Ann Thorac Surg 2012;93:1134-1140. doi:10.1016/j.athoracsur.2012.01.010
© 2012 The Society of Thoracic Surgeons
Original Articles: Adult Cardiac
Leaflet Replacement for Aortic Stenosis Using the 3f Stentless Aortic Bioprosthesis: Midterm Results
Petar Risteski, MD*,
Christine Adami,
Nestoras Papadopoulos, MD,
Abdel Sami Sirat, MD,
Anton Moritz, MD, PhD,
Mirko Doss, MD, PhD
Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Frankfurt, Germany
Accepted for publication January 3, 2012.
* Address correspondence to Dr Risteski, Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany (Email: docpsr{at}yahoo.com).
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Abstract
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Background: The 3f aortic bioprosthesis is a stentless valve resembling the native aortic valve. It has been postulated that improved hemodynamic performance with this prosthesis may translate into superior durability. We hereby report the midterm results using this valve substitute.
Methods: Fifty patients with severe aortic stenosis received the 3f aortic bioprosthesis between 2002 and 2004 in our unit. Clinical outcomes, effective orifice area, mean gradients, and ejection fraction were evaluated at discharge, at 6 and 12 months, and yearly thereafter.
Results: Mean follow-up was 52 ± 10 months and was complete in 96% of surviving patients. Hemodynamic performance of the 3f valve was satisfactory for substitutes in the range of 25 mm and 27 mm; smaller valve substitutes showed unfavorable hemodynamic performance with mean gradients of 18 ± 7 mm Hg for 21-mm prosthesis, and 14 ± 5 mm Hg for 23-mm prosthesis. Consequently, the regression of left ventricular hypertrophy was incomplete. Late mortality included 10 patients (valve-related in 1, cardiac-related in 3) for a survival of 77% ± 3% at 4 years. Four patients required reoperation owing to endocarditis in 2 and paravalvular leak in other 2. Freedom from reoperation was 93% at 4 years. Six patients experienced 9 neurologic events, accounting for 82% freedom from neurologic events.
Conclusions: Its unique design makes the 3f aortic bioprosthesis less complex to implant than conventional stentless valves, as only a single suture line is necessary. The hemodynamic profile and clinical performance of the prosthesis are inconsistent with the established stentless valves, especially with regard to higher incidence of neurologic complications seen during the follow-up.
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Introduction
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Replacement of the aortic valve with prosthesis is the recommended treatment for symptomatic patients with severe aortic valvular stenosis [1]. A biologic prosthesis is not currently seen as a better substitute than a mechanical valve for younger patients, mainly because of the limited durability of the former. Premature failure of bioprosthesis has long been attributed to inappropriate tissue type or characteristics [2] and an inadequate fixation process that fails to abolish its antigenicity [3]. At least as important, a faulty design process of a bioprosthesis, leading to a turbulent flow across it and thereby imposing significant physiologic stress on the leaflets, may be a strong factor leading to its rapid degeneration, as seen in congenital bicuspid valves [4].
Recently, a new biologic prosthesis was introduced, the 3f aortic bioprosthesis (model 1000, Medtronic Minneapolis, MN), that unlike the other conventional stentless valve substitutes, was designed not only to look like but more importantly to function like a native valve, as reported by the manufacturer [5]. The model 1000 bioprosthesis incorporates only three equal sections of equine pericardial tissue assembled in a loose and completely collapsible tubular structure, with a thin polyester suture ring along its inflow aspect. Thereby, it preserves the native aortic sinuses of the patient. Based on a simple idea that form follows function, the sides of this tube should collapse when subjected to external pressure, allowing the prosthesis to function like a native aortic valve. Thereby, this new design should allow for less, if any, turbulent flow across the valve and a more physiologic and proper distribution of stress on its leaflets. The preliminary in vitro studies performed by others [5] have shown that the opening and closing dynamics of the 3f aortic bioprosthesis are similar to those of the native aortic valve. This physiologic design and function may have the potential for translating into improved durability.
The early results from a large prospective multicenter US Food and Drug Administration trial, reported by us [6] as well as other groups [7,8], suggested that the early clinical and hemodynamic performances of the 3f aortic bioprosthesis are similar to those of the regular stentless aortic valves. Table 1
summarizes the early hemodynamic performance of the 3f bioprosthesis [6–8] as well as that of other well-established stentless valve substitutes reported in randomized trials [9–11].
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Table 1 Overview of the Early Hemodynamic Performance of the 3f Aortic Bioprosthesis and Other Stentless Valves in Common Use
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The US Food and Drug Administration approved this bioprosthesis for human implantation in the United States in October 2008, but midterm reports of the use of the 3f aortic bioprosthesis are scarce. Herein we report on the midterm outcomes after aortic valve replacement using the 3f aortic bioprosthesis.
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Patients and Methods
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Between January 2002 and September 2004, the 3f aortic bioprosthesis was implanted in 50 patients with severe aortic valve stenosis, as part of the US Food and Drug Administration approval study. The mean age of the patients was 75 ± 6 years (range, 60 to 86 years). Before inclusion in this study, all patients provided written informed consent. The consent form and the study protocol were approved by the ethics committee of our institution (approval number E 96/01).
All adult patients with severe aortic valve disease requiring aortic valve replacement with or without concomitant procedures, with the exception of other valvular replacements, were included in the study. Exclusion criteria were abnormal origin of the coronary arteries, calcified aortic root, and an aortic annulus-sinotubular junction mismatch owing to dilatation of the ascending aorta. Eight patients were intraoperatively excluded from the study for one or more of these criteria. Other exclusion criteria were defined as active aortic valve endocarditis or presence of bicuspid valve.
Implantation Technique
The implantation technique has been previously described in greater detail [6]. Briefly, we approached the aortic valve on cardiopulmonary bypass through a transverse aortotomy. Using such an approach as opposed to the oblique hockey stick aortotomy, an attempt was made to preserve and not disturb the aortic root geometry, thus allowing for exact orientation of the prosthesis leaflets. After removal of the calcified aortic leaflets, the aortic annulus was sized. Only sizers especially designed for the 3f aortic bioprosthesis were used. Early in the study, we chose to use a prosthesis of the larger size in case of an annulus diameter between two valve sizes. We altered this policy later in the study, and in case of an annulus diameter between two valve sizes, we chose to implant a prosthesis of the smaller size to prevent eventual obstruction caused by stuffing a larger valve into a smaller annulus. The valve was then implanted using only a single running suture line with 4-0 polypropylene on an RD1 needle (Johnson & Johnson Medical GmbH, Norderstedt, Germany) at the inflow portion of the prosthesis. In addition, the commissural tabs are attached to the aorta by three single 4-0 Cardionyl sutures (Cardionyl; Péters Laboratories, Bobigny-Cedex, France). The aortotomy was then closed in a conventional manner. The function of the implanted bioprosthesis was tested using transesophageal echocardiography as recommended [12].
Clinical Evaluation and Follow-Up
Follow-up examinations were scheduled for discharge from hospital, at 6 and 12 months, and at yearly intervals after the operation. All patients received evaluation of their clinical status, including the New York Heart Association classification, blood analysis, including signs of hemolysis and coagulation profile, and occurrence of early and late complications. Preoperative and all postoperative echocardiography studies were routinely performed by two experienced examiners using a single ultrasound machine (Vingmed System 5; GE Medical Systems, Milwaukee, WI). All data collected were entered in a central database. In addition to the standard imaging views, preoperative echocardiographic assessments also included the measurement of the annulus diameter and the size of the native aorta at the level of the sinotubular junction. A size mismatch between the aortic annulus and the sinotubular junction such as seen in patients with dilatation of the sinotubular junction rendered the patient unsuitable for implantation of this stentless valve. This was considered an exclusion criterion in our study.
Left ventricular mass index (LVMI) was calculated using the formula postulated by Devereux and Reichek [13], as follows:
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where EDD is left ventricular end-diastolic diameter (cm), PWTd is left ventricular posterolateral diastolic wall thickness (cm), IVSTd is interventricular septum diastolic thickness (cm), and BSA is body surface area of the patient [13].
We actively followed 47 patients. The mean follow-up accounted 52 months (range, 42 to 74 months) and was completed in 96% of the surviving patients. Only 2 patients were lost to follow-up. For purposes of this report we analyzed a total of 174.5 patient-years.
Anticoagulation Regimen
The postoperative anticoagulation regimen included subcutaneous low-molecular-weight heparin, adjusted for body weight, for the first few days and parallel oral anticoagulation with vitamin K antagonists. As soon as the international normalized ratio levels reached the therapeutic range of 2.5 to 3, heparin was stopped. Oral anticoagulation was continued for 3 months and principally directed and monitored by the patient's primary physician. After 3 months, oral anticoagulation was terminated in the absence of other indications for permanent anticoagulation.
Statistical Analysis
Statistical analysis of the data was performed by using the Stat-View software package, version 5.0 (SAS Institute Inc, Cary, NC). Categorical variables are expressed as proportions (%), and continuous variables are expressed as mean ± standard deviation. The Student's t test was applied to analyze normally distributed continuous data. Survival and freedom from event probabilities were estimated with the standard nonparametric Kaplan-Meier method [14].
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Results
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Early Morbidity and Mortality
Table 2
summarizes the preoperative patients' demographics as well as perioperative data. We did not observe a structural dysfunction, valve thrombosis, hemolysis, or a bleeding event during the early postoperative course. A single nonstructural valve dysfunction (2%) was noted, as a significant noninfectious paravalvular leak developed in a patient with heavy annulus calcification 7 months after the surgery, leading to a reoperation.
A single patient (2%) exhibited early Streptococcus faecalis–caused endocarditis on the operated valve at 4 months after the operation, a condition that required a repeat operation on the implanted prosthesis.
Mortality within 30 days of the operation occurred in 1 patient (2%). The reason for death was cardiac, namely the patient experienced acute myocardial infarction complicated with cardiogenic shock on the third postoperative day.
Midterm Morbidity and Mortality
The mean New York Heart Association functional class improved during the follow-up. After 1 and 4 years of follow-up, the mean New York Heart Association class fell to 1.35 ± 0.4 and 1.31 ± 0.4, respectively, compared with 2.9 ± 0.8 preoperatively (p < 0.001). At last follow-up, 82% of patients were in New York Heart Association class I.
Nine neurologic events occurred in 6 patients (12.8%) during the follow-up. Four of these patients were octogenarians and 3 of them had chronic atrial fibrillation. The fourth patient experienced severe and recurrent gastrointestinal bleedings from diverticulosis, only a few months after the operation, so the anticoagulation therapy had to be stopped. He was hospitalized and later acquired a ventilation-associated pneumonia that ultimately led to his death. Freedom from neurologic events was 82% at 4 years (Fig 1).
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Fig 1. Freedom from neurologic events was 82% at 4 years. Numbers above the ordinate axis indicate the number of patients at risk.
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Late endocarditis on the operated valve occurred in another patient (2%) in this group at 2 years postoperatively. This was caused by gram-negative bacilli and required a repeat operation.
Reoperations were required in 4 patients, 2 because of endocarditis as described earlier and 2 because of nonstructural dysfunction (paravalvular leaks). Structural valve dysfunction was not observed during the follow-up. Freedom from reoperation was 93% at 4 years (Fig 2).
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Fig 2. Freedom form reoperation was 93% ± 1% at 4 years. Numbers above the ordinate axis indicate the number of patients at risk.
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All-cause mortality included 10 patients (20%). A single patient (2%) died of valve-related causes leading to a severe global cardiac decompensation. Three patients (6%) died of cardiac-related causes including acute myocardial infarction, malignant ventricular arrhythmia, and congestive heart failure. The other 6 patients (12%) died of noncardiac-related causes, such as trauma, cancer, pneumonia, sepsis, or ruptured thoracoabdominal aneurysm. Survival at 4 years was 77% (Fig 3).
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Fig 3. Actuarial survival was 77% ± 3% at 4 years. Numbers above the ordinate axis indicate the number of patients at risk.
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Hemodynamic Performance of the 3f Aortic Bioprosthesis
Gradients at Different Sizes With Time
Figure 4
shows how the mean gradients across the 3f aortic bioprosthesis behaved during the follow-up. On average, the mean gradients showed a respectable decrease during the first year after implantation, only to remain relatively unchanged at 4 years of follow-up, averaging 18 ± 7 mm Hg for the 21-mm prosthesis, 14 ± 5 mm Hg for the 23-mm prosthesis, 8.7 mm Hg for the 25-mm prosthesis, and 4 mm Hg for the 27-mm prosthesis. Larger prostheses showed a tendency to be associated with smaller gradients. The decrease in mean gradients occurred early after the operation. In the case of the larger valve prostheses, some further decrease was also seen later.
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Fig 4. Transvalvular mean gradients at discharge (dark gray bars), at 1 year (light gray bars), and at 4 years (white bars).
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Only 1 patient had a mild residual aortic regurgitation at the last follow-up.
Regression of Left Ventricular Hypertrophy
Figure 5
shows the course of the LVMI through the follow-up, as measured by echocardiography. The LVMI did display a continuous rate of decrease during the follow-up, and the initial tendency was not lost during follow-up. Conclusive with the last follow-up, the LVMI failed to reach the normal or near-normal range. The LVMI, an expression of the left ventricular hypertrophy, showed 18% regression from discharge values at a mean follow-up of 4 years, rendering the regression relatively incomplete.
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Fig 5. The course of the left ventricular mass index (LVMI) through the follow-up, as measured by echocardiography. The left ventricular mass index, an expression of the left ventricular hypertrophy, showed 18% regression at a mean follow-up of 4 years.
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Patients With Mean Postoperative Gradients Greater Than 20 mm Hg
Nine patients showed discharge mean gradients of 20 mm Hg and greater. All of them had a small prosthesis implanted, and all except 2 were operated on early in the study, at that point when we were not aware of the danger associated with forcing a larger prosthesis into a smaller annulus. As soon as we recognized this problem and changed our approach to implant a smaller prosthesis rather than a larger one, we experienced this problem on rare occasions (2 from the last 20 patients).
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Comment
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Since the beginning of heart surgery, we have witnessed persistent efforts to manufacture a tissue valve with greater long-term durability. The 3f aortic bioprosthesis was developed specifically to address the durability problem encountered with previously designed artificial tissue valves.
The implantation of the 3f aortic bioprosthesis is simplified as with the other stentless valves. Unique to the implantation technique with the 3f aortic bioprosthesis is the lack of an outflow suture line and no need for reimplantation of the coronary ostia, together accounting for shorter implantation times. In our hands, the mean aortic cross-clamp and cardiopulmonary bypass times were 69 ± 19 minutes and 101 ± 59 minutes, respectively, comparable to the times achieved by the Oxford and Berne groups [7, 15]. In a previous report from our group, a conventional stented aortic bioprosthesis (Carpentier Edwards Perimount) in our hands took comparable cross-clamp time to be implanted as opposed to another stentless aortic bioprosthesis (Edwards Prima Plus), which required some 30 minutes longer (79 versus 108 minutes for stented versus stentless, respectively) [16].
It was shown previously in in vitro testing that the 3f aortic bioprosthesis, owing to the unique design, offered superior hemodynamic performance compared with an excellent commercially available tissue aortic valve [5]. Cox and coworkers [5] found the 3f aortic bioprosthesis to have lower transvalvular gradients and greater effective orifice areas for all valve sizes and at diverse cardiac outputs than the St. Jude Medical Toronto SPV aortic bioprosthesis (St. Jude Medical, Inc, St. Paul, MN). These results were reproducible in vivo in an animal model as well [14]. Mueller and von Seggesser [17] detected low transvalvular gradients for small aortic roots, ranging from 3.4 to 7.4 mm Hg (depending on cardiac output) for the 19-mm prosthesis, outperforming a standard stentless bioprosthesis. This favorable hemodynamic performance was not reproducible in our hands in humans. As shown above, the hemodynamic performance of this valve was satisfactory for substitutes in the range of 25 mm and 27 mm; smaller valve substitutes showed unfavorable hemodynamic profile with mean gradients of 18 ± 7 mm Hg for the 21-mm prosthesis, and 14 ± 5 mm Hg for the 23-mm prosthesis.
Next to avoiding oversizing of the valve, crucial to the adequacy of the systolic and diastolic function is the alignment of the commissural tabs. An excessive or large distal traction on the tabs makes the prosthesis leaflets restrictive, preventing them from fully opening during systole. A rather modest and insufficient distal traction on the tabs at the time of implantation will provide for a large coaptation height and surface, preventing a rapid and unobstructed opening of the valve during systole. Both the former and the latter mechanisms may also account for the elevated gradients in some of the 9 patients described with gradients of 20 mm Hg or greater as well as for the incompleteness of the left ventricular mass regression. The surgeon must avoid such a compromise. This issue was addressed by Duran and coworkers [18] in their work on aortic valve replacement with a freehand autologous pericardial strip. Contrary to the model 1000, the second generation of the 3f aortic bioprosthesis valve—the Enable valve—provides optimal alignment of the commissures by mounting the same valve in an expandable nitinol stent. The initial hemodynamic performance of the Enable valve seems to be superior to that of the model 1000 [19]. Although both 3f aortic bioprosthesis valves are still available on the market, we stopped implanting the model 1000 but continue to use the Enable valve in our department.
As the 3f aortic bioprosthesis valve substitute has a large coaptation height and therefore surface, residual regurgitation was scarce. Only 1 patient with mild (grade 2/4) residual regurgitation was observed at the last follow-up. Our experience is in consensus with the observations from the groups from Oxford, Berne, and Berlin [7, 8, 12]. Noninfective paravalvular leaks requiring reoperations were noted in 2 patients (4%). As other groups [12] implanting the same bioprosthesis using interrupted simple sutures instead of continuous technique noted no paravalvular leaks in their experience, it may be advisable to use simple suture in cases considered prone to development of paravalvular leaks, such as aortic annulus with heavily calcifications.
Six patients experienced 9 strokes during the course of the study. Freedom from neurologic events was 82% at 4 years, demonstrating inferiority to other well-established modern bioprostheses. The US Food and Drug Administration objective performance criteria cites such a severe complication after a biologic aortic valve replacement as being in the range of 2.5% per prosthesis per year [20, 21].
Although this report does not answer all questions regarding the durability of this valve, it does confirm the absence of any structural valve dysfunction at midterm follow-up. Whether this valve prosthesis, with its unique design that preserves the normal aortic root anatomy and function, represents a truly long-term bioprosthesis remains to be proven. The hemodynamic profile and clinical performance of the prosthesis is inconsistent with established stentless valves, especially with regard to the higher incidence of neurologic complications seen during follow-up.
This retrospective study reflects the disadvantages of selection bias inherent with such a design. We selected all consecutive patients in the enclosure period trying to minimize this bias. The study includes our learning curve, which may have negatively affected the outcomes. The study did not investigate the effect of aortic valve replacement with this particular prosthesis on coronary reserve and its effect on survival.
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Acknowledgments
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The authors disclose that in addition to departmental funding, this study was sponsored by the manufacturer of the valve substitute. The authors of this study had full and independent control of the design of the study, methods used, outcome parameters, analysis of data, and production of the written report. None of the investigators or patients received compensation to participate in this study.
The authors would like to express their gratitude to the manufacturer of the valve substitute, Medtronic, for funding the study.
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References
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Abstract
Introduction
