This document discusses the case of a 76-year-old man presenting with heart failure symptoms and recurrent cough syncope. Testing revealed cardiac amyloidosis due to a TTR gene mutation. For patients with TTR amyloidosis, treatment options include organ transplantation, TTR stabilizers in clinical trials, or enrollment in hospice. Given his age and comorbidities, the man's options included a left ventricular assist device, extended criteria transplant, or a clinical trial for TTR amyloidosis treatment. He was ultimately listed and transplanted within a month, and has since recovered well.

1. The Complex Patient:
VAD, Transplant, Exchange or Hospice?
Joseph G. Rogers, MD
Professor of Medicine
Division of Cardiology
Duke University
American College of Cardiology Annual Scientific Sessions
March 14, 2015
San Diego, CA
Disclosures: None
Lee Goldberg, MD
Professor of Medicine
Division of Cardiology
University of Pennsylvania

2. History of Present Illness
76 y/o man presents to ED for evaluation of recurrent cough syncope
• Multiple episodes over previous several months
• Several months of progressive heart failure symptoms
• Orthopnea/PND
• Abdominal distention
• PMH
• LV dysfunction
• Prostate Cancer: Radical Prostatectomy 1998
• HTN
• Gout
• CKD Stage 3: Cr 1.8, GFR 45
• Paroxysmal atrial fibrillation
• LE neuropathy attributed to prior back surgery

3. Meds/Exam
• Carvedilol 3.125 mg bid, allopurinol 200 mg daily, temisartan 80 mg
daily, gabapentin 600 mg at bedtime, warfarin, atorvastatin 10 mg
qHS, furosemide 40 mg daily
• No tobacco, social ETOH, retired executive, widower in relationship
• Fx: CAD, RAD, alzheimer’s
• Afeb-84-131/94
– WD/WN, NAD. Appeared younger than stated age
– Clear lungs
– Irregular rhythm, no murmur or gallop, JVP 4 cm above clavicle at 450
– Bilateral LE edema

4. Laboratory Evaluation
• Na=136, K=3.8, BUN/Cr= 38/1.8.
• INR=2.9, Hct=42%
• CK=339 with MB=10. Troponin T=0.10
• NT-proBNP=7031
• TSH=3.7
• UA: no proteinuria
• Blood type: AB

5. ECG

6. Echo

7. Cardiac Catheterization (after diuresis)
• Normal coronary arteries
• Hemodynamics
– RA=5, PA=35/13, PCWP=14
– CI=1.7
– SVO2=55%

8. Cardiac Biopsy
• Negative SPEP/UPEP
• Negative bone marrow
• No gene analysis performed

9. Cardiac Amyloid
• Three types
– AL – associated with plasma cell dyscrasia (multiple myeloma)
– TTR – mutant transthyretin protein – Familial
• Multiple mutations leading to variable phenotypes
• Val122Ile is associated with predominantly cardiac involvement – 3
to 4% of African Americans
– TTR – wildtype – Senile amyloid – usually cardiac only

10. Genetics Determine Phenotype
Heart Fail Rev (2015) 20:163–178

11. Clinical Syndrome
• Heart failure with preserved ejection fraction
• Heart failure with decreased ejection fraction
– Intolerance to vasodilators
– Intolerance to beta blockers
• Arrhythmias
• Peripheral neuropathy
• Orthostatic hypotension
• AL amyloid can impact many organs
• TTR depending on genotype can impact kidney and other
tissues

12. Prognosis
• Onset of advanced heart failure symptoms
– 6 month survival in AL amyloid
– 43 months in wild-type TTR
– 24 months in familial TTR
• AL amyloid
– Chemotherapy to suppress light chains can lead to some
regression
• TTR amyloid
– No therapy to slow disease
• Drugs now in clinical trial

13. Prognosis
Heart Fail Rev (2015) 20:163–178

14. Treatment
• AL Amyloid
– Treat the underlying plasma cell dyscrasia
– Heart transplant +/- stem cell transplant
• TTR
– Organ transplantation - heart/liver for familial
– Transthyretin stabilizers (diflunisal, tafamidis, AG-1)
– TTR silencers (ALNATTR02, ISIS-TTR(Rx))
– Degraders of amyloid fibrils (doxycycline/TUDCA)

15. Treatment Targets - TTR
Heart Fail Rev (2015) 20:163–178

16. Hospital Course
• Develops more NSVT
• Develops worsening dyspnea, hypotension and renal insufficiency
despite volume
• Started on dopamine

17. Discussion Points
• Should this man be enrolled in a clinical trial for the treatment of
TTR amyloid?
• Should this man be enrolled in hospice?
• Should he receive a DT LVAD?
• Should he receive an extended criteria transplant?
– Age
– Amyloid
– Renal insufficiency

20. Case Conclusion
• Transplanted < 1 month after listing
• Hospital course
– Extubated day of transplant
– To floor POD 1
– Discharged from hospital POD 5
• 2 readmissions
– 24 hours for hydration
– Laminectomy
• Just celebrated 3 year anniversary
– Rows daily
– Cr 1.8
– Normal coronary arteries