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Pathomorphologische Befunde nach Herztransplantation

Eine Monocenterstudie an 15.571 rechtsventrikulären Endomyokardbiopsieproben

Pathomorphological findings after heart transplantation: single center experience with 15,571 right ventricular biopsies

  • ORIGINALARBEIT
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Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Hintergrund

Neben der zellulären Abstoßungsdiagnostik bietet die histologische Untersuchung von rechtsventrikulären Myokardbiopsieproben (Bx) die Möglichkeit, Erkenntnisse über strukturelle Adaptationsprozesse zu gewinnen, die mit einer Herztransplantation (HTx)Transplantation einhergehen.

Material & Methoden

Zwischen 04/86 und 12/02 unterzogen sich 1.351 Patienten (mittleres Alter 46±15 Jahre, Männer=1.074, dKMP=803, KHK=362, Klappenerkrankung=48, andere=134) einer HTx. Von diesen Patienten wurden insgesamt 15.571 Bx lichtmikroskopisch auf das Bestehen einer akuten zellulären Rejektion (ACR, gemäß ISHLT) bzw. eines Quilty-Phänomens untersucht. Zusätzlich wurden immunhistochemische Untersuchungen (Avidin-Streptavidin-Methode) von T-Zellen (CD3, Klon SP7, DCS Innovative Diagnostik), Endothelzellen (CD31, Klon JC/70A, Dako) und vaskulären glatten Muskelzellen (α-Aktin, Klon 1A4, Dako) durchgeführt. Qualitative und quantitative Untersuchungen wurden zum Gehalt an Fibrose, Größe und Form der Herzmuskelzellen sowie vaskulärer Texturveränderungen durchgeführt. Die statistische Auswertung erfolgte anhand nicht-parametrischer Tests.

Ergebnisse

In 68% (N=10.544) der Bx fand sich kein Anhalt für ACR, ISHLT-Grade 1A-2 fanden sich in 23% (N=3.611), 3A und 3B in 7% (N=1.076) und Grad 4A und 4B in <1% (N=4) der Bx. 2% (N=307) der Bx wurden als nicht repräsentativ eingestuft. In Bx mit dem ISHLT-Grad „0“ fand sich bei 50% der Proben der immunhistochemische Nachweis von T-Zellen und in 10% ein Quilty-Phänomen. 10% der Bx wiesen morphologische Zeichen der mikrovaskulären TVP auf und bei 37% bestanden morphologische Hinweise auf das Vorliegen einer TVP. Der Fibrosegehalt (10–14%) der Bx zeigte keine statistisch relevante Veränderung im Zeitverlauf nach HTx.

Schlussfolgerungen

Immunhistochemische Untersuchungen sollten routinemäßig in Bx nach HTx durchgeführt werden. Das diagnostische Profil und die Indikation dieser Bx sollte durch die Graduierung vaskulärer Texturveränderungen und ihrer Folgen, sowie um eine Risikoabschätzung für das Überleben erweitert werden.

Summary

Background

Histological evaluation of right ventricular endomyocardial biopsies (Bx) is the gold standard for diagnosis of acute cellular rejection (ACR) after heart transplantation (HTx). Routine Bx also permit the description and evaluation of adaptative processes, i. e., vascular and myocardial textural changes, associated with the transplantation process.

Material & methods

A total of 15,571 Bx from 1,351 patients (mean age 46±15 yrs, male=1,074, female=277, dCMP=803, CAD=362, valvular disease=48, others=134) undergoing HTx between 04/86 and 12/02 were evaluated by light microscopy for ACR (according to ISHLT) and the Quilty phenomenon. Testing for immunohistochemical reactions (avidin-streptavidin method) to T-cells (CD3, clone SP7, DCS Innovative Diagnostik), endothelial cells (CD31, Klon JC/70A, Dako) and vascular smooth muscle cells (α-actin, clone 1A4, Dako) was performed. Qualitative and quantitative analysis was done for blood vessel structure, fibrosis, size and hypertrophy of heart muscle cells. All data were analyzed using non-parametric tests (p<0.05).

Results

In 68% (N=10,544) of Bx there was no evidence of acute cellular rejection, ISHLT grade 1A-2 was present in 23% (N=3,611), 3A and 3B in 7% (N=1,076) and grade 4A und 4B in <1% (N=4) of Bx. In total, 2% (N=307) of Bx were not suitable for further morphological evaluation. In 50% of Bx graded as showing no ACR according to the ISHLT scale there was positive immunohistochemical reaction for T cells and in 10% evidence of the Quilty phenomenon. Microvascular disease was present in 10% of Bx and in additional 37% of Bx microvasculopathy was suspected. In Bx vascularization was as follows: arterioles 103±31/mm2, capillaries 685±129/mm2, and ratio of capillaries to arterioles 13±6/mm2. Patients with evidence of microvasculopathy had more α-actin-positive blood vessels (147±47/ mm2 vs. 59±16/mm2, p<0.05), fewer capillaries (574±212/mm2 vs. 724±144/mm2, p<0.05) and a smaller ratio of capillaries to arterioles (9±6/mm2 vs. 16±5/mm2, p<0.05) than patients without. The amount of fibrosis in Bx (10–14%) did not change during the post-transplant period. The mean number of cardiac myocytes accounted for 440±89/mm2 and the mean area of cardiac myocytes was 2,060±452 μm2.

Conclusions

After HTx cell-mediated immunological reactions between the recipient and the graft are not necessarily associated with myocardial damage and/or lymphocyte infiltrates. Therefore we recommend routine immunohistochemical investigations in Bx after HTx. Microvasculopathy may be diagnosed in Bx after HTx using routine tissue processing methods, and its major targets have to be redefined by grading vascular textural changes with subsequent risk stratification for severe adverse events.

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  1. Deutsches Herzzentrum Berlin, Abteilung für Herz-, Thorax- und Gefäßchirurgie, Augustenburger Platz 1, 13353, Berlin, Germany

    N. E. Hiemann,  R. Hetzer &  R. Meyer

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  2. R. Hetzer
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  3. R. Meyer
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Hiemann, N.E., Hetzer, R. & Meyer, R. Pathomorphologische Befunde nach Herztransplantation. Z Herz- Thorax- Gefäßchir 19, 209–217 (2005). https://doi.org/10.1007/s00398-005-0508-y

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