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Erschienen in: Clinical Research in Cardiology 3/2014

01.03.2014 | Original Paper

Impact of type 2 diabetes mellitus and glucose control on fractional flow reserve measurements in intermediate grade coronary lesions

verfasst von: Sebastian Reith, Simone Battermann, Martin Hellmich, Nikolaus Marx, Mathias Burgmaier

Erschienen in: Clinical Research in Cardiology | Ausgabe 3/2014

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Abstract

Background

Hemodynamic relevance of intermediate grade coronary stenoses is accurately assessed by fractional flow reserve (FFR) measurements. However, the reliability of FFR in patients with type 2 diabetes mellitus (DM) and inadequate glucose control (IGC) is incompletely explored. This study aimed to investigate the impact of DM and IGC on the relationship between FFR measurements and quantitative coronary angiography (QCA)-derived morphological parameters.

Methods

We performed FFR and QCA in 266 intermediate grade lesions of 224 patients (113 non-DM and 111 DM) with stable coronary artery disease. Diabetic patients were categorized into groups with adequate (HbA1C <7 %) and inadequate (HbA1c ≥7 %) glucose control.

Results

Intermediate grade lesions from all-DM versus non-DM patients differed significantly in lesion length (LL) (10.91 ± 5.79 mm versus 9.23 ± 3.85 mm, p = 0.005) and hemodynamic relevance (FFR ≤0.8, 37.7 % versus 24.2 %, p = 0.018). FFR measurements in non-DM, all-DM and DM-IGC patients correlated significantly with percent diameter stenosis (%DS) [non-DM: r 2 = 0.075 (p = 0.007); all-DM: r 2 = 0.254 (p < 0.001), DM-IGC: r 2 = 0.301 (p < 0.001)] and LL [non-DM: r 2 = 0.356; all-DM: r 2 = 0.580, DM-IGC: r 2 = 0.513 (all p < 0.001)]. There was a better correlation between FFR and both %DS (p = 0.022) and LL (p = 0.011) among all-DM compared to non-DM patients. Receiver-operating curve analysis demonstrated that among all QCA-derived parameters LL had the best diagnostic efficacy to predict FFR ≤0.8 for non-DM (AUC 0.911, 95 % CI 0.861–0.960, best cut-off value 9.22 mm), all-DM (AUC 0.967, 95 % CI 0.942–0.991, best cut-off value 9.97 mm) and DM-IGC (AUC 0.960, 95 % CI 0.920–0.999, best cut-off value 9.97 mm) patients.

Conclusion

Our data in intermediate grade lesions suggest that FFR is reliable in DM patients and LL is the best predictor for hemodynamic relevance in patients without and with diabetes, irrespective of the glycemic state.
Literatur
1.
Zurück zum Zitat Tobis J, Azarbal B, Slavin L (2007) Assessment of intermediate severity coronary lesions in the catheterization laboratory. J Am Coll Cardiol 49(8):839–848PubMedCrossRef Tobis J, Azarbal B, Slavin L (2007) Assessment of intermediate severity coronary lesions in the catheterization laboratory. J Am Coll Cardiol 49(8):839–848PubMedCrossRef
2.
Zurück zum Zitat Pijls NH et al (1996) Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med 334(26):1703–1708PubMedCrossRef Pijls NH et al (1996) Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med 334(26):1703–1708PubMedCrossRef
3.
Zurück zum Zitat Kang SJ et al (2012) Usefulness of minimal luminal coronary area determined by intravascular ultrasound to predict functional significance in stable and unstable angina pectoris. Am J Cardiol 109(7):947–953PubMedCrossRef Kang SJ et al (2012) Usefulness of minimal luminal coronary area determined by intravascular ultrasound to predict functional significance in stable and unstable angina pectoris. Am J Cardiol 109(7):947–953PubMedCrossRef
4.
Zurück zum Zitat Briguori C et al (2001) Intravascular ultrasound criteria for the assessment of the functional significance of intermediate coronary artery stenoses and comparison with fractional flow reserve. Am J Cardiol 87(2):136–141PubMedCrossRef Briguori C et al (2001) Intravascular ultrasound criteria for the assessment of the functional significance of intermediate coronary artery stenoses and comparison with fractional flow reserve. Am J Cardiol 87(2):136–141PubMedCrossRef
5.
Zurück zum Zitat Gonzalo N et al (2012) Morphometric assessment of coronary stenosis relevance with optical coherence tomography: a comparison with fractional flow reserve and intravascular ultrasound. J Am Coll Cardiol 59(12):1080–1089PubMedCrossRef Gonzalo N et al (2012) Morphometric assessment of coronary stenosis relevance with optical coherence tomography: a comparison with fractional flow reserve and intravascular ultrasound. J Am Coll Cardiol 59(12):1080–1089PubMedCrossRef
6.
Zurück zum Zitat Reith S et al (2013) Relationship between optical coherence tomography derived intraluminal and intramural criteria and haemodynamic relevance as determined by fractional flow reserve in intermediate coronary stenoses of patients with type 2 diabetes. Heart 99(10):700–707PubMedCrossRef Reith S et al (2013) Relationship between optical coherence tomography derived intraluminal and intramural criteria and haemodynamic relevance as determined by fractional flow reserve in intermediate coronary stenoses of patients with type 2 diabetes. Heart 99(10):700–707PubMedCrossRef
7.
Zurück zum Zitat Iguchi T et al (2013) Impact of lesion length on functional significance in intermediate coronary lesions. Clin Cardiol 36(3):172–177PubMedCrossRef Iguchi T et al (2013) Impact of lesion length on functional significance in intermediate coronary lesions. Clin Cardiol 36(3):172–177PubMedCrossRef
8.
Zurück zum Zitat Jimenez-Quevedo P et al (2005) LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study. Eur Heart J 26(21):2307–2312PubMedCrossRef Jimenez-Quevedo P et al (2005) LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study. Eur Heart J 26(21):2307–2312PubMedCrossRef
9.
Zurück zum Zitat Nahser PJ Jr et al (1995) Maximal coronary flow reserve and metabolic coronary vasodilation in patients with diabetes mellitus. Circulation 91(3):635–640PubMedCrossRef Nahser PJ Jr et al (1995) Maximal coronary flow reserve and metabolic coronary vasodilation in patients with diabetes mellitus. Circulation 91(3):635–640PubMedCrossRef
10.
Zurück zum Zitat Di Carli MF et al (2003) Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol 41(8):1387–1393PubMedCrossRef Di Carli MF et al (2003) Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol 41(8):1387–1393PubMedCrossRef
11.
Zurück zum Zitat Jensen CJ et al (2011) Impact of hyperglycemia at admission in patients with acute ST-segment elevation myocardial infarction as assessed by contrast-enhanced MRI. Clin Res Cardiol 100(8):649–659PubMedCrossRef Jensen CJ et al (2011) Impact of hyperglycemia at admission in patients with acute ST-segment elevation myocardial infarction as assessed by contrast-enhanced MRI. Clin Res Cardiol 100(8):649–659PubMedCrossRef
12.
Zurück zum Zitat Sahinarslan A et al (2009) The reliability of fractional flow reserve measurement in patients with diabetes mellitus. Coron Artery Dis 20(5):317–321PubMedCrossRef Sahinarslan A et al (2009) The reliability of fractional flow reserve measurement in patients with diabetes mellitus. Coron Artery Dis 20(5):317–321PubMedCrossRef
13.
Zurück zum Zitat Dominguez-Franco AJ et al (2008) Long-term prognosis in diabetic patients in whom revascularization is deferred following fractional flow reserve assessment. Rev Esp Cardiol 61(4):352–359PubMedCrossRef Dominguez-Franco AJ et al (2008) Long-term prognosis in diabetic patients in whom revascularization is deferred following fractional flow reserve assessment. Rev Esp Cardiol 61(4):352–359PubMedCrossRef
14.
Zurück zum Zitat Yanagisawa H et al (2004) Application of pressure-derived myocardial fractional flow reserve in assessing the functional severity of coronary artery stenosis in patients with diabetes mellitus. Circ J 68(11):993–998PubMedCrossRef Yanagisawa H et al (2004) Application of pressure-derived myocardial fractional flow reserve in assessing the functional severity of coronary artery stenosis in patients with diabetes mellitus. Circ J 68(11):993–998PubMedCrossRef
15.
Zurück zum Zitat Anderson JL et al (2007) ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 50(7):e1–e157PubMedCrossRef Anderson JL et al (2007) ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 50(7):e1–e157PubMedCrossRef
16.
Zurück zum Zitat Ryden L et al (2013) ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 34(39):3035–3087PubMedCrossRef Ryden L et al (2013) ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 34(39):3035–3087PubMedCrossRef
17.
Zurück zum Zitat Reiber JH et al (1985) Assessment of short-, medium-, and long-term variations in arterial dimensions from computer-assisted quantitation of coronary cineangiograms. Circulation 71(2):280–288PubMedCrossRef Reiber JH et al (1985) Assessment of short-, medium-, and long-term variations in arterial dimensions from computer-assisted quantitation of coronary cineangiograms. Circulation 71(2):280–288PubMedCrossRef
18.
Zurück zum Zitat Tonino PA et al (2009) Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 360(3):213–224PubMedCrossRef Tonino PA et al (2009) Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 360(3):213–224PubMedCrossRef
19.
Zurück zum Zitat Sachs L (1992) Angewandte Statistik Anwendung statistischer Methoden. Springer, Berlin Sachs L (1992) Angewandte Statistik Anwendung statistischer Methoden. Springer, Berlin
20.
21.
Zurück zum Zitat DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44(3):837–845PubMedCrossRef DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44(3):837–845PubMedCrossRef
22.
Zurück zum Zitat Moses JW et al (2006) Drug-eluting stents in the treatment of intermediate lesions: pooled analysis from four randomized trials. J Am Coll Cardiol 47(11):2164–2171PubMedCrossRef Moses JW et al (2006) Drug-eluting stents in the treatment of intermediate lesions: pooled analysis from four randomized trials. J Am Coll Cardiol 47(11):2164–2171PubMedCrossRef
23.
Zurück zum Zitat Tentzeris I et al (2011) Long-term outcome after drug-eluting stent implantation in comparison with bare metal stents: a single centre experience. Clin Res Cardiol 100(3):191–200PubMedCrossRef Tentzeris I et al (2011) Long-term outcome after drug-eluting stent implantation in comparison with bare metal stents: a single centre experience. Clin Res Cardiol 100(3):191–200PubMedCrossRef
24.
Zurück zum Zitat de Waha A et al (2011) Long-term outcome after sirolimus-eluting stents versus bare metal stents in patients with diabetes mellitus: a patient-level meta-analysis of randomized trials. Clin Res Cardiol 100(7):561–570PubMedCrossRef de Waha A et al (2011) Long-term outcome after sirolimus-eluting stents versus bare metal stents in patients with diabetes mellitus: a patient-level meta-analysis of randomized trials. Clin Res Cardiol 100(7):561–570PubMedCrossRef
25.
Zurück zum Zitat Sels JW et al (2011) Fractional flow reserve in unstable angina and non-ST-segment elevation myocardial infarction experience from the FAME (fractional flow reserve versus angiography for multivessel evaluation) study. JACC Cardiovasc Interv 4(11):1183–1189PubMedCrossRef Sels JW et al (2011) Fractional flow reserve in unstable angina and non-ST-segment elevation myocardial infarction experience from the FAME (fractional flow reserve versus angiography for multivessel evaluation) study. JACC Cardiovasc Interv 4(11):1183–1189PubMedCrossRef
26.
Zurück zum Zitat Bishop AH, Samady H (2004) Fractional flow reserve: critical review of an important physiologic adjunct to angiography. Am Heart J 147(5):792–802PubMedCrossRef Bishop AH, Samady H (2004) Fractional flow reserve: critical review of an important physiologic adjunct to angiography. Am Heart J 147(5):792–802PubMedCrossRef
27.
Zurück zum Zitat De Bruyne B et al (2001) Fractional flow reserve in patients with prior myocardial infarction. Circulation 104(2):157–162PubMedCrossRef De Bruyne B et al (2001) Fractional flow reserve in patients with prior myocardial infarction. Circulation 104(2):157–162PubMedCrossRef
28.
Zurück zum Zitat Pilz G et al (2011) Influence of small caliber coronary arteries on the diagnostic accuracy of adenosine stress cardiac magnetic resonance imaging. Clin Res Cardiol 100(3):201–208PubMedCentralPubMedCrossRef Pilz G et al (2011) Influence of small caliber coronary arteries on the diagnostic accuracy of adenosine stress cardiac magnetic resonance imaging. Clin Res Cardiol 100(3):201–208PubMedCentralPubMedCrossRef
29.
Zurück zum Zitat Takiuchi S et al (2002) Hypertension attenuates the efficacy of hypoglycemic therapy for preserving coronary flow reserve in patients with type 2 diabetes. Hypertens Res 25(6):893–900PubMedCrossRef Takiuchi S et al (2002) Hypertension attenuates the efficacy of hypoglycemic therapy for preserving coronary flow reserve in patients with type 2 diabetes. Hypertens Res 25(6):893–900PubMedCrossRef
30.
Zurück zum Zitat Murtagh B et al (2003) Role of incremental doses of intracoronary adenosine for fractional flow reserve assessment. Am Heart J 146(1):99–105PubMedCrossRef Murtagh B et al (2003) Role of incremental doses of intracoronary adenosine for fractional flow reserve assessment. Am Heart J 146(1):99–105PubMedCrossRef
31.
Zurück zum Zitat Casella G et al (2004) Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve? Am Heart J 148(4):590–595PubMedCrossRef Casella G et al (2004) Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve? Am Heart J 148(4):590–595PubMedCrossRef
32.
Zurück zum Zitat De Luca G et al (2011) Effects of increasing doses of intracoronary adenosine on the assessment of fractional flow reserve. JACC Cardiovasc Interv 4(10):1079–1084PubMedCrossRef De Luca G et al (2011) Effects of increasing doses of intracoronary adenosine on the assessment of fractional flow reserve. JACC Cardiovasc Interv 4(10):1079–1084PubMedCrossRef
33.
Zurück zum Zitat Bartunek J et al (1995) Quantitative coronary angiography in predicting functional significance of stenoses in an unselected patient cohort. J Am Coll Cardiol 26(2):328–334PubMedCrossRef Bartunek J et al (1995) Quantitative coronary angiography in predicting functional significance of stenoses in an unselected patient cohort. J Am Coll Cardiol 26(2):328–334PubMedCrossRef
34.
Zurück zum Zitat Brosh D et al (2005) Effect of lesion length on fractional flow reserve in intermediate coronary lesions. Am Heart J 150(2):338–343PubMedCrossRef Brosh D et al (2005) Effect of lesion length on fractional flow reserve in intermediate coronary lesions. Am Heart J 150(2):338–343PubMedCrossRef
35.
Zurück zum Zitat Takayama T, Hodgson JM (2001) Prediction of the physiologic severity of coronary lesions using 3D IVUS: validation by direct coronary pressure measurements. Catheter Cardiovasc Interv 53(1):48–55PubMedCrossRef Takayama T, Hodgson JM (2001) Prediction of the physiologic severity of coronary lesions using 3D IVUS: validation by direct coronary pressure measurements. Catheter Cardiovasc Interv 53(1):48–55PubMedCrossRef
36.
Zurück zum Zitat Costa MA et al (2008) Impact of stent deployment procedural factors on long-term effectiveness and safety of sirolimus-eluting stents (final results of the multicenter prospective STLLR trial). Am J Cardiol 101(12):1704–1711PubMedCrossRef Costa MA et al (2008) Impact of stent deployment procedural factors on long-term effectiveness and safety of sirolimus-eluting stents (final results of the multicenter prospective STLLR trial). Am J Cardiol 101(12):1704–1711PubMedCrossRef
37.
Zurück zum Zitat D’Ascenzo F et al (2012) Incidence and predictors of coronary stent thrombosis: evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses. Int J Cardiol 167(2):575–584PubMedCrossRef D’Ascenzo F et al (2012) Incidence and predictors of coronary stent thrombosis: evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses. Int J Cardiol 167(2):575–584PubMedCrossRef
38.
Zurück zum Zitat Taggart DP (2013)The FREEDOM trial: a definitive answer to coronary artery bypass grafting or stents in patients with diabetes and multivessel coronary artery disease. Eur J Cardiothorac Surg Taggart DP (2013)The FREEDOM trial: a definitive answer to coronary artery bypass grafting or stents in patients with diabetes and multivessel coronary artery disease. Eur J Cardiothorac Surg
39.
Zurück zum Zitat Farkouh ME et al (2012) Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 367(25):2375–2384PubMedCrossRef Farkouh ME et al (2012) Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 367(25):2375–2384PubMedCrossRef
40.
Zurück zum Zitat Corpus RA et al (2004) Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention. J Am Coll Cardiol 43(1):8–14PubMedCrossRef Corpus RA et al (2004) Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention. J Am Coll Cardiol 43(1):8–14PubMedCrossRef
41.
Zurück zum Zitat Akin I et al (2010) Clinical outcomes in diabetic and non-diabetic patients with drug-eluting stents: results from the first phase of the prospective multicenter German DES.DE registry. Clin Res Cardiol 99(6):393–400PubMedCrossRef Akin I et al (2010) Clinical outcomes in diabetic and non-diabetic patients with drug-eluting stents: results from the first phase of the prospective multicenter German DES.DE registry. Clin Res Cardiol 99(6):393–400PubMedCrossRef
43.
Zurück zum Zitat Farhan S et al (2012) Comparison of HbA1c and oral glucose tolerance test for diagnosis of diabetes in patients with coronary artery disease. Clin Res Cardiol 101(8):625–630PubMedCrossRef Farhan S et al (2012) Comparison of HbA1c and oral glucose tolerance test for diagnosis of diabetes in patients with coronary artery disease. Clin Res Cardiol 101(8):625–630PubMedCrossRef
44.
Zurück zum Zitat Doerr R et al (2011) Oral glucose tolerance test and HbA(1)c for diagnosis of diabetes in patients undergoing coronary angiography: (corrected) the silent diabetes study. Diabetologia 54(11):2923–2930PubMedCrossRef Doerr R et al (2011) Oral glucose tolerance test and HbA(1)c for diagnosis of diabetes in patients undergoing coronary angiography: (corrected) the silent diabetes study. Diabetologia 54(11):2923–2930PubMedCrossRef
45.
Zurück zum Zitat Bartnik M et al (2004) The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart. Eur Heart J 25(21):1880–1890PubMedCrossRef Bartnik M et al (2004) The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart. Eur Heart J 25(21):1880–1890PubMedCrossRef
Metadaten
Titel
Impact of type 2 diabetes mellitus and glucose control on fractional flow reserve measurements in intermediate grade coronary lesions
verfasst von
Sebastian Reith
Simone Battermann
Martin Hellmich
Nikolaus Marx
Mathias Burgmaier
Publikationsdatum
01.03.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Research in Cardiology / Ausgabe 3/2014
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-013-0633-7

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