Special Report
`
`Percutaneous Transcatheter Implantation of an Aortic Valve
`Prosthesis for Calcific Aortic Stenosis
`First Human Case Description
`
`Alain Cribier, MD; Helene Eltchaninoff, MD; Assaf Bash, PhD; Nicolas Borenstein, MD;
`Christophe Tron, MD; Fabrice Bauer, MD; Genevieve Derumeaux, MD; Frederic Anselme, MD;
`François Laborde, MD; Martin B. Leon, MD
`
`Background—The design of a percutaneous implantable prosthetic heart valve has become an important area for
`investigation. A percutaneously implanted heart valve (PHV) composed of 3 bovine pericardial leaflets mounted within
`a balloon-expandable stent was developed. After ex vivo testing and animal implantation studies, the first human
`implantation was performed in a 57-year-old man with calcific aortic stenosis, cardiogenic shock, subacute leg ischemia,
`and other associated noncardiac diseases. Valve replacement had been declined for this patient, and balloon
`valvuloplasty had been performed with nonsustained results.
`Methods and Results—With the use of an antegrade transseptal approach, the PHV was successfully implanted within the
`diseased native aortic valve, with accurate and stable PHV positioning, no impairment of the coronary artery blood flow
`or of the mitral valve function, and a mild paravalvular aortic regurgitation. Immediately and at 48 hours after
`implantation, valve function was excellent, resulting in marked hemodynamic improvement. Over a follow-up period
`of 4 months, the valvular function remained satisfactory as assessed by sequential transesophageal echocardiography,
`and there was no recurrence of heart failure. However, severe noncardiac complications occurred, including a
`progressive worsening of the leg ischemia, leading to leg amputation with lack of healing, infection, and death 17 weeks
`after PHV implantation.
`Conclusions—Nonsurgical implantation of a prosthetic heart valve can be successfully achieved with immediate and
`midterm hemodynamic and clinical improvement. After further device modifications, additional durability tests, and
`confirmatory clinical implantations, PHV might become an important therapeutic alternative for the treatment of
`selected patients with nonsurgical aortic stenosis. (Circulation. 2002;106:3006-3008.)
`
`Key Words: stenosis, aortic 䡲 valves, prosthetic 䡲 prosthesis 䡲 catheterization
`
`Percutaneous catheter-based systems for the treatment of
`
`valvular heart disease have been designed and studied in
`animal models for several years.1– 4 Recently, Bonhoeffer et
`al,5,6 using a bovine jugular vein valve mounted within a
`stent, performed the first in-human percutaneous implanta-
`tions of artificial valves in children with right ventricle to
`pulmonary prosthetic conduits.
`The goals of our research project were to develop a
`biological heart valve, mounted on a specially designed
`balloon-expandable stent, which could be delivered percuta-
`neously via standard catheter-based techniques and implanted
`within a diseased aortic valve in calcific aortic stenosis. This
`concept was based on personal unpublished autopsy obser-
`vations on calcific aortic stenosis showing that a stent could
`effectively open while strongly adhering within the native
`
`diseased valve without impairing the coronary ostia or the
`mitral valve.
`An original percutaneous heart valve (PHV) was devel-
`oped (Percutaneous Valve Technologies, Inc), which con-
`sisted of 3 bovine pericardial
`leaflets mounted within a
`tubular, slotted, stainless steel balloon-expandable stent,
`14 mm in length, designed to achieve a diameter of 21 to
`23 mm. PHV function and durability were first tested in ex
`vivo pulse duplicator models. Valve durability passed 100
`million cycles (2 and a half years). In animal models, the
`PHV was accurately delivered by balloon inflation at various
`cardiac sites7 in 60 sheep. Acute and short-term valve
`functions were satisfactory. Implantation in the subcoronary
`aortic valve position was technically difficult in this animal
`model (which varies considerably from humans) and was
`
`Received September 5, 2002; revision received October 18, 2002; accepted October 20, 2002.
`From the Department of Cardiology (A.C., H.E., C.T., F.B., G.D., F.A.), Charles Nicolle Hospital, University of Rouen, Rouen, France; the Centre
`d’Experimentation et de Recherche Appliquée (CERA) (N.B., F.L.), Institut Montsouris, Paris, France; the Cardiovascular Research Foundation (M.B.L.),
`Lenox Hill Hospital, New York, NY; and Percutaneous Valve Technologies, Fort Lee, NJ (A.B.).
`Correspondence to Pr Alain Cribier, Service de Cardiologie, Hôpital Charles Nicolle, 1 rue de Germont, 76 000, Rouen, France. E-mail
`Alain.Cribier@chu-rouen.fr
`© 2002 American Heart Association, Inc.
`Circulation is available at http://www.circulationaha.org
`
`DOI: 10.1161/01.CIR.0000047200.36165.B8
`
`3006
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`Cribier et al
`
`Percutaneous Valve for Aortic Stenosis in Human
`
`3007
`
`Figure 1. The percutaneous valve crimped over the 30-mm-long
`balloon before implantation.
`
`frequently associated with early migration (⬍15 days) be-
`cause of the lack of any calcific or fibrotic lesion. Increase in
`valvular thickness was commonly observed at 1 to 3 months
`after implantation in the venous system (pulmonary valve)
`but not in the arterial system (descending aorta).
`
`Methods
`
`Patient
`The first human implantation of this PHV was a “last-resort” case in
`a 57-year-old man with severe calcific aortic stenosis for whom
`aortic valve replacement had been declined by several cardiac
`surgical teams because of hemodynamic instability and significant
`comorbidities. His medical history included peripheral vascular
`disease with aorto-bifemoral bypass in 1996, silicosis, lung cancer in
`1999, and chronic pancreatitis. He presented with cardiogenic shock
`(systolic blood pressure 80 mm Hg, cyanosis, and oliguria), bilateral
`pleural effusions and pulmonary edema, and subacute ischemia of
`the right
`leg due to recent occlusion of the right
`limb of the
`aorto-femoral bypass. Transthoracic echocardiography indicated a
`severely calcified bicuspid aortic valve with a mean transvalvular
`gradient of 30 mm Hg, valve area 0.6 cm2, and ejection fraction 14%.
`No myocardial contractility reserve was shown on dobutamine
`stress-echocardiography. Because of the severe peripheral vascular
`disease (the left limb of the aorto-femoral bypass was also severely
`narrowed), aortic valvuloplasty was performed with the transseptal
`antegrade approach with 20-mm-diameter balloon inflations. He
`sustained initial hemodynamic improvement with a reduction in
`gradient to 13 mm Hg and an increase in valve area to 1.06 cm2.
`During the ensuing week, however, his condition deteriorated with
`recurrence of cardiogenic shock and impending death (systolic blood
`pressure 70 mm Hg despite vasopressors and ejection fraction of 8%
`to 12%). Under these desperate circumstances, as a last-resort,
`potentially lifesaving intervention that might also bridge surgical
`valve replacement, the approval of our Institutional Ethics Commit-
`tee was obtained, and the patient and his relatives consented to
`attempted implantation of the investigational PHV.
`
`Procedure
`The procedure was undertaken under mild sedation and local
`anesthesia. A 5F catheter from the left femoral artery was used for
`continuous blood pressure monitoring, and the antegrade approach
`from the right femoral vein was used for PHV insertion. After
`standard transseptal catheterization, a straight 0.035-inch guidewire
`was advanced across the stenotic aortic valve through a balloon
`flotation catheter. After advancement of the balloon catheter into the
`descending aorta, the guidewire was exchanged for a stiff 260-cm-
`long guidewire, which was snared from the left femoral arterial
`access site and externalized via the arterial sheath. A 24F sheath was
`inserted into the right femoral vein, and the interatrial septum was
`dilated with a 10-mm-diameter balloon catheter. With the use of a
`mechanical crimping device, the PHV was securely crimped over a
`3-cm-long, 23-mm-diameter balloon catheter (NuMED) (Figure 1).
`The PHV was easily advanced through the sheath, across the
`interatrial septum, and within the diseased stenotic aortic valve. With
`the valvular calcification used as a marker, the PHV was placed at
`midposition of the aortic valve. The balloon was then maximally
`inflated, rapidly deflated, and immediately withdrawn (Figure 2).
`Hemodynamic assessment and left ventricular and supraaortic an-
`giograms were performed. A transesophageal echocardiography was
`obtained immediately after the procedure and repeated at day 7 and
`every 2 weeks thereafter to assess the PHV function.
`
`Results
`Cardiac standstill was present during the 20 seconds of final
`PHV deployment. Thereafter, the aortic pressure rose steadily
`and stabilized at 120/60 mm Hg. Immediately after the
`procedure, mean transvalvular gradient was 6 mm Hg, left
`ventricular end-diastolic pressure 25 mm Hg, cardiac index
`2.5 L/min per square meter, and calculated aortic valve area
`1.9 cm2 according to Gorlin’s formula.8 A left ventricular
`angiogram revealed a normal flow across the aortic valve, no
`mitral regurgitation, and an ejection fraction of 17%. A
`supraaortic angiogram demonstrated that both coronary ostia
`were patent and well removed from the valve apparatus and
`showed mild paravalvular aortic regurgitation (Figure 2).
`Procedure and fluoroscopy times were 126 and 24 minutes,
`respectively.
`Transesophageal echocardiography performed within 30
`minutes of PHV implantation revealed a completely excluded
`native aortic valve, circular stent geometry with a diameter of
`21 mm, optimal PHV function with a mean gradient of
`9 mm Hg, a valve area of 1.6 cm2 by planimetry in the
`cross-section view, and a moderate paravalvular regurgitation
`through a nonapposed calcified commissure of the bicuspid
`aortic valve.
`
`Figure 2. PHV delivery within the native
`calcific valve. Left, Maximal balloon infla-
`tion (23 mm) for valve delivery. Middle,
`The PHV in position at mid part of the
`native aortic valve, pushing aside the
`calcific leaflets. Right, Supraaortic angio-
`gram after PHV implantation showing no
`aortic regurgitation across the PHV and a
`mild paravalvular regurgitation (arrow).
`Both coronary ostia are patent and
`removed from the valve prosthesis. LCA
`indicates left coronary artery; RCA, right
`coronary artery.
`
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`3008
`
`Circulation
`
`December 10, 2002
`
`Follow-Up
`The postprocedural treatment included permanent anticoagu-
`lation with heparin and aspirin and intravenous administra-
`tion of vasopressors at decreasing doses over the first 4 weeks
`after PHV implantation.
`
`PHV Echocardiographic Assessment
`The PHV function remained satisfactory on transesophageal
`echocardiographies performed at 1, 4, 7, and 9 weeks after
`implantation. The PHV leaflets remained thin and mobile
`with no sign of PHV regurgitation and unchanged paraval-
`vular regurgitation. By planimetry, the aortic valve area was
`1.6, 1.6, 1.5, and 1.5 cm2, respectively, and the mean
`transvalvular gradient 15, 10, 8, and 14 mm Hg, respectively.
`The left ventricular ejection fraction remained poor, in the
`range of 13% to 20%.
`
`Clinical Evolution
`In the next 48 hours after PHV implantation, there was a
`dramatic clinical improvement with reduced signs of conges-
`tive heart failure, and the patient could resume off-bed
`activities.
`Several noncardiac-related complications occurred during
`the subsequent 4-month follow-up: an episode of pulmonary
`embolism at day 3, requiring intravenous fibrinolysis; an
`episode of septicemia at day 10, starting with septic shock;
`and a progressive worsening of the right
`leg ischemia,
`requiring a midthigh amputation 10 weeks after PHV implan-
`tation as the only possible option. The patient’s clinical
`condition progressively deteriorated after surgery, with per-
`manent infection and lack of healing of the amputation site,
`weight loss, and bedsore eschars, leading to death 17 weeks
`after PHV implantation. No acute episode of heart failure
`occurred over this follow-up period. Unfortunately, autopsy
`could not be obtained.
`
`Discussion
`This dramatic case demonstrates the feasibility of implanting
`a prosthetic heart valve percutaneously, with the use of
`standard interventional techniques, within the native diseased
`valve of a patient with calcific aortic stenosis. A successful
`short-term therapeutic result was achieved under
`life-
`threatening circumstances. A satisfactory PHV function was
`observed on transesophageal echocardiography, which re-
`mained unchanged over 9 weeks of sequential assessment.
`In aortic stenosis, emergency valve replacement is often
`rejected because of a prohibitive risk in the setting of
`cardiogenic shock.9 Balloon valvuloplasty, which can be
`successfully used as a bridge to surgery in such desperate
`situations,10 led to nonsustained improvement in our patient.
`PHV implantation could be easily, successfully, and safely
`performed with the transseptal approach. This antegrade
`approach, which was necessary because of severe peripheral
`artery disease, provided several advantages over the retro-
`
`grade route used in animals: The 24F sheath could be inserted
`percutaneously into the right femoral vein, the long guidewire
`exiting the left femoral artery provided excellent support for
`tracking the device, and the PHV tended to move in concert
`with the heart, making precise placement more predictable.
`Also, it is likely that the poor left ventricular contractility
`helped stabilize the system during PHV deployment. Imme-
`diate and midterm PHV function were satisfactory, associated
`with early clinical improvement. The left ventricular func-
`tion, however, remained severely depressed in this patient
`who had no myocardial contractility reserve. Finally, second-
`ary surgical valve replacement could never be considered
`because of noncardiac complications.
`At present, the PHV is targeted for end-stage patients with
`severe aortic stenosis not amenable to surgical valve replace-
`ment. Further indications might follow from ongoing chronic
`studies in animals with a newly designed PHV. The optimal
`anticoagulation regimen after PHV implantation (heparin
`followed by oral anticoagulant and/or antiplatelet therapy)
`will also be assessed in these studies. In the future, with
`further device modifications and corroborative clinical stud-
`ies, this less invasive, catheter-based approach to the treat-
`ment of aortic stenosis may become an important and
`versatile therapeutic alternative.
`
`Acknowledgments
`The authors thank Stanton Rowe and Stanley Rabinovitch from
`Percutaneous Valve Technologies, Inc, Fort Lee, NJ, for their
`support in the research program and in the development of the
`device.
`
`References
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