Primary Graft Dysfunction After Heart Transplantation

Abstract

Primary graft dysfunction (PGD) is a lifethreatening complication of heart transplantation that presents as left, right, or biventricular dysfunction occurring within the first 24 hours of transplant surgery for which there is no identifiable secondary cause. Myocardial injury caused by acute catecholamine toxicity and the release of multiple proinflammatory mediators in the donor, followed by ischaemiareperfusion injury sustained during retrieval, have been considered the predominant pathogenetic processes leading to PGD. Donor, recipient, and procedural factors contribute to the development and severity of the clinical syndrome. The changing donor and recipient characteristics over the last two decades, particularly the increasing donor and recipient age, have led to heightened risk of PGD. PGD is graded from mild to severe depending on the extent of circulatory support that is required to maintain haemodynamic stability and vital organ function. While advances in acute mechanical support devices have improved the outlook for patients with PGD, the rate of mortality remains high for those with severe PGD, reaching 40 %. Potential approaches to preventing or minimising the severity of PGD include optimising donor management, donor heart preservation, and donor/recipient matching.

Primary graft dysfunction after heart transplantation: a thorn amongst the roses

“…Previous studies had used the need for mechanical circulatory support as a criterion for diagnosis of primary graft dysfunction; however, the timing of initiation of therapy and endpoints differs from these studies, leading to significant variation in incidence reporting (2.3–32.4%) [4, 8–11]. With an increasing trend towards utilisation of marginal donor organ due to increasing waiting list pressures, a resultant reduction in threshold for initiation of ECMO support in certain patients to support the graft in the initial phase of reperfusion (first 24 h) may result in an over-estimation of the incidence of PGD [12]. This is especially true in high-risk recipients with a significant inflammatory milieu as a result of receiving a combination of in-hospital inotropic or short- or long-term mechanical circulatory support pre-transplant.…”

Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death

“…Primary graft dysfunction (PGD) refers to reduced heart function in the early post-operative period, due to left and/or right ventricular impairment requiring inotropes treatment and/or mechanical circulatory assist devices [ 63 , 99 , 100 ]. PDG occurs in the first 24 h following the transplant and its occurrence is associated with poor outcomes [ 63 , 100 ]. PDG requires inotropes administration and, in the most severe cases, mechanical and ventilatory support [ 100 ].…”

“…PDG occurs in the first 24 h following the transplant and its occurrence is associated with poor outcomes [ 63 , 100 ]. PDG requires inotropes administration and, in the most severe cases, mechanical and ventilatory support [ 100 ]. The causes are not clear, but likely include the increase in catecholamines plasma levels due to brain death, the ischemia during procurement and storage (then followed by reperfusion injury), and the need for high-dose inotropes or vasopressors to resuscitate the heart leading to β-Adrenergic Receptor (β-AR) desensitization and stunning [ 63 , 99 , 100 ].…”

“…Furthermore, the preexisting heart failure condition of the recipient is associated with high levels of systemic pro-inflammatory cytokines. The use of inotropes in the recipient may further contribute to heighten the cytokine levels and promote adverse cardiodepressant pathways [ 55 , 56 , 57 , 58 , 59 , 82 , 83 , 84 , 85 , 86 , 87 , 100 , 101 ].…”

Early Graft Dysfunction Following Heart Transplant: Prevention and Management

“…In spite of significant improvements in overall perioperative care of heart transplant recipients for the past few decades, we still experienced 5% to 10% risk of 30-day mortality, primarily related to early failure of the allograft. 2 Primary graft dysfunction (PGD) can occur within 24 hours after transplant, manifesting as left ventricular dysfunction, right ventricular dysfunction, or biventricular dysfunction, evidenced by left ventricular ejection fraction <40% by echocardiography. In addition, presence of cardiogenic shock more than 60 minutes based on systolic blood pressure <90 mm Hg and/or cardiac index <2 L/min/m 2 with adequate filling pressure was used as one of the criteria for PGD.…”