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Intravascular Ultrasound (IVUS) for detecting post-transplantation allograft vasculopathy in cardiac recipients

An article from the e-journal of the ESC Council for Cardiology Practice

Intravascular ultrasound (IVUS) provides circumferential cross sectional tomographic images of the vessel. Hence, it can detect the initial steps of the atherosclerotic process, identify intimal thickening and lipid deposition within the media. But, IVUS is a highly operator dependent method and requires advanced experience for applying and interpretation of the results and although it has been recommended as a new diagnostic tool for allograft vasculopathy, improved experience is needed.

Vascular imaging methods are directed to visualise the lumen in a biplane model. Although atherosclerosis and other vascular diseases resulting in luminal narrowing are mainly the pathologies of the vessel wall, most of the diagnostic tools show the luminal diameter.

Intravascular ultrasound (IVUS) is a unique method which offers circumferential cross sectional tomographic images of the vessel.

Small coronary arteries of the heart are highly sensitive to atherosclerotic invasion and only in advanced stages of the disease, conventional or magnetic resonance (MR) angiography may hand diagnostic data. However, IVUS can detect initial steps of the atherosclerotic process, identify intimal thickening and lipid deposition within the media.

Cardiac transplantation is a well known modern treatment modality of end stage heart failure. Although the possibility of obtaining an appropriate donor is extremely limited, successful transplantation procedures offer excellent results. The major problem in those recipients is allograft vasculopathy during the first postoperative year. The treatment of allograft vasculopathy is also an important issue because of its potential mortality and due to the fact that immunosupressive medication must be monitorised closely and carefully to avoid any rejection. Hence, specific and sensitive diagnostic techniques are essential for the follow up in cardiac transplantation.

Intravascular ultrasound (IVUS) is an alternative technique to coronary angiography. It reveals the structure and composition of the vessel wall by means of a circumferential view. IVUS application for diagnosis of coronary artery disease is a well explained method and its results in detecting allograft vasculopathy have been reported previously.

Annual coronary angiographic studies are often able to show allograft vasculopathy in post-transplantation patients before a clinical event occurs. Allograft vasculopathy is the most important cause of morbidity in the first post-transplant year. Conventional diagnostic techniques such as angiographic studies are the preferred methods, however they offer poorly specific data (1). Annual incidence of allograft vasculopathy reported in patients examined with only classic methods is up to 15% to 20%, where the incidence of diffuse intimal thickening reaches 80% at the end of the 1st year and 92% at the end of the 4th year in patients studied with IVUS (1). Subtle intimal thickening is the characteristic starting point of the pathology, which can only be visualised with IVUS (2).

Nevertheless, an accurate technique able to do an early diagnosis of postoperative vasculopathy is still needed. Coronary angiography is accepted as the most accurate and safe technique for detecting arterial pathologies. Its basic principle is to compare the healthy segment with a narrowed segment and the main criterion is luminal diameter. The limitation of this method is that at least a portion of the coronary tree must be accepted as “healthy”. On the other hand, coronary allograft vasculopathy, such as coronary artery disease, and other arterial disorders, are not the pathology of the lumen but of the wall. Hence, luminal narrowing exists at the end stage of wall thickening and the coronary angiography is never an early diagnostic method. Actually, “angiographically normal” segments are somehow diseased portions: There is no pure healthy angiographic arterial segment (2).  Although the luminal blood flow is a prognostic phenomenon, early diagnosis before the narrowing of the lumen may have potential benefits to perform an accurate treatment (3).

Intravascular Ultrasound (IVUS), is a diagnostic imaging technique which offers full thickness view of the arterial wall through the entire length of the branch. This method demonstrates the arterial wall and its surrounding tissues with objective data. But, IVUS is a highly operator dependent method and requires advanced experience for applying and interpretation of the results.

Coronary atherosclerosis is a diffuse pathology of the vessel involving long segments with no truly normal segment. Necropsy studies show that angiographically normal parts of the vessel tree are extremely involved by atherosclerotic processes (1). IVUS has the advantage with its cross sectional imaging of an entire segment of the vessel over angiography, which only shows a 2-dimensional view. This tomographic orientation of IVUS enables an interpretation of the whole thickness of the vessel wall. Although it delineates the structural features, echogenicity and thickness, the histopathological composition can not be read from an IVUS examination (1). In patients with clinical symptoms of coronary artery disease and normal angiographic findings, IVUS commonly detects atherosclerotic plaques at the sites which were reported as “normal”.  One point must be kept in mind: Atherosclerosis is the disease of the wall and not of the lumen! Initial changes begin in the vessel wall and luminal narrowing occurs only when the pathology extends to a progressed level (2). Preventive treatment modalities must be applied during the early phase of the disease, where they may fail in later stages of the disease and only palliative measures can be applied to those patients with minimal efficacy (2). IVUS is the only known technique which identifies normal arterial wall (intima, media and adventitia) and the abnormal changes (lipid, fibrous connective tissue and calcium) (3).

We performed intravascular ultrasound in four cardiac transplantation recipients and did not find any diagnostic superiority of this technique. The operator dependency of the technique, cost of the setup and disposable materials are the main disadvantages of this method. However, recently published data supporting the usefulness of IVUS suggest wider application for detecting allograft vasculopathy.
We have also performed IVUS in conjunction with coronary angiography and endomyocardial biopsy in postoperative follow-ups of our cardiac recipients. Although previously published studies support superiority of IVUS over conventional angiography, we did not observe any additional advantage in our relatively small patient group.

Although the radiological imaging of the great arteries such as of the aorta is successfully performed with computerised tomography (CT) or angiography (either conventional or MRI), examination of the small vessels with IVUS is superior where a small percentage of luminal narrowing may be extremely hazardous in those vessels (4). In addition, IVUS examination of the medium sized vessels supplies useful data to the clinician: For instance, IVUS can detect the efficacy of percutaneous transluminal angioplasty (PTA) and stenting in patients with iliac artery stenosis and to evaluate the adaptation of the stents to the arterial wall (5). Another important data of IVUS is visualisation of incompleteness in endarterectomised patients (5).

Another area of IVUS usage is follow up of patients with endovascular repair of aortic aneurysms. Limb thrombosis may be an important complication of stent-graft implantation and it may be decreased from 17% to 0% with IVUS follow up (6).

In a series of transplant donors assessed by IVUS, coronary atheromas were found in 17% of those younger than 20 years, 37% of those aged 20 to 29 years, and 60% of those aged 30 to 39 years, whereas angiography results were negative in 97% of this population (7).

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.


1. Tuzcu EM, De Franco AC, Goormastic M, Hobbs RE, Rincon G, Bott-Silverman C, McCarthy P, Stewart R, Mayer E, Nissen SE. JACC Vol 27 No 4 March 15, 1996: 839-46. Dichotomous pattern of coronary atherosclerosis 1 to 9 years after transplantation: Insights from systematic intravascular ultrasound imaging.

2. Mintz GS, Painter JA, Pichard AD, Kent KM, Satler LF, Popma JJ, Chuang YC, Bucher TA, Sokolowicz LE, Leon MB. JACC Vol 25 No7 June 1995: 1479-89. Athersclerosis in angiographicaly normal coronary artery reference segments: An intravascular ultrasound study with clinical correlations.

3. Nissen S. Coronary angiography and intravascular ultrasound. Am J Cardiol 2001 Feb 16; 87(4A):15A-20A

4. Fishman JE. Imaging of blunt aortic and great vessel trauma. J Thorac Imaging. 2000 Apr;15(2):97-103.

5. Vogt KG, Schroeder TV. Intravascular ultrasound for iliac artery imaging. Clinical review. J Cardiovasc Surg (Torino). 2001 Feb;42(1):69-75.

6. Powell A, Fox LA, Benenati JF, Katzen BT, Becker GJ, Zemel G. Postoperative management: buttock claudication and limb thrombosis. Tech Vasc Interv Radiol. 2001 Dec;4(4):232-5.

7. Nissen SE. Who is at risk for atherosclerotic disease? Lessons from intravascular ultrasound. Am J Med. 2002 Jun 3;112 Suppl 8A:27S-33S.

Notes to editor

Prof. Öztekin Oto MD, FESC; Kıvanç Metin, MD; Prof. Ömer Kozan, MD; Assoc. Prof. Nejat Sarıosmanoğlu, MD; Assoc. Prod. Baran Uğurlu, MD; Prof. Eyüp Hazan, MD.
Izmir, Turkey
Chairman of the ESC Working Group on Cardiovascular Surgery

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.