81 y/o African-American woman with PMH of NICM with LVEF of 35-40% and CKD stage 3 presented to ED with complaints of cough, increased lower extremity swelling, and progressive DOE. She endorsed noncompliance with her diet, indulging in fried chicken but compliance with her medications. During her last admission, she was noted to be bradycardic with episodes of ectopy with NSVT. Patient had undergone a coronary catheterization in 2010 that revealed no coronary artery disease and at that time, echocardiogram revealed normal LVEF. Three years later, patient was noted to have moderate global hypokinesis with LVEF of 35-40% and concentric LVH. Patient was admitted with decompensated heart failure as she had many times before. After consultation with a heart failure specialist, suspicion arose for amyloidosis given the gradual decline in EKG voltage over the years. A cardiac tissue biopsy was performed and pathology returned with ATTR (transthyretin/prealbumin) with LC MS/MS detected amino acid sequence abnormality in the transthryretin protein (Val122Ile) strongly suggestive of hereditary ATTR amyloidosis. Patient and patient’s family were referred for genetic counseling. Patient was discharged with follow up for tranplant evaluation.
Discussion:
ATTR amyloidosis has two forms, a hereditary form with over 100 mutations in the TTR gene, with the most common being in the Val122Ile structure, and a wild type, aka, senile systemic amyloidosis. The mutation of Val122Ile presents in 3-4 percent of African-American and Afro-Caribbean populations. This diagnosis should be suspected in Africans with left ventricular thickening. Although diurectics are the mainstay of therapy for amyloid cardiomyopathy, other treatments differ from those of systolic or diastolic CHF. Beta blockers, despite their proven benefit in improvement of morbidity and mortality in CHF, have no role and may worsen heart failure due to amyloid cardiomyopathy. ACE inhibitors may provoke severe hypotension in amyloid cardiomyopathy patients due to subclinical neuropathy that may manifest with their use. Amyloid fibrils additionally provide a hurdle in management therapies. Calcium channel blockers may evoke profound negative inotropic effects due to the abnormal binding of the medication to the fibrils. For those patients who develop atrial fibrillation in the setting of hypotension, caution must be exercised as digoxin binds to the fibrils, increasing susceptibilities to the development of digoxin toxicity. For those with familial ATTR amyloid, the source of the amyloidogenic protein is the liver, which means that transplantation of the liver can remove the mutant amyloidogenic TTR. If extension to the heart is already present, considerations should be made for liver and heart transplantation or heart transplantation alone.
Conclusions:
Amyloid are misfolded proteins that are normally soluble that become insoluble and deposit in organs or tissue leading to a disruption in normal function. When patients with a history of unexplained heart failure are admitted to the hospital for decompensated heart failure, Hospitalists must consider the diagnosis of amyloid cardiomyopathy, particularly if echocardiogram shows increased left ventricular wall thickness and EKG shows low voltage since there are significant differences in the management of amyloid cardiomyopathy compared to other etiologies of cardiomyopathy, including prompt referral for heart transplantation in some cases.