Transcatheter Aortic Valve Implantation

Number: 0826

Policy

1. Aetna considers transcatheter aortic valve implantation (TAVI) by means of a Food and Drug Administration (FDA)-approved aortic valve (e.g., the Edwards Sapien 3, Edwards Sapien XT, Edwards Sapien transcatheter heart valve, Medtronic CoreValve System) medically necessary for persons with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with an ejection fraction greater than 20 % who are inoperable for open aortic valve replacement and in whom existing co-morbidities would not preclude the expected benefit from correction of the aortic stenosis.

2. Aetna considers TAVI by means of an FDA-approved aortic valve (e.g., the Edwards Sapien 3, Edwards Sapien XT, Edwards Sapien transcatheter heart valve, Medtronic CoreValve System) medically necessary for:

1. persons with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with an ejection fraction greater than 20 % who are operative candidates for aortic valve replacement but who have a Society of Thoracic Surgeons operative risk score (see Appendix) greater than or equal to 8 % or are judged to be at 15 % or greater risk of mortality for surgical aortic valve replacement; and
2. persons with aortic valve stenosis who are determined to be at low-risk for death and complications with open-heart surgery.

3. Aetna considers TAVI by means of an FDA-approved aortic valve (e.g., Medtronic CoreValve System, and the Sapien 3) medically necessary for valve-in-valve replacement for persons with a degenerated bioprosthetic aortic valve who require another valve replacement procedure but who have a Society of Thoracic Surgeons operative risk score (see Appendix) greater than or equal to 8 % or are judged to be at 15 % or greater risk of mortality for surgical aortic valve replacement.

4. Aetna considers TAVI experimental and investigational for persons with aortic stenosis that can be safely treated by open-heart surgery, for persons with ongoing sepsis including endocarditis, and for all other indications (e.g., bicuspid aortic stenosis, native aortic valve regurgitation, and porcelain aorta; not an all-inclusive list) because its effectiveness for indications other than the one listed above has not been established.

5. Aetna considers combination of TAVI and left atrial appendage occlusion experimental and investigational because the effectiveness of this approach has not been established.

6. Aetna considers TAVI with pre-implantation balloon aortic valvuloplasty experimental and investigational because the effectiveness of this approach has not been established.

7. Aetna considers the use of embolic protection devices during TAVI experimental and investigational because the effectiveness of this approach has not been established.

See also CPB 0791 - Cardiac Devices and Procedures for Occlusion of the Left Atrial Appendage.

Background

Aortic stenosis is the most commonly acquired valvular heart disease in the Western countries.  Without surgery, the prognosis is extremely poor; with a 3-year survival rate of less than 30 %.  For symptomatic patients with severe aortic valve stenosis, the open heart approach for surgical aortic valve replacement (SAVR) is currently the gold standard treatment.  Cumulative surgical experience and technical advent have led to excellent peri-operative results with low morbidity and mortality.  Long-term results are convincing, and even in octogenarians, SAVR is feasible with acceptable results.  However, in very old patients with many co-morbidities, the outcome is less favorable, and many of these patients may be inoperable or carry an unacceptably high peri-operative risk. 

Examples of U.S. Food and Drug Administration (FDA) approved transcatheter aortic valves include the Edwards Sapien transcatheter heart valve, the Edwards Sapien XT transcatheter heart valve and the Medtronic CoreValve system. They are indicated for percutaneous aortic valve implantation in individuals with severe aortic stenosis who are judged by a heart team, including a cardiac surgeon, to be high risk or inoperable for open aortic valve replacement.

There are several TAVI/transcatheter aortic valve replacement (TAVR) systems currently being studied but have not received FDA approval. These include: Acurate TA transaortic valve replacement system; Engager TAVI system; and JenaValve transapical (TAVI) system.

Bleiziffer et al (2009) noted that suspicion had been expressed that survival might be impaired after antegrade TA as opposed to retrograde TF valve implantation in high-risk patients with aortic stenosis.  These researchers analyzed survival in patients undergoing TAVI with special emphasis on the access site for valvular implantation.  A total of 203 high-risk patients (European system for cardiac operative risk [EuroSCORE] of 22 % +/- 14 %; mean age of 81 +/- 7 years) underwent TAVI via a TA (n = 50) or TF (n = 153) access.  The TA implantation technique was chosen only in patients who had no access through diseased femoral arteries.  Thirty-day survival was 88.8 % after TF versus 91.7 % after TA implantation (p = 0.918).  The TA group had a significantly higher pre-operative brain natriuretic peptide value and a significantly higher incidence of peripheral vessel, cerebrovascular, and coronary heart disease.  Death within 30 days was valve-related in 25 % (TA) and 31 % (TF), cardiac in 25 % and 13 %, and non-cardiac in 50 % and 56 %, respectively (no significant differences).  Complications specific to the access site (peripheral vessel injury or apex complications) occurred in both groups, whereas neurological events did not occur in the TA group (p = 0.041).  The authors concluded that their patient and access site selection process, with the TF technique considered the access site of first choice, results in comparable morbidity and survival for either TF or TA TAVI.  Both techniques are associated with certain access site-specific complications that require highly qualified management.

Ye and colleagues (2010) reported clinical and echocardiographical outcomes of TA -TAVI in 71 patients (27 males and 44 females) who underwent TAVI with either 23- or 26-mm Edwards Lifesciences transcatheter valve.  All patients with symptomatic aortic stenosis were declined for conventional SAVR as a consequence of unacceptable operative risks and were not candidates for trans-femoral TAVI (TF-TAVI) because of poor arterial access.  Clinical and echocardiographical follow-ups were performed before discharge, at 1 and 6 months, and then yearly.  The mean follow-up was 12.9 +/- 11.5 months with a total of 917.3 months of follow-up.  Mean age was 80.0 +/- 8.1 years and predicted operative mortality was 34.5 % +/- 20.4 % by EuroSCORE and 12.1 % +/- 7.7 % by the STS risk score.  Valves were successfully implanted in all patients.  Twelve patients died within 30 days (30-day mortality: 16.9 % in all patients, 33 % in the first 15 patients, and 12.5 % in the remainder), and 10 patients died subsequently.  Overall survivals at 24 and 36 months were 66.3 % +/- 6.4 % and 58.0 % +/- 9.5 %, respectively.  Among 59 patients who survived at least 30 days, 24- and 36-month survivals were 79.8 % +/- 6.4 % and 69.8 % +/- 10.9 %, respectively.  Late valve-related complications were rare.  New York Heart Association (NYHA) functional class improved significantly from pre-operative 3.3 +/- 0.8 to 1.8 +/- 0.8 at 24 months.  The aortic valve area and trans-aortic mean gradient remained stable at 24 months (1.6 +/- 0.3 cm(2) and 10.3 +/- 5.9 mm Hg, respectively).  The authors concluded that these findings suggest that trans-apical TAVI (TA-TAVI) provides sustained clinical and hemodynamic benefits for up to 36 months in selected high-risk patients with symptomatic severe aortic stenosis. 

Attias and associates (2010) described the results of TF-TAVI using either the Sapien prosthesis (Edwards Lifesciences, Irvine, CA) or the CoreValve ReValving system (CoreValve ReValving Technology Medtronic, Minneapolis, MN).  Of 236 patients at high-risk or with contraindications to surgery, 83 were treated with TF-TAVI.  The Sapien was the only prosthesis available until May 2008 and, since then, was used as the first option, while the CoreValve system was used when contraindications to the Sapien prosthesis were present.  Patients were aged 81 +/- 9 years, 98 % in NYHA classes III/IV, with predicted surgical mortalities of 26 % +/- 14 % using the EuroSCORE and 15 % +/- 8 % using the STS risk score.  Seventy-two patients were treated with the Sapien prosthesis and 11 with the CoreValve system.  The valve was implanted in 94 % of the cases.  Thirty-day mortality was 7 %.  Overall, 1- and 2-year survival rates were 78 % +/- 5 % and 71 % +/- 7 %, respectively.  Among patients treated with the Sapien, the 1-year survival rate was 67 % +/- 12 % in the first 20 % of patients versus 86 % +/- 5 % in the last 80 % of patients (p = 0.02).  In uni-variate analysis, early experience was the only significant predictor of 1-year mortality.  The authors concluded that combining the use of the Sapien and the CoreValve prostheses increases the number of patients who can be treated by TF -TAVI and provides satisfactory results at 2 years in this high-risk population.

Rajani et al (2010) compared survival in patients with inoperable aortic stenosis who undergo TAVI against those managed medically.  Survival rates were compared in consecutive patients with severe symptomatic aortic stenosis who either underwent TAVI or continued on medical management following multi-disciplinary team assessment.  All patients had been turned down, or considered at unacceptably high risk, for SAVR.  Patients were reviewed in clinic or by telephone every 6 months.  Mortality data was obtained from the United Kingdom Office of National Statistics.  The study group included 85 patients aged 81 +/- 7 years (range of 62 to 94), of whom 48 were males.  A total of 38 patients underwent TAVI while 47 patients were deemed unsuitable based on echocardiographical, angiographical, or clinical criteria and remained on medical therapy.  The calculated EuroSCORE for the TAVI group was 11 +/- 2 and for the medical group 9 +/- 2 (p < 0.001).  TAVI-related procedural mortality was 2.6 %, and 30-day mortality was 5.2 %.  Among the medically-treated patients, 14 (30 %) underwent palliative balloon aortic valvuloplasty, with a trend toward improved survival (p = 0.06).  During overall follow-up of 215 +/- 115 days, there were a total of 18 deaths; TAVI, n = 5 (13 %); Medical, n = 13 (28 %) (p = 0.04).  The authors concluded that patients with severe aortic valve disease who are not suitable for SAVR have an improved prognosis if treated with TAVI rather than continuing on medical management alone.

Avanzas et al (2010) described early experience and medium-term follow-up with the CoreValve prosthesis at 3 Spanish hospitals.  The study included patients with severe symptomatic aortic stenosis.  Other inclusion criteria were: aortic valve annulus diameter in the range 20 to 27 mm; diameter of the ascending aorta at the level of the sino-tubular junction less than or equal to 40 mm (small prosthesis) or less than or equal to 43 mm (large prosthesis), and femoral artery diameter greater than 6 mm.  The study included 108 patients with a mean age of 78.6 +/- 6.7 years, a mean aortic valve area of 0.63 +/- 0.2 cm(2), and a mean EuroSCORE of 16 % +/- 13.9 % (range of 2.27 % to 86.4 %).  After valve implantation, the maximum echocardiographical trans-aortic valve gradient decreased from 83.8 +/- 23 to 12.6 +/- 6 mmHg.  No patient presented with greater than grade-2 residual aortic regurgitation on angiography.  The procedural success rate was 98.1 %.  No patient died during the procedure.  Definitive pace-maker implantation was carried out for atrio-ventricular block in 38 patients (35.2 %).  At 30 days, all-cause mortality and the rate of the combined end point of death, stroke, myocardial infarction or referral for surgery were 7.4 % and 8.3 %, respectively.  The estimated 1-year survival rate calculated using the Kaplan-Meier method was 82.3 % (for a median follow-up period of 7.6 months).  The authors concluded that their early experience indicates that percutaneous aortic valve replacement is a safe and practical therapeutic option for patients with severe aortic stenosis who are at a high surgical risk.

In the PARTNER trial, Leon and colleagues (2010) randomly assigned patients with severe aortic stenosis, whom surgeons considered not to be suitable candidates for surgery, to standard therapy (including balloon aortic valvuloplasty) or TF-TAVI of a balloon-expandable bovine peri-cardial valve.  The primary end point was the rate of death from any cause.  A total of 358 patients with aortic stenosis who were not considered to be suitable candidates for surgery underwent randomization at 21 centers (17 in the United States).  At 1 year, the rate of death from any cause (Kaplan–Meier analysis) was 30.7 % with TAVI, as compared to 50.7 % with standard therapy (HR with TAVI, 0.55; 95 % CI: 0.40 to 0.74; p < 0.001).  The rate of the composite end point of death from any cause or repeat hospitalization was 42.5 % with TAVI as compared to 71.6 % with standard therapy (HR, 0.46; 95 % CI: 0.35 to 0.59; p < 0.001).  Among survivors at 1 year, the rate of cardiac symptoms (NYHA class III or IV) was lower among patients who had undergone TAVI than among those who had received standard therapy (25.2 % versus 58.0 %, p < 0.001).  At 30 days, TAVI, as compared with standard therapy, was associated with a higher incidence of major strokes (5.0 % versus 1.1 %, p = 0.06) and major vascular complications (16.2 % versus 1.1 %, p < 0.001).  In the year after TAVI, there was no deterioration in the functioning of the bioprosthetic valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram.  The authors concluded that in patients with severe aortic stenosis who were not suitable candidates for surgery, TAVI, as compared with standard therapy, significantly reduced the rates of death from any cause, the composite end point of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major strokes and major vascular events.  Moreover, the authors stated that these findings can not be extrapolated to other patients with aortic stenosis.  Additional randomized trials are needed to compare TAVI with aortic valve replacement among high risk patients with aortic stenosis for whom surgery is a viable option and among low risk patients with aortic stenosis.

In an editorial that accompanied that afore-mentioned study, Lazar (2010) stated that "[d]espite the promising results of the PARTNER trial, surgical aortic-valve replacement remains the standard for the treatment of aortic stenosis.  TAVI should be reserved for patients at inordinately high risk who are not suitable candidates for surgery and who have decreased life expectancy.  Given the unknown durability of these prostheses and the high incidence of regurgitation, TAVI should not be performed in patients with long life expectancies". 

The editorialist noted that advanced age alone is not a reason to perform TAVI over an open aortic valve implantation; there needs to be other risk factors for open surgery.  It is important to define the criteria for high risk or inoperable aortic stenosis, since there are discrepancies among various risk-scoring systems in the prediction of the risk of death.  The EuroSCORE has been shown to consistently over-estimate the risk of death, whereas most people consider the STS risk score to be more accurate.  An analysis of data from the STS National Database on 108,687 isolated aortic-valve replacements shows that overall mortality is now 2.6 %, and the incidence of stroke is 1.3 %.  Among patients 80 to 85 years of age, 30-day mortality is less than 5 % and the rate of stroke is less than 2.5 %.  These values should be the yard-stick by which other strategies to treat aortic stenosis should be measured.

Clavel et al (2010) stated that patients with severe aortic stenosis and reduced left ventricular ejection fraction (LVEF) have a poor prognosis with conservative therapy but a high operative mortality when treated surgically.  Recently, TAVI has emerged as an alternative to SAVR for patients considered at high or prohibitive operative risk.  The objective of this study was to compare TAVI and SAVR with respect to post-operative recovery of LVEF in patients with severe aortic stenosis and reduced LV systolic function.  Echocardiographical data were prospectively collected before and after the procedure in 200 patients undergoing SAVR and 83 patients undergoing TAVI for severe aortic stenosis (aortic valve area less than or equal to 1 cm(2)) with reduced LV systolic function (LVEF less than or equal to 50 %).  Patients who underwent TAVI were significantly older (81 +/- 8 versus 70 +/- 10 years; p < 0.0001) and had more co-morbidities compared with patients who underwent SAVR.  Despite similar baseline LVEF (34 +/- 11 % versus 34 +/- 10 %), TAVI patients had better recovery of LVEF compared with SAVR patients (change in LVEF, 14 +/- 15 % versus 7 +/- 11 %; p = 0.005).  At the 1-year follow-up, 58 % of TAVI patients had a normalization of LVEF (greater than 50 %) as opposed to 20 % in the SAVR group.  On multi-variable analysis, female gender (p = 0.004), lower LVEF at baseline (p = 0.005), absence of atrial fibrillation (p = 0.01), TAVI (p = 0.007), and larger increase in aortic valve area after the procedure (p = 0.01) were independently associated with better recovery of LVEF.  The authors concluded that in patients with severe aortic stenosis and depressed LV systolic function, TAVI is associated with better LVEF recovery compared with SAVR; and TAVI may provide an interesting alternative to SAVR in patients with depressed LV systolic function considered at high surgical risk.

Dworakowski et al (2010) stated that TAVI is an alternative treatment option for patients with aortic stenosis deemed high-risk or unsuitable for aortic valve replacement.  The aim of this study was to assess the feasibility of TAVI in elderly patients, the delivery of this technology with a multi-disciplinary approach, and the use of traditional surgical scoring systems.  A total of 151 consecutive patients (mean age of 82.6 +/- 7.3 years) with severe aortic stenosis underwent TAVI with the Edwards Lifesciences Sapien bioprosthesis using the TA (n = 84; 56 %) or TF (n = 67; 44 %) approach.  These investigators analyzed procedural outcome, complications, functional status, and mid-term outcome of patients.  The multi-disciplinary team comprised interventional cardiologists, cardiothoracic surgeons, imaging specialists, cardiac anesthetists, and specialist nurses.  Atotal of 70 % of patients were in NYHA class III/IV, and EuroSCORE was 21.6 +/- 11.9.  Procedural success was achieved in 98 %.  Post-operative complications included stroke (6 %), complete atrio-ventricular block (5.3 %), renal failure requiring hemo-filtration (9.3 %), and vascular injury (8.6 %).  Overall 30-day mortality was 9.9 % (n = 15).  The EuroSCORE was a predictor of short-term mortality (logistic regression model, p < 0.05).  Thirty-day mortality post-TAVI for patients with EuroSCORE less than 20, 20 to 40, and greater than 40 was 5.4 %, 13.2 %, and 22.2 %, respectively.  The authors concluded that TAVI is a feasible treatment option in this patient group with promising short- to medium-term results.  Renal failure is the commonest short-term complication, and the incidence of vascular complications remains high.

Bollati et al (2010) noted that aortic valve disease is a growing cause of mortality and morbidity, especially in developed countries.  Whereas medical therapy is associated with an ominous prognosis, since the 1970s, SAVR has represented a standard therapy for fit patients.  Indeed, this approach is safe and feasible in younger patients without co-morbidities.  However, in unfit patients, surgery may be associated with a very high risk.  The advent of transcatheter valve replacement techniques, by means of percutaneous or TA approaches, has been recently introduced into mainstream clinical practice and is likely to radically change the treatment of aortic valve disease.  At present, further data are needed to thoroughly appraise the long-term risk-benefit balance of transcatheter valve replacement techniques.  For this reason, it can only be considered for high surgical risk patients, but early results are so promising that in the future, TAVI could became the first therapeutic choice, even for low risk patients.

Zahn et al (2011) reported the first results of the prospective multi-center German TAVI-Registry.  Between January 2009 and December 2009, a total of 697 patients (81.4 +/- 6.3 years, 44.2 % males, and logistic EuroScore 20.5 +/- 13.2 %) underwent TAVI.  Pre-operative aortic valve area was 0.6 +/- 0.2 cm(2) with a mean trans-valvular gradient of 48.7 +/- 17.2 mm Hg.  Transcatheter aortic valve implantation was performed percutaneously in the majority of patients [666 (95.6 %)].  Only 31 (4.4 %) procedures were done surgically: 26 (3.7 %) transapically and 5 (0.7 %) transaortically.  The Medtronic CoreValve prosthesis was used in 84.4 %, whereas the Sapien Edwards prosthesis was used in the remaining cases.  Technical success was achieved in 98.4 % with a post-operative mean trans-aortic pressure gradient of 5.4 +/- 6.2 mm Hg.  Any residual aortic regurgitation was observed in 72.4 % of patients, with a significant aortic insufficiency (greater than or equal to grade III) in 16 patients (2.3 %).  Complications included pericardial tamponade in 1.8 % and stroke in 2.8 % of patients.  Permanent pacemaker implantation after TAVI became necessary in 39.3 % of patients.  In-hospital death rate was 8.2 %, and the 30-day death rate 12.4 %.  The authors concluded that in this real-world registry of high-risk patients with aortic stenosis, TAVI had a high success rate and was associated with moderate in-hospital complications.  However, careful patient selection and continued hospital selection seem crucial to maintain these results.

In a prospective, multi-center, single-arm study, Buellesfeld et al (2011) evaluated the safety, device performance, and clinical outcome up to 2 years for patients undergoing TAVI.  This trial was conducted with symptomatic patients undergoing TAVI for the treatment of severe aortic valve stenosis using the 18-F Medtronic CoreValve prosthesis.  In all, 126 patients (mean age of 82 years, 42.9 % male, mean logistic European System for Cardiac Operative Risk Evaluation score 23.4 %) with severe aortic valve stenosis (mean gradient of 46.8 mm Hg) underwent the TAVI procedure.  Access was TF in all but 2 cases with subclavian access.  Retrospective risk stratification classified 54 patients as moderate surgical risk, 51 patients as high-risk operable, and 21 patients as high-risk inoperable.  The overall technical success rate was 83.1 %.  Thirty-day all-cause mortality was 15.2 %, without significant differences in the subgroups.  At 2 years, all-cause mortality was 38.1 %, with a significant difference between the moderate-risk group and the combined high-risk groups (27.8 % versus 45.8 %, p = 0.04).  This difference was mainly attributable to an increased risk of non-cardiac mortality among patients constituting the high-risk groups.  Hemodynamic results remained unchanged during follow-up (mean gradient of 8.5 +/- 2.5 mm Hg at 30 days and 9.0 +/- 3.4 mm Hg at 2 years).  Functional class improved in 80 % of patients and remained stable over time.  There was no incidence of structural valve deterioration.  The authors concluded that the TAVI procedure provides sustained clinical and hemodynamic benefits for as long as 2 years for patients with symptomatic severe aortic stenosis at increased risk for surgery.

Smith et al (2011) compared transcatheter versus surgical aortic-valve replacement in high-risk patients.  At 25 centers, these investigators randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either TAVI with a balloon-expandable bovine peri-cardial valve (either a TF or a TA approach) or surgical replacement.  The primary end point was death from any cause at 1 year.  The primary hypothesis was that TAVI is not inferior to surgical replacement.  The rates of death from any cause were 3.4 % in the TAVI  group and 6.5 % in the surgical group at 30 days (p = 0.07) and 24.2 % and 26.8 %, respectively, at 1 year (p = 0.44), a reduction of 2.6 percentage points in the TAVI group (upper limit of the 95 % CI: 3.0 percentage points; pre-defined margin, 7.5 percentage points; p = 0.001 for non-inferiority).  The rates of major stroke were 3.8 % in the TAVI group and 2.1 % in the surgical group at 30 days (p = 0.20) and 5.1 % and 2.4 %, respectively, at 1 year (p = 0.07).  At 30 days, major vascular complications were significantly more frequent with TAVI (11.0 % versus 3.2 %, p < 0.001); adverse events that were more frequent after surgical replacement included major bleeding (9.3 % versus 19.5 %, p < 0.001) and new-onset atrial fibrillation (8.6 % versus 16.0 %, p = 0.006).  More patients undergoing TAVI had an improvement in symptoms at 30 days, but by 1 year, there was not a significant between-group difference.  The authors concluded that in high-risk patients with severe aortic stenosis, transcatheter and surgical procedures for aortic-valve replacement were associated with similar rates of survival at 1 year, although there were important differences in peri-procedural risks.

Thomas et al (2011) stated that the Edwards SAPIEN aortic bioprosthesis European outcome (SOURCE) registry was designed to assess initial post-commercial clinical TAVI results of the Edwards SAPIEN valve in consecutive patients in Europe.  Cohort 1 consists of 1,038 patients enrolled at 32 centers.  One-year outcomes were presented.  Patients with the TA approach (n = 575) suffered more co-morbidities than TF patients (n = 463) with a significantly higher logistic EuroSCORE (29 % versus 25.8 %;  p = 0.007).  These groups are different; therefore, outcomes can not be directly compared.  Total Kaplan Meier 1-year survival was 76.1 % overall, 72.1 % for TA and 81.1 % for TF patients, and 73.5 % of surviving patients were in NYHA class I or II at 1 year.  Combined TA and TF causes of death were cardiac in 25.1 %, non-cardiac in 49.2 %, and unknown in 25.7 %.  Pulmonary complications (23.9 %), renal failure (12.5 %), cancer (11.4 %), and stroke (10.2 %) were the most frequent non-cardiac causes of death.  Multi-variable analysis identified logistic EuroSCORE, renal disease, liver disease, and smoking as variables with the highest HRs for 1-year mortality whereas carotid artery stenosis, hyperlipidemia, and hypertension were associated with lower mortality.  The authors concluded that the SOURCE Registry is the largest consecutively enrolled registry for TAVI procedures.  It demonstrated that with new transcatheter aortic techniques excellent 1-year survival in high-risk and inoperable patients is achievable and provides a benchmark against which future TAVI cohorts and devices can be measured.

Kalavrouziotis et al (2011) examined valve hemodynamics and clinical outcomes among patients with a small aortic annulus who underwent TAVI.  Between 2007 and 2010, a total of 35 patients (mean age of 79.2 +/- 9.4 years) with severe aortic stenosis and an aortic annulus diameter less than 20 mm (mean of 18.5 +/- 0.9 mm) underwent TAVI with a 23-mm Edwards SAPIEN bioprosthesis.  Echocardiographical parameters and clinical outcomes were assessed prior to discharge and at 6, 12, and 24 months.  Procedural success was achieved in 34 patients (97.1 %).  There was 1 in-hospital death.  Peak and mean transaortic gradients decreased from 76.3 +/- 33.0 mm Hg and 45.2 +/- 20.6 mm Hg at baseline to 21.8 +/- 8.4 mm Hg and 11.7 +/- 4.8 mm Hg post-procedure, respectively (both p < 0.0001).  Mean indexed effective orifice area (IEOA) increased from 0.35 +/- 0.10 cm(2)/m(2) at baseline to 0.90 +/- 0.18 cm(2)/m(2) post-procedure (p < 0.0001).  Severe prosthesis-patient mis-match (IEOA less than 0.65 cm(2)/m(2)) occurred in 2 patients (5.9 %).  At a mean follow-up of 14 +/- 11 months, gradients remained low and 30 of the 31 remaining survivors were in NYHA functional class I or II.  The authors concluded that in high-risk patients with severe aortic stenosis and a small aortic annulus, TAVI is associated with good post-procedural valve hemodynamics and clinical outcomes.  They stated that TAVI may provide a reasonable alternative to conventional AVR in elderly patients with a small aortic annulus.

Quality-of-life (QOL) is a critical measure of effectiveness of TAVI in patients with severe aortic stenosis. There are studies that showed a marked improvement in QOL in patients who underwent TAVI.  Ussia et al (2011) evaluated 1 year changes in QOL in patients who underwent TAVI.  A total of 149 consecutive patients underwent TAVI using the 18 Fr CoreValve (Medtronic Inc, Minneapolis, MN) or the Edwards Sapien XT heart valve (Edwards Lifescience, Irvine, CA).  Of these, 143 patients with successful prosthesis implantation comprised the study population.  The shorter SF-12 version 2 (SF-12v2) Health-Survey questionnaire provides scales for physical (physical component summary [PCS]) and mental (mental component summary [MCS]) health.  Among patients included in the present analysis, device success was obtained in 138 patients (96.5 %).  Mean pre-procedural SF-12v2 scores showed an important upgrading after TAVI: PCS improved from 28.3 to 44.0 at 5 months and 42.4 at 12 months (p < 0.001); MCS increased from 38.0 to 47.3 at 5 months and 48.2 at 12 months (p < 0.001).  Both the physical and mental score summaries at follow-up of these post-TAVI patients were not significantly different from the anticipated thresholds of the general Italian population over the age of 75 years.  New York Heart Association functional class improvement was reported in all patients.  The authors concluded that these findings showed a marked mid-term improvement in functional status as well as physical and mental health in patients who underwent TAVI.

Georgiadou et al (2011) assessed changes in QOL along with functional status and late survival after TAVI.  A total of 36 consecutive patients (80.5 +/- 5.9 years, 21 men and 15 women) with a logistic Euroscore of 29.7 +/- 13.7 underwent TAVI using the 18-Fr CoreValve prosthesis.  Aortic valve prosthesis was inserted retrograde using a femoral or a subclavian arterial approach.  QOL was evaluated by administering the Short Form 36 (SF-36) tool and SF-12v2 questionnaires before and 1 year after TAVI.  Transcatheter aortic valve implantation was successfully performed in all patients.  The estimated 1-year overall survival rate using Kaplan-Meier method was 68 %.  One-year follow-up also showed a marked improvement in echocardiographic parameters (peak gradient 76.2 +/- 26.1 versus 15.4 +/- 7.8 mm Hg, p < 0.001; aortic valve area 0.7 +/- 0.1 versus 2.6 +/- 2.7 cm(2), p < 0.001) with a significant change in NYHA functional class  (3 +/- 0.7 versus 1.2 +/- 0.4, p < 0.001).  Both pre-procedural summary SF-36 and SF-12v12 physical and mental scores showed a significant improvement 1 year after TAVI (21.6 versus 46.7, p < 0.001; 42.9 versus 55.2, p < 0.001; 22 versus 48.9, p < 0.001; 43.3 versus 52.2, p < 0.001, respectively).  The authors concluded that these findings showed a marked 1-year clinical benefit in functional status as well as physical and mental health in patients who underwent TAVI.

On November 2, 2011, the Food and Drug Administration (FDA) approved the Sapien transcatheter heart valve (THV) as a replacement of an aortic heart valve damaged by senile aortic valve stenosis without open-heart surgery.  The Sapien THV is made of bovine tissue and polyester supported with a stainless steel mesh frame.  To replace the diseased valve, the Sapien THV is compressed into the end of a long, thin, tube-like device called a delivery catheter.  The delivery catheter, which is slightly wider than a pencil, and the Sapien THV are inserted into the femoral artery and threaded to the site of the diseased valve.  The heart valve is then released from the delivery catheter and expanded with a balloon and is immediately functional. The RetroFlex 3 delivery system is used for the trans-femoral delivery of the Edwards Sapien transcatheter heart valve.

The FDA’s approval of the Sapien THV is based on a study in 365 patients who were not eligible for open-heart surgery.  Half of the patients received the Sapien valve; remaining patients received another treatment that did not require open-heart surgery.  One alternative procedure involved enlarging the aortic valve opening by stretching it with a balloon (balloon valvuloplasty).  Patients receiving the Sapien valve experienced 2.5 times more strokes and 8 times as many vascular and bleeding complications than patients who did not receive the implant; however, they were more likely to survive 1 year after surgery.  After 1 year, 69 % of the Sapien patients were alive compared with 50 % of those who received an alternative treatment.  The most common serious and potentially life-threatening side effects in patients receiving the Sapien valve and the procedure to implant the valve include death, stroke, perforation of the blood vessels, ventricle or valvular structures, damage to the conduction system in the heart, significant bleeding, and leaks around the new valve.

The Sapien THV is approved for patients who are not eligible for open-heart surgery for replacement of their aortic valve and have a calcified aortic annulus (calcium build-up in the fibrous ring of the aortic heart valve).  The Sapien THV is not indicated for patients who can be treated by open-heart surgery.  Patients who have congenital heart valve anomalies, have masses or an infection in their hearts, or can not tolerate anti-coagulation/anti-platelet therapy should not receive the Sapien THV.

According to the FDA-approved product labeling, transcatheter aortic valve implantation is not indicated for individuals who can be treated by open-heart surgery.  It is also contraindicated in persons who can not tolerate anti-coagulation/anti-platelet therapy, or who have active bacterial endocarditis, or other active infections.

In 2014, the U.S. Food and Drug Administration (FDA) approved the self-expanding transcatheter Medtronic CoreValve System for patients with severe aortic stenosis who are at high risk for surgery (Medtronic, 2014). This approval is based on the Hith Risk Study of the CoreValve U.S. Pivotal Trial that showed clinical outcomes at one year with the CoreValve System were superior to open-heart surgery. The head-to-head study, comparing transcatheter aortic valve replacement (TAVR) with the CoreValve System to traditional surgical aortic valve replacement, met its primary endpoint with survival at one year for patients receiving the CoreValve System (85.8 percent), which was statistically superior to patients receiving a surgical valve (80.9 percent).

For patients treated with the CoreValve System in the High Risk Study, rates of stroke were not statistically different than rates experienced by surgery patients (Medtronic, 2014). The rate of MACCE (major adverse cardiovascular or cerebral events) was significantly lower for CoreValve patients at one year, and overall hemodynamic performance was better in CoreValve patients than in surgical patients across all time points. 

According to the manufacturer, the CoreValve System's self-expanding frame provides controlled deployment, enabling physicians to accurately place the valve inside a patient's original valve, while conforming to the native annulus to provide a seal (Medtronic, 2014). The FDA approved the CoreValve platform, including the 23mm, 26mm, 29mm and 31mm size valves, all of which are delivered through an 18 Fr TAVR delivery system.

The U.S. Food and Drug Administration (FDA) approved the CoreValve System for valve-in-valve (VIV) procedures in high risk patients whose surgical aortic heart valves have failed (Medtronic, 2015). During the VIV procedure, the CoreValve System is placed inside a failing surgical heart valve with an inner diameter from 17-29 mm through a specialized delivery catheter, which is approved for use with the four CoreValve sizes (23mm, 26mm, 29mm and 31mm), as well as three delivery approaches (transfemoral, subclavian and direct aortic).

The manufacturer reported that outcomes from an Expanded Use Study, an observational arm of the CoreValve U.S. Pivotal Trial, demonstrated a combined rate of mortality and stroke of 4.2 percent at 30 days and 10.7 percent at 6 months (Medtronic, 2015). The study demonstrated significant improvements in hemodynamics and quality of life in patients with failed surgical heart valves. Results from the largest global VIV registry also showed the VIV approach resulted in considerable hemodynamic improvements, including a decrease in blood flow resistance. In this registry, positive procedural outcomes were maintained at one year follow-up with 89 percent survival, which the manufacturer states is comparable with other non-VIV TAVR studies (Dvir, et al., 2012).  

Gurvitch and colleagues (2011) stated that when bioprosthetic cardiac valves fail, re-operative valve replacement carries a higher risk of morbidity and mortality compared with initial valve replacement.  Transcatheter heart valve implantation may be a viable alternative to surgical aortic valve replacement for high-risk patients with native aortic stenosis, and valve-in-valve (V-in-V) implantation has been successfully performed for failed surgical bioprostheses in the aortic, mitral, pulmonic, and tricuspid positions.  Despite some core similarities to transcatheter therapy of native valve disease, V-in-V therapy poses unique clinical and anatomic challenges.  The authors noted that initial results with V-in-V therapy are very encouraging.  However, in the absence of vigorous evaluation and long-term follow-up, V-in-V therapy is probably best considered only for patients who present with a prohibitive re-operative risk.  Therapy of small (e.g., less than or equal to 2 mm aortic valves) should be approached with caution as significant residual gradients may remain with currently available valves.  Operators should be encouraged to share their experience, whether favorable or unfavorable.  They stated that future technologic advances may continue to improve both hemodynamic and clinical outcomes.

Piazza and colleagues (2012) reviewed the acute procedural outcomes of patients who underwent transcatheter aortic valve (TAV)-in-surgical aortic valve (SAV) implantation at the German Heart Center, Munich, and summarized the existing literature on TAV-in-SAV implantation (n = 47).  From January 2007 to March 2011, 20 out of 556 patients underwent a TAV-in-SAV implantation at the German Heart Center Munich.  Baseline characteristics and clinical outcome data were prospectively entered into a dedicated database.  The mean patient age was 75 +/- 13 years, and the mean logistic European System for Cardiac Operative Risk Evaluation and Society of Thoracic Surgeons' Risk Model scores were 27 +/- 13 % and 7 +/- 4 %, respectively.  Of the 20 patients, 14 had stented and 6 had stentless surgical bioprostheses.  Most cases (12 of 20) were performed via the TA route using a 23-mm Edwards Sapien prosthesis.  Successful implantation of a TAV in a SAV with the patient leaving the catheterization laboratory alive was achieved in 18 of 20 patients.  The mean trans-aortic valve gradient was 20.0 +/- 7.5 mm Hg.  None-to-trivial, mild, and mild-to-moderate para-valvular aortic regurgitation was observed in 10, 6, and 2 patients, respectively.  These investigators experienced 1 intra-procedural death following pre-implant balloon aortic valvuloplasty ("stone heart") and 2 further in-hospital deaths due to myocardial infarction.  The authors concluded that TAV-in-SAV implantation is a safe and feasible treatment for high-risk patients with failing aortic bioprosthetic valves and should be considered as part of the armamentarium in the treatment of aortic bioprosthetic valve failure.  

Ferrari (2012) stated that the advent of TAVI has opened new horizons in cardiac surgery and, in particular, the possibility of implanting stented valves within the degenerated stented bioprosthesis, the so-called "V-in-V" concept, has become a clinical practice in experienced cardiac centers.  The V-in-V procedure represents a minimally invasive approach dedicated to high-risk redo patients, and published preliminary reports have shown a success rate of 100 % with absence of significant valvular leaks, acceptable trans-valvular gradients and low complication rate.  However, this procedure is not riskless and the most important concerns are about the size mis-match and the right positioning within the degenerated bioprosthesis.

On October 19, 2012, the FDA expanded the approved indication for the Sapien THV to include patients with aortic valve stenosis who are eligible for surgery, but who are at high risk for serious surgical complications or death.  The manufacturer submitted a Premarket Application (PMA) in April 2011 based on data from the high-risk cohort (Cohort A) of The PARTNER Trial. Cohort A compared the outcomes of patients at high risk for traditional open-heart surgery randomized to receive either surgical aortic valve replacement or the SAPIEN valve via transfemoral or transapical delivery. The trial was successful in meeting its primary endpoint at one year, concluding that survival of high-risk patients treated with the SAPIEN valve was equivalent to those treated with traditional open-heart surgery. The high risk cohort of the PARTNER trial supporting the expanded approval included 348 surgical patients who received the Sapien THV and 351 similar patients who received AVR through open-heart surgery.  Both groups had similar death rates at 1 month, 1 year, and 2 years after the procedures.  Those who received the THV showed an increased risk for major vascular complications, such as artery dissection or perforation, and for stroke during the first month following the procedure.  Patients who received the AVR were more likely than the THV recipients to experience major vascular bleeding during the procedure.

Chao and associates (2013) stated that TAVI has emerged as an acceptable treatment modality for patients with severe aortic stenosis who are deemed inoperable by conventional SAVR.  However, the role of TAVI in patients who are potential surgical candidates remains controversial.  These investigators performed a systematic review using 5 electronic databases, identifying all relevant studies with comparative data on TAVI versus conventional SAVR.  The primary end-point was all-cause mortality.  A number of peri-procedural outcomes were also assessed according to the Valve Academic Research Consortium end-point definitions.  A total of 14 studies were quantitatively assessed and included for meta-analysis, including 2 randomized controlled trials (RCTs) and 11 observational studies.  Results indicated no significant differences between TAVI and conventional SAVR in terms of all-cause and cardiovascular related mortality, stroke, myocardial infarction or acute renal failure.  A subgroup analysis of RCTs identified a higher combined incidence of stroke or transient ischemic attacks in the TAVI group compared to the conventional SAVR group.  Transcatheter aortic valve implantation was also found to be associated with a significantly higher incidence of vascular complications, permanent pacemaker requirement and moderate or severe aortic regurgitation.  However, patients who underwent conventional SAVR were more likely to experience major bleeding.  Both treatment modalities appeared to effectively reduce the trans-valvular mean pressure gradient.  The authors concluded that the available data on TAVI versus conventional SAVR for patients at a higher surgical risk showed that major adverse outcomes such as mortality and stroke appeared to be similar between the 2 treatment modalities.  Evidence on the outcomes of TAVI compared with conventional SAVR in the current literature is limited by inconsistent patient selection criteria, heterogeneous definitions of clinical end-points and relatively short follow-up periods.  The indications for TAVI should therefore be limited to inoperable surgical candidates until long-term data become available.

Dubois and colleagues (2013) noted that TAVI has been proposed as a treatment alternative for patients with aortic valve stenosis at high or prohibitive risk for SAVR.  These researchers evaluated outcomes after treatment according to the decisions of the multi-disciplinary heart team.  At a tertiary center, all high-risk patients referred between March 1, 2008 and October 31, 2011 for symptomatic aortic stenosis were screened and planned to undergo SAVR, TAVI or medical treatment.  These investigators reported clinical outcomes as defined by the Valve Academic Research Consortium.  Of 163 high-risk patients, those selected for SAVR had lower logistic EuroSCORE and STS scores when compared with TAVI or medical treatment (median [interquartile range] 18 [12 to 26]; 26 [17 to 36]; 21 [14 to 32] % (p = 0.015) and 6.5 [5.1 to 10.7]; 7.6 [5.8 to 10.5]; 7.6 [6.1 to 15.7] % (p = 0.056)).  All-cause mortalities at 1 year in 35, 73 and 55 patients effectively undergoing SAVR, TAVI and medical treatment were 20, 21 and 38 %, respectively (p = 0.051).  Cardiovascular death and major stroke occurred in 9, 8 and 33 % (p < 0.001) and 6, 4 and 2 % (p = 0.62), respectively.  For patients undergoing valve implantation, device success was 91 and 92 % for SAVR and TAVI, respectively.  The combined safety end-point at 30 days was in favor of TAVI (29 %) versus SAVR (63 %) (p = 0.001).  In contrast, the combined efficacy end-point at 1 year tended to be more favorable for SAVR (10 versus 24% for TAVI, p = 0.12).  The authors concluded that patients who are less suitable for SAVR can be treated safely and effectively with TAVI with similar outcomes when compared with patients with a lower-risk profile undergoing SAVR.  Patients with TAVI or SAVR have better survival than those undergoing medical treatment only.

Chieffo et al (2013) compared outcomes after TF-TAVI with the Medtronic CoreValve (MCV) versus the Edwards SAPIEN/SAPIEN XT transcatheter heart valve (ESV) for severe aortic stenosis.  The data from databases of 4 experienced European centers were pooled and analyzed.  Due to differences in baseline clinical characteristics, propensity score matching was performed.  Study objectives were Valve Academic Research Consortium outcomes at 30 days and 1 year.  In total, 793 patients were included: 453 (57.1 %) treated with the MCV and 340 (42.9 %) with the ESV.  After propensity matching, 204 patients were identified in each group.  At 30 days, there were no differences in all-cause mortality (MCV, 8.8 % versus ESV, 6.4 %; HR: 1.422; 95 % CI: 0.677 to 2.984; p = 0.352), cardiovascular mortality (MCV, 6.9 % versus ESV, 6.4 %; HR: 1.083; 95 % CI: 0.496 to 2.364; p = 0.842), myocardial infarction (MCV, 0.5 % versus ESV, 1.5 %; HR: 0.330; 95 % CI: 0.034 to 3.200; p = 0.339), stroke (MCV, 2.9 % versus ESV, 1.0 %; HR: 3.061; 95 % CI: 0.610 to 15.346; p = 0.174), or device success (MCV, 95.6 % versus ESV, 96.6 %; HR: 0.770; 9 5% CI: 0.281 to 2.108; p = 0.611).  Additionally, there were no differences in major vascular complications (MCV, 9.3 % versus ESV, 12.3 %; HR: 0.735; 95 % CI: 0.391 to 1.382; p = 0.340) or life-threatening bleeding (MCV, 13.7 % versus ESV, 8.8 %; HR: 1.644; 95 % CI: 0.878 to 3.077; p = 0.120).  Medtronic CoreValve was associated with more permanent pacemakers (22.5 % versus 5.9 %; HR: 4.634; 95 % CI: 2.373 to 9.050; p < 0.001).  At 1 year, there were no differences in all-cause (MCV, 16.2 % versus ESV, 12.3 %; HR: 1.374; 95 % CI: 0.785 to 2.407; p = 0.266) or cardiovascular (MCV, 8.3 % versus ESV, 7.4 %; HR: 1.145; 95 % CI: 0.556 to 12.361; p = 0.713) mortality.  The authors concluded that no differences between the 2 commercially available TF-TAVI devices were observed at the adjusted analysis in Valve Academic Research Consortium outcomes except for the need for permanent pacemakers with the MCV.

Roy and colleagues (2013) evaluated the anecdotal use of TAVI in pure native aortic valve regurgitation (NAVR) for patients who were deemed surgically inoperable  Data on baseline patient characteristics, device and procedure parameters, echocardiographic parameters, and outcomes up to July 2012 were collected retrospectively from 14 centers that have performed TAVI for NAVR.  A total of 43 patients underwent TAVI with the CoreValve prosthesis (Medtronic, Minneapolis, MN) at 14 centers (mean age of 75.3 ± 8.8 years; 53 % female; mean logistic EuroSCORE, 26.9 ± 17.9 %; and mean Society of Thoracic Surgeons score, 10.2 ± 5.3 %).  All patients had severe NAVR on echocardiography without aortic stenosis and 17 patients (39.5 %) had the degree of aortic valvular calcification documented on CT or echocardiography.  Vascular access was TF (n = 35), subclavian (n = 4), direct aortic (n = 3), and carotid (n = 1).  Implantation of a TAVI was performed in 42 patients (97.7 %), and 8 patients (18.6 %) required a second valve during the index procedure for residual aortic regurgitation.  In all patients requiring 2nd valves, valvular calcification was absent (p = 0.014).  Post-procedure aortic regurgitation grade I or lower was present in 34 patients (79.1 %).  At 30 days, the major stroke incidence was 4.7 %, and the all-cause mortality rate was 9.3 %.  At 12 months, the all-cause mortality rate was 21.4 % (6 of 28 patients).  The authors concluded that this registry analysis demonstrated the feasibility and potential procedure difficulties when using TAVI for severe NAVR. They stated that acceptable results may be achieved in carefully selected patients who are deemed too high risk for conventional surgery, but the possibility of requiring 2 valves and leaving residual aortic regurgitation remain important considerations.  The findings of this small, predominantly retrospective voluntary registry of a novel indication for transcatheter valve therapy need to be validated in well-designed studies.

On August 16, 2019, the FDA approved an expanded indication for the SAPIEN 3 and SAPIEN 3 Ultra transcatheter heart valve (THV) systems for patients with aortic valve stenosis who are determined to be at low-risk for death and complications with open-heart surgery.

Mack and colleagues (2019) noted that among patients with aortic stenosis who are at intermediate- or high-risk for death with surgery, major outcomes are similar with TAVR and surgical aortic-valve replacement.  There is insufficient evidence regarding the comparison of the 2 procedures in patients who are at low-risk.  These researchers randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemoral placement of a balloon-expandable valve or surgery.  The primary endpoint was a composite of death, stroke, or re-hospitalization at 1 year.  Both non-inferiority testing (with a pre-specified margin of 6 percentage points) and superiority testing were performed in the as-treated population.  At 71 centers, 1,000 patients underwent randomization.  The mean age of the patients was 73 years, and the mean Society of Thoracic Surgeons risk score was 1.9 % (with scores ranging from 0 to 100 % and higher scores indicating a greater risk of death within 30 days after the procedure).  The Kaplan-Meier estimate of the rate of the primary composite endpoint at 1 year was significantly lower in the TAVR group than in the surgery group (8.5 % versus 15.1 %; absolute difference, -6.6 percentage points; 95 % CI: -10.8 to -2.5; p < 0.001 for non-inferiority; HR, 0.54; 95 % CI: 0.37 to 0.79; p = 0.001 for superiority).  At 30 days, TAVR resulted in a lower rate of stroke than surgery (p = 0.02) and in lower rates of death or stroke (p = 0.01) and new-onset atrial fibrillation (p < 0.001).  TAVR also resulted in a shorter index hospitalization than surgery (p < 0.001) and in a lower risk of a poor treatment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (p < 0.001).  There were no significant between-group differences in major vascular complications, new permanent pacemaker insertions, or moderate or severe para-valvular regurgitation.  The authors concluded that among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or re-hospitalization at 1 year was significantly lower with TAVR than with surgery.

Combination of Transcatheter Aortic Valve Implantation (TAVI) and Left Atrial Appendage Occlusion

In a pilot study, Attinger-Toller et al (2016) examined the safety and effectiveness of combining TAVR and left atrial appendage occlusion (LAAO) versus TAVR alone. A cohort of 52 patients undergoing concomitant TAVR and LAAO were compared with 52 patients undergoing isolated TAVR.  A primary safety end-point at 30 days, a clinical efficacy end-point from day 30 to last follow-up, and an LAAO effectiveness end-point from the 1st post-interventional day to the last follow-up were chosen.  The mean age of the study population was 85 ± 5 years.  The mean CHA2DS2-VASc score and HAS-BLED score were 3.9 ± 1.1 and 2.6 ± 0.9, respectively.  The mean STS score was 7.8 ± 5.5.  The median follow-up duration of the study population was 9.4 months (range of 0 to 48).  The primary safety end-point occurred in 10 patients in the concomitant group and in 7 patients in the isolated TAVR group (19 % versus 14 %; 95 % CI: 0.59 to 4.06).  The clinical and LAAO effectiveness end-points were achieved in 81 (79 %) (75 % versus 82 %; 95 % CI: 0.49 to 2.92) and 75 (73 %) patients (69 % versus 76 %; 95 % CI: 0.54 to 2.51), respectively.  The authors concluded that the findings of this study showed that concomitant TAVR and LAAO was feasible and appeared to be safe among patients with severe aortic stenosis and atrial fibrillation.  They stated that larger trials and longer follow-up are needed to confirm the safety and effectiveness of such an approach.

Transcatheter Aortic Valve Implantation With Preimplantation Balloon Aortic Valvuloplasty

Bagur and colleagues (2016) stated that pre-implantation balloon aortic valvuloplasty (BAV) is considered a routine procedure during TAVI to facilitate prosthesis implantation and expansion; however, it has been speculated that fewer embolic events and/or less hemodynamic instability may occur if TAVI is performed without pre-implantation BAV. These investigators reviewed the clinical outcomes associated with TAVI undertaken without pre-implantation BAV.  They conducted a search of Medline and Embase to identify studies that evaluated patients who underwent TAVI with or without pre-implantation BAV for pre-dilation.  Pooled analysis and random-effects meta-analyses were used to estimate the rate and risk of adverse outcomes.  A total of 16 studies involving 1,395 patients (674 with and 721 without pre-implantation BAV) fulfilled the inclusion criteria.  Crude device success was achieved in 94 % (1,311 of 1,395), and 30-day all-cause mortality occurred in 6 % (72 of 1,282) of patients.  Meta-analyses evaluating outcomes of strategies with and without pre-implantation BAV showed no statistically significant differences in terms of mortality (relative risk [RR] 0.61, 95 % CI: 0.32 to 1.14, p = 0.12), safety composite end-point (RR 0.85, 95 % CI: 0.62 to 1.18, p = 0.34), moderate-to-severe paravalvular leaks (RR 0.68, 95 % CI: 0.23 to 1.99, p = 0.48), need for post-dilation (RR 0.86, 95 % CI: 0.66 to 1.13, p = 0.58), stroke and/or transient ischemic attack (RR 0.72, 95 % CI: 0.30 to 1.71, p = 0.45), and permanent pacemaker implantation (RR 0.80, 95 % CI: 0.49 to 1.30, p = 0.37).  The authors concluded that their analysis suggested that TAVI procedures with or without pre-implantation BAV were associated with similar outcomes for a number of clinically relevant end-points.  They stated that further studies including a large number of patients are needed to ascertain the impact of TAVI without pre-implantation BAV as a standard practice.

Liao and associates (2016) noted that evidence regarding the safety and feasibility of TAVI without balloon pre-dilation (BP) is scarce. These investigators performed a literature search of PubMed, Embase, CENTRAL, and major conference proceedings from January 2002 to July 2015.  There were 18 studies incorporating 2,443 patients included in the present study.  No differences were observed in the baseline characteristics between patients without BP (no-BP) and with BP.  Compared with BP, no-BP had a shorter procedure time (no-BP versus BP, 124.2 versus 138.8 minutes, p = 0.008), used less-contrast medium (no-BP versus BP, 126.3 versus 156.3 ml, p = 0.0005) and had a higher success rate (odds ratio [OR] 2.24, 95 % CI: 1.40 to -3.58).  In addition, no-BP was associated with lower incidences of permanent pacemaker implantation (OR 0.45, 95 % CI: 0.3 to 0.67), grade 2 or greater paravalvular leakage (OR 0.55, 95 % CI: 0.37 to 0.83), and stroke (OR 0.57, 95 % CI: 0.32 to 1.0).  Furthermore, no-BP was associated with a 0.6-fold decreased risk for 30-day all-cause mortality (OR 0.60, 95 % CI: 0.39 to 0.92).  However, the difference in the risk for permanent pacemaker implantation, grade 2, or higher aortic regurgitation, stroke was noted to be significant only in the subgroup of the CoreValve-dominating studies.  The authors concluded that no-BP before TAVI was not only safe and feasible but was also associated with fewer complications and short-term mortality in selected patients especially using self-expandable valve.

Bernardi and co-workers (2016) stated that direct TAVR is regarded as having potential advantages over TAVR with balloon aortic valve pre-dilatation (BAVP) in reducing procedural complications, but there are few data to support this approach. Patients included in the Brazilian TAVR registry with CoreValve and Sapien-XT prosthesis were compared according to the implantation technique, with or without BAVP.  Clinical and echocardiographic data were analyzed in overall population and after propensity score matching.  A total of 761 consecutive patients (BAVP = 372; direct-TAVR = 389) were included.  Direct-TAVR was possible in 99 % of patients, whereas device success was similar between groups (BAVP = 81.2 % versus direct-TAVR = 78.1 %; p = 0.3).  No differences in clinical outcomes at 30 days and 1 year were observed, including all-cause mortality (7.6 % versus 10 %; p = 0.25 and 18.1 % versus 24.5 %; p = 0.07, respectively) and stroke (2.8 % versus 3.8 %; p = 0.85 and 5.5 % versus 6.8 %; p = 0.56, respectively).  Nonetheless, TAVR with BAVP was associated with a higher rate of new onset persistent left bundle branch block with the CoreValve (47.7 % versus 35.1 %; p = 0.01 at 1 year).  Mean gradient and incidence of moderate/severe aortic regurgitation were similar in both groups at 1 year (11 % versus 13.3 %; p = 0.57 and 9.8 ± 5.5 versus 8.7 ± 4.3; p = 0.09, respectively).  After propensity score matching analysis, all-cause mortality and stroke remained similar.  By multi-variable analysis, BAVP and the use of CoreValve were independent predictors of new onset persistent left bundle branch block.  The authors concluded that the 2 TAVR strategies, with or without BAVP, provided similar clinical and echocardiographic outcomes over a midterm follow-up although BAVP was associated with a higher rate of new onset persistent left bundle branch block, particularly in patients receiving a CoreValve.

In a retrospective, single-center study, Aggarwal and colleagues (2016) examined the necessity for BAV during transfemoral TAVI when using balloon-expandable valves. A total of 154 patients undergoing first-time, transfemoral TAVI for native aortic valve stenosis, with (n = 76), and without (n = 78), BAV as part of the procedure were included in this analysis.  Data collected included demographic, procedural, and outcome data.  Balloon aortic valvuloplasty did not alter Valve Academic Research Consortium (VARC)-2 defined procedural success or early safety compared to not performing a BAV, including mortality, degree of aortic regurgitation, or need for post-TAVI balloon dilatation, although there was a strong trend to reduced stroke when not performing a BAV.  There was a significantly reduced procedural time (p = 0.01) and fluoroscopic time (p < 0.001) without performing a BAV.  There were no differences in cerebral embolization (solid, gaseous, or total emboli) noted between the 2 groups, as measured on transcranial Doppler (TCD).  The authors concluded that TAVI can be effectively and safely performed without a BAV and this resulted in reduced procedural and fluoroscopic times, although embolization to the brain was not reduced; there was a trend toward reduced stroke risk.

Pagnesi et al (2016) noted that BP is historically considered a requirement before performing TAVI. As the procedure has evolved, it has been questioned whether it is actually needed, but data are lacking on mid-term outcomes.  These researchers evaluated the effect of BP before TAVI.  A total of 517 patients who underwent transfemoral TAVI from November 2007 to October 2015 were analyzed.  The devices implanted included the Medtronic CoreValve (n = 216), Medtronic Evolut R (n = 30), Edwards SAPIEN XT (n = 210), and Edwards SAPIEN 3 (n = 61).  Patients were divided into 2 groups depending on whether pre-implantation BAV (pre-BAV) was performed (n = 326) or not (n = 191).  Major adverse cardiac and cerebrovascular events (MACCE) were primarily evaluate.  Propensity score matching was used to adjust for differences in baseline characteristics and potential confounders (n = 113 pairs).  In the overall cohort, patients without pre-BAV had a significantly higher MACCE rate at 30 days, driven by a higher incidence of stroke (0.3 % pre-BAV versus 3.7 % no-pre-BAV, p < 0.01); MACCE and mortality at 1 year were, however, similar in both groups.  Independent predictors of MACCE at 1 year included serum creatinine, NYHA class 3 to 4, logistic European System for Cardiac Operative Risk Evaluation, and post-dilation.  Of note, the post-dilation rate was higher in the no-pre-BAV group (21.5 % pre-BAV versus 35.6 % no-pre-BAV, p < 0.001).  After propensity score matching, there were no differences in MACCE between the 2 groups.  The authors concluded that the findings of this study showed that, in selected patients and with specific transcatheter valves, TAVI without pre-BAV appeared to be associated with similar mid-term outcomes compared with TAVI with pre-BAV, but it may increase the need for post-dilation.

Bandali et al (2016) examined the feasibility and safety of direct TAVI by the transfemoral approach without BP using the Edwards SapienXT valve. A total of 81 patients (mean age of 84 years [95 % CI: 82 to 85.8], 62 % male, median EuroScore of 22.8 % [95 % CI: 20.5 to 27]) undergoing transfemoral TAVI (35 by direct implantation [direct group]; 46 with BP [balloon group]) between 2010 and 2013 were analyzed for safety and effectiveness end-points.  Procedural success was 100 %.  Pre and post-procedural peak gradients in the direct group were 66 mmHg (95 % CI: 59 to 72.8) and 14 mmHg (95 % CI: 12 to 17.8)(p < 0.0001) compared to 76.5 mmHg (95 % CI: 73.7 to 94.0) and 17 mmHg (95 % CI: 16 to 19)(p < 0.0001) in the balloon group.  Post-dilatation was performed in 4/35(11.4 %) of the direct group and 3/46(6.5 %) of the balloon group (p = 0.83).  Post procedure moderate AR was present in 1/35 (2.9 %) in the direct group and none in the balloon group.  In-hospital mortality (2.9 % direct versus 0 % balloon group), stroke (2.9 % versus 4.4 %), tamponade (2.9 % versus 2.2 %), major vascular complications (2.9 % versus 8.7 %) and new permanent pacing (2.2 % versus 0) were similar.  Pacing time, inflations, radiation dose and contrast use were all significantly lower in the direct group.  The authors concluded that direct implantation of the Edwards SapienXT valve during TAVI by the transfemoral route appeared feasible, safe, and effective in those without extreme calcification.

Vavuranakis et al (2017) evaluated the impact of BAV prior to TAVI. These investigators retrospectively studied 203 consecutive patients who were treated either with (pre-BAV-TAVI group) or without BAV (D-TAVI group).  Implantation depth (ID) was angiographically measured at non-coronary cusp (NCC) and left coronary cusp (LCC) at: the starting point (stage-1), before (stage-2), and after (stage-3) final bioprosthesis release.  Paravalvular regurgitation (PVR) and 1-year clinical follow-up were recorded.  Overall, from stage-1 to stage-3, prosthesis migrated toward the left ventricle, in both cusps and groups.  At NCC a forward migration was observed from stage-1 to stage-2 in both groups (p < 0.001).  In the pre-BAV-TAVI group only, at NCC, an upward migration decreased the ID from stage-2 to stage-3 (p = 0.022); PVR greater than or equal to grade 2, immediately after expansion was more frequently observed in pre-BAV-TAVI group (41 % versus 22 %, respectively; p = 0.024).  However, PVR was similar at discharge.  Clinical parameters were comparable between the 2 groups.  The authors concluded that the use of BAV prior to TAVI may have an impact on device final position, but not on short- and long-term clinical outcome.

Valve-In-Valve Replacement

Phan and co-workers (2016) stated that VIV implantation for degenerated aortic bioprostheses (BP) has emerged as a promising alternative to redo conventional aortic valve replacement (cAVR).  However there are concerns surrounding the safety and effectiveness of VIV.  In a systematic review, these investigators compared the outcomes and safety of transcatheter VIV implantation with redoes cAVR.  A total of 6 databases were systematically searched; and 18 relevant studies (823 patients) were included.  Pooled analysis demonstrated VIV achieved significant improvements in mean gradient (38 mmHg pre-operatively to 15.2 mmHg post-operatively, p < 0.001) and peak gradient (59.2 to 23.2 mmHg, p = 0.0003).  These improvements were similar to the outcomes achieved by cAVR.  The incidence of moderate para-valvular leaks (PVL) were significantly higher for VIV compared to cAVR (3.3 % versus 0.4 %, p = 0.022).  In terms of morbidity, VIV had a significantly lower incidence of stroke and bleeding compared to redo cAVR (1.9 % versus 8.8 %, p= 0.002 and 6.9 % versus 9.1 %, p = 0.014, respectively).  Peri-operative mortality rates were similar for VIV (7.9 %) and redo cAVR (6.1 %, p = 0.35).  The authors concluded that transcatheter VIV implantation achieved similar hemodynamic outcomes, with lower risk of strokes and bleeding, but higher PVL rates compared to redo cAVR.  They stated that future large randomized controlled trials (RCTs) and prospective registries are essential to compare the long-term effectiveness of transcatheter VIV with cAVR, and clarify the rates of PVLs.

Silaschi and associates (2017) noted that VIV is a new treatment for failing BP in patients with high surgical risk.  However, comparative data, using standard repeat surgical aortic valve replacement (redo-SAVR), are scarce.  These researchers compared outcomes after VIV with those after conventional redo-SAVR in 2 European centers with established interventional programs.  In-hospital databases were retrospectively screened for patients greater than or equal to 60 years, treated for failing aortic BP.  Cases of infective endocarditis or combined procedures were excluded; end-points were adjudicated according to the Valve Academic Research Consortium (VARC-2) criteria.  From 2002 to 2015, a total of 130 patients were treated (VIV: n = 71, redo-SAVR: n = 59).  Age and logistic EuroSCORE I scores were higher with VIV (78.6 ± 7.5 versus 72.9 ± 6.6 years, p < 0.01; 25.1 ± 18.9 versus 16.8 ± 9.3%, p < 0.01).  The 30-day mortality rate was not significantly different (4.2 and 5.1 %, respectively) (p = 1.0).  Device success was achieved in 52.1 % (VIV) and 91.5 % (p < 0.01).  No stroke was observed after VIV but in 3.4 % after redo-SAVR (p = 0.2).  Intensive care unit (ICU) stay was longer after redo-SAVR (3.4 ± 2.9 versus 2.0 ± 1.8 days, p < 0.01).  Mean trans-valvular gradients were higher post-VIV (19.7 ± 7.7 versus 12.2 ± 5.7 mmHg, p < 0.01), whereas the rate of permanent pace-maker implantation was lower (9.9 versus 25.4 %, p < 0.01).  Survival rates at 90 and 180 days were 94.2 and 92.3 % versus 92.8 and 92.8 % (p = 0.87), respectively.  The authors concluded that despite a higher risk profile in the VIV group, early mortality rates were not different compared with those of surgery.  Although VIV resulted in elevated trans-valvular gradients and therefore a lower rate of device success, mortality rates were similar to those with redo-SAVR.  These researchers stated that at present, both techniques serve as complementary approaches, and allow individualized patient care with excellent outcomes.

Spaziano and colleagues (2017) stated that TAVI for a failing surgical BP (TAV- in-SAV) has become an alternative for patients at high risk for redo surgical aortic valve replacement (redo-SAVR).  Comparisons between these approaches are non-existent.  These investigators compared clinical and echocardiographic outcomes of patients undergoing TAV-in-SAV versus redo-SAVR after accounting for baseline differences by propensity score matching.  Patients from 7 centers in Europe and Canada who had undergone either TAV- in-SAV (n = 79) or redo-SAVR (n = 126) were identified.  Significant independent predictors used for propensity scoring were age, NYHA functional class, number of prior cardiac surgeries, urgent procedure, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD) grade.  Using a caliper range of ± 0.05, a total of 78 well-matched patient pairs were found.  All-cause mortality was similar between groups at 30 days (6.4 % redo-SAVR versus 3.9 % TAV-in-SAV; p = 0.49) and 1 year (13.1 % redo-SAVR versus 12.3 % TAV-in- SAV; p = 0.80).  Both groups also showed similar incidences of stroke (0 % redo- SAVR versus 1.3 % TAV-in-SAV; p = 1.0) and new pace-maker implantation (10.3 % redo-SAVR versus 10.3 % TAV-in-SAV; p = 1.0).  The incidence of acute kidney injury requiring dialysis was numerically lower in the TAV-in-SAV group (11.5 % redo- SAVR versus 3.8 % TAV-in-SAV; p = 0.13).  The TAV-in-SAV group had significantly shorter median total hospital stay (12 days redo-SAVR versus 9 days TAV-in-SAV; p = 0.001).  The authors concluded that patients with aortic BP failure treated with either redo-SAVR or TAV-in-SAV had similar 30-day and 1-year clinical outcomes.

On June 5, 2017, the FDA approved an expanded indication for the Sapien 3 Transcatheter Heart Valve (THV) for patients with symptomatic heart disease due to failure of a previously placed bioprosthetic aortic or mitral valve whose risk of death or severe complications from repeat surgery is high or greater.

Hamilton and colleagues (2020) stated that valve-in-valve (ViV) TAVI is an alternative to redo-surgery in patients with failed surgical bioprostheses.  It remains unclear if outcomes vary when using either self-expanding (SE) or balloon-expandable (BE) valves.  These researchers compared outcomes between SE and BE transcatheter heart valves when used for ViV TAVI.  A systematic review of PubMed, Medline, and Embase was carried out identifying studies reporting outcomes following ViV TAVI.  Event rates were pooled for meta-analysis using a random-effects model.  The primary outcome was all-cause mortality at 12 months.  Secondary outcomes included 30-day and 3-year mortality in addition to standard safety outcomes after the procedure as per the Valve Academic Research Consortium criteria.  A total of 19 studies reporting outcomes for 1,772 patients were included: 924 in the SE group and 848 patients in the BE group.  There was no significant difference in all-cause mortality at 12 months (SE 10.3 % versus BE 12.6 %, p = 0.165, I2 = 0 %), or 3 years (SE 21.2 % versus BE 31.2 %, p = 0.407, I2 = 63.79).  SE valves had lower trans-valvular gradients after procedure and acute kidney injury (AKI), but higher rates of pace-maker insertion, moderate or severe para-valvular regurgitation and need for greater than or equal to 2 valves (all p < 0.05).  There were no differences in stroke, coronary obstruction, bleeding, or vascular complications.  Despite significant differences in key procedural outcomes between SE and BE valves when used for ViV TAVI, the authors found no difference in 12-month mortality.  These investigators stated that tailored device selection may further reduce the risk of adverse procedural outcomes, particularly over the longer term.

Re-Vascularization before TAVI

Kotronias and colleagues (2017) noted that recent recommendations suggested that in patients with severe aortic stenosis undergoing TAVI and co-existent significant coronary artery disease (CAD), the latter should be treated before the index procedure; however, the evidence basis for such an approach remains limited.  In a systematic review and meta-analysis, these researchers examined the clinical outcomes of patients with CAD who did or did not undergo re-vascularization before TAVI.  These investigators conducted a search of Medline and Embase to identify studies evaluating patients who underwent TAVI with or without percutaneous coronary intervention (PCI).  Random-effects meta-analyses with the inverse variance method were used to estimate the rate and risk of adverse outcomes.  A total of 9 studies involving 3,858 subjects were included in the meta-analysis.  Patients who underwent re-vascularization with PCI had a higher rate of major vascular complications (odd ratio [OR]: 1.86; 95 % confidence interval [CI]: 1.33 to 2.60; p = 0.0003) and higher 30-day mortality (OR: 1.42; 95 % CI: 1.08 to 1.87; p = 0.01).  There were no differences in effect estimates for 30-day cardiovascular mortality (OR: 1.03; 95 % CI: 0.35 to 2.99), myocardial infarction (OR: 0.86; 95 % CI: 0.14 to 5.28), acute kidney injury (OR: 0.89; 95 % CI: 0.42 to 1.88), stroke (OR: 1.07; 95 % CI: 0.38 to 2.97), or 1-year mortality (OR: 1.05; 95 % CI: 0.71 to 1.56).  The timing of PCI (same setting versus a priori) did not negatively influence outcomes.  The authors concluded that the findings of this meta-analysis suggested that re-vascularization before TAVI conferred no clinical advantage with respect to several patient-important clinical outcomes and may be associated with an increased risk of major vascular complications and 30-day mortality.  They stated that in the absence of definitive evidence, careful evaluation of patients on an individual basis is of paramount importance to identify patients who might benefit from elective re-vascularization.

Cerebral Embolic Protection Device During / Following Transcatheter Aortic Valve Implantation

Haussig and colleagues (2016) noted that stroke remains a major predictor of mortality after TAVI.  Cerebral protection devices might reduce brain injury as determined by diffusion-weighted magnetic resonance imaging (DWMRI).  In a single center, blinded, randomized clinical trial, these researchers examined the effect of a cerebral protection device on the number and volume of cerebral lesions in patients undergoing TAVI.  Brain MRI was performed at baseline, 2 days, and 7 days after TAVI.  Between April 2013 and June 2014, patients were randomly assigned to undergo TAVI with a cerebral protection device (filter group) or without a cerebral protection device (control group).  The last 1-month follow-up occurred in July 2014.  The primary end-point was the numerical difference in new positive post-procedure DWMRI brain lesions at 2 days after TAVI in potentially protected territories.  The first hierarchical secondary outcome was the difference in volume of new lesions after TAVI in potentially protected territories.  Among the 100 enrolled patients, mean (SD) age was 80.0 (5.1) years in the filter group (n = 50) and 79.1 (4.1) years in the control group (n = 50), and the mean (SD) procedural risk scores (logistic EuroScores) were 16.4 % (10.0 %) in the filter group and 14.5 % (8.7 %) in the control group.  For the primary end-point, the number of new lesions was lower in the filter group, 4.00 (interquartile range [IQR]: 3.00 to 7.25) versus 10.00 (IQR: 6.75 to 17.00) in the control group (difference, 5.00 [IQR: 2.00 to 8.00]; p < 0.001).  For the first hierarchical secondary end-point, new lesion volume after TAVI was lower in the filter group (242 mm3 [95 % CI: 159 to 353]) versus in the control group (527 mm3 [95 % CI: 364 to 830]) (difference, 234 mm3 [95 % CI: 91 to 406]; p = 0.001).  Considering adverse events (AEs), 1 patient in the control group died prior to the 30-day visit.  Life-threatening hemorrhages occurred in 1 patient in the filter group and 1 in the control group.  Major vascular complications occurred in 5 patients in the filter group and 6 patients in the control group; 1 patient in the filter group and 5 in the control group had acute kidney injury, and 3 patients in the filter group had a thoracotomy.  The authors concluded that among patients with severe aortic stenosis undergoing TAVI, the use of a cerebral protection device reduced the frequency of ischemic cerebral lesions in potentially protected regions.  Moreover, they stated that larger studies are needed to evaluate the effect of cerebral protection device use on neurological and cognitive function after TAVI and to devise methods that will provide more complete coverage of the brain to prevent new lesions.

In an editorial that accompanied the aforementioned study, Messe and Mack (2016) stated that "the findings from these preliminary studies suggest that embolic protection and deflection devices appear to represent a promising adjunct to improve the safety of TAVI.  Multiple additional industry-sponsored trials of embolic protection devices for patients undergoing TAVI are under way … additional studies are needed to determine the long-term implications of clinically silent cerebral infarcts detected on MRI … Embolic protection may not be feasible for every type of procedure, and other strategies for neuroprotection such as prophylactic medications, preconditioning, or selective brain cooling could have even broader implications and should be studies".

In a randomized trial, Van Mieghem and associates (2016) examined if the use of the filter-based Sentinel Cerebral Protection System (CPS) during TAVI can affect the early incidence of new brain lesions, as assessed by DWMRI, and neurocognitive performance.  From January 2013 to July 2015, a total of 65 patients were randomized 1:1 to TF-TAVI with or without the Sentinel CPS.  Patients underwent DWMRI and extensive neurological examination, including neurocognitive testing 1 day before and 5 to 7 days after TAVI.  Follow-up DW-MRI and neurocognitive testing was completed in 57 % and 80 %, respectively.  New brain lesions were found in 78%  of patients with follow-up MRI.  Patients with the Sentinel CPS had numerically fewer new lesions and a smaller total lesion volume (95 mm3 [IQR: 10 to 257] versus 197 mm3 [95 to 525]).  Overall, 27 % of Sentinel CPS patients and 13 % of control patients had no new lesions; 10 or more new brain lesions were found only in the control cohort (in 20 % versus 0 % in the Sentinel CPS cohort, p = 0.03).  Neurocognitive deterioration was present in 4 % of patients with Sentinel CPS versus 27 % of patients without (p = 0.017).  The filters captured debris in all patients with Sentinel CPS protection.  The authors concluded that filter-based embolic protection captured debris en route to the brain in all patients undergoing TAVI.  They stated that the findings of this study suggested that its use can lead to fewer and overall smaller new brain lesions, as assessed by MRI, and preservation of neurocognitive performance early after TAVI.  Moreover, they stated that the MISTRAL-C results should be considered hypothesis-generating and justify the larger randomized SENTINEL trial (NCT02214277) evaluating the Sentinel CPS that is currently recruiting patients in Germany and U.S.

In a meta-analysis, Bagur and associates (2017) examined if the use of EPD reduces silent ischemic and clinically evident cerebrovascular events associated with TAVI.  These researchers conducted a comprehensive search to identify studies that evaluated patients undergoing TAVI with or without EPD.  Random-effects meta-analyses were performed to estimate the effect of EPD compared with no-EPD during TAVI using aggregate data.  A total of 16 studies involving 1,170 patients (865/305 with/without EPD) fulfilled the inclusion criteria.  The EPD delivery success rate was reported in all studies and was achieved in 94.5 % of patients.  Meta-analyses evaluating EPD versus without EPD strategies could not confirm or exclude any differences in terms of clinically evident stroke (RR, 0.70; 95 % CI: 0.38 to 1.29; p = 0.26) or 30-day mortality (RR, 0.58; 95 % CI: 0.20 to 1.64; p = 0.30).  There were no significant differences in new-single, multiple, or total number of lesions.  The use of EPD was associated with a significantly smaller ischemic volume per lesion (standardized MD (SMD), -0.52; 95 % CI: -0.85 to -0.20; p = 0.002) and smaller total volume of lesions (SMD, -0.23; 95 % CI: -0.42 to -0.03; p = 0.02).  Subgroup analysis by type of valve showed an overall trend toward significant reduction in new lesions per patient using EPD (SMD, -0.41; 95 % CI: -0.82 to 0.00; p = 0.05), driven by self-expanding devices.  The authors concluded that the use of EPD during TAVI may be associated with smaller volume of silent ischemic lesions and smaller total volume of silent ischemic lesions.  However, EPD may not reduce the number of new-single, multiple, or total number of lesions.  There was only very low quality of evidence showing no significant differences between patients undergoing TAVI with or without EPD with respect to clinically evident stroke and mortality.

Jobanputra and colleagues (2017) stated that stroke is a devastating, potential complication of any cardiovascular procedure including TAVI.  Even clinically silent lesions as detected by MRI have been associated with poor long-term cognitive outcomes.  As a result, extensive efforts have been focused on developing stroke preventative strategies including the development of novel embolic protection devices.  These devices aim to reduce this risk by capturing or deflecting emboli away from the cerebral circulation.  These investigators provided an insight into the incidence and mechanisms of neurologic events during TAVI, explored the design features and initial human experience of each of the cerebral embolic protection devices that have been used during TAVI, and explained the major clinical trials of each of these devices with a focus on safety, effectiveness and other reported outcomes.  The authors concluded that the potential benefit of neuroprotection cannot be ignored as TAVI widens its scope to include younger and lower-risk patients wherein preventing a procedure related cerebral injury would potentially prevent long-term morbidity and mortality.

Testa and colleagues (2018) stated that the use of embolic protection devices (EPD) may theoretically reduce the occurrence of cerebral embolic lesions during TAVI.  Available evidence from single studies is inconclusive.  In a meta-analysis, these investigators evaluated the safety and efficacy profile of current EPD.  Major medical databases were searched up to December 2017 for studies that evaluated patients undergoing TAVI with or without EPD.  End-points of interest were 30-day mortality, 30-day stroke, the total number of new lesions, the ischemic volume per lesion, and the total volume of lesions.  A total of 8 studies involving 1,285 patients were included.  The EPD delivery success rate was reported in all studies and was achieved in 94.5 % of patients.  The use of EPD was not associated with significant differences in terms of 30-day mortality (OR 0.43 [0.18 to 1.05], p = 0.3); but it was associated with a lower rate of 30-day stroke (OR 0.55 [0.31 to 0.98], p = 0.04).  No differences were detected with respect to the number of new lesions (SMD -0.19 [-0.71 to 0.34], p = 0.49).  The use of EPD was associated with a significantly smaller ischemic volume per lesion (SMD, -0.52 [-0.85 to -0.20], p = 0.002) and smaller total volume of lesions (SMD, -0.23 [-0.42 to -0.03], p = 0.02).  The authors concluded that the use of an EPD in the setting of TAVI was not associated with a reduction in the rate of overall mortality.  The use of EPD, although according to evidence coming from a single non-randomized study, appeared able to reduce the rate of stroke.  The number of new ischemic cerebral lesions appeared unaffected by the use of an EPD.  However, the use of an EPD was associated with smaller volume of ischemic lesions, smaller total volume of ischemic lesions, and better neurocognitive parameters at follow‐up.  Moreover, they stated that available evidence is of low quality.

The authors stated that the main drawbacks of this meta‐analysis were the small number and the quality of the studies.  Patient‐level data were not available, thus precluding any adjustments for possible confounders, and the wide CIs made any conclusive statement possibly unreliable.  Other sources of heterogeneity related to the type of EPD, type of MRI scanner adopted, the timing of DW‐MRI, and neurocognitive assessment.

An UpToDate review on "Transcatheter aortic valve implantation: Complications" (Dalby and Panoulas, 2018) stated that "The clinical efficacy of embolic protection devices (EPDs) as potential means of reducing the risk of periprocedural stroke with TAVI has not been established".

Lam and colleagues (2019) performed a literature review according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis.  All searches were performed via PubMed, OvidSP, Medline, Web of Science Core Collection, and Cochrane Library.  Conference abstracts and proceedings were included.  Those that were out of scope of interest and review articles were excluded.  A total of 18 studies fulfilled the inclusion criteria of the 456 articles searched.  Regarding EPD use in TAVI, systematic review comparing EPD with no-EPD showed smaller total volume of cerebral lesions and smaller volume per lesion in patients with EPD in all studies.  They also performed better in post-operative neurocognitive assessments but could not demonstrate clinical prevention of embolic stroke in all studies.  While for EPD use in TEVAR, capture of embolic debris and absence of early post-operative neurocognitive deficit were demonstrated in all cases of 2 prospective pilot studies.  Concerning carbon dioxide flushing (CDF) in TEVAR, significant reduction in gaseous emboli released during stent-graft deployment was shown by 1 in-vitro study.  Successful CDF application in all patients, with only 1 case of post-operative non-disabling stroke, was also demonstrated by 1 cohort study.  The authors concluded that this systematic review of medical literature has demonstrated the safety and feasibility of EPD use in TAVI.  Although improvements in clinical outcomes have yet been demonstrated, there was level I evidence showing reduced embolic lesions in imaging.  These researchers stated that the use of EPD and CDF in TEVAR was suggested, but evidence remained inadequate to support routine clinical use.

Transcatheter Aortic Valve Implantation in Patients With Paradoxical Low-Flow, Low-Gradient Aortic Stenosis

Rodriguez-Gabella and associates (2018) noted that controversial data exist on clinical outcomes of patients with paradoxical low-flow, low-gradient aortic stenosis (PLF-LG-AS) undergoing valve replacement.  These researchers determined the clinical outcomes and treatment futility in patients with paradoxical low-flow (PLF), low-gradient (LG) severe aortic stenosis (AS) undergoing TAVI.  A total of 493 patients with severe symptomatic AS and preserved EF (greater than 50 %) undergoing TAVI were included.  Patients were divided in 2 groups: high gradient AS group (HG-AS; mean gradient greater than or equal to 40 mm Hg and stroke volume index greater than 35 ml/m2, n = 396); and PLF, LG AS group (PLF-LG-AS; mean AV gradient less than 40 mm Hg and indexed stroke volume less than or equal to 35 ml/m2, n = 97).  The primary end-point was treatment futility defined as death or poor functional status (NYHA class III and/or IV) at 6-month follow-up.  There were no differences in mortality between groups (PLF-LG-AS: 5 %, HG: 8 %; adjusted OR: 0.85, 95 % CI:0.29 to 2.46), but PLF-LG-AS patients remained more frequently in NYHA class III to IV (20 % versus 8 % in the HG group, adjusted OR: 2.46, 95 % CI:1.19 to 5.07); TAVI treatment futility was more frequent in the PLF-LG-AS group (24 % versus 14 %, adjusted OR: 1.90 [1.01 to 3.57]), and patients with PLF-LG-AS exhibited a higher rate of re-hospitalization for cardiovascular causes (9 % versus 5 %, adjusted OR: 2.95, 95 % CI:1.08 to 8.09).  Previous myocardial infarction (MI) and COPD were associated with treatment futility (p < 0.03 for both).  The authors concluded that TAVI was a futile treatment in 25 % of patients with PLF-LG-AS.  These results underscored the complexity and need for improving the clinical decision-making process and management of patients with PLF-LG-AS.

TAVI for Porcelain Aorta

In a systematic review, Useini and colleagues (2019) analyzed early and mid-term outcomes of patients undergoing TA-TAVI / TF-TAVI for aortic stenosis and porcelain aorta (PAo) in their institution.  Additionally, these investigators postulated that the TA approach may be associated with a more favorable neurological outcome than the TF approach.  Between 2011 and 2017, a total of 15 patients with PAo underwent TA-TAVI and 4 patients with PAo underwent TF-TAVI at the authors’ institution.  The assessment of PAo was performed either intra-operatively after aborted sternotomy or via CT for elective TAVI.  These researchers conducted mid-term follow-up.  Furthermore, a systematic review was performed to compare the mortality and neurological outcomes of TF-TAVI and TA-TAVI approaches.  TA-TAVI / TF-TAVIs were performed with 100 % device success, without para-valvular leakage of greater than or equal to 2 and without procedural death.  The 30-day mortality/stroke rates were 6.6 % / 0 % in TA-TAVI and 0 % / 25 % in TF-TAVI, respectively.  The 6-month, 1-year, and 2-year survival rates were in TA-TAVI / TF-TAVI 93 % / 75 %, 82 % / 66.6 %, and 50 % / 0 %, respectively.  The pooled results derived from the literature review were as follows: The prevalence of PAo in the TAVI population was 9.74 %; the mean logistic EuroSCORE was 41.9 % in TA-TAVI versus 16.2 % in TF-TAVI; the mean 30-day mortality was 5.9 % in TA-TAVI versus 6.3 % in TF-TAVI, and the mean stroke was 0.8 % in TA-TAVI versus 9 % in TF-TAVI.  The authors concluded that TA-TAVI showed promising early and mid-term outcomes in patients with Pao; TF-TAVI performed in patients with PAo was likely to be associated with higher rates of stroke than TA-TAVI.

TAVI for Bicuspid Aortic Stenosis

Makkar and colleagues (2019) stated that TAVR indications are expanding, leading to an increasing number of patients with bicuspid aortic stenosis undergoing TAVR.  Pivotal randomized trials conducted to obtain FDA approval excluded bicuspid anatomy.  These researchers compared the outcomes of TAVR with a balloon-expandable valve for bicuspid versus tricuspid aortic stenosis.  Registry-based prospective cohort study of patients undergoing TAVR at 552 US centers were included in this systematic review.  Participants were enrolled in the Society of Thoracic Surgeons (STS) / American College of Cardiology (ACC) Transcatheter Valve Therapies Registry from June 2015 to November 2018.  Primary outcomes were 30-day and 1-year mortality and stroke.  Secondary outcomes included procedural complications, valve hemodynamics, and QOL assessment.  Of 81,822 consecutive patients with aortic stenosis (2,726 bicuspid; 79,096 tricuspid), 2,691 propensity-score matched pairs of bicuspid and tricuspid aortic stenosis were analyzed (median age of 74 years; IQR 66 to 81 years; 39.1 %, women; mean [SD] STS-predicted risk of mortality, 4.9 % [4.0 %] and 5.1 % [4.2 %], respectively).  All-cause mortality was not significantly different between patients with bicuspid and tricuspid aortic stenosis at 30 days (2.6 % versus 2.5 %; HR, 1.04, [95 % CI: 0.74 to 1.47]) and 1 year (10.5 % versus 12.0 %; HR, 0.90 [95 % CI: 0.73 to 1.10]).  The 30-day stroke rate was significantly higher for bicuspid versus tricuspid aortic stenosis (2.5 % versus 1.6 %; HR, 1.57 [95 % CI: 1.06 to 2.33]).  The risk of procedural complications requiring open heart surgery was significantly higher in the bicuspid versus tricuspid cohort (0.9 % versus 0.4 %, respectively; absolute risk difference [RD], 0.5 % [95 % CI: 0 % to 0.9 %]).  There were no significant differences in valve hemodynamics.  There were no significant differences in moderate or severe paravalvular leak at 30 days (2.0 % versus 2.4 %; absolute RD, 0.3 % [95 % CI: -1.3 % to 0.7 %]) and 1 year (3.2 % versus 2.5 %; absolute RD, 0.7 % [95 % CI: -1.3 % to 2.7 %]).  At 1 year there was no significant difference in improvement in QOL between the groups (difference in improvement in the Kansas City Cardiomyopathy Questionnaire overall summary score, -2.4 [95 % CI: -5.1 to 0.3]; p = 0.08).  The authors concluded that in this preliminary, registry-based study of propensity-matched patients who had undergone TAVR for aortic stenosis, patients with bicuspid versus tricuspid aortic stenosis had no significant difference in 30-day or 1-year mortality, but had increased 30-day risk for stroke.  Because of the potential for selection bias and the absence of a control group treated surgically for bicuspid stenosis, randomized trials are needed to adequately examine the safety and efficacy of TAVR for bicuspid aortic stenosis.

The authors stated that this study had several drawbacks.  First, it had the inherent limitations of an observational study, including lack of center-independent adjudication of AEs, lack of an independent imaging core laboratory to confirm bicuspid anatomy and potential under-reporting of AEs.  Second, bicuspid aortic stenosis represents a heterogeneous anatomic cohort, with varying degrees of calcification.  It is possible that the operators selected the most favorable anatomic subsets of bicuspid aortic stenosis for TAVR while patients with highest-risk anatomical features were treated surgically.  Propensity-score matching was used to adjust for differences in baseline characteristics; however, it did not address this anatomic selection bias in the study.  Third, aortopathy is often seen in patients with bicuspid valves, but due to lack of data, the association between aortopathy and procedural complications such as aortic root rupture and aortic dissection was not assessed.  Fourth, this study included only patients treated with the contemporary balloon-expandable valves; thus, the results cannot be generalized to other valve types.

Computed Tomography Imaging Before TAVI

In a cross-sectional, observational study, Harries and colleagues (2020) described variations in CT in the context of TAVI (CT-TAVI) as currently performed in the United Kingdom.  A total of 408 members of the British Society of Cardiovascular Imaging (BSCI) were invited to complete a 27-item online CT-TAVI survey; 47 responses (12 % response rate) were received from 40 cardiac centers, 23 (58 %) of which performed TAVI on-site (TAVI centers).  Only 6 respondents (13 %) performed high-volume activity (greater than 200 scans per year) compared with 13 (28 %) performing moderate (100 to 200 scans per year) and 27 (59 %) performing low (0 to 99 scans per year) volume activity.  Acquisition protocols varied (41 % retrospective, 12 % prospective with wide padding, 47 % prospective with narrow padding), as did the phase of reporting (45 % systolic, 37 % diastolic, 11 % both, 6 % unreported).  Median dose length product was 675 mGy.cm (IQR of 477 to 954 mGy.cm).  Compared with non-TAVI centers, TAVI centers were more likely to report minimum ilio-femoral luminal diameter (n = 25, 96 % versus n = 7, 58 %, p = 0.003) and optimal tube angulation for intervention (n = 12, 46 % versus n = 1, 8 %, p = 0.02).  The authors concluded that this national survey formally described current CT-TAVI practice in the United Kingdom; high-volume activity was only present at 1 in 7 cardiac CT centers.  There is wide variation in scan acquisition, scan reporting and radiation dose exposure in cardiac CT centers.

The authors stated that this study had several drawbacks.  Despite attempts to obtain responses from United Kingdom cardiac CT centers, some centers that perform CT-TAVI were not captured.  Moreover, the survey only elicited responses (response rate only 12 %) from members of the BSCI, meaning that an unknown but likely significant number of those reporting CT-TAVI, for example, interventional cardiologists, have not been captured.  This introduced bias and influenced the external validity of the data, while reliance on self-reporting of data may also have introduced error.  Furthermore, some responses from different individuals originated from the same center.  Because these data were frequently discordant, reflecting intra-center variation, these investigators elected to include all responses from all respondents, which was also a source of bias.  The image quality of CT-TAVI scans obtained at United Kingdom cardiac CT centers was not analyzed in this study, but these researchers presumed that each center obtained diagnostic CT-TAVI images on the majority of occasions.  Finally and perhaps most importantly, no data on complications following CT-TAVI (e.g., contrast-induced nephropathy) were collected.  These researchers stated that future studies examining the relationship between CT-TAVI, peri-procedural complications and patient outcomes would be instructive and could inform optimal CT-TAVI scan acquisition protocols.

Mitral Regurgitation Prior to TAVI

Sethi and colleagues (2020) noted that mitral regurgitation (MR) is commonly encountered in patients with severe AS.  However, its independent impact on mortality in patients undergoing TAVI has not been established.  These researchers carried out a systematic search for studies reporting characteristics and outcome of patients with and without significant MR and/or adjusted mortality associated with MR post-TAVI.  They performed a meta-analysis of quantitative data.  A total of 17 studies with 20,717 patients compared outcomes and group characteristics; 21 studies with 32,257 patients reported adjusted odds of mortality associated with MR.  Patients with MR were older, had a higher Society of Thoracic Surgeons score, lower LVEF, a higher incidence of prior MI, atrial fibrillation (AF), and a trend towards higher NYHA class III/IV, but had similar mean gradient, gender, and CKD.  The MR patients had a higher unadjusted short-term (RR = 1.46, 95 % CI: 1.30 to 1.65) and long-term mortality (RR = 1.40, 95 % CI: 1.18 to 1.65).  However, 16 of 21 studies with 27,777 patients found no association between MR and mortality after adjusting for baseline variables.  In greater than 50 % of the patients (0.56, 95 % CI: 0.45 to 0.66) MR improved by at least 1 grade following TAVI.  The authors concluded that patients with MR undergoing TAVI had a higher burden of risk factors that could independently impact mortality.  However, there is a lack of robust evidence supporting an increased mortality in MR patients, after adjusting for other compounding variables; MR tended to improve in the majority of patients post-TAVI.

Appendix

The Society for Thoracic Surgeons operative risk score is available at it s webpage.

The European Association for Cardio-Thoracic Surgery’s Joint Task Force on the "Management of Valvular Heart Disease" (Vahanian et al, 2012) listed contraindications for TAVI:

Absolute contraindications

• Absence of a "heart team" and no cardiac surgery on the site
• Active endocarditis
• Appropriateness of TAVI, as an alternative to aortic valve replacement (AVR), not confirmed by a "heart team"
• Elevated risk of coronary ostium obstruction (asymmetric valve calcification, short distance between annulus and coronary ostium, small aortic sinuses)
• Estimated life expectancy less than 1 year
• For trans-femoral/subclavian approach: Inadequate vascular access (calcification, tortuosity, vessel size)
• Improvement of quality of life by TAVI unlikely because of co-morbidities
• Inadequate annulus size (less than 18 mm, greater than 29 mm) (contraindication when using the current devices)
• Plaques with mobile thrombi in the ascending aorta, or arch
• Severe primary associated disease of other valves with major contribution to the patient's symptoms that can be treated only by surgery
• Thrombus in the left ventricle

Relative contraindications

• Bicuspid or non-calcified valves
• For trans-apical approach: Severe pulmonary disease, left ventricular apex not accessible
• Hemodynamic instability
• Left ventricular ejection fraction less than 20 %
• Untreated coronary artery disease requiring revascularization

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered for indications listed in the CPB: :
33361	Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; percutaneous femoral artery approach
33362	open femoral artery approach
33363	open axillary artery approach
33364	open iliac artery approach
33365	transthoracic approach (eg, median sternotomy, medistinotomy)
33366	transapical exposure (eg, left thoracotomy)
33367	Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; cardiopulmonary bypass support with percutaneous peripheral arterial and venous cannulation (eg, femoral vessels) (List separately in addition to code for primary procedure)
33368	Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; cardiopulmonary bypass support with open peripheral arterial and venous cannulation (eg, femoral, iliac, axillary vessels) (List separately in addition to code for primary procedure)
33369	Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; cardiopulmonary bypass support with central arterial and venous cannulation (eg, aorta, right atrium, pulmonary artery) (List separately in addition to code for primary procedure)
Other CPT codes related to the CPB:
92986	Percutaneous balloon valvuloplasty; aortic valve
HCPCS codes covered if selection criteria are met:
Edwards Sapien, Edwards Sapien XT, Edwards Sapien 3, Medtronic CoreValve System - no specific code:
HCPCS codes not covered for indications listed in the CPB:
Embolic protection device - no specific code:
ICD-10 codes covered if selection criteria are met :
I06.0	Rheumatic aortic stenosis
I08.0	Rheumatic disorders of both mitral and aortic valves
I35.0 - I35.9	Nonrheumatic aortic valve disorders [stenosis]
Q23.0	Congenital stenosis of aortic valve [not covered for bicuspid aortic stenosis]
T82.01x+	Breakdown (mechanical) of heart valve prosthesis [degenerated bioprosthetic aortic valve]
T82.03x+	Leakage of heart valve prosthesis [degenerated bioprosthetic aortic valve]
T82.857+	Stenosis of cardiac prosthetic devices, implants and grafts [degenerated bioprosthetic aortic valve]
Z45.09	Encounter for adjustment and management of other cardiac device [replacement of a degenerated bioprosthetic aortic valve]
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
A40.0 - A40.9	Streptococcal sepsis
A41.01 - A41.9	Other sepsis
I06.1	Rheumatic aortic insufficiency
I33.0 - I33.9	Acute and subacute endocarditis
I70.0	Atherosclerosis of aorta [porcelain aorta]
Q23.1	Congenital insufficiency of aortic valve
T80.211A - T80.29XS	Infections following infusion, transfusion and therapeutic injection
T81.40xA - T81.49xS	Infection following a procedure
T88.0xx+	Infection following immunization

The above policy is based on the following references: