RESUMO
Antibodies directed against donor-specific human leukocyte antigens (HLAs) can be detected de novo after heart transplantation and play a key role in long-term survival. De novo donor-specific antibodies (dnDSAs) have been associated with cardiac allograft vasculopathy, antibody-mediated rejection, and mortality. Advances in detection methods and international guideline recommendations have encouraged the adoption of screening protocols among heart transplant units. However, there is still a lack of consensus about the correct course of action after dnDSA detection. Treatment is usually started when antibody-mediated rejection is present; however, some dnDSAs appear years before graft failure is detected, and at this point, damage may be irreversible. In particular, class II, anti-HLA-DQ, complement binding, and persistent dnDSAs have been associated with worse outcomes. Growing evidence points towards a more aggressive management of dnDSA. For that purpose, better diagnostic tools are needed in order to identify subclinical graft injury. Cardiac magnetic resonance, strain techniques, or coronary physiology parameters could provide valuable information to identify patients at risk. Treatment of dnDSA usually involves plasmapheresis, intravenous immunoglobulin, immunoadsorption, and ritxumab, but the benefit of these therapies is still controversial. Future efforts should focus on establishing effective treatment protocols in order to improve long-term survival of heart transplant recipients.
RESUMO
BACKGROUND: The reported prevalence of donor-transmitted coronary artery disease (TCAD) in heart transplantation (HT) is variable, and its prognostic impact remains unclear. OBJECTIVES: The goal of this study was to characterize TCAD in a contemporary multicentric cohort and to study its prognostic relevance. METHODS: This was a retrospective study of consecutive patients >18 years old who underwent HT in 11 Spanish centers from 2008 to 2018. Only patients with a coronary angiography (c-angio) within the first 3 months after HT were studied. Significant TCAD (s-TCAD) was defined as any stenosis ≥50% in epicardial coronary arteries, and nonsignificant TCAD (ns-TCAD) as stenosis <50%. Clinical outcomes were assessed by means of Cox regression and competing risks regression. Patients were followed-up for a median period of 6.3 years after c-angio. RESULTS: From a cohort of 1,918 patients, 937 underwent c-angio. TCAD was found in 172 patients (18.3%): s-TCAD in 65 (6.9%) and ns-TCAD in 107 (11.4%). Multivariable Cox regression analysis did not show a statistically significant association between s-TCAD and all-cause mortality (adjusted HR: 1.44; 95% CI: 0.89-2.35; P = 0.141); however, it was an independent predictor of cardiovascular mortality (adjusted HR: 2.25; 95% CI: 1.20-4.19; P = 0.011) and the combined event cardiovascular death or nonfatal MACE (adjusted HR: 2.42; 95% CI: 1.52-3.85; P < 0.001). No statistically significant impact of ns-TCAD on clinical outcomes was detected. The results were similar when reassessed by means of competing risks regression. CONCLUSIONS: TCAD was not associated with reduced survival in patients alive and well enough to undergo post-HT angiography within the first 3 months; however, s-TCAD patients showed increased risk of cardiovascular death and MACE.