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Journal of Cardiovascular Magnetic Resonance
Published in: Journal of Cardiovascular Magnetic Resonance 1/2017

Open Access 01-01-2017 | Research

Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study

Authors: Naja Dam Mygind, Marie Mide Michelsen, Adam Pena, Abbas Ali Qayyum, Daria Frestad, Thomas Emil Christensen, Adam Ali Ghotbi, Nynne Dose, Rebekka Faber, Niels Vejlstrup, Philip Hasbak, Andreas Kjaer, Eva Prescott, Jens Kastrup, the steering committee of the iPower study

Published in: Journal of Cardiovascular Magnetic Resonance | Issue 1/2017

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Abstract

Background

Even in absence of obstructive coronary artery disease women with angina pectoris have a poor prognosis possibly due to coronary microvascular disease. Coronary microvascular disease can be assessed by transthoracic Doppler echocardiography measuring coronary flow velocity reserve (CFVR) and by positron emission tomography measuring myocardial blood flow reserve (MBFR). Diffuse myocardial fibrosis can be assessed by cardiovascular magnetic resonance (CMR) T1 mapping. We hypothesized that coronary microvascular disease is associated with diffuse myocardial fibrosis.

Methods

Women with angina, a clinically indicated coronary angiogram with <50 % stenosis and no diabetes were included. CFVR was measured using dipyridamole (0.84 mg/kg) and MBFR using adenosine (0.84 mg/kg). Focal fibrosis was assessed by 1.5 T CMR late gadolinium enhancement (0.1 mmol/kg) and diffuse myocardial fibrosis by T1 mapping using a modified Look-Locker pulse sequence measuring T1 and extracellular volume fraction (ECV).

Results

CFVR and CMR were performed in 64 women, mean (SD) age 62.5 (8.3) years. MBFR was performed in a subgroup of 54 (84 %) of these women. Mean native T1 was 1023 (86) and ECV (%) was 33.7 (3.5); none had focal fibrosis. Median (IQR) CFVR was 2.3 (1.9; 2.7), 23 (36 %) had CFVR < 2 indicating coronary microvascular disease, and median MBFR was 2.7 (2.2; 3.0) and 19 (35 %) had a MBFR value below 2.5. No significant correlations were found between CFVR and ECV or native T1 (R 2  = 0.02; p = 0.27 and R 2  = 0.004; p = 0.61, respectively). There were also no correlations between MBFR and ECV or native T1 (R 2  = 0.1; p = 0.13 and R 2  = 0.004, p = 0.64, respectively). CFVR and MBFR were correlated to hypertension and heart rate.

Conclusion

In women with angina and no obstructive coronary artery disease we found no association between measures of coronary microvascular disease and myocardial fibrosis, suggesting that myocardial ischemia induced by coronary microvascular disease does not elicit myocardial fibrosis in this population. The examined parameters seem to provide independent information about myocardial and coronary disease.
Literature
1.
Jespersen L, Hvelplund A, Abildstrom SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734–44.CrossRefPubMed
2.
Jespersen L, Abildstrom SZ, Hvelplund A, Prescott E. Persistent angina: highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol. 2013;102:571–81.CrossRefPubMed
3.
Sicari R, Rigo F, Cortigiani L, Gherardi S, Galderisi M, Picano E. Additive prognostic value of coronary flow reserve in patients with chest pain syndrome and normal or near-normal coronary arteries. Am J Cardiol. 2009;103:626–31.CrossRefPubMed
4.
5.
Pepine CJ, Anderson RD, Sharaf BL, et al. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women’s Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010;55:2825–32.CrossRefPubMedPubMedCentral
6.
Meimoun P, Tribouilloy C. Non-invasive assessment of coronary flow and coronary flow reserve by transthoracic Doppler echocardiography: a magic tool for the real world. Eur J Echocardiogr. 2008;9:449–57.CrossRefPubMed
7.
Cortigiani L, Rigo F, Gherardi S, et al. Prognostic effect of coronary flow reserve in women versus men with chest pain syndrome and normal dipyridamole stress echocardiography. Am J Cardiol. 2010;106:1703–8.CrossRefPubMed
8.
Reis SE, Holubkov R, Lee JS, et al. Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease. Results from the pilot phase of the Women’s Ischemia Syndrome Evaluation (WISE) study. J Am Coll Cardiol. 1999;33:1469–75.CrossRefPubMed
9.
Murthy VL, Naya M, Foster CR, et al. Improved cardiac risk assessment with noninvasive measures of coronary flow reserve. Circulation. 2011;124:2215–24.CrossRefPubMedPubMedCentral
10.
von Scholten BJ, Hasbak P, Christensen TE, et al. Cardiac (82)Rb PET/CT for fast and non-invasive assessment of microvascular function and structure in asymptomatic patients with type 2 diabetes. Diabetologia. 2016;59:371–8.CrossRef
11.
12.
Fearon WF, Balsam LB, Farouque HM, et al. Novel index for invasively assessing the coronary microcirculation. Circulation. 2003;107:3129–32.CrossRefPubMed
13.
Saraste M, Koskenvuo J, Knuuti J, et al. Coronary flow reserve: measurement with transthoracic Doppler echocardiography is reproducible and comparable with positron emission tomography. Clin Physiol. 2001;21:114–22.CrossRefPubMed
14.
Lethen H, Tries P, Kersting S, Lambertz H. Validation of noninvasive assessment of coronary flow velocity reserve in the right coronary artery. A comparison of transthoracic echocardiographic results with intracoronary Doppler flow wire measurements. Eur Heart J. 2003;24:1567–75.CrossRefPubMed
15.
Caiati C, Montaldo C, Zedda N, et al. Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire. J Am Coll Cardiol. 1999;34:1193–200.CrossRefPubMed
16.
Hozumi T, Yoshida K, Akasaka T, et al. Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique. J Am Coll Cardiol. 1998;32:1251–9.CrossRefPubMed
17.
Hildick-Smith DJ, Maryan R, Shapiro LM. Assessment of coronary flow reserve by adenosine transthoracic echocardiography: validation with intracoronary Doppler. J Am Soc Echocardiogr. 2002;15:984–90.CrossRefPubMed
18.
Kaufmann PA, Namdar M, Matthew F, et al. Novel doppler assessment of intracoronary volumetric flow reserve: validation against PET in patients with or without flow-dependent vasodilation. J Nucl Med. 2005;46:1272–7.PubMed
19.
20.
Flett AS, Hayward MP, Ashworth MT, et al. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010;122:138–44.CrossRefPubMed
21.
Miller CA, Naish JH, Bishop P, et al. Comprehensive validation of cardiovascular magnetic resonance techniques for the assessment of myocardial extracellular volume. Circ Cardiovasc Imaging. 2013;6:373–83.CrossRefPubMed
22.
Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000;343:1445–53.CrossRefPubMed
23.
Higgins DM, Ridgway JP, Radjenovic A, Sivananthan UM, Smith MA. T1 measurement using a short acquisition period for quantitative cardiac applications. Med Phys. 2005;32:1738–46.CrossRefPubMed
24.
Moon JC, Messroghli DR, Kellman P, et al. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson. 2013;15:92.CrossRefPubMedPubMedCentral
25.
Prescott E, Abildstrom SZ, Aziz A, et al. Improving diagnosis and treatment of women with angina pectoris and microvascular disease: the iPOWER study design and rationale. Am Heart J. 2014;167:452–8.CrossRefPubMed
26.
Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837–47.CrossRefPubMed
27.
Fifth Joint Task Force of the European Society of Cardiology; European Association of Echocardiography; European Association of Percutaneous Cardiovascular Interventions; European Heart Rhythm Association; Heart Failure Association; European Association for Cardiovascular Prevention & Rehabilitation; European Atherosclerosis Society; International Society of Behavioural Medicine; European Stroke Organisation; European Society of Hypertension; European Association for the Study of Diabetes; European Society of General Practice/Family Medicine; International Diabetes Federation Europe; European Heart Network. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur J Prev Cardiol. 2012;19:585–667.CrossRef
28.
Lim HE, Shim WJ, Rhee H, et al. Assessment of coronary flow reserve with transthoracic Doppler echocardiography: comparison among adenosine, standard-dose dipyridamole, and high-dose dipyridamole. J Am Soc Echocardiogr. 2000;13:264–70.CrossRefPubMed
29.
Picano E. Stress Echocardiography. 5th Edition ed. Springer-Verlag: Berlin, 2009.
30.
Michelsen MM, Mygind ND, Pena A, et al. Peripheral reactive hyperemia index and coronary microvascular function in women with no obstructive CAD: the iPOWER study. JACC Cardiovasc Imaging. 2016;9:411–7.CrossRefPubMed
31.
Mygind ND, Michelsen MM, Pena A, et al. Coronary microvascular function and cardiovascular risk factors in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study. J Am Heart Assoc. 2016;5(3):e003064.CrossRefPubMedPubMedCentral
32.
Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Int J Cardiovasc Imaging. 2002;18:539–42.PubMed
33.
Sdringola S, Johnson NP, Kirkeeide RL, Cid E, Gould KL. Impact of unexpected factors on quantitative myocardial perfusion and coronary flow reserve in young, asymptomatic volunteers. JACC Cardiovasc Imaging. 2011;4:402–12.CrossRefPubMed
34.
Manabe O, Yoshinaga K, Katoh C, Naya M, deKemp RA, Tamaki N. Repeatability of rest and hyperemic myocardial blood flow measurements with 82Rb dynamic PET. J Nucl Med. 2009;50:68–71.CrossRefPubMed
35.
El FG, Kardan A, Sitek A, et al. Reproducibility and accuracy of quantitative myocardial blood flow assessment with (82)Rb PET: comparison with (13)N-ammonia PET. J Nucl Med. 2009;50:1062–71.CrossRef
36.
Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med. 2004;52:141–6.CrossRefPubMed
37.
Messroghli DR, Plein S, Higgins DM, et al. Human myocardium: single-breath-hold MR T1 mapping with high spatial resolution--reproducibility study. Radiology. 2006;238:1004–12.CrossRefPubMed
38.
Schulz-Menger J, Bluemke DA, Bremerich J, et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. J Cardiovasc Magn Reson. 2013;15:35.CrossRefPubMedPubMedCentral
39.
Olivotto I, Maron MS, Autore C, et al. Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2008;52:559–66.CrossRefPubMed
40.
Ng AC, Auger D, Delgado V, et al. Association between diffuse myocardial fibrosis by cardiac magnetic resonance contrast-enhanced T(1) mapping and subclinical myocardial dysfunction in diabetic patients: a pilot study. Circ Cardiovasc Imaging. 2012;5:51–9.CrossRefPubMed
41.
42.
Yi CJ, Wu CO, Tee M, et al. The association between cardiovascular risk and cardiovascular magnetic resonance measures of fibrosis: the Multi-Ethnic Study of Atherosclerosis (MESA). J Cardiovasc Magn Reson. 2015;17:15.CrossRefPubMedPubMedCentral
43.
Liu CY, Liu YC, Wu C, et al. Evaluation of age-related interstitial myocardial fibrosis with cardiac magnetic resonance contrast-enhanced T1 mapping: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2013;62:1280–7.CrossRefPubMed
44.
Sado DM, Flett AS, Banypersad SM, et al. Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease. Heart. 2012;98:1436–41.CrossRefPubMed
45.
Choi EY, Hwang SH, Yoon YW, et al. Correction with blood T1 is essential when measuring post-contrast myocardial T1 value in patients with acute myocardial infarction. J Cardiovasc Magn Reson. 2013;15:11.CrossRefPubMedPubMedCentral
46.
Graf S, Khorsand A, Gwechenberger M, et al. Typical chest pain and normal coronary angiogram: cardiac risk factor analysis versus PET for detection of microvascular disease. J Nucl Med. 2007;48:175–81.PubMed
47.
Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A et al. 2013 ESC guidelines on the management of stable coronary artery disease-addenda. Eur. Heart J. 1-32. 2013. 23-10-2015. Ref Type: Online Source.
48.
Sade LE, Eroglu S, Bozbas H, et al. Relation between epicardial fat thickness and coronary flow reserve in women with chest pain and angiographically normal coronary arteries. Atherosclerosis. 2009;204:580–5.CrossRefPubMed
49.
Reis SE, Holubkov R, Conrad Smith AJ, et al. Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J. 2001;141:735–41.CrossRefPubMed
50.
Tona F, Serra R, Di AL, et al. Systemic inflammation is related to coronary microvascular dysfunction in obese patients without obstructive coronary disease. Nutr Metab Cardiovasc Dis. 2014;24:447–53.CrossRefPubMed
51.
Tuccillo B, Accadia M, Rumolo S, et al. Factors predicting coronary flow reserve impairment in patients evaluated for chest pain: an ultrasound study. J Cardiovasc Med (Hagerstown). 2008;9:251–5.CrossRef
Metadata
Title
Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study
Authors
Naja Dam Mygind
Marie Mide Michelsen
Adam Pena
Abbas Ali Qayyum
Daria Frestad
Thomas Emil Christensen
Adam Ali Ghotbi
Nynne Dose
Rebekka Faber
Niels Vejlstrup
Philip Hasbak
Andreas Kjaer
Eva Prescott
Jens Kastrup
the steering committee of the iPower study
Publication date
01-01-2017
Publisher
BioMed Central
Published in
Journal of Cardiovascular Magnetic Resonance / Issue 1/2017
Electronic ISSN: 1532-429X
DOI
https://doi.org/10.1186/s12968-016-0295-5

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