Heart disease can progress on ERT, especially in older Fabry men

More than a third of Fabry disease patients show signs of cardiac disease progression despite use of enzyme replacement therapy (ERT), according to a recent study.

An existing diagnosis of the heart disease, called left ventricular hypertrophy (LVH), was found to be the strongest predictor that a person would see cardiac progression over time. Being male and older were also linked to both cardiac progression and other Fabry disease-related adverse events.

Given the fact that male patients younger than 30 and women younger than 50 remained relatively stable over more than 10 years, researchers believe this might offer “a window of opportunity” to start treatment and effectively prevent the progression of organ damage in Fabry disease.

The study, “Fabry disease: development and progression of left ventricular hypertrophy despite long-term enzyme replacement therapy,” was published in Heart.

Fabry disease is characterized by widespread organ damage due to the toxic accumulation of fatty molecules. This happens because patients lack the alpha-galactosidase A (alpha-Gal A) enzyme needed to break those molecules down.

Heart problems common, leading cause of death in Fabry disease

Among the common symptoms of Fabry disease are heart problems, which are the leading cause of death for patients. LVH occurs when the heart’s left ventricle — responsible for pumping oxygenated blood to the rest of the body — thickens and enlarges. These changes make it harder for the heart to pump blood and can ultimately lead to heart failure.

Enzyme replacement therapy is the standard Fabry treatment, providing patients with a working version of the alpha-Gal A enzyme. It is recommended these treatments be started as soon as possible to slow the progression of organ damage.

Some data indicate that life-threatening cardiac complications can be avoided if ERT is started soon enough, but long-term data on the issue are still being collected.

To learn more, the scientists examined the progression of heart disease among 60 Fabry disease patients in Switzerland receiving ERT.

When starting ERT (baseline), 22 patients had LVH. The presence of the cardiac condition was significantly associated with older age, male sex, and a history of chronic kidney failure and high blood pressure.

Recommended Reading

36% of patients showed signs of enlarging left ventricle over 10.5 years

Over a median follow-up of 10.5 years, 22 people (36%) showed signs of an increasing left ventricular mass index (LVMI), which reflects that the left ventricle is starting to enlarge. Once LVMI reaches a certain point, a person is clinically considered to have LVH.

Progressing LVMI over follow-up was significantly more common in patients who had LVH to begin with, occurring in about 68% of those individuals.

Still, seven people who hadn’t shown any signs of LVH when starting on ERT also saw an increased LVMI over follow-up. Among them, three reached the threshold meeting the diagnostic criteria for LVH.

Both sex and age were found to significantly influence the likelihood of LVMI increases over time, with patients seeing such progression being significantly older than those who did not progress.

Among patients younger than 30 years, there was no significant overall LVMI progression, but a significant progression was observed in age groups 30-50 and in those older than 50, where around half of patients in each group experienced LVMI increases.

Moreover, while 43% (17 of 39) of the men saw LVMI progression, this was seen in 24% of the women, or five of 21 patients. Among the men, this cardiac progression was age-dependent, occurring more often in patients older than 30.

Recommended Reading

LVH at baseline was significant predictor of Fabry-related adverse events

Overall, 19 people (31%) experienced a major Fabry disease-related event during follow-up, which again was linked to being male, older, and seeing LVMI progression over follow-up. As with cardiac progression, having LVH at baseline was a significant predictor of Fabry-related adverse events.

Nine people had cardiac adverse events, with one person experiencing sudden cardiac death. Non-cardiac events included the need for renal replacement therapy (i.e. dialysis or kidney transplant) or neurological issues.

“Our findings show that LVMI continues to progress despite ERT in a significant proportion of patients,” the researchers wrote.

Current recommendations indicate ERT should be started at the earliest signs of organ involvement. However, LVH is a relatively late indicator of heart involvement, according to the scientists.

“Further studies are needed to validate novel biomarkers of pre-hypertrophic [earlier] cardiac involvement to optimise the timing of treatment initiation,” the team concluded.