The present study demonstrates heterogeneous perfusion patterns between native vessels and different bypass grafts when using the first pass bolus technique, with, however, only small differences that are partly also present in different perfusion areas in patients without CAD. No significant difference in the peak enhancement (SImax) or myocardial contrast wash-in (upslope) exists between native coronaries and coronary arterial bypass grafts. However, contrast arrival expressed by the time from the appearance in the left ventricular cavity to peak myocardial enhancement or 50% of peak myocardial enhancement may be delayed, especially when grafts bypass occluded vessels. This, however, does not seem to be a limitation for adenosine perfusion in patients after CABG.
CABG is a common procedure for the treatment of significant CAD. Long-term graft patency and progression of CAD are the major factors limiting the initial clinical benefits of revascularization and patient survival. As exercise ECG has limitations (e.g. previous myocardial infarction and/or functional single-vessel disease), stress imaging tests are the preferred method for non-invasive testing in this subgroup [10]. There is little data on stress perfusion using adenosine [7, 8, 11], but it demonstrates reasonable diagnostic accuracy when compared to invasive angiography. However, diagnostic accuracy is reduced in patients with surgical revascularization [8]. The clinically most applicable analysis is the visual assessment of the contrast passage through the myocardium, as it is fast and yields good clinical results [12–14]. However, a reduction of peak enhancement, a delay in myocardial contrast arrival or a reduced speed of contrast wash-in purely by alteration of the contrast bolus due to bypass surgery may limit the use of the perfusion CMR technique.
Therefore we aimed to calculate these semiquantitative parameters to evaluate possible differences in first pass perfusion imaging in patients after bypass surgery depending on areas supplied by native vessels and vessels with arterial or venous bypasses. There are no direct comparisons between visual and semiquantitative analysis in the same patient population, as visual evaluation is believed to need higher contrast concentrations [4, 14] and semiquantitative evaluation to need lower [5, 15] concentrations, due to the loss of the relationship between signal intensity and contrast concentration, especially in the left ventricular cavity. For semiquantitative analysis the upslope is the most often used parameter [5, 12] and has demonstrated good correlation compared to angiography and PET for the detection of significant CAD [16], even with the use of higher gadolinium concentrations [6]. In a direct comparison between upslope, maximal SI, time to maximal SI and contrast arrival time, the upslope was the best parameter for the detection of ischemia [17].
Although lacking the direct comparison between semiquantitative and visual analysis, we are certain that at least to a large extent parameters such as maximal signal intensity, time to maximal signal intensity and the speed of contrast wash-in (upslope) play a role in the visual assessment of first pass perfusion. In order to evaluate a normal range of these parameters in a perfusion study that was classified as non pathological, they were calculated in patients with exclusion of CAD by invasive X-ray angiography.
As demonstrated in table 2 and figures 4 and 5 there is a considerable intra-patient range of the semiquantitative parameters. The difference in delay in reaching peak enhancement is significant between the LAD and the two other vessel territories. However, this range seems to represent a normal variety of contrast kinetics during adenosine vasodilatation in uncompromised epicardial blood flow and is, most importantly, considered as normal by the evaluating physician with the contrast concentration used. Coronary flow reserve in bypass grafts is no different than in native vessels, except if supplying infarcted myocardium [18]. Therefore we took care not to include segments with LGE, known to represent myocardial infarction, in order to evaluate the semiquantitative parameters on the vessel/graft and not on the myocardial level.
There was no difference in maximal SI or upslope between native vessels and CABG, while there is a significant trend towards a delayed contrast arrival. There is the tendency that the delay of contrast arrival is more pronounced in LIMA than in venous grafts. This can be explained by the longer distance the bolus needs to travel to reach the myocardium. We did not use the time between contrast arrival in the LV and the myocardium, although this would represent the real arrival time. But, as the time is short compared to the temporal resolution (one heart beat) and therefore prone to miscalculation, especially as the exact start of myocardial enhancement is sometimes difficult to identify, we have decided against this parameter. As the upslope is similar TSI50%max and TSImax can be used as parameters for contrast arrival. Although the mean contrast delay in heart beats is below one beat (figure 5), there was a considerable deviation reaching up to almost 4 heart beats in one case. Therefore, similar to the visual impression, there are cases where areas perfused by grafts and especially by LIMA grafts may show a delay. However, the delay caused by the longer distance of the bolus to reach the myocardium should be transmural, while in true perfusion defects, hypoenhancement is non-transmural in the majority of cases [19]. As stated above, the semiquantitative parameters in patients without significant CAD also demonstrate significant differences in the different vessel territories. However, the differences in the number of heart beats needed to reach SImax demonstrate a smaller range than in patients after CABG (fig. 5). The overall larger upslopes/SImax and shorter TSI50%max/TSImax in patients without CAD compared to post CABG (table 2) are probably due to the fact that maximal blood flow in patients with CAD may be reduced even without significant stenosis, as well as due to lower ejection fraction and areas of hypo- and akinesia. Importantly, there is no evidence that the upslope and/or SImax are reduced as an add-up effect, if e.g. TSI50%max is prolonged in areas supplied by CABG, as there is no significant tendency in the positive or negative direction of the add-up score (fig. 6).
CMR perfusion patterns may possibly be altered by simultaneous blood flow, although probably reduced via a significantly stenosed native vessel in addition to the bypass graft, if the native vessel is not occluded. Therefore, we carried out a separate analysis of areas supplied by the graft only (occluded native vessel) and by both graft and significantly stenosed native vessel. There is a significant trend that areas supplied by grafts only are more prone to delayed contrast arrival and reduced upslope (table 3). However, differences from native vessels remain small. Therefore, if the coronary and bypass status is unknown, the interpretation of adenosine first pass perfusion may be complicated by delays in contrast arrival. These delays are usually short but reach up to 4 heart beats in sporadic cases, especially if the native vessel is occluded.
Limitations
The two groups of patients demonstrate significant differences in terms of sex, prevalence of diabetes, ejection fraction and the presence of LGE. However, our group of patients without CAD represents the patient population that is frequently tested to exclude significant CAD and we gain our visual experience in normal perfusion studies. Additionally, a control group of patients with CAD but no significant stenosis is unlikely to have more homogenous perfusion patterns than patients with exclusion of CAD. The more pronounced increase in heart rate during adenosine stress is most probably due to the lesser medication with β-blockers in the patients without CAD (data not shown). The study aimed to compare the semiquantitative parameters in patients without any stenosis in bypasses and unbypassed native vessels. We therefore cannot be certain that the differences found may not be mistaken for real perfusion defects, assuming that the parameters assessed do reflect the visual impression of perfusion. However, these differences are small and can also be found in the patient population without CAD. An additional study may have to address this issue, especially taking into account the possible differences of the endo- and epicardium, as real perfusion defects are mostly non-transmural [19]. When comparing CMR perfusion and coronary angiography, it remains a comparison of functional and anatomical information. Additionally, there is always the possibility of anatomical mismatch when defining perfusion areas of coronaries within the two dimensional X-ray angiography. However, angiography was analyzed by a cardiologist familiar with invasive and perfusion technologies and care was taken not to include segments with uncertainty concerning the perfusing coronary artery or bypass graft. Therefore, not all segments per patient were analyzed. We are, however, certain by including core segments to have the least possible mixture of different vessel territories.