Original Article
Cardiac magnetic resonance imaging myocardial perfusion reserve index assessment in women with microvascular coronary dysfunction and reference controls Chrisandra L. Shufelt1, Louise E. J. Thomson2, Pavel Goykhman1, Megha Agarwal1, Puja K. Mehta1, Tara Sedlak1, Ning Li3, Edward Gill2, Bruce Samuels4, Babak Azabal4, Saibal Kar4, Kamlesh Kothawade1, Margo Minissian1, Piotr Slomka2, Daniel S. Berman2, C. Noel Bairey Merz1 1
Barbra Streisand Women’s Heart Center, 2S. Mark Taper Foundation Imaging Center, 3Biostatistics Center, 4Cedars-Sinai Heart Institute, Cedars-
Sinai Medical Center, Los Angeles, CA, USA Corresponding to: Chrisandra L. Shufelt, MD, MS. Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA. Email: [email protected].
Objective: We sought to comparatively assess cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index (MPRI) in women with confirmed microvascular coronary dysfunction (MCD) cases and reference control women. Background: Women with signs or symptoms of myocardial ischemia in the absence of obstructive coronary artery disease (CAD) frequently have MCD which carries an adverse prognosis. Diagnosis involves invasive coronary reactivity testing (CRT). Adenosine CMRI is a non-invasive test that may be useful for the detection of MCD. Methods: Fifty-three women with MCD confirmed by CRT and 12 age- and estrogen-use matched reference controls underwent adenosine CMRI. CMRI was assessed for MPRI, calculated using the ratio of myocardial blood flow at hyperemia/rest for the whole myocardium and separately for the 16 segments as defined by the American Heart Association. Statistical analysis was performed using repeated measures ANOVA models. Results: Compared to reference controls, MCD cases had lower MPRI values globally and in subendocardial and subepicardial regions (1.63±0.39 vs. 1.98±0.38, P=0.007, 1.51±0.35 vs. 1.84±0.34, P=0.0045, 1.68±0.38 vs. 2.04±0.41, P=0.005, respectively). A perfusion gradient across the myocardium with lower MPRI in the subendocardium compared to the subepicardium was observed for both groups. Conclusions: Women with MCD have lower MPRI measured by perfusion CMRI compared to reference controls. CMRI may be a useful diagnostic modality for MCD. Prospective validation of a diagnostic threshold for MPRI in patients with MCD is needed. Key Words: Cardiac myocardial resonance imaging (CMRI); microvascular coronary dysfunction (MCD); myocardial perfusion reserve index (MPRI) Submitted Jun 25, 2013. Accepted for publication Jul 20, 2013. doi: 10.3978/j.issn.2223-3652.2013.08.02 Scan to your mobile device or view this article at: http://www.thecdt.org/article/view/2666/3559
Introduction
diagnosis of MCD is based on endothelial and non-
Women with signs or symptoms of myocardial ischemia but no obstructive coronary artery disease (CAD) frequently have microvascular coronary dysfunction (MCD). The
endothelial dependent function determined using invasive
© Cardiovascular Diagnosis and Therapy. All rights reserved.
coronary reactivity testing (CRT). Patients with MCD have reduced coronary flow reserve and metabolic evidence of
www.thecdt.org
Cardiovasc Diagn Ther 2013;3(3):153-160
Shufelt et al. CMRI MPRI assessment in women with MCD
154
Scout 0
Stress (Ad) Rest
Cine 5
10
15
20
25
Gad
30
35
DE 40
45
50
Gad Gad
Figure 1 CMRI Protocol. The imaging protocol was completed within 50 minutes and included cine imaging in left ventricular long and short axis imaging planes, three slice first pass perfusion stress and rest imaging and delayed enhancement imaging. Gad, 0.05 mmol/kg gadolinium; Ad, adenosine; DE, delayed enhancement
ischemia (1). In the absence of CAD, MCD can occur due to iatrogenic dysfunction or as a counterpart to traditional coronary risk factors (2). To date, CRT remains the gold standard test for MCD which is an invasive, highly technical test that requires advanced trained interventional cardiologists and can be time consuming. Prior work suggests that adenosine cardiac magnetic resonance imaging (CMRI) may be a useful non-invasive method for detection of MCD (3-5). Global magnetic resonance perfusion imaging, together with ejection fraction, has been found to predict prognosis in women with signs and symptoms of ischemia but no obstructive CAD (6). The diagnosis of MCD carries adverse prognoses including increased rates of cardiovascular death, non-fatal myocardial infarction, stroke, and heart failure (7-10). Adenosine CMRI is a non-invasive imaging technique that may be useful for the detection of perfusion abnormalities consistent with MCD by comparison of rest to vasodilator stress myocardial perfusion. Myocardial perfusion reserve determined by CMRI correlates with invasive coronary flow reserve by Doppler flow wire (11), and CMRI has been found to be highly sensitive for evaluating coronary blood flow (12,13). We evaluated CMRI in patients diagnosed with MCD by CRT (cases) and reference controls using semi-quantitative CMRI myocardial perfusion reserve index (MPRI) analysis. Methods Subjects Fifty-three women with signs and symptoms of ischemic heart disease, ischemia on cardiac stress testing and no obstructive CAD underwent clinically indicated CRT for suspected MCD. Subsequently, all MCD cases and 12 asymptomatic reference controls who were age-, and estrogen-use matched to the case subjects underwent
© Cardiovascular Diagnosis and Therapy. All rights reserved.
CMRI. Reference controls qualified for participation by performing a maximal exercise Bruce protocol treadmill test that was within normal limits and had no traditional cardiac risk factors. All women were recruited from the Women’s Heart Center at the Cedars-Sinai Heart Institute in Los Angeles, California. This study was approved by the Cedars-Sinai internal review board and written informed consent was obtained for all subjects. MCD was defined as endothelial- or non-endothelialdependent vascular function abnormality found by CRT as previously published (9,14). Briefly, all women with signs or symptoms of ischemia underwent coronary angiography; Those with no obstructive CAD (defined as epicardial coronary artery stenosis of
Cardiac magnetic resonance imaging myocardial perfusion reserve index assessment in women with microvascular coronary dysfunction and reference controls Chrisandra L. Shufelt1, Louise E. J. Thomson2, Pavel Goykhman1, Megha Agarwal1, Puja K. Mehta1, Tara Sedlak1, Ning Li3, Edward Gill2, Bruce Samuels4, Babak Azabal4, Saibal Kar4, Kamlesh Kothawade1, Margo Minissian1, Piotr Slomka2, Daniel S. Berman2, C. Noel Bairey Merz1 1
Barbra Streisand Women’s Heart Center, 2S. Mark Taper Foundation Imaging Center, 3Biostatistics Center, 4Cedars-Sinai Heart Institute, Cedars-
Sinai Medical Center, Los Angeles, CA, USA Corresponding to: Chrisandra L. Shufelt, MD, MS. Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA. Email: [email protected].
Objective: We sought to comparatively assess cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index (MPRI) in women with confirmed microvascular coronary dysfunction (MCD) cases and reference control women. Background: Women with signs or symptoms of myocardial ischemia in the absence of obstructive coronary artery disease (CAD) frequently have MCD which carries an adverse prognosis. Diagnosis involves invasive coronary reactivity testing (CRT). Adenosine CMRI is a non-invasive test that may be useful for the detection of MCD. Methods: Fifty-three women with MCD confirmed by CRT and 12 age- and estrogen-use matched reference controls underwent adenosine CMRI. CMRI was assessed for MPRI, calculated using the ratio of myocardial blood flow at hyperemia/rest for the whole myocardium and separately for the 16 segments as defined by the American Heart Association. Statistical analysis was performed using repeated measures ANOVA models. Results: Compared to reference controls, MCD cases had lower MPRI values globally and in subendocardial and subepicardial regions (1.63±0.39 vs. 1.98±0.38, P=0.007, 1.51±0.35 vs. 1.84±0.34, P=0.0045, 1.68±0.38 vs. 2.04±0.41, P=0.005, respectively). A perfusion gradient across the myocardium with lower MPRI in the subendocardium compared to the subepicardium was observed for both groups. Conclusions: Women with MCD have lower MPRI measured by perfusion CMRI compared to reference controls. CMRI may be a useful diagnostic modality for MCD. Prospective validation of a diagnostic threshold for MPRI in patients with MCD is needed. Key Words: Cardiac myocardial resonance imaging (CMRI); microvascular coronary dysfunction (MCD); myocardial perfusion reserve index (MPRI) Submitted Jun 25, 2013. Accepted for publication Jul 20, 2013. doi: 10.3978/j.issn.2223-3652.2013.08.02 Scan to your mobile device or view this article at: http://www.thecdt.org/article/view/2666/3559
Introduction
diagnosis of MCD is based on endothelial and non-
Women with signs or symptoms of myocardial ischemia but no obstructive coronary artery disease (CAD) frequently have microvascular coronary dysfunction (MCD). The
endothelial dependent function determined using invasive
© Cardiovascular Diagnosis and Therapy. All rights reserved.
coronary reactivity testing (CRT). Patients with MCD have reduced coronary flow reserve and metabolic evidence of
www.thecdt.org
Cardiovasc Diagn Ther 2013;3(3):153-160
Shufelt et al. CMRI MPRI assessment in women with MCD
154
Scout 0
Stress (Ad) Rest
Cine 5
10
15
20
25
Gad
30
35
DE 40
45
50
Gad Gad
Figure 1 CMRI Protocol. The imaging protocol was completed within 50 minutes and included cine imaging in left ventricular long and short axis imaging planes, three slice first pass perfusion stress and rest imaging and delayed enhancement imaging. Gad, 0.05 mmol/kg gadolinium; Ad, adenosine; DE, delayed enhancement
ischemia (1). In the absence of CAD, MCD can occur due to iatrogenic dysfunction or as a counterpart to traditional coronary risk factors (2). To date, CRT remains the gold standard test for MCD which is an invasive, highly technical test that requires advanced trained interventional cardiologists and can be time consuming. Prior work suggests that adenosine cardiac magnetic resonance imaging (CMRI) may be a useful non-invasive method for detection of MCD (3-5). Global magnetic resonance perfusion imaging, together with ejection fraction, has been found to predict prognosis in women with signs and symptoms of ischemia but no obstructive CAD (6). The diagnosis of MCD carries adverse prognoses including increased rates of cardiovascular death, non-fatal myocardial infarction, stroke, and heart failure (7-10). Adenosine CMRI is a non-invasive imaging technique that may be useful for the detection of perfusion abnormalities consistent with MCD by comparison of rest to vasodilator stress myocardial perfusion. Myocardial perfusion reserve determined by CMRI correlates with invasive coronary flow reserve by Doppler flow wire (11), and CMRI has been found to be highly sensitive for evaluating coronary blood flow (12,13). We evaluated CMRI in patients diagnosed with MCD by CRT (cases) and reference controls using semi-quantitative CMRI myocardial perfusion reserve index (MPRI) analysis. Methods Subjects Fifty-three women with signs and symptoms of ischemic heart disease, ischemia on cardiac stress testing and no obstructive CAD underwent clinically indicated CRT for suspected MCD. Subsequently, all MCD cases and 12 asymptomatic reference controls who were age-, and estrogen-use matched to the case subjects underwent
© Cardiovascular Diagnosis and Therapy. All rights reserved.
CMRI. Reference controls qualified for participation by performing a maximal exercise Bruce protocol treadmill test that was within normal limits and had no traditional cardiac risk factors. All women were recruited from the Women’s Heart Center at the Cedars-Sinai Heart Institute in Los Angeles, California. This study was approved by the Cedars-Sinai internal review board and written informed consent was obtained for all subjects. MCD was defined as endothelial- or non-endothelialdependent vascular function abnormality found by CRT as previously published (9,14). Briefly, all women with signs or symptoms of ischemia underwent coronary angiography; Those with no obstructive CAD (defined as epicardial coronary artery stenosis of
