title: Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathy.
abstract: Impaired hyperemic myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM), despite normal epicardial coronary arteries, results in microvascular dysfunction. The aim of the present study was to determine the relative contribution of extravascular compressive forces to microvascular dysfunction in HCM. Eighteen patients with symptomatic HCM and normal coronary arteries and 10 age-matched healthy volunteers were studied with PET to quantify resting and hyperemic MBF at a subendocardial and subepicardial level. In HCM patients, MRI was performed to determine left ventricular (LV) mass index (LVMI) and volumes, echocardiography to assess diastolic perfusion time, heart catheterization to measure LV outflow tract gradient (LVOTG) and LV pressures, and serum NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP) as a biochemical marker of LV wall stress. Hyperemic MBF was blunted in HCM vs. controls (2.26 +/- 0.97 vs. 2.93 +/- 0.64 ml min(-1) g(-1), P < 0.05). In contrast to controls (1.38 +/- 0.15 to 1.25 +/- 0.19, P = not significant), the endocardial-to-epicardial MBF ratio decreased significantly in HCM during hyperemia (1.20 +/- 0.11 to 0.88 +/- 0.18, P < 0.01). This pattern was similar for hypertrophied septum and lateral wall. Hyperemic MBF was inversely correlated with LVOTG, NT-proBNP, left atrial volume index, and LVMI (all P < 0.01). Multivariate regression analysis, however, revealed that only LVMI and NT-proBNP were independently related to hyperemic MBF, with greater impact at the subendocardial myocardial layer. Hyperemic MBF is more severely impaired at the subendocardial level in HCM patients. The level of impairment is related to markers of increased hemodynamic LV loading conditions and LV mass. These observations suggest that, in addition to reduced capillary density caused by hypertrophy, extravascular compressive forces contribute to microvascular dysfunction in HCM patients.
authors.affiliation: Department of Cardiology, VU University Medical Center, Institute for Cardiovascular Research, Amsterdam, The Netherlands. p.knaapen@vumc.nl
authors.forename: Paul
authors.initials: P
authors.lastname: Knaapen
authors.forename: Tjeerd
authors.initials: T
authors.lastname: Germans
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Camici
authors.forename: Ornella E
authors.initials: OE
authors.lastname: Rimoldi
authors.forename: Folkert J
authors.initials: FJ
authors.lastname: ten Cate
authors.forename: Jurrien M
authors.initials: JM
authors.lastname: ten Berg
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Dijkmans
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Willem G
authors.initials: WG
authors.lastname: van Dockum
authors.forename: Marco J W
authors.initials: MJ
authors.lastname: Götte
authors.forename: Jos W R
authors.initials: JW
authors.lastname: Twisk
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Frans C
authors.initials: FC
authors.lastname: Visser
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003326:Coronary Circulation / Q000502:physiology*; D004699:Endocardium / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D010496:Pericardium / Q000502:physiology; D049268:Positron-Emission Tomography; D014463:Ultrasonography; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain