title: Evolution of hypertrophic cardiomyopathy in sarcomere mutation carriers.
abstract: OBJECTIVE
  The early natural history of sarcomere mutations and the evolution to hypertrophic cardiomyopathy (HCM) are poorly characterised. To describe phenotypic progression, we compared mutation carriers who developed HCM to those who did not during prospective longitudinal investigation.
  
  
  METHODS
  Sarcomere mutation carriers without baseline left ventricular hypertrophy (LVH) were studied during participation in a pilot clinical trial testing diltiazem versus placebo. 38 participants (mean±SD age 15.8±8.6 years) were followed for a median of 2.9 years (range 1.0-5.1 years) with imaging and biomarker analysis. 4 participants (mean baseline age 13.8±3.9 years) developed HCM and were compared to those without phenotypic progression.
  
  
  RESULTS
  Participants who developed HCM were all children/adolescents and members of families with more highly penetrant mutations. At baseline, participants who developed HCM had a higher left ventricular (LV) ejection fraction (74±2% vs 69±1%, p=0.02), lower global E' velocity (11.2±0.5 vs 14.8±0.4 cm/s, p<0.0001), higher N terminal pro peptide of B-type natriuretic peptide (NT-proBNP) values (208±72 vs 57±13 pg/mL, p=0.04), longer posterior mitral leaflets, and more prevalent ECG abnormalities. During follow-up, these parameters and cardiac troponin values continued to diverge in participants who developed HCM, although LV wall thickness stabilised.
  
  
  CONCLUSIONS
  LV relaxation, ECG changes, mitral leaflet length, and serum NT-proBNP concentrations appeared more prominently abnormal at baseline in preclinical sarcomere mutation carriers who imminently progressed to HCM. LVH appears to stabilise within 2 years of onset. Further investigation is needed to improve our understanding of the evolution of this disease.
  
  
  BACKGROUND
  NCT00319982; Post-results.
authors: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: Carolyn Y
authors: CY
authors: Ho
authors: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: Allison L
authors: AL
authors: Cirino
authors: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: Neal K
authors: NK
authors: Lakdawala
authors: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: John
authors: J
authors: Groarke
authors: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors: Anne Marie
authors: AM
authors: Valente
authors: Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, University of Sydney, and Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
authors: Christopher
authors: C
authors: Semsarian
authors: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors: Steven D
authors: SD
authors: Colan
authors: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: E John
authors: EJ
authors: Orav