title: Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.
abstract: OBJECTIVE
  Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients.
  
  
  RESULTS
  One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR.
  
  
  CONCLUSIONS
  Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF.
authors.affiliation: SDN Foundation, Institute of Diagnostic and Nuclear Development, Naples, Italy Department of Advanced Biomedical Sciences, Section of Cardiology, Federico II University, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Paolillo
authors.affiliation: Division of Cardiology, "Salvatore Maugeri" Foundation-IRCCS-Institute of Telese Terme (BN), Italy Department of Translational Medical Sciences, Section of Geriatrics, Federico II University, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Rengo
authors.affiliation: Department of Advanced Biomedical Sciences, Section of Imaging, Radiotherapy, Neuroradiology and Medical Physics, Federico II University, Naples, Italy Institute of Biostructures and Bioimages of the National Council of Research, Naples, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Pellegrino
authors.affiliation: Department of Translational Medical Sciences, Section of Geriatrics, Federico II University, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Formisano
authors.affiliation: Department of Translational Medical Sciences, Section of Geriatrics, Federico II University, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pagano
authors.affiliation: SDN Foundation, Institute of Diagnostic and Nuclear Development, Naples, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Gargiulo
authors.affiliation: Department of Advanced Biomedical Sciences, Section of Cardiology, Federico II University, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Savarese
authors.affiliation: Department of Advanced Biomedical Sciences, Section of Imaging, Radiotherapy, Neuroradiology and Medical Physics, Federico II University, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Carotenuto
authors.affiliation: Department of Translational Medical Sciences, Section of Geriatrics, Federico II University, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Petraglia
authors.affiliation: Department of Advanced Biomedical Sciences, Section of Cardiology, Federico II University, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rapacciuolo
authors.affiliation: Department of Advanced Biomedical Sciences, Section of Cardiology, Federico II University, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Perrino
authors.affiliation: Department of Translational Medical Sciences, Section of Clinical Pathology, Federico II University, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Piscitelli
authors.affiliation: Department of Cardiology Fatebenefratelli Hospital, Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Attena
authors.affiliation: Department of Public Health, Federico II University, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Del Guercio
authors.affiliation: Department of Translational Medical Sciences, Section of Geriatrics, Federico II University, Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Leosco
authors.affiliation: Department of Advanced Biomedical Sciences, Section of Cardiology, Federico II University, Naples, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Trimarco
authors.affiliation: SDN Foundation, Institute of Diagnostic and Nuclear Development, Naples, Italy Department of Advanced Biomedical Sciences, Section of Imaging, Radiotherapy, Neuroradiology and Medical Physics, Federico II University, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cuocolo
authors.affiliation: Department of Advanced Biomedical Sciences, Section of Cardiology, Federico II University, Naples, Italy fpperron@unina.it.
authors.forename: P
authors.initials: P
authors.lastname: Perrone-Filardi
mesh_terms: D019797:3-Iodobenzylguanidine; D000368:Aged; D015415:Biomarkers / Q000097:blood; D017548:Echocardiography, Transesophageal; D005260:Female; D006329:Heart Conduction System / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D006333:Heart Failure / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine
keywords: 123I-MIBG; cardiac sympathetic innervation; heart failure; insulin resistance