Aortic Valvuloplasty and Transcatheter Aortic Valve Replacement

Procedural Considerations

BAV is a procedure in which one or more balloons are placed across a stenotic valve and inflated to fracture the calcified aortic valve leaflets. The procedure results in separation of the commissures and stretching of the aortic valve annulus. The immediate hemodynamic results include an increase in aortic valve area (although rarely greater than 1.0 cm ² ) and a reduction of the transvalvular gradient. Despite only modest changes in the valve parameters, the procedure can lead to meaningful, albeit short-term, symptomatic improvement in patients.

The BAV procedure can be performed via a retrograde or an antegrade approach. The retrograde approach is more commonly utilized and involves access via the femoral artery with a 10 Fr to 14 Fr sheath. Anticoagulation is typically achieved with heparin dosing to achieve an activated clotting time (ACT) >250 but bivalirudin can be used in patients with heparin allergy. An extra-stiff guidewire (0.035 inch) is utilized for the procedure and is required for stabilization of the balloon during inflation and deflation. Care must be taken to position the wire with a gentle curve in the left ventricular (LV) apex to avoid the risk of ventricular perforation. Typically, a slightly undersized balloon, ~1 mm smaller than the annulus, is used to minimize risk of annular rupture while maximizing results. If an adequate result is not obtained with initial inflation, a larger balloon sized to the annulus may be used. The various balloons available (Zymed, Tyshack, Cristal) have different profiles and compliance curves and are typically inflated manually. Rapid ventricular pacing (160 to 180 bpm) via a temporary transvenous pacemaker can be utilized to stabilize the balloon during inflation by reducing forward cardiac output. Care must be taken to avoid prolonged pacing runs, which may cause ischemia and hemodynamic compromise. Vascular closure can be achieved by manual compression or the “preclose” technique with the Abbott Vascular Perclose device (Abbott Vascular Inc., California).

The antegrade transvenous approach has also been utilized for BAV and requires creation of a transcirculatory loop from the femoral vein to the ascending aorta via a transseptal puncture. An Inoue balloon (Toray, Tokyo, Japan) or a traditional valvuloplasty balloon can be used. One advantage of the Inoue balloon is the shape, which allows the waist of the balloon to fit the aortic valve annulus while the larger distal bulbous portion stretches the aortic leaflets more fully into the sinuses of Valsalva. Also, with one 26-mm balloon, multiple inflations can be performed at sizes ranging from 20 to 26 mm while assessing hemodynamic results in between. The potential benefits of the antegrade approach are reduced vascular complications, reduction of stroke, and greater increase in post-BAV area. However, it is more technically demanding given the need for a transseptal puncture and the subsequent looping of the guidewire in the LV apex.

Outcomes

The two largest registries that have evaluated BAV are the National Heart, Lung, and Blood Institute (NHLBI) and the Mansfield Scientific registries. The NHLBI registry evaluated 674 BAV patients immediately post procedure and up to 3 years later. High complication rates and in-hospital mortality were reported in this registry, with a 25% complication rate and a 3% mortality rate within the first 24 hours. The most common complication was the need for a transfusion in 20% due to vascular access issues. The cumulative cardiovascular mortality rate before discharge was 8%. Overall survival was 55% at 1-year, 35% at 2-year, and 23% at 3-year follow-up. Recurrent hospitalization (64%) and early restenosis were common. Echocardiography at 6 months demonstrated restenosis from the postprocedural valve area of 0.78 to 0.65 cm ² .

The Mansfield Scientific Aortic Valvuloplasty Registry contained 492 patients and demonstrated comparable results. Approximately 20.5% of patients had complications after the procedure, with a 4.9% 24-hour mortality rate and a 7.5% mortality rate during the index hospital stay. Restenosis was also demonstrated to be nearly ubiquitous.

Although improved patient selection and technical improvements have led to a modest decrease in complication rates over the past 20 years, postprocedural morbidity remains high. In a contemporary series of 262 high-risk surgical or inoperable AS patients, the most common complications after BAV were intraprocedural death (1.6%); stroke (1.99%); coronary occlusion (0.66%); severe aortic regurgitation (1.3%); need for permanent pacemaker (0.99%); severe vascular complication (6.9%)—perforation (1.6%), ischemic leg (2.6%), pseudoaneurysm (1.99%), arterial-venous fistula (0.66%); acute kidney injury (11.3%); and new hemodialysis (0.99%). At approximately 6 months, there was a 50% mortality rate, and restenosis was evident as early as a few days postprocedure.

Given the frequency of these complications, their prompt identification and management are imperative. Despite smaller sheaths, vascular complications remain frequent and operators must have the skill set to manage them utilizing endovascular techniques with covered stents and prolonged balloon inflations. The most devastating complication for patients remains cerebrovascular injury, which occurs in 1% to 2% of patients. The etiology is typically atheroembolism from the ascending aorta or calcific embolism from the valve. The use of embolic protection devices in the future may further mitigate these complications.

Indications

The 2014 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on valvular heart disease specify that BAV might be reasonable (Class IIB recommendation) as a bridge to SAVR or TAVR in patients with severe AS. In the prior 2006 ACC/AHA valve guidelines, BAV was given a Class IIB recommendation for palliation in patients with co-morbidities that prevent aortic valve replacement, but this recommendation was removed in the 2014 guidelines owing to a lack of evidence. The updated 2012 European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) valve guidelines also give a Class IIB recommendation for BAV as a bridge to SAVR or TAVR in hemodynamically unstable patients who are at high risk for surgery or in patients with symptomatic AS who require urgent major non-cardiac surgery. However, the ESC guidelines also state that BAV may be considered for palliation in patients unfit for SAVR or TAVR, but do not designate a formal class recommendation.

While BAV can be utilized as a bridge to TAVR in patients who are at extreme risk, it has also been utilized as a selection strategy for TAVR and SAVR in patients with severe AS but with other potential causes of their symptoms such as severe lung disease. Temporary improvement in symptoms after BAV would support aortic stenosis as the cause, and replacement of the aortic valve would be warranted. And last, BAV has been used to temporize patients with acute hemodynamic failure while formulating a decision between SAVR, TAVR, and medical therapy.

Next Generation BAV Devices

With the advent of TAVR, there has been renewed interest in BAV. Several new devices have now been developed with the hope of improving both the safety and efficacy of BAV as a stand-alone procedure, as well as improving preparation (predilatation) for subsequent TAVR. Four such devices are the InterValve V8 (InterValve, Plymouth, Minnesota), Bard TRUE™ dilatation balloon catheter (Bard Medical, Burlingame, California), the CardioSculpt scoring balloon (AngioScore, Fremont, California), and the Pi-Cardia LeafLex system (Pi-Cardia, Beit Oved, Israel) ( Figure 29-1 ).

The InterValve V8 ( Figure 29-1A ) and Bard TRUE™ balloon ( Figure 29-1B ) are Food and Drug Administration (FDA) approved and available for use. Both of these devices attempt to address limitations of the current devices. The InterValve V8 has a dumbbell shape, which allows it to lock into the valve anatomy and limit balloon movement. The waist of the balloon is 5 to 7 mm less than the proximal and distal bulbous segments of the balloon, and this shape is maintained throughout inflation. The proximal bulb allows for hyperextension of the leaflets into the sinus to enhance valve opening, and the smaller waist reduces the risk of annular dissection. Furthermore, a rapid balloon inflation and deflation time minimizes ischemic time and hypotension. The balloon comes in 22-, 24-, 26-, and 28-mm sizes. Bard TRUE™ dilatation balloon catheter is made of Kevlar composite balloon material with a precisely reproduced size and shape. It has also been designed for fast inflation and deflation, rewrapping, and puncture resistance. The balloon comes in sizes 20, 22, 24, and 26 mm × 4.5 cm length.

The CardioSculpt BAV ( Figure 29-1C ) and the Pi-Cardia LeafLex system ( Figure 29-1D ) are two devices undergoing investigation. The CardioSculpt device is a scoring balloon, which consists of a balloon encased in a nitinol scoring element. In theory, it also allows for better seating and stability of the device. Also the balloon has rapid deflation times and excellent rewrap, reducing deflated device profile. The Pi-Cardia LeafLex system is not a balloon but a catheter that delivers mechanical shock waves to fracture calcium within the aortic valve. This allows for increased leaflet compliance with an increase in aortic valve area. Clinical results from both these devices may demonstrate their efficacy and potential role in patients.

Historical Perspectives and Unmet Clinical Need

During the past 50 years, the standard of care for symptomatic AS has been SAVR, which in most patients is associated with prolonged survival, improved symptoms, and few procedural complications. However, both the risks and the recovery after SAVR are less favorable in elderly AS patients, especially those with multiple co-morbidities, including prior cardiac surgery, chronic lung disease, peripheral vascular disease, prior stroke, renal failure, coronary artery disease, and frailty. In addition, there are anatomic factors, such as porcelain aorta and chest wall deformities, that increase the risk of conventional SAVR. For these reasons, it is estimated that at least one-third of patients with symptomatic severe AS are either not candidates or are denied surgical therapy. This has prompted investigation into alternative less invasive catheter-based approaches such as BAV and TAVR. From the mid-1980s to the mid-1990s, BAV was selectively used in high-risk AS patients, but as previously discussed, the recognition of procedural complications, prohibitive early restenosis, and lack of mortality benefit relegated the use of BAV to a small clinical niche: either palliative therapy or as a bridge to definitive valve replacement.

The first catheter-based aortic valve replacement was performed in 1965 by Davies in a canine model for the temporary relief of aortic insufficiency. Andersen performed the first contemporary transcatheter aortic valve replacement procedure using a stent-based porcine bioprosthesis in pigs in 1992. The first implantation of a transcatheter valve in a human was performed by Bonhoeffer in 2000 involving the percutaneous replacement of a pulmonary valve in a right-ventricle to pulmonary-artery prosthetic conduit, using a bovine jugular valve to treat a 12-year-old boy with severe stenosis and regurgitation of the valved prosthesis. Cribier's first-in-human landmark TAVR procedure in 2002 was undertaken as a last resort in a patient with cardiogenic shock, failed BAV, and multiple co-mordibities. Since that time, TAVR has become the standard of care in patients who are “inoperable” and is an important alternative in patients who are high risk for surgery, with more than a dozen different device variations either commercially available or under active investigation.

Clinical Indications

In the current ESC/EACTS and ACC/AHA guidelines for the management of valvular heart disease, it is recommended that the following patients be considered for TAVR procedures: patients with severe, symptomatic, calcific stenosis of a trileaflet aortic valve who have aortic and vascular anatomy suitable for TAVR, an expected survival >12 months, and surgical risk assessment by a multidisciplinary heart team indicating the following:

• 1.

  A prohibitive surgical risk as defined by an estimated 50% or greater risk of mortality or irreversible morbidity at 30 days or other factors such as frailty, prior chest wall radiation therapy, porcelain aorta, severe hepatic or pulmonary disease

• 2.

  A high surgical risk with an expected 30-day mortality at least 15%, as an alternative to SAVR

All other indications for TAVR, including moderate surgical risk patients and bioprosthetic valve failure are currently under active investigation. It is notable that in the past several years with improved TAVR clinical outcomes and next generation TAVR systems, there has been a general downshifting of the risk strata, largely outside the United States, such that traditionally lower risk patients are being considered acceptable candidates for TAVR, especially in older patients (>80 years old), with one or two co-morbidities.

Heart Team Model and Risk Assessment

Given the complexity regarding the management of elderly patients with severe AS, a collaborative heart team model is essential for appropriate patient selection and subsequent care. This multidisciplinary team consists of experienced cardiac surgeons, interventional cardiologists, imaging specialists, heart failure specialists, cardiac anesthesiologists, intensivists, neurologists, geriatricians, nurses, and social workers. The coordinated approach of the heart team results in more comprehensive patient evaluations, facilitated gathering of essential data, improved communication with patients and families, superior decision making, and ultimately, better clinical outcomes. The importance of the heart team model is emphasized in both the European and the US TAVR guidelines.

Several different surgical risk algorithms are utilized by heart teams for the selection of patients for TAVR. The two most common risk assessment tools are the Society of Thoracic Surgeons (STS) score and the logistic EuroSCORE. The STS score is derived from outcomes data of 24 covariates in 67,292 patients undergoing isolated SAVR in the United States, while the logistic EuroSCORE is derived from 12 covariates from 14,799 patients undergoing all forms of cardiac surgery in Europe. While both have been shown to be accurate for estimating risk (i.e., 30-day surgical mortality) in low-risk patients with AS, their accuracy is far less precise in higher risk patients. The two scores differ predominantly in the covariates utilized in the respective models and in the populations studied. It is generally acknowledged that the STS score is more accurate at estimating SAVR mortality in higher risk populations. There is reasonable consensus that an STS score ≥8 is deemed to be high risk for SAVR and that these patients should also be considered for TAVR. While both the STS and logistic EuroSCORE can aid in the selection of patients for TAVR, they serve as only one aspect of the selection process and should be utilized in the context of the entire clinical picture.

Several important concepts relevant to risk assessment for TAVR require further consideration. In the unique patient population currently screened for possible TAVR (elderly patients with co-morbidities or anatomic limitations), many risk factors are not represented in the standard risk scores, including frailty, dementia, hepatic disease, and anatomic factors (e.g., porcelain aorta or “hostile” chest). These ignored or under-represented co-morbidities must be considered by the heart team during risk assessment. At the extreme end of the risk spectrum are the so-called futile AS patients, wherein there is little hope of meaningful quality of life and/or limited life expectancy (e.g., untreatable malignancy or severe dementia), despite successful TAVR therapy. Although this may be a difficult societal conundrum, it is the responsibility of the heart team to thoughtfully identify these patients, such that TAVR may be sensitively withheld as a treatment option. Importantly, surgical risk is a continuum and the categorization of risk status into discrete groups is somewhat arbitrary and depends on definitions that are changing over time and may be different in the rarified confines of a clinical trial versus real-world community standards. Finally, since the predictors of early and late outcomes after TAVR are different compared with SAVR, specific risk assessment models for TAVR would be clinically useful and are being actively evaluated.

Anatomic Screening and Need for Multimodality Imaging

The information gathered during multimodality anatomic screening should be utilized to make an informed judgment on the candidacy of a patient for TAVR and in the overall management of patients with AS. The salient imaging data needed for comprehensive TAVR screening include (1) confirmation of the diagnosis of tri-leaflet, calcific, and severe valvular AS; (2) determination of left ventricular size and function; (3) coronary artery anatomy; (4) peripheral vasculature of sufficient size and suitability for catheter access and prosthesis delivery; and (5) geometry, measurement, and calcium patterns of the left ventricular outflow tract, proximal aorta, and the aortic annulus for appropriate device selection. Imaging for anatomic screening consists of a combination of echocardiography, angiography, and multi-slice computed tomography (MSCT).

Echocardiography is clearly the gold standard for assessing the etiology and severity of AS. Other important anatomic findings best determined by echocardiography are left ventricular mass, size, and function; right ventricular size and function; and other valvular lesions (especially mitral and tricuspid regurgitation). Usually, transthoracic echocardiography is sufficient, but in some patients with difficult imaging planes transesophageal echocardiography is preferred. Coronary angiography is crucial in every patient to determine the need for concomitant revascularization, given the frequent co-existence of coronary artery disease and AS. Peripheral angiography is also recommended to assess tortuosity, size, and calcification of the distal aorta, iliac, and femoral vessels. However, MSCT with contrast is the best imaging study to quantitatively measure the lumen dimensions of peripheral arteries and their suitability for a given TAVR system. MSCT is also the recommended imaging study to determine the optimal transcatheter valve size, which may differ depending on the specific transcatheter valve type. These three-dimensional (3D) reproducible measurements of the annulus region using validated algorithms derived from high-quality contrast MSCT have become the global standard modality in selecting the correct valve size. Intraprocedural 3D echocardiography can also be used to confirm the annulus measurements and to assist in valve sizing. MSCT is also helpful in measuring the location and height of the coronary arteries; patterns of calcification in the aortic valve, aorta, and left ventricular outflow tract; and the shape, angulation, and size of the proximal aorta. Much of the success of TAVR and the recent improvements in clinical outcomes have been directly linked to meticulous preprocedural planning using the aforementioned multimodality imaging studies.

Procedural Considerations

TAVR is always performed in a sterile environment, either a catheterization laboratory or an operating room, with fluoroscopic and angiographic digital imaging capabilities. Most recently, there has been a growing interest in using a “hybrid” catheterization laboratory–operating room suite for TAVR. These hybrid procedure rooms combine the advantages of a high-resolution angiographic catheterization lab with the concomitant availability of a sterile environment for surgical management of complications and to facilitate nonpercutaneous alternative access routes.

The presence of cardiac anesthesiology to supervise sedation and analgesia control and to assist with hemodynamic monitoring and management has been an important requirement for TAVR to provide optimal care of these high-risk AS patients. There is growing controversy whether general anesthesia versus monitored anesthesia control (conscious sedation) is necessary or preferred in all or most patients during TAVR procedures. Similarly, the requirement of intraprocedural transesophageal echocardiography in every case has been highly debated. The more traditional approach incorporates general anesthesia with transesophageal echocardiography to help guide the procedure, including confirmation of valve sizing and positioning, assessment of paravalvular regurgitation, and rapid recognition of complications. Nevertheless, an increasing number of TAVR operators prefer a more “minimalist” approach, without general anesthesia and employing only transthoracic echocardiography, as needed. The reasons for this less invasive TAVR strategy are reduced resource consumption, fewer anesthesia-related complications, more rapid patient ambulation, and shorter durations of hospital stay. Thus far, experienced operators adopting this simplified approach have had equivalent procedural outcomes. Perhaps a stratified patient-specific approach is most reasonable, wherein lower risk patients or those with anticipated intubation morbidities (e.g., severe chronic obstructive pulmonary disease [COPD]), can be triaged to the minimalist strategy and the higher risk patients can be managed using a more intense strategy with general anesthesia and transesophageal echocardiography guidance. As sheath sizes decrease and operator experience increases, likely the majority of TAVR worldwide will be performed in catheterization laboratories using conscious sedation.

Technology Overview and Early Access Approaches

All TAVR systems are composed of three integrated components: a support frame (usually metallic), a bioprosthetic tri-leaflet valve, and a delivery catheter. The support frame is crimped onto the delivery catheter immediately prior to valve implantation and is expanded by either retracting a sheath or inflating an underlying balloon. Balloon-expandable TAVR systems (Edwards Lifesciences, Irvine, California) were the earliest used in patients and have undergone several generations of evolution. However, many technology features have remained constant over time, including the tubular-slotted metallic frame geometry, pericardial bioprosthetic valve leaflets sewn to the frame, a fabric “skirt” covering the bottom of the frame, and out-of-body circumferential crimping of the valve and frame assembly onto the delivery catheter. The Cribier-Edwards valve became available in 2004 and was used in many of the early feasibility cases in Europe and the United States. This TAVR system had both 23- and 26-mm valve sizes and a stainless steel frame with an attached equine pericardial trileaflet valve that was directly crimped onto a commercial balloon valvuloplasty catheter. Cribier's first case and many of the earliest cases were performed using an antegrade transfemoral vein approach, wherein after right femoral vein access, a transseptal puncture provided entry to the left heart, followed by positioning a stiff guidewire across both the mitral and aortic valves. Navigating these first generation devices and large-sized catheters with roughened distal edges across the interatrial septum and the tortuous intracardiac anatomy was challenging. The initial antegrade transfemoral vein transseptal access procedures required very experienced operators with advanced skills and resulted in many intraprocedural complications. Specifically, the generation of a large guidewire loop inside the left ventricle, which was required to avoid traction on the anterior mitral valve leaflet, was extremely difficult to maintain throughout the procedure and often resulted in severe mitral regurgitation with hemodynamic collapse.

Difficulties with the unpredictability of the antegrade transseptal approach resulted in modifications of both the access approach and the delivery catheter. A simpler and more familiar access site, typically used with BAV procedures, was the femoral artery with retrograde transaortic entry into the left ventricle. This can be accomplished with direct percutaneous access or through an open surgical exposure of the common femoral artery. Webb and colleagues reviewed their initial experience with the Cribier-Edwards valve via a retrograde transfemoral approach in a case series of 50 patients. For this purpose, a steerable delivery catheter with a deflectable tip was also developed to safely advance the TAVR system within the vasculature and to better align the valve assembly with the central valve orifice. In 2007, the next generation Edwards-SAPIEN (Edwards Lifescience, Irvine, California) transcatheter valve was introduced ( Figure 29-2A ). The major differences included a change from equine to bovine pericardium valve leaflet material, which enabled surgical valve-like consistency in tissue processing (decalcification, thickness, flexibility, and tensile strength), as well as further improvements in the delivery catheter. The third generation SAPIEN XT valve (20-, 23-, 26-, and 29-mm sizes) began clinical evaluations in 2010 and represented a more radical design change of all system components, with a major goal to importantly reduce the overall profile ( Figure 29-2B ). The support frame had less metal and was changed from stainless steel to a thinner cobalt alloy, the valve geometry was modified to allow partial closing in the open position, and the delivery catheter was reduced in diameter by 33% for all valve sizes, with improved transitions to facilitate advancement and crossing. The marked reduction in system profile was in part due to an endovascular docking maneuver, such that the valve was crimped onto the catheter shaft for arterial entry, and in the descending aorta, the balloon was pulled back underneath the valve for subsequent deployment. The SAPIEN XT is the current commercially available balloon expandable TAVR system in the United States.

Most recently, the fourth generation SAPIEN 3 device ( Figure 29-3A ) has completed enrollment in clinical trials in the United States (PARTNER II registry) and has received CE approval in Europe. The overall system profile has been further reduced, with most valve sizes introduced through a 14 Fr expandable sheath. The frame geometry has been modified with larger cells distally, and in addition to the internal skirt, an external skirt has been added to fill gaps and to prevent paravalvular regurgitation.