Associazione Nazionale Medici Cardiologi Ospedalieri



Transtyretin cardiac amyloidosis in elderly patients: always a wild type?

Costantino Jacopo Roma(RM) – Università degli studi di Roma “la Sapienza”, Policlinico Umberto I | Ballatore Federico Roma(RM) – Università degli studi di Roma “la Sapienza”, Policlinico Umberto I | Marchionni Giulia Roma(RM) – Università degli studi di Roma “la Sapienza”, Policlinico Umberto I

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.

Methods and results: In our centre, from September 2021 to June 2023, 52 patients older than 70 years received a diagnosis of cardiac ATTR (87% male, 13% female, mean age 81±5y). In all patients, blood tests showed a significant and stable increase in the values of troponin Ths (0.079 microg/L±0.074) and NT-proBNP (2000±1800 pg/ml), with the absence of a monoclonal component in the blood and urine, and miocardial bisphosphonate scintigraphy positive grade 2/3. All patients underwent genetic testing by amplification of exons 2,3 and 4 of the TTR gene with subsequent sequencing. Unexpectedly, in 10 elderly (70%male, 30% female, mean age 77±4 y) patients (19%) the genetic test resulted positive with 4 different mutations of pathogenetic significance (Val30Met; Ile68Leu; Val142Ile;, Phe84Leu). Three patients showed peripheral neuropathy with the presence of carpal tunnel syndrome, while isolated carpal tunnel syndrome was present in the remaining 7 cases. The three patients with neurologic involvement started Patisiran therapy, and 7 patients were treated with Tafamidis. First-degree relatives (16 consanguineous, average age 49±12 years) agreed to be subjected to genetic screening; of these 9 (3 male and 6 females, age 47±8 years) were positive for the corresponding mutation and underwent echocardiogram, MRI and myocardial scintigraphy. These tests were normal in 8 probands, included in an annual follow-up protocol to identify an early manifestation of the disease, and was diagnostic for amyloidosis in 1 patient who started specific therapy.

Conclusions: Our experience shows that 19% of patients older than 70 years with a diagnosis of 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 occurs.