Study: Left Atrial Strain Could Be a Sign of Fabry Cardiomyopathy

Left atrial (LA) strain, as part of a complete echocardiographic workup, may help physicians distinguish Fabry cardiomyopathy from other forms of left ventricular hypertrophy (LVH), according to a new study.

Corresponding author David Frumkin, MD, of Charité University Hospital, in Berlin, and colleagues, explained that in Fabry disease, patients suffer a progressive accumulation of sphingolipids in organs, including the heart, where it can lead to progressive LVH. Cardiovascular problems are a leading cause of death among people with Fabry, Frumkin and colleagues noted. The treatment for Fabry disease is enzyme replacement therapy (ERT) and novel chaperone therapy, but the outcome of such treatment can be influenced by how quickly the disease is diagnosed.

“Studies have demonstrated a benefit when ERT is initiated early in the course of disease, but efficacy is uncertain when started after the development of advanced cardiomyopathy,” Frumkin and colleagues said. “Early diagnosis of cardiac involvement as well as timely and effective treatment are therefore crucial to prevent irreversible cardiomyopathy.”

Impairment of left ventricular global longitudinal strain is known to be impaired in patients with Fabry cardiomyopathy, though it can also be a sign of other etiologies.

In addition to LVH, posterolateral strain impairment and papillary muscle hypertrophy have also been seen as “classical” echocardiographic signs of Fabry cardiomyopathy, but Frumkin and colleagues said their diagnostic accuracy in clinical practice is limited.

Existing research has demonstrated that impairment of phasic left atrial strain (LAS) is present in Fabry disease and other storage diseases, compared to healthy controls. Those studies suggest that Fabry cardiomyopathy might not only cause LVH and left ventricular fibrosis, but also affect the left atrium, leading to impairment of left atrium mechanics, the authors said. However, the evidence on that question is minimal.

Frumkin and colleagues decided to retrospectively analyze the echocardiographic assessments of 20 patients with Fabry disease confirmed by genetic testing and 20 patients with LVH caused by other factors. They then compared classical “red flags” of Fabry cardiomyopathy to LAS to see the relative diagnostic value of each.

Of the 20 patients in the control group, 12 patients had hypertrophic cardiomyopathy, 2 had hypertensive heart disease, and 6 had LVH combined with borderline myocarditis, the authors said.

The investigation showed that left atrial strain was significantly impaired in Fabry cardiomyopathy compared to the control group, while global and regional left ventricular strain was not. LAS conduction strain was most predictive of Fabry cardiomyopathy, with an area under the curve of 0.81 (95% CI, 0.66-0.96).

“Since Fabry disease is a systemic disease and sphingolipid accumulation is histologically proven to exceed the LV, it may be reasonable to integrate echocardiographic parameters exceeding LV geometry and function, such as impairment of LAS, into the diagnostic algorithm,” the authors wrote.

Frumkin and colleagues said it is not yet clear exactly why patients with Fabry cardiomyopathy appear to have significantly constrained LAS, though they said it could be “partially explained by impaired diastolic LV function and consecutively elevated LV filling pressures.”

Though more research is needed, the investigators said their findings could help bring additional accuracy to the important task of quickly diagnosing Fabry cardiomyopathy.

Reference

Frumkin D, Mattig I, Laule N, et al. Comparative analysis of phasic left atrial strain and left ventricular posterolateral strain pattern to discriminate Fabry cardiomyopathy from other forms of left ventricular hypertrophy. Echocardiography. Published online October 21, 2021. 2021;10.1111/echo.15224. doi:10.1111/echo.15224