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CLINICAL STUDIES: HEART FAILURE

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

Cornelia Piper, MD^*, Johannes Bilger, MD, Eva-Maria Henrichs, Heinz-Peter Schultheiss, MD, FESC, Dieter Horstkotte, MD, FESC^* and Andrea Doerner, PhD

^* Department of Cardiology, Heart Center North Rhine-Westphalia, University Hospital of the Ruhr University of Bochum, Bad Oeynhausen, Germany
Department of Cardiology, Benjamin Franklin Hospital, Free University of Berlin, Berlin, Germany

Manuscript received May 27, 1999; revised manuscript received December 30, 1999, accepted March 1, 2000.

Reprint requests and correspondence: Dr. Andrea Doerner, Department of Cardiology, Benjamin Franklin Hospital, Free University of Berlin, Hindenburgdamm 30, 12000 Berlin, Germany.
doerner{at}ukbf.fu-berlin.de

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.

Abbreviations and Acronyms   AR = aortic regurgitation   AS = aortic stenosis   CI = cardiac index   DCM = dilated cardiomyopathy   EF = ejection fraction   EXCH = Na+/Ca2+ exchanger   ICM = ischemic cardiomyopathy   MR = mitral regurgitation   NYHA = New York Heart Association   PLaorta = transaortic pressure loss   RFaorta = transaortic regurgitation   RFmitral = transmitral regurgitation   VAD = ventricular assist device

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