Inferior Outcomes on the Waiting List in Low-Volume Pediatric Heart Transplant Centers.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary.

The rapid development of angiogenic growth factor therapy for patients with advanced ischemic heart disease over the last 5 years offers hope of a new treatment strategy based on generation of new blood supply in the diseased heart. However, as the field of therapeutic coronary angiogenesis is maturing from basic and preclinical investigations to clinical trials, many new and presently unresolved issues are coming into focus. These include in-depth understanding of the biology of angiogenesis, selection of appropriate patient populations for clinical trials, choice of therapeutic end points and means of their assessment, choice of therapeutic strategy (gene versus protein delivery), route of administration, and the side effect profile. The present article presents a summary statement of a panel of experts actively working in the field, convened by the Angiogenesis Foundation and the Angiogenesis Research Center during the 72nd meeting of the American Heart Association to define and achieve a consensus on the challenges facing development of therapeutic angiogenesis for coronary disease.

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Regional angiogenesis induced in nonischemic tissue by an adenoviral vector expressing vascular endothelial growth factor.

The feasibility of a single administration of a replication-deficient adenovirus (Ad) vector encoding the cDNA for human vascular endothelial growth factor (VEGF) (AdCMV.VEGF) to induce neovascularization in vivo in normal tissue was evaluated in retroperitoneal adipose tissue. Following administration of AdCMV.VEGF (10(9) pfu/50 microliters), maximal VEGF cDNA expression was observed at 2-5 days in the injected adipose tissue. No VEGF protein was detected at > or = 10 days in injected adipose tissue, and there was no increase in serum VEGF levels at any time. In vivo quantification of the number of blood vessels using 30x visualization of the adipose tissue demonstrated an increase in vessel number by 10 days, plateauing by 30 days with a 123% increase in vessel number compared to the control vector AdCMV.Null, despite the fact that no VEGF protein was detected after 5 days. Consistent with the in vivo data, histologic quantification of capillary number demonstrated an increase by day 5, reaching a 38% increase over AdCMV.Null by day 30. These observations demonstrate that an Ad vector carrying the VEGF cDNA is capable of inducing the growth of new blood vessels in a regional fashion in a relatively avascular, normal organ. This suggests in vivo Ad-mediated gene transfer may be useful for therapeutic angiogenesis in the treatment of ischemic cardiovascular disease.

Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121.

A gene therapy strategy involving direct myocardial administration of an adenovirus (Ad) vector encoding the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) has been shown to be capable of "biological revascularization" of ischemic myocardium in an established porcine model [Mack, C.A. (1998). J. Thorac. Cardiovasc. Surg. 115, 168-177]. The present study evaluates the local and systemic safety of this therapy in this porcine ischemia model and in normal mice. Myocardial ischemia was induced in Yorkshire swine with an ameroid constrictor 21 days prior to vector administration. Ad(GV)VEGF121.10 (10(9) or 10(10) PFU), Ad5 wild type (10(9) PFU), AdNull (control vector with no transgene; 10(9) PFU), saline, or no injection (naive) was administered in 10 sites in the ischemic, circumflex distribution of the myocardium. Toxicity was assessed by survival, serial echocardiography, blood analyses, and myocardial and liver histology at 3 and 28 days after vector administration. All pigs survived to sacrifice, except for one animal in the Ad(GV)VEGF121.10 (10(10) PFU) group, which died as a result of oversedation. Echocardiograms of Ad(GV)VEGF121.10-treated pigs demonstrated no differences in pericardial effusion, mitral valve regurgitation, or regional wall motion compared with control pigs. Intramyocardial administration of Ad(GV)VEGF121.10 included only minimal myocardial inflammation and necrosis, and no hepatic inflammation or necrosis. Only a mild elevation of the white blood cell count was encountered on day 3, which was transient and self-limited in the Ad(GV)VEGF121.10 group as compared with the saline-treated animals. As a measure of inadvertent intravascular administration of vector, normal C57/BL6 mice received intravenous Ad(GV)VEGF121.10 (10(4), 10(6), 5 x 10(7), or 10(9) PFU), AdNull (5 x 10(7) or 10(9) PFU), or saline. Toxicity was assessed by survival, blood analyses, and organ histology at 3 and 7 days after vector administration. A separate group of C57/BL6 mice received intravenous AdmVEGF164 (Ad vector encoding the murine VEGF164 cDNA), Ad(GV)VEGF121.10, AdNull (10(8) PFU each group), or saline to assess duration of expression and safety of a homologous transgene. All mice survived to sacrifice except for 40% of the mice in the highest (10(9) PFU; a dose more than 10(3)-fold higher by body weight than the efficacious dose in pigs) Ad(GV)VEGF121.10 dose group, which died on days 5-6 after vector administration. The only differences seen in the blood analyses between treated and control mice were in the very high Ad(GV)VEGF121.10 dose group (10(9) PFU), which demonstrated an anemia as well as an increase in alkaline phosphatase when compared with all other treatment groups. Hepatic VEGF levels by ELISA in AdmVEGF164-treated mice did not persist beyond 14 days after vector administration, suggesting that persistent expression of a homologous VEGF gene transferred with an Ad vector is not a significant safety risk. Although this is not a chronic toxicity study, these data demonstrate the safety of direct myocardial administration of Ad(GV)VEGF121.10, and support the potential use of this strategy to treat human myocardial ischemia.

Exogenous control of cardiac gene therapy: evidence of regulated myocardial transgene expression after adenovirus and adeno-associated virus transfer of expression cassettes containing corticosteroid response element promoters.

OBJECTIVE: Because of the relative inaccessibility of the heart for repeated gene therapy, it would be useful to regulate the expression of transgenes delivered in a single dose of a gene therapy vector. Incorporation into the vector of a regulatable promoter that is responsive to pharmacologic agents that are widely used and well tolerated in clinical practice represents such a control strategy. METHODS: A replication-deficient adenovirus or an adeno-associated virus containing a chimeric promoter composed of 5 glucocorticoid response elements and the murine thrombopoietin complementary DNA (AdGRE.mTPO or AAVGRE.mTPO) was administered to the hearts of Sprague-Dawley rats. Platelet levels were evaluated as a reporter of transgene activity with or without dexamethasone. For comparison, rats received a control adenovirus vector, AdCMV.mTPO or AdCMV.Null, and the control adeno-associated virus vector AAVCMV.luc, which encodes for the firefly luciferase (luc) gene. RESULTS: Platelet elevation in the AdGRE.mTPO group peaked 4 days after dexamethasone administration, with a return to baseline 1 week after the initial corticosteroid dose. Subsequent dexamethasone administration at 2 and 4 weeks resulted in similar but progressively decreased responses. The AAVGRE.mTPO group had 5 peak platelet levels to a minimum of 2.2-fold with respect to baseline without diminution with subsequent dexamethasone administrations out to 169 days. In contrast, the AdCMV.Null and AAVCMV.luc groups demonstrated no increase in platelet counts and the AdCMV.mTPO group demonstrated a slow rise to a single peak platelet count independent of dexamethasone administration. CONCLUSION: It may be possible to control on demand the expression of a gene transferred to the heart. This strategy should be useful in cardiac gene therapy.

Retrograde autologous priming for cardiopulmonary bypass: a safe and effective means of decreasing hemodilution and transfusion requirements.

OBJECTIVES: The obligatory hemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusion in cardiac operations. We therefore examined whether retrograde autologous priming of the bypass circuit would result in decreased hemodilution and red cell transfusion. METHODS: Sixty patients having first-time coronary bypass were prospectively randomized to cardiopulmonary bypass with or without retrograde autologous priming. Retrograde autologous priming was performed at the start of bypass by draining crystalloid prime from the arterial and venous lines into a recirculation bag (mean volume withdrawal: 880 +/- 150 ml). Perfusion and anesthetic techniques were otherwise identical for the two groups. The hematocrit value was maintained at a minimum of 16% and 23% during and after cardiopulmonary bypass, respectively, in all patients. Patients were well matched for all preoperative variables, including established transfusion risk factors. Subsequent hemodynamic parameters, pressor requirements, and fluid requirements were equivalent in the two groups. RESULTS: The lowest hematocrit value during cardiopulmonary bypass was 22% +/- 3% versus 20% +/- 3% in patients subjected to retrograde autologous priming and in control patients, respectively (p = 0.002). One (3%) of 30 patients subjected to retrograde autologous priming had intraoperative transfusion, and seven (23%) of 30 control patients required transfusion during the operation (p = 0.03). The number of patients receiving any homologous red cell transfusions in the two groups during the entire hospitalization was eight of 30 (27%; retrograde autologous priming) versus 16 of 30 (53%; control) (p = 0.03). CONCLUSIONS: These data suggest that retrograde autologous priming is a safe and effective means of significantly decreasing hemodilution and the number of patients requiring red cell transfusion during cardiac operations.

Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart.

OBJECTIVES: Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, can be delivered to targeted tissues by means of a replication-deficient adenovirus (Ad) vector. We hypothesized that direct administration of Ad vector expressing the VEGF121 complementary deoxyribonucleic acid (AdGVVEGF121.10) into regions of ischemic myocardium would enhance collateral vessel formation and improve regional perfusion and function. METHODS: Yorkshire swine underwent thoracotomy and placement of an Ameroid constrictor (Research Instruments & MFG, Corvallis, Ore.) on the circumflex coronary artery. Three weeks later, myocardial perfusion and function were assessed by single photon emission computed tomography imaging (SPECT) with 99mTc-labeled sestamibi and by echocardiography during rest and stress. AdGVVEGF121.10 (n = 7) or the control vector, AdNull (n = 8), was administered directly into the myocardium at 10 sites in the circumflex distribution (10(8) pfu/site). Four weeks later, these studies were repeated and ex vivo angiography was performed. RESULTS: SPECT imaging 4 weeks after vector administration demonstrated significant reduction in the ischemic area at stress in AdGVVEFG121.10-treated animals compared with AdNull control animals (p = 0.005). Stress echocardiography at the same time demonstrated improved segmental wall thickening in AdGVVEGF121.10 animals compared with AdNull control animals (p = 0.03), with AdGVVEGF121.10 animals showing nearly normalized function in the circumflex distribution. Collateral vessel development assessed by angiography was also significantly greater in AdGVVEGF121.10 animals than in AdNull control animals (p = 0.04), with almost complete reconstitution of circumflex filling in AdGVVEGF121.10 animals. CONCLUSIONS: An Ad vector expressing the VEGF121 cDNA induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardial perfusion and function. Such a strategy may be useful in patients with ischemic heart disease in whom complete revascularization is not possible.

Risk analysis of primary versus reoperative coronary artery bypass grafting.

Reoperative coronary artery bypass grafting is being performed with increasing frequency, in part as a function of the increasing pool of patients who have undergone initial coronary artery bypass grafting and in part because of the natural progression of atherosclerosis. The great majority of patients require reoperation because of graft atherosclerosis or because of a combination of graft and native-vessel disease. Significant risk factors for reoperation include the lack of an internal mammary artery graft or incomplete revascularization at the time of the primary operation, age, and New York State Heart Association classification. Despite an increasing experience with reoperations, operative mortality remains high, approximately three to five times that of initial bypass operation. Similarly, reoperations are associated with increased morbidity, including increased rates of bleeding and low output states. Specific problems encountered at reoperation include graft atherosclerosis, progression of native-vessel disease, and a significant increase in perioperative bleeding. Bypass ischemic times tend to be longer. The use of retrograde cardioplegia and blood conservation programs may prove to be effective solutions for these problems. If perioperative results can be improved, it would appear that the long-term outlook for these patients is reasonably good.

Repair of atrial septal defect through a right thoracotomy.

Fifty-four patients underwent repair of atrial septal defects through a right thoracotomy between January 1985 and December 1991. The average patient was 5.7 years old. Defects repaired included 51 secundum, 2 sinus venosus, and 1 ostium primum defect. The average bypass time was 24 minutes. There was no operative or late mortality, and no morbidity directly related to the thoracotomy approach. The right thoracotomy incision is a safe and effective alternative to a median sternotomy for repair of atrial septal defects. The cosmetic result is superior to that of median sternotomy or bilateral submammary incision.

Operative strategies for resection of pulmonary sarcomas extending into the left atrium.

Pulmonary sarcomas may extend into the left atrium through the pulmonary veins, requiring the use of cardiopulmonary bypass for resection. The operative strategy for these complicated resections must account for the laterality of the tumor, the extent of atrial involvement, the severity of local invasion within the hemithorax, and intrinsic surgical heart disease, if present. We discuss these issues using an illustrative case of a patient with a right pulmonary sarcoma extending from the lateral chest wall into the left atrium.

Heparin-induced thrombocytopenia and thrombosis: presentation after cardiopulmonary bypass.

Heparin-induced thrombocytopenia and thrombosis syndrome was diagnosed in a 63-year-old woman 11 days after coronary artery bypass grafting. Her only presenting complaints were incisional leg pain and vague chest discomfort. The syndrome was suspected when her platelet count was found to be 37,000/microL. A subsequent ventilation-perfusion lung scan showed findings highly probable for pulmonary embolism. An inferior venacavogram obtained before a pulmonary angiogram revealed a large retrohepatic thrombus at the right atrial junction. The patient was successfully treated with the defibrinogenating agent ancrod (Arvin). A diagnosis of heparin-induced thrombocytopenia and thrombosis syndrome should be considered and heparin therapy should be avoided in patients with low platelet counts who have been previously treated with heparin.

Multiple primary lung carcinomas: prognosis and treatment.

From 1955 to 1990, 111 patients have been treated for multiple primary lung carcinomas. Criteria for diagnosis were: (1) different histology (n = 44); or (2) same histology, but disease-free interval at least 2 years (n = 39), origin from carcinoma in situ (n = 19), or metachronous disease in different lobe (n = 9) with no cancer in common lymphatics or extrapulmonary metastasis at the time of diagnosis. The second cancer was synchronous in 33 patients (30%) and metachronous in 78 (70%). Metachronous disease developed at a median interval of 48 months. Five-year survival for patients with metachronous and synchronous disease from the time of initial diagnosis of cancer was 70% and 44%, and 10-year survival was 42% and 23%, respectively. Survival after the development of a metachronous lesion was 23% at 5 years. Survival from the time of initial diagnosis was significantly better for metachronous versus synchronous, late (24 month disease-free interval) versus early metachronous disease, and adenocarcinoma versus epidermoid carcinoma. The first cancer was completely resected in 103 patients (93%), but complete resection of a metachronous tumor was possible in only 54 patients (69%). Complete resection of second primary cancers resulted in significantly (p less than 0.0001) prolonged 5-year survival compared with incomplete resection (38% versus 9%). Excluding patients requiring pneumonectomy, initial resection limited subsequent resection in only 7 patients (9%) with metachronous disease. We conclude that patients surviving treatment of primary lung cancers require lifelong screening for multiple primary lung carcinoma, and complete resection is recommended whenever possible.

Surgical repair of aorto-right ventricular tunnel in an infant.

A rare case of aorta to right ventricle tunnel with associated pulmonary stenosis was corrected on cardiopulmonary bypass in a 3-month-old infant. Both the aortic and ventricular openings were closed with a patch. Although the repair was successful and the child was discharged from the hospital, septicemia developed and she died later. Early repair of this defect is recommended.

The history of surgery for ischemic heart disease.

Myocardial revascularization had its beginnings in the early 1900s with extracardiac operations, such as sympathetic denervation and thyroid ablation. From there it evolved through neovascularization via pericardial poudrage and cardiopexy in the 1930s to 1950s, to mammary artery myocardial implantation in the 1940s and endarterectomy in the 1950s, to saphenous vein- and mammary artery-coronary artery bypass grafting in the 1960s. The history of the surgical treatment of myocardial ischemia is presented here in chronologic sequence to highlight the prescient thinking and the persistence of efforts, as well as the false starts and the rediscovery of old ideas, that have marked the development of this treatment.

Recurrent systemic embolization caused by aortic thrombi.

The aorta is a commonly unrecognized source of systemic embolization. Transesophageal echocardiography is a reliable method for visualization of the intima of the thoracic aorta and identification of aortic thrombi. Balloon embolectomy of the aorta can be used to remove thrombi and prevent further embolic events.

Combined aprotinin and erythropoietin use for blood conservation: results with Jehovah's Witnesses.

Despite recent advances in blood conservation techniques, major risks persist for excessive bleeding and blood transfusion after open heart operations. We reviewed the records of 100 consecutive patients undergoing first-time coronary artery bypass grafting at our institution to define these risks and develop a multimodality blood conservation program based on the results. This program was subsequently applied on a prospective basis to a select group of patients who refuse blood transfusion on religious grounds (Jehovah's Witnesses [JW]) (n = 15). Encouraging initial results with coronary artery bypass grafting in this group (n = 8) led to the application of the program to more complex operations (n = 7), including repeat bypass grafting with use of the internal mammary artery, repeat mitral valve replacement, aortic and mitral valve replacement with coronary artery bypass grafting, mitral valve replacement with bypass grafting, chronic type 1 dissection repair, aortic valve replacement, and atrial septal defect repair in 1 patient each. The blood conservation program employed in these patients included the use of (1) aprotinin (full Hammersmith regimen), (2) high-dose erythropoietin, (3) "maximal"-volume intraoperative autologous blood donation, (4) low-prime cardiopulmonary bypass, (5) exclusive use of intraoperative cell salvage, and (6) continuous reinfusion of shed mediastinal blood. There were no deaths in the JW group. Thromboembolic complications consisted of a transient posterior circulation stroke in only 1 patient (dissection repair). No blood or blood products were transfused compared with the transfusion of 5.1 +/- 7.8 units (mean +/- standard deviation) in the 100 primary coronary bypass patients in whom the blood conservation program was not employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone-induced complications after cardiac operation for obstructive hypertrophic cardiomyopathy.

The occurrence of unanticipated and seemingly unexplicable major complications of hepatic, pulmonary, and cardiac dysfunction after palliative operation for obstructive hypertrophic cardiomyopathy prompted a review of 71 sequential patients. Fifty-five patients had been treated preoperatively with beta-blockers, calcium-channel inhibitors, or both, and 16 had received amiodarone for six to 566 days (mean time, 210 days) at total doses ranging from 8 to 175 g (mean dose, 82 g) and had drug-free intervals prior to operation of zero to 457 days (mean time, 91 days). Comparisons were made between the two treatment groups and between those with and without major complications within the amiodarone-treated group. Preoperative cardiac studies, sex, age, functional class, and type of operation were not related to outcome for the entire patient cohort. In amiodarone-treated patients, the major findings were as follows: a 50% incidence of hepatic dysfunction with a tenfold increase in concentrations of serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase; a 25% incidence of pulmonary dysfunction necessitating a fourfold increase in the number of days of ventilator support; and a 19% incidence of low cardiac output syndrome with two deaths. Only 44% of the amiodarone-treated group had no serious complications. The incidence of major complications of the liver, lungs, and heart was 2%, 0%, and 2%, respectively, in patients not treated with amiodarone. Abnormal preoperative pulmonary function studies were predictive of prolonged postoperative ventilatory support. Discontinuation of amiodarone for several months prior to operation appeared to reduce the incidence of major complications. The necessary drug-free interval required preoperatively could not be determined from this retrospective experience.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct in vivo gene transfer to canine myocardium using a replication-deficient adenovirus vector.

BACKGROUND: Direct myocardial gene transfer is a mordality that involves the introduction of genetic information into myocardial tissue to achieve a therapeutic effect. This study was designed to characterize the temporal and spatial limits of gene expression and to determine the safety of direct myocardial gene transfer in a large animal model using replication-deficient adenovirus vectors. METHODS: Mongrel dogs underwent left thoracotomy and direct myocardial injections (100 microL/injection) of adenovirus vectors (10(9) pfu) carrying the DNA for the reporter enzyme chloramphenicol acetyl transferase or the angiogenic protein vascular endothelial growth factor. Two to 14 days after vector administration, regional protein expression was evaluated in myocardium and distant organs. Left ventricular function, assessed by echocardiography, and routine hematologic and biochemical indices were evaluated before and after vector administration. RESULTS: Peak levels of chloramphenicol acetyl transferase activity were detected 2 days after vector administration, and levels above baseline persisted for at least 14 days. Local chloramphenicol acetyl transferase activity was detected at distances at least as far as 1.5 cm from the site of injection. Chloramphenicol acetyl transferase activity in distant organs was less than 0.1% of that in injected myocardium 7 days after vector administration. Localized expression of vascular endothelial growth factor was achieved for up to 7 days after a single vector administration. Cardiac function and laboratory values were unchanged during the study. CONCLUSIONS: Adenovirus-mediated direct myocardial gene transfer can be accomplished safely in a large animal model, providing high levels of protein expression in a greater spatial distribution than previously reported, with minimal transfection of distant organs. Sustained and localized expression of a potent angiogenic mediator has been accomplished, which may provide an innovative strategy to stimulate angiogenesis in ischemic myocardium.

Outcome analysis of 245 CarboMedics and St. Jude valves implanted at the same institution.

BACKGROUND: Thromboembolism and valve-related death are major complications associated with prosthetic valve implants, but it is difficult to evaluate the relative incidence of these complications based on studies in which the implantation of only one valve is reported from any given institution. We therefore report the outcome of patients implanted at our institution during the same time period with either the recently released CarboMedics (CM) or the St. Jude Medical (SJ) valve prostheses. METHODS: Between October 1994 and January 1996, 245 consecutive patients received either SJ (116 patients) or CM (129 patients) valves at our institution. Follow up of these patients was 99.6% complete, for a total of 318.5 cumulative patient-years (median follow-up, 1.4 years). RESULTS: The 30-day mortality rates for SJ and CM implants were 3.4% and 3.1%, respectively. Actuarial survival and freedom from valve related mortality rates at 1.5 years for SJ and CM valves were 94%+/-2% versus 86%+/-3% (p = 0.03) and 100% versus 94%+/-2% (p = 0.005), respectively. There was no structural valve failure for either implant, but there were five thrombosed valves in the CM group and none in the SJ group (p = 0.04). All thrombosed valves were mitral (four mitral valve replacement, one aortic and mitral valve replacement). Two of the thrombosed valves were successfully explanted, whereas the three remaining patients died. Freedom from a thromboembolic event in the mitral position at 1.5 years, including thrombosed valves was 97%+/-3% and 83%+/-5% for SJ and CM valves, respectively (p = 0.04). CONCLUSIONS: The results of this study suggest that further evaluation of thromboembolic outcomes after CM compared with SJ valve implantation is warranted.