Makindo Medical Notes.com

Calcium-channel blockers are associated with significant worsening of heart failure and should be avoided. Bradycardia with 2:1 or complete heart block is common in amyloidosis and is much more likely to occur with Digoxin

About

• Excess amyloid deposited in the myocardium.
• Commonest cause of restrictive cardiomyopathy in the UK

Aetiology

• Deposition of a waxy substance formed by a protein within the myocardium
• Secondary structure of beta-pleated sheets which cannot be broken down
• Lead to local tissue damage and cardiac dysfunction
• Localized atrial amyloid deposits derived from ANP are associated with AF
• Causes a restrictive Cardiomyopathy
• Pericardial thickening due to deposition

Causes

• Most commonly seen with primary AL amyloid formed by light chains e.g. Myeloma
• Familial amyloidosis: Autosomal dominant mutation of the hepatically expressed protein transthyretin
• Senile systemic amyloidosis often with carpal tunnel syndrome

Pathology

• Thickening of all 4 chambers, with bi-atrial dilation
• Normal or mildly dilated right ventricle
• Left ventricular cavity that is normal to small
• Myocardial cells are separated and distorted by amyloid deposition

Clinical

• Progressive Heart failure - often diastolic due to a stiff myocardium and restrictive cardiomyopathy.
• Occasionally angina and systolic heart failure
• Arrhythmias, Cardiogenic shock, Thromboembolism

Investigations

• FBC, U&E, ESR. PPE and serum immunoglobulin free light chain (FLC) assay
• Biomarkers: BNP and troponins may be elevated
• Bone marrow to exclude myeloma with AL amyloid amyloidosis is often normal, even in the presence of congestive heart failure
• Endomyocardial biopsy done infrequently
• ECG: Low QRS voltages due to infiltration (all limb leads < 5 mm in height) with poor R-wave progression. AF or other arrhythmias, ST/T changes.
• Elevated BNP/NT-pro BNP: reflects high filling pressures,
• Echocardiogram shows a "bright or sparkling/granular appearance" to the myocardium. Thickened ventricular walls with a restrictive pattern of filling. Left ventricular ejection fraction in cardiac failure.
• Cardiac MRI: delayed enhancement pattern of gadolinium uptake in the myocardium
• Fat biopsy: Amyloid deposition can be found in the fat and histological examination of a sample obtained by needle aspiration of the subcutaneous abdominal fat has a high diagnostic yield
• Coronary angiography: Classical angina with a minimal epicardial coronary artery disease is seen with cardiac amyloidosis

Differentials

• Hypertensive heart disease: strong history of HTN and no other signs or findings of amyloid
• Hypertrophic cardiomyopathy: if treated with verapamil or diltiazem, they may experience worsening of heart failure, and this is a clue to the presence of amyloidosis

Management

• Treat underlying cause if possible. Patients with cardiac AL amyloidosis and evidence of active disease have a far worse prognosis than patients with transthyretin amyloidosis despite similar echocardiographic changes
• Atrial fibrillation: Cautious use of Digoxin as there is heightened sensitivity to Digoxin and an increased risk of associated ventricular arrhythmias.
• Sensitivity to calcium channel blockers which should be avoided
• Pacemaker for any significant conduction disease
• Ventricular arrhythmias: Unless sustained VT there appears to be little role for implantable defibrillators. Most patients with sudden death in cardiac amyloidosis are due to electromechanical dissociation
• AL Amyloid: treat the underlying plasma cell dyscrasia.
• Familial Amyloid: Liver transplantation may be lifesaving for familial forms of amyloidosis where the protein transthyretin (prealbumin) is produced in excess by the liver to make amyloid fibrils.