Levels of calcineurin inhibitors and incidence of postransplantational complications in younger heart transplantation recipients

    Authors

    Keywords

    calcineurin inhibitors, heart transplantation, outcomes

    DOI

    https://doi.org/10.15836/ccar2016.396

    Full Text

    **Introduction:** Recipient age is a well-established risk factor in heart transplantation. Although older recipients have worse survival, incidence of posttransplantational complications is higher in younger recipients, and so far there is no clear evidence of exact pathophysiological mechanism driving the latter. However, it is well known that younger patients have worse therapy compliance. (1, 2) In this study, we investigated if there is difference in achieving target immunosuppressive drugs levels according to age, and if it is associated with worse outcomes. **Patients and Methods:** This is a single center, retrospective study that included 114 adult consecutive patients who underwent heart transplantation from 2010.-2015., and of those 94 with at least 30-day follow up were selected for further analysis (median age 54, 71 male, median follow-up 28 months). Study population was divided into 2 groups according to age. We observed outcomes of overall survival, graft rejection episodes that were treated, and occurrence of vasculopathy. Immunosuppressive drug levels at days 30, 180, and 365 after heart transplantation were collected (**Table 1**). Pearson chi-squared, and Mann-Whitney tests were used for group comparisons, while Kaplan-Meier curves were used for survival analysis. ### Table 1: Patients achieving subtherapeutic immunosuppressive drug levels at 30, 180, and 365 days after heart transplantation according to age groups. Comparison of outcomes (graft rejection requiring treatment and vasculopathy) between study groups. | | **Younger patients (54 years)** | | | --- | --- | --- | --- | | N | 47 | 47 | | | Subtherapeutic immunosuppressive drug levels (calcineurin inhibitors) | | | | | - 30 days after heart transplantation | 25/47 (53%) | 13/47 (28%) | p=0.012 | | - 180 days after heart transplantation | 10/44 (23%) | 12/39 (31%) | P=0.407 | | - 365 days after heart transplantation | 3/38 (8%) | 2/29 (7%) | P=0.878 | | Graft rejection requiring treatment | 13/47 (28%) | 2/47 (4%) | p=0.002 | | Vasculopathy | 13/44 (30%) | 6/46 (13%) | p=0.055 | **Results:** Although significantly higher number of younger patients had subtherapeutic immunosuppressive drug levels at day 30, at other time points there was no difference; as well as there was no difference in outcomes among younger patients according to drug levels. Furthermore, taking into account all the patients, there was no difference in outcomes based solely on subtherapeutic drug levels. Study groups differed significantly only in incidence of graft rejection requiring treatment, that was more frequently observed in younger group of patients. **Conclusions:** In our study population we achieved target immunosuppressive drug levels harder in younger patient at 30-days after heart transplantation, however without influence on survival. Furthermore, younger patients had similar survival and occurrence of vasculopathy as older patients, and higher occurrence of graft rejection requiring treatment.

    Literature

    1. Grady KL, Jalowiec A, White-Williams C. Patient compliance at one year and two years after heart transplantation. J Heart Lung Transplant. 1998;17:383–94. https://pubmed.ncbi.nlm.nih.gov/9588583/
    2. Tjang YS, van der Heijden GJ, Tenderich G, Körfer R, Grobbee DE. Impact of recipient’s age on heart transplantation outcome. Ann Thorac Surg. 2008;85(6):2051–5. https://doi.org/10.1016/j.athoracsur.2008.02.015
    Cardiologia Croatica
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    Levels of calcineurin inhibitors and incidence of postransplantational complications in younger heart transplantation recipients

    Extended Abstract
    Issue10-11
    Published
    Pages396-397
    PDF via DOIhttps://doi.org/10.15836/ccar2016.396
    calcineurin inhibitors
    heart transplantation
    outcomes

    Authors

    Ivo Planinc*ORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Dora FabijanovićORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Jana Ljubas MačekORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Boško SkorićORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje JurinORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Jure SamardžićORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Nina JakušORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje GašparovićORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Maja ČikešORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Davor MiličićORCIDUniversity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia

    *Correspondence email: ivo.planinc@gmail.com

    Full Text

    Introduction: Recipient age is a well-established risk factor in heart transplantation. Although older recipients have worse survival, incidence of posttransplantational complications is higher in younger recipients, and so far there is no clear evidence of exact pathophysiological mechanism driving the latter. However, it is well known that younger patients have worse therapy compliance. (1, 2) In this study, we investigated if there is difference in achieving target immunosuppressive drugs levels according to age, and if it is associated with worse outcomes.

    Patients and Methods: This is a single center, retrospective study that included 114 adult consecutive patients who underwent heart transplantation from 2010.-2015., and of those 94 with at least 30-day follow up were selected for further analysis (median age 54, 71 male, median follow-up 28 months). Study population was divided into 2 groups according to age. We observed outcomes of overall survival, graft rejection episodes that were treated, and occurrence of vasculopathy. Immunosuppressive drug levels at days 30, 180, and 365 after heart transplantation were collected (Table 1). Pearson chi-squared, and Mann-Whitney tests were used for group comparisons, while Kaplan-Meier curves were used for survival analysis.

    Table 1: Patients achieving subtherapeutic immunosuppressive drug levels at 30, 180, and 365 days after heart transplantation according to age groups. Comparison of outcomes (graft rejection requiring treatment and vasculopathy) between study groups.

    N
    Younger patients (<54 years)
    47
    Older patients (>54 years)
    47
    Subtherapeutic immunosuppressive drug levels (calcineurin inhibitors)
    - 30 days after heart transplantation
    Younger patients (<54 years)
    25/47 (53%)
    Older patients (>54 years)
    13/47 (28%)
    Field 4
    p=0.012
    - 180 days after heart transplantation
    Younger patients (<54 years)
    10/44 (23%)
    Older patients (>54 years)
    12/39 (31%)
    Field 4
    P=0.407
    - 365 days after heart transplantation
    Younger patients (<54 years)
    3/38 (8%)
    Older patients (>54 years)
    2/29 (7%)
    Field 4
    P=0.878
    Graft rejection requiring treatment
    Younger patients (<54 years)
    13/47 (28%)
    Older patients (>54 years)
    2/47 (4%)
    Field 4
    p=0.002
    Vasculopathy
    Younger patients (<54 years)
    13/44 (30%)
    Older patients (>54 years)
    6/46 (13%)
    Field 4
    p=0.055

    Results: Although significantly higher number of younger patients had subtherapeutic immunosuppressive drug levels at day 30, at other time points there was no difference; as well as there was no difference in outcomes among younger patients according to drug levels. Furthermore, taking into account all the patients, there was no difference in outcomes based solely on subtherapeutic drug levels. Study groups differed significantly only in incidence of graft rejection requiring treatment, that was more frequently observed in younger group of patients.

    Conclusions: In our study population we achieved target immunosuppressive drug levels harder in younger patient at 30-days after heart transplantation, however without influence on survival. Furthermore, younger patients had similar survival and occurrence of vasculopathy as older patients, and higher occurrence of graft rejection requiring treatment.

    Literature

    1. 1.
      Grady KL, Jalowiec A, White-Williams C. Patient compliance at one year and two years after heart transplantation. J Heart Lung Transplant. 1998;17:383–94.PubMed
    2. 2.
      Tjang YS, van der Heijden GJ, Tenderich G, Körfer R, Grobbee DE. Impact of recipient’s age on heart transplantation outcome. Ann Thorac Surg. 2008;85(6):2051–5.DOI