Diffuse fibrosis, coronary microvascular dysfunction and systolic dysfunction in Wilson disease

Background Wilson disease (WD) causes intracellular copper accumulation in the body due to a genetic defect in the protein ATP7B. Cardiac involvement such as electrocardiographic abnormalities, rhythm abnormalities, heart failure and cardiac death have been reported, however pathophysiological mechanisms remain unclear. Objectives This study aimed to comprehensively assess the myocardium in WD patients without cardiac symptoms using multiparametric cardiovascular magnetic resonance imaging (CMR), including quantitative stress perfusion mapping and strain analysis. Methods WD patients (n=17, 41±16 years, 47% female) and volunteers (n=17, 39±15 years, 47% female) underwent multiparametric mapping at 1.5 T CMR including cine, native T1, native T2, adenosine stress perfusion mapping, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging. Symptoms of myocardial ischemia were quantified using Seattle Angina Questionnaire-7 (SAQ-7) and cardiovascular risk factors and medications were recorded. Results Both stress perfusion and MPR were lower in WD patients (2.95±0.58 vs 3.67±1.01 ml/min/g, and 3.4±0.8 vs 4.4±1.9), while ECV was higher, (29±3% vs 27±2%), p<0.05 for all. Left ventricular ejection fraction (LVEF) was lower in WD patients, (56±6% vs 61±6%, p =0.02), and LV ventricular global circumferential strain (LV GCS) was higher (-18±2% vs - 20±2%, p =0.005). Late gadolinium enhancement (LGE) was present in the right ventricular insertion point (RVIP) in 12/17 (71%) of the WD patients. Conclusions In this small mechanistic study, WD patients on stable treatment without apparent cardiac symptoms have early signs of diffuse fibrosis, coronary microvascular dysfunction (CMD) and systolic dysfunction, shedding light on pathophysiological mechanisms of cardiac dysfunction in copper accumulation.