Diastolic Dysfunction Increases the Risk of Primary Graft Dysfunction after Lung Transplant

Abstract

Rationale: Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality after lung transplant and is characterized by severe hypoxemia and infiltrates in the allograft. The pathogenesis of PGD involves ischemia-reperfusion injury. However, subclinical increases in pulmonary venous pressure due to left ventricular diastolic dysfunction may contribute by exacerbating capillary leak.Objectives: To determine whether a higher ratio of early mitral inflow velocity (E) to early diastolic mitral annular velocity (é), indicative of worse left ventricular diastolic function, is associated with a higher risk of PGD.Methods: We performed a retrospective cohort study of patients in the Lung Transplant Outcomes Group who underwent bilateral lung transplant at our institution between 2004 and 2014 for interstitial lung disease, chronic obstructive pulmonary disease, or pulmonary arterial hypertension. Transthoracic echocardiograms obtained during evaluation for transplant listing were analyzed for E/é and other measures of diastolic function. PGD was defined as Pa O 2 /FI O 2 less than or equal to 200 with allograft infiltrates at 48 or 72 hours after reperfusion. The association between E/é and PGD was assessed with multivariable logistic regression.Measurements and Main Results: After adjustment for recipient age, body mass index, mean pulmonary arterial pressure, and pretransplant diagnosis, higher E/é and E/é greater than 8 were associated with an increased risk of PGD (E/é odds ratio, 1.93; 95% confidence interval, 1.02-3.64; P = 0.04; E/é .8 odds ratio, 5.29; 95% confidence interval, 1.40-20.01; P = 0.01).Conclusions: Differences in left ventricular diastolic function may contribute to the development of PGD. Future trials are needed to determine whether optimization of left ventricular diastolic function reduces the risk of PGD.

Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post–lung transplantation survival

“…PGD accounts for the majority of early morbidity and mortality after transplant(23–25) and has been linked to various donor, recipient, and surgical characteristics(26–28). Recipient telomere lengths may potentially explain the previously reported association between reperfusion injury and native fibrotic, as opposed to obstructive, lung disease(29).…”

Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury

“…A variety of clinical risk factors for PGD have been identified with contributions from the donor (3)(4)(5)(6)(7), the recipient (3)(4)(5)(7)(8)(9)(10), and operative variables (4,5,8,11). In addition, a number of biomarkers have been associated with increased risk of PGD, including markers of innate and adaptive immune activation, epithelial and endothelial injury, coagulation, vascular permeability, and lipid peroxidation (2,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Double‐lung versus heart‐lung transplantation for precapillary pulmonary arterial hypertension: a 24‐year single‐center retrospective study

“…New‐onset LV dysfunction early after DLT in PH‐recipients has also been described by several authors . In patients with severe long‐standing PH, the LV is often chronically volume‐deprived, and as such, small, stiff, and dysfunctional.…”