Cardiac amyloidosis natural history, complications and prognosis

The presence or absence of cardiac involvement with amyloid is the most important prognostic factor. Untreated cardiac amyloidosis is associated with a very poor prognosis and a high mortality rate. The most common cardiac complications include heart failure, sudden cardiac death due to electromechanical dissociation and pericardial effusion.

• Untreated cardiac amyloidosis is associated with high rate of cardiac complications and eventually death.
• Cardiac involvement in AL amyloidosis is associated with a higher mortality rate compared with that in senile amyloidosis and familial forms of amyloidosis.^[1]
• Also, heart failure in AL type amyloidosis is more difficult to treat as compared with that associated with TTR type amyloid.

The following are the complications of cardiac amyloidosis:

• Congestive heart failure^[2][3]
• Sudden cardiac death (SCD)^[4]
  • Largely due to electromechanical dissociation; unlike other disease states where sudden cardiac death is predominantly due to other causes such as ventricular arrhythmia
• Myocardial infarction^[5]
• Pericardial effusion^[6]
• Cardiac tamponade^[7]
  • It should be noted, however, that the classic echocardiographic signs of cardiac tamponade, such as right atrial indentation and right ventricular compression, are not seen in cardiac tamponade associated with cardiac amyloidosis due to the stiffness of the atrial and ventricular walls. Therefore a high degree of suspicion should be maintained in patients with heart failure and a mild to moderate pericardial effusion.^[6]
• Valvular heart diseases, with aortic stenosis being the most common followed by mitral regurgitation
• Atrial fibrillation^[8]
• Tachyarrhythmias^[9]
• Ventricular arrhythmias^[10]
• Sick sinus syndrome (occasionally)
• Heart blocks and other conduction defects
  • Higher degree blocks are unusual in cardiac amyloidosis associated with AL type amyloidosis, but in the TTR type, progressive conduction system disease is common and requires pacemaker implantation. Frequently, the electrophysiologic function appears to be abnormal in the His-Purkinje system. Prolonged infra-His conduction time is an independent predictor of sudden death in these patients. ^[11]
• Syncope or presyncope^[5]
• Increased sensitivity to digoxin with the potential for digoxin toxicity and digoxin related arrhythmias
  • The amyloid protein tends to bind the digoxin and increase its local concentration in the conduction system for instance.
• Ascites (fluid accumulation in the abdomen)
• Stroke and claudication due to intracardiac thrombus causing thromboembolism.^[12][13]
  • Risk factors include:
    • Atrial fibrillation
    • Atrial dysfunction due to infiltration of the atria by amyloid
    • Left ventricular diastolic dysfunction
    • Increased right ventricular wall thickness
    • Tachycardia

• Cardiac amyloidosis is a chronic and progressive condition.
• A cardiologist may estimate the prognosis according to the thickness of the left ventricle and to the degree of restriction in the heart (diastolic dysfunction).
• The extent of cardiac involvement is the most important predictor of survival in patients with AL amyloidosis.^[1]

• Studies have shown that cardiac troponin T and N-terminal proBNP are powerful prognostic indicators in AL amyloidosis.
• Based on the combined levels of both the indicators, a staging system has been developed for risk stratification of patients with AL amyloidosis.
• Two prognostic models for risk stratification were designed using threshold values for troponins and NT-proBNP.
• The threshold values used for the markers were: NT-proBNP < 332 ng/L, cTnT < 0.035 μg/L, and cTnI <0.1 μg/L.^[14][15]

Updated Staging System

• In 2009 another staging system was proposed which incorporates serum free light chain (serum FLC) levels into the Mayo staging system.
• The threshold values used for the table below are:
  • NT-proBNP <332 ng/L
  • cTnT <0.035 μ<g/L
  • Serum FLC <500mg/L

Mortality increased as the stage increased.

Prognosis Based on Pathologic Findings

The presence of nodular deposits, thick perimyocytic layers of amyloid, and small myocyte diameters on endomyocardial biopsy are associated with a worse prognosis. ^[16]

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