DOCSLIB.ORG

Transthyretin Amyloid Cardiomyopathy (ATTR-CM)—

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Transthyretin Amyloid Cardiomyopathy (ATTR-CM)— BIOEQUIVALENCE / VYNDALINK / REFS When you’ve decided VYNDAMAX is appropriate for your patient, VyndaLink may be able to help ATTR-CM is a progressive, fatal Enroll your patients in VyndaLink for support or send prescriptions directly to an in-network Specialty Pharmacy disease—recognize the signs The VyndaLink team can: and symptoms to diagnose and treat 2,3 Conduct a benefits verification to Determine payer requirements and Identify Specialty Pharmacy options based your appropriate patients determine your patient’s coverage provide information about the prior on your patient’s insurance coverage. Transthyretin amyloid for VYNDAMAX, including out-of- authorization process and appeals VYNDAMAX is available through multiple pocket costs. process as needed.* Specialty Pharmacies in our defined distribution network. VYNDAMAX—once-daily, oral medication for patients with wild-type or hereditary ATTR-CM *Please note where a PA is required, the physician must submit required information directly to the patient’s insurer. cardiomyopathy (ATTR-CM)— Get started at www.VyndaLink.com a disease that may be present in Download the enrollment form. Completed form can be sent online at www.VyndaLinkPortal.com or Proven to reduce mortality and 1 AM PM patients with heart failure faxed to 1-888-878-8474. Call 1-888-222-8475 (Monday-Friday, 8 -8 ET) with any questions. CV-related hospitalization Consider prescribing oral VYNDAMAX for References: 1. 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. 2. Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid bril proteins and amyloidosis: chemical identication and clinical classication International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209-213. 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(9):1166.e1-1166.e10. 4. Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. patients with wild-type or hereditary ATTR-CM Circulation. 2017;135(14):1357-1377. 5. Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS. Transthyretin cardiac amyloidosis in older Americans. J Card Fail. 2016;22(12):996-1003. 6. Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on A safety prole similar to placebo pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018;28(1):10-21. 7. Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;63(2):161-172. 8. González-López E, López-Sainz A, Garcia-Pavia P. Diagnosis and treatment of transthyretin cardiac amyloidosis. Rev Esp Cardiol. 2017;70(11):991-1004. 9. Reynolds M, Veverka K, Gertz M, et al. Ocular manifestations of familial transthyretin amyloidosis. Am J Ophthalmol. 2017;183:156-162. 10. 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 affected patients earlier? Amyloid. 2017;24(4):224-228. 11. Dang J, Abulizi M, Mokte A, et al. Renal infarction and its consequences for renal function in patients with cardiac amyloidosis. Mayo Clin Proc. 2019. doi:10.1016/j.mayocp.2019.02.012 12. Khalighi MA, ATTR-CM=transthyretin amyloid cardiomyopathy; CV=cardiovascular. Dean Wallace W, Palma-Diaz MF. Amyloid nephropathy. Clin Kidney J. 2014;7(2):97-106. 13. Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404-2412. 14. Bokhari S, Morgenstern R, Weinberg R, et al. Standardization of 99mTechnetium pyrophosphate imaging methodology to diagnose TTR cardiac amyloidosis. J Nucl Cardiol. 2018;25(1):181-190. 15. American Society of Nuclear Cardiology (ASNC). ASNC cardiac amyloidosis practice points: 99mtechnetium-pyrophosphate imaging for transthyretin cardiac amyloidosis. Available at: https://www.asnc.org/les/19110 ASNC Amyloid Practice Points WEB(2).pdf Published February 2016. Updated February 2019. Accessed November 8, 2019. 16. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. 17. Tankisheva E. A phase 1, open-label, randomized, crossover, multiple dose, pivotal bioequivalence INDICATION INDICATION study to compare PF-06291826 4 × 20 mg tafamidis meglumine and 61 mg: tafamidis free acid soft gelatin capsules administered under fasted conditions to healthy volunteers. Full Clinical Study Report [protocol B3461056]. July 23, 2018. 18. Data on le. VYNDAQEL® (tafamidis meglumine) and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or VYNDAQEL® (tafamidis meglumine) and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or Pzer Inc., New York, NY. hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. IMPORTANT SAFETY INFORMATION IMPORTANT SAFETY INFORMATION IMPORTANT SAFETY INFORMATION (continued) Adverse Reactions Adverse Reactions Specific Populations In studies in patients with ATTR-CM, the frequency of adverse events in patients treated with VYNDAQEL was similar to placebo. In studies in patients with ATTR-CM, the frequency of adverse events in patients treated with VYNDAQEL was similar to placebo. Pregnancy: Based on findings from animal studies, VYNDAQEL and VYNDAMAX may cause fetal harm when administered to Specific Populations Specific Populations a pregnant woman. Pregnancy: Based on findings from animal studies, VYNDAQEL and VYNDAMAX may cause fetal harm when administered to Pregnancy: Based on findings from animal studies, VYNDAQEL and VYNDAMAX may cause fetal harm when administered to Lactation: There are no available data on the presence of tafamidis in human milk, the effect on the breastfed infant, or the a pregnant woman. a pregnant woman. Lactation: There are no available data on the presence of tafamidis in human milk, the effect on the breastfed infant, or the Lactation: There are no available data on the presence of tafamidis in human milk, the effect on the breastfed infant, or the effect on milk production. Tafamidis is present in rat milk. When a drug is present in animal milk, it is likely the drug will be effect on milk production. Tafamidis is present in rat milk. When a drug is present in animal milk, it is likely the drug will be effect on milk production. Tafamidis is present in rat milk. When a drug is present in animal milk, it is likely the drug will be present in human milk. Breastfeeding is not recommended during treatment with VYNDAQEL and VYNDAMAX. present in human milk. Breastfeeding is not recommended during treatment with VYNDAQEL and VYNDAMAX. present in human milk. Breastfeeding is not recommended during treatment with VYNDAQEL and VYNDAMAX. Please see accompanying Full Prescribing Information including Patient Information at the end of this document. Please see accompanying Full Prescribing Information including Patient Information at the end of this document. Please see accompanying Full Prescribing Information including Patient Information at the end of this document. PP-VDM-USA-0194 © 2020 Pzer Inc. All rights reserved. Prescription only. March 2020 ABOUT ATTR-CM / FULL PRESCRIBING INFORMATION, INCLUDING PATIENT INFORMATION SYMPTOMS Transthyretin amyloid cardiomyopathy—a fatal, underdiagnosed cardiomyopathy caused by Signs and symptoms that may present in patients with ATTR-CM1,3-12 aggregated misfolded proteins, called amyloid fibrils, that accumulate in the myocardium1-3 Transthyretin amyloid cardiomyopathy— Cardiovascular Ocular a fatal, underdiagnosed cardiomyopathy • Heart failure • Vitreous opacity caused by aggregated misfolded proteins, • Intolerance to standard HF • Glaucoma Subtypes of ATTR-CM1,2: Patients present with symptoms of heart failure and may called amyloid fibrils, that accumulate in the therapies 1-3 • Low voltage relative to LV also present with other manifestations, such as atrial myocardium thickness Musculoskeletal/Orthopedic —Wild-type ATTR (wtATTR) 3,4 fibrillation and carpal tunnel syndrome, often bilateral • Echocardiography showing • Biceps tendon rupture —Hereditary ATTR (hATTR) increased LV wall thickness • Lumbar spinal stenosis • Cardiac arrhythmia • Carpal tunnel syndrome » In the United States, Val122lle and Thr60Ala are the Patients with ATTR-CM may also present • Aortic stenosis • Hip/knee arthroplasty most common mutations that typically manifest as Once diagnosed, untreated patients have a median survival with noncardiac manifestations that may not cardiomyopathy symptoms4 of ~2 to 3.5 years4 typically be present in other cardiovascular Nervous system diseases4 Autonomic Renal • Autonomic neuropathy • Renal impairment • Gastrointestinal complaints • Cardiorenal syndrome Transthyretin amyloid cardiomyopathy is frequently • Unexplained weight loss misdiagnosed, and delayed diagnosis can lead to significant Please note, VYNDAMAX is not indicated to • Orthostatic hypotension clinical consequences for patients4 treat all of the symptoms of ATTR-CM shown • Sexual
Load more

Recommended publications
  • Cardiac Amyloidosis
    Cardiac Amyloid: Contemporary Approach to Diagnosis and Advances in Treatment Cardiac Nursing Symposium October 17, 2019 Dana Miller AGPCNP-BC, CHFN The University of Kansas Medical Center Heart Failure Nurse Practitioner Oc Octob Learning objectives • Describe the different types of cardiac amyloidosis (Disease) • Recognize clinical manifestations of cardiac amyloidosis • Implement strategies for diagnosis of cardiac amyloidosis (Diagnosis) • Utilize recent clinical evidence for decisions about treatment of cardiac amyloidosis (Drugs and devices) What is the disease amyloidosis? • First described by Rudolf Virchow in 1858 describing the reaction of tissue deposits with iodine and sulfuric acid. • A disorder of misfolded proteins • Proteins circulate in the bloodstream and perform many functions in the body • Should be dissolved, in other words, liquid • In amyloid they become solid and deposit in organs and tissues in the body and cause problems Red flags for Cardiac Amyloidosis • Echocardiography • Low voltage on ECG and thickening of the septum/posterior wall>1.2 cm (unexplained increase in thickness) • Thickening of the RV free wall, valves Intolerance to bet blockers or ACEI Low normal BP inpatients with a previous history of HTN Donnelly and Hanna, 2017 JACC 2014 Red flags for AL • HFpEF + Nephrotic syndrome • Macroglossia and/or periorbital purpura • Orthostatic hypotension • Peripheral neuropathy • MGUS • Donnelly and Hanna, 2017 Red flags for ATTR • White male age>60 with HFpEF + history of carpal tunnel syndrome and or/spinal
    [Show full text]
  • Recent Advances in the Diagnosis and Management of Amyloid Cardiomyopathy
    Faculty Opinions Faculty Reviews 2021 10:(31) Recent advances in the diagnosis and management of amyloid cardiomyopathy Petra Nijst 1,2 W.H. Wilson Tang 3* 1 Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium 2 Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium 3 Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA Abstract Amyloidosis is a disorder characterized by misfolded precursor proteins that form depositions of fibrillar aggregates with an abnormal cross-beta-sheet conformation, known as amyloid, in the extracellular space of several tissues. Although there are more than 30 known amyloidogenic proteins, both hereditary and non-hereditary, cardiac amyloidosis (CA) typically arises from either misfolded transthyretin (ATTR amyloidosis) or immunoglobulin light-chain aggregation (AL amyloidosis). Its prevalence is more common than previously thought, especially among patients with heart failure and preserved ejection fraction (HFpEF) and aortic stenosis. If there is a clinical suspicion of CA, focused echocardiography, laboratory screening for the presence of a monoclonal protein (serum and urinary electrophoresis with immunofixation and serum free light-chain ratio), and cardiac scintigraphy with 99mtechnetium-labeled bone-tracers are sensitive and specific initial diagnostic tests. In some cases, more advanced/invasive techniques are necessary and, in the last several years, treatment options for both AL CA and ATTR CA have rapidly expanded. It is important to note that the aims of therapy are different. Systemic AL amyloidosis requires treatment targeted against the abnormal plasma cell clone, whereas therapy for ATTR CA must be targeted to the production and stabilization of the TTR molecule.
    [Show full text]
  • A Guide to Transthyretin Amyloidosis
    A Guide to Transthyretin Amyloidosis Authored by Teresa Coelho, Bo-Goran Ericzon, Rodney Falk, Donna Grogan, Shu-ichi Ikeda, Mathew Maurer, Violaine Plante-Bordeneuve, Ole Suhr, Pedro Trigo 2016 Edition Edited by Merrill Benson, Mathew Maurer What is amyloidosis? Amyloidosis is a systemic disorder characterized by extra cellular deposition of a protein-derived material, known as amyloid, in multiple organs. Amyloidosis occurs when native or mutant poly- peptides misfold and aggregate as fibrils. The amyloid deposits cause local damage to the cells around which they are deposited leading to a variety of clinical symptoms. There are at least 23 different proteins associated with the amyloidoses. The most well-known type of amyloidosis is associated with a hematological disorder, in which amyloid fibrils are derived from monoclonal immunoglobulin light-chains (AL amyloidosis). This is associated with a clonal plasma cell disorder, closely related to and not uncommonly co-existing with multiple myeloma. Chronic inflammatory conditions such as rheumatoid arthritis or chronic infections such as bronchiectasis are associated with chronically elevated levels of the inflammatory protein, serum amyloid A, which may misfold and cause AA amyloidosis. The hereditary forms of amyloidosis are autosomal dominant diseases characterized by deposition of variant proteins, in dis- tinctive tissues. The most common hereditary form is transthyretin amyloidosis (ATTR) caused by the misfolding of protein monomers derived from the tetrameric protein transthyretin (TTR). Mutations in the gene for TTR frequently re- sult in instability of TTR and subsequent fibril formation. Closely related is wild-type TTR in which the native TTR protein, particu- larly in the elderly, can destabilize and re-aggregate causing non- familial cases of TTR amyloidosis.
    [Show full text]
  • Cardiac Amyloidosis
    Cardiac Amyloidosis Ronald Witteles, MD Stanford University & Brendan M. Weiss, MD University of Pennsylvania Amyloidosis: What is it? • Amylum – Starch (Latin) • Generic term for many diseases: • Protein misfolds into β-sheets • Forms into 8-10 nm fibrils • Extracellular deposition into amyloid deposits Types of Amyloid – Incomplete List • Systemic: • Light chains (AL) – “Primary ” • Transthyretin (ATTR) – “Senile ” or “Familial ” or “FAC” or “FAP” • Serum amyloid A (AA) – “Secondary ” • Localized – Not to be memorized! • Beta-2 microglobulin (A-β2) – Dialysis (osteoarticular structures) • Apolipoprotein A-1 (AApoA-I) – Age-related (aortic intima, cardiac, neuropathic) • Apolipoprotein A-2 (AApoA-2) – Hereditary (kidney) • Calcitonin (ACal) – Complication of thyroid medullary CA • Islet amyloid polypeptide (AIAPP) – Age-related (seen in DM) • Atrial natriuretic peptide (AANF) – Age-related (atrial amyloidosis) • Prolactin (APro) – Age-related, pituitary tumors • Insulin (AIns) – Insulin-pump use (local effects) • Amyloid precursor protein (ABeta) – Age-related/hereditary (Alzheimers) • Prion protein (APrPsc) – Hereditary/sporadic (spongiform encephalopathies) • Cystatin-C (ACys) – Hereditary (cerebral hemorrhage) • Fibrinogen alpha chain (AFib) – Hereditary (kidney) • Lysozome (ALys) – Hereditary (Diffuse, especially kidney, spares heart) • Medin/Lactadherin – Age-related (medial aortic amyloidosis) • Gelsolin (AGel) – Hereditary (neuropathic, corneal) • Keratin – Cutaneous AL: A Brief Dive into Hematology… Plasma cells: Make antibodies
    [Show full text]
  • Intraoperative Death Due to Nodular Amyloidosis Cardiomyopathy Associated with Fat Pulmonary Embolism
    Rom J Leg Med [21] 15-18 [2013] DOI: 10.4323/rjlm.2013.15 © 2013 Romanian Society of Legal Medicine Intraoperative death due to nodular amyloidosis cardiomyopathy associated with fat pulmonary embolism Mihai Ceauşu1, Lăcrămioara Luca2, Sorin Hostiuc3,*, Dana Sîrbu4, Adrian Sîrbu4, Ruxandra Negoi5 _________________________________________________________________________________________ Abstract: Cardiac amyloidosis is caused by extracellular deposits containing low molecular weight protein subunits arranged in a beta sheet configuration. By gross examination amyloid deposits are identifiable as localized tan, waxy appearing lesions affecting almost always the atria (usually atrial endocardium), valve leaflets, ventricular, but also in the coronary lumen, sometimes leading to severe coronary stenosis. Fat pulmonary embolism is a known complication of femoral fractures, being more frequent in untreated cases compared to those suffering surgical interventions. We present a case in which a female patient with cardiac amyloidosis died on the operating table, the direct cause of death being fat pulmonary emboli, and discuss the involvement of the associated cardiac amyloidosis in thanatogenesys. Key Words: cardiac amyloidosis, fat embolism, intraoperative death, femoral fracture. ardiac amyloidosis (amyloid associated with fibrous replacement lesions), but also the cardiomyopathy, AC) is caused by coronary lumen, sometimes leading to severe coronary C extracellular deposits containing low molecular weight stenosis (>75%) [5]. protein subunits arranged in a beta sheet configuration, Cardiac amyloidosis is almost always associated leading to restrictive cardiomyopathy [1] and electrical with amyloid deposits located in other organs [5]. The conduction disturbances [2, 3]. extent of amyloid deposition can be graded from 1 to 4 AC may mimic constrictive pericarditis, coronary (less than 10%, 10 to 25%, 26 to 50%, and more than artery disease, valve heart disease, and idiopathic 50% involvement of the myocardium, respectively) hypertrophic or congestive cardiomyopathy [4].
    [Show full text]
  • The Prevalence of Advanced Interatrial Block and Its Relationship to Left Atrial Function in Patients with Transthyretin Cardiac Amyloidosis
    Journal of Clinical Medicine Article The Prevalence of Advanced Interatrial Block and Its Relationship to Left Atrial Function in Patients with Transthyretin Cardiac Amyloidosis Thomas Lindow 1,2,3,* and Per Lindqvist 4 1 Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, NSW 2065, Australia 2 Department of Clinical Physiology, Research and Development, Växjö Central Hospital, Region Kronoberg, 351 88 Växjö, Sweden 3 Clinical Physiology, Clinical Sciences, Lund University, 221 00 Lund, Sweden 4 Department of Clinical Physiology, Surgical and Perioperative Sciences, Umeå University, 901 87 Umeå, Sweden; [email protected] * Correspondence: [email protected]; Tel.: +46-730-62-60-07 Abstract: Background: Advanced interatrial block (aIAB), which is associated with incident atrial fibrillation and stroke, occurs in the setting of blocked interatrial conduction. Atrial amyloid depo- sition could be a possible substrate for reduced interatrial conduction, but the prevalence of aIAB in patients with transthyretin cardiac amyloidosis (ATTR-CA) is unknown. We aimed to describe the prevalence of aIAB and its relationship to left atrial function in patients with ATTR-CA in com- parison to patients with HF and left ventricular hypertrophy but no CA. Methods: The presence of aIAB was investigated among 75 patients (49 patients with ATTR-CA and 26 with HF but no CA). A comprehensive echocardiographic investigation was performed in all patients, including left atrial Citation: Lindow, T.; Lindqvist, P. strain and strain rate measurements. Results: Among patients with ATTR-CA, 27% had aIAB and in The Prevalence of Advanced patients with HF but no CA, this figure was 21%, (p = 0.78).
    [Show full text]
  • "Survival Guide" to the Clinics
    Perelman School of Medicine University of Pennsylvania SURVIVAL GUIDE TO THE CLINICS 2018 •♦ Introduction ♦• The transition from the basic sciences to the clinics is naturally intimidating. You’ll soon be immersed in an unfamiliar environment that will demand greater responsibility and commitment than anything you’ve previously encountered in medical school. But fear not! Working with patients is (hopefully) what you went to med school for in the first place. Though your white coat may feel awkward, you are more than ready to begin navigating the corridors of HUP. While your clerkship year will occasionally be anxiety provoking and exhausting, it will more often be exhilarating, exciting, and fun. You’ll interact daily and influentially with patients, become a valuable member of medical and surgical teams, see the practical application of the things you’ve learned, and finally sense yourself becoming a true clinician (it feels like a slight tingle). This guide is intended to help ease your transition into the clinics. Each rotation and each site has its own distinct flavor. What is expected of you as a student will vary from one rotation to the next and from team to team. Rather than attempt to describe every detail of each rotation, this Survival Guide presents general objectives, opportunities, and responsibilities, as well as some helpful advice from previous students. Above all, your fellow classmates and upperclassmen will be a tremendous resource throughout this core clinical year. Enthusiasm, dedication, and flexibility are the keys to performing well and learning in the clinics. Throughout your clinical experience, you’ll interact with an incredibly diverse group of attendings, residents, and students in a variety of medical environments.
    [Show full text]
  • Online Event | Friday, 18 September 2020 | 16:40–18:10 CET
    ONLINE eevventent th th 14 18 SEPTEMBER 2020 (CEST) PRESIDENT Joan Bladé Hospital Clínic. Barcelona, Spain www.isa2020.org 2 International Symposium on Amyloidosis WELCOME LETTER On behalf of the international Society of Amyloidosis (ISA) and the PETHEMA Foundation it is my pleasure to invite you to the XVII ISA Symposium. It will be held from September 14th to 18th, 2020 in an on-line format. It was planned for March 1-5 in Tarragona as a regular meeting, but it was postponed and later transformed at the virtual form because of the COVID-19 pandemic. The Symposium will consist of a five days scientific event. All types of amyloidosis will be covered: TTR (hereditary and wild-type), light chain (AL), AA as well as less frequent forms. There will be key lectures, plenary sessions, industry sponsored symposia, oral presentations plus meet-the-expert sessions and poster exhibition. This Symposium is attended by all the outstanding researchers in all the fields of amyloidosis plus about 800 delegates particularly interested in these diseases. The ISA 2020 is a unique opportunity to learn on basic biology, early diagnosis and recognition of unusual forms, best prognostication and response assessment, new drug targets and the role of novel agents, including immunotherapy, as well as the updated results from early phase and large randomized clinical trials. Please join us for this exciting conference on amyloidosis. Welcome to ISA 2020!!! Joan Bladé President ISA Symposium 2020 Hematology Department, Hospital Clinic. Barcelona Spain International Symposium on Amyloidosis 3 COMMITTEES Principal Organizers of the XVII International Symposium on Amyloidosis : • Joan Bladé, President.
    [Show full text]
  • Clinical Trial Results
    CLINICAL TRIAL RESULTS This summary reports the results of only one study. Researchers must look at the results of many types of studies to understand if a study medicine works, how it works, and if it is safe to prescribe to patients. The results of this study might be different than the results of other studies that the researchers review. Sponsor: Pfizer, Inc. Medicine(s) Studied: Vyndaqel® (Tafamidis meglumine) Protocol Number: B3461026 (Fx1B-303) Dates of Trial: 22 September 2009 to 20 November 2019 Title of this Trial: A Trial to Measure the Safety and Efficacy of Vyndaqel Treatment in Patients With Transthyretin Amyloid Cardiomyopathy [Open-Label Safety and Efficacy Evaluation of FX-1006A in Patients With V122I or Wild-Type Transthyretin (TTR) Amyloid Cardiomyopathy] Date(s) of this Report: 25 September 2020 – Thank You – Pfizer, the Sponsor, would like to thank you for your participation in this clinical trial and provide you a summary of results representing everyone who participated. If you have any questions about the study or results, please contact the doctor or staff at your study site. 090177e1950968bb\Approved\Approved On: 29-Sep-2020 05:49 (GMT) 1 WHY WAS THIS STUDY DONE? Transthyretin amyloid cardiomyopathy is a type of heart disease that is caused by a certain kind of protein building up in the heart muscle. This protein is called transthyretin, or “TTR”. TTR is normally made by your liver and carries things like hormones and Vitamin A throughout your body. In patients with transthyretin amyloid cardiomyopathy, TTR breaks apart and clumps together in fibers called “amyloid”.
    [Show full text]
  • Introduction to Cardiac Amyloidosis
    Introduction to cardiac amyloidosis Marianna Fontana Professor of Cardiology National Amyloidosis Centre, Royal Free London NHS Foundation Trust and Division of Medicine, UCL, London Amyloid • Abnormal extracellular fibrillar protein deposit in tissues • Pathognomonic green birefringence after Congo red staining • > 30 different amyloid fibril proteins Merlini G. Hematology Am Soc Hematol Educ Program 2017;1:1–12 Sipe et al. Amyloid 2014;21:221–4 Amyloidosis • Disease caused by amyloid deposits: localised or systemic • Systemic amyloidosis is usually fatal • Causes about 1 per 2000 deaths in the UK • Diagnosis & treatment are difficult • Major recent advances & better outcomes • Still a major unmet medical need Pinney JH et al, Br J Haematol 2013;161:525-532 Cardiac amyloid fibrils AL Monoclonal Ig Light chains due to plasma cell dyscrasia (MGUS) • Plasma cell dyscrasia usually subtle (i.e., not overt myeloma) • AL often diagnosed late ATTR • Wild-type (normal) transthyretin (TTR) • Hereditary (mutated) transthyretin (TTR) Grogan et al. Heart 2017;103:1065–72; Donnelly & Hanna. Cleve Clin J Med 2017;84:12–26 Systemic AL amyloidosis Amyloidosis AL AA Fibrinogen Transthyretin Apo AI-A2 Lysozyme Gelsolin LECT2 Liver Nerves Kidneys Nerves Kidneys Any organ Kidneys Kidneys Kidneys Heart Liver Kidneys Liver Gut Heterogeneity of systemic AL amyloidosis AA, amyloid A; Apo, apolipoprotein; LECT2, leukocyte chemotactic factor 2 Images provided by presenter Sipe et al. Amyloid 2016;23:209–13 Wild-type transthyretin (ATTR) amyloidosis • Amyloid fibril protein is ‘normal’ (non-mutated) transthyretin (TTR) • Wild-type ATTR amyloidosis (ATTRwt) is a cardiomyopathy • Increasingly recognised cause of heart failure in elderly (94% males, over 50s) • Carpal tunnel syndrome is common (>50%) • Cardiac ATTR amyloid deposits are present in ~25% males over 80 yrs of age • Majority not diagnosed with amyloidosis in life Lane T, et al.
    [Show full text]
  • Cardiac Amyloidosis: Diagnosis and Treatment Strategies
    Curr Oncol Rep (2017) 19:46 DOI 10.1007/s11912-017-0607-4 CARDIO-ONCOLOGY (EH YANG, SECTION EDITOR) Cardiac Amyloidosis: Diagnosis and Treatment Strategies Mirela Tuzovic1 & Eric H. Yang 1 & Arnold S. Baas2 & Eugene C. Depasquale2 & Mario C. Deng2 & Daniel Cruz 2 & Gabriel Vorobiof1,3 # Springer Science+Business Media New York 2017 Abstract Cardiac amyloidosis in the United States is most pathophysiology of amyloid, many patients are still diagnosed often due to myocardial infiltration by immunoglobulin protein, late in the disease course. This review investigates the current such as in AL amyloidosis, or by the protein transthyretin, such understanding and new research on the diagnosis and treatment as in hereditary and senile amyloidosis. Cardiac amyloidosis strategies in patients with cardiac amyloidosis. Myocardial am- often portends a poor prognosis especially in patients with sys- yloid infiltration distribution occurs in a variety of patterns. temic AL amyloidosis. Despite better understanding of the Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid bur- This article is part of the Topical Collection on Cardio-oncology den and the amyloid subtype, respectively. While for AL amy- Electronic supplementary material The online version of this article loid, treatment success largely depends on early diagnosis, for (doi:10.1007/s11912-017-0607-4) contains supplementary material, ATTR amyloid, new investigational agents that reduce produc- which is available to authorized users. tion of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnos- * Gabriel Vorobiof tic detection and improvements in early disease recognition will [email protected] undoubtedly facilitate a larger proportion of patients to receive Mirela Tuzovic early therapy when it is most effective.
    [Show full text]
  • The Journal of Emergency Medicine VOLUME 56, NUMBER 2 2019
    The Journal of Emergency Medicine VOLUME 56, NUMBER 2 2019 CONTENTS Original Contributions 127 Predictors of Short Intensive Care Unit Stay for Patients with Diabetic Ketoacidosis Using a Novel Emergency Department– Based Resuscitation and Critical Care Unit Victoria L. Zhou, Frances S. Shofer, Nikita G. Desai, Ilona S. Lorincz, Nikhil K. Mull, David H. Adler, John C. Greenwood 135 Early Lactate Dynamics in Critically Ill Non-Traumatic Patients in a Resuscitation Room of a German Emergency Department (OBSERvE-Lactate-Study) Andre Kramer, Norman Urban, Stephanie Do¨ll, Thomas Hartwig, Maryam Yahiaoui-Doktor, Ralph Burkhardt, Sirak Petros, Andre´ Gries, Michael Bernhard 145 Missed Opportunities: Integrating Palliative Care into the Emergency Department for Older Adults Presenting as Level I Triage Priority from Long-Term Care Facilities Ashley S. Mogul, David M. Cline, Jennifer Gabbard, Casey Bryant Clinical Reviews in Emergency Medicine 153 Blunt Thoracolumbar-Spine Trauma Evaluation in the Emergency Department: A Meta-Analysis of Diagnostic Accuracy for History, Physical Examination, and Imaging James VandenBerg, Kevin Cullison, Susan A. Fowler, Matthew S. Parsons, Christopher M. McAndrew, Christopher R. Carpenter 166 Emergency Medicine Evaluation and Management of Small Bowel Obstruction: Evidence-Based Recommendations Brit Long, Jennifer Robertson, Alex Koyfman Selected Topics: Sports Medicine 177 Predicted Risk for Exacerbation of Exercise-Associated Hyponatremia from Indiscriminate Postrace Intravenous Hydration of Ultramarathon Runners Martin D. Hoffman 185 The Dangers of Spear Tackling: A Case Report of a NEXUS-Negative High School Football Player Jason S. Ferderber, Allan B. Wolfson Ultrasound in Emergency Medicine 191 The Potential Role of Ultrasound in the Work-Up of Appendicitis in the Emergency Department Patrick D.
    [Show full text]