4096Cardiac manifestation in wilson disease. The CARMA Wilson study. A comprehensive clinical and cardiac imaging trial

Abstract

Background: Wilson disease (WD) is a genetic disorder affecting copper metabolsim due to mutations on the chromosome 13. Pathological hepatic and neurological findings are typical characteristics. However, cardiac involvement of WD has never been investigated systematically before. Aim of the present study was to evaluate cardiac manifestation of WD in one of the largest cohort of patients suffering from WD in Germany. Method(s): Patients with proven WD by liver biopsy have undergone laboratory (Troponine T, NT-pro BNP, Creatine kinase and neurological clinical examination. Patiens were referred to 3T cardiac magnetic resonance (CMR) including Cine-, T1-, T2-, T2*-, myocardial strain and late gadolinium enhancement sequences. In addition, 3D echocardiography, electrocardiogram (ECG) and long-term ECG were performed. Result(s): 46 patients (age 44.2+/-13.3 years, 21 female) were included. Clinical presentation differed from inconspicuous findings to inability to walk. No patient reported cardiac symptoms. In CMR mean left ventricular systolic function was 66+/-4% and right ventricular function was 45.2+/-3 and was not significantly different than the control group (LVEF 64.7+/-2.5%, p 0.92; RVEF 47.6+/-9.6%, p=0.83). Three patients with serous neurological affections of WD presented diffuse LGE accumulation. Furthermore we found LGE at the right ventricular insertion point in 92% of all patients. This was significantly more frequent than the in controls (8%) (p<0.001). There was no evidence of edema or capillary leak. No patient had pericardial effusion. In 15 patients (31%) and 4% (n=2) of the controls (p<0.001) left ventricular clefts were obvious (Image a and c LGE- and b and d cine sequences of 2 patients, white arrow indicating left ventricular cleft). In ECG and long-term ECG 23 patients (47%) showed ventricular ectopic beats. In 1 patient complete atrioventricular block was evident and needed a permanent pacemaker. Conclusion(s): Cardiac manifestation of WD seems possible. CMR is capable of revealing subclinical pathological findings. Cardiac involvement as fibrosis may affect prognosis in WD. Whether the increased rate of left ventricular clefts in WD is due to specific pathogenic gene variants remains unclear and will be investigated soon.