Value of Referring for Genetic Testing in Diagnosis of ATTRv

Mutations in the transthyretin (TTR) gene resulting in misfolded TTR protein deposition in major organs and systems causes hereditary transthyretin amyloidosis (hATTR or ATTRv [variant]), a progressive and fatal disease. Multisystem dysfunction is the ultimate outcome, and a mixed phenotype of both cardiomyopathy and polyneuropathy is commonly experienced by patients. Genetic testing can facilitate early diagnosis essential to optimizing patient outcomes.

In a selected sample of patients presenting with symptoms of heart failure, the number of patients with TTR mutations and their demographics were compared with patients possessing mutations associated with other inherited cardiovascular diseases that mimic ATTRv symptoms, confounding diagnoses. Demographic and clinical data for patients in the United States and Canada suspected of having ATTRv with cardiomyopathy or a family history of ATTRv were gathered from a database of patients enrolled in the hATTR Compass program using a confidential genetic testing program. Using a panel of 92 genes associated with inherited cardiovascular conditions, next-generation DNA sequencing was applied. Because of limitations of data collection and program participation, the investigators recognized that symptoms were possibly underrepresented.

A total of 321 patients were referred for genetic testing by heart failure nursing specialists among 142 participating institutions in the United States. From this group, 17 of these patients had TTR mutations and 36 exhibited other non-TTR–related inherited cardiomyopathies.

Non-TTR mutation patients were younger overall than TTR mutation patients, averaging age 55 years versus 70 years, respectively. Not surprisingly, most patients did not have or did not know of a family history of hATTR in either the non-TTR or TTR mutation groups (97% and 94%, respectively). TTN, which is associated with dilated cardiomyopathy, was the most common non-TTR cardiomyopathy-related mutation. P.V142I, which is typically associated with a predominant cardiomyopathy phenotype, was the most common TTR mutation. When comparing TTR mutation patients with non-TTR mutation patients, a higher percentage of non-TTR mutation patients reported autonomic, motor, and sensory dysfunction. In both the TTR mutation and non-TTR patient groups, heart disease was very common.

The authors concluded that patients with ATTRv can present with symptoms of cardiomyopathy as well as polyneuropathy. Diagnosis of ATTRv remains clinically challenging because many, if not most, patients are not aware of their family history of ATTRv, and ATTRv symptoms are similar to other heritable cardiovascular diseases, which may confound diagnosis. Therefore, it is essential to remain clinically vigilant and aware of the range of symptoms that should prompt clinical suspicion of ATTRv. In these cases, referring patients for genetic testing to facilitate diagnosis is critical. Early diagnosis will permit the early introduction of disease-modifying treatment for this lethal disease.

Source: Bell C, Dolinksy J, Gabriel A, et al. Referral and diagnosis of hereditary transthyretin amyloidosis by heart failure nursing specialists in the United States: insights from a genetic testing program. Presented at: 2021 Annual Meeting of American Association of Heart Failure Nurses, June 17-19, 2021. Poster P008.

Related Items

Subscribe to Amyloidosis News

Stay up to date with Amyloidosis News & updates by subscribing to receive the free AMN e‑Newsletter.

I'd like to receive: