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AboutAbout ATTR-CMUrgencySuspectDetectDiagnostic flowchartAbout ATTR-PNUrgencyAwarenessPartnershipStudy DesignStudy DesignAbout ATTR-PNUrgencyAwarenessPartnershipEfficacy & SafetyPivotal efficacyLong-term survivalSubgroup analysisKey secondary endpointsEarly efficacy measuresSafety profileATTR-PNPivotal efficacyPivotal efficacy ALTLong-term efficacyMutations efficacyLong-term survivalSafety profileDosingATTR-CM dosingATTR-PNPivotal efficacyPivotal efficacy ALTLong-term efficacyMutations efficacyLong-term survivalSafety profileMOD/MOARole of TTRATTR-CM MODATTR-CM MOAATTR-PNATTR-PN MODATTR-PN MOASupport & ResourcesMaterialsVideosATTR-PNATTR-PN MODATTR-PN MOA

Vyndaqel 61mg is indicated for the treatment of wild‑type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy
(ATTR-CM).1

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Refer to section 4.8 of the SmPC for how to report adverse reactions.

Suspect the signs of ATTR-CM with cardiac and noncardiac clues1Consider the following clinical clues, especially in combination, to raise suspicion for ATTR-CM and the need for further testing. 
  • Heart failure with preserved ejection fraction (HFpEF)2-4 or other cardiac conditions (e.g severe aortic stenosis3 or cardiac arrhythmias)1 in patients typically over the age of 602-4
In a retrospective cohort study of 382 patients with ATTR-CM, 69% (265 patients) had atrial fibrillation​​​​​​​5
  • ECG: Low QRS voltage relative to LV mass1
  • Echo: LV wall thickness ≥12 mm1
Behind the cardiac clues 
  • In ATTR-CM, diastolic function is impaired due to amyloid fibril deposition in the myocardium, resulting in thicker and inelastic ventricles, thereby decreasing stroke volume. It is not until the later stages of ATTR-CM disease that ejection fraction drops6,7
  • Prevalence among older HFpEF patients  
    • ~10% of HFpEF patients referred to a dedicated center had ATTR-CM confirmed by endomyocardial biopsy8*  
    • ~13% of hospitalized patients with HFpEF and increased LV wall thickness had wtATTR-CM confirmed by scintigraphy2†  
    • In patients undergoing transcatheter aortic valve replacement (TAVR) for severe calcific aortic stenosis, prevalence of ATTR-CM was 16% overall and 22% among men3 

Reduced longitudinal strain with apical sparing should raise suspicion of ATTR-CM7,9

Illustrative representation.

A prospective analysis in 108 patients (61% women, age range: 57-74 years) seen at the Johns Hopkins University HFpEF Clinic who underwent endomyocardial biopsy (EMB) to evaluate myocardial tissue histopathology. Approximately 10% had ATTR-CM confirmed.8 A prospective, cross-sectional, single-center study at a tertiary university hospital in Madrid, Spain. Included 120 patients ≥60 years of age (59% women, mean age: 82 ± 8 years) admitted for HFpEF, with LV ejection fraction ≥50% and LV hypertrophy ≥12 mm. 99mtechnetium-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-OPD) scintigraphy was used to confirm ATTR-CM. wtATTR was confirmed in 13% (13.3%; 95% Cl: 7.2-19.5) of the patients.2
  • Carpal tunnel syndrome1
  • Lumbar spinal stenosis1
  • Peripheral and autonomic nervous system dysfunction1
  • Biceps tendon rupture1
In a study of patients with wATTR-CM, 46% had carpal tunnel syndrome10
Behind the noncardiac clues 

Bilateral carpal tunnel syndrome and lumbar spinal stenosis

  • Often seen in ATTR-CM due to amyloid deposition in these areas; lumbar spinal stenosis is principally seen in wtATTR-CM12,13
  • Bilateral carpal tunnel syndrome and lumbar spinal stenosis are known clinical predictors of ATTR-CM and may precede heart failure symptoms by several years12,14 
  • Among patients undergoing carpal tunnel release surgery, 10.2% had amyloid deposits15

Biceps tendon rupture 

  • Among patients with wtATTR-CM, biceps tendon rupture has been observed in 33% of patients, occurring in the dominant arm in 95% and bilaterally in 24% of patients16

Hip and knee arthroplasty

  • In a study of 313 patients (172 with ATTR-CM), hip and knee arthroplasty surgeries were more frequent than in the general population, and on average, arthroplasty occurred 7.2 years before ATTR-CM diagnosis17

Nervous system dysfunction 

  • Nervous system dysfunction, including polyneuropathy and autonomic dysfunction, including gastrointestinal complaints and/or unexplained weight loss18 
  • Gastrointestinal complaints due to autonomic dysfunction include chronic diarrhoea, constipation, or both18 
  • Orthostatic hypotension due to autonomic dysfunction is another symptom that may occur with ATTR-CM18
European Society of Cardiology (ESC) recommendations 

The ESC Working Group recommends screening for ATTR-CM if LV wall thickness is ≥12 mm + the presence of ≥1 red flag or clinical scenario11

 Download resources to 
help suspect ATTR-CM Clinical findings that should further raise suspicion of ATTR-CM1,19

ECG1,19

  • Discrepancy between LV thickness and QRS voltage
  • Atrioventricular block, in the presence of increased wall thickness

CMR1,19

  • Marked ECV expansion, abnormal nulling time for the myocardium or diffuse late gadolinium enhancement on CMR

Echo1,19,20

  • Increased LV wall thickness
  • Reduction in longitudinal strain with apical sparing
  • Hypertrophic phenotype with associated infiltrative features

Biomarkers1,11,19

  • Mild increase in troponin levels on repeated occasions
  • Disproportionately elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) to degree of heart failure
ATTR-CM=transthyretin amyloid cardiomyopathy; CMR=cardiac magnetic resonance; ECG=electrocardiography; Echo=echocardiography; hATTR-CM=hereditary transthyretin amyloid cardiomyopathy; HFpEF=heart failure with preserved ejection fraction; LV=left ventricular; QRS=Q wave, R wave, S wave; wtATTR-CM=wild-type transthyretin amyloid cardiomyopathy.
Explore More Pivotal and 5-year data for ATTR-CM View the Body of Evidence ATTR-CM MOD Learn the Mechanism of Disease
NEXT: ATTR-CM safety profile
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. doi:10.1016/j.jchf.2019.04.010Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36(38):2585-2594. doi:10.1093/eurheartj/ehv338Castano A, Drachman BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163-178. doi:10.1007/s10741-014-9462-7Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126(10):1286-1300. doi:10.1161/CIRCULATIONAHA.111.078915Donnellan 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. doi:10.1016/j.jacep.2020.04.019Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011;32(6):670-679. doi:10.1093/eurheartj/ehq426Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018;28(1):10-21. doi:10.1016/j.tcm.2017.07.004 Hahn VS, Yanek LR, Vaishnav J, et al. Endomyocardial biopsy characterization of heart failure with preserved ejection fraction and prevalence of cardiac amyloidosis. JACC Heart Fail. 2020;8(9):712-724. doi:10.1016/j.jchf.2020.04.007 Narotsky DL, Castaño 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. doi:10.1016/j.cjca.2016.05.008 Connors LH, Sam F, Skinner M, et al. Heart failure resulting from age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290. doi:10.1161/CIRCULATIONAHA.115.018852Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis. A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur J Heart Fail. 2021;23(4):512-526. Doi:10.1002/ejhf.2140Nakagawa M, Sekijima Y, Yazaki M, et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23(1):58-63. doi:10.3109/13506129.2015.1135792 Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223-228. doi:10.3109/03009734.2014.895786 Papoutsidakis N, Miller EJ, Rodonski A, Jacoby D. Time course of common clinical manifestations in patients with transthyretin cardiac amyloidosis: delay from symptom onset to diagnosis. J Card Fail. 2018;24(2):131-133. doi:10.1016/ j.cardfail.2017.12.005 Sperry BW, Reyes BA, lkram A, et al. Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol. 2018;72(17):2040-2050. doi:10.1016/j.jacc.2018.07.092 Geller HI, Singh A, Alexander KM, Mirto TM, Falk RH. Association between ruptured distal biceps tendon and wild-type transthyretin cardiac amyloidosis. JAMA. 2017;318(10):962-963. doi:10.1001/jama.2017.9236Rubin J, Alvarez J, Teruya S, et al. Hip and knee arthroplasty are common among patients with transthyretin cardiac amyloidosis, occurring years before cardiac amyloid diagnosis: can we identify affected patients earlier? Amyloid. 2017;24(4):226-230. doi:10.1080/13506129.2017.1375908Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63-76. doi:10.1185/03007995.2012.754348Maurer MS, Bokhari S, Damy T, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail. 2019;12(9):1-11. doi:10.1161/CIRCHEARTFAILURE.119.006075 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. J Nucl Cardiol. 2019;26(6):2065-2123doi:10.1007/s12350-019-01760-6. Addendum: J Nucl Cardiol. Published online July 1, 2021. doi:10.1007/s12350-020-02455-z 
VYNDAQEL Prescribing InformationLoading
About ATTR-CM

Legal Category: S1A.Further information available upon request

PP-VYN-IRL-0177. December 2022

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