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Prognostic value of myocardial lactate dehydrogenase subunit ratio in heart transplant recipients
E Missov1, A M Boularan, C Bonifacj
1Service de Cardiologie and INSERM U-390, Centre Hospitalier Universitaire de Montpellier, France. missov@cardio.ucsf.edu
Insights
Low heart/muscle subunit ratios (H/M) in lactate dehydrogenase (LDH) isoenzymes predict cardiac death from allograft coronary artery disease (CAD) in heart transplant patients. This finding may improve early risk assessment for transplant recipients.
Area of Science:
- Cardiology
- Transplantation Immunology
- Biochemistry
Background:
- Allograft coronary artery disease (CAD) is a significant long-term risk for heart transplant recipients.
- Current methods for early detection of allograft CAD are lacking.
- Lactate dehydrogenase (LDH) isoenzymes reflect myocardial metabolism and oxygenation.
Purpose of the Study:
- To investigate the prognostic value of myocardial LDH composition for predicting adverse events in severe allograft CAD.
- To determine if LDH isoenzyme profiles can serve as an early indicator of allograft CAD risk.
Main Methods:
- Eighty-eight heart transplant recipients were followed for a median of 4.3 years.
- LDH isoenzymes and heart/muscle (H/M) subunit ratios were analyzed in 526 endomyocardial biopsy samples.
- Prognostic factors for allograft CAD mortality were assessed using multivariate analysis.
Main Results:
- Eleven patients (12%) died from allograft CAD.
- Patients who died had significantly lower H/M ratios compared to event-free patients, detectable as early as 6 months post-transplant.
- An H/M ratio threshold of 2.75 predicted significantly higher mortality (p=.0003), with the H/M ratio being the strongest independent predictor (p=.001).
Conclusions:
- Reduced myocardial aerobic metabolism, indicated by low H/M ratios, strongly predicts cardiac death in severe allograft CAD.
- LDH isoenzyme analysis in routine endomyocardial biopsies could offer valuable clinical prognostic information.
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 < or =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.