Nicht-invasive Überwachung von Abstoßungsreaktionen nach Herztransplantation

 

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Hintergrund und Fragestellung: Die Endomyokardbiopsie ist der Goldstandard zur Abstoßungsüberwachung nach Herztransplantation. Bei Anwendung dieser invasiven Methode ist aufgrund von Abstoßungsreaktionen mit einer Mortalitätsrate von 5 - 6 % im ersten postoperativen Jahr zu rechnen. Das Ziel dieser retrospektiven Analyse war es, die diagnostische Zuverlässigkeit einer nichtinvasiven elektrophysiologischen Methode zur Abstoßungsüberwachung zu überprüfen.

Patienten und Methodik: Dazu wurde täglich die QRS-Komplexamplitude des intramyokardialen Elektrogramms über einen Schrittmacher mit Telemetriefunktion in dem Zeitraum eines Jahres gemessen. Als Kriterium für den Verdacht einer Abstoßung wurde der Abfall der QRS-Komplexamplitude von mehr als 8 % gewertet. Von 734 Patienten wurden 558 in die Studie eingeschlossen. Eine Biopsie wurde nur dann vorgenommen, wenn die nichtinvasiven Methoden (QRS-Komplexamplitude plus Echokardiographie) diskrepante Ergebnisse zeigten.

Ergebnisse: Keiner der Patienten starb an einer Abstoßungsreaktion, 273 wurden mindestens einmal und 285 nie biopsiert. Die Methode erreichte eine Sensitivität von 0,9777, eine Spezifität von 0,9634, einen negativen prädiktiven Wert von 0,9850 und einen positiven prädiktiven Wert von 0,9459.

Folgerung: Die tägliche elektrophysiologische nichtinvasive Abstoßungsüberwachung scheint der invasiven Endomyokardbiopsie überlegen zu sein, da die durch Abstoßungsreaktionenen bedingte Mortalitätsrate bei gleichzeitiger geringerer Zahl an Endomyokardbiopsien deutlich reduziert werden konnte.

Non-invasive monitoring of rejection after cardiac transplantation. The method and retrospective analysis of data on 734 patients

Background and objective: Endomyocardial biopsy is the gold standard for monitoring rejection in cardiac recipients. The death rate due to rejection with this invasive method is 5-6 % in the first postoperative year. The aim of this retrospective data analysis from cardiac recipients was to prove the diagnostic reliability of a non-invasive electrophysiological method for rejection monitoring.

Patients and methods: We daily analyzed the QRS-complex amplitude of the intramyocardial electrogram, which we received over a period from one year via a pacemaker with a telemetric capability. The diagnostic guideline for a suspected rejection was the reduction of the QRS-complex amplitude by more than 8 %. Out of 734 patients 558 were included in the study. Biopsy was only performed when the non-invasive rejection monitoring data (QRS-complex amplitude plus echocardiography) showed a discrepancy for rejection.

Results: None of the patients died due to rejection, 273 at least once underwent a biopsy, and 285 never had a biopsy. The method reached a sensitivity of 0.9777, a specificity of 0.9634, a negative predictive value of 0.9850, and a positive predictive value of 0.9459.

Conclusion: Daily electrophysiological non-invasive monitoring of rejection seems to be superior to endomyocardial biopsy. Death of patients due to rejection can be minimised. The number of necessary biopsies can be drastically reduced when compared to the usual number performed.

Literatur

• 1 Avitall B, Payne D, Connolly R. et al . Heterotopic heart transplantation: electrophysiologic changes during acute rejection.  J Heart Transplant. 1988;  7 176-182
  Google Scholar
• 2 Ballester M, Bordes R, Tazelaar H D. et al . Evaluation of biopsy classification for rejection: relation to detection of myocardial damage by monoclonal antimyosin antibody imaging.  J Am Coll Cardiol. 1998;  31 1357-1361
  Google Scholar
• 3 Becker A E, Heijmans C D, Essed C E. Chronic non-ischaemic congestive heart disease and endomyocardial biopsies. Worth the extra?.  Eur Heart J. 1991;  12 218-223
  Google Scholar
• 4 Billingham M E. Diagnosis of cardiac rejection by endomyocardial biopsy.  Heart Transplant. 1982;  1 25
  Google Scholar
• 5 Billingham M E, Cary N RB, Hammond E H. et al . A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart Rejection Study Group.  J Heart Transplant. 1990;  9 587-593
  Google Scholar
• 6 Boucek M M, Faro A, Novick R J, Bennett L E, Keck B M, Hosenpud J D. The Registry of the International Society for Heart and Lung Transplantation: fourth official pediatric report - 2000.  J Heart Lung Transplant. 2001;  20 39-52
  Google Scholar
• 7 Copeland J G, Rosado L J, Sethi G, Huston C. Heart transplantation: current status.  Clin Transpl. 1990;  95-102
  Google Scholar
• 8 Costanzo-Nordin M, Winters G, Fisher S, O¿Sullivan J, Heroux A L, Kao W. Endocardial infiltrates in the transplanted heart: clinical significance emerging from analysis of 5026 endomyocardial biopsy specimen.  J Heart Lung Transplant. 1993;  12 741-747
  Google Scholar
• 9 Dandel M, Hummel M, Mueller J, Wellnhofer E, Meyer R, Ewert R. Reliability of tissue doppler wall motion monitoring after heart transplantation for the replacement of invasive routine screenings by optimally timed cardiac biopsies and catheterization.  Circulation. 2000;  102 II-489 (suppl 2))
  Google Scholar
• 10 Dandel M, Hummel M, Müller J. et al . Clinical value of pulsed-wave tissue Doppler imaging parameters in the follow-up of patients after heart transplantation.  Circulation. 1999;  100 391
  Google Scholar
• 11 Everett J, Palmer M, Jessurum J, Shumway S. Noninvasive diagnosis of cardiac allograft rejection in an orthotopic canine model.  Ann Thorac Surg. 1996;  62 1337-1340
  Google Scholar
• 12 Goldstein D J, Garfein E S, Aaronson K, Zuech N, Michler R E. Mitral valve replacement and tricuspid valve repair after cardiac transplantation.  Ann Thorac Surg. 1997;  63 1463-1465 (5)
  Google Scholar
• 13 Grasser B, Iberer F, Schreier G. et al . Intramyocardial electrogram variability in the monitoring of graft rejection after heart transplantation.  Pace. 1998;  21 2345-2349
  Google Scholar
• 14 Grauhan O, Müller J, Pfitzmann R. et al . Humoral rejection after heart transplantation: reliability of intramyocardial electrogram recordings (IMEG) and myocardial biopsy.  Transpl Int. 1997;  10 439-445
  Google Scholar
• 15 Grauhan O, Schnalke F, Müller J. et al . Elektrophysiologische Veränderungen der Kardiomyozyten bei Abstoßung nach herztransplantation.  Transplantationsmedizin. 1998;  19 79-84
  Google Scholar
• 16 Grauhan O, Müller J, Knosalla C. et al . Das intramyokardiale Elektrokardiogramm (IMEG) in der Diagnose humoral vermittelten Abstoßung nach Herztransplantation.  Zeitschrift für Kardiologie. 1996;  85 745-752
  Google Scholar
• 17 Guggenmoos-Holzmann I, Wernecke K D. Medizinische Statistik. Berlin: Blackwell Wissenschafts-Verlag 1996: 161ff
  Google Scholar
• 18 Hammond E H, Yowell R L, Nunoda S, Menlove R L, Renlund D G, Bristow M. Vascular (humoral) rejection in heart transplantation: Pathologic observations and clinical implications.  J Heart Transplant. 1989;  8 430-443
  Google Scholar
• 19 Hetzer R, Potapov E V, Müller J, Loebe M, Hummel M, Weng Y. Daily noninvasive rejection monitoring improves long-term survival in pediatric heart transplantation.  Ann Thorac Surg. 1998;  66 1343-1349
  Google Scholar
• 20 Hetzer R, Albert W, Hummel M. et al . Status of patients presently living 9 to 13 years after orthotopic heart transplantation.  Ann Thorac Surg. 1997;  64 1661-1668
  Google Scholar
• 21 Hosenpud J D, Bennett L E, Keck B M, Boucek M M, Novick R. The Registry of the International Society for Heart and Lung Transplantation: Seventeenth official report - 2000.  J Heart Lung Transplant. 2000;  19 909-931
  Google Scholar
• 22 Irwin E, Bianco R, Clack R. et al . Use of epicardial electrograms for detecting allograft rejection.  Ann Thorac Surg. 1992;  54 669-675
  Google Scholar
• 23 Jones B M, Taylor F J, Wright O M. et al . Quality of life after heart transplantation in patients assigned to douple- or triple-drug therapy.  J Heart Transplant. 1990;  9 392-396
  Google Scholar
• 24 Knosalla C, Grauhan O, Müller J. et al . Intramyocardial electrogramm recordings (IMEG) for diagnosis of cellular and humoral mediated cardiac allograft rejection.  Ann Thorac Cardiovasc Surg. 2000;  6 89-94
  Google Scholar
• 25 Knosalla C, Hummel M, Müller J, Grauhan O, Ewert R, Hetzer R. Diagnosis of heart allograft rejection.  Current Opinion in Organ Transplantation. 2000;  5 118-125
  Google Scholar
• 26 Koike K, Hesslein P, Dasmahapatra H. et al . Telemetric detection of cardiac allograft rejection. Correlation of electrophysiological, histological, and biocemical changes during unmodified rejection.  Circulation. 1988;  78 l106-112
  Google Scholar
• 27 Lieback E, Meyer R, Nowrocki M, Bellach J, Hetzer R. Noninvasive diagnosis of cardiac rejection through echocardiographic tissue characterisation.  Ann Thorac Surg. 1994;  57 1164-1170
  Google Scholar
• 28 McCarthy P M, Billingham M E, Flavin T F, Hunt S, Stinson E B. Immunsupression and rejection. Futura Publishing Company; New York In: Smith JA, McCarthy PM, Sarris GE, Stinson EB, Reitz BA,ed. The Stanford manual of cardiopulmonary transplantation 1996: 99-125
  Google Scholar
• 29 Moidl R, Chevtchik O, Simon P. et al . Noninvasive monitoring of peak filling rate acoustic quantification echocardiography accureately detects acute allograft rejection.  J Heart Lung Transplant. 1999;  18 194-201
  Google Scholar
• 30 Moran A M, Lipshultz S E, Rifai N. et al . Non-invasive assessment of rejection in pediatric transplant patients: serologic and echocardiographic prediction of biopsy-proven myocardial rejection.  J Heart Lung transplant. 2000;  19 756-764
  Google Scholar
• 31 Park J W, Warnecke H, Deng M, Schüler S, Heinrich K W, Hetzer R. Early diastolic left ventricular function as a marker of acute cardiac rejection: a prospective serial echocardiographic study.  Int J Cardiol. 1992;  37 351-359
  Google Scholar
• 32 Perez-Trevino C, Diaz-Arauzo A, Lopez-Cuellar M, Jurado J. Endomyocardial Biopsy.  Gac Med Mex. 1972;  104 399-405 (5)
  Google Scholar
• 33 Pirolo J S, Shuman T S, Brunt E M, Liptay M J, Cox J L, Ferguson T B. Noninvasive detection of cardiac allograft rejection by prospective telemetric monitoring.  Journal of Thoracic and Cardiovascular surgery. 1992;  103 969-79
  Google Scholar
• 34 Puig M, Ballester M, Matias-Guiu X. et al . Burden of myocardial damage in cardiac allograft rejection: scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis.  J Nucl Cardiol. 2000;  7 132-139
  Google Scholar
• 35 Sahar G, Stamler A, Erez E. et al . Etiological factors influencing the development of atrioventricular valve incompetence after heart transplantation.  Transplant Proc. 1997;  29 2675-2676
  Google Scholar
• 36 Sharles L D, Cary N R, Large S R, Wallwork J. Error rates with which endomyocardial biopsy specimens are graded for rejection after cardiac transplantation.  Am J Cardiol. 1992;  70 527-530
  Google Scholar
• 37 Shumway S J, Kaye M P. The International Society for Heart Transplantation Registry.  Clin Transpl. 1988;  1-4
  Google Scholar
• 38 Spiegelhalter D J, Stovin P GI. An analysis of repeated biopsies following cardiac transplantation.  Stat Med. 1982;  2 33-40
  Google Scholar
• 39 Taylor D O, Yowell R L, Kfoury A G, Hammond E H, Renlund D G. Allograft coronary artery disease: clinical correlations with circulating anti-HLA antibodies and the immunohistopathologic pattern of vascular rejection.  J Heart Lung Transplant. 2000;  19 518-521
  Google Scholar
• 40 Valentine H, Fowler M, Hunt S. et al . Changes in Doppler echocardiographic indixes of left ventricular functions as potential markers of acute cardiac rejection.  Circulation. 1987;  76 86-92
  Google Scholar
• 41 Ventura H O, Muhammed K. Historical perspectives on cardiac transplantation: the past as prologue to challenges for the 21st century.  Curr Opin Cardiol. 2001;  16 118-123
  Google Scholar
• 42 Yankah A C, Musci M, Weng Y. et al . Tricuspid valve dysfunction and surgery after orthotopic cardiac transplantation.  Euro J Cardio Thora Surg. 2000;  17 343-348
  Google Scholar
• 43 Zerbe T R, Arena V. Diagnostic reliability of endomyocardial biopsy for assessment of cardiac allograft rejection.  Hum Pathol. 1988;  19 1307-1317
  Google Scholar

Korrespondenz

Dr. Johannes Müller

Deutsches Herzzentrum Berlin

Augustenburger Platz 1

13353 Berlin

Phone: 030/45932033

Fax: 030/45932170

Email: jmueller@dhzb.de