Prognostic value of myocardial lactate dehydrogenase subunit ratio in heart transplant recipients

Background: Allograft coronary artery disease (CAD) is a major long-term complication in heart transplant recipients. Unfortunately, methods for early estimation of the likelihood of development of the disease are not currently available. Lactate dehydrogenase (LDH) is composed of heart and muscle subunits. The prevalence of these subunits in LDH isoenzymes (LDH1 through LDH5) is an accurate indicator of myocardial metabolism and allows indirect estimation of oxygen availability to cardiocytes. This study investigated the prognostic value of myocardial LDH composition for the occurrence of morbid events in patients with severe allograft CAD. Methods: Eighty-eight heart transplant recipients were followed up for a median of 4.3 years. The isoenzymes of LDH and the ratio of the heart and muscle subunits (H/M) were determined in 526 endomyocardial biopsy samples. Results: Eleven patients (12%) died from allograft CAD during follow-up. They had significantly lower H/M ratios compared with event-free patients, with clear differences as early as 6 months after operation. A threshold value of 2.75 was derived from receiver operating characteristic curve analysis. Patients showing H/M values less than or equal to 2.75 had a significantly higher mortality rate than did those with higher values (p =.0003). Importantly, the H/M ratio emerged as the most powerful independent prognostic factor of death by allograft CAD (p =.001) in a multivariate model. Conclusions: Poor myocardial aerobic metabolism estimated through low H/M values was highly predictive of cardiac death resulting from severe allograft CAD. Analysis of LDH isoenzyme profile in routine endomyocardial biopsies might be of clinical value.