Early Experience With the Toronto Stentless Porcine Valve Kit Wang, FRCS, Sujay Shad, FRCS, Paul D. Waterworth, FRCS, Asghar Khaghani, FRCS, John R. Pepper, FRCS, and Magdi H. Yacoub, FRCS The Royal Brompton Hospital, London, and Harefield Hospital, Middlesex, England

Stentless porcine valves in the aortic position offer many theoretic advantages, but their clinical performance has not been adequately defined. We evaluated the clinical and echocardiographic results of 103 patients who had aortic valve replacement with the Toronto stentless por- cine valve over a 2-year period. There were 67 men with a mean age of 68 years. The predominant native valve lesion was aortic stenosis (64%), and 4 patients had prosthetic valve dysfunction. Forty-two patients had con- comitant procedures. The 30-day mortality rate was 3.3% (n = 2) for isolated valve replacement and 5.8% (n = 6) for the series. The sole determinant of early death was poor left ventricular function. There were three late deaths due to nonvalve-related complications over a

S tented bioprostheses in the aortic position have the disadvantage of relatively high transvalvular gradi-

ents in small valve sizes and limited durability. The design of stentless valves allows for a larger valve orifice, particularly in small valve sizes [l]. In addition, stentless aortic valves allow the components of the valve to change in size and shape during the different parts of the cardiac cycle and thus to reduce the stress imposed on the valve cusps. This may delay the onset of degeneration [Z, 31. The Toronto stentless porcine valve (St. Jude Medical, Inc, St. Paul, MN) is a stentless aortic valve fixed at low pressure with its aortic sinuses and subannular tissue trimmed to 1.5 to 2.0 mm from the base of the leaflets and its outer wall covered by Dacron cloth. The aim of our study was to evaluate the early clinical results of the Toronto stentless porcine valve and to perform sequen- tial studies of its hemodynamic performance.

Material and Methods

Patient Population Over a 2-year period (July 1992 to July 1994), 103 patients underwent aortic valve replacement with the Toronto stentless porcine valve at the Royal Brompton (n = 57) and Harefield (n = 46) Hospitals. The only exclusion criteria in patient selection were the presence of active endocarditis and patient age younger than 35 years,

Presented at the VI International Symposium for Cardiac Bioprosthews,

Vancouver, BC, Canada, July 29-31, 1994.

Address reprint requests to Prof Yacoub, Department of Cardiothoracic Surgery, Harefield Hospital, Harefield, UB9 hJH, United Kingdom.

0 1995 by The Society of Thoracic Surgeons

median follow-up of 11.87 months. In addition, pros- thetic valve endocarditis developed in 1 patient, necessi- tating a homograft valve replacement at 6 weeks. Dopp- ler echocardiography performed at 3 to 6 months showed low peak and mean transvalvular gradients, with no substantial change at 1 year. None of the patients showed signs of clinically significant aortic regurgitation, al- though echocardiography demonstrated trivial or mild regurgitation in 12 patients at discharge or early follow- up, which was less marked or absent at 1 year. We conclude that the Toronto stentless porcine valve appears to offer promising early results.

(Ann Thornc Surg 1995;6O:S402-5)

although this was increased to 45 years later in our study (homograft or pulmonary autograft were preferable). The mean age was 68 years (range, 35 to 85 years) (Fig l), with a preponderance of men (n = 67). The predominant lesions were stenosis (n = 66), regurgitation (n = 15), mixed pathology (n = 22), and prosthetic valve dysfunc- tion (n = 4). Two patients had previous coronary artery bypass grafting. The preoperative left ventricular func- tion was estimated in all patients by left ventriculography or echocardiography and judged to be good (ejection fraction greater than 0.50), moderate (ejection fraction behveen 0.30 and 0.50), or poor (ejection fraction less than 0.30). The results of left ventricular function assessment were as follows: good in 52 (50%), moderate in 43 (42%), and poor in 8 (8%). New York Heart Association func- tional class was I in 4 (5X), II in 51 (50%,), III in 42 (40%), and IV in 5 (5%).

Operative Technique and Procedures The aortic valve was exposed by a curved aortotomy, starting as a vertical incision on the anterior aspect of the ascending aorta just below the aortic clamp, curving horizontally at a point 2 to 3 cm above the commissure between the right and noncoronary cusps, and then extending downward along the middle of the noncoro- nary sinus to a level 2 to 3 mm above the attachment of the cusp. This incision has many advantages, providing excellent exposure of the valve and allowing tailoring of the aortic sinuses and the sinotubular junction if neces- sary. After excision of the aortic valve and meticulous removal of all calcified tissue, the root is sized at the level of the bottom of the cusps. The bioprosthesis chosen

0003-4975/95/$9.50 0003-4975(95)00265-M

Ann Thorac Surg 1995;6O:S402-5

CARDIAC BIOPROSTHESES WONG ET AL s403 TORONTO STENTLESS PORCINE VALVE

% of population 50

n=37

40 I

30 i I

20 I

10 n=2 n=2

o- .-

35-39 40-49 50-59 60-69 70-79 80-89

should have an external diameter equal to or 1 mm smaller than the measurement made. We believe it is essential not to oversize the valve regardless of the size of the ascending aorta and the sinotubular junction, which if enlarged can easily be tailored at aortic closure. The valve was inserted freehand bv the two-suture line technique, similar to that used by us for the insertion of freehand homografts [4].

The sizes of valves inserted were 20 mm (n = l), 21 mm (n = l), 23 mm (n = 15), 25 mm (n = 30), 27 mm (n = 28), and 29 mm (n = 28). Forty-two patients (41”i,) had concomitant procedures, including CABG (n = 40), mitral valve repair and CABG (n = I), and mitral valve repair (n = 1). The mean cross-clamp and bypass times were 82 minutes (range, 38 to 140 minutes) and 103 minutes (range, 60 to 185 minutes), respectively, for aortic valve replacement alone, and 102 minutes (range, 55 to 162 minutes) and 142 minutes (range, 82 to 290 minutes) when concomitant procedures were performed. Contin- uous coronary perfusion was used in 17 patients.

Follow-up Early mortality was defined as any death within 30 days or during initial hospitalization. All patients were seen at 6 weeks, 3 to 6 months, and 11 to 14 months after the operation. Follow-up assessment of all patients included documentation of functional class, the presence of an early diastolic murmur, and any complications, particu- larly thromboembolic episodes and endocarditis. Fol- low-up was complete in 97% of the patients; 82% (n = 73) completed their 3- to 6-month visit and 52% (n = 46) their ll- to 14-month visit. The median follow-up was 11.87 months (range, 1.64 to 14.75 months).

Hemodynamic Follo7~~-z4y Transthoracic continuous wave and color flow Doppler echocardiography was performed at discharge, ie, when the patient was ambulant and at 3 to 6 months and 11 to 14 months. Mean and peak gradients were derived from the velocity across the valve (modified Bernoulli’s equa-

tion), and effective valve orifice was calculated using the continuity equation 14). Aortic regurgitation was graded as mild, moderate, or severe in accordance with the indices defined by Perry and associates 161. Regurgitation not severe enough to be measured by these criteria was considered trivial.

Statistical Analysis Fisher’s exact test was used to compare frequencies of the different variables, with p less than 0.05 considered sig- nificant. Logistic regression was used to analyze deter- minants of early mortality.

Results

Early Mortality and Morbidity The early mortality rate for isolated aortic valve replace- ment was 3.3% (2 of 61). One patient aged 67 years died of a pulmonary embolus, and another aged 81 years died suddenly 1 day after discharge from the hospital. The early mortality rate for the series was 5.8% (n = 6). The other four deaths were due to low cardiac output in 3 patients with severe coronary artery disease, of whom 2 had unstable angina (aged 61, 68, and 85 years), and a perforated duodenal ulcer in a woman aged 73 years.

Logistic regression was used to analyze factors affect- ing early death. Possible covariates included age, sex, etiology, functional class, left ventricular function, reop- erative surgery, concomitant procedures, and cross- clamp times. Poor left ventricular function was the only incremental risk factor for early mortality. Age greater than 65 years and functional class were almost significant and would be expected to be significant in a larger study. Five of the six deaths were in patients older than 65 years.

Major complications occurred in 3 patients. One pa- tient required reoperation for a pericardial tamponade, and another required exploration for bleeding. The last patient had a perioperative cerebrovascular accident and was therefore not classified as having a valve-related complication.

Late Mortality There were three non-valve-related deaths, ie, end-stage heart failure, pancreatic cancer, and pulmonary embolus from deep vein thrombosis. Postmortem examination in all patients showed normal valve prostheses.

Endocarditis and Value-Related Thomboembolic Complications Sta@zylococcus aureus endocarditis developed in 1 patient and was successfully treated by emergency homograft valve replacement 6 weeks after her operation. At oper- ation, there was extensive destruction of the aortic root with multiple abscesses. There were no episodes of valve-related thromboembolism in any of the patients. We did not prescribe anticoagulant agents for any of our patients in the early postoperative period, and only patients who had CABG received aspirin.

s404 CARDIAC BIOPROSTHESES WOLG ET AL TORONTO STENTLESS PORCINE VALVE

Ann Thorac Surg 1995;605402-5

Table 1. Sequential Echocardiograplzic Follow-up”

Valve Size (mm) Follow-up

Number of Patients

Peak Mean Gradient Gradient (mm Hg) (mm Hg)

Effective Orifice Area

km’)

20 3-6 mo

ly 21 3-6 mo

ly 23 3-6 mo

lY 25 3-6 mo

ly 27 3-6 mo

ly 29 3-6 mo

lY

9 4

20 12 21 14 21 15

a Values are expressed 2s mean or mean i standard deviation.

Hemodynamic Follow-up Table 1 shows the average mean and peak transvalvular gradients and effective orifice area in relation to the valve sizes. These gradients were low even in small valve sizes, with good effective valve areas. The gradients were lower in the majority of cases at 1 year of follow-up. Echocar- diographic studies showed central aortic regurgitation at discharge and at 3 to 6 months in 11.6% (n = 12) of the patients (trivial in 11 and mild in 1). However, only 1 of these 12 patients was found to have trivial regurgitation at 1 year. None of the patients had an audible early diastolic murmur at any stage.

Comment

Homograft aortic valve replacement offers distinct ad- vantages, including excellent hemodynamics, few valve- related complications, and longer durability than stented bioprosthetic valves [7]. Their advantages in the setting of endocarditis [8] and aortic valve reoperations [9] have also been demonstrated. Their main disadvantage apart from durability is limited availability, and stentless por- cine valves may provide a readily available alternative.

Although stentless porcine xenografts share many of the advantages of homograft valves, they have some theoretic limitations in design, which include the pres- ence of a Dacron sleeve, which adds bulk and increases the risk of infection. In addition, most unstented xe- nografts, including the Toronto stentless porcine valve, have a circular proximal border (in contrast to the scal- loped edges of a homograft), which does not fit the natural shape of the aortic annulus and could limit expansion of the root. Furthermore, apart from the Free- style Bioprosthetic valve (Medtronic Corp, Minneapolis, MN), freestanding root replacement is not possible.

An important consideration in the use of stentless xenografts is that all glutaraldehyde-treated xenograft tissue undergoes faster degeneration compared with homografts [lo, 111. The main determinant of structural

10.9 4.6 1.3 7.2 3.0 1.8

23 9.7 0.5 12.76 5.4 0.7

13.1 z 7.9 5.6 t- 3.3 2 + 2.1 9.4 i 5.3 4.0 + 2.2 1.6 2 0.6

13.4 k 6.7 6.7 -t 2.8 1.2 -t 0.4 10.2 ? 5.6 4.3 2 2.5 1.7 + 1.1

9.7 i 4.1 4.1 2 1.8 1.6 i 0.6 10.4 7 5.4 4.4 ? 2.3 1.5 k 0.5

8.6 I+ 5.7 3.6 i 2.4 2.3 ? 1.2 7.8 + 4.8 3.5 f 1.9 2.2 -+ 1.4

valve deterioration in stented porcine valves is the age of the patient (higher in adolescents and children) [ll]. The exact age after which accelerated degeneration starts to occur is not known, and it is not known whether stentless xenografts will be able to address this problem. We have therefore restricted the selection of patients to those older than 45 years, except for 2 patients who were included during the early phase of our study. This is reflected by the higher mean age of our patients.

Our study has also shown that unstented xenografts can be inserted with cross-clamp times similar to those for freehand homograft insertion. The operative risk is similar to that reported for other valve substitutes [12, 131, though it is higher than the operative mortality reported from our center recently for isolated homovital homograft aortic valve replacement (0.6%) [lo]. This difference may be explained by the older population in the present series (mean age 68 years, versus 45 years in the homovital series). We have also noted a low incidence of valve-related complications, with only one case of prosthetic valve endocarditis. There were no cases of valve-related thromboembolism even though we did not prescribe anticoagulant agents for these patients in the early and late postoperative period.

One of the main determinants of both early and long-term results of unstented valve implantation is the ability to achieve full competence, without obstruction from crowding of the valve, in a reliable and repeatable manner. The extensive experience [lo, 14, 151 with the use of unstented homografts has established the essential techniques to achieve reliability and prevent turbulence due to obstruction or regurgitation. The main points include matching the shape and size of the unstented valve to the aortic root and tailoring the ascending aorta and sinotubular junction if necessary. The positioning of the commissures is also of great importance; they should be equidistant and under appropriate tension, usually about 1 cm above the original commissure if the native valve was tricuspid or modified in a bicuspid valve. We

Ann Thorac Surg 7995:60:5402-5

CARDIAC BIOPROSTHESES WONG ET AL s405 TORONTO STENTLESS PORCINE VALVE

have used simple interrupted 410 braided sutures placed in the host annulus 1.5 to 2.0 mm apart and a continuous 4/O monofilament for the upper suture line. None of our patients demonstrated pronounced aortic regurgitation clinically or by color flow Doppler echocardiographic analysis. This may explain why the trivial to mild regur- gitation observed in 11.6% of our patients in the early echocardiographic studies tended to diminish with time.

Another interesting finding is that the sequential trans- valvular gradients in our patients appeared to decrease in most cases at follow-up. These changes are at present not statistically significant, and it is perhaps still too early to comment on them.

In conclusion, our early results suggest that the To- ronto stentless porcine valve provides good valve hemo- dynamics and has a low incidence of valve-related com- plications. However, further evaluation is required, particularly with reference to its long-term performance and durability as compared with that of the homograft.

We thank Dr Derek Robinson, Department of Mathematics and Statistics, University of Sussex, Brighton, and Dr Mario Petrou for their help in statistical analysis.

References

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3. Christie GW, Barratt-Boycs BG. On stress reduction in bioprosthetic heart valve leaflets by the use of a flexible stent. J Cardiac Surg 1991;6:476-81.

4. Ross DN, Yacoub MH. Homograft replacement of the aortic valve. Prog Cardiovasc Dis 1969;11:275-93.

5. Skjaerpe T, Hegranes L, Hatle L. Non-invasive estimation of valve area in patients with aortic stenosis by Doppler ultra- sound and two dimensional echocardiography. Circulation 7985;72:810-8.

6. Perry GJ, Helmcke F, Nanda MC, Byard C, Soto 8. Evalua- tion of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol 1987;9:952-9.

7. Ross DN, Yacoub MH. Homograft replacement of the aortic valve. A critical review. Prog Cardiovasc Dis 1969;9:275-9.

8. Petrou M, Wong K, Albertucci M, Brecker SJ, Yacoub MH. An evaluation of unstented aortic homografts for the treat- ment of prosthetic aortic valve endocarditis. Circulation (in press).

9. Albertucci M, Wong K, Petrou M, et al. The use of unstented homograft valves for aortic valve reoperations. Review of a 23 year experience. J Thorac Cardiovasc Surg 1994;107: 152-61.

10. Yacoub MH, Rasmi N, Sundt TM, et al. Fourteen year experience with homovital homografts for aortic valve re- placement. J Thorac Cardiovasc Surg (in press).

11. Jamieson WRE, Rosado LJ, Munro AI, et al. Carpentier- Edwards standard porcine bioprosthesis: primary tissue failure (structural valve deterioration) by age groups. Ann Thorac Surg 1988;46:155-62.

12. Jones EL, Weintraub WS, Craver JM, et al. Ten-year experi- ence with the porcine bioprosthetic valve: interrelationship of valve survival and patient survival in 1,050 valve replace- ments. Ann Thorac Surg 1990;49:370-84.

13. Akins CW, Carroll DL, Buckley MJ, Daggett WM, Hilgen- berg AD, Austen WC. Late results with Carpentier-Edwards porcine bioprosthesis. Circulation 1990;82(Suppl 4):65-74.

14. Barratt-Boyes BG, Roche AHO, Subramanyan R, Pemberton JR, Whitlock RML. Long term follow-up of patients with the antibiotic sterilized aortic homograft valve inserted free hand in the aortic position. Circulation 1987;75:768-77.

15. McGiffin DC, O’Brien MF, Stafford EG, Gardner MA, Pohner PG. Long-term results of viable cryopreserved aortic al- lograft valves: continuing evidence for superior valve dura- bility. J Cardiac Surg 1988;3(Supp1):28Y -96.