TY - JOUR
T1 - Cardiac magnetic resonance reveals incipient cardiomyopathy traits in adult patients with phenylketonuria
AU - Tanacli, Radu
AU - Hassel, Jan Hendrik
AU - Gebker, Rolf
AU - Berger, Alexander
AU - Gräfe, Michael
AU - Schneeweis, Christopher
AU - Doeblin, Patrick
AU - Fleck, Eckart
AU - Stehning, Christian
AU - Tacke, Frank
AU - Pieske, Burkert
AU - Spranger, Joachim
AU - Plöckinger, Ursula
AU - Ziagaki, Athanasia
AU - Kelle, Sebastian
N1 - Publisher Copyright:
© 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2021/9
Y1 - 2021/9
N2 - BACKGROUND: Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collat-eral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. METHODS AND RESULTS: Thirty-nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10-year mean phenylalanine concentration, 924±330 µmol/L) and 39 age-and sex-matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten-year mean plasma levels of pheny-lalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end-diastolic thickness, 7.0±17 versus 8.8±1.7 mm [P<0.001]; lateral thickness, 6.1±1.4 versus 6.8±1.2 mm [P=0.004]), more dilated left ventricular cavity (end-diastolic volume, 87±14 versus 80±14 mL/m2 [P=0.0178]; end-systolic volume, 36±9 versus 29±8 mL/m2 [P<0.001]), lower ejection fraction (59±6% versus 64±6% [P<0.001]), reduced systolic deformation (global circumferential strain, −29.9±4.2 % versus −32.2±5.0 % [P=0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m2 [P<0.001]). T1 native values were decreased (936±53 versus 996±26 ms [P<0.001]), with particular low values in patients with phenylalanine >1200 µmol/L (909±48 ms). Both mean phenylalanine (P=0.013) and tyrosine (P=0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. CONCLUSIONS: Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early-stage cardiomyopathy. Regular cardiology follow-up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipi-demia, are recommended.
AB - BACKGROUND: Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collat-eral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. METHODS AND RESULTS: Thirty-nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10-year mean phenylalanine concentration, 924±330 µmol/L) and 39 age-and sex-matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten-year mean plasma levels of pheny-lalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end-diastolic thickness, 7.0±17 versus 8.8±1.7 mm [P<0.001]; lateral thickness, 6.1±1.4 versus 6.8±1.2 mm [P=0.004]), more dilated left ventricular cavity (end-diastolic volume, 87±14 versus 80±14 mL/m2 [P=0.0178]; end-systolic volume, 36±9 versus 29±8 mL/m2 [P<0.001]), lower ejection fraction (59±6% versus 64±6% [P<0.001]), reduced systolic deformation (global circumferential strain, −29.9±4.2 % versus −32.2±5.0 % [P=0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m2 [P<0.001]). T1 native values were decreased (936±53 versus 996±26 ms [P<0.001]), with particular low values in patients with phenylalanine >1200 µmol/L (909±48 ms). Both mean phenylalanine (P=0.013) and tyrosine (P=0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. CONCLUSIONS: Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early-stage cardiomyopathy. Regular cardiology follow-up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipi-demia, are recommended.
KW - Cardiac magnetic resonance
KW - Cardiomyopathy
KW - Dyslipidemia
KW - Phenylketonuria
KW - T1 native
UR - http://www.scopus.com/inward/record.url?scp=85114845607&partnerID=8YFLogxK
U2 - 10.1161/JAHA.120.020351
DO - 10.1161/JAHA.120.020351
M3 - Article
C2 - 34423658
AN - SCOPUS:85114845607
SN - 2047-9980
VL - 10
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 17
M1 - e020351
ER -