Myocardial fibrosis, diastolic dysfunction and elevated liver stiffness in the Fontan circulation
Gruschen R Veldtman,
Wojciech Mazur,
Tarek Alsaied,
Ryan A Moore,
Sean M Lang,
Vien Truong,
Adam M Lubert,
Konstantin Averin,
Jonathan R Dillman,
Andrew T Trout,
Michael D Taylor,
Quan He,
David LS Morales,
Andrew N Redington,
Bryan H Goldstein
Affiliations
Gruschen R Veldtman
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Wojciech Mazur
4 The Ohio Heart and Vascular Center, The Christ Hospital, Cincinnati, Ohio, USA
Tarek Alsaied
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Ryan A Moore
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Sean M Lang
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Vien Truong
Department of Cardiology, The Christ Hospital Health Network, Cincinnati, Ohio, USA
Adam M Lubert
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Konstantin Averin
Department of Pediatrics, Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada
Jonathan R Dillman
Department of Radiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Andrew T Trout
Department of Radiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Michael D Taylor
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Quan He
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
David LS Morales
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Andrew N Redington
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Bryan H Goldstein
Department of Pediatrics, The Heart Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Introduction Single ventricle diastolic dysfunction and hepatic fibrosis are frequently observed in patients with a Fontan circulation. The relationship between adverse haemodynamics and end-organ fibrosis has not been investigated in adolescents and young adults with Fontan circulation.Methods Prospective observational study of Fontan patients who had a cardiac catheterisation. Cardiac MRI with T1 mapping was obtained to measure extracellular volume (ECV), a marker of myocardial fibrosis. Hepatic magnetic resonance elastography was performed to assess liver shear stiffness. Serum biomarkers of fibrosis including matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were measured. Very high ECV was defined as >30% and elevated serum biomarkers as >75th percentile for each biomarker.Results 25 Fontan patients (52% female) with mean age of 16.3±6.8 years were included. Mean ECV was 28%±5%. There was a significant correlation between ECV and systemic ventricular end-diastolic pressure (r=0.42, p=0.03) and between ECV and liver stiffness (r=0.45, p=0.05). Patients with elevated ECV demonstrated elevations in MMPs and TIMPs. Similarly, patients with elevated MMPs and TIMPs had greater liver stiffness compared with patients with normal levels of these biomarkers.Conclusions In Fontan patients, cardiac magnetic resonance evidence of myocardial fibrosis is associated with diastolic dysfunction, increased liver stiffness and elevated circulating biomarkers of fibrosis. These findings suggest the presence of a profibrotic milieu, with end-organ implications, in some patients with Fontan circulation.
