When to Rule Out Transthyretin Cardiac Amyloidosis**Also known as transthyretin amyloid cardiomyopathy (ATTR-CM).Learn how to screen your patients and when diagnostic testing is warrantedPatients meeting the below criteria warrant diagnostic testingHFpEF1Echocardiography2-5- LV wall thickness ≥12 mm on an echocardiogram2-5†‡
Additional echocardiogram images- Reduction in longitudinal strain with apical sparing4-6§
- Apical sparing on a bullseye strain map—the lack of amyloid deposition in the apex may result in a “cherry on top” pattern, in which a red circle at the apex (preserved strain) is surrounded by lighter shades of red or blue (reduced strain)
- Changes to the interatrial septum and valves4,6§
- Thickening of interatrial septum (yellow arrow) and valves (white arrow) >0.5 cm4,6
Additional cardiac features to consider are4:- Increased echogenicity of the myocardium (sparkling, hyper-refractile “texture” of the myocardium)
- Atrial enlargement and dysfunction
- Grade 2 or worse diastolic dysfunction with high E/A ratio (>1.5) and reduced E deceleration time (<150 ms)
- Increased pressures (>35 mmHg for PA, ≥10 mmHg for RA)
Reproduced with permission from ASNC. 2021 American Society of Nuclear Cardiology.PA=pulmonary artery; RA=right atrium.Electrocardiography4- Discordance between LV wall thickness and QRS voltage on ECG4,5,7‡
- Low QRS voltage not present in all cases
- Prevalence varies between ATTR cardiac amyloidosis (20%) and AL amyloidosis (60%)
While these patient characteristics may be suggestive of ATTR cardiac amyloidosis, they are not exhaustive.4,8 ATTR cardiac amyloidosis is also prevalent in patients with severe aortic stenosis, carpal tunnel syndrome, lumbar spinal stenosis, and autonomic or sensory polyneuropathy9
While these patient characteristics may be suggestive of ATTR cardiac amyloidosis, they are not exhaustive.4,8 ATTR cardiac amyloidosis is also prevalent in patients with severe aortic stenosis, carpal tunnel syndrome, lumbar spinal stenosis, and autonomic or sensory polyneuropathy9
Additional cardiac symptoms- Refractory to standard HF therapies (eg, ACEi, ARB, and BB)9
- Cardiac arrythmias (eg, atrial fibrillation)10
- Aortic stenosis11
- Atrioventricular block, in the presence of increased wall thickness6
- Mild increase in troponin levels on repeated occasions1
Cardiac magnetic resonance imaging5,12Certain cardiac magnetic resonance imaging features are suggestive of ATTR cardiac amyloidosis. The presence of at least 1 of these features warrants further evaluation:
- Increased LV wall thickness or mass
- Biatrial enlargement
- Small pericardial and/or pleural effusions
- Abnormal LGE patterns (diffuse, subendocardial, patchy)
- Difficulty in achieving myocardial nulling
- Significantly increased ECV (>0.40) on T1 map
Reproduced from Oerlemans MIFJ, Rutten KHG, Minnema MC, Raymakers RAP, Asselbergs FW, de Jonge N. Cardiac amyloidosis: the need for early diagnosis. Neth Heart J. 2019;27(11):525-536. doi:10.1007/s12471-019-1299-1, under Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; BB=beta blocker; ECV=extracellular volume; LGE=late gadolinium enhancement; LV=left ventricular.Additional noncardiac symptomsCertain noncardiac symptoms should also raise suspicion of ATTR cardiac amyloidosis
Musculoskeletal/Orthopedic- Carpal tunnel syndrome14,15
- In 2 studies of patients with wtATTR cardiac amyloidosis, ~50% had carpal tunnel syndrome
- Lumbar spinal stenosis16
- One study of 47 patients identified the presence of TTR amyloid on surgical spine specimens in 21% of patients (n=10/47) undergoing LSS surgery17
- Biceps tendon rupture1,14,18
- Hip/knee arthroplasty15
Nervous system
Autonomic
- GI complaints19
- In an observational registry, 63% of patients with hATTR-CM reported experiencing gastrointestinal symptoms
- Autonomic neuropathy18
- Unexplained weight loss20
- Orthostatic hypotension18
- Sexual impotence18
Peripheral - Peripheral sensory motor dysfunction18
- Peripheral neuropathy18
Renal8,21
- Renal impairment
- Cardiorenal syndrome
Ocular18
GI=gastrointestinal; LSS=lumbar spinal stenosis; TTR=transthyretin.Next: Suspect ATTR cardiac amyloidosis? See how diagnosis is confirmed Continue LoadingACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; BB=beta blocker; CMR=cardiac magnetic resonance; ECV=extracellular volume.Per the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure, a left ventricular wall thickness of ≥14 mm, along with other clinical parameters, should heighten suspicion of ATTR cardiac amyloidosis.9Illustrative representation.ACC=American College of Cardiology; AHA=American Heart Association; AL=amyloid light-chain; ATTR=transthyretin amyloidosis; ECG=electrocardiogram; HFpEF=heart failure with preserved ejection fraction; HFSA=Heart Failure Society of America; LV=left ventricular.
References:Witteles RM, Bokhari S, Damy T, et al. Screening for transthyretin amyloid cardiomyopathy in everyday practice. JACC Heart Fail. 2019;7(8):709-716. Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568. Kittleson MM, Ruberg FL, Ambardekar AV, et al. 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023;81(11):1076-1126. Cuddy SAM, Chetrit M, Jankowski M, et al. Practical points for echocardiography in cardiac amyloidosis. J Am Soc Echocardiogr. 2022;35(9):A31-A40.Data on file. Pfizer Inc., New York, NY. Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 1 of 2—evidence base and standardized methods of imaging. Circ Cardiovasc Imaging. 2021;14(7):e000029. Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135(14):1357-1377. Maurer MS, et al; THAOS Investigators. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032.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(9):1166.e1-1166.e10. Donnellan E, Wazni OM, Hanna M, et al. Atrial fibrillation in transthyretin cardiac amyloidosis: predictors, prevalence, and efficacy of rhythm control strategies. JACC Clin Electrophysiol. 2020;6(9):1118-1127. Sueyoshi T, Ueda M, Jono H, et al. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011;42(9):1259-1264. Oerlemans MIFJ, Rutten KHG, Minnema MC, Raymakers RAP, Asselbergs FW, de Jonge N. Cardiac amyloidosis: the need for early diagnosis. Neth Heart J. 2019;27(11):525-536. González-López E, López-Sainz Á, Garcia-Pavia P. Diagnosis and treatment of transthyretin cardiac amyloidosis. Progress and hope. Rev Esp Cardiol (Engl Ed). 2017;70(11):991-1004. Rubin J, Alvarez J, Teruya S, et al. Hip and knee arthroplasty are common among patients with transthyretin cardiac amyloidosis, occurring years before cardiac amyloidosis: can we identify affected patients earlier? Amyloid. 2017;24(4):226-230. Yanagisawa A, Ueda M, Sueyoshi T, et al. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol. 2015;28(2):201-207. Maurer MS, Smiley D, Simsolo E, et al. Analysis of lumbar spine stenosis specimens for identification of amyloid. J Am Geriatr Soc. 2022;70(12):3538-3548. Nativi-Nicolau J, Maurer MS. Amyloidosis cardiomyopathy: update in the diagnosis and treatment of the most common types. Curr Opin Cardiol. 2018;33(5):571-579. Wixner J, Mundayat R, Karayal ON, et al. THAOS: gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease. Orphanet J Rare Dis. 2014;9:61. Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22(2):123-131. Dang J, Abulizi M, Moktefi A, et al. Renal infarction and its consequences for renal function in patients with cardiac amyloidosis. Mayo Clin Proc. 2019;94(6):961-975.