Left ventricular systolic dysfunction in asymptomatic Marfan syndrome patients is related to the severity of gene mutation: insights from the novel three dimensional speckle tracking echocardiography

PLoS One. 2015 Apr 22;10(4):e0124112. doi: 10.1371/journal.pone.0124112. eCollection 2015.


Background: In asymptomatic Marfan syndrome (MFS) patients we evaluated the relationship between the types of fibrillin-1 (FBN1) gene mutation and possible altered left ventricular (LV) function as assessed by three-dimensional speckle tracking echocardiography (3D-STE).

Methods and results: Forty-five MFS patients (mean age 24 ± 15 years) and 40 age-matched healthy controls were studied. Genetic evaluation for the FBN1 gene was carried on 32 MFS patients. Gene mutation (n = 15, 47%) was classified as mild when the mutation resulted in nearly normally functioning protein, while mutations resulting in abnormally function protein were considered to be severe (n = 17, 53%). All patients and controls underwent 3D-STE for evaluation of LV function by an echocardiographer blinded to the results of the genetic testing. Compared to controls, MFS patients had significantly lower 3D-STE derived LV ejection fraction (EF, 57.43 ± 7.51 vs. 62.69 ± 4.76%, p = 0.0001), global LV longitudinal strain (LS, 14.85 ± 2.89 vs. 17.90 ± 2.01%, p = 0.0001), global LV circumferential strain (CS, 13.93 ± 2.81 vs. 16.82 ± 2.17%, p = 0.0001) and global LV area strain (AS, 25.76 ± 4.43 vs. 30.51 ± 2.61%, p = 0.0001). Apart from the global LV LS all these parameters were significantly lower in patients with severe gene mutation than in those with mild mutation (p < 0.05). In the multivariate linear regression analysis only the type of mutation had a significant influence on the 3D-STE derived LVEF (p = 0.017), global CS (p = 0.005) and global AS (p = 0.03).

Conclusions: In asymptomatic MFS patients latent LV dysfunction can be detected using 3D STE. The LV dysfunction is mainly related to the severity of gene mutation, suggesting possible primary cardiomyopathy in MFS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asymptomatic Diseases
  • Cardiomyopathies / diagnostic imaging
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / pathology
  • Case-Control Studies
  • Child
  • Echocardiography, Three-Dimensional
  • Female
  • Fibrillin-1
  • Fibrillins
  • Gene Expression
  • Humans
  • Male
  • Marfan Syndrome / diagnostic imaging
  • Marfan Syndrome / genetics*
  • Marfan Syndrome / pathology
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Mutation*
  • Regression Analysis
  • Stroke Volume
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / genetics*
  • Ventricular Dysfunction, Left / pathology


  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins

Grants and funding

This work was supported by the Competence Network for Congenital Heart Defects funded by the Federal Ministry of Education and Research (BMBF), Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.