By the end of this presentation, the clinician will be able to:

In 1838, Matthias Schleiden rst used the term “amyloid” to describe the composi­tion of a type of starch in plants. Before the word amyloid came into practice, “lar­daceous” or “waxy” was used to describe amyloid disease processes in the human body [1]. In 1856, Dr. Samuel Wilks, a British physician, biographer, and an avid user of the phrase “lardaceous disease,” described a 52-year-old male patient with lardaceous kidneys, heart, and spleen. This was most likely the rst case of primary amyloidosis reported in literature [1, 2]. However, the term “amyloid” persisted because of Virchow’s experiment. He added iodine to the sulfated glycosaminogly­cans (corpora amylacea) from brain tissue and what resulted was a color reaction from brown to blue, similar to starch [3].

A 62-year-old female arrived at the hospital with fatigue, dyspnea, an abnormal mammogram, and pulmonary edema for at least 3 months. Her medical history included bilateral carpal tunnel syndrome (CTS), and her family history was posi­tive for breast cancer. The EKG revealed a previous myocardial infarct and a single run of supraventricular tachycardia with normal sinus rhythm. Her chest X-ray was signicant for mild bilateral pleural effusions and increased pulmonary congestion, which explained the orthopnea experienced by the patient. Laboratory tests showed highly elevated brain natriuretic peptide (BNP) (NT-proBNP, 2959pg/ml) and tro­ponin I of less than 0.3ng/ml. The patient was hospitalized. An echocardiogram performed during hospitalization was notable for right and left ventricular (LV) systolic dysfunction, decreased ejection fraction (EF) (<20%), and right and left atrial dilation. Other echo ndings were within normal limits. Former echocardio­grams were unavailable. Cardiac index measured in the cardiac catheterization lab­oratory was 2.2L/min/kg2 (N: 2.5–4.0). 99m technetium-pyrophosphate scan did not reveal any tracer uptake by the myocardium. Cardiac magnetic resonance imag­ing (CMR) revealed a normal LV wall thickness of 1.3cm without late gadolinium enhancement (LGE) in the basal short-axis cine view. Urine protein electrophoresis turned out to be 62mg/dl; however, serum protein electrophoresis with immuno­xation (SPIE) was within normal limits. The clinicians considered a diagnosis of monoclonal gammopathy of undetermined signicance. Serum-free light chain assay (SFLC) and bone marrow biopsy were taken into consideration as MRI and SPIE were normal, and the patient was negative for CRAB criteria for multiple myeloma. The authors never consulted hematology and oncology services [8]. Despite aggressive medical management, her initial symptoms continued to worsen, and she required hospital admission after 8 months for severe cardiogenic shock. Repeated measurement of the cardiac index was done, and it had gone down from

urine immunoxation showed abnormal free lambda light chains. Subsequent tests (cardiac and bone marrow biopsies) could not be performed as the patient, unfortu­nately, passed away. Her clinical status had faded very rapidly [8].

2. Breast cancer

In this ill-fated cardiology case, cardiac amyloidosis was misdiagnosed as MGUS due to normal apparent imaging and lack of resources [8]. Multiple reasons come into play when we dig deeper into the root causes.

There are nine types of amyloidosis that have cardiac involvement. Usually, inva­sive and noninvasive diagnostic tests are combined to assist in diagnosing cardiac amyloidosis. It typically presents with both cardiac and extracardiac organ involve­ment. Such symptoms and signs are known as red ags. They include but are not limited to skin bruising, macroglossia, proteinuria, vitreous deposits, and unex­plained elevated troponin. The current position statement published by the European Society of Cardiology (ESC) states that if the clinical picture, EKG, echocardio­gram, and CMR point toward cardiac amyloidosis, then scintigraphy and monoclo­nal protein assessment must be made. If both are positive, histological analysis is the next step to conrm the subtype. Histological conrmation should also be done if both CMR and hematologic tests are positive (or CMR is inconclusive) and scin­tigraphy is negative. If tests reveal no monoclonal spike and grade 1 uptake on scintigraphy, a biopsy becomes necessary for diagnosis. Grade 2–3 on scintigraphy indicates ATTR amyloidosis, and the patient must undergo genetic testing to distin­guish between acquired and hereditary forms (Fig.11.1) [9].

software. After upgrading their system, a second look at the images showed longi­tudinal strain of −2 without apical sparing. It is interesting to note that LGE was nearly absent, and left ventricular wall thickness was normal in this patient despite having advanced disease. Septal thickness was also within normal limits initially. Although unlikely, the patient might have had recent AL amyloidosis on top of pre­existing dilated cardiomyopathy. One can argue against this assumption due to the abrupt clinical decline and heart failure progression. Lack of LGE could have been falsely absent due to the high amyloid burden and small cellular volume. Due to the fact that profound heart failure due to amyloidosis could not have occurred until there was myocardial inltration, CMR was rechecked, and difculty in nulling the myocardium was seen, which was earlier reasoned to be a motion artifact. The char­acteristic above is seen explicitly in inltrative disorders. In the presence of normal wall thickness, absence of LGE, and normal SPIE, labeling the nulling as a motion artifact seemed appropriate [8].