title: Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis.
abstract: OBJECTIVE
  The purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis.
  
  
  BACKGROUND
  Effort angina is common in subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD).
  
  
  METHODS
  Thirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2-dimensional echocardiography. Global left ventricular myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF/rest MBF) adjusting for rest rate pressure product.
  
  
  RESULTS
  Compared with the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 ml/g/min vs. 0.88 ± 0.23 ml/g/min; p = 0.004), stress MBF (0.85 ± 0.29 ml/g/min vs. 1.85 ± 0.45 ml/g/min; p < 0.0001), and CFR (1.19 ± 0.38 vs. 2.23 ± 0.88; p < 0.0001) and higher minimal coronary vascular resistance (111 ± 40 ml/g/min/mm Hg vs. 70 ± 19 ml/g/min/mm Hg; p = 0.004). Of note, almost all subjects with amyloidosis (>95%) had significantly reduced peak stress MBF (<1.3 ml/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased left ventricular mass, and age were the only independent predictors of impaired coronary vasodilator function.
  
  
  CONCLUSIONS
  Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis.
authors.affiliation: Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: sdorbala@partners.org.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Dorbala
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Divya
authors.initials: D
authors.lastname: Vangala
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Bruyere
authors.affiliation: Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Christina
authors.initials: C
authors.lastname: Quarta
authors.affiliation: Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jenna
authors.initials: J
authors.lastname: Kruger
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Padera
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Courtney
authors.initials: C
authors.lastname: Foster
authors.affiliation: Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanley
authors.affiliation: Noninvasive Cardiovascular Imaging Program, Heart and Vascular Center, Departments of Radiology and Medicine (Cardiology), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Di Carli
authors.affiliation: Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Rodney
authors.initials: R
authors.lastname: Falk
mesh_terms: D000686:Amyloidosis / Q000473:pathology / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000502:physiology; D009202:Cardiomyopathies / Q000473:pathology / Q000503:physiopathology*; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D008297:Male; D055806:Microvessels / Q000502:physiology*; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed; D014666:Vasomotor System / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology
keywords: PET; amyloidosis; coronary microvascular function; myocardial blood flow; strain