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Isolation and Physiological Analysis of Mouse Cardiomyocytes
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Subclinical myocardial dysfunction in Rett syndrome.

Claudio De Felice1, Silvia Maffei, Cinzia Signorini

  • 1Neonatal Intensive Care Unit, University General Hospital, Azienda Ospedaliera Universitaria Senese, Viale M. Bracci 16, Siena, Italy. geniente@gmail.com

European Heart Journal. Cardiovascular Imaging
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PubMed
Summary

Rett syndrome (RTT) patients exhibit subclinical biventricular dysfunction, impacting heart function. This myocardial dysfunction is partly linked to increased oxidative stress (OS) markers, particularly F2-Isoprostanes.

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Area of Science:

  • Cardiology
  • Neuroscience
  • Genetics

Background:

  • Rett syndrome (RTT) is a rare neurodevelopmental disorder linked to methyl-CpG-binding protein 2 (MeCP2) mutations.
  • RTT patients have a significantly increased risk of sudden cardiac death, not fully explained by known cardiac issues.
  • Emerging evidence suggests MeCP2 plays a role in cardiomyocyte development and that RTT involves increased oxidative stress (OS).

Purpose of the Study:

  • To investigate subclinical biventricular dysfunction in RTT patients.
  • To determine if myocardial dysfunction in RTT correlates with oxidative stress markers.
  • To explore the role of MeCP2 in cardiac function within the context of RTT.

Main Methods:

  • Echocardiography was used to assess biventricular systo-diastolic parameters in typical and atypical RTT patients and controls.
  • Oxidative stress markers, including plasma and intra-erythrocyte non-protein-bound iron (NPBI) and plasma F2-Isoprostanes (F2-IsoPs), were measured.
  • Correlations between echocardiographic measures and OS levels were analyzed.

Main Results:

  • RTT patients showed reduced longitudinal biventricular function (e.g., reduced annular plane excursion and S' wave velocities).
  • No significant changes in left ventricular ejection fraction were observed, but peak-early filling parameters and right ventricular systolic pressure were reduced.
  • Increased OS markers were found, with F2-Isoprostanes significantly correlating with left ventricular systolic dysfunction.

Conclusions:

  • RTT is associated with unrecognized subclinical systo-diastolic biventricular myocardial dysfunction.
  • A reduced preload was evidenced in RTT patients.
  • The observed biventricular dysfunction is partially attributed to oxidative stress-induced damage.