Clinical and genetic characterization of patients with hypertrophic cardiomyopathy and right atrial enlargement

J Cardiovasc Med (Hagerstown). 2017 Apr;18(4):249-254. doi: 10.2459/JCM.0000000000000361.

Abstract

Aims: Prevalence and clinical significance of right atrial enlargement (RAE) has been poorly characterized in hypertrophic cardiomyopathy.

Methods: One hundred and sixty consecutive patients with hypertrophic cardiomyopathy (35.5 ± 20 years; 64% men) were studied. They underwent clinical examination, standard ECG, M-mode, 2D and Doppler echocardiography, stress test and ECG Holter monitoring. Major adverse cardiac events were considered: cardiac death (sudden death, heart failure death); cardiac transplant; resuscitated cardiac arrest or appropriate implantable cardioverter defibrillator discharge. Genetic analysis of eight sarcomeric genes was performed using Sanger sequencing.

Results: RAE was observed in 22 patients (14%), associated with left atrial enlargement in all cases. Patients with RAE were likely to have restrictive mitral pattern (P < 0.001) and had higher New York Heart Association (P < 0.001), N-terminal prohormone of brain natriuretic peptide (P < 0.001), left atrial volume index (P < 0.001), lateral (P = 0.04) and septal (P = 0.002) E/e', systolic pulmonary artery pressure (P < 0.001) and lower ejection fraction (all P < 0.001). On cardiopulmonary exercise testing, peak VO2 was lower and VE/VCO2 higher in patients with RAE (P < 0.001). During a mean follow-up of 4 ± 2.1 years, 30 major adverse cardiac events in 24 patients (15%) were observed. Cox proportional hazards regression analysis identified RAE as an independent predictor of major adverse cardiac events (odds ratio = 2.6; confidence interval 1.5-4.6; P = 0.001). In patients with RAE who were genetically tested, there was a higher prevalence of sarcomeric gene mutations (68%), double mutations (16%) and troponin T mutations (21%).

Conclusion: RAE is present in a small subset of patients with hypertrophic cardiomyopathy, and largely reflects increased pulmonary pressures because of severe diastolic and/or systolic left ventricular dysfunction. Patients with RAE had a higher prevalence of sarcomeric gene mutations, troponin T mutations and complex genotypes. In conclusion, RAE may serve as a very useful marker of disease progression and adverse outcome in patients with sarcomeric hypertrophic cardiomyopathy.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cardiomegaly / diagnostic imaging
  • Cardiomegaly / genetics*
  • Cardiomegaly / mortality
  • Cardiomegaly / therapy
  • Cardiomyopathy, Hypertrophic / diagnostic imaging
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / mortality
  • Cardiomyopathy, Hypertrophic / therapy
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • DNA Mutational Analysis
  • Death, Sudden, Cardiac / etiology
  • Death, Sudden, Cardiac / prevention & control
  • Defibrillators, Implantable
  • Echocardiography, Doppler
  • Electric Countershock / instrumentation
  • Electrocardiography, Ambulatory
  • Exercise Test
  • Female
  • Genetic Predisposition to Disease
  • Heart Atria / diagnostic imaging
  • Heart Transplantation
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Resuscitation
  • Risk Factors
  • Treatment Outcome
  • Troponin T / genetics*
  • Young Adult

Substances

  • Troponin T