Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study.
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 (R2= 0.02; p = 0.27 and R2= 0.004; p = 0.61, respectively). There were also no correlations between MBFR and ECV or native T1 (R2= 0.1; p = 0.13 and R2= 0.004, p = 0.64, respectively). CFVR and MBFR were correlated to hypertension and heart rate.


CONCLUSIONS
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.
Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. naja.dam.mygind.02@regionh.dk.|Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. naja.dam.mygind.02@regionh.dk.
Naja Dam
ND
Mygind
Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Marie Mide
MM
Michelsen
Department of Cardiology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Adam
A
Pena
Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Abbas Ali
AA
Qayyum
Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
Daria
D
Frestad
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Thomas Emil
TE
Christensen
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Adam Ali
AA
Ghotbi
Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Nynne
N
Dose
Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Rebekka
R
Faber
Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Niels
N
Vejlstrup
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Philip
P
Hasbak
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Andreas
A
Kjaer
Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Eva
E
Prescott
Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jens
J
Kastrup
D000368:Aged; D000787:Angina Pectoris / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D003287:Contrast Media / Q000008:administration & dosage; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003718:Denmark; D015150:Echocardiography, Doppler; D005260:Female; D005355:Fibrosis; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008833:Microcirculation; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009206:Myocardium / Q000473:pathology*; D009942:Organometallic Compounds / Q000008:administration & dosage; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D014665:Vasodilator Agents / Q000008:administration & dosage; D016387:Women's Health
D003287:Contrast Media; D009942:Organometallic Compounds; D014665:Vasodilator Agents; C090600:gadobutrol
Angina pectoris; Cardiovascular magnetic resonance; Coronary flow velocity reserve; Diffuse fibrosis; Doppler echocardiography; Extracellular volume; Microvascular dysfunction; Positron emission tomography; T1 mapping; Women