients

Outcomes

TAVIa

Surgical Repaira

RR for TAVI vs Surgical Repair (95% CI)

I2

30-day post-procedure mortality

508/8552 (5.9%)

804/29,323 (2.7%)

1.02 (0.76 to 1.36)

72.3%

All-cause mortality

3625/8803 (41.1%)

5438/29,450 (18.6%)

1.16 (0.87 to 1.53)

96.6%

Stroke incidence

191/4293 (4.4%)

213/4348 (4.9%)

0.79 (0.66 to 0.95)

0%

Myocardial infarction incidence

57/2820 (2.0%)

59/2746 (2.1%)

0.91 (0.64 to 1.29)

21.5%

Vascular complication incidence

203/2489 (8.2%)

35/2682 (1.3%)

5.5 (2.42 to 12.4)

67.5%

Residual regurgitation incidence

268/2831 (9.5%)

36/2823 (1.3%)

6.3 (4.55 to 8.71)

0%

Requirement for permanent pacemaker incidence

527/3449 (15.3%)

236/3653 (6.4%)

1.68 (0.94 to 3.00)

83.2%

New-onset AF incidence

165/1192 (13.8%)

376/1281 (29.4%

0.38 (0.26 to 0.55)

64.6%

Major bleeding incidence

321/2074 (15.4%)

416/2298 (18.1%)

0.73 (0.65 to 0.83)

24.2%

Acute kidney injury incidence

294/3446 (8.5%)

396/3528 (11.2%)

0.73 (0.53 to 1.01)

68.4%

Table Key: Adapted from Villablanca et al. (2016). (27)

AF: atrial fibrillation; CI: confidence interval; RR: relative risk; TAVI: transcatheter aortic valve implantation.

a Values are n/N (%).

Earlier systematic reviews focused largely on nonrandomized comparative studies because only 1 RCT had been published at the time of the reviews (the PARTNER trial). Panchal et al. (2013) reported on results from a meta-analysis of 17 studies that included 4659 patients, 2267 treated with TAVI, and 2392 treated with open surgery. (31) Patients in the TAVI group were more severely ill, as evidenced by a EuroSCORE for predicted 30-day mortality, which was higher by a mean of 3.7 points compared with patients undergoing open surgery. On combined analysis, there were no differences between groups for 30-day mortality, mortality at longest follow-up, cardiovascular mortality, MI, stroke, or TIA. Patients in the open surgery group had a higher incidence of major bleeding complications (RR=1.42; 95% CI, 1.20 to 1.67; p<0.001). In a similar meta-analysis (2013) that included 17 studies reporting on 4873 patients, there were no differences between TAVI and open surgery in early mortality (OR=0.92; 95% CI, 0.70 to 1.2) or mid-term mortality, defined as between 3 months and 3 years (HR=0.99; 95% CI, 0.83 to 1.2). (32)

Randomized Controlled Trials

SAPIEN PARTNER A Trial

Smith et al. (2011) published results from the cohort of patients in the PARTNER trial of the SAPIEN valve who were at high risk for open surgery, but still suitable candidates. (33) The inclusion and exclusion criteria were generally the same as those for the prior cohort, except that these patients were classified as high risk for surgery rather than unsuitable for surgery. For high risk, patients had to have a predicted perioperative mortality of 15% or higher, as determined by a cardiac surgeon and cardiologist using clinical judgment. An STS Risk Score of 10 or higher was included as a guide for high risk, but an STS Risk Score threshold was not a required criterion for enrollment. The executive committee of the PARTNER trial reviewed all patient selection decisions and approved the classification of patients as high risk for surgery. A total of 3105 patients were screened for aortic valve surgery, and 22.5% of them were included in the cohort of patients deemed high risk for surgery.

A total of 699 patients were randomized to TAVI or surgical aortic valve repair. The primary hypothesis was that TAVI was noninferior to open AVR, using a one-sided noninferiority boundary of 7.5% absolute difference in mortality at one year. Patients were first evaluated to determine if they were eligible for TAVI via the transfemoral approach. Four hundred ninety-two patients were eligible for transfemoral TAVI; the remaining 207 were categorized as the transapical placement cohort. Within each cohort (transfemoral and transapical), patients were randomized to surgical aortic valve repair (n=351) or TAVI (n=348).

The primary outcome was death from any cause at one-year follow-up. A second powered endpoint was noninferiority at one year for patients undergoing TAVI by the transfemoral approach. Secondary end points were cardiovascular mortality, NYHA functional class, rehospitalizations, 6MWT, valve performance as measured by echocardiography, and procedural complications (MI, stroke, AKI, vascular complications, bleeding). Mean age of enrolled patients was 83.6 years in the TAVI 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 patients in the TAVI group with a creatinine level greater than 2.0 mg/dL (11.1% vs 7.0%, p=0.06).

Death from any cause at 1 year following enrollment was 24.2% for the TAVI group and 26.8% for the open AVR group (between-group difference, p=0.44). The upper limit of the 95% CI for the between-group difference was a 3.0% excess mortality in the TAVI group, which was well within the noninferiority boundary of 7.5%. Thus, the criterion of noninferiority was met (p=0.001). For the subgroup of patients who underwent TAVI by the transfemoral approach, results were similar, with 22.2% mortality in the TAVI group and 26.4% mortality in the open AVR group (p=0.002 for noninferiority). The secondary outcomes of cardiovascular mortality (14.3% vs 13.0%, p=0.63) and rehospitalizations (18.2% vs 15.5%, p=0.38) did not differ significantly between the TAVI and the open AVR groups, respectively. The percentage of patients in NYHA class I or II at 1 year was similar between groups at 1 year, as was an improvement on the 6MWT. On subgroup analysis, there was a significant effect for sex, with women deriving greater benefit than men (p=0.045), and a significant effect for prior coronary artery bypass graft, with patients who had not had prior coronary artery bypass graft deriving greater benefit in the TAVI group.

Certain complication rates showed significant differences between groups. Stroke or TIA at 1 year was higher for the TAVI group (8.3% vs 4.3%, respectively, p=0.04). Vascular complications occurred in 18.0% of patients undergoing TAVI compared with 4.8% in the open AVR group (p=0.01), and major vascular complications were also higher in the TAVI group (11.3% vs 3.5%, p=0.01). On the other hand, major bleeding was more common in the open group (25.7%) compared with the TAVI group (14.7%; p=0.01).

Five-year results from the PARTNER trial were reported by Mack et al. (2015). (29) At 5-year follow-up, in the intention-to-treat population, the risk of death from any cause did not differ significantly between patients treated with TAVI (67.8%) and those treated with surgical repair (62.4%; HR=1.04; 95% CI, 0.86 to 1.24; p=0.76). As reported in the original PARTNER trial findings, moderate or severe aortic regurgitation - primarily paravalvular regurgitation - was more common among TAVI-treated patients. Among TAVI-treated patients, the presence of aortic regurgitation was associated with increased 5-year mortality risk (72.4% for moderate or severe aortic regurgitation vs 56.6% for mild aortic regurgitation or less; p=0.003).

Reynolds et al. (2012) published QOL results from the PARTNER A trial. (34) QOL outcomes were evaluated using the KCCQ summary score, the SF-12, and the EQ-5D. Of 699 patients in the trial, 628 completed baseline QOL measures. Patients in both the TAVI group and the SAVR group demonstrated significant improvements in all QOL measures over the 12 months following treatment. The TAVI group had superior improvement at 1 month on the KCCQ (mean difference, 9.9; 95% CI, 4.9 to 14.9; p<0.001), but this difference was no longer present at 6 or 12 months. A similar pattern of results was reported for the SF-12 and EQ-5D measures.

Genereux et al. (2014) published a follow-up study from the PARTNER A trial reporting on bleeding complications. (35) Using an as-treated approach, this analysis included 313 patients treated with surgical repair, 240 patients treated with transfemoral TAVI, and 104 patients treated with transapical TAVI. Seventy-one (22.7%) patients treated with surgery had major bleeding complications within 30 days of the procedure, compared with 27 (11.3%) of those treated with transfemoral TAVI and 9 (8.8%) of those treated with transapical TAVI (p<0.001).

U.S. CoreValve High Risk Study

Adams et al. (2014) published results of the U.S. CoreValve High Risk Study. (36) This RCT compared SAVR with TAVI using the CoreValve device in patients who had severe aortic stenosis and were considered at increased risk of death during surgery. The study randomized 795 patients in a 1:1 ratio to TAVI or open AVR. Patients were considered to be at “increased surgical risk” if 2 cardiac surgeons and 1 interventional cardiologist estimated that the risk of death within 30 days of surgery was 15% or more and that the risk of death or irreversible complications within 30 days after surgery was less than 50%. The primary analysis was based on the as-treated population, which included all patients who underwent attempted implantation. For the study’s primary outcome, the rate of death from any cause at 1 year was lower in the TAVI group (14.2%) than in the surgical group (19.1%; absolute risk reduction, 4.9%; upper boundary of 95% CI, -0.4%, which was less than the predefined noninferiority margin of 7.5%-point difference between groups; noninferiority, p<0.001; superiority, p=0.04). Major vascular complications and permanent pacemaker implantations were significantly more frequent in the TAVI group than in the surgical group: at 30 days, major vascular complications occurred in 5.9% of the TAVI group compared with 1.7% of the surgical group (p=0.003), while permanent pacemaker implantation was required in 19.8% of the TAVI group compared with 7.1% of the surgical group (p<0.001). In contrast to the PARTNER trial, the TAVI group did not have a higher rate of any stroke at 1 year postprocedure (8.8%) than the surgical group (12.6%; p=0.10).

Two-year follow-up results from the U.S. CoreValve High Risk Study were published in 2015 by Reardon et al. (2015). (30) At that point, the mortality benefits seen with TAVI were maintained.

A 3-year follow-up analysis was reported by Deeb et al. (2016), which found sustained improvements in the TAVI-treated group for all-cause mortality, stroke, and MACCE compared with the surgical group. (37) At 3 years, 37.3% (n=142) of TAVI-treated patients experienced all-cause mortality or stroke, which was significantly less than the 46.7% (n=160) of surgical patients for the same outcome (p=0.006). In the TAVI group, MACCE was observed in 40.2% (n=153) of patients; in the surgical group, MACCE occurred in 47.9% (n=164) of patients (p=0.025). Other outcomes that were improved in the TAVI group compared with surgery were life-threatening or disabling bleeding, AKI, aortic valve area, and mean aortic valve gradient. More TAVI-treated patients required implantation of a pacemaker (28.0%) than did surgical patients (14.5%; p<0.001); also, more patients in the TAVI group (6.8%) had moderate atrial regurgitation than in the surgery group (0.0%) at 3 years. The authors noted the improvement in mean aortic valve gradient for both cohorts (TAVR, 7.62 mm Hg vs SAVR, 11.40 mm Hg; p<0.001).

Additional analyses of the CoreValve study have focused on the impact of patient and prosthesis mismatch (e.g., Zorn et al., 2016). (38)

Nonrandomized Comparative Studies

Since the publication of the pivotal RCTs and systematic reviews described previously, a number of nonrandomized studies have compared surgical with transcatheter aortic valve repair. (39-41) Given the availability of RCT evidence, these studies provide limited additional information on the efficacy of TAVI.

Section Summary: TAVI Outcomes in Patients at High Risk for Open Surgery

The most direct evidence related to the use of TAVI for aortic stenosis in patients who are at high but not prohibitive risk of surgery comes from 2 industry-sponsored RCTs. The PARTNER RCT in high-risk patients who were eligible for SAVR reported no differences between TAVI and open AVR in terms of mortality at 1 year and most major secondary outcomes. The noninferiority boundaries for this trial included an upper limit of 7.5% absolute increase in mortality. The reported mortality for the TAVI group was lower than that for the open group, although not significantly better. QOL was also similar at 1 year between the TAVI and AVR groups. Stroke and TIA were significantly more common for the TAVI group, occurring at a rate of almost 2 times that reported for open surgery. Other secondary outcomes were similar between groups, except for higher rates of vascular complications in the TAVI group and higher rates of major bleeding in the open surgery group. As in the first PARTNER cohort, there is concern about the generalizability of results because the patient selection process relied largely on the judgment of surgeons and cardiologists participating in the trial. The U.S. CoreValve High Risk Study reported that TAVI was noninferior to open surgical repair. Although unlike the PARTNER A RCT, stroke rates were not higher in patients who underwent TAVI, a requirement for permanent pacemaker was more common in the TAVI group. Follow-up analyses of the U.S. CoreValve High Risk Study showed sustained improvements in the TAVI group for the outcome of all-cause mortality and a number of secondary outcomes. The incidence of pacemaker implantation continued to be higher in TAVI-treated patients.

TAVI Outcomes in Patients at Intermediate or Low Risk for Open Surgery

Most research on TAVI has focused on its use as an alternative to open surgery in patients with at least a high risk of surgery. Five RCTs identified have evaluated the use of TAVI in patients not at high risk of open surgery. Discussion included the intermediate- and low-risk groups as is consistent with the literature but summarize the efficacy of TAVI for both populations separately.

Systematic Reviews

Several systematic reviews and meta-analyses were published in 2017 and 2018, (42-50) including many overlapping RCTs and observational studies. Garg et al. (2017) included all 5 RCTs published through 2017, and therefore the next paragraph will focus on that review. (44)

Garg et al. (2017) published a systematic review and meta-analyses that included RCTs and prospective observational studies comparing TAVI with SAVR published between January 2000 and March 2017 including low-to-intermediate surgical risk patients with severe aortic stenosis. (44) Five RCTs (n=4425 patients) were included and are discussed in the following section. The meta-analytic results pooling the RCTs are shown in Table 3.

Table 3. TAVI vs Surgical Repair in Low- or Intermediate-Risk Patients

Outcomes

TAVI

Surgical Repair

RR for TAVI vs Surgical Repair (95% CI)

p

I2

30-day mortality

3.1

3.0

1.04 (0.73 to 1.47)

0.84

0

Stroke incidence

7.3

8.1

0.91 (0.74 to 1.11)

0.35

0

Acute kidney injury incidence

1.8

4.7

0.38 (0.26 to 0.54)

<0.001

0

Myocardial infarction incidence

3.1

3.1

1.00 (0.71 to 1.41)

1.00

0

Major vascular complication incidence

7.3

3.2

3.09 (1.51 to 6.35)

0.002

66

Requirement for permanent pacemaker incidence

20.0

7.9

3.10 (1.44 to 6.66)

0.004

92

Table Key: Adapted from Garg (2017). (44)

Values are percent unless other noted.

CI: confidence interval; RR: relative risk; TAVI: transcatheter aortic valve implantation.

Zhou et al. (2016) reported on a meta-analysis comparing TAVI with surgical repair in patients at low or intermediate risk of open surgery. (51) Seven studies were included, 3 RCTs (NOTION [2015], (52) STACCATO [2012], (53) Leon et al. [2016] (54)), and 4 observational studies (total N=6214 patients; n=3172 [51.0%] treated with TAVI). The main meta-analytic results are summarized in Table 4. Importantly, this review included a meta-analytic result for mortality at 1 year.

Table 4. TAVI vs Surgical Repair in Low- or Intermediate-Risk Patients

Outcomes

TAVI

Surgical Repair

OR for TAVI vs Surgical Repair (95% CI)

p

I2

Short-term postprocedure mortality

2.59

3.94

0.09

56

Short-term cardiovascular mortality

1.96

3.15

0.11

68

Acute kidney injury incidence

1.92

4.8

0.002

61

Stroke incidence

3.57

4.90

0.01

42

Myocardial infarction incidence

0.7

1.7

<0.001

10

Major vascular complication incidence

7.2

3.6

0.006

86

Requirement for permanent pacemaker incidence

11.9

6.1

0.001

88

All-cause mortality (1 year)

10.1

12.2

0.26

67

Table Key: Adapted from Zhou et al. (2016). (51)

Values are percent unless other noted.

CI: confidence interval; OR: odds ratio; TAVI: transcatheter aortic valve implantation.

Earlier systematic reviews came to similar conclusions. (55,56) In 2016, Siemieniuk et al. also reported on a systematic review and meta-analysis comparing TAVI with surgical repair in patients at low or intermediate risk of open surgery, with the aim of evaluating valve durability and need for reinterventions. (57)

Overall, the results suggest that for intermediate and low operative risk patients, periprocedural and short-term (1-year) mortality rates do not differ significantly between TAVI and open aortic valve repair. However, similar to the high- and prohibitive-risk populations, TAVI is associated with higher rates of major vascular complications, paravalvular regurgitation, and need for permanent pacemakers, but lower rates of major bleeding.

Randomized Controlled Trials

Five RCTs including patients with severe aortic stenosis who were at low and/or intermediate risk for open surgery have been published. The RCTs are summarized in Tables 5 and 6 and the following paragraphs.

Table 5. Characteristics of RCTs Comparing TAVI With SAVR in Patients at Low and Intermediate Surgical Risk

Interventions

Study; Trial; Sponsor

Countries

Sites

Dates

Participants

TAVR

SAVR

Nielsen et al. (2012) (53); STACATTO

Sponsored by Participating hospitals and Danish Heart Foundation

Denmark

2

Nov 2008-May 2011

• Mean age, 81 y

• No significant coronary artery disease

• Any surgical risk

STS PROM 3.3)

• n= 34

• Edwards Sapien

THV

• n=36

• Conventional open heart surgery with

CPB

Thyregod et al. (2015) (52); Søndergaard et al. (2016) (58); NOTION (NCT01057173)

Sponsored by Danish Heart Foundation

Denmark,

Sweden

3

Dec 2009-Apr 2013

• Mean age, 79 y

• No significant coronary artery disease

• Any surgical risk (mean STS PROM,

% low-risk)

• n= 145

• Core-

Valve

• n=135

• Conventional open heart surgery with

CPB

Reardon et al.

(2016) (59);

CoreValve U.S. Pivotal (NCT01240902)

Sponsored by Manufacturer

U.S.

45

Feb 2011-Sept 2012

• Mean age, 81 y

• STS score <7a (median, 5.3)

• Symptomatic

class ≥II)

• n= 202

• Core-

Valve

• n=181

• Conventional open heart surgery with

CPB

Leon et al.

(2016) (54); PARTNER 2A

(NCT01314313)

Sponsored by Manufacturer

U.S., Canada

57

Dec 2011-Nov 2013

• Mean age, 82 y

• Symptomatic (NYHA class ≥II)

• STS PROM ≥4 and ≤8 or

• STS PROM <4 with coexisting conditions

(mean, 5.8)

• n=1011

• SAPIEN

XT

• n=1021

• Conventional

surgery

Reardon et al.

(2017) (60); SURTAVI

(NCT01586910)

Sponsored by Manufacturer

U.S., Spain,

Netherlands, Germany, UK, Canada, Switzerland,

Sweden

87

• Mean age, 80 y

• STS PROM ≥4 and <15 (mean, 4.5)

• Symptomatic

class ≥II)

n=879

• Core-

Valve

• n=867

• Conventional surgery with coronary revascularizat

ion if needed

Table Key: CPB: cardiopulmonary bypass; NYHA: New York Heart Association; RCT: randomized controlled trial; SAVR: surgical aortic valve replacement; STS PROM: Society of Thoracic Surgeons predicted risk of mortality score; TAVI: transcatheter aortic valve implantation; TAVR: transcatheter aortic valve replacement; THV: Transcatheter heart valve.

a Includes analysis of a subset of originally randomized patients.

Leon et al. (2016) reported on results of a multicenter noninferiority RCT comparing TAVI with the Edwards SAPIEN XT valve system in patients with severe aortic stenosis who were at intermediate risk for open surgery, stratified by access route (transfemoral or transthoracic). (54) Eligible patients had degenerative aortic valve stenosis, with NYHA functional class II or higher, and were in STS PROM score of 4 or greater (or <4 if determined by a heart team to have an “intermediate-risk patient profile with important comorbidities not represented in the STS Risk Calculator algorithm.”) The trial used a noninferiority design, with a primary composite end point of death from any cause or disabling stroke (score of ≥2 on the modified Rankin Scale) at 2 years and a noninferiority margin of 1.2 (ie, noninferiority was considered met if upper bound of 2-sided CI for the RR for the primary outcome was <1.2).

A total of 2032 patients were randomized to TAVI (n=1011) or surgical repair (n=1021), with 1550 considered suitable for transfemoral placement (76.3%) and 482 (23.7%) requiring transthoracic access. At baseline, the mean STS Risk Score was 5.8%; 81.3% had a score between 4% and 8%. The primary outcome results and select additional results of the trial are summarized in Table 6. Also, similar to other TAVI trials, the frequency and severity of paravalvular regurgitation was higher after TAVI than in surgical repair. The presence paravalvular regurgitation was associated with all-cause mortality during follow-up (HR for moderate or severe paravalvular regurgitation vs none or trace, 2.85; 95% CI, 1.57 to 5.21; p<0.001).

Table 6. RCTs Comparing TAVI With Surgical Repair in Intermediate or Unselected Risk

Study

Primary Outcome

Results of Primary Outcomes, %

All Cause Mortality (2y), %

New Permanent Pacemaker (2y), %

TAVI

Surg

TE (95% CI)

p

TAVI

Surg

p

TAVI

Surg

p

Neilsen et al. (2012) (53)

Death from any cause, stroke, or renal failure at 30 d

All patients

14.7

2.8

RD (NR)

0.07

NR

NR

NR

NR

Thyregod et al. (2015) (52)

Death from any cause, stroke or MI at 1 y

All patients

13.1

16.3

RD = -3.2

0.43a

4.9

7.5

0.38

34.1

1.6

<0.001

Reardon et al. (2016) (59)

Death from any cause at 2 y

STS score ≤ 7

26.3

15

HR (NR)

0.01

See previous columns

27.7

10.5

<0.001

Leon et al. (2016) (54)

Death from any cause or disabling stroke at 2 y

All patients

19.3

21.1

HR = 0.92 (0.75 to 1.08)

16.7

18

0.45

11.8

10.9

0.29

Transfemoral access

16.8

20.4

HR=0.79 (0.62 to 1.00)

14.2

17.2

0.11

11.4

10.8

0.71

Transthoracic access

27.7

23.4

HR=1.21 (0.84 to 1.74)

25.2

20.7

0.26

13.1

8.6

0.13

Reardon et al. (2017) (60)

Death from any cause or disabling stroke at 2 y

All patients

12.6

14

RD = 1.4 (-5.2 to 2.3) b

11.4

11.6

-3.8 to 3.3b

25.9

6.6

15.9 to 22.7b

Table Key: CI: confidence interval; HR: hazard ratio; RD: risk difference; MI: myocardial infarction; NR; not reported: Surg: surgical repair; TAVI: transcatheter aortic valve implantation; TE: treatment effect.

a Superiority.

b Bayesian credible interval.

Thyregod et al. (2015) reported on the results of the NOTION RCT, which compared TAVI with surgical repair in 280 patients with severe aortic stenosis who were 70 years or older, regardless of the predicted risk of death after surgery. (52) Patients randomized to TAVI underwent implantation of the CoreValve self-expanding prosthesis by the femoral (preferred) or subclavian route. The trial was powered to detect an absolute risk reduction of 10% or a RR reduction of 66.7% in primary outcome at 1 year. At baseline, 81.8% of the study population was considered to be at low risk (STS Risk Score <4). Some of the main findings from NOTION are summarized in Table 6. In addition, TAVI-treated patients had lower rates of major or life-threatening bleeding (11.3% vs 20.9%, p=0.03), cardiogenic shock (4.2% vs 10.4%, p=0.05), stage 2 or 3 AKI (0.7% vs 6.7%, p=0.01), and new-onset or worsening atrial fibrillation (16.9% vs 57.8%, p<0.001) than surgical repair patients, all respectively. Both groups showed improvements in NYHA functional class. However, more TAVI-treated patients were in NYHA functional class II at 1-year follow-up (29.5% vs 15.0%, p=0.01).

In a 2-year follow-up of the NOTION trial, Søndergaard et al. (2016) reported slight improvements in the TAVI-treated group (n=142) compared with the surgical repair group (n=134), although between-group differences were almost exclusively not statistically significant. (58) For the composite rate of death at 2 years, the between-group difference was also statistically insignificant (18.8% of surgical repair patients vs 15.8% of TAVI-treated patients; p=0.43). A similar difference was observed for all-cause mortality (8.0% of patients treated with TAVI experienced all-cause mortality vs 9.8% of the surgical repair patients; p=0.54). Cardiovascular mortality rates, stroke rates, and MI were likewise marginally improved in the TAVI-treated patients, although the only significant difference was found for atrial fibrillation and permanent pacemaker implantation. For the former outcome, there were 60.0% of surgical patients, compared with 22.7% of TAVI patients (p<0.001); for the latter, only 4.2% of surgical patients received implantation vs 41.3% of the TAVI group (p<0.001). As a secondary outcome, moderate aortic regurgitation was improved at 2 years for the TAVI group (15.4%) compared with the surgical group (0.9%; p<0.001). The authors noted that the variety of risk levels observed in the patients limited their results, as did the exclusion of patients with coronary artery disease. Further, the trial was limited by its lack of power for subgroup analyses, and its inability to reveal any significant differences between groups with certainty. Overall, the results showed that TAVI-treated patients had comparable, if not improved, outcomes when treated alongside patients who received SAVR.

A previous RCT, the STACCATO trial, was designed to compare transapical TAVI using the SAPIEN valve with surgical aortic valve repair in operable patients with isolated aortic stenosis, without selection based on the predicted risk of death after surgery. However, the trial was prematurely terminated due to an increase in adverse events in the TAVI arm. The available results were reported by Nielsen et al. (2012). (53) The trial was limited by a design that assumed a low event rate (2.5%). Also, operators’ experience with the device and implantation techniques at the time of the trial might not be representative of current practice.

Reardon et al. (2016) reported on an analysis of patients from the U.S. Pivotal High Risk Trial who had STS score less than 7.0% at baseline. (59) The trial was described in a previous section on high surgical risk. Of the 750 total patients in the trial, 383 (202 TAVR; 181 SAVR) had a STS PROM score of 7% or less, with a median STS PROM score of 5.3%. All-cause mortality at 2 years for TAVR vs SAVR in the subgroup with STS score less than 7.0 was 15% (95% CI, 9% to 20%) vs 26% (95% CI, 20% to 33%; p=0.01). The rates of stroke at 2 years for TAVR vs SAVR were 11% vs 15% (p=0.50).

Reardon et al. (2017) published 2-year results from an RCT (SURTAVI trial) that compared clinical outcomes for 1746 patients at intermediate surgical risk randomized to transcatheter aortic valve replacement (TAVR) or SAVR. (60) For the primary outcome (composite death at 2 years), an improvement was observed in the TAVR-treated group, compared with surgery (12.6% of TAVR patients vs 14.0% of SAVR patients [95% credible interval, -5.2% to 2.3%]; posterior probability, >0.999). Rates of death, MI, and disabling stroke were comparable between groups, as were secondary outcomes that included echocardiographic measurement of aortic valve gradient and paravalvular regurgitation (data reported in the supplemental material). More patients were assigned to the CoreValve bioprosthesis (n=724) than received Evolut R bioprosthesis (n=137), which might have affected the results; also, a considerable number of patients withdrew consent before surgery, resulting in an as-treated population of 1660. Finally, the authors acknowledged a gap in knowledge of how baseline characteristics of patients who received surgery differed from those who did not. The authors noted the low 30-day surgical mortality ratio (0.38; observed-to-expected) and the similarity of this rate between groups (2.2% of the TAVR patients vs 1.7% of surgical patients).

Noncomparative Studies

The literature search focused on studies describing issues unique to the risk-benefit tradeoff for TAVI in individuals at intermediate or low surgical risk.

Fanning et al. (2016) reported on a prospective observational study evaluating clinical and subclinical (magnetic resonance imaging) neurologic injury in 40 individuals at intermediate surgical risk who were undergoing TAVI with the Edwards SAPIEN XT valve. (61) Following the procedure, 60 patients had new lesions on diffusion-weighted imaging, suggestive of acute ischemia.

Section Summary: TAVI Outcomes in Patients at Intermediate or Low Risk for Open Surgery

Five RCTs have evaluated TAVI in patients with low or intermediate risk for open surgery.

Intermediate Risk

Most in these RCTs were intermediate risk, and two of them included only intermediate surgical risk patients. The primary outcomes were generally a composite of death and stroke; most RCTs were noninferiority studies. The rates of the primary outcome were noninferior for TAVI compared with SAVR and numerically lower, although not statistically significantly lower in 3 of the 5 RCTs including the 2 RCTs exclusively enrolling intermediate risk. The rates of adverse events differed between groups, with bleeding, cardiogenic shock, and AKI higher in patients randomized to open surgery and permanent pacemaker requirement higher in patients randomized to TAVI. Subgroup analyses of meta-analyses and the transthoracic arm of the Leon RCT suggested that the benefit of TAVI may be limited to patients who are candidates for transfemoral access. Two-year follow-up results were published for NOTION, PARTNER 2A, CoreValve U.S. Pivotal and SURTAVI trials, but reported outcomes did not include rates of reoperation. A number of recently completed meta-analyses evaluated mortality for TAVR vs SAVR at the 30-day mark. Mortality rates were found to be comparable between the 2 procedures.

Low Risk

Limited data are available comparing TAVI with SAVR in patients at low risk for open surgery. The NOTION trial was the only trial with predominantly low surgical risk patients. The STACCATO trial also included some patients at low surgical risk. One systematic review of these 2 RCTs and 4 observational studies with propensity score matching comparing TAVI with SAVR in patients at low surgical risk reported that the 30-day and in-hospital mortality rates were similar for TAVI (2.2%) and SAVR (2.6%). However, TAVI was associated with increased risk of mortality with longer follow-up (median 2 years; 17.2% vs 12.7%). TAVI was associated with reduced risk of bleeding and renal failure and an increase in vascular complications and pacemaker implantation compared with SAVR.

TAVI Outcomes for “Valve-in-Valve” Approach

TAVI has been used as a “valve-in-valve” replacement approach for patients with degenerated bioprosthetic valves or failed TAVI. The evidence for outcomes after the use of TAVI for “valve-in-valve” replacement consists of case series. The largest case series published to date is from the Global Valve-in-Valve registry. The most recent results from this registry were reported through May 2013, including 459 patients. (62) Included patients were from 38 cardiac centers who had a prior surgical bioprosthetic valve replacement that had failed. Failure was due to stenosis in 181 (39.4%) patients, regurgitation in 139 (30.3%), or a combination in 139 (30.3%). The balloon-expandable and self-expandable devices were used in 246 (53.6%) and 213 (46.4%) patients, respectively. At 30 days, mortality was 7.6% (35/459), with a higher mortality rate in patients with failure due to stenosis (10.5% vs 4.3% in the regurgitation group vs 7.2% in the combined group; p=0.04). At 30 days, 35 (7.6%) patients had died. Patients in the stenosis group had a higher 30-day mortality rate (10.5% vs 4.3% in the regurgitation group vs 7.2% in the combined group; p=0.04). The overall 1-year mortality rate was 16.8%, with a higher mortality rate in the stenosis group (23.4%) than the other 2 groups (8.8% in the regurgitation group vs 16.1% in the combined group; p=0.01). At 1 year, 86.2% of patients were in NYHA functional class I or II.

Other case series are smaller and generally from a single center. A 2012 case series from Europe using the CoreValve enrolled 27 patients from a single cardiology center. (63) There were 2 deaths within 30 days. Improvements in the aortic valve gradient and the degree of regurgitation were noted. Adverse events included stroke (7.4%), kidney failure (7.4%), life-threatening bleeding (7.4%), and access site complications (11.1%). Another 2012 case series from Europe treated 18 patients with a degenerated bioprosthetic valve and symptoms due to valve dysfunction. (64) Implantation was successful in 17 of 18 patients. Complications included AKI in 3 of 18 patients, major bleeding in 4 of 18 patients, and major access site complications in 1 of 18 patients. At a median follow-up of 11 months, the mortality rate was 5.6%, and symptoms were improved in all patients in NYHA class II or lower. A 2014 series from Australia, including 12 patients who underwent valve-in-valve replacement of a degenerated bioprosthetic valve, reported successful valve implantation for all patients, with 1 case complicated by cardiac arrest during bioprosthetic valve predilation. (65) No periprocedural deaths, MIs, neurologic events, or major vascular complications occurred. After 1624 and 1319 days, respectively, 2 patients had died. The remaining patients had a median survival of 581 days, and all were in NYHA class I or II functional status.

Smaller case series have reported on valve-in-valve implantation for patients with failed TAVI. For example, a 2012 publication from Canada reported on 21 patients with transcatheter valve failure due to aortic regurgitation. (66) The procedure was successful in 19 of 21 patients; the remaining 2 patients required conversion to open surgery. Mortality at 30 days was 14.3% and was 24% at 1 year. Aortic regurgitation was absent in 4 patients, mild in 13 patients, and moderate in 2 patients.

Raval et al. (2014) reported on results from a systematic review of multiple types of valve-in-valve replacement procedures, including 31 studies that evaluated outcomes after transcatheter aortic valve-in-valve replacement, 13 of which were case reports. (67) Pooled analyses of study results are not reported, but reviewers reported a high rate (90%-93%) of success for valve-in-valve TAVI procedures for series that report procedural success.

Section Summary: TAVI Outcomes for “Valve-in-Valve” Approach

The evidence related to the use of TAVI for valve-in-valve replacement after failed TAVI or degenerated bioprosthetic valve consists of case series (the largest of which included 459 patients) and a systematic review of the available case series. These series have reported high rates of technical success of valve implantation but often have also reported high rates of short-term complications. At 1 year postprocedure, reported mortality rates are often high, but high proportions of patients have improvement in heart failure - related symptoms.

Adverse Events and Complications After TAVI

Summary of Complications

Conte et al. (2017) analyzed both periprocedural and early complications (0-3 days and 4-30 days postoperative, respectively) in patients from the U.S. CoreValve High Risk Study. (68) There were no statistically significant differences in all-cause mortality, stroke, MI, or major infection in either the periprocedural period (0-3 days) or between 4 and 30 days postprocedure. Major vascular complication rate within 3 days was significantly higher with TAVR (6.4% vs 1.4%, p=0.003). Life-threatening or disabling bleeding (12.0% vs 34.0%, p<0.001), encephalopathy (7.2% vs 12.3%, p=0.02), atrial fibrillation (8.4% vs 18.7% p<0.001), and AKI (6.1% vs 15.0%, p<0.001) were significantly higher with SAVR.

A meta-analysis of complications associated with TAVI was published by Khatri et al. (2013). (69) This analysis included all publications with at least 100 patients and with data on at least 1 type of complication. Forty-nine studies (total N=16,063 patients) were identified. The most common adverse event was heart block requiring a pacemaker insertion, which occurred in 13.1% of patients. Vascular complications occurred in 10.4% of patients. The third most common complication was acute renal failure requiring therapy in 4.9% of patients, followed by moderate-to-severe aortic regurgitation in 4.5%, stroke in 2.9%, valve embolization in 1.3%, MI in 1.1%, and coronary obstruction in 0.8%.

Giordana et al. (2014) published a meta-analysis on predictors of all-cause mortality after TAVI. (70) They included 25 studies with 8874 patients who underwent TAVI for severe symptomatic aortic stenosis that reported predictors of mortality at 30 days or mid-term follow-up. Most (51.1%) patients underwent the procedure via the transfemoral approach, with 33.7% and 1.7% receiving a transapical or direct aortic/subclavian approach, respectively. A SAPIEN balloon-expandable valve was used in 5392 (60.8%) patients, while a CoreValve self-expandable valve was used in 1899 (21.4%) patients. Three studies did not report the type of valve implanted. At 30 days, 663 (7.5%) patients died, 712 (8.02%) developed AKI, 1224 (13.8%) developed major bleeding, 782 (8.8%) developed major vascular complications, and 1106 (12.5%) required pacemaker implantation. At mid-term follow-up (median, 365 days), 1917 (21.6%) patients had died. The strongest predictors of 30-day mortality were higher AKI stage (≥2; OR=18.0; 95% CI, 6.25 to 52), preprocedural hospitalization for at least 1 week (OR=9.36; 95% CI, 2.55 to 35), periprocedural acute MI (OR=8.54; 95% CI, 2.57 to 33.52), and preprocedural increased pro-brain natriuretic peptide levels (OR=5.35; 95% CI, 1.74 to 16.5). The strongest predictors of mid-term mortality were increased pro-brain natriuretic peptide levels (OR=11; 95% CI, 1.51 to 81), stage 3 AKI (OR=6.80; 95% CI, 2.55 to 15.66), left ventricular ejection fraction less than 30% (OR=6.67; 95% CI, 3.5 to 12.76), and periprocedural acute MI (OR=6.52; 95% CI, 2.34 to 18.14).

Some studies have specifically reported on 1 or more complications in large numbers of patients. Representative studies of this type are reviewed next.

Vascular Access Complications

The most common complications following TAVI are vascular related to the access site. Van Mieghem et al. (2012) pooled results from prospective databases on 986 patients undergoing transfemoral TAVI from 5 clinical centers in Europe. (71) The rate of major vascular complications was 14.2%. Major bleeding occurred at a rate of 17.8% and life-threatening/disabling bleeding at a rate of 11%. Czerwinska-Jelonkiewicz et al. (2014) reported on vascular complication rates for 89 consecutive patients treated at a single institution; 44 patients had vascular complications, 17 (20.5%) of which were considered major incidents. (72)

Acute Kidney Injury

AKI is relatively common following TAVI. In 218 patients treated at a U.S. academic medical center, stage 2 or higher AKI occurred in 8.3% (18/218). (73) Half the patients with AKI (9/18) required dialysis. Mortality at 30 days (44.4% vs 3.0%, p<0.001) and 1 year (55.6% vs 16.0%, p<0.001) were much higher in patients with AKI than in those without AKI, respectively. In a similar study of 248 patients from an academic center in Europe, stage 2 or higher AKI was more common, occurring in 35.9% (89/248) of patients. Mortality was also increased at 30 days (13.5% vs 3.8%, p<0.001) and at 1 year (31.5% vs 15.0%, p<0.001) for patients with AKI. (74)

Permanent Pacemaker Requirement

A pacemaker requirement due to conduction abnormalities is another relatively frequent complication following TAVI, and predictors and rates of permanent pacemaker requirement have been a focus of a number of studies.

Siontis et al. (2014) conducted a meta-analysis to determine predictors of permanent pacemaker implantation after TAVI. (75) Reviewers included 41 studies that made available individual patient-level data, which included 11,210 patients treated with TAVI, of whom 17% required a permanent pacemaker after aortic valve implantation. Between 2% and 51% of patients across the individual studies required a permanent pacemaker. For patients receiving the CoreValve, the median rate of permanent pacemaker placement was 28% (interquartile range, 24%-35%), whereas, for those receiving the SAPIEN valve, the median permanent pacemaker placement rate was 6% (interquartile range, 5%-7%). In pooled analyses, factors significantly associated with permanent pacemaker requirement after TAVI included male sex (RR=1.23, p<0.01), baseline first-degree atrioventricular block (RR=1.52, p<0.01), and intraprocedural atrioventricular block (RR=3.49, p<0.01).

Several studies not included in the Siontis review have addressed the need for permanent pacemaker placement after TAVI. Gensas et al. (2014) reported on rates and predictors of permanent pacemaker requirements after TAVI in patients enrolled in a multicenter Brazilian registry. (76) Four hundred eighteen patients were treated with TAVI between 2008 and 2012. The authors reported on outcomes for 353 who survived the procedure and who had not had a previous permanent pacemaker. A quarter (25.2%) of patients required a permanent pacemaker by 30 days postprocedure. In multivariable analysis, CoreValve device (vs SAPIEN XT; OR=4.24; 95% CI, 1.56 to 11.49; p<0.000), baseline right bundle branch block (OR=4.41; 95% CI, 2.20 to 8.82; p<0.001), and requirement for balloon predilatation of the aortic valve (OR=1.75; 95% CI, 1.02 to 3.02; p=0.04) were independent predictors of a requirement for permanent pacemaker.

Abdel-Wahab et al. (2014) reported on results of an RCT comparing CoreValve with the SAPIEN valve and found that patients in the balloon-expandable group less frequently required placement of a new permanent pacemaker (17.3% vs 37.6%, p=0.001). (77)

Lenders et al. (2014) compared permanent pacemaker requirement rates based on the depth of implantation for patients treated with CoreValve. (78) Two hundred thirty-two patients were treated with CoreValve, some with a newer-generation delivery catheter (the AccuTrak; n=112) and some with an older-generation delivery catheter (n=120). Groups were similar at baseline. Mean depth of implantation was 8.4 mm in the non-AccuTrak group and 7.1 mm in the AccuTrak group (p=0.034). In patients without a permanent pacemaker before valve implantation, 33 (32.3%) patients in the non-AccuTrak group received a permanent pacemaker after implantation, compared with 21 (21.4%) in the AccuTrak group (p=0.094). Among all patients, the mean depth of implantation was significantly lower (lower in relation to a reference line connecting the lower edges of the 3 aortic valve cusps) in patients who required a new permanent pacemaker (8.9 mm) compared with those who did not (6.9 mm; p=0.002).

Boerlage-Van Dijk et al. (2014) reported on predictors of cardiac conduction abnormalities in 121 patients who received a CoreValve implant at a single center between 2007 and 2011. (79) For the analysis of new left bundle branch block, 34 patients were excluded because of preprocedural left bundle branch block or a ventricular-paced rhythm. For the analysis of permanent pacemaker implantation, 16 patients were excluded, 10 patients because of preprocedural pacemaker implantation, 5 because they died before the required observation period for possible pacemaker indication, and 1 because the patient needed a pacemaker implantation due to a sick sinus syndrome, which was unrelated to TAVI and discovered during observation after TAVI. After the TAVI procedure, 23 (21.9%) patients required pacemaker implantation, most commonly due to total atrioventricular block (n=21 [91.3%]). Forty-seven patients developed a new left bundle branch block after the TAVI procedure, which was temporary in 19%. Significant predictors of pacemaker requirement were mitral annular calcification and preexisting right bundle branch block, while prosthesis size and prosthesis depth were significant predictors of new left bundle branch block.

In another series reporting on predictors of cardiac conduction abnormalities after CoreValve implantation, Kim et al. (2015) reported on 117 patients without preexisting permanent pacemakers who underwent CoreValve placement, of whom 12 required a pacemaker postimplantation. (80) In multivariable analysis, the strongest predictors of pacemaker requirement were the perimeter stretching index (OR=1.548; 95% CI, 1.239 to 1.935; p<0.001) and the device depth (OR=1.262; 95% CI, 1.034 to 1.543, p=0.02).

Section Summary: Adverse Events and Complications After TAVI

In addition to complication rates reported in randomized and nonrandomized studies evaluating outcomes after TAVI, 2 meta-analyses and a number of cohort studies have reported specifically on complications after TAVI, particularly vascular access complications, AKI, and the need for a permanent pacemaker. Given the high requirements for new permanent pacemakers after TAVI, particularly with the CoreValve, studies have focused on predictors of new conduction abnormalities, identifying the use of a CoreValve device (vs the SAPIEN device), insertion depth, and preexisting right bundle branch block as significant predictors of pacemaker requirement.

Summary of Evidence

For individuals who have severe symptomatic aortic stenosis who are at prohibitive risk for open surgery who receive TAVI, the evidence includes an RCT comparing TAVI with medical management in individuals at prohibitive risk of surgery, a single-arm prospective trial, multiple case series, and multiple systematic reviews. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related mortality and morbidity. For patients who are not surgical candidates due to excessive surgical risk, the PARTNER B trial reported on results for patients treated with TAVI by the transfemoral approach compared with continued medical care with or without balloon valvuloplasty. There was a large decrease in mortality for the TAVI patients at 1 year compared with medical care. This trial also reported improvements in other relevant clinical outcomes for the TAVI group. There was an increased risk of stroke and vascular complications in the TAVI group. Despite these concerns, the overall balance of benefits and risks from this trial indicate that health outcomes are improved. For patients who are not surgical candidates, no randomized trials have compared the self-expandable valve with best medical therapy. However, results from the single-arm CoreValve Extreme Risk Pivotal Trial met trialists’ prespecified objective performance goal. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have severe symptomatic aortic stenosis who are at high risk for open surgery who receive TAVI, the evidence includes 2 RCTs comparing TAVI with surgical repair in individuals at high risk for surgery, multiple nonrandomized comparative studies, and systematic reviews of these studies. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related mortality and morbidity. For patients who are high risk for open surgery and are surgical candidates, the PARTNER A trial reported noninferiority for survival at 1 year for the balloon-expandable valve compared with open surgery. In this trial, TAVI patients also had higher risks for stroke and vascular complications. Nonrandomized comparative studies of TAVI vs open surgery in high-risk patients have reported no major differences in rates of mortality or stroke between the 2 procedures. Since the publication of the PARTNER A trial, the CoreValve High Risk Trial demonstrated noninferiority for survival at 1 and 2 years for the self-expanding prosthesis. This trial reported no significant differences in stroke rates between groups. In an RCT directly comparing the self-expandable with the balloon-expandable valve among surgically high-risk patients, the devices had similar 30-day mortality outcomes, although the self-expandable valve was associated with higher rates of residual aortic regurgitation and need for a new permanent pacemaker. Evidence from RCT and nonrandomized studies has suggested that TAVI with a self-expanding device is associated with higher rates for permanent pacemakers postprocedure. However, survival rates appear to be similar between device types, and the evidence does not support the superiority of one device over another in all patients. Two sex-specific studies were also identified in a literature search with the objective of observing mortality rates in women undergoing TAVI or SAVR. Results were varied, and further study is needed. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have severe symptomatic aortic stenosis who are at intermediate risk for open surgery who receive TAVI, the evidence includes 3 RCTs comparing TAVI with surgical repair including individuals at intermediate surgical risk, 2 RCTs only in patients with intermediate risk, and multiple systematic reviews and nonrandomized cohort studies. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related mortality and morbidity. Five RCTs have evaluated TAVI in patients with intermediate risk for open surgery. Three of them, which included over 4000 patients combined, reported noninferiority of TAVI vs SAVR for their composite outcome measures (generally including death and stroke). A subset analysis of patients (n=383) with low and intermediate surgical risk from a fourth trial reported higher rates of death at 2 years for TAVI vs SAVR. The final study (N=70) had an unclear hypothesis and reported 30-day mortality rates favoring SAVR (15% vs 2%, p=0.07) but used a transthoracic approach. The rates of adverse events differed between groups, with bleeding, cardiogenic shock, and acute kidney injury higher in patients randomized to open surgery and permanent pacemaker requirement higher in patients randomized to TAVI. Subgroup analyses of meta-analyses and the transthoracic arm of the Leon et al. RCT has suggested that the benefit of TAVI may be limited to patients who are candidates for transfemoral access. Although several RCTs have 2 years of follow-up postprocedure, it is uncertain how many individuals require reoperation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have severe symptomatic aortic stenosis who are at low risk for open surgery who receive TAVI, the evidence includes 2 RCTs comparing TAVI with surgical repair in individuals selected without specific surgical risk criteria but including patients at low surgical risk, systematic reviews, and nonrandomized cohort studies. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related mortality and morbidity. Limited data are available comparing SAVR with TAVI in patients who had severe aortic stenosis with low risk for open surgery. A systematic review including the low surgical risk patients of these 2 RCTs, and 4 observational studies, with propensity score matching, reported that the 30-day and in-hospital mortality rates were similar for TAVI (2.2%) and SAVR (2.6%). However, TAVI was associated with increased risk of mortality with longer follow-up (median, 2 years; 17.2% vs 12.7%). TAVI was associated with reduced risk for bleeding, renal failure and, an increase in vascular complications and pacemaker implantation compared with SAVR. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have valve dysfunction and aortic stenosis or regurgitation after aortic valve repair who receive transcatheter aortic “valve-in-valve” implantation, the evidence includes case series (largest with 459 patients) and systematic reviews of case series. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related mortality and morbidity. These case series have reported high rates of technical success of valve implantation and improvement in heart failure symptoms for most patients. However, they have also reported high rates of short-term complications and high rates of mortality at 1 year postprocedure. There is a lack of evidence comparing valve-in-valve replacement with alternative treatment approaches. The evidence is insufficient to determine the effects of the technology on health outcomes..

Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

The Blue Cross Blue Shield Association (BCBSA) obtained input from 2 specialty societies (1 of which provided 2 responses) and 2 academic medical centers (1 of which provided 3 responses) while this policy was under review in 2016. Although there was no support for the use of valve-in-valve transcatheter aortic valve implantation (TAVI) to replace a failed bioprosthetic valve in general use, there was general support for the use of valve-in-valve TAVI for patients at high and prohibitive risk for surgery.

Practice Guidelines and Position Statements

American College of Cardiology and American Heart Association

The American College of Cardiology and the American Heart Association (2014) published joint guidelines on the management of valvular heart disease. (81) Both groups issued a joint focused update in 2017. (82) These guidelines made the following recommendations on the choice of surgical or transcatheter intervention for treatment of aortic stenosis (see Table 7).

Table 7. Recommendations on Surgical or Transcatheter Intervention for Aortic Stenosis

Recommendation

COR

LOE

“Surgical AVR is recommended in patients who meet an indication for AVR with low or intermediate surgical risk.”

I

A

“For patients in whom TAVR or high-risk surgical AVR is being considered, members of a Heart Valve Team should collaborate to provide optimal patient care”

I

C

“TAVR is recommended for symptomatic patients with severe AS and high risk for SAVR, depending on patient-specific procedural risks, values and preferences.”

I

A

“TAVR is recommended for symptomatic patients with severe AS, prohibitive risk for SAVR and a predicted post-TAVR survival >12 mo.”

I

A

“TAVR is a reasonable alternative to SAVR for symptomatic patients with severe AS and intermediate surgical risk, depending on patient-specific procedural risks, values and preferences”

IIa

B

“For severely symptomatic patients with bioprosthetic stenosis or regurgitation at high or prohibitive risk for reoperation, and in whom improvement in hemodynamics is anticipated, valve-in-valve TAVR is reasonable”

IIa

B

“Percutaneous aortic balloon dilation may be considered as a bridge to surgical or transcatheter AVR in severely symptomatic patients with severe AS.”

IIb

C

“TAVR is not recommended in patients in whom existing comorbidities would preclude the expected benefit from correction of AS.”

III

B

Table Key: AS: aortic stenosis; AVR: aortic valve replacement; COR: class of recommendation; LOE: level of evidence; SAVR: surgical aortic valve replacement; TAVR: transcatheter aortic valve replacement.

European Society for Cardiology and European Association for Cardio-Thoracic Surgery

The European Society for Cardiology and the European Association for Cardio-Thoracic Surgery (2017) published joint guidelines on the management of valvular heart disease. (83) These guidelines made the following recommendations on the use of TAVI (see Table 8).

Table 8. Recommendations on Surgical or Transcatheter Intervention for Aortic Stenosis

Recommendation

COR

LOE

“TAVI is recommended in patients who are not suitable for SAVR as assessed by the Heart Team.”

I

B

“In patients who are at increased surgical risk (STS or EuroSCORE II ≥4% or logistic EuroSCORE I ≥10% or other risk factors not included in these scores such as frailty, porcelain aorta, sequelae of chest radiation), the decision between SAVR and TAVI should be made by the Heart Team according to the individual patient characteristics, with TAVI being favoured in elderly patients suitable for transfemoral access.”

I

B

Table Key: COR: class of recommendation; LOE: level of evidence; SAVR: surgical aortic valve replacement; STS: Society of Thoracic Surgeons; TAVI: transcatheter aortic valve replacement

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 9.

Table 9. Summary of Key Trials

NCT No.

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT01586910a

Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI)

2500

Oct 2017 (ongoing)

NCT02956915

Evaluation of Length of Stay and Predisposing Factors of Late Discharge After Transfemoral Transcatheter Aortic Valve Implantation Using the SAPIEN-3 Prosthesis: A French Multicenter Prospective Observational Trial

300

Dec 2017 (ongoing)

NCT01057173

Transcatheter Versus Surgical Aortic Valve Implantation in Patients With Severe Aortic Valve Stenosis (NOTION)

280

Apr 2018

NCT01645202

A Randomized Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: Medtronic CoreValve Versus Edwards SAPIEN XT (The CHOICE Trial)

240

Dec 2018

NCT01240902a

Medtronic CoreValve® U.S. Pivotal Trial

1650

Aug 2019

NCT02661451a

Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure: A Randomized Trial (TAVR UNLOAD)

600

May 2020

NCT02436655

Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: (AVATAR Trial): A Multicentre Randomized Controlled Trial

312

Jun 2020

NCT01314313a

The PARTNER II Trial "Placement of AoRTic TraNscathetER Valves Trial" (US) [Edwards Study 2010-12]

6650

Sep 2020

NCT02163850a

SALUS Trial: TranScatheter Aortic Valve RepLacement System Pivotal Trial The Safety and Effectiveness of the Direct Flow Medical Transcatheter Aortic Valve System

878

Dec 2021

NCT01737528

Society of Thoracic Surgeons and American College of Cardiology Transcatheter Valve Therapy Registry (STS/ACC TVT Registry)

16,000

Jun 2022

NCT02249000

Safety and Clinical Performance of the Self-expanding Transcatheter BIOVALVE Prosthesis in Subjects With Severe Symptomatic Aortic Stenosis Suitable for Transfemoral Transcatheter Aortic Valve Implantation

86

Dec 2022

NCT03361046

Evaluation of Clinical Outcomes of Transcatheter Aortic Valve-in-Valve Implantation in Polish Population – Observational Multicenter Registry

150

May 2024

Table Key: NCT: national clinical trial.

a Denotes industry-sponsored or cosponsored trial.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

33361, 33362, 33363, 33364, 33365, 33366, 33367, 33368, 33369

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation. Jun 21 2005; 111(24):3316-3326. PMID 15967862

2. Coeytaux RR, Williams JW, Jr., Gray RN, et al.. Percutaneous heart valve replacement for aortic stenosis: state of the evidence. Ann Intern Med. Sep 7 2010; 153(5):314-324. PMID 20679543

3. 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. Apr 1993; 21(5):1220-1225. PMID 8459080

4. 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. Aug 1 2006; 114(5):e84-231. PMID 16880336

5. Iung 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. Dec 2005; 26(24):2714-2720. PMID 16141261

6. 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. Nov 15 1995; 26(6):1522-1528. PMID 7594080

7. Meredith IT, Walton A, Walters DL, et al. Mid-term outcomes in patients following transcatheter aortic valve implantation in the CoreValve Australia and New Zealand Study. Heart Lung Circ. Mar 2015; 24(3):281-290. PMID 25456213

8. 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. Apr 2011; 100(4):265-276. PMID 21165626

9. 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. Oct 21 2010; 363(17):1597-1607. PMID 20961243

10. 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. Nov 1 2011; 124(18):1964-1972. PMID 21969017

11. Makkar RR, Fontana GP, Jilaihawi H, et al. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. May 3 2012; 366(18):1696-1704. PMID 22443478

12. Svensson LG, Blackstone EH, Rajeswaran J, et al. Comprehensive analysis of mortality among patients undergoing TAVR: results of the PARTNER trial. J Am Coll Cardiol. Jul 15 2014; 64(2):158-168. PMID 25011720

13. Kapadia SR, Tuzcu EM, Makkar RR, et al. Long-term outcomes of inoperable patients with aortic stenosis randomly assigned to transcatheter aortic valve replacement or standard therapy. Circulation. Oct 21 2014; 130(17):1483-1492. PMID 25205802

14. 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. Dec 21 2015; 8(14):1797-1806. PMID 26718510

15. Popma JJ, Adams DH, Reardon MJ, et al. Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J Am Coll Cardiol. May 20 2014; 63(19):1972-1981. PMID 24657695

16. Reardon MJ, Adams DH, Coselli JS, et al. Self-expanding transcatheter aortic valve replacement using alternative access sites in symptomatic patients with severe aortic stenosis deemed extreme risk of surgery. J Thorac Cardiovasc Surg. Dec 2014; 148(6):2869-2876 e2861-2867. PMID 25152474

17. Mack MJ, Brennan JM, Brindis R, et al. Outcomes following transcatheter aortic valve replacement in the United States. JAMA. Nov 20 2013; 310(19):2069-2077. PMID 24240934

18. Yakubov SJ, Adams DH, Watson DR, et al. 2-year outcomes after iliofemoral self-expanding transcatheter aortic valve replacement in patients with severe aortic stenosis deemed extreme risk for surgery. J Am Coll Cardiol. Sep 22 2015; 66(12):1327-1334. PMID 26383718

19. Baron SJ, Arnold SV, Reynolds MR, et al. Durability of quality of life benefits of transcatheter aortic valve replacement: Long-term results from the CoreValve US extreme risk trial. Am Heart J. Dec 2017; 194:39-48. PMID 29223434

20. Osnabrugge RL, Arnold SV, Reynolds MR, et al. Health status after transcatheter aortic valve replacement in patients at extreme surgical risk: results from the CoreValve U.S. trial. JACC Cardiovasc Interv. Feb 2015; 8(2):315-323. PMID 25700755

21. Linke A, Wenaweser P, Gerckens U, et al. Treatment of aortic stenosis with a self-expanding transcatheter valve: the International Multi-centre ADVANCE Study. Eur Heart J. Oct 7 2014; 35(38):2672-2684. PMID 24682842

22. 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. Aug 2008; 4(2):242-249. PMID 19110790

23. 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. Mar 16 2010; 55(11):1080-1090. PMID 20096533

24. Zahn R, Gerckens U, Grube E, et al. Transcatheter aortic valve implantation: first results from a multi-centre real-world registry. Eur Heart J. Jan 2011; 32(2):198-204. PMID 20864486

25. 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. Jan 25 2011; 123(3):299-308. PMID 21220731

26. Panoulas VF, Francis DP, Ruparelia N, et al. Female-specific survival advantage from transcatheter aortic valve implantation over surgical aortic valve replacement: Meta-analysis of the gender subgroups of randomised controlled trials including 3758 patients. Int J Cardiol. Jan 1 2018; 250:66-72. PMID 29169764

27. 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. Dec 15 2016; 225:234-243. PMID 27732927

28. 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; Available at: https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016036772. Accessed March 7, 2018.

29. 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. Jun 20 2015; 385(9986):2477-2484. PMID 25788234

30. Reardon MJ, Adams DH, Kleiman NS, et al. 2-year outcomes in patients undergoing surgical or self-expanding transcatheter aortic valve replacement. J Am Coll Cardiol. Jul 14 2015; 66(2):113-121. PMID 26055947

31. Panchal HB, Ladia V, Desai S, et al. A meta-analysis of mortality and major adverse cardiovascular and cerebrovascular events following transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis. Am J Cardiol. Sep 15 2013; 112(6):850-860. PMID 23756547

32. Takagi H, Niwa M, Mizuno Y, et al. A meta-analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement. Ann Thorac Surg. Aug 2013; 96(2):513-519. PMID 23816417

33. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. Jun 9 2011; 364(23):2187-2198. PMID 21639811

34. 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. Aug 7 2012;60(6): 548-558. PMID 22818074

35. Genereux P, Cohen DJ, Williams MR, et al. Bleeding complications after surgical aortic valve replacement compared with transcatheter aortic valve replacement: insights from the PARTNER I Trial (Placement of Aortic Transcatheter Valve). J Am Coll Cardiol. Mar 25 2014; 63(11):1100-1109. PMID 24291283

36. Adams DH, Popma JJ, Reardon MJ, et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. May 8 2014; 370(19):1790-1798. PMID 24678937

37. Deeb GM, Reardon MJ, Chetcuti S, et al. 3-year outcomes in high-risk patients who underwent surgical or transcatheter aortic valve replacement. J Am Coll Cardiol. Jun 7 2016; 67(22):2565-2574. PMID 27050187

38. Zorn GL, 3rd, Little SH, Tadros P, et al. Prosthesis-patient mismatch in high-risk patients with severe aortic stenosis: A randomized trial of a self-expanding prosthesis. J Thorac Cardiovasc Surg. Apr 2016; 151(4):1014-1022, 1023 e1011-1013. PMID 26614412

39. Muneretto C, Bisleri G, Moggi A, et al. Treating the patients in the 'grey-zone' with aortic valve disease: a comparison among conventional surgery, sutureless valves and transcatheter aortic valve replacement. Interact Cardiovasc Thorac Surg. Jan 2015; 20(1):90-95. PMID 25320140

40. Minutello RM, Wong SC, Swaminathan RV, et al. Costs and in-hospital outcomes of transcatheter aortic valve implantation versus surgical aortic valve replacement in commercial cases using a propensity score matched model. Am J Cardiol. May 15 2015; 115(10):1443-1447. PMID 25784513

41. Sedaghat A, Al-Rashid F, Sinning JM, et al. Outcome in TAVI patients with symptomatic aortic stenosis not fulfilling PARTNER study inclusion criteria. Catheter Cardiovasc Interv. Nov 15 2015; 86(6):1097-1104. PMID 26032437

42. Arora S, Strassle PD, Ramm CJ, et al. Transcatheter versus surgical aortic valve replacement in patients with lower surgical risk scores: a systematic review and meta-analysis of early outcomes. Heart Lung Circ. Aug 2017; 26(8):840-845. PMID 28169084

43. Arora S, Vaidya SR, Strassle PD, et al. Meta-analysis of transfemoral TAVR versus surgical aortic valve replacement. Catheter Cardiovasc Interv. Oct 25 2017. PMID 29068166

44. Garg A, Rao SV, Visveswaran G, et al. Transcatheter aortic valve replacement versus surgical valve replacement in low-intermediate surgical risk patients: a systematic review and meta-analysis. J Invasive Cardiol. Jun 2017; 29(6):209-216. PMID 28570236

45. Singh K, Carson K, Rashid MK, et al. Transcatheter aortic valve implantation in intermediate surgical risk patients with severe aortic stenosis: a systematic review and meta-analysis. Heart Lung Circ. Feb 2018; 27(2):227-234. PMID 28473216

46. Ando T, Takagi H, Grines CL. Transfemoral, transapical and transcatheter aortic valve implantation and surgical aortic valve replacement: a meta-analysis of direct and adjusted indirect comparisons of early and mid-term deaths. Interact Cardiovasc Thorac Surg. Sep 1 2017; 25(3):484-492. PMID 28549125

47. Gozdek M, Raffa GM, Suwalski P, et al. Comparative performance of transcatheter aortic valve-in-valve implantation versus conventional surgical redo aortic valve replacement in patients with degenerated aortic valve bioprostheses: systematic review and meta-analysis. Eur J Cardiothorac Surg. Mar 1 2018; 53(3):495-504. PMID 29029105

48. Khan SU, Lone AN, Saleem MA, et al. Transcatheter vs surgical aortic-valve replacement in low- to intermediate-surgical-risk candidates: A meta-analysis and systematic review. Clin Cardiol. Nov 2017; 40(11):974-981. PMID 29168984

49. Tam DY, Vo TX, Wijeysundera HC, et al. Transcatheter vs surgical aortic valve replacement for aortic stenosis in low-intermediate risk patients: a meta-analysis. Can J Cardiol. Sep 2017; 33(9):1171-1179. PMID 28843328

50. Witberg G, Lador A, Yahav D, et al. Transcatheter versus surgical aortic valve replacement in patients at low surgical risk: A meta-analysis of randomized trials and propensity score matched observational studies. Catheter Cardiovasc Interv. Feb 1 2018. PMID 29388308

51. 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. Nov 12 2016; 228:723-728. PMID 27886617

52. Thyregod HG, Steinbruchel DA, Ihlemann N, et al. Transcatheter versus surgical aortic valve replacement in patients with severe aortic valve stenosis: 1-year results from the all-comers NOTION randomized clinical trial. J Am Coll Cardiol. May 26 2015; 65(20):2184-2194. PMID 25787196

53. Nielsen HH, Klaaborg KE, Nissen H, et al. A prospective, randomised trial of transapical transcatheter aortic valve implantation vs. surgical aortic valve replacement in operable elderly patients with aortic stenosis: the STACCATO trial. EuroIntervention. Jul 20 2012; 8(3):383-389. PMID 22581299

54. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. Apr 28 2016; 374(17):1609-1620. PMID 27040324

55. 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. Jan 15 2016; 117(2):252-257. PMID 26639040

56. 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. Aug 18 2015; 66(7):804-812. PMID 26271063

57. 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. Sep 28 2016; 354:i5130. PMID 27683246

58. Søndergaard L, Steinbruchel 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. Jun 2016; 9(6). PMID 27296202

59. Reardon MJ, Kleiman NS, Adams DH, et al. Outcomes in the randomized corevalve us pivotal high risk trial in patients with a Society of Thoracic Surgeons Risk Score of 7% or less. JAMA Cardiol. Nov 1 2016; 1(8):945-949. PMID 27541162

60. Reardon MJ, Van Mieghem NM, Popma JJ, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med. Apr 6 2017; 376(14):1321-1331. PMID 28304219

61. Fanning JP, Wesley AJ, Walters DL, et al. Neurological injury in intermediate-risk transcatheter aortic valve implantation. J Am Heart Assoc. Nov 15 2016; 5(11). PMID 27849158

62. Dvir D, Webb JG, Bleiziffer S, et al. Transcatheter aortic valve implantation in failed bioprosthetic surgical valves. JAMA. Jul 2014; 312(2):162-170. PMID 25005653

63. 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. Oct 1 2012; 5(5):689-697. PMID 23048050

64. 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. Mar 2012; 7(11):1275-1284. PMID 22278193

65. Subban V, Savage M, Crowhurst J, et al. Transcatheter valve-in-valve replacement of degenerated bioprosthetic aortic valves: a single Australian Centre experience. Cardiovasc Revasc Med. Nov-Dec 2014; 15(8):388-392. PMID 25456416

66. Toggweiler S, Wood DA, Rodes-Cabau J, et al. Transcatheter valve-in-valve implantation for failed balloon-expandable transcatheter aortic valves. JACC Cardiovasc Interv. May 2012; 5(5):571-577. PMID 22625197

67. Raval J, Nagaraja V, Eslick GD, et al. Transcatheter valve-in-valve implantation: a systematic review of literature. Heart Lung Circ. Nov 2014; 23(11):1020-1028. PMID 25038030

68. Conte JV, Hermiller J, Jr., Resar JR, et al. Complications after self-expanding transcatheter or surgical aortic valve replacement. Semin Thorac Cardiovasc Surg. Autumn 2017; 29(3):321-330. PMID 29195573

69. Khatri PJ, Webb JG, Rodes-Cabau J, et al. Adverse effects associated with transcatheter aortic valve implantation: a meta-analysis of contemporary studies. Ann Intern Med. Jan 1 2013; 158(1):35-46. PMID 23277899

70. Giordana F, D'Ascenzo F, Nijhoff F, et al. Meta-analysis of predictors of all-cause mortality after transcatheter aortic valve implantation. Am J Cardiol. Nov 1 2014; 114(9):1447-1455. PMID 25217456

71. 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. Nov 1 2012; 110(9):1361-1367. PMID 22819428

72. Czerwinska-Jelonkiewicz K, Michalowska I, Witkowski A, et al. Vascular complications after transcatheter aortic valve implantation (TAVI): risk and long-term results. J Thromb Thrombolysis. May 2014; 37(4):490-498. PMID 24132402

73. Genereux P, Kodali SK, Green P, 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. Jan 1 2013; 111(1):100-105. PMID 23040657

74. 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. Sep 2012; 8(5):563-570. PMID 22995082

75. Siontis GC, Juni P, Pilgrim T, et al. Predictors of permanent pacemaker implantation in patients with severe aortic stenosis undergoing TAVR: a meta-analysis. J Am Coll Cardiol. Jul 15 2014; 64(2):129-140. PMID 25011716

76. Gensas CS, Caixeta A, Siqueira D, et al. Predictors of permanent pacemaker requirement after transcatheter aortic valve implantation: insights from a Brazilian registry. Int J Cardiol. Aug 1 2014; 175(2):248-252. PMID 24880480

77. Abdel-Wahab M, Mehilli J, Frerker C, et al. Comparison of balloon-expandable vs self-expandable valves in patients undergoing transcatheter aortic valve replacement: the CHOICE randomized clinical trial. JAMA. Apr 16 2014; 311(15):1503-1514. PMID 24682026

78. Lenders GD, Collas V, Hernandez JM, et al. Depth of valve implantation, conduction disturbances and pacemaker implantation with CoreValve and CoreValve Accutrak system for Transcatheter Aortic Valve Implantation, a multi-center study. Int J Cardiol. Oct 20 2014; 176(3):771-775. PMID 25147076

79. Boerlage-Van Dijk K, Kooiman KM, Yong ZY, et al. Predictors and permanency of cardiac conduction disorders and necessity of pacing after transcatheter aortic valve implantation. Pacing Clin Electrophysiol. Nov 2014; 37(11):1520-1529. PMID 25040838

80. Kim WJ, Ko YG, Han S, et al. Predictors of permanent pacemaker insertion following transcatheter aortic valve replacement with the CoreValve revalving system based on computed tomography analysis: an Asian multicenter registry study. J Invasive Cardiol. Jul 2015; 27(7):334-340. PMID 26136283

81. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. Jun 10 2014; 63(22):2438-2488. PMID 24603192

82. Nishimura RA, O'Gara PT, Bonow RO. Guidelines update on indications for transcatheter aortic valve replacement. JAMA Cardiol. Sep 1 2017; 2(9):1036-1037. PMID 28768333

83. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. Sep 21 2017; 38(36):2739-2791. PMID 28886619

84. Center for Medicare & Medicaid Services. Decision Memo for transcatheter aortic valve replacement (TAVR) (CAG-00430N). 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=ACAAAAAAAgAAAA%3d%3d&. Accessed March 2, 2018.

85. Transcatheter Aortic Valve Implantation for Aortic Stenosis. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2018 April) Surgery 7.01.132

Policy History:

Date Reason
11/1/2018 Document updated with literature review. Coverage revised in final bullet point of each statement to include the word “or” in these statements: “Patient is not an operable candidate for open surgery, as judged by at least two cardiovascular specialists (cardiologist and/or cardiac surgeon)…” Previously stated “(cardiologist and cardiac surgeon).” Added “Intermediate risk: Society of Thoracic Surgeons predicted operative risk score of 3% to 7%” to Note 2. References and rationale completely revised.
7/15/2017 Document updated with literature review. Coverage changed for transcatheter aortic valve replacement with a transcatheter heart valve system approved for use for repair of a degenerated bioprosthetic valve may be considered medically necessary when criteria are met. Previously this indication was considered experimental, investigational and/or unproven.
7/1/2016 Reviewed. No changes.
11/1/2015 Document updated with literature review. 1. The following was added to the conditional medically necessary statement: Transcatheter aortic valve replacement, with an FDA-approved transcatheter heart valve system performed via an approach consistent with the device’s FDA-approved labeling may be considered medically necessary when criteria are met. 2. The following additional criteria to define severe aortic stenosis were added to the *NOTE: specific to the SAPIEN or CoreValve device to include an aortic valve area index of less than or equal to 0.6cm 2 /m 2 . The words peak aortic were added to the peak aortic-jet velocity greater than 4.0m/sec criteria and the aortic valve area of less than 0.8 cm 2 was changed to 1 cm 2 . An additional ** NOTE was added to the coverage section to provide FDA guidance related to high risk, extreme risk or inoperable patients for open surgery. The following lists of procedural approaches were removed from the experimental, investigational and/or unproven Coverage statement: Procedures performed via the transaxillary, transiliac, transaortic or other approaches.
3/1/2014 Document updated with literature review. The following was added to the coverage section: 1) “Left ventricular ejection fraction >20%;” and “patients who are operable candidates but are at high risk for open surgery” were added to existing criteria for Transcatheter aortic valve replacement, performed via the transfemoral approach, for patients with aortic stenosis. 2) Transcatheter aortic valve replacement, performed via the transapical approach, may be considered medically necessary for patients with aortic stenosis when additional criteria are met. 3) Transcatheter aortic valve replacement is considered experimental, investigational, and/or unproven for all other indications, including but not limited to: Patients with a degenerated bio-prosthetic valve (“Valve-in-Valve” implantation) or Procedures performed via the transaxillary, transiliac, transaortic, or other approaches. 4) FDA definition of high risk for open surgery was added to the coverage section. CPT/HCPCS code(s) updated.
1/1/2013 Document updated. The following was added under coverage: Transcatheter aortic valve replacement performed via approaches other than transfemoral, including but not limited to the transapical approach for any indication is considered experimental, investigational and unproven. CPT/HCPCS code(s) updated.
10/15/2012 Document updated with literature review. Title changed from “Transcatheter Heart Valve Replacement”. The following was added: Transcatheter aortic valve replacement, performed via the transfemoral approach, may be considered medically necessary for patients with aortic stenosis when stated criteria are present. Transcatheter aortic valve replacement is considered experimental, investigational, and unproven for all other indications, including but not limited to, patients at high risk for open surgery but who are operable candidates. Transcatheter aortic valve replacement performed via the transapical approach for any indication is considered experimental, investigational, and unproven. Transcatheter Pulmonary Valve Implantation was moved from this document to SUR707.029.
6/15/2011 Document updated with literature review. Coverage unchanged. The following was added: Medtronic Melody® Transcatheter Pulmonary Valve (TPV) and Ensemble® Transcatheter Valve Delivery System was added. The number of the policy was changed from SUR717.015 to SUR707.028.
3/1/2011 New Medical Document converted from position statement. Percutaneous heart valve replacement is considered experimental, investigational, and unproven by any method.
1/1/2011 Position Statement. Percutaneous heart valve replacement is considered experimental, investigational, and unproven by any method.

Archived Document(s):

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