Influence of coronary territory on flow profiles of saphenous vein grafts

Coronary artery by-pass surgery (CABG) remains the optimal treatment for complex coronary artery disease [1], but despite the survival benefit of CABG, long-term graft patency remains a concern. Current European guidelines on CABG recommend intraoperative graft assessment with specific cut-off values for mean graft flow (MGF) and pulsatility index (PI) by transit-time flowmetry (TTFM) technique [2]. However, a limitation of current guideline recommendations is that they do not take into account the known differences in physiological pattern of flow between the right and left coronary artery territories [2].

The transmyocardial pressure is higher on the left side of the heart compared to the right, as the left ventricle provides circulatory support for the high-pressure systemic circulation, and hence a larger fraction of the myocardial blood flow in the left coronary territory takes place during ventricular diastole [3–5]. These differences in coronary blood flow of the left and right coronary territory might therefore be expected to influence flow in by-pass grafts. Few studies, however, have specifically addressed flow in left- vs. right-sided grafts, and have included cohorts of both arterial and venous conduits. Hence, current evidence for any potentially clinically relevant difference is scarce and contradictory [6–8].

The aim of this study was to compare all TTFM parameters MGF, PI, percentage of diastolic filling (%DF), and percentage of backward flow (%BF) in saphenous vein grafts (SVGs) supplying the left and right coronary territories in a larger cohort of CABG patients. Results were then analysed according to on-pump (ONCABG) vs. off-pump (OPCABG). We hypothesized that the higher pressure on the left side would particularly influence diastolic run off in SVGs.

As demonstrated by Transit-time flowmetry in patients undergoing CABG, our study has shown that saphenous vein grafts (SVGs) anastomosed to the left and right coronary territory have comparable mean graft flow (MGF), pulsatility index (PI), and percentage of backward flow (%BF) irrespective of surgical technique (OPCABG or ONCABG). However, SVGs anastomosed to the left territory have a significantly higher diastolic filling (%DF) than SVGs anastomosed to the right territory both during OPCABG and ONCABG. Moreover, compared to ONCABG, a significantly higher %BF was found in OPCABG SVGs supplying the left coronary territory (Table 4). In a multi-regression analysis, grafting to the left territory was weakly associated with higher PI and strongly associated with higher %DF of SVGs.

In keeping with our finding of no significant difference between territories with respect to MGF, the study by Tokuda et al. [6], including a mixture of arterial and venous grafts, found no statistically significant difference in MGF between grafts anastomosed to the left or the right coronary territory [6]. On the other hand, the study by Kim et al. [7], including a total of 117 arterial conduits (all operated as OPCABG), found a higher MGF in grafts anastomosed to the left than to the right territory. However, as only arterial grafts were assessed, the structural and physiological differences between arterial and venous conduits [11, 12] may explain these conflicting results, and further research is thus warranted to address this topic.

In further concordance with our results of no significant territory-related difference in PI, the study by Tokuda et al. [6] also found no statistically significant difference between grafts anastomosed to the left or the right territory with respect to PI [6]. In contrast to this finding, the study by Kim et al. [7] found a higher PI in grafts anastomosed to the right coronary territory. Again, since the study by Kim et al. [7] only included arterial conduits, this may well explain these conflicting results. Another explanation for why a higher PI may be found in right-sided grafts may be due to the position of the TTFM probe during measurement. Repositioning of the heart into anatomical position at the end of surgery will obscure the distal end of the graft. Consequently, TTFM measurement is often performed proximally on right-sided grafts, where PI is usually higher, as the high pressured forward flow from the aorta results in higher systolic peak flows in the proximal segment of a by-pass graft and hence in a bigger difference between maximum flow and minimum flow [9], as further explained in the following. In theory, a slightly higher PI may well be expected in grafts anastomosed to the left territory, as the PI is obtained by dividing the difference between maximum and minimum flow by the mean flow: \( \frac{\Big({Q}_{Max}-{Q}_{\mathit{\operatorname{Min}}\Big)}}{Q_{Mean}} \). Therefore, a larger difference between maximum and minimum flow, resulting in a higher PI value, may be expected on the left side of the heart where the higher transmyocardial pressure results in a higher pressure amplitude between systole and diastole [13]. Indeed, the multi-regression analysis suggested that grafting to the left territory was weakly associated with higher PI in SVGs.

In agreement with our study suggesting Tokuda et al. [6] and Kim et al. [7] both demonstrated a higher %DF in grafts anastomosed to the left compared to the right coronary territory compared. As previously noted, a higher %DF is indeed expected on the left side of the heart due to the higher transmyocardial pressure, which lowers systolic coronary flow, irrespective of conduit type (arterial or venous) or surgical technique. However, it is important to acknowledge that the established differences in %DF found in our study is of a mere 5%-points. Although this may reach statistical significance, the established difference is in most situations clinically insignificant.

Tokuda et al. [6] also found no significant difference in %BF in left vs. right-sided by-pass grafts. In contrast, however, Kim et al. [7] found a higher %BF in grafts anastomosed to the left coronary territory. Notably, all grafts were performed by OPCABG technique, which is consistent with our results showing higher %BF only in OPCABG SVGs anastomosed to the left coronary territory (Table 4). A higher %BF is indeed expected on the left side due to the higher transmyocardial pressure, which forces blood backward during isovolumetric contraction. However, these differences were also too small to be of any clinical relevance.

No other parameters were significantly different in grafts anastomosed in OPCABG vs. ONCABG surgery. Notwithstanding this however, previously published papers on TTFM parameters in OPCABG vs. ONCABG found a higher MGF in grafts performed with the latter technique [14–16]. In a prospective study [14] including a total of 266 grafts (203 OPCABG vs. 63 ONCABG) in 100 patients, Taggart and colleagues reported a lower MGF in SVGs performed by OPCABG technique despite a higher mean arterial pressure when compared to ONCABG (p < 0.05) [14]. The authors suggested that these findings might be related to vasodilatation following a period of myocardial ischaemia. Indeed, it has been well documented that despite the use of cardioplegia, cross-clamping in ONCABG leads to global myocardial ischaemia and subsequent acidosis with resultant dilatation of coronary arteries [17]. Thus, a higher MGF may be expected in ONCABG vs. OPCABG by-pass grafts. Although our results did demonstrate a numerically higher MGF in the ONCABG SVG cohort, this difference did not reach clinical or statistical significance.

Of note, the multi-regression analysis of this study showed significant associations between the four TTFM parameters, which suggests that these parameters should thus be considered complementary rather than in isolation when assessing quality of SVGs intraoperatively [4, 5, 10]. This is supported by studies demonstrating that high quality grafts, as determined by angiographic graft patency assessment, have high MGF due to good run-off with concomitant low PI, predominant %DF, and little %BF [6, 18–22].

Saphenous vein grafts supplying the left coronary artery territory have a higher diastolic flow (%DF) when compared to right-sided SVGs, irrespective of whether the procedure is performed ONCABG or OPCABG. Furthermore, multi-regression analysis suggests that SVGs grafted to the left coronary territory are weakly associated with higher PI. The magnitude of differences are numerically small and unlikely to be of clinical significance.