Transcatheter Aortic Valve Replacement (TAVR)

Severe symptomatic aortic stenosis carries a poor prognosis. Until relatively recently, surgical aortic valve replacement has been the standard of care in adults with severe symptomatic aortic stenosis. However, the risks associated with surgical aortic valve replacement are increased in elderly patients and those with concomitant severe systolic heart failure or coronary artery disease, as well as in patients with comorbidities such as cerebrovascular and peripheral arterial disease, chronic kidney disease, and chronic respiratory dysfunction.

Transcatheter aortic valve replacement (TAVR) was developed as an alternative to the surgical approach in this high-risk and inoperable population. TAVR is a minimally invasive, catheter-based procedure to replace the function of the aortic valve. Indicated for patients at intermediate or greater risk for open heart surgery, TAVR may be an excellent option for certain patients because the prevalence of aortic stenosis and comorbidities may increase the risks associated with surgical aortic valve replacement (SAVR). The entire procedure typically takes approximately 1-2 hours. A heart team comprising cardiac surgeons, interventional cardiologists, and other aortic stenosis experts may determine what the best procedure is as well as take into account other considerations such as whether the patient should receive a mild sedative or general anesthesia.

At the start of the procedure, surgeons make a small incision in one of three places, the groin, the neck, or an intercostal space. A thin, flexible catheter with the heart valve is guided through the incision into the artery and to the diseased valve. The TAVR heart valve is placed in the diseased or failing surgical valve; it begins working immediately. The catheter is then removed and the incision closed.

Currently available devices in the United States include the self-expandable Evolut R and Evolut PRO valves, the balloon-expandable Sapien3 and Sapien 3 Ultra valves, and the mechanically-expandable Lotus Edge valve.

Inclusion criteria

No established indications or guidelines exist yet for transcatheter aortic valve replacement (TAVR) in the United States. In clinical trials,[7, 9] the inclusion criteria were as follows:

• Patients with calcific aortic valve stenosis with the following echocardiographic criteria: mean gradient greater than 40 mm Hg or jet velocity more than 4 m/s and an initial aortic valve area (AVA) below 0.8 cm2 or indexed effective orifice area (EOA) of less than 0.5 cm2/m2; qualifying AVA baseline measurement must be within 45 days of the date of the procedure

• A cardiac interventionalist and two experienced cardiothoracic surgeons agree that medical factors either preclude operation or are high risk for surgical aortic valve replacement (SAVR), based on a conclusion that the probability of death or serious irreversible morbidity exceeds the probability of meaningful improvement; the surgeons' consult notes shall specify the medical or anatomic factors leading to that conclusion and include a printout of the calculation of the Society of Thoracic Surgeons (STS) score to additionally identify the risks in the patient; at least one of the cardiac surgeon assessors must have physically evaluated the patient

• Patient is deemed to have symptomatic aortic valve stenosis, as differentiated from symptoms related to comorbid conditions and as demonstrated by New York Heart Association (NYHA) functional class II or greater

In the European Union, TAVR is commercially available, and the procedure is performed in patients with severe aortic stenosis who are high-risk surgical candidates with a logistic EuroScore of more than 20%[10] and in patients who have a contraindication to SAVR.

Contraindications to transcatheter aortic valve replacement (TAVR) and exclusion criteria are as follows:

• Evidence of an acute myocardial infarction (MI) at 1 month (30 days) or less before the intended treatment (defined as Q-wave MI, or non–Q-wave MI with total creatine kinase [CK] elevation of CK-MB [muscle/brain] twice the normal level in the presence of MB elevation and/or troponin level elevation [World Health Organization definition])

• Aortic valve is a congenital unicuspid or congenital bicuspid valve or is noncalcified

• Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation >3+)

• Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation, or mechanical heart assistance within 30 days of the screening evaluation

• Need for emergency surgery for any reason

• Hypertrophic cardiomyopathy with or without obstruction

• Severe left ventricular (LV) dysfunction with an LV ejection fraction (LVEF) of less than 20%

• Severe pulmonary hypertension and right ventricular (RV) dysfunction

• Echocardiographic evidence of intracardiac mass, thrombus, or vegetation

• A known contraindication or hypersensitivity to all anticoagulation regimens or an inability to undergo anticoagulation for the study procedure

• Native aortic annulus smaller than 18 mm or larger than 25 mm as measured with echocardiography

• Magnetic resonance imaging (MRI)-confirmed stroke or transient ischemic attack (TIA) within 6 months (180 days) of the procedure

• Renal insufficiency (creatinine level >3 mg/dL) and/or end-stage renal disease requiring chronic dialysis at the time of screening

• Estimated life expectancy of less than 12 months (365 days) owing to noncardiac comorbid conditions

• Severe incapacitating dementia

• Significant aortic disease, including abdominal aortic or thoracic aneurysm, defined as a maximal luminal diameter of 5 cm or greater, marked tortuosity (hyperacute bend), aortic arch atheroma (especially if thick [>5 mm], protruding, or ulcerated] or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe "unfolding" and tortuosity of the thoracic aorta

• Severe mitral regurgitation[9, 11]  In a retrospective study (2008-2012) that evaluated whether high-risk patients with concomitant severe aortic stenosis and mitral valve disease should undergo double valve surgery (surgical aortic valve replacement and mitral valve surgery), investigators found that long-term survival in these patients may be similar to those for patients undergoing TAVR, but that surgical correction of double valvular disease in this patient population may not have a mortality benefit relative to TAVR alone.[12]

Best practices

A multidisciplinary team approach and the patient’s active participation in choosing the most appropriate form of treatment for aortic stenosis (transcatheter aortic valve replacement [TAVR] vs surgical aortic valve replacement [SAVR]) is critically important. Ideally, such a team would include the patient’s primary cardiologist, interventional cardiologist, cardiac surgeon, cardiac imaging specialist (echocardiography and computed tomography scanning or cardiac magnetic resonance imaging), cardiac anesthesiologist, nurse practitioners, and cardiac rehabilitation specialist. Such an approach would result in the best possible course of individualized treatment leading to the best possible clinical outcome.

Evolut transcatheter aortic valve replacement (TAVR) platform

There are two commercially available Medtronic heart valves, the Evolut R, and Evolut PRO valves, that come in different sizes. The Evolut TAVR platform, built on the proven foundation of the CoreValve valve, can be recaptured and repositioned. Its self-expanding nitinol frame enhances the ability to conform and seal to the native annulus. The supra-annular leaflet position keeps the working portion of the valve above and unconstrained by the native annulus. The Evolut PRO system features a unique valve design with an outer wrap that adds surface area contact between the valve and the native aortic annulus to further advance valve sealing performance. The supra-annular valve design maximizes leaflet coaptation and promotes single-digit gradients and large effective orifice areas (EOAs). The Evolut TAVR Systems commissure height and leaflet cuts are designed to minimize leaflet stress, as follows:

• Taller leaflet design provides a 12% reduction in stress when compared to traditional valve designs
• Reduces risk of collagen degeneration that could lead to tearing and valve failure ^[37]
• Reduced leaflet stress is “likely to have improved performance in long-term applications” ^[38]

The self-expanding nitinol frame provides accurate, controlled deployment with valve function occurring at approximately two-thirds deployment, providing time to assess the valve position and performance before making the decision to deploy or recapture. The valve is made from strong and pliable porcine pericardial tissue, making it durable and allowing for a low-profile delivery. The Evolut TAVR platform has the ability to treat the broadest annulus range, and the Evolut TAVR system maintains its outer diameter as it enters the vessel. The risk of major vascular complications increases as the outer diameter of the catheter increases.[39]  The outer diameter does not change as the system is advanced to the annulus with a vessel indication down to the following:

• ≥5.5 mm for Evolut PRO TAVs 23, 26, 29 mm and for Evolut R TAV 34 mm (20Fr outer diameter is 16Fr equivalent)
• ≥5.0 mm for Evolut R TAVs 23, 26, 29 mm (18Fr outer diameter is 14Fr equivalent)

The first-generation CoreValve device is no longer commercially available.

Clinical trials

The Evolut platform has demonstrated excellent safety and efficacy compared with surgery in extreme, high, intermediate, and low surgical risk patients. More recently, the Evolut Platform demonstrated significantly less composite death, disabling stroke, and heart failure hospitalization compared with SAVR in low-risk patients at 1 year and was noninferior relative to SAVR at 2 years.[40]

Figure 1. Evolut Low-Risk Trial 1-Year Results[40]

Table 1. Evolut Platform Clinical Trial Results (Open Table in a new window)

Table 2. Evolut TAVR Profile Sizing Information (Open Table in a new window)

Sapien 3 TAVR

The Edwards E-Sheath outer diameter increases from 6.0 to 8.2 mm once the delivery system is advanced through the vessel—a 35% increase.

Table 3: Sapien TAVR Profile Sizing Information (Open Table in a new window)

Clinical trials

The Sapien platform has also demonstrated success in extreme, high, intermediate, and low surgical risk patients. More recently, the Sapien 3 demonstrated significantly lower rates of composite death, stroke, or rehospitalization compared to SAVR in low-risk patients at 1 year.​[42]

Figure 2. PARTNER 3 Trial 1-Year Results[42]

Table 4. Sapien Platform Clinical Trial Results (Open Table in a new window)

Lotus Edge TAVR

Figure 3. Lotus Edge Valve System Information

Clinical trials

The Lotus platform has demonstrated safety in high-risk patients, but there have been no completed clinical trials in intermediate- or low-risk patients.[44]

Table 5. Lotus Platform Clinical Trial Results (Open Table in a new window)

Structural valve deterioration/durability

There are many factors that can affect valve durability. Lack of valvular circularity may contribute to undue stresses on leaflet tissue, as well as irregular leaflet motion, which may result in reduced durability.[i] Poor flow characteristics, due to an obstructive design,  may affect EOA and gradient adversely, thereby  impacting the longevity of the tissue.[ii] Design elements that produce points of stasis could  produce an increased risk of thrombosis, resulting in  suboptimal clinical results.[iii]

Additionally, there have been recent updates to structural valve deterioration definitions, with the focus around hemodynamic stability. (2017 EAPCI/ESC/EACTS definition: Moderate or severe haemodynamic  SVD: mean gradient ≥ 20  mm Hg or mean gradient ≥ 10 mm Hg change from  baseline or moderate/  severe intra-prosthetic  aortic regurgitation (AR)  (new or worsening from  baseline).) [iv]

• The NOTION Trial: self-expanding TAVR vs. SAVR in lower risk patients > 70 years eligible for surgery (more than 80% of patients had an STS ,3%.). TAVR had less SVD out to 6 years (4.8% vs. 24.0%). [v]
• Similarly, in the CoreValve US High Risk Pivotal Trial 5-year outcomes reported low SVD for TAVR vs. SAVR (9.5% vs. 26.6%). [vi]
• The CHOICE Registry is a randomized study of first generation self-expanding TAVR vs. balloon-expandable. The 5-year results showed lower SVD for self-expanding vs. balloon-expandable TAVR (0.0% VS. 6.6%). [vii]

[i] 43 Gunning PS, Saikrishnan N, Yoganathan AP, McNamara LM. Total ellipse of the heart valve: the impact of eccentric  stent distortion on the regional dynamic deformation of pericardial tissue leaflets of a transcatheter aortic valve  replacement. J R Soc Interface. December 6, 2015;12(113):20150737.

[ii] Flameng W, Herregods MC, Vercalsteren M, Herijgers P, Bogaerts K, Meuris B. Prosthesis-patient mismatch  predicts structural valve degeneration in bioprosthetic heart valves. Circulation. May 18, 2010;121(19):2123-2129. 

[iii] Midha PA, Raghav V, Sharma R, et al. The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the  Neosinus. Circulation. October 24, 2017;136(17):1598-1609.

[iv] Capodanno D, Petronio AS, Prendergast B, et al. Standardized definitions of structural deteriora-tion and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Car-diovascular Interventions (EAPCI). Eur Heart J 2017;38:3382–90.

[v] Søndergaard L, Ihlemann N, Capodanno D, et al. Durability of Transcatheter and Surgical Bioprosthetic Aortic Valves in  Patients at Lower Surgical Risk. J Am Coll Cardiol. February 12, 2019;73(5):546-553.

[vi] Gleason, TG, Reardon, MJ, Popma, JJ, et al. 5-year Outcomes from the Randomized CoreValve US Pivotal High Risk Trial: Final Results. J Am Coll Cardiol. September 2018; 72(13 Supplement).

[vii] Adbel-Wahab, M. Five-year outcomes after TAVI with balloon-expandable vs. self-expanding valves: Results from the CHOICE randomised clinical trial. Presented at EuroPCR 2019.

Patient-prosthesis mismatch

“Patient-prosthesis mismatch (PPM) occurs when the effective orifice area (EOA) of a normally functioning prosthesis is too small in relation to the patient’s body size …”vi. In order to avoid PPM, TAVR valve selection and their hemodynamics (EOA and mean gradients) may be an important consideration for patients and impact of activity levels.[i]

Native valves have an EOA of 3-4 cm2.[ii],[iii]  Patients will experience symptoms of AS when the area is less than half.vii  As patient-prosthesis mismatch (PPM)  is associated with poorer exercise  capacity, a larger EOA may result in  a quicker return to activity.[iv] Patient-prosthesis mismatch (PPM) drives gradients higher, particularly during exercise.  Severe PPM has been associated with increased mortality.[v] This is particularly important for patients who are more active and expected to live longer. Evidence suggests that a large EOA reduces PPM and allows patients to maintain  a higher exercise capacity.viii,[vi],[vii] An STS/ACC TVT Registry™ recent analysis examined the incidence and predictors of  prosthesis-patient mismatch (PPM) after TAVI in over 60,000  patients and indicated patient outcomes may improve when steps are taken to reduce and limit PPM.[viii] Several studies have demonstrated lower gradients and less PPM with self- expanding as compared to balloon-expandable prosthesis.[ix],[x],[xi] Additionally, a retrospective analysis of 30 day TTE outcomes reported normal reference values by native annular diameters showing intra-annular Sapien 3 TAVR was are higher risk of PPM.[xii]

[i] Baim DS, Grossman W. Complications of cardiac catheterization. In: Baim DS, Grossman W, eds. Cardiac Catheterization, Angiography and Intervention. Baltimore, MD: Williams & Wilkins; 1996:129.

[ii] Dahou A, Mahjoub H, Pibarot P. Prosthesis-Patient Mismatch After Aortic Valve Replacement. Curr Treat Options Cardiovasc Med. November 2016;18(11):67.

[iii] Head SJ, Mokhles MM, Osnabrugge RL, et al. The impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27 186 patients with 133 141 patient-years. Eur Heart J. June 2012;33(12):1518-1529.

[iv] Van Slooten YJ, van Melle JP, Freling HG, et al. Aortic valve prosthesis-patient mismatch and exercise capacity in adult patients with congenital heart disease. Heart. January 2016;102(2):107-113.

[v] Zorn GL 3rd, Little SH, Tadros P, et al. Prosthesis-patient mismatch in high-risk patients with severe aortic stenosis: A randomized trial of a self-expanding prosthesis. J Thorac Cardiovasc Surg. April 2016;151(4):1014-1023.e1-3.

[vi] Pibarot P, Dumesnil JG. Hemodynamic and clinical impact of prosthesis patient mismatch in the aortic valve position and its prevention. J Am Coll Cardiol. October 2000;36(4):1131-1141.

[vii] Bleiziffer S, Eichinger WB, Hettich I, et al. Impact of patient-prosthesis mismatch on exercise capacity in patients after bioprosthesis aortic valve replacement. Heart. May 2008;94(5):637-641.

[viii] Herrmann HC, Daneshvar SA, Fonarow GC, et al. Prosthesis-Patient Mismatch in 62,125 Patients Following Transcatheter Aortic Valve Replacement: From the STS/ ACC TVT Registry. J Am Coll Cardiol. December 4, 2018;72(22):2701-2711.

[ix] Jilaihawi H, Chin D, Spyt T, et al. Prosthesis-patient mismatch after transcatheter aortic valve implantation with the  Medtronic-CoreValve bioprosthesis. Eur Heart J. April 2010;31(7):857-864.

[x] Dvir D, Webb JG, Bleiziffer S, et al. Transcatheter aortic valve implantation in failed bioprosthetic surgical valves. JAMA. July 2014;312(2):162-170.

[xi] Pibarot P, Simonato M, Barbanti M, et al. Impact of Pre-Existing Prosthesis-Patient Mismatch on Survival Following Aortic Valve-in-Valve Procedures. JACC Cardiovasc Interv. January 22, 2018;11(2):133-141.

[xii] Hahn RT, Leipsic J,  Douglas PS. et al.  Comprehensive  Echocardiogrpahic  Assessment of Normal  Transcatheter Valve  Function. J Am Coll  Cardiol. January  2019;12(1):25-34.

Stroke and neurologic injury

Early data from TAVI clinical trials suggest that TAVI could increase the risk of stroke compared to SAVR or standard medical therapy in patients with aortic stenosis.[i],[ii] Other randomized trials have shown a similar or lower risk for all stroke and/or disabling stroke for TAVI compared to SAVR.[iii],[iv],[v] The SURTAVI trial demonstrated a numerically lower rate of stroke in TAVI compared to SAVR out to 24 months.[vi]

[i] Smith, CR., et al. Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients. N Engl J Med 2011; 364:2187-2198.

[ii] Leon, MB., et al. Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery. N Engl J Med 2010; 363:1597-1607.

[iii] Leon MB, Smith CR, Mack MJ, et al. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med. April 28, 2016;374(17):1609-1620.

[iv] Adams, DH., et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Prosthesis. N Engl J Med 2014; 370:1790-1798 DOI: 10.1056/NEJMoa1400590

[v] Thyregod, HGH., et al. Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Valve Stenosis: 1-Year Results From the All-Comers NOTION Randomized Clinical Trial. JACC. Volume 65, Issue 20, 26 May 2015, Pages 2184-2194

[vi] Popma JJ. SURTAVI: Two Year Complete Results from a Randomized Trial of a Self-expanding Transcatheter Heart Valve vs. Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis at Intermediate Surgical Risk. Presented at TCT 2018.

Aortic regurgitation

Newer generation valves with the addition for pericardial wraps or tissue skirt have seen improvements in PVL, similar to mechanically-expandable valves. xxv

Valve thrombosis

Design elements that produce points of stasis could increase risk of thrombosis, resulting in suboptimal clinical results.vii A supra-annular design decreases the likelihood of a neo-sinus — allowing adequate washing behind the native leaflets.[i] Intra-annularity may be a risk factor for thrombosis formation.v,vii The presence of reduced leaflet motion (RLM) is associated with increased risk of stroke or transient ischemic attack (TIA).[ii]

[i] Vahidkhah K, Barakat M, Abbasi M, et al. Valve thrombosis following transcatheter aortic valve replacement: significance of blood stasis on the leaflets. Eur J Cardiothorac Surg. May 1, 2017;51(5):927-935

[ii] Makki N, Shreenivas S, Kereiakes D, Lilly S. A meta-analysis of reduced leaflet motion for surgical and transcatheter aortic valves: Relationship to cerebrovascular events and valve degeneration. Cardiovasc Revasc Med. October-November 2018;19(7 Pt B):868-873.

Conduction disturbances

Conduction disturbance continues to be a key consideration in all TAVR procedures. There is a need for further evidence around conduction disturbance, procedural efficiencies, operator experience and the factors surrounding it. The need for a permanent pacemaker is a known risk of both transcatheter and surgical valve replacement. 

While some early generation TAVR devices were associated with a pacemaker rate of >20%, current commercially available devices report pacemaker rates of < 15%. [i],[ii],[iii]

[i] Forrest, J., et al. 30-Day Safety and Echocardiographic Outcomes Following TAVR with the Self-Expanding Repositionable Evolut PRO System. JACC: Cardiovascular Interventions Volume 11, Issue 2, 22 January 2018, Pages 160-168

[ii] Kodali, SK., et al. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012 May 3;366(18):1686-95. doi: 10.1056/NEJMoa1200384.

[iii] Forrest, J., et al. 30-Day Outcomes Following TAVR with the Evolut PRO Valve in Commercial Use: A Report From the STS/ACC TVT Registry™​. Presented at TCT 2018.

Annular rupture

Annular rupture is a rare complication of TAVR. Predisposing factors include small sinotubular junction or annular size, bulky and dense calcification, aggressive BAV, and porcelain aorta. Once annular rupture occurs, it is associated with high mortality. Management includes decisions for comfort care and sedation, attempts at medical management with pericardial drainage and autotransfusion of smaller leaks, or emergent conversion to an open operation.[9]

Post-TAVR coronary access

Post-TAVR PCI management is an important consideration for the lifetime management of low risk patients. Per the literature, the need to reaccess the coronaries is a very infrequent occurrence and a procedure with a very high success rate.

• Prevalence of CAD in patients with severe aortic stenosis undergoing TAVR ranges from 40% to 75%. [i]
• Single and multicenter studies report a range of 1.9%-5.7% of aortic valve replacement (TAVR or SAVR) patients required PCI post TAVR. [ii] ^{[, iii, iv]}
• The duration of time between the index AVR procedure and PCI varied widely for both TAVR and SAVR patients. (Mean days from index AVR to PCI Procedure: TAVR: 699.8±406.9 days, SAVR: 822.1 ±527.1 days. Linearized rate of PCI post AVR in patients (per year): TAVR: 0.008 SAVR: 0.009.) ^vii
• Clinical data show that coronary access post-TAVR is technically feasible and generally reported positive outcomes for all TAV types with an average PCI success rate of 93.8%. ^{vi , vii , viii [, v, vi, vii, viii]}
• For most TAVR patients, the risk of a future failed PCI attempt is low (0.4%) and therefore may not be as important as other, more acute procedural concerns.

  • Given the average PCI success rate of 93.8% and the post-TAVR PCI rate of 5.7%^v,vii,viii, the mean calculated risk for an unsuccessful PCI is 0.4% – meaning a 99.6% rate of favorable outcomes.

Figure 4. Evolut TAVR Frame Cell for Coronary Access

[i] Yudi, et. al. Coronary Angiography and Percutaneous Coronary Intervention After Transcatheter Aortic Valve Replacement. JACC. Mar 2018, 71 (12) 1360-1378; DOI: 10.1016/j.jacc.2018.01.057

[ii]    Tanaka A , Jabbour RJ, Testa L, et al. Incidence, technical safety and feasibility of coronary angiography and intervention following self-expanding transcatheter aortic valve replacement. Cardiovasc Revasc Med. Published online February 14, 2019.

[iii]   Kleiman NS. Coronary Intervention After Self-Expanding Transcatheter or Surgical Aortic Valve Replacement in the SURTAVI Trial. Presented at CRT 2019; Washington, D.C.

[iv]   Allali A, El-Mawardy M, Schwarz B, et al. Incidence, feasibility and outcome of percutaneous coronary inter vention af ter transcatheter aortic valve implantation with a self-expanding prosthesis. Results from a single center experience. Cardiovasc Revasc Med. September 2016;17(6):391-398.

[v]   Htun WW, Grines C, Schreiber T. Feasibility of coronary angiography and percutaneous coronary intervention after transcatheter aortic valve replacement using a Medtronic™ self-expandable bioprosthetic valve. Catheter Cardiovasc Interv. June 2018;91(7):1339-1344.

[vi]  Zivelonghi C, Pesarini G, Scarsini R, et al. Coronary Catheterization and Percutaneous Interventions After Transcatheter Aortic Valve Implantation. Am J Cardiol. August 15, 2017;120(4):625-631

[vii]   Chetcuti S, Kleiman N, Matthews R, Popma JJ, Moore J. TCT-743 Percutaneous Coronary Intervention after Self-Expanding Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. November 2016;68(18_Suppl):B300-B301.

[viii]   Blumenstein J, Kim WK, Liebetrau C, et al. Challenges of coronary angiography and intervention in patients previously treated by TAVI. Clin Res Cardiol. August 2015;104(8):623-639.

Valve embolization

Valve embolization generally occurs in one or more of the following conditions:

• Undersizing of the bioprosthesis

• Malposition

• Inappropriate capture during rapid ventricular pacing

In cases of aortic embolization, it is extremely important not to remove the guidewire from across the bioprosthetic valve until it is anchored in the distal aorta to prevent it from turning. A balloon catheter is placed in the proximal end of the prosthetic valve, and the valve is pulled distal to the left subclavian artery when it can be deployed or fully expanded. After fixing the embolized prosthesis, a new valve is then implanted in the aortic position. If, prior to fixing the embolized valve, the guidewire position is lost, the valve may become inverted, jeopardizing the antegrade blood flow through it, and, if left untreated, it is uniformly fatal. Valve embolization into the left ventricle is uniformly fatal. Aortography is recommended after valve manipulation to evaluate for any aortic dissection.[27]

Renal insufficiency

Acute renal failure after TAVR has an incidence of 12%-28% and may progress to require dialysis in 1.4% of cases. The important risk factors for development of renal failure include hypertension (OR = 4.66), transfusion requirement (OR = 3.47), and COPD (OR = 2.64). Acute renal failure is less common in patients undergoing transcatheter aortic valve implantation than in those undergoing surgical aortic valve replacement (2.5% vs 8.7%).[27]

Vascular complications

Vascular complications include aortic or iliofemoral dissection, vascular perforation, vessel rupture or avulsion, bleeding requiring significant blood transfusions, or additional percutaneous or surgical interventions.[27] These are the most frequent adverse outcomes of TAVR and are especially common with the TF approach.

These complications relate to the large-caliber sheaths necessary for device deployment, as well as severe atherosclerosis of the arteries, which is common.[28] Center/operator experience, the degree and location of vascular calcification (higher risk of complications in longer and more severely calcified arterial segments), vascular tortuosity, and sheath-to-artery ratio (higher risk of complications with larger sheath sizes) are predictors of major vascular complications.[28, 29] The incidence of major vascular complications ranges from 2%-26% with TF access (related to vessel size, tortuosity, and degree of aortoiliac occlusive disease) and 5%-7% with TA access.

Ventricular perforation

Ventricular perforation is a rare complication of TF TAVR. Its management includes pericardial drainage and autotransfusion or conversion to open closure.

For obtaining informed consent, it is critical to appropriately inform patients and their family about the benefits and risks of the procedure so the patient is ultimately able to make a voluntary decision. A central goal in this interaction is the exchange of relevant detailed information about treatment strategies delivered in terminology that is understood by the patient and family. It is important to recognize that risk tolerance and patient expectations vary across many patient populations. Thus, a thorough review of personalized risk/benefit profile is essential for each patient undergoing transcatheter aortic valve replacement (TAVR).

Patients who are considered for TAVR should undergo the preprocedural workup below.

Echocardiography is used to confirm the severity of aortic stenosis, aortic valve anatomy, and extent of calcification and to evaluate the diameter of the aortic annulus, ascending aorta, sinus of Valsalva, the distance of the aortic valve leaflets to sinotubular junction, the presence of concomitant severe other valvular disease, and the LVEF.

CT angiography of the aortic root is used to determine the optimal image orientation for valve positioning.

Left and right cardiac catheterization is used to evaluate for concomitant coronary artery disease or pulmonary hypertension that may require treatment prior to TAVR.

CT angiography of the thoracoabdominal and iliofemoral arteries is used to evaluate the diameter, tortuosity of the vessels, and calcifications and to plan for the access site.[9, 27]

The equipment required for TAVR depends on the specific approach to the procedure and the performing center protocols.

CoreValve

The current, third-generation 18F CoreValve System has 3 components, as follows:

• A self-expanding nitinol support frame with cells configured in a diamond cell design, which anchors a trileaflet porcine pericardial tissue valve

• An 18F delivery catheter

• A disposable loading system

  Transcatheter Aortic Valve Replacement (TAVR). Medtronic CoreValve.

Edwards-SAPIEN valve

The Edwards SAPIEN valve is a trileaflet bioprosthesis made of bovine pericardium mounted on a balloon-expandable stainless-steel stent. This system is currently available in two sizes: (1) a 23-mm valve with a stent height of 14.3 mm and (2) a 26-mm valve with a stent height of 16.1 mm.

The second-generation device, Edwards SAPIEN XT, is made of a cobalt-chromium alloy, which provides the same radial strength with a reduced valve profile. This valve is currently commercially available in Europe and is approved for the TF approach. It is under investigation for the TA approach. The system will be available in 21-mm and 29-mm sizes in the future.[27]

Retroflex balloon catheter

The retroflex balloon catheter is used for valvuloplasty of the stenotic native aortic valve prior to implantation of an Edwards SAPIEN transcatheter heart valve. The device is not intended for postdilation of deployed transcatheter heart valves.

Crimper

The crimper is used in preparing the Edwards SAPIEN transcatheter heart valve for implantation by manually and symmetrically compressing the overall diameter of the bioprosthesis from its expanded size to its minimal delivery profile. The provided cylindrical gauge is used to confirm that the collapsed profile of the valve system will feasibly move through the introducer sheath. A measuring ring is used to calibrate the balloon inflation to its desired size and to determine the amount of saline/contrast mixture in the syringe required for balloon inflation at the time of deployment.

Retroflex guiding catheter

This catheter has a deflectable tip that changes direction when activated by the rotation of an actuator incorporated in the handle. The catheter is then used to direct the valve delivery system through the arterial system, around the aortic arch, and across the aortic valve, providing a less traumatic passage. The retroflex catheter assists in centering and supporting the valve as it crosses the calcified and stenotic native valve.

The Novoflex catheter is a newer-generation catheter that allows loading of the Edwards SAPIEN XT prosthesis onto the balloon while in the body, decreasing the sheath size dramatically.

Ascendra delivery system

This delivery catheter is used for the TA approach. The catheter allows for easy manipulation of the valve to improve orientation of the bioprosthesis.

Delivery sheath

This a 25-cm–long hydrophilic-coated sheath that is advanced into the abdominal aorta to decrease vascular complications, as the bioprosthetic valve and the deflecting guide catheter are introduced into the aorta. The sheaths are equipped with a hemostatic mechanism to decrease blood loss. The TF delivery system requires a 22F and 24F sheath for the 23-mm and 26-mm valves, respectively. See Table 3.

The TA sheath is 26F, is shorter, and has a flexible tip to minimize trauma as it is introduced in to the left ventricle.[9, 27, 30]

Anesthesia

Transcatheter aortic valve implantation can be performed under conscious sedation or general anesthesia. General anesthesia is preferred if TEE echocardiography is performed.

Positioning

The patient remains in the supine position during the procedure.

Testing and medications

Patients are pretreated with aspirin (81-325 mg) daily and clopidogrel 300-mg loading dose at least one hour prior to the procedure and continued at 81-mg oral daily dose. After the procedure, aspirin (at least 81 mg daily) is continued indefinitely, and clopidogrel 81 mg daily is continued for 1-6 months.

Adjunctive antacids are to be considered.

Routing laboratory tests prior to the procedure include complete blood cell (CBC) count, international normalized ratio (INR), partial thromboplastin time (PTT), albumin and transaminase levels, renal function testing, and 12-lead electrocardiography (ECG). Cardiac biomarker levels (ie, CK and CK-MB) are also tested within 48 hours of the procedure.

To minimize the risk of prosthetic valve infection, prophylactic intravenous antibiotic therapy at least 1 hour before the procedure is also recommended. The authors use cefuroxime 750 mg IV 1 hour preprocedure, and the dose is repeated 6 and 12 hours after the procedure. In patients who are allergic to penicillin (or cephalosporins), vancomycin may be considered.

The patient should be observed with a temporary pacemaker in a cardiovascular ICU for up to 48 hours to monitor for any conduction system abnormalities. If no conduction system disturbances are detected, the patient is monitored for an additional 72 hours and then discharged.

The patient should continue taking aspirin 81-325 mg daily and clopidogrel 75 mg daily for at least 3 months following the procedure.

Both transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) may be used to guide the procedure and evaluate for complications, as needed.

Continuous invasive hemodynamic monitoring should be used throughout the procedure.

The procedure can be performed in the cardiac catheterization laboratory or in a hybrid operating room. A fixed fluoroscopy unit is required and should be capable of providing high-quality images, as well as storing the reference images. Cardiopulmonary bypass equipment should be available easily in case of complications. The room should also be equipped with supplies required to treat vascular and coronary complications.

The Edwards SAPIEN valve may be implanted via a TF or TA approach, and the Medtronic CoreValve system can be delivered through a femoral, subclavian, or direct aortic approach (direct aortic access can be achieved through either a ministernotomy or a minithoracotomy).[9, 31]

Vascular complications have been associated with significant mortality and may be prevented by accurate screening. Table 2 summarizes the minimal vessel diameter required for different transcatheter aortic valve systems.

Table 2. Minimum Required Arterial Access Diameter for Transcatheter Aortic Valve Replacement (TAVR) (Open Table in a new window)

Venous access

Central venous access (preferably jugular or subclavian) is obtained, and a 5F balloon-tip pacing wire is positioned in a stable location within the right ventricle under fluoroscopy. After the pacing system is tested, the backup pacing rate is set at 50 beats per minute.

Arterial access

First, arterial access is obtained on the contralateral side to the planned 18F sheath for the CoreValve system. Then, arterial access for the 18F sheath is obtained. Arterial puncture can be performed percutaneously under angiographic or ultrasound guidance to ensure cannulation of the anterior common femoral artery, as this is essential for successful percutaneous closure. Alternatively, surgical cutdown can be used for access per performing center protocol and patient’s vascular anatomy.

Once access has been obtained, anticoagulation is administered to maintain an activated clotting time (ACT) of 250 seconds or more.

Crossing the native aortic valve

A 5F-6F graduated pigtail catheter is advanced to the ascending aorta, and the distal tip of the catheter is positioned in the noncoronary cusp of the native aortic valve.

The optimal annular viewing plane using contrast injections under fluoroscopy is then identified to allow visualization of all 3 coronary sinuses in the same plane, preferably in the left anterior oblique projection.

An Amplatz left (AL) diagnostic catheter is then advanced to the ascending aorta over a standard J-tip guidewire through the primary access sheath. The J-tip guidewire is then exchanged for a 0.035-inch straight-tip guidewire, which is used to cross the native valve. After crossing the aortic valve, the AL catheter is advanced into the left ventricle.

The straight-tip guidewire is exchanged for an exchange-length J-tip guidewire, and the AL catheter is exchanged for a 6F pigtail catheter. The guidewire is removed, and, after appropriate flushing, the pigtail catheter is connected to the pressure transducer. Using both pigtail catheters, the simultaneous pressures across the native aortic valve are recorded, and the pressure gradient is measured.

The distal portion of a 0.035-inch super-stiff guidewire is carefully pigtail-shaped to prevent inadvertent left ventricular perforation, and, in right anterior oblique projection, it is advanced through the pigtail catheter in the apex of the left ventricle. Maintaining the super-stiff guidewire position, the pigtail catheter is removed.

Balloon aortic valvuloplasty

Predilation of the aortic valve is then performed using an appropriately sized balloon. Balloon sizing should be directed to 1:1 (or less) sizing of the minimal annular diameter via CT angiography or echocardiography, with a maximum balloon size of 25 mm.

The valvuloplasty balloon is inserted through the 18F introducer sheath and advanced to the ascending aorta. Rapid pacing testing is then performed. A successful result is defined as 1-to-1 pacing capture with an immediate drop in pressure, reduction of the systolic-diastolic waveform, and reduction of the peak systolic pressure to less than 60 mm Hg. This is usually achieved by pacing at 180-200 beats per minute.

It is important to have the CoreValve prepared and mounted on the delivery system and ready to implant prior to BAV should acute severe aortic regurgitation and hemodynamic compromise result from valvuloplasty.

At this point, the valvuloplasty balloon is positioned across the aortic valve, while strict fluoroscopic surveillance of the distal tip of the super-stiff guidewire in the left ventricle is maintained.

After BAV is performed, the balloon is removed while maintaining the guidewire position. Aortography is then performed to assess the degree of aortic regurgitation.[9, 27, 31, 32]

CoreValve implantation

After valvuloplasty, the CoreValve device is advanced over the high-support 0.035-inch guidewire under careful fluoroscopic surveillance of the guidewire tip in the left ventricle. It is important to prevent the guidewire from moving forward as the device is advanced across the aortic arch.

The CoreValve bioprosthesis is then positioned across the aortic valve within the aortic annulus (< 6 mm below the annulus).

The annulus is defined as the angiographic floor of the native valve cusps.

After optimal positioning of the CoreValve delivering system is confirmed with fluoroscopy, the deployment is started by slow and clockwise turning of the microknob. As the inflow aspect of the bioprosthesis begins to flare outward, aortography is performed sequentially. Once annular contact is made, the device should not be advanced into a lower position.

Valve deployment is continued rapidly to the two-thirds deployment point; then, optimal placement of the bioprosthesis is confirmed with angiography. Valve position and function are also evaluated using hemodynamics and echocardiography.

When the optimal position is achieved, the microknob is continually turned until both frame loops disengage. Orthogonal views under fluoroscopy are used to confirm the frame loops have detached from the delivery catheter tabs.

The CoreValve delivery system is withdrawn carefully into the ascending aorta, avoiding contact with the inflow portion of the frame.

Table 3. Summary of Approved Sizes for CoreValve (Open Table in a new window)

During implantation, if resistance to deployment is encountered (eg, clicking of the microknob) or if the microknob is tight or stuck, apply mild upward pressure to the macro slider while turning the microknob. It the device still does not deploy, the bioprosthesis should be removed and another system used.

During the final deployment step, if one of the frame loops is still attached to the catheter tab, the catheter is slightly advanced under fluoroscopy; if necessary, the handle is gently rotated clockwise and counterclockwise (< 180° in each direction) to disengage the loop from the catheter tab.

Postdeployment

Once the CoreValve is deployed, the delivery system is withdrawn to the descending aorta while maintaining the guidewire position in the left ventricle, and the delivery system is removed through the 18F introducer sheath.

A 6F pigtail catheter is advanced into the left ventricle over the guidewire, and the guidewire is removed. Using the 2 pigtail catheters and 2 transducers, simultaneous left ventricular and aortic pressures are recorded, and the mean pressure gradient across the aortic valve is documented.

Postimplant aortography is performed to assess the degree of residual stenosis within the frame, the degree of aortic regurgitation, and patency of the coronary arteries (see videos below).

The 18F introducer sheath is then removed and the access site closed using percutaneous closure devices or surgically in the case of surgical cutdown. Using a 5F pigtail catheter from the contralateral side, angiography of the primary iliac and femoral arteries is performed to rule out any potential vascular complications.

The pigtail catheter is removed over a standard J-tip guidewire, the 6F introducer sheath removed, and the access site closed.

The Edwards SAPIEN valve may be implanted via a TF or TA approach.

Transfemoral approach

Vascular access

After the side of access for the prosthetic valve sheath is decided, the artery on that side is cannulated percutaneously or via surgical cutdown. Femoral access is also obtained on the contralateral side for aortic angiography using a 5F-6F pigtail catheter. A 6F venous access is also obtained for a temporary pacemaker lead, which is used for rapid ventricular pacing. If vascular access is obtained percutaneously for the valve delivery sheath, it can be preclosed with 2 suture-mediated closure devices. If a surgical cutdown is performed, the common femoral artery should not be dissected completely in the posterior aspect, as sheath insertion is easier when the artery is partially anchored.

Temporary pacemaker insertion

A temporary ventricular stimulation lead is placed in the right ventricle. Appropriate capturing is ensured, and a rapid ventricular pacing test is performed at a rate of 180-220 beats per minute.

Aortic angiography

Ascending aortic angiography is performed in a projection that places all of the aortic cusps in line and perpendicular to the image intensifier. Ideally, the projection is previously determined to minimize radiation and contrast exposures.

Crossing the native valve

At this point, intravenous heparin is administered, and once the ACT is confirmed to be therapeutic, the aortic valve is crossed as described above (see Crossing the native aortic valve).

Insertion of delivery sheath

The inserted 8F arterial sheath is then removed, maintaining the guidewire position in the apex of the left ventricle; then, serial dilation of the common femoral artery is performed with arterial dilators of increasing size (16F-25F). This is followed by insertion of the delivery sheath and positioning of the tip in the descending aorta.

Balloon aortic valvuloplasty

Under rapid ventricular pacing, balloon valvuloplasty of the native aortic valve is performed as described above (see Balloon aortic valvuloplasty). A 20- or 23-mm retroflex balloon is used for implantation of the 23- or 26-mm Edwards SAPIEN bioprosthesis.

Edwards SAPIEN valve implantation

The prosthetic valve and the delivery system are inserted through the sheath over the extra-stiff guidewire while the wire position is maintained in the left ventricle. When the delivery system reaches the aortic arch, the retroflex catheter is activated to allow safe passage of the valve delivery system across the aortic arch, and the system is then advanced into the ascending aorta.

The Edwards SAPIEN valve is then positioned in the aortic position, maintaining a 60:40 ratio of ventricular-aortic positioning, in the predetermined reference projection with the aortic annulus situated perpendicular to the screen. The appropriate valve position is confirmed using angiography and echocardiography.

Rapid ventricular pacing is started, and, after the systolic blood pressure has reached and maintained at its nadir, the aortic valve is deployed. Balloon inflation is held 3-5 seconds before deflation, and the rapid pacing is then stopped to avoid traction on the valve while the balloon catheter is being withdrawn. At this point, the delivery system is straightened and withdrawn. Paravalvular leaks are evaluated with echocardiography and angiography, and the transvalvular gradient is measured.

Arterial sheath removal

The sheath is removed with close monitoring of blood pressure and simultaneous contrast administration through a pigtail catheter placed at the level of iliac bifurcation. Contrast extravasation or significant hypotension indicates vascular rupture, which should be treated immediately using a covered stent or surgery. Prior to surgical arterial repair, emergent tamponade of the ruptured vessel using a large size sheath and/or closure of the iliac artery or abdominal aorta with a large size balloon is performed.

Closure of the arteriotomy site

The arteriotomy site is closed surgically or percutaneously with the previously placed preclosure device(s). With the new-generation Edwards SAPIEN XT device, preclosing with a single 10F device can be performed.

Transapical approach

In the TA approach, femoral arterial and venous access is obtained for aortic root angiography and temporary pacemaker placement for rapid ventricular pacing, as described above (see Venous access).

A small left lateral thoracotomy is performed, the subcutaneous tissue is dissected until the left ventricular apex is visible, and a pursestring suture then is placed in a muscular segment of the apicolateral wall. Heparin is then administered, and, once the ACT is confirmed to be in the therapeutic range, a direct puncture of the left ventricle is performed and a 7F or 8F sheath is inserted directly into the left ventricle.

A 0.035-inch J-tip guidewire is advanced into the descending aorta through the native aortic valve while being guided with a Judkins right catheter. It is important to ensure the wire is free of the papillary muscles or mitral chordal structures to avoid complications with the insertion of the delivery sheath.

After the wire is advanced into the descending aorta, it is exchanged for an extra-stiff Amplatz 0.035-inch 270-cm–long guidewire, and the Judkins right catheter is removed. At this point, the sheath is exchanged for a 26F delivery sheath that is inserted 3-4 cm into the left ventricle. Using a 20-mm retroflex balloon, BAV under rapid ventricular pacing is performed.

The Ascendra delivery system is advanced into the sheath and de-aired. The valve-catheter ensemble is then advanced into the aortic position, maintaining a ratio of 50:50 aortic-ventricular positioning. The optimal position of the prosthetic valve is confirmed using echocardiography and angiography guidance.

The aortic valve is deployed under rapid ventricular pacing when blood pressure is at its nadir and during a patient breath-hold, and the balloon is then deflated and removed. The degree of aortic regurgitation and valve position are evaluated with TEE guidance.

Postdilation of the valve may be performed as indicated.

If no further interventions are required, the delivery sheath is removed, the access site repaired, and anticoagulation reversed. The left lateral thoracotomy site is closed surgically over a drain.[9, 27, 30]

The objectives of pharmacotherapy are to prepare the patient for the procedure, to prevent complications, and reduce morbidity.

Class Summary

It inhibits prostaglandin synthesis, which prevents the formation of platelet-aggregating thromboxane A2.

Clopidogrel (Plavix)

Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to platelet receptors and subsequent ADP-mediated activation of the glycoprotein (GP) IIb/IIIa complex, thereby inhibiting platelet aggregation. Antiplatelet therapy with aspirin (162-325 mg) and clopidogrel (300 mg) is started at least 24 hours prior to transcatheter aortic valve implantation.

Aspirin (Bayer Aspirin, Ascriptin Maximum Strength, Ecotrin, Bufferin)

Patients are pretreated with aspirin (81-325 mg) daily and clopidogrel 300-mg loading dose at least one hour prior to the procedure and continued at 81-mg oral daily dose. Antiplatelet therapy with aspirin (162-325 mg) and clopidogrel (300 mg) is started at least 24 hours prior to transcatheter aortic valve implantation.

Class Summary

Prophylactic intravenous antibiotic therapy at least 1 hour before the procedure is also recommended.

Cefuroxime (Ceftin, Zinacef)

Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity of first-generation cephalosporins; it adds activity against Proteus mirabilis, Haemophilus influenzae, E coli, Klebsiella pneumoniae, and Moraxella catarrhalis.

The dose is repeated 6 and 12 hours after the procedure. In patients who are allergic to penicillin (or cephalosporins), vancomycin may be considered.

Vancomycin

This is a potent antibiotic that is directed against gram-positive organisms and is active against enterococcal species. Vancomycin is used in conjunction with for prophylaxis in penicillin-allergic patients. Dose adjustment may be necessary in patients with renal impairment.