For decades, a diagnosis of cardiac amyloidosis carried very little with it. The condition was understood, the mechanism was well described, and the treatment options were close to nothing. It was a diagnosis of academic interest more than clinical urgency.

That has changed completely. Targeted therapies now exist for both major forms of the disease. Survival has improved. Symptoms can be controlled. And that shift has created a new problem, which is that the diagnosis needs to be made while there is still enough healthy heart muscle left to protect.

This article explains what cardiac amyloidosis is, how it presents, how it is diagnosed, and what treatment looks like in Australia today.

What Amyloidosis Actually Is

Your body constantly manufactures proteins. Each one is folded into a precise three-dimensional shape, does its job, and is then broken down and recycled in an orderly way.

Amyloidosis is what happens when that process fails. A protein misfolds, taking on the wrong shape. Instead of being cleared away, the misfolded protein clumps together into tough, resistant strands called fibrils. The body struggles to break these down, so they build up in organs over years, gradually disrupting the tissue around them.

Which organ suffers depends on which protein is misbehaving. That, in turn, determines the type of amyloidosis, the symptoms, and the treatment.

The Two Types That Affect the Heart

There are many forms of amyloidosis. Two account for the overwhelming majority of cardiac cases.

AL amyloidosis, which starts in the bone marrow

AL stands for light chain. Abnormal plasma cells in the bone marrow produce misfolded light chain proteins, which are a component of antibodies. These deposit throughout the body, and the heart and kidneys are usually hit hardest. AL amyloidosis is fundamentally a blood condition, and it needs a haematologist and a cardiologist working together.

ATTR amyloidosis, which starts in the liver

ATTR stands for transthyretin, a transport protein made by the liver that carries thyroid hormone and vitamin A around the bloodstream. It comes in two forms. The hereditary form is caused by a gene mutation. The wild-type form has no mutation at all and simply happens with ageing. Wild-type ATTR is now recognised as a significant and badly underdiagnosed cause of heart failure in older adults, especially men over 65.

What Amyloid Does to the Heart

When amyloid fibrils deposit in the heart muscle, mainly in the left ventricle, the walls thicken and lose their elasticity. The heart becomes stiff.

A stiff heart can still squeeze normally. What it cannot do is relax. Between beats, the ventricle needs to expand and fill with blood, and stiffened walls resist that expansion. Less blood goes in, so less blood comes out. This is heart failure with preserved ejection fraction, sometimes called diastolic heart failure, and it explains why the pumping function on a scan can look reassuringly normal in a patient who feels profoundly unwell.

A normal pumping function does not mean a normal heart. Amyloidosis is the classic example of a heart that squeezes well and still fails.

The Symptoms to Know

Symptoms come on slowly and are rarely specific to amyloidosis, which is exactly why the diagnosis is so often missed. Each one on its own could be attributed to ageing, deconditioning, or a more common heart problem.

Two further clues are worth knowing about. Frothy urine can indicate significant protein loss through the kidneys, which is more typical of AL amyloidosis. And carpal tunnel syndrome, particularly in both hands and severe enough to need surgery, is increasingly recognised as an early sign of ATTR amyloidosis that can precede any heart symptoms by several years.

When Amyloidosis Should Be Considered

Certain clinical pictures should prompt the question directly. The most important are:

• A thickened heart wall on an echocardiogram with unexplained heart failure, particularly when the muscle looks unusually bright or speckled
• Significant protein loss in the urine without another clear cause
• Numbness, tingling, or burning in the hands or feet occurring alongside cardiac symptoms
• Blood pressure that falls on standing, causing dizziness or fainting
• Thickened heart walls with a surprisingly low voltage tracing on the ECG, which is a paradox and a genuine red flag

How the Diagnosis Is Made

Diagnosis combines imaging, blood and urine testing, and sometimes a tissue sample. The pathway depends on which type is suspected.

Echocardiogram

The heart ultrasound is the starting point. In amyloidosis it typically shows thickened walls, impaired relaxation, and a characteristic pattern of abnormal muscle strain. It raises the suspicion but cannot confirm the diagnosis on its own.

The bone scan (technetium pyrophosphate scan)

This nuclear medicine scan changed everything for ATTR amyloidosis. Transthyretin amyloid fibrils soak up the tracer used in a bone scan, producing a strongly positive heart signal that is highly specific for ATTR. In the right clinical setting, and once AL has been excluded on blood tests, a positive scan can confirm ATTR cardiac amyloidosis without any biopsy at all.

Blood and urine tests

Serum free light chains and urine protein testing look for the abnormal proteins of AL amyloidosis. These must always be checked before a bone scan is interpreted, because AL amyloidosis can occasionally produce a false positive scan result. Getting the order wrong is a real diagnostic trap.

Bone marrow biopsy

Required to confirm AL amyloidosis, by identifying the abnormal plasma cells producing the faulty light chains.

Cardiac MRI

MRI with contrast shows a characteristic pattern of enhancement throughout the heart muscle that strongly supports the diagnosis and helps distinguish amyloidosis from other causes of a thickened heart, such as hypertrophic cardiomyopathy.

Treatment, and Why It Has Changed So Much

The goal of treatment is to stop new amyloid being laid down, giving the body a chance to clear some of what is already there and preventing further damage to the heart. Treatment is type-specific, and it is coordinated between cardiology and haematology.

Tafamidis, for ATTR cardiac amyloidosis

Tafamidis stabilises the transthyretin protein in its correct shape, so it cannot misfold and clump. The landmark ATTR-ACT trial showed it reduced deaths and hospitalisations compared with placebo in ATTR cardiac amyloidosis. It is approved in Australia and represents the first genuine disease-modifying treatment for a condition that previously had none.

Patisiran, for hereditary ATTR amyloidosis

Patisiran takes a different approach. It is an RNA interference therapy that switches off transthyretin production in the liver, sharply reducing the amount of protein available to misfold in the first place. Less raw material means less amyloid.

Daratumumab, for AL amyloidosis

AL amyloidosis is treated at its source, in the bone marrow. Daratumumab, an antibody that targets and depletes abnormal plasma cells, is combined with chemotherapy and has become the standard of care for newly diagnosed AL amyloidosis. By shutting down the cells making the faulty light chains, it can allow existing deposits to be partly cleared by the body over time.

Clinical trials

Research is moving quickly. Gene silencing therapies, new stabilising drugs, and agents designed to actively dissolve amyloid already deposited in the heart are all in trials. The Australian Amyloidosis Network maintains a current list of trials and the centres running them.

Why Timing Matters So Much

These treatments work best before the heart has sustained irreversible damage. They can slow or halt the disease. They cannot rebuild muscle that has already been replaced by amyloid. Waiting is not a neutral choice.

That places real value on self-advocacy. If you or a family member has unexplained heart failure, particularly with a thickened heart wall, nerve symptoms, or a history of carpal tunnel surgery, it is entirely reasonable to ask your cardiologist whether amyloidosis has been considered and whether the relevant tests have been done. It is a fair question, and a good cardiologist will welcome it.

Conclusion

Cardiac amyloidosis has gone from a diagnosis that offered little beyond comfort to a treatable condition with meaningful therapies and improving outcomes. The medicine caught up. What has not fully caught up is how quickly the condition gets recognised.

If the picture in this article sounds familiar, the useful next step is a conversation, not a wait. The treatments exist. The diagnosis needs to be made in time to use them.

Related Reading

• HFrEF and HFpEF: Understanding the Two Types of Heart Failure
• The Echocardiogram: What It Shows and Why It Matters
• Shortness of Breath and the Heart: When Breathlessness Is a Cardiac Signal
• Swollen Legs and the Heart: What the Swelling Is Telling You
• What Is a BNP Test? Understanding This Key Heart Failure Blood Test
• Hypertrophic Cardiomyopathy (HCM): What It Means and Why the Outlook Is Excellent
• Understanding Your Cardiovascular Risk Factors