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

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

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

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

ECG

Echo

Cardiac Catheterization (after diuresis)

• Normal coronary arteries

• Hemodynamics – RA=5, PA=35/13, PCWP=14

– CI=1.7

– SVO2=55%

Cardiac Biopsy

• Negative SPEP/UPEP

• Negative bone marrow

• No gene analysis performed

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

Genetics Determine Phenotype

Heart Fail Rev (2015) 20:163–178

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

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

Prognosis

Heart Fail Rev (2015) 20:163–178

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)

Treatment Targets - TTR

Heart Fail Rev (2015) 20:163–178

Hospital Course

• Develops more NSVT

• Develops worsening dyspnea, hypotension and renal insufficiency

despite volume

• Started on dopamine

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

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