Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Recognise infiltrative red flags, separate AL from ATTR safely and start subtype-specific treatment without avoidable delay.
Infiltrative cardiomyopathy includes amyloid, sarcoid, iron and storage disease. In cardiac amyloidosis, misfolded light chain (AL) or transthyretin (ATTR) fibrils cause wall thickening, restrictive physiology, arrhythmia and conduction disease.
The diagnostic sequence matters more than any single image. Monoclonal-protein testing determines whether bone scintigraphy can support a non-biopsy ATTR diagnosis; ambiguous or discordant cases require expert biopsy and mass-spectrometry typing.
Treatment combines careful congestion control, rhythm/conduction management and disease-specific therapy. AL is a haematological emergency; ATTR treatment and hereditary-family care should begin through an amyloidosis service.
A clonal plasma-cell disorder produces unstable immunoglobulin light chains that misfold and deposit in myocardium and other organs. Cardiac involvement may progress rapidly and makes specialist assessment time-critical.
Age-related instability of normal transthyretin permits amyloid formation, commonly affecting the heart in later life. Earlier carpal tunnel, lumbar stenosis or biceps rupture may precede cardiac symptoms.
A pathogenic TTR variant destabilises the protein and can cause cardiomyopathy, neuropathy or both. Age alone cannot exclude hereditary disease; TTR sequencing distinguishes hereditary from wild-type ATTR, and a pathogenic variant has implications for relatives.
Sarcoid inflammation, iron overload and lysosomal storage disorders affect myocardium through granuloma, toxic accumulation or intracellular storage. Their imaging, systemic features and disease-specific tests differ from amyloid.
Misfolded light-chain or transthyretin fibrils deposit extracellularly between cardiac cells; other infiltrative disorders accumulate different material or inflammatory lesions. Normal myocardial architecture becomes progressively disrupted.
Infiltration increases apparent wall thickness and reduces compliance without necessarily increasing true muscle mass. A normal-sized or small, stiff ventricle often requires higher pressure to fill.
Rising diastolic pressure enlarges both atria and causes pulmonary and systemic venous congestion. Stroke-volume reserve becomes constrained, so tachycardia or excessive preload reduction may be poorly tolerated.
Atrial and conduction-system infiltration promotes atrial fibrillation, sinus-node dysfunction and atrioventricular block. Patchy scar may also support ventricular arrhythmia, although sudden death can be electromechanical.
Autonomic neuropathy can lower vascular tone, while renal or neurological involvement complicates volume control and function. The resulting hypotension makes conventional vasodilating heart-failure treatment difficult to tolerate.
HFpEF or restrictive failure with increased wall thickness, biatrial enlargement, small cavity, valve/interatrial-septal thickening and pericardial effusion.
Low or relatively modest QRS voltage despite thick walls, pseudo-infarct pattern, AF and progressive AV conduction disease are clues, not mandatory criteria.
Bilateral carpal tunnel often years earlier, lumbar stenosis, spontaneous biceps rupture, peripheral/autonomic neuropathy and family history.
Nephrotic proteinuria, macroglossia, periorbital purpura, bruising, weight loss or a known plasma-cell disorder increases urgency.
Rapid HF progression, hypotension and disproportionate troponin/NT-proBNP with any monoclonal abnormality requires urgent specialist assessment.
Syncope, symptomatic bradycardia, high-grade block or ventricular arrhythmia needs monitored assessment; sudden death may be electromechanical as well as tachyarrhythmic.
Longstanding pressure overload can create thick walls and diastolic dysfunction. A convincing hypertension history and ECG voltage proportionate to wall thickness support hypertensive remodelling, but neither feature alone excludes amyloid.
Sarcomeric HCM is a separate disease that often produces asymmetric hypertrophy, dynamic obstruction or a familial phenotype. Restrictive physiology, voltage–wall-thickness discordance and characteristic extracardiac red flags instead raise suspicion of amyloid.
Valve obstruction causes concentric hypertrophy, exertional symptoms and heart failure. Restricted calcified cusps and a valve-level Doppler gradient identify the loading lesion, although amyloid may coexist.
Pericardial restraint also causes high filling pressure, biatrial enlargement and right-sided congestion. Respiratory ventricular interdependence and characteristic venous-flow changes support constriction; pericardial thickening or calcification may be present but is not required.
Fabry disease, iron overload and cardiac sarcoidosis can mimic wall thickening, scar or conduction disease. Targeted systemic examination, CMR pattern and specific laboratory or genetic testing discriminate.
Progressive stiffness causes pulmonary and systemic congestion while fixed stroke volume produces fatigue, hypotension and organ hypoperfusion. A narrow volume margin makes both overload and over-diuresis hazardous.
Atrial infiltration and enlargement promote fibrillation and mechanical atrial dysfunction. Blood stasis and amyloid-related atrial disease can create substantial intracardiac thrombus and embolic risk.
Progressive infiltration of the sinus node and atrioventricular conduction system causes bradycardia or high-grade block. Syncope may result and pacing assessment is often required.
Ventricular arrhythmia can occur, but electromechanical dissociation or severe bradyarrhythmia may also cause sudden death. This mixed mechanism limits reliance on ejection fraction alone for risk assessment.
AL may involve kidneys and other organs, while hereditary ATTR may cause progressive peripheral and autonomic neuropathy. Multisystem disease worsens frailty, treatment tolerance and overall prognosis.
Serum electrophoresis without immunofixation, or serum testing without urine, is not an adequate AL exclusion.
Older patients may have both a monoclonal gammopathy and ATTR; tissue typing prevents the wrong disease-specific treatment.
Planar blood-pool activity can mimic cardiac uptake; SPECT confirms that tracer is in myocardium.
It raises suspicion but also occurs in other hypertrophic states and cannot type amyloid.
TTR sequencing after ATTR diagnosis identifies variant disease and changes family care.
Ordering DPD without a complete monoclonal screen and calling any uptake ATTR.
Treating a monoclonal protein as proof that deposits are AL without amyloid typing.
Delaying suspected cardiac AL in a routine cardiology queue.
Using high-dose diuresis or vasodilators without regard to preload sensitivity and autonomic hypotension.
Starting a TTR stabiliser before confirming ATTR and excluding AL.
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An older adult with thickened ventricular walls has grade 3 DPD uptake, but serum immunofixation identifies a monoclonal protein. What is the best next step?
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes
Confirm ATTR and exclude AL first; specialist initiation. Limited evidence in very advanced NYHA IV disease; reassess around transplantation and pregnancy.
Specialist initiation after subtype confirmation; limited data if CrCl below 30 mL/min and none on dialysis, so use caution. Not recommended in hepatic impairment; an early eGFR change may reflect haemodynamics.
A stiff small ventricle is preload-sensitive; excessive diuresis can cause hypotension, renal injury and low output. Monitor potassium and renal function.