title: Genetic variants of the renin-angiotensin-aldosterone system and reverse remodeling after cardiac resynchronization therapy.
abstract: BACKGROUND
  Reverse remodeling (RR) after cardiac resynchronization therapy (CRT) is associated with favorable clinical outcomes in heart failure (HF). The renin-angiotensin-aldosterone system (RAAS) is involved in the remodeling process.
  
  
  RESULTS
  We assessed the association between RR and 8 common RAAS gene variants, which were determined by TaqMan assays, in 156 outpatients with chronic HF. RR was defined as a >15% decrease in left ventricular end systolic volume (LVESV) at 9 (interquartile range 7-12) months after CRT. We matched 76 patients who did not show RR (RR-) to 80 RR+ control subjects by age, sex, HF etiology, New York Heart Association (NYHA) functional class and left ventricular ejection fraction (LVEF). The frequency of the minor allele of the NR3C2 gene (rs5522 C/T), encoding the mineralocorticoid receptor, was higher in RR- than in RR (24/126 vs 10/150; P value after false discovery rate correction: <.0193). Conversely, LVESV decreased significantly less after CRT in carriers of the NR3C2 minor C allele (P = .02). After adjustment for age, sex, NYHA functional class, previous myocardial infarction, atrial fibrillation, and LVEF, RR- remained independently associated with NR3C2 C allele carriage (odds ratio 3.093, 95% confidence interval 1.253-7.632).
  
  
  CONCLUSIONS
  The association of RR- after CRT with a common polymorphism in the mineralocorticoid receptor gene involved in aldosterone signaling suggests a possible role for variants in RAAS genes in progressive LV function decline, despite apparently effective CRT.
authors.affiliation: CNR Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy. renata_de_maria@hotmail.com
authors.forename: Renata
authors.initials: R
authors.lastname: De Maria
authors.forename: Maurizio
authors.initials: M
authors.lastname: Landolina
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gasparini
authors.forename: Boris
authors.initials: B
authors.lastname: Schmitz
authors.forename: Jonica
authors.initials: J
authors.lastname: Campolo
authors.forename: Marina
authors.initials: M
authors.lastname: Parolini
authors.forename: Antonio
authors.initials: A
authors.lastname: Sanzo
authors.forename: Paola
authors.initials: P
authors.lastname: Galimberti
authors.forename: Michele
authors.initials: M
authors.lastname: Bianchi
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Brand
authors.forename: Oberdan
authors.initials: O
authors.lastname: Parodi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Lunati
mesh_terms: D000368:Aged; D058406:Cardiac Resynchronization Therapy; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D014644:Genetic Variation; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D010865:Pilot Projects; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*; D013223:Statistics as Topic; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: C561839:NR3C2 protein, human; D018161:Receptors, Mineralocorticoid