Reply
Authors: Lisa B. VanWagner, Hongyan Ning, Maureen Whitsett, Josh Levitsky, Sarah Uttal, John T. Wilkins, Michael M. Abecassis, Daniela P. Ladner, Anton I. Skaro, Donald M. Lloyd‐Jones
Journal: Hepatology (2017)

Potential conflict of interest: Dr. VanWagner is on the speaker's bureau for Salix. She received grants from Novartis. Reply: We thank Xue et al. for their interest in our publication that reported on the development of the Cardiovascular Risk in Orthotopic Liver Transplantation (CAR‐OLT) score.1 The authors raise concerns that CAR‐OLT score development did not include intraoperative factors that may differentially affect the occurrence of cardiovascular complications and death after OLT. Furthermore, they imply that if intraoperative factors were included in CAR‐OLT, the discrimination of the score might be improved. We agree that intraoperative factors play an important role in the prevalence of postoperative cardiovascular events. Risk for perioperative cardiac complications and mortality increases with length of the surgical procedure, blood loss, transfusion requirements, fluid shifts, major vascular involvement, and anatomical location.2 Reperfusion events unique to OLT are often associated with intense hemodynamic instability, vasopressor use, metabolic acidosis, electrolyte derangements, blood loss, coagulopathy, and sudden hypothermia.2 Major vascular injury, delayed graft function, and hemorrhage are common intraoperative stressors. Thrombotic events, including intracardiac thrombus, may occur following reperfusion of the liver graft, further overwhelming the right ventricle and compromising left preload and myocardial perfusion. In the early postoperative period, a rapid rise in blood pressure and systemic vascular resistance may unmask previously unrecognized systolic dysfunction or ischemia. Thus, we too hypothesized that intraoperative factors may contribute to cardiovascular events. As stated in the Materials and Methods section and provided in Supporting Table S2, we analyzed a multitude of intraoperative factors including intraoperative laboratory values suggestive of postreperfusion syndrome (serum potassium, arterial pH, lactic acid), massive blood loss (transfusion requirements, lowest hemoglobin), prolonged operative time, hemodynamic instability (use of inotropic agents, total fluid volume), and thrombotic complications (transesophageal echocardiogram findings).1 Addition of these variables to the CAR‐OLT did not improve model fit based on the Akaike information criterion (see Materials and Methods). We also want to emphasize that we were not trying to merely predict posttransplant cardiovascular outcomes but to create a clinically useful preoperative tool to help with management of high–cardiovascular risk OLT candidates. Once a patient is in the operating room, it is typically too late to change clinical course because the decision to proceed with OLT has already been made. Thus, the variables included in the CAR‐OLT score represent those clinical covariates that are available prior to operating room entry. We have provided the transplant community with a mobile and web‐based application to help other centers determine the clinical utility of this risk score (www.carolt.us). We encourage ongoing communication about risk model performance in other populations and whether addition of further variables in specific subpopulations might improve risk model performance.