title: Sympathetic denervation is associated with microvascular dysfunction in non-infarcted myocardium in patients with cardiomyopathy.
abstract: OBJECTIVE
  Sympathetic denervation typically occurs in the infarcted myocardium and is associated with sudden cardiac death. Impaired innervation was also demonstrated in non-infarcted myocardium in ischaemic and dilated cardiomyopathy (ICMP and DCMP). Factors affecting sympathetic nerve integrity in remote myocardium are unknown. Perfusion abnormalities, even in the absence of epicardial coronary artery disease, may relate to sympathetic dysfunction. This study was aimed to assess the interrelations of myocardial blood flow (MBF), contractile function, and sympathetic innervation in non-infarcted remote myocardium.
  
  
  RESULTS
  Seventy patients with ICMP or DCMP and LVEF ≤35% were included. [(15)O]H2O- and [(11)C]hydroxyephedrine (HED) PET was performed to quantify resting MBF, hyperaemic MBF, and sympathetic innervation. Cardiovascular magnetic resonance (CMR) imaging was performed to assess left ventricular function, mass, wall thickening, and scar size. Wall thickening, [(11)C]HED retention index (RI), and MBF were assessed in remote segments without scar, selected on CMR. [(11)C]HED RI was correlated with resting MBF (r = 0.41, P < 0.001) and hyperaemic MBF (r = 0.55, P < 0.001) in remote myocardium in both ICMP and DCMP. In addition, LV volumes (r = -0.40, P = 0.001), LV mass (r = -0.31, P = 0.008), and wall thickening (r = 0.45, P < 0.001) correlated with remote [(11)C]HED RI. Multivariable analysis revealed that hyperaemic MBF (B = 0.79, P < 0.001), wall thickening (B = 0.01, P = 0.03), and LVEDV (B = -0.03, P = 0.02) were independent predictors for remote [(11)C]HED RI.
  
  
  CONCLUSIONS
  Hyperaemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperaemic MBF is the primary cause of this relation remains unclear.
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, HV 1081, The Netherlands Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mischa T
authors.initials: MT
authors.lastname: Rijnierse
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, HV 1081, The Netherlands Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Cornelis P
authors.initials: CP
authors.lastname: Allaart
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, HV 1081, The Netherlands Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: de Haan
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Harms
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Huisman
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, HV 1081, The Netherlands Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: LiNa
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, HV 1081, The Netherlands Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Aernout M
authors.initials: AM
authors.lastname: Beek
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, HV 1081, The Netherlands Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, Amsterdam, HV 1081, The Netherlands Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands p.knaapen@vumc.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Knaapen
mesh_terms: D000368:Aged; D001783:Blood Flow Velocity; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000401:mortality; D015331:Cohort Studies; D003326:Coronary Circulation / Q000502:physiology; D005260:Female; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000401:mortality; D055414:Myocardial Perfusion Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D013562:Sympathectomy / Q000379:methods*
keywords: cardiomyopathy; cardiovascular magnetic resonance; myocardial perfusion imaging; positron emission tomography; sympathetic innervation