Relationship Between Pressure-Derived Collateral Blood Flow and Diabetes Mellitus in Patients with Stable Angina Pectoris: A Stu

Collaterals are vessels structured as a connecting network between different coronary arteries. They are probably remnants of the embryonic arterial network and may develop under influence of various stimuli. The pressure gradient between the normal and stenotic vascular regions appears to be the most important factor for collateral development.1 However, there are considerable variations between patients with ischemic heart disease with respect to collateral development. The factors responsible for these variations are not clearly known.2 Predominant localization of the collaterals in the human heart is the subendocardium where a dense plexus develops. The proliferation of collateral arteries is not a process of passive dilatation but of active proliferation and remodeling. The histological structure of these vessels is that of abnormally thin walled arteries. Macroscopically identifiable interconnecting larger vessels have a normal arterial wall structure but show extensive subintimal and endothelial proliferation.3 Endothelial cells are also important in this collateral growth and maturation process.4–5 Diffuse endothelial dysfunction appears to be responsible for more complicated course and less favorable outcome of coronary artery disease (CAD) in patients with diabetes mellitus (DM).6–9 DM is known to stimulate angiogenesis in the retina. However, the functionally more important collateral vessels of the heart are not a product of angiogenesis but rather of “arteriogenesis’’. In this study, we investigated the effect of DM on coronary collaterals which are the product of arteriogenesis. Coronary angiography, the most commonly used technique for studying collateral circulation, may not be accurate in assessing collateral circulation because most collaterals are situated intramurally or are too small to visualize angiographically.10 Intracoronary pressure measurement is a relatively new technique to provide accurate and quantitative information about the collateral circulation,11–14 and it can be easily applied during the coronary intervention. We therefore sought the effects of DM on coronary collateral vessels in patients with CAD by using intracoronary pressure measurement technique. METHODS Patient population. We studied 40 patients with CAD referred to our clinic between November 1998 and October 1999 who met the following criteria: 1) clinically stable angina pectoris; 2) ischemic symptoms lasting over 3-month period; 3) verified myocardial ischemia by at least one non-invasive test; 4) more than 70% stenosis in one coronary artery; and 5) PTCA and/or stent implantation for this vessel. Written informed consent was obtained from all patients. Quantitative coronary angiographic analysis and intracoronary pressure measurements. Left and right coronary arteriography and left ventriculography were performed in all patients. Quantitative coronary angiographic analysis (QCA) and all coronary pressure measurements were performed both pre- and post-revascularization procedure. QCA was performed on all patients by a computer-assisted program (Philips Integris Angiographic Systems). The angiographic projection showing maximal severity of the diameter narrowing was used for assessment of stenosis severity with the guiding catheter used as a scaling device and percent diameter stenosis of the target lesion was calculated. After angiography, fiber-optic pressure monitoring guidewire (Pressure wire, 0.014´´ RADI Medical Systems, Inc., Reading, Massachusetts) was advanced and positioned distal to the stenosis to be dilated. The same wire was used as a guidewire for the angioplasty catheter. Proximal aortic (Pa) and distal pressures (Pd) were recorded simultaneously under baseline and hyperemic conditions. Adenosine was the hyperemic agent used; 20 mg intracoronary bolus was given for the left system and 15 mg was given for the right coronary artery. Myocardial fractional flow reserve (FFRmyo) was calculated during hyperemic and basal conditions as the ratio of mean distal coronary pressure (Pd) to mean aortic pressure (Pa). During the angioplasty or stent implantation procedure and total occlusion with balloon, distal pressure was recorded as coronary wedge pressure (CWP: P occlusion). One high-pressure and relatively long inflation was performed to enable reliable and stable coronary wedge pressure recording. As a more valuable parameter, collateral flow index (CFI) was determined by the ratio of simultaneously measured CWP (Pocc: mmHg) to mean aortic pressure (Pa, mmHg, obtained from the guiding catheter) (CFI: CWP/Pa). We neglected the measurement of the central venous pressure because we did not include the cases in which this pressure was expected to be elevated. Angiographic evidence of collateral vessel development has been graded according to Rentrop classification as follows: 0 = no collateral filling; I = filling of side branches of the artery to be perfused by collateral vessels; II = partial filling of the epicardial artery; and III = complete filling. Left ventriculographies were evaluated and scores of the regional walls perfused by the ischemia related artery were graded according to CASS criteria from 0–V as follows: 0 = normal function; I = mild hypokinesia; II = moderate hypokinesia; III = severe hypokinesia; IV = akinesia; and V = dyskinesia. Statistical analysis. Statistical analysis was performed by using SPSS for Windows. Data were expressed as mean ± SD. A p-value Baseline characteristics. The study population was expressed as two groups according to whether they had DM or not. As shown in Tables 1 and 2, the two groups were well matched in terms of baseline clinical and angiographic characteristics. Results of QCA and intracoronary pressure measurements. There was no difference between the two groups with respect to lesion length, reference vessel diameter, regional wall motion scores (Table 2) and mean percent stenosis both before and after stent implantation (Table 3). Basal and hyperemic mean aortic and mean distal pressures both before and after stent implantation were not different between the two groups. Also, mean FFRmyo both before and after stent implantation were not different between the two groups. There was no correlation between angiographically assessed collateral scores and physiologic parameters (CWP, CFI). After revascularization, FFRmyo increased significantly from 0.62 ± 0.10 to 0.91 ± 0.05 (p

1. Chilian WM, Mass HJ, Williams SE, et al. Microvascular occlusion promote coronary collateral growth. Am J Physiol 1990;258:H1103–H11011. 2. Sabri MN, DiSciascio G, Cowley MJ, et al. Coronary collateral recruitment: Functional significance and relation to rate of vessel closure. Am Heart J 1991;121:876–889. 3. Schaper W, Görge G, Wincker B, Schaper J. The collateral circulation in the heart. Prog Cardiovasc Disease 1988;31:55–57. 4. Glasser SP, Selwyn AP, Ganz P. Atherosclerosis: Risk factors and the vascular endothelium. Am Heart J 1996;131:379–384. 5. Schaper W, Sharma HS, Quinker W, et al. Molecular biologic concepts of coronary anastomoses. J Am Coll Cardiol 1990;15:513–518. 6. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors and 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Interventional Trial. Diabetes Care 1993;16:434–444. 7. Smith JW, Marcus FI, Serokman R, for the Multicenter Post-infarction Research Group. Prognosis of patients with diabetes mellitus after acute myocardial infarction. Am J Cardiol 1984;54:718–721. 8. Abbott RD, Donahue RP, Kannel WB, Wilson PF. The impact of diabetes on survival following myocardial infarction in men vs. women: The Framingham study. JAMA 1988;260:3456–3460. 9. Cohen RA. Dysfunction of vascular endothelium in diabetes mellitus. Circulation 1993;87(Suppl V):V67–V76. 10. Gensini GG, daCosta BCB. The coronary collateral circulation in living man. Am J Cardiol 1969;24:393–400. 11. Pijls NHJ, Bech JW, El Gamal HIH, et al. Quantification of recruitable coronary collateral blood flow in conscious humans and its potential to predict future ischemic events. J Am Coll Cardiol 1995;25:1522–1558. 12. Pijls NHJ, Van Son JMA, Kirkeeide RL, et al. Experimental basis of determining maximum coronary, myocardial and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation 1993;87:1354–1367. 13. Seiler C, Fleish M, Garachemani A, et al. Coronary collateral quantization in patients with coronary artery disease using intravascular flow velocity or pressure measurements. J Am Coll Cardiol 1998;32:1272–1279. 14. Van Liebergen RAM, Piek JJ, Koch KT, et al. Quantification of collateral flow in humans: A comparison of angiographic, echocardiographic and hemodynamic variables. J Am Coll Cardiol 1999;33:670–677. 15. Schaper W, Ito WD. Molecular mechanisms of coronary collateral vessel growth. Circ Res 1996;79:911–919. 16. Folkman J, Klagsburn M. Angiogenic factors. Science 1987;235:442–447. 17. Banal S, Jaklish MT, Shou M, et al. Angiographic induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 1994;89:2183–2189. 18. Paranti A, Morbidelli L, Cui XL, et al. Nitric oxide is an upstream signal of vascular endothelial growth factor induced extracellular signal-regulated kinase 1/2 activation in postcapillary endothelium. J Biol Chem 1998;273:4220–4226. 19. Tesfamarium B, Brown ML, Deykin D, Cohen RA. Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. J Clin Invest 1990;85:1167–1172. 20. Williamson JR, Ostrow E, Eades D, et al. Glucose induced microvascular functional changes in non-diabetic rats are stereospecific and prevented by an aldose reductase inhibitor. J Clin Invest 1990;85:1167–1172. 21. Pieper GM, Peiter BA. Amelioration by L-Arginin of a dysfunctional arginine/nitric oxide pathway in diabetic endothelium. J Cardiovascular Pharmacol 1995;25:397–403. 22. Morimoto S, Hiasa Y, Hamai K, et al. Influence factors on coronary collateral development. Kokyu To Junkan 1989;37:1103–1107. 23. Ramirez ML, Fernandez de la Reguera G. Coronary collateral circulation: Its importance and significance in ischemic cardiopathy. Arch Inst Cardiol Mex 1983;53:397–405. 24. Abac? A, Oguzhan A, Kahraman S, et al. Effects of diabetes mellitus on the formation of coronary collateral vessels. Circulation 1999;99:2239–2242. 25. Cohen M, Sherman W, Rentrop KP, Gorlin R. Determinants of collateral filling observed during sudden controlled coronary artery occlusion in human subjects. J Am Coll Cardiol 1989;13:297–303. 26. Pijls NHJ, De Bruyne B. Assessment of collateral blood flow by coronary pressure measurement. In: Coronary Pressure. Kluwer Academic Publishers, 2000: pp. 327–351. 27. Meier B, Lueethy P, Finci L, et al. Coronary wedge pressure in relation to spontaneously visible and recruitable collaterals. Circulation 1987;75:906–913. 28. Schaper J, Weicrauch D. Collateral vessel development in porcine and canine heart. In: Schaper W, Schaper J (eds). Collateral Circulation. Boston MA: Kluwer Academic Publishers, 1993: pp. 65–102.