Arrhythmia Linked to Fibrosis in Asymptomatic Patients with Scleroderma, Study Suggests

A device designed to continuously record heart rhythm showed that asymptomatic patients with scleroderma have significant arrhythmia, according to a pilot study.

Findings also suggested that arrhythmia — irregular heart rhythm — is associated with fibrosis, or scarring, and the levels of cardiovascular biomarkers.

The study, “Incidental significant arrhythmia in scleroderma associates with cardiac magnetic resonance measure of fibrosis and hs-TnI and NT-proBNP,” was published in the journal Rheumatology.

Heart disease in scleroderma is characterized by fibrosis in the myocardium, the cardiac muscle, with or without inflammation. Although arrhythmia is common, it is not clinically relevant in all patients with fibrosis.

Most research on heart disease in scleroderma has not differentiated between incidental (associated with another disorder) and primary disease. Researchers have also not evaluated the value of an implantable loop recorder (ILR) — a device that records heart rhythm for up to three years — to screen for significant arrhythmia in asymptomatic but high-risk patients.

Furthermore, researchers have yet to determine the correlation between cardiac magnetic resonance (CMR) findings — such as functional measures and fibrosis — and abnormalities in the cardiac system.

To shed more light on these issues, a team led by researchers at Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, in the U.K., analyzed 20 scleroderma patients with no known cardiovascular disease based on readings from an ILR inserted under the skin and cardiac imaging. Patients were evaluated every three months over three years.

Assessed parameters included fasting lipid (fat) profile and glucose, creatine kinase — a biomarker of muscle disease activity — high-sensitivity cardiac troponin I (hs-TnI, a biomarker of  acute myocardial infarction), and N-terminal pro-brain natriuretic peptide (NT-proBNP), which is produced in response to changes in pressure inside the heart and is a biomarker of pulmonary arterial hypertension.

ILR findings were available for 19 patients — mean age of 53 years, mean disease duration of 7.5 years.

Results showed that eight patients experienced significant arrhythmias over the three-year period: one with complete heart block, two with non-sustained ventricular tachycardia (abnormally fast heartbeat), and five with atrial arrhythmias — originating in the heart’s upper chambers.

The median time from ILR insertion to significant arrhythmia was 12 months.

All three patients with serious arrhythmias (complete heart block or non-sustained ventricular tachycardia) had diffuse cutaneous scleroderma with interstitial lung disease. Their mean disease duration was two years.

Patients with significant arrhythmia showed higher initial serum levels of hs-TnI and NT-proBNP, but an unchanged amount of creatine kinase. They also had higher CMR-extracellular volume, which is indicative of diffuse fibrosis.

Five of the 14 patients with CMR data available exhibited focal fibrosis, though only one developed significant arrhythmia.

Greater initial levels of hs-TnI and NT-proBNP were also observed in patients with fibrosis. The higher these values, the lower the myocardial perfusion reserve — the maximum possible increase in myocardial blood flow above initial conditions.

Six participants needed medical treatment, including one permanent pacemaker implant, one anticoagulation treatment, and four cases of anti-arrhythmic pharmacotherapy.

The researchers concluded that almost half of the scleroderma patients analyzed “had a clinically significant arrhythmia,” and that “ILR arrhythmias appeared to be associated with hs-TnI, NT-proBNP and CMR measure of diffuse … fibrosis.”

They suggested that the “disease phenotype [namely diffuse scleroderma], CMR-extracellular volume (indicating diffuse fibrosis), and cardiac biomarkers may identify at-risk patients that would benefit from ILR screening.”