How Does Amyloid Affect the Heart
Understanding Cardiac Amyloid Disease
Cardiac amyloidosis is a rare medical condition in which abnormal proteins called amyloid accumulate in the heart. These proteins do not fold correctly, making them insoluble and sticky.
As they build up, they invade spaces between the heart muscle cells. This buildup causes the heart walls, especially the lower chambers (ventricles), to get much thicker and stiffer than usual.
Types of Amyloid Involved with the Heart
There are several types of amyloidosis, but only a few commonly affect the heart:
- AL Amyloidosis (Light Chain Type)
- Abnormal plasma cells in the bone marrow make too many light chain proteins.
- These light chains transform into amyloid and deposit in different organs, including the heart, kidneys, digestive system, and nerves.
- Transthyretin Amyloidosis (ATTR)
- Transthyretin is a protein responsible for moving thyroid hormone and vitamin A through the body.
- Hereditary (Familial) ATTR: Gene mutations make the transthyretin protein unstable and likely to form amyloid.
- Wild-Type ATTR: The protein is normal by structure, but as people (mainly men over 60) age, it becomes prone to misfolding and forms amyloid, mainly affecting the heart and sometimes the carpal tunnel ligaments.
Other Rare Types
- Over 20 proteins can become amyloid, but most do not involve the heart.
Below is a table that summarizes these forms:
| Type | Protein Involved | Affected Organs | Hereditary or Acquired |
|---|---|---|---|
| AL (Light Chain) | Immunoglobulin light chain | Heart, kidney, GI tract, nerves | Acquired |
| ATTR (Hereditary) | Mutated transthyretin | Heart, nerves | Hereditary |
| ATTR (Wild Type) | Normal transthyretin | Heart, carpal tunnel | Age-related (Acquired) |
How Cardiac Amyloid Affects the Heart Structure
The heart is a muscle divided into four chambers: two upper collecting chambers (atria) and two lower pumping chambers (ventricles). The right ventricle moves blood to the lungs; the left ventricle sends blood to the rest of the body.
Amyloid proteins mostly target the ventricles as they build up. This leads to much thicker heart walls (ventricular wall thickening), but not from extra muscle. The space-filling amyloid protein causes this thickening. Under the microscope, amyloid deposits separate and surround individual heart muscle fibers.
These deposits also make the heart muscle less elastic. The heart cannot relax and fill with blood as easily, making the heart stiff. As a result, the amount of blood the heart pumps out drops.
Visual Representation
| Normal Heart | Heart with Amyloid Build-Up |
|---|---|
| Thin, flexible walls | Thickened, stiff walls due to amyloid |
| Efficient muscle action | Disrupted muscle fibers, reduced elasticity |
Key Features and Symptoms
Symptoms can develop slowly and might be mistaken for other kinds of heart disease. Some common features of cardiac amyloidosis include:
- Shortness of breath, especially during activity
- Swelling in the legs and ankles
- Fatigue
- Irregular heartbeat (atrial fibrillation)
- Episodes of chest pain or tightness
- Fainting or dizziness
- Symptoms related to other organs (for AL amyloid), like tingling in hands and feet (neuropathy)
- History of carpal tunnel syndrome, often years before heart symptoms appear
How Cardiac Amyloidosis Differs from Other Heart Diseases
A key difference from typical heart disease is that the heart is not necessarily weak in amyloidosis. Instead, the heart is stiff and thick but not able to fill with enough blood. This leads to symptoms of heart failure, with not enough blood reaching the body’s tissues. Amyloid can also disrupt the heart’s electrical pathways, leading to arrhythmias such as atrial fibrillation.
Impact on Heart Function
- Reduced Heart Compliance: The heart cannot stretch easily to fill with blood during relaxation.
- Restrictive Cardiomyopathy: The heart stays thick and stiff, making it hard to fill the chambers, but pumping strength (systolic function) may stay normal, at least early on.
- Congestive Heart Failure: Pressure builds up in the heart and lungs, causing fluid retention.
- Progression of Disease: As more amyloid accumulates, heart function drops further and symptoms worsen.
Common Terms Related to Cardiac Amyloidosis
| Term | Meaning |
|---|---|
| Amyloidosis | A disease of abnormal protein deposits |
| Cardiac amyloidosis | Amyloid builds up in the heart |
| Light chain amyloid (AL) | Misfolded immunoglobulin light chains |
| Transthyretin amyloidosis | Amyloid from the transport protein transthyretin |
| Restrictive cardiomyopathy | Stiffness and thickening make filling difficult |
| Atrial fibrillation | Fast, irregular heart rhythm |
Amyloid Outside the Heart
Amyloid proteins can deposit elsewhere besides the heart. For example:
- Kidneys, leading to kidney disease and protein in the urine
- Gastrointestinal tract, causing issues such as diarrhea or weight loss
- Nerves, resulting in tingling, numbness, or burning pain (neuropathy)
- Carpal tunnel, often causing hand numbness or weakness from pressure on nerves
When amyloidosis is “systemic,” these protein deposits spread throughout several organs.
Diagnosis
Cardiac amyloidosis is often hard to diagnose because its symptoms are similar to those of other heart conditions. Medical professionals use a mix of methods to look for it:
- Blood Tests: Can show abnormal proteins
- Urine Tests: Sometimes reveal proteins spilled from the kidneys
- Echocardiogram (Heart Ultrasound): May show thick but stiff walls, abnormal heart movement, or signs of heart failure
- Cardiac MRI: Gives a clear view of heart tissue, shows patterns typical of amyloid
- Biopsy: Examining heart tissue under a microscope confirms if amyloid is present; sometimes belly fat or another area is tested first
- Genetic Testing: For patients with suspected hereditary ATTR amyloidosis
- Nuclear Medicine Scans: Special radioactive tracers highlight amyloid deposits in the heart without needing a biopsy
Risk Factors
Various things can increase the risk of developing this condition:
- Age (more common over 60)
- Male sex (especially for wild-type ATTR)
- Family history of ATTR amyloidosis
- Chronic inflammation or diseases affecting plasma cells (for AL amyloid)
Disease Course and Prognosis
The type of amyloidosis and how early it is found influence how the disease progresses.
- AL amyloidosis often acts quickly and can involve many organs
- Hereditary ATTR amyloidosis may affect nerves, heart, or both, depending on the gene change
- Wild-type ATTR amyloidosis tends to progress slowly but still causes heart problems over time
Overall health, age, and presence of other organ problems influence outcomes.
Management of Cardiac Amyloidosis
Treatment depends on the type of amyloidosis and its effects on the organs.
For AL Amyloidosis
- Target abnormal plasma cells to stop light chain production.
- Use chemotherapy drugs and immune-targeting treatments.
- Provide supportive care for affected organs.
For ATTR Amyloidosis
- Use medications to stabilize transthyretin and stop amyloid from forming.
- Some drugs aim to clear or remove existing amyloid from tissues.
- New RNA-based medicines can lower transthyretin protein production.
- Provide heart support medicines for symptoms.
Other Medical Responses
- Use diuretics to help remove excess fluid.
- Prescribe medications for arrhythmias (e.g., for atrial fibrillation; sometimes, pacemakers are needed).
- Use anticoagulation to prevent blood clots if irregular heartbeat is present.
Table: Common Treatments for Each Type
| Amyloidosis Type | Main Treatment Approach | Symptom Relief |
|---|---|---|
| AL | Chemotherapy, immune drugs | Diuretics, heart support |
| Hereditary ATTR | Medication to stabilize TTR | Fluid control |
| Wild-Type ATTR | TTR stabilization, supportive | HR/rhythm control |
Organ Transplant and Advanced Care
In some cases, when heart failure is severe and the patient is otherwise healthy, doctors may consider a heart transplant. This is rare and reserved for those whose amyloid disease does not affect many other organs. Doctors may consider a liver transplant for patients with hereditary ATTR amyloidosis, because the liver makes most transthyretin.
Prevalence and Incidence
Cardiac amyloidosis is uncommon, but recent medical advances and improved tests have led to more frequent diagnoses, especially among older patients with heart failure symptoms and thick heart walls on imaging. Wild-type ATTR is sometimes identified in men in their seventies or beyond who have heart failure with preserved ejection fraction.
Special Features
- Many patients with ATTR amyloidosis report a history of carpal tunnel syndrome long before heart symptoms start.
- AL amyloidosis is sometimes found after unexplained kidney problems or nervous system issues.
- Family medical history can be a clue for hereditary ATTR amyloidosis.
Summary Table: Major Features
| Feature | AL Amyloidosis | ATTR Hereditary | ATTR Wild-Type |
|---|---|---|---|
| Symptoms start at (years) | Usually 50s-60s | Variable, often 40s-60s | Over 60 |
| Commonly affected organs | Heart, kidney, nerves | Heart, nerves | Heart, carpal tunnel |
| Genetic link | No | Yes (inherited) | No |
| Speed of symptom worsening | Fast | Slow to moderate | Slow |
Final Points
Recognizing the disease early, understanding its broad impact, and knowing the specific type are key. Researchers keep advancing treatment, especially with new drugs that target the process by which amyloid forms. Experts with experience in rare protein diseases provide the best amyloidosis care.
