Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system.

BACKGROUND: A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). METHODS: After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema). RESULTS: Our results showed a significant improvement in gas exchange [elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03)] in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin-eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control. CONCLUSIONS: These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.

Brain stem death induces pro-inflammatory cytokine production and cardiac dysfunction in sheep model.

INTRODUCTION: Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-h ovine model of BSD. METHODS: Twelve healthy female sheep (37-42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 h. Plasma and BAL endothelin-1 and cytokines (IL-1ß, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma. RESULTS: Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 h post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1 × 109 cells/L [95% confidence interval (CI) 2.06-4.14] vs. 6 × 109 cells/L [95%CI 3.92-7.97]; p < 0.01) and BAL (4.5 × 109 cells/L [95%CI 0.41-9.41] vs. 26 [95%CI 12.29-39.80]; p = 0.03) after 6 h of BSD induction vs baseline. A significant increase in ANP production (20.28 pM [95%CI 16.18-24.37] vs. 78.68 pM [95%CI 53.16-104.21]; p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 [95%CI 2.69-5.83] ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 h. CONCLUSIONS: BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.

Bronchiolitis obliterans syndrome and survival following lung transplantation for patients with sarcoidosis.

BACKGROUND: End-stage sarcoidosis is characterized by severe pulmonary fibrosis and is often poorly responsive to medical therapy. Lung transplantation, therefore, may be the only treatment option. Currently, there are few studies evaluating long-term outcomes following transplantation for these patients. Our aim was to evaluate post-transplant morbidity and survival of patients with sarcoid compared to recipients transplanted for idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively examined 300 lung transplant recipients using a dedicated database. Over a 10-year period, 15 (5.0%) patients with sarcoidosis and 48 (16%) patients with IPF were identified. Primary outcome measures included rate and time to onset of bronchiolitis obliterans syndrome (BOS) and survival. RESULTS: Recipients in the sarcoid group were younger and predominantly female compared to recipients in the IPF group. Five of 15 (33%) sarcoid patients developed BOS versus 15 of 48 (31%) IPF patients (p=1.0). There was no significant difference in the time to BOS onset. Median survival was 1,365 days for the sarcoid group and 1,593 days for the IPF group (Hazard Ratio 0.94 by Kaplan-Meier analysis; [95% CI] 0.33-2.67; p = 0.90). CONCLUSIONS: We observe similar long term outcomes following lung transplantation for sarcoid and IPF recipients. Transplantation remains a treatment option for end-stage sarcoidosis, as BOS and survival rates are comparable to IPF.

Analysis of morbid events and risk factors for death after cardiac transplantation.

Risk factors for death after cardiac transplantation performed at the University of Alabama at Birmingham from January 1981 to July 1985 included (by multivariate analysis) higher calculated preoperative pulmonary vascular resistance (early and constant phases), morphology of cardiomyopathy (versus ischemic heart disease) (constant phase only) and black race (constant phase). Overall actuarial survival was 71% at 1 year and 48% at 3 years (including azathioprine and cyclosporine eras). The hazard function for death was highest immediately after operation and declined rapidly thereafter, merging with a constant phase of risk at about 3 months. The most favorable group for long-term survival was the group of white patients with ischemic heart disease and low pulmonary vascular resistance. When such patients had a pulmonary vascular resistance less than 3 units.m2, the 3 year survival rate exceeded 85%. The most common causes of death were acute rejection (24%) and infection (17%). The risk of infection remained highest during the first several months after any period of augmented immunosuppression.

Comparison of endocardial and epicardial programmed stimulation for the induction of ventricular tachycardia.

Twenty-seven patients who had pairs of stainless steel wire electrodes placed on the right and the left ventricle during cardiac surgery underwent both epicardial and endocardial programmed ventricular stimulation to assess the inducibility of ventricular tachycardia. Twenty-six of the patients had coronary artery disease and were studied to evaluate map-guided surgery for treatment of ventricular arrhythmias. Burst ventricular pacing and up to three ventricular extrastimuli coupled to two drive train cycle lengths were delivered from the right and left ventricular epicardial wire electrodes and from endocardial catheter electrodes placed at the apex and outflow tract of the right ventricle. Ventricular tachycardia was reproducibly induced in three patients by both endocardial and epicardial stimulation. In one patient ventricular tachycardia was reproducibly induced by epicardial stimulation, but nonreproducible, nonsustained ventricular tachycardia was induced by endocardial stimulation. Ventricular tachycardia remained inducible by both endocardial and epicardial stimulation in three instances (two patients) during drug therapy. A negative study (less than 10 consecutive ventricular beats induced) was obtained in 23 patients by both endocardial and epicardial stimulation. The patients were followed up for 12 to 43 months (average 31). Sudden death or documented ventricular tachycardia occurred in two of the three patients with a positive study by both endocardial and epicardial stimulation. Nineteen (83%) of the 23 patients with concordantly negative studies remained free of arrhythmias. On the basis of concordant results of endocardial and epicardial stimulation (p = 0.001) these results suggest that epicardial stimulation of the right and the left ventricle is an acceptable method to assess the postoperative inducibility of ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring the bioenergetics of cardiac allograft rejection using in vivo P-31 nuclear magnetic resonance spectroscopy.

Monitoring human cardiac allograft rejection is currently accomplished by endomyocardial biopsy. Available noninvasive methods for identifying rejection have lacked the necessary sensitivity or specificity, or both, for routine clinical application. In vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy has been used for monitoring phosphorus metabolism in both animal models and humans. In the present study this technique was employed as a noninvasive means to assess the bioenergetic processes that occur during cardiac allograft rejection in a rat model. Brown Norway rat hearts were transplanted subcutaneously into the anterior region of the neck of Lewis rat recipients (allografts). Control isografts employed Lewis donors and recipients. Phosphocreatine to inorganic phosphate (PCr/Pi), phosphocreatine to beta-adenosine triphosphate (PCr/ATP beta), beta-adenosine triphosphate to inorganic phosphate (ATP beta/Pi) ratios and pH of the transplanted hearts were monitored using surface coil P-31 NMR spectroscopy (at 4.7 tesla) daily for 7 days. To allow recovery from the compromise induced by the surgical procedure, the measurements obtained on day 2 were taken as a baseline. PCr/Pi was unchanged or increased in the isografts but decreased continually in allografts, with the difference becoming significant by day 4 when compared with levels in day 2 allografts (p less than 0.005) and by day 3 when compared with levels in the isograft group (p less than 0.05). PCr/ATP beta in isografts did not change throughout the study; however, allografts demonstrated a significant decrease as early as day 3 (p less than 0.01), although a significant difference between isografts and allografts did not become manifest until day 4 (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteritis in cardiac rejection after transplantation.

During a 4-year experience with cardiac transplantation, 33 hearts were obtained by autopsy or surgical resection for retransplantation. Arteritis was a feature common to all rejected hearts (14 of 14), but was absent in explanted hearts without rejection (0 of 19) (p = 0.001). Monitoring of acute cardiac rejection by endomyocardial biopsy (863 biopsies) was also reviewed, with special reference to the incidence of arteritis. Among the 16 patients with arteritis on 1 or more biopsies, 44% (7 patients, confidence limits 29 to 60%) suffered fatal rejection or underwent retransplantation because of irreversible rejection. Arteritis was seen in the small vessels obtained by endomyocardial biopsy in 4 of 5 persons who underwent biopsy within 3 days of death or retransplantation due to rejection and on none of the 6 persons who underwent biopsy within 3 days of death or retransplantation for causes other than rejection. Thus, arteritis is an important indicator for severe acute rejection, and although often reversible, may identify patients at higher risk for fatal rejection. Arteritis occurred in transplanted hearts subjected to varying combinations of cyclosporine, azathioprine and steroid therapy and could not be correlated with any drug regimen.

A comparison of aortic valve replacement with viable cryopreserved and fresh allograft valves, with a note on chromosomal studies.

We examined the long-term clinical function and fate of allograft aortic valves, preserved by two differing methods, for aortic valve replacement: (1) fresh allografts stored at 4 degrees C refrigeration (group I) and (2) viable allografts cryopreserved in liquid nitrogen at -196 degrees C (group II). A total of 316 aortic valve replacement operations were performed, 124 in group I (December 1969 to May 1975) and 192 in group II (June 1975 to December 1986). Concomitant surgical procedures (eg, coronary artery bypass grafting and mitral valve replacement) were necessary in 120 operations. The overall immediate 30 day mortality was 6.0% (confident limits 4.6% to 7.7%), and the survival rates were 83% at 4 years and 60% at 15 years. Endocarditis and technical factors concerning reoperation showed no difference between the two groups according to parametric estimates and hazard function analyses. However, there was a marked difference in reoperation for valve degeneration: 23 patients in group I and 0 patients in group II. The freedom from reoperation for valve degeneration at 10 years was 89% for group I and 100% for group II, and at 15 years it was 59% for group I. The hazard function for group I reflected the late rising risk of degeneration. The freedom from thromboembolism of both groups (aortic valve replacement with or without bypass grafting) was 97% at 10 years and 96% at 15 years. Group II explanted valves (operation for technical malalignment reasons) has consistently shown evidence of persisting viability on tissue culture, on metabolic studies, and on histologic appearances. Chromosomal studies have shown the donor origin of these cells. The superior results with the cryopreserved valve is considered to be due to persisting viability, which appears to be the key to durability.

Aortic wall stress profile after repair of coarctation of the aorta. It is related to subsequent true aneurysm formation?

UNLABELLED: True aneurysm formation at the site of coarctation repair has been increasingly recognized after synthetic patch aortoplasty. A mathematical model was developed to determine the aortic wall stress profile after coarctation repair with this technique. METHODS: A two-dimensional nonlinear mathematical model and a three-dimensional finite element model were developed for different physiologic, geometric, and materials properties variables, which were incorporated into an idealized coarctation repair. RESULTS: The models demonstrated that the major variable affecting stress levels in the aortic wall after coarctation repair was the patch geometry. If the patch was allowed to balloon out, the aortic wall stress increased out of proportion to the increase in aortic diameter because of nonlinear effects. The maximal aortic wall stress concentration occurred opposite the patch. Patch stiffness was also an important variable, with a lower stiffness (subclavian flap repair) leading to a higher aortic wall stress for the same patch geometry as a synthetic patch repair. Inferences: Development of true aneurysms after coarctation repair by synthetic patch aortoplasty is likely to result from excessive aortic wall stress due to patch geometry.

Have the results of mitral valve replacement improved?

To test the contention that the results of cardiac surgery are better in recent years, we analyzed patients undergoing isolated or combined mitral valve replacement in an earlier era (1975 to July, 1979; n = 478) and a later era (July, 1979, to July, 1983; n = 341). Patients in the later era were older, had a higher left ventricular end-diastolic pressure, and a higher prevalence of ischemic mitral valve disease and a lower one of rheumatic mitral disease. Patients operated on in the later era had, on the average, longer and more extensive operations. Patients in the later era had a slightly but inconclusively lower 2 week and 4 1/2 year survival rate than those in the earlier era; their hazard functions were similar. A higher proportion of the deaths in the later era than in the earlier era were due to chronic heart failure. However, neither the era nor the specific year in which a patient was operated on was a risk factor for death in a multivariate analysis. By contrast, in many subsets of patients with congenital and ischemic heart disease, the risks have been shown to be lower in the current era. Continuing delay in advising mitral valve replacement and imperfections in the methods for myocardial protection are probably responsible for this lack of improvement across time.

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.

Cardiac transplant coronary artery disease. A multivariable analysis of pretransplantation risk factors for disease development and morbid events.

Coronary artery disease after cardiac transplantation is a major obstacle to long-term survival. The development and progression of coronary artery disease after cardiac transplantation was analyzed in 217 consecutive patients undergoing transplantation. The actuarial freedom from any coronary artery disease (by angiography or autopsy) was 81% at 2 years and 20% at 8 years after transplantation. Coronary artery disease was more prevalent in male than female patients (30% versus 50% free of coronary artery disease at 5 years, p = 0.01). By multivariable analysis, pretransplantation risk factors identified for coronary artery disease included pretransplantation positive cytomegalovirus serologic status of the recipient (p = 0.002) and older donor age (p = 0.07). Progression of coronary artery disease was variable in both time of onset and rate. Earlier detection did not result in more rapid progression. Coronary events severe enough for retransplantation (n = 8) and/or death from coronary artery disease (n = 9) occurred in 15 patients, of whom four underwent retransplantation. The actuarial freedom from coronary events was 88% at 5 years and 79% at 8 years. By multivariable analysis, only male recipient (p = 0.05) was a risk factor for coronary events. Seven of the 15 patients (47%) with coronary events died suddenly of coronary artery disease without prior angiographic evidence of severe coronary disease. Coronary artery disease is progressive. Improved surveillance methods are required to detect the disease and institute timely intervention to prevent the occurrence of unanticipated death.

An analysis of valve re-replacement after aortic valve replacement with biologic devices.

Biologic valve re-replacement was examined in a series of 1343 patients who underwent aortic valve replacement at The Prince Charles Hospital, Brisbane, with a cryopreserved or 4 degrees C stored allograft valve or a xenograft valve. A parametric model approach was used to simultaneously model the competing risks of death without re-replacement and re-replacement before death. One hundred eleven patients underwent a first re-replacement for a variety of reasons (69 patients with xenograft valves, 28 patients with 4 degrees C stored allograft valves, and 14 patients with cryopreserved allograft valves). By multivariable analysis younger age at operation was associated with xenograft, 4 degrees C stored allograft, and cryopreserved allograft valve re-replacement. However, this effect was examined in the context of longer survival of younger patients, which increases their exposure to the risk of re-replacement as compared with that in older patients whose decreased survival reduced their probability of requiring valve re-replacement. In patients older than 60 years at the time of aortic valve replacement, the probability of re-replacement (for any reason) before death was similar for xenografts and cryopreserved allograft valves but higher for 4 degrees C stored valves. However, in patients younger than 60 years, the probability of re-replacement at any time during the remainder of the life of the patient was lower with the cryopreserved allograft valve compared with the xenograft valve and 4 degrees C stored allografts.

Intrapulmonary shunting in primary pulmonary hypertension: an observation in two patients treated with epoprostenol sodium.

Continuous intravenous infusion of epoprostenol sodium in selected patients with primary pulmonary hypertension improves symptoms and survival. This report describes two patients with primary pulmonary hypertension treated with epoprostenol in whom intrapulmonary shunting and severe hypoxemia occurred. Intrapulmonary shunting was confirmed by contrast echocardiography showing delayed appearance of bubbles in the left cardiac chambers after peripheral venous injection of agitated saline solution.

The effect of synthetic patch repair of coarctation on regional deformation of the aortic wall.

BACKGROUND: A long-term complication of synthetic patch repair of coarctation is true aneurysm formation. AIM: An in vitro study was undertaken to determine the effects of patch angioplasty on aortic geometry and strain adjacent to the patch. METHODS: Segments of human descending thoracic aorta were subject to 10 pressure loading cycles (10-120 mm Hg; 1.36-16.32 kPa) before and after simulated coarctation repair with a synthetic patch. Local curvature and strain were estimated by fitting a geometric model to reconstructed three-dimensional surface marker points. RESULTS: In the control aortas, when pressure increased from 11 +/- 1.0 to 124 +/- 4.0 mm Hg (1.5 +/- 0.14 to 16.86 +/- 0.54 kPa), average circumferential curvature decreased from 0.1543 +/- 0.03 to 0.1065 +/- 0.03 mm(-1). The average major extension reached a maximum of 1.43 +/- 0.08. After patch implantation, the average circumferential curvature was reduced relative to control at all pressures. Average major extensions were significantly greater than paired control values and reached a maximum of 1.55 +/- 0.08 at 122 +/- 4.0 mm Hg (16.59 +/- 0. 54 kPa). Substantial strain inhomogeneity was observed and major extensions were greatest immediately adjacent to the patch. INFERENCE: Synthetic patch repair of coarctation of the aorta increases wall strain and produces significant regional gradients in strain. With control aortic material properties there may be a substantial increase in wall stress immediately adjacent to the aorta, which could lead to true aneurysm formation.

Prophylactic value of preincision intra-aortic balloon pump: analysis of a statewide experience.

OBJECTIVE: The objective of this study was to determine whether preincision use of an intra-aortic balloon pump improves survival and shortens postoperative length of stay in hemodynamically stable, high-risk patients undergoing coronary artery bypass grafting. METHODS: A post hoc analysis of the Alabama CABG Cooperative Project database was performed by using propensity scores to model the likelihood of receiving a prophylactic preincision intra-aortic balloon pump. Every patient receiving a prophylactic preincision balloon pump was matched with another patient of similar propensity score who did not receive one. We then compared outcomes for matched pairs. RESULTS: There were 7581 patients of whom 592 received a prophylactic preincision balloon pump. Patients with preoperative renal insufficiency, heart failure, or left main coronary artery disease, or who had undergone previous bypass grafting were significantly more likely to receive a prophylactic preincision balloon pump. By using propensity scores, we matched 550 patients who received a prophylactic preincision balloon pump with 550 who did not. Survival did not significantly differ by whether a prophylactic preincision balloon pump was used. However, surviving patients who received a preincision balloon pump had a significantly shorter postbypass length of stay (7 +/- 7.3 days) than did matched patients not receiving a balloon pump (8 +/- 6.2 days; P <.05). CONCLUSIONS: No survival advantage was found for use of a prophylactic intra-aortic balloon pump in hemodynamically stable, high-risk patients undergoing bypass grafting, as opposed to placing a balloon pump on an "as needed" basis during or after the operation. However, the patients receiving the balloon pump had improved convalescence as shown by significantly shorter length of stay.

Aortic valve infection. Risk factors for death and recurrent endocarditis after aortic valve replacement.

Patients (n = 195) undergoing aortic valve replacement (n = 209) for native or prosthetic valve endocarditis were studied to determine risk factors for death and recurrent endocarditis and also to determine the valve type least likely to be associated with recurrent endocarditis. Ten-year survival was 60%, the highest risk of dying occurring within the first 3 postoperative months. Risk factors for death in this early phase included increased urea concentration, higher New York Heart Association functional class, prosthetic valve endocarditis, infection status (lower in patients with healed endocarditis), longer duration of cardiopulmonary bypass, and nonuse of an allograft valve. In the late phase (beyond 3 months), risk factors included age at operation and Staphylococcus aureus infection (only in New York Heart Association functional class V). Ten years after aortic valve replacement, 79% of valves were free of recurrent endocarditis. The highest risk of recurrence was in the first 4 months. Longer duration of cardiopulmonary bypass was a weak risk factor for recurrent endocarditis in the early phase, and in the late phase risk factors were S. aureus infection (only in New York Heart Association functional classes III, IV, and V) and the use of now discontinued biologic valves. Allograft aortic valve replacement was shown to be associated with a low and constant risk of recurrent endocarditis, whereas other valve types were associated with a high early risk. The allograft valve should be the preferred replacement device for aortic root infection.

Evolving trends in risk profiles and causes of death after heart transplantation: a ten-year multi-institutional study.

BACKGROUND: As therapeutic options evolve for advanced heart failure, the appropriate role for cardiac transplantation will require survival analyses that reflect changing trends in causes of death and patient and institutional risk profiles. Results from multi-institutional studies could be used to monitor progress in individual centers. METHODS: Between 1990 and 1999, 7290 patients undergoing cardiac transplantation in 42 institutions entered a formal outcomes study. Changing survival, causes of death, and patient risk profiles were analyzed. Multivariable risk-factor equations were applied to a single institution (300 primary heart transplants) to examine differences in risk-adjusted expected versus observed actuarial outcomes over time. RESULTS: Overall survival in the 42 institutions improved during the decade (P =.02). One- and 3-year cardiac transplant research database survival was as follows: era 1 (1990-1992), 84% and 76%, respectively; era 2 (1993-1995), 85% and 79%, respectively; and era 3 (1996-1999), 85% and 79%, respectively. Causes of death changed over time. Pretransplantation risk profiles increased over time (P =.0001), with increases in reoperations, devices, diabetes, severely ill recipients, pulmonary vascular resistance, sensitization, ischemic times, donor age, and donor inotropic support. Three-year actuarial survival in a single institution was 3% less than risk-adjusted predicted survival in era 1, 1% higher than predicted in era 2, and 7% higher than predicted in era 3. CONCLUSIONS: Survival after cardiac transplantation is gradually improving, despite increasing risk profiles. Further improvement requires periodic re-evaluation of risk profiles and causes of death to target areas of surveillance, therapy, and research. By using these methods, progress at individual institutions can be assessed in a time-related, risk-adjusted manner that also reflects changing institutional experience, expertise, or both.

An analysis of risk factors for death and mode-specific death after aortic valve replacement with allograft, xenograft, and mechanical valves.

From September 1967 to January 1990, a total of 2100 patients underwent 2366 aortic valve replacements with a variety of allograft, xenograft, and mechanical valves. Concomitant procedures were performed in 764 patients. Actuarial survival at 12 years was 59.6% (70% confidence limits 57.8% to 61.4%). Hazard function for death was highest immediately after operation, falling to merge with a slowly rising phase of risk at approximately 3 months. Actuarial freedom from sudden death at 12 years was 88.0% (70% confidence limits 86.7% to 89.3%). The shape of the hazard function for sudden death was similar to that for death. Actuarial freedom from death with cardiac failure at 12 years was 87.9% (70% confidence limits 86.5% to 89.2%). The shape of the hazard function for death with cardiac failure was also similar to that for death. Risk factor analysis revealed the important deleterious impact on long-term survival resulting from impaired left ventricular structure and function because of aortic valve disease. No current-era valve used in this study (allograft, xenograft, or mechanical) was a risk factor for death. Both aortic wall disease and endocarditis necessitating aortic valve replacement substantially decreased long-term patient survival. Aortic valve replacement is advisable much earlier in the natural history of aortic valve disease before secondary left ventricular damage occurs.

Competing outcomes after heart transplantation: a comparison of eras and outcomes.

To understand the time relatedness of the various causes of death after heart transplantation, a study was undertaken to examine the relative importance of each of these causes of death across time, as well as between eras. The analysis, which was in the competing outcomes domain, involved 326 patients undergoing primary heart transplantation between November 1981 and June 1994, of which 122 patients died. Two eras were considered--an earlier era (1981 to 1986) and a later era (1987 to 1994). During the later era, the estimated survival rate at 1 year and 5 years was 85% and 69%, respectively. During the first posttransplantation year, patients in the earlier era were three times more likely to die of early graft failure than in the later era, but the difference may have been due to chance (p > 0.2). During the first posttransplantation year, patients were three times as likely to die of acute rejection in the earlier era (p = 0.02). Patients surviving 3 or more years in both eras had a similar (approximately 3%) likelihood of death from coronary artery disease over the ensuing 4 years. In the later era, the risk of dying of malignancy (2.5%), infection (3.2%), or miscellaneous other causes (4.1%) was as likely after 3 years as dying of coronary artery disease (3.2%). Competing outcomes analysis is a useful means of portraying the distribution of multiple time-related causes of death. In the current era, the deleterious long-term effects of immunosuppression (malignancy and infection), as well as coronary artery disease, threaten long-term survival.