Amyloidosis Flashcards
Cardiac Amyloidosis - ECG and Echo
The ECG typically shows low-voltage complexes with poor R wave progression in the chest leads (a pseudoinfarction pattern).
Cardiac amyloidosis is associated with a ‘global speckled’ pattern on echo. A transthoracic echocardiogram is performed, reported as ‘significant increase in echogeneity, symmetrical left ventricular wall thickening, impaired bilateral diastolic ventricular dysfunction, bilaterally enlarged atria, pulmonary artery systolic pressure 45 mmHg, a 5mm pericardial effusion’
Cardiac Amyloidosis (AL Amyloid 2dry to Lymphoma/Myeloma) - Example Question
A 72 year old female presents with a 6 month history of gradual onset, progressive exertional dyspnoea associated bilateral increased lower limb pitting oedema. She has no previous cardiac history and prior to 6 months ago, had no limitations to exercise tolerance. Her past medical history includes B cell lymphoma diagnosed four years ago and in remission one course of chemotherapy. On examination, jugular venous pulse is raised at 6cm above the angle of Louis. A soft systolic murmur and bibasal inspiratory crackles can be heard on auscultation. Abdominal examination demonstrates a pulsatile 3cm liver edge. Her BP is 125/77 mmHg, HR 68 and sinus, Sats 92% on 2l, RR 22. ECG reveals sinus rhythm of low voltage. Chest radiography demonstrates bibasal alveolar shadowing with prominent upper lobe vasculature.
Urine dip is as follows: blood -ve, leucocytes -ve, nitrates -ve protein 3+ pH 5.5.
Blood tests are as follows:
Hb 11.1 g/dl
Platelets 275 * 109/l
WBC 8.3 * 109/l
Na+ 139 mmol/l K+ 4.9 mmol/l Urea 7.4 mmol/l Creatinine 140 µmol/l CRP 3 mg/l Trop <0.03 (normal range < 0.03)
Bilirubin 6 µmol/l
ALP 32 u/l
ALT 260 u/l
A transthoracic echocardiogram is performed, reported as significant increase in echogeneity, symmetrical left ventricular wall thickening, impaired bilateral diastolic ventricular dysfunction, bilaterally enlarged atria, pulmonary artery systolic pressure 45 mmHg, a 5mm pericardial effusion
What is the most likely underlying diagnosis for this patient?
Amyloid cardiomyopathy
Other options: Non-ST elevation myocardial infarction (NSTEMI) Idiopathic dilated cardiomyopathy Chemotherapy induced cardiomyopathy Viral pericarditis leading to tamponade
A clinical picture of decompensated congestive cardiac failure is described with subtle details of hepatomegaly (possible congested, possibly related to the underlying diagnosis), associated heavy proteinuria, echogenic TTE and low voltage criteria ECG, on a background of previous B cell lymphoma. The unifying diagnosis is amyloid cardiomyopathy, likely secondary to AL amyloid from B cell dyscrasia, with cardiac, renal and possibly liver involvement. There is no evidence of a sudden onset cardiac event suggestive of an ischaemic cause. Echocardiogram does not demonstrate ventricular dilation, only impaired function. A 5mm pericardial effusion is not sufficiently significant to cause tamponade. Although chemotherapy induced cardiomyopathy is possible, it is difficult to tie in the delayed onset from end of treatment with renal involvement. It also does not explain the echogenic pictures on transthoracic echo
RA and AA Amyloidosis: Example Question
A 55-year-old woman with a background of long-standing rheumatoid arthritis presents with worsening fatigue and weight loss, diarrhoea, and leg swelling. Additionally, she mentions pain in her wrists with ‘pins and needles’ at the tips of thumb and first two digits, which bothers her at night.
On examination she has waxy skin plaques about the axillary folds, macroglossia, hepatosplenomegaly, pitting oedema of the legs, and peripheral neuropathy. The faecal occult blood test is positive. Serum chemistry noted only mild hypoalbuminaemia. Urinalysis shows proteinuria with no haematuria.
Which of the following is the most appropriate next step in diagnosis?
Serum protein electrophoresis X-ray of vertebral column and skull > Biopsy of skin, rectal mucosa, or abdominal fat Renal biopsy Endomyocardial biopsy
Long-standing rheumatoid arthritis is a common cause of systemic ‘AA’ amyloidosis.This leads to amyloid deposition in multiple areas (skin, kidneys, tongue, gastrointestinal tract, or peripheral nerves) which can lead to a complex presentation. Common presentations of systemic amyloidosis are carpal tunnel syndrome, macroglossia, axillary skin plaques, hepatosplenomegaly and nephrotic syndrome; all of which are demonstrated in this patient.
Skin, rectal mucosa or abdominal fat pad biopsy are useful to confirm the diagnosis of AA amyloidosis. Multiple myeloma is a cause of ‘AL’ amyloidosis, however in this patient you would assume other features present also, such as bone pains and spontaneous fractures. If myeloma was suspected, X-rays of the vertebral column would prove helpful.
Renal and endomyocardial biopsy can show amyloid deposition, however these more invasive procedures should only be considered when the more superficial biopsies have proven inconclusive.
Amyloidosis
Amyloidosis
Overview
amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid
amyloid is derived from many different precursor proteins
in addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid P
other non-fibrillary components include apolipoprotein E and heparan sulphate proteoglycans
the accumulation of amyloid fibrils leads to tissue/organ dysfunction
Classification
systemic or localized
further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)
Diagnosis
Congo red staining: apple-green birefringence
serum amyloid precursor (SAP) scan
biopsy of rectal tissue
AA Amyloidosis
Amyloidosis is a rare disorder caused by deposition of abnormal amyloid protein. It can affect multiple systems including the kidneys, heart and peripheral nerves.
AA amyloidosis occurs secondary to a poorly controlled chronic inflammatory condition such as ankylosing spondylitis or rheumatoid arthritis. The key to treatment is to address the underlying condition.
AL amyloidosis is not linked to another condition and results from abnormal plasma cells producing excessive amounts of light chains in a process similar to multiple myeloma.
