title: Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker--Rationale and design of the trial.
abstract: BACKGROUND
  Dual chamber pacing is known to have detrimental effect on cardiac performance and heart failure occurring eventually is associated with increased mortality. Experimental studies of pacing in dogs have shown contractile dyssynchrony leading to diffuse alterations in extracellular matrix. In parallel, studies on experimental ischemia/reperfusion injury have shown efficacy of valsartan to inhibit activity of matrix metalloproteinase-9, to increase the activity of tissue inhibitor of matrix metalloproteinase-3 and preserve global contractility and left ventricle ejection fraction.
  
  
  OBJECTIVE
  To present rationale and design of randomized blinded trial aimed to assess whether 12 month long administration of valsartan will prevent left ventricle remodeling in patients with preserved left ventricle ejection fraction (LVEF ≥ 40%) and first implantation of dual chamber pacemaker.
  
  
  METHODS
  A total of 100 eligible patients will be randomized into three parallel arms: placebo, valsartan 80 mg/daily and valsartan 160 mg/daily added to previously used drugs. The primary endpoint will be assessment of valsartan efficacy to prevent left ventricle remodeling during 12 month follow-up. We assess patients' functional capacity, blood plasma activity of matrix metalloproteinases and their tissue inhibitors, NT-proBNP, tumor necrosis factor alpha, and Troponin T. Left ventricle function and remodeling is assessed echocardiographically: M-mode, B-mode, tissue Doppler imaging.
  
  
  CONCLUSIONS
  If valsartan proves effective, it will be an attractive measure to improve long term prognosis in aging population and increasing number of pacemaker recipients. ClinicalTrials.org (NCT01805804).
authors: II Department of Cardiology in Zabrze, Medical University of Silesia, ul. Skłodowskiej 10, 41-800 Zabrze, Poland. Electronic address: atomasik@sum.edu.pl.
authors: Andrzej
authors: A
authors: Tomasik
authors: II Department of Cardiology in Zabrze, Medical University of Silesia, ul. Skłodowskiej 10, 41-800 Zabrze, Poland. Electronic address: wjachec@interia.pl.
authors: Wojciech
authors: W
authors: Jacheć
authors: II Department of Cardiology in Zabrze, Medical University of Silesia, ul. Skłodowskiej 10, 41-800 Zabrze, Poland. Electronic address: wojciechowskac@wp.pl.
authors: Celina
authors: C
authors: Wojciechowska
authors: II Department of Cardiology in Zabrze, Medical University of Silesia, ul. Skłodowskiej 10, 41-800 Zabrze, Poland. Electronic address: d.kawecki@interia.pl.
authors: Damian
authors: D
authors: Kawecki
authors: II Department of Cardiology in Zabrze, Medical University of Silesia, ul. Skłodowskiej 10, 41-800 Zabrze, Poland. Electronic address: bmjbialkowska@gmail.com.
authors: Beata
authors: B
authors: Białkowska
authors: Department of Biochemistry in Zabrze, Medical University of Silesia, ul. Jordana 19, 41-800 Zabrze, Poland. Electronic address: eromuk@gmail.com.
authors: Ewa
authors: E
authors: Romuk
authors: Dr n. med. FRYDA Medical Laboratory Ltd., ul. Skłodowskiej 10, 41-800 Zabrze, Poland. Electronic address: gabrysiak@fryda.pl.
authors: Artur
authors: A
authors: Gabrysiak
authors: Department of Biochemistry in Zabrze, Medical University of Silesia, ul. Jordana 19, 41-800 Zabrze, Poland. Electronic address: ebirkner@wp.pl.
authors: Ewa
authors: E
authors: Birkner
authors: Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Medical University of Silesia, ul. Szpitalna 2, 41-800 Zabrze, Poland. Electronic address: karzab@sum.edu.pl.
authors: Zbigniew
authors: Z
authors: Kalarus
authors: II Department of Cardiology in Zabrze, Medical University of Silesia, ul. Skłodowskiej 10, 41-800 Zabrze, Poland. Electronic address: ewakozielska@wp.pl.
authors: Ewa
authors: E
authors: Nowalany-Kozielska
mesh_terms: D054537:Atrioventricular Block / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004452:Echocardiography; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000276:immunology; D010138:Pacemaker, Artificial / Q000009:adverse effects*; D010446:Peptide Fragments / Q000276:immunology; D012107:Research Design; D013318:Stroke Volume; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000068756:Valsartan / Q000008:administration & dosage*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068756:Valsartan; D020782:Matrix Metalloproteinases
keywords: Dual chamber pacing; Heart failure; Left ventricle remodeling; Valsartan