Is there a need for surveillance endomyocardial biopsies in heart transplantation?
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Biopsy, Needle↗
Biomedical subjects
D C Naftel
Publications and source records attributed to D C Naftel.
Death after rejection with severe hemodynamic compromise in pediatric heart transplant recipients: a multi-institutional study.
BACKGROUND: Rejection with severe hemodynamic compromise results in high mortality in adult transplant patients. This study determines the incidence, outcome and risk factors for rejection with severe hemodynamic compromise in a multi-institutional study of pediatric heart transplant recipients. METHODS: Data from 847 patients transplanted between 1/1/93 and 12/31/98 at 18 centers in the Pediatric Heart Transplant Study were analyzed. Rejection with severe hemodynamic compromise was defined as a clinical event occurring beyond 1 week postoperatively, which led to augmentation of immunosuppression and use of inotropic therapy. Actuarial freedom from such rejection and death after rejection were determined and risk factors sought. RESULTS: Among 1,033 rejection episodes in 532 patients, 113 (11%) episodes were associated with severe hemodynamic compromise in 95 patients. The highest risk for severe rejection was in the first year. Risk factors were older recipient age (p >.05) and non-white race (p >.001). Survival after an episode was poor (60%), and biopsy score did not affect outcome. Deaths were due to rejection (n = 14), other cardiac causes (n = 17), infection (n = 5), lymphoma (n = 2), pulmonary causes (n = 2), and thrombosis (n = 1). CONCLUSIONS: Rejection with severe hemodynamic compromise occurs in 11% of pediatric patients, irrespective of age, sex or biopsy score, and mortality is high. Non-white race and older recipient age are independent risk factors for rejection with severe hemodynamic compromise. Aggressive treatment and close surveillance should be crucial components of protocols aimed at reducing the high mortality.
Adolescent↗
Cardiac transplant outcome of patients supported on left ventricular assist device vs. intravenous inotropic therapy.
BACKGROUND: Although the left ventricular assist device (LVAD) has been increasingly used as a bridge to transplant, its effect on post-transplant outcome is uncertain. We, therefore, designed this study using the Cardiac Transplant Research Database to compare patients supported on an LVAD before transplant with those treated with intravenous inotropic medical therapy. METHODS AND RESULTS: Of the 5,880 patients transplanted between 1990 and 1997, a total of 502 received support from LVADs and 2,514 received intravenous inotropic medical therapy at the time of transplant. Kaplan-Meier analysis showed no significant difference in post-transplant survival between the LVAD and medical-therapy groups (p = 0.09). Results of a multivariate Cox regression analysis were consistent with that of the Kaplan-Meier analysis and did not identify LVAD as a significant risk factor for mortality. The percentage of patients who received LVADs as a function of total transplants increased from 2% in 1990 to 16% in 1997. Furthermore, although the number of extracorporeal LVADs remained relatively constant, the number of intracorporeal LVADs increased over time. Multivariate parametric analysis found that the risk factors for post-transplant death in the LVAD group were extracorporeal LVAD use (p = 0.0004), elevated serum creatinine (p = 0.05), older donor age (p = 0.03), increased donor ischemic time (p < 0.0001), and earlier year of transplant (p = 0.03). CONCLUSIONS: Given a limited donor supply, the intracorporeal LVAD helps the sickest patients survive to transplant and provides post-transplant outcome similar to that of patients supported on inotropic medical therapy. Therefore, patients supported on LVADs before transplant may receive the greatest marginal benefit when compared with other transplant candidates.
Cardiotonic Agents↗
Long-term performance of heart valve prostheses.
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Animals↗
Replacement of the aortic root in patients with Marfan's syndrome.
BACKGROUND: Replacement of the aortic root with a prosthetic graft and valve in patients with Marfan's syndrome may prevent premature death from rupture of an aneurysm or aortic dissection. We reviewed the results of this surgical procedure at 10 experienced surgical centers. METHODS: A total of 675 patients with Marfan's syndrome underwent replacement of the aortic root. Survival and morbidity-free survival curves were calculated, and risk factors were determined from a multivariable regression analysis. RESULTS: The 30-day mortality rate was 1.5 percent among the 455 patients who underwent elective repair, 2.6 percent among the 117 patients who underwent urgent repair (within 7 days after a surgical consultation), and 11.7 percent among the 103 patients who underwent emergency repair (within 24 hours after a surgical consultation). Of the 675 patients, 202 (30 percent) had aortic dissection involving the ascending aorta. Forty-six percent of the 158 adult patients with aortic dissection and a documented aortic diameter had an aneurysm with a diameter of 6.5 cm or less. There were 114 late deaths (more than 30 days after surgery); dissection or rupture of the residual aorta (22 patients) and arrhythmia (21 patients) were the principal causes of late death. The risk of death was greatest within the first 60 days after surgery, then rapidly decreased to a constant level by the end of the first year. CONCLUSIONS: Elective aortic-root replacement has a low operative mortality. In contrast, emergency repair, usually for acute aortic dissection, is associated with a much higher early mortality. Because nearly half the adult patients with aortic dissection had an aortic-root diameter of 6.5 cm or less at the time of operation, it may be prudent to undertake prophylactic repair of aortic aneurysms in patients with Marfan's syndrome when the diameter of the aorta is well below that size.
Adolescent↗
Gene polymorphisms for plasminogen activator inhibitor-1/tissue plasminogen activator and development of allograft coronary artery disease.
BACKGROUND: Impaired fibrinolytic activity has been linked to the presence and severity of allograft vasculopathy (Tx CAD). This impairment may be associated with the presence of certain fibrinolytic protein gene polymorphisms. METHODS AND RESULTS: To investigate the relation between donor-specific fibrinolytic protein genotypes and Tx CAD, we identified donor plasminogen activator inhibitor-1 (PAI-1) HindIII and tissue plasminogen activator (TPA) EcoRI restriction fragment length polymorphisms-based genotypes by Southern blot analysis in 48 recipients of cardiac allografts and correlated these genotypes with the development of CAD. No association was found between donor TPA genotypes and the presence of Tx CAD. Among the 48 patients, 17% were homozygous for the 1/1 PAI-1 genotype, 51% for the 2/2 PAI-1 genotype, and 32% for the 1/2 PAI-1 genotype. The actuarial freedom from any CAD for the recipients with each respective donor PAI-1 genotype at 12 and 24 months was 100% and 100% for the 1/1 PAI-1 genotype, 92% and 92% for the 1/2 PAI-1 genotype, and 75% and 45% for the 2/2 PAI-1 genotype (P=0.03). Recipients with a diseased 2/2 PAI-1 genotyped allograft had longer ischemic times (P=0.02) than those recipients with a Tx CAD-free allograft. CONCLUSIONS: These data suggest that recipients with a 2/2 PAI-1 genotype are at a significant risk of developing Tx CAD. This genotype may serve as a useful screening tool for predicting the future development of Tx CAD.
Adult↗
A prospective algorithm for the management of air leaks after pulmonary resection.
BACKGROUND: Air leaks (ALs) are a common complication after pulmonary resection, yet there is no consensus on their management. METHODS: An algorithm for the management of chest tubes (CT) and ALs was applied prospectively to 101 consecutive patients who underwent elective pulmonary resection. Air leaks were graded daily as forced expiratory only, expiratory only, inspiratory only, or continuous. All CTs were kept on 20 cm of suction until postoperative day 2 and were then converted to water seal. On postoperative day 3, if both a pneumothorax and AL were present, the CT was placed to 10 cm H2O of suction. If a pneumothorax was present without an AL, the CT was returned to 20 cm H2O of suction. Air leaks that persisted after postoperative day 7 were treated with talc slurry. RESULTS: There were 101 patients (67 men); on postoperative day 1, 26 had ALs and all were expiratory only. Univariable analysis showed a low ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) (p = 0.005), increased age (p = 0.007), increased ratio of residual volume to total lung capacity (RV/TLC) (p = 0.04), increased RV (p = 0.02), and an increased functional residual capacity (FRC) (p = 0.02) to predict the presence of an AL on postoperative day 1. By postoperative day 2, 22 patients had expiratory ALs. After 12 hours of water seal, 13 of the 22 patients' ALs had stopped, and 3 more sealed by the morning of postoperative day 3. However, 2 of the 6 patients whose ALs continued experienced a pneumothorax. Five of the 6 patients with ALs on postoperative day 4 still had ALs on postoperative day 7, and all were treated by talc slurry through the CT. All ALs resolved within 24 hours after talc slurry. CONCLUSIONS: Most ALs after pulmonary resection are expiratory only. A low FEV1/FVC ratio, increased age, increased RV/TLC ratio, increased RV, and an increased FRC were predictors of having an ALs on postoperative day 1. Conversion from suction to water seal is an effective way of sealing expiratory AL, and pneumothorax is rare. If an expiratory AL does not stop by postoperative day 4 it will probably persist until postoperative day 7, and talc slurry may be an effective treatment.
Adult↗
Pretransplantation risk factors for death after heart transplantation: the Henri Mondor experience.
BACKGROUND AND METHODS: Risk factors for death after primary heart transplantation were identified by analyzing our total experience with 234 patients who underwent transplantation at our institution from May 28, 1979, to May 27, 1996. RESULTS: There were 205 male and 29 female patients. Mean recipient age was 48.5+/-10.9 years (standard deviation). Recipient diagnosis included ischemic cardiomyopathy in 103 (44%), idiopathic cardiomyopathy in 98 (42%), valvular heart disease in 17 (7%), congenital heart disease in 4 (2%), and other diagnoses in 12 (5%) patients. Donor age was 32+/-10.2 years. Graft ischemic time was 138.1+/-51.8 minutes. The operative mortality rate was 23.5%. Actuarial survival estimates for all patients at 1, 5, and 10 years were 62%, 50%, and 44%, respectively. The three most common causes of death (both early and late) after primary heart transplantation were infection (27.4%), acute rejection (18.9%), and early graft failure (17.9%). Multivariate logistic regression analysis identified older recipient age (p = 0.007), higher preoperative pulmonary vascular resistance (p = 0.01), recipient preoperative hepatic insufficiency (p = 0.001), and gender mismatch (p = 0.02) as independent predictors of early death (within 3 months of the procedure). Multivariate proportional hazard regression analysis revealed that recipient idiopathic cardiomyopathy (p = 0.02) and recipient preoperative liver failure (p = 0.01) were independent risk factors for late death (after 3 months). CONCLUSION: These results underscore the importance of adequate recipient selection and recipient/donor matching for short- and long-term survival after primary heart transplantation.
Adolescent↗
Risk of death or incapacitation after heart transplantation, with particular reference to pilots.
Pilots who have received a heart transplant may subsequently want to resume flying. This study was undertaken to determine whether a group of heart transplant recipients who had a particularly low risk of sudden unexpected death could be identified from clinical data. An event, "rapid-onset death," was defined incorporating a number of possible causes of death that could result in a heart transplant recipient-pilot losing control of an airplane. The survival of 3676 patients undergoing a first heart transplantation was 85% and 73% at 1 and 5 years, respectively, the hazard function having a high early phase of risk. When time zero was moved to the beginning of the second year after transplantation, the freedom from "rapid-onset death" at posttransplantation year 2 and posttransplantation year 5 was 96.8% and 88%, respectively. For patients who had both a "normal" coronary angiogram and no episodes of acute heart rejection during the first year transplantation, the probability of "rapid onset death" during the second posttransplantation year was 1.4%, and given the same circumstances, during the third posttransplantation year the risk of "rapid-onset death" was 1.6%. This information is potentially useful to the Federal Aviation Administration for policy decisions regarding this issue.
Adolescent↗
Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database.
BACKGROUND: Controversy exists regarding donor and recipient factors that promote the development and progression of coronary artery disease after heart transplantation and the likelihood of coronary artery disease causing death or retransplantation. METHODS: To investigate this issue in a large cohort of patients, we analyzed 5963 postoperative angiograms performed in 2609 of the 3837 patients undergoing heart transplantation at 39 institutions between January 1990 and December 1994. Coronary artery disease was classified as mild, moderate, or severe on the basis of left main involvement, primary vessel stenoses, and branch stenoses. Coronary artery disease was considered severe if left main stenosis was > 70% or 2 or more primary vessels stenoses were > 70% or branch stenoses were > 70% in all 3 systems. RESULTS: By the end of 5 years after heart transplantation, coronary artery disease was present in 42% of the patients, mild in 27%, moderate in 8%, and severe in 7%. Coronary artery disease-related events (death or retransplantation) had an actuarial incidence of 7% at 5 years and occurred in 2 of 3 of the patients with development of angiographically severe coronary artery disease. By multivariable logistic analysis, risk factors for donor coronary artery disease included older donor age (P < .0001) and donor hypertension (P=.0002). By multivariable analysis in the hazard function domain, risk factors identified for the earlier onset of allograft coronary artery disease included older donor age (P < .0001 ), donor male sex (P=.0006), donor hypertension (P=.07), recipient male sex (P=.02), and recipient black race (P=.01). The actuarial incidence of severe coronary artery disease was 9% at 5 years. CONCLUSIONS: Angiographic coronary artery disease is very common after heart transplantation, occurring in approximately 42% of the patients by 5 years. Older donor age, donor hypertension, and male donor or recipient predict earlier onset of angiographic allograft coronary artery disease. Although severe angiographic allograft coronary artery disease occurs in only 7% of the patients at 5 years, its presence is highly predictive of subsequent coronary artery disease-related events or retransplantation.
Adolescent↗
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.
Adolescent↗
Influence of study goals on study design and execution.
From the viewpoint of a clinician who makes recommendations to patients about choosing from the multiple possible management schemes, quantitative information derived from statistical analyses of observational studies is useful. Although random assignment of therapy is optimal, appropriately performed studies in which therapy has been nonrandomly "assigned" are considered acceptable, albeit occasionally with limitations in inferences. The analyses are considered most useful when they generate multivariable equations suitable for predicting time-related outcomes in individual patients. Graphic presentations improve communication with patients and facilitate truly informed consent.
Child↗
Predicting outcome after cardiac transplantations: lessons from the Cardiac Transplant Research Database.
Survival and quality of life after transplantation are limited by posttransplant events such as rejection and infection. The description and subsequent prediction of these and other events is the goal of the Cardiac Transplant Research Database group. This paper provides a description of the purpose, methods of data collection and analysis, and results of the published data from the Cardiac Transplant Research Database. A review of the analyses of death, rejection, and infection is made along with a discussion of the clinical application of these data. Utilizing the data from the Cardiac Transplant Research Database, the clinician may apply established risk factors for posttransplant adverse events to individual patients.
Data Interpretation, Statistical↗
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.
Adolescent↗
Predicting outcome after listing for heart transplantation in children: comparison of Kaplan-Meier and parametric competing risk analysis. Pediatric Heart Transplant Study Group.
After listing for pediatric heart transplantation, at any point in time one of the following possibilities could have occurred; death, transplantation, removal from the list because of clinical improvement, or continuing to wait. In the setting of those competing outcomes, the Kaplan-Meier estimate portrays the time-relatedness of an event while ignoring the effect of the other possible outcomes. The competing outcomes method, however, depicts the time relatedness of an event while solving for all possible events simultaneously. The competing outcomes method may potentially provide more accurate information regarding the actual proportion of patients experience an outcome after listing.
Adolescent↗
The incremental risk of female sex in heart transplantation: a multiinstitutional study of peripartum cardiomyopathy and pregnancy. Cardiac Transplant Research Database Group.
BACKGROUND: Controversy remains regarding the reason females seem to be at increased risk for rejection after heart transplantation. Therefore this study was performed to define the effect of a pretransplantation diagnosis of peripartum cardiomyopathy and the effect of previous pregnancy on the outcome (incidence of rejection and death) of females after heart transplantation. METHODS: In this multiinstitutional study of 3244 adult (greater than 13 years of age) heart transplant recipients, (a) the outcome of 40 females who underwent transplantation for peripartum cardiomyopathy was compared with that of 200 females of childbearing age (13 to 45 years) who underwent transplantation for other indications and (b) the posttransplantation outcome of 543 females with a history of pregnancy was compared with that of 101 nulliparous adult females and 2562 adult males. RESULTS: The posttransplantation outcome of females with a history of peripartum cardiomyopathy was similar to that of females of childbearing age who underwent transplantation for other indications. However, parous females had a significantly shorter time to first rejection (p < 0.0001) and greater cumulative rejection than nulliparous females or males. By multivariable analysis, the risk factors for cumulative rejection at 1 year were a history of pregnancy (p < 0.0001), younger recipient age (p < 0.0001), induction therapy (p < 0.0001), and the number of human leukocyte antigen-DR mismatches (p = 0.007). CONCLUSION: Our data suggest that it is previous pregnancy, and not sex per se, that is associated with an increased frequency of rejection in females after heart transplantation.
Actuarial Analysis↗
Heart transplant rejection with hemodynamic compromise: a multiinstitutional study of the role of endomyocardial cellular infiltrate. Cardiac Transplant Research Database.
BACKGROUND: The natural history of patients experiencing hemodynamic compromise with rejection has been incompletely characterized. This multiinstitutional study examined the outcome of such episodes, particularly with regard to the extent of cellular infiltrate on the index endomyocardial biopsy. METHODS: From January 1, 1990, through June 30, 1994, 3367 patients in the Cardiac Transplant Research Database experienced 4137 episodes of rejection. Severe hemodynamic compromise occurred in approximately 5% of the rejection episodes, and this proportion remained relatively constant over time. RESULTS: Recipient risk factors for rejection with severe hemodynamic compromise included black race, female recipient sex, and diabetes. The 3-month actuarial survival rate was 60% after rejection with severe hemodynamic compromise versus 95% after rejection with no or mild compromise. Low initial biopsy score conferred a higher early survival, but a lower survival at 2 years after rejection with severe hemodynamic compromise. Among patients who survive an initial rejection episode with severe hemodynamic compromise, survival at 2 years after an episode was 46% among those who had a low initial biopsy score versus 84% with a high biopsy score. CONCLUSIONS: Rejection with hemodynamic compromise, although rare, represents a major complication of heart transplantation with a poor long-term outcome. Survivors of hemodynamically compromising rejection episodes associated with low biopsy scores in the International Society for Heart and Lung Transplantation grading system have a significantly worse long-term outcome than survivors of episodes associated with high scores. These findings suggest that immunologic mechanisms other than lymphocytic infiltration of the cardiac allograft are important and distinct causes of allograft dysfunction.
Actuarial Analysis↗
Serial measurements of interleukin-6, interleukin-8, tumor necrosis factor-alpha, and soluble vascular cell adhesion molecule-1 in the peripheral blood plasma of human cardiac allograft recipients.
BACKGROUND: Cardiac allograft rejection is largely an inflammatory response that, if allowed to proceed unchecked, will result in hemodynamic compromise or cardiogenic shock. Soluble mediators produced during an inflammatory response could potentially provide information regarding the initiation, progression, and outcome of a rejection episode. To test this hypothesis, we investigated the use of plasma cytokine measurements for interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF alpha) in combination with measurements of soluble vascular cell adhesion molecule-1 (VCAM-1), an adhesion molecule, as a means for the detection of cardiac allograft rejection. METHODS: Serial enzyme-linked immunosorbent assays were performed on plasma samples collected from 29 patients three times per week during the first 8 weeks after transplantation. RESULTS: IL-6 plasma concentrations increased fivefold in the first week after transplantation (p < 0.001 vs pretransplantation levels) and thereafter remained at low levels for the next 6 weeks, with a small increase during the 8 weeks after transplantation (p = 0.006). In contrast, TNF-alpha, IL-8, and VCAM-1 levels remained low during the first 6 weeks after transplantation followed by a rise in mean VCAM-1 levels from 841 +/- 38 to 979 +/- 52 ng/ml at week 8. To determine the relationship of levels of each of the four soluble factors with rejection, the mean values obtained during the time interval 1 to 5 days before rejection were compared to mean values obtained during rejection and at other periods of no rejection (baseline). Cytokine levels were not predictive of rejection (no difference in levels 0 to 5 days before rejection versus baseline, p > 0.3 for IL-6, IL-8, TNF-alpha). However, VCAM-1 levels increased 0 to 5 days before rejection compared with baseline (914 +/- 40 vs 844 +/- 30 ng/ml, p = 0.06). CONCLUSIONS: IL-6 levels are increased immediately after heart transplantation. Circulating IL-6, IL-8, and TNF alpha levels do not predict rejection during the first 8 weeks after transplantation. Soluble VCAM-1 increases within 5 days before rejection and may potentially serve as a noninvasive marker for early rejection.
Adolescent↗