Flow demand and peripheral vascular resistance in revascularized areas are the fundamental factors that influence graft flow and patency; however, they have not yet been fully explored, probably because vascular resistance varies as a result of continuously being adjusted according to oxygen consumption and left ventricular work. Thus, vascular resistance cannot be reliably quantified in clinical studies. In an attempt to circumvent these difficulties, we examined location of stenosis (distal vs. proximal) and history of MI and PCI in the relevant area, all of which are presumably associated with the status and size of revascularized myocardial areas and flow demand, to determine how these factors influence graft flow and patency.
Competitive flow can be avoided by appropriate target assessment, graft selection, and configuration [6, 7]. Functional assessment of native coronary stenosis, such as by assessing FFR or coronary flow velocity reserve (CFVR), has raised some issues. Van de Hoef and colleagues reported that results of FFR and CFVR were discordant in 31% or 37% of target vessels at cut-off FFR values of 0.75 or 0.80, respectively [8]. This discordance is characteristic of microvascular disease (MVD); adverse cardiac events and deaths were significantly associated with normal FFR and abnormal CFVR in that study [8]. Additionally, in patients with multivessel disease, including chronic total occlusion (CTO), FFR in collateral donating branches can be overestimated [9].
In the present study, we assessed native coronary stenosis by using quantitative coronary angiography to ascertain the MLD and reference diameter, both of which are traditional but standard measures. Additionally, off-pump CABG favours use of TTFM [10] because cardiopulmonary bypass can reduce systemic vascular resistance and increase graft flow by inducing a hyperaemic state, thus creating a major bias in flow measurements [11]. Moreover, to minimize any bias caused by bypass grafts or targets, we excluded all sequential and composite graft and bypass grafts that were not the sole bypass grafts in the relevant vascular region. For example, when there was a bypass graft to a diagonal branch, we excluded ITA to LAD bypasses in case of any negative interactions [12].
We found that FI was significantly associated with distal lesions, history of MI in the LCX and RCA areas, and history of PCI in the LAD. The cut-off values were higher by 3% for LAD and 6% for LCX for distal lesions than for proximal lesions. These findings suggest that severity of stenosis and CABG strategy should be modified according to whether the stenosis is located distally or proximally and the size of the area to be revascularized. Competitive flow that is attributable simply to moderately stenotic native targets does not remain the primary mechanism for FI at later stages.
We were unable to determine cut-off values for SVG to LCX and RCA grafts, in the case of SVG to LCX possibly because SVG patency is not influenced by the severity of stenosis and there were too few grafts with FI to demonstrate a significant difference. In comparison, as shown in Table 2, for distal RCA, the incidence of FI in SVGs was as high as 47.1%, which is comparable to that for GEA, irrespective of MLD. SVGs have been widely accepted as providing high pressure capacity and being more reliable than arterial grafts for targets with moderate stenosis. The results of this study suggest that SVG is reliable irrespective of stenosis severity provided that flow demand in the grafted area is adequate.
PCI had a negative impact on graft flow only in ITA to LAD grafts, likely because PCI is indicated for LCX and RCA only when the vessel is sufficiently large. Possible mechanisms for reduced graft flow, higher rate of FI, and graft failure after PCI include the following. First, stenosis in the LAD may have been less severe in patients who had undergone PCI than in those who had not. Although, there was not a statistically significant difference in severity of stenosis and MLD, the incidence of angiographic competitive flow was higher in the PCI than in the no-PCI group. Second, revascularized areas were sometimes made smaller by sacrificing epicardial coronary vessels, such as the LAD, diagonal or septal branch (Fig. 2). A third possible mechanism is microvascular disease (MVD) distal to a PCI. It is widely accepted that PCI can cause microembolization of atherosclerotic debris or thrombus to distal myocardial tissue. Additionally, drug-eluting stents may adversely affect peripheral vascular function. Shin and colleagues reported that coronary segments distal to drug-eluting stents have more severe vasoconstriction than those distal to bare metal stents. These researchers suspected endothelial dysfunction in the myocardium distal to the treated vessel [13]. De Villa and colleagues have proposed normalized perfusion pressure, secondary inflammation, and platelet activation as possible mechanisms for MVD [14]. Fourth, patients who present with MVD are vulnerable to developing restenosis after PCI and therefore tend to be referred for CABG. De Villa and colleagues reported that lower coronary flow responses to adenosine and cold pressor tests are associated with restenosis after PCI [14]. Guidelines for revascularization recommend CABG only for proximal lesions of the LAD in patients with multivessel disease [15]. However, in our experience, graft flow is significantly reduced in ITA to LAD distal lesions with prior PCI and the incidence of FI and graft failure are as high as 32 and 12%, respectively. Both proximal and distal LAD stenosis should be carefully managed by the cardiovascular team, otherwise PCI to LAD distal lesions may cause MVD and compromise the efficacy of future CABG.
Recently, hybrid procedures comprising in situ ITA to LAD bypass grafting with drug-eluting stents for non-LAD vessels have been increasingly performed on patients at high risk of sternotomy [16, 17]. Rosenblum and colleagues reported finding no significant differences between such hybrid procedures and CABG using bilateral ITA over a mean duration of follow-up of 2.83 years and concluded that hybrid revascularization is effective in appropriately selected patients [18]. Patients are usually selected for hybrid revascularization when the morphology of LAD lesions contraindicates PCI [15, 19]. However, CABG is not necessarily appropriate in patients with morphology that contraindicates PCI, except for those with CTO. Even in vessels with CTO, small revascularized areas and a history of PCI have negative impacts on ITA to LAD grafts. Inversely, ITA grafting may be more beneficial than PCI in some patients with LAD in whom PCI would be appropriate. Moreover, the latest randomized study found no significant advantage of bilateral ITA over single ITA over a 5 year follow-up [20]. Detailed assessment of the suitability of coronary lesions for ITA or CABG and precise prediction of graft patency would contribute to improving outcomes of both hybrid revascularization and CABG using multiple arteries or both ITAs.
This study has the following limitations. First, it was retrospective and therefore not randomized. Second, we were unable to reliably examine FFR because it cannot be measured in target vessels with CTO and was not performed in other patients in some of the referral hospitals during the study period. Especially for in-stent stenosis, FFR or intravascular ultrasonography may be more reliable than angiography. However, these investigations had been performed only for selected vessels or patients, such as those with moderate stenosis or who were candidates for re-stenting. Difficulty in assessment or overestimation of in-stent stenosis may have introduced bias. Third, there may have been too few patients, especially for examining the effects of PCI in the LCX and RCA. We speculate that prior PCI in the LCX and RCA would show a statistically significant negative impact with greater numbers of patients and bypass grafts. Fourth, indications for PCI were not precisely defined because these procedures were performed using several different devices and techniques over more than a decade in a number of different hospitals. Of note, PCI has been performed more aggressively by cardiologists in Japan than in other countries. Fifth, myocardial flow demand in an area with a history of MI correlates with the extent of remaining viability. Unfortunately, viability had not been assessed by the appropriate specific preoperative investigations. Sixth, blood pressure or dose of catecholamine may have introduced biases in flow measurements. However, we could not precisely define these factors because this study was retrospective and the measurements had been taken intraoperatively. Finally, the most important limitation is the lack of a standard protocol for preoperative assessment and resultant uncertainty about all aspects of assessment and previous treatment.
