Early diagnosis of hereditary cardiac amyloidosis(attrv) in a carrier: when is endomyocardial biopsy indicated?

Abstract Background Hereditary transthyretin amyloidosis (ATTRv) is a rare, adult–onset, autosomal dominant genetic disorder caused by mutations in the TTR gene. The growing availability of effective therapies determining a greater benefit the earlier they start, highlights the importance of identifying cardiac involvement even in the absence of left ventricular hypertrophy. Clinical Case A 58–year–old man came to our observation for exertional dyspnea and received a diagnosis of hereditary transthyretin amyloidosis (Val142Leu). Family screening led to the identification of the 56–year–old brother who was carrier of the same mutation. This patient was symptomatic for palpitations. Blood tests, including cardiac Troponin and NTproBNP, were normal. The ECG showed sinus rhythm, with normal atrioventricular and intraventricular conduction but frequent premature ventricular contractions. Transthoracic echocardiogram was normal, including strain rate evaluation. In order to identify early cardiac involvement, the patient underwent cardiac magnetic resonance imaging and biphosphonate scintigraphy that were negative for cardiac involvement. Neurological examination showed initial bilateral carpal tunnel syndrome. Due to the presence of premature ventricular contractions, the patient underwent to an endomyocardial biopsy which unpredictably showed a slight focal positivity to Congo Red staining, and immunohistochemistry confirmed a slight focal positivity for transthyretin. Therefore, the patient started therapy with Tafamidis. At 12–month follow up cardiac scintigraphy was still negative as well as ventricular thickness resulted within normal limits. Conclusion This case shows that in ATTR mutation carriers, an initial cardiac involvement can be present even in the absence of left ventricular hypertrophy and positive bisphosphonate scintigraphy. In the presence of clinical symptoms and/or suspicious signs of disease, such as arrhythmias, an endomyocardial biopsy may be indicated in order to start disease modifying therapy earlier.