Antibody-mediated rejection in heart transplantation

The role of antibody-mediated rejection in predicting survival among heart recipients has been studied in clinical transplantology for over 20 years. This condition is a significant risk factor for heart failure and graft vasculopathy. Antibody-mediated rejection results from activation of the humoral immune system and production of donorspecific antibodies that cause myocardial injury through the complement system. The presence of donor-specific antibodies is associated with lower allograft survival. Treatment of antibody-mediated rejection should take into account the rejection category and the presence or absence of graft dysfunction. The main principle of treatment is to suppress humoral immunity at different levels. World clinical practice has made significant inroads into the study of this issue. However, further research is required to identify and develop optimal treatment regimens for patients with humoral rejection in cardiac transplantation.

Validation of Coronary Angiography-Derived Vessel Fractional Flow Reserve in Heart Transplant Patients with Suspected Graft Vasculopathy

Cardiac transplant-related vasculopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, coronary angiography-derived vessel fractional flow reserve (vFFR) has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease. Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic coronary artery disease, data on the use of vFFR in heart transplant recipients suffering from cardiac transplant-related arteriopathy are lacking. The aim of the presented study was to validate coronary angiography-derived vessel fractional flow reserve to calculate fractional flow reserve in HTx patients with and without cardiac transplant-related vasculopathy. A prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography was conducted. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/s in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Overall, 18059 FFR values were extracted from the FFR pullback curves from 23 HTx patients. The mean age was 59.3 ± 9.7 years, the mean time after transplantation was 5.24 years [IQR 1.20, 11.25]. A total of 39 vessels from 23 patients (24 LAD, 11 LCX, 4 RCA) were analyzed. Mean distal vFFR was 0.87 ± 0.14 whereas invasive distal FFR was 0.88 ± 0.17. An excellent correlation was found between invasive distal FFR and vFFR (r = 0.92; p < 0.001). The correlation of the pullback tracing was high, with a correlation coefficient between vFFR and invasive FFR pullback values of 0.72 (95% CI 0.71 to 0.73, p < 0.001). The mean difference between vFFR and invasive FFR pullback values was −0.01 with 0.06 of SD (limits of agreements −0.12 to 0.13). In HTx patients, coronary angiography-derived FFR correlates excellently with invasively measured wire-derived FFR. Therefore, angiography derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy.

RISK FACTORS OF SMOKING AFTER HEART TRANSPLANTATION

While cessation of smoking is a requirement for cardiac transplantation prior to listing, some patients return to smoking after recovery. Since 1993, we have covertly tested the smoking habits of our recipients of cardiac transplants (with ethical approval) by calculating urinary cotinine: a level of > 500 ng / mL suggesting continuing tobacco use. Survival, causes of death and the occurrence of graft coronary artery disease (GCAD) were retrospectively analyzed in terms of the amount of positive and negative levels of cotinine. At some point after transplantation, one hundred and four out of 380 (27.4 percent) patients tested positive for active smoking, and 57 (15.0 percent) tested positive repeatedly. Because of GCAD (21.2 percent vs. 12.3 percent, p<0.05), and because of malignancy (16.3 percent vs. 5.8 percent, p<0.001), smokers experienced slightly more deaths. Smoking after heart transplantation reduced median survival from 16.28 years to 11.89 years in the univariate study. After accounting for the impact of pretransplant smoking in a time-dependent multivariate study, the most relevant determinant of total mortality remained posttransplant smoking (p < 0.00001). We conclude that by accelerating the production of graft vasculopathy and malignancy, cigarette smoking after cardiac transplantation has a substantial effect on survival. We hope that this information will prevent recipients of cardiac transplants from relapsing and will intensify efforts to increase the rate of cessation. Keywords: heart transplantation, Cardiac allograft vasculopathy, smoking, malignancy