Transtyretin cardiac amyloidosis in the elderly patient: always a wild type?

Abstract

Abstract Background Transthyretin amyloidosis (ATTR) exists in two forms: a genetic form transmitted by autosomal dominant inheritance (ATTRv) and a wild type form (ATTRwt). Clinically, the hereditary form tends to have an early onset in adulthood and it is characterized by a particular tropism for nervous as well as cardiac tissue. In contrast, the "wild type" form has a later onset with major cardiac involvement and neurological manifestations usually limited to carpal tunnel syndrome (1). Methods and results in our centre, from January to October 2022, 20 patients older than 75 years received a diagnosis of cardiac ATTR (73% male, 27% female, mean age 83±5). In all patients, blood tests showed a significant and stable increase in the values of troponin Ths (0.070± 0.074 ng/mL) and NT-proBNP (1533±1204 pg/ml), with the absence of a monoclonal component in the blood and urine, and miocardial bisphosphonate scintigraphy positive grade 2/3. All patients showed absence of peripheral neuropathy with the presence of carpal tunnel syndrome in 9 cases. Before starting therapy with Tafamidis all patients underwent genetic testing by amplification of exons 2,3 and 4 of the TTR gene with subsequent sequencing. Unexpectedly, in 3 elderly male patients (15%) the genetic test resulted positive with 3 different mutations of pathogenetic significance (Val50Met; Ile88Leu; Val142Ile). First-degree relatives (10 consanguineous, average age 49±12 years) agreed to be subjected to genetic screening; of these 4 (1 male and 3 females, age 47±8 years) were positive for the corresponding mutation and underwent echocardiogram, MRI and myocardial scintigraphy. All of these tests were normal and they were included in an annual follow-up protocol at the to identify an early manifestation of the disease. Conclusions our experience shows that 15% of patients older than 75 years and diagnosed with cardiac ATTR may be affected by a genetic form. Making genetic diagnosis in this context is particularly important for screening family members: current therapies are in fact much more effective if started early before organ damage can occur (2).