Endomyocardial biopsy for monitoring heart transplant patients: 11-years-experience at a german heart center

Abstract

Background: Heart transplantation (HTX) has become an established therapy for patients with end-stage heart failure. Endomyocardial biopsy (EMB) still represents the gold standard for routine surveillance of heart transplant rejection. The objective of this article is to report our experience regarding the use of EMB in monitoring heart transplant recipients.

Methods: We evaluated retrospectively all patients who underwent orthotopic HTX between 2000 and 2011 at our hospital. From all patients, we created a follow-up, determined the number of EMB events and described the complications associated with this procedure.

Results: HTX was performed in 142 cases at our center in the last 11 years (1.3% of the total of 10693 cardiac surgical operations in that period). Further 9 patients visited our department for monitoring after HTX performed at an external center (total: 151). For all patients, a total of 1896 EMB events have been recorded. The majority of biopsies were performed through the right internal jugular vein. The overall complication rate was 1% (n=19).

Conclusions: The histological examination of right ventricular EMB still represents the gold standard of care for cardiac allograft rejection monitoring. EMB is an invasive, but safe and dedicated diagnostic procedure. However, the usefulness of recent non-invasive diagnostic approaches as an adjunct tool in monitoring for rejection remains to be further analyzed.

Keywords: Endomyocardial biopsy; allograft rejection; cardiac transplantation; histopathological evaluation; immunosuppression.

Figure 1

Cardiac Surgery at the University of Erlangen between 2000 and 2011. CABG = Coronary Artery Bypass Grafting; VP = Valve Procedures; TAVI = Transcatheter Aortic Valve Implantation; AS = Aortic Surgery; VAD = Ventricular Assist Device; HTX = Heart Transplantation; AOCS = Any Other Cardiac Surgery.

Figure 2

Distribution of 1896 biopsies scored by the International Society for heart and Lung Transplantation (ISHLT) guidelines [Billingham 1990], and revised in 2005 [Stewart 2005]. Grade 0R = no rejection; grade 1R = mild; grade 2R = moderate; grade 3R = severe rejection.

Figure 3

Time schedule of 1896 performed biopsies scored by the ISHLT guidelines. Grade 0R = no rejection; grade 1R = mild; grade 2R = moderate; grade 3R = severe rejection.

Figure 4

Transesophageal echocardiography: A: Transgastric view showed the right ventricle inflow tract with a disrupted chordae on the tricuspid valve. B: The Colour-Doppler sonography demonstrated a severe tricuspid regurgitation.

Figure 5

A: EMB negative for cellular and humoral rejection (grade 0R) showing mild interstitial edema suggesting mild ischemic effect (note isolated inflammatory cells without forming aggregates). B: Grade 1R revealed compact interstitial mononuclear cell aggregate without evident myocyte damage. C: This case of 2R showed a focus of myocyte damage (muscle fiber between arrows was infiltrated and damaged by mononuclear cells. D: This less compact inflammatory aggregate encased multiple degenerating cardiomyocytes (2R).

Figure 6

A: Severe rejection (3R) with one compact (left) and one diffuse infiltrate with extensive myocyte damage that superficially may mimic ischemic damage. B: higher magnification of A.

Figure 7

Spectrum of Quilty and Quilty-like findings. A: Overview of this case showed multiple endocardial and subendocardial aggregates. B: Type A Quilty with the aggregate completely confined to the endocardial connective tissue and respecting the adjacent myocardium. C: This larger Quilty replaced the most superficial subendocardial myocardium but no evidence of unequivocal myocyte damage was seen (red line points to the probable original endocardium-myocardium-border). D: Another type B Quilty with clear-cut evidence of subendocardial myocyte damage. Such cases are difficult to classify properly.

Figure 8

Examples of difficult-to-classify cases. A: This biopsy showed a small old scar associated with a mononuclear aggregate without fiber damage (probably perioperative scar or ischemic damage). Presence of fibrofatty tissue suggests deep localization and an increased risk of perforation. B: Ischemic change from another case showing interstitial scarring with scattered mononuclear inflammatory cells. C: Another case with scarring with minute mononuclear aggregates and evidence of active myocyte damage. Although it looks ischemic, such findings are highly suspicious of cellular rejection and should be classified as such. D: Another biopsy with loose mononuclear aggregates encasing some myocytes and associated with prominent fibrosis. Although this finding might be suggestive of post-ischemic change or site of previous biopsy, it cannot be definitely distinguished from cellular rejection and should therefore be classified as evidence of cellular rejection.

Figure 9

A: On HE-stained section, humoral rejection showed edematous change and signs of endothelial damage in small capillaries highlighted by nuclear enlargement and hyperchromasia, note absence of cellular rejection. B: Strong C4d immunostaining in endothelial cells.