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Choice of therapy for symptomatic severe aortic stenosis
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Choice of therapy for symptomatic severe aortic stenosis
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2016. | This topic last updated: Dec 06, 2016.

INTRODUCTION — Aortic valve replacement (AVR) has been the mainstay of treatment of symptomatic severe aortic stenosis (AS). The role of transcatheter aortic valve implantation (TAVI, also known as transcatheter aortic valve replacement or TAVR) as an alternative to surgical aortic valve replacement (SAVR) is established in some patient subsets and evolving in others. A multidisciplinary team approach is recommended in approaching patients with symptomatic AS.    

This topic will review choice of therapy for symptomatic severe AS including SAVR, TAVI, and palliative medical therapy. Estimating the risk of aortic valve surgery, medical therapy of symptomatic AS, percutaneous aortic valvuloplasty, and complications of TAVI are discussed separately. (See "Indications for valve replacement in aortic stenosis in adults" and "Choice of prosthetic heart valve for surgical replacement" and "Estimating the mortality risk of valvular surgery" and "Medical management of symptomatic aortic stenosis" and "Percutaneous balloon aortic valvotomy".)

CHOICE OF THERAPY FOR SYMPTOMATIC AORTIC STENOSIS — For patients with symptomatic severe native aortic valve stenosis, a choice is made between surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI), or no intervention based upon estimated surgical risk and other factors.  

Approach to choosing therapy — For patients with symptomatic severe aortic stenosis (AS), our approach to choice of therapy (SAVR, TAVI, or no valve intervention) involves the following steps:

The first step is to refer the patient for evaluation by a multidisciplinary heart valve team (including a cardiologist with expertise in structural valve interventions and a cardiothoracic surgeon)

The Heart Valve team then assesses the patient’s anticipated life expectancy with SAVR or TAVI and whether the patient’s quality of life is likely to improve with SAVR or TAVI:

If life expectancy with AVR is >1 year and the patient’s quality of life is likely to improve with SAVR or TAVI, the next step is evaluation by the Heart Valve Team of the risk of mortality and morbidity with SAVR (including the Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM]) [1,2].

If life expectancy with SAVR or TAVI is ≤1 year or the patient’s quality of life is unlikely to improve with SAVR or TAVI, palliative therapy with medical management is recommended. (See "Medical management of symptomatic aortic stenosis".)

For patients with extreme surgical risk (≥50 percent probability of death or serious irreversible complication) or with an absolute contraindication to SAVR not captured by STS-PROM, TAVI is recommended rather than medical therapy. Asymptomatic patients with severe AS and prohibitive surgical risk should have frequent clinical evaluation to monitor for symptom onset. (See 'TAVI versus medical therapy in inoperable patients' below.) Examples of absolute contraindications to SAVR include porcelain aorta or hostile chest (ie, chest conditions that make operation through a sternotomy or thoracotomy prohibitively hazardous).

When TAVI is performed, a transfemoral approach when feasible is the access of first choice. (See 'Access site for TAVI' below.)

For patients with symptomatic severe AS with an absolute contraindication to SAVR, TAVI is an approved therapy in extreme-, high-, and intermediate-risk groups. For patients with low surgical risk (as determined by STS-PROM <4) with an absolute contraindication to SAVR, use of TAVI is an off-label use.

For patients at high surgical risk (STS-PROM >8 with <50 percent probability of death), we determine whether transfemoral TAVI is feasible (see "Imaging for transcatheter aortic valve implantation", section on 'Determining eligibility for peripheral vascular access' and "Transcatheter aortic valve implantation: Periprocedural management", section on 'Delivery techniques'):

If yes, then we recommend transfemoral TAVI.

If no, then the Heart Valve Team undertakes an individualized risk-benefit assessment of SAVR versus alternative (non-transfemoral) access TAVI. Factors to consider in the assessment are discussed below. (See 'Individualized risk-benefit assessment' below and 'Access site for TAVI' below.)

In patients with intermediate surgical risk (STS-PROM 4 to 8), we determine whether transfemoral TAVI is feasible (see "Imaging for transcatheter aortic valve implantation", section on 'Determining eligibility for peripheral vascular access' and "Transcatheter aortic valve implantation: Periprocedural management", section on 'Delivery techniques'):

If yes, then the Heart Valve Team should perform an individualized risk-benefit assessment of transfemoral TAVI versus SAVR. Factors to consider in the assessment are discussed below. (See 'Individualized risk-benefit assessment' below.)

If no, then we recommend SAVR. If a relative contraindication to SAVR is present, an individualized risk-benefit assessment of SAVR versus alternative access TAVI is performed. (See 'Individualized risk-benefit assessment' below.)

In patients with low surgical risk (STS-PROM <4), we suggest SAVR. Participation in a clinical trial comparing SAVR with TAVI is a reasonable alternative in this patient population. In patients with a relative contraindication to SAVR, we perform an individualized risk/benefit assessment of SAVR versus off-label TAVI. Among patients treated with TAVI, a transfemoral approach when feasible is preferred to alternative access.

The above approach is similar to that in the 2014 American Heart Association/American College of Cardiology valve guideline (table 1) [2]. Recommendations for TAVI in intermediate-risk patients are based on studies published after those guidelines. (See 'In high-risk symptomatic patients' below.)

Individualized risk-benefit assessment — Decision-making by a multidisciplinary heart valve team should take into consideration a patient’s life expectancy, frailty, comorbidities, specific anatomy, values, and preferences. An individualized risk-benefit assessment of SAVR versus TAVI is performed in the following clinical settings:

For patients with high surgical risk who are not candidates for transfemoral TAVI, an individualized risk-benefit analysis is performed comparing SAVR and alternative access TAVI.

For patients with intermediate surgical risk who are candidates for transfemoral TAVI, an individualized risk-benefit analysis is performed comparing transfemoral TAVI versus SAVR.

For patients with low surgical risk who have a relative contraindications for SAVR, an individualized risk-benefit analysis is performed comparing off-label TAVI versus SAVR. Transfemoral TAVI when feasible is preferred to alternative access TAVI.

A key issue influencing the choice of TAVI versus SAVR is lack of data on very long-term outcomes with TAVI. Clinical factors influencing the choice between TAVI and SAVR include the patient’s values and preferences, age, estimated life expectancy with AVR, as well as presence of concurrent conditions.

Factors that favor SAVR include presence of another indication for cardiac surgery (eg, need for coronary artery bypass graft or mitral valve surgery), patient age <75 years old, patient characteristics favoring mechanical valve replacement (eg, age <65 with long life-expectancy, and absence of contraindications for anticoagulation), as well as anatomic risk factors such as severe left ventricular outflow calcification or severely calcified bicuspid valve. Mechanical valves can be implanted only surgically. Factors that favor mechanical valve replacement include age <65, long life-expectancy, and absence of contraindication for anticoagulation. (See "Choice of prosthetic heart valve for surgical replacement", section on 'Recommendations for valve choice'.)

Factors that favor TAVI include patient age ≥75 years and presence of risk factors for SAVR (such as frailty, prior mediastinal irradiation, or cirrhosis) not captured by the STS-PROM score. As discussed above, for patients with high surgical risk (STS-PROM score >8 but < 50 percent probability of death), the feasibility of transfemoral TAVI is a major factor favoring proceeding with TAVI. The feasibility of TAVI is also a factor favoring TAVI in patients with intermediate surgical risk (STS-PROM score 4 to 8).

Although women experience more major bleeding and vascular complications with TAVI, female sex is an independent predictor of lower mortality after TAVI compared with women undergoing surgery (as well as compared with men undergoing TAVI). Thus, sex-specific mortality risk following TAVI is opposite of that following SAVR, for which women have higher mortality risk than men. We suggest including female sex as a factor since a mortality benefit has been observed with TAVI versus SAVR among women with intermediate to high surgical risk. (See 'Sex-specific differences in outcomes' below.)        

Access site for TAVI — As TAVI technology has evolved, nearly all (>95 percent) of cases can be performed via transfemoral access; alternative (nontransfemoral) sites are predominantly subclavian or direct aortic, transapical, and least commonly transcarotid. When transfemoral access for TAVI is feasible, it is preferred to alternative access, since there is greater experience with transfemoral access and reported outcomes are superior with transfemoral access. Furthermore, the benefits of TAVI over surgery in the PARTNER 2 Trial and United States Pivotal Trial were greatest in the transfemoral cohorts. However, it is unclear how much of the excess mortality seen in patients undergoing alternative access TAVI is caused by the alternative access procedure per se and how much is caused by excess risk associated with the burden of peripheral vascular disease, mandating the need for alternative access. (See 'By access site' below.)

Preprocedural assessment for TAVI includes assessment of the iliofemoral system and aorta, generally by multidetector computed tomography with optional invasive angiography to detect contraindications to vascular (transfemoral, subclavian, or aortic) access such as plaques with mobile thrombi in the ascending aorta or arch, or inadequate vessel size or extensive calcification or tortuosity. For the transapical approach, severe pulmonary disease, severe left ventricular disease, or other conditions may render the left ventricular apex inaccessible. Extensive ascending aortic calcification is an infrequent contraindication to the direct aortic approach, as a soft spot for catheter entry can usually be found.

SURGICAL RISK ASSESSMENT

Estimation of risk — Operative risk assessment (including identification of high and prohibitive risk) includes consideration of estimated operative mortality, frailty, compromised major organ system, and comorbidities (table 2). Accurate estimation of the risk of surgical aortic valve replacement (SAVR) performed by an experienced cardiothoracic surgeon and multidisciplinary valve team is vital to appropriate evaluation of potential candidates. Risk assessment for valvular surgery is discussed further separately. (See "Estimating the mortality risk of valvular surgery".)

Contraindications to SAVR — SAVR is not a treatment option in patients with extreme surgical risk (ie, ≥50 percent probability of death or serious irreversible complication) or with an absolute contraindication not captured by Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM).

Absolute contraindications not captured by STS-PROM include "porcelain aorta" (heavy circumferential calcification or severe atheromatous plaques of the entire ascending aorta extending to the arch such that aortic cross-clamping is not feasible) and hostile chest (chest conditions such as severe radiation damage or complications from prior surgery that make operation through sternotomy or thoracotomy prohibitively hazardous [3].

Relative contraindications not captured by STS-PROM include frailty, severe liver disease/cirrhosis, prior coronary artery bypass graft surgery with vulnerable graft location as assessed by computed tomography, and severe pulmonary hypertension or severe right ventricular dysfunction [3].

CONTRAINDICATIONS TO TAVI — Patients with a number of conditions are generally excluded from transcatheter aortic valve replacement (TAVI) [4,5].

Absolute contraindications include the following clinical issues:

Estimated life expectancy <12 months due to noncardiac comorbid conditions.

Improvement of quality of life by TAVI unlikely because of comorbidities.

Severe other valve disease with major contribution to the patient’s symptoms if treatable only by surgery.

Additional absolute contraindications are related to anatomic issues and clinical conditions:

Inadequate annulus size: Native aortic annulus size as measured by multidetector computed tomography (MDCT) is <18 mm (for a native valve), <17 mm (for a surgical valve), or >the largest annulus size for which a TAVI device is available (30 mm). This criterion is subject to change as the range of available device sizes changes. In clinical practice, inability to select an appropriate valve due to size issues is a very rare event.

Note that valve size numbers do not correspond to actual annular measurements. Deciding which size valve to select for a given manufacturer is complex and is made using MDCT imaging area and perimeter measurements, with different metrics preferred for different valve types.

Active endocarditis.

Recent thrombus.

Elevated risk of coronary ostium obstruction (asymmetric valve calcification, short distance between annulus and coronary ostium, small aortic sinuses). (See "Imaging for transcatheter aortic valve implantation", section on 'Coronary ostia'.)

Relative contraindications include the following:

Noncalcified aortic valves

Evidence (such as creatine kinase [CK] plus CK-MB elevation and/or troponin elevation) of an acute myocardial infarction within one month before the intended treatment.

Untreated coronary artery disease requiring revascularization, particularly if coronary artery bypass graft surgery is deemed necessary.

Hemodynamic instability requiring inotropic support, or mechanical heart assistance within 30 days of screening evaluation.

Respiratory instability requiring mechanical ventilation within 30 days of screening evaluation.

Need for emergency surgery.

Hypertrophic cardiomyopathy with or without obstruction.

Severe pulmonary hypertension and right ventricular dysfunction.

A known contraindication or hypersensitivity to all anticoagulation regimens or inability to be anticoagulated for the study procedure.

Echocardiographic evidence of intracardiac mass, chronic thrombus, or vegetation

While a congenitally bicuspid aortic valve was previously considered an exclusion criterion for TAVI, TAVI has been successfully performed in many patients with this disorder, as discussed separately. Once severe calcific stenosis is present, reliable identification of the number of valve leaflets is problematic, so it is likely that TAVI has been performed in many patients with a congenital bicuspid valve. (See "Management of adults with bicuspid aortic valve disease", section on 'Transcatheter aortic valve implantation'.)

Contraindications to particular access sites are discussed above. (See 'Access site for TAVI' above.)

SELECTION OF TAVI VALVE TYPE

Patient-specific considerations — For the majority of patients undergoing transcatheter aortic valve replacement (TAVI), either a Edwards Sapien 3, CoreValve EvolutR, LOTUS, or one of the later generation devices are suitable. For patients treated at a center having sufficient experience with and access to many types of valves, there are certain patient-specific issues that might influence the choice of valve system type:

Most valves types, but not all, cover the full range of annulus size.  

In a patient deemed to be at high risk of annulus rupture (eg, a patient with a small highly calcified annulus), a self-expanding rather than a balloon-expandable valve may be chosen to reduce the risk of annular rupture (as one of several potential strategies to attempt to reduce the risk of rupture). Annular rupture has been observed almost exclusively after use of a balloon-expandable valve and very rarely after use of a self-expandable valve [6]. (See "Transcatheter aortic valve implantation: Overview of complications", section on 'Annular rupture'.)

If there are concerns about coronary obstruction, then a valve system with recapturable technology may be favored.

When performing a valve-in-valve procedure to treat a small surgical bioprosthetic valve, a supra-annular TAVI valve might offer greater effective orifice area.

If there is a spur of asymmetric calcification protruding into the outflow tract, then choice of a valve with external sealing skirt may be preferable

Center-specific considerations — Operators have generally selected the type of TAVI valve to implant based upon local practice, operator training, medical center experience, and availability (based upon the regulatory approval status) rather than specific patient-related factors. Individual center procedure volume is an important factor in establishing and maintaining optimum patient outcomes. As a consequence, many centers have acquired experience with three or less valve systems. While this situation is changing, particularly in countries where there are multiple approved devices, maintenance of sufficient experience with each device used continues to be important for optimum patient outcomes. The differences in patient selection and procedural steps among competing device types are greater for various TAVI systems than for most other interventional cardiovascular procedures.

Regulatory status — Regulatory approvals govern the availability of TAVI technologies.  

United States Food and Drug Administration approvals include the following:

The Edwards SAPIEN XT and SAPIEN 3 (balloon-expandable) and the Medtronic CoreValve and CoreValve Evolut R (self-expanding) systems are approved for patients with symptomatic severe native calcific aortic stenosis who are judged by a heart valve team, including a cardiothoracic surgeon, to be at high or greater risk for open surgical therapy (ie, Society of Thoracic Surgeons operative risk score ≥8 percent or are judged by the heart team to be at a ≥15 percent risk of mortality at 30 days).

The Edwards SAPIEN XT, Medtronic CoreValve and CoreValve Evolut R are also approved for patients with failure (stenosis, regurgitation, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart valve team, including a cardiothoracic surgeon, to be at high or greater risk for open surgical therapy (ie, Society of Thoracic Surgeons operative risk score ≥8 percent or at a ≥15 percent risk of mortality at 30 days).

A number of TAVI systems have CE mark approval:

The following devices are approved for use in Europe in patients with severe aortic stenosis at high or greater risk for surgical valve replacement: Medtronic CoreValve, Edwards SAPIEN, Direct Flow Medical (fully repositionable), St. Jude Medical Portico (repositionable prior to deployment), Medtronic Engager (transapical), Boston Scientific Lotus (repositionable prior to deployment), Medtronic Evolut R (self-expanding and repositionable prior to deployment), and SAPIEN 3 are approved for patients with severe aortic stenosis with high or greater risk for open surgical valve replacement. The Evolut R valve is also approved for use in Europe in patients with severe aortic stenosis at intermediate risk for surgical valve replacement.

The CoreValve and CoreValve Evolut R, and the Sapien XT valve are approved for valve-in-valve use in patients with high or greater risk for open surgical valve replacement.  

EVIDENCE — Transcatheter aortic valve replacement (TAVI) techniques are rapidly evolving, and results of published trials support the use of TAVI as the standard of care in certain patient subsets, and as a viable alternative to surgery in others. (See 'Approach to choosing therapy' above.)

For patients with symptomatic severe aortic stenosis (AS), comparisons between surgical aortic valve replacement (SAVR) m and TAVI are grouped according to surgical risk as described below.

A systematic review evaluated the effect of TAVI on functional status and quality of life in 60 observational studies (56 pre-post comparisons and four head-to-head comparative studies) and two randomized controlled trials [7]. The review found that TAVI improved physical function at 12 months and New York Heart Association class at 6 to 11 months and at 12 to 23 months. A limitation of this analysis is that there were few head-to-head studies, and survivor bias may cause overestimation of the benefits.

A systematic review found very limited evidence on the values and preferences of adults with AS [1]. The available evidence suggested considerable variability in individual values and preferences, which highlights the importance of shared-decision making.

TAVI versus medical therapy in inoperable patients — Evidence of a benefit of balloon-expandable TAVI compared with standard medical care for AS was provided by the Placement of Aortic Transcatheter Valves (PARTNER) multicenter trial (cohort B) [8-11]. The investigators randomly assigned 358 patients with severe AS who were not considered surgical candidates to either standard therapy (including balloon aortic valvotomy (see "Percutaneous balloon aortic valvotomy") or TAVI with an Edwards SAPIEN valve via transfemoral approach. The mean age was 83 years and the mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) was 11.7 percent. The two treatment groups were similar, although the logistic EuroSCORE was slightly lower in the TAVI group (mean 26.4 versus 30.4). (See "Estimating the mortality risk of valvular surgery".)

The following findings were noted:

At one year, the mortality rate was reduced with TAVI compared with standard therapy, including balloon aortic valvotomy (30.7 versus 50.7 percent). At two years, the mortality rates for TAVI and standard therapy were 43.4 and 68 percent; at three years, the mortality rates were 54.1 percent and 80.9 percent, and at five years, the mortality rates were 71.8 and 93.6 percent.

Among survivors at one, two, three, and five years, functional class was better with TAVI versus standard therapy (eg, 86 versus 60 percent in New York Heart Association functional class I or II at five years).

The stroke rate was significantly higher in the TAVI group than in the standard therapy group at 30 days (6.7 versus 1.7 percent), at two years (13.8 versus 5.5 percent), and three years (15.7 versus 5.5 percent). At five years, the risk of stroke was similar in the TAVI and standard therapy groups (16 versus 18.2 percent). A competing risk analysis showed no continuous hazard of stroke associated with TAVI after the initial procedural risk [11].

In the standard therapy group, balloon aortic valvotomy was performed in 82.3 percent at one year and in 85.3 percent at two years. Moderate or severe transvalvular aortic regurgitation was observed in 16.9 percent at 30 days and 15.2 percent at one year.  

In the TAVI group, moderate or severe paravalvular aortic regurgitation was identified in 12.4 percent at 30 days, in 8.8 percent at one year, and in 4.5 percent at three years.

Given the results of the PARTNER cohort B study, it was determined that a randomized trial comparing self-expanding TAVI and medical therapy could not be performed. The CoreValve Extreme Risk United States Pivotal Trial, a prospective single-arm study, compared TAVI with the self-expanding CoreValve to a pre-specified estimate of 12-month mortality or major stroke with medical therapy (43 percent, based upon results of a meta-analysis and data from the PARTNER cohort B) [12].

For the 489 patients (mean age 83 years; mean STS-PROM 10.3) who underwent attempted treatment with the CoreValve transcatheter heart valve, the rate of all-cause mortality or major stroke at 12 months was 26 percent, which was significantly lower than the prespecified performance goal of 43 percent.

Procedural events at 30 days included life-threatening/disabling bleeding in 12.7 percent, major vascular complications in 8.2 percent, and need for permanent pacemaker placement in 21.6 percent.

TAVI versus SAVR — While individual trials have targeted specific surgical risk groups, meta-analyses have pooled these groups to examine pooled outcomes and subgroup differences. A meta-analysis included four trials (the largest trial with 2032 intermediate-risk patients, two studies with 699 and 795 high-risk patients, and one study with 280 low-risk patients) to assess outcomes at two years [13].

Mortality was reduced with TAVI as compared with SAVR (hazard ratio [HR] 0.87, 95% CI 0.76 to 0.99) with homogeneity across the trials. The mortality reduction with TAVI versus SAVR was robust among patients undergoing transfemoral TAVI (HR 0.80, 95% CI 0.69 to 0.93) but not present among patients undergoing transthoracic TAVI. Similarly, there was a borderline significant interaction for sex (p = 0.05), with a significant mortality reduction with TAVI versus SAVR among women (HR 0.68, 95% CI 0.50 to 0.91) but not among men (HR 0.99, 95% CI 0.77 to 1.28).

Acute kidney injury, new-onset atrial fibrillation, and major bleeding were less frequent with TAVI while major vascular complications, incidence of permanent pacemaker implantation, and paravalvular regurgitation were less frequent with SAVR.

In high-risk symptomatic patients — In the above described meta-analysis in which nearly all patients had intermediate to high surgical risk, transfemoral TAVI (but not transthoracic TAVI) was associated with lower mortality than SAVR [13]. A randomized trial found similar mortality rates at five years in high-risk patients with AS after balloon-expandable TAVI and SAVR [14,15]. In contrast, another randomized trial found a lower mortality rate at one year following self-expanding TAVI compared with surgical valve replacement in high-risk patients with AS [16]. Since data are not convincing that outcomes are different with different types of transcatheter heart valves, TAVI (with either balloon-expandable or self-expanding valve) is recommended for high-risk patients who are candidates for a transfemoral approach. (See 'Approach to choosing therapy' above.)

As noted above, a randomized trial comparing balloon-expandable TAVI with SAVR found similar mortality rates in the two treatment arms but there were higher rates of moderate to severe aortic regurgitation following TAVI [14,15,17]. The 699 patients in cohort A of the PARTNER trial were randomly assigned to undergo either balloon-expandable TAVI (by transfemoral or transapical approach) or SAVR. The mean age was 84 years and the mean STS-PROM was 11.7 percent. The following findings were noted:

Mortality rates in the TAVI and surgical group were similar at 30 days (3.4 and 6.5 percent, p = 0.07), one year (24.3 and 26.8 percent), two years (33.9 and 35 percent), and five years (67.8 and 62.4 percent).

Combined strokes and transient ischemic attacks were more frequent after TAVI than after SAVR at 30 days (5.5 versus 2.4 percent, p = 0.04) and at one year (8.7 versus 4.3 percent, p = 0.04) with a borderline significant difference at two years (11.2 versus 6.5 percent, p = 0.05) and no significant difference at five years (15.9 versus 14.7 percent).

More patients undergoing TAVI reported symptom improvement at 30 days, but at one year, symptom improvement was similar in the two groups.

Differences in other 30-day adverse event rates were also observed:

TAVI was associated with more frequent major vascular complications (11 versus 3.2 percent).

SAVR was associated with more frequent major bleeding (19.5 versus 9.3 percent) and new-onset atrial fibrillation (16 versus 8.6 percent).

Moderate or severe paravalvular aortic regurgitation was more frequent after TAVI than after surgery at 30 days, one, and two years (6.9 versus 0.9 percent at two years; 14 versus 1 percent at five years). The presence of paravalvular aortic regurgitation was associated with increased late mortality as discussed below. (See "Transcatheter aortic valve implantation: Overview of complications", section on 'Paravalvular regurgitation'.)

As noted above, a randomized trial comparing self-expanding TAVI with SAVR found a lower mortality rate in patients undergoing TAVI. In the United States CoreValve High Risk Study, 795 patients with severe AS with high estimated surgical risk were randomly assigned to self-expanding TAVI or SAVR [16]. The mean age was 83.2 years and the mean STS-PROM was 7.4 percent.

Mortality rate at one year was lower in the TAVI group than in the surgical group (14.2 versus 19.1 percent).

Major vascular complications, cardiac perforation, and permanent pacemaker implantation were more frequent after TAVI. Life-threatening or disabling bleeding, acute kidney injury, and new-onset or worsening atrial fibrillation were more frequent after surgery.

TAVI was noninferior to surgical therapy with respect to echocardiographic indices of valve stenosis, functional status, and quality of life at one year.

Exploratory analyses suggested a reduced rate of major adverse cardiovascular and cerebrovascular events at one year and no increase in risk of stroke at one year with TAVI.

In intermediate-risk patients — A meta-analysis of four randomized trials with 3179 patients with severe AS (nearly all symptomatic) at predominantly intermediate risk of perioperative death examined the effect of TAVI versus SAVR on outcomes at median follow-up of two years [18]. The included trials were the PARTNER 2A, US Pivotal, NOTION, and STACCATO trials [16,19-21]. Baseline risk estimates were derived from a systematic review of observational studies of bioprosthetic SAVR [22].

Transfemoral TAVI compared with SAVR resulted in reduced mortality (HR 0.79, 95% CI 0.88-0.94; 30 fewer per 1000 patients) and reduced acute kidney injury (relative risk [RR] 0.38, 95% CI 0.27-0.53, 53 fewer per 1000 patients). The point estimate for stroke also suggested a benefit for transfemoral TAVI compared with SAVR but the confidence interval overlapped no effect (RR 0.80, 95% CI 0.61-1.01, 20 fewer per 1000 patients).

TAVI compared with SAVR resulted in reduced atrial fibrillation and major bleeding, with greater reductions in bleeding among patients undergoing transfemoral TAVI versus transapical TAVI.  

In contrast, TAVI compared with SAVR resulted in more frequent worsened symptoms of heart failure (one point worse on New York Heart Association scale; odds ratio 1.29, 95% CI 1.08-1.55, 59 more per 1000 patients), aortic valve re-intervention (RR 3.25; 95% CI 1.29-8.14, 7 more per 1000 patients), permanent pacemaker insertion (RR 2.45, 95% CI 1.17-5.14, 134 more per 1000 patients) , and moderate or severe aortic valve regurgitation (RR 12.22, 95% CI 5.17-28.88, 80 more per 1000 patients).

For alternative (nontransfemoral) access TAVI compared with SAVR, the point estimates suggested increased mortality (HR 1.34, 95% CI 0.91-1.97, 57 more per 1000 patients) and stroke (HR 1.67, 95% CI 0.97-2.87, 45 more per 1000) but the confidence intervals overlapped with no effect.  

Limitations of the meta-analysis include use of only bioprosthetic valves for SAVR in the included trials and the limited duration of follow-up. In addition, the transthoracic component of the meta-analysis pooled data from the STACCATO trial (comparing transapical TAVI with SAVR) with the transthoracic subgroup of the PARTNER 2A trial. The STACCATO trial has been criticized since it was not limited to patients requiring alternative access, preprocedural multidetector computed tomography (MDCT) was not performed (unlike PARTNER 2A and current clinical practice), the device success rate was unusually low (79 percent) compared with rates seen in higher-risk patients, and the rate of adverse events was unusually high, which triggered early termination of the study [21]. In addition, the transapical route is now far less commonly used than other (subclavian and transaortic) alternatives to the transfemoral route.

The largest trial included in the meta-analysis is the PARTNER 2A trial, which randomly assigned 2032 intermediate-risk patients with severe AS to undergo either TAVI (with a balloon-expandable valve) or SAVR [19]. The mean STS-PROM score was 5.8. Prior to randomization, patients were separated into two cohorts on the basis of an evaluation of the peripheral arteries: 76.3 percent were included in the transfemoral-access cohort and 23.7 percent were included in the transthoracic-access (transapical or transaortic) cohort.

The rate of death from any cause or disabling stroke was similar in the TAVI and SAVR groups. At two years, the Kaplan-Meier event rates were similar: 19.3 percent in the TAVI group and 21.1 percent in the SAVR group.

In the transfemoral-access cohort, TAVI resulted in a lower event rate than SAVR (HR 0.79; 95% CI 0.62-1.00).

In the transthoracic-access cohort, outcomes were similar in the TAVI and SAVR groups (HR 1.21; 95% CI 0.79-1.65).

TAVI resulted in larger aortic valve areas (mean 1.7 versus 1.5 cm2 at 30 days) and lower 30-day rates of acute kidney injury (1.3 versus 3.1 percent), severe bleeding (10.4 versus 43.4 percent), and new onset atrial fibrillation (9.1 versus 26.4 percent).

SAVR resulted in less paravalvular aortic regurgitation (moderate or severe in 0.6 versus 3.7 percent at 30 days) and lower rates of major vascular complications (5 versus 7.9 percent at 30 days). Patients in the TAVI group with moderate or severe paravalvular aortic regurgitation at 30 days had higher mortality during two-year follow-up than did patients with no or trace aortic regurgitation.

An observational study suggested that TAVI with a balloon-expandable SAPIEN XT valve may be superior to SAVR for intermediate-risk patients [23]. The study included 1077 patients with symptomatic severe AS with intermediate-risk (STS-PROM score generally ≥4 percent; mean 5.2 percent) who underwent TAVI with a SAPIEN 3 valve. TAVI was performed via the transfemoral route in 88 percent of patients. Outcomes were compared with those for 944 patients in the SAVR arm of the PARTNER 2A randomized trial using a prespecified propensity score analysis. However, it is possible that residual confounders could have influenced the results.

At one-year follow-up, all-cause mortality for the TAVI group was 7.4 percent (6.5 percent in the transfemoral access subgroup). Complications included disabling stroke (in 2 percent), aortic valve re-intervention (in 1 percent), and moderate or severe paravalvular regurgitation (in 2 percent).

The primary composite end point was death from any cause, all strokes, and incidence of moderate or severe aortic regurgitation. TAVI was superior to SAVR for the composite end point, as well as for the individual outcomes of death and stroke. Surgery was superior to TAVI in causing less frequent moderate or severe aortic regurgitation.  

In low-risk symptomatic patients — Limited data are available on the best strategy for valve replacement in patients with severe AS with low surgical risk. The NOTION trial was the only trial with predominantly low surgical risk patients included in the above described meta-analysis. Other randomized trials in patients with low surgical risk are in progress.

The NOTION trial was small and not fully reflective of the population of low surgical risk patients with AS; thus, it is insufficient to establish the noninferiority of TAVI compared with SAVR. The Nordic Aortic Valve Intervention Trial (NOTION) randomly assigned 280 patients with severe AS with low and intermediate surgical risk to receive a self-expanding TAVI or SAVR [20]. Most (81.8 percent) of the patients were considered low risk and the mean STS-PROM was 3. However, the minimum age was 70 years old with mean age of 79, so the trial population was not fully representative of a low-risk population. The composite primary outcome (death from any cause, stroke, or myocardial infarction at one year) and its components were similar in the two groups (13.1 versus 16.3 percent for the composite outcome). TAVI patients had larger improvements in effective orifice area but more frequently required pacemaker implantation, had more aortic valve regurgitation, and worse New York Heart Association functional class at one year. SAVR-treated patients had more major bleeding, cardiogenic shock, acute kidney injury, and new-onset or worsening atrial fibrillation.

By access site — As described above, subgroup analyses of meta-analyses and individual trials indicate that patients undergoing transfemoral TAVI have better outcomes than patients undergoing alternative (nontransfemoral) access TAVI. As an additional example, a meta-analysis of 27 observational studies and one randomized trial with a total of 17,020 patients undergoing TAVI found that 30-day mortality was 4.7 percent with the transfemoral approach and 8.1 percent with an alternative approach [24]. One-year mortality was 16.4 percent with transfemoral access and 24.8 percent with nontransfemoral access. Transfemoral access was associated with a higher rate of vascular complications (OR 2.1; 5% CI 1.48-2.99) but a lower rate of surgical conversion (OR 0.59; 95% CI 0.42-0.81), while rates of bleeding and cerebrovascular events were similar to those with alternative access. However, the available data are not adequate to determine how much of the excess mortality seen in patients undergoing alternative access TAVI is caused by the alternative access procedure and how much is caused by excess comorbidity associated with the need for alternative access.

Balloon-expandable versus self-expanding valves for aortic stenosis — Data directly comparing clinical outcomes in patients with AS treated with balloon-expandable versus self-expanding valves are limited and a direct comparison of long-term clinical outcomes is not available.

The randomized CHOICE trial in 241 high-risk patients with AS found that procedural success was more frequent with a balloon-expandable Edwards SAPIEN XT valve compared with a self-expanding CoreValve [25] but one-year clinical outcomes were not significantly different [26]. However, these results are no longer relevant, since both tested valve have been superseded by later designs (SAPIEN 3 and EvolutR).

Further study, including an adequately powered study with current valve designs with long-term outcomes, is needed to compare balloon- and self-expanding valve types. As discussed below, observational studies of long-term outcomes have not found a significant difference related to device type (eg, United Kingdom registry discussed below). (See 'Data from registries' below.).

Data from registries — Additional information on outcomes following TAVI come from registry studies. Reports from the Society of Thoracic Surgeons/American College of Cardiology registry, the United Kingdom Transcatheter Aortic Valve Implantation registry, and the German Aortic Valve Registry (GARY) have included the following outcome data for patients with intermediate to high median risk (ie, STS-PROM 7.1 [27] or 5 [28] or logistic Euroscore 18.5 [29,30]):

Early mortality rates of 5.2 percent in-hospital [28] and 7 percent at 30 days [27,29].

In-hospital stroke rates were 1.9 and 4.1 percent in two of these studies [27,29].

One-year mortality rates were 23.7 and 21.4 percent in two of these studies [27,30].

In the United Kingdom registry, mortality at two, three, and five years was 26.3, 38.8, and 54.5 percent [29,30].

In the United Kingdom registry, stroke within 30 days of TAVI was the only independent procedural predictor of mortality at three and five years [29]. Independent predictors of three-year mortality were renal dysfunction, atrial fibrillation, respiratory dysfunction, and ventricular dysfunction. Coronary artery disease and age were independent predictors of mortality at five years. Device type, access route, and paravalvular leak did not independently predict long-term outcome.

Sex-specific differences in outcomes — Although women experience more major bleeding and vascular complications, female sex is an independent predictor of lower one-year mortality after TAVI. Thus, sex-specific mortality risk following TAVI is opposite of that following SAVR, for which women have higher mortality risk than men. We suggest including female sex as a factor when weighing the potential risks and benefits of TAVI versus SAVR, since the data suggest that TAVI as superior to SAVR for women with high-risk symptomatic AS.      

In the above described four trial meta-analysis with predominantly intermediate- to high-risk patients, there was a borderline significant interaction for sex (p = 0.05), with a significant mortality reduction with TAVI versus SAVR among women (HR 0.68, 95% CI 0.50-0.91) but not among men (HR 0.99, 95% CI 0.77-1.28) [13].

A patient-level meta-analysis that included five studies with a total of 11,310 patients evaluated sex-specific outcomes [31]. Following TAVI, women had higher rates of major vascular complications, major bleeding events, and stroke but a lower rate of moderate or greater aortic regurgitation. Thirty-day mortality rates were similar in women and men (6.5 percent for both) but female sex was an independent predictor of reduced mortality at follow-up at a median of 387 days (adjusted HR 0.79; 95% CI 0.73-0.86).

The largest single study of sex-specific outcomes included 2559 high-risk and inoperable patients with AS undergoing TAVI in the randomized and nonrandomized portions of the PARTNER trial [32]. Although women had lower baseline rates of hyperlipidemia, diabetes mellitus, smoking, and renal disease, they had significantly higher STS-PROM scores (11.9 versus 11.1 percent). Following TAVI, women had higher rates of vascular complications (17.3 versus 10 percent) and major bleeding (10.5 versus 7.7 percent) but less frequent moderate or greater paravalvular regurgitation (6 versus 14.3 percent). Thirty-day mortality rates were similar in women and men (6.5 versus 5.9 percent) but the one-year mortality rate was significantly lower in women (19 versus 24.9 percent). In multivariable analyses adjusting for baseline factors and for procedural complications, female sex was independently associated with lower one-year mortality.

A subgroup analysis of cohort A of the PARTNER trial (high-risk symptomatic AS patients randomly assigned to TAVI or SAVR) found that women had lower mortality rates with TAVI compared with SAVR at six months and two-year follow-up, driven by the transfemoral arm [33]. These differences in six-month and two-year mortality rates were not observed in men.

SUMMARY AND RECOMMENDATIONS

Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are the mainstay of treatment of symptomatic aortic stenosis (AS), as they improve symptoms and prolong survival. SAVR or TAVI are not indicated in patients with comorbidities that would preclude an expected benefit from correction of AS. (See 'Approach to choosing therapy' above.)

A multidisciplinary heart valve team (including cardiologists, structural valve interventionalists, cardiovascular surgeons, anesthesiologists, and nurses) should collaborate to optimize care for patients with symptomatic severe AS. The heart valve team should assess an individual patient’s life expectancy, frailty, comorbidities, specific anatomy, values, and preferences. (See 'Approach to choosing therapy' above and 'Individualized risk-benefit assessment' above.)

If life expectancy with SAVR or TAVI is ≤1 year or the patient’s quality of life is unlikely to improve with SAVR or TAVI, palliative therapy with medical management is recommended. (See 'Approach to choosing therapy' above and "Medical management of symptomatic aortic stenosis".)

If life expectancy with AVR is >1 year and the patient’s quality of life is likely to improve with SAVR or TAVI, the next step is evaluation by the Heart Valve Team of the risk of mortality and morbidity with SAVR (including the Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] and identification of contraindications to SAVR) (See 'Approach to choosing therapy' above.)  

For patients with symptomatic severe AS, an extreme surgical risk (≥50 percent probability of death or serious irreversible complication) or an absolute contraindication to SAVR, we recommend TAVI rather than medical therapy (Grade 1B). (See 'TAVI versus medical therapy in inoperable patients' above.)

For patients with symptomatic severe AS with high surgical risk (ie, STS-PROM>8 with <50 percent probability of death), we recommend transfemoral TAVI when feasible (Grade 1B). When transfemoral TAVI is not feasible, the Heart Valve Team should perform an individualized risk-benefit assessment of SAVR versus alternative access TAVI. (See 'In high-risk symptomatic patients' above.)

For patients with symptomatic severe AS with intermediate surgical risk (ie, STS-PROM 4 to 8), if transfemoral TAVI is feasible, the Heart Valve Team should perform an individualized risk-benefit assessment of SAVR versus transfemoral TAVI. (See 'In intermediate-risk patients' above.).

Individualized risk-benefit assessment of SAVR versus TAVI includes consideration of multiple factors that may occur in combination. As examples, factors that suggest SAVR may be more appropriate include other indications for surgery, lack of femoral access, and younger age (longer life expectancy), while factors that suggest that TAVI may be more appropriate include relative contraindications for surgery and older age (shorter life expectancy). (See 'Individualized risk-benefit assessment' above.)

For patients with symptomatic severe AS with intermediate surgical risk (ie, STS-PROM 4 to 8), if transfemoral TAVI is not feasible, we recommend SAVR rather than TAVI (Grade 1B). In patients with a relative contraindication to SAVR not captured by STS-PROM, an individualized risk-benefit assessment of SAVR versus alternate access TAVI is performed. (See 'In intermediate-risk patients' above.).

For patients with symptomatic severe AS with low surgical risk (ie, STS-PROM <4), we suggest SAVR rather than TAVI (Grade 2C). (See 'In low-risk symptomatic patients' above.)

Data directly comparing clinical outcomes with balloon-expandable and self-expanding valve are limited. Further study, including an adequately powered study with long-term outcomes, is needed to compare balloon- and self-expanding valve types. (See 'Balloon-expandable versus self-expanding valves for aortic stenosis' above.)

The long-term durability of transcatheter bioprosthetic valves is not yet known. (See 'Evidence' above.)

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