Chronic Symptom Burden Is Significant and Highlights the Need for Improved Detection and Recognition of Symptoms

Pathogenic variants in the transthyretin (TTR) gene cause hereditary TTR amyloidosis (hATTR). In the United States, V142I is one of the most common variants and confers approximately a 60% heart failure risk. There is a dearth of understanding of the natural history and progression of cardiac amyloidosis (CA).

While fully manifested CA can be identified using echocardiography with global longitudinal strain (GLS), it is unclear whether subclinical myocardial amyloid deposition can be detected using GLS.

In patients who harbor pathogenic TTR variants (TTR+), early recognition is critical because new therapies for hATTR have been developed.

In TTR+ individuals from the unselected population-based BioMe Biobank, researchers conducted a retrospective assessment of GLS to detect early features of CA prior to the diagnosis of hATTR.

Among 30,223 BioMe Biobank participants with available sequencing data that could be linked to the electronic health record, the investigators identified TTR+.

Based on patients with available echocardiograms and without known diagnoses of amyloidosis or cardiomyopathy, the researchers focused on 43 adult carriers of the V142I variant who ranged in age from 23 years to 90 years, with a median age of 63 years. Nearly three-quarters (74%) of these patients were female.

By postprocessing stored echocardiographic images to calculate GLS and segmental strain, speckle tracking echocardiography was conducted.

Among all ages of undiagnosed TTR+ adults in an unselected patient population, subnormal GLS was prevalent, perhaps signaling downstream hATTR. Among TTR V142I carriers not diagnosed with amyloidosis, prevalence of abnormal GLS increases with age, and subnormal GLS is common. Of 17 patients with >1 echo, 94.1% showed a decline in GLS over time, with a mean decrease of 2.9% over a median of 4.5 years.

In most subjects, even when GLS was normal, an “apical sparing”-type strain pattern was detected. In addition, even in younger individuals, GLS decreases over time in TTR+ patients. Additional investigations of subclinical features in hATTR are warranted to understand the potential role of early disease-modifying treatment.

Source: Kontorovich AR, Zhao W, Trivieri M, et al. Presented at: American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). March 28-30, 2020. Abstract 1110-156.

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