Introduction
In simple terms, amyloidosis is a protein disorder. Cardiac amyloidosis results from the accumulation of abnormal proteins, called amyloid, within the heart muscles, called the myocardium. The nature of these proteins is not stable and they are highly insoluble aggregates. They change their shapes and bind to each other forming amyloid fibrils. Amyloid fibrils then alter the tissue architecture of organs resulting in cell death and other neurodegenerative disorders. Furthermore, the newly formed amyloid fibrils are incredibly stable, strong, and distinctly organized and thus are tough to break down. These qualities make them destructive in nature and give them the ability to accumulate in tissues. Besides the heart, amyloidosis frequently affects other vital organs such as kidneys, lungs, liver, spleen, and the nervous system.
What Causes Cardiac Amyloidosis?
Cardiac amyloidosis (also known as "stiff heart syndrome") happens when amyloid deposits replace typical heart muscle. This kind of restrictive cardiomyopathy is the most common one. The conduction system, which carries electrical signals across the heart, may be impacted by cardiac amyloidosis. Heart blocks and irregular heartbeats, or arrhythmias, may result from this.
It is possible to inherit the illness. Familial cardiac amyloidosis is the term for this. It may also arise as a consequence of another illness that causes inflammation, such as a certain kind of blood or bone malignancy. Men are affected with cardiac amyloidosis more frequently than women. Those under 40 are not likely to get the condition.
Which Kinds of Amyloidosis Impact the Heart?
Different proteins that generate amyloid fibrils are responsible for different types of amyloidosis. Knowing the type of protein is of trivial importance because it helps in correct treatment by addressing medications to the respective protein. More than 95 percent of instances of cardiac amyloidosis are caused by two specific proteins.
1. Transthyretin Amyloidosis (ATTR Amyloidosis): This type of amyloidosis is caused by the liver-produced protein transthyretin, which misfolds and creates amyloid fibrils that accumulate in the heart and other areas including the tissues in the wrist, neck, or nerves. Accordingly, cardiac ATTR amyloidosis patients may experience cardiac issues in addition to carpal tunnel syndrome, cervical stenosis, and/or neuropathy.
ATTR amyloidosis comes in two forms.
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The most prevalent kind of ATTR amyloidosis is known as wild-type ATTR amyloidosis (wtATTR). The condition is linked to aging and is not hereditary. More males than women are affected by it, and it often affects those above the age of 70.
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A hereditary genetic mutation in the TTR gene that encourages the transthyretin protein to misfold is the cause of hereditary ATTR amyloidosis (hATTR), often referred to as mutant ATTR amyloidosis. As early as thirty years old, individuals may be afflicted with this type of cardiac amyloidosis, which also affects the nervous system.
2. Amyloid Light-Chain Amyloidosis (AL Amyloidosis): The "light chain" proteins that cause amyloid light-chain amyloidosis (AL amyloidosis) are made by bone marrow-derived plasma cells. Although they can accumulate in many body tissues and organs, the amyloid fibrils linked to light-chain proteins primarily deposit in the tongue, gastrointestinal tract, kidney, liver, heart, and peripheral nerves. AL amyloidosis is more common in adults over the age of 40, with the majority of cases diagnosed in people above the age of 65.
What Are Cardiac Amyloidosis Symptoms and Signs?
Amyloid buildup in the heart can also be referred to as plaque buildup which hinders the smooth flow of blood within the heart and eventually affects the pumping mechanism. Cardiac amyloidosis can shorten life expectancy and induce symptoms of heart failure. Feeling light-headed, swelling in the lower extremities such as legs, ankles, and abdomen, fatigue, palpitations, and shortness of breath are some cardiac amyloidosis symptoms. A classical sign of cardiac amyloidosis is non-flexible heart muscles, also called stiff heart syndrome, wherein after investigation, the heart tissues present rigidity and restrictiveness, thus the name, restrictive cardiac amyloidosis. Regardless of the type of protein causing the amyloidosis, suffering patients undergo a progressive inclination in the thickening of cardiac muscles and tissues. This thickening of the cardiac walls, in turn, results in the accumulation of fluids all over the body. Additionally, discomfort is experienced during vigorous and strenuous activities, and this discomfort is generally referred to as angina. Weight loss is another symptom, but it is easily masked by fluid retention. Patients also have increased difficulty in breathing, especially whilst lying down.
How Is Cardiac Amyloidosis Diagnosed?
A detailed medical history is recorded before diagnosis of the clinical manifestations seen in the patient. Medical history indefinitely helps in a more efficient and quick diagnosis of cardiovascular diseases. There are some routine tests that a healthcare provider may request to confirm the diagnosis.
Exams and Tests:
Cardiac amyloidosis symptoms can be associated with several different illnesses. It may be challenging to diagnose the problem as a result.
Symptoms could include:
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Unusual cardiac murmurs or lung crackles.
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Low blood pressure that decreases after standing up.
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Larger veins in the neck.
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Enlarged liver.
It is possible to do the following tests:
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Protein testing in the blood and urine.
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CT (computed tomography) scans of the abdomen or chest are thought to be the "gold standard" for diagnosing this illness.
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Coronary angiography.
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Echocardiography.
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ECG, or electrocardiogram.
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MRI (magnetic resonance imaging) - Cardiac magnetic resonance imaging (MRI) has also proven to be a helpful asset by producing a detailed image of the heart’s muscular structure
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Nuclear cardiograms (RNV, MUGA).
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PET, or positron emission tomography.
An ECG may reveal irregularities in the heartbeat or cardiac signals. It might also display low voltage, or "low signal" signals. The diagnosis is verified by a heart biopsy. It is common practice to perform a biopsy on an additional site, like the kidney, bone marrow, or abdomen. A cardiac biopsy is an advanced diagnostic measure where the tissue is stained to check for cardiac amyloids. This helps confirm the presence of the particular form of amyloid present in the heart and thus can aid in specific treatment measures. ATTR type of cardiac amyloidosis requires genetic testing due to its nature of presence, as discussed above. Overall, a precise assessment of the cardiac system is vital for the correct diagnosis of cardiac amyloidosis and its variants.
What Is the Treatment of Cardiac Amyloidosis?
There are two paths to follow for the accurate treatment of cardiac amyloidosis -
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Treating the consequence of amyloidosis to the heart’s structure.
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Attempting to slow the progression of amyloidosis within the heart by precise therapy such as chemotherapy or drug therapy.
The most suitable treatment plan varies from patient to patient and is dependent on various factors. Doctors and a team of multidisciplinary experts are the ones who can produce prime care and treatment modalities for suitable cases. Amyloidosis is not cancer, but chemotherapy or chemotherapy-like drugs can be used to destroy the strongly built amyloid fibrils.
Furthermore, multiple clinical trials are ongoing to find a treatment for ATTR due to its genetic nature. High-grade conduction abnormalities are common in ATTR amyloidosis, which can be treated with pacemakers if it occurs. Patients who undergo traditional kidney dialysis may still end up accumulating amyloids, but modern procedures of kidney dialysis help in removing amyloid proteins too.
What Is the Prognosis for Those Suffering From Cardiac Amyloidosis?
The kind of amyloidosis determines life expectancy and the extent of heart damage. Due to the more severe effects that AL cardiac amyloidosis has on the body, early detection and treatment are critical and are linked to better results. Recently, medications that lower the quantity of the proteins causing ATTR cardiac amyloidosis have been produced, prolonging the lives of those affected and improving their quality of life.
Conclusion
Over the years, there has been a significant shift in the pattern of cardiac amyloidosis due to increased disease prevalence and breakthroughs in treatment and drug alternatives. Whenever possible, a multidisciplinary approach is preferable when treating cardiac amyloidosis. Furthermore, the best defense against the pain and exhaustion that cardiac amyloidosis brings into everyday life is safe, consistent exercise. The use of contemporary cardiovascular imaging techniques has made it possible to identify cardiac amyloidosis early on. For the diagnosis of restricted cardiac amyloidosis, early detection is crucial. More importantly, early detection and identification of cardiac amyloidosis contribute to the development of therapy options that have a good chance of changing the disease's path
