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Transvenous Endomyocardial Biopsy-Application of a Method for Diagnosing Heart Disease PHILIP CAVES* JOHN Coltartt MARGARET BILL

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Transvenous Endomyocardial Biopsy-Application of a Method for Diagnosing Heart Disease PHILIP CAVES* JOHN Coltartt MARGARET BILL Postgrad Med J: first published as 10.1136/pgmj.51.595.286 on 1 May 1975. Downloaded from Postgraduate Medical Journal (May 1975) 51, 286-290. Transvenous endomyocardial biopsy-application of a method for diagnosing heart disease PHILIP CAVES* JOHN COLTARTt F.R.C.S. M.D., M.R.C.P. MARGARET BILLINGHAM ALAN RIDER M.B., B.S. M.D. EDWARD STINSON M.D. Divisions of Cardiology and Cardiovascular Surgery, Stanjord University Medical Center, Stanford, California Introduction jugular vein (Caves et al., 1973a). Subsequently, Although biopsy of the kidney, liver, and many development of a technique for percutaneous intro- other organs is routine in clinical medicine, biopsy duction of the biopsy forceps into the internal jugular of the heart is infrequently performed. In con- vein in man provided the means by which serial sequence, little is known of the serial histological endomyocardial biopsies could be obtained from changes which occur in non-fatal myocardial disease. the human heart (Caves et al., 1973b). copyright. Published techniques for obtaining myocardial This paper describes the technique and instrument biopsies have included percutaneous needle biopsy developed at Stanford which have been used for the of the left ventricle, catheter needle biopsy of the performance of over 500 cardiac biopsy procedures. interventricular septum, and open thoracotomy. The associated morbidity and mortality with these methods have precluded their widespread acceptance The instrument and biopsy technique (Shirey et al., 1972). The cardiac biopsy instrument is illustrated in Transvenous biopsy of the endomyocardium of Fig. 1. Opening and closing the instrument handle the right or left ventricle using a catheter forceps was at one end of the flexible catheter controls the posi- http://pmj.bmj.com/ first described 13 years ago by Sakakibara and tion of the jaws at the other end. The jaws are con- Konno in Japan (1962). Despite the availability of structed from steel and consist of one fixed and one the Konno-Sakakibara bioptome in this country, mobile part, each of which ends in a hollow cup there have been few reports of its use outside Japan. 15 mm in diameter. The edges of the cup are In 1972, a modified Konno-Sakakibara bioptome sufficiently sharp to provide removal of the specimen was first used at Stanford to obtain biopsies from by cutting action rather than avulsion. The length the dog heart after orthotopic cardiac transplanta- of the catheter is 50 cm. on October 2, 2021 by guest. Protected tion. For the first time it was possible to correlate The biopsy forceps are introduced percutaneously the day-by-day changes in graft histology with (Fig. 2) under local anaesthetic. A 16 Medicut indirect parameters of graft function such as the cannula is inserted directly into the right internal electrocardiogram. It was soon demonstrated that jugular vein. A flexible guidewire is inserted through histological examination of the biopsy specimens the cannula and a 9F Desilets-Hoffman false catheter permitted an accurate assessment of the recipient and sheath are passed over the guidewire into the dog's immune response to the donor heart. Serial vein. After removal of the guidewire and false biopsies of the transplanted heart could thus be catheter, the biopsy forceps are introduced through used to monitor acute cardiac allograft rejection, the sheath and the rubber plug is inserted into the and a technique was developed for the performance luerlok connection on the sheath to prevent leakage of repeated cardiac biopsy in the dog via the external of blood. The forceps are advanced to the apex of the right ventricle under fluoroscopic control (Fig. 3). * Present address: Department of Cardiovascular Surgery, Royal Infirmary Edinburgh, Scotland. The open jaws of the instrument are easily pressed t Present address: Cardiac Department, St Thomas's against the endomyocardium from this approach, Hospital, London. since the catheter has only a gentle curve in it where Postgrad Med J: first published as 10.1136/pgmj.51.595.286 on 1 May 1975. Downloaded from Transvenous endomyocardial biopsy 287 a copyright. http://pmj.bmj.com/ FIG. 1. (a) The Caves-Schulz-Stanford cardiac biopsy forceps; (b) close-up view of the jaws. it passes through the tricuspid valve. The jaws are Results and discussion closed and the instrument is withdrawn steadily. A Diagnosis of acute rejection in heart transplant on October 2, 2021 by guest. Protected slight jerk occurs as a biopsy specimen is removed recipients from the endomyocardium. After removal of the The principal use of this new cardiac biopsy biopsy specimen from the jaws of the instrument, technique has been in the diagnosis and management the forceps may be reintroduced to obtain further of early acute rejection episodes in heart transplant specimens as necessary. Finally, the patient is recipients. The transplanted heart has proved to be positioned upright and the sheath is removed from uniquely valuable in assessing the clinical use of the vein while pressure is applied over the puncture cardiac biopsy because impressive and readily site. Bleeding is, thus, immediately controlled and observed changes in the endomyocardial histology the vein remains patent for subsequent use. The evolve so rapidly during acute graft rejection episodes biopsy procedure may be completed within 5 min, (Fig. 4). However, before the histological changes using only a few seconds of fluoroscopy time. seen on biopsies of the transplanted heart could be The electrocardiogram is monitored throughout accepted as reliable evidence of the host immune the procedure and a routine chest X-ray film is response to the graft, it was important to answer obtained afterwards. several questions. Postgrad Med J: first published as 10.1136/pgmj.51.595.286 on 1 May 1975. Downloaded from 288 P. Caves et al. that there was excellent correlation between the #16 medicut histological changes seen in these specimens and so, more recently, only one biopsy specimen has been routinely obtained during each procedure. Further confirmation that the samples obtained are represen- tative has come from biopsies performed not long Head before the death of three recipients. The histological changes seen in these biopsies have been the same as those seen throughout the myocardium at autopsy. (b) Would the histological changes seen in the biopsies be specific and reliable in the diagnosis and management of acute graft rejection? It was found that on each occasion the biopsy histology appeared to be normal, the patients were clinically well without evidence of rejection. Con- catheter introd versely, histological evidence of advancing rejection 9F Percutaneou was invariably followed by confirmatory clinical signs which prompted initiation of increased im- * munosuppressive treatment. Importantly, rejection episodes were histologically evident in patients 2-4 days before rejection could be established clinically on the basis of significant changes in the electro- cardiogram or physical examination. Routine serial biopsy in the early post-transplant period may, Bioptwne thus, give the first indication of an acute rejection copyright. episode and permit the earlier initiation of increased immunosuppressive treatment before serious damage FIG. 2. Technique used for the insertion of the biopsy forceps into the right internal jugular vein. is caused to the graft by the host immune response. Serial endomyocardial biopsies also permitted an (a) Would the small specimen obtained be repre- accurate assessment of the response to immuno- sentative of the entire myocardium? suppressive treatment (Fig. 4.) When regression of To answer this question two or more biopsies the histological changes of rejection occurred, it were taken from different sites in the right ventricle correlated well with the normalization of clinical during each biopsy procedure. It was soon obvious parameters. http://pmj.bmj.com/ on October 2, 2021 by guest. Protected ... FIG. 3. Plain chest X-ray film taken during a biopsy procedure showing the forceps in the apex of the right ventricle. Postgrad Med J: first published as 10.1136/pgmj.51.595.286 on 1 May 1975. Downloaded from Transvenous endomyocardial biopsy 289 f- tN .lI i R ft-i '-I| f ilIM | 1 .......- 4..so --. -~~~....S....> copyright. ~~4 E#.*- http://pmj.bmj.com/ FIG. 4. (a) Biopsy obtained from a heart transplant recipient 16 days post-transplantation. on October 2, 2021 by guest. Protected Acute rejection is present with oedema and an infiltrate of mononuclear cells. (b) Biopsy from the same patient on post-transplant day 33 following a course of increased immuno- suppression. The myocardium now appears normal with complete reversal of the previously seen histological changes. (c) Would multiple cardiac biopsies be simple and the injection of the local anaesthetic and is left with a safe-and acceptable to the cardiac transplant tiny incision which quickly heals to an imperceptible recipient? scar without suturing. No serious complications have Our experience to date has confirmed that these occurred. Three patients have been found to have a criteria have been satisfied and frequent biopsy of small right pneumothorax on postoperative chest the donor heart is now a routine aspect of clinical films, and two patients developed supraventricular management during the first 2 months after trans- arrhythmias during the biopsy which required plantation. With the described technique, one to four cardioversion to sinus rhythm. The risk of this pro- biopsy specimens can be obtained in 3-5 min, using cedure is similar to that of right heart catheterization 20-60 sec fluoroscopy time. The patient feels only by a central vein, and, thus, would appear to be Postgrad Med J: first published as 10.1136/pgmj.51.595.286 on 1 May 1975. Downloaded from 290 P. Caves et al. substantially less than that associated with left patients may be of particular value in the determina- ventricular needle biopsy by percutaneous puncture tion of long-term prognosis. Hopefully, biochemical (haemorrhage, cardiac tamponade, ventricular fibril- analyses will be performed on the biopsy specimens lation, myocardial infarction) (Shirey et al., 1972).
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