title: Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non-responders.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) play an important role in the pathogenesis of structural alterations of the failing heart through their ability to regulate negatively the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodelling. We studied whether LV reverse remodelling after CRT was associated with changes of circulating miRNAs in patients with heart failure (HF) and dyssynchrony.
  
  
  RESULTS
  A prospective, non-randomized self-control trial was performed in 81 patients with HF eligible for CRT. At baseline, to select the HF miRNA profile, we evaluated the expression of 84 miRNAs (implicated in the pathogenesis of structural alterations of the failing heart) in three groups of patients: healthy subjects (healthy group, n = 15); patients with HF (HF group, n = 81); and patients without HF matched for age, sex, and concomitant disease with HF patients (control group, n = 60). At 12 months, the selected miRNA profile was evaluated in plasma from responder (n = 55) and non-responder HF patients (n = 26) to CRT. In the test cohort, the HF patients were characterized by lower expression of 48 miRNAs (all P < 0.04) as compared with healthy subjects. In the validation cohort, the HF patients were characterized by lower expression of 24 miRNAs (all P < 0.03) as compared with control patients. At 12 months, 55 patients (68%) were considered responders and 26 non-responders to CRT (32%). Responders showed an increase in expression of 19 miRNAs (all P < 0.03) compared with baseline expression, whereas in the non-responders we observed an increase of six miRNAs (all P < 0.05) compared with baseline expression. At follow-up, miRNAs were differentially expressed between responders and non-responders. The responders were characterized by higher expression of five miRNAs (miRNA-26b-5p, miRNA-145-5p, miRNA-92a-3p, miRNA-30e-5p, and miRNA-29a-3p; P < 0.01 for all) as compared with non-responders.
  
  
  CONCLUSIONS
  In responders, reverse remodelling is associated with favourable changes in miRNAs that regulate cardiac fibrosis, apoptosis, and hypertrophy.
authors.affiliation: Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
authors.forename: Clara
authors.initials: C
authors.lastname: Di Filippo
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Potenza
authors.forename: Celestino
authors.initials: C
authors.lastname: Sardu
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Rizzo
authors.forename: Mario
authors.initials: M
authors.lastname: Siniscalchi
authors.forename: Emilio
authors.initials: E
authors.lastname: Musacchio
authors.forename: Michelangela
authors.initials: M
authors.lastname: Barbieri
authors.forename: Ciro
authors.initials: C
authors.lastname: Mauro
authors.forename: Nicola
authors.initials: N
authors.lastname: Mosca
authors.forename: Francesco
authors.initials: F
authors.lastname: Solimene
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Mottola
authors.forename: Aniello
authors.initials: A
authors.lastname: Russo
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
authors.forename: Michele
authors.initials: M
authors.lastname: D'Amico
mesh_terms: D000328:Adult; D000368:Aged; D058406:Cardiac Resynchronization Therapy; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000235:genetics / Q000628:therapy; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000235:genetics / Q000628:therapy; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D035683:MicroRNAs
keywords: Cardiac resynchronization therapy; Heart failure; MicroRNAs