Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of “unknown” heart failure (HF), associated with a high rate of hospitalizations due to HF.
HF is a complex syndrome of signs and symptoms that suggest that the efficiency of the heart as a pump is impaired. It is caused by structural and/or functional abnormalities of the heart, which lead to reduced cardiac output and/or high filling pressures at rest or with stress.[13]
There are numerous and varied causes of HF, requiring different treatment and management strategies. A detailed history is essential to identify the underlying cause of HF.[13]
Some specific causes of HF include coronary artery disease and myocardial infarction, hypertension, valve dysfunction, congenital heart disease, obesity, myocarditis, arrhythmia, diabetes, and restrictive cardiomyopathy, including cardiac amyloidosis.[13][14]
Pulmonary rales, hepatojugular reflux, third heart sound (gallop rhythm), laterally displaced apical impulse, and elevated jugular venous pressure.[13]
Orthopnea, cough, rapid/irregular heartbeat, dyspnea/paroxysmal nocturnal dyspnea, edema, and fatigue.[13]
Cardiac amyloidosis (CA) is an under-recognized, infiltrative heart disease that causes a restrictive cardiomyopathy that can result in HF.[1][2] It is characterized by extracellular deposition of misfolded proteins forming amyloid fibrils that can deposit in different organs. This can lead to cardiac dysfunction and organ failure, frequently presenting as HF. CA is often misdiagnosed as another condition or is delayed in its recognition due to both low disease awareness and overlapping symptoms with HF and related diseases.[3][4][6][7][15] Patients with CA typically exhibit congestive HF with preserved ejection fraction (HFpEF), HF with mid-range ejection fraction (HFmrEF) or, often at a later stage of HF, HF with reduced ejection fraction (HFrEF).[4][16][17][18]
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Transthyretin (TTR) is mainly produced in the liver (also to a small extent in the eye and choroid plexus). TTR is the main transport protein for retinol binding protein (RBP) and retinol (vitamin A), and secondary transporter of Thyroxine (T4). The TTR protein is a tetramer (i.e. consists of four identical subunits). In ATTR amyloidosis, the TTR tetramer becomes unstable and dissociates into monomers that subsequently misfold, leading to initiation of the oligomerization processes and formation of amyloid fibrils that accumulate in organs and tissues, including the heart.[2][3][4]
There are two forms of ATTR-CM: hereditary ATTR and wild-type ATTR amyloidosis.[2][4][20][21][22]
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Heart failure (HF) is a complex syndrome of signs and symptoms that suggest that the efficiency of the heart as a pump is impaired. It is caused by structural and/or functional abnormalities of the heart, which lead to reduced cardiac output and/or high filling pressures at rest or with stress.[1][2][3]
There are numerous and varied causes of HF, requiring different treatment and management strategies. A detailed history is essential to identify the underlying cause of HF.[1][2][3]
Some specific causes of HF include coronary artery disease and myocardial infarction, hypertension, valve dysfunction, congenital heart disease, obesity, myocarditis, arrhythmia, diabetes and restrictive cardiomyopathy, including cardiac amyloidosis. [1][2][3]
Pulmonary rales, hepatojugular reflux, third heart sound (gallop rhythm), laterally displaced apical impulse, elevated jugular venous pressure.
Orthopnoea, cough, rapid/irregular heartbeat, dyspnoea/paroxysmal nocturnal dyspnoea, oedema, fatigue.
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Cardiac amyloidosis (CA) is an underrecognized, infiltrative heart disease characterized by extracellular deposition of misfolded protein, that causes a restrictive cardiomyopathy that can result in HF.[3][4] It is characterised by extracellular deposition of misfolded protein that has formed insoluble amyloid fibrils. This leads to cardiac dysfunction and organ failure, frequently presenting as HF, meaning that a diagnosis of CA is frequently missed. CA is often misdiagnosed as another condition or is delayed in its recognition due to both low disease awareness and overlapping symptoms with HF and related diseases.[5][6][7][8] [9][10][11] Patients with CA typically exhibit congestive HF with preserved ejection fraction (HFpEF) or, often at a later stage of HF, present with HF with reduced ejection fraction (HFrEF). [8][11][12]
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Transthyretin (TTR) is mainly produced in the liver (also small extent in eye and choroid plexus). TTR is the main transport protein for retinol binding protein (RBP) and retinol (vitamin A), and secondary transporter of Thyroxine (T4). The TTR protein is a tetramer (e.g. consist of four identical subunits). In ATTR amyloidosis, the TTR tetramer becomes unstable and dissociates into monomers that subsequently misfold, leading to initiation of the oligomerisation processes and formation of amyloid fibrils that accumulate in organs and tissues, including the heart. [4][7][8]
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In recent years, our understanding of ATTR-CM has greatly increased, contributing to increased awareness among the cardiology community. Research is constantly ongoing to address the gaps in our knowledge of ATTR-CM. An improved understanding will help to reduce misdiagnosis and underdiagnosis.
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