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Extensive coronary calcification compromises myocardial perfusion in the absence of high grade stenosis
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Abstracts / Atherosclerosis 235 (2014) e27–e83
54 - Imaging of coronary arteries or the heart EAS-0026. EFFECT OF CORONARY CALCIUM SCORE ON SUBENDOCARDIAL FUNCTION IN PATIENTS WITH SYNDROME X: A TISSUE DOPPLER DOBUTAMINE STRESS ECHOCARDIOGRAPHY STUDY T. Bengrid MD a, Y. Zhao MD b, M.Y. Henein MD a a Umeå Heart Centre, Umea University, Umea, Sweden; Department, Beijing Anzhen Hospital, Beijing, China
b
Ultrasound
Objectives: Syndrome X patients remain a clinical challenge in their management. We aimed to determine the relationship between coronary calcification and stress changes in subendocardial function as shown by left ventricular (LV) long axis amplitude and systolic and diastolic velocities. Methods: We examined 35 patients with Syndrome X (24 female, mean age 62 years), had> 1mm ST shift on exercise test but no obstructive disease. No patient had prior coronary event, valve disease or LVEF <55%. All patients underwent dobutamine stress echocardiography (DSE) including Mmode and tissue Doppler and CT coronary calcium scoring CAC) using a multidetector CT system Results: LV long axis amplitude increased at septal site (from 13.12 to 14.82.6 mm, P¼0.003), but failed to do so at the lateral site (from 14.72.8 to 15.23.5 mm, P¼0.5). Systolic velocities (s’) increased (from 7.92.6 to 12.83.5 cm/s, and from 7.21.5 to 12.42.2 cm/s, P¼0.0001 for both), at the two sites, respectively. However, early diastolic velocities (e’) failed to increase (from 9.62.9 to 10.52.6 cm/s (P¼0.2) and from 8.21.6 to 8.12.2 cm/s (P¼0.8) as it does in normals. CAC range was 0-1356 (mean 205.49). No relationship between CAC score and any of the long axis measurements. Conclusion: In a group of patients with syndrome X and normal resting LV size and function systolic and diastolic long axis ‘subendocardial’ function including amplitude and diastolic velocities, at peak stress were significantly abnormal. Since these disturbances are independent of the extent of CAC calcification, they may suggest an evidence for microcirculation disease, which is likely to compromise early diastolic coronary circulation. 54 - Imaging of coronary arteries or the heart EAS-0077. EXTENSIVE CORONARY CALCIFICATION COMPROMISES MYOCARDIAL PERFUSION IN THE ABSENCE OF HIGH GRADE STENOSIS M.Y. Heneina, T. Bengrida, N. Rachela, Y. Zhaob, B. Johanssona, A. Schmermundc a Department of Public Health and Clinical Medicine and Heart Centre, Umeå University, Umea, Sweden; b Ultrasound Department, Capital Medical University, Beijing, China; c Medicine, Bethanien Hospital, Frankfurt, Germany
Objectives: To evaluate the relationship between coronary artery calcification (CAC) assessed by multi-detector computed tomography (MDCT) and myocardial perfusion assessed by cardiac magnetic resonance imaging (CMR) in symptomatic patients. Methods: Retrospective analysis of 120 patients (age 65.18.9 years, 88 males) who presented with chest pain to Bethanien Hospital, Germany, who underwent CAC scoring using MDCT, CMR and conventional coronary angiography. Patients were divided into high grade (HG) stenosis (n¼67, age 65.19.4 years) and no HG stenosis (n¼53, age 65.18.6 years) Results: Of the 59 (49.2%) patients with a perfusion defect on CMR, 39 (66.1%) had HG stenosis and 20 (33.9%) no-HG stenosis (p¼0.018). Thirty-four (28.3%) patients had a perfusion defect at rest, 25 of whom (73.5%) had HG stenosis and 9(26.5%) had no-HG stenosis (p¼0.011). Twenty-five (20.8%) patients had reversible perfusion defects with stress, but with no relationship to the presence of HG stenosis (p¼0.58). At rest, the incidence of HG stenosis and perfusion defects had a linear
trend (p¼0.002). Furthermore, combining resting and stress myocardial perfusion defects correlated with the presence of HG stenosis (p¼0.02). CAC differed in the two groups with perfusion defects according to rest or stress (p¼0.006), and correlated only with stress (p¼0.04) findings. In patients with no-HG stenosis, the presence of CAC correlated only with stress perfusion defects (p¼0.019) and a CAC score >0 was associated with a higher incidence of defects compared with a CAC score ¼ 0 (p¼0.03), at rest and with stress. A CAC score >1000 was associated with a higher incidence of perfusion defects compared to a score p¼0.009) Conclusion: In symptomatic patients, extensive CAC is related to the extent of stress-induced reversible myocardial perfusion abnormalities suggesting compromised flow reserve as a potential mechanism. These findings support the important role of CAC score measurement in such patients, given the known prognostic value of both CAC and myocardial perfusion 54 - Imaging of coronary arteries or the heart EAS-0585. SIGNIFICANT ACCUMULATION OF OXLDL/BETA2-GLYCOPROTEIN I COMPLEXES IN ARTERIAL LESIONS OF WHHL RABBITS: PET/CT IMAGING USING AN AUTO ANTIBODY'S SCFV VARIANT T. Sasakia, Y. Matsunamia, F. Takenakaa, S. Kitab, H. Hiranoc, L. Shend, K. Kobayashia, E. Matsuuraa a
Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; b IVD Development Department, Medical and Biological Laboratories Co Ltd, Ina, Japan; c Engineering Department, SHI Accelerator Service Ltd, Tokyo, Japan; d Technology Research Laboratory, Shimadzu Corporation, kyoto, Japan Objectives: The oxidative modification of LDL and its interaction with b2glycoprotein I (oxLDL/b2GPI complexes) in the arterial walls play a central role in the development of atherosclerotic lesions. We have developed a IgG antibody specific for oxLDL/bGPI complexes to be used as an immunologic probe for the non-invasive detection of atherosclerotic plaques. The aim of the study was to assess the clinical utility of a variant of the antibody as a PET/CT in vivo imaging probe in the diagnosis and management for atherothrombotic cardiovascular diseases (CVD), as well as to clarify its atherogenic role. Methods: An immuno-reactive single chain fragment (scFv) and its probes were prepared by radiolabeling with 64Cu via DOTA. The probes were injected intravenously into the Watanabe heritable hyperlipidemic (WHHL) rabbits for in vivo imaging and post-mortem examinations. The blood samples were collected from all rabbits and serum levels of oxLDL/ b2GPI complexes and IgG/IgM titers against oxLDL/b2GPI complexes were measured. Results: WHHL rabbits had significantly higher plasma levels of oxLDL/ b2GPI complexes as compared to controls, while IgG/IgM titers of antioxLDL/b2GPI complexes were not raised. Immunohistochemical staining of atherosclerotic plaques demonstrated that scFv co-localized with macrophages and lipid deposits. The area of plaques in aortic arch was significantly larger than plaques in thoracic and abdominal segments. Autoradiographic and bio-distribution analysis of 64Cu-laeled scFv deposition confirmed the significant antibody accumulation in aortic arch (1.4 to 2.8-fold) of the WHHL rabbits. The PET/CT fusion images clearly demonstrated aortic arch lesions only in the WHHL rabbits. Conclusion: Our results demonstrated that the scFv was specific and preferentially accumulated in atherosclerotic plaques capable of providing an accurate in vivo imaging detection of the lesion. The scFv (a variant lacking the Fc region) can be used as a probe suitable for clinical PET imaging of atherosclerosis with high enough sensitivity and specificity. 55 - Intima media thickness and other imaging of peripheral arteries EAS-0945. RELATIONSHIP BETWEEN TRIGLICERYDE TO HIGH DENSITY LIPOPROTEIN CHOLESTEROL RATIO AND CAROTID INTIMA MEDIA THICKNESS IN ADOLESCENTS
Abstracts / Atherosclerosis 235 (2014) e27–e83
54 - Imaging of coronary arteries or the heart EAS-0026. EFFECT OF CORONARY CALCIUM SCORE ON SUBENDOCARDIAL FUNCTION IN PATIENTS WITH SYNDROME X: A TISSUE DOPPLER DOBUTAMINE STRESS ECHOCARDIOGRAPHY STUDY T. Bengrid MD a, Y. Zhao MD b, M.Y. Henein MD a a Umeå Heart Centre, Umea University, Umea, Sweden; Department, Beijing Anzhen Hospital, Beijing, China
b
Ultrasound
Objectives: Syndrome X patients remain a clinical challenge in their management. We aimed to determine the relationship between coronary calcification and stress changes in subendocardial function as shown by left ventricular (LV) long axis amplitude and systolic and diastolic velocities. Methods: We examined 35 patients with Syndrome X (24 female, mean age 62 years), had> 1mm ST shift on exercise test but no obstructive disease. No patient had prior coronary event, valve disease or LVEF <55%. All patients underwent dobutamine stress echocardiography (DSE) including Mmode and tissue Doppler and CT coronary calcium scoring CAC) using a multidetector CT system Results: LV long axis amplitude increased at septal site (from 13.12 to 14.82.6 mm, P¼0.003), but failed to do so at the lateral site (from 14.72.8 to 15.23.5 mm, P¼0.5). Systolic velocities (s’) increased (from 7.92.6 to 12.83.5 cm/s, and from 7.21.5 to 12.42.2 cm/s, P¼0.0001 for both), at the two sites, respectively. However, early diastolic velocities (e’) failed to increase (from 9.62.9 to 10.52.6 cm/s (P¼0.2) and from 8.21.6 to 8.12.2 cm/s (P¼0.8) as it does in normals. CAC range was 0-1356 (mean 205.49). No relationship between CAC score and any of the long axis measurements. Conclusion: In a group of patients with syndrome X and normal resting LV size and function systolic and diastolic long axis ‘subendocardial’ function including amplitude and diastolic velocities, at peak stress were significantly abnormal. Since these disturbances are independent of the extent of CAC calcification, they may suggest an evidence for microcirculation disease, which is likely to compromise early diastolic coronary circulation. 54 - Imaging of coronary arteries or the heart EAS-0077. EXTENSIVE CORONARY CALCIFICATION COMPROMISES MYOCARDIAL PERFUSION IN THE ABSENCE OF HIGH GRADE STENOSIS M.Y. Heneina, T. Bengrida, N. Rachela, Y. Zhaob, B. Johanssona, A. Schmermundc a Department of Public Health and Clinical Medicine and Heart Centre, Umeå University, Umea, Sweden; b Ultrasound Department, Capital Medical University, Beijing, China; c Medicine, Bethanien Hospital, Frankfurt, Germany
Objectives: To evaluate the relationship between coronary artery calcification (CAC) assessed by multi-detector computed tomography (MDCT) and myocardial perfusion assessed by cardiac magnetic resonance imaging (CMR) in symptomatic patients. Methods: Retrospective analysis of 120 patients (age 65.18.9 years, 88 males) who presented with chest pain to Bethanien Hospital, Germany, who underwent CAC scoring using MDCT, CMR and conventional coronary angiography. Patients were divided into high grade (HG) stenosis (n¼67, age 65.19.4 years) and no HG stenosis (n¼53, age 65.18.6 years) Results: Of the 59 (49.2%) patients with a perfusion defect on CMR, 39 (66.1%) had HG stenosis and 20 (33.9%) no-HG stenosis (p¼0.018). Thirty-four (28.3%) patients had a perfusion defect at rest, 25 of whom (73.5%) had HG stenosis and 9(26.5%) had no-HG stenosis (p¼0.011). Twenty-five (20.8%) patients had reversible perfusion defects with stress, but with no relationship to the presence of HG stenosis (p¼0.58). At rest, the incidence of HG stenosis and perfusion defects had a linear
trend (p¼0.002). Furthermore, combining resting and stress myocardial perfusion defects correlated with the presence of HG stenosis (p¼0.02). CAC differed in the two groups with perfusion defects according to rest or stress (p¼0.006), and correlated only with stress (p¼0.04) findings. In patients with no-HG stenosis, the presence of CAC correlated only with stress perfusion defects (p¼0.019) and a CAC score >0 was associated with a higher incidence of defects compared with a CAC score ¼ 0 (p¼0.03), at rest and with stress. A CAC score >1000 was associated with a higher incidence of perfusion defects compared to a score p¼0.009) Conclusion: In symptomatic patients, extensive CAC is related to the extent of stress-induced reversible myocardial perfusion abnormalities suggesting compromised flow reserve as a potential mechanism. These findings support the important role of CAC score measurement in such patients, given the known prognostic value of both CAC and myocardial perfusion 54 - Imaging of coronary arteries or the heart EAS-0585. SIGNIFICANT ACCUMULATION OF OXLDL/BETA2-GLYCOPROTEIN I COMPLEXES IN ARTERIAL LESIONS OF WHHL RABBITS: PET/CT IMAGING USING AN AUTO ANTIBODY'S SCFV VARIANT T. Sasakia, Y. Matsunamia, F. Takenakaa, S. Kitab, H. Hiranoc, L. Shend, K. Kobayashia, E. Matsuuraa a
Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; b IVD Development Department, Medical and Biological Laboratories Co Ltd, Ina, Japan; c Engineering Department, SHI Accelerator Service Ltd, Tokyo, Japan; d Technology Research Laboratory, Shimadzu Corporation, kyoto, Japan Objectives: The oxidative modification of LDL and its interaction with b2glycoprotein I (oxLDL/b2GPI complexes) in the arterial walls play a central role in the development of atherosclerotic lesions. We have developed a IgG antibody specific for oxLDL/bGPI complexes to be used as an immunologic probe for the non-invasive detection of atherosclerotic plaques. The aim of the study was to assess the clinical utility of a variant of the antibody as a PET/CT in vivo imaging probe in the diagnosis and management for atherothrombotic cardiovascular diseases (CVD), as well as to clarify its atherogenic role. Methods: An immuno-reactive single chain fragment (scFv) and its probes were prepared by radiolabeling with 64Cu via DOTA. The probes were injected intravenously into the Watanabe heritable hyperlipidemic (WHHL) rabbits for in vivo imaging and post-mortem examinations. The blood samples were collected from all rabbits and serum levels of oxLDL/ b2GPI complexes and IgG/IgM titers against oxLDL/b2GPI complexes were measured. Results: WHHL rabbits had significantly higher plasma levels of oxLDL/ b2GPI complexes as compared to controls, while IgG/IgM titers of antioxLDL/b2GPI complexes were not raised. Immunohistochemical staining of atherosclerotic plaques demonstrated that scFv co-localized with macrophages and lipid deposits. The area of plaques in aortic arch was significantly larger than plaques in thoracic and abdominal segments. Autoradiographic and bio-distribution analysis of 64Cu-laeled scFv deposition confirmed the significant antibody accumulation in aortic arch (1.4 to 2.8-fold) of the WHHL rabbits. The PET/CT fusion images clearly demonstrated aortic arch lesions only in the WHHL rabbits. Conclusion: Our results demonstrated that the scFv was specific and preferentially accumulated in atherosclerotic plaques capable of providing an accurate in vivo imaging detection of the lesion. The scFv (a variant lacking the Fc region) can be used as a probe suitable for clinical PET imaging of atherosclerosis with high enough sensitivity and specificity. 55 - Intima media thickness and other imaging of peripheral arteries EAS-0945. RELATIONSHIP BETWEEN TRIGLICERYDE TO HIGH DENSITY LIPOPROTEIN CHOLESTEROL RATIO AND CAROTID INTIMA MEDIA THICKNESS IN ADOLESCENTS