P008. Referral and Diagnosis of Hereditary Transthyretin Amyloidosis by Heart Failure Nursing Specialists in the United States: Insights From a Genetic Testing Program

Abstract

<h3>Background</h3> Hereditary transthyretin amyloidosis (hATTR or ATTRv [variant]) is a progressive and fatal disease caused by mutations in the transthyretin gene (<i>TTR</i>) that result in the deposition of misfolded TTR protein in major organs and systems, leading to multisystem dysfunction. Patients often experience a mixed phenotype of both cardiomyopathy and polyneuropathy. Early diagnosis, which can be facilitated with genetic testing, is key to achieving optimal patient outcomes. <h3>Objective</h3> Describe the number of patients with <i>TTR</i> mutations and their demographics in comparison with patients with mutations associated with other inherited cardiovascular diseases that can mimic the symptoms of hATTR, in a selected sample of patients presenting with symptoms of heart failure. <h3>Methods</h3> This analysis collected demographic and clinical data from patients enrolled in the hATTR Compass program, a confidential genetic testing program offered in the United States (including Puerto Rico) and Canada for patients suspected of having hATTR with cardiomyopathy or with a family history of hATTR. DNA next-generation sequencing was performed using a panel of 92 genes associated with inherited cardiovascular conditions. Symptoms reported may be underrepresented because of limitations of data collection and program participation. <h3>Results</h3> Among 142 participating institutions in the United States, 321 patients were referred for genetic testing by heart failure nursing specialists. Of this group, 17 had <i>TTR</i> mutations and 36 had mutations associated with other non-<i>TTR</i> related inherited cardiomyopathies. More patients in the non-<i>TTR</i> mutation group were female compared with the <i>TTR</i> mutation patients (58% and 47%, respectively). Non-<i>TTR</i> mutation patients were younger than <i>TTR</i> mutation patients, on average (55 and 70 years, respectively). Most patients in both the non-<i>TTR</i> and <i>TTR</i> mutation groups (97% and 94%, respectively) did not have or did not know of a family history of hATTR. The most common non-<i>TTR</i> cardiomyopathy-related mutation was <i>TTN</i>, which is associated with dilated cardiomyopathy. The most common <i>TTR</i> mutation was p.V142I, which is typically associated with a predominant cardiomyopathy phenotype. Compared with <i>TTR</i> mutation patients, a higher proportion of non-<i>TTR</i> mutation patients reported sensory dysfunction, motor dysfunction, and autonomic dysfunction each. Heart disease was very common in both the non-<i>TTR</i> and <i>TTR</i> mutation patient groups (<b>Table 1</b>). <h3>Conclusion</h3> Patients with hATTR can present with both polyneuropathy and cardiomyopathy symptoms. Diagnosis of hATTR is challenging, as many patients do not have a known family history of hATTR, and symptoms of hATTR can overlap with other inherited cardiovascular diseases. It is critical to recognize the multiple symptoms that should raise clinical suspicion of hATTR and to refer patients for genetic testing to facilitate diagnosis. Prompt diagnosis will allow for early initiation of disease modifying therapy for this debilitating and fatal disease.