Outcome of the Development of Early Restrictive Physiology after Heart Transplantation

Purpose Cardiac allograft vasculopathy (CAV) is one of the major factors limiting long-term survival. A severe form of CAV is small vessel disease which results in restrictive cardiac physiology (RCP). This RCP causes a very stiff heart which leads to significant reduction in cardiac index and elevation of cardiac pressures. The pathophysiology behind this RCP is most likely due to small vessel CAV with scarring and fibrosis. The outcome of patients with this RCP has not been well established. Methods Between 2010 and 2017 we assessed 23 heart transplant patients who developed RCP defined by right atrial pressure ≥ 15 mmHg, pulmonary artery diastolic pressure ≥ 15 mmHg, pulmonary capillary wedge ≥ 15 mmHg, and cardiac index ≤ 2.2 mm. Subsequent outcomes after diagnosis of RCP were 3-year survival, freedom from CAV (angiographic stenosis>30%), non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), development of donor-specific antibodies (DSA) and re-hospitalizations. 1-year freedom from acute cellular rejection (ACR) was also assessed as risk factors for the development of RCP. The study group was compared with a case-controlled group 2:1 matched by age, gender, and era. Results The average time from transplant to the diagnosis of RCP was 1.5 ± 1.4 years. The RCP group compared to control had significantly lower subsequent 3-year survival, 3-year freedom from CAV, NF-MACE and hospitalizations. There was also a lower freedom from 1-year cellular rejection episodes and DSA in the RCP group compared to control. (See table) Conclusion Heart transplant patients who develop early RCP appear to have significantly reduced survival. ACR and DSA are associated with the development of RCP. As these patients do not appear to have a reversible cause, appropriate patients may be assessed for re-transplantation.