More than half of adults with Fabry at risk of cardiac events: MRI study
Scans show irregular heartbeat, heart failure as most common
More than half of adults with Fabry disease were found to have heart involvement that put them at risk for cardiac events — here, primarily associated with irregular heartbeat and heart failure, according to a new MRI study.
While an enlarged heart muscle and scar tissue formation were associated with worse cardiac events, the strongest predictor was the thickness of the muscle on the left side of the heart.
“Our study contributes to the evidence that [MRI] can be used to identify patients at high risk of adverse cardiac events,” the researchers wrote.
Among the individuals with Fabry in the study, 16.3% “reached at least one cardiac endpoint,” the team noted. For 9.1%, that was heart failure, while atrial fibrillation, or an irregular heartbeat, affected 12.7% of participants. “Cardiac death (1.8%) [was] rare in our patient [group],” the team noted.
Titled “Clinical and CMR characteristics associated with cardiac events in patients with Fabry disease,” the study was published in the International Journal of Cardiology.
Using MRI scans to ID risk of cardiac events
Fabry disease is a rare genetic disorder marked by the toxic buildup of fatty molecules, mainly globotriaosylceramide (Gb3 or Gl-3), in lysosomes, the cell’s recycling compartments. Organs affected include the heart, nervous system, and kidneys, which can lead to life-threatening symptoms.
Heart involvement may trigger scar tissue formation, known as fibrosis, and the enlargement of heart muscles on the left side of the heart, called left ventricular hypertrophy.
Cardiac magnetic resonance (CMR) — an MRI of the heart — has been shown to be an accurate way to assess the extent of heart muscle enlargement and scar formation.
Still, because Fabry is a rare disease, “there is limited data on the relation of CMR findings with cardiac outcome” among patients, the researchers wrote.
To learn more, a team led by researchers from Switzerland decided to “investigate the impact of clinical characteristics and CMR findings on cardiac outcome in patients with [Fabry].”
CMR was conducted among 55 Fabry patients, with a mean age of 33 at diagnosis. Among them, 47 had classic Fabry, while eight had the late-onset form. Classic Fabry typically begins in childhood or adolescence, while late-onset generally starts after age 30.
About two-thirds of patients were receiving enzyme replacement therapy.
Left ventricular hypertrophy (LVH) was assessed with CMR, while scar formation was measured using MRI plus late gadolinium enhancement (LGE). The primary outcome was defined as the first adverse cardiac event, which included either cardiac death, heart failure, or various types of irregular heartbeat.
Heart muscle involvement was seen in 28 Fabry patients (50.9%), as either LVH or LGE indicated. Among the 54 who underwent LGE, both LVH and LGE were simultaneously present in 19 (35.2%) patients. Only one woman had LGE without LVH.
Nine participants (16.3%) met the primary cardiac outcome measure over a median 4.9-year follow-up. Patients with cardiac events were older at diagnosis (mean 48 vs. 30.1) and at the time of CMR (mean 59.3 vs. 36.7) compared with non-cardiac event patients. The proportion of those with late-onset disease among the group with cardiac events was higher than among the cardiac event-free group (44.4% vs. 8.7%).
Elevated levels of two blood markers for heart damage were more common among patients with cardiac events than among patients without such complications: Troponin-T (83.3% vs. 21.1%) and NT-pro-BNP (66.7% vs. 23.1%). LVH was present in all cardiac event participants compared to 39.1% in patients without cardiac outcomes.
Cardiac events more common with enlarged left heart muscles
Other measures of the extent of LVH also were significantly higher in cardiac event patients, including maximal left ventricular wall thickness, indexed left ventricular mass, and left atrial volume index. Eight of the nine patients with cardiac events had LGE.
Atrial fibrillation, a type of irregular heartbeat, was the most common cardiac event, detected in seven patients (12.7%), with five diagnosed with heart failure (9.1%). Atrial fibrillation also was the first sign of an adverse cardiac event in six of the nine, with four developing other major adverse cardiac events during follow-up.
Patients without LVH were free of cardiac events during follow-up. Six (10.9%) had nonsustained ventricular tachycardia, a fast, abnormal heart rhythm.
Clinical factors such as patient age and the late-onset form of the disease were associated with a higher risk for cardiac events. Elevated Troponin-T at study start, but not NT-proBNP, was associated with a higher risk for cardiac events.
The extent of LGE, or more scar tissue, was a significant predictor of cardiac events, with a 10% LGE increase associated with a 25% increase in the risk of cardiac events.
After adjustment for factors that may influence these findings, maximal left ventricular wall thickness was the only independent predictor of the combined cardiac outcome.
Further statistical analysis found LVH was significantly linked with worse outcomes compared to not having LVH. Additionally, patients with LGE at study start had worse event-free survival than those without LGE.
“Our results confirm that, in patients with [Fabry disease], both LVH and LGE are associated with the development of adverse cardiac events,” the researchers concluded. “In addition, our data suggests a link between maximal left ventricular wall thickness and adverse, cardiac events.”