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Flotats A. Cardiac denervation and morpho-functional changes, two sides of the same coin in wild-type transthyretin amyloid cardiomyopathy? J Nucl Cardiol 2025; 45:102145. [PMID: 39870299 DOI: 10.1016/j.nuclcard.2025.102145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 01/10/2025] [Indexed: 01/29/2025]
Affiliation(s)
- Albert Flotats
- Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Sant Quintí 89, F Block, Basement-2, 08041 Barcelona, Spain.
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Feo MSD, Cambieri C, Galosi E, Frantellizzi V, Chimenti C, Luigetti M, Sciarrone MA, Graziani F, Leonardi L, Musumeci B, Libonati L, Moret F, D’Andrea E, Di Giulio M, Garibaldi M, Forcina F, Truini A, De Vincentis G, Inghilleri M, Ceccanti M. Exploring Cardiac Sympathetic Denervation in Transthyretin-Mediated Hereditary Amyloidosis (ATTRv): Insights from 123I-mIBG Scintigraphy. Diagnostics (Basel) 2025; 15:508. [PMID: 40002660 PMCID: PMC11854682 DOI: 10.3390/diagnostics15040508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 02/13/2025] [Accepted: 02/17/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Hereditary transthyretin-mediated amyloidosis (ATTRv) is a rare disease characterized by the deposition of amyloid in the heart and peripheral nerves, particularly affecting small fibers. This study aims to evaluate autonomic cardiac involvement in ATTRv. Methods: Twelve patients with ATTRv and twelve sex- and age-matched healthy subjects underwent 123I-mIBG scintigraphy to evaluate the early and late heart-to-mediastinum ratio (eH/M and lH/M), 99mTc-HDP bone scan scintigraphy, and neurophysiological assessments. Data were analyzed in relation to functional cardiac and neurologic scales (NYHA and FAP scales). Results: Patients with ATTRv exhibited significant cardiac denervation, as demonstrated by the reduction in early and late H/M ratios compared to the control group (eH/M: 1.48 ± 0.08 vs. 1.89 ± 0.05, p < 0.001; lH/M: 1.39 ± 0.08 vs. 2.01 ± 0.05, p < 0.001). Values of eH/M and lH/M < 1.6 effectively differentiated patients with ATTRv from the healthy controls. Cardiac denervation correlated with interventricular septal thickness and the Perugini score but was not related to neurophysiological assessments or NYHA and FAP scales. Conclusions: Ultimately, 123I-mIBG scintigraphy is an effective tool for assessing cardiac denervation in patients with ATTRv.
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Affiliation(s)
- Maria Silvia De Feo
- Department of Radiological Sciences, Oncology and Anatomo Pathology, Sapienza University of Rome, 00151 Rome, Italy; (M.S.D.F.)
| | - Chiara Cambieri
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
| | - Eleonora Galosi
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
| | - Viviana Frantellizzi
- Department of Radiological Sciences, Oncology and Anatomo Pathology, Sapienza University of Rome, 00151 Rome, Italy; (M.S.D.F.)
| | - Cristina Chimenti
- Department of Clinical, Anesthesiological and Cardiovascular Sciences, I School of Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Marco Luigetti
- Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | | | - Francesca Graziani
- Department of Cardiovascular Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Luca Leonardi
- Neuromuscular and Rare Disease Centre, Neurology Unit, Sant’Andrea Hospital, 00189 Rome, Italy
| | - Beatrice Musumeci
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Laura Libonati
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
| | - Federica Moret
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
| | - Edoardo D’Andrea
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
| | - Matteo Di Giulio
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
| | - Matteo Garibaldi
- Department of Neurology, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00185 Rome, Italy
| | - Francesca Forcina
- Department of Neurology, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00185 Rome, Italy
| | - Andrea Truini
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
| | - Giuseppe De Vincentis
- Department of Radiological Sciences, Oncology and Anatomo Pathology, Sapienza University of Rome, 00151 Rome, Italy; (M.S.D.F.)
| | - Maurizio Inghilleri
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
- IRCCS Neuromed, 86077 Pozzilli, Italy
| | - Marco Ceccanti
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy (M.C.)
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Brette JB, Colombat M, Fournier P, Moninhas M, Marcheix B, Lairez O, Cariou E. Descriptive study of the clinical and myocardial status of a population with anatomopathological aortic valve amyloidosis. Cardiovasc Pathol 2024; 73:107674. [PMID: 39025343 DOI: 10.1016/j.carpath.2024.107674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 07/06/2024] [Accepted: 07/07/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND Aortic stenosis (AS) and transthyretin (ATTR) cardiac amyloidosis (CA) share the same clinical profiles and cardiac phenotype. Amyloid deposits have been frequently reported in aortic valves of patients with severe AS referred for surgical aortic valve replacement (SAVR). The aim of this study was to determine the clinical and myocardial status of patients with aortic valve amyloidosis after aortic valve surgery. METHODS AND RESULTS We performed a retrospective descriptive study of 46 patients who underwent SAVR for severe AS with amyloid deposits upon histological analysis. All patients were screened for cardiac involvement. Amyloid deposits typing was successful in 35 (76%) patients and 28 (80%) were ATTR. Two (4%) had positive bone scintigraphy and among the 5 myocardial biopsies performed during surgery, 80% were positive for ATTR deposits. CONCLUSION ATTR is the predominant type in the presence of amyloid deposits on the aortic valve after surgery for severe AS but is only rarely accompanied by cardiac uptake on bone scintigraphy. Early stages of myocardial involvement are frequent and myocardial biopsy is more sensitive for detection of mild amyloid deposits than bone scintigraphy.
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Affiliation(s)
- Jean-Baptiste Brette
- Department of Cardiology, Toulouse University Hospital, France; Cardiac Imaging Center, Toulouse University Hospital, France
| | - Magali Colombat
- Medical School, Toulouse III Paul Sabatier University, Toulouse, France; Department of Pathology, IUCT Oncopôle, Toulouse France
| | - Pauline Fournier
- Department of Cardiology, Toulouse University Hospital, France; Cardiac Imaging Center, Toulouse University Hospital, France
| | - Maxime Moninhas
- Department of Cardiology, Toulouse University Hospital, France; Cardiac Imaging Center, Toulouse University Hospital, France
| | - Bertrand Marcheix
- Medical School, Toulouse III Paul Sabatier University, Toulouse, France; Department of Cardiac Surgery, Toulouse University Hospital, France
| | - Olivier Lairez
- Department of Cardiology, Toulouse University Hospital, France; Cardiac Imaging Center, Toulouse University Hospital, France; Department of Nuclear Medicine, Toulouse University Hospital, France; Medical School, Toulouse III Paul Sabatier University, Toulouse, France.
| | - Eve Cariou
- Department of Cardiology, Toulouse University Hospital, France; Cardiac Imaging Center, Toulouse University Hospital, France
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Dicorato MM, Basile P, Muscogiuri G, Carella MC, Naccarati ML, Dentamaro I, Guglielmo M, Baggiano A, Mushtaq S, Fusini L, Pontone G, Forleo C, Ciccone MM, Guaricci AI. Novel Insights into Non-Invasive Diagnostic Techniques for Cardiac Amyloidosis: A Critical Review. Diagnostics (Basel) 2024; 14:2249. [PMID: 39410653 PMCID: PMC11475987 DOI: 10.3390/diagnostics14192249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/03/2024] [Accepted: 10/07/2024] [Indexed: 10/20/2024] Open
Abstract
Cardiac amyloidosis (CA) is a cardiac storage disease caused by the progressive extracellular deposition of misfolded proteins in the myocardium. Despite the increasing interest in this pathology, it remains an underdiagnosed condition. Non-invasive diagnostic techniques play a central role in the suspicion and detection of CA, also thanks to the continuous scientific and technological advances in these tools. The 12-lead electrocardiography is an inexpensive and reproducible test with a diagnostic accuracy that, in some cases, exceeds that of imaging techniques, as recent studies have shown. Echocardiography is the first-line imaging modality, although none of its parameters are pathognomonic. According to the 2023 ESC Guidelines, a left ventricular wall thickness ≥ 12 mm is mandatory for the suspicion of CA, making this technique crucial. Cardiac magnetic resonance provides high-resolution images associated with tissue characterization. The use of contrast and non-contrast sequences enhances the diagnostic power of this imaging modality. Nuclear imaging techniques, including bone scintigraphy and positron emission tomography, allow the detection of amyloid deposition in the heart, and their role is also central in assessing the prognosis and response to therapy. The role of computed tomography was recently evaluated by several studies, above in population affected by aortic stenosis undergoing transcatheter aortic valve replacement, with promising results. Finally, machine learning and artificial intelligence-derived algorithms are gaining ground in this scenario and provide the basis for future research. Understanding the new insights into non-invasive diagnostic techniques is critical to better diagnose and manage patients with CA and improve their survival.
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Affiliation(s)
- Marco Maria Dicorato
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Paolo Basile
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Giuseppe Muscogiuri
- Department of Radiology, IRCCS Istituto Auxologico Italiano, San Luca Hospital, 20149 Milan, Italy
| | - Maria Cristina Carella
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Maria Ludovica Naccarati
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Ilaria Dentamaro
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Marco Guglielmo
- Department of Cardiology, Division of Heart and Lungs, Utrecht University, Utrecht University Medical Center, 3584 Utrecht, The Netherlands;
- Department of Cardiology, Haga Teaching Hospital, 2545 The Hague, The Netherlands
| | - Andrea Baggiano
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; (A.B.); (S.M.); (L.F.); (G.P.)
| | - Saima Mushtaq
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; (A.B.); (S.M.); (L.F.); (G.P.)
| | - Laura Fusini
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; (A.B.); (S.M.); (L.F.); (G.P.)
| | - Gianluca Pontone
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; (A.B.); (S.M.); (L.F.); (G.P.)
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
| | - Cinzia Forleo
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Marco Matteo Ciccone
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Andrea Igoren Guaricci
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
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Galán Dávila L, Martinez Valle F, Buades Reinés J, Gonzalez-Moreno J, Losada López I, Sevilla T, Muñoz Beamud F, Bárcena Llona JE, Romero Acebal M, Setaro F, Primiano D, Tarilonte P. A description of variant transthyretin amyloidosis (ATTRv) stage 1 patients and asymptomatic carriers in Spain: the EMPATIa study. Orphanet J Rare Dis 2024; 19:323. [PMID: 39242501 PMCID: PMC11378489 DOI: 10.1186/s13023-024-03304-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 08/06/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND Variant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain. METHODS National, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected. RESULTS The mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group. CONCLUSIONS The EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment.
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Affiliation(s)
- Lucía Galán Dávila
- Neurology Department, Hospital Clínico San Carlos, IdISSC, Madrid, Spain
| | | | - Juan Buades Reinés
- Internal Medicine Department, Hospital Universitario Son Llàtzer, Palma, Spain
- Balearic Research Group in Genetic Cardiopathies, Sudden Death and TTR Amyloidosis, Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma, Spain
| | - Juan Gonzalez-Moreno
- Internal Medicine Department, Hospital Universitario Son Llàtzer, Palma, Spain
- Balearic Research Group in Genetic Cardiopathies, Sudden Death and TTR Amyloidosis, Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma, Spain
| | - Inés Losada López
- Internal Medicine Department, Hospital Universitario Son Llàtzer, Palma, Spain
- Balearic Research Group in Genetic Cardiopathies, Sudden Death and TTR Amyloidosis, Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma, Spain
| | - Teresa Sevilla
- Neurology Department, Hospital Universitari i Politècnic La Fe & IIS La Fe, Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
- Neurology Department, Universitat de València, Valencia, Spain
| | | | | | - Manuel Romero Acebal
- Neurology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain
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Eda Y, Ishii S, Onagi S, Katoh N, Ako J. Coexistence of variant-type transthyretin and immunoglobulin light-chain amyloidosis: a case report. Eur Heart J Case Rep 2024; 8:ytae264. [PMID: 38872953 PMCID: PMC11171424 DOI: 10.1093/ehjcr/ytae264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 05/08/2024] [Accepted: 05/23/2024] [Indexed: 06/15/2024]
Abstract
Background Determining the type of amyloid deposits is clinically important for choosing the specific therapies for cardiac amyloidosis. Case summary A 78-year-old woman who had been experiencing fluid retention and dyspnoea on exertion for 6 months was referred to our hospital for the management of heart failure with left ventricular hypertrophy. Since 99mTc-hydroxymethylene diphosphonate scintigraphy showed mild cardiac uptake and significant elevation of serum free lambda chain (with a difference of 263 mg/L in free light chain), we suspected immunoglobulin light-chain amyloidosis (AL), and endomyocardial biopsy was performed. The deposit site within the myocardial tissue exhibited positive for Congo red staining and transthyretin immunostaining, however negative or non-specific for light-chain immunostaining including lambda and kappa staining. Genetic testing confirmed a mutation in V122I, variant-type transthyretin amyloidosis (ATTRv). Despite the administration of patisiran, her condition exhibited progressive deterioration. Additionally, she displayed macroglossia, an atypical manifestation in ATTRv amyloidosis. Further biopsies from tongue and abdominal wall fat culminated in a final diagnosis: the coexistence of ATTRv and AL (of the lambda type). Although treatment with melphalan and dexamethasone was started, she passed away 24 months after the initial visit. When the endomyocardial biopsy specimen underwent mass spectrometry as a post hoc analysis, both ATTR and AL amyloid were significantly detected. Discussion Coexistence of ATTRv and AL within cardiac amyloidosis is extremely uncommon. In situations where incongruities arise between the amyloid type determined via immunohistochemistry findings and the amyloid type assumed based on other clinical findings, mass spectrometry should be considered.
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Affiliation(s)
- Yuko Eda
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0374, Japan
| | - Shunsuke Ishii
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0374, Japan
| | - Suzuho Onagi
- Institute for Biomedical Sciences, Shinshu University, Matsumoto, Nagano, Japan
| | - Nagaaki Katoh
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Junya Ako
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0374, Japan
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Beauvais D, Labeyrie C, Cauquil C, Francou B, Eliahou L, Not A, Echaniz-Laguna A, Adam C, Slama MS, Benmalek A, Leonardi L, Rouzet F, Adams D, Algalarrondo V, Beaudonnet G. Detailed clinical, physiological and pathological phenotyping can impact access to disease-modifying treatments in ATTR carriers. J Neurol Neurosurg Psychiatry 2024; 95:489-499. [PMID: 37875336 PMCID: PMC11103288 DOI: 10.1136/jnnp-2023-332180] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 09/27/2023] [Indexed: 10/26/2023]
Abstract
BACKGROUND Hereditary transthyretin amyloidosis is a life-threatening autosomal dominant systemic disease due to pathogenic TTR variants (ATTRv), mostly affecting the peripheral nerves and heart. The disease is characterised by a combination of symptoms, organ involvement and histological amyloid deposition. The available disease-modifying ATTRv treatments (DMTs) are more effective if initiated early. Pathological nerve conduction studies (NCS) results are the cornerstone of large-fibre polyneuropathy diagnosis, but this anomaly occurs late in the disease. We investigated the utility of a multimodal neurological and cardiac evaluation for detecting early disease onset in ATTRv carriers. METHODS We retrospectively analysed a cohort of ATTRv carriers with normal NCS results regardless of symptoms. Multimodal denervation and infiltration evaluations included a clinical questionnaire (Lauria and New York Heart Association (NYHA)) and examination, intra-epidermal nerve fibre density assessment, autonomic assessment based on heart rate variability, Sudoscan, meta-iodo-benzyl-guanidine scintigraphy, cardiac biomarkers, echocardiography, MRI and searches for amyloidosis on skin biopsy and bone scintigraphy. RESULTS We included 130 ATTRv carriers (40.8% men, age: 43.6±13.5 years), with 18 amyloidogenic TTR gene mutations, the majority of which was the late-onset Val30Met variant (42.3%). Amyloidosis was detected in 16.9% of mutation carriers, including 9 (6.9%) with overt disease (Lauria>2 or NYHA>1) and 13 asymptomatic carriers (10%) with organ involvement (small-fibre neuropathy or cardiomyopathy). Most of these patients received DMT. Abnormal test results of unknown significance were obtained for 105 carriers (80.8%). Investigations were normal in only three carriers (2.3%). CONCLUSIONS Multimodal neurological and cardiac investigation of TTRv carriers is crucial for the early detection of ATTRv amyloidosis and initiation of DMT.
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Affiliation(s)
- Diane Beauvais
- AP-HP, Service de neurologie, CHU Bicêtre, Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares, CERAMIC, FILNEMUS Network, Le Kremlin-Bicêtre, France
- Department of Neurology (Nerve-Muscle Unit), AOC National Reference Center for Neuromuscular Disorders, University Hospital of Bordeaux (CHU Pellegrin), Bordeaux, France
| | - Céline Labeyrie
- AP-HP, Service de neurologie, CHU Bicêtre, Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares, CERAMIC, FILNEMUS Network, Le Kremlin-Bicêtre, France
| | - Cécile Cauquil
- AP-HP, Service de neurologie, CHU Bicêtre, Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares, CERAMIC, FILNEMUS Network, Le Kremlin-Bicêtre, France
| | - Bruno Francou
- AP-HP, Laboratoire de Génétique Moléculaire, Pharmacogénétique et Hormonologie, CHU Bicêtre, Le Kremlin-Bicêtre, France
| | | | - Adeline Not
- AP-HP, Service de neurologie, CHU Bicêtre, Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares, CERAMIC, FILNEMUS Network, Le Kremlin-Bicêtre, France
| | - Andoni Echaniz-Laguna
- AP-HP, Service de neurologie, CHU Bicêtre, Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares, CERAMIC, FILNEMUS Network, Le Kremlin-Bicêtre, France
- Université de Paris-Saclay, INSERM U1195, Le Kremlin-Bicêtre, France
| | - Clovis Adam
- AP-HP, Service d'Anatomopathologie Clinique, CHU Bicêtre, Le Kremlin-Bicêtre, France
| | - Michel S Slama
- AP-HP, Département de Cardiologie, CHU Bichat, Paris, France
| | - Anouar Benmalek
- Faculté de Pharmacie, Université Paris-Saclay, Gif-sur-Yvette, France
| | - Luca Leonardi
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sant'Andrea Hospital, Sapienza University of Rome, Roma, Italy
| | - François Rouzet
- AP-HP, Service de Médecine nucléaire, CHU Bichat, Paris, France
| | - David Adams
- AP-HP, Service de neurologie, CHU Bicêtre, Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares, CERAMIC, FILNEMUS Network, Le Kremlin-Bicêtre, France
- Université de Paris-Saclay, INSERM U1195, Le Kremlin-Bicêtre, France
| | - Vincent Algalarrondo
- AP-HP, Département de Cardiologie, CHU Bichat, Paris, France
- Université Paris Cité, Paris, France
| | - Guillemette Beaudonnet
- AP-HP, Service de neurologie, CHU Bicêtre, Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares, CERAMIC, FILNEMUS Network, Le Kremlin-Bicêtre, France
- AP-HP, Unité de Neurophysiologie Clinique et Epileptologie (UNCE), CHU Bicêtre, Le Kremlin-Bicêtre, France
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8
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Adams D, Sekijima Y, Conceição I, Waddington-Cruz M, Polydefkis M, Echaniz-Laguna A, Reilly MM. Hereditary transthyretin amyloid neuropathies: advances in pathophysiology, biomarkers, and treatment. Lancet Neurol 2023; 22:1061-1074. [PMID: 37863593 DOI: 10.1016/s1474-4422(23)00334-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 08/08/2023] [Accepted: 08/31/2023] [Indexed: 10/22/2023]
Abstract
Hereditary transthyretin (TTR) amyloid polyneuropathy is an autosomal dominant life-threatening disorder. TTR is produced mainly by the liver but also by the choroid plexus and retinal pigment epithelium. Detailed clinical characterisation, identification of clinical red flags for misdiagnosis, and use of biomarkers enable early diagnosis and treatment. In addition to liver transplantation and TTR stabilisers, three other disease-modifying therapies have regulatory approval: one antisense oligonucleotide (inotersen) and two small interfering RNAs (siRNAs; patisiran and vutrisiran). The siRNAs have been shown to stop progression of neuropathy and improve patients' quality of life. As none of the disease-modifying therapies can cross the blood-brain barrier, TTR deposition in the CNS, which can cause stroke and cognitive impairment, remains an important unaddressed issue. CRISPR-Cas9-based one-time TTR editing therapy is being investigated in a phase 1 clinical study. Identification of the earliest stages of pathogenesis in TTR variant carriers is a major challenge that needs addressing for optimal management.
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Affiliation(s)
- David Adams
- Department of Neurology, Bicêtre Centre Hospitalo Universitaire, AP-HP, INSERM U 1195, University Paris Saclay, Le Kremlin Bicetre, France.
| | - Yoshiki Sekijima
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan
| | - Isabel Conceição
- Department of Neurosciences and Mental Health, Centro Hospitalar Universitario Lisboas Norte-Hospital de Santa Maria and Centro de Estudos Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Marcia Waddington-Cruz
- Centro de Estudos em Paramiloidose Antonio Rodrigues de Mello, National Amyloidosis Referral Center, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Michael Polydefkis
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Andoni Echaniz-Laguna
- Department of Neurology, Centre Hospitalo Universitaire, AP-HP, INSERM U 1195, University Paris Saclay, Le Kremlin Bicetre Cedex, France
| | - Mary M Reilly
- Department of Neuromuscular Disease, University College London Institute of Neurology and the National Hospital of Neurology and Neurosurgery, London, UK
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9
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Bekele AT. Natriuretic Peptide Receptors (NPRs) as a Potential Target for the Treatment of Heart Failure. Curr Heart Fail Rep 2023; 20:429-440. [PMID: 37710133 DOI: 10.1007/s11897-023-00628-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/22/2023] [Indexed: 09/16/2023]
Abstract
PURPOSE OF REVIEW Heart failure is defined as a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. The natriuretic peptide is known to exert its biological action on the kidney, heart, blood vessels, renin-angiotensin system, autonomous nervous system, and central nervous system. The natriuretic peptide-natriuretic receptor system plays an important role in the regulation of blood pressure and body fluid volume through its pleiotropic effects. RECENT FINDINGS The clinical and animal studies suggest that natriuretic peptide-natriuretic receptors are important targets for the treatment of heart failure and other cardiovascular diseases. Even though attempts targeting natriuretic peptide receptors are underway for heart failure treatment, they seem insufficient despite the receptor systems' potential. This review summarizes natriuretic peptide-natriuretic receptor system's physiological actions and potential target for the treatment of heart failure. Natriuretic peptides play multiple roles in different parts of the body, almost all of the activities related to this receptor system appear to have the potential to be harnessed to treat heart failure or symptoms associated with heart failure.
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Affiliation(s)
- Adamu T Bekele
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia.
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10
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Radiolabeled Thioflavin-T Derivative PET Imaging for the Assessment of Cardiac Amyloidosis. Curr Cardiol Rep 2022; 24:1883-1891. [PMID: 36378483 DOI: 10.1007/s11886-022-01811-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/13/2022] [Indexed: 11/16/2022]
Abstract
PURPOSE OF REVIEW Cardiac amyloidosis (CA) is an often under-recognized cause of heart failure with preserved ejection fraction. The goal of the current paper was to review imaging modalities available for detecting cardiac amyloidosis. We wished to determine what modalities are available for the diagnosis of cardiac amyloidosis and what modalities could be utilized in the future. RECENT FINDINGS Early and delayed planar imaging of the chest currently plays a central role in the workup and diagnosis of CA. However, novel positron emission tomography (PET) tracers could play a large role in CA imaging in the future. There is an increasing body of literature supporting the use of targeted amyloid-binding PET radiotracers such as 11C-Pittsburgh compound B (11C-PIB), 18F-florbetapir, -flutemetamol, and -florbetaben for the detection of cardiac amyloid. While planar imaging currently plays a large role in the workup of CA, PET imaging could play an increasing important role in the future. The quantitative abilities of novel PET tracers could theoretically allow for the serial monitoring of patients and detection of response to therapy, and the sensitive nature of the tracers could allow for even earlier disease detection. Further work with large randomized controlled trial data is needed in the development and validation of PET tracers for cardiac amyloid and represents an exciting development within the realm of nuclear cardiology.
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11
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Heart diseases (autonomic dysfunctions)—Myocardial innervation imaging: 123I-MIBG planar scintigraphy and SPECT. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00057-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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12
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Myocardial innervation imaging: MIBG in clinical practice. IMAGING 2021. [DOI: 10.1556/1647.2021.00021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Abstract
123I-metaiodobenzylguanidine (MIBG) is a radiolabeled norepinephrine analog that can be used to investigate myocardial sympathetic innervation. 123I MIBG scintigraphy has been investigated with interest in many disease settings. In patients with systolic heart failure (HF), 123I MIBG scintigraphy can capture functional impairment and rarefaction of sympathetic terminals (which manifest as reduced early and late heart-to-mediastinum [H/M] ratio on planar scintigraphy), and increased sympathetic outflow (which can be visualized as high washout rate). These findings have been consistently associated with a worse outcome: most notably, a phase 3 trial found that patients with a late H/M 1.60 have a higher incidence of all-cause and cardiovascular mortality and life-threatening arrhythmias over a follow-up of less than 2 years. Despite these promising findings, 123I MIBG scintigraphy has not yet been recommended by major HF guidelines as a tool for additive risk stratification, and has then never entered the stage of widespread adoption into current clinical practice. 123I MIBG scintigraphy has been evaluated also in patients with myocardial infarction, genetic disorders characterized by an increased susceptibility to ventricular arrhythmias, and several other conditions characterized by impaired sympathetic myocardial innervation. In the present chapter we will summarize the state-of-the-art on cardiac 123I MIBG scintigraphy, the current unresolved issues, and the possible directions of future research.
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13
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Palmiero G, Vetrano E, Rubino M, Monda E, Dongiglio F, Lioncino M, Di Fraia F, Caiazza M, Verrillo F, Capodicasa L, Cerciello G, Manganelli F, Catalano M, D'Arienzo D, De Rimini ML, Ascione R, Golino P, Caso P, Ascione L, Limongelli G. The Role of New Imaging Technologies in the Diagnosis of Cardiac Amyloidosis. Heart Fail Clin 2021; 18:61-72. [PMID: 34776084 DOI: 10.1016/j.hfc.2021.07.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Cardiac amyloidosis is an infiltrative disorder caused by transthyretin or immunoglobulin free light-chain deposition, which determines clinical disease with similar phenotype but different time course, prognosis and therapy. Multimodality imaging is the cornerstone for disease diagnosis and management. Multimodality imaging has revolutionized the approach to the disease favoring its awareness and simplifying its diagnosis, especially in ATTR cardiac amyloidosis. This describes the different imaging tools, from the traditional to the more novel ones, and highlights the different approach in each different setting (prognosis, subtyping, prognosis, monitoring disease progression, and response to therapy).
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Affiliation(s)
- Giuseppe Palmiero
- Department of Cardiology, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy; Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy.
| | - Erica Vetrano
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Marta Rubino
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Emanuele Monda
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Francesca Dongiglio
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Michele Lioncino
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Francesco Di Fraia
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Martina Caiazza
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Federica Verrillo
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Laura Capodicasa
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Giuseppe Cerciello
- Haematology Unit (Building n. 2), Department of Clinical Medicine and Surgery, AOU Policlinico "Federico II", via Sergio Pansini 5, 80131 Naples, Italy
| | - Fiore Manganelli
- Neurology Unit (Building n. 17), Department of Neurosciences, Reproductive Medicine and Odontostomatology, AOU Policlinico "Federico II", via Sergio Pansini 5, 80131 Naples, Italy
| | - Mara Catalano
- Department of Nuclear Imaging, AORN Cardarelli Hospital, via Antonio Cardarelli 9, 80131 Naples, Italy
| | - Davide D'Arienzo
- Department of Nuclear Medicine, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Maria Luisa De Rimini
- Department of Nuclear Medicine, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Raffaele Ascione
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Paolo Golino
- Department of Cardiology, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Pio Caso
- Department of Cardiology, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Luigi Ascione
- Department of Cardiology, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy
| | - Giuseppe Limongelli
- Inherited and Rare Cardiovascular Diseases Unit, AORN Ospedale dei Colli - Monaldi Hospital, via Leonardo Bianchi SNC, 80131 Naples, Italy; Institute of Cardiovascular Sciences, University College of London and St. Bartholomew's Hospital, London, UK
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14
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Gimelli A, Liga R, Agostini D, Bengel FM, Ernst S, Hyafil F, Saraste A, Scholte AJHA, Verberne HJ, Verschure DO, Slart RHJA. The role of myocardial innervation imaging in different clinical scenarios: an expert document of the European Association of Cardiovascular Imaging and Cardiovascular Committee of the European Association of Nuclear Medicine. Eur Heart J Cardiovasc Imaging 2021; 22:480-490. [PMID: 33523108 DOI: 10.1093/ehjci/jeab007] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 01/08/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiac sympathetic activity plays a key role in supporting cardiac function in both health and disease conditions, and nuclear cardiac imaging has always represented the only way for the non-invasive evaluation of the functional integrity of cardiac sympathetic terminals, mainly through the use of radiopharmaceuticals that are analogues of norepinephrine and, in particular, with the use of 123I-mIBG imaging. This technique demonstrates the presence of cardiac sympathetic dysfunction in different cardiac pathologies, linking the severity of sympathetic nervous system impairment to adverse patient's prognosis. This article will outline the state-of-the-art of cardiac 123I-mIBG imaging and define the value and clinical applications in the different fields of cardiovascular diseases.
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Affiliation(s)
- Alessia Gimelli
- Department of Imaging, Fondazione Toscana/CNR Gabriele Monasterio1, via Moruzzi n.1, Pisa 56124, Italy
| | - Riccardo Liga
- Cardiac-Thoracic-Vascular Department, Università di Pisa, Pisa, Italy
| | - Denis Agostini
- Department of Nuclear Medicine, University Hospital of Normandy, CHU Cote de Nacre, Caen, France
| | - Frank M Bengel
- Department of Nuclear Medicine, Hannover Medical School (MHH), Hannover, Germany
| | - Sabine Ernst
- Royal Brompton and Harefield NHS Foundation Trust, National Heart and Lung Institute, Imperial College, London, UK
| | - Fabien Hyafil
- Department of Nuclear Medicine, European Hospital Georges-Pompidou, DMU IMAGINA, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris, France
| | - Antti Saraste
- Turku PET Centre, University of Turku, Turku, Finland.,Heart Center, Turku University Hospital, Turku, Finland
| | - Arthur J H A Scholte
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Hein J Verberne
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Derk O Verschure
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Cardiology, Zaans Medical Center, Zaandam, the Netherlands
| | - Riemer H J A Slart
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Centre, University Medical Center Groningen, Groningen, The Netherlands.,Faculty of Science and Technology, Biomedical Photonic Imaging, University of Twente, Enschede, The Netherlands
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15
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Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, Fontana M, Gheysens O, Gillmore JD, Glaudemans AWJM, Hanna MA, Hazenberg BPC, Kristen AV, Kwong RY, Maurer MS, Merlini G, Miller EJ, Moon JC, Murthy VL, Quarta CC, Rapezzi C, Ruberg FL, Shah SJ, Slart RHJA, Verberne HJ, Bourque JM. 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:e000029. [PMID: 34196223 DOI: 10.1161/hci.0000000000000029] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Sharmila Dorbala
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Yukio Ando
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Japan
| | - Sabahat Bokhari
- Columbia University Medical Center/New York Presbyterian Hospital, Columbia University, NY
| | - Angela Dispenzieri
- Division of Hematology, Division of Cardiovascular Diseases, and Department of Radiology, Division of Nuclear Medicine, Department of Medicine, Mayo Clinic, Rochester, MN
| | - Rodney H Falk
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Victor A Ferrari
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Marianna Fontana
- National Amyloidosis Centre, Division of Medicine, University College London, London, United Kingdom
| | - Olivier Gheysens
- Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium
| | - Julian D Gillmore
- National Amyloidosis Centre, Division of Medicine, University College London, London, United Kingdom
| | - Andor W J M Glaudemans
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Mazen A Hanna
- Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH
| | - Bouke P C Hazenberg
- Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Arnt V Kristen
- Department of Cardiology, University of Heidelberg, Heidelberg, Germany
| | - Raymond Y Kwong
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Mathew S Maurer
- Columbia University Medical Center/New York Presbyterian Hospital, Columbia University, NY
| | - Giampaolo Merlini
- Amyloidosis Research and Treatment Center, Foundation Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
- Department of Molecular Medicine, University of Pavia, Italy
| | - Edward J Miller
- Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT
| | - James C Moon
- National Amyloidosis Centre, Division of Medicine, University College London, London, United Kingdom
| | | | - C Cristina Quarta
- National Amyloidosis Centre, Division of Medicine, University College London, London, United Kingdom
| | - Claudio Rapezzi
- Cardiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater-University of Bologna, Bologna, Italy
| | - Frederick L Ruberg
- Amyloidosis Center and Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, MA
| | - Sanjiv J Shah
- Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Riemer H J A Slart
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Hein J Verberne
- Division of Hematology, Division of Cardiovascular Diseases, and Department of Radiology, Division of Nuclear Medicine, Department of Medicine, Mayo Clinic, Rochester, MN
- Department of Cardiology, University of Heidelberg, Heidelberg, Germany
| | - Jamieson M Bourque
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Molecular Medicine, University of Pavia, Italy
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16
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Jamal F, Rosenzweig M. Amyloidosis with Cardiac Involvement: Identification, Characterization, and Management. Curr Hematol Malig Rep 2021; 16:357-366. [PMID: 34106429 PMCID: PMC8367912 DOI: 10.1007/s11899-021-00626-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Amyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available. RECENT FINDINGS New imaging methods have proven to be considerably valuable in the identification of cardiac amyloid infiltration. For treating clinicians, a diagnostic algorithm for patients with suspected amyloidosis with or without cardiomyopathy is shown to help classify disease and to direct appropriate genetic testing and management. For patients with light chain disease, recently introduced treatments adopted from multiple myeloma therapies have significantly extended progression-free and overall survival as well as organ response. In addition, new medical interventions are now available for those with transthyretin amyloidosis. Although cardiac amyloidosis contributes significantly to the morbidity and mortality associated with systemic disease, new tools are available to assist with diagnosis, prognosis, and management.
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Affiliation(s)
- Faizi Jamal
- Department of Medicine, Division of Cardiology, City of Hope, Duarte, CA, USA
| | - Michael Rosenzweig
- Department of Hematology, City of Hope, 1500 E Duarte Rd. Duarte, CA, Duarte, CA, 91010, USA.
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17
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Vidal-Perez R, Vázquez-García R, Barge-Caballero G, Bouzas-Mosquera A, Soler-Fernandez R, Larrañaga-Moreira JM, Crespo-Leiro MG, Vazquez-Rodriguez JM. Diagnostic and prognostic value of cardiac imaging in amyloidosis. World J Cardiol 2020; 12:599-614. [PMID: 33391613 PMCID: PMC7754383 DOI: 10.4330/wjc.v12.i12.599] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 09/28/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
Amyloidosis is an infiltrative disease caused by extracellular protein deposition that has accumulated a lot of scientific production in recent years. Different types of amyloidosis can affect the heart. Transthyretin amyloidosis and light chain amyloidosis are the two most common types of cardiac amyloidosis. These entities have a poor prognosis, so accurate diagnostic techniques are imperative for determining an early therapeutic approach. Recent advances in cardiac imaging and diagnostic strategies show that these tools are safe and can avoid the use of invasive diagnostic techniques to histological confirmation, such as endomyocardial biopsy. We performed a review on the diagnostic and prognostic implications of different cardiac imaging techniques in cardiac amyloidosis. We mainly focus on reviewing echocardiography, cardiac magnetic resonance, computed tomography and nuclear imaging techniques and the different safety measurements that can be done with each of them.
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Affiliation(s)
- Rafael Vidal-Perez
- Servicio de Cardiología, Unidad de Imagen y Función Cardíaca, Complexo Hospitalario Universitario A Coruña (CHUAC), Santiago de Compostela 15706, A Coruña, Spain
| | - Raquel Vázquez-García
- Servicio de Cardiología, Complexo Hospitalario Universitario A Coruña (CHUAC), A Coruña 15006, A Coruña, Spain
| | - Gonzalo Barge-Caballero
- Servicio de Cardiología, Complexo Hospitalario Universitario A Coruña, Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco, Instituto de Investigación Biomédica de A Coruña (INIBIC), Centro de Investigación Biomédica en Red (CIBERCV)-Instituto de Salud Carlos III, A Coruña 15006, A Coruña, Spain
| | - Alberto Bouzas-Mosquera
- Servicio de Cardiología, Unidad de Imagen y Función Cardíaca, Complexo Hospitalario Universitario A Coruña (CHUAC), Santiago de Compostela 15706, A Coruña, Spain
| | - Rafaela Soler-Fernandez
- Servicio de Cardiología, Complexo Hospitalario Universitario A Coruña (CHUAC), A Coruña 15006, A Coruña, Spain
| | | | - Maria Generosa Crespo-Leiro
- Servicio de Cardiología, Complexo Hospitalario Universitario A Coruña, Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco, Instituto de Investigación Biomédica de A Coruña (INIBIC), Centro de Investigación Biomédica en Red (CIBERCV)-Instituto de Salud Carlos III, A Coruña 15006, A Coruña, Spain
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18
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Gimelli A, Aimo A, Vergaro G, Genovesi D, Santonato V, Kusch A, Emdin M, Marzullo P. Cardiac sympathetic denervation in wild-type transthyretin amyloidosis. Amyloid 2020; 27:237-243. [PMID: 32441155 DOI: 10.1080/13506129.2020.1769059] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Tissue accumulation of misfolded transthyretin (TTR) may occur because of TTR gene mutations (variant amyloid TTR amyloidosis, ATTRv), or as an age-related phenomenon (wild-type ATTR, ATTRwt). Cardiac sympathetic denervation has been reported in ATTRv, but has never been investigated in ATTRwt. METHODS Fifteen consecutive patients with ATTRwt cardiomyopathy (81% men, median age 82 years, no one with prior myocardial infarction) underwent Cadmium Zinc Telluride tomographic imaging for amyloid burden (99mTc-hydroxymethylene diphosphonate - 99mTc-HMDP), innervation (123I-metaiodobenzylguanidine - 123I-MIBG), and perfusion (99mTc-tetrofosmin). RESULTS Median summed 99mTc-HMDP score was 60 (58-62), denoting a severe and diffuse amyloid burden. Planar 123I-MIBG examination showed decreased early and late H/M ratios (late H/M ratio: 1.5 [1.3-1.6], range 1.2-1.9, reference value ≥2.0). Summed 123I-MIBG score was 12 (6-22), with the most prominent denervation in the infero-septal, inferior, and infero-lateral regions; summed rest score was 7 (5-11), with lowest degrees of myocardial perfusion in the inferior and infero-septal regions. The correlation between amyloid burden (as relative 99mTc-HMDP uptake) and innervation (as relative 123I-MIBG uptake) did not achieve statistical significance at both segmental (p = .252) and regional level (p = .251). Nevertheless, denervation tended to worsen in parallel with the amyloid burden, and 123I-MIBG scores increased with 99mTc-HMDP scores. Segments and regions with prominent hypoperfusion also showed a higher degree of denervation (r = 0.500 and 0.591, respectively; both p < .001). CONCLUSIONS Patients with ATTRwt cardiomyopathy display cardiac sympathetic denervation, particularly in the inferior and septal myocardial wall. Myocardial hypoperfusion has a similar regional pattern, while the amyloid burden is more extensive.
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Affiliation(s)
| | - Alberto Aimo
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Giuseppe Vergaro
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy.,Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
| | | | | | | | - Michele Emdin
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy.,Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
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19
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Frantellizzi V, Cosma L, Pani A, Pontico M, Conte M, De Angelis C, De Vincentis G. Role of Nuclear Imaging in Cardiac Amyloidosis Management: Clinical Evidence and Review of Literature. Curr Med Imaging 2020; 16:957-966. [PMID: 33081658 DOI: 10.2174/1573405615666191210103452] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 10/28/2019] [Accepted: 11/19/2019] [Indexed: 11/22/2022]
Abstract
Cardiac amyloidosis (CA) is an infiltrative disease characterized by the extracellular deposition of fibrils, amyloid, in the heart. The vast majority of patients with CA has one of two types between transthyretin amyloid (ATTR) and immunoglobulin light chain associated amyloid (AL), that have different prognosis and therapeutic options. CA is often underdiagnosed. The histological analysis of endomyocardial tissue is the gold standard for the diagnosis, although it has its limitations due to its invasive nature. Nuclear medicine now plays a key role in the early and accurate diagnosis of this disease, and in the ability to distinguish between the two forms. Recent several studies support the potential advantage of bone-seeking radionuclides as a screening technique for the most common types of amyloidosis, in particular ATTR form. This review presents noninvasive modalities to diagnose CA and focuses on the radionuclide imaging techniques (bone-seeking agents scintigraphy, cardiac sympathetic innervation and positron emission tomography studies) available to visualize myocardial amyloid involvement. Furthermore, we report the case of an 83-year old male with a history of prostate cancer, carcinoma of the cecum and kidney cancer, submitted to bone scan to detect bone metastasis, that revealed a myocardial uptake of 99mTC-HMPD suggestive of ATTR CA. An accurate and early diagnosis of CA able to distinguish beyween AL and ATTR CA combined to the improving therapies could improve the survival of patients with this disease.
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Affiliation(s)
- Viviana Frantellizzi
- Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Laura Cosma
- Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Arianna Pani
- School of Clinical Pharmacology and Toxicology, University of Milan, Milan, Italy
| | - Mariano Pontico
- Program in Morphogenesis & Tissue Engineering, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Miriam Conte
- Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Cristina De Angelis
- Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Giuseppe De Vincentis
- Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
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20
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Jonker DL, Hazenberg BPC, Nienhuis HLA, Slart RHJA, Glaudemans AWJM, Noordzij W. Imaging cardiac innervation in hereditary transthyretin (ATTRm) amyloidosis: A marker for neuropathy or cardiomyopathy in case of heart failure? J Nucl Cardiol 2020; 27:1774-1784. [PMID: 30374850 PMCID: PMC7599160 DOI: 10.1007/s12350-018-01477-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 10/01/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nuclear imaging modalities using 123Iodine-metaiodobenzylguanidine (123I-MIBG) and bone seeking tracers identify early cardiac involvement in ATTRm amyloidosis patients. However, little is known whether results from 123I-MIBG scintigraphy actually correlate to markers for either cardiac autonomic neuropathy or cardiomyopathy. METHODS All TTR mutation carriers and ATTRm patients who underwent both 123I-MIBG and 99mTechnetium-hydroxymethylene diphosphonate (99mTc-HDP) scintigraphy were included. Cardiomyopathy was defined as NT-proBNP > 365 ng/L, and cardiac autonomic neuropathy as abnormal cardiovascular reflexes at autonomic function tests. Late 123I-MIBG heart-to-mediastinum ratio (HMR) < 2.0 or wash-out > 20%, and any cardiac 99mTc-HDP uptake were considered as abnormal. RESULTS 39 patients (13 carriers and 26 ATTRm patients) were included in this study. Patients with cardiomyopathy, with or without cardiac autonomic neuropathy, had lower late HMR than similar patients without cardiomyopathy [median 1.1 (range 1.0-1.5) and 1.5(1.2-2.6) vs 2.4 (1.4-3.8) and 2.5 (1.5-3.7), respectively, P < 0.001]. Late HMR and wash-out (inversely) correlated with NT-proBNP r = - 0.652 (P < 0.001) and r = 0.756 (P < 0.001), respectively. Furthermore, late HMR and wash-out (inversely) correlated with cardiac 99mTc-HDP uptake r = - 0.663 (P < 0.001) and r = 0.617 (P < 0.001), respectively. CONCLUSION In case of heart failure, 123I-MIBG scintigraphy reflects cardiomyopathy rather than cardiac autonomic neuropathy in ATTRm patients and TTR mutation carriers. 123I-MIBG scintigraphy may already be abnormal before any cardiac bone tracer uptake is visible.
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Affiliation(s)
- Daphne L. Jonker
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Bouke P. C. Hazenberg
- Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Hans L. A. Nienhuis
- Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Riemer H. J. A. Slart
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Biomedical Photonic Imaging, University of Twente, Enschede, The Netherlands
| | - Andor W. J. M. Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Walter Noordzij
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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21
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Monfort A, Banydeen R, Demoniere F, Courty B, Codiat R, Neviere R, Inamo J. Restrictive cardiac phenotype as primary cause of impaired aerobic capacity in Afro-Caribbean patients with val122ile variant transthyretin amyloid cardiomyopathy. Amyloid 2020; 27:145-152. [PMID: 32024385 DOI: 10.1080/13506129.2020.1722098] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background: Impaired aerobic capacity in cardiac amyloidosis patients may be related to limited inotropic myocardial reserve and heart rate (HR) response limiting cardiac output rise. This study sought to investigate whether chronotropic incompetence (CI) and blunted HR recovery would be prevalent in patients with mutant transthyretin (ATTRv) cardiomyopathy.Methods and results: Eighteen ATTRv (Val122Ile) patients (72 ± 8-year) and 15 age-matched controls (73 ± 3-year) were prospectively enrolled. Patients' medical records, pulmonary function and cardiopulmonary exercise testing, including non-invasive cardiac hemodynamics and chronotropic response were studied. Compared with age-matched controls, maximal workload (91 ± 8 vs. 65 ± 20 watts) and peak VO2 (19.5 ± 3.0 vs. 14.4 ± 4.1 mL.kg-1.min-1) were lower in ATTRv patients. Despite reaching similar age-predicted maximal HR, ATTRv patients displayed smaller changes in stroke volume (SV) index relative to change in VO2 (49 ± 26 vs. 67 ± 18%). Adequate chronotropic-metabolic index was prevalent in ATTRv patients. HR recovery, as percent decrease in peak HR at 1 and 3-min, was blunded ATTv patients.Conclusions: In Val122Ile ATTRv patients, chronotropic response was appropriate relative to exercise intensity with only few patients displaying CI. HR response to exercise was further characterised by blunted HR recovery in ATTRv patients suggesting lower parasympathetic activity and greater sympathetic stimulation compared with controls.
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Affiliation(s)
- Astrid Monfort
- Department of Cardiology CHU Martinique, University Hospital of Martinique, Fort de France, France.,Cardiovascular Research Team EA7525, Antilles University, Pointe-à-Pitre, France
| | - Rishika Banydeen
- Cardiovascular Research Team EA7525, Antilles University, Pointe-à-Pitre, France.,Department of Epidemiology and Biostatistics CHU Martinique, University Hospital of Martinique, Fort de France, France
| | - Fabrice Demoniere
- Department of Cardiology CHU Martinique, University Hospital of Martinique, Fort de France, France
| | - Baptiste Courty
- Department of Cardiology CHU Martinique, University Hospital of Martinique, Fort de France, France
| | - Rebecca Codiat
- Department of Cardiology CHU Martinique, University Hospital of Martinique, Fort de France, France
| | - Remi Neviere
- Department of Cardiology CHU Martinique, University Hospital of Martinique, Fort de France, France.,Cardiovascular Research Team EA7525, Antilles University, Pointe-à-Pitre, France
| | - Jocelyn Inamo
- Department of Cardiology CHU Martinique, University Hospital of Martinique, Fort de France, France.,Cardiovascular Research Team EA7525, Antilles University, Pointe-à-Pitre, France
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22
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Khor YM, Cuddy S, Falk RH, Dorbala S. Multimodality Imaging in the Evaluation and Management of Cardiac Amyloidosis. Semin Nucl Med 2020; 50:295-310. [PMID: 32540027 PMCID: PMC9440475 DOI: 10.1053/j.semnuclmed.2020.01.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Systemic amyloidosis is a heterogeneous group of disorders where misfolded proteins deposit in the various organs as nonbranching fibrils with a β-pleated-sheet structure called amyloid. Extensive extracellular deposition of these amyloid fibrils eventually leads to organ dysfunction. Involvement of the heart, termed as cardiac amyloidosis, leads to heart failure if left untreated and carries high morbidity and mortality. Current interest in cardiac amyloidosis is growing rapidly thanks to the recent development of effective targeted treatment options, driving the need for better and earlier detection of the condition, which is largely underdiagnosed and far commoner than recognized. Timely diagnosis of cardiac amyloidosis is challenging, but is poised to improve with emergence of newer noninvasive imaging techniques, potentially obviating the need for endomyocardial biopsy in some patients and providing prognostic information. With recent advances in the therapeutic options for cardiac amyloidosis, an area of immense interest is the adoption of imaging as biomarkers for longitudinal assessment of disease progression and treatment response. In this article, we provide an overview of cardiac amyloidosis, discuss the role of imaging modalities in cardiac amyloidosis, and explore future directions for imaging in cardiac amyloidosis.
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Affiliation(s)
- Yiu Ming Khor
- Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Singapore
| | - Sarah Cuddy
- CV imaging program, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA
| | - Rodney H Falk
- Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA
| | - Sharmila Dorbala
- Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Division of Nuclear Medicine, Department of Radiology, Brigham and Women's Hospital, Boston, MA.
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23
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Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy. J Neurol 2020; 268:2109-2122. [PMID: 31907599 PMCID: PMC8179912 DOI: 10.1007/s00415-019-09688-0] [Citation(s) in RCA: 163] [Impact Index Per Article: 32.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 12/11/2022]
Abstract
Amyloid transthyretin (ATTR) amyloidosis with polyneuropathy (PN) is a progressive, debilitating, systemic disease wherein transthyretin protein misfolds to form amyloid, which is deposited in the endoneurium. ATTR amyloidosis with PN is the most serious hereditary polyneuropathy of adult onset. It arises from a hereditary mutation in the TTR gene and may involve the heart as well as other organs. It is critical to identify and diagnose the disease earlier because treatments are available to help slow the progression of neuropathy. Early diagnosis is complicated, however, because presentation may vary and family history is not always known. Symptoms may be mistakenly attributed to other diseases such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), idiopathic axonal polyneuropathy, lumbar spinal stenosis, and, more rarely, diabetic neuropathy and AL amyloidosis. In endemic countries (e.g., Portugal, Japan, Sweden, Brazil), ATTR amyloidosis with PN should be suspected in any patient who has length-dependent small-fiber PN with autonomic dysfunction and a family history of ATTR amyloidosis, unexplained weight loss, heart rhythm disorders, vitreous opacities, or renal abnormalities. In nonendemic countries, the disease may present as idiopathic rapidly progressive sensory motor axonal neuropathy or atypical CIDP with any of the above symptoms or with bilateral carpal tunnel syndrome, gait disorders, or cardiac hypertrophy. Diagnosis should include DNA testing, biopsy, and amyloid typing. Patients should be followed up every 6–12 months, depending on the severity of the disease and response to therapy. This review outlines detailed recommendations to improve the diagnosis of ATTR amyloidosis with PN.
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24
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Fukushima K, Nakano S, Matsunari I. Cardiac Amyloidosis: Current Diagnostic Strategies Using Multimodality Imaging. ANNALS OF NUCLEAR CARDIOLOGY 2020; 6:67-73. [PMID: 37123486 PMCID: PMC10133936 DOI: 10.17996/anc.20-00130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 07/27/2020] [Accepted: 07/27/2020] [Indexed: 05/02/2023]
Abstract
Amyloidosis is a systemic disorder in which abnormal amyloid proteins deposit in body organs, leading to organ dysfunction and death. Cardiac amyloid deposition, causing a sort of restrictive cardiomyopathy and associated with increased risk of mortality. Most cases of cardiac amyloidosis are of either light chain or transthyretin type. Early and accurate diagnosis of cardiac amyloidosis may improve outcomes. However, diagnosis requires systematic approach including electrocardiography and biomarkers when encountered suspicious candidate. Diagnosis by multimodality noninvasive imaging have been substantially studied and established for differentiation from subtypes. Recent advance in the treatment of amyloidosis offers therapeutic monitoring and prognosis.
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Affiliation(s)
- Kenji Fukushima
- Department of Nuclear Medicine, Heart Center, Saitama Medical University International Medical Center, Saitama, Japan
- Department of Cardiology, Heart Center, Saitama Medical University International Medical Center, Saitama, Japan
- Reprint requests and correspondence: Kenji Fukushima, MD, PhD, Department of Nuclear Medicine, Heart Center, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350–1298, Japan / E-mail:
| | - Shintaro Nakano
- Department of Cardiology, Heart Center, Saitama Medical University International Medical Center, Saitama, Japan
| | - Ichiro Matsunari
- Department of Nuclear Medicine, Saitama Medical University, Saitama, Japan
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25
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Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, Fontana M, Gheysens O, Gillmore JD, Glaudemans AWJM, Hanna MA, Hazenberg BPC, Kristen AV, Kwong RY, Maurer MS, Merlini G, Miller EJ, Moon JC, Murthy VL, Quarta CC, Rapezzi C, Ruberg FL, Shah SJ, Slart RHJA, Verberne HJ, Bourque JM. 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; 26:2065-2123. [PMID: 31468376 DOI: 10.1007/s12350-019-01760-6] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Sharmila Dorbala
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
| | - Yukio Ando
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Sabahat Bokhari
- Columbia University Medical Center/New York Presbyterian Hospital, Columbia University, New York, NY, USA
| | - Angela Dispenzieri
- Division of Hematology, Division of Cardiovascular Diseases, and Department of Radiology, Division of Nuclear Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Rodney H Falk
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
| | - Victor A Ferrari
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Marianna Fontana
- Division of Medicine, National Amyloidosis Centre, University College London, London, UK
| | - Olivier Gheysens
- Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium
| | - Julian D Gillmore
- Division of Medicine, National Amyloidosis Centre, University College London, London, UK
| | - Andor W J M Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Mazen A Hanna
- Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Bouke P C Hazenberg
- Department of Rheumatology & Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Arnt V Kristen
- Department of Cardiology, University of Heidelberg, Heidelberg, Germany
| | - Raymond Y Kwong
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
| | - Mathew S Maurer
- Columbia University Medical Center/New York Presbyterian Hospital, Columbia University, New York, NY, USA
| | - Giampaolo Merlini
- Amyloidosis Research and Treatment Center, Foundation Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Edward J Miller
- Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - James C Moon
- Division of Medicine, National Amyloidosis Centre, University College London, London, UK
| | | | - C Cristina Quarta
- Division of Medicine, National Amyloidosis Centre, University College London, London, UK
| | - Claudio Rapezzi
- Cardiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater-University of Bologna, Bologna, Italy
| | - Frederick L Ruberg
- Amyloidosis Center and Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA
| | - Sanjiv J Shah
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Riemer H J A Slart
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Hein J Verberne
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jamieson M Bourque
- Departments of Medicine and Radiology, Cardiovascular Imaging Center, University of Virginia, Charlottesville, VA, USA
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26
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González-Duarte A, Berk JL, Quan D, Mauermann ML, Schmidt HH, Polydefkis M, Waddington-Cruz M, Ueda M, Conceição IM, Kristen AV, Coelho T, Cauquil CA, Tard C, Merkel M, Aldinc E, Chen J, Sweetser MT, Wang JJ, Adams D. Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis. J Neurol 2019; 267:703-712. [PMID: 31728713 PMCID: PMC7035216 DOI: 10.1007/s00415-019-09602-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 10/21/2019] [Accepted: 10/23/2019] [Indexed: 12/13/2022]
Abstract
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.
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Affiliation(s)
- Alejandra González-Duarte
- Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Sección XVI, Tlalpan, CdMx, CP 01400, México City, Mexico.
| | | | | | | | | | | | | | | | - Isabel M Conceição
- CHULN, Hospital de Santa Maria and Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | | | - Teresa Coelho
- Hospital de Santo António, Centro Hospitalar Universitário Do Porto, Porto, Portugal
| | - Cécile A Cauquil
- AP-HP Université Paris Saclay, CHU Bicêtre, Le Kremlin Bicêtre, France
| | | | | | | | | | | | | | - David Adams
- AP-HP, Université Paris Saclay, CHU Bicêtre, Université Paris-Sud, INSERM 1195, Paris, France
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27
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Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, Fontana M, Gheysens O, Gillmore JD, Glaudemans AWJM, Hanna MA, Hazenberg BPC, Kristen AV, Kwong RY, Maurer MS, Merlini G, Miller EJ, Moon JC, Murthy VL, Quarta CC, Rapezzi C, Ruberg FL, Shah SJ, Slart RHJA, Verberne HJ, Bourque JM. 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 Card Fail 2019; 25:e1-e39. [PMID: 31473268 DOI: 10.1016/j.cardfail.2019.08.001] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Sharmila Dorbala
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
| | - Yukio Ando
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Sabahat Bokhari
- Columbia University Medical Center/New York Presbyterian Hospital, Columbia University, New York, New York
| | - Angela Dispenzieri
- Division of Hematology, Division of Cardiovascular Diseases, and Department of Radiology, Division of Nuclear Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Rodney H Falk
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
| | - Victor A Ferrari
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Marianna Fontana
- Division of Medicine, National Amyloidosis Centre, University College London, London, United Kingdom
| | - Olivier Gheysens
- Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium
| | - Julian D Gillmore
- Division of Medicine, National Amyloidosis Centre, University College London, London, United Kingdom
| | - Andor W J M Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Mazen A Hanna
- Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
| | - Bouke P C Hazenberg
- Department of Rheumatology & Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Arnt V Kristen
- Department of Cardiology, University of Heidelberg, Heidelberg, Germany
| | - Raymond Y Kwong
- Cardiac Amyloidosis Program, Cardiovascular Imaging Program, Departments of Radiology and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
| | - Mathew S Maurer
- Columbia University Medical Center/New York Presbyterian Hospital, Columbia University, New York, New York
| | - Giampaolo Merlini
- Amyloidosis Research and Treatment Center, Foundation Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Edward J Miller
- Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - James C Moon
- Division of Medicine, National Amyloidosis Centre, University College London, London, United Kingdom
| | | | - C Cristina Quarta
- Division of Medicine, National Amyloidosis Centre, University College London, London, United Kingdom
| | - Claudio Rapezzi
- Cardiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater-University of Bologna, Bologna, Italy
| | - Frederick L Ruberg
- Amyloidosis Center and Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
| | - Sanjiv J Shah
- Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Riemer H J A Slart
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Hein J Verberne
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jamieson M Bourque
- Departments of Medicine and Radiology, Cardiovascular Imaging Center, University of Virginia, Charlottesville, Virginia
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28
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Nicol M, Baudet M, Cescau A, Harel S, Royer B, Sarda-Mantel L, Cohen-Solal A, Arnulf B, Logeart D. Prognostic Value of Iodine-123-Metaiodobenzylguanidine Scintigraphy in Light-Chain Amyloidosis. Circ Cardiovasc Imaging 2019; 12:e009465. [DOI: 10.1161/circimaging.119.009465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Martin Nicol
- Assistance Publique Hopitaux de Paris, Groupe Hospitalier Saint-Louis Lariboisière, Paris, France (M.N., A.C., M.B., A. C.-S., D.L
| | - Mathilde Baudet
- Assistance Publique Hopitaux de Paris, Groupe Hospitalier Saint-Louis Lariboisière, Paris, France (M.N., A.C., M.B., A. C.-S., D.L
| | - Arthur Cescau
- Assistance Publique Hopitaux de Paris, Groupe Hospitalier Saint-Louis Lariboisière, Paris, France (M.N., A.C., M.B., A. C.-S., D.L
| | | | | | - Laure Sarda-Mantel
- in Haematology Department, L.S.-M
- in Nuclear Medicine Department). Université de Paris, Paris, France (L.S.-M., A.C.-S., B.A., D.L.)
| | - Alain Cohen-Solal
- Assistance Publique Hopitaux de Paris, Groupe Hospitalier Saint-Louis Lariboisière, Paris, France (M.N., A.C., M.B., A. C.-S., D.L
- in Nuclear Medicine Department). Université de Paris, Paris, France (L.S.-M., A.C.-S., B.A., D.L.)
- Inserm U942, Paris, France (A.C.-S., D.L.)
| | - Bertrand Arnulf
- in Cardiology Department, S.H., B.R., B.A
- in Nuclear Medicine Department). Université de Paris, Paris, France (L.S.-M., A.C.-S., B.A., D.L.)
| | - Damien Logeart
- Assistance Publique Hopitaux de Paris, Groupe Hospitalier Saint-Louis Lariboisière, Paris, France (M.N., A.C., M.B., A. C.-S., D.L
- in Nuclear Medicine Department). Université de Paris, Paris, France (L.S.-M., A.C.-S., B.A., D.L.)
- Inserm U942, Paris, France (A.C.-S., D.L.)
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Strategies to improve the quality of life in patients with hereditary transthyretin amyloidosis (hATTR) and autonomic neuropathy. Clin Auton Res 2019; 29:25-31. [PMID: 31506870 PMCID: PMC6763624 DOI: 10.1007/s10286-019-00624-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 07/30/2019] [Indexed: 12/11/2022]
Abstract
Purpose Hereditary transthyretin amyloidosis (hATTR) is a severe adult-onset progressive disease mainly involving the peripheral nervous system and the heart, with a prominent impact on the autonomic nervous system. This review summarizes the clinical aspects of autonomic dysfunction in hATTR, and their impact on quality of life as well as potential therapeutic options. Methods Literature review. Results Autonomic dysfunction, causing neurogenic orthostatic hypotension, gastroparesis, constipation, diarrhea, bladder dysfunction, and erectile dysfunction in males, has a major impact on the quality of life of patients with hATTR. Improvement of qualify of life in patients with hATTR implies periodic symptomatic screening and early management, taking into consideration comorbidities and medication side effects. The specific effect of the disease-modifying treatment on this aspect remains to be unraveled. Conclusions Management of autonomic dysfunction in patients with hAATR is feasible and can result in improved qualify of life. Novel disease-modifying treatments for hAATR may contribute to improve autonomic dysfunction, although specific studies are required.
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Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol 2019; 15:387-404. [PMID: 31209302 DOI: 10.1038/s41582-019-0210-4] [Citation(s) in RCA: 276] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/18/2019] [Indexed: 02/06/2023]
Abstract
Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis with polyneuropathy (also known as familial amyloid polyneuropathy) is a condition with adult onset caused by mutation of transthyretin (TTR) and characterized by extracellular deposition of amyloid and destruction of the somatic and autonomic PNS, leading to loss of autonomy and death. This disease represents a model of the scientific and medical progress of the past 30 years. ATTRv amyloidosis is a worldwide disease with broad genetic and phenotypic heterogeneity that presents a diagnostic challenge for neurologists. The pathophysiology of the neuropathy is increasingly understood and includes instability and proteolysis of mutant TTR leading to deposition of amyloid with variable lengths of fibrils, microangiopathy and involvement of Schwann cells. Wild-type TTR is amyloidogenic in older individuals. The main symptoms are neuropathic, but the disease is systemic; neurologists should be aware of cardiac, eye and kidney involvement that justify a multidisciplinary approach to management. Infiltrative cardiomyopathy is usually latent but present in half of patients. Disease-modifying therapeutics that have been developed include liver transplantation and TTR stabilizers, both of which can slow progression of the disease and increase survival in the early stages. Most recently, gene-silencing drugs have been used to control disease in the more advanced stages and produce some degree of improvement.
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Correction to: Reference Ranges for the Size of the Fetal Cardiac Outflow Tracts From 13 to 36 Weeks Gestation: A Single-Center Study of Over 7000 Cases. Circ Cardiovasc Imaging 2019; 12:e000025. [PMID: 30866649 DOI: 10.1161/hci.0000000000000025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Pelletier-Galarneau M, Abikhzer G, Giraldeau G, Harel F. Molecular Imaging of Cardiac Amyloidosis. Curr Cardiol Rep 2019; 21:12. [DOI: 10.1007/s11886-019-1097-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Algalarrondo V, Piekarski E, Eliahou L, Le Guludec D, Slama MS, Rouzet F. Can Nuclear Imaging Techniques Predict Patient Outcome and Guide Medical Management in Hereditary Transthyretin Cardiac Amyloidosis? Curr Cardiol Rep 2018; 20:33. [PMID: 29574587 DOI: 10.1007/s11886-018-0976-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
PURPOSE OF REVIEW Nuclear imaging recently gained a key role in the diagnosis and prognostic assessment of transthyretin (TTR)-related cardiac amyloidosis. This review aims at summarizing the state-of-the art regarding the implementation of nuclear imaging in the management of hereditary mutated TTR-cardiac amyloidosis (mTTR-CA). RECENT FINDINGS Although cardiac uptake of bone tracers is acknowledged as a specific marker of TTR amyloid cardiac burden, recent studies validated the implementation of bone scan in the flow chart for non-invasive diagnosis and follow-up of CA in multicenter trials. Simultaneously, cardiac denervation evidenced by MIBG scintigraphy proved to be a strong and independent prognostic marker of poor outcome in mTTR-CA. By its unique ability to assess both amyloid burden and cardiac denervation, nuclear imaging may prove useful as part of multimodality imaging tools to trigger treatment initiation and monitoring in patients with mTTR-CA.
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Affiliation(s)
- Vincent Algalarrondo
- Cardiology Department, Antoine Béclère Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), UMR-S 1180, University of Paris-Sud, Clamart, France.,French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies (CRMR-NNERF), Bicêtre, France
| | - Eve Piekarski
- Nuclear Medicine Department and DHU FIRE, Bichat Claude Bernard Hospital, AP-HP, University Paris VII, Paris, France.,Inserm UMR-S 1148, Paris, France
| | - Ludivine Eliahou
- Cardiology Department, Antoine Béclère Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), UMR-S 1180, University of Paris-Sud, Clamart, France.,French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies (CRMR-NNERF), Bicêtre, France
| | - Dominique Le Guludec
- Nuclear Medicine Department and DHU FIRE, Bichat Claude Bernard Hospital, AP-HP, University Paris VII, Paris, France.,Inserm UMR-S 1148, Paris, France
| | - Michel S Slama
- Cardiology Department, Antoine Béclère Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), UMR-S 1180, University of Paris-Sud, Clamart, France.,French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies (CRMR-NNERF), Bicêtre, France
| | - François Rouzet
- Nuclear Medicine Department and DHU FIRE, Bichat Claude Bernard Hospital, AP-HP, University Paris VII, Paris, France. .,Inserm UMR-S 1148, Paris, France.
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