Pathophysiology of severe primary graft dysfunction in orthotopic heart transplantation

Abstract

Background: A series of insults on the donor heart result in pathophysiological changes that manifest as primary graft dysfunction (PGD) post-orthotopic heart transplantation. The objectives of this study were: (i) describe the pathophysiology of severe PGD using an established cardiovascular model; and (ii) the evolution of the pathophysiology during recovery from severe PGD.Methods: Hemodynamic data from 20 consecutive patients with severe PGD (need for mechanical circulatory support, MCS) at baseline (T0), 6 h (T6) and "recovery" (explant of support), and 20 consecutive patients without severe PGD were used to model the pathophysiology using the cardiovascular model described by Burkhoff and Dickstein.Results: There was a progressive (from T0 to T6) up-and leftward shift in the diastolic pressure-volume relationship, especially of the right ventricle (RV), resulting in reduced capacitance. RV end-systolic elastance (Ees) was significantly elevated in severe PGD but preload-recruitable stroke work (PRSW) was significantly lower compared to patients without severe PGD. "Recovery" (after liberation from MCS) was associated with improvement in RV Ees, chamber capacitance and PRSW, although they remained significantly lower than patients without severe PGD. Conclusion:Severe PGD of the dominant right heart failure phenotype is characterized by reduced chamber capacitance, increased "stiffness" and impaired contractility.Complete normalization was not required for successful weaning of MCS.

Acute complication posttransplant: primary allograft dysfunction

“…By the time of recovery, these abnormalities had improved, but remained below the values seen in patients without severe PGD (Fig. 1) [8 ▪ ].…”

“…Ees, end-systolic elastance; α, stiffness constant (derived EDP = β[e α(EDV-V0) -1], where V0 is the volume at zero pressure (unstressed volume), and α and β are constants determined by the mechanical properties of the heart, that defines the nonlinear end-diastolic pressure-volume relation). Reproduced from [8 ▪ ] with permission from John Wiley and Sons.…”