Jeffrey Teuteberg, MD

All Publications

• Gene expression profiling to study racial differences after heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Khush, K. K., Pham, M. X., Teuteberg, J. J., Kfoury, A. G., Deng, M. C., Kao, A., Anderson, A. S., Cotts, W. G., Ewald, G. A., Baran, D. A., Hiller, D., Yee, J., Valantine, H. A. 2015; 34 (7): 970-977

  Abstract

  The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.We determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race.In 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p < 0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels.African Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups.

  View details for DOI 10.1016/j.healun.2015.01.987

  View details for Web of Science ID 000356998800014

  View details for PubMedID 25840504

  View details for PubMedCentralID PMC4475410

• Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients. Transplantation Deng, M. C., Elashoff, B., Pham, M. X., Teuteberg, J. J., Kfoury, A. G., Starling, R. C., Cappola, T. P., Kao, A., Anderson, A. S., Cotts, W. G., Ewald, G. A., Baran, D. A., Bogaev, R. C., Shahzad, K., Hiller, D., Yee, J., Valantine, H. A. 2014; 97 (6): 708-714

  Abstract

  Gene expression profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of gene expression profiling test scores within a patient may predict risk of future events of allograft dysfunction or death.Patients from the IMAGE study with rejection surveillance gene expression profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene expression profiling score variability was defined as the standard deviation of an individual's cumulative test scores. Gene expression profiling ordinal score (range, 0-39), threshold score (binary value=1 if ordinal score ≥ 34), and score variability were studied in multivariate Cox regression models to predict future clinical events.Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, gene expression profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were <0.001, 0.46, and 0.773, for gene expression profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4-2.3).The variability of a heart recipient's gene expression profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal gene-expression profiling test score.

  View details for DOI 10.1097/01.TP.0000443897.29951.cf

  View details for PubMedID 24637869

  View details for PubMedCentralID PMC3983476

• Prognosis of Right Ventricular Failure in Patients With Left Ventricular Assist Device Based on Decision Tree With SMOTE IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE Wang, Y., Simon, M., Bonde, P., Harris, B. U., Teuteberg, J. J., Kormos, R. L., Antaki, J. F. 2012; 16 (3): 383-390

  Abstract

  Right ventricular failure is a significant complication following implantation of a left ventricular assist device (LVAD), which increases morbidity and mortality. Consequently, researchers have sought predictors that may identify patients at risk. However, they have lacked sensitivity and/or specificity. This study investigated the use of a decision tree technology to explore the preoperative data space for combinatorial relationships that may be more accurate and precise. We retrospectively analyzed the records of 183 patients with initial LVAD implantation at the Artificial Heart Program, University of Pittsburgh Medical Center, between May 1996 and October 2009. Among those patients, 27 later required a right ventricular assist device (RVAD+) and 156 remained on LVAD (RVAD-) until the time of transplantation or death. A synthetic minority oversampling technique (SMOTE) was applied to the RVAD+ group to compensate for the disparity of sample size. Twenty-one resampling levels were evaluated, with decision tree model built for each. Among these models, the top six predictors of the need for an RVAD were transpulmonary gradient (TPG), age, international normalized ratio (INR), heart rate (HR), aspartate aminotransferase (AST), prothrombin time, and right ventricular systolic pressure. TPG was identified to be the most predictive variable in 15 out of 21 models, and constituted the first splitting node with 7 mmHg as the breakpoint. Oversampling was shown to improve the senstivity of the models monotonically, although asymptotically, while the specificity was diminished to a lesser degree. The model built upon 5X synthetic RVAD+ oversampling was found to provide the best compromise between sensitivity and specificity, included TPG (layer 1), age (layer 2), right atrial pressure (layer 3), HR (layer 4,7), INR (layer 4, 9), alanine aminotransferase (layer 5), white blood cell count (layer 5,6, &7), the number of inotrope agents (layer 6), creatinine (layer 8), AST (layer 9, 10), and cardiac output (layer 9). It exhibited 85% sensitivity, 83% specificity, and 0.87 area under the receiver operating characteristic curve (RoC), which was found to be greatly improved compared to previously published studies.

  View details for DOI 10.1109/TITB.2012.2187458

  View details for Web of Science ID 000303997700011

  View details for PubMedID 22334033

• Decision tree for adjuvant right ventricular support in patients receiving a left ventricular assist device JOURNAL OF HEART AND LUNG TRANSPLANTATION Wang, Y., Simon, M. A., Bonde, P., Harris, B. U., Teuteberg, J. J., Kormos, R. L., Antaki, J. F. 2012; 31 (2): 140-149

  Abstract

  Right ventricular (RV) failure is a significant complication after implantation of a left ventricular assist device (LVAD). It is therefore important to identify patients at risk a priori. However, prognostic models derived from multivariate analyses have had limited predictive power.This study retrospectively analyzed the records of 183 LVAD recipients between May 1996 and October 2009; of these, 27 later required a RVAD (RVAD(+)) and 156 remained on LVAD only (RVAD(-)) until transplant or death. A decision tree model was constructed to represent combinatorial non-linear relationships of the pre-operative data that are predictive of the need for RVAD support.An optimal set of 8 pre-operative variables were identified: transpulmonary gradient, age, right atrial pressure, international normalized ratio, heart rate, white blood cell count, alanine aminotransferase, and the number of inotropic agents. The resultant decision tree, which consisted of 28 branches and 15 leaves, identified RVAD(+) patients with 85% sensitivity, RVAD(-) patients with 83% specificity, and exhibited an area under the receiver operating characteristic curve of 0.87.The decision tree model developed in this study exhibited several advantages compared with existing risk scores. Quantitatively, it provided improved prognosis of RV support by encoding the non-linear, synergic interactions among pre-operative variables. Because of its intuitive structure, it more closely mimics clinical reasoning and therefore can be more readily interpreted. Further development with additional multicenter, longitudinal data may provide a valuable prognostic tool for triage of LVAD therapy and, potentially, improve outcomes.

  View details for DOI 10.1016/j.healun.2011.11.003

  View details for Web of Science ID 000300545100005

  View details for PubMedID 22168963

  View details for PubMedCentralID PMC3273573

• The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Costanzo, M. R., Dipchand, A., Starling, R., Anderson, A., Chan, M., Desai, S., Fedson, S., Fisher, P., Gonzales-Stawinski, G., Martinelli, L., McGiffin, D., Parisi, F., Smith, J., Taylor, D., Meiser, B., Webber, S., Baran, D., Carboni, M., Dengler, T., Feldman, D., Frigerio, M., Kfoury, A., Kim, D., Kobashigawa, J., Shullo, M., Stehlik, J., Teuteberg, J., Uber, P., Zuckermann, A., Hunt, S., Burch, M., Bhat, G., Canter, C., Chinnock, R., Crespo-Leiro, M., Delgado, R., Dobbels, F., Grady, K., Kao, W., Lamour, J., Parry, G., Patel, J., Pini, D., Pinney, S., Towbin, J., Wolfel, G., Delgado, D., Eisen, H., Goldberg, L., Hosenpud, J., Johnson, M., Keogh, A., Lewis, C., O'Connell, J., Rogers, J., Ross, H., Russell, S., Vanhaecke, J. 2010; 29 (8): 914-956

  View details for DOI 10.1016/j.healun.2010.05.034

  View details for Web of Science ID 000280570000020

  View details for PubMedID 20643330

• Gene-Expression Profiling for Rejection Surveillance after Cardiac Transplantation NEW ENGLAND JOURNAL OF MEDICINE Pham, M. X., Teuteberg, J. J., Kfoury, A. G., Starling, R. C., Deng, M. C., Cappola, T. P., Kao, A., Anderson, A. S., Cotts, W. G., Ewald, G. A., Baran, D. A., Bogaev, R. C., Elashoff, B., Baron, H., Yee, J., Valantine, H. A. 2010; 362 (20): 1890-1900

  Abstract

  Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy.We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation.During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P=0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P<0.001).Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)

  View details for DOI 10.1056/NEJMoa0912965

  View details for Web of Science ID 000277815600007

  View details for PubMedID 20413602

• Molecular testing for long-term rejection surveillance in heart transplant recipients: Design of the Invasive Monitoring Attenuation Through Gene Expression (IMAGE) trial JOURNAL OF HEART AND LUNG TRANSPLANTATION Pham, M. X., Deng, M. C., Kfoury, A. G., Teuteberg, J. J., Starling, R. C., Valantine, H. 2007; 26 (8): 808-814

  Abstract

  Acute rejection continues to occur beyond the first year after cardiac transplantation, but the optimal strategy for detecting rejection during this late period is still controversial. Gene expression profiling (GEP), with its high negative predictive value for acute cellular rejection (ACR), appears to be well suited to identify low-risk patients who can be safely managed without routine invasive endomyocardial biopsy (EMB).The Invasive Monitoring Attenuation Through Gene Expression (IMAGE) study is a prospective, multicenter, non-blinded, randomized clinical trial designed to test the hypothesis that a primarily non-invasive rejection surveillance strategy utilizing GEP testing is not inferior to an invasive EMB-based strategy with respect to cardiac allograft dysfunction, rejection with hemodynamic compromise (HDC) and all-cause mortality.A total of 199 heart transplant recipients in their second through fifth post-transplant years have been enrolled in the IMAGE study since January 13, 2005. The study is expected to continue through 2008.The IMAGE study is the first randomized, controlled comparison of two rejection surveillance strategies measuring outcomes in heart transplant recipients who are beyond their first year post-transplant. The move away from routine histologic evaluation for allograft rejection represents an important paradigm shift in cardiac transplantation, and the results of this study have important implications for the future management of heart transplant patients.

  View details for DOI 10.1016/j.healun.2007.05.017

  View details for Web of Science ID 000248992200005

  View details for PubMedID 17692784

• Biventricular assist device utilization for patients with morbid congestive heart failure - A justifiable strategy CIRCULATION Tsukui, H., Teuteberg, J. J., Murali, S., McNamara, D. M., Buchanan, J. R., Winowich, S., Stanford, E., Mathier, M. A., Cadaret, L. M., Kormos, R. L. 2005; 112 (9): I65-I72

  Abstract

  The rationale for the use of a biventricular assist device (BiVAD) for morbid congestive heart failure (MCHF) has been questioned because of historically unacceptable rates of postimplant and post-transplant mortality as well as perceived barriers to their outpatient management.All patients who received a Thoratec BiVAD from January 1990 to December 2003 at the University of Pittsburgh were studied retrospectively. There were a total of 73 patients (32% ischemic, 21% idiopathic, and 47% other) who had a BiVAD implanted. Before implantation, 100% were on > or =1 inotropic agent, and 77% had an intra-aortic balloon pump. Overall survival was 69%; 42 patients (84%) received cardiac transplantation, 5 patients (10%) were weaned, and 3 (6%) remained supported on BiVAD. If the 14 patients with postcardiotomy failure and acute myocardial infarction with shock are excluded, the overall survival improves to 75%. Five-year actuarial survival after heart transplantation was 58%. Of the 29 patients implanted before 2000, the 4-month actuarial freedom from driveline infections, bloodstream infections, and neurological events was 10%, 54%, and 48%, respectively, whereas the rates of these events for the 44 patients implanted after 2000 improved to 70%, 79%, and 80%, respectively. Since 2000, 21 (48%) patients were discharged from the hospital, of whom 38% went to an outpatient residence, 33% to a skilled nursing facility, and 29% to home. Once discharged, > or =1 readmission occurred in 45% and > or =2 readmissions in 48%.BiVAD support for MCHF has an acceptable overall mortality and survival to transplantation. Morbidity has been significantly reduced in the past 4 years, and management as an outpatient is achievable.

  View details for DOI 10.1161/CIRCULATIONAHA.104.524934

  View details for Web of Science ID 000231741600011

  View details for PubMedID 16159867