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The transcatheter route is an emerging approach to treating valvular disease in high-risk patients. The 1st clinical antegrade transcatheter placement of an aortic valve prosthesis was reported in 2002. We describe the first retrograde transcatheter implantation of a new aortic valve prosthesis, in a 62-year-old man with inoperable calcific aortic stenosis and multiple severe comorbidities.
Via the right femoral artery, a Cook introducer was advanced into the abdominal aorta. The aortic valve was crossed with a straight wire, and a pigtail catheter was advanced into the left ventricle to obtain pressure-gradient and anatomic measurements. An 18-mm valvuloplasty balloon was then used to predilate the aortic valve. Initial attempts to position the prosthetic valve caused a transient cardiac arrest. Implantation was achieved by superimposing the right coronary angiogram onto fluoroscopic landmarks in the same radiographic plane. A balloon-expandable frame was used to deliver the valve. After device implantation, the transvalvular gradient was <5 mmHg. The cardiac output increased from 1 to 5 L/min, and urine production increased to 200 mL/h. The patient was extubated on the 2nd postimplant day. Twelve hours later, he had to be reintubated because of respiratory distress and high pulmonary pressures. His condition deteriorated, and he died of biventricular failure and refractory hypotension on day 5. Despite the severe hypotension, valve function was satisfactory on echo-Doppler evaluation.
In our patient, retrograde transcatheter implantation of a prosthetic aortic valve yielded excellent hemodynamic results and paved the way for further use of this technique in selected high-risk patients.
Efforts to develop a percutaneously implantable heart valve date back to 1965, when Davies1 described an umbrella-like device for relieving experimentally induced aortic insufficiency in dogs. Since that time, other researchers2–11 have published their experience with percutaneous valve implantation in animal models. In 2002, Bonhoeffer and his group12,13 performed the 1st percutaneous valve implantation in the pulmonary position in a human being. That same year, Cribier and coworkers14 described the 1st clinical antegrade transcatheter placement of an aortic valve.
We report the 1st retrograde transcatheter implantation of an aortic valve in a 62-year-old man with inoperable calcific aortic stenosis, intractable congestive heart failure, severe pulmonary hypertension, renal failure, and passive liver congestion.
Over the past 7 years, we have developed a biologic valve15 (the Paniagua Heart Valve [PHV]; Endoluminal Technology Research, Miami, Fla) that has a collapsed profile of 2 mm and can be inserted with an 11F or a 16F introducer, depending on the mounting frame and final valve diameter. These characteristics are highly suited to retrograde transcatheter delivery.
The PHV was evaluated in a left-heart and systemic circulation simulator (Vivitro Systems; Victoria, Canada). This system includes a processor-controlled stepper motor that drives a piston cylinder, forcing contraction and relaxation of the left ventricular sac. The aortic valve was mounted in its relative anatomic position. To achieve the same density and viscosity as blood, the system was filled with a mixture of 70% water and 30% glycerol. Sodium chloride (0.9%) was added to allow flow to be measured with an electromagnetic probe. The PHV was tested under physiologic conditions (cardiac output, 5 L/min; heart rate, 70/min; blood pressure, 180/80 mmHg) and pathologic states of hypotension (70/40 mmHg) and hypertension (320/250 mmHg). Echo-Doppler studies were performed with a 7.5-MHz transducer in the in vitro model. The PHV had no transvalvular gradient and no backflow (regurgitation) under physiologic conditions. Its opening gradient was 5 mmHg. Valve opening and closing characteristics were excellent. During extreme hypertension (320/250 mmHg), no prolapse was seen. Two-dimensional echocardiographic images showed complete apposition of the leaflets and the typical “Mercedes-Benz” sign. Pulsed Doppler studies of the acute in vitro model showed physiologic forward flow velocities and no evidence of regurgitation.
We tested the PHV in a long-term in vitro model for more than 2 years (236 million opening and closing cycles) and observed no device dysfunction or deterioration in materials.
In 2000, we began a series of short- and long-term animal experiments, some of which are ongoing. The initial studies were performed in Costa Rica and Miami Beach, Florida, using sheep and calf models. All the animals were treated humanely, according to the standard procedures for animal research used at the Biomedical Research Institute, Mount Sinai Medical Center, Miami Beach, Florida. Eleven sheep and 6 calves, weighing 30 to 60 kg each, underwent transcatheter implantation of the PHV. Eight long-term and 9 short-term animal studies were performed.
Vascular access was achieved percutaneously or by surgical exposure of a peripheral artery (femoral or carotid). The arterial entry site was enlarged with dilators. Baseline and postimplant angiograms were then obtained. The PHV was implanted in the descending aorta of 11 animals and in the ascending aorta of the other 6 animals. The prosthesis was introduced with a customized delivery system and was deployed in the selected anatomic position under fluoroscopic guidance. A balloon-expandable stent was used in 1 case, and a self-expanding stent was used in the other 16 cases; all stents were oversized by 10% in order to exert enough radial force to hold the valve in place without migration. Prophylactic antibiotics were given. After the valve was delivered, its position and function were verified with transthoracic Doppler ultrasonography. Complications occurred in 2 of the sheep: in 1 of them, the self-expanding stent failed to open, causing fatal aortic thrombosis. In the other case, the animal died suddenly of postoperative vascular complications at the access site. No migration of the stented valves occurred.
Autopsies were scheduled for 3 weeks, 6 months, and 13 months after PHV implantation. One calf was euthanized at 3 weeks. Pathologic examination of the implantation site showed ecchymoses and superficial hemorrhage without evidence of perforation or dissection. The harvested prosthesis functioned competently in the left-heart simulator and showed no histologic evidence of rejection. Six sheep were euthanized 6 months after implantation. Another calf was euthanized 13 months after implantation of a self-expanding stent in the descending thoracic aorta. A computed tomographic scan of the valve showed no calcification. The remaining animals were also euthanized at 13 months. When euthanized, all of the animals were in excellent condition. All explanted PHVs showed endothelialization without an inflammatory reaction.
A 62-year-old man had a history of infrapopliteal peripheral vascular disease and severe aortic stenosis, which developed into severe pulmonary hypertension, biventricular failure, passive liver congestion, and chronic renal failure (baseline creatinine level, 2.7 mg/dL). He was admitted to Centro Medico de Caracas Hospital with severe pulmonary edema, left pleural effusion, pulmonary hypertension, right-sided heart failure, hepatomegaly, ascites, and significant scrotal and lower-limb edema. Despite aggressive diuretic and inotropic support, his condition failed to improve and oliguric renal failure developed.
Transthoracic echocardiography showed global hypokinesis with an ejection fraction of 0.15, an api-cal thrombus, a peak aortic gradient of 50 mmHg, and an aortic valve area of 0.6 cm2. The native valve showed eccentric calcification with decreased opening excursion and fusion of the 3 leaflets. The pulmonary pressure was 60 mmHg, as assessed from the tricuspid regurgitant jet and a presumed right atrial pressure of 10 mmHg. The coronary arteries had no significant disease, and the native aortic valve area was 0.53 cm2 according to the Gorlin formula. Because of the patient's low ejection fraction, comorbidities, and generally hopeless situation, his case was declined by 3 surgical groups. He was offered a PHV by his treating cardiologist, and the case was discussed at length with the family. They understood the procedure's risks and benefits, as well as the alternative options, and they wanted to proceed. The hospital's institutional review board approved the procedure for compassionate use as a possible life-saving strategy.
On 3 April 2003, in the cardiac catheterization laboratory, the patient underwent mild sedation and local anesthesia of both groins. A 6F catheter was advanced from the left femoral artery to the ascending aorta to allow initial coronary angiography and continuous blood-pressure monitoring. Two sheaths were placed in the left femoral vein: 1 sheath for right-sided heart catheterization and the other for placing a temporary pacemaker in the right ventricle. The right femoral artery was surgically exposed to allow optimal control of the access site and to prevent local complications related to the severe peripheral vascular disease. A 16F Cook introducer (Cook, Inc.; Bloomington, Ind) was advanced into the abdominal aorta. A straight wire was then used to cross the aortic valve, and a calibrated pigtail catheter was advanced into the left ventricle. The transvalvular peak gradient was 36 mmHg. An Amplatz Super Stiff™ wire (Boston Scientific Corporation; Natick, Mass) was positioned in the left ventricle through the pigtail catheter. Intravascular ultrasonography was performed with a 20-MHz, 6F catheter and a Galaxy™ ultrasound imaging system (Boston Scientific). By means of planimetry, we estimated that the aortic valve area was 0.6 cm2. An 18-mm-diameter valvuloplasty balloon (Scimed, Boston Scientific), 6 cm in length, was placed in the aortic valve and fully inflated. To deliver the device, we used a Cheatham-Platinum (CP) 8Z28 Stent (NuMED; Hopkinton, NY) and a 20-mm balloon-in-balloon catheter. The 20-mm chemically sterilized PHV was oversized by 10% to fit the diameter of the left ventricular outflow tract. The prosthesis was manually crimped to a diameter of 4 mm and was then advanced over the wire to the aortic valve plane.
During placement of the valve, the patient had a cardiac arrest, which was probably related to aortic outflow obstruction. The PHV was withdrawn into the aortic arch (Fig. 1), and cardiopulmonary resuscitation was initiated. Sinus rhythm was restored in less than a minute, and the patient had no neurologic sequelae. He was intubated and kept comfortable with mild general anesthesia. By using fluoroscopic landmarks and overlapping images of the right coronary ostium, both in the same 40° left anterior oblique orientation with 20° cranial angulation, we were able to deploy the PHV successfully in the subcoronary position (Fig. 2). We noticed a waist in the PHV in the aortic valve plane but refrained from a further attempt to enhance the valve diameter, for fear of causing a vascular rupture.
The implantation and fluoroscopy procedures took 130 and 22 minutes, respectively. After the valve was deployed, the patient's hemodynamic values improved significantly. The aortic pressure increased from 80/50 to 110/60 mmHg, and the transvalvular gradient decreased from 36 to <5 mmHg (Fig. 3). Immediately after valve expansion, a complete atrioventricular block occurred, and cardiac pacing was required for 45 seconds, after which the heart spontaneously returned to sinus rhythm. The cardiac output increased from 1.0 to 2.8 L/min (later, 4.8 L/min), and urine production increased to 200 mL/h.
Gadolinium-enhanced aortography showed no regurgitation through the PHV (Fig. 4). Only a small paravalvular leak was present, and both coronary ostia were patent. A right anterior oblique cranial view showed that the stent had completely expanded in a circular fashion. Intravascular ultrasonography (Fig. 5) with a 20-MHz probe confirmed excellent expansion of the stent, as well as good mobility and apposition of the PHV leaflets. The PHV was located eccentrically (Fig. 6) because of severe calcification and poststenot-ic dilatation of the coronary sinus and aortic valve leaflets. The diameter of the valve perfectly matched that of the outflow tract and the area of aortic calcification. We used the Gorlin formula16 to calculate the PHV area, although that formula has not been validated for this particular setting. According to the Gorlin formula, the aortic valve area was 1.27 cm2 when the cardiac output was 2.8 L/min, and the valve area was 2.2 cm2 when the cardiac output was 4.8 L/min.
Transthoracic echocardiography, performed within 30 minutes after PHV implantation, revealed a completely excluded native aortic valve and a circular stent geometry with a 20-mm diameter. Prosthetic valve function was optimal, with a mean gradient of 5 mmHg, a valve area of 1.6 cm2 as measured by planimetry in a cross-sectional view, and mild paravalvular regurgitation between the PHV and the heavily calcified aortic valve leaflets.
Twenty-four hours after device implantation, transesophageal echocardiography (TEE) showed satisfactory PHV hemodynamics. Serial echo-Doppler studies confirmed good valve function even when the patient was hypotensive. Nevertheless, the left ventricular ejection fraction remained poor, ranging from 0.10 to 0.20.
After valve implantation, permanent anticoagulation therapy was initiated with intravenous heparin and antiplatelet agents (aspirin and clopidogrel). During the first 48 hours, the patient's pulmonary and peripheral congestion was dramatically reduced. His urine output increased to 200 mL/h, and he was extubated on the 2nd day. On the 3rd day, however, he developed respiratory distress, and his pulmonary pressure increased to systemic levels (90 mmHg). A pulmonary embolism was suspected; therefore, aggressive anticoagulation was continued. Reintubation was required. Within the next 48 hours, biventricular failure was followed by refractory hypotension, and the patient died on postimplant day 5. Despite the severe hypotension, the valve function remained satisfactory, as evaluated with echo-Doppler methods. Unfortunately, permission for an autopsy could not be obtained.
In 2000, Bonhoeffer and colleagues12 performed the 1st percutaneous replacement of a failed pulmonary valve in a right ventricle-to-pulmonary artery prosthetic conduit. In the 1st clinical transcatheter aortic valve procedure, performed in 2002, Cribier and co-authors14 used the antegrade approach. This approach was chosen because their device required a 24F sheath (outer diameter, 26F), which would have been difficult to advance through the arterial system. However, the antegrade approach has several disadvantages, including the need for a transseptal procedure with the risk of perforation and cardiac tamponade; the need for an atrial septal defect to be created; the risk of advancing the wire through the mitral subvalvular apparatus; and the risk of rupturing the mitral valve during balloon inflation, especially if the wire is between the mitral chordae tendineae.
Ours is the 2nd report of percutaneous valve implantation in the aortic position. However, it is the 1st case to involve retrograde implantation of such a valve, thereby confirming the feasibility of this approach, which follows standard interventional techniques. By implanting the PHV percutaneously, we obtained a successful short-term therapeutic result in an otherwise hopeless situation. The cardiac arrest that occurred during the initial placement of the device in the aortic valve plane may have been related to outflow obstruction with a decreased blood supply to the coronary arteries in a patient with no cardiac reserve. Before valve implantation, the patient's cardiac output was incompatible with life. After device implantation, the patient recovered impressively. When he was in the intensive care unit, receiving inotropic and vasodilator support, his cardiac output increased dramatically, as did the valve area calculated with the Gorlin equation. The PHV functioned satisfactorily at all times, as confirmed by both transthoracic and transesophageal echocardiography. Even when the patient was hypotensive, the valve's opening and closing function was adequate.
The waist seen in the PHV after deployment was due to overexpansion of the borders of the stent (both upper and lower). Because there was no gradient across the valve and because intravascular ultrasonography showed good stent apposition to the aorta, no further dilation was attempted.
The cause of the patient's acute collapse after a period of significant improvement is unclear. We ruled out antegrade migration of the valve with coronary ostial obstruction, because this complication causes sudden death if the device occludes the left main coronary artery, or results in significant electrocardiographic changes if it occludes the right coronary ostium or both arteries. Retrograde migration causes severe mitral insufficiency, which was not seen on echo-Doppler studies. During TEE, the valve was seated in the aortic valve plane, both coronary ostia were visible, and no mitral insufficiency was detected. Across the PHV, 2-m/s jets were accompanied by early peaks, indicating a lack of significant obstruction.
Another possible explanation is sepsis, but the patient's temperature and white blood cell count were normal. Daily blood cultures also yielded negative results. At the time of collapse, the patient's pulmonary pressure increased from 60 to 90 mmHg. This clinical event suggests a pulmonary embolism as the most likely diagnosis. The patient's condition was too unstable for confirmatory testing. Thrombolytic agents were contraindicated because of the recent need for cardiopulmonary resuscitation.
The optimal anticoagulation regimen for use after PHV implantation still needs to be defined. Currently, it consists of heparin, followed by oral anticoagulant, antiplatelet therapy, or the two in combination.
In the treatment of valvular disease, the percutaneous route is a new approach that can be expected to benefit many patients in the future. At present, this procedure is limited to terminally ill patients who have severe aortic valve stenosis that is not amenable to surgical valve replacement. With time, further device modifications should allow transcatheter treatment of valvular disease to become a widely used technique.
The authors thank the personnel of the cardiac catheterization laboratory and intensive care unit at Centro Medico de Caracas, Caracas, Venezuela; and Guillermo Villoria, MD, Francisco Mejia, MD, Maria G. Hernandez, MD, José F. Condado, BSc, and Carolyne Ortiz, BSc, for their invaluable support during the procedure. We also thank Virginia Fairchild for her editorial assistance. We especially thank the patient's family for their trust in this new technology.
Address for reprints: David Paniagua, MD, 6624 Fannin, Suite 2220, Houston, TX 77030
Authors DP, RDF, EI, and CM have a financial interest in Endoluminal Technology Research, Miami, Florida, which makes the heart valve used in this patient.