P5414Factors influencing mortality in a long-term follow-up after heart transplantation; role of immunomonitoring

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Alyaydin ◽  
H Welp ◽  
C Pogoda ◽  
R Pistulli ◽  
H Reinecke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Transplantation ◽  
Body Mass ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Allograft Vasculopathy ◽  
Cox Regression Analysis ◽  
Group 2 ◽  
Group 1

Abstract Background Despite relevant improvements in the last years, increased mortality limits the success of heart transplantation therapy. Although many factors influencing mortality have been identified, the most studies analyzed relatively short follow-up time following heart transplantation. Purpose Therefore, the aim of our present study was to evaluate risk factors for enhanced mortality with emphasis on quantitative changes in immunological blood cells late after heart transplantation. Methods 174 patients with a mean time after heart transplantation of 13.1±6.5 years were retrospectively analyzed using data collected during follow-up visits in our center. Clinical examinations, results of laboratory tests, including immunomonitoring of CD4+, CD8+, CD19+ cells and natural killer cells, ultrasound vessel visualization and coronary angiography were evaluated with respect to the all-cause mortality. Results In patients who were still alive at the time of data analysis (group 1, n=134), glomerular filtration rate, erythrocyte count, hemoglobin and mean corpuscular hemoglobin concentration were significantly increased compared to the group encompassing patients who died before this time point (group 2, n=40) (p<0.05 for all). In contrast, c- reactive protein (CRP), leukocyte count, triglycerides and N-terminal pro-brain natriuretic peptide were significantly decreased in group 1 versus group 2 (p<0.05 for all). In the first group the patients were relevantly less frequently on dialysis, presented lower NYHA classes, later onset of cardiac allograft vasculopathy and received hearts from donors with lower body mass (p<0.05 for all). Additionally, patients from the first group were characterized by significantly higher CD4 and lower CD8 percentages as well as a tendency towards higher CD19 cell count. In a multivariate cox regression analysis CD4 percentage (hazard ratio (HR): 0.454, confidence interval (CI): 0.236–0.871; p=0.018), onset of cardiac allograft vasculopathy (HR: 0.422, CI: 0.190–0.941; p=0.035) and CRP (HR: 0.325, CI: 0.170–0.621; p=0.018) were independent risk factors for increased mortality. Conclusions Increased inflammation, anemia, renal and heart insufficiency, early onset of cardiac allograft vasculopathy, worse functional status and donor associated factors such as higher body mass correlated significantly with enhanced mortality among patients after heart transplantation. In contrast to the early phase following heart transplantation, where the suppression of CD4+ cell number contributes to the decrease in the frequency of acute rejections, aggressive reduction of CD4+ cells by high doses of immunosuppressive agents late after cardiac transplantation may augment risk of mortality. It may be explained due to the creation of a subclinical chronic immunosuppressive condition and potentiation of side effects of immunosuppressive drugs.

Abstract 14944: Elevated Peak Immune Monitoring Early After Transplantation is Associated with Angiographic Cardiac Allograft Vasculopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Richard Cheng ◽  
Babak Azarbal ◽  
Aaron Yung ◽  
Frank Liou ◽  
Jignesh K Patel ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Immune Monitoring ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
P Value ◽  
Operating Characteristics ◽  
Allograft Vasculopathy ◽  
Group 2 ◽  
Group 1

Introduction: Early immune monitoring (IM) as measured by adenosine triphosphate release from activated lymphocytes is associated with coronary plaque progression by intravascular ultrasound. Hypothesis: Elevated IM is also associated with angiographic cardiac allograft vasculopathy (CAV). Methods: Patients transplanted between January 2007 and December 2011 with early post-transplant IM assays and annual angiographic follow-up were included. IM score was defined as the peak value of assays performed between two-months to mid-year after transplantation. A receivers operating characteristics (ROC) analysis was performed to determine an optimal IM assay cutoff. International Society of Heart Lung Transplantation CAV grading was used, 1 for mild, 2 for moderate, and 3 for severe. Patients were divided into two groups based on the cutoff score, and freedom from angiographic CAV was compared. Results: 232 patients were included in the analysis. Mean age at transplantation was 56.7 ± 11.8 years and 25.9% were female. Peak IM assays occurred at 104.1 ± 43.7 days after transplantation, with an average of 3.2 ± 1.8 assays measured per patient. A ROC analysis determined an optimal IM assay cutoff of 458 ng ATP/ml. Group 1, n = 178, was defined as having peak IM assays <458 ng ATP/ml. Group 2, n = 54, was defined as having peak IM assays ≥458 ng ATP/ml. Mean peak IM assays for Group 1 and Group 2 were 243.1 ± 115.5 and 592.9 ± 155.5 ng ATP/ml, respectively. Mean clinical and angiographic follow-up were 4.0 ± 1.5 and 3.5 ± 1.6 years, respectively. As demonstrated in Figure 1, CAV1 occurred in 80 of 178 patients (44.9%) in Group 1, and 35 of 54 patients (64.8%) in Group 2, p-value 0.008 (Log Rank). CAV2/3 occurred in 6 of 178 patients (3.4%) in Group 1, and 8 of 54 patients (14.8%) in Group 2, p-value 0.002. Conclusions: Early elevated peak IM is associated with decreased freedom from angiographic CAV and suggests the potential use of IM in the tailoring of immunosuppression regimens for preventing CAV.

scholarly journals Immunological monitoring in cardiac allograft vasculopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E Alyaydin ◽  
H Welp ◽  
R Pistulli ◽  
A Dell Aquila ◽  
J Sindermann ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Absolute Count ◽  
Allograft Vasculopathy ◽  
Group 2

Abstract Background The interaction of immunological determinants and classic cardiovascular risk factors can accelerate the development of cardiac allograft vasculopathy (CAV) with deleterious consequences for the graft function in heart transplantation (HTx). When it comes to immunological risk assessment, inverse CD4/CD8 ratio can be a poor prognostic marker in coronary artery disease, but its influence is unclear in CAV. Aim To evaluate the role of the T-lymphocyte count in peripheral blood as well as CD4/CD8 ratio as a predictive marker for CAV severity in a very long-term follow-up after HTx. Methods We performed a retrospective analysis of patient data collected during routine clinical follow-up visits. These data included innate and adaptive immune cell count in peripheral blood (lymphocyte count, CD3+, CD4+, CD8+ and CD19+ T cells and NK cells). Results The study population consisted of 174 patients with a mean follow-up of 13.1±6.5 years and a mean age at the time of HTx of 45.2±15.0 years. CAV was diagnosed in 71 patients (40.8%), more than half of which underwent interventional procedure or surgical therapy (n=40, 56.3%). A comparison of the cytoimmunological profile of patients with no CAV or mild disease (group 1, n=134) vs. with CAV requiring treatment (group 2, n=40), revealed significantly reduced percentage of CD4+ T cells (46.4±11.4% vs. 41.2±9.6%, p=0.01) and elevated percentage of CD8+ T lymphocytes in group 2 (28.3±14.1% vs. 35.8±13.7%, p=0.003). Thus, the CD4/CD8 ratio was altered in therapy requiring CAV (2.3±2.0 vs. 1.5±1.0, respectively, p&lt;0.001). However, we observed no differences in the absolute count of T-helper cells (CD4+ T cells: 692.2±329.2 vs. 653.8±390.5 cells/μL, p=0.54) and cytotoxic T lymphocytes (CD8+ T cells: 474.7±450.2 vs. 600.0±469.0 cells/μL, p=0.13). Further analysis showed no differences regarding lymphocyte count and absolute count or percentage of CD3+ and CD19+ T cells as well as NK cells. Inverse CD4/CD8 ratio (&lt;1) was associated with greater risk for therapy requiring CAV (OR 2.8, 95% CI 1.3 – 5.9, p=0.009) in a univariate logistic regression analysis. Conclusions Decreased CD4+ T cell count along with increased cytotoxic T lymphocyte count resulting in inverse CD4/CD8 ratio is associated with increased CAV severity in HTx. Given the possible interactions with the immunosuppressive agents and prednisolone, monitoring of the cytomimmunological profile can help identify patients at risk and be useful in establishing therapeutic strategies. FUNDunding Acknowledgement Type of funding sources: None.

Perioperative Risk Factors of Cardiac Allograft Vasculopathy in the Long-Term Follow-up

2016 ◽  
Vol 48 (5) ◽  
pp. 1736-1741 ◽  
Author(s):  
B. Szyguła-Jurkiewicz ◽  
M. Zakliczyński ◽  
W. Szczurek ◽  
M. Skrzypek ◽  
M. Gąsior ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Perioperative Risk ◽  
Allograft Vasculopathy ◽  
Perioperative Risk Factors ◽  
Long Term Follow Up

P6310Risk predictors of cardiac allograft vasculopathy after heart transplantation: results from the United States Organ Procurement and Transplantation Network

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Fluschnik ◽  
B Geelhoed ◽  
P M Becher ◽  
F J Brunner ◽  
B Schrage ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Heart Transplantation ◽  
Organ Procurement ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Allograft Vasculopathy ◽  
Related Risk ◽  
Male Sex ◽  
New Onset

Abstract Background Cardiac allograft vasculopathy (CAV) is a major long-term complication after heart transplantation leading to chronic graft failure and increased mortality. Purpose The aim of this study was to determine recipient- and donor-related risk factors for the development of CAV in patients after heart transplantation. Methods Overall, data from 34,994 heart transplant recipients prospectively enrolled from July 2004 to March 2015 in the Organ Procurement and Transplantation Network (OPTN) were analyzed. Patients aged <18 years and those without information about CAV and re-transplantation were excluded. Multivariable-adjusted analyses were performed to identify recipient- and donor-related risk factors for new-onset CAV. The mean follow-up time was 66.8 months. Analyses are based on OPTN data as of March 6, 2017. Results Of 34,994 patients after heart transplantation, 12,668 (36.2%) patients developed CAV. Mean age was 52±12 years for the recipients (76.1% men) and 31±12 years for the donors (71.0% men), respectively. In recipients, male sex (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.09–1.19, p<0.001), African American ethnicity (HR 1.11, 95% CI 1.06–1.17, p<0.001), body mass index (BMI) (HR per 5 kg/m2 increase 1.08, 95% CI 1.06–1.11, p<0.001) and smoking (HR 1.07, 95% CI 1.01–1.13, p=0.03) were associated with incident CAV. Moreover, recipients with ischemic (HR 1.30, 95% CI 1.09–1.55, p=0.003) and hypertrophic cardiomyopathy (HR 1.26, 95% CI 1.02–1.57, p=0.03) had a higher risk for new-onset CAV than patients with other cardiomyopathies. In donors, age (HR 1.11, 95% CI 1.10–1.11, p<0.001), male sex (HR 1.28 95% CI 1.22–1.34, p<0.001), BMI (HR per 5 kg/m2 increase 1.04, 95% CI 1.02–1.05, p<0.001), smoking (HR 1.09, 95% CI 1.04–1.13, p<0.001), diabetes (HR 1.21 95% CI 1.09–1.36, p<0.001) and arterial hypertension (HR 1.13, 95% CI 1.07–1.20, p<0.001) were associated with new-onset CAV. Contrarily, African American (HR 0.93, 95% CI 0.88–0.98, p=0.007) and Hispanic ethnicity (HR 0.94, 95% CI 0.89–0.99, p=0.03) seemed to be protective. Conclusion Both recipient and donor male sex as well as the classical cardiovascular risk factors BMI and smoking were associated with incident CAV. On the donor side, additionally, diabetes and arterial hypertension were related to new-onset CAV. Diverse ethnicities were differentially related to new-onset CAV. Further studies are needed to clarify whether modification of cardiovascular risk factors as well as improved donor selection will reduce CAV burden.

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