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
INTRODUCTION AND OBJECTIVES: Degenerative aortic stenosis (DAS) is the most frequent valvular heart disease. It remains unclear how to identify asymptomatic DAS patients with normal left ventricular ejection fraction who have a high probability of event occurrence and would thus benefit from early intervention. Here, we describe a protocol for exercise hemodynamics in true asymptomatic patients with moderate or severe DAS and assess the prognostic value of the data obtained in this population. METHODS: This study involved a prospective single-centre registry of consecutive asymptomatic patients with moderate or severe DAS. Patients underwent cardiopulmonary exercise testing to confirm symptom absence during exercise and then right heart catheterization (RHC) at rest and during exercise. Events were defined as death, surgical aortic valve replacement, or transcatheter aortic valve implantation according to clinical guidelines. RESULTS: Thirty-three patients underwent baseline and exercise RHC. The mean aortic valve area was 1.08 cm2 and the aortic gradient was 39mmHg. The mean pulmonary artery pressure was 21mmHg with a pulmonary artery occlusion pressure of 14mmHg and cardiac output of 5.6 L/min. The mean pulmonary artery pressure at peak exercise was 34mmHg. After a mean follow-up of 27 months, 8 patients experienced an event (24%). There were no differences in baseline variables, aortic valve area, or cardiopulmonary exercise testing parameters between the event and event-free groups. Patients with an event did not have higher pulmonary or filling pressures after peak exercise but had lower pulmonary artery oxygen saturation on effort (median, 48% vs 57%, P=.03). CONCLUSIONS: Exercise RHC is feasible and safe in this population. Peak pulmonary artery oxygen saturation might identify patients with increased risk of serious adverse events.