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Biomedical subjects

James K Kirklin

Publications and source records attributed to James K Kirklin.

At least 37 records · Page 2Linked to original sources

Predictors of quality of life at 5 to 6 years after heart transplantation.

BACKGROUND: Only a few researchers have examined quality of life (QOL) outcomes more than 5 years after heart transplantation. Therefore, the purpose of this study was to describe QOL (overall, satisfaction with, and perceived importance); identify differences in QOL by age, sex, and race; and identify predictors of QOL at 5 to 6 years after heart transplantation. METHODS: A nonrandom sample of 231 patients (60 years of age, 76% men, 90% white, 79% married, and fairly well educated) who were 5 to 6 years after heart transplantation were investigated. Patients completed 12 QOL instruments via self-report. Data analyses included descriptive statistics, chi2, independent t-tests, correlations, and stepwise multiple regression. Level of significance was set at 0.05. RESULTS: Patient satisfaction with all areas of life was high at 5 to 6 years after heart transplantation. Similarly, patients believed that these same areas of life were very important. Yet areas of QOL with lower levels of satisfaction were identified. Patients who were > or =60 years were more satisfied with their QOL than patients <60 years. At 5 to 6 years after heart transplantation, almost 80% of variance in QOL was explained by psychological, physical, social, clinical, and demographic variables. CONCLUSIONS: At 5 to 6 years after heart transplantation, patients were very satisfied with their QOL, although differences in level of satisfaction were identified by demographic variables, and areas of QOL with lower levels of satisfaction were identified. Understanding those variables that contribute to QOL in the long term after heart transplantation provides direction for assisting patients to improve their QOL.

Adult↗

Is biopsy-proven cellular rejection an important clinical consideration in heart transplantation?

PURPOSE OF REVIEW: Immunosuppression strategies to prevent allograft rejection represent the cornerstone of long-term survival after heart transplantation. Endomyocardial biopsy has defined rejection in clinical cardiac transplantation and established a threshold for therapy. With the development of more effective immunosuppression modalities and the asymptomatic nature of most histologic rejection episodes, controversy exists regarding the need to augment immunosuppression based purely on histologic findings. RECENT FINDINGS: The frequency of histologic rejection has declined with current immunosuppression. Resolution of lower grades of histologic rejection without treatment is the norm in both pediatric and adult heart transplant studies. Recurrent rejection episodes have been linked to the subsequent development of allograft coronary artery disease, and late rejection (even if asymptomatic) is associated with decreased survival in pediatric heart transplant recipients. Black race is a risk factor for recurrent rejection and reduced survival after late cellular rejection. Apoptosis of inflammatory cells is more evident during and after histologic rejection treated with corticosteroids. Despite numerous noninvasive modalities evaluated for the detection of rejection, to date noninvasive methods cannot reliably predict histologic rejection. SUMMARY: Histologic rejection appears less common with current immunosuppressive strategies, and controversy exists about the need to treat asymptomatic rejection. It remains unproven whether non-treatment of moderate or greater rejection (>/=3A) increases the likelihood of recurrent rejection, which if present, may increase the risk of allograft coronary disease and/or reduced long-term survival.

Biopsy, Needle↗

Live three-dimensional transthoracic echocardiographic assessment of left atrial tumors.

This preliminary study demonstrates the superiority of live three-dimensional transthoracic echocardiography (3D TTE) over two-dimensional (2D) TTE in the assessment of left atrial (LA) tumors in four patients studied by us (three myxomas, one hemangioma, all subsequently pathologically proven). Because of the unique ability of live 3D TTE to systematically section and view the contents of an intracardiac mass, LA myxomas in the three patients studied could be more confidently diagnosed by noting isolated echolucent areas consistent with hemorrhage/necrosis in the tumor mass. On the other hand, a definite echolucent area was found by 2D TTE in only two of the three patients with myxoma. In the fourth patient with a hemangioma, live 3D TTE showed much more extensive and closely packed echolucencies with little solid tissue as compared to a myxoma consistent with a highly vascularized tumor. In contrast, 2D TTE demonstrated only two isolated echolucencies in the tumor suggesting an erroneous diagnosis of myxoma.

Echocardiography↗

Transesophageal echocardiographic diagnosis of aortic arch-left innominate vein fistula.

We present a patient with aortic arch-left innominate vein (LIV) fistula diagnosed by transesophageal echocardiography. Also, an interrupted linear echo was noted within the dilated LIV with flow signals moving across the area of interruption, suggestive of left innominate vein pseudo-aneurysm or dissection. The patient subsequently underwent successful surgical repair of the fistula.

Adult↗

Palliation of allograft vasculopathy with transluminal angioplasty: a decade of experience.

OBJECTIVES: The goal of this study was to examine the outcomes of percutaneous coronary interventions (PCI) and the predictors for restenosis after cardiac transplantation. BACKGROUND: The role of PCI as definitive therapy for allograft coronary disease (ACD) remains contentious. METHODS: Between January 1, 1990 and December 31, 2000, 62 patients (1.5 to 15.5 years after transplant) underwent 151 procedures resulting in PCIs of 219 lesions. Follow-up after PCI angiography was usually obtained at three and six months, then yearly. Repeat PCI was routinely done to lesions with >60% restenosis. RESULTS: The primary procedural success was 97%. Repeat PCI occurred in 74 of 219 lesions (34%); PCI-related mortality was 2.6% (4 of 151). The freedom from re-PCI (of same vessel site) was 75% at six months, 65% at one year, and 57% at four years. The freedom from restenosis was 95% at one month, 81% at three months, and 57% at six months. Multivariate predictors of freedom from restenosis were the use of stents, higher anti-proliferative immunosuppressant dose, and an era effect. In the setting of one-vessel disease at first PCI, the two-year freedom for ACD death or graft loss was 74%, compared with 75% for two-vessel and 27% for three-vessel disease (p = 0.009). CONCLUSIONS: Despite the increasing effectiveness of PCI for localized ACD, the survival after development of advanced ACD remains poor. Stents appear to increase effectiveness of PCI for ACD, but other factors in the current era contribute to improved outcomes.

Angioplasty, Balloon, Coronary↗

Selection of patients and techniques of heart transplantation.

Cardiac transplantation remains the primary therapeutic choice for most patients under 65 years of age with advanced heart failure who remain symptomatic despite maximal medical therapy. Cardiac transplantation should be reserved for those patients most likely to benefit in terms of both life expectancy and quality of life. The concept of survival benefit margin must be balanced with the principles of utility in the selection process. A critical component of outcomes research for advanced heart failure will be the generation of accurate data and analyses which predict long-term survival and quality of life with various therapeutic modalities. Patients with multiple comorbidities have inferior survival and might be considered for alternative therapies. We currently recommend the bicaval techniques as the transplant technique of choice except in small infants and children.

Female↗

Risk factors for recurrent rejection in pediatric heart transplantation: a multicenter experience.

BACKGROUND: Cardiac allograft rejection remains as a primary cause of death in the first 3 years after pediatric heart transplantation. Multiple episode of acute rejection in adult heart transplant recipients may accelerate the development of graft vasculopathy. We sought to quantify the time-related probability of recurrent rejection and identify risk factors for the development of recurrent rejection. METHODS: We analyzed data from 847 pediatric recipients who underwent transplantation between January 1, 1993 and December 31, 1998 at 22 centers in the Pediatric Heart Transplant Study (PHTS). Recurrent rejection and risk factors were evaluated using univariate and multivariate analyses. RESULTS: Five hundred fifty two patients had 1,072 rejection events and were the subject of the analyses. The highest risk of recurrent rejection occurs within 1 month after resolution of a previous rejection episode. Risk factors for recurrent rejection include the number of previous rejection events, the elapsed time since a previous rejection episode, and subjects of either Hispanic or African-American descent. Rejection associated with hemodynamic compromise and late rejection is associated with higher mortality. CONCLUSIONS: Recurrent rejection is a risk factor for mortality, especially in the presence of hemodynamic compromise. This association appears independent of the time post-transplantation. Use of surveillance biopsies appears warranted throughout the life of the transplant individual. Retransplantation should be considered among these subjects with recurrent rejection.

Adult↗

Current outcomes following heart transplantation.

Survival after cardiac transplantation has improved progressively since its inception over 35 years ago, with current 1 year survival approaching 90% and 7 year survival approaching 75%. In view of continued severe donor shortages, allocation must balance the survival benefit margin for recipients with terminal heart failure (higher risk for death with multiple co-morbidities and refractory low output state) and the charge to maximize graft survival. Continued improvement in short and longer-term survival will depend on an understanding of the early and late risk factors after cardiac transplantation and the development of methods and treatments to neutralize them. Specific risk factors vary for the specific causes of mortality, which include primarily early graft failure, infection, and rejection during the first post transplant year; and allograft vasculopathy and malignancy in later years. Evolving trends in risk profiles and survival indicate that patients undergoing cardiac transplantation have experienced a gradual increase in risk profile over the past decade, and have improved survival. Patient-specific risk profiling will play an increasing role in the allocation of transplantation and other emerging therapies for patients with advanced heart failure.

Adult↗

Definitive diagnosis of cor triatriatum with common atrium by three-dimensional transesophageal echocardiography in an adult.

We describe an adult patient, in whom three-dimensional transesophageal echocardiography was able to make a definitive diagnosis of cor triatriatum associated with common atrium. The lesion mimicked a classical partial atrio-ventricular septal defect on both transthoracic and transesophageal two-dimensional echocardiography. We found only two cases in the literature describing the existence of cor triatriatum with common atrium, none diagnosed by echocardiography.

Cor Triatriatum↗

Usefulness of live three-dimensional transthoracic echocardiography in the characterization of atrial septal defects in adults.

In this report we present 12 adult patients in whom surgical or percutaneous intervention was considered for repair of atrial septal defect (ASD). Location, size, and surrounding atrial anatomy of the ASD were assessed prior to intervention in all patients with standard and live three-dimensional transthoracic echocardiography (3D TTE). In the four patients in whom intraoperative three-dimensional transesophageal echocardiographic reconstruction (3D TEE) was done, 3D TTE measurements of maximum dimension, maximum circumference, and maximum area of ASD agreed well with 3D TEE. In the seven patients who underwent transcatheter closure device insertion, live 3D TTE measurements of maximum dimension, maximum circumference, and maximum area of ASD agreed well with the sizing balloon. Additionally, since the sizing balloon measures a stretched diameter and area, a live 3D TTE stretched ASD diameter and area (derived from the actual live 3D TTE maximum circumference) were calculated and demonstrated improved agreement with the sizing balloon measurements. In all patients, > or =5 mm of atrial tissue was visualized surrounding the ASD. Further, with the addition of contrast enhancement, characterization of a small patent foramen ovale (<5 mm) was possible in one patient. Live 3D TTE accurately defined ASD location, size, and surrounding atrial anatomy in all patients studied by us. ASD characterization by live 3D TTE agreed well with 3D TEE and sizing balloon measurements.

Adolescent↗

Quantification of mitral regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area.

We evaluated 44 consecutive patients who underwent standard two-dimensional (2D) and live three-dimensional (3D) transthoracic echocardiography (TTE), as well as left heart catheterization with left ventriculography. Mitral regurgitant vena contracta area (VCA) was obtained by 3D TTE by systematic and sequential cropping of the acquired 3D TTE data set. Assessment of mitral regurgitation (MR) by ventriculography was compared to measurements of VCA by 3D TTE and to 2D TTE measurements of MR jet area to left atrial area (RJA/LAA), RJA alone, vena contracta width (VCW), and calculated VCA. VCA from 3D TTE closely correlated with angiographic grading (rs=0.88) with very little overlap. VCA of <0.2 cm2 correlated with mild MR, 0.2-0.4 cm2 with moderate MR, and >0.4 cm2 with severe MR by angiography. Ventriculographic grading also correlated well with 2D TTE measurements of RJA/LAA (rs=0.79) and RJA alone (rs=0.76) but with more overlap. Assessment of VCW and calculated VCA by 2D TTE agreed least with ventriculography (rs=0.51 and rs=0.55, respectively). Live 3D TTE color Doppler measurements of VCA can be used for quantitative assessment of MR and is comparable to assessment by ventriculography.

Adult↗

Allogeneic bone marrow inhibits T-cell activation and clonal expansion in vitro.

BACKGROUND: Donor bone marrow infusion has long been used to enhance graft survival or induce tolerance in T cell depleted solid organ allograft recipients. However, the mechanisms through which bone marrow cells affect tolerance remain obscure. We studied the affect of allogeneic bone marrow cells on the activation of allospecific T cells in vitro. METHODS: Carboxyfluorescein-diacetate succinimidyl ester-labeled CBA/Ca strain CD8+ splenocytes, bearing T-cell receptor alpha and beta transgenes from the BM3.3 T-cell clone specific for the major histocompatibility complex class I antigen Kb, were placed in culture with irradiated C57BL/6J stimulator cells in the presence of increasing numbers of C57BL/6J or Balb/cJ bone marrow cells for 1 to 3 days. Responder cells were individually analyzed for proliferative history, expression of activation-associated antigens, and intracellular cytokine production. RESULTS: Allogeneic bone marrow cells exert a dose-dependent inhibitory effect on proliferation of allospecific CD8+ T cells in mixed lymphocyte culture. However, the inhibited T-cell subpopulations show physiologic changes associate with the early stages of T-cell activation, including expression of CD69 and early decrease of surface T-cell expression. Unlike cells not co-cultured with bone marrow, these cells fail to reexpress the T-cell receptor (TCR) by 72 hr of culture. The observed inhibitory effect is also associated with a decrease in the proportion of CD8+ cells expressing interleukin-2 and interferon-gamma. CONCLUSIONS: Collectively, these results suggest that peripheral allospecific T cells undergo the initial stages of activation on exposure to antigen in the presence of bone marrow cells, but the cell cycle is arrested and TCR reexpression is inhibited. We speculate that bone marrow cells effect this inhibition through a receptor-ligand interaction that modulates the transmembrane signal pathway for the TCR.

Animals↗

Infection in ventricular assist devices: prevention and treatment.

Infection is one of the most important challenges to the use of implanted mechanical circulatory support systems (MCSS), particularly as we enter the era of permanent device use in patients who are not candidates for cardiac transplantation. This paper describes the pathogenesis of MCSS infection, with particular attention to the role of biofilm-forming bacteria. Suggestions are presented for the prevention and treatment of infections in implanted MCSS.

Heart Failure↗