ECG Parameter May Help ID Fabry Patients at Risk for Pacemaker

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Many Fabry disease patients with heart involvement develop a slow and irregular heartbeat, called bradyarrhythmia, late in the disease course when heart damage is already advanced, according to a small study in Italy.

The finding adds to previous studies reporting bradyarrhythmia as a late symptom of Fabry, discouraging its use as marker for the early identification of the disease, the researchers noted.

Follow-up variations in QRS, a parameter of electrocardiogram (ECG), were strongly associated with bradyarrhythmia onset and the future need for a pacemaker, highlighting that regular ECG assessments are important for people with Fabry.

A pacemaker is a small device that’s surgically implanted in the chest to help control a person’s heartbeat. It’s usually recommended for people with irregular and/or slower-than-normal heartbeat.

The study, “Prevalence and predictors of bradyarrhythmias requiring permanent pacing in patients with Anderson–Fabry disease,” was published in the form of a brief communication in the Journal of Cardiovascular Electrophysiology.

In Fabry disease, deficient activity of the alpha-galactosidase A (Gal A) enzyme leads to the toxic accumulation of fatty molecules inside cells, which can damage several organs, especially the kidney, heart, and brain.

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More than 50% of Fabry patients show heart involvement, which usually manifests as left ventricular hypertrophy (LVH), irregular heartbeat (arrhythmias), heart scarring, and functional problems, and is the leading cause of death. LVH refers to the enlargement and thickening of the walls of the heart’s main pumping chamber.

As such, identifying markers leading to early diagnosis of Fabry disease and early detection of heart involvement is crucial to prevent further damage.

In patients with heart damage, “easy and cost‐effective markers of risk for PM [pacemaker] requirement may help prevent clinical complications, including [fainting] and sudden death,” the researchers wrote.

A team of researchers at the Careggi University Hospital, Italy, evaluated the frequency of pacemaker implantation in Fabry patients and the most significant predictors for needing one. They also assessed whether bradyarrhythmia was an onset symptom of Fabry.

The researchers retrospectively analyzed the data of 82 Fabry patients (52 women and 40 men) who were followed for at least a year at their center between 1994 and 2020. Heart involvement was defined through the presence of LVH. Patients’ median age at diagnosis was 41, and they were followed for a median of 6.9 years.

Men showed overall more severe heart disease than women and were more likely to die (23% vs. 1.9%) during follow-up. Nevertheless, men were more frequently given standard enzyme replacement therapy (ERT) than women (73.3% vs. 30.7%).

Results showed that 39 patients (47.6%) had heart involvement, most of them already at diagnosis (32.9%), and five of them (three women and two men; 13%) required pacemaker implantation — representing 6% of all patients.

Their median age at implantation was 59 years, and all but one patient had already been diagnosed with Fabry and were on ERT. The exception was a 54‐year‐old woman with a history of gradual heart disease that was wrongly classified as sarcomeric hypertrophic cardiomyopathy, the most common genetic cardiovascular disease.

Pacemaker implantation was always performed in the context of advanced cardiomyopathy, or heart muscle abnormalities.

When looking at potential predictive factors of bradyarrhythmia and the need for a pacemaker, the researchers found that EGC parameters indicative of slower transmission of electrical signals in the heart and a greater enlargement of the heart walls were significantly associated with pacemaker implantation.

Notably, a higher-than-normal QRS duration (greater than 200 milliseconds) at diagnosis and a greater increase in follow-up ECG assessments were the most significant predictors of the onset of bradyarrhythmia and pacemaker implantation.

QRS is a parameter of ECG that reflects the velocity by which electrical signals travel through the heart ventricles to activate them.

In addition, “the absence of patients requiring PM [pacemaker] among those with QRS stability during [follow-up] underlines the importance of ECG for the selection of patients worthy of closer monitoring,” the research team wrote.

“QRS variation at serial ECG evaluation is a useful marker to identify patients at risk of PM requirement,” the researchers added, noting that larger studies are needed to confirm the predictive value of QRS evaluations in terms of Fabry disease patients requiring a pacemaker.

Moreover, severe bradyarrhythmia was never the initial manifestation of Fabry, “occurring late in the disease course and always in the context of advanced cardiac involvement,” the researchers wrote.

This was consistent with previous reports, which together “discourage systematic initiatives aimed at screening populations with juvenile bradyarrhythmias for the early identification of [Fabry disease],” the researchers said.