A.L.P. Caforio

Coronary flow reserve by contrast-enhanced echocardiography : A new noninvasive diagnostic tool for cardiac allograft vasculopathy

Noninvasive tests have proven unsatisfactory in cardiac allograft vasculopathy (CAV) diagnosis. We assessed coronary flow reserve (CFR) by contrast‐enhanced transthoracic echocardiography (CE‐TTE) in heart transplantation (HT). CFR was assessed in the left anterior descending coronary artery in 73 HT recipients (59 male, aged 50 ± 12 years at HT), at 8 ± 4.5 years post‐HT. CFR measurements were taken blindly from coronary angiographies. CFR cut points were the standard value of ≤2 and those defined by receiver operating characteristics (ROC) curve analysis. CFR was lower in patients with CAV (2.3 ± 0.7 vs. 3.2 ± 0.5, p < 0.0001). The ≤2 cut point was 100% specific and 38% sensitive. The ≤2.7 cut point, optimal by ROC analysis, was 87% specific and 82% sensitive. Accuracy rose from 71% with the standard ≤2 cut point to 85% with the optimal cut point of ≤2.7. CFR by CE‐TTE may offer promise as a novel, easily repeatable and accurate noninvasive tool in CAV detection. However, further longitudinal studies in larger patient cohorts are warranted before widespread adoption can be advocated.

Can C4d immunostaining on endomyocardial biopsies be considered a prognostic biomarker in heart transplant recipients

Background. The aim of this study was to assess the significance of positive C4d capillary immunostaining of endomyocardial biopsies and its correlation to clinical outcome in adult heart transplant recipients. Methods. Nine hundred eighty-five endomyocardial biopsies from 107 heart transplant recipients were evaluated. Immunostaining for detection of intragraft C4d capillary deposition was performed on paraffin-embedded tissue using anti-human C4d polyclonal antibody. Results. Positive staining of C4d was present in 36 patients (34%) and antibody-mediated rejection in eight patients (7%). The patients were subdivided into four groups on the basis of their C4d, circulating antidonor antibodies (donor-specific antibodies [DSAs]), and graft function: group 1=C4d positive, DSA negative, and no graft dysfunction; group 2=C4d positive, DSA positive, and no graft dysfunction; group 3=C4d positive, DSA positive, and signs of graft dysfunction, and group 0 (control)=all negative. An higher mortality risk was found in C4d-positive patients, when compared with negative ones (unadjusted hazard ratios: group 1: 18, group 2: 61, and group 3: 32-fold risk; P<0.0001). Conclusions. Antibody-mediated rejection is a complex and ongoing phenomenon with different phenotypic features. C4d positive predicts worse prognosis. C4d negative and DSA can be used as early mortality predictors in patients without signs of graft dysfunction.

Antibody-mediated Rejection Without Acute Graft Dysfunction in Adult ABO-compatible Heart Transplantation: a Case of Accommodation

Humoral rejection in heart transplantation is associated with graft dysfunction, circulating anti-donor antibodies and C4d deposits in endomyocardial biopsies. Detecting C4d capillary positivity is of diagnostic and prognostic value. C4d positivity can be found in solid-organ transplants in cases of accommodation, a form of humoral rejection without graft dysfunction. Accommodation might reflect a change in antibodies or in the antigen, or the graft acquiring a resistance to injury by antibodies and complement. We present a case of accommodation in the setting of adult ABO-compatible orthotopic heart transplantation, which was diagnosed according to the recently introduced ISHLT criteria for humoral rejection: despite this immunologic profile, the patient never showed signs of graft dysfunction. Physicians should be aware of the accommodation phenomenon so they can identify this subset of patients and assess its long-term effects on chronic rejection and outcome in transplanted patients.