Considerations for prostheses choice in multiple valve surgery.

OBJECTIVES: The prosthesis type for multiple valve surgery (replacement of two or more diseased native or prosthetic valves, replacement of two diseased valves with repair/reconstruction of a third, or replacement of a single diseased valve with repair/reconstruction of a second valve) remains inadequately evaluated. The clinical performance of multiple valve surgery with bioprostheses (BP) and mechanical prostheses (MP) was assessed to compare patient survival and composites of valve-related complications. METHODS: Between 1975 and 2000, 1245 patients had multiple valve surgery (BP 785, mean age 62.0 ± 14.7 years; and MP 460, mean age 56.9 ± 12.9 years). There were 1712 procedures performed [BP 969(56.6%) and MP 743(43.4%). Concomitant coronary artery bypass (conCABG) was BP 206(21.3%) and MP 105(14.1%) (p = 0.0002). The cumulative follow-up was BP 5131 years and MP 3364 years. Independent predictors were determined for mortality, valve-related complications and composites of complications. RESULTS: Unadjusted patient survival at 12 years was BP 52.1 ± 2.1% and MP 54.8 ± 4.6% (p = 0.1127), while the age adjusted survival was BP 48.7 ± 2.3% and MP 54.4 ± 5.0%. The predictors of overall mortality were age [Hazard Ratio (HR) 1.051, p < 0.0001], previous valve (HR 1.366, p = 0.028) and conCABG (HR 1.27, p = 0.021). The actual freedom from valve-related mortality at 12 years was BP 85.6 ± 1.6% and MP 91.0 ± 1.6% (actuarial p = 0.0167). The predictors of valve-related mortality were valve type (BP > MP) (2.61, p = 0.001), age (HR 1.032, p = 0.0005) and previous valve (HR 12.61, p < 0.0001). The actual freedom from valve-related reoperation at 12 years was BP 60.8 ± 1.9% and MP85.6 ± 2.1% (actuarial p < 0.001). The predictors of valve-related reoperation were valve type (MP > BP) (HR 0.32, p < 0.0001), age (HR 0.99, p = 0.0001) and previous valve (HR 1.38, p = 0.008) CONCLUSIONS: Overall survival (age adjusted) is differentiated by valve type over 10 and 12 years and valve-related mortality and valve-related reoperation favours the use of mechanical prostheses, overall for multiple valve surgery.

Medtronic Mosaic porcine bioprosthesis: assessment of 12-year performance.

BACKGROUND: The Mosaic porcine bioprosthesis (Medtronic, Inc, Minneapolis, Minn) was approved in 2000 by the US Food and Drug Administration. Clinical performance was evaluated in 6 centers. METHODS: From 1994 to 2000, 797 patients (mean age 69 years) had aortic valve replacement (AVR) and 232 (mean 67 years) had mitral valve replacement (MVR). Concomitant coronary artery bypass grafting was performed with aortic valve replacement (45.4%) and mitral valve replacement (43.5%). Mean follow-ups were 7.5 years for aortic position and 7.3 years for mitral position. RESULTS: Early mortalities were 2.8% for AVR and 3.0% for MVR. Late mortalities were 4.2%/patient-year for AVR and 5.1%/patient-year for MVR. Overall 12-year survivals were 55.8% ± 3.7% for AVR and 43.9% ± 7.4% for MVR. Twelve-year freedoms from valve-related mortality were 87.1% ± 3.1% for AVR and 82.5% ± 7.7% for MVR. Twelve-year freedoms from reoperation were 84.0% ± 3.3% for AVR and 82.5% ± 7.5% for MVR. Freedoms from structural valve deterioration (SVD) by explant reoperation at 12 years for AVR were 93.3% ± 2.6% for patients at least 60 years old and 75.9% ± 9.3% for patients younger than 60 years. Freedoms from SVD by explant reoperation at 10 years for MVR were 95.3% ± 7.8% for patients at least 70 years old and 84.0% ± 9.3% for patients younger than 70 years. Hemodynamic performance data at 1 year for AVR (sizes 21-27 mm) were mean systolic gradient range 13.7 ± 4.8 to 10.3 ± 3.2 mm Hg and effective orifice area range 1.5 ± 0.3 to 2.5 ± 0.4 cm(2). For MVR (sizes 25-31 mm), data were mean diastolic gradient range 6.7 ± 1.7 to 3.7 ± 0.9 mm Hg and effective orifice area range 1.9 ± 0.3 to 2.4 ± 0.6 cm(2). CONCLUSIONS: Overall performance of Mosaic porcine bioprosthesis to 12 years is satisfactory. Freedoms from SVD by explant reoperation were most satisfactory for aortic position in patients at least 60 years old and mitral position in patients at least 70 years old. Overall actuarial freedom from SVD by explant reoperation is encouraging for patients with MVR.

St Jude Medical Epic porcine bioprosthesis: results of the regulatory evaluation.

BACKGROUND: The St Jude Medical Epic heart valve (St Jude Medical, Inc, St Paul, Minn) is a tricomposite glutaraldehyde-preserved porcine bioprosthesis. The St Jude Medical Biocor porcine bioprosthesis is the precursor valve to the St Jude Medical Epic valve. The Epic valve is identical to the Biocor valve except that it is treated with Linx AC ethanol-based calcium mitigation therapy. METHODS: The St Jude Medical Epic valve was implanted in 761 patients (mean age 73.9 ± 9.2 years) between 2003 and 2006 in the US Food and Drug Administration regulatory study in 22 investigational centers. The position distribution was 557 aortic valve replacements, 175 mitral valve replacements, and 29 double valve replacements. Concomitant coronary artery bypass grafting was performed in 50.8% of patients undergoing aortic valve replacement and 36.6% of those undergoing mitral valve replacement. RESULTS: The early mortality was 3.6% in aortic and 2.3% in mitral valve replacement. The follow-up was 1675.5 patient-years with a mean of 2.2 ± 1.2 years/patient. Late mortality was 5.2%/patient-year in aortic and 6.6%/patient-year in mitral valve replacement. The late major thromboembolism rate was 0.98%/patient-year for aortic and 2.6%/patient-year for mitral valve replacement. There were 19 reoperations, including 2 for structural valve deterioration, 1 for thrombosis, 9 for nonstructural dysfunction, and 7 for prosthetic valve endocarditis. The actuarial freedom from reoperation owing to structural valve deterioration for aortic valve replacement at 4 years for age 60 years or less was 93.3% ± 6.4%; for ages 61 to 70 years, 98.1% ± 1.9%; and for older than 70 years, 100% (P = .0006 > 70 vs ≤ 60 years). There were no events of structural deterioration with mitral valve replacement. The actuarial freedom from major thromboembolism for all patients at 4 years was 93.6% ± 1.0%. The 2 cases of structural valve deterioration occurred in aortic valves that became perforated without calcification causing aortic regurgitation. CONCLUSIONS: The performance of the St Jude Medical Epic porcine bioprosthesis is satisfactory at 4 years for both aortic and mitral valve replacement. This study establishes the early clinical performance including durability of this porcine bioprosthesis.

Effect of prosthesis-patient mismatch on long-term survival with aortic valve replacement: assessment to 15 years.

BACKGROUND: The effect of prosthesis-patient mismatch on long-term survival after aortic valve replacement has received considerable attention but there remains controversy. This study was performed to determine the predictors of mortality after aortic valve replacement and influence of prosthesis-patient mismatch on survival. METHODS: Contemporary mechanical prostheses and bioprostheses were implanted in 3,343 patients with aortic valve replacement between 1982 and 2003. The mean age was 68.06 +/- 11.20 years (median 70.06; range, 19 to 94), and the mean follow-up was 6.18 +/- 4.96 years, for a total of 20,666 years of follow-up. Prosthesis-patient mismatch was classified by effective orifice area index categories: normal (> 0.85 cm(2)/m(2)), 1,547 (46.3%); mild-to-moderate (> 0.65 cm(2)/m(2) to < or = 0.85 cm(2)/m(2)), 1,584 (47.4%); and severe (< 0.65 cm(2)/m(2)), 212 (6.3%). RESULTS: The predictors of overall mortality were age, age categorization, New York Heart Association functional class III/IV, concomitant coronary artery bypass graft surgery, prosthesis type, preoperative congestive heart failure, diabetes mellitus, renal failure, and chronic obstructive pulmonary disease. All categories of effective orifice area indexes were not predictive of overall mortality, late mortality, or early mortality. The 15-year overall survival was differentiated by effective orifice area index categories: 38.1% +/- 2.1%, 37.0% +/- 2.2%, and 22.1% +/- 6.5%, respectively, for the three categories. Survival adjusted for the covariates (effective orifice area index, age, basal mass index, and ejection fraction) determined no effect except severe effective orifice area index when adjusted for ejection fraction more than 50% (p = 0.049). CONCLUSIONS: Prosthesis-patient mismatch is not a predictor of overall standard unadjusted mortality to 15 years after aortic valve replacement, regardless of the category of effective orifice area index.

Seven-year results with the St Jude Medical Silzone mechanical prosthesis.

OBJECTIVE: The Artificial Valve Endocarditis Reduction Trial was stopped on January 21, 2000, due to a higher incidence of paraprosthetic leak in the St Jude Medical Silzone prosthesis compared with the conventional prosthesis. The Artificial Valve Endocarditis Reduction Trial investigators reported the 2-year results in 2002. This retrospective study assessed the influence on thromboembolism and paraprosthetic leak to 7 years. METHODS: A total of 253 patients had 254 operations: 80 aortic valve replacements, 139 mitral valve replacements, and 35 multiple replacements with placement of Silzone prostheses. The mean age was 58.6 years (range 21-84 years, median age 59.8 years), and there were 126 women (49.8%) and 74 concomitant procedures (coronary artery bypass 28.9%). RESULTS: Major paraprosthetic leak (repair, re-replacement, or mortality) occurred in 10 of the original procedures after 30 days (3 aortic valve replacements, 3 mitral valve replacements, 4 multiple replacements). Nine occurrences in 8 patients-5 early (2 years)-were managed. Seven were managed with definitive re-replacement. One was an early nonoperative fatality. There was 1 late fatality after the second late paraprosthetic leak reoperation. One of the 10 procedures occurring after 2 years had mild to moderate aortic valve replacement paraprosthetic leak managed as an incidental re-replacement at the time of correction of supra valvular patch stenosis. One additional occurrence, in addition to the 8 patients (<30 days), was considered a technical error and not related to the Silzone prosthesis and was replaced with a Silzone prosthesis. The linearized rate of paraprosthetic leak within the first 2 years of follow-up was 1.3%/patient-year and after 2 years was 0.4%/patient-year. The linearized occurrence rate for major thromboembolism was 0.42%/patient-year for aortic valve replacement and 1.71%/patient-year for mitral valve replacement. CONCLUSIONS: Paraprosthetic leak with the St Jude Medical Silzone prosthesis was managed both during the early (2years) intervals with re-replacement. Late managed events may be manifestations of earlier occurring paraprosthetic leak. Follow-up echocardiograms should meet standards of care, 6 to 12 months after surgery and at the slightest suspicion of dysfunction. There is no advanced continuing risk of the St Jude Medical Silzone prosthesis.

Effect of prosthesis-patient mismatch on long-term survival with mitral valve replacement: assessment to 15 years.

BACKGROUND: The effect of prosthesis-patient mismatch on long-term survival after mitral valve replacement (MVR) has received limited attention. This study was performed to determine the predictors of mortality after MVR and influence of prosthesis-patient mismatch on survival. METHODS: Contemporary mechanical prostheses and bioprostheses were implanted in 2,440 patients with MVR between 1982 and 2002. The mean age was 63.9 +/- 12.1 years and the mean follow-up was 6.1 +/- 4.6 years, a total of 14,797.7 years of follow-up. Prosthesis-patient mismatch was classified by effective orifice area index categories: normal, greater than 1.2 cm(2)/m(2) (345, 14.2%); mild-to-moderate, equal to or less than 1.2 to greater than 0.9 cm(2)/m(2) (1,696, 69.5%); and severe, equal to or less than 0.9 cm(2)/m(2) (399, 16.4%). RESULTS: The predictors of overall mortality were age, age categorization, New York Heart Association III-IV, concomitant coronary artery bypass, ventricular dysfunction, prosthesis type, body mass index, and pulmonary hypertension. All categories of effective orifice area indices (EOAIs) were not predictive of overall mortality, late mortality, or early mortality. The 15-year survival was not differentiated by EOAI categories; 32.0 +/- 4.4%, 32.9 +/- 2.1%, and 36.6 +/- 6.3%, respectively, for the three categories. Pulmonary hypertension influenced mortality by EOAI categories; normal versus mild-to-moderate (p = 0.0317) and normal versus severe (p = 0.0320). The EOAI was not an independent predictor of mortality in the consideration of patients with pulmonary hypertension but there is an interaction between pulmonary hypertension and mild-to-moderate (p = 0.023) and severe (p = 0.031) EOAI. CONCLUSION: Prosthesis-patient mismatch is not a predictor of overall mortality to 15 years after MVR regardless of the category of effective orifice area index. The preoperative variable, pulmonary hypertension, influences overall mortality in the presence of mild-to-moderate and severe prosthesis-patient mismatch in the survival analysis.

Patient outcome after aortic valve replacement with a mechanical or biological prosthesis: weighing lifetime anticoagulant-related event risk against reoperation risk.

OBJECTIVE: Although the results of aortic valve replacement with different valve prostheses are well documented in terms of survival, the risks of (valve-related) events are less well explored. METHODS: We used a dataset of 3934 patients who underwent aortic valve replacement with either a bioprosthesis (73%) or a mechanical prosthesis (27%) between 1982 and 2003 to simulate the outcome of patients after aortic valve replacement with either valve type. With the use of microsimulation, we compared total age and gender-specific life expectancy, event-free life expectancy, reoperation-free life expectancy, lifetime risks of reoperation, and valve-related events for both valve types. RESULTS: The total follow-up was 26,467 patient-years. The mean follow-up was 6.1 years in the biological arm and 8.5 years in the mechanical arm. The mean age at implantation was 70 and 58 years for biological and mechanical prostheses, respectively, and the percentage of concomitant coronary artery bypass grafting was 47% and 28%, respectively. For a 60-year-old man, simulated life expectancy in years for biological versus mechanical prostheses was 11.9 versus 12.2, event-free life expectancy was 9.8 versus 9.3, and reoperation-free life expectancy was 10.5 versus 11.9. Lifetime risk of reoperation was 25% versus 3%. Lifetime risk of bleeding was 12% versus 41%. CONCLUSION: Even for patients aged 60 years, event-free life expectancy is better with a bioprosthesis. Although the chance of reoperation is higher, the lifetime risk of bleeding is lower compared with a mechanical prosthesis. Comparing lifetime event risks between different types of valve prostheses provides more insight into patient outcome after aortic valve replacement and aids patient selection and counseling.

Mitral valve disease: if the mitral valve is not reparable/failed repair, is bioprosthesis suitable for replacement?

OBJECTIVE: The durability of mitral bioprostheses has long been known to be inferior to aortic bioprostheses. Mitral valve reconstruction/repair is currently recommended for most mitral valve procedures. The choice of prostheses for non-reparable or failed mitral valve repairs has not been specified or given appropriate attention within the literature. The objective of this study is to address the role of bioprostheses in the specific subset of non-reparable or failed repair patients by using the knowledge of the general durability of mitral porcine bioprostheses, inclusive of the Carpentier-Edwards mitral porcine bioprosthesis. METHODS: The CE-SAV was implanted in 1135 patients (1175 operations) for mitral valve replacement (MVR) from 1982 to 2000. The mean age was 65.0+/-12.1 years (range 13-86 years). The mean follow-up was 6.4+/-4.5 years, 7555.9 patient-years and 98.3% complete. The evaluation considered freedom from structural valve deterioration (SVD) and freedom from composites of complications, as well as risk assessment. RESULTS: For the 51-60 year age group, the actual and actuarial freedom from SVD was, at 18 years, 56.0+/-4.1% and 14.7+/-5.8%; for the 61-70 year age group was, at 18 years, 69.6+/-2.6% and 26.5+/-5.9%, respectively. For the >70 group, at 15 years was 92.2+/-2.0% and 69.0+/-9.7%, respectively. There were a total of 256 SVD events with 31 fatalities and 226 reoperations with 10 fatalities (4.42%). The predictors of SVD were age (hazard ratio [HR] 0.98, p=0.0002), concomitant CAB (HR 0.66, p=0.020) and valve size (HR 1.08, p=0.034). The overall actual freedom, at 15-18 years, for >70 age group was, for valve-related reoperation, 94.3+/-1.5%; and for valve-related mortality was 87.8+/-2.3%. CONCLUSIONS: The CE-SAV mitral porcine bioprosthesis cannot be recommended as representative of prosthesis-type of choice for non-reparable or failed repair of native mitral valves for ages 70 years of age. The clinical performance of the CE-SAV is similar to other mitral bioprostheses.

Spontaneous hemothorax and neurofibromatosis: a review of a lethal combination.

We present a case report of spontaneous hemothorax associated with neurofibromatosis. On review of the literature, a significant mortality rate of 36% is revealed in addition to a surgical mortality of 33%. Treatment options are reviewed and potential management strategies are discussed.

Early antithrombotic therapy for aortic valve bioprostheses: is there an indication for routine use?

BACKGROUND: Consensus reports over the past 10 years from the United States, Europe, United Kingdom, and Canada have not provided consistent guidelines for antithrombotic therapy of aortic valve bioprostheses for the three-month period after surgery. This study was conducted to determine if antithrombotic therapy was protective against TE with aortic bioprostheses 30 days or less after aortic valve replacement (AVR). METHODS: From 1994 to 2000, 1,372 patients implanted with three currently marketed aortic bioprostheses, Medtronic Mosaic (Medtronic, Inc, Minneapolis, MN) (415 patients), Carpentier-Edwards SAV (462), and Carpentier-Edwards PERIMOUNT (495) (Edwards Lifesciences, Irvine, CA), with a mean age of greater than 70 years were evaluated. Patient populations were comparable, inclusive of concomitant coronary artery bypass grafting (CABG) for the overall populations and for patients greater than 70 years. RESULTS: There were 37 thromboembolic (TE) events: major TE, 14; reversible ischemic neurologic deficit (RIND), 12; and minor TE, 11. There were 4 TE deaths. Multivariate (stepwise logistic regression) analysis revealed no predictive risk factors for overall TE. For the combination of major TE plus RIND there were two predictive risk factors with analysis of 12 risk variables: preoperative cerebrovascular accident (odds ratio [OR] 4.45, 95% confidence interval [CI] 1.17 to 16.87, p = 0.028); and concomitant CABG (OR 3.19, 95% CI 1.16 to 8.76, p = 0.025). Neither anticoagulant nor antiplatelet therapies gave significant protection. CONCLUSIONS: There does not appear to be an indication for routine antithrombotic management. The study supports the potential use of antithrombotic therapy for comorbidities of preoperative cerebrovascular accident and concomitant CABG but not atrial fibrillation, left ventricular dysfunction, or elderly age greater than 70 years. Vascular burden and advanced age are likely contributing factors to these independent predictors. There may still be a need for, or at least consideration of, a randomized trial for AVR with bioprostheses.

15-year comparison of supra-annular porcine and PERIMOUNT aortic bioprostheses.

The second-generation Carpentier-Edwards bioprostheses, the supra-annular porcine valve and the PERIMOUNT pericardial valve, have been evaluated longitudinally for several years. This study compared clinical performance over 15 years. Aortic valve replacement was performed with a supra-annular porcine valve in 1,823 patients (group 1) aged 19-89 years (mean, 68.9 +/- 10.9 years) and with a PERIMOUNT pericardial bioprosthesis in 1,430 patients (group 2) aged 16-90 years (mean, 69.5 +/- 10.4 years). The groups were similar except for concomitant coronary artery bypass in 43% of group 1 and 18% of group 2 ( p < 0.001). Overall survival at 15 years was 29.3% +/- 1.5% for group 1 and 35.2% +/- 3.1% for group 2 ( p = 0.0009). The actual freedom from valve-related mortality was 88.5% +/- 0.9% for group 1 and 84.9% +/- 1.7% for group 2. The actual freedom from structural valve deterioration at 15 years was similar overall, and for patients aged > 60 years, between the groups, but was dissimilar (group 2 > group 1) for age group 2), sex (male > female), age, and concomitant coronary artery bypass. Both bioprostheses provided satisfactory clinical performance at 15 years after aortic valve replacement.

Mitral valve reconstruction: experience related to early and late mortality and reoperation.

BACKGROUND AND AIM OF THE STUDY: The present authors' experience with mitral valve reconstruction was reviewed to determine the influence of anatomical and functional abnormalities on mortality and reoperation. METHODS: Between 1991 and 2001, a total of 397 patients (mean age 59.0 +/- 13.4 years) underwent mitral valve reconstruction at the authors' institution. Patients were grouped according to the Carpentier functional classification as follows: type I, n = 88 (mean age 57.4 years; range: 24-81 years); type II, n = 169 (mean age 59.8 years; range: 16-81 years); type IIIa, n = 44 (mean age 52.8 years; range: 22-78 years); type IIIb, n = 85 (mean age 65.1 years; range: 33-82 years); and congenital (C), n = 11 (mean age 36.2 years; range: 18-65 years). RESULTS: The total follow up was 1,485.8 patient-years (pt-yr). Early mortality was: type I, 3.4% (n = 3); type II, 0; type IIIa; 2.3% (n = 1); type IIIb, 9.4% (n = 8); and C, 0 (p = 0.0028, IIIb > II and C). The late mortality was: type I, 2.1%/pt-yr (n = 6); type II, 1.1%/pt-yr (n = 7); type IIIa, 1.8%/pt-yr (n = 4); type IIIb, 4.3%/pt-yr (n = 12); and C, 1.7%/pt-yr (n = 1) (p = 0.0035 IIIb > II). The overall survival at 10 years was 79.6 +/- 4.2% (p <0.001, II > IIIb; p = 0.029, I > IIIb; p = 0.046, II > I). The reoperations were: type I, 1.4%/pt-yr (n = 4); type II, 1.9%/pt-yr (n = 12); type IIIa, 0.9%/pt-yr (n = 2); type IIIb, 0.4%/pt-yr (n = 1); and C, 0 (p = 0.0435 II > IIIb). Among the 19 reoperations there were 17 replacements, one re-repair, and one annuloplasty. The failures were predominantly type II, posterior (n = 5) and anterior (n = 5), or a combination (n = 2). The overall freedom from reoperation was 92.0 +/- 2.2% (p = NS between groups). CONCLUSION: Mitral valve reconstruction can be performed in all four functional categories with generally satisfactory results, except possibly for functional ischemic disease. The results of surgery for degenerative disease afford the opportunity for early surgical management, if proven techniques are adhered to in order to minimize the risk of reoperation. The repair of ischemic disease due primarily to ventricular dysfunction is in a state of evolution.

Medtronic mosaic porcine bioprosthesis: investigational center experience to six years.

BACKGROUND AND AIM OF THE STUDY: The findings of this single-center experience with the Medtronic Mosaic porcine bioprosthesis were evaluated to determine the clinical performance of the valve. METHODS: Between 1994 and 2000, a total of 657 patients was implanted with the prosthesis. Aortic valve replacement (AVR) was performed in 415 patients (mean age 70.5+/-10.7 years; range: 26-89 years) and mitral valve replacement (MVR) in 242 patients (mean age 70.5+/-9.5 years; range: 19-86 years). Concomitant coronary artery bypass (CAB) was performed in 51.1% and 46.7% of AVR and MVR patients, respectively. The majority of patients were aged over 70 years (59.8% AVR, 58.7% MVR). RESULTS: Survival at six years was 73.0+/-2.4% after AVR, and 74.0+/-5% after MVR (p = NS). Actual freedom from valve-related mortality at six years was 98+/-1% for AVR and 96+/-1% for MVR; freedom from overall thromboembolism (TE) was 86+/-3% for AVR and 89+/-2% for MVR. After AVR, 42 thromboembolic events occurred in 39 patients (23 minor; 14 major; three reversible ischemic neurologic deficits (RIND); two thrombosis). After AVR, the late TE rate was 2.1% per pt-yr, and the major rate 0.6% per pt-yr (exclusive of thrombosis). The overall TE rate after AVR was 2.9% per pt-yr (major rate 1% per pt-yr). After MVR, 25 events occurred in 24 patients (10 minor; eight major; five RIND; two thrombosis). After MVR, the late TE rate was 2.6% per pt-yr, and the major rate 0.7% per pt-yr (exclusive of thrombosis). The overall TE rate after MVR was 3.5% per pt-yr (major rate 1.1% per pt-yr). There were four cases of structural valve deterioration (SVD) (two each after AVR and MVR). Reoperation was performed in three of four cases of thrombosis, and in two of four cases of SVD. CONCLUSION: The Medtronic Mosaic porcine bioprosthesis is safe and effective. The rate of SVD after six years was low, being zero in the aortic position of patients aged >60 years, and zero also in the mitral position of patients aged <60 years. The incidence of early and late thromboembolism was contributed to by the advanced age of the patient population.

Mycophenolate pharmacokinetics in early period following lung or heart transplantation.

BACKGROUND: The available pharmacokinetic and pharmacodynamic data on mycophenolic acid (MPA), the pharmacologically active metabolite of mycophenolate mofetil (MMF), are derived largely from renal transplant patients, not thoracic transplant recipients. OBJECTIVE: To evaluate, in a pilot study, the pharmacokinetics of MPA at 3 different times in the early period (up to the first 9 mo) following lung or heart transplantation. METHODS: Nine patients were entered into this open-label study. Upon administration of a steady-state morning MMF dose, blood samples were collected at 0, 20, 40, 60, and 90 minutes and at 2, 4, 6, 8, 10, and 12 hours after the dose at 3 times (denoted as sampling periods 1, 2, and 3) in the early posttransplant period. Total MPA concentrations were measured by a validated HPLC method with ultraviolet detection and followed by ultrafiltration of pooled samples for unbound MPA concentrations. Pharmacokinetic parameters (maximal concentration [C(max)], dose-normalized C(max), time to C(max), minimum concentration, predose concentration, AUC, dose-normalized AUC, free fraction, free AUC) were calculated by traditional noncompartmental methods. RESULTS: Patient characteristics included 7 men and 2 women, 5 lung and 4 heart transplant recipients, mean +/- SD age 53 +/- 11 years, and weight 77 +/- 14 kg. All patients were receiving prednisone and cyclosporine (with the exception of 2 pts. on tacrolimus during sampling periods 2 and 3). Sampling periods 1, 2, and 3 occurred on posttransplant days 15 +/- 13, 56 +/- 33, and 125 +/- 73, respectively. No significant differences were found between sampling periods in any pharmacokinetic parameter. Drug exposure as evaluated by AUC was 39.95 +/- 44.86, 25.24 +/- 25.68, and 43.96 +/- 38.67 micro g*h/mL during sampling periods 1, 2, and 3, respectively, (p > 0.05). CONCLUSIONS: As of September 26, 2003, this is the first study to systematically evaluate MPA pharmacokinetics in thoracic transplant recipients at 3 different time points during the early posttransplant period. Wide interpatient variability in MPA pharmacokinetics was observed, thus emphasizing the need to individualize dosing of MMF and to further evaluate important pharmacokinetic/pharmacodynamic parameters and endpoints that impact on clinical outcomes. Further studies involving more patients and pharmacodynamic outcomes are underway to help identify optimal MMF strategies.

Traumatic rupture of the thoracic aorta: third decade of experience.

BACKGROUND: Traumatic rupture of the thoracic aorta is a relatively common injury of deceleration accidents, usually high-speed motor vehicle accidents. Spinal cord injury has been a well-documented complication of surgical management. The use of nonheparinized partial bypass with a centrifugal pump was evaluated for protection against spinal cord injury and reduction of risk of associated injuries. METHODS: From 1989 to 1999, the third decade of the authors' experience, traumatic rupture was diagnosed in 58 patients (male 46 and female 12; mean age 39.9 years, range 17 to 85). Associated injuries were documented in 98.3% (57 patients). In all, 45 patients (77.6%) had the opportunity for definitive surgical management; 42 (93.3%) were managed with partial cardiopulmonary bypass, 35 without the use of heparin. Full cardiopulmonary bypass was utilized in 1 patient while 2 had repair without cardiopulmonary bypass support. Thirteen patients did not have the opportunity for definitive surgical management, 1 death on arrival, 8 (61.5%) suspected, and 4 (30.8%) diagnosed. RESULTS: There were 6 deaths in the surgical group, 5 in nonheparinized patients. The causes were intraoperative hypovolemia (2), anoxic brain death after intraoperative cardiac arrest (1), sepsis (1), and adult respiratory distress syndrome (1). The other was in the simple aortic cross-clamp group from intraoperative pulmonary compromise. There was one spinal cord injury, paraparesis in 1 of the 2 patients managed without bypass support. The total hospital stay ranged from 8 to 112 days, primarily owing to management of associated injuries. Of the 13 patients who did not have the opportunity for definitive surgical management, 5 had unsuccessful emergency thoracotomy and 3 survived the hospital course without surgery. Of the total population, the overall mortality was 27.6%, whereas the mortality of the potentially operable patients was 25.8%. Of the surgical group, the intraoperative mortality was 6.7% and 30-day mortality was 13.3%. CONCLUSIONS: Spinal cord injury was prevented by the use of partial cardiopulmonary bypass. Nonheparinized bypass was likely to be a contributory factor to lack of mortality directly related to associated injuries.