title: Alterations in the expression of genes related to contractile function and hypertrophy of the left ventricle in chronically paced patients from the right ventricular apex.
abstract: OBJECTIVE
  Long-term right ventricular apical (RVA) pacing may lead to left ventricular (LV) remodelling and heart failure. This study assessed changes in the expression of genes regulating LV contractile function and hypertrophy, after permanent RVA pacing and investigated whether such changes proceed or even predict LV remodelling.
  
  
  RESULTS
  We enrolled 52 consecutive patients (age 79.1 ± 7.7 years, 34 males) who underwent pacemaker implantation for bradycardic indications: Group A, 24 individuals with atrioventricular conduction disturbances and group B, 28 patients with sinus node disease. In group A, peripheral blood mRNA levels of gene sarcoplasmic reticulum calcium ATPase decreased at 3, 6, and 12 months' follow-up, while α-myosin heavy chain (MHC) decreased and β-MHC increased until 6 months follow-up. In this group, 25% of patients demonstrated significant LV remodelling. At 4 years, LV end-systolic diameter increased from 29.67 ± 3.39 mm at baseline to 35.38 ± 4.22 mm, LV end-diastolic diameter increased from 50 ± 4.95 to 56.71 ± 5.52 mm, and ejection fraction declined from 63.04 ± 10.22 to 52.83 ± 10.81%. Early alterations in gene expression were associated with a deterioration in LV function and geometry that became apparent months later. In group B, echocardiographic indexes and mRNA levels of the evaluated genes demonstrated no statistically significant changes.
  
  
  CONCLUSIONS
  Permanent RVA pacing in patients with preserved ejection fraction is associated with alterations in the expression of genes regulating LV contractile function and hypertrophy, measured in the peripheral blood. These alterations are traceable at an early stage, before echocardiographic changes are apparent and are associated with LV remodelling that becomes evident in the long term.
authors: University Hospital of Heraklion, PO box 1352, Stavrakia, Heraklion Crete, Greece.
authors: Eva G
authors: EG
authors: Arkolaki
authors: University Hospital of Heraklion, PO box 1352, Stavrakia, Heraklion Crete, Greece esimant@hotmail.com.
authors: Emmanuel N
authors: EN
authors: Simantirakis
authors: Medical School of Heraklion, Stavrakia, Heraklion Crete, Greece.
authors: Joanna E
authors: JE
authors: Kontaraki
authors: University Hospital of Heraklion, PO box 1352, Stavrakia, Heraklion Crete, Greece.
authors: Stavros I
authors: SI
authors: Chrysostomakis
authors: University Hospital of Heraklion, PO box 1352, Stavrakia, Heraklion Crete, Greece.
authors: Alexandros P
authors: AP
authors: Patrianakos
authors: Medical School of Heraklion, Stavrakia, Heraklion Crete, Greece.
authors: Gregory I
authors: GI
authors: Chlouverakis
authors: University Hospital of Heraklion, PO box 1352, Stavrakia, Heraklion Crete, Greece.
authors: Eleni S
authors: ES
authors: Nakou
authors: University Hospital of Heraklion, PO box 1352, Stavrakia, Heraklion Crete, Greece.
authors: Panos E
authors: PE
authors: Vardas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001919:Bradycardia / Q000628:therapy; D024722:Cardiac Myosins / Q000097:blood*; D002304:Cardiac Pacing, Artificial / Q000379:methods; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000628:therapy; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008297:Male; D018995:Myosin Heavy Chains / Q000097:blood*; D010138:Pacemaker, Artificial; D011446:Prospective Studies; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000097:blood*; D012804:Sick Sinus Syndrome / Q000150:complications*; D013318:Stroke Volume; D016277:Ventricular Function, Left / Q000235:genetics*; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D015415:Biomarkers; C501641:MYH7 protein, human; D024722:Cardiac Myosins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains
keywords: Gene expression; Right ventricular apical pacing; Ventricular remodelling