Large Variations in Phenylalanine Concentrations Associate Adverse Cardiac Remodelling in Adult Patients With...

Area of Science:

• Cardiology
• Metabolic Disorders
• Medical Imaging

Background:

• Adult patients with phenylketonuria (PKU) often have elevated phenylalanine (Phe) levels despite dietary restrictions.
• Current treatments aim to prevent neuropsychiatric issues but long-term cardiac consequences are not fully understood.
• Previous observations suggested early cardiomyopathic characteristics in adult PKU patients.

Purpose of the Study:

• To longitudinally evaluate the cardiac phenotype in adult patients with PKU.
• To investigate the association between phenylalanine levels and cardiac remodeling.
• To assess cardiac function and hemodynamics using advanced imaging techniques.

Main Methods:

• Fifteen adult PKU patients underwent serial cardiac magnetic resonance (CMR) imaging over a mean of 8.3 years.
• CMR protocols included volumetric assessment, parametric mapping (T1, T2, ECV), myocardial strain, and hemodynamic evaluation.
• A control group of 20 matched subjects underwent identical CMR assessments for comparison.

Main Results:

• PKU patients showed decreased LV end-diastolic and end-systolic volumes, but increased LV mass and longer T1 times.
• While ejection fraction and systolic strain were unchanged, early diastolic forces became more negative, and aortic distensibility decreased.
• A greater decrease in Phe concentration correlated with longer T1 times, increased extracellular volume, and reduced systolic function.

Conclusions:

• Long-term reduction in Phe levels in PKU patients is associated with detrimental cardiac remodeling, including impaired systolic function and increased fibrosis.
• These findings highlight the potential negative impact of Phe variability on cardiac health.
• Periodic cardiovascular assessment is crucial for adult PKU patients.