Persistent Heart Failure Despite Medical Therapy Leading to a Diagnosis of Cardiac Amyloidosis

Cardiac amyloidosis is restrictive cardiomyopathy, commonly classified as either light-chain amyloidosis (AL) or transthyretin amyloidosis (ATTR), which can be further subdivided into wild-type (systemic senile amyloidosis) and hereditary ATTR amyloidosis. Advanced-stage, silent, and clinically undiagnosed amyloidosis has a poor prognosis, with a survival rate of six months and up to five years. We present a 72-year-old female with a past medical history of heart failure, with preserved ejection fraction, atrial fibrillation, systemic lupus erythematosus (SLE), and stage 3b chronic kidney disease, who presented with persistent shortness of breath, lower extremity pitting edema, jugular venous distension, and dyspnea despite optimal medical therapy. The patient was diagnosed with preserved heart failure in the past and was on guideline-directed medical therapy for over five years with no history of cardiac disease in the family. The patient's previous echocardiogram revealed an ejection fraction of 65%. In order to determine the etiology of the patient's cardiomyopathy, she underwent cardiac magnetic resonance imaging (CMR), monoclonal gammopathy testing, and a Technetium pyrophosphate (99mTc-PYP) scintigraphy, of which the latter two were unrevealing. The CMR revealed increased wall thickness and multiple segments of midmyocardial to subendocardial late gadolinium enhancement, suggestive of infiltrative disease. Due to inconclusive testing, the patient underwent an endomyocardial biopsy and was determined to have wild-type, systemic senile amyloidosis, which held a poor prognosis. The patient was started on tafamidis, a new Food and Drug Administration (FDA)-approved therapy for systemic senile amyloidosis, and was discharged on the new medication, with frequent follow-up visits scheduled. Current treatment guidelines for cardiac amyloidosis include loop diuretics and spironolactone. Medications such as beta-blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers are not clinically effective. There are currently new medications on the horizon, such as tafamidis, which stabilizes the transthyretin tetramer and reduces the formation of amyloid. This case highlighted that patients who have persistent symptoms of heart failure, despite guideline-directed medical therapy, and without a history of genetic cardiac conditions, may also have a diagnosis of cardiac amyloidosis. Cardiac amyloidosis is often misdiagnosed or diagnosed late in the disease course; therefore, there is a need for increasing awareness of early diagnosis and treatment, including new FDA-approved medications for a better chance of survival.