Influence of post-transplant ischemia-reperfusion injury and cellular rejection on the development of cardiac allograft vasculopathy

    Authors

    Keywords

    cardiac allograft vasculopathy, heart transplantation, high-sensitive troponine, cellular rejection

    DOI

    https://doi.org/10.15836/ccar2018.361

    Full Text

    Introduction : Cardiac allograft vasculopathy (CAV) is a chronic heart transplant complication (HTx) that presents a treatment challenge owing to the diffuse pattern of coronary artery involvement. Severe forms of the disease are not suitable for revascularization, which is why retransplantation often remains the only treatment option. ( 1 - 3 ) Patients and Methods : Out of a total of 176 patients following HTx, between 2001 and 2015, 129 patients were subjected to at least one coronary artery angiography by which 45 patients were CAV positive (and additionally in two patients based on clinical and autopsy findings). The mean age was 51.6±12.6 years, 78% of patients were male and the average follow-up was 3 years (IQR 2-6 years). The presence of CAV was evaluated by coronary artery angiography and analyzed with respect to the duration of ischemic time (IT), the early concentration of high-sensitive troponin T (hsTnT) and the degree of cellular graft rejection (CR). Results: Early hsTnT values (within 3 months after HTx) are significantly higher with prolonged IT (p=0.040) but have no predictive significance for CAV (p=0.529) or more frequent CR. IT does not correlate with the frequency of significant CR. Patients with severe CAV had significantly shorter survival than those without CAV or with mild/moderate forms of disease (p=0.016) ( Figure 1 ). CR, expressed as an average patient rejection index, significantly increases the risk of CAV (p<0.001, OR 16.0), including episodes of mild CR during the first year after HTx. CAV was proven in 36% of CAV patients (N=47/131) and was the cause of direct later mortality in 10.2% of patients. Freedom from CAV at the end of the 1st year was 86%, 2nd 75%, 5th 57% and 10th 25%. Patient survival curves depending on the degree of vasculopathy: CAV-free patients or those with mild-to-moderate CAV (CAV1/CAV2) had significantly longer survival in comparison to patients with severe CAV (CAV3). Conclusion : More pronounced reperfusion-ischemic injury, determined by longer IT, correlated with higher concentrations of hsTnT early after HTx. The prolonged IT does not present predisposition for a stronger CR, later development of CAV or shorter survival. CAV patients have significantly shorter survival only in more severe forms of the disease, while milder and moderate forms are more effectively treated and therefore do not affect survival. Cellular rejection is associated with higher risk of CAV development, which may have important implications in clinical monitoring and treatment.

    Cardiologia Croatica
    Back to search

    Influence of post-transplant ischemia-reperfusion injury and cellular rejection on the development of cardiac allograft vasculopathy

    Extended Abstract
    Issue11-12
    Published
    Pages361-362
    PDF via DOIhttps://doi.org/10.15836/ccar2018.361
    cardiac allograft vasculopathy
    heart transplantation
    high-sensitive troponine
    cellular rejection

    Authors

    Jana Ljubas Maček*ORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Boško SkorićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Marijan PašalićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje GašparovićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Jure SamardžićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Ivo PlanincORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Maja ČikešORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Daniel LovrićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje JurinORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Nina JakušORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Dora FabijanovićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Davor MiličićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia

    Full Text

    Introduction : Cardiac allograft vasculopathy (CAV) is a chronic heart transplant complication (HTx) that presents a treatment challenge owing to the diffuse pattern of coronary artery involvement. Severe forms of the disease are not suitable for revascularization, which is why retransplantation often remains the only treatment option. ( 1 - 3 ) Patients and Methods : Out of a total of 176 patients following HTx, between 2001 and 2015, 129 patients were subjected to at least one coronary artery angiography by which 45 patients were CAV positive (and additionally in two patients based on clinical and autopsy findings). The mean age was 51.6±12.6 years, 78% of patients were male and the average follow-up was 3 years (IQR 2-6 years). The presence of CAV was evaluated by coronary artery angiography and analyzed with respect to the duration of ischemic time (IT), the early concentration of high-sensitive troponin T (hsTnT) and the degree of cellular graft rejection (CR). Results: Early hsTnT values (within 3 months after HTx) are significantly higher with prolonged IT (p=0.040) but have no predictive significance for CAV (p=0.529) or more frequent CR. IT does not correlate with the frequency of significant CR. Patients with severe CAV had significantly shorter survival than those without CAV or with mild/moderate forms of disease (p=0.016) ( Figure 1 ). CR, expressed as an average patient rejection index, significantly increases the risk of CAV (p<0.001, OR 16.0), including episodes of mild CR during the first year after HTx. CAV was proven in 36% of CAV patients (N=47/131) and was the cause of direct later mortality in 10.2% of patients. Freedom from CAV at the end of the 1st year was 86%, 2nd 75%, 5th 57% and 10th 25%. Patient survival curves depending on the degree of vasculopathy: CAV-free patients or those with mild-to-moderate CAV (CAV1/CAV2) had significantly longer survival in comparison to patients with severe CAV (CAV3). Conclusion : More pronounced reperfusion-ischemic injury, determined by longer IT, correlated with higher concentrations of hsTnT early after HTx. The prolonged IT does not present predisposition for a stronger CR, later development of CAV or shorter survival. CAV patients have significantly shorter survival only in more severe forms of the disease, while milder and moderate forms are more effectively treated and therefore do not affect survival. Cellular rejection is associated with higher risk of CAV development, which may have important implications in clinical monitoring and treatment.