All that glitters is not gold

William Shakespeare, The Merchant of Venice

Act II - Scene VII - Prince of Morocco• All that glisters is not gold;

Often have you heard that told:Many a man his life hath soldBut my outside to behold:Gilded tombs do worms enfold.Had you been as wise as bold,Young in limbs, in judgement oldYour answer had not been inscroll'dFare you well, your suit is cold.

• The first record of this phrase is from French theologian Alain de Lille who said "Do not hold everything gold that shines like gold."

CC/History of present illness

• 50 yo Caucasian female with vertigo• Sudden onset after lunch, never happened before,

still symptomatic• Worse with movement, associated with nausea• “room spinning”, no tinnitus or hearing loss• Better lying still• Can not walk or change positions because of

symptoms

Recent History

• Three separate clinic visits in last 9 months for shortness of breath, cough, wheezing attributed to allergies from cats, mold and improved after prednisone. Has established care in last 2 months with pulmonology and cardiology with diagnosis of asthma, chf, and obstructive sleep apnea

Past history

• Medical: heart failure, asthma, sleep apnea• Surgical: hysterectomy performed 4 days ago and

discharged home 2 days ago for dysfunctional uterine bleed, fibroids, prior right oophorectomy for cyst and laparotomy for adhesion and bowel obstruction

• Social: no tobacco, alcohol or illicit drugs, works as housewife, former furniture salesperson and secretary, husband is trucker, 2 healthy children

• Family: mother – liver cancer, father – Alzheimer, brother – diabetes mellitus

Meds/allergies

• Coreg 3.125 mg bid

• Lasix 40 mg daily

• Spironolactone 25 mg daily

• Advair 250/50 1 puff bid

• Singulair 10 mg daily

• Allergy: PCN

Exam

• 5’2” 155#, bp 120/80, hr 85, resp 16, oxygen saturation 93% on 2L NC, temp 96.7

• Neuro: Finger to nose, dysmetric left hand, any head movement reproduces vertigo and nausea

• HEENT: Nystagmus with leftward gaze• Cardiac: S1S2 normal• Pulm: clear but diminished on bases• Extremities: trace pedal edema.

Labs• Wbc 15, hemoglobin 15, platelet 270 with 90%

neutrophils, 5% lymph, 5% monocytes, no bands.• Sodium 140, potassium 2.8, chloride 98,

bicarbonate 26, BUN 7, creatinine 1, glucose 124, calcium 8.2, magnesium 2, total protein 5.1, albumin 2.5, total bilirubin 0.8, AST 34, ALT 50, pro BNP 20443, troponin ranged from 0.39—0.67—1.06—0.73, TSH 3.3, UA – 1+ protein

• Uterine pathology – cervix had some nabothian cysts, endometrium was weakly proliferative, and myometrium showed intravascular leiomyomatosis, adenomyosis and adenomatoid tumor

cxr

EKG

Old labs• Bnp 256• Echo – abnormal LV systolic function with LVEF 40%,

mild mitral and aortic regurgitation, concentric LVH, mild elevation of right ventricle systolic pressure

• Bedside spirometry – FVC 2.23 L or 73% predicted, FEV1 1.68 L or 67% predicted, FEF 25-75% is 1.28 L/s or 46% predicted, FEV1/FVC 75% predicted, no change with bronchodilator

• Spirometry a month ago – FVC 2.53 L or 87% predicted, FEV1 2.12 L or 87% predicted with ratio 84% and FEF 25-75 79% predicted.

• Cardiolite – diminished LVEF 35% with global hypokinesis and akinesis of intraventricular septum, no wall motion abnormalities, no reversible defects to suggest myocardial ischemia

• Aggregate apnea/hypopnea index 5.1 but during REM sleep 19.8

Differential diagnoses vertigo

• Peripheral: vestibular neuronitis, BPPV, Meniere, autoimmune inner ear disease

• Central: migraine, TIA, CVA, acoustic neuroma

Central

• MRI brain –showed acute left superior cerebellar distribution infarct.

• MRA brain – negative

Other investigations• Carotid doppler – normal• Echo – left ventricular ejection fraction 35-40%,

moderate concentric left ventricular hypertrophy, 3+ MR, 1+ TR, grade 3 diastolic dysfunction, echogenic speckling of ventricular myocardium, moderate right and left atrial dilation, restrictive filling of LV

• CT thorax – no PE, moderate bilateral pleural effusion, right greater than left, heart enlarged, no mediastinal adenopathy, wedge shaped enhancement pattern on spleen, anasarca

echo

CT thorax

Labs

• Thoracentesis – transudate, 700 mL removed with cytology negative for malignancy

• Negative hypercoagulability screen

• TEE showed thrombus in left atrial appendage 1 X 3 cm.

Differential diagnoses cardiomyopathy

• Restrictive

• Hypertrophic

• Dilated

Restrictive Cardiomyopathy

• Restricted LV filling with rigid LV wall

• amyloidosis, endomyocardial fibrosis (equatorial Africa or less common in Asia and S America), eosinophilic or Loeffler endomyocarditis, hemochromatosis, glycogen storage disease, treatment from heart transplant, radiation fibrosis

Dilated Cardiomyopathy

• LV dilation diffusely

• From alcohol, peripartum, neuromuscular dystrophies, doxorubicin, cocaine, Takotsubo, arrhythmogenic right ventricuar cardiomyopathy/dysplasia, LV noncompaction, other drugs (trastuzumab, cyclophosphamide, imatinib)

Hypertrophic cardiomyopathy

• Asymmetric LV hypertrophy of interventricular septum with increased outflow tract pressure gradient

• Risk for SCD in young athletes

• Ekg shows LVH with widespread deep broad Q waves

Congo red staining of uterine tissue

Congo red staining of stomach tissue

Congo red stain of bone marrow

Further labs• IgA normal, IgG 269 (nl 681-1648), IgM normal• Serum protein electrophoresis shows

hypogammaglobulinemia with immunofixation showing small monoclonal lambda

• Urine protein electrophoresis shows monoclonal band of free lamba light chains

• Beta 2 microglobulin 2.46 (nl 0.7-1.8)• Kappa light chain normal, Lambda light chain 13.7 (nl

0.57-2.63)• 24 hr urine protein 876• Bone marrow aspirate with 12% plasma cells and biopsy

showed 10% CD38/CD138 cytoplasmic lambda monoclonal plasma cells identified, normal cytogenetics, multiple myeloma FISH negative for del chromosomes 13q and 17p and FGFR3/IgH and BCL-1/IgH translocations

• LC MS on peptides from uterine tissue - AL amyloid

Amyloidosis – deposition of amyloid protein fibril

• AA – serum amyloid A from inflammatory disorders, infections, occasionally neoplasms

• AL – light chain, monoclonal plasma cell disorder similar to multiple myeloma

• AH – heavy chain• ATTR – transthyretin, senile cardiac amyloidosis • Cryopyrin associated periodic syndrome• Others – renal, CNS, localized• Diagnosis – organ biopsy, subcutaneous fat pad

biopsy, rectal mucosa biopsy• Labs – Congo red, H and E, kappa/lambda light chain,

LC MS, B2M

AL amyloidosis

• Renal - proteinuria• Cardiac - diastolic/systolic dysfunction• Nerve - Peripheral neuropathy• GI - nausea, vomit, diarrhea, early satiety,

macroglossia, splenic involvement• Heme - easy bruising, may develop

periorbital ecchymosis• Skin - nail dystrophy

Treatment

• Prognosis is worse with multisystem involvement• Not candidate for cardiac transplant due to renal

and gastrointestinal involvement• Not candidate for stem cell transplant due to

elevated troponin• Melphalan and dexamethasone is good choice but

it is toxic to stem cells• Recommendation -- bortezomib and

dexamethasone for 6 cycles at 3 wk intervals.

References

• http://ci.yuma.az.us • http://www.amyloidosis.org• http://emedicine.medscape.com/• Miller AL, Falk RH, Levy BD, Loscalzo J. A

Heavy Heart. NEJM. 2010;363:1464-9.• Fauci AS, Braunwald E, Kasper DL, et al.

Harrison’s Principles of Internal Medicine. New York: McGraw-Hill; 2008.

• http://en.wikipedia.org/wiki/All_that_glitters_is_not_gold

Thank youACP, Dr. YturriPathology: Drs. Sloop, AusmusCardiology: Dr. GaleoNeurology: Dr. CulceaOffice: Ms. Hansen