The Future of Surgical Revascularization in Stable Ischemic Heart Disease

T Bruce Ferguson Jr; Cheng Chen


Future Cardiol. 2014;10(1):63-79. 

In This Article

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).

Figure 1.

Intraoperative, real-time near-infrared fluorescence angiography illustration of simultaneous imaging of the coronary artery bypass grafting bypass conduit with the native target vessel epicardial coronary artery. The in situ LIMA graft is shown, along with the target vessel epicardial coronary artery native circumflex marginal branches in this single frame from the 1020 frame, 34 s image data sequence captured with each indocyanin green dye fluorophobe injection.
LIMA: Left internal mammary artery; OM: Obtuse marginal.

Figure 2.

Five single frames from the 1020 frame, 34 s video image data sequence following injection of indocyanin green dye. Each frame illustrates a single time point in the full-phase angiography sequence: baseline, arterial, microvascular, venous and residual, from a patient undergoing off-pump coronary artery bypass. The ECG (green) and blood pressure (red) are shown on the top tracing for the 26 cardiac cycles captured. The analysis of myocardial perfusion change is derived from the arterial and microvascular image data.

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).

Figure 3.

The complex angiography and perfusion analysis compares the myocardial perfusion surrounding the target vessel epicardial coronary artery immediately before and after grafting. Any change is quantified, as illustrated here. (A) The pregrafting data are normalized to 1 (blue), and (B) the postgrafting (red) are expressed as a multiple of the baseline. The RICMP is shown, with the blue curve as baseline native target vessel epicardial coronary artery perfusion, the red curve as native plus graft perfusion, and the green curve as the calculated difference in perfusion as a result of the bypass graft contribution. (C) Synchronized image at 16.6 s, illustrating native (graft temporary occluded) perfusion, compared with (D), which is a synchronized image at 16.6 s with perfusion from native coronary and graft combined.
RICMP: Revascularization-induced change in regional myocardial perfusion.

Figure 4.

Real-time assessment of global change in myocardial perfusion as a result of three-vessel bypass grafting (facing page). For each region, (A) anterior, (B) lateral and (C) inferior, the change in regional myocardial perfusion is shown in the same format as in Figure 3; these data can be combined to assess the global change in perfusion with complete bypass grafting. In all three areas of this patient's heart, there was a substantial increase in target vessel epicardial coronary artery perfusion as a result of bypass grafting.
RICMP: Revascularization-induced change in regional myocardial perfusion.

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.

Figure 5.

Change in regional myocardial perfusion as a result of collateral flow. This patient had a 10-year history of a chronically occluded right coronary artery, which was nongraftable. Arterial grafts were placed to the anterior and lateral (circumflex obtuse marginal) regions, and the inferior regional perfusion was assessed before (with both new grafts occluded) and after (grafts open) grafting. As a result of this new flow to the anterior and lateral regions, and the collateral network in this heart, there was a 2.7-fold increase in perfusion to the inferior wall, despite the inability to graft the right coronary artery target vessel.
RICMP: Revascularization-induced change in regional myocardial perfusion.

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.