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Cardiac involvement and clinical follow up of patients with hereditary transthyretin related amyloidosis associated with Glu89Gln mutation


Cardiac involvement is common in hereditary transthyretin – related amyloidosis (ATTR), but there is a significant phenotypic heterogeneity depending on the mutation.

Patients and methods

We evaluated forty consecutive ATTR patients with Glu89Gln mutation, focusing on cardiac involvement - 18 male, 22 female at a mean age of 57.6±6,7 years. A clinical examination, 12–channel ECG, conventional 2D, Doppler and tissue Doppler echocardiography were performed. The patients were followed for 36 months in the range from 2 to 78 months.


Median age of symptoms development was 52, 3±6, 4 years. Cardiac onset was found in 5 (12,5%) patients. Cardiomyopathy and peripheral polyneuropathy were evident at diagnosis in all patients. Echocardiography revealed a significant increase in wall thickness of both left and right ventricles (septum – 18,6±3,4 mm; posterior wall – 17,5±2,5 mm; RV free wall – 8,4±2,0 mm). Varying degrees of LV diastolic dysfunction were found – Grade 1 in 11 (27,5%) patients, Grade 2 in 12 (30%) and Grade 3 in 17 (42,5%) patients. A reduced LV ejection fraction was found in 9 (22,5%) patients. A common finding were significantly reduced mitral annulаr systolic velocities (s´septum-5,4±2,0 cm/s, s lat.-5,7±1,9 cm/s), registered in all the evaluated patients, pointing to an impaired LV longitudinal systolic function. The systolic myocardial velocities of the tricuspid annulus and TAPSE values were reduced respectively 6,9±2,1cm/s and 12,8±3 mm in 14 of the patients (35%). Pericardial effusion was found in 13 (32,5%) patients.

Pathological ECG was present in 35(87,5%) of the evaluated patients. Atrial fibrillation was registered in 4 (10%) patients, A-V block first degree in 8 (20%), low voltage in 15 (37,5%), left bundle branch block in 3 (7,5%), left anterior fascicular block in 9 (22,5%), pathological Q wave in 14 (35%), right bundle branch block in 2 (5%), and pace-maker rhythm in 2 (5%). Rhythm and conduction disturbances on ECG were found in 24 patients (60%).

The following events occurred during the follow-up period: two deaths (5,4%) (one patient due to ischemic stroke; and another due to heart failure). Two other patients suffered from ischemic strokes. 24-hour Holter ECG revealed short periods of atrial fibrillation and an oral anticoagulant was initiated. A sinus pause > 3 s was observed in one of the patients and a permanent pace-maker was implanted. Four new cases (10%) with symptomatic heart failure, requiring diuretic treatment were observed. In 15 patients a worsening of the symptoms from the peripheral neuropathy were found.


Our study confirms that ATTR associated with the Glu89Gln mutation has a mixed phenotype – neurological and cardiac and an unfavorable prognosis. Our findings imply that patients and carriers of Glu89Gln require close multidisciplinary (both cardiological and neurological) follow-up in order to initiate treatment in time.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Gospodinova, M., Sarafov, S., Guergueltcheva, V. et al. Cardiac involvement and clinical follow up of patients with hereditary transthyretin related amyloidosis associated with Glu89Gln mutation. Orphanet J Rare Dis 10 (Suppl 1), P54 (2015).

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