Jeffrey Teuteberg

All Publications

• Patient Satisfaction Remains High from 3-6 Months After Lvad Implant: Findings from Mcs A-qol Grady, K. L., Wortman, K., Cummings, P., Buono, S., Lindenfeld, J., Teuteberg, J., Rich, J., Cella, D., Yancy, C., Pham, D., McILvennan, C., Allen, L. A., Kiernan, M., Beiser, D., Murks, C., Lee, C., Denfeld, Q., Klein, L., Eshelbrenner, C., Long, J., Walsh, M., Stehlik, J., Adler, E., Ruo, B., Kallen, M., Hahn, E. A. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2020: S130–S131

  View details for Web of Science ID 000579889600350

• Evaluation of a Health Care Performance Improvement Initiative to Facilitate Optimal Clinical Outcomes in Patients Receiving Ventricular Assist Device Support. Progress in transplantation (Aliso Viejo, Calif.) Lockard, K. L., Dunn, E., Kunz, N., Pearsol, A., Schaub, R. D., Severyn, D. A., Lohmann, D., McCall, M., Morelli, B., Teuteberg, J. J., Kormos, R. L., Sciortino, C. M., Dew, M. A. 2020: 1526924820958129

  Abstract

  BACKGROUND: Ventricular assist device (VAD) patients are at high risk for morbidities and mortality. One potentially beneficial component of the Joint Commission VAD Certification process is the requirement that individual VAD programs select 4 performance measures to improve and optimize patients' clinical outcomes.PROBLEM STATEMENT: Review of patient data after our program's first certification visit in 2008 showed that, compared to national recommendations and published reports, our patients had suboptimal outcomes in 4 areas after device implantation: length of hospital stay, receipt of early (<48 hours) postsurgical physical therapy, driveline infection incidence, and adequacy of nutritional status (prealbumin ≥18 mg/dL).METHODS: Plan-Do-Study-Act processes were implemented to shorten length of stay, increase patient receipt of early physical therapy, decrease driveline infection incidence, and improve nutritional status. With 2008 as our baseline, we deployed interventions for each outcome area across 2009 to 2017. Performance improvement activities included staff, patient, and family didactic, one-on-one, and hands-on education; procedural changes; and outcomes monitoring with feedback to staff on progress. Descriptive and inferential statistics were examined to document change in the outcomes.OUTCOMES: Across the performance improvement period, length of stay decreased from 40 to 23 days; physical therapy consults increased from 87% to 100% of patients; 1-year driveline infection incidence went from 38% to 23.5%; and the percentage of patients with prealbumin within the normal range increased from 84% to 90%.IMPLICATIONS: Performance improvement interventions may enhance ventricular assist device patient outcomes. Interventions' sustainability should be evaluated to ensure that gains are not lost over time.

  View details for DOI 10.1177/1526924820958129

  View details for PubMedID 32985349

• Ethical decision-making in simultaneous heart-liver transplantation. Current opinion in organ transplantation Cheng, X. S., Wall, A., Teuteberg, J. 2020

  Abstract

  PURPOSE OF REVIEW: Simultaneous heart-liver (SHL) transplants are only a small proportion of overall heart and liver transplantation, they have been increasing in frequency and thus challenge the equitable allocation of organs.RECENT FINDINGS: The incidence of SHL transplants is reviewed along with the outcomes of SHL transplants and their impact on the waitlist, particularly in the context of solitary heart and liver transplantation. The ethical implications, most importantly the principles of utility and equity, of SHL transplant are addressed. In the context of utility, the distinction of a transplant being life-saving versus life-enhancing is investigated. The risk of hepatic decompensation for those awaiting both solitary and combined organ transplantation is an important consideration for the principle of equity. Lastly, the lack of standardization of programmatic approaches to SHL transplant candidates, the national approach to allocation, and the criteria by which programs are evaluated are reviewed.SUMMARY: As with all multiorgan transplantation, SHL transplantation raises ethical issues of utility and equity. Given the unique patient population, good outcomes, lack of alternatives, and overall small numbers, we feel there is continued ethical justification for SHL, but a more standardized nationwide approach to the evaluation, listing, and allocation of organs is warranted.

  View details for DOI 10.1097/MOT.0000000000000806

  View details for PubMedID 32881719

• The Stanford acute heart failure symptom score for patients hospitalized with heart failure. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Almond, C. S., Chen, S., Dykes, J. C., Kwong, J., Burstein, D. S., Rosenthal, D. N., Kipps, A. K., Teuteberg, J., Murray, J. M., Kaufman, B. D., Hollander, S. A., Profita, E., Yarlagadda, V. Y., Sacks, L. D., Chen, C. 2020

  Abstract

  BACKGROUND: Currently, there are no simple tools to evaluate the acute heart failure (HF) symptom severity in children hospitalized with acute decompensated HF (ADHF). We sought to develop an inpatient HF score (HFS) that could be used as a clinical tool and for clinical trials.METHODS: Pediatric HF clinicians at Stanford reviewed the limitations of existing HFSs, which include lack of calibration to the inpatient setting, omission of gastrointestinal symptoms, need for multiple age-based tools, and scores that prioritize treatment intensity over patient symptoms. To address these, we developed an acute HFS corresponding to the 3 cardinal symptoms of HF: difficulty with breathing, feeding, and activity. The score was iteratively improved over a 3-year pilot phase until no further changes were made. The inter-rater reliability (IRR) across a range of providers was assessed using the final version. Peak HFSs were analyzed against mortality and length of stay (LOS) for all pediatric HF discharges between July and October 2019.RESULTS: The final HFS was a 4-point ordinal severity score for each of the 3 symptom domains (total score 0-12). Among clinicians who scored 12 inpatients with ADHF simultaneously, the intraclass correlation (ICC) was 0.94 (respiratory ICC = 0.89, feeding ICC = 0.85, and activity ICC = 0.80). Score trajectory reflected our clinical impression of patient response to HF therapies across a range of HF syndromes including 1- and 2-ventricle heart disease and reduced or preserved ejection fraction. Among the 28 patients hospitalized during a 3-months period (N = 28), quartiles of peak score were associated with LOS (p < 0.01) and in-hospital mortality (p < 0.01): HFS 0 to 3 (median LOS of 5 days and mortality of 0%), HFS 4 to 6 (median LOS of 18 days and mortality of 0%), HFS 5 to 9 (median LOS of 29 days and mortality of 23%), and HFS 10 to 12 (median LOS of 121 days and mortality of 50%).CONCLUSION: This simple acute HFS may be a useful tool to quantify and monitor day-to-day HF symptoms in children hospitalized with ADHF regardless of etiology or age group. The score has excellent IRR across provider levels and is associated with major hospital outcomes supporting its clinical validity. Validation in a multicenter cohort is warranted.

  View details for DOI 10.1016/j.healun.2020.08.002

  View details for PubMedID 33032871

• Outcomes Among Patients With Left Ventricular Assist Devices Receiving Maintenance Outpatient Hemodialysis: A Case Series. American journal of kidney diseases : the official journal of the National Kidney Foundation Franz, D. D., Hussein, W. F., Abra, G., Diskin, C. D., Duggal, V., Teuteberg, J. J., Chang, T. I., Schiller, B. 2020

  Abstract

  RATIONALE & OBJECTIVE: The incidence of left ventricular assist device (LVAD) implantation as destination therapy for heart failure is increasing and kidney failure requiring maintenance hemodialysis is a common complication. As little is known about the safety or efficacy of outpatient hemodialysis among patients with LVADs, this study sought to describe their clinical course.STUDY DESIGN: Case series of patients with a LVAD undergoing maintenance outpatient hemodialysis whose clinical data were obtained from an electronic medical record.SETTING & PARTICIPANTS: Adults who received an LVAD, survived to hospital discharge, and were subsequently treated with maintenance hemodialysis by a non-profit dialysis provider between 2011 and 2019.RESULTS: Eleven patients were included. Six had a known prior history of chronic kidney disease. Patients underwent outpatient hemodialysis for a mean duration of 165.2 days (range 31-542) during which they were treated with 544 total dialysis sessions. Six of these sessions were stopped early due to dialysis-related adverse events (1.1%). Over 80% of follow-up time was spent out of hospital, however, 54.5% of patients were rehospitalized within one month of starting outpatient hemodialysis. The most common reason for hospitalization was infection (32.1%), followed by hypervolemia (14.3%), and cerebrovascular accident (CVA) or transient ischemic attack (TIA) (10.7%). Four patients recovered kidney function, one underwent combined heart and kidney transplantation, two continued treatment, two died, and two were lost to follow-up.LIMITATIONS: Retrospective design, small number of cases, and lack of complete follow-up data.CONCLUSIONS: Approximately half of the patients with complete follow-up either recovered kidney function or underwent combined heart and kidney transplantation. This case series demonstrates that outpatient hemodialysis centers, in partnership with LVAD treatment teams, can successfully provide hemodialysis to patients on LVAD support.

  View details for DOI 10.1053/j.ajkd.2020.04.018

  View details for PubMedID 32711070

• (ReBOOT) REmote moBile Outpatient MOnitoring in heart Transplant: A pilot study. The Canadian journal of cardiology Moayedi, Y., Hershman, S. G., Henricksen, E. J., Lee, R., Han, J., Bougouin, W., Khush, K. K., Ross, H. J., Teuteberg, J. J. 2020

  View details for DOI 10.1016/j.cjca.2020.07.005

  View details for PubMedID 32681856

• Predicting Where Patients Will Be, Rather Than Just Seeing Where They Are: Establishing Trajectories of Cardiac Allograft Vasculopathy. Circulation Moayedi, Y., Teuteberg, J. J. 2020; 141 (24): 1968–70

  View details for DOI 10.1161/CIRCULATIONAHA.120.047571

  View details for PubMedID 32539613

• Updated definitions of adverse events for trials and registries of mechanical circulatory support: A consensus statement of the mechanical circulatory support academic research consortium. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kormos, R. L., Antonides, C. F., Goldstein, D. J., Cowger, J. A., Starling, R. C., Kirklin, J. K., Rame, J. E., Rosenthal, D., Mooney, M. L., Caliskan, K., Messe, S. R., Teuteberg, J. J., Mohacsi, P., Slaughter, M. S., Potapov, E. V., Rao, V., Schima, H., Stehlik, J., Joseph, S., Koenig, S. C., Pagani, F. D. 2020

  View details for DOI 10.1016/j.healun.2020.03.010

  View details for PubMedID 32386998

• Use of Temporary Mechanical Circulatory Support for Management of Cardiogenic Shock Before and After the United Network for Organ Sharing Donor Heart Allocation System Changes. JAMA cardiology Varshney, A. S., Berg, D. D., Katz, J. N., Baird-Zars, V. M., Bohula, E. A., Carnicelli, A. P., Chaudhry, S., Guo, J., Lawler, P. R., Nativi-Nicolau, J., Sinha, S. S., Teuteberg, J. J., van Diepen, S., Morrow, D. A., Critical Care Cardiology Trials Network Investigators 2020

  Abstract

  Importance: The new United Network for Organ Sharing (UNOS) donor heart allocation system gives priority to patients supported with nondischargeable mechanical circulatory support (MCS) devices while awaiting heart transplant. Whether there has been a change in temporary MCS use in cardiac intensive care units (CICUs) since the implementation of this policy is unknown.Objectives: To examine whether the UNOS donor heart allocation system revision in October 2018 was associated with changes in temporary MCS use in CICUs and whether temporary MCS use differed between US transplant centers and US nontransplant centers and Canadian centers.Design, Setting, and Participants: In this cohort study, 14 centers from the Critical Care Cardiology Trials Network (CCCTN), a multicenter network of tertiary CICUs in North America, contributed 2-month snapshots of consecutive medical CICU admissions between September 1, 2017, and September 1, 2018 (prerevision period), and October 1, 2018, and September 1, 2019 (postrevision period). CICUs were classified as US transplant centers (n=7) or other CICUs (US nontransplant centers or Canadian centers; n=7).Exposure: Revision to the UNOS donor heart allocation system.Main Outcomes and Measures: Treatment with temporary MCS (intra-aortic balloon pump, microaxial intracardiac ventricular assist device, percutaneous centrifugal ventricular assist device, venoarterial extracorporeal membrane oxygenation, or surgically implanted, nondischargeable MCS device) during hospital admission.Results: A total of 384 admissions for acute, decompensated, heart failure-related cardiogenic shock (ADHF-CS) were included, among which 248 (64.6%) were to US transplant centers; 126 admissions (51%) were in the prerevision period and 122 (49%) were in the postrevision period. The mean (SD) patient age was 61.2 (14.6) years; 246 patients (64.1%) were male. The proportion of admissions with ADHF-CS managed with temporary MCS at US transplant centers significantly increased from 25.4% (32 of 126 admissions) before to 42.6% (52 of 122 admissions) after the UNOS allocation system changes (P=.004). In other CICUs, the proportion did not significantly change (24.5% [13 of 53 admissions] to 24.1% [20 of 83 admissions]; P=.95). After multivariable adjustment, patients admitted to US transplant centers in the postrevision period were more likely to receive temporary MCS compared with those admitted in the prerevision period (adjusted odds ratio, 2.19; 95% CI, 1.13-4.24; P=.02).Conclusions and Relevance: In the year after implementation of the new UNOS donor heart allocation system, temporary MCS use in patients admitted with ADHF-CS increased in US transplant centers but not in other CICUs. Whether this shift in practice will affect outcomes of patients with ADHF-CS or organ distribution should be evaluated.

  View details for DOI 10.1001/jamacardio.2020.0692

  View details for PubMedID 32293644

• The Society of Thoracic Surgeons Intermacs 2019 Annual Report: The Changing Landscape of Devices and Indications. The Annals of thoracic surgery Teuteberg, J. J., Cleveland, J. C., Cowger, J., Higgins, R. S., Goldstein, D. J., Keebler, M., Kirklin, J. K., Myers, S. L., Salerno, C. T., Stehlik, J., Fernandez, F., Badhwar, V., Pagani, F. D., Atluri, P. 2020; 109 (3): 649–60

  Abstract

  BACKGROUND: The field of mechanical circulatory support has been impacted by the approval of new continuous-flow left ventricular assist devices (LVADs) and changes to the United States heart allocation system.METHODS: Primary isolated continuous-flow LVAD implants in The Society of Thoracic Surgeons Intermacs registry from January 2014 through September 2019 were evaluated. Survival and freedom from major adverse events were compared between axial-flow, centrifugal-flow with hybrid levitation (CF-HL), and centrifugal-flow with full magnetic levitation (CF-FML) devices.RESULTS: Of 2603 devices implanted in 2014, 1824 (70.1%) were axial flow and 1213 (46.6%) were destination therapy (DT); through September 2019, 1752 devices were implanted, but only 37 (2.1%) were axial flow and 1230 (70.2%) were DT. Implants were performed in 13,016 patients between 2014 and 2018. Patients receiving implants in 2017-2018 compared with 2014-2016 were more likely to be at Intermacs profile 1 (17.1% vs 14.3%, P < .001) and to have preimplant temporary mechanical circulatory support (34.8% vs 29.3%, P < .001). Overall survival and freedom from major adverse events were higher with CF-FML devices. In multivariable analysis ofsurvival between CF-HL and CF-FML, device type wasnot a significant early hazard, but the use of CF-HL devices had a late hazard ratio for death of 3.01 (P<.001).CONCLUSIONS: Over the past 5 years, centrifugal-flow LVADs have become the dominant technology and DT the most common implant strategy. While outcomes with CF-FML devices are promising, comparisons with other devices from nonrandomized registry studies should be made with caution.

  View details for DOI 10.1016/j.athoracsur.2019.12.005

  View details for PubMedID 32115073

• Understanding risk factors and predictors for stroke subtypes in the ENDURANCE trials. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Cho, S., Starling, R. C., Teuteberg, J., Rogers, J., Pagani, F., Shah, P., Uchino, K., Hiivala, N. 2020

  Abstract

  BACKGROUND: Stroke is a devastating morbidity associated with left ventricular assist device (LVAD) support. We report a comprehensive analysis of stroke subtypes in the ENDURANCE destination therapy (DT) and ENDURANCE Supplemental (DT2) trials.METHODS: Patients in the combined HeartWare LVAD (HVAD) cohorts of the DT and DT2 trials were included. Neurologic events included ischemic stroke (ischemic cerebrovascular accident [ICVA]), hemorrhagic stroke (hemorrhagic cerebrovascular accident [HCVA]), and transient ischemic attack (TIA). Peri-operative strokes were defined as occurring within 2 weeks of the implant.RESULTS: A total of 604 patients received an HVAD in the DT (n = 296) and DT2 (n = 308) trials. Over 2 years, 178 (29.5%) had at least 1 cerebrovascular accident (CVA). Forty-four (7.3%) had HCVAs, 116 (19.2%) had ICVAs, and 44 (7.3%) had TIAs. Thirty (5.0%) had peri-operative stroke. In multivariable analysis, sub-therapeutic international normalized ratio (INR) values were independently associated with peri-operative stroke. Supra- and/or sub-therapeutic INR values, peripheral vascular disease, and presence of left ventricular thrombus were independently associated with ICVA. No aspirin and supra- and/or sub-therapeutic INR values were independently associated with TIA. No aspirin, supra- and/or sub-therapeutic INR values, and prior stroke and/or TIA were associated with HCVA. In further analysis, mean arterial pressure (MAP) was higher in the ICVA (86.8mmHg, p = 0.0024) and TIA (88.8mmHg, p<0.0001) groups, but not in HCVA, than in the No-CVA group (81.4mmHg). Time in therapeutic range for INR was 65.3% for the No-CVA group, 62.9% (p = 0.59) for HCVA, 65.1% (p = 0.97) for ICVA, and 63.2% (p = 0.62) for TIA.CONCLUSIONS: Supra- and sub-therapeutic INR values at the time of CVA were associated with all stroke subtypes >14 days post-implant. MAP was higher among those with ICVA and TIA but not with HCVA compared to without CVA. Our study demonstrates the challenges of anti-thrombotic therapy and blood pressure management in LVAD population.

  View details for DOI 10.1016/j.healun.2020.01.1330

  View details for PubMedID 32044205

• Use of direct oral anticoagulants after heart transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Henricksen, E. J., Tremblay-Gravel, M., Moayedi, Y., Yang, W., Lee, R., Ross, H. J., Hiesinger, W., Teuteberg, J. J., Khush, K. K. 2020

  View details for DOI 10.1016/j.healun.2019.12.007

  View details for PubMedID 32007373

• Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound. Clinical transplantation Moayedi, Y., Fan, C. P., Tremblay-Gravel, M., Miller, R. J., Kawana, M., Henricksen, E., Parizo, J., Wainwright, R., Fearon, W. F., Ross, H. J., Khush, K. K., Teuteberg, J. J. 2020: e14098

  Abstract

  Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor derived atherosclerosis (DA), early discontinuation of prednisone and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS).Retrospective single center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥ 0.5 mm, CAV development was defined as MIT ≥ 1 mm or an increase in MIT ≥ 0.5 mm at year 1 compared to baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV.Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51±11 years, 70% were male, 58% were Caucasian and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA- vs. 59% in DA+(p=0.012). Donor age was a strong predictor of DA (p=0.016). Significant risk factors for CAV included male sex (HR= 4.141, p=0.001), non-Caucasian race (HR= 1.98, p= 0.011), BMI < 18 kg/m2 (HR=4.596, p=0.042), longer ischemic time (HR=1.374, p=0.028), older donor age (HR=1.158, p=0.009) and rejection with hemodynamic compromise within the first year (HR=2.858, p=0.043). Prednisone discontinuation within 1-year was associated with a lower risk of CAV (HR 0.58 p=0.047). Initiation of proliferation signal inhibitors (PSI) within 2 years resulted in fewer cases of CAV (HR 0.397 p<0.001).In patients with an angiogram at 1 year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.

  View details for DOI 10.1111/ctr.14098

  View details for PubMedID 32970884

• Ethical considerations regarding heart and lung transplantation and mechanical circulatory support during the COVID-19 pandemic: an ISHLT COVID-19 Task Force statement. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Holm, A. M., Mehra, M. R., Courtwright, A., Teuteberg, J., Sweet, S., Potena, L., Singer, L. G., Farrero, M., Shullo, M. A., Benza, R., Ensminger, S., Aslam, S. 2020

  Abstract

  To understand the challenges for thoracic transplantation and mechanical circulatory support during the current coronavirus disease 2019 pandemic, we propose separating the effects of the pandemic into 5 distinct stages from a healthcare system perspective. We discuss how the classical ethical principles of utility, justice, and efficiency may need to be adapted, and we give specific recommendations for thoracic transplantation and mechanical circulatory support centers to balance their clinical decisions and strategies for advanced heart and lung disease during the current pandemic.

  View details for DOI 10.1016/j.healun.2020.04.019

  View details for PubMedID 32505492

• Defining Optimal Outcomes in Patients with Left Ventricular Assist Devices. ASAIO journal (American Society for Artificial Internal Organs : 1992) Kanwar, M. K., McIlvennan, C. K., Lohmueller, L. C., Bailey, S. H., Rogers, J. G., Teuteberg, J., Cowger, J. 2020

  Abstract

  Left ventricular assist devices (LVADs) have consistently and successfully improved mortality associated with end-stage heart failure. However, the definition of an "optimal" outcome post LVAD as a benchmark remains debatable. We retrospectively examined patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) between 2012 and 2016 to assess 1 year post-LVAD "optimal outcome" defined as a patient who was alive on device or transplanted, New York Heart Association functional class I/II, had no more than 2 hospitalizations at year 1, and no major adverse event. We identified the features predicting a nonoptimal outcome at 1 year. Finally, we focused on 3 years outcomes in patients implanted as destination therapy. Of the 12,566 patients in INTERMACS who received an LVAD, only 3,495 (27.8%) met our definition of optimal LVAD outcome at 1 year. These patients tended to be younger, male, and were four times more likely to be supported as bridge to transplantation. For those with optimal outcome at year 1, their chances of long-term survival were better than those who were alive at year 1, but did not meet criteria for an optimal outcome. In the destination therapy population, only 14% of patients met the definition of an optimal outcome at 3 years. Despite significantly improved survival in patients with end-stage heart failure treated with LVAD therapy, majority patients had nonoptimal outcomes at 1 and 3 years post implant, by our definition. There is a pressing need to create a benchmark to define optimal outcomes post LVAD, both in our clinical trials and practice.

  View details for DOI 10.1097/MAT.0000000000001228

  View details for PubMedID 32701625

• To Kidney or Not to Kidney: Applying Lessons Learned from the Simultaneous Liver-Kidney Transplant Policy to Simultaneous Heart-Kidney Transplantation. Clinical transplantation Cheng, X. S., Khush, K. K., Wiseman, A., Teuteberg, J., Tan, J. C. 2020

  Abstract

  As the medical community is increasingly offering transplantation to patients with increasing comorbidity burdens, the number of simultaneous heart-kidney (SHK) transplants is rising in the United States. How to determine eligibility for SHK transplant versus heart transplant alone is an important unknown. In this review, we situate this problem in the broader picture of organ shortage. We critically appraise available literature on outcomes in SHK versus heart transplant alone. We posit staged kidney-after-heart transplantation as a plausible alternative to SHK transplantation and review the pros and cons. Drawing lessons from the field of simultaneous liver-kidney transplant, we argue for an analogous policy for SHK transplant with standardized minimal eligibility criteria and a modified Safety Net provision. The new policy will serve as a starting point for comparing simultaneous versus staged approaches and refining the medical eligibility criteria for SHK.

  View details for DOI 10.1111/ctr.13878

  View details for PubMedID 32279361

• Recent Trends of Infectious Complications Following Heart Transplantation. Transplantation Multani, A., Moayedi, Y., Puing, A., Henricksen, E., Garvert, D. W., Gomez, C. A., Tremblay-Gravel, M., Bunce, P. E., Luikart, H., Ross, H. J., Khush, K. K., Montoya, J. G., Teuteberg, J. J. 2020

  Abstract

  Heart transplantation is a life-saving procedure that has seen improvements in transplant and patient outcomes due to advances in immunosuppression and prevention of posttransplantation infectious episodes (IEps). This study systematically evaluates IEps in the modern era of heart transplantation at Stanford University Medical Center.This is a single-center retrospective review that includes 279 consecutive adult heart transplantation recipients from January 2008 to September 2017. Baseline demographic, clinical, serological, and outcomes information were collected. Kaplan-Meier estimator was used to assess survival stratified by IEp occurrence within the first year.A total of 600 IEps occurred in 279 patients (2.15 IEps per patient) during a median follow-up period of 3 years. Overall survival was 83.3% [95% CI (76.2 to 88.4)] at 1 year posttransplantation for those with any IEp compared to 93.0% [95% CI (87.2,96.4)] in those without IEp (p=0.07). Bacterial IEps were the most common (n=375, 62.5%), followed by viral (n=180, 30.0%), fungal (n=40, 6.7%), and parasitic (n=5, 0.8%). IEps by Gram-negative bacteria (n=210) outnumbered those by Gram-positive bacteria (n=142). Compared to prior studies from our center, there was a decreased proportion of viral (including cytomegalovirus), fungal (including Aspergillus spp. and non-Aspergillus spp. molds), and Nocardia infections. There were no IEps due to Mycobacterium tuberculosis, Pneumocystis jirovecii, or Toxoplasma gondii.A significant reduction in viral, fungal, and Nocardia IEps after heart transplantation was observed, most likely due to advancements in immunosuppression and preventive strategies, including pretransplant infectious diseases screening and antimicrobial prophylaxis.

  View details for DOI 10.1097/TP.0000000000003307

  View details for PubMedID 32413012

• Impact of cytomegalovirus infection on gene expression profile in heart transplant recipients. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kanwar, M. K., Khush, K. K., Pinney, S., Sherman, C., Hall, S., Teuteberg, J., Uriel, N., Kobashigawa, J. 2020

  Abstract

  Cytomegalovirus (CMV) infection has been implicated in the pathogenesis of allograft rejection in heart transplant (HT) recipients. The effect of a CMV infection on the gene expression profiling (GEP, AlloMap) scores in the absence of acute rejection is not known.Data from 14,985 samples collected from 2,288 adult HT recipients enrolled in Outcomes AlloMap Registry were analyzed. Patients with known CMV serology at the time of HT who had at least 1 AlloMap score reported during follow-up were included. AlloMap scores for those patients with CMV (but no ongoing rejection) were compared with those who were never infected. An exploratory analysis on the impact of CMV on available donor-derived cell-free DNA (AlloSure) was also performed.A total of 218 patients (10%) were reported to have CMV infection after transplantation. AlloMap score in those samples with CMV infection (n = 311) had a GEP score (34; range: 29-36) significantly higher than the GEP score from samples (n = 14,674) obtained in the absence of CMV infection (30; range: 26-34; p < 0.0001). Both asymptomatic viremia and CMV disease demonstrated significantly higher AlloMap scores than no CMV infection samples (median scores: 33, 35, and 30, respectively; p < 0.0001). AlloSure levels, available for 776 samples, were not significantly different (median: 0.23% in 18 samples with CMV infection vs 0.15% in 776 samples without CMV infection; p = 0.66).CMV infection in HT recipients is associated with an increase in AlloMap score, whereas AlloSure results do not appear to be impacted. This information should be considered when clinically interpreting abnormal/high AlloMap scores in HT recipients.

  View details for DOI 10.1016/j.healun.2020.11.008

  View details for PubMedID 33341360

• 2019 STS/Intermacs Annual Report Writing Committee's Response. The Annals of thoracic surgery Pagani, F. D., Teuteberg, J., Cleveland, J., Atluri, P., Kirklin, J., Habib, R. 2020

  View details for DOI 10.1016/j.athoracsur.2020.07.102

  View details for PubMedID 33144112

• Clinical Practice Patterns in Temporary Mechanical Circulatory Support for Shock in the Critical Care Cardiology Trials Network (CCCTN) Registry. Circulation. Heart failure Berg, D. D., Barnett, C. F., Kenigsberg, B. B., Papolos, A., Alviar, C. L., Baird-Zars, V. M., Barsness, G. W., Bohula, E. A., Brennan, J., Burke, J. A., Carnicelli, A. P., Chaudhry, S., Cremer, P. C., Daniels, L. B., DeFilippis, A. P., Gerber, D. A., Granger, C. B., Hollenberg, S., Horowitz, J. M., Gladden, J. D., Katz, J. N., Keeley, E. C., Keller, N., Kontos, M. C., Lawler, P. R., Menon, V., Metkus, T. S., Miller, P. E., Nativi-Nicolau, J., Newby, L. K., Park, J., Phreaner, N., Roswell, R. O., Schulman, S. P., Sinha, S. S., Snell, R. J., Solomon, M. A., Teuteberg, J. J., Tymchak, W., van Diepen, S., Morrow, D. A. 2019; 12 (11): e006635

  Abstract

  BACKGROUND: Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units.METHODS: The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions.RESULTS: Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%-50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%-100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use.CONCLUSIONS: There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity.

  View details for DOI 10.1161/CIRCHEARTFAILURE.119.006635

  View details for PubMedID 31707801

• Survival Outcomes After Heart Transplantation: Does Recipient Sex Matter? Circulation. Heart failure Moayedi, Y., Fan, C. P., Cherikh, W. S., Stehlik, J., Teuteberg, J. J., Ross, H. J., Khush, K. K. 2019; 12 (10): e006218

  Abstract

  BACKGROUND: Currently, women represent <25% of heart transplant recipients. Reasons for this female underrepresentation have been attributed to selection and referral bias and potentially poorer outcomes in female recipients. The aim of this study was to compare long-term posttransplant survival between men and women, when matched for recipient and donor characteristics.METHODS AND RESULTS: Using the International Society for Heart and Lung Transplantation Registry, we performed descriptive analyses and estimated overall freedom from posttransplant death stratified by sex using Kaplan-Meier survival methods. Male and female recipients were matched according to the Index for Mortality Prediction After Cardiac Transplantation and Donor Risk Index score using 1:1 propensity score matching. The study cohort comprised 34198 heart transplant recipients (76.3% men, 23.7% women) between 2004 and 2014. Compared with men, women were more likely younger (51 [39-59] versus 55 [46-61] years; P<0.001) and had a different distribution of heart failure etiology (P<0.001). In general, the prevalence of comorbidities was lower in women than in men. Women were less likely to have diabetes mellitus (19.1% versus 26.2%; P<0.001), hypertension (40.7% versus 47.9%; P<0.001), peripheral vascular disease (2.4% versus 3.3%; P=0.002), tobacco use (36.5% versus 52.3%; P<0.001), and prior cardiovascular surgery (38.6% versus 50.7%; P<0.001). Women were more likely to have a history of malignancy (10.5% versus 5.3%; P<0.001), require intravenous inotropes (41.4% versus 37.2%; P<0.001), and were less likely supported by an intra-aortic balloon pump (3.3% versus 3.8%; P=0.03) or durable ventricular assist device (22% versus 31.5%; P<0.001). Transplanted male recipients had a higher Index for Mortality Prediction After Cardiac Transplantation score (5 [2-7] versus 4 [1-6]; P<0.001). When male and female heart transplant recipients were matched for recipient and donor characteristics, there was no significant survival difference (P=0.57).CONCLUSIONS: Overall survival does not differ between men and women after cardiac transplantation. Women who survive to heart transplantation appear to have lower risk features than male recipients but receive hearts from higher risk donors.

  View details for DOI 10.1161/CIRCHEARTFAILURE.119.006218

  View details for PubMedID 31597452

• OUTCOMES OF PATIENTS WITH INFECTION RELATED TO VENTRICULAR ASSIST DEVICE AFTER HEART TRANSPLANTATION Moayedi, Y., Multani, A., Bunce, P., Tremblay-Gravel, M., Gomez, C., Garvert, D., Duclos, S., Hiesinger, W., Ross, H., Khush, K., Montoya, J., Teuteberg, J. WILEY. 2019: 55

  View details for Web of Science ID 000491488701171

• Outcomes of patients with infection related to a ventricular assist device after Heart Transplantation. Clinical transplantation Moayedi, Y., Multani, A., Bunce, P. E., Henricksen, E., Lee, R., Yang, W., Gomez, C. A., Garvert, D. W., Tremblay-Gravel, M., Duclos, S., Hiesinger, W., Ross, H. J., Khush, K. K., Montoya, J. G., Teuteberg, J. J. 2019: e13692

  Abstract

  BACKGROUND: Despite significant advances in durable mechanical support survival, infectious complications remain the most common adverse event after ventricular assist device (VAD) implantation and the leading cause of early death after transplantation. In this study, we aim to describe our local infectious epidemiology and review short term survival and infectious incidence rates in the post transplantation period and assess risk factors for infectious episodes after transplantation.METHODS: Retrospective single-center study of all consecutive adult heart transplant patients from 2008-2017. Survival data was estimated and summarized using the Kaplan-Meier method. We quantified and evaluated the difference in the incidence rate between patients with and without infection using a Fine-Gray model. The outcome of interest is the time to first infection diagnosis with post-transplant death as the competing event.RESULTS: Among 282 heart transplantations, 74 (26.5%) underwent LVAD implantation. Twenty-one patients (28.3%) developed an infection while supported by an LVAD. When compared to patients supported by an LVAD without a preceding infection, BMI was significantly greater (31.2 vs. 27.8 kg/m2, p=0.03). Median follow-up post transplantation was 3.01 years. Significant risk factors for the competing risk regression for infection after heart transplantation include LVAD infection (HR 1.94, [95% CI] 1.11-3.39, p=0.020) and recipient COPD (HR 2.14, [95% CI] 1.39-3.32, p=0.001) when adjusted for recipient age, gender, hypertension, diabetes mellitus and body mass index.CONCLUSIONS: Patients with LVAD-related infection had a significantly increased risk of infectious complications after heart transplantation. Further research on the avoidance of induction agents and reduced maintenance immunosuppression in this patient population is warranted This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.13692

  View details for PubMedID 31403741

• Outcomes in patients undergoing cardiac retransplantation: A propensity matched cohort analysis of the UNOS Registry. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Miller, R. J., Clarke, B. A., Howlett, J. G., Khush, K. K., Teuteberg, J. J., Haddad, F. 2019

  Abstract

  BACKGROUND: Cardiac retransplantation accounts for approximately 3% of cardiac transplantation and is considered a risk factor for increased mortality. However, factors inherent to retransplantation including previous sternotomy, sensitization, and renal dysfunction may account for the increased mortality. We assessed whether retransplantation was associated with all-cause mortality after adjusting for such patient risk factors.METHODS: We conducted a retrospective cohort study of adult and pediatric patients enrolled in the United Network for Organ Sharing database. We identified patients undergoing cardiac retransplantation based on transplant listing diagnosis and history of previous transplant. We used propensity-score matching to identify a matched cohort undergoing initial heart transplantation.RESULTS: In total, 62,112 heart transplant recipients were identified, with a mean age 46.6 ± 19.1 years. Of these, 2,202 (3.4%) underwent late cardiac retransplantation (>1 year after initial transplant and not for acute rejection). Compared with a matched group of patients undergoing initial heart transplantation, patients undergoing late retransplantation had comparable rates of all-cause mortality at 1 year (13.6% vs 13.8%, p = 0.733). In addition, overall mortality was not significantly different after matching (unadjusted hazard ratio [HR] 1.08, p = 0.084). In contrast, patients undergoing retransplantation within 1 year of initial transplant or for acute rejection remained at increased risk of mortality post-transplant after similar matching (unadjusted HR 1.79, p < 0.001).CONCLUSIONS: After matching for comorbidities, late retransplantation in the adult population was not associated with an increase in all-cause mortality. Our findings highlight the importance of assessing indication acuity and comorbid conditions when considering retransplant candidacy.

  View details for DOI 10.1016/j.healun.2019.07.001

  View details for PubMedID 31378576

• Risk Assessment in Patients with a Left Ventricular Assist Device Across INTERMACS Profiles Using Bayesian Analysis ASAIO JOURNAL Kanwar, M. K., Lohmueller, L. C., Teuteberg, J., Kormos, R. L., Rogers, J. G., Benza, R. L., Lindenfeld, J., McIlvennan, C., Bailey, S. H., Murali, S., Antaki, J. F. 2019; 65 (5): 436–41

  View details for DOI 10.1097/MAT.0000000000000910

  View details for Web of Science ID 000474149400009

• Infectious complications after heart transplantation in patients screened with gene expression profiling JOURNAL OF HEART AND LUNG TRANSPLANTATION Moayedi, Y., Gomez, C. A., Fan, C. S., Miller, R. H., Bunce, P. E., Tremblay-Gravel, M., Foroutan, F., Manlhiot, C., Yee, J., Shullo, M. A., Khush, K. K., Ross, H. J., Montoya, J. G., Teuteberg, J. J. 2019; 38 (6): 611–18

  View details for DOI 10.1016/j.healun.2019.01.006

  View details for Web of Science ID 000468597800006

• Thrombotic events with proliferation signal inhibitor-based immunosuppression in cardiac transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Witkowsky, O., Teuteberg, J., Althouse, A. D., Shullo, M. 2019; 38 (6): 619–26

  View details for DOI 10.1016/j.healun.2019.01.004

  View details for Web of Science ID 000468597800007

• Preimplant Phosphodiesterase-5 Inhibitor Use Is Associated With Higher Rates of Severe Early Right Heart Failure After Left Ventricular Assist Device Implantation. Circulation. Heart failure Gulati, G., Grandin, E. W., Kennedy, K., Cabezas, F., DeNofrio, D. D., Kociol, R., Rame, J. E., Pagani, F. D., Kirklin, J. K., Kormos, R. L., Teuteberg, J., Kiernan, M. 2019; 12 (6): e005537

  Abstract

  Background Early right heart failure (RHF) occurs commonly in left ventricular assist device (LVAD) recipients, and increased right ventricular (RV) afterload may contribute. Selective pulmonary vasodilators, like phosphodiesterase-5 inhibitors (PDE5i), are used off-label to reduce RV afterload before LVAD implantation, but the association between preoperative PDE5i use and early RHF after LVAD is unknown. Methods and Results We analyzed adult patients from the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support) who received a continuous flow LVAD after 2012. Patients on PDE5i were propensity-matched 1:1 to controls. The primary outcome was the incidence of severe early RHF, defined as the composite of death from RHF within 30 days, need for RV assist device support within 30 days, or use of inotropes beyond 14 days. Of 11544 continuous flow LVAD recipients, 1199 (10.4%) received preoperative PDE5i. Compared to controls, patients on PDE5i had higher pulmonary artery systolic pressure (53.4 mmHg versus 49.5 mmHg) and pulmonary vascular resistance (2.6 WU versus 2.3 WU; P<0.001 for both). Before propensity matching, the incidence of severe early RHF was higher among patients on PDE5i than in controls (29.4% versus 23.1%; unadjusted odds ratio (OR), 1.32; 95% CI, 1.17-1.50). This association persisted after propensity matching (PDE5i, 28.9% versus control 23.7%; OR, 1.31; 95% CI, 1.09-1.57), driven by a higher incidence of prolonged inotropic support. Similar results were observed across a wide range of subgroups stratified by markers of pulmonary vascular disease and RV dysfunction. Conclusions Patients treated with preoperative PDE5i had markers of increased RV afterload and HF severity compared to unmatched controls. Even after propensity matching, patients receiving preimplant PDE5i therapy had higher rates of post-LVAD RHF.

  View details for DOI 10.1161/CIRCHEARTFAILURE.118.005537

  View details for PubMedID 31181953

• Short-term outcomes of en bloc combined heart and liver transplantation in the failing Fontan CLINICAL TRANSPLANTATION Vaikunth, S. S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D. N., Teuteberg, J., Woo, Y., Lui, G. K. 2019; 33 (6)

  View details for DOI 10.1111/ctr.13540

  View details for Web of Science ID 000473087200014

• Parvovirus B19-induced severe anemia in heart transplant recipients: Case report and review of the literature CLINICAL TRANSPLANTATION Pinto, N. C., Newman, C., Gomez, C. A., Khush, K. K., Moayedi, Y., Lee, R., Teuteberg, J. J., Montoya, J. G. 2019; 33 (4)

  View details for DOI 10.1111/ctr.13498

  View details for Web of Science ID 000465099100016

• Outcomes with ambulatory advanced heart failure from the Medical Arm of Mechanically Assisted Circulatory Support (MedaMACS) Registry. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Ambardekar, A. V., Kittleson, M. M., Palardy, M., Mountis, M. M., Forde-McLean, R. C., DeVore, A. D., Pamboukian, S. V., Thibodeau, J. T., Teuteberg, J. J., Cadaret, L., Xie, R., Taddei-Peters, W., Naftel, D. C., Kirklin, J. K., Stevenson, L. W., Stewart, G. C. 2019; 38 (4): 408–17

  Abstract

  BACKGROUND: The outlook for ambulatory patients with advanced heart failure (HF) and the appropriate timing for left ventricular assist device (LVAD) or transplant remain uncertain. The aim of this study was to better understand disease trajectory and rates of progression to subsequent LVAD therapy and transplant in ambulatory advanced HF.METHODS: Patients with advanced HF who were New York Heart Association (NYHA) Class III or IV and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 4 to 7, despite optimal medical therapy (without inotropic therapy), were enrolled across 11 centers and followed for the end-points of survival, transplantation, LVAD placement, and health-related quality of life. A secondary intention-to-treat survival analysis compared outcomes for MedaMACS patients with a matched group of Profile 4 to 7 patients with LVADs from the INTERMACS registry.RESULTS: Between May 2013 and October 2015, 161 patients were enrolled with INTERMACS Profiles 4 (12%), 5 (32%), 6 (49%), and 7 (7%). By 2 years after enrollment, 75 (47%) patients had reached a primary end-point with 39 (24%) deaths, 17 (11%) undergoing LVAD implantation, and 19 (12%) receiving a transplant. Compared with 1,753 patients with Profiles 4 to 7 receiving LVAD therapy, there was no overall difference in intention-to-treat survival between medical and LVAD therapy, but survival with LVAD therapy was superior to medical therapy among Profile 4 and 5 patients (p = 0.0092). Baseline health-related quality of life was lower among patients receiving a LVAD than those enrolled on continuing oral medical therapy, but increased after 1 year for survivors in both cohorts.CONCLUSIONS: Ambulatory patients with advanced HF are at high risk for poor outcomes, with only 53% alive on medical therapy after 2 years of follow-up. Survival was similar for medical and LVAD therapy in the overall cohort, which included the lower severity Profiles 6 and 7, but survival was better with LVAD therapy among patients in Profiles 4 and 5. Given the poor outcomes in this group of advanced HF patients, timely consideration of transplant and LVAD is of critical importance.

  View details for PubMedID 30948210

• Impact of Hemodynamic Ramp Test-Guided HVAD Speed and Medication Adjustments on Clinical Outcomes. Circulation. Heart failure Uriel, N., Burkhoff, D., Rich, J. D., Drakos, S. G., Teuteberg, J. J., Imamura, T., Rodgers, D., Raikhelkar, J., Vorovich, E. E., Selzman, C. H., Kim, G., Sayer, G. 2019; 12 (4): e006067

  Abstract

  BACKGROUND: Hemodynamic ramp (HR) tests can guide the optimization of left ventricular assist device (LVAD) speed and direct medical therapy. We investigated the effects of HR-guided LVAD management.METHODS AND RESULTS: This prospective, multicenter, randomized, pilot study compared outcomes in LVAD patients using an HR-guided (HR group) versus a standard transthoracic echocardiography-guided (control group) management strategy. Patients were enrolled and randomized 1 to 3 months post-HVAD implantation and followed for 6 months. Twenty-two patients (57±10 years, 73% male) were randomized to the HR group and 19 patients (51±13 years, 63% male) to the control group. HR group patients had double the number of LVAD speed changes (1.68 versus 0.84 changes/patient, P=0.09 with an incidence rate ratio 2.0, 95% CI, 0.9-4.7) with twice the magnitude of rotations per minute changes (130 versus 60 rotations per minute/patient, P=0.004) during the study. The HR group also had 2-fold greater heart failure medication changes (4.32 versus 2.53 changes/patient, P=0.072, incidence rate ratio 1.7 with 95% CI, 0.8-3.5) predominantly because of changes in diuretic dose (40 versus 0 mg/patient, P<0.001). The HR group had numerically but not statistically higher event-free survival (62% versus 46%, P=0.087; hazard ratio, 0.46 with 95% CI, 0.2-1.2), with numerically but not statistically lower events per patient-year ( P=0.084). There were no significant differences in the 6-minute walk or Kansas City Cardiomyopathy Questionnaire tests at 6 months.CONCLUSIONS: In this randomized pilot study of LVAD patient management we demonstrated the feasibility of standardized HR testing at multiple institutions and that a strategy guided by hemodynamics was associated with more LVAD speed and medication adjustments and a nonsignificant reduction in adverse events. A pivotal study to demonstrate the clinical benefit of HR testing is warranted.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03021239.

  View details for PubMedID 30946600

• Impact of Hemodynamic Ramp Test-Guided HVAD Speed and Medication Adjustments on Clinical Outcomes The RAMP-IT-UP Multicenter Study CIRCULATION-HEART FAILURE Uriel, N., Burkhoff, D., Rich, J. D., Drakos, S. G., Teuteberg, J. J., Imamura, T., Rodgers, D., Raikhelkar, J., Vorovich, E. E., Selzman, C. H., Kim, G., Sayer, G. 2019; 12 (4)

  View details for DOI 10.1161/CIRCHEARTFAILURE.119.006067

  View details for Web of Science ID 000469340000009

• Outcomes with ambulatory advanced heart failure from the Medical Arm of Mechanically Assisted Circulatory Support (MedaMACS) Registry JOURNAL OF HEART AND LUNG TRANSPLANTATION Ambardekar, A., Kittleson, M. M., Palardy, M., Mountis, M. M., Forde-McLean, R. C., DeVore, A. D., Pamboukian, S., Thibodeau, J. T., Teuteberg, J. J., Cadaret, L., Xie, R., Taddei-Peters, W., Naftel, D. C., Kirklin, J. K., Stevenson, L. W., Stewart, G. C. 2019; 38 (4): 408–17

  View details for DOI 10.1016/j.healun.2018.09.021

  View details for Web of Science ID 000465437900011

• Short-Term Outcomes of en bloc Combined Heart and Liver Transplantation in the Failing Fontan. Clinical transplantation Vaikunth, S. S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D. N., Teuteberg, J., Joseph Woo, Y., Lui, G. K. 2019: e13540

  Abstract

  Patients with failing Fontan physiology and liver cirrhosis are being considered for combined heart and liver transplantation. We performed a retrospective review of our experience with en bloc combined heart and liver transplantation in Fontan patients > 10 years old from 2006-18 per Institutional Review Board approval. Six females and 3 males (median age 20.7, range 14.2-41.3 years) underwent en bloc combined heart and liver transplantation. Indications for heart transplant included ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia and/or lymphatic abnormalities. Indication for liver transplant included portal hypertension and cirrhosis. Median Fontan/single ventricular end diastolic pressure was 18/12 mm Hg, respectively. Median Model for End-Stage Liver Disease excluding International Normalized Ratio score was 10 (7-26), eight patients had a Varices, Ascites, Splenomegaly, Thrombocytopenia score of>2, and all patients had cirrhosis. Median cardiopulmonary bypass and donor ischemic times were 262 (178-307) and 287 (227-396) minutes, respectively. Median intensive care and hospital stay were 19 (5-96) and 29 (13-197) days, respectively. Survival was 100% and rejection was 0% at 30 days and 1 year post-transplant. En bloc combined heart and liver transplantation is an acceptable treatment in the failing Fontan patient with liver cirrhosis. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30891780

• Parvovirus B19-Induced Severe Anemia in Heart Transplant Recipients: Case Report and Review of the Literature. Clinical transplantation Pinto, N. C., Newman, C., Gomez, C. A., Khush, K. K., Moayedi, Y., Lee, R., Teuteberg, J. J., Montoya, J. G. 2019: e13498

  Abstract

  We report a case of a 64-year-old woman who developed transfusion-dependent anemia after cardiac transplantation, the etiology of which was unknown after initial comprehensive evaluation. At the suggestion of the Transplant Infectious Diseases consultant, microbial agents with red blood cell tropism pertinent to this patient such as Parvovirus B 19 (B19V) were investigated. The B19V viral load by PCR in peripheral blood was >100,000,000 copies/ml and after treatment with intravenous immunoglobulin (IVIG), her anemia resolved. Here, we summarize the clinical and virologic characteristics, treatment, and outcome of fifteen cases of B19V-induced anemia in heart transplant recipients. Spontaneous recovery from anemia secondary to B19V has also been reported in some heart transplant recipients, possibly due to an absence of their B19V P-antigen receptor and/or reduction of their immunosuppression. Therefore, in heart transplant patients, B19V should be suspected early as a cause of severe anemia of unknown etiology. The extent that B19V-induced anemia is underdiagnosed in heart transplant recipients is unknown. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30776137

• Tolerability of Sacubitril/Valsartan in Patients With Durable Left Ventricular Assist Devices. ASAIO journal (American Society for Artificial Internal Organs : 1992) Sharma, A., Moayedi, Y., Duclos, S., Teuteberg, J., Banerjee, D. 2019

  View details for DOI 10.1097/MAT.0000000000000957

  View details for PubMedID 31294722

• The Society of Thoracic Surgeons Intermacs Database Annual Report: Evolving Indications, Outcomes, and Scientific Partnerships. The Annals of thoracic surgery Kormos, R. L., Cowger, J., Pagani, F. D., Teuteberg, J. J., Goldstein, D. J., Jacobs, J. P., Higgins, R. S., Stevenson, L. W., Stehlik, J., Atluri, P., Grady, K. L., Kirklin, J. K. 2019; 107 (2): 341–53

  Abstract

  BACKGROUND: The Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), a joint effort among the National Heart, Lung, and Blood Institute, the Food and Drug Administration, the Centers for Medicare and Medicaid Services, and others, was established in 2005 at the University of Alabama at Birmingham. The registry examined clinical outcomes and quality-of-life metrics of patients who received an Food and Drug Administration-approved durable mechanical circulatory support (MCS) device to treat advanced heart failure. On January 1, 2018, the Intermacs Database became part of The Society of Thoracic Surgeons National Database, providing additional resources for quality assessment and improvement and scientific advancement.METHODS: The Intermacs Database Annual Report summarizes outcomes in patients (≥19 years of age) who underwent durable MCS implant between June 23, 2006, and December 31, 2017. Outcomes are presented for patients who underwent isolated continuous flow left ventricular assist device (CF LVAD) support, CF LVAD support with concomitant right ventricular assist device (RVAD) implant, or total artificial heart implant. Analyses of patients with CF LVADs are stratified by axial flow and centrifugal flow configurations. Because of the association of era with outcomes, the survival analyses are restricted to isolated CF LVADs implanted in the 2012 to 2016 era.RESULTS: There were 25,145 adult patients with MCS reported to Intermacs, of whom 18,539 (74%) received CF LVADs, 667 (2.6%) had an RVAD with CF LVAD, 339 received a total artificial heart (1.3%), and 20 (0.07%) received an isolated RVAD. Of the CF LVADs, mean age was 57 ± 1 years, 26% were listed for transplantation, and 51% were in cardiogenic shock (profile 1 to 2) preoperatively. CF LVADs included 14,527 axial flow (78%) and 4,012 centrifugal flow (22%) devices. Intermacs patient phenotype has evolved over time to include more patients with profile 3 (26% in 2006 to 2011 versus 35% in 2012 to 2016) and fewer patients with profile 2 (40% versus 35%), patients with better markers of preoperative renal and hepatic function, and more patients who received implants for destination therapy(29% versus 48%) indication. In 2017, centrifugal flowimplants (51%) approximated that of axial flow devices (49%). Mean CF LVAD support duration was 20 months (31,563 patient-years). One-year survival for isolated CF LVADs was 83% and 5-year survival was 46%. One-year survivals for centrifugal versus axial flow devices were 85% and 84%, respectively. Patients who required concomitant RVAD support had 1- and 5-year survivals of 58% and 28%, respectively. Freedom from all-cause readmission was 70% at 1 month and 20% at 1 year. At 1 year, stroke occurred in 20% of patients on centrifugal flow and 13% of patients on axial flow support (p < 0.001), gastrointestinal bleeding affected 20% of patients with centrifugal flow devices and 25% of patients with axial flow devices (p < 0.001), and pump-related infection occurred in 28% of patients with centrifugal flow devices versus 25% of patients with axial flow devices (p= 0.01). Neurologic dysfunction (19% of deaths) and multisystem organ dysfunction (15%) were the most common causes of death.CONCLUSIONS: With the evolution of MCS, patient phenotype and outcomes are also changing over time. CF LVAD support is increasingly being used in the less ill patient phenotype and more patients are supported for destination therapy. Mean survival is now approaching 5 years, but adverse events, especially neurologic events, continue to have a detrimental impact on the success of CF LVAD support.

  View details for PubMedID 30691584

• The Society of Thoracic Surgeons Intermacs database annual report: Evolving indications, outcomes, and scientific partnerships. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kormos, R. L., Cowger, J., Pagani, F. D., Teuteberg, J. J., Goldstein, D. J., Jacobs, J. P., Higgins, R. S., Stevenson, L. W., Stehlik, J., Atluri, P., Grady, K. L., Kirklin, J. K. 2019; 38 (2): 114–26

  Abstract

  BACKGROUND: The Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), a joint effort among the National Heart, Lung, and Blood Institute, the Food and Drug Administration, the Centers for Medicare and Medicaid Services, and others, was established in 2005 at the University of Alabama at Birmingham. The registry examined clinical outcomes and quality-of-life metrics of patients who received an Food and Drug Administration-approved durable mechanical circulatory support (MCS) device to treat advanced heart failure. On January 1, 2018, the Intermacs Database became part of The Society of Thoracic Surgeons National Database, providing additional resources for quality assessment and improvement and scientific advancement.METHODS: The Intermacs Database Annual Report summarizes outcomes in patients (≥19 years of age) who underwent durable MCS implant between June 23, 2006, and December 31, 2017. Outcomes are presented for patients who underwent isolated continuous flow left ventricular assist device (CF LVAD) support, CF LVAD support with concomitant right ventricular assist device (RVAD) implant, or total artificial heart implant. Analyses of patients with CF LVADs are stratified by axial flow and centrifugal flow configurations. Because of the association of era with outcomes, the survival analyses are restricted to isolated CF LVADs implanted in the 2012 to 2016 era.RESULTS: There were 25,145 adult patients with MCS reported to Intermacs, of whom 18,539 (74%) received CF LVADs, 667 (2.6%) had an RVAD with CF LVAD, 339 received a total artificial heart (1.3%), and 20 (0.07%) received an isolated RVAD. Of the CF LVADs, mean age was 57 ± 1 years, 26% were listed for transplantation, and 51% were in cardiogenic shock (profile 1 to 2) preoperatively. CF LVADs included 14,527 axial flow (78%) and 4,012 centrifugal flow (22%) devices. Intermacs patient phenotype has evolved over time to include more patients with profile 3 (26% in 2006 to 2011 versus 35% in 2012 to 2016) and fewer patients with profile 2 (40% versus 35%), patients with better markers of preoperative renal and hepatic function, and more patients who received implants for destination therapy (29% versus 48%) indication. In 2017, centrifugal flow implants (51%) approximated that of axial flow devices (49%). Mean CF LVAD support duration was 20 months (31,563 patient-years). One-year survival for isolated CF LVADs was 83% and 5-year survival was 46%. One-year survivals for centrifugal versus axial flow devices were 85% and 84%, respectively. Patients who required concomitant RVAD support had 1- and 5-year survivals of 58% and 28%, respectively. Freedom from all-cause readmission was 70% at 1 month and 20% at 1 year. At 1 year, stroke occurred in 20% of patients on centrifugal flow and 13% of patients on axial flow support (p < 0.001), gastrointestinal bleeding affected 20% of patients with centrifugal flow devices and 25% of patients with axial flow devices (p < 0.001), and pump-related infection occurred in 28% of patients with centrifugal flow devices versus 25% of patients with axial flow devices (p= 0.01). Neurologic dysfunction (19% of deaths) and multisystem organ dysfunction (15%) were the most common causes of death.CONCLUSIONS: With the evolution of MCS, patient phenotype and outcomes are also changing over time. CF LVAD support is increasingly being used in the less ill patient phenotype and more patients are supported for destination therapy. Mean survival is now approaching 5 years, but adverse events, especially neurologic events, continue to have a detrimental impact on the success of CF LVAD support.

  View details for PubMedID 30691593

• Risk Assessment in Patients with a Left Ventricular Assist Device Across INTERMACS Profiles Using Bayesian Analysis. ASAIO journal (American Society for Artificial Internal Organs : 1992) Kanwar, M. K., Lohmueller, L. C., Teuteberg, J., Kormos, R. L., Rogers, J. G., Benza, R. L., Lindenfeld, J., McIlvennan, C., Bailey, S. H., Murali, S., Antaki, J. F. 2019

  Abstract

  Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types, and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012 to 2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort), we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3, and 12 months post implant according to disease severity (IM profiles), device type (axial versus centrifugal) and strategy (bridge to transplantation or destination therapy). Fifteen percentage (n = 308) were categorized as IM profile 1, 36% (n = 752) as profile 2, 33% (n = 672) as profile 3, and 15% (n = 311) as profile 4-7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long-term (1 year) mortality for patients with severe HF (Profiles 1-3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC, 0.68-0.74), as well as bridge to transplantation or destination therapy indication (AUC, 0.66-0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models. Bayesian algorithms allow for risk stratification after LVAD implantation across different IM profiles, device types, and implant strategies.

  View details for PubMedID 30688695

• Infectious complications after heart transplantation in patients screened with gene expression profiling. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Moayedi, Y., Gomez, C. A., Fan, C. P., Miller, R. J., Bunce, P. E., Tremblay-Gravel, M., Foroutan, F., Manlhiot, C., Yee, J., Shullo, M. A., Khush, K. K., Ross, H. J., Montoya, J. G., Teuteberg, J. J. 2019

  Abstract

  BACKGROUND: The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (<1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection.METHODS: The primary aim was to assess the incidence and nature of IEp. The secondary aim was to evaluate the effect of potential risk factors, such as recipient age; sex; body mass index; panel-reactive antibodies; cytomegalovirus (CMV) primary mismatch; prednisone, tacrolimus, and sirolimus levels; and gene expression profile (GEP) score, in the development of IEp.RESULTS: The OAR comprises 1,504 patients, of whom 220 patients (14.6%) had an IEp during a median follow-up period of 382 days (interquartile range [IQR] 230 to 579 days). The cause-specific 5-year hazard ratio for any infection was 2.029 (p = 0.12). The pattern of early infection was consistent with nosocomial and opportunistic causes, whereas later infection was consistent with late-onset opportunistic and community-acquired etiologies. Sixty-two percent of the infections occurred early. In the time-dependent analysis, higher prednisone dose (log prednisone, hazard ratio [HR] 1.30, p = 0.022) was the most significant risk factor for all IEp.CONCLUSIONS: In the OAR cohort, the majority of infections occurred within 1 year after transplantation. Clinicians may consider more aggressive prednisone withdrawal in low-risk patients to reduce IEp.

  View details for PubMedID 30704838

• Thrombotic events with proliferation signal inhibitor‒based immunosuppression in cardiac transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Witkowsky, O., Teuteberg, J., Althouse, A. D., Shullo, M. 2019

  Abstract

  BACKGROUND: Some literature exists potentially linking proliferation signal inhibitors (PSIs) to venous thromboembolism (VTE). We sought to determine the impact of PSIs on development of VTE in heart transplant (HT) patients while controlling for other risk factors.METHODS: The incidence and predisposing factors of VTE were analyzed in this retrospective review of patients >18 years who underwent HT January 2000 to October 2016. Re-transplants, multiorgan transplants, or patients that expired within 30 days post-HT were excluded. VTE incidence rates are reported as number of events per 100 person-years. Cox proportional hazards models were used to assess the relationship between PSI exposure (time-varying covariate) and VTE.RESULTS: Of 561 HT recipients, 112 received PSIs, started a median of 1.5 years post-HT. There were 102 total VTE events: 78 in PSI-naive patients during 2,547 patient-years (3.0 events per 100 person-years) vs 24 in PSI-exposed patients during 544 patient-years (4.4 events per 100 person-years). Cox proportional hazards models with PSI exposure as a time-varying covariate indicated the increased risk was statistically significant (unadjusted hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.31 to 3.49, p = 0.002). A VTE history was significantly associated with increased risk of VTE post-HT (HR 1.58, 95% CI 1.07 to 2.35, p = 0.022); however, the risk remained significant when adjusting for potential confounders, including previous VTE (HR 2.0, 95% CI 1.18 to 3.38, p = 0.010).CONCLUSIONS: Exposure to PSIs is associated with a significant increase in risk for VTE even when controlling for other risk factors. When considering the use of PSI-based immunosuppression after HT, the risk of VTE over time should be weighed against the potential benefit.

  View details for PubMedID 30685236

• Innovations in Ventricular Assist Devices for End-Stage Heart Failure ANNUAL REVIEW OF MEDICINE, VOL 70 Miller, R. H., Teuteberg, J. J., Hunt, S. A., Klotman, M. E. 2019; 70: 33–44

  View details for DOI 10.1146/annurev-med-041217-011015

  View details for Web of Science ID 000460209700003

• INTERMACS profiles and outcomes of ambulatory advanced heart failure patients: A report from the REVIVAL Registry. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kittleson, M. M., Shah, P., Lala, A., McLean, R. C., Pamboukian, S., Horstmanshof, D. A., Thibodeau, J., Shah, K., Teuteberg, J., Gilotra, N. A., Taddei-Peters, W. C., Cascino, T. M., Richards, B., Khalatbari, S., Jeffries, N., Stevenson, L. W., Mann, D., Aaronson, K. D., Stewart, G. C. 2019

  Abstract

  Ambulatory patients with advanced heart failure (HF) are often considered for advanced therapies, including durable mechanical circulatory support (MCS). The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles are a commonly used descriptor of disease severity in patients receiving MCS devices, but their role in defining the prognosis of ambulatory patients is less well established, especially for Profiles 6 and 7.Registry Evaluation of Vital Information on Ventricular Assist Devices in Ambulatory Life is a prospective observational study of 400 outpatients from 21 MCS and cardiac transplant centers. Eligible patients had New York Heart Association Class II to IV symptoms despite optimal medical and electrical therapies with a recent HF hospitalization, heart transplant listing, or evidence of high neurohormonal activation.The cohort included 33 INTERMACS Profile 4 (8%), 83 Profile 5 (21%), 155 Profile 6 (39%), and 129 Profile 7 (32%). Across INTERMACS profiles, there were no differences in age, gender, ejection fraction, blood pressure, or use of guideline-directed medical therapy. A lower INTERMACS profile was associated with more hospitalizations, greater frailty, and more impaired functional capacity and quality of life. The composite end point of death, durable MCS, or urgent transplant at 12 months occurred in 39%, 27%, 24%, and 14% subjects with INTERMACS Profiles 4, 5, 6, and 7, respectively (p = 0.004).Among ambulatory patients with advanced HF, a lower INTERMACS profile was associated with a greater burden of HF across multiple dimensions and a higher composite risk of durable MCS, urgent transplant, or death. These profiles may assist in risk assessment and triaging ambulatory patients to advanced therapies.

  View details for DOI 10.1016/j.healun.2019.08.017

  View details for PubMedID 31522912

• A novel therapy for an unusual problem: IL-1 receptor antagonist for recurrent post-transplant pericarditis. Clinical transplantation Parizo, J. T., Moayedi, Y., Nieman, K., Town, K., Teuteberg, J. J., Khush, K. K. 2019

  Abstract

  Heart transplant (HTx) recipients are at increased risk of pericardial disease. Idiopathic recurrent pericarditis has not been previously described following HTx. We describe a 35-year-old male who was admitted with pericarditis and moderate pericardial effusion ten months after HTx. Two weeks before his admission, his prednisone had been tapered off. A thorough infectious workup and endomyocardial biopsy was unrevealing. He was started on colchicine with the addition of tapering prednisone regimen of 40 mg daily due to unresolved pain. Over the next several years he had three recurrent episodes of pericarditis requiring re-initiation of prednisone with extensive investigations negative for rejection, autoimmune and infectious causes. Cardiac MRI confirmed pericardial inflammation. Due to his recurrent course and inability to wean off prednisone, anakinra, an IL-1 receptor antagonist, was started at 100 mg sc daily. This allowed successful discontinuation of prednisone. He is now 34 months post-transplant without recurrence on anakinra and colchicine maintenance. Due to the overlap between idiopathic recurrent pericarditis and auto-inflammatory diseases, there is growing evidence for utilizing IL-1 receptor antagonists in this condition. While pericarditis is common in the HTx population, this is the first report of successful use of an IL-1 receptor blocker for pericarditis in this population. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.13699

  View details for PubMedID 31437316

• Safety and Efficacy of PCSK9 Inhibitors After Heart Transplantation. The Canadian journal of cardiology Moayedi, Y., Kozuszko, S., Knowles, J. W., Chih, S., Oro, G., Lee, R., Fearon, W. F., Ross, H. J., Teuteberg, J. J., Khush, K. K. 2019; 35 (1)

  Abstract

  Dyslipidemia is common in patients undergoing heart transplantation and is associated with the progression of cardiac allograft vasculopathy. Two monoclonal antibodies directed against PCSK9i-evolocumab and alirocumab-are currently available. However, their use, safety and efficacy in the post-transplant setting have not been studied. We present our experience with 6 heart transplant recipients treated with a PCSK9i. A > 70% reduction in LDL-cholesterol was observed after evolocumab therapy. PCSK9 inhibitors are a potentially lipid-lowering therapeutic option for heart transplant patients with suboptimal LDL despite maximal tolerated statin doses.

  View details for PubMedID 30595172

• Gene expression profiling and racial disparities in outcomes after heart transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Moayedi, Y., Fan, C. S., Miller, R. J., Tremblay-Gravel, M., Posada, J. G., Manlhiot, C., Hiller, D., Yee, J., Woodward, R., McCaughan, J. A., Shullo, M. A., Hall, S. A., Pinney, S., Khush, K. K., Ross, H. J., Teuteberg, J. J. 2019

  Abstract

  African Americans (AAs) have lower survival rates after heart transplantation (HTx) than Caucasians. The aim of this analysis was to evaluate racial differences in gene expression and their associations with survival and the composite outcome of death, retransplant, rejection with hemodynamic compromise, and graft dysfunction in the Outcomes AlloMap Registry.Registry participants included low-risk Caucasian and AA heart transplant recipients with a baseline and at least 1 follow-up gene expression test (AlloMap(C)) within the first year after HTx. The Kaplan-Meier method with delayed entry was used to describe differences in outcomes. Multivariable Cox hazard regression was used to evaluate the associations of overall gene expression profiling score, MARCH8 and FLT3 expression, and tacrolimus levels with each outcome, and stratified Cox models were developed to quantify race-specific associations.Among 933 eligible recipients, 737 (79%) were Caucasian and 196 (21%) were AA. Compared with Caucasians, AAs were significantly younger (55 vs 59 years, p < 0.001), with higher rates of non-ischemic cardiomyopathy (68% vs 50%, p < 0.001), sensitization (>10% panel reactive antibody, 16% vs 9.1%, p = 0.009), and human leukocyte antigen mismatches (7 vs 7, p = 0.01), but less frequent primary cytomegalovirus serostatus mismatch (14.31% vs 27.3%, p < 0.001). Overall, AAs had an increased adjusted mortality risk (hazard ratio [HR] 4.13, p = 0.007). Higher tacrolimus levels were associated with decreased mortality in AAs (HR 0.62, p = 0.009). Overall gene expression profiling score was associated with increased mortality among Caucasians (HR 1.21, p = 0.048). In Caucasians, but not AAs, overexpression of MARCH8 was associated with increased mortality (HR 2.90, p = 0.001). FLT3 upregulation was associated with increased mortality (HR 2.42, p = 0.033) in AAs. There was an inverse relationship between FLT3 expression and tacrolimus levels (-0.029 and -0.176, respectively) in Caucasians and AAs.AAs have a significantly higher mortality risk after HTx than Caucasians, even in the low-risk Outcomes AlloMap Registry population. AAs and Caucasians had differential outcomes based upon the varying expression of MARCH8 and FLT3 genes following HTx.

  View details for DOI 10.1016/j.healun.2019.05.008

  View details for PubMedID 31201087

• Perceived Generational, Geographic, and Sex-Based Differences in Choosing a Career in Advanced Heart Failure. Circulation. Heart failure Moayedi, Y., Hershman, S. G., Ross, H. J., Khush, K. K., Teuteberg, J. J. 2019; 12 (7): e005754

  View details for DOI 10.1161/CIRCHEARTFAILURE.118.005754

  View details for PubMedID 31296097

• Interpreting Neurologic Outcomes in a Changing Trial Design Landscape: An Analysis of HVAD Using a Hybrid Intention to Treat Population. ASAIO journal (American Society for Artificial Internal Organs : 1992) Mahr, C., Thinh Pham, D., Mokadam, N. A., Silvestry, S. C., Cowger, J., Kiernan, M. S., D'alessandro, D. A., Coglianese, E. E., Faraz Masood, M., Kormos, R. L., Jacoski, M. V., Teuteberg, J. J. 2018

  Abstract

  Randomized controlled trials can provide optimal clinical evidence to assess the benefits of new devices, and it is these data that often shape device usage in real-world practice. However, individual clinical trial results sometimes appear discordant for the same device, and alternative devices are sometimes not employed in similar patient populations. To make sound evidence-based decisions, clinicians routinely rely on cross-trial comparisons from different trials of similar but not identical patient populations to assess competing technology when head-to-head randomized comparisons are unavailable.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  View details for PubMedID 30562168

• Current Use of Hearts From Hepatitis C Viremic Donors. Circulation. Heart failure Moayedi, Y., Fan, C. P., Gulamhusein, A. F., Manlhiot, C., Ross, H. J., Teuteberg, J. J., Khush, K. K. 2018; 11 (12): e005276

  Abstract

  BACKGROUND: Strategies to improve donor heart utilization are required in the setting of limited donor availability. One innovative strategy is to consider the use of hepatitis C viremic (HCV) nucleic acid amplification test positive donors in hepatitis C-negative recipients, given the availability of highly effective direct acting antiviral agents. We utilized United Network for Organ Sharing data to evaluate the geographic distribution, clinical characteristics, and post-transplant outcomes of HCV+ donor hearts.METHODS AND RESULTS: The United Network for Organ Sharing registry was queried for all HCV+ recovered donors and those considered for heart donation classified by sex, age group, United Network for Organ Sharing region, and cause of death from January 1, 2014, to December 31, 2017. Propensity score matching (3:1) was applied to the recipients based on the index for mortality prediction after cardiac transplantation score and donor risk index. A total of 1306 HCV+ donors were recovered from 2014 to 2017 of whom 1078 (82.5%) were 18 to 49 and predominantly from the Appalachia region (United Network for Organ Sharing regions 2, 3, and 11). A total of 64 (5%) HCV+ donor hearts were transplanted in this interval. The match-adjusted risk difference in survival was estimated to be 0.87% ( P=0.83) at 12 months.CONCLUSIONS: To meet the demands of heart transplantation, we must consider additional strategies to expand the donor pool. From 2014 to 2017, despite availability of highly effective direct acting antiviral therapy, only 5% of HCV+ donor hearts were accepted for transplantation. National efforts may be required to capitalize on this resource while we continue to carefully monitor the safety of this novel approach.

  View details for PubMedID 30562093

• The Incremental Value of Right Ventricular Size and Strain in the Risk Assessment of Right Heart Failure Post - Left Ventricular Assist Device Implantation. Journal of cardiac failure Aymami, M., Amsallem, M., Adams, J., Sallam, K., Moneghetti, K., Wheeler, M., Hiesinger, W., Teuteberg, J., Weisshaar, D., Verhoye, J., Woo, Y. J., Ha, R., Haddad, F., Banerjee, D. 2018; 24 (12): 823–32

  Abstract

  BACKGROUND: Right heart failure (RHF) after left ventricular assist device (LVAD) implantation is associated with high morbidity and mortality. Existing risk scores include semiquantitative evaluation of right ventricular (RV) dysfunction. This study aimed to determine whether quantitative evaluation of both RV size and function improve risk stratification for RHF after LVAD implantation beyond validated scores.METHODS AND RESULTS: From 2009 to 2015, 158 patients who underwent implantation of continuous-flow devices who had complete echocardiographic and hemodynamic data were included. Quantitative RV parameters included RV end-diastolic (RVEDAI) and end-systolic area index, RV free-wall longitudinal strain (RVLS), fractional area change, tricuspid annular plane systolic excursion, and right atrial area and pressure. Independent correlates of early RHF (<30 days) were determined with the use of logistic regression analysis. Mean age was 56 ± 13 years, with 79% male; 49% had INTERMACS profiles ≤2. RHF occurred in 60 patients (38%), with 20 (13%) requiring right ventricular assist device. On multivariate analysis, INTERMACS profiles (adjusted odds ratio 2.38 [95% confidence interval [CI] 1.47-3.85]), RVEDAI (1.61 [1.08-2.32]), and RVLS (2.72 [1.65-4.51]) were independent correlates of RHF (all P < .05). Both RVLS and RVEDAI were incremental to validated risk scores (including the EUROMACS score) for early RHF after LVAD (all P < .01).CONCLUSIONS: RV end-diastolic and strain are complementary prognostic markers of RHF after LVAD implantation.

  View details for PubMedID 30539717

• Innovations in Ventricular Assist Devices for End-Stage Heart Failure. Annual review of medicine Miller, R. J., Teuteberg, J. J., Hunt, S. A. 2018

  Abstract

  The number of patients with end-stage heart failure (HF) continues to increase over time, but there has been little change in the availability of organs for cardiac transplantation, intensifying the demand for left ventricular assist devices (LVADs) as a bridge to transplantation. There is also a growing number of patients with end-stage HF who are not transplant candidates but may be eligible for long-term support with an LVAD, known as destination therapy. Due to this increasing demand, LVAD technology has evolved, resulting in transformative improvements in outcomes. Additionally, with growing clinical experience patient management continues to be refined, leading to iterative improvements in outcomes. With outcomes continuing to improve, the potential benefit from LVAD therapy is being considered for patients earlier in their course of advanced HF. We review recent changes in technology, patient management, and implant decision making in LVAD therapy. Expected final online publication date for the Annual Review of Medicine Volume 70 is January 27, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  View details for PubMedID 30296900

• Planned Concomitant Left and Right Ventricular Assist Device Insertion to Avoid Long-term Biventricular Mechanical Support: Bridge to Right Ventricular Recovery. The heart surgery forum Salna, M., Shudo, Y., Teuteberg, J. J., Banerjee, D., Ha, R. V., Woo, Y. J., Hiesinger, W. 2018; 21 (5): E412–E414

  Abstract

  INTRODUCTION: The planned use of a temporary right ventricular assist device (RVAD) at the time of left ventricular assist device (LVAD) implantation may prevent the need for a permanent biventricular assist device (BiVAD). Herein we describe our RVAD weaning protocol that was effectively employed in 4 patients to prevent the need for permanent BiVAD.METHODS: Four patients in refractory cardiogenic shock underwent planned RVAD insertion during LVAD implantation due to severely depressed right ventricular function with dilation preoperatively. A standardized RVAD weaning protocol was employed in these 4 patients in preparation for decannulation.RESULTS: Temporary RVADs were successfully placed in all 4 patients at the time of LVAD implantation. All patients survived to RVAD decannulation and discharge and were alive at the time of most recent follow-up (range, 528-742 days post-RVAD decannulation).CONCLUSION: Planned implantation of a temporary RVAD in high risk patients may avoid the need for biventricular mechanical support in the future.

  View details for PubMedID 30311895

• Right ventricular load adaptability metrics in patients undergoing left ventricular assist device implantation. The Journal of thoracic and cardiovascular surgery Amsallem, M., Aymami, M., Hiesinger, W., Zeigler, S., Moneghetti, K., Marques, M., Teuteberg, J., Ha, R., Banerjee, D., Haddad, F. 2018

  Abstract

  OBJECTIVE: Several right load adaptability metrics have been proposed as predictors of right heart failure (RHF) following left ventricular assist device implantation. This study sought to validate and compare the prognostic value of these indices.METHODS: This retrospective study included 194 patients undergoing continuous-flow left ventricular assist device implantation. The primary end point was unplanned right atrial assist device (RVAD) need within 30days after left ventricular assist device implantation; the secondary end points included clinical RHF syndrome without RVAD need and the composite of RHF or RVAD need. Load adaptability indices or interventricular ratios were divided into surrogates of ventriculoarterial coupling (RV area change:end-systolic area), indices reflecting adaptation proportionality (Dandel's index=tricuspid regurgitation velocity-time integral normalized for average RV radius in diastole or systole), and simple ratios (eg, pulse pressure:right atrial pressure or right arterial pressure:pulmonary arterial wedge pressure).RESULTS: Mean age was 55±13years with 77% of men. RHF occurred in 75 patients with 30 patients requiring RVAD implantation. Among right heart metrics, right arterial pressure (normalized odd ratio, 1.62; 95% confidence interval, 1.15-2.38), right arterial pressure:pulmonary arterial wedge pressure (normalized odds ratio, 1.59; 95% confidence interval, 1.08-2.32) and pulse pressure:right arterial pressure<2.0 (normalized odds ratio, 2.56; 95% confidence interval, 1.16-5.56) were associated with RVAD need (all P values<.02). These 3 metrics significantly added incremental prognostic value to the Interagency Registry for Mechanically Assisted Circulatory Support classification score in a similar range, whereas only RAP was incremental to the Michigan score. Correlates of RHF not requiring RVAD included RV end-systolic area index and the Dandel indices, which provided similar incremental value to the Interagency Registry for Mechanically Assisted Circulatory Support, Michigan, and European Registry for Patients with Mechanical Circulatory Support scores.CONCLUSIONS: Although associated with outcome, right load adaptability indices do not appear to provide strong incremental value when compared with simple metrics.

  View details for PubMedID 30482529

• Risk evaluation using gene expression screening to monitor for acute cellular rejection in heart transplant recipients. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Moayedi, Y., Foroutan, F., Miller, R. J., Fan, C. S., Posada, J. G., Alhussein, M., Tremblay-Gravel, M., Oro, G., Luikart, H. I., Yee, J., Shullo, M. A., Khush, K. K., Ross, H. J., Teuteberg, J. J. 2018

  Abstract

  BACKGROUND: Gene expression profiling (GEP) was developed for non-invasive surveillance of acute cellular rejection. Despite its widespread use, there has been a paucity in outcome data for patients managed with GEP outside of clinical trials.METHODS: The Outcomes AlloMap Registry (OAR) is an observational, prospective, multicenter study including patients aged ≥ 15 years and ≥ 55 days post-cardiac transplant. Primary outcome was death and a composite outcome of hemodynamically significant rejection, graft dysfunction, retransplantation, or death. Secondary outcomes included readmission rates and development of coronary allograft vasculopathy and malignancies.RESULTS: The study included 1,504 patients, who were predominantly Caucasian (69%), male (74%), and aged 54.1 ± 12.9 years. The prevalence of moderate to severe acute cellular rejection (≥2R) was 2.0% from 2 to 6 months and 2.2% after 6 months. In the OAR there was no association between higher GEP scores and coronary allograft vasculopathy (p = 0.25), cancer (p = 0.16), or non-cytomegalovirus infection (p = 0.10). Survival at 1, 2, and 5 years post-transplant was 99%, 98%, and 94%, respectively. The composite outcome occurred in 103 patients during the follow-up period. GEP scores in dual-organ recipients (heart-kidney and heart-liver) were comparable to heart-alone recipients.CONCLUSIONS: This registry comprises the largest contemporary cohort of patients undergoing GEP for surveillance. Among patients selected for GEP surveillance, survival is excellent, and rates of acute rejection, graft dysfunction, readmission, and death are low.

  View details for PubMedID 30352779

• A Bayesian Model to Predict Survival After Left Ventricular Assist Device Implantation JACC-HEART FAILURE Kanwar, M. K., Lohmueller, L. C., Kormos, R. L., Teuteberg, J. J., Rogers, J. G., Lindenfeld, J., Bailey, S. H., McIlvennan, C. K., Benza, R., Murali, S., Antaki, J. 2018; 6 (9): 771–79

  Abstract

  This study investigates the use of a Bayesian statistical models to predict survival at various time points in patients undergoing left ventricular assist device (LVAD) implantation.LVADs are being increasingly used in patients with end-stage heart failure. Appropriate patient selection continues to be key in optimizing post-LVAD outcomes.Data used for this study were derived from 10,277 adult patients from the INTERMACS (Inter-Agency Registry for Mechanically Assisted Circulatory Support) who had a primary LVAD implanted between January 2012 and December 2015. Risk for mortality was calculated retrospectively for various time points (1, 3, and 12 months) after LVAD implantation, using multiple pre-implantation variables. For each of these endpoints, a separate tree-augmented naïve Bayes model was constructed using the most predictive variables.A set of 29, 26, and 31 pre-LVAD variables were found to be predictive at 1, 3, and 12 months, respectively. Predictors of 1-month mortality included low Inter-Agency Registry for Mechanically Assisted Circulatory Support profile, number of acute events in the 48 h before surgery, temporary mechanical circulatory support, and renal and hepatic dysfunction. Variables predicting 12-month mortality included advanced age, frailty, device strategy, and chronic renal disease. The accuracy of all Bayesian models was between 76% and 87%, with an area under the receiver operative characteristics curve of between 0.70 and 0.71.A Bayesian prognostic model for predicting survival based on the comprehensive INTERMACS registry provided highly accurate predictions of mortality based on pre-operative variables. These models may facilitate clinical decision-making while screening candidates for LVAD therapy.

  View details for PubMedID 30098967

  View details for PubMedCentralID PMC6119115

• The 2018 ISHLT/APM/AST/ICCAC/STSW Recommendations for the Psychosocial Evaluation of Adult Cardiothoracic Transplant Candidates and Candidates for Long-term Mechanical Circulatory Support PSYCHOSOMATICS Dew, M., DiMartini, A. F., Dobbels, F., Grady, K. L., Jowsey-Gregoire, S. G., Kaan, A., Kendall, K., Young, Q., Abbey, S. E., Butt, Z., Crone, C. C., De Geest, S., Doligalski, C. T., Kugler, C., McDonald, L., Ohler, L., Painter, L., Petty, M. G., Robson, D., Schloglhofer, T., Schneekloth, T. D., Singer, J. P., Smith, P. J., Spaderna, H., Teuteberg, J. J., Yusen, R. D., Zimbrean, P. C. 2018; 59 (5): 415–40

  Abstract

  The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients' receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs' unique needs and goals.

  View details for PubMedID 30197247

• Substantial Reduction in Driveline Infection Rates With the Modification of Driveline Dressing Protocol. Journal of cardiac failure Lander, M. M., Kunz, N., Dunn, E., Althouse, A. D., Lockard, K., Shullo, M. A., Kormos, R. L., Teuteberg, J. J. 2018

  Abstract

  BACKGROUND: Driveline infection (DLI) is a cause of morbidity and mortality in patients with continuous-flow left ventricular assist devices (CF-LVADs). We hypothesized that an alternate dressing protocol would decrease the rate of DLIs.METHODS AND RESULTS: A retrospective review of CF-LVAD implants at a single institution from January 2010 to October 2015 was conducted. Patients were divided into implants before (group 1) and after (group 2) the introduction of the new protocol on September 1, 2012. Patients were followed until death, transplantation, change in dressing type, or 2 years. 153 patients were included: 61 in group 1 and 92 in group 2. Group 1 had fewer HVADs than group 2 (27.9% vs 71.7%; P < .001) and more destination therapy, although the latter was not statistically significant (50.8% vs 34.8%; P = .118). At 24 months, the freedom from DLI was 53% in group 1 and 89% in group 2 (P = .01). Group 1 had a significantly greater risk of DLI than group 2 (incident rate ratio 3.18, 95% confidence interval 1.23-8.18; P = .016).CONCLUSIONS: Dramatic improvement in freedom from DLI at 2 years was achieved with a new driveline dressing protocol. This demonstrates that DLI rates can be improved with alternate percutaneous site care techniques in CF-LVAD patients.

  View details for PubMedID 30098380

• The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support JOURNAL OF HEART AND LUNG TRANSPLANTATION Dew, M., DiMartini, A. F., Dobbels, F., Grady, K. L., Jowsey-Gregoire, S. G., Kaan, A., Kendall, K., Young, Q., Abbey, S. E., Butt, Z., Crone, C. C., De Geest, S., Doligalski, C. T., Kugler, C., McDonald, L., Ohler, L., Painter, L., Petty, M. G., Robson, D., Schloeglhofer, T., Schneekloth, T. D., Singer, J. P., Smith, P. J., Spaderna, H., Teuteberg, J. J., Yusen, R. D., Zimbrean, P., ISHLT, APM, AST, ICCAC, STSW 2018; 37 (7): 803–23

  Abstract

  The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients' receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs' unique needs and goals.

  View details for PubMedID 29709440

• Accepting hepatitis C virus infected donor hearts for transplantation: Multi-step consent, unrealized opportunity, and the Stanford experience. Clinical transplantation Moayedi, Y., Gulamhusein, A. F., Ross, H. J., Teuteberg, J. J., Khush, K. K. 2018: e13308

  Abstract

  The current mismatch between supply of and demand for donor organs has prompted transplant clinicians to consider innovative solutions to broaden the donor pool. Despite a 10% increase in the number of organ donors available from 2015 to 2016, wait times remain unacceptable for the 4,000 patients listed for heart transplantation in the United States (US). (1) Many hearts that would otherwise be acceptable go unused because the donors have hepatitis C virus (HCV). Advancements and availability of highly efficacious and safe direct acting antiviral (DAA) therapy for chronic HCV allows consideration of use of organs from viremic, nucleic acid testing (NAT) positive donors in HCV negative recipients. We describe Stanford's experience with using organs from HCV infected donors for heart transplantation and the associated ethical implications and programmatic planning required, as put forth in the recent American Society of Transplantation (AST) meeting report (May 2017).(2) This article is protected by copyright. All rights reserved.

  View details for PubMedID 29869354

• New Horizons on the 50th Anniversary of Heart Transplantation in Canada: "Where There Is Death, There Is Hope" CANADIAN JOURNAL OF CARDIOLOGY Moayedi, Y., Alhussein, M., Posada, J., Kozuszko, S., Khush, K. K., Teuteberg, J. J., Badiwala, M. V., Ross, H. J. 2018; 34 (6): 694–95

  View details for PubMedID 29703422

• OUTCOME OF EN-BLOC COMBINED HEART AND LIVER TRANSPLANTATION IN THE ADULT FAILING FONTAN Vaikunth, S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D., Teuteberg, J., Woo, Y., Lui, G. K. ELSEVIER SCIENCE INC. 2018: 539

  View details for DOI 10.1016/S0735-1097(18)31080-5

  View details for Web of Science ID 000429659701389

• RIGHT VENTRICULAR LOAD ADAPTABILITY IN PATIENTS UNDERGOING CONTINUOUS-FLOW LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION Amsallem, M., Aymami, M., Hiesinger, W., Zeigler, S., Moneghetti, K., Marques, M., Wheeler, M., Teuteberg, J., Ha, R., Banerjee, D., Haddad, F. ELSEVIER SCIENCE INC. 2018: 1624

  View details for DOI 10.1016/S0735-1097(18)32165-X

  View details for Web of Science ID 000429659703274

• Outcomes of Heart Failure Admissions Under Observation Versus Short Inpatient Stay JOURNAL OF THE AMERICAN HEART ASSOCIATION Masri, A., Althouse, A. D., McKibben, J., Thoma, F., Mathier, M., Ramani, R., Teuteberg, J., Marroquin, O., Lee, J. S., Mulukutla, S. R. 2018; 7 (3)

  Abstract

  Patients with heart failure (HF) are admitted either under observation (OBS) or inpatient stays; however, there is little data on whether this designation reflects the clinical status of a patient, with significant logistical and financial implications. We sought to compare the outcomes of patients with HF admitted OBS versus inpatient stay (≤2 days; INPT).From January 1, 2008 to September 30, 2015, our multisite health system saw 21 339 unique patients totaling 52 493 hospital admissions with a primary diagnosis of HF. Patients were excluded if they underwent cardiac surgery (n=611), heart transplantation (n=187), or left ventricular assist device insertion (n=198), or if they died during hospitalization (n=1839). Of the remaining 50 654 discharges, 2 groups were identified: INPT group and OBS group. Outcomes were HF readmission, all-cause readmission, and all-cause mortality within 1 year of discharge. Hazard ratios were computed using the Andersen-Gill method in the Cox proportional-hazards model. A total of 8709 admissions (17%) occurred in the INPT group and 2648 admissions (5%) occurred in the OBS group. HF readmission rate at 1 year was 55.3% in INPT versus 66.5% in OBS (hazard ratio, 0.75; 95% confidence interval, 0.71-0.80; P<0.01). All-cause readmission rate at 1 year was 70.7% in INPT versus 82.5% in OBS (hazard ratio, 0.74; 95% confidence interval, 0.70-0.78; P<0.01). All-cause mortality at 1 year occurred in 25.2% of INPT versus 24.2% of OBS (hazard ratio, 1.03; 95% confidence interval, 0.95-1.12; P=0.46).HF admissions designated INPTs were associated with lower readmission rates and equivalent mortality to those designated OBS.

  View details for PubMedID 29432132

• 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