Cardiac Amyloidosis

Initiate evaluation in patients with heart failure and otherwise unexplained increased LV wall thickness, especially when echocardiography shows a restrictive filling pattern, biatrial enlargement, and symmetric LV thickening. A mean LV wall thickness greater than 12 mm without hypertension or another adequate cause of hypertrophy is a recognized trigger for amyloid cardiomyopathy assessment; LV thickness of at least 15 mm with restrictive Doppler findings is particularly suggestive. jacc+1jaccEarly Identification of Transthyretin-Related Hereditary Cardiac Amyloidosis∗Wolters KluwerThe role of echocardiography and 99mTc-HDP scintigraphy in... : Medicine

Prioritize amyloid testing when increased wall thickness coexists with peripheral or autonomic neuropathy, renal dysfunction or proteinuria, gastrointestinal involvement, carpal-tunnel-spectrum symptoms, unexplained atrial arrhythmia, or a family history compatible with dominantly inherited ATTR. Hereditary ATTR is late-onset and may involve peripheral and autonomic nerves as well as myocardium; wild-type ATTR predominantly affects men older than 60 years and is principally cardiac. Nature+1NatureAmyloidosis Diagnosis and Treatment Strategies | Pathology | Clinical Sciences | Health sciences | Topics | Nature IndexjaccEarly Identification of Transthyretin-Related Hereditary Cardiac Amyloidosis∗

Do not wait for reduced ejection fraction. Cardiac ATTR disease commonly presents with heart failure despite preserved EF, and cardiac involvement is a dominant determinant of morbidity and mortality in AL, wild-type ATTR, and hereditary ATTR amyloidosis. AHA Journals+1AHA JournalsUpdates in Cardiac Amyloidosis: A ReviewWolters KluwerThe role of echocardiography and 99mTc-HDP scintigraphy in... : Medicine

At first suspicion, order all three monoclonal-protein studies together: serum free-light-chain assay, serum immunofixation electrophoresis, and urine immunofixation electrophoresis. This panel is required before a noninvasive ATTR diagnosis because scintigraphy identifies myocardial tracer uptake but does not independently exclude AL amyloid. jaccjaccCardiac Scintigraphy With Technetium-99m-Labeled Bone-Seeking Tracers for Suspected Amyloidosis: JACC Review Topic of the Week

If all monoclonal-protein studies are negative and echocardiography and/or CMR supports amyloid cardiomyopathy, obtain 99mTc-PYP scintigraphy in U.S. practice; DPD or HMDP are equivalent bone-avid tracers in other settings. Diagnose ATTR cardiac amyloidosis noninvasively only when myocardial uptake is grade 2 or 3 and SPECT confirms myocardial rather than blood-pool activity. jaccjaccCardiac Scintigraphy With Technetium-99m-Labeled Bone-Seeking Tracers for Suspected Amyloidosis: JACC Review Topic of the Week

If serum or urine immunofixation identifies a monoclonal protein, or if free-light-chain testing is abnormal, do not use a positive PYP scan to assign ATTR. Bone scintigraphy alone is insufficient in suspected AL disease, and biopsy is required for amyloid typing. In one reported diagnostic error, grade 3 PYP uptake occurred with AL cardiomyopathy confirmed by endomyocardial biopsy and mass spectrometry; the false ATTR attribution delayed needed plasma-cell treatment. AHA Journals+1AHA JournalsASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 2 of 2—Diagnostic Criteria and Appropriate UtilizationjaccCardiac Scintigraphy With Technetium-99m-Labeled Bone-Seeking Tracers for Suspected Amyloidosis: JACC Review Topic of the Week

Use biopsy when monoclonal protein is present, scintigraphy is not diagnostic, imaging and laboratory data conflict, or another amyloid type is plausible. Confirm tissue amyloid with Congo red staining and determine fibril type; mass spectrometry was used to establish AL type in the PYP-positive AL case. Nature+1NatureAmyloidosis Diagnosis and Treatment Strategies | Pathology | Clinical Sciences | Health sciences | Topics | Nature IndexjaccCardiac Scintigraphy With Technetium-99m-Labeled Bone-Seeking Tracers for Suspected Amyloidosis: JACC Review Topic of the Week

Use diuretics and sodium restriction to control peripheral edema, ascites, and congestion, while reassessing blood pressure, renal function, and orthostatic symptoms with each titration. Amyloid cardiomyopathy often has restrictive physiology, and peripheral edema or ascites may be amplified by hypoalbuminemia in systemic disease. ACCACC[PDF] Apparent Natural History of Cardiac Amyloidosis - ACC.org

Avoid automatically applying conventional neurohormonal heart-failure regimens. Beta-blockers, nondihydropyridine calcium-channel blockers, vasodilators including ACE inhibitors or ARBs, and digoxin are identified as agents often to avoid in cardiac amyloidosis because hemodynamic intolerance and restrictive physiology may limit use; individualize decisions when another compelling indication exists. ACCACC[PDF] Apparent Natural History of Cardiac Amyloidosis - ACC.org

For neurogenic orthostatic hypotension or autonomic dysfunction, midodrine or droxidopa may be useful. This decision is most relevant in hereditary ATTR with autonomic involvement and in systemic amyloidosis with symptomatic hypotension that constrains diuresis or other cardiac management. jacc+1jaccEarly Identification of Transthyretin-Related Hereditary Cardiac Amyloidosis∗ACC[PDF] Apparent Natural History of Cardiac Amyloidosis - ACC.org

For confirmed wild-type or variant ATTR cardiac amyloidosis with NYHA class I-III heart-failure symptoms, prescribe tafamidis to reduce cardiovascular morbidity and mortality. The FDA-approved regimens are tafamidis 61 mg orally once daily or tafamidis meglumine 80 mg orally once daily; tafamidis stabilizes the TTR tetramer, slowing dissociation, fibril formation, and cardiac deposition. jacc+1jacc2023 ACC Expert Consensus Decision Pathway on ... - JACCjacc2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

Set expectations that tafamidis slows progression rather than reliably regressing established disease; initiate it early after ATTR confirmation rather than delaying until advanced functional decline. Economic burden is a meaningful treatment tradeoff: at 2020 list prices, the AHA/ACC/HFSA guideline classified tafamidis as low value at more than $180,000 per quality-adjusted life-year gained. jacc+1jacc2023 ACC Expert Consensus Decision Pathway on ... - JACCjacc2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

If AL cardiac amyloidosis is confirmed or remains plausible because monoclonal studies are abnormal, direct care urgently toward plasma-cell–targeted therapy rather than ATTR therapy alone. The ACC pathway depicts AL regimens built around cyclophosphamide, bortezomib, dexamethasone, and daratumumab, while contemporary review evidence describes daratumumab as an addition to standard therapy, particularly in relapsed or refractory AL disease. jacc+1jacc2023 ACC Expert Consensus Decision Pathway on ... - JACCOxford AcademicCardiac amyloidosis: Innovations in diagnosis and treatment

After ATTR is identified, distinguish hereditary from wild-type disease because hereditary ATTR is a dominantly inherited systemic disorder with frequent neurologic and autonomic involvement, whereas wild-type disease is primarily cardiac. This distinction changes family implications and the scope of neurologic and systemic assessment. Nature+1NatureAmyloidosis Diagnosis and Treatment Strategies | Pathology | Clinical Sciences | Health sciences | Topics | Nature IndexjaccEarly Identification of Transthyretin-Related Hereditary Cardiac Amyloidosis∗

Cardiac ATTR amyloidosis carries substantial mortality, with reported median survival ranging from 2 to 6 years depending on disease stage at diagnosis. This supports early diagnostic action in patients with a compatible phenotype rather than serial observation of unexplained wall thickening or restrictive heart failure. NEJMNEJMPatisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis

For ATTR prognostic staging, NT-proBNP greater than 3,000 ng/L and estimated GFR below 45 mL/min/1.73 m² are proposed cutoffs: neither abnormality corresponds to stage I, whereas both correspond to stage III. Use these measures to communicate risk and to prioritize timely advanced-heart-failure and amyloidosis-center involvement. ACCACC[PDF] Apparent Natural History of Cardiac Amyloidosis - ACC.org

For AL staging, the cited framework assigns one point each for troponin T greater than 0.025, NT-proBNP greater than 1,800, and free light chain greater than 18 mg/dL. Biomarker elevation should increase urgency for comprehensive cardiac evaluation, but staging should not delay biopsy-based typing and hematology-directed treatment when a clonal process is suspected. ACCACC[PDF] Apparent Natural History of Cardiac Amyloidosis - ACC.org