Procedure

Endomyocardial biopsy – jugular/subclavian vein approach

Department of Cardiac Surgery, Medical University Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria

^* Corresponding author: ^* Tel.: +43-512-504-23806; fax: +43-512-504-22528. E-mail: juliane.kilo{at}uklibk.ac.at

	Summary

Top Summary Indications Surgical technique Grading of rejection Results References

 
Endomyocardial biopsy (EMB) is a diagnostic procedure mainly to survey the sufficiency of immunosuppressive therapy after cardiac transplantation. Other indications for EMB remain controversial. After insertion of an introducer sheet in Seldinger's technique, four to six biopsies are taken from the right ventricle by fluoroscopic guidance. EMB is a very safe operation with a low complication rate which can be rapidly performed with little inconvenience for the patient if performed by a skilled surgeon.

Key Words: Endomyocardial biopsy • Cardiac transplantation • Rejection monitoring

	Indications

Top Summary Indications Surgical technique Grading of rejection Results References

 
The most important indication for endomyocardial biopsy is cardiac allograft rejection monitoring. Acute cellular rejection significantly contributes to mortality and morbidity after cardiac transplantation, accounting for 6.7% of mortality during the first month and for 12% of mortality during the first year after transplantation [1].

Symptoms of cardiac allograft rejection may consist of signs of left ventricular dysfunction, arrhythmias, and constitutional symptoms like fever, myalgias and flu-like symptoms [2,3,4]. However, most patients remain asymptomatic [2]. Therefore, endomyocardial biopsies are performed repeatedly after transplantation with continuously increasing intervals. The schedule at our institution is as follows:

• Weekly during the first month
  
  • Week 4: additionally coronary angiography + intravascular ultrasound
    
  
  
• Every two weeks during months two and three
  
• Monthly during months four to six
  
• Every two months during month seven to twelve
  
  • Month twelve: additionally coronary angiography + intravascular ultrasound
    
  
  
• Once annually to biannually during further follow-up or at any suspect for rejection
  

If relevant rejection was detected in endomyocardial biopsy, the next biopsy is scheduled approximately two weeks later to verify success of treatment.

Further indications for endomyocardial biopsy may include unexplained cardiomyopathy [5], unexplained ventricular arrhythmias [6], myocarditis [7], cardiac hemachromatosis [8], amyloidosis [9], anthracycline cardiotoxicity [10], suspect of cardiac sarcoidosis, giant cell myocarditis, hypereosinophilic syndrome, or endocardial fibroelastosis [11]. However, in most cases, the diagnosis can be made non-invasively, and the likelihood of finding a treatable disease is only 2.2% [11].

	Surgical technique

Top Summary Indications Surgical technique Grading of rejection Results References

 
Right internal jugular vein approach
Endomyocardial biopsy is performed in a supine position in local anesthesia. Routine anesthesiologic monitoring (3-lead ECG, non-invasive blood pressure monitoring, oxygen saturation measurement) is placed before the intervention. The head of the patient is placed on a flat cushion to facilitate puncture. The table is positioned head-low to increase central venous filling (Photo 1).

View larger version (106K): [in this window] [in a new window]   Photo 1 Sonography of the neck is performed to evaluate diameter of the right jugular vein, its relation to the carotid artery and its course, which is marked with a permanent marker.

View larger version (104K): [in this window] [in a new window]   Photo 2 Local anesthesia is installed with 5–10 ml of Xylocaine 2%.

View larger version (74K): [in this window] [in a new window]   Photo 3 Under continuous palpation of the carotid artery, the internal jugular vein is punctured, and a guide wire inserted.

View larger version (56K): [in this window] [in a new window]   Photo 4 In Seldinger's technique, a 9 French silicone-locked catheter introducer sheet is inserted (Input TSTM, Medtronic, Minneapolis, MN, USA). The bioptome is introduced through the silicone lock.

Click on image to view video Video 1 The bioptome (Schulz Bioptome®, Aesculap, Tuttlingen, Germany) is introduced via the sheet and directed to the right atrium, rotated to the left lateral side of the patient, directed through the tricuspid valve to the right ventricular septum.

Click on image to view video Video 2 The jaws are opened, the ventricular wall is touched, jaws are closed and the bioptome with the specimen is slowly withdrawn.

View larger version (131K): [in this window] [in a new window]   Photo 5 In that fashion, a minimum of four to six biopsies are taken, preferentially from different places of the right ventricle in order to increase validity of the histological diagnosis. If histological procurement is performed on the same day, the biopsy specimens are stored in saline (0.9%); otherwise, storage in 4% buffered formalin is preferable.

View larger version (119K): [in this window] [in a new window]   Photo 6 Once the specimens are securely stored, the introducer sheet is removed; the puncture site secured with Steri-StripTM (3M Health Care, St. Paul, MN, USA) and compression is placed on the puncture site to avoid local hematoma.

Subclavian vein approach
Endomyocardial biopsy can also be performed via the left or right subclavian vein. However, this approach is not preferable for a variety of reasons:

• Local anesthesia is less effective, because of the clavicle.
  
• The risk of pneumothorax is significantly higher as compared to puncture of the internal jugular vein.
  
• Due to the anatomical course of the great veins, direction of the bioptome is more difficult.
  

At our institution there are two indications for endomyocardial biopsy via the subclavian vein:

• If the right internal jugular vein is not susceptible for puncture (e.g. in case of thrombosis), or
  
• For patients early after transplantation, who still need a central venous line. In these cases, the introducer sheet can be installed via a preexisting line and/or replaced by a new central venous catheter after the intervention (Photo 7).
  

View larger version (64K): [in this window] [in a new window]   Photo 7 The preexisting central line is cut, the guide wire inserted through the distal lumen of the catheter and directed to the right atrium. The catheter is removed and the introducer sheet inserted in Seldinger's technique.

	Grading of rejection

Top Summary Indications Surgical technique Grading of rejection Results References

• Grade 0: no evidence of rejection
  
• Grade Ia: focal perivascular or interstitial infiltrate without myocardial injury
  
• Grade Ib: multifocal or diffuse sparse infiltrate without myocardial injury
  
• Grade II: single focus or dense infiltrate with myocyte injury
  
• Grade IIIa: multifocal dense infiltrates with myocyte injury
  
• Grade IIIb: diffuse, dense infiltrates with myocyte injury
  
• Grade IV: diffuse and extensive polymorphous infiltrate with myocyte injury; may have hemorrhage, edema, and microvascular injury (Photos 8 and 9).
  

View larger version (145K): [in this window] [in a new window]   Photo 8 Microscopic appearance of myocardial tissue without signs of rejection (ISHLT grade 0).

View larger version (129K): [in this window] [in a new window]   Photo 9 Microscopic appearance of myocardial tissue with severe rejection (ISHLT grade IV).

• Grade 0 R: no rejection
  
• Grade 1 R: mild rejection (Grades I A, I B and II)
  
• Grade 2 R: moderate rejection (Grade III A)
  
• Grade 3 R: severe rejection (Grade III B and IV)
  

Additionally, biopsy specimens can also be frozen for immunohistochemical studies, as C4d-staining for assessment of humoral rejection [16] or for detection of viruses in myocarditis [17].

	Results

Top Summary Indications Surgical technique Grading of rejection Results References

 
Endomyocardial biopsy is a very safe procedure and procedural mortality ranges from 0–0.4% [12,18,19,20,21]. However, a number of potential complications are inherent in the operation:

• Perforation/pericardial tamponade (Incidence: 0–0.5%; [12,18,19,20,21])
  
• Tricuspid valve damage (14%; [22])
  
• Bleeding at puncture site (venous/arterial due to accidental arterial puncture) (0.14–0.4%; [18,20,21])
  
• Pneumothorax (0.1%; [19])
  
• Arrhythmias (supraventricular/ventricular tachycardia/complete heart block) (0.25–1.1%; [18,20,21])
  
• Coronary artery to right ventricle fistulae (8%; [23])
  

Overall, complications are infrequent for skilled surgeons, and especially life-threatening complications are rarely encountered [12,18,19,20,21].

	References

Top Summary Indications Surgical technique Grading of rejection Results References

 

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2. Mills RM, Naftel DC, Kirklin JK, Van Bakel AB, Jaski BE, Massin EK, Eisen HJ, Lee FA, Fishbein DP, Bourge RC. Heart transplant rejection with hemodynamic compromise: a multiinstitutional study of the role of endomyocardial cellular infiltrate. Cardiac transplant research database. J Heart Lung Transplant 1997;16:813–821.[Medline]
3. Scott CD, Dark JH, McComb JM. Arrhythmias after cardiac transplantation. Am J Cardiol 1992;70:1061–1063.[CrossRef][Medline]
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16. Poelzl G, Ullrich R, Huber A, Ulmer H, Antretter H, Hoefer D, Mairinger T, Laufer G, Pachinger O, Schwarzacher S. Capillary deposition of the complement fragment C4d in cardiac allograft biopsies is associated with allograft vasculopathy. Transpl Int 2005;18:313–317.[CrossRef][Medline]
17. Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R, Hare J, Bricker JT, Bowles KR, Towbin JA. Detection of viruses in myocardial tissues by polymerase chain reaction: evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol 2003;42:466–472.[Abstract/Free Full Text]
18. Deckers JW, Hare JM, Baughman KL. Complications of transvenous right ventricular endomyocardial biopsy in adult patients with cardiomyopathy: a seven-year survey of 546 consecutive diagnostic procedures in a tertiary referral center. J Am Coll Cardiol 1992;19:43–47.[Abstract]
19. Knisley BL, Mastey LA, Collins J, Kuhlman JE. Imaging of cardiac transplantation complications. Radiographics 1999;19:321–339.[Abstract/Free Full Text]
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