Catheter-Based Therapies: Current Practices and Considerations

Abstract

In just over a decade, there have been paradigm shifts globally in the catheter-based therapies available for the management of patients with severe aortic stenosis. The use of transcatheter aortic valve replacement (TAVR) has been a crucial turning point in the field of cardiology as it granted an option for a minimally invasive method to replace a valve for patients who may or may not be suitable for cardiac surgery. In this chapter, we discuss the current practices and considerations as well as the ongoing evolution of catheter-based approaches for TAVR. The predominant focus of the chapter will be on aortic valve device modifications, prototypes of valves, device delivery systems, and the various techniques. However, discussions on indications/contraindications, proper work-up, preparation, equipment and personnel, complications, and post-procedural management & surveillance will also be reviewed.

1. Introduction

Aortic valve stenosis is a common valvular disease that occurs due to narrowing and stiffening of the valve which restricts blood flow in the body. It is a systolic murmur heard loudest at the 2nd intercostal space in the right upper sternal border. The murmur radiates to the carotids and is described as crescendo-decrescendo. Some causes of the narrowing include calcification of the valve due to aging, congenital valve abnormalities, and rheumatic heart disease. Most people with aortic stenosis can be asymptomatic for years before developing worsening symptoms such as shortness of breath, syncope, fatigue, palpitations, and/or angina. The valve can be repaired or replaced with different procedures depending on the patient’s condition. Valve replacement is done by aortic valve replacement surgery or transcatheter aortic valve replacement (TAVR). TAVR is a minimally invasive procedure that replaces the aortic valve in patients who are not candidates for surgery. This procedure has significantly evolved over the years and has become part of the standard of care to improve patient outcomes in aortic stenosis.

2. History

For decades since the inception of the first surgical aortic valve repair in 1962, the only treatment option available for surgically high-risk patients suffering from severe aortic stenosis (AS) was medical management. In 1985, Alain Cribier performed the first catheter-based balloon aortic valvuloplasty in a 77-year-old inoperable female [1]. Unfortunately, this still provided little to no long-term improvements in outcomes for patients. On May 1, 1989, Henning R. Andersen successfully developed and implanted the first percutaneous synthetic aortic valve in an 80-kg closed chest pig in Aarhus University Hospital of Denmark (Figure 1) [2, 3].

Figure 1.

Henning Rud Andersen preparing an 80 kg pig in 1989 in the animal lab of Aarhus University Hospital (image obtained from Ref. [2]).

His inspiration stemmed from the works of Andreas Grüntzig and Charles Dotter who pioneered and performed the first-in-man percutaneous transluminal coronary angioplasty in 1977 in Zurich, Switzerland. Their works led to their nomination for the Nobel Prize in Medicine the following year. Augmenting what these two pioneers established, it was their student Julio Palmaz who then went on to invent and successfully implant the first balloon-expandable coronary stents. According to Andersen, it was in February 1989 during a conference lecture about balloon-expandable stents led by Palmaz in Scottsdale, Arizona when he suddenly thought of the idea of attempting such balloon-expandable stents but with larger diameters with collapsible valve tissue on the inside to mimic the structure and function of heart valves [2]. Andersen believed that if he utilized a very similar technique as Grüntzig and Palmaz, then he would be able to also perform percutaneous artificial heart valve implantations without the need for surgery. Upon returning to Denmark from the conference, Andersen spent several months creating his own valve prototypes utilizing iron and steel wires of various thickness and stiffness which he would buy from local hardware stores. These early valves were roughly ∼25 mm in diameter and consisted of 15–16 loops closed by soldering [2]. Over the next 3 years, Andersen continued to optimize durability and functionality of his device on pigs. Eventually he went on to add high loops for the commissure posts to be able to mount biological leaflets which he would harvest from pig hearts purchased from a local slaughterhouse (Figure 2).

Figure 2.

Early handmade prototype of an aortic valve with three high loops for mounting leaflets harvested from pig valves (image obtained from Ref. [2]).

Andersen credited J. Michael Hasenkam, a young cardiovascular surgeon in-training at the time, for this idea of mounting on biological leaflets to his new device. He also credited his medical student, Lars Lyhne Knudsen, for assisting him in developing various stents and mounting the leaflets and valves within. Andersen et al. went on to implant 35 more devices in-vitro in pigs. Their work was initially widely rejected and even ridiculed by journals, as well as many cardiothoracic surgeons around the world. In May 1992, their work was finally accepted and published by European Heart Journal [3]. In 1995, Andersen, Hasenkam, and Knudsen obtained a patent for their new invention. Over the next few years, their work rapidly began to gain recognition and other groups replicated their techniques utilizing both self-expandable and balloon-expandable valves on dogs, sheep, and pigs, all with positive outcomes.

On April 16, 2002, at the Charles Nicolle University Hospital in Rouen, France, Alain Cribier became the first to successfully perform aortic valve placement in an adult human patient [4]. Cribier went on to repeat his success utilizing both the traditional retrograde approach as well as the antegrade atrial trans-septal approach [5, 6]. All his implantations were performed under conscious sedation without the need for extracorporeal circulation and on high-risk inoperable patients, some of which were already in a state of cardiogenic shock. His trans-septal approach proved to be time-consuming, complex, and associated with more complications. Furthermore, interventionalists were becoming more comfortable with percutaneous techniques via various arterial access sites (more recently including the carotid artery). Thus, the anterograde methodology was abandoned. In 2003, Cribier’s startup company, Percutaneous Valve Technologies, was acquired by Edwards Lifesciences for $125 million. Thus, the Cribier-Edwards bioprosthetic valve became the first-generation of in-human transcatheter aortic valve replacement (TAVR) valves. In 2004, the first TAVR procedure was performed in the United States by Dr. William O’Neill at Henry Ford Hospital.

In the subsequent years, many clinical scientists, biotechnological companies, investors, and physicians joined this attractive and fiercely growing industry. Many augmented the devices and delivery systems while others continued to work on improving the technique itself. In 2007, the Edwards SAPIEN valve, made of bovine pericardium, was introduced as a life-saving option for prohibitive high surgical risk patients [7, 8]. Meanwhile that same year, Webb et al. demonstrated the feasibility and efficacy of the retrograde approach for TAVR [9].

The first clinical trials which successfully elucidated the feasibility and safety of TAVR were the Registry of Endovascular Critical Aortic Stenosis Treatment (RECAST) and the Initial Registry of EndoVascular Implantation of Valves in Europe (I-REVIVE) [5, 6].

By 2009, the two predominant valves in the industry were the self-expandable CoreValve ReValving system (CoreValve Inc., Irvine, California) and the balloon-expandable Edwards SAPIEN valve (Edwards Lifescience, Irvine, California). In 2009, CoreValve Inc. was acquired by Medtronic for over $700 million, thus allowing rapid global marketing, larger clinical trials, and continuous device refinement to minimize procedural complications and optimize outcomes. At the time, two momentous clinical trials which enrolled nearly 10,000 patients—the CoreValve/Evolut trial and the PARTNER (Placement of Aortic Transcatheter Valves) trial—demonstrated significant superiority with TAVR compared to medical management in patients with severe AS with high surgical risk [10]. Thus, prompt approval for TAVR by the U.S. Food and Drug Administration followed in 2011. By 2014, TAVR was being performed in over 50 countries, in over 720 centers around the world [11].

In 2016, positive results from the PARTNER II and the Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trials proved the balloon expandable Edwards SAPIEN XT and Medtronic’s CoreValve self-expanding valve to be non-inferior to surgery with respect to stroke and mortality even in patients who were intermediate surgical risk [12]. In 2019, published results from the PARTNER 3 trial revealed that the newer-generation SAPIEN 3 Ultra TAVR valve demonstrated superiority to surgery in both primary and numerous secondary endpoints in even low surgical patients [13]. As of 2023, the three-year follow-up outcomes from the ongoing Evolut Low Risk trial paired with the PARTNER 3 outcomes, continue to demonstrate overall non-inferiority of TAVR to SAVR in low-risk patients [14]. These promising results continue to be sustained. By 2025, over a quarter million TAVRs are projected to be performed annually around the world [11]. As more other ongoing global clinical trials continue to suggest both feasibility and safety of TAVR regardless of surgical risk, the paradigm global shifts towards perfecting the solution to severe aortic stenosis are expected to continue.

3. Indications

Today, TAVR is an FDA-approved treatment option for patients with severe native calcific AS of all risk profiles and for patients with failed surgical bioprosthetic valves. Preliminary results from clinical trials investigating outcomes in patients with low surgical risks are ongoing. We determine this risk using the Society of Thoracic Surgeon (STS) scoring system. A score greater than or equal to 4% (predicted risk of surgical mortality at 30 days) is the cutoff in today’s practice in determining eligibility for TAVR. The EuroSCORE II is an alternative scoring system that can be used for risk stratification. An STS score of ≥8% or a EuroSCORE II >15–20% indicates high risk.

According to the American Heart Association (AHA) guidelines and the European Society of Cardiology (ESC) guidelines, patients with severe low-flow low-gradient AS who have a left ventricular ejection fraction of less than 50% should also undergo TAVR regardless of the presence or absence of symptomatology [15]. If ejection fraction is preserved in these patients, the AHA issues a class 1 recommendation for intervention whereas Europe issues a class IIa recommendation. Asymptomatic patients with severe AS who have a preserved ejection fraction, should only undergo intervention on a case-by-case basis such as in patients with rapid rates of stenosis, severely elevated serum levels of B-type natriuretic peptide (Pro-BNP), or exercise intolerance [15, 16, 17, 18, 19].

Both North American and European guidelines mutually share the same criteria to classify severity and type of AS. We define severe high gradient AS a maximum velocity greater than or equal to 4.0 m/s with a mean transaortic gradient greater than or equal to 40 mmHg typically associated with an aortic valve area of <1.0 cm². We define low-flow low gradient severe AS having a valve area of less than 1.0 cm² with a concomitant maximum velocity less than 4.0 m/s and a mean transaortic gradient less than 40 mmHg. Although both North American and European societies agree on the indication of TAVR for older and high-risk patients. The European guidelines currently remain more conservative in their approach in younger patients requiring bioprosthetic valves. TAVR is generally considered in these patients only after the age of 75. The AHA however, recommends considerations of TAVR in patients above the age of 65 [15]. A schematic for diagnosis and treatment of AS adopted from the 2020 AHA guidelines is shown in Figure 3 [16].

Figure 3.

A schematic for management of AS adopted from the 2020 AHA guidelines (image obtained from Ref. [16]).

Factors that favor TAVR over SAVR include age, frailty, higher surgical risk, redo surgery, patients with prior radiation therapy to the chest, presence of a porcelain aorta, and the availability of a healthy percutaneous access sites. Factors that favor SAVR include younger age, bicuspid aortic valve, multivessel CAD, aortopathy requiring intervention, and concomitant significant valvulopathy necessitating cardiac surgery. As of now, there are no recommendations for early transcatheter intervention in patients with moderate AS. Clinical trials such as the TAVR UNLOAD trial in which we are assessing the safety and efficacy of TAVR in patients with moderate AS have been initiated and are currently ongoing. The indications for TAVR are anticipated to continuously evolve in years to come.

4. Contraindications

It is imperative for clinicians to be aware of both absolute and relative contraindications for TAVR. Absolute clinical contraindications include patient life expectancy of less than 12 months, myocardial infarction within the last 30 days, stroke within the last 6 months, patient intolerance to an anticoagulation/antiplatelet regimen, the absence of a Heart Team and cardiothoracic surgical team, and active bacteremia or endocarditis. Absolute anatomical contraindications include heavy aortic or left ventricular outflow tract disease and calcification, a short distance between the coronary ostia and the native aortic annulus, annulus size that is too small (less than 18 mm) or too large (greater than 29 mm), and the presence of mobile plaques and thrombi in the aorta and unsuitable access options [20].

Relative contraindications for TAVR include severe left ventricular dysfunction (EF <20%), inadequate heavily calcified femoral arteries, hemodynamic instability, severe pulmonary hypertension resulting in right ventricular dysfunction, hypertrophic cardiomyopathy, and severe mitral regurgitation.

5. Pre-procedural work-up

Appropriate patient selection via individual risk stratification, optimal valve sizing, and determining feasibility of different access routes are all factors that are carefully and meticulously worked up prior to TAVR. This pre-screening is an ever-changing multifaceted selection process that utilizes a multidisciplinary approach. A Heart Team consisting of an interventional cardiologist, cardiac surgeon, clinical cardiologist, and anesthetist are responsible for actively performing the pre-procedural screening and work-up. However, because these patients are generally elder with many comorbidities, physicians from even other specialties often participate in pre-procedural optimization.

The confirmation of severe AS is done with echocardiography demonstrating a valve area of <1.0 cm² mean pressure gradient of 40 mmHg or greater or a maximum aortic velocity of 4.0 m/s or greater. This step is heavily operator dependent as any misalignment of the probe can result in underestimation of the pressure gradient and jet velocity. The measured valve area should be indexed to the patient’s body surface area ≤ 0.6 cm²/m² in patients with normal left ventricular ejection fraction. Note that patients with low-flow, low gradient severe AS may have aortic velocities and valve gradients that are falsely lower. If these patients demonstrate a reduced ejection fraction, then we use low-dose dobutamine echocardiography (maximum dose 20 μg/kg/min) to mimic normal physiological flow and obtain accurate values. If valve area remains ≤1.0 cm² and peak velocity exceeds 4.0 m/s, then a diagnosis of true severe AS is made regardless of the flow rate. If the aortic valve area increases to greater than 1.0 cm² during dobutamine echocardiography, then a diagnosis of pseudo-severe AS or moderate AS can be assumed, and the patient should undergo heart failure therapy and close clinical follow-up.

Transesophageal echocardiography tends to underestimate the severity of AS when compared to transthoracic echocardiography [21]. In the majority of patients, transthoracic echocardiography is adequate enough to confidently establish a diagnosis of severe AS. However, when there are discordant findings, we look for other tests to help guide our decision-making. Thus, in addition to echocardiography, we utilize computed tomography to confirm the severity of AS. Similar to that of coronary calcium scoring, computed tomography allows us to use the Agatston algorithm to quantitate the severity of aortic valve calcifications. We utilize calcium score cutoffs of 2065 in males and 1275 in females for severe AS [22]. Recent studies have revealed that an elevated pre-TAVR calcium score from computed tomography is an independent risk factor for acute stroke, thus providing prognostication capabilities as well [23]. Computed tomography also provides the added benefit of a three-dimensional visualization of the valve and left ventricular outflow tract as two-dimensional imaging often results in underestimation of the severity of stenosis. This is largely due to the fact that the continuity equation which we use to calculate valve area from stroke volume states that flow passing through the outflow tract equals the flow through the aortic valve and assumes a circular outflow tract though in reality, the tract is frequently oval. Computed tomography angiography of the chest, abdomen, and pelvis is generally also done to help confirm valve size but more importantly, to visualize the patient’s vasculature and determine the optimal entry point for access, if any.

Because the association of coronary artery disease and AS is strong, conventional guidelines recommended left heart catheterization prior to TAVR in order to assess presence of unstable coronary disease and determine if revascularization or bypass grafting should be performed prior to AVR. Depending on heart catheterization findings, the Heart Team may elect to proceed with SAVR versus TAVR. However, recent studies published by AHA revealed that revascularization TAVR did not result in improved clinical outcomes and in fact, was associated with an increased risk of major vascular complications and 30-day mortality [24].

Other conventional preprocedural testing includes carotid duplex ultrasonography, pulmonary function testing, and assessing baseline ambulatory function status, complete blood counts, and renal function. Carotid ultrasonography allows clinicians to screen for internal carotid artery stenosis which is believed by many to correlate with risk of periprocedural stroke. However, some studies have since emerged showing no statistically significant benefit in performing carotid ultrasonography [25, 26]. For now however, it remains a part of preprocedural workup at many centers. Pulmonary function testing remains a routine part of the risk stratification and STS scoring of patients undergoing valve replacement as the severity of the patient’s lung disease continue to show direct correlation to peri-procedural mortality [27].

We universally assess for baseline functional status with a simple outpatient six-minute walk test during which we assess both speed, gait, and ability to complete the test. It is a simple and cheap test that helps us further risk stratify patients and to monitor functional status pre and post procedurally. Among high-risk adults undergoing TAVR, the six-minute walk test does not predict post-procedural outcomes but does however predict long-term mortality [28].

Renal function is also important to assess as both acute and chronic kidney disease are associated with adverse events in patients undergoing valve replacement [29]. In patients who develop acute kidney injuries, studies have shown a four-fold increase in postoperative mortality [30, 31]. A baseline complete blood count allows to assess platelet counts and for any anemia. Finally, a preprocedural international normalized ratio and type and screen are also obtained as part of preprocedural blood work.

6. Contemporary devices

Contemporary TAVR devices consist of balloon-expandable valves, self-expanding valves, mechanically expanding valves, and delivery systems/sheaths. In the last two decades, technological advancements have significantly improved devices by incorporating and enhancing features that allow for recapture, easier deployment, repositioning, all while reducing associated complications such as perivalvular leaks and stroke [32]. As TAVR continues to undergo procedural modifications and indications, these devices are expected to continue to evolve. As of 2023, there are three newer-generation valves that are FDA-approved for commercial TAVR in the US: the SAPIEN 3 Ultra (Edwards Lifesciences), Evolut PRO+ (Medtronic), and Portico (Abbott Laboratories). Other valves such as the ACURATE Neo/Neo2 (Boston Scientific), JenaValve (JenaValve Technology), Myval THV (Meril Life Sciences), Allegra (New Valve Technologies) have Conformite Europeenne (CE) markings by the European Union and actively undergoing review for potential US FDA-approval in the near future.

Balloon-expandable valves are intra-annular valves that include the Sapien system and the Myval system. They require transient rapid ventricular pacing with concomitant valve-balloon inflation. Close monitoring of the pacer lead is imperative in order to avoid risk of pacing lead perforation. The cons of these valves are that they are not able to be repositioned. Additionally, sicker patients may not be able to tolerate rapid ventricular pacing, thus hemodynamics must be very closely monitored. One major advantage of these valves is that they have a lower frame height thus allowing for easier coronary access [33, 34]. They have delivery sheaths that typically allow for better controllable flexibility and steerability, and thus are preferred in patients with difficult vascular anatomy.

Self-expanding valves are typically supra-annular but newer prototypes that are intra-annular are now being manufactured. These valves do not require rapid ventricular pacing. They offer the advantage of being able to be repositioned and retrievable. The cons of these valves include limited maneuverability. They also tend to create a greater challenge for coronary access due to their larger frame sizes. Self-expanding valves tend to have higher rates of pacemaker implantations and paravalvular leaks (Figure 4) [35].

Figure 4.

Various types of contemporary transcatheter aortic valves.

6.1 SAPIEN 3 Ultra (Edwards Lifesciences)

The balloon-expandable SAPIEN 3 Ultra transcatheter aortic valve is the fifth-generation valve in the Sapien series and is available in four sizes (20, 23, 26, and 29 mm). Its design consists of three bovine pericardial tissue leaflets with a cobalt-chromium frame. The novel modifications of this device include the polyethylene terephthalate cuff that has significantly minimized the rate and degree of paravalvular leaks. The Ultra has a greater frame height than the previous generation, allowing an even greater reduction of paravalvular leaks [36]. It is neither retrievable nor repositionable. The Commander Delivery System (Edwards Lifesciences) consists of an inner balloon on which the valve is crimped prior to advancement. A transfemoral approach is preferred using a 14 or 16 French (F) Edwards eSheath and crimper. In cases in which femoral access is not feasible or appropriate, a transaortic or transapical approach may also be utilized. In such cases, a Certitude delivery system is needed. This system is compatible with 18 and 21-F sheaths. The 21-F sheath is reserved for the larger 29 mm valve. The PARTNER trials are the largest clinical trials that have reported outcomes of the SAPIEN 3 which led to FDA approvals in all four risk profiles. When compared to the SAVR cohort from PARTNER II, TAVR with the SAPIEN 3 valve demonstrated lower rates of mortality (7% vs. 12.4%) and stroke (4.5% vs. 7.9%) at 1-year follow up in low-risk patients [13].

6.2 Myval (Meril Life Sciences)

The balloon expandable Myval heart valve obtained its CE mark in 2019. It consists of a tri-leaflet made of bovine pericardium on a cobalt alloy frame as well as a polyethylene terephthalate cuff similar to the SAPIEN 3 that is in place both internally and externally to reduce paravalvular leaks. It comes in nine sizes (20, 21.5, 23, 24.5, 26, 27.5, 29, 30.5, and 32 mm). The valves should be crimped over Navigator THV Balloon Delivery System (Meril Life Sciences) prior to advancement through the introducer.

6.3 Evolut PRO+/FX (Medtronic)

The self-expanding supra-annular Evolut Pro+ is a new generation FDA-approved valve in the Evolut series and offers the lowest delivery profile for 23–29 mm valves, capable of treating vessels down to 5.0 mm. Valves from this series have been the most extensively studied and most commonly implanted. It is available in four sizes (23, 26, 29, and 34 mm). Its design consists of three porcine pericardial tissue leaflets mounted on a frame made of nitinol. The novel modification of this device is the newly added porcine external skirt which minimizes paravalvular leaks [37]. Valves of the Evolut series have been shown to cause greater rates of conduction disturbances and pacemaker dependency compared to some of the other valves [38]. However, the data available on the Pro+ thus far has shown lower rates of pacemaker implantation. The delivery system allows the valve to be recaptured up to three times. In the US Evolut PRO Study, zero patients experienced moderate paravalvular leak during the same follow-up period used in the PARTNER II SAPIEN 3 trial, in which moderate paravalvular leak was seen in 3.4% of patients. In 2022, Medtronic announced their next generation of Evolut valve—the Evolut FX. They have significantly improved commissural alignment which we anticipate will allow better coronary flow and access when needed. The FX also allows for easier tracking as it now has gold markers built into the frame. These prototype modifications should overall help improve alignment and allow for symmetric implantations. Multicenter studies are ongoing but preliminary data has thus far shown favorable outcomes.

6.4 ACURATE Neo/Neo2 (Boston Scientific)

The ACURATE Neo2 is a self-expanding supra-annular nitinol alloy stent available in three sizes: small (21–23 mm), medium (23–25 mm), and large (25–27 mm). Its design consists of porcine leaflets mounted on a large-cell nitinol frame that allows for easy coronary access. An 18-F sheath is required for transfemoral approach. A simple two-step deployment provides the operator with greater ease of deployment. The global SAVI registry revealed very positive outcomes in terms of pacemaker implantation rates and stroke (8.2% and 1.9% respectively) [39].

6.5 Portico (Abbott Laboratories)

The self-expanding intra-annular Portico TAVI system was approved by the FDA in 2021. It is available in four sizes (23, 25, 27, and 29 mm). Its design consists of bovine leaflets mounted on a large-cell nitinol frame. The annular and large-cell design allows for easy coronary access. It is fully re-sheathable. An 18-F sheath is required and used with its FlexNav delivery system which Abbott claims to need 76% less insertion force than the Evolut PRO.

6.6 LOTUS Edge (Boston Scientific)

The LOTUS Edge is the second of the LOTUS mechanically expandable valve series that allows for hemodynamic evaluation and repositioning as needed prior to deployment. The expansion is mediated by a mechanical controlled system. Mortality rates in patients who have undergone TAVR with LOTUS were very comparable to the rates from SAPIEN 3 [40]. The LOTUS edge was FDA-approved in 2019. Since then, the newest generation (Mantra) has been created as well. At this time however, these valves have been recalled due to issues with its delivery system, but due to a substantial number of patients in whom the valve was implanted, operators need to be familiar with the valve and its design.

7. Equipment and personnel

The care of a patient with severe aortic stenosis should be collaboratively under a Heart Team that consists of a primary cardiologist, an interventional cardiologist, cardiothoracic surgeon, radiologist, and anesthetist. We discussed the meticulous workup and pre-screening measures necessary prior to fully committing to a transcatheter approach. Depending on the comorbidities of the patient, additional specialists may be invited to help fine-tune and optimize patients prior to undergoing TAVR. This multidisciplinary team is needed even post-procedurally to ensure proper follow-up and care should any complications arise.

Centers who wish to pursue TAVR are recommended to have an active valvular heart disease program with at least two surgeons experienced in valvular surgery. A heart catheterization laboratory, high quality radiology and imaging department should also available. Access to multiple echocardiographic modalities is also necessary. A hybrid operating room is preferred but not mandatory.

The American College of Cardiology, along with partnering societies (AATS, SCAI, STS, ACCF) clearly delineate the components needed for centers to establish and maintain a TAVR program. Quality is the primary endpoint. These are assessed with several various metrics. Due to the learning curves associated with the procedure, having adequate volume of patients is necessary. It has been shown that roughly 30–45 cases are needed for operators to plateau in their procedure times and success rates [41, 42]. The slope for major post-procedural outcomes however remains steep for roughly the first 100 cases [43]. Thus, proceduralists are expected to have documented involvement with 100 cases with half (50) requiring them to be the primary operator. Table 1 summarizes current requirements to establish TAVR programs.

ACC requirements for new TAVR programs [45]
There should be documentation of a multidisciplinary approach and of patient access to all forms of therapy for aortic valve disease (TAVR, SAVR, and palliative and medical care) using an SDM process.; For all patients with aortic stenosis meeting criteria for valve replacement, there should be documentation of the following: Completion of an evaluation by both a cardiac surgeon and a cardiologist with knowledge and experience in both TAVR and SAVR Education of patients regarding the treatment recommendations and options by the multidisciplinary team Use of an SDM process incorporating patient preference For patients undergoing TAVR, there should be documentation of evaluation by 1 surgeon involved in the TAVR program For this requirement to fulfill CMS coverage criteria, the NCD should be updated as it currently recommends evaluation by surgeons for all patients having TAVR
The proposed TAVR proceduralist for a new TAVR program should document the following: Prior TAVR experience with participation in 100 transfemoral TAVRs lifetime, including 50 TAVRs as primary operator Being board eligible or certified in either interventional cardiology or cardiothoracic surgery Certification of device-specific training on device(s) to be used.
The TAVR sites must have: The site must have documented expertise, state of the art technology and dedicated board-certified imager. Echocardiography: TTE, TEE and 3D CT Scan and MR imaging
The proposed TAVR surgeon for a new TAVR program should document the following: 100 lifetime SAVRs or 25 per prior year or 50 over 2 years and ≥20 SAVRs in the year prior to TAVR program initiation Board eligible or certified by the American Board of Thoracic Surgery or equivalent
The institution should document the following prior to expanding into alternative-access TAVR (e.g., transapical, direct aortic, brachiocephalic arteries, transcaval): Completion of 80 TAVRs using transfemoral access with an STS/ACC TVT Registry 30-day risk-adjusted TAVR all-cause mortality “as expected” or “better than expected”
The institution should document the following concerning its SAVR program: ≥2 hospital-based cardiac surgeons who both spend ≥50% time at the hospital with the proposed TAVR program Minimum hospital SAVR volume†: 40 per prior year or 80 over 2 years Quality assessment/quality improvement program: Active participation in the STS National Database or a validated state/multi-institutional consortium that gathers and reports risk adjusted and benchmarked outcomes Quality metric: STS 2- or 3-star rating for isolated AVR and AVR plus CABG in both reporting periods during the most recent reporting year
The institution should document the following resources and experience: PCI Minimum volume: 300 PCI/year Active participation in the NCDR/Cath PCI Registry or a validated state/multi-institutional consortium that gathers and reports risk-adjusted and benchmarked outcomes Quality metric: PCI in-hospital risk-adjusted mortality (NQF endorsed) above the bottom 25th percentile for the most recent 4 consecutive quarters. Vascular interventions Physicians experienced and competent in vascular arterial interventions Pacemaker capabilities Experienced and competent physicians for temporary and permanent pacemaker placement and management On-site services should be available 24 hours/day and 7 days/week to handle conduction disturbances as a result of TAVR
Quality assessment/quality improvement program requirements: Active participation of institution in STS/ACC TVT Registry and STS National Database or a validated state/multi-institutional consortium registry Registry submission of all cases using FDA-approved TAVR/SAVR technology, including off-label uses Registry documentation that data submissions meet performance metrics for completeness and accuracy as defined by each registry Multidisciplinary team quarterly meetings with documentation of the following: Review of institutional reports for TAVR (quarterly) and SAVR (semi-annually) from the STS/ACC TVT Registry and STS National Database or an alternative approved registry Assessment and proposed actions if site performance for TAVR and SAVR is suboptimal relative to volume and quality requirements, including national benchmarking of performance metrics Presentation of selected TAVR/SAVR cases at quarterly mortality/morbidity conferences

Table 1.

TAVR program recommendations and requirements in the United States as of 2018 per official statement by ACC and its partnering societies. Obtained from Bavaria et al. (obtained from Ref. [44]).

8. Techniques

The TAVR procedure is commonly performed in a hybrid room that has both Cath lab and operating room abilities, although some are performing the procedure in a standard cardiac catheterization laboratory. Primarily driven by visualization on fluoroscopy correlating to previously performed CT scan. At times, various Heart Teams will use transesophageal echocardiographic coregistration with fluoroscopy. There are various accesses used, with transfemoral arterial approach being the most common one. Approximately more than 95% of cases are completed this way. The femoral route has also shown lower rates of complications. However, when this method cannot be used due to severe tortuosity or diseased iliofemoral arterial vessels, an alternative route can be chosen based on the particular valve being used, patient’s risk factors, or if a patient has unfavorable iliofemoral artery characteristics [44].

The alternative common access options include transubclavian access, transthoracic approach (transapical antegrade and transaortic retrograde), and transcarotid approach.

• Transsubclavian/transaxillary approach is done by a surgical cut-down to the subclavian artery or percutaneous axillary artery access for insertion of the valve. The axillary artery’s proximal third (between the medial border of pectoralis minor and lateral border of the first rib) demonstrates an ideal area for both surgical and percutaneous methods.

• Transaortic approach is performed by a direct insertion of the valve delivery system into the ascending aorta via a sheath in the aorta from a lateral thoracotomy or median sternotomy.

• Transapical approach is best for patients who have severe peripheral artery disease or heavily calcified aorta/ascending arch. These patients typically are at a higher risk for stroke or other embolic events.

• Transcarotid approach is done with a surgical-cut of the common carotid artery. It is important to use neurologic monitoring with this approach.

• Transcaval approach involves the femoral vein and percutaneous electrosurgical techniques to puncture from the inferior vena cava into the aorta (Table 2) [44].

Access	Procedural success (%)	30 D mortality	Major and life-threatening bleeding	Neurological events (TIA/stroke)	New pacemaker implantation (%)
Trans-femoral (3–14)	95–100	2.1–5%‡; 5.2–9.7%†	9.3–28.1%‡; 3.5–11.4%†	1.4–6.7% (30 days stroke); 2.3–4.1% (1 year stroke)	3.4–34.1; 5.9–20.1
Trans-axyllarian (16)	97.9	5.7%	7.8% life threatening; 36.2% major bleeding	2.1%	24.7
Trans-aortic (17–24)	87–100	6.1–13%	0.3–12%	0–3.2%	0–14
Trans-apical (13, 25–28)	90–96	4.6–14%	3.6–6.1%	1.3–4.1%	5.4–11.0
Trans-carotid (29)	100	6.3%	4.2%	3.1% (all TIAs, stroke not reported)	26.5
Trans-caval (30, 31)	100	8%	12%; (6% transcaval related)	5%	16

Table 2.

Procedural outcomes per access site [46].

^†

Data derived from TVT. Gary. UK TAVI. Observant and France2 registries.

^‡

Data derived from Partner A, Partner B, Partner II, Notion and SURTAVI trials.

9. Procedure

9.1 Edwards SAPIEN 3 transcatheter heart valve (THV)

Sterile technique is to be followed during the device preparation and implantation (Figure 5) [47].

Figure 5.

Edwards commander delivery system [47].

Rinsing procedure:

1. The THV comes in a jar. Examine the valve before opening the device for any signs of damage. If there are signs of leaking, missing seals, etc. the valve should not be used for implantation.

2. Place two sterile bowls with approximately 500 mL of sterile saline to fully rinse out the glutaraldehyde sterilant from the heart valve.

3. Next, carefully remove the THV from the jar without touching the tissue. Compare the THV serial identification number with the one on the jar lid. Check again for any damage to the THV.

4. Rinse the THV in first bowl of sterile saline. Make sure the saline completely covers the THV and the holder. Submerge both and slowly swirl the saline for approximately 1 minute. Transfer the THV and holder to second bowl. Again, slowly swirl the saline for another minute. Leave the THV in the second bowl until needed. This is to keep the THV hydrated and prevent the tissue from drying. CAUTION: The THV should be the only thing placed in the rinse bowl. Direct contact should also be avoided during the rinse process [47].

Preparing the device components:

1. Inspect all the components for any signs of damage. Check to see if the Edwards Commander delivery system is unflexed and make sure the balloon catheter is advanced in the flex catheter.

2. Flush out the flex catheter.

3. Remove the distal balloon cover carefully from the delivery system.

4. From the distal end of the guidewire, remove the stylet and put aside. Flush the guidewire with heparinized saline and insert the stylet back through the distal portion of guidewire lumen.

5. Cover the flex catheter tip with proximal balloon cover and put the delivery system in default position. Unscrew the loader cap located in loader tube and flush it. Place this loader cap on the proximal balloon cover and on the flex catheter.

6. Advance the balloon catheter into the flex catheter. Remove the proximal balloon over the balloon shaft in the blue section.

7. Put a 3-way stopcock to the balloon inflation port. Fill a syringe with about 20 mL diluted contrast medium and attach that to the 3-way stopcock as well.

8. Fill the inflation device and then lock it and attach to stopcock.

9. Close the 3-way stopcock to inflation device and then de-air the system using a 500 cc syringe. Release the plunger slowly and have zero-pressure in the system.

10. Close the 3-way stopcock towards the delivery system. Transfer contrast medium to the syringe based on the delivery system and THV size.

11. Close stopcock to the syringe and remove the syringe. Lock the Inflation device until THV deployment (Table 3) [47].

THV size (mm)	Inflation volume (mL)
20	11
23	17
26	23
29	33

Table 3.

Inflation volume with corresponding THV size.

Mount the THV onto the delivery system:

1. Place two sterile bowls with approximately 100 mL of sterile saline to rinse the Qualcrimp crimping accessory.

2. Submerge this accessory in the first bowl and slowly swirl it for about 1 minute. Repeat this in the second bowl.

3. Remove ID tag from the THV. Attach the crimp stopper to the base and click into place.

4. Have the crimper in the open position and place the THV in the crimper aperture.

5. Make sure the THV is parallel to the Qualcrimp edge. Place both the Qualcrimp accessory and the THV in the crimper aperture. The delivery system should be inserted within the THV in the Valve Crimp section by having the inflow of the THV on the distal end of the delivery system.

6. The THV should be crimped until it is at the Qualcrimp Stop which is on the 2 piece Crimp stopper.

7. Carefully remove the Qualcrimp crimping accessory from the THV and remove the Qualcrimp Stop therefore leaving the Final Stop in place.

8. Crimp the THV fully until it also reaches the Final Stop. Repeat the crimp of the THV two more times.

9. Next, pull at the balloon shaft and lock it in the default position.

10. With heparinized saline, flush the loader and advance the THV into the loader until the tip is exposed.

11. Place the loader cap to the loader, re-flush the delivery system, and close the stopcock to the delivery system. Remove stylet and flush the guidewire of the system [47].

THV delivery:

1. Prepare the Edwards eSheath introducer and insert the loader into the sheath.

2. Advance the delivery system through the sheath until the THV is out of the sheath. Then retract the loader to be at the proximal end of the delivery system.

3. Begin valve alignment in a straight section of the aorta by unlocking the balloon lock and pulling the balloon catheter back. Engage the balloon lock and position the THV in between the valve alignment markers.

4. Advance the catheter with using the flex wheel. Confirm the position of the THV with the aortic annulus. Adjust position as necessary.

5. Begin the THV deployment by unlocking the inflation device. Start rapid pacing; balloon inflation can begin once the systolic blood pressure is down to 50 mmHg or lower. Inflate the balloon and deploy the THV. Hold for 3 seconds and make sure the inflation device barrel is empty. Deflate the balloon and turn off the pacemaker [47].

System removal:

1. Retract the device while unflexing the delivery system. Remove the devices when the ACT level is appropriate. Close the access site [47].

9.2 Medtronic Evolut FX transcatheter aortic valve

See Figures 6–8.

Figure 6.

Available valve sizes.

Figure 7.

Delivery catheter system (catheter) [48].

Figure 8.

Evolut FX loading system [48].

9.2.1 Anatomical criteria

See Table 4.

Size	Aortic annulus diameter	Aortic annulus perimeter (π × aortic annulus diameter)
23 mm	17^a/18 mm to 20 mm	53.4^a/56.5 mm to 62.8 mm
26 mm	20 mm to 23 mm	62.8 mm to 72.3 mm
29 mm	23 mm to 26 mm	72.3 mm to 81.7 mm
34 mm	26 mm to 30 mm	81.7 mm to 94.2 mm

Table 4.

Anatomical aortic annulus diameter and perimeters with corresponding valve sizes.

Inspection and rinsing:

1. Carefully inspect the device packaging for any signs of damage. Remove the product from the package.

2. Inspect the product for any signs of defects.

3. Remove the locking clips on the rinsing bowls and remove the bowls from the integrated loading bath.

4. Detach the locking clips from the distal and proximal trays.

5. From the distal tray, raise the tray tab to the tray tab holder on the proximal tray.

6. Add cold, sterile saline to the integrated loading bath [48].

Catheter and loading system preparation:

1. Attach a 10 mL syringe with sterile saline on the proximal end of the handle to the capsule flush port. Keep the syringe attached until the loading is complete.

2. Lift the distal end of catheter to a vertical direction. Open the capsule to reveal the paddle attachment.

3. Next flush the capsule flush port. Make sure there is no leakage noted during flushing. If any leakage is noted, use a new system.

4. While flushing the capsule flush port, immerse the capsule in the cold saline bath.

5. Use a locking clip to position the catheter tip into the loading bath.

6. Put the loading system in the integrated loading bath [48].

Rinsing of the bioprosthesis:

1. Place 500 mL of sterile saline into three rinsing bowls.

2. Carefully remove the bioprosthesis from the packaging by using blunt foreceps.

3. Check the serial number attached on the tag of the bioprosthesis with the serial number on the container.

4. Remove the serial number tag from the bioprosthesis cautiously.

5. Place the bioprosthesis in one of the sterile rinsing bowls.

6. Carefully mix the bioprosthesis by hand in order to remove the glutaraldehyde.

7. Rinse the bioprosthesis in the second and third rinsing bowls. Leave it in the third bowl until ready to be used [48].

Loading procedure of bioprosthesis:

1. Immerse the bioprosthesis in the integrated loading bath.

2. Make sure the capsule guide tube is open (unlocked) with the locking collar at proximal end of capsule guide tube.

3. Advance the capsule guide tube over the catheter shaft and across the catheter tip.

4. Once across, advance the locking collar to the distal end of the capsule guide tube until it is locked (closed). Continue advancing until it reaches the distal end of the capsule.

5. Make sure the backplate is placed in the inflow cone and the uncovered part is facing up.

6. Place the inflow portion into the inflow cone. Check to make sure the bioprosthesis frame paddle has a “C” facing up and it is aligned with the paddle attachment pockets.

7. Place the outflow cone into the inflow cone until it is locked.

8. In the distal end of the inflow cone place the catheter tip guide tube. Place the distal catheter tip in the catheter tip guide tube.

9. Withdraw the catheter tip guide tube to place the bioprosthesis frame paddles in the attachment pockets.

10. Advance the capsule guide tube so the distal part covers the paddle attachment pockets as well as the top part of the outflow struts.

11. Continue advancing until the capsule catches the bioprosthesis outflow struts and until the distal end of the capsule guide tube covers the commissure pad.

12. From the outflow cone, remove the backplate and the catheter tip guide tube.

13. Advance the inflow cone to crimp the inflow portion of bioprosthesis frame. Move the locking collar to the proximal end of the guide tube.

14. Continue progressing until the capsule comes out 5 mm of the catheter tip.

15. Disconnect the capsule guide tube with the outflow and inflow cone.

16. Next, advance the capsule until the gap closes between the capsule and catheter tip.

17. Rotate the deployment knob towards the arrows to relive stress.

18. Inspect the capsule to make sure it is not misloaded and dree of bends.

19. Place a 10 mL syringe of sterile saline to the stability layer flush port.

20. Remove the loading stylet from guidewire lumen.

21. Place a 10 mL syringe of sterile saline on the proximal end of the handle to the wire lumen flush port.

22. Place a 10 mL syringe of sterile saline to the Evolut FX inline sheath flush port and flush it.

23. Check the loaded bioprosthesis under fluoroscopy before placing in the patient. After checking, leave the bioprosthesis immersed in sterile saline [48].

Implantation of bioprosthesis:

1. Achieve vascular access with a primary and secondary access artery. The primary access will place the Evolut FX device and the secondary access will place the reference pigtail.

2. Place a central line and insert a temporary pacemaker.

3. Place an introducer sheath into both accesses. Give anticoagulant, maintain ACT greater than 250 seconds.

4. Advance a pigtail catheter to the ascending aorta and fix the distal tip in the noncoronary cusp of the aortic valve.

5. Place an angiographic catheter over a J-tip guidewire in the primary access and progress to the ascending aorta.

6. Next, exchange the J-tip guidewire for a straight-tip guidewire and advance it across the aortic valve into the left ventricle. Then advance the angiographic catheter into the left ventricle.

7. Replace the straight-tip guidewire with an exchange length J-tip guidewire. Replace the angiographic catheter for a 6 french pigtail.

8. Take out the guidewire and connect the catheter to the transducer. Advance the pigtail catheter and place into the apex of the left ventricle. Remove the pigtail catheter with the guidewire in the left ventricle.

9. Advance the device over the guidewire with the delivery catheter flush ports towards the left side of the patient for better commissure alignment. Place the catheter tip and capsule through the access site and insert the Evolut FX inline sheath. Use fluoroscopy to watch the guidewire in the left ventricle.

10. With fluoroscopic assistance, advance the guidewire to the aortic annulus and advance the device through the valve. With angiogram make sure the pigtail catheter is in the correct position in the noncoronary cusp of the aortic root. The bioprosthesis should be at a target dept. of 3 mm in comparison to the valve annulus.

11. Rotate the deployment knob towards the arrows to deploy the bioprosthesis. Adjust valve position as needed and position the bioprosthesis in order for the radiopaque markers to be at the level of the native valve annulus.

12. Confirm the deployment with fluoroscopy or a second radiographic view [48].

9.3 Commissural alignment

ALIGN TAVR was a study done in 2020 which was the first complete evaluation of the importance of commissural alignment in TAVR. The study compared the effect of the initial deployment orientation of the 483 SAPIEN 3, 100 ACURATE-neo, and 245 Evolut transcatheter heart valves on the final orientation of commissural alignment. 828 patients from 5 centers were studied who had undergone the TAVR procedure from March 2016 to September 2019. The patient’s pre-TAVR computed tomography (CT) imaging and procedure fluoroscopy were studied. The pre-TAVR CT had coplanar fluoroscopic views added to it to help determine the commissural alignment. The severe overlap in between the coronary arteries and neocommisural posts were defined as 0° to 20° apart. The different types of valves were classified differently. The Evolut and ACURATE-neo deployment commissural post were defined as center back (CB), center front (CF), inner curve (IC), and outer curve (OC). The Sapien 2 valve had commissural post at clock position 3, 6, 9, and 12. This study showed that valve alignment can be optimized. The SAPIEN 3’s orientation did not have an impact on alignment. While ACURATE-neo commissural post showed less coronary artery overlap at the CB or IC in deployment versus in CF or OC. The Evoult “Hat” had less overlap at OC or CF at initial deployment versus IC or CB. This study showed the significance of optimizing valve alignments in order to avoid coronary artery overlap [49].

9.4 To TEE or not to TEE

Commonly the TAVR procedure is performed with a transesophageal echocardiography (TEE) probe in place. However there has been recent studies that suggest a different approach with similar results. This “Minimalist TAVR approach” is completed with no continuous TEE and the valve is placed with just angiography. A post-TAVR transthoracic echo (TTE) is done to allow for signs of early complications and view any para-valvular leaks. This is then followed by long term echocardiography completed within 1 month and 1 year to view the function of the prosthetic valve and see if there were any other changes due to the procedure such as pulmonary hypertension, mitral regurgitation, or tricuspid regurgitation [50].

10. Complications

As in any procedure, complications with TAVR can occur intra- and post-procedure. Some common complications include: (1) valve function (Paravalvular leakage (PVL)), (2) vascular access/bleeding complications (injury at arterial access site and/or vascular closure problems), (3) valve deployment (including malpositioning, annular rupture), (4) organ injuries (such as stroke, myocardial ischemia/injury, and acute kidney injury), (5) arrhythmic abnormalities like high-degree atrioventricular block and atrial fibrillation, and (6) in some cases death.

10.1 Paravalvular aortic regurgitation

Longer-Term complications include PVR. Patients with moderate and severe PVR had a three-time increase in 30-day mortality. Diagnosis of PVR includes multiple modalities such as doppler echocardiography, cardiac magnetic resonance, and angiography.

10.2 Vascular access bleeding

Access complications 30 days post procedure have ranged from 11% for high-risk cohorts [51]. Risk factors include severe tortuosity, percutaneous preclosure device failure, sheath-to-artery ratio, and presence of circumferential calcification. A mechanical factor that may increase bleeding risk is use of large delivery catheters. Of the various techniques, the transapical approach has been associated with related risk of myocardial tears [52]. Due to new technological advances, newer TAVR devices now have a 14F inner diameter instead of a 24–26F inner diameter sheaths required in the first TAVR systems. This has correlated with a decrease in vascular complications by 11–14%.

10.3 Valve deployment

Transcatheter heart valve malpositioning can occur due to lack of proper visualization or in inadequate ventricular pacing. Valve migration can also occur. Annular rupture is a very rare, unpredictable, and life-threatening complication typically related to balloon aortic valvuloplasty or balloon-expandable valves.

10.4 Aortic dissection

Aortic dissection is a rare and possibly fatal complication of the procedure. Approximately 0.6–1.9% incidence rate has been shown after a TAVR procedure. Any part of the ascending or descending aorta can be involved in the dissection depending on which access approach was used. If post procedure an aortic dissection is suspected, aortic angiography can be used. The patient can have various symptoms and signs including chest pain, abdominal pain, and hypotension. It is important to note that the treatment of aortic dissection will vary based on the site and type of dissection. Type A dissections need to be treated with surgery while Type B can be medically managed [53].

10.5 Organ injuries

Stroke and brain injury: Stroke is a feared neurological complication to suffer from after a TAVR. Incidence of stroke is approximately 1.6% and can be a source of morbidity [54].

Myocardial ischemia/injury: Coronary obstruction may occur after a TAVR and can be treated with percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or valve repositioning/retrieval.

• With native aortic valve procedures—Coronary obstruction can happen rarely after a TAVR in approximately 0.7% of cases [51].

• With valve-in-valve procedures—Coronary obstruction is more commonly seen up to 3.5 [55].

Acute kidney injury (AKI): A significant amount of TAVR patients do suffer from renal insufficiency. AKI have been associated with a worse outcome and approximately 2.24% of patients required dialysis. A study titled the PROTECT-TAVI (PROphylactic effecT of furosEmide-induCed diuresis with matched isotonic intravenous hydraTion in Transcatheter Aortic Valve Implantation) had 112 patients undergoing TAVR who were randomly assigned to intravenous hydration with normal saline matched with urine output with diuresis (RenalGuard group) versus a control group of just normal saline. The study showed the rate of AKI was lower in the RenalGuard group than the control group [51, 55].

10.6 Arrhythmic complications

High grade heart block: Having a history of baseline conduction abnormalities (such as bundle branch blocks) have been a known risk factor for having a post-procedural pace maker (PPM) placed. It may also depend on the type of valve placed, Sapien vs. CoreValve. One study noted, that post TAVR, PPM was placed in 1.8–8.5% of patients who received the Sapien versus 19.1–42.5% of patients who received CoreValve [56].

New onset atrial fibrillation (NOAF): This is also commonly seen after a TAVR. In one study it was identified that 31.9% of patients had NOAF in a 46-hour time period postoperatively [57].

10.7 Valve-in-valve implantation complications

For patients with a failed bioprosthetic valve, the types of complications are similar to those patients with native aortic valve stenosis. However, coronary artery obstruction is more common and paravalvular regurgitation and PPM placement are less frequent [58].

Due to new transcatheter heart valves that now have external covering sealing skirts, these new devices have led to a lower rate of PVL from 8.3% of the first-generation device to 5.4% with the second-generation device and down to 3.4% with the third-generation device.

11. Adjunctive devices: cerebral embolic protection devices

Cerebral embolic protection devices (CEPD) are used in order to prevent cerebral embolization during the procedure and thus may help lower the stroke risk with the TAVR procedure. There are many types of CEPD that have their own set of pros and cons. Overall the filtration needs to protect the major cerebral arteries throughout the entire procedure [59].

11.1 Sentinel CEPD

This device is the most studied CEPD and only FDA-approved device for commercial use. It can be implanted through a 6-French sheath through a radial or brachial access. There are two filters in the delivery system. One filter is to be placed in the brachiocephalic trunk and the other is placed in the left common carotid artery. With this the left subclavian artery is not covered. Therefore, there is not a complete cerebral protection with this device. There have been a few clinical trials comparing the Sentinel to unprotected groups. The CLEANTAVI and MISTRAL-C randomized controlled trials showed a reduction in the amount of new ischemic brain lesions in the protected areas in the Sentinel versus the unprotected groups. The PROTECTED TAVR trial studied whether TAVR reduces the risk of periprocedural stroke with CEP use. This was a large, randomized, prospective trial in which CEP was successfully deployed in 94.4% of patients. The results showed that the incidence of procedural complications did not differ significantly between patients who underwent TAVR with CEP versus without CEP. However, there was a 95% confidence interval with the outcome therefore it did not rule out the overall benefit of use of CEP in TAVR procedure [60].

11.2 TriGUARD embolic deflector device

This system contains a single-use, biocompatible filter mesh. It can be implanted through a 9-French transfemoral sheath using fluoroscopy to be deployed in the aortic arch. This device covers the right brachiocephalic, left common carotid, and subclavian artery. Therefore, it prevents cerebral embolization by redirecting the debris to the descending aorta. The device is stabilized in a stable position by being anchored in the right brachiocephalic artery ostium. The TriGUARD’s safety was initially confirmed in the DEFLECT 1 trial as it also showed 80% of patients had successful coverage of all three branches. The second-generation of this device, TriGUARD HDH was invented and then also evaluated in other studies. The DEFLECT III trial showed less neurological deficits as defined by the National Institutes of Health Stroke Scale (NIHSS) and cognitive function improvement [59]. TriGUARD 3 is an update of the current TriGUARD HDH that provides easier usage, extensive coverage of all three major branches, and less interference with the TAVR. This device contains a biocompatible nitinol filter mesh which has a smaller pore size compared to the previous TriGUARD HDH which helps prevent smaller particles from getting into the cerebral circulation. It can be delivered through an 8-French transfemoral sheath. This device does not need a stabilizer as there is enough stability offered through the nitinol shaft and from the circumferential device pressure from the aortic arch. The REFLECT II trial proved that the TriGUARD group had higher safety when compared to the unprotected group (15.9% vs. 7%). This study had successful device positioning in 59.3% of the patients [59].

11.3 Point-guard system™ dynamic cerebral embolic protection (Transverse Medical, Inc, Denver, CO, USA)

This device has a filter mesh in a flexible nitinol frame that can cover all the major branches of the aortic arch. This is stabilized during positioning through its isolation zone. Currently this system is not widely available for use as there is not enough clinical data. The CENTER trial will be initiated to evaluate this system [59].

11.4 Emblok embolic protection system (Innovatice Cardiovascular Solutions, Grand Rapids, MI, USA)

This system not only offers cerebral protection during TAVR but also protects the abdominal and peripheral vasculature. The device can be implanted through an 11-French transfemoral sheath with a pigtail catheter and is then advanced into the aorta. This device was studied and proven to have successful deployment. The study noted that no cerebrovascular or cardiovascular events were seen at 30 days follow-up. However further studies need to be done to see improvement in clinical outcomes using this device [59].

Overall, the introduction of CEPD was done in order to help lower the risk of stroke after the TAVR procedure and to help prevent cerebral embolization. However, in studies involving CEPD, there has not been a significant reduction noticed in stroke rate. This could be seen due to limiting number of studies and sample size used. The PROTECTED TAVR trial had a 95% confidence interval therefore it did not rule out the overall benefit of the use of CEP in TAVR procedure [60]. Nevertheless, CEPD may be an asset in the future for cerebral embolic protection with technical improvements.

12. Post-procedure management

Post TAVR care includes routine follow-up clinically. This includes getting an echocardiogram prior to discharge, at 1 month follow-up, then at 6–12 months, and followed by annually. Echocardiogram is used to watch for long term complications as well as assess the transvalvular gradient over time.

12.1 Antithrombotic treatment

Antithrombotic therapy post TAVR depends on a few factors such as the simultaneous indication of antiplatelet therapy (history of recent coronary artery stent placement) and/or the simultaneous indication of anticoagulation (history of atrial fibrillation). Regardless it is important for patients to be on antithrombotic therapy at least for the first 3–6 months following the procedure.

For patients without a simultaneous indication of antiplatelet therapy or dual antiplatelet therapy (DAPT), it is recommended to treat with a single antiplatelet therapy (SAPT) for life. Typically, this includes Aspirin 75–100 mg daily. If aspirin is contraindicated for the patient, the alternative is clopidogrel (Plavix) 75 mg daily.

For patients with no indication of anticoagulation, it is recommended to be on DAPT with Aspirin and Plavix during the first 3–6 months (depending on valve type). Then followed by lifelong SAPT.

For patients with a simultaneous indication of dual antiplatelet therapy such that they had a recent coronary artery stenting, the duration of DAPT and the specific agents depends on the concurrent indication. After that period, it is recommended to continue with daily SAPT for life rather than anticoagulation.

Generally triple antithrombotic therapy (anticoagulation and DAPT) is typically avoided due to increase bleeding risks [61].

12.2 Endocarditis prophylaxis

Patients with prosthetic valves are at high risk for endocarditis. Rates are the highest during the first year of placement and then decrease over time. Therefore, it is vital to properly educate patients about infective endocarditis. This includes discussing the importance of regular dental care and antimicrobial prophylaxis before procedures that may lead to bacteremia. Recommended prophylaxis for penicillin tolerant and penicillin allergic patients included Amoxicillin and Clindamycin, respectively [62].

12.3 Durability of valves at 5–10 years

There are not many studies completed so far that show data regarding the long-term durability of the valve. In a study completed in the UK, using the UK TAVR registry, looked into patients who underwent TAVR over a span of 5 years. The study had 241 patients with 149 patients having the self-expandable valve and 80 patients with a balloon-expandable valve. The patients were evaluated post-procedure and echocardiographic follow-up ranging from 5 to 10 years. Most of the patients had none to trivial aortic regurgitation at follow-up. This study concluded that 91% of the patients did not have structural valve degeneration at 5 and 10 years post- TAVR follow up [63]. The NOTION trial spans over 10 years and is the longest clinical trial comparing randomized patients undergoing a TAVR versus SAVR. It was completed in Denmark and Sweden and enrolled patients between 2009 and 2013. The study shows patients who had a TAVR procedure had comparable risk for all-cause mortality, myocardial infarction, and stroke as patients who had a SAVR completed.

12.4 Redo TAVR (ViV TAVR)

Failed TAVRs can be challenging to approach and involve many factors to consider such as patient’s advancing age, co-morbidities, transcatheter heart valve (THV) design, and tissue ingrowth. Late degeneration of THVs in patients will likely increase in the future therefore it is vital to know how to fix this issue. Redo TAVR has shown to be an effective and safe treatment in these situations [64].

12.5 Cardiac rehabilitation

Inpatient cardiac rehabilitation (CR) after TAVR has been shown to be strongly associated with improved clinical performance. One prospective cohort multicenter study looked at the multicomponent cardiac rehab effects on 136 patients. They took into consideration of the Frailty-Index, Short Form-12, six-minute walk distance, and work load on a bicycle. This study showed an improvement on physical activity and functional capacity after TAVR [65].

13. Future directions

TAVR is an innovative procedure that will always play a significant role in revolutionizing the management of aortic stenosis. This procedure has become more common and usually the first choice for many patients. There have been many successes in clinical outcome and cost effectiveness. Although the indication, procedure, and devices have evolved, we forsee that TAVR will continue to iterate in order to strive for perfection.