scholarly journals Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction

2014 ◽  
Vol 8s1 ◽  
pp. CMC.S15719 ◽  
Author(s):  
Van-Khue Ton ◽  
Monica Mukherjee ◽  
Daniel P. Judge
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Amyloid Fibrils ◽  
Missense Mutations ◽  
Preserved Ejection Fraction ◽  
Wild Type ◽  
Cardiac Amyloid ◽  
Neurologic Involvement ◽  
Emerging Therapies ◽  
Intracellular Stress Response

Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in familial TTR amyloidosis. Certain mutations are more likely to affect the heart, while others cause more neurologic involvement. Extracellular fibril deposition triggers intracellular stress response, upregulation of the inflammatory cascades, apoptosis, and organ dysfunction. Recent studies suggest that TTR cardiac amyloid may be a significant contributor to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Summarized in this review are the molecular pathways underlying the cellular toxicity of TTR amyloid fibrils and the emerging therapies aimed at TTR tetramer stabilization, abrogation of TTR synthesis in the liver, or inhibition of amyloidogenesis.

scholarly journals Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction

2021 ◽  
Author(s):  
Rajeev Malhotra ◽  
Christopher J. Nicholson ◽  
Dongyu Wang ◽  
Vijeta Bhambhani ◽  
Samantha Paniagua ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Arterial Stiffness ◽  
Ejection Fraction ◽  
Vascular Calcification ◽  
Matrix Gla Protein ◽  
Preserved Ejection Fraction ◽  
Wild Type ◽  
Incident Heart Failure

Objective: Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction. MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the association of ucMGP levels with vascular calcification, arterial stiffness including carotid-femoral pulse wave velocity (PWV), and incident heart failure in community-dwelling adults from the Framingham Heart Study. To further investigate the link between MGP and arterial stiffness, we compared aortic PWV in age- and sex-matched young (4-month-old) and aged (10-month-old) wild-type and Mgp +/− mice. Among 7066 adults, we observed significant associations between higher levels of ucMGP and measures of arterial stiffness, including higher PWV and pulse pressure. Longitudinal analyses demonstrated an association between higher ucMGP levels and future increases in systolic blood pressure and incident heart failure with preserved ejection fraction. Aortic PWV was increased in older, but not young, female Mgp +/− mice compared with wild-type mice, and this augmentation in PWV was associated with increased aortic elastin fiber fragmentation and collagen accumulation. Conclusions: This translational study demonstrates an association between ucMGP levels and arterial stiffness and future heart failure with preserved ejection fraction in a large observational study, findings that are substantiated by experimental studies showing that mice with Mgp heterozygosity develop arterial stiffness. Taken together, these complementary study designs suggest a potential role of therapeutically targeting MGP in heart failure with preserved ejection fraction.

scholarly journals Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction

2015 ◽  
Vol 36 (38) ◽  
pp. 2585-2594 ◽  
Author(s):  
Esther González-López ◽  
Maria Gallego-Delgado ◽  
Gonzalo Guzzo-Merello ◽  
F. Javier de Haro-del Moral ◽  
Marta Cobo-Marcos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction ◽  
Wild Type ◽  
Transthyretin Amyloidosis

scholarly journals Cardiac Amyloidosis Wild Type (ATTR-CAwt) and Associated Cardiac Arrhythmias: A Case Report and Literature Review

2021 ◽  
pp. 263246362199858
Author(s):  
Rangadham Nagarakanti ◽  
Kesavan Sankaramangalam ◽  
Sindhu Nagarakanti ◽  
Danyaal Moin ◽  
Kenneth Dulnuan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Case Report ◽  
Mortality Rate ◽  
Literature Review ◽  
Ejection Fraction ◽  
Cardiac Arrhythmias ◽  
Cardiac Amyloidosis ◽  
Clinical Signs ◽  
Preserved Ejection Fraction ◽  
Wild Type

Cardiac amyloidosis wild type (ATTR-CAwt) is often the underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF) and has a high mortality rate. There is usually a long delay between the appearance of clinical signs and the diagnosis of ATTR-CAwt but a short duration between diagnosis and death. ATTR-CAwt was associated with significant clinical arrhythmias. We report a case of ATTR-CAwt, the process of its diagnosis, and the associated clinical arrhythmias and their management. We also reviewed the literature of this underdiagnosed and potentially fatal condition and the current existing therapies.

Acute heart failure with preserved ejection fraction and long-term Readmisions

2008 ◽  
Vol 7 ◽  
pp. 62-63
Author(s):  
J NUNEZ ◽  
L MAINAR ◽  
G MINANA ◽  
R ROBLES ◽  
J SANCHIS ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Acute Heart Failure ◽  
Preserved Ejection Fraction

Galectin-3 in Heart Failure – Linking Fibrosis, Remodelling and Progression

2010 ◽  
Vol 6 (2) ◽  
pp. 33 ◽  
Author(s):  
Christopher R deFilippi ◽  
G Michael Felker ◽  
◽  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Stratification ◽  
Cardiac Fibrosis ◽  
The Elderly ◽  
Preserved Ejection Fraction ◽  
Heart Failure Patients ◽  
Large Populations ◽  
Galectin 3

For many with heart failure, including the elderly and those with a preserved ejection fraction, both risk stratification and treatment are challenging. For these large populations and others there is increasing recognition of the role of cardiac fibrosis in the pathophysiology of heart failure. Galectin-3 is a novel biomarker of fibrosis and cardiac remodelling that represents an intriguing link between inflammation and fibrosis. In this article we review the biology of galectin-3, recent clinical research and its application in the management of heart failure patients.

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