36 th Annual Advances in Heart Disease Transthyretin Amyloid - PDF document

12/7/19 36 th Annual Advances in Heart Disease Transthyretin Amyloid Cardiomyopathy: Screening and Management Strategies Mary O. Gray, M.D. Medical Director, Cardiology Clinical Services Zuckerberg San Francisco General 1 Disclosures No Financial Relationship With Any Commercial Interest 2 1

12/7/19 Objectives > Recognize clinical manifestations and natural history of cardiac transthyretin amyloidosis, a disabling and life-threatening disease. > Develop more effective screening and diagnostic strategies for transthyretin amyloid cardiomyopathy within everyday practice. > Implement standard therapy for heart failure with preserved EF and consider new treatments for this protein misfolding disorder. 3 Heart Failure with Preserved LVEF: Evidence-Based Diagnosis Circulation 2018;138:861-870 4 2

12/7/19 Transthyretin: TTR TTR wild-type or mutant: TTRwt or TTRm Transthyretin Amyloidosis: ATTRwt or ATTRm Transthyretin Amyloid Cardiomyopathy: ATTR-CM 5 Genotype & Phenotype: Mutant Transthyretin Amyloidosis Akcea Therapeutics 6 3

12/7/19 Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice J Am Coll Cardiol HF 2019;7(8):709-716 7 Screening for Transthyretin Amyloid Cardiomyopathy J Am Coll Cardiol HF 2019;7(8):709-716 8 4

12/7/19 Screening for Transthyretin Amyloid Cardiomyopathy J Am Coll Cardiol HF 2019;7(8):709-716 9 10 5

12/7/19 Screening for Transthyretin Amyloid Cardiomyopathy J Am Coll Cardiol HF 2019;7(8):709-716 11 Transthyretin Cardiac Amyloidosis: AR Consortium Circ Heart Fail 2019;12:e006075 12 6

12/7/19 Transthyretin Cardiac Amyloidosis: AR Consortium Circ Heart Fail 2019;12:e006075 13 Transthyretin Cardiac Amyloidosis: AR Consortium Circ Heart Fail 2019;12:e006075 14 7

12/7/19 15 Circ Heart Fail 2019;12:e006075 16 8

12/7/19 Case Presentation Ø 89 yo man with HTN. Referred due to shortness of breath. Ø Atrial fibrillation. Ventricular pacemaker implanted in 2005. Ø NM pharmacologic stress: No infarction. No inducible ischemia. Ø Apixaban 5, benazepril 20, furosemide 40, metoprolol 50. 17 Case Presentation Ø Chronic heart failure with preserved LV ejection fraction Ø ACC/AHA Stage C. NYHA Class III. Musculoskeletal conditions. Ø Normal volume status on loop diuretic and sodium restriction. Ø BP and HR management with medications and pacemaker. 18 9

12/7/19 Case Presentation Echocardiogram Normal LV cavity Mild concentric LVH LVEF 50 to 55% Dilated IVC collapses Severe tricuspid regurgitation. RA enlargement. Normal PA pressure. 19 Case Presentation 20 10

12/7/19 Case Presentation 21 Case Presentation 22 11

12/7/19 Case Presentation Ø IV administration of 13.9 mCi Tc-99m Pyrophosphate (PYP). Ø Planar imaging & SPECT-CT at 1-hour and 3-hour time points. Ø Semi-quantitative and quantitative analysis per ASNC 2016. 23 Case: Cardiac Sodium Pyrophosphate Scan Anterior Chest 1 Hour Anterior Chest 3 Hours Visual Score 3 24 12

12/7/19 Case: Cardiac Sodium Pyrophosphate Scan Region of Interest @ 1 Hour Region of Interest @ 3 Hours H/CL ratio 1.5 25 Cardiac Sodium Pyrophosphate Scan Fusion Coronal SPECT-CT Image 26 13

12/7/19 Circ Heart Fail 2019;12:e006075 27 ATTR-CM: Considerations for Heart Failure Therapy > Loop diuretics are the mainstay of heart failure management. > Individuals may not tolerate beta blockers and ACE inhibitors. > Calcium channel blockers and digoxin are contraindicated. > Atrial fibrillation: Rate control, anticoagulation, rhythm control. Ventricular Assist Device, Liver Transplant, Heart Transplant 28 14

12/7/19 29 Transthyretin: TTR TTR wild-type or mutant: TTRwt or TTRm Transthyretin Amyloidosis: ATTRwt or ATTRm Transthyretin Amyloid Cardiomyopathy: ATTR-CM 30 15

12/7/19 Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) N Engl J Med 2018;379:1007-1016 31 Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) N Engl J Med 2018;379:1007-1016 32 16

12/7/19 Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) N Engl J Med 2018;379:1007-1016 33 Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) N Engl J Med 2018;379:1007-1016 34 17

12/7/19 Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) N Engl J Med 2018;379:1007-1016 35 Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) N Engl J Med 2018;379:1007-1016 36 18

12/7/19 Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) N Engl J Med 2018;379:1007-1016 37 Objectives > Recognize clinical manifestations and natural history of cardiac transthyretin amyloidosis, a disabling and life-threatening disease. > Develop more effective screening and diagnostic strategies for transthyretin amyloid cardiomyopathy within everyday practice. > Implement standard therapy for heart failure with preserved EF and consider new treatments for this protein misfolding disorder. 38 19