Is myocardial Na+/Ca2+ exchanger transcription a marker for different stages of myocardial dysfunction? Quantitative polymerase chain reaction of the messenger RNA in endomyocardial biopsies of patients with heart failure.

Objectives: This study was designed to determine the stage of myocardial dysfunction at which an upregulation of the Na+/Ca2+ exchanger (EXCH) transcription takes place.

Background: Because EXCH is an important regulator of intracellular calcium homeostasis, alterations in EXCH expression may occur before the onset of end-stage heart failure (HF) to maintain normal intracellular Ca2+ concentrations. We analyzed whether the EXCH transcription level is correlated to the degree of myocardial dysfunction and whether it can be a suitable molecular marker to define the transition to myocardial decompensation early on.

Methods: By quantitative polymerase chain reaction technique, the level of EXCH transcription was analyzed in myocardial biopsies from 40 patients with various degrees of myocardial dysfunction due to valvular heart disease (VHD; n = 22) or dilated cardiomyopathy (DCM; n = 18). Additionally, biopsies from 7 individuals with excluded heart disease and explanted heart tissue from 13 patients with end-stage HF were investigated.

Results: The level of EXCH transcription of controls (2.6 +/- 1.2 attomoles [amol]/ng total RNA) did not differ from that of patients with DCM (2.3 +/- 1.5 amol/ng) or VHD (2.1 +/- 1.5 amol/ng). No alteration in the EXCH transcription was found in VHD and DCM patients with respect to the severity of myocardial dysfunction. However, patients with end-stage HF showed a four-fold increase in EXCH transcription, amounting to 8.9 +/- 1.9 amol/ng (p < 0.05).

Conclusions: The upregulation in EXCH transcription either occurs very late in human heart failure or is a phenomenon of heart transplantation in end-stage HF. Consequently, myocardial EXCH transcription cannot be used as a marker for early myocardial decompensation.