title: Association of impaired left ventricular twisting-untwisting with vascular dysfunction, neurohumoral activation and impaired exercise capacity in hypertensive heart disease.
abstract: OBJECTIVE
  We investigated the association between left ventricular (LV) torsional deformation and vascular dysfunction, fibrosis, neurohumoral activation, and exercise capacity in patients with normal ejection fraction
  
  
  RESULTS
  In 320 newly-diagnosed untreated hypertensive patients and 160 controls, we measured: pulse wave velocity (PWV); coronary flow reserve (CFR) by Doppler echocardiography; global longitudinal strain and strain rate, peak twisting, the percentage changes between peak twisting, and untwisting at mitral valve opening (%dpTw - UtwMVO ), at peak (%dpTw - UtwPEF ), and the end of early LV diastolic filling (%dpTw - UtwEDF ) by speckle tracking imaging; transforming growth factor (TGFb-1), metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloptoteinase-1(TIMP-1), markers of collagen synthesis, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Oxygen consumption (VO2 ), measured by means of cardiopulmonary exercise test, was assessed in a subset of 80 patients. The PWV, CFR, longitudinal strain and strain rate, %dpTw-UtwMVO , %dpTw-UtwPEF , and %dpTw-UtwEDF were impaired in hypertensive patients compared with controls. In multivariable analysis, CFR, PWV, LV mass, and systolic blood pressure were independent determinants of longitudinal strain, strain rate, and untwisting markers (P < 0.05). Increased TGFb-1 was related with increased collagen synthesis markers, TIMP-1 and MMP-9 and these biomarkers were associated with impaired longitudinal systolic strain rate, untwisting markers, CFR and PWV (P < 0.05). Delayed untwisting as assessed by reduced %dpTw - UtwEDF was related with increased NT-proBNP and reduced VO2 (P < 0.05).
  
  
  CONCLUSIONS
  Impaired LV untwisting is associated with increased arterial stiffness and coronary microcirculatory dysfunction, and is linked to reduced exercise capacity and neurohumoral activation in hypertensive heart disease. A fibrotic process may be the common link between vascular dysfunction and abnormal myocardial deformation.
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Tzortzis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Triantafyllidi
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: John
authors.initials: J
authors.lastname: Parissis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: Costas
authors.initials: C
authors.lastname: Papadopoulos
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Venetsanou
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Trivilou
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Paraskevaidis
authors.affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Rimini 1, Haidari, Athens, 12462 Greece.
authors.forename: John
authors.initials: J
authors.lastname: Lekakis
mesh_terms: D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D004452:Echocardiography; D005260:Female; D006331:Heart Diseases / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D008943:Mitral Valve / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D020780:Matrix Metalloproteinase 9
keywords: Arterial stiffness; Coronary flow reserve; LV diastolic dysfunction; LV twisting and untwisting; Pulse wave velocity