The incidence of calcific aortic stenosis (CAS) is increasing because of prolonged life expectancy. A subset of elderly patients cannot undergo surgical valve replacement, because of poor ventricular function and comorbidities. Percutaneous balloon aortic valvuloplasty (BAV) provides temporary improvement, but is associated with a high mid-term restenosis rate. Hence, a percutaneous bioprosthetic aortic heart valve is of interest. Cribier described the experience at his institution with BAV, the development of a percutaneous heart valve (PHV), and the outcomes in the initial 14 patients with end-stage CAS who received a PHV.

The limitation of BAV is the achieved final aortic valve area is only 1.0 cm², and on average is in the range of 0.8-0.9 cm².  In 148 consecutive patients over 80 years of age who underwent BAV, performed by Cribier and colleagues, the complications were in an acceptable range. Death occurred in 4 patients (2.7%), stroke in 3 patients (2.0%), ventricular fibrillation in 1 patient (1.0%), and surgical femoral complication at the puncture site in 8 patients (5.0%).

The indications at Cribier’s institution for BAV are: Elderly patient (mean age 84 years) at very high surgical risk due to severely depressed left ventricular (LV) function or comorbidities; major myocardial dysfunction (including cardiogenic shock) to improve LV function before valve replacement (bridge to surgery); urgent surgery for noncardiac disease; and repeat BAV for symptomatic restenosis (up to 4-5 times).

Beginning in 1994, Cribier and colleagues examined the use of implanted stents into the native valve with CAS, which they considered the best way to address the problem of restenosis to maintain an open aortic valve. In 12 patients, a stent was implanted within the valve, regardless of the degree of calcification, without occluding the coronary arteries and impairing function of mitral valve, and totally opened the valve. Post-mortem studies showed that a 23 mm stent resulted in an extremely large orifice, the best possible result in patients with CAS.

Cribier and colleagues worked with industry to develop a PHV, with the idea of suturing the PHV with the tricuspid valve using 3 anchoring struts. The concept was to crimp the PHV over a balloon, go across the native aortic valve and then inflate the balloon after removing the sheath and deliver the PHV. The goals were to develop a biologic valve mounted in a specific stent that could be delivered percutaneously via standard catheter-based techniques, within the diseases native valve. The initial target population was patients with severe CAS who are deemed inoperable or at unacceptable risk for surgical valve replacement.

The first PHV was made in 1999 by Percutaneous Valve Technologies, a US company. This 1st generation PHVs was made of polyurethane, and were tested in animals. The 2nd generation PHVs, made of bovine pericardium, was tested extensively in vitro and was the first one implanted in a human; it resulted in excellent flow with parallel edges, which compared favorably with the flow obtained with surgically implanted prosthetic valves. In animals, a very good aortic valve area (AVA) was obtained, the leaflets were very supple, and the orifice was 1.7 cm².

In 1999, Cribier and colleagues began PHV implantation in animal models (> 100 implantations) in various cardiac sites, including the native aortic valve, native pulmonary valve, and the descending aorta. Crossing the brachial cephalic trunk was possible, introducing a 24 Fr introduce, when implanting in the native aortic valve or descending aorta. Notably, the diameter of the brachial cephalic trunk in sheep is comparable to the femoral artery in humans—which allowed thinking about the concept of inserting the PHV through the femoral artery in patients using the same technique.

Notably, in the sheep model, at 1 month post-implantation the PHV implanted in the pulmonary valve was working normally. In 1 sacrificed animal, the PHV looked like a native valve. In this model, it is not usual to see the PHV functioning at 1 month because of the well-demonstrated fast deterioration of a bioprosthesis implanted in a pulmonary artery or venous blood of animals. In their previous experience, a number of animals were lost because of dysfunction of the bioprosthesis, due to the valve becoming very thick and remaining open. Therefore, implanting a bioprosthetic valve in the pulmonary artery is not a good model to study the long-term efficacy of a PHV.

So, implantation of the PHV in the native aortic valve in the animal model was studied.  In one successful case, the PHV was implanted at the origin of the aorta; the coronary arteries were patent and LV function good. At post-mortem, the coronary arteries were above the level of the PHV, with correction positioning of the valve.

Two difficult problems in this model are ensuring the correct position of the PHV and the risk of mobilization. In the animal model, especially in sheep, the distance between the ostia of the coronary arteries and the insertion of the mitral valve is only 4-5 mm. So, implantation is extremely difficult, as is the correct positioning of the PHV.  Also, when the PHV was implanted, the risk of mobilization was very high, because there was no calcium or fibrosis to maintain the stent in place, in contrast to what would be seen in patients. The number of migratory valves was very high.

PHV implantation in the descending aorta was the most interesting model, performed to determine the 6-months results. The PHV was implanted from the carotid artery into the descending aorta, at 6 months it was functioning well, without regurgitation, and at 6 months functioning ideally with excellent opening of 1.7 cm², no deterioration of the valve. To date, in the animals in which the PHV has been implanted in the descending aorta, the results show no or little thickening of the leaflets, very clean aspect with pannus or calcification possibly seen in just 1 case for which confirmation is pending, and the 6-month histopathology results are pending.

In April 2002, PHV implantation in humans began. The first person to receive a PHV was a 57-year-old man, with severe CASand in cardiogenic shock. Surgical valve replacement was declined by three surgical teams, because of the patient’s hemodynamic status and comorbidities. The patient had subacute ischemia of the right leg (aorto-bifemoral bypass in 1996, recent occlusion of right limb), and comorbidities included silicosis, lung cancer (lobectomy in 1999), chronic pancreatitis, and an LVEF of 10%. A BAV performed by Cribier and colleagues failed and the patient returned 2 days later in cardiogenic shock. The PHV was implanted using the antegrade approach, with no aortic regurgitation. Hemodynamic results included decreasing gradient to zero and no decrease in diastolic pressure. At day 8 post-implantation the patient was out of bed and undertaking normal activities within the hospital. The patient survived 4.5 months and died of leg amputation complications.

After this first case, Cribier and colleagues worked on improving the PHV for human implantation with the company Percutaneous Valve Technologies. The latest prototype has a tricuspid valve made of equine pericardium and 23 mm stainless steel vent. The in vitro durability is anticipated to be greater than 5 years based on testing. Presently, there is only 1 size of stent, with a maximum diameter of 23 mm, delivery pressure of 4-5 Atm, crimped diameter 6 mm, and sheath 24-Fr (compatible with 22-Fr or 20-Fr). It can also be used for abdominal aortic aneurysms. Implantation of this PHV within a diseased valve is possible without obstructing the right coronary artery or left main artery, as demonstrated by post-mortem studies.

The 2 methods for PHV implantation are the antegrade trans-septal approach (ATSA), which is the gold standard, and the retrograde approach. The steps in the ATSA are: 1) pre-dilation of the native valve with 23 mm balloon, 2) trans-septal catheterization, the lateral view is best to cross the septum, 3) insert stiff guidewire from the right femoral vein (RFV) to left femoral artery (LFA), 4) trans-septal dilation with 10 mm balloon, 5) percutaneous introduction of a 24-Fr sheath in the RFV, 6) PHV/balloon assembly advanced to native valve, 7) PHV delivery within native valve during brief rapid atrial pacing, and 8) supra-aortic angiogram with or without a selective coronary angiography to check exact position of the PHV. Local anesthesia is used, the procedure duration is about 90 min, and fluoroscopy time about 25 min. The limitation of this approach is the learning curve, it is somewhat difficult to learn, and particular attention must be paid to achieving and maintaining an ideal loop when the guidewire is advanced from the RFV into the left ventricle, which requires 3 persons (1 for the valve and delivery system, 1 for guidewire entering RFV, and 1 for guidewire exiting femoral artery)—all to maintain the loop during the procedure. Not maintaining the ideal loop could result in, for example, a position that pushes away the anterior leaflet of the mitral valve, creating an acute regurgitation, which could lead to transitory collapse of the patient. The average time for femoral puncture site compression is 15 minutes.

The retrograde approach is elegant, fast, and easier to handle. The steps are: 1) pre-dilation of the native valve with 23 mm balloon from RFA, with stimulation of the heart in such a way that the balloon is not moving during inflation, 2) introduce 24-Fr sheath in the RFA (many limitations, especially in older patients, who have vessel tortuosity and lots of atheroma; the left femoral artery diameter must be above 7 mm), 3) PHV advanced to native valve, 4) PHV delivery within native valve during brief rapid atrial pacing, 5) supra-aortic angiogram with or without a selective coronary angiography, 6) percutaneous closure of RFA, with two 10-Fr Prostar.  Retrograde approach is performed under local anesthesia, procedure duration 60 minutes, and fluoroscopy time 20 minutes. Achieved AVA is 1.6 cm², which is larger than can be achieved by surgery. The main limitation of the retrograde approach is the difficulty of crossing the valve from above, because the guidewire is crossing the valve on the side, inside the commissure, and if the valve is extremely calcific, the reduced diameter may make it difficult to cross with the crimped valve on the balloon. Cribier and colleagues experienced 3 failures in crossing the valve in their series of patients. Therefore, they are now working on improving the device to avoid this problem.

The feasibility of human implantation was studied in compassionate cases, in which death was imminent. To date, 20 patients have received a PHV (50% male). Of these, 15 are in the prospective I-REVIVE study. Patient characteristics include: Mean age 78 years, range 57-91 years; NYHA class IV in all by inclusion criteria; cardiogenic shock in 4 persons. All patients were formally declined by 2 cardiac surgeons, according to inclusion criteria, due to associated multiple cardiac and non-cardiac factors. The Parsonnet’s score was 52±7 (range 42-66) in these patients. Associated cardiac factors in this population were: severe CAD in 4 patients, recent AMI in 1, EF ú 25% in 4, cardiogenic shock in 4, porcelain aorta in 4, mitral stenosis in 2. Extra-cardiac factors were evolving cancer in 5, recent stroke in 2, renal failure 6, diabetes (insulin) 5, carotid dissection 5, COPD 8, morbid obesity 1, liver cirrhosis 1, ongoing infection 1, thorax irradiation 1.

Procedural Results: Antegrade approach used in 13 cases, retrograde in 7 cases. Success was achieved in 17 of 20 patients. Technical failures occurred in 4 patients. In 1 patient, there was balloon/valve assembly migration in a case of massive aortic regurgitation post-BAV; the patient was in cardiogenic shock, early death followed. There were 3 failures of retrograde crossing of the native valve.

The hemodynamic results were very satisfactory. Mean gradient (mm Hg) was 8.5 post-implantation, compared to 4.3 pre-implantation (p=0.0076). The AVA was 0.56 cm² pre-implantation and 1.69 cm² post-implantation (p=0.0076).

Procedural complications were: 1 stroke while crossing the aortic valve with the guidewire; RV perforation with the pacemaker lead and tamponade in a patient under major steroid treatment for pulmonary fibrosis; death during pre-dilation of the native valve in a patient in cardiogenic shock; death after the end of a successful procedure after removal of the RFA sheath.

Aortic regurgitation of some degree seen in nearly all patients, but it was grade 1 or 2 in most patient, which is acceptable. In some patients, it was grade 3. In all of the cases, the aortic regurgitation was coming from a gap between the stent and the distorted native valve with lots of calcium deposit. One solution is increasing the stent size. A 26 mm stent is nearly ready for use. The LVEF nearly doubled in all patients with reduced EF pre-implantation. At the time of this presentation, 8 patients were surviving (1 to 6 months), with no sign of heart failure. All of the deaths except for one was due to a non-cardiac cause.