Incidence of and Risk Assessment for Adverse Cardiovascular Outcomes After Liver Transplantation: A Systematic Review

Abstract

Background: Cardiovascular events represent a major source of morbidity and mortality after liver transplantation and will likely increase given the aging population and nonalcoholic fatty liver disease as a leading indication for transplant. The optimal cardiovascular risk stratification approach in this evolving patient population remains unclear. The aims of this systematic review are to: (1) refine the definition, (2) characterize the incidence, and (3) identify risk factors for cardiovascular events post-liver transplantation. Additionally, we evaluated performance characteristics of different cardiac testing modalities.

Methods: MEDLINE via PubMed, EMBASE, Web of Science, and Scopus were searched for studies published between 2002 and 2016 (model of end-stage liver disease era). Two authors independently reviewed articles to select eligible studies and performed data abstraction.

Results: Twenty-nine studies representing 57 493 patients from 26 unique cohorts were included. Definitions of cardiovascular outcomes were highly inconsistent. Incidence rates were widely variable: 1% to 41% for outcomes of 6 months or shorter and 0% to 31% for outcomes longer than 6 months. Multivariate analyses demonstrated that older age and history of cardiac disease were the most consistent predictors of cardiovascular events posttransplant (significant in 8/23 and 7/22, studies, respectively). Predictive capacity of various cardiac imaging modalities was also discrepant.

Conclusions: The true incidence of cardiovascular outcomes post-liver transplant remains unknown in large part due to lack of consensus regarding outcome definition. Overall, poor data quality and gaps in knowledge limit the ability to clearly identify predictors of outcomes, but existing data support a more aggressive risk stratification protocol for patients of advanced age and/or with preexisting cardiac disease.

Figure 1

Flow diagram of studies included in the systematic review

Figure 2

List of variables identified to have significant predictive value for CV outcomes post-LT *Cardiac Disease includes: CAD/CHF/HTN/CVA ^Includes Standard TTE data and data from DSE #2 studies indicated higher risk in males; 1 study higher risk in females †Higher risk in NAFLD/Crypto in 3 studies; PBC/PSC had lower risk in 1 study and higher in another study ‡Includes pretransplant ICU status, ventilator status, pressor requirement and operative time