Mark F. O'Brien

Allograft aortic valve replacement: long-term follow-up.

Aortic valve replacement using an allograft aortic valve has been performed on 804 patients. From December 1969 to May 1975, 124 patients received a nonviable allograft valve sterilized by incubation with low-dose antibiotics and stored for weeks by refrigeration at 4 degrees C (series 1). From June 1975 to January 1994, 680 patients received viable allograft valves, now cryopreserved early within 2 hours of collection from transplant recipient donors, 6 hours for multiorgan donor valves and 23 hours (mean) for autopsy valves from donor death. The 30-day mortality was 8.9% +/- 5% (95% confidence limits) for series I and 2.8% +/- 1% (95% confidence limits) for series II. Actuarial patient survival including hospital mortality at 15 years was 56% +/- 5% for series I and 62% +/- 5% for series II. The probability of a thromboembolic event was low, freedom at 15 years being 95% +/- 1% for patients receiving allografts with or without associated coronary bypass procedures and 81% +/- 5% for patients having allografts with other associated procedures (eg, mitral valve operations). Actuarial freedom from endocarditis was similar for the two series, 91% +/- 3% (series I) and 94% +/- 2% (series II) at 15 years. The freedom from valve incompetence, from reoperation for all causes, and from structural deterioration demonstrated clearly the inferiority of the 4 degrees C stored allograft valves. For structural deterioration as identified clinically, at reoperation and at death, freedom from this event at 15 years was 45% +/- 6% for series I and 80% +/- 5% for series II (p value for the difference is 0).(ABSTRACT TRUNCATED AT 250 WORDS)

The viable cryopreserved allograft aortic valve.

One hundred and twenty‐four patients underwent aortic valve replacement with a nonviable 4°C refrigerated aortic allograft valve. One hundred and eighty‐four patients underwent aortic valve replacement with a viable cryopreserved aortic allograft valve in a later era. The longest follow‐up was 16 years for the group with the nonviable valve and 11 years for the group with the viable valves. Within this time frame, reoperation was required in 23 patients with nonviable valves for leaflet perloration or rupture whereas no patients in the group with viable valves developed this complication (p < 0.0001). The prevalence of endocarditis and thromboembolism was very low in both groups. Viability of leaflet tissue is associated with an important improvement in durability over nonviable allograft valves. Consequently, long‐term follow‐up results of allograft valves might be best expressed in terms of viability. The current evidence suggests that the viable cells are donor in origin. The viable cryopreserved aortic allograft valve offers significant advantages over current nonviable allograft valves, mechanical valves, and bioprostheses.

Allograft aortic valve replacement: long-term comparative clinical analysis of the viable cryopreserved and antibiotic 4 degrees C stored valves.

Aortic valve replacement with or without concomitant procedures was performed using an allograft aortic valve in 534 patients. From December 1969 to May 1975 (group I), a 4°C stored valve was used (124 patients) and from June 1975 to July 1990 (group II), a cryopreserved valve (410 patients) was used. The 30‐day mortality was 8.9% (confidence limits [CL] 6.2%–12.3%) for group I and 2.7% (CL 1.9%‐3.8%) for group II. Actuarial patient survival including early hospital mortality at 14 years was 57% for group I and 71% for group II (p = 0.014). Actuarial freedom from thromboembolism for all patients (n = 534) was 94% at 14 years, and for patients who underwent isolated aortic valve replacement with or without coronary artery bypass graft (n = 457) was 97% at 14 years (p = 0.017). Actuarial freedom from allograft valve endocarditls at 14 years was 92% in group I and 94% in group II (p = 0.36). The actuarial freedom from moderate or severe allograft valve incompetence at 14 years was 50% (group I) and 78% (group II) (p = 0.27). Reoperation was undertaken for endocarditis, leaflet structural deterioration (SD), or technical reasons. The actuarial freedom from reoperation (all causes) at 14 years was 63% (group I) and 86% (group II) (p = 0.39). Reoperation for SD occurred in 34 patients in group I and three patients in group II. The actuarial freedom from reoperation for SD at 14 years was 67% (group I) and 95% (group II) (p = 0.001). To reflect a more accurate depiction of the prevalence of SD, patients were analyzed according to the development of “assumed structural deterioration” (at reoperation, at death with moderate or severe allograft valve incompetence and macroscopic valve deterioration on autopsy, and in the presence of moderate or severe allograft valve incompetence in patients not undergoing reoperation). The actuarial freedom from “assumed structural deterioration” at 14 years was 51% (group I) and 85% (group II) (p = 0.000003). The long‐term results confirm the low incidence of thromboembolism and endocarditis regardless of the method of preservation and demonstrate the overall acceptable performance of the viable cryopreserved allograft valve and its superiority over the 4°C stored valve.

Allograft aortic valve implantation: techniques for all types of aortic valve and root pathology.

The geometry and degree of symmetry of the diseased aortic root and valve dictate the technical method of implantation of the allograft aortic valve. Five methods are available that are suitable for the full range of aortic root disease: the small aortic root with a valve annulus diameter less than 21 mm, the common aortic valve lesions (valve annulus diameter, 21 to 29 mm), the aneurysmal noncoronary sinus, the moderately large annulus (valve annulus diameter greater than 30 mm), and the aneurysmal aortic root and dilated annulus. Implantation methods include the subcoronary technique, miniroot inclusion technique, and aortic root replacement. Technical variations such as valve inversion during implantation, valve rotation, and continuous or interrupted suture methods are important in certain techniques. The allograft aortic valve is a versatile device that can be used in the surgical management of the full range of aortic valve and aortic root pathology.

The prevalence of infective endocarditis after aortic valve replacement.

Replacement valve endocarditis occurred in 3.7% of 2443 patients who underwent primary or redo aortic valve replacements at The Prince Charles Hospital between December 31, 1969 and January 1, 1992, based on a cross-sectional follow-up in 1992 which was 98.8% complete. Because some patients had re-replacements during the study period, a total of 2686 operations were considered for analysis. A variety of replacement devices were used, including 571 allografts (21%), 1152 xenografts (43%), and 880 mechanical valves (36%). Insertion of an allograft valve resulted in a constant risk of endocarditis which, by multivariable hazard function analysis, negated the effect of any early-phase factors (p < 0.0001). With other replacement devices, the risk of infection peaked early after operation (9 weeks) and then gave way to a constant risk. Compared with the risk associated with allograft valves, constant risk was higher when the replacement device was a Carpentier-Edwards xenograft (n = 1021, p = 0.02) and lower when a St. Jude Medical mechanical valve was used (n = 505, p = 0.05). In nonallograft recipients, the presence of active preoperative endocarditis (p < 0.0001) or a concomitant synthetic synthetic aortic root replacement (p = 0.0006) increased the magnitude of the early peaking risk. Regardless of replacement device, constant risk was increased in patients with renal dysfunction (p = 0.01), in younger patients 0.04). When preoperative endocarditis was caused by Staphylococcus aureus, culture-positive postoperative wound infection was associated with increased risk of replacement valve infection (p < 0.001) and when it occurred, the same organism was usually responsible (86%). Identification of patients at increased risk for replacement valve infection may lead to reduced morbidity through strategies such as selective use of replacement devices and antimicrobial prophylaxis.

Multicenter study of stentless valve replacement in the small aortic root

OBJECTIVE A clinical study was conducted to evaluate the results of stentless porcine valves in patients with a small aortic root (19- and 21-mm aortic anulus). METHODS Of 567 patients, from 4 surgical institutions, 171 patients (30.1%) had a small aortic root, comprising 163 cases with calcified aortic stenosis and 8 cases with predominant valvular insufficiency. Sixty patients had associated mitral or coronary lesions. Mean age was 72 +/- 4.2 years. Forty-seven patients with a small aortic root had a 19-mm anulus, and 124 patients had a 21-mm anulus. The body surface area was, respectively, 1.55 +/- 0.2 m2 and 1.78 +/- 0.45 m2. Hemodynamic evaluation of the stentless valve comprised serial measures of mean gradients, effective orifice area, and left ventricular mass reduction. Complication rates for secondary events were evaluated over a 6-year period. RESULTS The hospital mortality rate was 3.5%. The mean gradients after the first year were 9 +/- 2 mm Hg and 6 +/- 1.7 mm Hg in patients with a 19-mm and a 21-mm anulus, respectively. Effective orifice area was 1.45 +/- 0.3 cm2 and 1.72 +/- 0.4 cm2. Gradients and surfaces remained stable throughout the study period. Aortic regurgitation was zero to trace. Left ventricular mass at discharge and at 1 year were, respectively, 296 +/- 127 g and 215 +/- 102 g for patients with a 19-mm anulus and 281 +/- 75 g and 236 +/- 15 g for patients with a 21-mm anulus. CONCLUSIONS Stentless valves are a suitable device for elderly patients with small aortic roots, which leave only mild residual obstruction.

Establishment of a viable homograft cardiac valve bank: a rapid method of determining homograft viability.

A method for determining the viability of homograft valves has been developed based on sequential measurements of glucose and pH levels of the culture medium in which cardiac valves have been maintained for short periods at 37 degrees C. Viable valves, as determined by tissue culture, showed a characteristic pattern of glucose utilization and pH reduction that was absent in nonviable valves. Upon explantation of valve leaflet fragments into tissue culture, only fragments from valves that metabolized glucose produced viable fibroblast cultures. The method reported here is rapid, requires no specialized equipment, is nondestructive, and can directly determine the viability of the valve homograft within 24 to 48 hours.

IgG Antibodies Against Common Gut Bacteria Are More Diagnostic for Crohn's Disease Than IgG Against Mannan or Flagellin

INTRODUCTIONAntibodies to bakers yeast (mannan) have been widely used to aid in diagnosis of Crohns disease. Recently, there has been interest in antibodies against a flagellin from Clostridium coccoides subphylum. We hypothesized that reactivity with these antigens is a surrogate marker for a generalized increased IgG response against intestinal microbiota in Crohns disease.METHODSWe compared the diagnostic utility of IgG antibodies against flagellin and mannan with two complex surface antigen preparations, one derived from B. vulgatus (Bv), the other from over 20 common mucosa-associated microbiota, a multibacterial membrane preparation (MBP). IgG antibodies were measured in sera from two age- and sex-matched populations: 120 Crohns patients (CD) and 160 gastroenterology controls (CON) comprising 40 ulcerative colitis (UC) and 120 non-IBD patients.RESULTSIgG was elevated against all antigen preparations in Crohns but statistical analysis of receiver operator characteristic (ROC) plots showed that IgG against the complex antigen preparations MBP and Bv had better diagnostic accuracy to distinguish the two populations (CD and CON) than IgG against mannan (P ≤ 0.01) or flagellin (P ≤ 0.04). Concentrations of antibody reactive with distinct individual antigens correlated weakly.DISCUSSIONThe findings support our hypothesis that measurement of IgG reactivity against individual antigens gives an indication of a generalized increased IgG response against individual intestinal microbiota in Crohns, rather than measuring specific immune responses important for pathogenesis. The data are consistent with either a mucosal defect that facilitates increased exposure to microbial antigens or an altered immune response, both of which could occur due to known genetic and molecular defects in Crohns disease.

A study of the cells in the explanted viable cryopreserved allograft valve.

From June 1975 to December 1987, 231 patients underwent aortic valve replacement with a viable cryopreserved allograft aortic valve. Throughout this era, a uniform procurement and preservation was used to maintain leaflet fibroblast viability. The allograft valve was obtained from coronors autopsies within 24 hours of death, and more recently from organ donors, incubated for 24 hours in low dose antibiotic solution followed immediately by cryopreservation (mean time interval 39 hours after donor death). Viability was ensured by monitoring glucose utilization of the aortic and pulmonary valves and by demonstrating fibroblast growth in tissue cultured from the pulmonary valve. A uniform protocol for valve preparation was used during the entire experience.

Long-Term Results of the Viable Cryopreserved Allograft Aortic Valve: Continuing Evidence for Superior Valve Durability

From December 1969 to May 1975, 124 patients underwent aortic valve replacement with an allograft aortic valve sterilized by incubation in a low dose antibiotic solution and stored by refrigeration at 4°C (4°C stored valve group). From June 1975 to December 1987, 231 patients received an allograft aortic valve, sterilized by the same low dose antibiotic solution, but stored by cryopreservation in liquid nitrogen at — 196°C (cryopreserved valve group). The 4°C stored valves were essentially nonviable, whereas the cryopreserved valves were viable at implantation. Of the 355 aortic valve replacements, associated procedures were performed in 127 patients. The 30‐day mortality was 8.9% (confidence limits [C.L.] 6.2%...12.3%) (4°C stored) and 4.8% (C.L. 3.3%...6.7%) (cryopreserved). Actuarial survival was similar in both groups, being 71% and 67% at 10 years in the 4°C stored and cryopreserved valve groups, respectively (P = .18). The probability of a thromboembolic event was low, but appeared higher in the 4°C stored valve group (actuarial freedom at 10 years, 90%) than the cryopreserved valve group (actuarial freedom at 10 years, 98%) (P =.01) probably related to associated mitral valve surgery. The actuarial freedom from allograft valve endocarditis at 10 years was 94% and 95% for the 4°C stored and cryopreserved valve groups, respectively (P = .23).