2 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 sold But my outside to behold: Gilded tombs do worms enfold. Had you been as wise as bold, Young in limbs, in judgement old Your answer had not been inscroll'd Fare 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."
3 CC/History of present illness 50 yo Caucasian female with vertigoSudden onset after lunch, never happened before, still symptomaticWorse with movement, associated with nausea“room spinning”, no tinnitus or hearing lossBetter lying stillCan not walk or change positions because of symptoms
4 Recent HistoryThree 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
5 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 obstructionSocial: no tobacco, alcohol or illicit drugs, works as housewife, former furniture salesperson and secretary, husband is trucker, 2 healthy childrenFamily: mother – liver cancer, father – Alzheimer, brother – diabetes mellitus
7 Exam5’2” 155#, bp 120/80, hr 85, resp 16, oxygen saturation 93% on 2L NC, temp 96.7Neuro: Finger to nose, dysmetric left hand, any head movement reproduces vertigo and nauseaHEENT: Nystagmus with leftward gazeCardiac: S1S2 normalPulm: clear but diminished on basesExtremities: trace pedal edema.
8 LabsWbc 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+ proteinUterine pathology – cervix had some nabothian cysts, endometrium was weakly proliferative, and myometrium showed intravascular leiomyomatosis, adenomyosis and adenomatoid tumor
11 Old labsBnp 256Echo – abnormal LV systolic function with LVEF 40%, mild mitral and aortic regurgitation, concentric LVH, mild elevation of right ventricle systolic pressureBedside spirometry – FVC 2.23 L or 73% predicted, FEV L or 67% predicted, FEF 25-75% is 1.28 L/s or 46% predicted, FEV1/FVC 75% predicted, no change with bronchodilatorSpirometry a month ago – FVC 2.53 L or 87% predicted, FEV L or 87% predicted with ratio 84% and FEF % predicted.Cardiolite – diminished LVEF 35% with global hypokinesis and akinesis of intraventricular septum, no wall motion abnormalities, no reversible defects to suggest myocardial ischemiaAggregate apnea/hypopnea index 5.1 but during REM sleep 19.8
13 MRI brain –showed acute left superior cerebellar distribution infarct. MRA brain – negativeCentral
14 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 LVCT thorax – no PE, moderate bilateral pleural effusion, right greater than left, heart enlarged, no mediastinal adenopathy, wedge shaped enhancement pattern on spleen, anasarca
19 Restrictive Cardiomyopathy Restricted LV filling with rigid LV wallamyloidosis, 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
21 Hypertrophic cardiomyopathy Asymmetric LV hypertrophy of interventricular septum with increased outflow tract pressure gradientRisk for SCD in young athletesEkg shows LVH with widespread deep broad Q waves
25 Further labs IgA normal, IgG 269 (nl 681-1648), IgM normal Serum protein electrophoresis shows hypogammaglobulinemia with immunofixation showing small monoclonal lambdaUrine protein electrophoresis shows monoclonal band of free lamba light chainsBeta 2 microglobulin 2.46 (nl )Kappa light chain normal, Lambda light chain 13.7 (nl )24 hr urine protein 876Bone 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 translocationsLC MS on peptides from uterine tissue - AL amyloid
26 Amyloidosis – deposition of amyloid protein fibril AA – serum amyloid A from inflammatory disorders, infections, occasionally neoplasmsAL – light chain, monoclonal plasma cell disorder similar to multiple myelomaAH – heavy chainATTR – transthyretin, senile cardiac amyloidosisCryopyrin associated periodic syndromeOthers – renal, CNS, localizedDiagnosis – organ biopsy, subcutaneous fat pad biopsy, rectal mucosa biopsyLabs – Congo red, H and E, kappa/lambda light chain, LC MS, B2M
27 AL amyloidosis Renal - proteinuria Cardiac - diastolic/systolic dysfunctionNerve - Peripheral neuropathyGI - nausea, vomit, diarrhea, early satiety, macroglossia, splenic involvementHeme - easy bruising, may develop periorbital ecchymosisSkin - nail dystrophy
28 Treatment Prognosis is worse with multisystem involvement Not candidate for cardiac transplant due to renal and gastrointestinal involvementNot candidate for stem cell transplant due to elevated troponinMelphalan and dexamethasone is good choice but it is toxic to stem cellsRecommendation -- bortezomib and dexamethasone for 6 cycles at 3 wk intervals.
29 References http://ci.yuma.az.us http://www.amyloidosis.org Miller AL, Falk RH, Levy BD, Loscalzo J. A Heavy Heart. NEJM ;363:Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill; 2008.
30 Thank you ACP, Dr. Yturri Pathology: Drs. Sloop, Ausmus Cardiology: Dr. GaleoNeurology: Dr. CulceaOffice: Ms. Hansen