Cardiac amyloidosis is an infiltrative disease that remains an under-diagnosticated cause of heart failure. Diagnostic algorithms focus on identifying the two most frequent forms of the disease, light chains amyloidosis (AL) and transthyretin amyloidosis (ATTR), by the initial use of 99mTc-DPD scintigraphy coupled to assessment of monoclonal proteins. Etiological distinction is and of pivotal importance since the availability of specific disease modifying treatments.
We report the case of a 61-year-old man hospitalized for new onset of heart failure. Past medical history highlights bilateral carpal tunnel syndrome and monoclonal gammopathy of undetermined significance (MGUS). Cardiovascular examination reveals clinical signs of pulmonary and peripheric congestion. ECG shows conduction disturbances and low QRS voltage. Transthoracic echocardiography reveals left ventricular hypertrophy, normal systolic function (LVEF 58%), 3rd degree LV diastolic disfunction and mild pericardial effusion. Laboratory tests shows abnormal levels of TnT and pro-BNP. A diagnosis of cardiac amyloidosis is considered, and further exams are executed: cardiac magnetic resonance, haematological laboratory tests and 99mTc-DPD scintigraphy (tab. 1). Since both bone scintigraphy and monoclonal proteins tests are positive, diagnosis of cardiac amyloidosis cannot be made without non-invasive modalities (fig.1) and the patient is referred to an Amyloidosis Centre. Haematological evaluation and abdominal fat pad biopsy show stability of haematological disease and confirms the deposition of amyloidogenic TTR both in wild-type and mutated Ile88Arg variants. The results of genetic analysis confirms the presence of a heterozygous mutation of TTR gene (p.Ile88Arg – c.263T>G) (fig. 2). This mutation is not reported in database ClinVar nor in gnomAD, but according to the ACMG criteria it can be considered likely pathogenic. Considering the final diagnosis of cardiac hATTR the patient is considered eligible for treatment with Tafamidis.
DISCUSSION AND CONCLUSION
Despite clinical history with cardiac conduction system abnormalities and bilateral carpal tunnel syndrome, some gene TTR variants can bring false negative results at 99mTc-DPD scintigraphy, so ATTR form should not be excluded basing on non-invasive modalities. Performing a compete diagnostic workup led us to discover a new TTR pathogenic variant and confirm ATTR form without performing endomyocardial biopsy.