Right ventricular remodeling in restrictive ventricular septal defect.

Area of Science:

• Cardiovascular Research
• Pediatric Cardiology
• Translational Medicine

Background:

• Restrictive ventricular septal defects (rVSD) often lack immediate hemodynamic impact, leading to clinical observation.
• The absence of clear therapeutic strategies for rVSD increases the risk of poor patient outcomes.
• Subclinical right ventricular (RV) dysfunction and molecular remodeling in rVSD remain poorly understood.

Purpose of the Study:

• To investigate the hypothesis that rVSD induces subclinical RV diastolic dysfunction.
• To identify molecular remodeling changes in the RV myocardium following rVSD.
• To evaluate potential non-invasive markers for early detection of RV dysfunction in rVSD.

Main Methods:

• Surgical creation of rVSD in a porcine model.
• Echocardiography and hemodynamic assessments at 6 weeks post-surgery.
• Myocyte contractility experiments, proteomics, and Western blot analysis of RV myocardium.

Main Results:

• rVSD induced significant RV diastolic dysfunction, evidenced by a reduced tricuspid valve E/A ratio.
• RV myocytes exhibited impaired contraction and relaxation.
• Increased mitochondrial proteins (fatty acid, TCA cycle) and upregulated desmin protein were observed in the RV myocardium.

Conclusions:

• rVSD leads to subclinical RV diastolic dysfunction, myocyte impairment, and molecular remodeling.
• Desmin upregulation may serve as an early marker for RV dysfunction in rVSD.
• Tricuspid valve E/A ratio is a potential non-invasive tool for assessing rVSD patients, potentially influencing clinical management towards early repair.