Bio


He is currently a Professor of Medicine at Stanford where he serves as the Section Chief of Heart Failure, Cardiac Transplantation, and Mechanical Circulatory Support. He sees patients both in the clinic and in the hospital who have advanced heart failure or who have received cardiac transplantation or mechanical circulatory support.

His research interests are in clinical outcomes in patients after transplant and mechanical support as well as novel approaches to immunosuppression. He has participated in many single-center and multi-institutional research studies and has published widely in the fields of transplant and mechanical support. He served as President of the International Society of Heart and Lung Transplantation in 2018.

Clinical Focus


  • Heart Transplant
  • Mechanical Circulatory Support
  • Heart Failure
  • Advanced Heart Failure and Transplant Cardiology

Academic Appointments


Administrative Appointments


  • Section Chief, Heart Failure, Cardiac Transplantation, Mechanical Circulatory Support, Cardiovascular Medicine (2017 - Present)

Professional Education


  • Residency: University of Chicago Hospitals Internal Medicine Residency (1999) IL
  • Residency: University of Chicago Medical Center Dept of Cardiovascular Diseases (2003) IL
  • Board Certification: American Board of Internal Medicine, Cardiovascular Disease (2017)
  • Board Certification: American Board of Internal Medicine, Advanced Heart Failure and Transplant Cardiology (2010)
  • Fellowship: Brigham and Women's Hospital Heart Transplant (2004) MA
  • Fellowship, University of Chicago, Cardiovascular Medicine (2003)
  • Residency, University of Chicago, Internal Medicine (1999)
  • Medical Education: Pritzker School of Medicine University of Chicago Registrar (1996) IL

All Publications


  • Prognostic Performance of the IABP-SHOCK II Risk Score Among Cardiogenic Shock Subtypes in the Critical Care Cardiology Trials Network Registry. American heart journal Alviar, C. L., Li, B. K., Keller, N. M., Bohula-May, E., Barnett, C., Berg, D. D., Burke, J. A., Chaudhry, S., Daniels, L. B., DeFilippis, A. P., Gerber, D., Horowitz, J., Jentzer, J. C., Katrapati, P., Keeley, E., Lawler, P. R., Park, J., Sinha, S. S., Snell, J., Solomon, M. A., Teuteberg, J., Katz, J. N., van Diepen, S., Morrow, D. A., CCCTN Investigators 2024

    Abstract

    BACKGROUND: Risk stratification has potential to guide triage and decision-making in cardiogenic shock (CS). We assessed the prognostic performance of the IABP-SHOCK II score, derived in Europe for acute myocardial infarct-related CS (AMI-CS), in a contemporary North American cohort, including different CS phenotypes.METHODS: The Critical Care Cardiology Trials Network (CCCTN) coordinated by the TIMI Study Group is a multicenter network of cardiac intensive care units (CICU). Participating centers annually contribute ≥2 months of consecutive medical CICU admissions. The IABP-SHOCK II risk score includes age >73 years, prior stroke, admission glucose >191 mg/dl, creatinine >1.5 mg/dl, lactate >5 mmol/l, and post-PCI TIMI flow grade <3. We assessed the risk score across various CS etiologies.RESULTS: Of 17,852 medical CICU admissions 5,340 patients across 35 sites were admitted with CS. In patients with AMI-CS (n=912), the IABP-SHOCK II score predicted a >3-fold gradient in in-hospital mortality (low risk = 26.5%, intermediate risk =52.2%, high risk = 77.5%, p<0.0001; c-statistic=0.67; Hosmer-Lemeshow p=0.79). The score showed a similar gradient of in-hospital mortality in patients with non-AMI-related CS (n=2,517, p<0.0001) and mixed shock (n=923, p<0.001), as well as in left ventricular (<0.0001), right ventricular (p = 0.0163) or biventricular (<0.0001) CS. The correlation between the IABP-SHOCK II score and SOFA was moderate (r2=0.17) and the IABP-SHOCK II score revealed a significant risk gradient within each SCAI Stage.CONCLUSIONS: In an unselected international multicenter registry of patients admitted with CS, the IABP- SHOCK II score only moderately predicted in-hospital mortality in a broad population of CS regardless of etiology or irrespective of right, left, or bi-ventricular involvement.

    View details for DOI 10.1016/j.ahj.2023.12.018

    View details for PubMedID 38190931

  • Interhospital Variation in Admissions Managed With Critical Care Therapies or Invasive Hemodynamic Monitoring in Tertiary Cardiac Intensive Care Units: An Analysis From the Critical Care Cardiology Trials Network Registry. Circulation. Cardiovascular quality and outcomes Donnelly, S., Barnett, C. F., Bohula, E. A., Chaudhry, S. P., Chonde, M. D., Cooper, H. A., Daniels, L. B., Dodson, M. W., Gerber, D., Goldfarb, M. J., Guo, J., Kontos, M. C., Liu, S., Luk, A. C., Menon, V., O'Brien, C. G., Papolos, A. I., Pisani, B. A., Potter, B. J., Prasad, R., Schnell, G., Shah, K. S., Sridharan, L., So, D. Y., Teuteberg, J. J., Tymchak, W. J., Zakaria, S., Katz, J. N., Morrow, D. A., van Diepen, S. 2024: e010092

    Abstract

    Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers.The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability.The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively.In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites.

    View details for DOI 10.1161/CIRCOUTCOMES.123.010092

    View details for PubMedID 38179787

  • Changing Strategy Between Bridge to Transplant and Destination LVAD Therapy After The First 3 Months: Analysis of the STS- INTERMACS Database. Journal of cardiac failure Rali, A. S., Inampudi, C., Zalawadiya, S., Shah, A., Teuteberg, J. J., Stewart, G. C., Cantor, R. S., Deng, L., Jacobs, J. P., Kirklin, J. K., Stevenson, L. W. 2023

    Abstract

    Left ventricular assist devices (LVADs) have been implanted as bridge to transplantation (BTT), bridge to candidacy (BTC) or destination therapy (DT) based on relative and absolute contraindications to transplantation. Multiple factors may lead to change in the strategy of support after LVAD implantation.From INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) 2012-2020, 11,262 patients survived to 3 months on continuous flow LVADs with intent of BTT or DT. Pre-implant characteristics and early events post-LVAD were analyzed in relation to changes in BTT or DT strategy during the next 12 months.Among 3216 BTT patients at 3 months, later transplant de-listing or death without transplant occurred in 536 (16.7%) and, was more common with age, Profiles 1-2, renal dysfunction, and independently for prior cardiac surgery (HR 1.25, 95% CI 1.04-1.51, p = 0.02). Post-LVAD events of infections, gastrointestinal bleeding, stroke, and right heart failure defined by inotropic therapy predicted de-listing and death, as did in-hospital location at 3 months (HR 1.67, 95% CI 1.20-2.33, p =0.0024). Of 8046 patients surviving to 3 months with intent as destination therapy, 750 (9.3%) subsequently underwent listing or transplant, often with initial history of acute HF (HR 1.70, 95% CI 1.27-2.27, p = 0.0012) or malnutrition-cachexia (1.73, 95% CI 1.14-2.63, p = 0.0099). Multiple gastrointestinal bleeding events (≥4) with LVAD increased transition from BTT to DT (HR 4.22, 95% CI 1.46-12.275, p = 0.0078) but also from DT to BTT (HR 5.17, 95% CI 1.92-13.9, p = 0.0011).Implant strategies change over time in relation to pre-implant characteristics and adverse events post implant. Pre-implant recognition of factors predicting later change in implant strategy will refine initial triage, while further reduction of post-LVAD complications will expand options including eventual consideration of heart transplant.

    View details for DOI 10.1016/j.cardfail.2023.09.011

    View details for PubMedID 37898382

  • Combined Heart Liver Transplantation in the Patients with Advanced Liver Disease and/or Hepatocellular Carcinoma: Why Can't Liver Pull the Heart? American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Shingina, A., Bansal, N., Cedars, A., Chen, S., Daugherty, T., Emamaullee, J., Ganger, D., Ge, J., Heller, T., Hughes, D., Kay, J., Ortega Legaspi, J., Menachem, J., Montenovo, M., Sack, J., Reardon, L., Schiano, T., Simpson, K., Teuteberg, J., Tompkins, R., Vodkin, I., Wu, F., Lui, G. 2023

    View details for DOI 10.1016/j.ajt.2023.10.008

    View details for PubMedID 37839708

  • HLA sensitization is associated with an increased risk of primary graft dysfunction after heart transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Han, J., Rushakoff, J., Moayedi, Y., Henricksen, E., Lee, R., Helen Luikart, R. N., Shalakhti, O., Gragert, L., Benck, L., Malinoski, D., Kobashigawa, J., Teuteberg, J., Khush, K. K., Patel, J., Kransdorf, E. 2023

    Abstract

    PURPOSE: Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HT). Human leukocyte antigen (HLA) sensitization increases the risk of rejection and adverse outcomes after HT. We sought to determine the association between pre-transplant HLA sensitization, as measured using the calculated panel reactive antibody (cPRA) value, and the risk of PGD.METHODS: Consecutive adult HT recipients (n=596) from 1/2015 to 12/2019 at two US centers were included. Severity of PGD was based on the 2014 ISHLT consensus statement. For each recipient, unacceptable HLA antigens were obtained and locus-specific cPRA (cPRA-LS) and pre-HT donor specific antibodies (DSA) were assessed.RESULTS: There were 90 (15.1%) cases of mild-moderate PGD and 37 (6.2%) cases of severe PGD. Univariable logistic modeling showed that peak cPRA-LS for all loci and HLA-A was associated with increased severity of PGD as an ordinal variable (all loci: OR 1.78, 95% CI: 1.01-1.14, p=0.025, HLA-A: OR 1.14, 95% CI: 1.03-1.26, p=0.011). Multivariable analysis showed peak cPRA-LS for HLA-A, recipient beta-blocker use, total ischemic time, donor age, prior cardiac surgery, and UNOS status 1 or 2 were associated with increased severity of PGD. Presence of DSA to HLA-B was associated with trend toward increased risk of mild to moderate PGD (OR 2.56, 95% CI: 0.99-6.63, p=0.053) but DSA to other HLA loci were not associated with PGD. Neither HLA mismatch nor T- or B-cell crossmatch was associated with PGD.CONCLUSION: Sensitization for all HLA loci and specifically HLA-A are associated with an increased severity of PGD. These factors should be included in pre-HT risk stratification in order to minimize the risk of PGD.

    View details for DOI 10.1016/j.healun.2023.09.017

    View details for PubMedID 37802261

  • Pregnancy in Heart Transplantation After Dobbs v.Jackson. Journal of cardiac failure Farr, M., Teuteberg, J. 2023; 29 (10): 1452-1455

    View details for DOI 10.1016/j.cardfail.2023.06.025

    View details for PubMedID 37827600

  • Prognostic Significance of Hemodynamic Parameters in Patients with Cardiogenic Shock. European heart journal. Acute cardiovascular care Berg, D. D., Kaur, G., Bohula, E. A., Baird-Zars, V. M., Alviar, C. L., Barnett, C. F., Barsness, G. W., Burke, J. A., Chaudhry, S. P., Chonde, M., Cooper, H. A., Daniels, L. B., Dodson, M. W., Gerber, D. A., Ghafghazi, S., Gidwani, U. K., Goldfarb, M. J., Guo, J., Hillerson, D., Kenigsberg, B. B., Kochar, A., Kontos, M. C., Kwon, Y., Lopes, M. S., Loriaux, D. B., Miller, P. E., O'Brien, C. G., Papolos, A. I., Patel, S. M., Pisani, B. A., Potter, B. J., Prasad, R., Rowsell, R. O., Shah, K. S., Sinha, S. S., Smith, T. D., Solomon, M. A., Teuteberg, J. J., Thompson, A. D., Zakaria, S., Katz, J. N., van Diepen, S., Morrow, D. A. 2023

    Abstract

    Invasive hemodynamic assessment with a pulmonary artery catheter is often used to guide management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting hemodynamic parameters in CS.The Critical Care Cardiology Trials Network (CCCTN) is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018-2022) who underwent invasive hemodynamic assessment within 24 hours of CICU admission were included. Associations of hemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score.Among the 3,603 admissions with CS, 1,473 had hemodynamic data collected within 24 hours of CICU admission. Median cardiac index was 1.9 (IQR, 1.6-2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66-86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for intensity of background pharmacologic and mechanical hemodynamic support. These parameters were also associated with higher presenting serum lactate.In a contemporary CS population, presenting hemodynamic parameters reflecting decreased systemic arterial tone and indicators of right ventricular dysfunction are associated with adverse outcomes and presenting lactate.

    View details for DOI 10.1093/ehjacc/zuad095

    View details for PubMedID 37640029

  • Novel Measures to Assess Ventricular Assist Device Patient-reported Outcomes: Findings from the MCS A-QOL Study. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Grady, K. L., Kallen, M. A., Beiser, D. G., Lindenfeld, J., Teuteberg, J., Allen, L. A., McIlvennan, C. K., Rich, J., Yancy, C., Lee, C. S., Denfeld, Q. E., Kiernan, M., Walsh, M. N., Adler, E., Ruo, B., Stehlik, J., Kirklin, J. K., Bedjeti, K., Cella, D., Hahn, E. A. 2023

    Abstract

    BACKGROUND: Generic and heart failure-specific measures do not capture unique aspects of living with a VAD. Using state-of-the-science psychometric measurement methods, we developed a measurement system to assess post-ventricular assist device (VAD) adjustment and HRQOL.METHODS: Patients were recruited from 10/26/16-2/29/20 from 12 U.S. VAD programs. We created a dataset of participants (n=620) enrolled before left (L)VAD implantation, with data at 3- or 6- months post-implantation (Group1 [n=154]), and participants enrolled after LVAD implantation, with data at one timepoint (Group 2 [n=466]). We constructed five item banks: three modified from existing measures and two new measures. Analyses included item response theory (IRT) modeling, differential item functioning tests for systematic measurement bias, and indicators of reliability and validity.RESULTS: Of 620 participants, 56% (n=345) were implanted as destination therapy, 51% (n=316) were <12 months post-implantation, mean age=57.3 years, 78% (n=485) male, 70% (n=433) White, 58% (n=353) married/partnered, and 58% (n=357) with >high school education. We developed five new VAD item banks/measures: 6-item VAD Team Communication; 12-item Self-efficacy Regarding VAD Self-care; 11-item Being Bothered by VAD Self-care and Limitations; 7-item Satisfaction with Treatment; and 11-item Stigma. Cronbach's alpha reliability ranged from good (≥0.80) to excellent (≥0.90) for item banks/measures. All measures, except VAD Team Communication, demonstrated at least moderate correlations (≥0.30) with construct validity indicators.CONCLUSIONS: These measures meet IRT modeling assumptions and requirements; scores demonstrate reliability and validity. Use of these measures may assist VAD clinicians to inform patients about VADs as a treatment option and guide post-VAD interventions.

    View details for DOI 10.1016/j.healun.2023.08.007

    View details for PubMedID 37591454

  • Pulmonary Artery Catheter Use and Mortality in the Cardiac Intensive Care Unit. JACC. Heart failure Kadosh, B. S., Berg, D. D., Bohula, E. A., Park, J. G., Baird-Zars, V. M., Alviar, C., Alzate, J., Barnett, C. F., Barsness, G. W., Burke, J., Chaudhry, S. P., Daniels, L. B., DeFilippis, A., Delicce, A., Fordyce, C. B., Ghafghazi, S., Gidwani, U., Goldfarb, M., Katz, J. N., Keeley, E. C., Kenigsberg, B., Kontos, M. C., Lawler, P. R., Leibner, E., Menon, V., Metkus, T. S., Miller, P. E., O'Brien, C. G., Papolos, A. I., Prasad, R., Shah, K. S., Sinha, S. S., Snell, R. J., So, D., Solomon, M. A., Ternus, B. W., Teuteberg, J. J., Toole, J., van Diepen, S., Morrow, D. A., Roswell, R. O. 2023

    Abstract

    The appropriate use of pulmonary artery catheters (PACs) in critically ill cardiac patients remains debated.The authors aimed to characterize the current use of PACs in cardiac intensive care units (CICUs) with attention to patient-level and institutional factors influencing their application and explore the association with in-hospital mortality.The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Between 2017 and 2021, participating centers contributed annual 2-month snapshots of consecutive CICU admissions. Admission diagnoses, clinical and demographic data, use of PACs, and in-hospital mortality were captured.Among 13,618 admissions at 34 sites, 3,827 were diagnosed with shock, with 2,583 of cardiogenic etiology. The use of mechanical circulatory support and heart failure were the patient-level factors most strongly associated with a greater likelihood of the use of a PAC (OR: 5.99 [95% CI: 5.15-6.98]; P < 0.001 and OR: 3.33 [95% CI: 2.91-3.81]; P < 0.001, respectively). The proportion of shock admissions with a PAC varied significantly by study center ranging from 8% to 73%. In analyses adjusted for factors associated with their placement, PAC use was associated with lower mortality in all shock patients admitted to a CICU (OR: 0.79 [95% CI: 0.66-0.96]; P = 0.017).There is wide variation in the use of PACs that is not fully explained by patient level-factors and appears driven in part by institutional tendency. PAC use was associated with higher survival in cardiac patients with shock presenting to CICUs. Randomized trials are needed to guide the appropriate use of PACs in cardiac critical care.

    View details for DOI 10.1016/j.jchf.2023.04.007

    View details for PubMedID 37318422

  • The 2023 International Society for Heart and Lung Transplantation Guidelines for Mechanical Circulatory Support: A 10- Year Update. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Saeed, D., Feldman, D., Banayosy, A. E., Birks, E., Blume, E., Cowger, J., Hayward, C., Jorde, U., Kremer, J., MacGowan, G., Maltais, S., Maybaum, S., Mehra, M., Mohacsi, P., Schweiger, M., Schroeder, S. E., Shah, P., Slepian, M., Tops, L. F., Alvarez, P., Arabia, F., Aslam, S., Benson-Louis, L. 4., Birati, E., Buchholz, H. W., Cedars, A., Christensen, D., Ciarka, A., Coglianese, E., Cogswell, R., Cook, J., Copeland, J., Costello, J. G., Drakos, S. G., Eghtesady, P., Elliot, T., Estep, J. D., Eulert-Grehn, J., Fabrizio, D. R., Garbade, J., Gelow, J., Guglin, M., Hernandez-Montfort, J., Horstmanshof, D., John, R., Kanwar, M., Khaliel, F., Kim, G., Kumar, S., Lavee, J., Leache, M., Leprince, P., Lim, S., Loforte, A., Maly, J., Najjar, S., Netuka, I., Pamboukian, S. V., Patel, S. R., Pinney, S., Pluym, C. V., Potapov, E., Robson, D., Rochlani, Y., Russell, S., Sandau, K., Sandoval, E., Sayer, G., Schettle, S., Schibilsky, D., Schloglhofer, T., Schmitto, J., Siddique, A., Silvestry, S., Slaughter, M. S., Sun, B., Takayama, H., Tedford, R., Teuteberg, J. J., Ton, V., Uriel, N., Vierecke, J., Zimpfer, D., D'Alessandro, D. 2023

    View details for DOI 10.1016/j.healun.2022.12.004

    View details for PubMedID 37245143

  • Rethinking Donor and Recipient Risk Matching in Europe and North America: Using Heart Transplant Predictors of Donor and Recipient Risk. Circulation. Heart failure Moayedi, Y., Rodenas-Alesina, E., Mueller, B., Fan, C. S., Cherikh, W. S., Stehlik, J., Teuteberg, J. J., Ross, H. J., Khush, K. K. 2023; 16 (5): e009994

    Abstract

    In Europe, there is greater acceptance of hearts from higher-risk donors for transplantation, whereas in North America, the donor heart discard rate is significantly higher. A Donor Utilization Score (DUS) was used to compare European and North American donor characteristics for recipients included in the International Society for Heart and Lung Transplantation registry from 2000 to 2018. DUS was further evaluated as an independent predictor for 1-year freedom from graft failure, after adjusting for recipient risk. Lastly, we assessed donor-recipient risk matching with the outcome of 1-year graft failure.DUS was applied to the International Society for Heart and Lung Transplantation cohort using meta-modeling. Posttransplant freedom from graft failure was summarized by Kaplan-Meier survival. Multivariable Cox proportional hazard regression was applied to quantify the effects of DUS and Index for Mortality Prediction After Cardiac Transplantation score on the 1-year risk of graft failure. We present 4 donor/recipient risk groups using the Kaplan-Meier method.European centers accept significantly higher-risk donor hearts compared to North America. DUS 0.45 versus 0.54, P<0.005). DUS was an independent predictor for graft failure with an inverse linear relationship when adjusted for covariates (P<0.001). The Index for Mortality Prediction After Cardiac Transplantation score, a validated tool to assess recipient risk, was also independently associated with 1-year graft failure (P<0.001). In North America, 1-year graft failure was significantly associated with donor-recipient risk matching (log-rank P<0.001). One-year graft failure was highest with pairing of high-risk recipients and donors (13.1% [95% CI, 10.7%-13.9%]) and lowest among low-risk recipients and donors (7.4% [95% CI, 6.8%-8.0%]). Matching of low-risk recipients with high-risk donors was associated with significantly less graft failure (9.0% [95% CI, 8.3%-9.7%]) than high-risk recipients with low-risk donors (11.4% [95% CI, 10.7%-12.2%]) Conclusions: European heart transplantation centers are more likely to accept higher-risk donor hearts than North American centers. Acceptance of borderline-quality donor hearts for lower-risk recipients could improve donor heart utilization without compromising recipient survival.

    View details for DOI 10.1161/CIRCHEARTFAILURE.122.009994

    View details for PubMedID 37192289

  • PROMIS Physical, Mental and Social Health Outcomes Improve from Before to Early After LVAD Implant: Findings from the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) Study. Journal of cardiac failure Hahn, E. A., Allen, L. A., Lee, C. S., Denfeld, Q. E., Stehlik, J., Cella, D., Lindenfeld, J., Teuteberg, J. J., McIlvennan, C. K., Kiernan, M. S., Beiser, D. G., Walsh, M. N., Adler, E. D., Ruo, B., Kirklin, J. K., Klein, L., Bedjeti, K., Cummings, P. D., Burns, J. L., Vela, A. M., Grady, K. L. 2023

    Abstract

    Study participants (n=272) completed 12 Patient-Reported Outcomes Measurement Information System (PROMIS) physical, mental and social health measures (questionnaires) prior to implantation of a left ventricular assist device (LVAD) and again at 3 and 6 months post-implant. All but one PROMIS measure demonstrated significant improvement from pre-implant to 3 months; there was little change between 3 and 6 months. Because PROMIS measures were developed in the general population, patients with an LVAD, their caregivers and their clinicians can interpret the meaning of PROMIS scores in relation to the general population, helping them to monitor a return to normalcy in everyday life.

    View details for DOI 10.1016/j.cardfail.2023.03.013

    View details for PubMedID 37004864

  • COMPLETE HEART BLOCK POST TRANSPLANT- A RARE CASE OF CARDIAC SARCOIDOSIS RECURRENCE Bahl, A., Yogeswaran, V., Khush, K., Teuteberg, J., Cheng, R. ELSEVIER SCIENCE INC. 2023: 2650
  • Primary Graft Dysfunction Is Associated With Development of Early Cardiac Allograft Vasculopathy, but Not Other Immune-mediated Complications, After Heart Transplantation. Transplantation Han, J., Moayedi, Y., Henricksen, E. J., Waddell, K., Valverde-Twiggs, J., Kim, D., Luikart, H., Zhang, B. M., Teuteberg, J., Khush, K. K. 2023

    Abstract

    We investigated associations between primary graft dysfunction (PGD) and development of acute cellular rejection (ACR), de novo donor-specific antibodies (DSAs), and cardiac allograft vasculopathy (CAV) after heart transplantation (HT).A total of 381 consecutive adult HT patients from January 2015 to July 2020 at a single center were retrospectively analyzed. The primary outcome was incidence of treated ACR (International Society for Heart and Lung Transplantation grade 2R or 3R) and de novo DSA (mean fluorescence intensity >500) within 1 y post-HT. Secondary outcomes included median gene expression profiling score and donor-derived cell-free DNA level within 1 y and incidence of cardiac allograft vasculopathy (CAV) within 3 y post-HT.When adjusted for death as a competing risk, the estimated cumulative incidence of ACR (PGD 0.13 versus no PGD 0.21; P = 0.28), median gene expression profiling score (30 [interquartile range, 25-32] versus 30 [interquartile range, 25-33]; P = 0.34), and median donor-derived cell-free DNA levels was similar in patients with and without PGD. After adjusting for death as a competing risk, estimated cumulative incidence of de novo DSA within 1 y post-HT in patients with PGD was similar to those without PGD (0.29 versus 0.26; P = 0.10) with a similar DSA profile based on HLA loci. There was increased incidence of CAV in patients with PGD compared with patients without PGD (52.6% versus 24.8%; P = 0.01) within the first 3 y post-HT.During the first year after HT, patients with PGD had a similar incidence of ACR and development of de novo DSA, but a higher incidence of CAV when compared with patients without PGD.

    View details for DOI 10.1097/TP.0000000000004551

    View details for PubMedID 36801852

  • Validity of Patient-Reported Outcomes Measurement Information System Physical, Mental, and Social Health Measures After Left Ventricular Assist Device Implantation and Implications for Patient Care. Circulation. Cardiovascular quality and outcomes Hahn, E. A., Walsh, M. N., Allen, L. A., Lee, C. S., Denfeld, Q. E., Teuteberg, J. J., Beiser, D. G., McIlvennan, C. K., Lindenfeld, J., Klein, L., Adler, E. D., Stehlik, J., Ruo, B., Bedjeti, K., Cummings, P. D., Vela, A. M., Grady, K. L. 2023: e008690

    Abstract

    BACKGROUND: A better understanding is needed of the burdens and benefits of left ventricular assist device (LVAD) implantation on patients' physical, mental, and social well-being. The purpose of this report was to evaluate the validity of Patient-Reported Outcomes Measurement Information System (PROMIS) measures for LVAD patients and to estimate clinically important score differences likely to have implications for patient treatment or care.METHODS: Adults from 12 sites across all US geographic regions completed PROMIS measures ≥3 months post-LVAD implantation. Other patient-reported outcomes (eg, Kansas City Cardiomyopathy Questionnaire-12 item), clinician ratings, performance tests, and clinical adverse events were used as validity indicators. Criterion and construct validity and clinically important differences were estimated with Pearson correlations, ANOVA methods, and Cohen d effect sizes.RESULTS: Participants' (n=648) mean age was 58 years, and the majority were men (78%), non-Hispanic White people (68%), with dilated cardiomyopathy (55%), long-term implantation strategy (57%), and New York Heart Association classes I and II (54%). Most correlations between validity indicators and PROMIS measures were medium to large (≥0.3; p<0.01). Most validity analyses demonstrated medium-to-large effect sizes (≥0.5) and clinically important differences in mean PROMIS scores (up to 14.8 points). Ranges of minimally important differences for 4 PROMIS measures were as follows: fatigue (3-5 points), physical function (2-3), ability to participate in social roles and activities (3), and satisfaction with social roles and activities (3-5).CONCLUSIONS: The findings provide convincing evidence for the relevance and validity of PROMIS physical, mental, and social health measures in patients from early-to-late post-LVAD implantation. Findings may inform shared decision-making when patients consider treatment options. Patients with an LVAD, their caregivers, and their clinicians should find it useful to interpret the meaning of their PROMIS scores in relation to the general population, that is, PROMIS may help to monitor a return to normalcy in everyday life.REGISTRATION: URL: https://clinicaltrials.gov; Unique: identifier: NCT03044535.

    View details for DOI 10.1161/CIRCOUTCOMES.121.008690

    View details for PubMedID 36752104

  • Participating in the Peer Review Process: The Journal of Cardiac Failure Construct. Journal of cardiac failure Joyce, E., McIivennan, C. K., Esquivel, J. H., Sauer, A. J., Correa, A., Blumer, V., Youmans, Q. R., Alvarez-Garcia, J., Chang, H., Overbey, J., Deych, E., Sinha, S. S., Morris, A., Defilippis, E. M., Reza, N., Code, J., Hajduczok, A. G., Fudim, M., Rollins, B., Vader, J. M., Pina, I. L., Teuteberg, J., Zieroth, S., Starling, R. C., Gulati, M., Mentz, R. J., Lala, A. 2022

    View details for DOI 10.1016/j.cardfail.2022.11.007

    View details for PubMedID 36529605

  • Characteristics, Therapies, and Outcomes of In-Hospital vs Out-of-Hospital Cardiac Arrest in Patients Presenting to Cardiac Intensive Care Units: From the Critical Care Cardiology Trials Network (CCCTN). Resuscitation Carnicelli, A. P., Keane, R., Brown, K. M., Loriaux, D. B., Kendsersky, P., Alviar, C. L., Arps, K., Berg, D. D., Bohula, E. A., Burke, J. A., Dixson, J. A., Gerber, D. A., Goldfarb, M., Granger, C. B., Guo, J., Harrison, R. W., Kontos, M., Lawler, P. R., Elliott Miller, P., Nativi-Nicolau, J., Kristin Newby, L., Racharla, L., Roswell, R. O., Shah, K. S., Sinha, S. S., Solomon, M. A., Teuteberg, J., Wong, G., van Diepen, S., Katz, J. N., Morrow, D. A. 2022

    Abstract

    BACKGROUND: Cardiac arrest (CA) is a common reason for admission to the cardiac intensive care unit (CICU), though the relative burden of morbidity, mortality, and resource use between admissions with in-hospital (IH) and out-of-hospital (OH) CA is unknown. We compared characteristics, care patterns, and outcomes of admissions to contemporary CICUs after IHCA or OHCA.METHODS: The Critical Care Cardiology Trials Network is a multicenter network of tertiary CICUs in the US and Canada. Participating centers contributed data from consecutive admissions during 2-month annual snapshots from 2017 to 2021. We analyzed characteristics and outcomes of admissions by IHCA vs OHCA.RESULTS: We analyzed 2,075 admissions across 29 centers (50.3% IHCA, 49.7% OHCA). Admissions with IHCA were older (median 66 vs 62 years), more commonly had coronary disease (38.3% vs 29.7%), atrial fibrillation (26.7% vs 15.6%), and heart failure (36.3% vs 22.1%), and were less commonly comatose on CICU arrival (34.2% vs 71.7%), p<0.001 for all. IHCA admissions had lower lactate (median 4.3 vs 5.9) but greater utilization of invasive hemodynamics (34.3% vs 23.6%), mechanical circulatory support (28.4% vs 16.8%), and renal replacement therapy (15.5% vs 9.4%); p<0.001 for all. Comatose IHCA patients underwent targeted temperature management less frequently than OHCA patients (63.3% vs 84.9%, p<0.001). IHCA admissions had lower unadjusted CICU (30.8% vs 39.0%, p<0.001) and in-hospital mortality (36.1% vs 44.1%, p<0.001).CONCLUSION: Despite a greater burden of comorbidities, CICU admissions after IHCA have lower lactate, greater invasive therapy utilization, and lower crude mortality than admissions after OHCA.

    View details for DOI 10.1016/j.resuscitation.2022.12.002

    View details for PubMedID 36521683

  • Clinician and Algorithmic Application of the 2019 and 2022 Society of Cardiovascular Angiography and Intervention Shock Stages in the Critical Care Cardiology Trials Network Registry. Circulation. Heart failure Patel, S. M., Berg, D. D., Bohula, E. A., Baird-Zars, V. M., Barnett, C. F., Barsness, G. W., Chaudhry, S., Daniels, L. B., van Diepen, S., Ghafghazi, S., Goldfarb, M. J., Jentzer, J. C., Katz, J. N., Kenigsberg, B. B., Lawler, P. R., Miller, P. E., Papolos, A. I., Park, J., Potter, B. J., Prasad, R., Singam, N. S., Sinha, S. S., Solomon, M. A., Teuteberg, J. J., Morrow, D. A., CCCTN Investigators, Alviar, C. L., Kontos, M. C., Sabatine, M. S., Berg, D. D., Murphy, S. A., Butler, K., Menon, V., Cremer, P., Abou Hassan, O., Hughes, D., Reyaldeen, R., Rutkowski, K., Hollenberg, S., Bakhshi, A., Caruso, E., Cruz, J., Ricketti, D., Weinstock, J., Granger, C., Newby, K., Brown, K., Carnicelli, A., Echols, E., Harrison, R., Keane, R., Loriaux, D., Genovese, L., Dewanjee, A., Raja, A., Robert, C., Zakaria, S., Metkus, T., Schulman, S., Burke, J., Maitz, T., Racharla, L., Vadhar, S., Cornell, K., Gladden, J., Jentzer, J., Brown, A., Carter, L., Miltner, K., Rassekh, N., Thompson, K., Keller, N., Alviar, C., Petit Del, D., Selig, K., Roswell, R., Bar-Cohen, R., Coleman, K., Grayver, E., Pierce, M., Robinson, G., Coleman, K., Snell, J., Jahan, N., Majid, S., Gerber, D., Sanchez, P., Patel, A., Wendling, B., Mahanta, M., Tymchak, W., Hogg, N., Keeley, E., Bhattal, G., Leach, D., Long, S., Bostick, J., Osman, A., Phreaner, N., Correa, M., Kormuskins, E., Mody, A., Rehman, A., Sedighi, R., Smith, D., Toomu, A., Toomu, S., Tran, I., Katrapati, P., Kassem, K., Zhang, S., Vincent, S., Dangerfield, C., Orgel, R., Ozen, Z., Prosser, E., Wade, T., Shah, K., Almajed, J., Fang, J., Hanff, T., Hong, J., Fordyce, C., Wong, G., Chow, J., Noronha, A., Kontos, M., Dow, S., Vo, C., Spillman, D., Love, K., Phommalinh, M., Thomas, A. 2022: e009714

    Abstract

    BACKGROUND: Algorithmic application of the 2019 Society of Cardiovascular Angiography and Intervention (SCAI) shock stages effectively stratifies mortality risk for patients with cardiogenic shock. However, clinician assessment of SCAI staging may differ. Moreover, the implications of the 2022 SCAI criteria update remain incompletely defined.METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Between 2019 and 2021, participating centers (n=32) contributed at least a 2-month snapshot of consecutive medical CICU admissions. In-hospital mortality was assessed across 3 separate staging methods: clinician assessment, Critical Care Cardiology Trials Network algorithmic application of the 2019 SCAI criteria, and a revision of the Critical Care Cardiology Trials Network application using the 2022 SCAI criteria.RESULTS: Of 9612 admissions, 1340 (13.9%) presented with cardiogenic shock with in-hospital mortality of 35.2%. Both clinician and algorithm-based staging using the 2019 SCAI criteria identified a stepwise gradient of mortality risk (stage C-E: 19.0% to 83.7% and 14.6% to 52.2%, respectively; Ptrend<0.001 for each). Clinician assignment of SCAI stages identified higher risk patients compared with algorithm-based assignment (stage D: 49.9% versus 29.3%; stage E: 83.7% versus 52.2%). Algorithmic application of the 2022 SCAI criteria, with incorporation of the vasoactive-inotropic score, more closely approximated clinician staging (mortality for stage C-E: 21.9% to 70.5%; Ptrend<0.001).CONCLUSIONS: Both clinician and algorithm-based application of the 2019 SCAI stages identify a stepwise gradient of mortality risk, although clinician-staging may better allocate higher risk patients into advanced SCAI stages. Updated algorithmic staging using the 2022 SCAI criteria and vasoactive-inotropic score further refines risk stratification.

    View details for DOI 10.1161/CIRCHEARTFAILURE.122.009714

    View details for PubMedID 36458542

  • The Impact of the COVID-19 Pandemic on the Transplant Pharmacist Workforce JOURNAL OF PHARMACY PRACTICE Khalil, K., Lyons, J., Teuteberg, J. J., Henricksen, E. J. 2022: 8971900221131906

    Abstract

    Background: The COVID-19 pandemic has placed an unprecedented strain on the US healthcare system, greatly impacting transplant centers. Objective: The purpose of this survey was to evaluate the impact of the COVID-19 pandemic on the transplant pharmacist workforce. Methods: A survey was disseminated electronically to assess the impact of the COVID-19 pandemic on the transplant pharmacist workforce. Respondents were asked to give background regarding transplant center, patient, population, and departmental staffing. Results: There were 67 total respondents from 56 transplant centers. In response to the COVID-19 pandemic, 55% of centers reported stopping non-life saving transplants, and a majority (89%) stopped living donor transplants altogether. The banning of caregivers on-site during education, reduction of bedside education teaching, and cancelling of group teaching classes occurred at 46%, 40%, and 22% of centers, respectively. Consequently, 42% of pharmacists surveyed felt that their confidence in patient and caregiver's understanding of medications had decreased since these changes have been implemented. Conclusions: Pharmacist perception of patient and caregiver understanding of transplant medications has decreased since before the COVID-19 pandemic. As health systems strategize resource allocation throughout the pandemic, the importance of patient education must be prioritized to sustain and improve transplant outcomes.

    View details for DOI 10.1177/08971900221131906

    View details for Web of Science ID 000865139000001

    View details for PubMedID 36206374

    View details for PubMedCentralID PMC9548482

  • Critical Care Cardiology Trials Network (CCCTN): a cohort profile. European heart journal. Quality of care & clinical outcomes Metkus, T. S., Baird-Zars, V. M., Alfonso, C. E., Alviar, C. L., Barnett, C. F., Barsness, G. W., Berg, D. D., Bertic, M., Bohula, E. A., Burke, J., Burstein, B., Chaudhry, S. P., Cooper, H. A., Daniels, L. B., Fordyce, C. B., Ghafghazi, S., Goldfarb, M., Katz, J. N., Keeley, E. C., Keller, N. M., Kenigsberg, B., Kontos, M. C., Kwon, Y., Lawler, P. R., Leibner, E., Liu, S., Menon, V., Miller, P. E., Newby, L. K., O'Brien, C. G., Papolos, A. I., Pierce, M. J., Prasad, R., Pisani, B., Potter, B. J., Roswell, R. O., Sinha, S. S., Shah, K. S., Smith, T. D., Snell, R. J., So, D., Solomon, M. A., Ternus, B. W., Teuteberg, J. J., van Diepen, S., Zakaria, S., Morrow, D. A. 2022

    Abstract

    The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicenter research network to conduct randomized clinical trials (RCTs) in patients with cardiac critical illness.The CCCTN was founded in 2017 with 16 centers and has grown to a research network of over 40 academic and clinical centers in the United States and Canada. Each center enters data for consecutive cardiac intensive care unit (CICU) admissions for at least two months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterized utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicenter collaboration, the CCCTN has established a robust research network to facilitate multicenter registry-based randomized trials in patients with cardiac critical illness.The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomized controlled trials in this important patient population.

    View details for DOI 10.1093/ehjqcco/qcac055

    View details for PubMedID 36029517

  • Improving nutrition practices for postoperative high-risk heart transplant and ventricular assist device implant patients in circulatory compromise: A quality improvement pre- and post-protocol intervention outcome study. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition Modir, R., Hadhazy, E., Teuteberg, J., Hiesinger, W., Tulu, Z., Hill, C. 2022

    Abstract

    Patients undergoing heart transplant (HT) and ventricular assist device (VAD) implant may experience intra- and postoperative complications requiring high-dose vasopressor agents and/or mechanical circulatory support. These complications increase the risk of nonocclusive bowel ischemia (NOBI) and inadequate enteral nutrition (EN) delivery, and guidance for this high-risk patient population is limited. To optimize nutrition support practices in this patient population at our institution, we created the High-Risk Nutrition Support Protocol (HRNSP) to improve nutrient delivery and promote safer EN practices in the setting of NOBI risk factors after HT and VAD implant.We developed and implemented a nutrition support protocol as a quality improvement (QI) initiative. Data were obtained before (n = 62) and after (n = 52) protocol initiation. We compared nutrition and clinical outcomes between the pre- and post-intervention groups.Fewer calorie deficits (P < 0.001), fewer protein deficits (P < 0.001), a greater proportion of calorie/protein needs met (P < 0.001), zero NOBI cases (0%), and decreased intensive care unit (ICU) length of stay (LOS) (P = 0.005) were observed with 100% (n = 52 of 54) HRNSP implementation success. Increased use of parenteral nutrition did not increase central line-associated bloodstream infections (P = 0.46). There was no difference in hospital LOS (P = 0.44) or 90-day and 1-year mortality (P = 0.56, P = 0.35).This single-center, QI pre- and post-protocol intervention outcome study suggests that implementing and adhering to a nutrition support protocol for VAD implant/HT patients with hemodynamic complications increases nutrient delivery and is associated with reduced ICU LOS and NOBI.

    View details for DOI 10.1002/ncp.10854

    View details for PubMedID 35606342

  • Combining donor derived cell free DNA and gene expression profiling for non-invasive surveillance after heart transplantation. Clinical transplantation Henricksen, E. J., Moayedi, Y., Purewal, S., Twiggs, J. V., Waddell, K., Luikart, H., Han, J., Feng, K., Wayda, B., Lee, R., Shudo, Y., Jimenez, S., Khush, K. K., Teuteberg, J. J. 2022: e14699

    Abstract

    BACKGROUND: Donor-derived cell free DNA (dd-cfDNA) and gene expression profiling (GEP) offer non-invasive alternatives to rejection surveillance after heart transplantation, however there is little evidence on the paired use of GEP and dd-cfDNA for rejection surveillance.METHODS: A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd-cfDNA and GEP. The primary outcomes were survival and rejection-free survival at one year post-transplant.RESULTS: In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), p< 0.01. At one-year, there were no differences between the paired testing and GEP groups in survival (98.4% v. 94.7%, p = 0.23) or rejection-free survival (81.3% v. 73.7% p = 0.28).CONCLUSIONS: Compared to post-transplant rejection surveillance with GEP alone, pairing dd-cfDNA and GEP testing was associated with similar survival and rejection-free survival at one year while requiring significantly fewer biopsies. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/ctr.14699

    View details for PubMedID 35559582

  • Modeling Effects of Immunosuppressive Drugs on Human Hearts Using Induced Pluripotent Stem Cell-Derived Cardiac Organoids and Single-Cell RNA Sequencing. Circulation Sallam, K., Thomas, D., Gaddam, S., Lopez, N., Beck, A., Beach, L., Rogers, A. J., Zhang, H., Chen, I. Y., Ameen, M., Hiesinger, W., Teuteberg, J. J., Rhee, J. W., Wang, K. C., Sayed, N., Wu, J. C. 2022; 145 (17): 1367-1369

    View details for DOI 10.1161/CIRCULATIONAHA.121.054317

    View details for PubMedID 35467958

  • Outcomes With Phosphodiesterase-5 Inhibitor Use After Left Ventricular Assist Device: A STS-INTERMACS Analysis. Circulation. Heart failure Grandin, E. W., Gulati, G., Nunez, J. I., Kennedy, K., Rame, J. E., Atluri, P., Pagani, F. D., Kirklin, J. K., Kormos, R. L., Teuteberg, J., Kiernan, M. S. 2022: CIRCHEARTFAILURE121008613

    Abstract

    BACKGROUND: Elevated right ventricular afterload following continuous-flow left ventricular assist device (CF-LVAD) may contribute to late right heart failure (LRHF). PDE5i (phosphodiesterase-5 inhibitors) are used to treat pulmonary hypertension and right heart dysfunction after CF-LVAD, but their impact on outcomes is uncertain.METHODS: We queried Interagency Registry for Mechanically Assisted Circulatory Support from 2012 to 2017 for adults receiving a primary CF-LVAD and surviving ≥30 days from index discharge. Patients receiving early PDE5i (ePDE5i) at 1 month were propensity-matched 1:1 with controls. The primary outcome was the cumulative incidence of LRHF, defined using prevailing Interagency Registry for Mechanically Assisted Circulatory Support criteria; secondary outcomes included all-cause mortality and major bleeding.RESULTS: Among 9627 CF-LVAD recipients analyzed, 2463 (25.6%) received ePDE5i and 1600 were propensity-matched 1:1 with controls. Before implant, ePDE5i patients had more severe RV dysfunction (13.1% versus 9.6%) and higher pulmonary vascular resistance (2.8±2.7 versus 2.2±2.4 WU), both P<0.001, but clinical factors were well-balanced after propensity-matching. In the unmatched cohort, ePDE5i patients had a higher 3-year cumulative incidence of LRHF, mortality, and major bleeding, but these differences were attenuated in the propensity-matched cohort: LRHF 40.8% versus 35.7% (hazard ratio, 1.14 [95% CI, 0.99-1.32]; P=0.07); mortality 38.6% versus 35.8% (hazard ratio, 0.99 [95% CI, 0.86-1.15]; P=0.93); major bleeding 51.2% versus 46.0% (hazard ratio, 1.12 [95% CI, 0.99-1.27]; P=0.06).CONCLUSIONS: Compared with propensity-matched controls, adult CF-LVAD patients receiving ePDE5i had similar rates of LRHF, mortality, and major bleeding. While intrinsic patient risk factors likely account for more adverse outcomes with ePDE5i in the unmatched cohort, there is no obvious benefit of ePDE5i in the LVAD population.

    View details for DOI 10.1161/CIRCHEARTFAILURE.121.008613

    View details for PubMedID 35332780

  • What If the Destination Is Transplant? Outcomes of Destination Therapy Patients Who Were Transplanted. ASAIO journal (American Society for Artificial Internal Organs : 1992) Atluri, P., Silvestry, S. C., Teuteberg, J. J., Milano, C. A., Selzman, C. H., Cowger, J. A. 1800; 68 (2): 178-183

    Abstract

    We sought to characterize patients who underwent heart transplant (HTx) following destination therapy (DT) implant in the combined ENDURANCE/ENDURANCE Supplemental Trials (DT/DT2). A post hoc analysis of the DT/DT2 trials was performed. Baseline characteristics and adverse events between the HTx and no-HTx cohorts were analyzed. Reasons for transplant were examined. Time to HTx was compared with contemporaneous HVAD BTT trial patients. Of the 604 DT/DT2 HVAD patients, 80 (13%) underwent HTx. The HTx cohort was younger (53.6±11.1 vs. 65.2±10.8, P<0.0001) with fewer Caucasians (60.0% vs. 76.5%, P=0.002), less ischemic cardiomyopathy (42.5% vs. 58.8%, P=0.01), and atrial fibrillation (38.8% vs. 54.4%, P=0.01). The HTx cohort had longer 6-minute walk distances (183.6 vs. 38.0 m, P=0.02). Most HTx in DT/DT2 were categorized as elective (n=63, 79%) and, of these, 70% were due to modification of behavioral issues and weight loss. Adverse events were the main indication for urgent HTx (n=17, 21%). Median times to HTx were longer in DT/DT2 (550.0 days) versus BTT/lateral (285.2 days). In this post hoc analysis of the DT/DT2 trials, over 1 in 10 underwent heart transplantation within 3 years of HVAD support. In DT therapy patients, consideration for transplant following DT VAD implant may be feasible.

    View details for DOI 10.1097/MAT.0000000000001425

    View details for PubMedID 35089262

  • Evolution of Late Right Heart Failure With Left Ventricular Assist Devices and Association With Outcomes. Journal of the American College of Cardiology Rame, J. E., Pagani, F. D., Kiernan, M. S., Oliveira, G. H., Birati, E. Y., Atluri, P., Gaffey, A., Grandin, E. W., Myers, S. L., Collum, C., Kormos, R. L., Kirklin, J. K., Teuteberg, J. J. 2021; 78 (23): 2294-2308

    Abstract

    A revised definition of right heart failure (RHF) for the Society of Thoracic Surgeons Intermacs database of left ventricular assist devices (LVADs) was introduced in June 2014.The purpose of this study was to determine the prevalence and severity of RHF over time and the association of RHF status at 3 months with 12-month outcomes after LVAD.All patients in Society of Thoracic Surgeons Intermacs with follow-up and supported at least 3 months with a continuous flow LVAD implanted between June 2, 2014 and March 31, 2017 without a simultaneous RVAD. RHF was defined as both documentation and manifestations of elevated central venous pressures.There were 6,118 patients included with an incidence of RHF at 3, 6, and 12 months postimplant categorized as mild in 5%, 6%, and 6% and moderate in 5%, 3%, and 3%, respectively. For those with no RHF at 3 months, there was a low incidence of subsequent RHF at 6 and 12 months. The lack of RHF at 3 months, compared with mild and moderate RHF, was associated with a lower 12-month cumulative incidence of mortality (6.9% vs 16.7% vs 28.1%; P < 0.0001) and a lower 12-month cumulative incidence of stroke (7.4% vs 9.5% vs 11.0%; P = 0.0095), gastrointestinal bleeding (14.8% vs 24.2% vs 23.6%; P < 0.0001), and rehospitalization (65.2% vs 73.2% vs 71.2%; P < 0.0001).In patients surviving 3 months with LVAD support alone, mild or moderate RHF occurred in nearly 1 of 10 patients at 12 months. Patients with late RHF had worse survival and a higher cumulative incidence of major adverse events.

    View details for DOI 10.1016/j.jacc.2021.09.1362

    View details for PubMedID 34857091

  • Implantable hemodynamic monitoring and management of left ventricular assist devices: Optimal or optional? JTCVS open Lampert, B. C., Teuteberg, J. J. 2021; 8: 18-23

    View details for DOI 10.1016/j.xjon.2021.09.026

    View details for PubMedID 36004193

  • Impact of diabetes mellitus on clinical outcomes after heart transplantation. Clinical transplantation Feng, K. Y., Henricksen, E. J., Wayda, B., Moayedi, Y., Lee, R., Han, J., Multani, A., Yang, W., Purewal, S., Puing, A. G., Basina, M., Teuteberg, J. J., Khush, K. K. 2021

    Abstract

    PURPOSE: Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center.METHODS: We performed a retrospective study (range 01/2008 - 07/2018), n = 244. The primary outcome was survival; secondary outcomes included acute rejection, cardiac allograft vasculopathy, infection requiring hospitalization, macrovascular events, and dialysis initiation post-transplant. Comparisons were performed using Kaplan-Meier and multivariable Cox regression analyses.RESULTS: Pretransplant DM was present in 75 (30.7%) patients and was associated with a higher risk for infection requiring hospitalization (p<0.05), but not with survival or other outcomes. Among the 144 patients without pretransplant DM surviving to one year, 29 (20.1%) were diagnosed with PTDM at the 1-year follow-up. After multivariable adjustment, PTDM diagnosis at 1-year remained associated with worse subsequent survival (hazard ratio 2.72, 95% confidence interval 1.03-7.16). Predictors of PTDM at 1-year included cytomegalovirus seropositivity and higher prednisone dose (>5mg/day) at 1-year follow-up.CONCLUSIONS: Compared to HTx recipients without baseline DM, those with baseline DM have a higher risk for infections requiring hospitalization, and those who develop DM after HTx have worse survival. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/ctr.14460

    View details for PubMedID 34390599

  • Patient-Specific Computational Fluid Dynamics Reveal Localized Flow Patterns Predictive of Post-Left Ventricular Assist Device Aortic Incompetence. Circulation. Heart failure Shad, R., Kaiser, A. D., Kong, S., Fong, R., Quach, N., Bowles, C., Kasinpila, P., Shudo, Y., Teuteberg, J., Woo, Y. J., Marsden, A. L., Hiesinger, W. 2021: CIRCHEARTFAILURE120008034

    Abstract

    BACKGROUND: Progressive aortic valve disease has remained a persistent cause of concern in patients with left ventricular assist devices. Aortic incompetence (AI) is a known predictor of both mortality and readmissions in this patient population and remains a challenging clinical problem.METHODS: Ten left ventricular assist device patients with de novo aortic regurgitation and 19 control left ventricular assist device patients were identified. Three-dimensional models of patients' aortas were created from their computed tomography scans, following which large-scale patient-specific computational fluid dynamics simulations were performed with physiologically accurate boundary conditions using the SimVascular flow solver.RESULTS: The spatial distributions of time-averaged wall shear stress and oscillatory shear index show no significant differences in the aortic root in patients with and without AI (mean difference, 0.67 dyne/cm2 [95% CI, -0.51 to 1.85]; P=0.23). Oscillatory shear index was also not significantly different between both groups of patients (mean difference, 0.03 [95% CI, -0.07 to 0.019]; P=0.22). The localized wall shear stress on the leaflet tips was significantly higher in the AI group than the non-AI group (1.62 versus 1.35 dyne/cm2; mean difference [95% CI, 0.15-0.39]; P<0.001), whereas oscillatory shear index was not significantly different between both groups (95% CI, -0.009 to 0.001; P=0.17).CONCLUSIONS: Computational fluid dynamics serves a unique role in studying the hemodynamic features in left ventricular assist device patients where 4-dimensional magnetic resonance imaging remains unfeasible. Contrary to the widely accepted notions of highly disturbed flow, in this study, we demonstrate that the aortic root is a region of relatively stagnant flow. We further identified localized hemodynamic features in the aortic root that challenge our understanding of how AI develops in this patient population.

    View details for DOI 10.1161/CIRCHEARTFAILURE.120.008034

    View details for PubMedID 34139862

  • Impact of thoracotomy approach on right ventricular failure and length of stay in left ventricular assist device implants: an intermacs registry analysis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Lampert, B. C., Teuteberg, J. J., Cowger, J., Mokadam, N. A., Cantor, R. S., Benza, R. L., Ganapathi, A. M., Myers, S. L., Hiesinger, W., Woo, J., Pagani, F., Kirklin, J. K., Whitson, B. A. 2021

    Abstract

    INTRODUCTION: Traditionally, implantation of Left Ventricular Assist Devices (LVADs) is performed via median sternotomy. Recently, less invasive thoracotomy approaches are growing in popularity as they involve less surgical trauma, potentially less bleeding, and may preserve right ventricular function. We hypothesized implantation of LVADs via thoracotomy has less perioperative right ventricular failure (RVF) and shorter postoperative length of stay (LOS).METHODS: Continuous flow LVAD implants from Intermacs between February 6, 2014 - December 31, 2018 were identified. Patients implanted via thoracotomy were propensity matched in a 1:1 ratio with patients implanted via sternotomy. Outcomes were compared between sternotomy and thoracotomy approach and by device type (axial, centrifugal-flow with hybrid levitation (CF-HL), centrifugal-flow with full magnetic levitation devices (CF-FML)). The primary outcome was time to first moderate or severe RVF. Secondary outcomes included survival and LOS.RESULTS: Overall 978 thoracotomy patients were matched with 978 sternotomy patients. Over the study period, 242 thoracotomy patients and 219 sternotomy patients developed RVF with no significant difference in time to first moderate to severe RVF by surgical approach overall (p=0.27) or within CF-HL (p=0.36) or CF-FML devices (p=0.25). Survival did not differ by implant technique (150 deaths in thoracotomy group, 154 deaths in sternotomy group; p=0.58). However, sternotomy approach was associated with a significantly shorter LOS (17 Vs 18 days, p=0.009).CONCLUSION: As compared to sternotomy, implantation of continuous flow LVADs via thoracotomy approach does not reduce moderate to severe RVF or improve survival but does reduce post-operative LOS. Device type did not influence outcomes and most centers did a small volume of thoracotomy implants.

    View details for DOI 10.1016/j.healun.2021.05.022

    View details for PubMedID 34229917

  • Long-term survival in patients with post-LVAD right ventricular failure: multi-state modelling with competing outcomes of heart transplant. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Shad, R., Fong, R., Quach, N., Bowles, C., Kasinpila, P., Li, M., Callon, K., Castro, M., Guha, A., Suarez, E. E., Lee, S., Jovinge, S., Boeve, T., Shudo, Y., Langlotz, C. P., Teuteberg, J., Hiesinger, W. 2021

    Abstract

    BACKGROUND: Multicenter data on long term survival following LVAD implantation that make use of contemporary definitions of RV failure are limited. Furthermore, traditional survival analyses censor patients who receive a bridge to heart transplant. Here we compare the outcomes of LVAD patients who develop post-operative RV failure accounting for the transitional probability of receiving an interim heart transplantation.METHODS: We use a retrospective cohort of LVAD patients sourced from multiple high-volume centers based in the United States. Five- and ten-year survival accounting for transition probabilities of receiving a heart transplant were calculated using a multi-state Aalen Johansen survival model.RESULTS: Of the 897 patients included in the study, 238 (26.5%) developed post-operative RV failure at index hospitalization. At 10 years the probability of death with post-op RV failure was 79.28% vs 61.70% in patients without (HR 2.10; 95% CI 1.72 - 2.57; p=< .001). Though not significant, patients with RV failure were less likely to be bridged to a heart transplant (HR 0.87, p=.4). Once transplanted the risk of death between both patient groups remained equivalent; the probability of death after a heart transplant was 3.97% in those with post-operative RV failure shortly after index LVAD implant, as compared to 14.71% in those without.CONCLUSIONS AND RELEVANCE: Long-term durable mechanical circulatory support is associated with significantly higher mortality in patients who develop post-operative RV failure. Improving outcomes may necessitate expeditious bridge to heart transplant wherever appropriate, along with critical reassessment of organ allocation policies.

    View details for DOI 10.1016/j.healun.2021.05.002

    View details for PubMedID 34167863

  • Coronavirus disease 2019 in heart transplant recipients: Risk factors, immunosuppression, and outcomes. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Genuardi, M. V., Moss, N., Najjar, S. S., Houston, B. A., Shore, S., Vorovich, E., Atluri, P., Molina, M., Chambers, S., Sharkoski, T., Hsich, E., Estep, J. D., Owens, A. T., Alexander, K. M., Chaudhry, S., Garcia-Cortes, R., Molina, E., Rodrigo, M., Wald, M. J., Margulies, K. B., Hanff, T. C., Zimmer, R., Kilic, A., Mclean, R., Vidula, H., Dodd, K., Blumberg, E. A., Mazurek, J. A., Goldberg, L. R., Alvarez-Garcia, J., Mancini, D., Teuteberg, J. J., Tedford, R. J., Birati, E. Y. 2021

    Abstract

    BACKGROUND: COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear.METHODS: We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant.RESULTS: The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR=7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy.CONCLUSIONS: We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.

    View details for DOI 10.1016/j.healun.2021.05.006

    View details for PubMedID 34140222

  • COST-EFFECTIVENESS AND SYSTEM-WIDE IMPACT OF USING HEPATITIS C-VIREMIC DONORS FOR HEART TRANSPLANT Wayda, B., Sandhu, A., Parizo, J., Teuteberg, J., Khush, K. ELSEVIER SCIENCE INC. 2021: 3417
  • Phosphodiesterase type 5 inhibitors after left ventricular assist device: no free lunch? ESC heart failure Grandin, E. W., Teuteberg, J. J. 2021

    View details for DOI 10.1002/ehf2.13393

    View details for PubMedID 33969639

  • The Range of Cardiogenic Shock Survival by Clinical Stage: Data From the Critical Care Cardiology Trials Network Registry. Critical care medicine Lawler, P. R., Berg, D. D., Park, J., Katz, J. N., Baird-Zars, V. M., Barsness, G. W., Bohula, E. A., Carnicelli, A. P., Chaudhry, S., Jentzer, J. C., Menon, V., Metkus, T., Nativi-Nicolau, J., Phreaner, N., Sinha, S. S., Teuteberg, J. J., van Diepen, S., Morrow, D. A., Critical Care Cardiology Trials Network Investigators 2021

    Abstract

    OBJECTIVES: Cardiogenic shock presents with variable severity. Categorizing cardiogenic shock into clinical stages may improve risk stratification and patient selection for therapies. We sought to determine whether a structured implementation of the 2019 Society for Cardiovascular Angiography and Interventions clinical cardiogenic shock staging criteria that is ascertainable in clinical registries discriminates mortality in a contemporary population with or at-risk for cardiogenic shock.DESIGN: We developed a pragmatic application of the Society for Cardiovascular Angiography and Interventions cardiogenic shock staging criteria-A (at-risk), B (beginning), C (classic cardiogenic shock), D (deteriorating), or E (extremis)-and examined outcomes by stage.SETTING: The Critical Care Cardiology Trials Network is an investigator-initiated multicenter research collaboration coordinated by the TIMI Study Group (Boston, MA). Consecutive admissions with or at-risk for cardiogenic shock during two annual 2-month collection periods (2017-2019) were analyzed.PATIENTS: Patients with or at-risk for cardiogenic shock.MEASUREMENTS AND MAIN RESULTS: Of 8,240 CICU admissions reviewed, 1,991 (24%) had or were at-risk for cardiogenic shock. Distributions across the five stages were as follows: A: 33%; B: 7%; C: 16%; D: 23%; and E: 21%. Overall in-hospital mortality among patients with established cardiogenic shock was 39%; however, mortality varied from only 15.8% to 32.1% to 62.5% across stages C, D, and E (Cochran-Armitage ptrend < 0.0001). The Society for Cardiovascular Angiography and Interventions stages improved mortality prediction beyond the Sequential Organ Failure Assessment and Intra-Aortic Balloon Pumpin Cardiogenic Shock II scores.CONCLUSIONS: Although overall mortality in cardiogenic shock remains high, it varies considerably based on clinical stage, identifying stage C as relatively lower risk. We demonstrate a pragmatic adaptation of the Society for Cardiovascular Angiography and Interventions cardiogenic shock stages that effectively stratifies mortality risk and could be leveraged for future clinical research.

    View details for DOI 10.1097/CCM.0000000000004948

    View details for PubMedID 33861557

  • 2019 STS/Intermacs Annual Report Writing Committee's Response ANNALS OF THORACIC SURGERY Pagani, F. D., Teuteberg, J., Cleveland, J., Atluri, P., Kirklin, J., Habib, R. 2021; 111 (2): 734
  • Donor and Recipient Size Matching in Heart Transplantation with Predicted Heart and Lean Body Mass. Seminars in thoracic and cardiovascular surgery Miller, R. J., Hedman, K. n., Amsallem, M. n., Tulu, Z. n., Kent, W. n., Fatehi, A. n., Clarke, B. n., Heidenreich, P. n., Hiesinger, W. n., Khush, K. K., Teuteberg, J. n., Haddad, F. n. 2021

    Abstract

    Donor and recipient size matching during heart transplant can be assessed using weight or predicted heart mass (PHM) ratios. We developed sex-specific allomteric equations for PHM and predicted lean body mass (PLBM) using the United Kingdom Biobank (UKB) and evaluated their predictive value in the United Network of Organ Sharing (UNOS) database. Donor and recipient size matching was based on weight, PHM and PLBM ratios. PHM was calculated using the Multi-ethnic Study of Atherosclerosis and UKB equations. PLBM was calculated using the UKB and National Health and Nutrition Examination Survey (NHANES) equations. Relative prognostic utility was compared using multivariable Cox analysis, adjusted for predictors of one-year survival in the Scientific Registry of Transplant Recipients (SRTR) model. Of 53,648 adult patients in the UNOS database between 1996 and 2016, 6528 (12.2%) died within the first year. In multivariable analysis, undersized matches by any metric were associated with increased one-year mortality (all p<0.01). Oversized matches were at increased risk using PHM or PLBM (all p<0.01), but not weight ratio. There were significant differences in classification of size matching by weight or PHM in sex-mismatched donor-recipient pairs. A significant interaction was observed between pulmonary hypertension and donor undersizing (hazard ratio 1.15, p=0.026) suggesting increased risk of undersizing in pulmonary hypertension. Donor and recipient size matching with simplified PHM and PLBM offered an advantage over total body weight and may be more important for sex-mismatched donor-recipient pairs. Donor undersizing is associated with worse outcomes in patients with pulmonary hypertension.

    View details for DOI 10.1053/j.semtcvs.2021.01.001

    View details for PubMedID 33444763

  • Concordance of Treatment Effect: An Analysis of The Society of Thoracic Surgeons Intermacs Database. The Annals of thoracic surgery Pagani, F. D., Cantor, R., Cowger, J., Goldstein, D., Teuteberg, J., Mahr, C., Atluri, P., Kilic, A., Maozami, N., Habib, R., Naftel, D., Kirklin, J. K. 2021

    Abstract

    The Society of Thoracic Surgeons (STS) Intermacs Registry represents a real-world data source of durable, left ventricular assist devices that can address knowledge gaps not informed through randomized clinical trials. We sought to compare survival with contemporary left ventricular assist device technologies using multiple analytic approaches to assess concordance of treatment effects and to validate prior STS Intermacs observations.Patients (aged > 19 years) enrolled into STS Intermacs between August 2017 - June 2019 were stratified by device type (centrifugal device with hybrid levitation [CF-HL] or full magnetic levitation [CF-FML]). The primary outcome was 1-year survival assessed by three statistical methodologies (multivariable regression, propensity score matching, and instrumental variable analysis).Of 4,448 patients, 2,012 (45.2%) received CF-HL and 2,436 (54.8%) received CF-FML. One-year survival for CF-FML was 88% vs. 79% for CF-HL (overall p < .001), with a hazard ratio for mortality of 3.18 for CF-HL (p<0.0001) after risk adjustment. With propensity score matching (n=1400 each cohort), 1-year survival was 87% for CF-FML vs. 80% for CF-HL, with a hazard ratio of 3.20 for mortality with CF-HL (p<0.0001) after risk adjustment. With an instrumental variable analysis, the probability of receiving CF-HL was associated with a hazard ratio of 3.11 (p<0.0001).Statistical methodology using propensity score matching and instrumental variable analysis increased the robustness of observations derived from real-world data and demonstrates the feasibility of performing comparative effectiveness research using STS Intermacs. These analyses provide additional evidence supporting a survival benefit of CF-FML versus CF-HL.

    View details for DOI 10.1016/j.athoracsur.2021.05.017

    View details for PubMedID 34087236

  • Long-Term Neurocognitive Outcome in Patients With Continuous Flow Left Ventricular Assist Device. JACC. Heart failure Cho, S. M., Floden, D., Wallace, K., Hiivala, N., Joseph, S., Teuteberg, J., Rogers, J. G., Pagani, F. D., Mokadam, N., Tirschwell, D., Li, S., Starling, R. C., Mahr, C., Uchino, K. 2021

    Abstract

    The authors sought to examine the long-term cognitive outcome of patients with continuous flow left ventricular assist device (CF-LVAD).Data on long-term neurocognitive outcome in LVAD are limited. We examined the neurocognitive outcome of patients who received a CF-LVAD as destination therapy.Patients with HeartWare (HVAD) and HeartMate II who were enrolled in the ENDURANCE and ENDURANCE Supplemental trials were eligible. Cognition was evaluated with neuropsychological testing preoperatively and at 6, 12, and 24 months after implantation. General linear models identified demographic, disease, and treatment factors that predicted decline on each neurocognitive measure.Of 668 patients who completed baseline testing and at least 1 follow-up evaluation, 552 were impaired at baseline on at least 1 cognitive measure. At each follow-up, approximately 23% of tested patients declined and 20% improved relative to baseline on at least 1 cognitive measure. Of those who were intact at baseline, only 10%-12% declined in delayed memory and 11%-16% declined in executive function at all 3 follow-ups. For patients impaired at baseline, delayed memory decline was associated with the HVAD device and male sex, whereas executive function decline was associated with the HVAD device and stroke during CF-LVAD support. For patients intact at baseline, male sex and history of hypertension were associated with decline in immediate memory and executive function, respectively.Neurocognitive function remained stable or improved for most patients (∼80%) with CF-LVAD at 6, 12, and 24 months after implantation. Male sex, hypertension, HVAD, and stroke were associated with cognitive decline.

    View details for DOI 10.1016/j.jchf.2021.05.016

    View details for PubMedID 34509403

  • Cost-effectiveness and system-wide impact of using Hepatitis C-viremic donors for heart transplant. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Wayda, B., Sandhu, A. T., Parizo, J., Teuteberg, J. J., Khush, K. K. 2021

    Abstract

    The advent of direct-acting antiviral therapy for Hepatitis C (HCV) has made using HCV-viremic donors a viable strategy to address the donor shortage in heart transplantation. We employed a large-scale simulation to evaluate the impact and cost-effectiveness of using HCV-viremic donors for heart transplant.We simulated detailed histories from time of listing until death for the real-world cohort of all adults listed for heart transplant in the United States from July 2014 to June 2019 (n = 19,346). This population was imputed using historical data and captures "real-world" heterogeneity in geographic and clinical characteristics. We estimated the impact of an intervention in which all candidates accept HCV+ potential donors (n = 472) on transplant volume, waitlist outcomes, and lifetime costs and quality-adjusted life years (QALYs).The intervention produced 232 more transplants, 132 fewer delistings due to deterioration, and 50 fewer waitlist deaths within this 5-year cohort and reduced wait times by 3% to 11% (varying by priority status). The intervention was cost-effective, adding an average of 0.08 QALYs per patient at a cost of $124 million ($81,892 per QALY). DAA therapy and HCV care combined account for 11% this cost, with the remainder due to higher costs of transplant procedures and routine post-transplant care. The impact on transplant volume varied by blood type and region and was correlated with donor-to-candidate ratio (ρ = 0.71).Transplanting HCV+ donor hearts is likely to be cost-effective and improve waitlist outcomes, particularly in regions and subgroups experiencing high donor scarcity.

    View details for DOI 10.1016/j.healun.2021.09.002

    View details for PubMedID 34635381

  • Characteristics and Outcomes of COVID-19 in Patients on Left Ventricular Assist Device Support. Circulation. Heart failure Birati, E. Y., Najjar, S. S., Tedford, R. J., Houston, B. A., Shore, S. n., Vorovich, E. n., Atluri, P. n., Urgo, K. n., Molina, M. n., Chambers, S. n., Escobar, N. n., Hsich, E. n., Estep, J. D., Alexander, K. M., Teuteberg, J. J., Chaudhry, S. P., Ravichandran, A. n., DeVore, A. D., Margulies, K. B., Hanff, T. C., Zimmer, R. n., Kilic, A. n., Wald, J. W., Vidula, H. n., Martens, J. n., Blumberg, E. A., Mazurek, J. A., Owens, A. T., Goldberg, L. R., Alvarez-Garcia, J. n., Mancini, D. M., Moss, N. n., Genuardi, M. V. 2021: CIRCHEARTFAILURE120007957

    Abstract

    The coronavirus disease 2019 (COVID-19) pandemic continues to afflict millions of people worldwide. Patients with end-stage heart failure and left ventricular assist devices (LVADs) may be at risk for severe COVID-19 given a high prevalence of complex comorbidities and functional impaired immunity. The objective of this study is to describe the clinical characteristics and outcomes of COVID-19 in patients with end-stage heart failure and durable LVADs.The Trans-CoV-VAD registry is a multi-center registry of LVAD and cardiac transplant patients in the United States with confirmed COVID-19. Patient characteristics, exposure history, presentation, laboratory data, course, and clinical outcomes were collected by participating institutions and reviewed by a central data repository. This report represents the participation of the first 9 centers to report LVAD data into the registry.A total of 40 patients were included in this cohort. The median age was 56 years (interquartile range, 46-68), 14 (35%) were women, and 21 (52%) were Black. Among the most common presenting symptoms were cough (41%), fever, and fatigue (both 38%). A total of 18% were asymptomatic at diagnosis. Only 43% of the patients reported either subjective or measured fever during the entire course of illness. Over half (60%) required hospitalization, and 8 patients (20%) died, often after lengthy hospitalizations.We present the largest case series of LVAD patients with COVID-19 to date. Understanding these characteristics is essential in an effort to improve the outcome of this complex patient population.

    View details for DOI 10.1161/CIRCHEARTFAILURE.120.007957

    View details for PubMedID 33813838

  • Classifying and Risk Stratifying Heart Failure: Easy as A, B, C? JACC. Cardiovascular imaging Teuteberg, J. J. 2021

    View details for DOI 10.1016/j.jcmg.2020.12.017

    View details for PubMedID 33582057

  • Impact of using higher-risk donor hearts for candidates with pre-transplant mechanical circulatory support. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Han, J., Moayedi, Y., Yang, W., Henricksen, E. J., Lee, R., Purewal, S., Chang, E., Duclos, S., Lyapin, A., Feng, K., Hiesinger, W., Teuteberg, J. J., Khush, K. K. 2021

    Abstract

    We evaluated post-heart transplant (HTx) outcomes after use of higher-risk donor hearts for candidates supported with pre-HTx mechanical circulatory support (MCS).In this retrospective analysis of the national United Network for Organ Sharing registry, a total of 9,915 adult candidates on MCS underwent HTx from January 1, 2010 to March 31, 2019. Multi-organ, re-transplant, and congenital heart disease patients were excluded. Higher-risk donor organs met at least one of the following criteria: left ventricular ejection fraction <50%, donor to recipient predicted heart mass ratio <0.86, donor age >55 years, or ischemic time >4 hours. Primary outcome was 1 year post-transplant survival.Among HTx recipients, 3688 (37.2%) received higher-risk donor hearts. Candidates supported with pre-HTx extracorporeal membrane oxygenation or biventricular assist device (n = 374, 3.8%) who received higher-risk donor hearts had comparable 1 year survival (HR: 1.14, 95% CI: [0.67-1.93], p = 0.64) to recipients of standard-risk donor hearts, when adjusted for recipient age and sex. In candidates supported with intra-aortic balloon pump (n = 1391, 14.6%), transplantation of higher-risk donor hearts did not adversely affect 1 year survival (HR: 0.80, 95% CI: [0.52-1.22], p = 0.30). Patients on durable left ventricular assist devices (LVAD) who received higher-risk donor hearts had comparable 1 year survival to continued LVAD support on the waitlist, but mortality was increased compared to those who received standard-risk donor hearts (HR: 1.37, 95% CI: [1.11-1.70], p = 0.004).Patients requiring pre-HTx temporary MCS who received higher-risk donor hearts had comparable 1 year post-transplant survival to those who received standard-risk donor hearts. Stable patients on durable LVADs may benefit from waiting for standard-risk donor hearts.

    View details for DOI 10.1016/j.healun.2021.09.016

    View details for PubMedID 34815161

  • Predicting post-operative right ventricular failure using video-based deep learning. Nature communications Shad, R., Quach, N., Fong, R., Kasinpila, P., Bowles, C., Castro, M., Guha, A., Suarez, E. E., Jovinge, S., Lee, S., Boeve, T., Amsallem, M., Tang, X., Haddad, F., Shudo, Y., Woo, Y. J., Teuteberg, J., Cunningham, J. P., Langlotz, C. P., Hiesinger, W. 2021; 12 (1): 5192

    Abstract

    Despite progressive improvements over the decades, the rich temporally resolved data in an echocardiogram remain underutilized. Human assessments reduce the complex patterns of cardiac wall motion, to a small list of measurements of heart function. All modern echocardiography artificial intelligence (AI) systems are similarly limited by design - automating measurements of the same reductionist metrics rather than utilizing the embedded wealth of data. This underutilization is most evident where clinical decision making is guided by subjective assessments of disease acuity. Predicting the likelihood of developing post-operative right ventricular failure (RV failure) in the setting of mechanical circulatory support is one such example. Here we describe a video AI system trained to predict post-operative RV failure using the full spatiotemporal density of information in pre-operative echocardiography. We achieve an AUC of 0.729, and show that this ML system significantly outperforms a team of human experts at the same task on independent evaluation.

    View details for DOI 10.1038/s41467-021-25503-9

    View details for PubMedID 34465780

  • Cardiopulmonary Exercise Testing With Echocardiography to Assess Recovery in Patients With Ventricular Assist Devices. ASAIO journal (American Society for Artificial Internal Organs : 1992) Christle, J. W., Moneghetti, K. J., Duclos, S., Mueller, S., Moayedi, Y., Khush, K. K., Haddad, F., Hiesinger, W., Myers, J., Ashley, E. A., Teuteberg, J. J., Wheeler, M. T., Banerjee, D. 2021; 67 (10): 1134-1138

    Abstract

    The left ventricular assist device (LVAD) is an established treatment for select patients with end-stage heart failure. Some patients recovered and are considered for explantation. Assessing recovery involves exercise testing and echo ramping on full and minimal LVAD support. Combined cardiopulmonary exercise testing with simultaneous echo ramping (CPET-R) has not been well studied. Patients were included if they had CPET within the previous 6 months, were clinically stable, and had an INR >2.0 on the day of examination. Patients had CPET-R on two occasions within 14 days: (a) with LVAD at therapeutic speed and (b) with LVAD at the lowest speed possible. Six patients were between 29 and 75 years (two female). One patient did not complete a turn-down test due to evidence of ischemia on initial CPET-R subsequently confirmed as a significant coronary artery stenosis on angiography. There were no significant differences in CPET or echo metrics between LVAD speeds. Two patients were explanted due to presumed LV recovery and remained event free for 30 and 47 months, respectively. Serial CPET-R seems safe and feasible for the evaluation of LV and global function and may result in improved clinical decision making for LVAD explantation.

    View details for DOI 10.1097/MAT.0000000000001383

    View details for PubMedID 34570726

  • Evolution of Late Right Heart Failure With Left Ventricular Assist Devices and Association With Outcomes JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Rame, J., Pagani, F. D., Kiernan, M. S., Oliveira, G. H., Birati, E. Y., Atluri, P., Gaffey, A., Grandin, E., Myers, S. L., Collum, C., Kormos, R. L., Kirklin, J. K., Teuteberg, J. J. 2020; 78 (23): 2294-2308
  • 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
  • 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

  • DD-CFDNA AS A RISK FACTOR FOR INITIATING DE-NOVO DONOR SPECIFIC ANTIBODIES IN HEART TRANSPLANTATION Depasquale, E., Kobashigawa, J., Pinney, S., Teuteberg, J., Khush, K. LIPPINCOTT WILLIAMS & WILKINS. 2020: S131–S132
  • 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. n., Fan, C. P., Tremblay-Gravel, M. n., Miller, R. J., Kawana, M. n., Henricksen, E. n., Parizo, J. n., Wainwright, R. n., 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

  • 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. n., Teuteberg, J. n., 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. n., Moayedi, Y. n., Puing, A. n., Henricksen, E. n., Garvert, D. W., Gomez, C. A., Tremblay-Gravel, M. n., Bunce, P. E., Luikart, H. n., 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. n., Sherman, C. n., Hall, S. n., Teuteberg, J. n., Uriel, N. n., Kobashigawa, J. n. 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

  • 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. n., Teuteberg, J. n., Sweet, S. n., Potena, L. n., Singer, L. G., Farrero, M. n., Shullo, M. A., Benza, R. n., Ensminger, S. n., Aslam, S. n. 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

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

    View details for DOI 10.1016/j.athoracsur.2020.07.102

    View details for PubMedID 33144112

  • 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. n., Cowger, J. n. 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

  • 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

  • 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
  • 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 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
  • 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

  • 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
  • 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

  • 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
  • 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)
  • 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
  • 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

  • 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

  • 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

  • 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
  • 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. n., Lala, A. n., McLean, R. C., Pamboukian, S. n., Horstmanshof, D. A., Thibodeau, J. n., Shah, K. n., Teuteberg, J. n., Gilotra, N. A., Taddei-Peters, W. C., Cascino, T. M., Richards, B. n., Khalatbari, S. n., Jeffries, N. n., Stevenson, L. W., Mann, D. n., 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. n., Nieman, K. n., Town, K. n., 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. n., Fan, C. S., Miller, R. J., Tremblay-Gravel, M. n., Posada, J. G., Manlhiot, C. n., Hiller, D. n., Yee, J. n., Woodward, R. n., McCaughan, J. A., Shullo, M. A., Hall, S. A., Pinney, S. n., 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. n., Hershman, S. G., Ross, H. J., Khush, K. K., Teuteberg, J. J. 2019; 12 (7): e005754
  • 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

  • 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

  • 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

  • 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

  • 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
  • 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
  • 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