What is the pathophysiology of cardiac amyloidosis?

Updated: Mar 25, 2020
  • Author: Gyanendra K Sharma, MD, FACC, FASE; Chief Editor: Terrence X O'Brien, MD, MS, FACC  more...
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Answer

The characteristic abnormality in amyloidosis is an abnormal folding of a protein, rendering it to be insoluble. [6] These abnormalities may be a result of genetic mutations or excess formation. Various proteins may form amyloid fibrils; light chain amyloidosis (AL) is the most common type of systemic amyloidosis that results from the proliferation of plasma cells in the bone marrow. The plasma cell burden in AL is about 5-10% and is a marker of poor prognosis. [7, 8] Lambda light chains are 3 times more likely involved than kappa chains.

Most cases of AL are associated with a benign monoclonal gammopathy. Only rarely is AL seen in patients with multiple myeloma, lymphoma, or macroglobulinemia. Amyloid deposition in the tissues causes disruption of architecture, induces oxidant stress, and results in organ dysfunction. Multiorgan involvement is common. Cardiac involvement is most common in the AL variety but is also seen in secondary, hereditary, and senile amyloidosis.

Cardiac amyloid deposition is most common in the myocardium but is also seen in the atria, pericardium, endocardium, and vasculature. The myocardium becomes thick (mean weight 500 g) with a rubbery consistency. [9] High-grade infiltration (>50%) of myocardium is most common in the AL variety, and 90% of cases have vascular involvement. [10] Epicardial vessels are typically spared, but microvascular involvement is common, resulting in tissue ischemia and infarction. [11, 12, 13] Resultant myocardial fibrosis adds to the myocardial dysfunction, causing heart failure and cardiac arrhythmias.

The ventricular cavities are typically normal in size, but the ventricles are stiff, which cause restrictive ventricular filling and biatrial enlargement. Pericardial involvement is common and leads to pericardial effusion. [14] Endocardial involvement may result in atrioventricular valve dysfunction. Intracardiac thrombosis is common and seen in about 33% cases in autopsy specimens. [15] The thickening of the left heart valves is common in patients with AL, is associated with advanced age, and increases all-cause mortality. [16] These patients have poor functional class and worse systolic and diastolic function. [16]

Conduction system abnormalities (ie, bundle branch block and atrioventricular block) are frequent in amyloidosis. In a small series, severe sinoatrial node fibrosis was seen in 30% cases. [17]


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