Coronary microvascular dysfunction, diffuse fibrosis and systolic dysfunction in Wilson disease – a multiparametric quantitative stress perfusion CMR study (RF_FR_393)

Wilson disease (WD) causes 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. This study aimed to evaluate presence of coronary microvascular dysfunction (CMD) in WD patients without apparent cardiac symptoms using comprehensive multiparametric cardiovascular magnetic resonance imaging (CMR) including quantitative adenosine stress perfusion mapping, compared to age- and sex-matched healthy volunteers.



Methods:

WD patients (n=17, 41±16 years, 47% female) and volunteers (n=17, 39±15 years, 47% female) underwent 1.5 T CMR including native T1, native T2, and automated quantitative perfusion mapping in rest and adenosine stress, as well as cine, 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. Endo- and epicardial borders were outlined in the short-axis native T1, T2, ECV and perfusion maps and global values were acquired. Cine images were analyzed in short-axis and long-axis to acquire volumes, mass and feature-tracking strain values. LGE images were assessed by one observer for location and type of LGE. Liver native T1 were measured in the native T1 maps.





Results:

There were no differences in cardiovascular risk factors or medications. SAQ-7 summary score for the WD patients was 100 [95 - 100]. Results of multiparametric CMR mapping are shown in Table 1, with typical examples in Figure 1 and 2. Left ventricular ejection fraction (LVEF) was lower in the WD patients compared to volunteers, (56±6% vs 61±6%) and left ventricular global circumferential strain (LV GCS) was higher (-18±2% vs -20±2%), p< 0.05 for both. Moreover, ECV was higher, (29±3% vs 27±2% p=0.004), and stress perfusion (2.95±0.58 vs 3.67±1.01 ml/min/g, p=0.017) and MPR were lower (3.4±0.8 vs 4.4±1.9, p=0.044) in the WD patients. Late gadolinium enhancement (LGE) was present in the right ventricular insertion point (RVIP) in 12/17 of the WD patients, and in the lateral wall as non-ischemic fibrosis in 3/17 WD patients.

 

Conclusion:

In this small mechanistic study, WD patients have higher ECV, lower systolic function together with a reduced vasodilator stress response compared to age- and sex-matched volunteer. Despite no apparent cardiac symptoms in this cohort of relatively young, well-treated WD patients there are signs of diffuse fibrosis, presence of CMD and systolic dysfunction shedding light on pathophysiological mechanisms of cardiac dysfunction in copper accumulation.