Is There a Unifying Diagnosis?

Kiran Mogali, Mustafa Ahmed, Juan Aranda, James Hill

48 y/o male with nonsustained VT

History

▪ 48 y/o male with double vision and dysarthria for 3 weeks

▪ Severe nausea and vomiting with 60 pound weight loss last year - diagnosed

with severe gastroparesis of unknown etiology

▪ Past Medical History: No other medical problems

▪ Family History: Father and paternal aunt died of “heart failure” in their 60s

▪ Social History: No tobacco, alcohol or illicit drug use

▪ Medications: Azithromycin, Prednisone

ROS & Physical Exam

▪ ROS: Negative for fever, cough, chest pain, dyspnea, palpitations

▪ Vitals: BP 125/85 (supine) 95/70 (standing); HR 78 (supine) 90

(standing); RR 16; Temp 97 F; SpO2 99% on room air; Weight 170 lbs

▪ Cardiac exam: RR, S1/S2 normal, No murmurs, No S3, JVP measured at 9

cm H2O, No Hepato-Jugular reflex, No pedal edema

▪ Respiratory: Clear to auscultation bilaterally, No wheezing or ronchi

▪ Neuro exam: Left facial palsy, horizontal gaze paralysis and gait ataxia

Work-up

▪ CBC, BMP, LFT, TSH, B12, Folate, Thiamine and Ferritin were WNL

▪ MRI of brain/spine, CSF studies, Autoimmune, Infectious and

Neoplastic work-up were unrevealing

▪ Cardiac enzymes were WNL

▪ NTpBNP elevated at 2100 (Normal <125 pg/ml)

▪ CRP elevated at 47 (Normal <5 mg/L)

Electrocardiogram

CXR

Echocardiogram - PLAX

Echocardiogram – Apical 4 Chamber

TR Jet

Mitral Inflow Doppler

▪ E = 70 cm/s, A = 40 cm/s

▪ E/A = 1.75

▪ Medial e’ = 5.4 cm/sec

▪ Lateral e’ = 7.0 cm/sec

▪ Medial E/e’ = 13

▪ Lateral E/e’ = 10

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What would be your next step?

A) Fat pad biopsy

B) Coronary Angiogram

C) Cardiac MRI

D) Endomyocardial Biopsy

E) EP Study

Decision making

▪ Differential Diagnosis

▪ Amyloidosis

▪ Storage Disorders: Fabry, Danon, Mucopolysaccharidoses

▪ Friedriech’s ataxia

▪ Sarcoidosis

▪ Hemochromatosis

▪ The etiology of NSVT was thought to be due to underlying cardiomyopathy. Suspicion

for ischemic process was very low at this time

Low voltage QRS complexes

Moderate LV thickening on echo

Biventricular systolic dysfunction

Suspicious for infiltrative heart disease

Cardiac MRI

Decision making

▪ Amyloidosis work-up:

▪ Serum and urine protein electrophoresis, Immuno-fixation essay - negative

for abnormal monoclonal spike

▪ Abdominal fat pad biopsy - negative (sensitivity 50-75%)

▪ Gastric mucosal biopsy - negative (sensitivity 85%)

▪ In summary, the patient has unexplained… ▪ Severe gastroparesis

▪ Orthostatic hypotension

▪ Sensory and motor neuropathy

▪ Infiltrative Cardiomyopathy

Decision making

▪ What would you do next? What is your working diagnosis?

▪ Endomyocardial Biopsy + R/LHC

▪ Clinical suspicion for amyloid remained high

▪ Strong family history of heart failure

▪ MRI findings of infiltrative process

▪ LHC: Normal coronary arteries

Hemodynamics

Simultaneous LV/PCW Tracing

Simultaneous LV/PA Tracing

Simultaneous RV/LV Tracing

Simultaneous RA/LV Tracing

Endomyocardial Biopsy

Amyloid Deposition Congo Red Stain

Final Diagnosis

▪ Familial Transthyretin Related Amyloidosis

▪ Immunohistochemistry for transthyretin on endomyocardial biopsy: Positive

▪ DNA sequence analysis for TTRA mutation: Positive

▪ Both children tested positive for this mutation

▪ SPEP, UPEP, IFE negative - not a light chain deposition disease

▪ Fat pad & gastric biopsy negative - amyloid deposition is often patchy

Familial TTRA

▪ Transthyretin is a normal plasma transport protein secreted by liver

▪ Disease caused by mutations that destabilize this protein

▪ Autosomal dominant inheritance, Incidence in US is 1 per million

▪ Familial TTRA can present as…

▪ Familial Amyloid Polyneuropathy

▪ Familial Amyloid Cardiomyopathy

▪ Nephropathy in late stages

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What is your recommended treatment?

A) Isolated Heart Transplant

B) Combined Heart/Liver Transplant

C) Stem Cell Transplant

D) Supportive Care

Management

▪ Supportive treatment

▪ Liver transplant halts progression of neuropathy, but can accelerate amyloid

cardiomyopathy

▪ Drugs that stabilize TTR protein - under investigation

▪ Genetic testing of family members and early intervention

▪ Our patient was referred for palliative care as he was not a candidate for

transplant due to advanced disease with cardiac involvement

Questions??