Swelling, breathlessness and the thick-walled heart

Over nine months she has become breathless on hills and now stops after one flight of stairs. Both ankles swell by evening and she has gained 4 kg. She sleeps on two pillows but has no current breathlessness at rest, chest pain or haemoptysis.

Twice she has felt close to fainting after standing, without injury or loss of consciousness. Ask about true syncope, rapid deterioration, palpitations, reduced urine output and resting symptoms because these change an outpatient assessment into urgent acute care.

Her urine has been persistently frothy for six months. She has no visible haematuria, dysuria or known diabetes. Appetite is reduced and she has lost 6 kg despite recent fluid-related weight gain. She alternates between constipation and loose stools.

There is numbness in both feet and dizziness on standing. Her hands tingle at night; right carpal-tunnel decompression three years ago gave incomplete relief. These clues suggest multisystem disease but are not individually diagnostic.

She has noticed that her tongue feels larger and she sometimes bites its edge. Bruising appears around her eyes after rubbing them and on her forearms after minor knocks. There is no overt gastrointestinal bleeding.

She has fatigue but no persistent focal bone pain, recurrent infection, thirst or confusion. Absence of classic myeloma symptoms does not exclude a small plasma-cell clone producing pathogenic light chains.

Hypertension was diagnosed four years ago and is usually around 130/75 mmHg on amlodipine 5 mg. She also takes furosemide 20 mg, started two weeks ago, and occasional ibuprofen. No chemotherapy, inflammatory disease or chronic infection. Ask about herbal products and medicines that worsen fluid balance or renal function.

Her father developed heart failure aged 82 but there is no known inherited neuropathy or cardiomyopathy. She is an accountant caring for her mother. Her friend had myeloma, so she fears cancer; she wants reassurance from a scan rather than a biopsy.

Alert and comfortable at rest. Pulse 88/min and regular, seated BP 112/70 mmHg, respiratory rate 18/min, oxygen saturation 96% on air and temperature 36.6°C. On standing, BP falls to 88/58 mmHg with light-headedness and pulse 92/min; sit her down safely.

The limited heart-rate response may reflect autonomic involvement or medication effects. Syncope, shock, resting hypoxaemia, severe chest pain or pulmonary oedema would interrupt the station and require acute assessment.

There is mild periorbital purpura and macroglossia with tooth indentation. No palpable lymphadenopathy. Inspect for bruising, nutritional loss and signs of an alternative systemic disorder while preserving dignity.

Macroglossia and periorbital purpura strongly raise suspicion for AL amyloidosis in this context, but diagnosis still requires evidence of amyloid and accurate typing. Do not tell the patient that an examination sign proves myeloma.

JVP is elevated, heart sounds are quiet and there is no loud valve murmur. Bibasal fine crackles and bilateral pitting oedema to mid-shin are present. Peripheries are warm. The apex is not markedly displaced.

This supports congestion with a restrictive or infiltrative phenotype. Carefully assess volume because excessive diuresis can worsen low-output symptoms and orthostatic hypotension; a normal-sized heart or lack of a dramatic murmur does not reassure.

The abdomen is soft without ascites or organomegaly. There is reduced pinprick and vibration in a stocking distribution with preserved power and ankle reflexes reduced. Tinel testing is not a substitute for a full neuropathy assessment.

Complete the examination with urinalysis, weight and functional assessment. Look for alternative causes of neuropathy and oedema. Avoid forcing prolonged gait or exertion testing after symptomatic orthostatic hypotension.

Urine albumin:creatinine ratio is 420 mg/mmol; laboratory protein:creatinine ratio confirms heavy proteinuria. Serum albumin is 24 g/L, creatinine 126 micromol/L with eGFR 42 mL/min/1.73 m², and adjusted calcium is normal. Haemoglobin is 108 g/L; platelets are normal.

Serum and urine immunofixation identify a lambda monoclonal light chain; the serum free-light-chain ratio is markedly abnormal after interpretation in the context of renal function. Use the complete monoclonal screen: serum electrophoresis alone is not sufficiently sensitive to exclude AL amyloidosis.

ECG shows low limb-lead voltages and first-degree AV block. Echocardiography reports concentric wall thickening, biatrial enlargement, restrictive filling, reduced longitudinal strain with relative apical sparing and preserved ejection fraction. This pattern raises suspicion but does not type amyloid.

NT-proBNP is markedly elevated and high-sensitivity troponin is persistently above the reference range without an acute rise-and-fall pattern. Interpret biomarkers with renal function, rhythm and volume status; they contribute to cardiac severity assessment rather than serving as a binary diagnostic test.

Cardiac magnetic resonance shows diffuse subendocardial late gadolinium enhancement and abnormal myocardial tissue characteristics compatible with cardiac amyloidosis. A DPD scan shows grade 2 cardiac uptake.

Because a monoclonal protein is present, grade 2 uptake cannot establish ATTR non-invasively. AL amyloidosis, ATTR with an incidental monoclonal gammopathy, or less commonly dual pathology remain possible. Tissue confirmation and expert amyloid typing are required before disease-specific treatment.

Abdominal fat aspiration is non-diagnostic. This does not exclude amyloidosis. After multidisciplinary discussion of bleeding risk, yield and organ involvement, a renal biopsy demonstrates Congo-red-positive deposits with apple-green birefringence under polarised light.

Validated proteomic typing identifies lambda light-chain amyloid. Bone-marrow assessment demonstrates a small plasma-cell clone. The clone size does not reflect the severity of organ injury; treatment urgency is driven by the toxic precursor and cardiac involvement, not only by the percentage of plasma cells.

This is a multisystem infiltrative disorder with restrictive cardiac disease, nephrotic-range protein loss, autonomic and peripheral neuropathy, macroglossia and periorbital purpura. AL amyloidosis is the leading diagnosis, with ATTR amyloidosis plus an incidental monoclonal gammopathy an important alternative until tissue is typed.

Hypertensive heart disease does not explain the low voltages, multisystem features or degree of proteinuria. Other considerations include light-chain deposition disease, another plasma-cell disorder, diabetic or immune renal disease and alternative cardiomyopathies, but the plan must first exclude rapidly progressive AL disease.

Arrange urgent coordinated review by haematology and the NHS National Amyloidosis Centre, while cardiology and nephrology manage current organ problems. Specify who is contacting whom and when; ‘refer to several MDTs’ is not an adequate endpoint.

Assess cardiac biomarkers, rhythm, blood pressure, renal function, proteinuria, thrombotic and bleeding risks and functional status promptly. Advanced cardiac AL can deteriorate quickly, so a routine months-long monoclonal-gammopathy pathway would be unsafe.

Seek histological proof where feasible and type deposits in an experienced laboratory. A positive monoclonal screen does not by itself prove AL; conversely, a positive DPD scan cannot diagnose ATTR non-invasively when monoclonal studies are abnormal.

Bone-marrow assessment characterises the clone but does not replace tissue typing. If a low-risk tissue site is negative, reconsider an involved-organ biopsy with specialist input rather than falsely closing the diagnosis.

For confirmed systemic AL amyloidosis, specialist treatment suppresses the light-chain-producing clone as rapidly and deeply as safely possible, using a contemporary risk-adapted regimen. Choice and dose depend on cardiac stage, neuropathy, renal function, frailty and treatment availability; do not prescribe a memorised chemotherapy protocol in a PACES answer.

Use cautious diuresis with daily weight, symptoms, renal function, electrolytes and blood pressure. Standard heart-failure drugs may be poorly tolerated in restrictive amyloid cardiomyopathy because of hypotension and fixed stroke volume. Review NSAIDs and other contributors. Address nephrotic thrombosis risk and anticoagulation individually rather than automatically treating every patient.

‘The heart scan suggests that an abnormal protein may be collecting in the heart, but the same process may also explain the protein leaking from your kidneys, the blood-pressure drop and the nerve symptoms. High blood pressure alone would not explain the full pattern.’

‘We have found an abnormal light-chain protein, but that does not by itself tell us exactly which protein is in the tissues. The nuclear scan can strongly support one type only when the light-chain tests are normal. We therefore need a small tissue sample and specialist typing before choosing treatment. Some people have a small bone-marrow cell population rather than classical myeloma; I will not label this until the tests are complete.’

Explore what she fears about biopsy and what caring responsibilities make urgent appointments difficult. Explain the proposed biopsy site, expected benefit, material bleeding and organ-specific risks, alternatives and what delay could mean. Offer a supporter and coordinate appointments where possible without trading away urgency.

Advise urgent assessment for syncope, breathlessness at rest, chest pain, rapidly worsening oedema, marked reduction in urine, new palpitations or neurological symptoms. Use teach-back to confirm why typing—not merely finding amyloid—determines treatment.

Stop the outpatient sequence and manage ABCDE with acute cardiology and critical-care input. Look for arrhythmia, sepsis, bleeding, pulmonary embolism, over-diuresis and low-output cardiac amyloid. Do not give large unmonitored fluid boluses or assume the orthostatic diagnosis explains shock.

With a convincing cardiac phenotype and grade 2–3 bone-tracer uptake, expert review may support a non-biopsy ATTR diagnosis after confirming the required testing and scan quality. Genetic testing is then needed to distinguish hereditary from wild-type ATTR where appropriate; do not infer wild-type disease from age alone.

The monoclonal gammopathy may be incidental. Stop framing treatment around plasma-cell suppression and follow the ATTR pathway, including specialist assessment, genetic testing and phenotype-appropriate therapy. Continue to manage cardiac and neurological complications while explaining why the diagnosis changed.

Explore the feared harm, offer specialist pathology and procedural counselling, consider whether another site offers a better risk–yield balance and provide time for a supporter or second opinion where clinically safe. Respect a capacitous refusal, but explain that empirical AL or ATTR treatment without secure typing may be ineffective or harmful; agree the safest monitoring and revisit plan.

Strong: Connects congestion, proteinuria, autonomic symptoms, neuropathy, carpal tunnel, bruising, macroglossia and weight change.

Incomplete: Takes a heart-failure history but misses renal, neurological and soft-tissue clues.

Unsafe: Attributes the entire picture to mild hypertension without investigating systemic disease.

Strong: Assesses orthostatic safety, congestion, soft-tissue clues and neuropathy, then states the limits of each sign.

Incomplete: Lists amyloid signs without assessing haemodynamic reserve or functional impact.

Unsafe: Forces exertion despite symptomatic hypotension or treats macroglossia as proof of myeloma.

Strong: Uses complete monoclonal studies, imaging and tissue typing; recognises why DPD cannot label ATTR here.

Incomplete: Suspects amyloid but gives no safe route from phenotype to typed diagnosis.

Unsafe: Diagnoses ATTR from DPD despite a monoclonal protein, or diagnoses AL from the clone alone.

Strong: Makes an urgent amyloid/haematology referral while coordinating cardiac, renal and supportive care with named ownership.

Incomplete: Says ‘refer to MDT’ without urgency, organ staging or an interim plan.

Unsafe: Delays cardiac AL assessment, prescribes empirical chemotherapy or applies routine heart-failure escalation despite hypotension.

Strong: Explains the difference between detecting and typing amyloid, addresses cancer fear and negotiates biopsy without coercion.

Incomplete: Provides technically correct information but does not discover the biopsy or caring concerns.

Unsafe: Calls the condition myeloma before confirmation, guarantees a scan diagnosis or dismisses refusal.

Treat amyloidosis as a multisystem diagnosis: the heart, kidneys, nerves, blood pressure and soft tissues may tell one story.

A monoclonal protein is neither proof of AL nor a harmless incidental finding until the amyloid type is secure.

Bone-tracer uptake can support non-biopsy ATTR only after a complete monoclonal screen is negative in the right phenotype.

A negative fat biopsy does not exclude amyloid when clinical probability remains high.

Cardiac AL requires urgent specialist assessment; support congestion carefully and suppress the pathological precursor after typing.

Give a two-minute explanation of why the DPD scan does not settle the diagnosis in Anita. Then hand over to haematology using one sentence for phenotype, one for severity, one for diagnostic status and one definite request.