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Biomedical subjects

J K Kirklin

Publications and source records attributed to J K Kirklin.

At least 55 records · Page 3Linked to original sources
PubMed1997

Usefulness of transesophageal echocardiography in the assessment of aortic graft dehiscence.

The diagnosis and site of graft dehiscence determined by transesophageal echocardiography (TEE), transthoracic echocardiography (TTE), and aortography in 6 patients, and by computed tomography (CT) scan in 3 patients were compared with surgery. Sensitivity of TEE was 100%, aortography 83%, CT scan 67%, and TTE 33%; TEE accurately identified severe aortic regurgitation (3), graft narrowing (2), distal aortic dissection (1), and a fistulous communication between the aortic root and the right ventricle (1) when compared with surgery or aortography.

Adult↗
PubMed1997

Replacement of an intracorporeal left ventricular assist device.

An intracorporeal left ventricular assist device was placed as a bridge to cardiac transplantation in a 51-year-old man after an acute myocardial infarction. After 126 days of support, the left ventricular assist device malfunctioned. The pump, which had a tear in its pneumatic drive line, was successfully replaced.

Equipment Design↗
PubMed1997

Ventricular assist devices as a bridge to cardiac transplantation. A prelude to destination therapy.

OBJECTIVE AND BACKGROUND: Ventricular assist devices (VADs) have been used for temporary circulatory support pending transplantation or recovery of the native heart. Outcome in 38 patients treated at the authors' institution with VADs pending transplantation was analyzed to provide information relevant to the future use of VADs as permanent implants. METHODS: Thoratec (Thoratec Laboratories, Pleasanton, CA) or HeartMate (Thermo Cardiosystems, Woburn, MA) VADs were used in all cases. Patients were considered for VAD placement if they were candidates for cardiac transplantation and fulfilled the criteria for the Food and Drug Administration investigational Device Exemption trials. The following adverse events were included in the analysis; death during VAD support, device malfunction, bleeding, neurologic events, support-related events that preclude transplantation, and device-related infections. Patient survival and complication rates were quantified using the Kaplan-Meier method, competing risk analysis, and hazard functions. RESULTS: Nineteen patients had transplantation. Three patients had VAD removal after cardiac recovery and 16 died without transplantation. The duration of VAD support ranged from 0 to 279 days. The hazard function for death during VAD support had an early phase that lasted for 2 weeks after VAD placement, and early death was related to the preimplant condition of the patient. Device-related infections were noted in 11 patients. Seven of these patients had transplantation after clearing the infection, whereas four died without transplantation. Neurologic events occurred in seven patients. There were no device malfunctions that led to patient death. CONCLUSIONS: The absence of fatal device malfunctions suggests that longer term support with current VAD designs is feasible. Appropriate patient selection, infection control, and avoidance of thromboembolic neurologic complications will be crucial to the success of permanent VAD use.

Adult↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

Infection after pediatric heart transplantation: results of a multiinstitutional study. The Pediatric Heart Transplant Study Group.

BACKGROUND: Detailed information regarding the spectrum and predictors of infection after heart transplantation in children is limited because of relatively small numbers of patients at any single institution. We therefore used combined data obtained from the Pediatric Heart Transplant Study Group to gain additional information regarding infectious complications in the pediatric population. METHODS: To determine the time-related risk of infection and death related to infection in a large pediatric patient population, we analyzed data related to 332 pediatric patients (undergoing heart transplantation between January 1, 1993, and December 31, 1994) from 22 institutions in the Pediatric Heart Transplant Study Group. RESULTS: Among the 332 total patients, 276 infections were identified in 136 patients. Of those patients with development of infection, a single infection episode was reported in 54% of patients, 21% had two infections, and 25% had three or more infections. Of the 276 infections, 164 (60%) were bacterial, 51 (18%) were due to cytomegalovirus, 35 (13%) were other viral (noncytomegalovirus) infections, 19 (7%) were fungal, and 7 (2%) were protozoal. Bacterial infections were more common in infants younger than 6 months of age at time of transplantation, comprising 73% of all infections as compared with 49% in patients older than 6 months of age. The incidence of bacterial infection peaked during the first month after transplantation, with the actuarial likelihood of a bacterial infection among all patients reaching 25% at 2 months. The most common sites of bacterial infection were blood and lung (74% of bacterial infections). Cytomegalovirus accounted for 59% of viral infections, with a peak hazard occurring at 2 months after transplantation. Among all infections, cytomegalovirus was less common in infants younger than 6 months of age (8% of all infections) than in older patients (25%). By multivariate analysis, risk factors for early infection included younger recipient age (p = 0.05), mechanical ventilation at time of transplantation (p = 0.0002), positive donor cytomegalovirus serologic study result with negative recipient result (p = 0.004), and longer donor ischemic time (p = 0.04). The overall mortality rate from infection was 5%, with an actuarial freedom from death related to infection of 92% at 1 year after transplantation. The mortality rate was high in patients with fungal infections (52%), yet was low for those with cytomegalovirus infection (6%). Infections accounted for 27% of the overall mortality rate in infants younger than 6 months of age, compared with 16% for older patients. CONCLUSIONS: Although most infections in pediatric heart transplant recipients are successfully treated, infection remains an important cause of posttransplantation morbidity and death, especially in infants. Bacterial infections predominate within the first month after transplantation, whereas the peak hazard for viral infections occurs approximately 2 months after transplantation. Cytomegalovirus infections are common in the pediatric transplant population, but death related to cytomegalovirus is low.

Actuarial Analysis↗
PubMed1997

Outcome of listing for heart transplantation in infants younger than six months: predictors of death and interval to transplantation. The Pediatric Heart Transplantation Study Group.

BACKGROUND: The major limiting factor to successful heart transplantation in infants is the limited supply of donors. To examine the impact of donor limitations on survival after listing, a multiinstitutional study was designed to identify risk factors for death while waiting and for longer interval to transplantation. METHODS: Between January 1 and December 31, 1993, 118 infants 6 months of age or younger (86 younger than 29 days) were listed for heart transplantation from 21 institutions. The primary diagnosis was hypoplastic left-sided heart syndrome (HLHS) in 70 (59%), other congenital defects in 32 (27%), cardiomyopathy or myocarditis in 13 (11%), and other diagnoses in 3. Among the 48 patients without HLHS, 32 (67%) required inotropic, mechanical, or prostaglandin support, whereas 16 (33%) did not. RESULTS: At 6 months after listing, only 6% remained on the list awaiting transplantation, 59% underwent transplantation. 31% died while waiting, and 4% were removed from the list. The greatest mortality rate before transplantation was among patients with HLHS in whom the actuarial mortality rate if they were unable to receive a transplant was 77% at 6 months, compared with 52% in patients without HLHS and without inotropic or mechanical support (p = 0.05). By multivariable analysis, risk factors for death while waiting included inotropic support (p = 0.02), smaller size (p = 0.0007), and blood type O (p = 0.003). Surgical procedures before listing did not significantly influence pretransplantation mortality rates. The interval from listing to transplantation increased with young age (p = 0.01) in patients without HLHS and smaller size (p = 0.001) and blood group O (p = 0.0006) for patients with HLHS. The effect of blood type O on mortality rates and longer interval to transplantation was due to the distribution of type O donor hearts to non-type O recipients. Palliative operations after listing did not favorably influence survival; nine patients underwent first-stage Norwood while waiting, and six died before transplantation. CONCLUSIONS: The mortality rate is unacceptably high among infants awaiting transplantation, particularly in patients with HLHS. Infants receiving intravenous inotropes or mechanical support at listing are at high risk of early death while waiting. The distribution of blood group O donors to non-blood group O recipients results in higher mortality rates among blood group O recipients. Greater emphasis should be placed on medical strategies to improve survival while waiting and on expanding existing graft resources.

ABO Blood-Group System↗
PubMed1996

Secular trends in cardiac transplant recipient and donor management in the United States, 1990 to 1994. A multi-institutional study. Cardiac Transplant Research Database Group.

BACKGROUND: The growth of the US cardiac transplant waiting list has outpaced the increase in donors, resulting in a widening gap between the number of waiting recipients and available donors. These trends have generated concern that longer waiting times may result in more patients deteriorating to urgent status and that transplanting only patients who are in an advanced state of decompensation will reduce posttransplant survival. Furthermore, the shortage of donors may result in extending the guidelines for donor acceptability to a degree that increases graft failure and posttransplant mortality. We measured these secular trends in the Cardiac Transplant Research Database to provide current data on time-dependent changes in US cardiac transplant practice and survival. METHODS AND RESULTS: At the time of this analysis, the Cardiac Transplant Research Database included all 2749 patients transplanted from January 1, 1990, to June 30, 1994, in the 25 participating transplant centers. During this 4.5-year period, the median waiting time for recipients who received a transplant increased from 2.7 to 3.5 months (P < .0001), and the proportion of recipients whose status was urgent at transplantation increased from 41% to 60% (P < .0001). Donor ischemic time increased from 150 to 166 minutes (P < .0001), and the proportion of donors requiring pressor support increased from 68% to 85% (P < .0001). Despite these changes in practice, the 1-year survival rate remained constant at 84% during this 4.5-year interval. There was no significant difference in 1-year survival rate between urgent status patients (83%) and nonurgent status patients (85%) (P = .08). CONCLUSIONS: The widening gap between the number of waiting recipients and the number of donors has resulted in a continuing trend toward transplanting urgent status recipients and to a liberalization of donor acceptance criteria. Despite these changes, posttransplant survival has remained constant.

Adult↗
PubMed1996

Outcome of cardiac transplantation in children. Survival in a contemporary multi-institutional experience. Pediatric Heart Transplant Study.

BACKGROUND: Meaningful analysis of survival and risk factors for death in children who undergo heart transplantation is problematic because of the small number of heart transplantations performed at individual institutions. METHODS AND RESULTS: To more accurately examine survival and risk factors for death in children undergoing heart transplantation, we analyzed 191 patients between 1 and 18 years old who received transplants at 22 centers in the Pediatric Heart Transplant Study between January 1, 1993, and December 31, 1994. Cardiac diagnosis was congenital heart disease in 74 patients (39%), dilated cardiomyopathy in 73 (38%), and other in 44 (23%). Actuarial survival was 93% at 1 month, 82% at 1 year, and 81% at 2 years after transplantation. The major causes of death (n = 31) were rejection (29% of deaths), early graft failure (19%), infection (16%), sudden death (13%), and other causes (23%). By multivariate analysis, risk factors for death were assist devices (P = .02), nonidentical ABO blood types (P = .05), and younger age (P = .10). CONCLUSIONS: Contemporary survival for pediatric heart transplant recipients > or = 1 year old is comparable to survival after adult heart transplantation. Risk factors for death are the need for assist devices, nonidentical ABO blood types, and younger age. Rejection is the most common cause of death after pediatric heart transplantation.

Adolescent↗
PubMed1996

Infections during extended circulatory support: University of Alabama at Birmingham experience 1989 to 1994.

BACKGROUND: The University of Alabama at Birmingham experience with investigational ventricular assist devices (VADs) used as a bridge to transplantation has increased over the past several years; it now includes 27 VAD implantations with 13 VAD runs lasting for extended periods (ie, > 30 days). A review of complications experienced by patients during extended VAD runs is warranted before the further development and testing of chronically implanted mechanical circulatory support devices. METHODS: This study focuses on the infectious complications of extended VAD support; it includes 13 patients who were supported by either a Thoratec or HeartMate VAD for longer than 30 days pending cardiac transplantation. Infection was defined as any positive culture. The infections were classed according to site and severity as follows: class I were patient-related non-blood-borne infections, class II were blood-borne infections, class III were VAD percutaneous site infections, and class IV were infections of the blood-contacting surfaces or intracorporeal components of the VAD. RESULTS: The 8 Thoratec and 5 HeartMate patients were supported for a total of 1,648 days with a range of 33 to 279 days per patient. Every patient had at least one infection; however, there were 6 patients who had no class II or IV infections during the period of support. One of these 6 patients died of a stroke, whereas the other 5 patients survived VAD support. No trends were identified for a change in the incidence of bacterial compared with fungal infections during the course of VAD support. There was no trend for a greater number of infections in patients who died during VAD support compared with those who survived. Neither class II nor IV infections precluded transplantation. Three patients died during VAD support; 1 died as a direct consequence of fungal infection. Eight patients received transplants. One patient had an unanticipated recovery of cardiac function and the VAD was removed. Support in 1 patient is ongoing. CONCLUSIONS: Infection during VAD support pending cardiac transplantation is an important cause of morbidity and mortality in patients maintained for longer than 30 days by circulatory assist. Infectious complications will probably be a prominent component of the risk associated with the use of chronically implanted mechanical circulatory assist devices and will likely have an important effect on the quality of life experienced by these patients.

Bacterial Infections↗
PubMed1996

Semiquantitative measurement of cytokine messenger RNA in endomyocardium and peripheral blood mononuclear cells from human heart transplant recipients.

BACKGROUND: Cytokines play a central role in inflammatory responses and in specific immune responses directed toward alloantigens. The pattern and quantity of cytokines produced in graft rejection can yield valuable information regarding the cellular and molecular mechanisms of the antigraft response. METHODS: We used the polymerase chain reaction to semiquantitatively measure changes in the amount of messenger RNA from the interleukin-1 beta, interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-alpha, interferon-gamma, interleukin-1 receptor antagonist, and the interleukin-2 receptor genes in the peripheral blood and endomyocardium of cardiac allograft recipients during the first 8 weeks after transplantation. A total of 328 samples of resting (n = 251) and stimulated (n = 77, stimulated with phytohemagglutinin and lipopolysaccharide for 18 hours) peripheral blood mononuclear cells collected from 16 patients were measured. To measure intragraft cytokine levels, we analyzed 150 endomyocardial biopsy specimens from 19 patients. RESULTS: No elevation in expression was seen before injection, but, after the onset of rejection and concomitant with treatment, there was a decrease in detectable mRNA (p < 0.05) for the pro-inflammatory monokines interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha in resting peripheral blood mononuclear cells, and a decrease for the T-cell derived cytokines interleukin-4 and interleukin-10 in stimulated peripheral blood mononuclear cells. These changes in mRNA expression occurred coincidentally with decreases in the percentage of lymphocytes and monocytes in the peripheral blood after administration of rejection therapy. In endomyocardial biopsy specimens, there were no detectable changes in the quantities of cytokine mRNA specimens for the interferon-gamma, interleukin-6, interleukin-10, interleukin-1ra, and interleukin-1 beta genes before rejection. In general, the levels of these cytokines were near the lower limits of detection by our assay in endomyocardial biopsies, mRNA from the interleukin-2, interleukin-4, tumor necrosis factor-alpha, and interleukin-2R genes were undetectable. CONCLUSIONS: We conclude that changes in the expression of cytokine mRNA in both peripheral blood mononuclear cells and endomyocardial biopsy specimens as measured by the semiquantitative polymerase chain reaction method used in this study does not effectively predict rejection. The decline in peripheral blood mononuclear cell cytokine mRNA after rejection treatment is likely due to changes in the proportion of lymphocytes and monocytes in the peripheral blood in concert with a steroid-induced downregulation by cytokine gene transcription.

Biopsy↗
PubMed1996

Risk factors for early, cumulative, and fatal infections after heart transplantation: a multiinstitutional study.

BACKGROUND AND METHODS: By multivariable analysis, risk factors were identified for initial infection of any type, cumulative infections during the first 6 months and fatal infection among 2210 heart transplant recipients at 30 institutions. RESULTS AND CONCLUSIONS: Of the 1218 infections in 695 patients, bacterial infections were most frequent (47%), followed by viral (42%), fungal (8%), and protozoal (4%). Risk factors for earlier infection included older recipient age (p < 0.0001), ventilator support at time of transplant (p < 0.0001), ventricular assist device at time of transplant (p = 0.02), OKT3 induction therapy (p < 0.0001), donor black race (p = 0.0007), and positive donor cytomegalovirus serology (for cytomegalovirus infection) (p = 0.0007). Cumulative infections during the first 6 months were increased by older recipient age (p < 0.0001), ventilator support at transplant (p = 0.0004), ventricular assist at transplant (p = 0.009), Black donor (p = 0.03), female donor (p = 0.03), and OKT3 induction therapy (p = 0.005). The actuarial freedom from fatal infection was 96% at 1 year and 95% at 3 years. Risk factors for death from infection included very old (p = 0.002) and very young recipients (p = 0.004), ventilator support at time of transplant (p = 0.004), older donor (p < 0.0001), and longer donor ischemic time (p = 0.02). The risk of death from infection within the first 3 months exceeded 20% among older recipients (> 55 years) on ventilator support at time of transplantation who received an older (> 50 years) donor heart.

Actuarial Analysis↗