In SSA, the amyloidogenic protein is transthyretin. This tetramer is produced by the liver and is normally responsible for transportation of thyroid hormones. Under certain circumstances, transthyretin dissociates into monomers that are then deposited in various tissues of the body.
Autopsy reports show that 25% of patients over 80 years have evidence of transthyretin cardiac amyloid deposition.1
In the majority of patients, the deposits are small and asymptomatic. A few patients develop more extensive infiltration, leading to a restrictive cardiomyopathy. This typically presents as biventricular heart failure, although it may be picked up incidentally on echocardiography.
SSA almost exclusively affects men; the reasons for which remain unclear.
SSA is typically a diagnosis of exclusion, where underlying malignancy or hereditary and AL amyloidosis have been ruled out. summarises features that may tend towards a diagnosis of SSA. As the name suggests, this form of amyloid does have systemic distribution. Outside the heart, lung involvement predominates but SSA is also found in the gastrointestinal tract, liver, spleen, bone marrow, kidneys and endocrine glands.
Features suggestive of senile systemic amyloidosis
The characteristic signs seen in light chain amyloidosis (AL), such as macroglossia, nephrotic syndrome and bruising around the eyes (panda eyes), are usually absent in SSA. However, there is a strong association with carpal tunnel syndrome. The electrocardiogram (ECG) voltage in AL and hereditary amyloidosis is typically low, whereas in SSA this tends to be normal.
However, the myocardium may be thicker in SSA than AL. One study found a mean intraventricular septum thickness of 17.8 mm in patients with SSA, compared to 14.3 mm in an AL group.2
Several studies have noted that AL patients develop symptomatic heart failure with much thinner ventricular walls than SSA patients. The evidence would suggest that light chains in AL amyloidosis have an intrinsic toxic effect on myocytes.3
Patients with AL typically deteriorate rapidly with a median survival of 5–11 months, whereas SSA patients have a median survival of 60–75 months.4
While the ‘gold standard’ for the diagnosis of amyloidosis is biopsy of affected tissue, in SSA the heart may frequently be the only site involved. Endomyocardial biopsy is a procedure with significant risk and other sites for biopsy should be rigorously sought if possible. Serum amyloid-P (SAP) scanning, a radiolabelling technique for quantifying amyloid load, is unsuitable for visualising hollow organs such as the heart.5
Medical treatment using diuretics and antiarrhythmics may render the patient asymptomatic. Anticoagulation should be used in atrial arrhythmias as the risk of thromboembolism is particularly high. A permanent pacemaker may be required if atrioventricular conduction block occurs. The definitive treatment for SSA is cardiac transplantation and, while the majority of patients are older and will not meet the selection criteria, at least three patients have been successfully transplanted for SSA. All were men, but unusually two were under 60 years of age6
and the third was 68 years of age.7
- Senile systemic amyloidosis (SSA) is very common in older patients and is under-recognised as a cause of heart failure. It is important for doctors to be familiar with the features of amyloid-associated cardiomyopathy to enable treatment to be directed appropriately. A diagnosis of SSA should be considered in older men presenting with atrial fibrillation and a thickened heart on echocardiography, especially if there is a history of carpal tunnel syndrome.
- SSA has a much better prognosis than light chain amyloidosis, the most common form of amyloidosis, so the two need to be distinguished from one another.
- Cardiac biopsy is a hazardous procedure and should be avoided in older patients unless completely necessary, but common investigations may strongly point to the diagnosis.