Multi-detector CT coronary angiography in the work-up of potential candidates for lung transplantation.

Since the first lung transplantation in man in 1963 (1), several thousands of
lung transplantations have been performed and lung transplantation is now a
generally accepted therapy for the management of a wide range of end stage lung
diseases. In 1998, the first edition of the International Guidelines for the
Selection of Lung Transplant Candidates was developed which was updated in 2006
(2). These guidelines assist physicians worldwide in referring potential
candidates for lung transplantation. Absolute and relative contraindications
are considered as well as factors that may be of importance in the decision to
refer patients to a lung transplantation clinic but also to list and
potentially (sometimes temporally) de-list lung transplant candidates as well.
Selection criteria for placement on the active waiting list for lung
transplantation vary between centres, but the presence of more than 1
significant (luminal reduction >50%) coronary artery disease (CAD) is
traditionally considered an absolute contraindication for lung transplantation
since this may limit survival after transplantation. Diffuse CAD with
non-significant stenoses (luminal reduction < 50%) or isolated significant
stenosis (luminal reduction > 50%) is considered a relative contraindication
for lung transplantation. In patients with limited CAD (single-vessel disease
and good left ventricular function) lung transplantation has recently been
performed in combination with cardiac surgery with good results (3), and even
in patients who underwent bypasses for 2- and 3-vessel disease (4). Therefore,
the assessment of potential coronary artery disease remains an important part
of the routine workup of potential lung transplantation candidates.
The true incidence of CAD in patients considered candidates for lung
transplantation is not known. However, many of these patients with end-stage
lung disease also have a significant smoking history. Consequently,
conventional coronary angiography is often routinely performed as part of the
lung transplantation screening program in patients over 40 years (or 50 years,
depending on the local protocol). In a study of 118 lung transplantation
candidates > 40 years who underwent coronary angiography, significant CAD
(luminal reduction >= 70% in diameter) was found in 21 patients (18%) (5). In
another study, in which coronary angiography was performed in 101 candidates >
50 years, an incidence of 17% of significant CAD was found (6). In our
hospital, 30 patients are screened yearly for lung transplantation. Two thirds
of the patients screened for lung transplantation are > 40 years and undergo
coronary angiography, and 20% had CAD (unpublished data). This is in good
agreement with the literature.
Conventional coronary angiography is the gold standard to exclude significant
and non-significant CAD, but the procedure is invasive, relatively costly and
may result in patient morbidity. Although the frequency of serious
complications (such as significant bleeding, heart and lung problems including
heart failure, stroke, heart attack and local damage to organs, nerves and
blood vessels) is low, it is not insignificant. In addition, access site
vascular complications (e.g., femoral hematoma, arterial pseudoaneurysm,
fistula) are a well-described risk of coronary angiography with an incidence of
1-6% of all catheterizations (7).
Multi-detector Computed Tomography (CT) coronary angiography has emerged as a
non-invasive patient-friendly imaging modality that permits evaluation of both
the coronary lumen and coronary vessel wall (8-13). Recent developments in
multi-detector CT technology have resulted in a markedly improved resolution
when compared to earlier CT scanner generations. Current state-of-art 64-slice
CT scanners offer high quality, nearly motion-free, isotropic image quality in
patients with a low (<70 beats/minute) and stable heart rhythm (8-13). The
diagnostic performance to detect significant obstructive lesions (>50% luminal
diameter stenosis) is high. The sensitivity, specificity, positive and negative
predictive values are 90%, 94%, 70% and 95% respectively (8-13). However,
previous studies using 16- and 64-slice CT scanners have shown an inverse
relationship between heart rate and image quality concerning coronary artery
visualization and stenoses detection (14, 15). Consequently, in order to
achieve a high accuracy in the detection of coronary artery stenosis, the heart
rate is usually lowered to <65-70 beats/min using pre-medication such as
beta-blockers or nitro-glycerine. Patients screened for lung transplantation
frequently have basal heart rates as high as 90-100 beats/min. However,
beta-blockers are contra-indicated in patients with bronchial hyperactivity
(e.g., asthma), COPD patients on beta agonist therapy and pulmonary arterial
hypertension (PAH) whereas nitro-glycerine is contraindicated in PAH patients.
Alternative drugs such as Ivabradine are available and can be safely used in
most patients.
The most recent dual-source CT scanners and 128-slice or even 256- and
320-slice CT scanners are believed to further improve coronary artery imaging.
Using dual-source CT scanners, pre-medication is not warranted in patients with
a heart rate > 70 beats/min to obtain sufficient quality for coronary artery
imaging (16, 17) with a negative predictive value of 98% and 100%,
respectively. Whether pre-medication is warranted with single source 128-, 256-
or 320-slice CT scanners is unknown since the experience with these new CT
scanners is limited at the moment. In addition, it is also unknown whether
these new CT scanners are able to detect diffuse non-significant CAD (luminal
reduction <50%) with high accuracy.
In the present study, candidates for lung transplantation who will undergo
conventional angiography as part of their screening work-up, are asked to
participate in this study and to undergo CT coronary angiography as well. If
the present study demonstrates that the negative predictive value of CT
coronary angiography for the presence of CAD in lung transplantation candidates
is as high as in patients with a clinical suspicion of cardiovascular disease,
conventional angiography may only be indicated in a subgroup of lung
transplantation candidates in whom CT coronary angiography reveals CAD.

1. To assess the feasibility of performing CT coronary angiography in potential
candidates for lung transplantation.
2. To assess the accuracy, especially the negative predictive value, of CT
coronary angiography in the detection of both significant and diffuse
non-significant CAD as compared to the gold standard conventional angiography
in patients who are potential candidates for lung transplantation.

The study will start in the Erasmus MC as a pilot study first (Objective 1).
Prospective, multi-centre (2 Dutch and 1 Belgian University Medical Centres),
blinded cohort study in patients who are potential candidates for lung
transplantation.

The individual patient will not benefit from participation into this study
since the data from CT coronary angiography will be analyzed separately and
only for research purposes. These data will not be provided to the treating
physician.

So far, diagnostic invasive coronary angiography is used in order to assess the
presence of CAD that may exclude patients from lung transplantation.
Multi-detector CT coronary angiography has emerged as a non-invasive
patient-friendly, inexpensive imaging modality that permits evaluation of both
the coronary lumen and coronary vessel wall. If CT coronary angiography will
achieve the same negative predictive values in potential lung transplantation
candidates as has been described in other patient groups, diagnostic invasive
coronary angiography may be reduced to only 20-25% of the patients who now
undergo this examination as part of the routine work-up.