Prof. Rainer Leyh, Prof. Peter Heuschmann
Dr. Mehmet Özkur, Dr. Maria Lazariotou, Dr. Martin Wagner
Federal Ministery of Education and Research
ongoing; present: enrollment
The catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. Recent studies indicate that a Val108/158Met polymorphism on COMT is common, which results in three genotypes that also translate in respective phenotypes of enzyme activity: the homozygous HH ("high"-"high" enzyme activity) and LL ("low"-"low") and the heterozygous HL ("high"-"low") phenotypes, respectively, with wide variation in the response to endogenous and exogenous catecholamines.
In patients undergoing cardiac surgery including cardio-pulmonary bypass (CPB), i.v. positive inotropic and vasoconstrictive agents such as noradrenalin are commonly used to support cardiopulmonary function. There is growing evidence, that in particular in the COMT-LL phenotype, the risk of vasodilatory shock, acute kidney injury and ICU- and in-hospital stay are dramatically increased. Understanding the pathophysiology of COMT and its association to clinical outcomes will most likely be helpful to support patient care, if strategies are established to adjust catecholamine therapy according to COMT activity type in the future.
The aim of the current pilot study is to investigate the prevalence of the described phenotypes of COMT activity and their impact on cardiac and renal endpoints, such as acute kidney injury, vasodilatory shock, in patients undergoing cardiac surgery at the University Hospital Würzburg. We will further investigate the phenotype according to COMT enzyme activity by determining detailed data about comorbidities and clinical endpoints such as cardiac function and congestive heart failure, questionnaires on anxiety and depression and chronic kidney disease. Blood, urine and tissue samples will be collected, and biomarkers will be measured that are predictive for COMT activity and may represent surrogates or mediators of clinical outcomes. The insights derived from the proposed study will support the planning of future large prospective studies for verifying these hypotheses.