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Spectrum of transthyretin gene mutations and clinical characteristics of Polish patients with cardiac transthyretin amyloidosis
Affiliations- Department of Cardiomyopathy, Institute of Cardiology, Warsaw, Poland
- Department of Cardiac and Vascular Diseases, John Paul II Hospital, Jagiellonian University Medical College, Krakow, Poland
- Department of Medical Biology, Institute of Cardiology, Warsaw, Poland
- Department of Neurology, Medical University of Warsaw, Poland
- Rapid Diagnosis Department, Emergency Room, Institute of Cardiology, Warsaw, Poland
- Department of Nuclear Medicine, Institute of Cardiology, Warsaw, Poland
- Unit for Screening Studies in Inherited Cardiovascular Diseases, The Cardinal Stefan Wyszynski Institute of Cardiology, Warsaw, Poland
- Department of Nuclear Medicine, John Paul II Hospital, Jagiellonian University Medical College, Krakow, Poland
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Abstract
Background: Transthyretin amyloidosis (ATTR) is a rare, life-threatening systemic disorder. We present first findings on the cardiac hereditary ATTR in Poland.
Methods: Sixty-eight consecutive patients with suspected or known cardiac amyloidosis were evaluated, including blood tests, standard 12-lead electrocardiography (ECG) and transthoracic echocardiography. ATTR was confirmed histologically or non-invasively using 99mTc-DPD scintigraphy. Transthyretin (TTR) gene sequencing was performed.
Results: In 2017–2019, 10 unrelated male patients were diagnosed with hereditary ATTR. All patients had very uncommon TTR gene mutations: 7 patients had p.Phe53Leu mutation, 2 patients had p.Glu109Lys mutation and 1 patient had p.Ala101Val mutation. The age of onset ranged from 49 to 67 years (mean [SD] age, 58.7 [6.4] years). On ECG, most patients (70%) had pseudoinfarct pattern and/or low QRS voltage. The maximal wall thickness (MWT) on echocardiography varied considerably among the patients from moderate (16 mm) to massively increased (30 mm). Most patients (90%) had decreased left ventricular ejection fraction (mean [SD], 43 [11] %). On follow-up, we observed progressive heart failure in almost all cases. The first patient with p.Phe53Leu mutation died of heart failure, the second died suddenly, the third successfully underwent combined heart and liver transplant with 15 months survival from the surgery. The patient with p.Ala101Val mutation died of stroke.
Conclusions: According to available data, this is the first time that the types of TTR mutations and the clinical characteristics of Polish patients with cardiac hereditary ATTR have been described. Previous literature data about Polish background in families with p.Phe53Leu mutation and the present results, suggest that this TTR mutation might be endemic in the Polish population.
Abstract
Background: Transthyretin amyloidosis (ATTR) is a rare, life-threatening systemic disorder. We present first findings on the cardiac hereditary ATTR in Poland.
Methods: Sixty-eight consecutive patients with suspected or known cardiac amyloidosis were evaluated, including blood tests, standard 12-lead electrocardiography (ECG) and transthoracic echocardiography. ATTR was confirmed histologically or non-invasively using 99mTc-DPD scintigraphy. Transthyretin (TTR) gene sequencing was performed.
Results: In 2017–2019, 10 unrelated male patients were diagnosed with hereditary ATTR. All patients had very uncommon TTR gene mutations: 7 patients had p.Phe53Leu mutation, 2 patients had p.Glu109Lys mutation and 1 patient had p.Ala101Val mutation. The age of onset ranged from 49 to 67 years (mean [SD] age, 58.7 [6.4] years). On ECG, most patients (70%) had pseudoinfarct pattern and/or low QRS voltage. The maximal wall thickness (MWT) on echocardiography varied considerably among the patients from moderate (16 mm) to massively increased (30 mm). Most patients (90%) had decreased left ventricular ejection fraction (mean [SD], 43 [11] %). On follow-up, we observed progressive heart failure in almost all cases. The first patient with p.Phe53Leu mutation died of heart failure, the second died suddenly, the third successfully underwent combined heart and liver transplant with 15 months survival from the surgery. The patient with p.Ala101Val mutation died of stroke.
Conclusions: According to available data, this is the first time that the types of TTR mutations and the clinical characteristics of Polish patients with cardiac hereditary ATTR have been described. Previous literature data about Polish background in families with p.Phe53Leu mutation and the present results, suggest that this TTR mutation might be endemic in the Polish population.
Keywords
cardiac amyloidosis, hereditary transthyretin amyloidosis, transthyretin amyloidosis, transthyretin cardiomyopathy, transthyretin mutation
About this articleTitle
Spectrum of transthyretin gene mutations and clinical characteristics of Polish patients with cardiac transthyretin amyloidosis
Journal
Issue
Article type
Original Article
Pages
985-993
Published online
2020-08-11
Page views
3062
Article views/downloads
1040
DOI
10.5603/CJ.a2020.0104
Pubmed
Bibliographic record
Cardiol J 2022;29(6):985-993.
Keywords
cardiac amyloidosis
hereditary transthyretin amyloidosis
transthyretin amyloidosis
transthyretin cardiomyopathy
transthyretin mutation
Authors
Monika Gawor
Katarzyna Holcman
Maria Franaszczyk
Marta Lipowska
Piotr Michałek
Anna Teresińska
Zofia T. Bilińska
Paweł Rubiś
Magdalena Kostkiewicz
Wojciech Szot
Piotr Podolec
Jacek Grzybowski
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