A 52-year-old woman presents with fatigue, peripheral edema, and periorbital purpura. She states that the symptoms of fatigue and peripheral edema have developed gradually over the past few months, but the periorbital skin changes occurred abruptly after sneezing. She also experiences dyspnea after moderate exertion, which is abnormal for her. Her vitals are within normal limits. Her jugular veins are distended, and there are third and fourth heart sounds. Her lungs are clear bilaterally and she has pitting edema around the ankles. A urinalysis reveals significant proteinuria, and an ECG shows low voltages throughout all the leads. The patient is admitted and a cardiac biopsy is performed. The tissue is stained with Congo red and shows apple-red birefringence under polarized light.
Which of the following is the correct diagnosis?
A. Amyloid cardiomyopathyAmyloid cardiomyopathy. The stain showing apple-red birefringence should lead the reader to suspect amyloidosis as the cause of this patient’s restrictive cardiomyopathy. There are several types of amyloidosis that can cause restrictive cardiomyopathy, and in this case the patient most likely has the AL form that is a primary disease process resulting from a plasma cell dyscrasia. In this form of the disease, light chain proteins are deposited in tissues throughout the body, and the heart is commonly affected with a poor prognosis. The periorbital purpura is fairly specific for the AL form. Inherited amyloidosis and senile amyloidosis fall into a separate category called ATTR amyloidosis, which results from an autosomal dominant mutation in the gene encoding transthyretin. The AA form occurs as a secondary disease process that results from deposition of serum amyloid A protein. It may occur with chronic inflammatory conditions such as rheumatoid arthritis or inflammatory bowel disease; however, this form does not commonly lead to heart disease. Treatment in AL amyloidosis is twofold: chemotherapy for the underlying process, and treatment of the heart failure with typical agents (although ACE inhibitors and β-blockers are typically not tolerated in amyloid cardiomyopathy).
(B) Hypertrophic cardiomyopathy would show an S4 but not an S3 on examination, and would show left ventricular hypertrophy on ECG (not low voltages as is seen with infiltrative processes like amyloidosis). (C) Rheumatoid arthritis can cause inflammation of heart structures (pericarditis, endocarditis, etc.), but she has no other suggestive symptoms. It may cause AA amyloidosis; however, this form does not typically affect the heart. (D) Hemochromatosis can cause a restrictive cardiomyopathy but this typically presents in men with skin darkening, arthritis, diabetes, and liver disease. (E) Temporal arteritis is a vasculitis that presents in older patients with fever, headache, jaw claudication, and tenderness over the temporal arteries. It is often associated with polymyalgia rheumatica. Biopsy of the temporal artery shows intimal thickening and granulomatous inflammation.