The Future of Surgical Revascularization in Stable Ischemic Heart Disease

Physiologic Imaging in Revascularization

What intraoperative evidence exists to support these findings, and the premise that the framework for CABG needs to evolve? Again, the nonphysiologic setting of conventional CABG has hampered the real-time evaluation of the physiologic consequences of grafting, both at a TVECA and global level. Intraoperative conventional angiography has proven to be overly cumbersome and associated with elevated risk of iatrogenic postoperative renal insufficiency. Transit-time flometry can be used to evaluate flow in grafts, but not TVECAs, and the absence of visualization makes a realistic evaluation of issues, such as competitive flow, difficult to assess accurately.^[67,68] Moreover, it cannot assess myocardial perfusion or changes in myocardial perfusion as a result of TVECA grafting.

We have spent the past 6 years using near-infrared fluorescence imaging technology to study the physiology of revascularization at the time of CABG. Importantly, the majority of these cases have been performed as off-pump coronary artery bypass (OPCABs) on a beating heart, allowing for the immediate physiologic evaluation of grafting.^[69]

The opportunity to combine both full-phase angiography and perfusion into a single, real-time assessment of physiology makes this approach unique and unprecedented. Moreover, within each of these components, additional attributes are present:

• The angiographic evaluation differs from conventional angiography in that:

  • It uses the nontoxic fluorophobeindocyanin green rather than nonionic contrast;

  • There is no ionizing radiation with this fluorescent technique;

  • This imaging is carried out under normal, baseline conditions of blood flow and myocardial perfusion;

  • The fluorescent technique illuminates in the arterial phase both the native TVECA and the graft to visualize flow down both vessels, competitive flow interactions, whether grafting has compromised the native coronary flow and the anastomosis integrity (Figure 1).

• The perfusion evaluation is new, and is a consequence of capturing all three phases of fluorescent full-phase angiography over multiple cardiac cycles. These are the arterial (analogous to conventional angiography), the microvascular and the venous phases; perfusion is assessed by analyzing meta-data from the image data file (Figure 2).

Using this technology, it is possible to quantify the change in regional myocardial perfusion associated with the TVECA, in real time. Using a specific data acquisition protocol, this imaging technology and software compares regional myocardial perfusion before and after grafting, and quantifies the difference, if any, that results from the bypass graft (Figure 3). Importantly, the intensity of fluorescence and the magnitude of change in fluorescence intensity from a defined region of the myocardium is directly proportional to myocardial perfusion under controlled conditions. During CABG, this technology quantifies the real-time impact on perfusion of a widely patent graft for each of the TVECAs addressed at surgery, to document the global change in perfusion (Figure 4).

Our experience with physiologic imaging at revascularization has generated visual and physiologic data to challenge several long-standing assumptions about surgical revascularization. Data from over 500 patients who underwent CABG using the standard anatomy-based criteria for revascularization, have documented that not all widely patent bypass grafts to TVECAs result in a change in myocardial perfusion. Rather, overall, approximately 20–23% of grafts do not result in a perfusion change in the supplied myocardium.

This observation underscores the issue of incomplete anatomic, but functionally complete revascularization. In addition, it has implications from myocardial perfusion, intermediate-term graft patency and myocardial integrity perspectives. Since we are quantifying a change in myocardial perfusion, it might be that the 23% of grafts without a change result from grafting an anatomic, but not functional stenosis:

• There is no myocardial deficit of ischemia or perfusion to be corrected when grafting beyond an anatomic but nonfunctional stenosis;

• There is no physiologic drive (i.e., ischemia and/or perfusion deficit documented by FFR) to keep a graft beyond an anatomic but nonfunctional stenosis open in the intermediate term. That regional myocardial area already has sufficient flow and perfusion from other areas of the heart, principally through the development of extensive collaterals.^[64–66] A technically perfect graft with documented angiographic patency in real time at surgery likely does not fail over time due to a technical issue; rather, attrition is almost certainly due to the underlying dynamic of myocardial perfusion;

• Grafting one regional area of the heart might have considerable influence on perfusion to other areas, depending upon the influence of myocardial integrity factors. This is demonstrated in Figure 5.

In a study by Lindstaedt et al. optimizing revascularization strategies using intracoronary pressure measurements, 24% of patient with multivessel disease had the surgical revascularization strategy changed as a result of FFR data, including which vessels to graft and where to place them for optimal functional results.^[70]

In an important prospective study by Botman et al., 164 patients eligible for CABG using a traditional anatomic-based revascularization strategy underwent FFR measurement in all vessels identified (angiographic stenosis ≥70%) as target vessels for bypass grafting.^[71] At coronary angiography after 1 year, 8.9% of the bypass grafts on functionally significant lesions (FFR ≤0.75) were occluded and 21.4% of the bypass grafts on functionally nonsignificant lesions (FFR >0.75) were occluded.^[71] These are the first data to suggest that a target vessel coronary artery with anatomic, but not functional criteria for bypass grafting, results in increased graft failure at 1 year. This remains an important consideration, since the FAME study demonstrated that 20% of angiographic stenoses between 71 and 90% had no functionality associated with them, and 65% of stenoses between 50 and 70% had no functionality associated with them. In the PREVENT IV trial, graft failure was not without consequence for repeat revascularization.^[27] However, graft failure on protocol-specified 12–18-month angiography was not associated with increased mortality or MI, perhaps suggesting that the graft failure occurred in part because there was a sufficient (and potentially protective) amount of perfusion to that target vessel myocardium to begin with; there was no physiologic 'functional drive' to maintain graft patency.^[72] The values of approximately 25% across all of these studies and our imaging study suggest that with anatomy-based CABG, approximately a quarter of grafts are placed to anatomic, but not functional stenoses.

In aggregate, these data support the concept of FFR-guided CABG,^[69] where TVECAs with functional stenoses would be bypassed, and anatomic but nonfunctional stenoses would be bypassed when, in the surgeon's judgment, revascularization of that vessel would be important for perioperative morbidity. While complicating the CABG strategy, standardizing revascularization based on targeted functionality instead of anatomy could well improve CABG outcomes beyond today's results, as was clearly demonstrated in the FAME trial.

Future Cardiol. 2014;10(1):63-79. © 2014 Future Medicine Ltd.