title: Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT.
abstract: BACKGROUND
  Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III-IV) after CRT using (11)C-hydroxyephedrine (HED) PET/CT.
  
  
  METHODS
  Ten IHF patients (mean age = 68; range = 55-81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps.
  
  
  RESULTS
  At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with "impaired innervation" (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01).
  
  
  CONCLUSIONS
  As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage.
  
  
  CONCLUSIONS
  These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation.
  
  
  CONCLUSIONS
  This work might contribute to identify imaging parameters that could predict the response to CRT therapy.
authors.affiliation: Nuclear Medicine, IRCCS AOU San Martino-IST, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Selene
authors.initials: S
authors.lastname: Capitanio
authors.affiliation: Nuclear Medicine, Hematology-Oncology and Laboratory Medicine Department, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nanni
authors.affiliation: CNR Institute of Bioimages and Molecular Physiology, Milan, Section of Genoa, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marini
authors.affiliation: Nuclear Medicine, Hematology-Oncology and Laboratory Medicine Department, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Bonfiglioli
authors.affiliation: Istitute of Cardiology, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Martignani
authors.affiliation: Nuclear Medicine, IRCCS AOU San Martino-IST, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Bassam
authors.initials: B
authors.lastname: Dib
authors.affiliation: Nuclear Medicine, Hematology-Oncology and Laboratory Medicine Department, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fuccio
authors.affiliation: Istitute of Cardiology, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boriani
authors.affiliation: Nuclear Medicine, IRCCS AOU San Martino-IST, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Picori
authors.affiliation: Nuclear Medicine, Hematology-Oncology and Laboratory Medicine Department, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Boschi
authors.affiliation: Nuclear Medicine, IRCCS AOU San Martino-IST, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morbelli
authors.affiliation: Nuclear Medicine, Hematology-Oncology and Laboratory Medicine Department, Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant' Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fanti
authors.affiliation: Nuclear Medicine, IRCCS AOU San Martino-IST, Department of Health Sciences, University of Genoa, Genoa, Italy. Electronic address: Sambuceti@unige.it.
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D058406:Cardiac Resynchronization Therapy; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011941:Receptors, Adrenergic / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D011941:Receptors, Adrenergic; C065363:3-hydroxyephedrine; D004809:Ephedrine
keywords: (11)C-hydroxyephedrine; Cardiac resynchronization therapy; Heart failure; PET/CT; Sympathetic innervation