โ ๏ธ Important: Calcium-channel blockers can significantly worsen heart failure in amyloidosis and must be avoided.
๐ Digoxin may precipitate severe bradycardia or complete heart block because of increased myocardial sensitivity.
๐งฌ About
- Excess amyloid protein deposits within the myocardium.
- Commonest cause of restrictive cardiomyopathy in the UK.
- Leads to stiff ventricles โ impaired diastolic filling โ progressive heart failure.
โ๏ธ Aetiology
- Amyloid fibrils are insoluble proteins with ฮฒ-pleated sheet secondary structure.
- They cannot be broken down, accumulate in tissues, and disrupt normal function.
- Localised atrial deposits (from ANP) โ associated with atrial fibrillation.
- Pericardial thickening can occur due to deposition.
๐งพ Causes
- Primary AL amyloidosis: Monoclonal light chains (e.g. multiple myeloma).
- Familial amyloidosis: Autosomal dominant mutation in transthyretin (TTR).
- Senile systemic amyloidosis: Common in elderly, often with carpal tunnel syndrome.
๐ฌ Pathology
- Thickening of all 4 chambers with bi-atrial dilatation.
- Normal/small LV cavity; RV often only mildly dilated.
- Myocytes distorted by infiltrated amyloid โ impaired contractility.
๐ฉบ Clinical Features
- Progressive heart failure (diastolic >> systolic).
- Angina-like chest pain, arrhythmias, thromboembolism.
- Syncope or sudden death due to conduction disease or electromechanical dissociation.
๐งช Investigations
- Bloods: FBC, U&E, ESR, serum free light chains, immunoglobulins.
- Biomarkers: BNP & troponin often elevated (reflect high filling pressures).
- ECG: Low-voltage QRS complexes (limb leads < 5 mm), poor R-wave progression, AF common.
- Echocardiogram: โGranular sparklingโ myocardium, thickened walls, restrictive filling pattern.
- Cardiac MRI: Gadolinium enhancement showing diffuse infiltration.
- Biopsy: Endomyocardial rarely needed; fat pad aspiration often diagnostic.
- Coronary angiography: Angina with minimal coronary disease is a red flag for amyloidosis.
๐ Differentials
- Hypertensive heart disease: Clear history of HTN; no amyloid markers.
- Hypertrophic cardiomyopathy: May mimic, but worsening with verapamil/diltiazem suggests amyloidosis.
๐ฉน Management
- โ ๏ธ Avoid calcium channel blockers and be cautious with Digoxin.
- Atrial fibrillation: Anticoagulation and cautious rate control.
- Pacemaker: For significant conduction disease.
- ICD: Limited benefit; most sudden deaths due to electromechanical dissociation, not VT/VF.
- AL amyloidosis: Treat underlying plasma cell dyscrasia (e.g. chemo).
- Familial TTR amyloidosis: Liver transplantation can be curative; new drugs (e.g. tafamidis) stabilise transthyretin.
๐ Teaching Pearl
Cardiac amyloidosis is a โzebraโ cause of restrictive cardiomyopathy.
๐ Clues: HF with preserved EF, low-voltage ECG, sparkling myocardium on echo, and unusual drug sensitivities (Digoxin/CCBs). Always consider it in elderly patients with heart failure + carpal tunnel syndrome.
