Wilson disease is characterized by the abnormal build-up of copper in the body. This alone can lead to multiorgan disease, most notably in the liver, the heart, and the neurological system.
In the 1980s, scientists began to notice a number of cardiac deaths in patients with Wilson disease. They thus suggested that cardiac deterioration be included among the clinical manifestations of the disease. Further research revealed a close association between Wilson disease and cardiomyopathy, arrhythmias, and conduction dysfunction.
“The epidemiology of this condition has remained poorly characterized, probably due to the lack of routine cardiac evaluation in [Wilson disease] patients,” Chevalier and colleagues wrote in the Journal of Inherited Metabolic Disease.
When new diseases are characterized, it is not uncommon for their secondary effects to only surface later. The characterization of Wilson disease during the early days of its discovery was hampered by both the relative rarity of this disease and the low number of cardiac investigations performed on patients with this disease.
Read more about Wilson disease etiology
Early studies indicate that cardiac dysfunction in patients with Wilson disease is more of an incidental, peripheral discovery: a literature review indicates that myocardial copper accumulation can result in cardiomyopathy and arrhythmias, although these manifestations are rare.
Later studies alerted physicians to the possibility that cardiac dysfunction is more of a hallmark of Wilson disease than an incidental finding: a later study reported that patients with Wilson disease have a 29% higher incidence of atrial fibrillation and a 55% excess risk of developing congestive cardiac failure, even after adjusting for confounders.
The Extent of Cardiac Disease in a Population of Patients With Wilson Disease
We now turn our attention to a study written by Wang et al in the European Journal of Gastroenterology & Hepatology. The purpose of their study was to understand cardiac health as measured via electrocardiography in a cohort of patients with Wilson disease.
They recruited 126 patients with Wilson disease between January 2011 and December 2020. Out the 126 patients identified, 29.4% reported having cardiac manifestations. Nine patients demonstrated manifestations of cardiac disease, with symptoms such as dizziness, discontinuous chest tightness, and palpitations. An electrocardiogram conducted in this subpopulation revealed abnormalities consistent with cardiac dysfunction.
“Cardiac involvement is not rare in adult [Wilson disease] patients,” the authors of the study concluded. “We suggest that cardiac evaluation should be routinely performed in the population.”
In a separate study published in the Journal of Inherited Metabolic Disease, Chevalier and colleagues conducted a literature review to better understand the relationship between Wilson disease and cardiac involvement.
They conducted a literature review using academic search engines and included studies published between 1959 and December 2020. Keywords included “Wilson disease,” “cardiomyopathy,” “arrhythmias,” and “dysautonomia,” among other similar keywords. A total of 32 publications were included in their final review.
From the very onset, researchers discovered that sudden deaths with cardiac involvement were not uncommon among patients with Wilson disease. Although the exact manifestations underpinning this outcome is uncertain, it is reasonable to suggest a link between the 2 conditions.
Electrocardiogram abnormalities have also been frequently reported among patients with Wilson disease; scientists believe that the deposition of copper in the heart may play a role in electrocardiographic dysregulation. Scientists have suggested 24-hour cardiac monitoring in patients with Wilson disease in order to aid in diagnosis and follow-up.
These signs of possible cardiac involvement should encourage physicians to conduct more thorough assessments of the heart. A transthoracic echocardiogram is one of the most potent tools in analyzing the morphological changes in cardiac structure and function. In order to chart cardiac dynamic changes, this procedure is best performed at baseline and at follow-up.
Another important investigative tool that can be used to track cardiac health are biomarkers of cardiac damage, specifically troponin and brain natriuretic peptide (BNP). These can be easily conducted and are supportive of other efforts to characterize cardiac health in patients with Wilson disease.
“It has been hypothesized that myocardial copper overload may be responsible for inflammation of the myocardium (myocarditis), which would improve with appropriate therapy for [Wilson disease],” Chevalier et al wrote.
Monitoring Cardiac Health During Follow-up
Given the growing body of evidence of how copper accumulation in the heart can lead to cardiac abnormalities, physicians must make it a point to carry out routine cardiac health examinations in patient follow-ups. In a clinical setting, this might mean conducting electrocardiograms, echocardiography, cardiac biomarkers, and so on. These investigations are relatively cheap but can offer significant clues to the extent of cardiac damage.
The bigger point here is that the mere accumulation of copper in an organ (in this case, the heart) can result in dysfunction that can be deadly when left untreated. Today, Wilson disease is typically treated with chelating agents, and one might be tempted to believe that Wilson disease is an illness that is easily treatable without long-term consequences. However, Wilson disease is rarely diagnosed immediately, and the years it goes undetected can cause significant multi-organ dysfunction.
To preserve the quality of life of patients with Wilson disease, it is vital that physicians leave no stone unturned.
References
Chevalier K, Benyounes N, Obadia MA, et al. Cardiac involvement in Wilson disease: review of the literature and description of three cases of sudden death. J Inherit Metab Dis. Published online July 19, 2021. doi:10.1002/jimd.12418
Wang C, Gao H, Sun J, et al. Cardiac involvement in Wilson’s disease: a retrospective cohort study. Eur J Gastroenterol Hepatol. Published online July 7, 2022. doi:10.1097/MEG.0000000000002432
