Amyloid Heart Disease: Diagnosis & Treatment - Amyloid Heart... · Amyloid Heart Disease: Diagnosis...
Transcript of Amyloid Heart Disease: Diagnosis & Treatment - Amyloid Heart... · Amyloid Heart Disease: Diagnosis...
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Amyloid Heart Disease:Diagnosis & Treatment
Sitaramesh Emani, MDAdvanced Heart Failure &
Cardiac Transplant
Relevant Disclosures
• St. Jude Medical (Thoratec)‒ Consultant‒ Grant Funding
• Gilead‒ Grand Funding
• Boston Scientific‒ Advisory Board
• CareDx‒ Advisory Board
• I will discuss investigational agents
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Amyloid Review
• Defined by the deposition of abnormal fibrils‒ Misfolding of proteins
causing insolubility• Abnormal β-sheet cross
formation
‒ Abnormality a common final finding – various underlying causes
‒ Deposition into organ tissue leads to dysfunction
• Pathognomonic feature is apple green birefringence on Congo Red staining
3Wechalekar AD, et al., Lancet 2016;387:2641-54
Amyloid Review
• Light-chain amyloid (AL)‒ Related to plasma cell dyscrasias (MGUS, myeloma)
• Hereditary amyloid‒ Often liver based
• Transthyretin‒ Familial ATTR or wild-type ATTR
• Reactive amyloid (AA or SAA)‒ Secondary to chronic inflammatory conditions
• Senile amyloidosis (SSA)
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Amyloid Review
• Many organs can be affected
• Cardiac involvement associated with increased morbidity and mortality
• High prevalence of cardiac involvement, especially with certain types‒ AL‒ ATTRwt
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Clinical Findings
• Can affect many/multiple organs
• Cardiac involvement most associated with M&M
• Non-cardiac involvement‒ Kidneys‒ Neuropathy‒ GI system
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Clinical Cardiac Findings
• Development of restrictive cardiomyopathy
• Right-heart failure symptoms
• Low cardiac output
• Hypotension
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When to suspect amyloid
• “Classic Findings”‒ Macroglossia‒ Periorbital purpura‒ Low-voltage EKG‒ Speckled pattern on echocardiogram‒ Unanticipated/unexpected LV thickening
• In presence of other problems‒ Renal disease (especially proteinuria)‒ Hematologic disease (MGUS, myeloma)‒ Unexplained neuropathy with heart failure symptoms
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Role of Cardiac Imaging
• Echo findings:‒ LV thickening‒ Increased echogenicity of myocardium (“sparkling”)‒ Preserved EF‒ Pericardial effusion‒ Diastolic abnormalities/restrictive pattern
• Findings not specific to amyloid
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Cardiac MRI
• Key component of evaluation
• Major feature: diffuse, sub-endocardial LGE
• 4 chamber thickening
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Biopsies
• “Tissue is the issue”
• Pathological specimen needed to evaluate subtype‒ Mass spectroscopy
• Any potentially involved organ is fair game‒ Fat pad – poor negative predictive value but easy to
get‒ Rectal biopsy‒ Endomyocardial biopsy
• Biopsies are not 100% sensitive
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Treatment of Cardiac Amyloid
• Standard GDMT ‒ No/poor evidence to support use‒ Difficult to tolerate for most (hypotension)
• Supportive/symptomatic therapies‒ Diuretics (sometimes need combination therapy)‒ But also pre-load dependent
• Device Therapy‒ Increased risk of SCD/ventricular arrhythmias‒ However, primary prevention ICD survival benefit unclear‒ Bradycardia risk with evidence of conduction disease
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Stanford Protocol for ICD
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Varr BC, et al., Heart Rhythm 2014;11:158-162
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Treatment of Amyloid
• Current strategies‒ RNA inhibitors‒ Fibril formation stabilizers & inhibitors‒ Immunotherapeutic targeting of fibrils
• Therapy in conjunction with hematology
• Dependent on type of amyloid
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Therapies for Amyloid
• AL type‒ Chemotherapy aimed at plasma cells‒ Doxycycline – reduces light chain fibril formation
• ATTR‒ Liver transplant if discovered early‒ Combined heart-liver if a candidate
• Unfortunately, disease often discovered late in process‒ Diflunisal (NSAID) – binds and stabilizes fibrils‒ Tafamidis – protein stabilizer (in clinical trials)‒ RNA inhibitors – reduce production (in early trials)
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References
Beal EW, Mumtaz K, Hayes D, Jr., Whitson BA, Black SM. Combined heart-liver transplantation: Indications, outcomes and current experience. Transplantation reviews 2016.
Chakraborty R, Muchtar E, Gertz MA. Newer Therapies for Amyloid Cardiomyopathy. Curr Heart Fail Rep 2016.
Fontana M, Martinez-Naharro A, Hawkins PN. Staging Cardiac Amyloidosis With CMR: Understanding the Different Phenotypes. JACC Cardiovasc Imaging 2016.
Gertz MA, Benson MD, Dyck PJ, et al. Diagnosis, Prognosis, and Therapy of TransthyretinAmyloidosis. J Am Coll Cardiol 2015;66:2451-66.
Judge DP, Lee YZ, Sharma K. Untangling Wild-Type Transthyretin Amyloidosis. J Am Coll Cardiol2016;68:1021-3.
Narotsky DL, Castano A, Weinsaft JW, Bokhari S, Maurer MS. Wild-Type Transthyretin Cardiac Amyloidosis: Novel Insights From Advanced Imaging. Can J Cardiol 2016;32:1166 e1- e10.
Selvanayagam JB, Hawkins PN, Paul B, Myerson SG, Neubauer S. Evaluation and management of the cardiac amyloidosis. J Am Coll Cardiol 2007;50:2101-10.
Varr BC, Zarafshar S, Coakley T, et al. Implantable cardioverter-defibrillator placement in patients with cardiac amyloidosis. Heart Rhythm 2014;11:158-62.
Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet 2016;387:2641-54.
Zhao L, Fang Q. Recent advances in the noninvasive strategies of cardiac amyloidosis. Heart Fail Rev 2016.
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Thank [email protected]
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