Recanalization of a Total Occlusion With Marked Retrograde Collateral Supply: Impact of Collateral Circulation on Fractional Flow Reserve Measurements of Donor Artery

ABSTRACT: Fractional flow reserve (FFR)-based coronary interventions of intermediate-severity lesions are safe, cost effective, and have prognostic importance. Although FFR is not affected by heart rate or blood pressure, collateral circulation might affect FFR results. Intermediate stenosis at the donor artery might be overestimated with FFR measurement due to coronary steal. Moreover, the amount of collateral circulation might be a strong determinant of this inaccurate measurement. In this report, we present 8 patients who underwent percutaneous coronary intervention for totally or subtotally occluded recipient vessels that were collateralized by a vessel with intermediate-degree stenosis proximal to the separation of the donor side branch evaluated by quantitative coronary angiography (QCA). In patients with Rentrop grade-2 or grade-3 collateral flow, FFR value of the donor artery was increased at least 0.10 after revascularization of the recipient artery. However, FFR value did not change significantly in patients with Rentrop grade-0 or grade-1 collateral flow following revascularization. In this case series, we suggest that well-developed collateral circulation might result in overestimation of the FFR value in the donor artery with mild stenosis. Therefore, in patients undergoing intervention to the recipient artery with a well-developed collateral supply and an intermediate stenosis at the donor artery, hemodynamic significance of the stenotic lesion should be evaluated not only before but also after coronary intervention. However, if there is no sufficient collateral circulation to totally occluded arteries, FFR values of donor arteries seem to be relatively stable both before and after PCI to the recipient artery.

J INVASIVE CARDIOL 2014;26(6):E70-E75

Key words: total occlusion, donor coronary artery,intermediate stenosis, collateral flow, fractional flow reserve

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Fractional flow reserve (FFR) is frequently used to evaluate the hemodynamic significance of coronary artery stenosis with intermediate anatomic severity. FFR-based coronary interventions of intermediate severity lesions are safe, cost effective, and have prognostic importance.^1-4 Although FFR is not affected from heart rate or blood pressure, collateral circulation might affect FFR results.⁵ Intermediate stenosis at the donor artery might be overestimated with FFR measurement due to coronary steal. Moreover, the amount of collateral circulation might be a strong determinant of this inaccurate measurement. In this report, we presented 8 patients who underwent PCI for totally or subtotally occluded vessels that were collateralized by a vessel with intermediate-degree stenosis proximal to the separation of the donor side branch.

Case Series. Eight patients with totally or subtotally occluded coronary arteries that were supplied by collateral arteries with mild stenosis proximal to the separation of the collateral side branches were included in the study. Patients presenting with acute coronary syndromes and total occlusion of the infarct-related artery were excluded. Before the revascularization procedure, myocardial viability was detected at the occluded vessel site. Before the PCI procedure to the totally or subtotally occluded coronary artery, severity of stenosis of the donor artery was evaluated by quantitative coronary angiography (QCA) and FFR for all patients.

The myocardium at risk distal to the total occlusion (expressed as the myocardial jeopardy index; MJI) was angiographically estimated using the modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) score, which has been previously described.⁶ In brief, the left ventricle is divided into regions according to pathological studies in humans, evaluating the relative proportion of myocardium perfused by each coronary artery^.7,8 Location (proximal, mid, or distal) of the culprit lesion, vessel dominance, site of occlusion, and size of the major branches of the infarct-related artery were taken into consideration in creating a template that calculated the percentage of jeopardized myocardium for a given site of occlusion.⁹

FFR measurements were made using Volcano FFR wire (Volcano Corporation, Inc) as previously described.¹⁰ Before each FFR measurement, calibration of the wire was performed at the tip of the catheter. Then, the wire was advanced and positioned to the distal side of the stenotic lesion, followed by a bolus of 200 µg isosorbide dinitrate to avoid any form of epicardial vasoconstriction. Maximal hyperemia was induced by 90 µg and 120 µg intracoronary adenosine for right and left coronary arteries, respectively. After measurements, the pressure wire was pulled back until the sensor was close to the tip of the guiding catheter to ensure that no drift had occurred.

After successful revascularization of the recipient arteries, FFR measurements of donor arteries were repeated as described above. If final FFR value was less than 0.8, PCI was also planned for the donor artery. Collateral flow was graded according to Rentrop classification from 0 to 3. Patients were then divided into two groups according to Rentrop grade (group 1 = Rentrop grade 2 or grade 3; group 2 = Rentrop grade 0 or grade 1). Data are presented as median (min-max) and pre- and postprocedural FFR values were compared by two related sample tests (Wilcoxon). Postprocedural difference in FFR values, mean QCA values, and ages were compared using Mann-Whitney U-test.

Results. Patient demographics are presented in Table 1. Six male and 2 female patients were evaluated. Initial coronary angiograms of the 8 patients are shown in corresponding Figure 1 to 8. Four patients were found in group 1 (Rentrop grade 2 or 3) and 4 patients were found in group 2 (Rentrop grade 0 or 1). Mean age was 57 years (range, 51-67 years) in group 1 and 62.5 years (range, 53-75 years) in group 2 (P=.38). The PCI procedure was successfully performed to the right coronary artery (RCA) in 5 cases, circumflex (CX) artery in 1 case, and left anterior descending (LAD) coronary artery in 2 cases.

FFR measurements of the donor arteries before and after PCI and MJI are presented in Table 2 and Figure 9. Median FFR measurements increased after successful PCI in group 1 (0.65 [min-max, 0.62-0.70] vs 0.79 [min-max, 0.72-0.86]; P=.05). However, median FFR measurements remained stable despite successful recipient artery PCI in group 2 (0.77 [min-max, 0.65-0.89] vs 0.78 [min-max, 0.67-0.88]; P=.58). Mean increase in FFR value in group 1 was statistically significant compared with group 2 (0.135 vs 0.007; P=.02).

Severity of stenosis in the donor arteries was also evaluated by QCA. There was no significant difference in severity between groups (median severity, 68% [range, 55%-76%] in group 1 vs 60.5% [range, 52%-74%] in group 2; P=.38). Myocardial jeopardy index of the two groups was also similar (19.87% in group 1 vs 15.25% in group 2; P=.30). 

Discussion. In our case series, FFR results of donor arteries changed after revascularization of the recipient arteries, especially in patients with Rentrop grade-2 or grade-3 collateral flow and mild anatomic stenosis detected by QCA. FFR values increased at least 0.10 in patients with Rentrop grade-2 or grade-3 collateral circulation after the revascularization procedure. However, FFR value did not change significantly in patients with Rentrop grade-0 or grade-1 collateral flow and high percent stenosis by QCA. We think the effect of coronary steal on the donor artery was minimal due to poorly developed collateral circulation and ischemia was prominent because of high-grade anatomic occlusion. In the literature, there were only a few case reports showing increase in FFR value of the donor artery following PCI to the recipient artery.^11-13 A previous report of a patient with well-developed collateral circulation from the donor artery revealed an increase in the FFR value from 0.84 to 0.96 after PCI to the recipient artery.11 However, another report of a patient with a mild LAD stenosis revealed no alteration in FFR value after surgical revascularization of occluded RCA and CX arteries.¹⁴

Collateral circulation is an important alternative source of blood supply to the jeopardized myocardium of critically occluded arteries. Well-developed collateral circulation might help to sustain viability and contractility at the ischemic myocardial tissue.^15,16 Extensive amounts of myocardium that is perfused by collateral circulation might provoke myocardial ischemia at the donor artery region by coronary steal syndrome. However, poor collateral circulation or small areas at ischemic risk might not result in an evident blood shift to the recipient artery. We also detected stable FFR results in patients with poor collaterals despite similar MJI, supporting this hypothesis. 

Although FFR is not affected by heart rate, contractility, or blood pressure,¹⁷ in case of an intermediate-degree stenosis determined by QCA in the donor coronary artery, hemodynamic evaluation of the occlusion by FFR might overestimate the severity due to collateral blood flow. However, if the stenosis demonstrated by QCA is severe, FFR measurement seems more reliable independent of the collateral circulation. FFR results are restrictive for donor artery interventions in order to augment coronary blood flow to both the donor and recipient myocardia in conditions in which there is no chance of revascularization of totally occluded recipient artery.

Myocardial jeopardy index was successfully used to estimate the amount of myocardium at risk in patients presenting with myocardial infarction.9 However, there was no relation between MJI and FFR measurements in our patient group. Myocardial jeopardy index is highly dependent to the occluded vessel and most of our patients presented with RCA occlusions. There were only 2 patients with LAD occlusions and high amounts of myocardium at risk. This might have affected the results of our study. Further large-scale studies with equal distribution of the occluded vessels might clarify our results.

To date, there is no clinical study evaluating the effect of collateral circulation on FFR value of donor arteries after revascularization of the recipient artery. In this case series, despite an insufficient number of patients, we suggest that well-developed collateral circulation might cause overestimation of the FFR value in the donor artery with intermediate-degree stenosis. Therefore, in patients undergoing intervention for the recipient artery with a well-developed collateral and intermediate stenosis at the donor artery, hemodynamic significance of stenotic lesion should be evaluated not only before but also after coronary intervention. However, if there is no sufficient collateral circulation to the totally occluded recipient arteries, FFR values of donor arteries seem to be relatively stable both before and after PCI to the recipient artery. In addition to QCA, intravascular ultrasound and coronary computed tomography angiography might also be used as supporting modalities to define the anatomic severity of the donor artery occlusions.

In patients with an occluded coronary artery that was supplied by a well-developed retrograde collateral vessel, anatomic significance and localization of the donor artery lesion (distal or proximal to the septal collaterals in the LAD), intensity of the collateral flow, dominance of the recipient artery, MJI of the occluded vessel, existence of stenotic lesions distal to the total occlusion site, presence of unnoticed epicardial or atrial collaterals, and elevated left ventricular end-diastolic pressure might affect the hemodynamic significance of the stenotic lesion at the donor artery. Hemodynamic evaluation should be repeated after successful revascularization of the recipient artery, which might minimize the coronary steal syndrome. However, in case of insufficient collateral circulation to the totally occluded recipient arteries, repeated FFR measurement of donor arteries seems unnecessary. These data might help to reduce unnecessary donor artery interventions and surgical referrals, which will preclude the potential complications of these procedures.

Study limitations. In this case series, an insufficient number of patients was the main limitation that might affect the statistical analysis results. To increase the reliability of our results, new studies with a sufficient number of patients should be planned. Although patients presenting with acute coronary syndromes were excluded in our study, many patients with totally occluded vessels and retrogradely supplied collaterals undergo revascularization procedures during daily clinical practice. Our results require validation in patients with acute coronary syndrome.

References

1. Fearon WF, Tonino PA, De Bruyne B, Siebert U, Pijls NH. Rationale and design of the fractional flow reserve versus angiography for multivessel evaluation (FAME) study. Am Heart J. 2007;154(4):632-636.
2. Miller LH, Toklu B, Rauch J, Lorin JD, Lobach I, Sedlis SP. Very long-term clinical follow-up after fractional flow reserve-guided coronary revascularization. J Invasive Cardiol. 2012;24(7):309-315.
3. Muller O, Mangiacapra F, Ntalianis A, et al. Long-term follow-up after fractional flow reserve-guided treatment strategy in patients with an isolated proximal left anterior descending coronary artery stenosis. JACC Cardiovasc Interv. 2011;4(11):1175-1182.
4. Misaka T, Kunii H, Mizukami H, Sakamoto N, Nakazato K, Takeishi Y. Long-term clinical outcomes after deferral of percutaneous coronary intervention of intermediate coronary stenoses based on coronary pressure-derived fractional flow reserve. J Cardiol. 2011;58(1):32-37.
5. Peelukhana SV, Back LH, Banerjee RK. Influence of coronary collateral flow on coronary diagnostic parameters: an in vitro study. J Biomech. 2009;42(16):2753-2759.
6. Graham MM, Faris PD, Ghali WA, et al. Validation of three myocardial jeopardy scores in a population-based cardiac catheterization cohort. Am Heart J. 2001;142(2):254-261.
7. Brandt PW, Partridge JB, Wattie WJ. Coronary arteriography; method of presentation of the arteriogram report and a scoring system. Clin Radiol. 1977;28(4):361-365.
8. Kalbfleisch H, Hort W. Quantitative study on the size of coronary artery supplying areas postmortem. Am Heart J. 1977;94(2):183-188.
9. Ortiz-Pérez JT, Meyers SN, Lee DC, et al. Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging. Eur Heart J. 2007;28(14):1750-1758.
10. Pijls NHJ. Fractional flow reserve to guide coronary revascularization. Circ J. 2013;77(3):561-569.
11. Kurisu S, Mitsuba N, Ishibashi K, et al. A pitfall of fractional flow reserve associated with the presence of collateral circulation. Intern Med. 2011;50(22):2811-2813.
12. Matsuo H, Kawase Y. Physiological impact of CTO recanalization assessed by coronary pressure measurement: a case report. Catheter Cardiovasc Interv. 2013;82(4):E459-E464. Epub 2013 Apr 11.
13. Sachdeva R, Uretsky BF. The effect of CTO recanalization on FFR of the donor artery. Catheter Cardiovasc Interv.  2011;77(3):367-369.
14. Sasai H, Sakakura K, Yuri K, et al. Fractional flow reserve for a mild stenosis on the donor artery to chronic total occlusion. Cardiovasc Interv Ther. 2013;28(2):193-196. Epub 2012 Oct 18.
15. Hasanović A, Kulenović A, Sisić F. The role of collateral circulation in preserving myocardial function. Bosn J Basic Med Sci. 2006;6(4):29-31.
16. Chouraqui P, Asman A, Guetta V, et al. Noninvasive detection of collateral flow to the infarct-related coronary artery in patients after myocardial infarction by Tl-201 tomographic imaging. J Nucl Cardiol. 2003;10(6):669-675.
17. De Bruyne B, Bartunek J, Sys SU, Pijls NHJ, Heyndrickx GR, Wijns W. Simultaneous coronary pressure and flow velocity measurements in humans: feasibility, reproducibility, and hemodynamic dependence of coronary flow velocity reserve, hyperemic flow versus pressure slope index, and fractional flow reserve. Circulation. 1996;94(8):1842-1849.

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From Marmara University Faculty of Medicine, Department of Cardiology, Istanbul, Turkey.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted September 12, 2013, provisional acceptance given September 25, 2013, final version accepted November 20, 2013.

Address for correspondence: Erdal Durmus, MD, Department of Cardiology, Faculty of Medicine, Marmara University, Fevzi Cakmak Mahallesi, Mimar Sinan Caddesi, No: 41 Ustkaynarca, Pendik / İstanbul / Turkey. Email: drerdalin@hotmail.com