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Ann Thorac Surg 1996;62:1340-1341
© 1996 The Society of Thoracic Surgeons

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Invited Commentary

Invited Commentary

German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

See also page 1337.

To our knowledge, seven articles have been published that report animal experiments of intramyocardial electrogram (IMEG) rejection monitoring on the basis of a decline of the QRS-complex amplitude [1–7]. This work from Everett and associates is the eighth article on this subject. All authors, except for Avitall and associates [2], who only used one bipolar ring electrode for recording of the IMEG, could find a correlation between alterations of the IMEG amplitude and the histologic findings of endomyocardial biopsy specimens, proving a sensitivity between 89% and 100% and a specificity between 77% and 90% in comparison with biopsy histology.

Three reasons could be identified for the decline of the IMEG amplitude during rejection episodes: (1) a reduced slew rate, (2) a diminished amplitude, and (3) a prolonged period of the myocyte membrane potential measured during depolarization [8]. These changes can easily be detected by the QRS-complex decrease of the IMEG but not in the surface electrocardiogram, where the changes are concealed by summation effects.

The cause of these measurable effects is probably an increase in the nitric oxide synthase content and therefore of nitric oxide content induced by immunologic reactions (cytokines, activation of complement cascade, membrane attack complex), which has an indirect toxic effect on the cell membrane (influencing the sodium and calcium channel).

In spite of these findings, which indicate a causative relation between electrophysiologic changes and cardiac allograft rejection, and in spite of the experimental results, this method could not be established in the clinical routine follow-up of heart transplant patients except in some European institutes, although Warnecke, Müller, and their colleagues [10–12] have shown that by applying up-to-date telemetric technology even transtelephonic follow-up of the patients is possible.

However, because of circadian variations, physical activity, and changes in the endogenic catecholamine level, which influence the amplitude of the IMEG, these recordings have to be done at night when the patient is asleep, which is possible with the available technique. The results obtained by the application of the described method in humans are comparable with the data obtained in animal experiments.

Since 1988, at the German Heart Institute Berlin, the transtelephonic follow-up method has been used in more than 1,000 patients. This was responsible for the complete abolition of routine biopsy and resulted in a 75% reduction in the number of biopsies, as these were only performed in indicated cases. Death caused by unrecognized acute rejection could be lowered to a rate less than 0.4%. Due to the high sensitivity of the method and the daily transtelephonic follow-up, the number of outpatient visits could be reduced by 50%. Patients come in only when suspicion of rejection is indicated by a decline of the amplitude of the IMEG. According to the specificity of the method, some patients will also be called in when no rejection is present. In such cases, an infection with a cardiotrophic virus (cytomegalovirus) is the most likely differential diagnosis. The in-hospital assessment of this infection, which has led to significant electrophysiologic changes, is advantageous for the patient.

Disadvantages of the method as it is clinically applied at present are (1) the varying distance between anode and cathode of the unipolar lead configuration, which leads to variability of the QRS amplitude, (2) the scarring process around the electrodes in the long-term course, and (3) the necessity of implantation of a device for telemetric data transfer. Experimental investigations showed that bipolar leads supply a more consistent QRS-complex amplitude and therefore a higher sensitivity for rejection monitoring than unipolar leads. The number of bipolar electrodes necessary for reliable sensitivity therefore is lower than the number of unipolar electrodes [7].

This work from Everett and associates shows that also in animals with orthotopic cardiac transplantation a reliable sensitivity and specificity can be reached with a four-electrode configuration. In this context, it confirms experimentally the results of clinical experience gained in humans and gives hints for further improvements.

References

1. Koike K, Hesslein PS, Dasmahapatra HK, et al. Telemetric detection of cardiac allograft rejection. Circulation 1988;78(Suppl 1):106–12.
2. Avitall B, Payne DD, Connolly RJ, et al. Heterotopic heart transplantation: electrophysiologic changes during acute rejection. J Heart Transplant 1988;7:176–82.[Medline]
3. Rosenbloom M, Laschinger JC, Saffitz JE, Cox JL, Bolman M, Branham BH. Noinvasive detection of cardiac allograft rejection by analysis of the unipolar peak-to-peak amplitude of intramyocardial electrograms. Ann Thorac Surg 1989;47:407–11.[Abstract]
4. Pirolo JS, Tweddell JS, Brunt EM, et al. Influence of activation origin, lead number and lead configuration on the noninvasive electrophysiologic detection of cardiac allograft rejection. Circulation 1991;84(Suppl 3):344–54.
5. Irwin ED, Bianco RW, Clack R, et al. Use of epicardial electrocardiograms for detecting cardiac allograft rejection. Ann Thorac Surg 1992;54:669–75.[Abstract]
6. Grauhan O, Warnecke H, Mueller J, et al. Intramyocardial electrogram recordings for diagnosis and therapy monitoring of cardiac allograft rejection. Eur J Cardiothorac Surg 1993;7:489–94.[Abstract]
7. Knosalla C. Das intramyokardiale Elektrogramm (IMEG). In: Hetzer R, ed. Fortschritte der Herz- Thorax- und Gefäßchirurgle. Darmstadt: Steinkopff, 1995.
8. Grauhan O, Schnalke F, Mueller J, Knosalla C, Siegel G, Hetzer R. Electrophysiological alterations of myocytes during rejection after heart transplantation. Langenbecks Arch Chir 1996;(Suppl 1):129–32.
9. Yang X, Chowdhury N, Brett J, et al. Induction of myocardial nitric oxide synthetase by cardiac allograft rejection. J Clin Invest 1994;94:714–21.
10. Warnacke H, Schüler S, Goetze H-J, et al. Noinvasive monitoring of cardiac allograft rejection by intramyocardial electrogram recordings. Circulation 1986;74(Suppl 3):72–6.[Abstract/Free Full Text]
11. Warnecke H, Müller J, Cohnert T, et al. Clinical heart transplantation without routine endomyocardial biopsy. J Heart Transplant 1992;11:1093–102.
12. Müller J, Warnecke H, Spiegelsberger S, Hummel M, Cohnert T, Hetzer R. Reliable noninvasive rejection monitoring in childhood. J Heart Lung Transplant 1993;12:189–98.[Medline]

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This Article Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Roland Hetzer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Müller, J. Articles by Hetzer, R. Search for Related Content PubMed Articles by Müller, J. Articles by Hetzer, R. Related Collections Related Article