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  • 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

  • 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
  • INDEPENDENT PROGNOSTIC VALUES OF CLINICAL RISK SCORES, RIGHT VENTRICULAR SYSTOLIC PRESSURE, AND N-TERMINAL PRO-B-TYPE PEPTIDE IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: INSIGHTS FROM SUPERVISED AND UNSUPERVISED MODELS Tremblay-Gravel, M., Kobayashi, Y., Boralkar, K., Li, X., Bouajila, S., Nishi, T., Amsallem, M., Moneghetti, K., Selej, M., Ozen, M., Demirci, U., Ashley, E. A., Wheeler, M., Knowlton, K., Kouznetsova, T., Haddad, F. ELSEVIER SCIENCE INC. 2019: 718
  • 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

  • The Thyroid Axis in Peripartum Cardiomyopathy: A Potential Contributor to a Multifaceted Disease. The Canadian journal of cardiology Tremblay-Gravel, M., Pacheco, C. 2019; 35 (6): 710–11

    View details for DOI 10.1016/j.cjca.2019.04.019

    View details for PubMedID 31151705

  • Risk evaluation using gene expression screening to monitor for acute cellular rejection in heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Moayedi, Y., Foroutan, F., Miller, R. H., Fan, C. S., Posada, J., Alhussein, M., Tremblay-Gravel, M., Oro, G., Luikart, H. I., Yee, J., Shullo, M. A., Khush, K. K., Ross, H. J., Teuteberg, J. J. 2019; 38 (1): 51–58
  • Approaching Higher Dimension Imaging Data Using Cluster-Based Hierarchical Modeling in Patients with Heart Failure Preserved Ejection Fraction. Scientific reports Kobayashi, Y., Tremblay-Gravel, M., Boralkar, K. A., Li, X., Nishi, T., Amsallem, M., Moneghetti, K. J., Bouajila, S., Selej, M., Ozen, M. O., Demirci, U., Ashley, E., Wheeler, M., Knowlton, K. U., Kouznetsova, T., Haddad, F. 2019; 9 (1): 10431

    Abstract

    Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality, accounting for the majority of heart failure (HF) hospitalization. To identify the most complementary predictors of mortality among clinical, laboratory and echocardiographic data, we used cluster based hierarchical modeling. Using Stanford Translational Research Database, we identified patients hospitalized with HFpEF between 2005 and 2016 in whom echocardiogram and NT-proBNP were both available at the time of admission. Comprehensive echocardiographic assessment including left ventricular longitudinal strain (LVLS), right ventricular function and right ventricular systolic pressure (RVSP) was performed. The outcome was defined as all-cause mortality. Among patients identified, 186 patients with complete echocardiographic assessment were included in the analysis. The cohort included 58% female, with a mean age of 78.7 ± 13.5 years, LVLS of -13.3 ± 2.5%, an estimated RVSP of 38 ± 13 mmHg. Unsupervised cluster analyses identified six clusters including ventricular systolic-function cluster, diastolic-hemodynamic cluster, end-organ function cluster, vital-sign cluster, complete blood count and sodium clusters. Using a stepwise hierarchical selection from each cluster, we identified NT-proBNP (standard hazard ratio [95%CI] = 1.56 [1.17-2.08]) and RVSP (1.37 [1.09-1.78]) as independent correlates of outcome. When adding these parameters to the well validated Get with the Guideline Heart Failure risk score, the Chi-square was significantly improved (p = 0.01). In conclusion, NT-proBNP and RVSP were independently predictive in HFpEF among clinical, imaging, and biomarker parameters. Cluster-based hierarchical modeling may help identify the complementally predictive parameters in small cohorts with higher dimensional clinical data.

    View details for DOI 10.1038/s41598-019-46873-7

    View details for PubMedID 31320698

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

    Abstract

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

    View details for DOI 10.1016/j.healun.2019.05.008

    View details for PubMedID 31201087

  • 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