Makindo Medical Notes

⚠️ Important: Calcium-channel blockers can significantly worsen heart failure in amyloidosis and must be avoided. 💊 Digoxin may precipitate severe bradycardia or complete heart block because of increased myocardial sensitivity.

🧬 About

• Excess amyloid protein deposits within the myocardium.
• Commonest cause of restrictive cardiomyopathy in the UK.
• Leads to stiff ventricles → impaired diastolic filling → progressive heart failure.

⚗️ Aetiology

• Amyloid fibrils are insoluble proteins with β-pleated sheet secondary structure.
• They cannot be broken down, accumulate in tissues, and disrupt normal function.
• Localised atrial deposits (from ANP) → associated with atrial fibrillation.
• Pericardial thickening can occur due to deposition.

🧾 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.

🔬 Pathology

• Thickening of all 4 chambers with bi-atrial dilatation.
• Normal/small LV cavity; RV often only mildly dilated.
• Myocytes distorted by infiltrated amyloid → impaired contractility.

🩺 Clinical Features

• Progressive heart failure (diastolic >> systolic).
• Angina-like chest pain, arrhythmias, thromboembolism.
• Syncope or sudden death due to conduction disease or electromechanical dissociation.

🧪 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: “Granular sparkling” 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.

📋 Differentials

• Hypertensive heart disease: Clear history of HTN; no amyloid markers.
• Hypertrophic cardiomyopathy: May mimic, but worsening with verapamil/diltiazem suggests amyloidosis.

🩹 Management

• ⚠️ 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.

📝 Teaching Pearl

Cardiac amyloidosis is a “zebra” cause of restrictive cardiomyopathy. 🔑 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.