Unveiling wild-type transthyretin cardiac amyloidosis as a significant and potentially modifiable cause of heart failure with preserved ejection fraction

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.

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March 2020 at a glance: heart failure with preserved ejection fraction, left atrial myopathy, atrial fibrillation and cardiac amyloidosis

European Journal of Heart Failure ◽

10.1002/ejhf.1509 ◽

2020 ◽

Vol 22 (3) ◽

pp. 389-390

Author(s):

Marianna Adamo ◽

Carlo Mario Lombardi ◽

Marco Metra

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ejection Fraction ◽

Left Atrial ◽

Cardiac Amyloidosis ◽

Preserved Ejection Fraction

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Tissue is the Issue: Endomyocardial Biopsy Characterization of Heart Failure with Preserved Ejection Fraction and Incident Cardiac Amyloidosis

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2019.07.150 ◽

2019 ◽

Vol 25 (8) ◽

pp. S53

Author(s):

Virginia S. Hahn ◽

Wendy Ying ◽

Yi Zhen Joan Lee ◽

Lisa R. Yanek ◽

Dhananjay Vaidya ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Endomyocardial Biopsy ◽

Cardiac Amyloidosis ◽

Preserved Ejection Fraction

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PREVALENCE OF TRANSTHYRETIN CARDIAC AMYLOIDOSIS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: A POPULATION BASED STUDY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(20)31318-8 ◽

2020 ◽

Vol 75 (11) ◽

pp. 691

Author(s):

Omar Farid Abou-Ezzeddine ◽

Daniel Davies ◽

Jasmine A. Sexton ◽

Christopher G. Scott ◽

Ahmed Fayyaz ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cardiac Amyloidosis ◽

Population Based ◽

Preserved Ejection Fraction ◽

Population Based Study

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

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316664 ◽

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.

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Cardiac Amyloidosis: Overlooked, Underappreciated, and Treatable

Annual Review of Medicine ◽

10.1146/annurev-med-052918-020140 ◽

2020 ◽

Vol 71 (1) ◽

pp. 203-219 ◽

Cited By ~ 5

Author(s):

Jonah Rubin ◽

Mathew S. Maurer

Keyword(s):

Heart Failure ◽

Cardiac Amyloidosis ◽

Restrictive Cardiomyopathy ◽

Preserved Ejection Fraction ◽

Wild Type ◽

Immunoglobulin Light Chain ◽

Future Directions ◽

Life And Death ◽

Recent Developments

Cardiac amyloidosis (CA) is an infiltrative and restrictive cardiomyopathy that leads to heart failure, reduced quality of life, and death. The disease has two main subtypes, transthyretin cardiac amyloidosis (ATTR-CA) and immunoglobulin light chain cardiac amyloidosis (AL-CA), characterized by the nature of the infiltrating protein. ATTR-CA is further subdivided into wild-type (ATTRwt-CA) and variant (ATTRv-CA) based on the presence or absence of a mutation in the transthyretin gene. CA is significantly underdiagnosed and increasingly recognized as a cause of heart failure with preserved ejection fraction. Advances in diagnosis that employ nuclear scintigraphy to diagnose ATTR-CA without a biopsy and the emergence of effective treatments, including transthyretin stabilizers and silencers, have changed the landscape of this field and render early and accurate diagnosis critical. This review summarizes the epidemiology, pathophysiology, diagnosis, prognosis, and management of CA with an emphasis on the significance of recent developments and suggested future directions.

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