Abraham Charles Yankah

Accelerated degeneration of allografts in the first two years of life

Between January 1988 and May 1994, 53 of 159 patients have received cryopreserved aortic and pulmonary allografts for reconstruction of the pulmonary circuit in the first 2 years of life with body weight ranging from 2.2 to 18 kg (mean, 8.2 +/- 3.4 kg). The implanted allografts ranged in internal diameter from 9 to 23 mm (mean, 16.3 +/- 3.5 mm). Of the 38 survivors who regularly had postoperative echocardiographic examinations 15 (39.5%) underwent cardiac catheterization 1 to 31 months after operation. Allograft dysfunction (gradient > or = 50 mm Hg with or without pulmonary insufficiency) was confirmed in 9 patients leading to reoperation in 5 and valvulo-angioplasty in 4. At 48 months actuarial survival was 64%. In the aortic and pulmonary allografts freedom from wall calcification at 20 months was 19% and 100%, respectively. Freedom from valve dysfunction in patients with aortic and pulmonary allografts was 53% and 88%, respectively; it was 49% in allografts with an internal diameter of 17 mm or smaller. Freedom from reoperation in all patients was 78%. In conclusion, young age, antigenicity (ABO compatibility), and type of allograft seemed to be independent risk factors for early allograft conduit degeneration and late valve dysfunction. Pulmonary allografts seemed to be more resistant to early wall calcification and valve dysfunction than aortic allografts.

Tricuspid valve dysfunction and surgery after orthotopic cardiac transplantation

OBJECTIVE The study examines the prevalence of tricuspid regurgitation and biopsy-induced flail tricuspid leaflets after orthotopic heart transplantation and evaluates the results of the tricuspid valve surgery. METHODS By a computerized search of the databases 647 of 889 patients who survived heart transplantation for more than 30 days were identified for this study. The primary tool for rejection monitoring in our institution is the daily observation of intramyocardial ECG (IMEG) based on day-by-day changes of the maximal QRS complex amplitude. Endomyocardial biopsy with 45-cm-long sheath bioptome was performed only in doubtful IMEG and echocardiographic data and at times of annual routine heart catheterization. Tricuspid regurgitation was diagnosed clinically and by echocardiography as mild, moderate and severe. Eleven patients received prosthetic valve replacements (four bioprostheses and seven mechanical valves) and six patients underwent valve reconstruction. The choice of xenograft valve was dictated by the condition of renal function. Patient survival and incidence of tricuspid regurgitation and freedom from operation for severe tricuspid regurgitation were analyzed with Kaplan-Meier method. RESULTS The prevalence of tricuspid regurgitation was 20.1%. Mild and moderate tricuspid regurgitation was seen in 14.5 and 3.1% of the patients, respectively, who were responsive to medical therapy and remained clinically stable in NYHA class I-II. Severe tricuspid regurgitation was seen in 16 (2.5%) patients who presented signs of an acute right heart dysfunction. Tricuspid valve pathology at operation revealed biopsy-induced rupture of the Chordae tendineae at various valve segments mostly the anterior and posterior leaflets. There was one hospital death (<30 day) and five late deaths due to infection, arrhythmia and trauma and no procedural-related or directly cardiac related death. Ten patients (62.5%) are alive at a mean follow-up time of 29.9 months (range 4-81 months) and nine survivors are in NYHA class I-II and one in class III. CONCLUSIONS Severe tricuspid regurgitation in transplanted hearts is associated mainly with biopsy-induced injury or endocarditis. Other regimes of rejection monitoring may help to eliminate this complication. Apart from our preference of valve repair, the choice of valve substitute may be influenced by the presence or the prospect of chronic renal failure. Heart transplant patients can safely undergo valve surgery with acceptable mortality, low morbidity and excellent intermediate-term clinical results. Mild to moderate functional tricuspid regurgitation is responsive to medical therapy and non-progressive and occur in 17.6% of orthotopic transplanted hearts without having a detrimental effect on the right ventricular performance.

Comparison of porcine xenografts and homografts for pulmonary valve replacement in children

BACKGROUND Due to the limited availability of homografts, different alternatives are used for replacement of the pulmonary valve. This study investigates the value of porcine stentless pulmonary xenografts in pediatric cardiac patients. METHODS Twenty-three pediatric xenograft (size 10 to 21 mm) recipients were compared with 23 homograft (size 9 to 21 mm) recipients. RESULTS Hospital mortality was 2 of 23 patients in the xenograft group and 3 of 23 in the homograft group (NS). Six out of 20 xenografts and 1 of 19 homografts were stenotic after 1 year (p = 0.011). Xenograft stenoses were mainly located at the distal anastomosis, while the leaflets were preserved. Homografts showed valvular stenoses and wall calcification. The 1 year freedom from reoperation was 77% in the xenograft and 93% in homograft recipients (NS), and from transcatheter intervention 84% and 100% (p = 0.004), respectively. Transcatheter intervention in 7 xenograft patients and 1 homograft recipient improved stenosis gradients from 65 to 40 mm Hg (mean) in 6 out of 8 patients. Explanted xenografts showed a loss of elastic membranes and proliferating connective tissue scars coated with activated endothelium. CONCLUSIONS Xenografts demonstrated a higher incidence of supravalvular obstructions, which were possibly due to unfavorable hemodynamics at the distal anastomosis. Histological findings additionally indicated a pronounced immunological response. Interventional angioplasty lowered the rate of reoperation. Thus, the use of xenografts in children can be accepted as a second choice when a homograft is unavailable.

Short-course cyclosporin a therapy for definite allograft valve survival immunosuppression in allograft valve operations

This study was designed to determine the effect of short-course cyclosporin A therapy (10 mg/kg daily for 14 days) on allograft valve survival across the histocompatibility barriers in the following rat models; (1) syngeneic Lewis to Lewis (herein referred to as autografts), (2) weakly allogeneic AS to Lewis (RT1 compatible, non-RT1-incompatible), and (3) strongly allogeneic CAP to Lewis (RT1 and non-RT1-incompatible). Cyclosporin A-treated and untreated recipient animals (Lewis) received allovital and antibiotic-treated viable allografts implanted into the infrarenal aorta. Second-set skin grafting was performed 3 weeks after heterotopic valve implantation to test for immunogenicity and presensitization. The animals (Lewis) were sacrificed serially on days 20, 50, 100, and 150 for immunofluorescence study using mouse monoclonal antibodies (OX6) directed at class II endothelial surface antigens. The allografts in weakly allogenic strains showed no humoral response under a short course of cyclosporin A. The cyclosporin A-untreated allovital grafts and the viable (antibiotic-treated) valves demonstrated fibrocalcification on the 100th and 150th postoperative days, respectively. In conclusion, it seems that a short course of nontoxic immunosuppression could arrest allograft rejection and thus prevent early degeneration of allografts. Furthermore, antibiotic-treated viable allografts seemed to be more durable than allovital grafts.

Risk factors for early degeneration of allografts in pulmonary circulation.

OBJECTIVE The aim of this study was to define risk factors for early degeneration of allografts in pulmonary circulation and to recommend some guidelines to minimize them. METHODS Between January 1988 and March 1995, 202 patients with various types of congenital heart disease received cryopreserved allograft conduits for reconstruction of their right ventricular outflow tract. We report on 63 patients receiving allografts ranging from 9-24 mm size within the first 2 years of life. RESULTS Survivors have been followed for 4-67 months. Survival at 5 years, including hospital mortality, was 66%. Two patients died at reoperation. Of the patients 19.6% (9/46) had early structural deterioration (SD) of their vascular allografts at a mean of 15.2 months after implantation. Seven of these have already been reoperated with allograft exchange. Freedom of reoperation was 66% at 5 years. Infants showed 48% freedom of reoperation at 5 years compared to 90% in the 1-2 years age group, while freedom of SD was 59% in infants at 48 months compared to 87% in the 1-2 years age group. Of allografts with SD in the infant group 66% had an allograft size of < 14 mm. In aortic allografts freedom of SD was 62% compared to 93% in pulmonary allografts. Freedom of allograft wall calcification was 46% at 18 months in all patients. In the statistical analysis, only infant age (P = 0.03) and aortic allograft (P = 0.02) were shown to be significant risk factors for early SD. CONCLUSION The use of pulmonary allografts, avoidance of relatively short and small conduits of < 14 mm in diameter, might improve the durability of allografts in infants and small children.

Geometric mismatch between homograft (allograft) and native aortic root: a 14-year clinical experience

OBJECTIVES We evaluated the effect of homograft/native aortic root geometric matching and mismatching on valve survival and myocardial remodeling. METHODS Between January 1, 1987 and March 2000, a total of 292 patients, aged 1.5-78 years (mean, 46.2 years), underwent freehand subcoronary aortic valve (AVR; n=207) and root (ARR; n=85) replacement with matched and mismatched cryopreserved homografts. All patients had pre- and postoperative two-dimensional Doppler echocardiographic studies. Two-hundred and forty-three survivors, excluding children with complete data on sizing, were followed at a total follow-up time of 1269 patient-years. Seventy percent received matched and 30% received mismatched aortic homografts. The homograft valve sizes ranged from 19 to 28 mm. RESULTS Hospital death for elective first operation was 2.3%, and late death after a mean follow-up of 52 months was 7.9%. The patient survival at 14 years was 92+/-2%. By linear regression analysis, matched homografts were equal to or 1-2 mm less than the native aortic annulus (r(2)=0.73). The valve survival in patients with AVR and ARR was 72+/-4 and 80+/-8% at 14 years, respectively. The freedom from reoperation was 92+/-5, 77+/-4 and 48+/-10% at 14 years for matched, oversized and undersized homografts, respectively (P=0.001). The postoperative cardiac index of patients with 22 and 24 mm homografts was 3.8-4.1 l/m(2), and there was a regression of the left ventricular mass and end-diastolic diameter (P=0.001). CONCLUSIONS The aortic homograft offers an excellent long-term clinical result. A mismatched homograft is a risk factor for postoperative aortic incompetence, reinfection with pseudoaneurysmal formation and reoperation for the freehand subcoronary implantation technique during the first 7 years of the postoperative period. It is prudent therefore to avoid mismatched homografts and use rather a properly sized stentless xenograft if a root replacement is not indicated.

The use of aortic allografts for surgical management of mycotic infections and aneurysms of the thoracic aorta

The use of synthetic grafts for replacing abdominal and thoracic aorta became attractive to surgeons because of their ready availability and lack of developing aneurysmal dilatation and calcification. The latter complications were experienced in homografts used in the early and late 1950s after their introduction by Dubost in 1952 (1). However the high rate of prosthetic infections, despite long-term antibiotic therapy in the infected area became a great concern. Subsequently antibiotic-impregnated synthetic grafts were introduced with some improvements in the results (2, 3). Improved cryopreservation techniques and homograft banking have brought a renaissance of the old concept of arterial reconstruction with vascular homografts, especially in vascular surgical procedures involved with mycotic aneurysms and prosthetic infections (4–7). The low incidence of infections with homografts in our series of native and prosthetic valve endocarditis as well as other series (8–10) prompted us to use cryopreserved arterial allografts for replacing mycotic aneurysms and infected aortic grafts.

286. Orthotope Transplantation allogener Aortenklappen

SummaryThe present technique of transplantation of the aortic valve allograft in the subcoronary position (n = 35) provides normal anatomy and hemodynamics of the aortic root and valves. The aortic valve allograft is not thrombogenic and therefore requires no postoperative anticoagulant therapy. Postoperative invasive studies in 25 patients indicate that there was practically no gradient across the valve or regurgitation into the left ventricle. Animal experiments with inbred rat strains have demonstrated that the degree of maintenance of endothelial cells and increased degeneration are dependent on immunogenetic histoincompatibility.ZusammenfassungDurch die gegenwärtige Operationstechnik bei Transplantation allogener Aortenklappen in subkoronare Position (n=35) wird die normale Anatomie and Hamodynamik der Aortenwurzel und der Taschenklappen gewährleistet. Die allogene Aortenklappe ist nicht thrombogen. Die postoperative Anticoagulantientherapie ist daher nicht notwendig. Bei 25 invasiv Nachuntersuchten bestand praktisch kein Druckgradient fiber dem Transplantat noch ein Reflux in die linke Kammer. Wie bei Versuchen mit Ratteninzuchtstämmen könnte bei den allogenen Transplantaten in Abhän-gigkeit der immunogenetischen Histoinkompatibilität der Endothelerhaltungsgrad abnehmen während die Degeneration des Transplantates zunimmt.