Cardiac phosphorus-31 two-dimensional chemical shift imaging in patients with hereditary hemochromatosis Michael F.H. Schocke a, *, Heinz Zoller c , Wolfgang Vogel c , Christian Wolf a , Christian Kremser a , Peter Steinboeck b , Gerhard Poelzl b , Otmar Pachinger b , Werner R. Jaschke a , Bernhard Metzler b a Department of Radiology, University Hospital of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Tyrol, Austria b Division of Cardiology, Department of Internal Medicine, University Hospital of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Tyrol, Austria c Division of Gastroenterology, Department of Internal Medicine, University Hospital of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Tyrol, Austria Received 27 June 2003; accepted 26 January 2004 Abstract Hemochromatosis is a hereditary iron overload syndrome characterized by increased iron storage, followed by liver cirrhosis and is often associated with restrictive cardiomyopathy. The purpose of this study was to detect alterations of cardiac high-energy phosphate metabolism in patients with hereditary hemochromatosis (HHC) prior to the development of structural heart diseases. Therefore cardiac phosphorus-31 two-dimensional chemical shift imaging ( 31 P 2D CSI) was employed. Twenty-four male patients (mean age 47.2  12 years) homozygous for the C282Y mutation in the hemochromatosis associated HFE gene and twentyfour male healthy volunteers (mean age 47  11 years) as age-matched controls were included in this study. Using a 1.5-Tesla whole-body magnetic resonance scanner, electrocardiograph- triggered transversal 31P 2D CSI was performed. Left ventricle mean phosphocreatine (PCr) to -adenosine triphosphate (-ATP) ratios of patients with HHC (1.60  0.41) were significantly decreased in comparison to healthy volunteers (1.93  0.36; p = 0.004). Furthermore, we detected moderate, negative correlations between left ventricular PCr to -ATP ratios and transferrin saturation, cholesterol, low-density lipoprotein as well as triglyceride. This study shows that 31P 2D CSI permits the detection of alterations of cardiac high-energy phosphate metabolism in patients with HHC, but without any evidence for heart disease. The decreased PCr to -ATP ratios in HHC might be caused by mitochondrial impairment due to cardiac iron overload. © 2004 Elsevier Inc. All rights reserved. Keywords: Cardiac 31 P 2D CSI; Hereditary hemochromatosis; Echocardiography; High-energy phosphate metabolism 1. Introduction Hereditary hemochromatosis (HHC) is an autosomal re- cessive disorder of iron metabolism that affects approxi- mately 1 in 200 –300 individuals of Northern European descent [1,2]. HHC is characterized by increased iron ab- sorption and progressive deposition in various organs, in- cluding liver, pancreas, pituitary gland and heart. The liver is predominantly affected by the iron overload, resulting in hepatomegaly and cirrhosis [3]. Previous analyses of sur- vival and causes of death among patients with primary hemochromatosis have shown that those patients suffer more frequently from liver cirrhosis, liver cancer and car- diomyopathy as compared to the normal population, result- ing in substantial morbidity and mortality [4–6]. Further- more, patients with hemochromatosis diagnosed in the precirrhotic stage and treated sufficiently have a normal life expectancy, whereas cirrhotic patients showed a shortened life expectancy and a high risk of liver cancer, even when complete iron depletion has been achieved [4]. Although 83% of patients with HHC were found to be homozygous for a mutation in the HFE gene, which causes a substitution of a cystein to tyrosin at position 282 (C282Y) of the predicted aminoacid sequence, recent results from popula- tion screening studies suggest that only 1–50% of C282Y homozygous patients present with clinically significant iron overload [7–9]. Therefore, diagnosis should be improved in order to enable a successful therapy. Cardiac phosphorus-31 magnetic resonance spectros- copy ( 31 P MRS) was established for in vivo examination of * Corresponding author. Tel.: +43-512-504-22761; fax: +43-512-504- 22758. E-mail address: michael.schocke@uibk.ac.at (M.F.H. Schocke). Magnetic Resonance Imaging 22 (2004) 515–521 0730-725X/04/$ – see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.mri.2004.01.023