sanjiv j. shah, md, fase · amyloidosis. february 14, 2016. sanjiv j. shah, md, fase. associate...
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A M E R I C A N S O C I E T Y O F E C H O C A R D I O G R A P H Y
AmyloidosisF E B R U A R Y 1 4 , 2 0 1 6
Sanjiv J. Shah, MD, FASEAssociate Professor of Medicine
Division of Cardiology, Department of MedicineNorthwestern University
Feinberg School of Medicine
S T A T E - O F - T H E - A R T 2 0 1 6
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A M E R I C A N S O C I E T Y O F E C H O C A R D I O G R A P H Y
Love-Making Reveals a Broken Heart:
A 46-Year-Old Man with Recurrent Hemoptysis
During Sexual IntercourseF E B R U A R Y 1 4 , 2 0 1 6
Sanjiv J. Shah, MD, FASEAssociate Professor of Medicine
Division of Cardiology, Department of MedicineNorthwestern University
Feinberg School of Medicine
S T A T E - O F - T H E - A R T 2 0 1 6
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Case presentation
• 46-year-old man w/history of type 2 diabetes• Chief complaint:
» Recurrent hemoptysis during sexual intercourse» Chest pain» Shortness of breath
• Physical exam: normal• ECG in office:
» Normal sinus rhythm, normal voltage» Left anterior fascicular block
• CXR: normal
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Pulmonary work-up: negative
• Pulmonary function testing• Chest CT• Bronchoscopy with BAL• Transbronchial biopsy
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Stress echocardiography
• Findings at rest:» Normal LV size» Normal LVEF and wall motion» Moderate concentric LVH» No significant valvular disease» Grade 3 diastolic dysfunction
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Stress echocardiography
• Stress test:» Bruce protocol» Chest pain at 6 minutes» Total exercise time = 8 minutes (9.4 METs)
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Stress echocardiography
REST STRESS
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Cardiac catheterization
• Angiographically normal coronary arteries
• Normal hemodynamics
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Adenosine Perfusion
Stress
Rest
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Adenosine Perfusion
Stress
Rest
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Summary of MRI findings
• Normal LV size and systolic function• Moderate concentric LVH• No focal hyper-enhancement• Mild mitral regurgitation• Diffuse reversible subendocardial
hypoperfusion with adenosine (in the absence of significant CAD microvascular dysfunction)
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Unifying diagnosis?
• Microvascular ischemia:» Cardiac syndrome X? » May explain exertional dyspnea, chest pain
• What about exertional hemoptysis?• Is this Hickam’s Dictum or can we
push forward and satisfy Occam’s Razor?
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Unifying diagnosis?
• Occam’s Razor:» “pluritas non est ponenda sine necessitas”» “plurality should not be posited without
necessity”
• Hickam’s Dictum:» “Patients can have as many diseases as
they damn well please”
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DDx of hemoptysis during intercourse
• Cardiogenic» Heart failure» Mitral stenosis» Coronary artery disease» Systemic hypertension
• Vascular» Pulmonary vascular problem
—Pulmonary embolism—Vasculitis
Fuks L, et al. Respir Med 2009
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Another look at the echo…
Apical 4-chamber view Tissue Doppler
s’=5 cm/s
e’=4 cm/s
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Global longitudinal strain (GLS)
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Global longitudinal strain (GLS)
“Cherry on top”
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Another look at the cardiac MRI
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Mechanisms of contrast enhancement in myocardial infarction.
Adapted from: Mahrholdt H et al. Eur Heart J 2005;26:1461-1474
© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: [email protected]
Normal Myocardium Acute Infarction Chronic Scar
Intact Cell Membrane Ruptured Cell Membrane Collagen matrix
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20
Extracellular Volume Fraction (Ve) in our patient on CMR T1 mapping:
20
Ve% of Whole Myo
4CH 43.8%
SA Base 40.4%
SA Mid 37.8%
Normal < 25%
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Repeat right heart cath w/exercise
REST 1-MIN. OF EXERCISE
100
50
0
PA 38/15 (24) PA 78/40 (54)
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Repeat right heart cath w/exercise
REST 1-MIN. OF EXERCISE
100
50
0
PCWP 15 PCWP 37
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Case summary• 46-year-old diabetic man with hemoptysis during
intercourse, angina, dyspnea• Pulmonary work-up negative• Normal LVEF but severely reduced longitudinal
systolic and diastolic function• Increased, diffuse protein infiltration in the
myocardium + subendocardial ischemia• Marked exercise-induced pulmonary venous
hypertension due to severe diastolic dysfunction
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What’s the diagnosis?
AMYLOID PROTEIN
APPLE-GREEN BIREFRINGENCE
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Case summary• Patient treated with:
» Bortezomib (Velcade)» Warfarin» Spironolactone » Bumetanide (low dose)
• Marked improvement in functional status• Underwent autologous stem cell transplantation
with uneventful course• No sign of recurrence of amyloid
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Systemic amyloidoses
• Group of disorders characterized by extra-cellular deposition of fibrillar protein
• Deposits composed of amyloid fibrils progressive end-organ dysfunction
• > 20 proteins form amyloid fibrils in vivo• 2 predominant types involve the heart:
» AL: typically assoc. w/plasma cell dyscrasia» Transthyretin (TTR)-associated:
—Hereditary (mutation) and senile (wild-type)
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Cardiac amyloid: rare disease?
• Annual incidence of systemic amyloid:» 6-10 cases per million in United States
• But…» Amyloidosis likely under-recognized» Transthyretin (TTR) amyloid may be common
—3-4% of African Americans carry V122I mutation in TTR gene
—Wild-type (senile) TTR amyloidosis increasing in prevalence
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Cardiac amyloid: rare disease?
Amyloid
Noamyloid
Amyloid
NoAmyloid
92%
32%
68%
8%
Age > 75 years Age < 75 years
Circulation. 2010; 122: A17926
In older patients with HF an preserved EF, amyloid deposition is common
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Cardiac amyloidosis
• Primary (AL) amyloid (light chains)» Order serum immunofixation, not SPEP
• Familial (TTR) amyloid» Due to TTR gene mutation (3-4% of AAs have
V122I)» Neuropathy, cardiomyopathy
• Secondary (AA) amyloid» Cardiac involvement is rare
• Senile cardiac amyloid» Due to wild-type TTR accumulation
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Clinical clues for the diagnosis
• Bilateral carpal tunnel syndrome• Macroglossia• Easy bruising, decreased Factor X levels• Heart failure with…
» Kussmaul’s sign» Peripheral neuropathy» Autonomic dysfunction / orthostatic hypotension» Continuous low-level troponin release
• Low BP, low volts, and thick heart
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Typical echo findings
Loss of longitudinal cardiac function
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Typical echo findings
Severely reduced longitudinal tissue velocities “5-5-5 sign”
e’ a’
s’
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Typical cardiac MRI findings
Diffuse subendocardial delayed enhancement
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Typical cardiac MRI findings
Diffuse subendocardial delayed enhancement
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Speckle-tracking: “cherry on the top”
“Cherry on top”
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Speckle-tracking: “cherry on the top”
Phelan D, et al. Heart 2012
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Speckle-tracking: “cherry on the top”
CARDIAC AMYLOID
HYPERTROPHIC CM AORTIC STENOSIS
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Cardiac amyloidosis: key echo findings
• Severely reduced longitudinal function» TDI e’, a’, and s’
typically < 5 cm/s» Absolute global
longitudinal strain < 15% (often < 10%)
• Preserved radial and apical function
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Cardiac amyloid: echo pearls
• “Sparkling texture” on echo:» Still helpful in era of harmonic imaging» Look at renal function: if no severe CKD or ESRD,
sparkling appearance (especially with severely decreased longitudinal function), think infiltrative (most commonly amyloid)
• Remember to look at tissue Doppler s’, e’, and a’ velocities: » They will be severely reduced (< 5 cm/s) in
most cases of cardiac amyloid
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Cardiac amyloid can be treated!
• Cardiac amyloid: not a death sentence» Primary (AL) amyloidosis:
—Stem cell transplantation or—Cardiac transplant followed by stem cell tx
» Familial or wild-type TTR amyloidosis: —Several novel drugs in pipeline (TTR stabilizers,
RNA interference, RNA anti-sense molecules)—Phase 3 clinical trials in TTR cardiac amyloid:
ATTR-ACT and ENDEAVOUR—Heart-liver transplant
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Primary (AL) cardiac amyloid: improved survival with stem-cell tx
Historical controls (N=24)Dubrey et al. Heart 1997
Northwestern all patients (N=26)Chemo only (N=7)Chemo + stem cell tx (N=19)
Friedman J….Shah SJ. ACC 2014
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Take home points
• Amyloidosis is not 1 disease• Prognosis of amyloidosis varies by organ
involvement and type of amyloid• Echo clues:
» Sparkling, granular texture of myocardium» Thick LV out of proportion to ECG voltage» Severely reduced longitudinal
systolic/diastolic function» “Cherry on the top” on speckle-tracking
• Cardiac amyloid: not a death sentence
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N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
thank you!