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Camafort M, Kasiakogias A, Agabiti-Rosei E, Masi S, Iliakis P, Benetos A, Jeong JO, Lee HY, Muiesan ML, Sudano I, Tsioufis C. Hypertensive heart disease in older patients: considerations for clinical practice. Eur J Intern Med 2025; 134:75-88. [PMID: 39955235 DOI: 10.1016/j.ejim.2024.12.034] [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: 09/27/2024] [Revised: 12/21/2024] [Accepted: 12/30/2024] [Indexed: 02/17/2025]
Abstract
Appropriate management of older people with hypertension is essential to reduce the burden of hypertensive heart disease and further cardiovascular sequelae but there may be challenges given the presence of concurrent senescent changes, comorbidities and impairment in functionality. It is recommended that frailty level and functional status are assessed periodically to understand patient needs and to guide treatment decisions. Office blood pressure should be measured with an appropriate cuff as per standard guidelines. There should be a high index of suspicion for orthostatic hypotension and white coat/masked hypertension, both common in older individuals. Cardiac imaging often identifies age-related changes that may not result from hypertension alone, including smaller ventricular volumes, a sigmoid septum and non-ischaemic fibrosis. Diastolic dysfunction is common and other pathologies, including cardiac amyloidosis, may need to be considered in the presence of red flags. Screening for atrial fibrillation during blood pressure evaluation is advised. Decisions for blood pressure management should follow current recommendations and take into consideration the patient's age and tolerance. There is limited evidence regarding heart failure management in older patients, however, disease-modifying therapy as per guidelines should be pursued. Sufficient outcome data are lacking for this patient group and a multidisciplinary approach is often needed to design optimal therapy.
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Affiliation(s)
- Miguel Camafort
- Hypertension Unit, Department of Internal Medicine, Hospital Clinic, University of Barcelona, Spain; Biomedical Research Network Center for the Pathophysiology of Obesity and Nutrition (CIBER-OBN), Carlos III Health Institute, Spain
| | - Alexandros Kasiakogias
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece.
| | - Enrico Agabiti-Rosei
- Department of Clinical and Experimental Sciences, University of Brescia, Italy and IRCCS Multimedica, Milan, Italy
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Panagiotis Iliakis
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Athanase Benetos
- Department of Geriatric Medicine and INSERM DCAC, CHRU-Nancy, Université de Lorraine, Nancy, France
| | - Jin-Ok Jeong
- Division of Cardiology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Hae-Young Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Maria Lorenza Muiesan
- Department of Clinical and Experimental Sciences, Centro per la Prevenzione e Cura dell'ipertensione Arteriosa, University of Brescia and ASST Spedali Civili, Brescia, Italy
| | - Isabella Sudano
- University Hospital Zurich University Heart Center, Cardiology and University of Zurich, Zurich, Switzerland
| | - Costas Tsioufis
- First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
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Honda K, Tasaki M, Yamano T, Ueda M, Naiki H, Tanaka N, Morinaga Y, Miyagawa-Hayashino A. High frequency of occult transthyretin and apolipoprotein AI-type amyloid in aortic valves removed by valve replacement for aortic stenosis. Amyloid 2025; 32:22-28. [PMID: 39526702 DOI: 10.1080/13506129.2024.2426508] [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: 07/22/2024] [Revised: 10/01/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND A high incidence of valvular involvement of amyloid in the setting of aortic stenosis (AS) has been reported. Amyloid derived from ApoAI (AApoAI) can form local amyloid deposits in the aortic valve. Although a high prevalence of concomitant severe AS and cardiac transthyretin-type amyloidosis (ATTR) has been reported, the prevalence of valvular involvement by ATTR and AApoAI is unclear. METHODS Using immunostaining and mass spectrometry, we analysed amyloid proteins in 97 aortic valves removed for valve replacement due to AS at Kyoto Prefectural University of Medicine between 2014 and 2021. Clinical information was also reviewed. RESULTS Amyloid deposits were found in 44 cases (45%), of which 30 cases (68%) involved ATTR and 33 cases (75%) AApoAI. Statistical analysis showed significantly lower age and E/e' among amyloid-positive cases compared with amyloid-negative cases and significantly lower brain natriuretic peptide, higher fractional shortening, and higher left ventricular ejection fraction among ATTR-positive cases compared with ATTR-negative cases. Seven recent patients underwent bone scintigraphy and ATTR cardiomyopathy was observed in only one case. CONCLUSIONS AS symptoms can manifest earlier in patients with amyloid or ATTR deposition in the aortic valve than in patients without such deposition, even though left ventricular function is preserved.
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Affiliation(s)
- Kohei Honda
- Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masayoshi Tasaki
- Department of Clinical Biosciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto, Japan
| | - Tetsuhiro Yamano
- Department of Infection Control and Molecular Laboratory Medicine/Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mitsuharu Ueda
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hironobu Naiki
- Department of Molecular Pathology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Noriyuki Tanaka
- Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yukiko Morinaga
- Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Aya Miyagawa-Hayashino
- Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Gerra L, Bucci T, Lam HM, Mantovani M, Argyris AA, Alobaida M, Sandhu K, Mills J, Boriani G, Lip GYH. Impact of amyloidosis on outcomes after transcatheter aortic valve implantation. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2025:S1885-5857(25)00045-3. [PMID: 39922557 DOI: 10.1016/j.rec.2025.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 01/23/2025] [Indexed: 02/10/2025]
Abstract
INTRODUCTION AND OBJECTIVES Data on the impact of amyloidosis on outcomes after transcatheter aortic valve implantation (TAVI) are limited. The objective of this study was to evaluate the 1-year risk of adverse events post-TAVI in patients with amyloidosis. METHODS Patients undergoing TAVI (between 2005 and 2023) were categorized into 2 groups based on the presence of amyloidosis. The primary outcome was the 1-year risk of a composite endpoint: heart failure (HF), ischemic stroke, pacemaker implantation, acute kidney injury, and all-cause death. Secondary outcomes assessed the individual components of the composite. Propensity score matching was used to balance the groups, and Cox regression was used to assess the risk of adverse outcomes associated with amyloidosis. Composite outcomes were analyzed for early (30-days) and long-term (30-days to 1 year) follow-up. RESULTS Data from 589 TAVI patients with amyloidosis (mean age 78.9±8.2 years, 31.9% female) were compared with 52 296 individuals without amyloidosis (mean age 78.1±8.8 years, 40.3% female). After propensity score matching, patients with amyloidosis had a significantly higher 1-year risk of adverse events (HR, 1.27; 95%CI, 1.08-1.49). Specifically, patients with amyloidosis showed an increased risk of HF (HR, 1.37; 95%CI, 1.10-1.70). Stroke risk (HR, 1.67; 95%CI, 1.16-2.40) and pacemaker implantation (HR, 2.25; 95%CI, 1.15-4.41) were higher during long-term follow-up, while no differences were found for acute kidney injury or all-cause mortality between the 2 groups. CONCLUSIONS Among patients undergoing TAVI, those with amyloidosis are at a higher risk of adverse events, particularly HF, and have an increased risk of pacemaker implantation and stroke in the long-term.
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Affiliation(s)
- Luigi Gerra
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Divisione di Cardiologia, Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Policlinico di Modena, Modena, Italy. https://x.com/@GerraLuigi
| | - Tommaso Bucci
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Dipartimento di Scienze Internistiche, Anestesiologiche e Cardiovascolari, Università Sapienza di Roma, Rome, Italy
| | - Ho Man Lam
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
| | - Marta Mantovani
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Divisione di Cardiologia, Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Policlinico di Modena, Modena, Italy
| | - Antonios A Argyris
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
| | - Muath Alobaida
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Department of Basic Science, Prince Sultan Bin Abdulaziz College for Emergency Medical Services, King Saud University, Riyadh, Saudi Arabia
| | - Kully Sandhu
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
| | - Joseph Mills
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
| | - Giuseppe Boriani
- Divisione di Cardiologia, Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Policlinico di Modena, Modena, Italy
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Department of Clinical Medicine, Danish Center for Health Services Research, Aalborg University, Aalborg, Denmark; Department of Cardiology, Lipidology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
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Marques N, Aguiar Rosa S, Cordeiro F, Menezes Fernandes R, Ferreira C, Bento D, Brito D, Cardim N, Lopes L, Azevedo O. Portuguese recommendations for the management of transthyretin amyloid cardiomyopathy (Part 1 of 2): Screening, diagnosis and treatment. Developed by the Task Force on the management of transthyretin amyloid cardiomyopathy of the Working Group on Myocardial and Pericardial Diseases of the Portuguese Society of Cardiology. Rev Port Cardiol 2025; 44 Suppl 1:7-48. [PMID: 39956765 DOI: 10.1016/j.repc.2024.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 11/19/2024] [Indexed: 02/18/2025] Open
Affiliation(s)
- Nuno Marques
- Cardiology Department, Unidade Local de Saúde do Alentejo Central, Portugal; Faculdade de Medicina e Ciências Biomédicas, Universidade do Algarve, Portugal; ABC-RI - Algarve Biomedical Center Research Institute, Portugal; Active Ageing Competence Center, Portugal.
| | - Sílvia Aguiar Rosa
- Cardiology Department, Hospital de Santa Marta, Unidade Local de Saúde São José, Lisboa, Portugal; Centro Clínico Académico de Lisboa, Lisboa, Portugal; Nova Medical School, Lisboa, Portugal
| | - Filipa Cordeiro
- Cardiology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
| | | | - Catarina Ferreira
- Cardiology Department, Hospital de S. Pedro, Unidade Local de Saúde de Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | - Dina Bento
- Cardiology Department, Hospital de Faro, Unidade Local de Saúde do Algarve, Portugal
| | - Dulce Brito
- Cardiology Department, Hospital de Santa Maria, Lisboa, Portugal; CCUL@RISE, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
| | - Nuno Cardim
- Cardiology Department, Hospital CUF-Descobertas, Lisbon, Portugal; Nova Medical School, Lisboa, Portugal
| | - Luís Lopes
- Institute of Cardiovascular Science, University College London, UK; St Bartholomew's Hospital, Barts Heart Centre, London, UK
| | - Olga Azevedo
- Cardiology Department, Hospital Senhora da Oliveira, Guimarães, Portugal
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Stein-Merlob AF, Swier R, Vucicevic D. Evolving Strategies in Cardiac Amyloidosis: From Mechanistic Discoveries to Diagnostic and Therapeutic Advances. Cardiol Clin 2025; 43:93-110. [PMID: 39551565 PMCID: PMC11819944 DOI: 10.1016/j.ccl.2024.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2024]
Abstract
Diagnosis and treatment of cardiac amyloidosis have rapidly evolved over the past decade by harnessing mechanisms of disease pathogenesis. Cardiac amyloidosis is caused by myocardial deposition of fibrils formed by misfolded proteins, namely transthyretin (ATTR) and immunoglobulin light chains (AL). Advances in noninvasive imaging have revolutionized diagnosis of ATTR cardiomyopathy (CM). Novel treatments for ATTR-CM utilize a range of therapeutic techniques, including protein stabilizers, interfering RNA, gene editing, and monoclonal antibodies. AL-CM, primarily driven by plasma cell dyscrasias, requires treatment with chemotherapy and consideration for autologous stem cell transplant. These incredible advances aim to improve patient outcomes in cardiac amyloidosis.
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Affiliation(s)
- Ashley F. Stein-Merlob
- Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Rachel Swier
- Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Darko Vucicevic
- Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Ahmanson-UCLA Cardiomyopathy Center, Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA
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Bastos-Fernandez M, Lopez-Otero D, Lopez-Pais J, Pubul-Nuñez V, Neiro-Rey C, Lado-Baleato O, Gude-Sampedro F, Alvarez-Barredo M, Gonzalez-Salvado V, Pena-Gil C, Martinon-Martinez J, de la Fuente Rey A, Otero-Garcia O, Jimenez-Ramos V, Garcia-Rodeja F, Tasende-Rey P, Ruiz-Donate J, Sanmartin-Pena XC, Martinez-Monzonis A, Gonzalez-Juanatey JR. Echocardiographic phenotype in severe aortic stenosis with and without transthyretin cardiac amyloidosis: the AMY-TAVI study. Eur Heart J Cardiovasc Imaging 2025; 26:261-272. [PMID: 39437308 DOI: 10.1093/ehjci/jeae263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 06/24/2024] [Accepted: 09/15/2024] [Indexed: 10/25/2024] Open
Abstract
AIMS The relative apical sparing pattern of left ventricular (LV) longitudinal strain (RELAPS > 1) has been described as a typical sign of cardiac amyloidosis (CA). The objective was to validate this pattern in concomitant CA and aortic stenosis (AS) and to identify new echocardiographic variables suggestive of CA in the presence of AS. METHODS AND RESULTS Three hundred and twenty-four consecutive patients (age 81.5 ± 5.8 years, 51% women) with AS who underwent transcatheter aortic valve implantation (TAVI) were prospectively included. 2D speckle tracking echocardiography was performed. Following TAVI, 99mTc-DPD scintigraphy and protein electrophoresis were performed to screen for CA. Thirty-eight patients (11.7%) showed cardiac uptake in scintigraphy: 14 patients (4.3%) with Grade 1, 13 (4%) with Grade 2, and 11 (3.4%) with Grade 3. Patients with Grades 2 and 3 (AS-CA group) had more LV hypertrophy (LV mass index: 188 vs. 172 g/m2, P = 0.032), lower transvalvular aortic pressure gradient (P < 0.003), and higher prevalence of low-gradient AS (50% vs. 19%, P = 0.001), as well as greater diastolic and systolic dysfunction. Strain analysis was limited to 243 patients due to poor acoustic window and restrictions imposed by the COVID-19 pandemic (81 lost: 79 in AS alone, 1 each in AS-DPD1 and AS-CA groups). RELAPS > 1 was more prevalent in AS-CA group (74% vs. 44%, P = 0.006). An echocardiographic prediction model (GRAM score) for CA in the presence of AS, which is more sensitive and specific than RELAPS > 1 alone, is proposed using the LV mass, maximum aortic gradient, and RELAPS > 1, in addition to age (area under the curve: 0.85, 95% confidence interval: 0.77-0.93). CONCLUSION RELAPS > 1 is more prevalent in AS-CA but can occur in almost half of AS patients without CA, which reduces its value as a screening tool. A more sensitive and specific prediction score for CA in patients with severe AS is proposed.
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Affiliation(s)
- Maria Bastos-Fernandez
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Diego Lopez-Otero
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- CIBERCV, Center for Biomedical Research in Cardiovascular Diseases Network, Santiago de Compostela, Spain
| | - Javier Lopez-Pais
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Virginia Pubul-Nuñez
- Nuclear Medicine Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Carmen Neiro-Rey
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Oscar Lado-Baleato
- Research Methods Group (RESMET), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Francisco Gude-Sampedro
- Department of Statistics, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Maria Alvarez-Barredo
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Violeta Gonzalez-Salvado
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Carlos Pena-Gil
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Jesus Martinon-Martinez
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Antía de la Fuente Rey
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Oscar Otero-Garcia
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Victor Jimenez-Ramos
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Federico Garcia-Rodeja
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Pablo Tasende-Rey
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Javier Ruiz-Donate
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Xoan Carlos Sanmartin-Pena
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Amparo Martinez-Monzonis
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Jose R Gonzalez-Juanatey
- Cardiology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- CIBERCV, Center for Biomedical Research in Cardiovascular Diseases Network, Santiago de Compostela, Spain
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Masri A, Chen Y, Colavecchia AC, Benjumea D, Crowley A, Jhingran P, Kent M, Wogen J, Pankratova C, Jimenez Alvir JM, Bhambri R. Coexisting Calcific Aortic Stenosis and Transthyretin Cardiac Amyloidosis: Real-World Evaluation of Clinical Characteristics and Outcomes. J Am Heart Assoc 2025; 14:e033251. [PMID: 39817522 DOI: 10.1161/jaha.123.033251] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 08/01/2024] [Indexed: 01/18/2025]
Abstract
BACKGROUND The coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and aortic stenosis (AS) is increasingly recognized, but the clinical consequences are unclear. We aimed to characterize clinical outcomes in AS plus ATTR-CA compared with only AS or ATTR-CA. METHODS AND RESULTS In a retrospective cohort study, patients with AS only, ATTR-CA only, or AS plus ATTR-CA were identified using all-payer claims data (2015-2021). Eligible patients had ≥1 claim for AS or cardiac amyloidosis (excluding light-chain cardiac amyloidosis); were aged ≥60 years; and were continuously enrolled in medical plans for ≥6 months after diagnosis. Ad hoc subanalyses were conducted in patients with aortic valve replacement at first diagnosis (surrogate for severe AS). Of 355 430 eligible patients, 345 771 (97.3%), 8453 (2.4%), and 1239 (0.3%) were included in the AS-only, ATTR-CA-only, and AS-plus-ATTR-CA cohorts, respectively; 41 312 (11.9%), 14 (0.2%), and 212 (17.1%) had aortic valve replacement. Two-year mortality rates were 16.1% (95% CI, 15.9-16.2), 14.8% (95% CI, 13.9-15.7), and 19.2% (95% CI, 16.9-21.8) in the AS-only, ATTR-CA-only, and AS-plus-ATTR-CA cohorts; heart failure hospitalization rates were 29.4% (95% CI, 29.2-29.5), 22.8% (95% CI, 21.9-23.8), and 48.7% (95% CI, 45.7-51.7). AS plus ATTR-CA was associated with increased risk of death (HR, 1.3 [95% CI, 1.1-1.4]; P<0.0001) and heart-failure hospitalization (HR, 1.9 [95% CI, 1.8-2.1]; P<0.0001) versus AS alone. In the aortic valve replacement subgroup, AS plus ATTR-CA was associated with an increased mortality rate (HR, 1.4 [95% CI, 1.1-1.8]; P=0.003) but not heart failure hospitalization (HR, 1.1 [95% CI, 0.9-1.3]; P=0.07) versus AS only. CONCLUSIONS Patients with AS plus ATTR-CA experience worse clinical outcomes than patients with AS only. Increased awareness of these coexisting conditions may help facilitate earlier screening and improve prognosis.
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Affiliation(s)
- Ahmad Masri
- Division of Cardiovascular Medicine Knight Cardiovascular Institute, Oregon Health & Science University Portland OR USA
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Arima N, Ochi Y, Kubo T, Murakami Y, Nishino K, Yamamoto H, Satou K, Tamura S, Okawa M, Takata H, Shimizu Y, Baba Y, Yamasaki N, Kitaoka H. Prospective Multicenter Screening With High-Sensitivity Cardiac Troponin T for Wild-Type Transthyretin Cardiac Amyloidosis in Outpatient and Community-Based Settings. Circ J 2024; 89:24-30. [PMID: 39370278 DOI: 10.1253/circj.cj-24-0479] [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] [Indexed: 10/08/2024]
Abstract
BACKGROUND High-sensitivity cardiac troponin T (hs-cTnT) was proposed as a simple and useful diagnostic tool for cardiac amyloidosis (CA). We performed exploratory systemic screening using hs-cTnT to detect wild-type transthyretin CA (ATTRwt-CA) in outpatient and community-based settings. METHODS AND RESULTS This study was a prospective multicenter study including 8 internal medicine clinics in Kochi Prefecture, Japan. Consecutive individuals aged ≥70 years who visited those clinics as outpatients were enrolled. Patients with a prior diagnosis of CA or a history of heart failure hospitalization were excluded. We measured hs-cTnT levels in the enrolled individuals at each clinic, and those with elevated hs-cTnT levels (≥0.03ng/mL) received further detailed examination, including remeasurement of hs-cTnT. The diagnosis of ATTRwt-CA was confirmed by biopsy-proven transthyretin. Of 1,141 individuals enrolled in the study, 55 (4.8%) had elevated hs-cTnT levels. Of the 33 patients who underwent further examination, 22 had elevated hs-cTnT levels at remeasurement. Finally, 2 men were diagnosed with ATTRwt-CA. The prevalence of ATTRwt-CA was 9.1% (2/22) among patients with elevated hs-cTnT levels at two examinations, and at least 0.18% (2/1,141) in the whole study population. CONCLUSIONS Measurement of hs-cTnT will help to screen for patients with undiagnosed ATTRwt-CA in primary care practice.
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Affiliation(s)
- Naoki Arima
- Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University
| | - Yuri Ochi
- Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University
| | - Toru Kubo
- Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University
| | | | | | | | | | | | | | | | | | - Yuichi Baba
- Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University
| | - Naohito Yamasaki
- Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University
| | - Hiroaki Kitaoka
- Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University
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9
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SadrAldin R, Ahmed J, Alkaf F, Ahmed MK, Mousa ZB, AlQahtani SA, Farghaly H, AlAsiri Z, Alodhaib R, Bin Shigair S, Alqarni A, AlAmri H, Almoghairi A, Alahmari S, Bakhsh A. Prevalence of transthyretin cardiac amyloidosis in patients with aortic stenosis. AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE 2024; 14:384-395. [PMID: 39839566 PMCID: PMC11744221 DOI: 10.62347/hjht9161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 12/13/2024] [Indexed: 01/23/2025]
Abstract
BACKGROUND Transthyretin cardiac amyloidosis (ATTRCA) is a prevalent disease, and it can be associated with heart failure (HF), left ventricle hypertrophy (LVH), atrial fibrillation (AF), and aortic stenosis (AS). AIM The study aims to detect the prevalence of ATTRCA in the symptomatic AS population. METHOD A single-center prospective study screening for ATTRCA in patients diagnosed with symptomatic severe AS undergoing aortic valve (AV) intervention. RESULTS A total of 27 patients were enrolled, of which 15 (56%) were men. The mean age was 72.8 ± 10.5 years. HF symptoms were present in 11 (40.7%) patients at New York Heart Association (NYHA) class II, while 15 (55.6%) patients had NYHA class III symptoms. AF was present in 6 (22.2%) patients. The mean left ventricle ejection fraction (LVEF) was 49.4 ± 9.75%, and the mean stroke volume (SV) was 37.4 ± 8.7 ml/m2. The interventricular septal thickness (IVS) was 1.2 ± 0.18 cm. The AS mean gradient was 46 ± 12 mmHg, and the aortic valve area (AVA) was 0.69 ± 0.16 cm2. The ATTRCA was diagnosed by bone scintigraphy in 5 (18.5%) AS patients. Perugini scores of 2 and 3 were considered positive for ATTRCA with the heart/contralateral lung (H/CL) ratio of 1.48 ± 0.35. There was no difference in LVEF between patients with ATTRCA and those without ATTRCA 50 ± 9.8% vs 47 ± 9.3%; p-value 0.55. The ATTRCA had a lower SV of 33.9 ± 6.9 ml/m2 compared to patients without ATTRCA 37.5 ± 8.8 ml/m2; p-value of 0.34. There was no significant difference in LVH or IVS thickness between the patients with ATTRCA and those without ATTRCA. The left ventricle (LV) mass index in ATTRCA was 87 ± 21 g/m2 compared to patients without ATTRCA 98.7 ± 26 g/m2, with a p-value 0.38, and the IVS thickness was 1.1 ± 0.22 cm compared to patients without ATTRCA 1.2 ± 0.18 cm; p-value 0.17. The left atrial (LA) volumes were significantly higher in the ATTRCA group 55.5 ± 25.6 ml/m2 compared to patients without ATTRCA 37.5 ± 10.9 ml/m2 with a significant p-value 0.028. The mean AV gradient was lower in ATTRCA patients at 40.8 ± 8.4 mmHg, compared to patients without ATTRCA at 46.1 ± 12.1 mmHg; it did not reach a statistical significance p-value 0.3. There was a significant difference in LV relative longitudinal strain (LS) between patients with ATTRCA 11.8 ± 3.2 and those without ATTRCA 63.3 ± 22.6 with a significant p-value 0.001. CONCLUSION ATTRCA is prevalent in AS patients; bone scintigraphy is recommended for screening AS patients for ATTRCA.
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Affiliation(s)
- Rozana SadrAldin
- Prince Sultan Cardiac Centre, Heart Function Unit, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Jamal Ahmed
- Prince Sultan Cardiac Centre, Heart Function Unit, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Fahmi Alkaf
- Prince Sultan Cardiac Centre, Heart Function Unit, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Mohammed K Ahmed
- Prince Sultan Cardiac Centre, Division of Echocardiography, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Zakaria Bin Mousa
- Prince Sultan Cardiac Centre, Division of Echocardiography, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Saad A AlQahtani
- Prince Sultan Military Medical City, Department of Nuclear MedicineRiyadh, Saudi Arabia
| | - Hussein Farghaly
- Prince Sultan Military Medical City, Department of Nuclear MedicineRiyadh, Saudi Arabia
| | - Zahra AlAsiri
- Prince Sultan Cardiac Centre, Department of NursingRiyadh, Saudi Arabia
| | - Raneem Alodhaib
- Prince Sultan Cardiac Centre, Department of NursingRiyadh, Saudi Arabia
| | - Shehana Bin Shigair
- Prince Sultan Cardiac Centre, Heart Function Unit, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Abdullah Alqarni
- Prince Sultan Military Medical City, Department of Nuclear MedicineRiyadh, Saudi Arabia
| | - Hussein AlAmri
- Prince Sultan Cardiac Centre, Division of Interventional Cardiology, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Abdulrahman Almoghairi
- Prince Sultan Cardiac Centre, Division of Interventional Cardiology, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Saeed Alahmari
- Prince Sultan Cardiac Centre, Division of Echocardiography, Department of Adult CardiologyRiyadh, Saudi Arabia
| | - Abeer Bakhsh
- Prince Sultan Cardiac Centre, Heart Function Unit, Department of Adult CardiologyRiyadh, Saudi Arabia
- King Abdullah Medical City, Department of Adult CardiologyMakkah, Saudi Arabia
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10
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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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11
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Annabi M, Carter‐Storch R, Zaroui A, Galat A, Oghina S, Kharoubi M, Bezard M, Derumeaux G, Fanen P, Lemonnier F, Poullot E, Itti E, Gallet R, Teiger E, Pibarot P, Damy T, Clavel M. Prevalence, Characteristics, and Impact on Prognosis of Aortic Stenosis in Patients With Cardiac Amyloidosis. J Am Heart Assoc 2024; 13:e034723. [PMID: 38904242 PMCID: PMC11255711 DOI: 10.1161/jaha.124.034723] [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: 01/27/2024] [Accepted: 05/23/2024] [Indexed: 06/22/2024]
Abstract
BACKGROUND Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA. METHODS AND RESULTS We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light-chain (AL) CA. CA patients' echocardiograms were re-analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population-based controls, all types of CA had higher age- and sex-standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09-3.64]; ATTRv: SRR, 3.41; 95%CI [1.64-4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25-14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56-1.14]; ATTRv: SRR, 1.27; 95%CI [0.85-1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71-4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all-cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42-1.19]; P=0.19). CONCLUSIONS Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.
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Affiliation(s)
- Mohamed‐Salah Annabi
- Institut Universitaire de Cardiologie et de PneumologieUniversité LavalQuébecCanada
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM U955, Team «Senescence, Metabolism and Cardiovascular Diseases»Paris‐Est Créteil University (UPEC)CréteilFrance
| | - Rasmus Carter‐Storch
- Institut Universitaire de Cardiologie et de PneumologieUniversité LavalQuébecCanada
- Department of CardiologyOdense University HospitalOdenseDenmark
| | - Amira Zaroui
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - Arnault Galat
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - Silvia Oghina
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
| | - Mounira Kharoubi
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - Mélanie Bezard
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - Geneviève Derumeaux
- INSERM U955, Team «Senescence, Metabolism and Cardiovascular Diseases»Paris‐Est Créteil University (UPEC)CréteilFrance
- AP‐HP, Department of PhysiologyHenri Mondor Hospital, FHU‐SENECCréteilFrance
| | - Pascale Fanen
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - François Lemonnier
- AP‐HP, Henri Mondor HospitalLymphoid Malignancies UnitCréteilFrance
- Univ Paris Est Créteil, INSERM, IMRBCréteilFrance
| | - Elsa Poullot
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- Univ Paris Est Créteil, INSERM, IMRBCréteilFrance
- Department of PathologyAP‐HP Henri Mondor HospitalCréteilFrance
| | - Emmanuel Itti
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - Romain Gallet
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - Emmanuel Teiger
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - Philippe Pibarot
- Institut Universitaire de Cardiologie et de PneumologieUniversité LavalQuébecCanada
| | - Thibaud Damy
- Referral Center for Cardiac Amyloidosis, Mondor Amyloidosis Network, GRC Amyloid Research Institute and Cardiology DepartmentAPHP Henri Mondor HospitalCréteilFrance
- INSERM Unit U955Clinical Epidemiology and Ageing (CEpiA, Paris‐Est Créteil University, Val‐de‐Marne)CréteilFrance
| | - Marie‐Annick Clavel
- Institut Universitaire de Cardiologie et de PneumologieUniversité LavalQuébecCanada
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12
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Fatima K, Uddin QS, Tharwani ZH, Kashif MAB, Javaid SS, Kumar P, Zia MT, Javed M, Butt MS, Asim Z. Concomitant transthyretin cardiac amyloidosis in patients undergoing TAVR for aortic stenosis: A systemic review and meta-analysis. Int J Cardiol 2024; 402:131854. [PMID: 38367883 DOI: 10.1016/j.ijcard.2024.131854] [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: 09/01/2023] [Revised: 01/15/2024] [Accepted: 02/10/2024] [Indexed: 02/19/2024]
Abstract
OBJECTIVE Transcatheter aortic valve replacement (TAVR) is a successful treatment for aortic stenosis (AS) patients, and previous studies indicate favorable outcomes for those with concomitant aortic stenosis and transthyretin-associated cardiac amyloidosis (TTRCA-AS). However, the impact of TAVR on more adverse outcomes in TTRCA-AS patients compared to those with AS alone is still uncertain, with conflicting findings reported in the literature. METHODS PubMed and Scopus were extensively searched from inception till August 2021. Studies were included if they reported data for prevalence and outcomes including mortality and cardiovascular-related hospitalization events in TTRCA-AS patients referred for TAVR. The data for these outcomes were pooled using a random effects model and forest plots were created. RESULTS After initially screening 146 articles, 6 were shortlisted for inclusion in our analysis. Pooled analysis demonstrated a 13.3% [95% CI: 10.9-16.5; p = 0.307] prevalence of TTRCA in patients with AS undergoing TAVR. The incidence of mortality and cardiovascular (CV) hospitalization in patients with TTRCA-AS undergoing TAVR were 28.3% [95% CI: 18.7-39.0, p = 0.478] and 21.1% [95% CI: 10.2-34.5, p = 0.211], respectively. CONCLUSION The overall pooled TTRCA-AS prevalence was reported to be 13.3% in AS patients who underwent TAVR. Furthermore, transthyretin-associated CA was found to be associated with an increased risk of mortality and hospitalization. Large patient population studies are required to assess the safety and efficacy of TAVR in TTRCA-AS patients, as current research report data from small patient cohorts.
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Affiliation(s)
- Kaneez Fatima
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Qazi Shurjeel Uddin
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | | | | | - Syed Sarmad Javaid
- Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan
| | - Prince Kumar
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Muhammad Twaha Zia
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Maarij Javed
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Malaika Saeed Butt
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Zoraiz Asim
- Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan
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13
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Alqarni A, Aljizeeri A, Bakhsh AM, El-Zeftawy HAM, Farghaly HR, Alqadhi MAM, Algarni M, Asiri ZM, Osman A, Haddadin H, Alayary I, Al-Mallah MH. Best Practices in Nuclear Imaging for the Diagnosis of Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in KSA: The Eagle Eyes of Local Experts. Diagnostics (Basel) 2024; 14:212. [PMID: 38248088 PMCID: PMC10814030 DOI: 10.3390/diagnostics14020212] [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: 11/01/2023] [Revised: 12/19/2023] [Accepted: 12/28/2023] [Indexed: 01/23/2024] Open
Abstract
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart muscle. Variable symptoms of ATTR-CM can lead to a delayed diagnosis. Recognizing the diagnostic indicators is crucial to promptly detect this condition. A targeted literature review was conducted to examine the latest international consensus recommendations on a comprehensive diagnosis of ATTR-CM. Additionally, a panel consisting of nuclear medicine expert consultants (n = 10) and nuclear imaging technicians (n = 2) convened virtually from the Kingdom of Saudi Arabia (KSA) to formulate best practices for ATTR-CM diagnosis. The panel reached a consensus on a standard diagnostic pathway for ATTR-CM, which commences by evaluating the presence of clinical red flags and initiating a cardiac workup to assess the patient's echocardiogram. Cardiac magnetic resonance imaging may be needed, in uncertain cases. When there is a high suspicion of ATTR-CM, patients undergo nuclear scintigraphy and hematologic tests to rule out primary or light-chain amyloidosis. The expert panel emphasized that implementing best practices will support healthcare professionals in KSA to improve their ability to detect and diagnose ATTR-CM more accurately and promptly. Diagnosing ATTR-CM accurately and early can reduce morbidity and mortality rates through appropriate treatment.
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Affiliation(s)
- Abdullah Alqarni
- Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; (A.A.); (H.R.F.)
| | - Ahmed Aljizeeri
- King Abdulaziz Cardiac Center, Ministry of the National Guard Health Affairs, Riyadh 14626, Saudi Arabia;
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh 21423, Saudi Arabia
| | | | | | - Hussein R. Farghaly
- Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia; (A.A.); (H.R.F.)
| | | | - Mushref Algarni
- King Fahad Military Medical Complex, Dhahran 34313, Saudi Arabia;
| | | | - Ahmed Osman
- Pfizer Inc., Riyadh 13244, Saudi Arabia; (A.O.)
| | - Haya Haddadin
- Pfizer Gulf FZ LLC, Dubai 29553, United Arab Emirates;
| | | | - Mouaz H. Al-Mallah
- Houston Methodist, Weill Cornell Medical College, Houston, TX 77030, USA
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14
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Aimo A, Camerini L, Fabiani I, Morfino P, Panichella G, Barison A, Pucci A, Castiglione V, Vergaro G, Sinagra G, Emdin M. Valvular heart disease in patients with cardiac amyloidosis. Heart Fail Rev 2024; 29:65-77. [PMID: 37735319 PMCID: PMC10904406 DOI: 10.1007/s10741-023-10350-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/13/2023] [Indexed: 09/23/2023]
Abstract
Cardiac amyloidosis (CA) is an underdiagnosed condition caused by the deposition of misfolded proteins, namely immunoglobulin light chains and transthyretin, in the extracellular spaces of the heart. Any cardiovascular structure can be affected by amyloid infiltration, including the valves. Amyloid accumulation within the cardiac valves may lead to their structural and functional impairment, with a profound impact on patients' prognosis and quality of life. The most common forms of valvular disease in CA are aortic stenosis (AS), mitral regurgitation (MR), and tricuspid regurgitation (TR). CA and AS share similar risk factors, disease mechanisms, and remodeling patterns, which make their diagnosis particularly challenging. Patients with both CA and AS experience worse outcomes than CA or AS alone, and transcatheter aortic valve replacement may represent a useful therapeutic strategy in this population. Data on MR and TR are quite limited and mainly coming from case reports or small series. This review paper will summarize our current understanding on the epidemiology, disease mechanisms, echocardiographic features, clinical implications, and therapeutic options of AS, MR, and TR in patients with CA.
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Affiliation(s)
- Alberto Aimo
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy.
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
| | - Lara Camerini
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy
| | - Iacopo Fabiani
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Paolo Morfino
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy
| | - Giorgia Panichella
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy
| | - Andrea Barison
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Angela Pucci
- Histopathology Department, University Hospital of Pisa, Pisa, Italy
| | - Vincenzo Castiglione
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Giuseppe Vergaro
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Gianfranco Sinagra
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI) and University of Trieste, Trieste, Italy
| | - Michele Emdin
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127, Pisa, Italy
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
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15
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Duca F, Kronberger C, Willixhofer R, Bartko PE, Bergler-Klein J, Nitsche C. Cardiac Amyloidosis and Valvular Heart Disease. J Clin Med 2023; 13:221. [PMID: 38202228 PMCID: PMC10779781 DOI: 10.3390/jcm13010221] [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: 11/13/2023] [Revised: 12/18/2023] [Accepted: 12/27/2023] [Indexed: 01/12/2024] Open
Abstract
Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or of light chain (AL) origin may affect any structure of the heart, including the valves. The recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of the epidemiology, diagnosis, treatment and prognosis of this dual pathology. Despite being of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis are rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis by including studies on epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.
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Affiliation(s)
| | | | | | | | | | - Christian Nitsche
- Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (F.D.); (C.K.); (R.W.); (P.E.B.); (J.B.-K.)
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16
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Jaiswal V, Agrawal V, Khulbe Y, Hanif M, Huang H, Hameed M, Shrestha AB, Perone F, Parikh C, Gomez SI, Paudel K, Zacks J, Grubb KJ, De Rosa S, Gimelli A. Cardiac amyloidosis and aortic stenosis: a state-of-the-art review. EUROPEAN HEART JOURNAL OPEN 2023; 3:oead106. [PMID: 37941729 PMCID: PMC10630099 DOI: 10.1093/ehjopen/oead106] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 10/03/2023] [Accepted: 10/04/2023] [Indexed: 11/10/2023]
Abstract
Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aortic valve replacement. Diagnostic workup for cardiac amyloidosis in patients with aortic stenosis is based on a multi-parametric approach considering clinical assessment, electrocardiogram, haematologic tests, basic and advanced echocardiography, cardiac magnetic resonance, and technetium labelled cardiac scintigraphy like technetium-99 m (99mTc)-pyrophosphate, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, and 99mTc-hydroxymethylene diphosphonate. However, a biopsy is the traditional gold standard for diagnosis. The prognosis of patients with coexisting cardiac amyloidosis and aortic stenosis is still under evaluation. The combination of these two pathologies worsens the prognosis. Regarding treatment, mortality is reduced in patients with cardiac amyloidosis and severe aortic stenosis after undergoing transcatheter aortic valve replacement. Further studies are needed to confirm these findings and to understand whether the diagnosis of cardiac amyloidosis could affect therapeutic strategies. The aim of this review is to critically expose the current state-of-art regarding the association of cardiac amyloidosis with aortic stenosis, from pathophysiology to treatment.
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Affiliation(s)
- Vikash Jaiswal
- Department of Cardiovascular Research, Larkin Community Hospital, South Miami, FL, USA
| | - Vibhor Agrawal
- Department of Medicine, King George’s Medical University, Lucknow, India
| | - Yashita Khulbe
- Department of Medicine, King George’s Medical University, Lucknow, India
| | - Muhammad Hanif
- Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Helen Huang
- University of Medicine and Health Science, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Maha Hameed
- Department of Internal Medicine, Florida State University, Sarasota Memorial Hospital, Sarasota, FL, USA
| | - Abhigan Babu Shrestha
- Department of Internal Medicine, M Abdur Rahim Medical College, Dinajpur, Bangladesh
| | - Francesco Perone
- Cardiac Rehabilitation Unit, Rehabilitation Clinic ‘Villa delle Magnolie’,81020 Castel Morrone, Caserta, Italy
| | | | - Sabas Ivan Gomez
- Department of Cardiovascular Research, Larkin Community Hospital, South Miami, FL, USA
| | - Kusum Paudel
- Department of Medicine, Kathmandu University School of Medical Science, Dhulikhel, Kathmandu 45209, Nepal
| | - Jerome Zacks
- Department of Cardiology, The Icahn Medical School at Mount Sinai, NewYork 10128, USA
| | - Kendra J Grubb
- Division of Cardiothoracic Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Salvatore De Rosa
- Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Alessia Gimelli
- Department of Imaging, Fondazione Toscana/CNR Gabriele Monasterio, Pisa 56124, Italy
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17
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Hussain B, Duhan S, Mahmood A, Al-Alawi L, Vargas C, Khan S, Ali Z, Waqar F, Alfonso C, Cuevas C, Alexander T. Prevalence and Prognostic Implications of Amyloidosis in Valvular Heart Disease. Curr Probl Cardiol 2023; 48:101811. [PMID: 37209794 DOI: 10.1016/j.cpcardiol.2023.101811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 05/13/2023] [Indexed: 05/22/2023]
Abstract
There has been less emphasis on the prognostic impact of amyloidosis in patients with valvular heart disease (VHD). We aimed to determine the prevalence of amyloidosis in VHD and its clinical implications in terms of mortality. Patients hospitalized for VHD were identified using National Inpatient Sample 2016-2020 which were divided into 2 cohorts: with and without amyloidosis. Among 5,728,873 patients hospitalized with VHD, 11,715 patients had amyloidosis in which mitral valve disease has the highest prevalence (7.6%) followed by aortic (3.6%), and tricuspid valve disease (1%). Underlying amyloidosis is associated with higher mortality in VHD (OR 1.45, CI 1.2-1.7, P<0.001), mainly mitral valve disease (OR 1.44, CI 1.1-1.9, P<0.01). Patients with amyloidosis have higher adjusted mortality rates (5-6% vs 2.6%, P<0.01), longer mean length of stay (7.1 vs 5.7 days, P<0.001), but they have lower valvular intervention rates. In hospitalized VHD patients, underlying amyloidosis is associated with higher in-hospital mortality.
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Affiliation(s)
- Bilal Hussain
- The Brooklyn Hospital Center, Internal Medicine, Brooklyn, NY.
| | - Sanchit Duhan
- Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD
| | - Ahmed Mahmood
- Cardiology Department, Corpus Christi Medical Center, Corpus Christi, TX
| | - Luay Al-Alawi
- Cardiology Department, Corpus Christi Medical Center, Corpus Christi, TX
| | - Carlos Vargas
- Cardiology Department, Corpus Christi Medical Center, Corpus Christi, TX
| | - Sohail Khan
- Interventional Cardiology, Marshfield Medical Center, Marshfield, WI
| | - Zuhair Ali
- Graduate Medical Education, HCA Houston Healthcare, Houston, TX
| | - Fahad Waqar
- Interventional Cardiology, University of Cincinnati, Cincinnati, OH
| | | | - Christel Cuevas
- Cardiology Department, Corpus Christi Medical Center, Corpus Christi, TX
| | - Thomas Alexander
- Cardiology Department, Corpus Christi Medical Center, Corpus Christi, TX
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18
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Ladefoged B, Pedersen ALD, Clemmensen TS, Poulsen SH. Strain-derived myocardial work in wild-type transthyretin cardiac amyloidosis with aortic stenosis-diagnosis and prognosis. Echocardiography 2023; 40:1079-1087. [PMID: 37622477 DOI: 10.1111/echo.15681] [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: 05/22/2023] [Revised: 07/28/2023] [Accepted: 08/17/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND Several echocardiographic parameters have been suggested to differentiate wild-type transthyretin cardiac amyloidosis (ATTRwt) from other causes of hypertrophy. These studies have all been performed in small samples of mixed cardiac amyloidosis. The purpose of this study was to investigate the role of echocardiographic parameters in patients with ATTRwt and aortic stenosis (AS) versus patients with AS. The secondary aim was to investigate the role of myocardial work in the prognosis of patients with ATTRwt. METHODS The sensitivity and specificity of the relative apical sparing ratio (RAS), the apical-to-basal ratio (AB), the ejection-fraction-to-global-longitudinal-strain ratio (EF/GLS), and the global myocardial work index (GWI) were calculated using receiver-operated characteristics curves and area under the curve (AUC) in patients with ATTRwt and AS (n = 50) versus patients with AS (n = 354). Multivariable regression was used to assess the prognostic value of GWI in patients with ATTRwt (n = 212). RESULTS When used to identify AS from ATTRwt + AS, GWI had a sensitivity of 80% and specificity of 70%. The AUC of GWI was larger than that of AB (p = .01) and EF/GLS (p > .01) but not RAS (p = .15). In patients with ATTRwt multivariable regression found age predicted mortality with an estimate of HR = 1.086 (CI: 1.034-1.141) while GWI predicted survival with an estimate of HR = .837 (CI: .733-.956) per 100 mmHg*% increase. CONCLUSION GWI was demonstrated to be a viable classifier in ATTRwt and AS versus AS. GWI was demonstrated to independently predict survival in patients with ATTRwt. Further studies examining the role of myocardial work in ATTRwt are warranted.
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Affiliation(s)
- Bertil Ladefoged
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
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19
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Kittleson MM, Ruberg FL, Ambardekar AV, Brannagan TH, Cheng RK, Clarke JO, Dember LM, Frantz JG, Hershberger RE, Maurer MS, Nativi-Nicolau J, Sanchorawala V, Sheikh FH. 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2023; 81:1076-1126. [PMID: 36697326 DOI: 10.1016/j.jacc.2022.11.022] [Citation(s) in RCA: 208] [Impact Index Per Article: 104.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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20
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Cersosimo A, Bonelli A, Lombardi CM, Moreo A, Pagnesi M, Tomasoni D, Arabia G, Vizzardi E, Adamo M, Farina D, Metra M, Inciardi RM. Multimodality imaging in the diagnostic management of concomitant aortic stenosis and transthyretin-related wild-type cardiac amyloidosis. Front Cardiovasc Med 2023; 10:1108696. [PMID: 36998972 PMCID: PMC10043370 DOI: 10.3389/fcvm.2023.1108696] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 02/21/2023] [Indexed: 03/17/2023] Open
Abstract
Severe aortic stenosis (AS) is the most common valvular heart disease with a prevalence rate of more than 4% in 75-year-old people or older. Similarly, cardiac amyloidosis (CA), especially "wild-type transthyretin" (wTTR), has shown a prevalence rate ranging from 22% to 25% in people older than 80 years. The detection of the concomitant presence of CA and AS is challenging primarily because of the similar type of changes in the left ventricle caused by AS and CA, which share some morphological characteristics. The aim of this review is to identify the imaging triggers in order to recognize occult wtATTR-CA in patients with AS, clarifying the crucial step of the diagnostic process. Multimodality imaging methods such as echocardiography, cardiac magnetic resonance, cardiac computed tomography, and DPD scintigraphy will be analyzed as part of the available diagnostic workup to identify wtATTR-CA early in patients with AS.
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Affiliation(s)
- Angelica Cersosimo
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Andrea Bonelli
- ASST Grande Ospedale Metropolitano Niguarda, “A. De Gasperis” Department, Cardiology IV, Milan, Italy
| | - Carlo M. Lombardi
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Antonella Moreo
- ASST Grande Ospedale Metropolitano Niguarda, “A. De Gasperis” Department, Cardiology IV, Milan, Italy
| | - Matteo Pagnesi
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Daniela Tomasoni
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Gianmarco Arabia
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Enrico Vizzardi
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Marianna Adamo
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Davide Farina
- ASST Spedali Civili di Brescia, Division of Radiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Marco Metra
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Riccardo M. Inciardi
- ASST Spedali Civili di Brescia, Division of Cardiology and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
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21
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Caponetti AG, Accietto A, Saturi G, Ponziani A, Sguazzotti M, Massa P, Giovannetti A, Ditaranto R, Parisi V, Leone O, Guaraldi P, Cortelli P, Gagliardi C, Longhi S, Galiè N, Biagini E. Screening approaches to cardiac amyloidosis in different clinical settings: Current practice and future perspectives. Front Cardiovasc Med 2023; 10:1146725. [PMID: 36970351 PMCID: PMC10033591 DOI: 10.3389/fcvm.2023.1146725] [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: 01/17/2023] [Accepted: 02/20/2023] [Indexed: 03/29/2023] Open
Abstract
Cardiac amyloidosis is a serious and progressive infiltrative disease caused by the deposition of amyloid fibrils in the heart. In the last years, a significant increase in the diagnosis rate has been observed owing to a greater awareness of its broad clinical presentation. Cardiac amyloidosis is frequently associated to specific clinical and instrumental features, so called "red flags", and it appears to occur more commonly in particular clinical settings such as multidistrict orthopedic conditions, aortic valve stenosis, heart failure with preserved or mildly reduced ejection fraction, arrhythmias, plasma cell disorders. Multimodality approach and new developed techniques such PET fluorine tracers or artificial intelligence may contribute to strike up extensive screening programs for an early recognition of the disease.
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Affiliation(s)
- Angelo Giuseppe Caponetti
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Antonella Accietto
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Giulia Saturi
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Alberto Ponziani
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Maurizio Sguazzotti
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Paolo Massa
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Alessandro Giovannetti
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Raffaello Ditaranto
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Vanda Parisi
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Ornella Leone
- Department of Pathology, Cardiovascular and Cardiac Transplant Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Pietro Guaraldi
- IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy
| | - Pietro Cortelli
- IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy
- Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Christian Gagliardi
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Bologna, Italy
| | - Simone Longhi
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Bologna, Italy
| | - Nazzareno Galiè
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Elena Biagini
- Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Bologna, Italy
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22
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Khedraki R, Robinson AA, Jordan T, Grodin JL, Mohan RC. A Review of Current and Evolving Imaging Techniques in Cardiac Amyloidosis. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2023; 25:43-63. [PMID: 38239280 PMCID: PMC10795761 DOI: 10.1007/s11936-023-00976-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/30/2022] [Indexed: 03/07/2023]
Abstract
Purpose of review Establishing an early, efficient diagnosis for cardiac amyloid (CA) is critical to avoiding adverse outcomes. We review current imaging tools that can aid early diagnosis, offer prognostic information, and possibly track treatment response in CA. Recent findings There are several current conventional imaging modalities that aid in the diagnosis of CA including electrocardiography, echocardiography, bone scintigraphy, cardiac computed tomography (CT), and cardiac magnetic resonance (CMR) imaging. Advanced imaging techniques including left atrial and right ventricular strain, and CMR T1 and T2 mapping as well as ECV quantification may provide alternative non-invasive means for diagnosis, more granular prognostication, and the ability to track treatment response. Summary Leveraging a multimodal imaging toolbox is integral to the early diagnosis of CA; however, it is important to understand the unique role and limitations posed by each modality. Ongoing studies are needed to help identify imaging markers that will lead to an enhanced ability to diagnose, subtype and manage this condition.
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Affiliation(s)
- Rola Khedraki
- Section of Advanced Heart Failure, Division of Cardiovascular Medicine, Scripps Clinic, Prebys Cardiovascular Institute, 9898 Genesee Ave., AMP-300, La Jolla, San Diego, CA 92037, USA
| | - Austin A. Robinson
- Section of Advanced Heart Failure, Division of Cardiovascular Medicine, Scripps Clinic, Prebys Cardiovascular Institute, 9898 Genesee Ave., AMP-300, La Jolla, San Diego, CA 92037, USA
| | - Timothy Jordan
- Section of Advanced Heart Failure, Division of Cardiovascular Medicine, Scripps Clinic, Prebys Cardiovascular Institute, 9898 Genesee Ave., AMP-300, La Jolla, San Diego, CA 92037, USA
| | - Justin L. Grodin
- Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, USA
| | - Rajeev C. Mohan
- Section of Advanced Heart Failure, Division of Cardiovascular Medicine, Scripps Clinic, Prebys Cardiovascular Institute, 9898 Genesee Ave., AMP-300, La Jolla, San Diego, CA 92037, USA
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23
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Arshad S, Goldberg YH, Bhopalwala H, Dewaswala N, Miceli NS, Birks EJ, Vaidya GN. High Prevalence of Cardiac Amyloidosis in Clinically Significant Aortic Stenosis: A Meta-Analysis. Cardiol Res 2022; 13:357-371. [PMID: 36660066 PMCID: PMC9822671 DOI: 10.14740/cr1436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 10/28/2022] [Indexed: 12/23/2022] Open
Abstract
Background There is growing evidence of coexistence of aortic stenosis (AS) and transthyretin cardiac amyloidosis (CA). Not screening AS patients at the time of hospital/clinic visit for CA represents a lost opportunity. Methods We surveyed studies that reported the prevalence of CA among AS patients. Studies that compared patients with aortic stenosis with cardiac amyloidosis (AS-CA) and AS alone were further analyzed, and meta-regression was performed. Results We identified nine studies with 1,321 patients of AS, of which 131 patients had concomitant CA, with a prevalence of 11%. When compared to AS-alone, the patients with AS-CA were older, more likely to be males, had higher prevalence of carpal tunnel syndrome, right bundle branch block. On echocardiogram, patients with AS-CA had thicker interventricular septum, higher left ventricular mass index (LVMI), lower myocardial contraction fraction, and lower stroke volume index. Classical low-flow low-gradient (LFLG) physiology was more common among patients with AS-CA. Patients with AS-CA had higher all-cause mortality than patients with AS alone (33% vs. 22%, P = 0.02) in a follow-up period of at least 1 year. Conclusions CA has a high prevalence in patients with AS and is associated with worse clinical, imaging, and biochemical parameters than patients with AS alone.
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Affiliation(s)
- Samiullah Arshad
- Department of Medicine, University of Kentucky, Lexington, KY, USA,Corresponding Author: Samiullah Arshad, Department of Medicine, University of Kentucky, Lexington, KY, USA.
| | | | - Huzefa Bhopalwala
- Department of Medicine, Appalachian Regional Healthcare, Whitesburg, KY, USA
| | - Nakeya Dewaswala
- Division of Cardiology (Advanced Heart Failure and Transplantation), Gill Heart and Vascular Institute, University of Kentucky, Lexington KY, USA
| | - Nicholas S. Miceli
- College of Management, School of Business, Park University, Parkville, MO, USA
| | - Emma J. Birks
- Division of Cardiology (Advanced Heart Failure and Transplantation), Gill Heart and Vascular Institute, University of Kentucky, Lexington KY, USA
| | - Gaurang N. Vaidya
- Division of Cardiology (Advanced Heart Failure and Transplantation), Gill Heart and Vascular Institute, University of Kentucky, Lexington KY, USA
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24
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Transthyretin Cardiac Amyloidosis. Cardiol Clin 2022; 40:541-558. [DOI: 10.1016/j.ccl.2022.06.008] [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: 11/18/2022]
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25
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Nitsche C, Koschutnik M, Donà C, Radun R, Mascherbauer K, Kammerlander A, Heitzinger G, Dannenberg V, Spinka G, Halavina K, Winter MP, Calabretta R, Hacker M, Agis H, Rosenhek R, Bartko P, Hengstenberg C, Treibel T, Mascherbauer J, Goliasch G. Reverse Remodeling Following Valve Replacement in Coexisting Aortic Stenosis and Transthyretin Cardiac Amyloidosis. Circ Cardiovasc Imaging 2022; 15:e014115. [PMID: 35861981 DOI: 10.1161/circimaging.122.014115] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 06/09/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Dual pathology of severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR) is increasingly recognized. Evolution of symptoms, biomarkers, and myocardial mechanics in AS-ATTR following valve replacement is unknown. We aimed to characterize reverse remodeling in AS-ATTR and compared with lone AS. METHODS Consecutive patients referred for transcatheter aortic valve replacement (TAVR) underwent ATTR screening by blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) before intervention. ATTR was diagnosed by DPD and absence of monoclonal protein. Reverse remodeling was assessed by comprehensive evaluation before TAVR and at 1 year. RESULTS One hundred twenty patients (81.8±6.3 years, 51.7% male, 95 lone AS, 25 AS-ATTR) with complete follow-up were studied. At 12 months (interquartile range, 7-17) after TAVR, both groups experienced significant symptomatic improvement by New York Heart Association functional class (both P<0.001). Yet, AS-ATTR remained more symptomatic (New York Heart Association ≥III: 36.0% versus 13.8; P=0.01) with higher residual NT-proBNP (N-terminal pro-brain natriuretic peptide) levels (P<0.001). Remodeling by echocardiography showed left ventricular mass regression only for lone AS (P=0.002) but not AS-ATTR (P=0.5). Global longitudinal strains improved similarly in both groups. Conversely, improvement of regional longitudinal strain showed a base-to-apex gradient in AS-ATTR, whereas all but apical segments improved in lone AS. This led to the development of an apical sparing pattern in AS-ATTR only after TAVR. CONCLUSIONS Patterns of reverse remodeling differ from lone AS to AS-ATTR, with both groups experiencing symptomatic improvement by TAVR. After AS treatment, AS-ATTR transfers into a lone ATTR cardiomyopathy phenotype.
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Affiliation(s)
- Christian Nitsche
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Matthias Koschutnik
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Carolina Donà
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Richard Radun
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Katharina Mascherbauer
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Andreas Kammerlander
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Gregor Heitzinger
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Varius Dannenberg
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Georg Spinka
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Kseniya Halavina
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Max-Paul Winter
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | | | - Marcus Hacker
- Division of Nuclear Medicine (R.C., M.H.), Medical University of Vienna
| | - Hermine Agis
- Division of Hematology (H.A.), Medical University of Vienna
| | - Raphael Rosenhek
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Philipp Bartko
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Christian Hengstenberg
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
| | - Thomas Treibel
- Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom (T.T.)
| | - Julia Mascherbauer
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
- Karl Landsteiner University of Health Sciences, Department of Internal Medicine III, University Hospital St. Pölten, Krems, Austria (J.M.)
| | - Georg Goliasch
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria (C.N., M.K., C.D., R. Radun, K.M., A.K., G.H., V.D., G.S., K.H., M.-P.W., R. Rosenhek, P.B., C.H., J.M., G.G.)
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Cannata F, Chiarito M, Pinto G, Villaschi A, Sanz-Sánchez J, Fazzari F, Regazzoli D, Mangieri A, Bragato RM, Colombo A, Reimers B, Condorelli G, Stefanini GG. Transcatheter aortic valve replacement in aortic stenosis and cardiac amyloidosis: a systematic review and meta-analysis. ESC Heart Fail 2022; 9:3188-3197. [PMID: 35770333 DOI: 10.1002/ehf2.13876] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 12/03/2021] [Accepted: 02/24/2022] [Indexed: 01/15/2023] Open
Abstract
AIMS Aortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve replacement (TAVR) have a concomitant diagnosis of CA. CA-AS population suffers from reduced functional capacity and worse prognosis than AS patients. As the prognostic impact of TAVR in patients with CA-AS has been historically questioned and in light of recently published evidence, we aim to provide a comprehensive synthesis of the efficacy and safety of TAVR in CA-AS patients. METHODS AND RESULTS We performed a systematic review and meta-analysis of studies: (i) evaluating mortality with TAVR as compared with medical therapy in CA-AS patients and (ii) reporting complications and clinical outcomes of TAVR in CA-AS patients as compared with patients with AS alone. A total of seven observational studies were identified: four reported mortality with TAVR, and four reported complications and clinical outcomes after TAVR of patients with CA-AS compared with AS alone patients. In patients with CA-AS, the risk of mortality was lower with TAVR (n = 44) as compared with medical therapy (n = 36) [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07-0.73, I2 = 0%, P = 0.001, number needed to treat = 3]. The safety profile of TAVR seems to be similar in patients with CA-AS (n = 75) as compared with those with AS alone (n = 536), with comparable risks of stroke, vascular complications, life-threatening bleeding, acute kidney injury, and 30 day mortality, although CA-AS was associated with a trend towards an increased risk of permanent pacemaker implantation (OR 1.76, 95% CI 0.91-4.09, I2 = 0%, P = 0.085). CA is associated with a numerically higher rate of long-term mortality and rehospitalizations following TAVR in patients with CA-AS as compared with those with AS alone. CONCLUSIONS TAVR is an effective and safe procedure in CA-AS patients, with a substantial survival benefit as compared with medical therapy, and a safety profile comparable with patients with AS alone except for a trend towards higher risk of permanent pacemaker implantation.
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Affiliation(s)
- Francesco Cannata
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, Pieve Emanuele-Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | - Mauro Chiarito
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, Pieve Emanuele-Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | - Giuseppe Pinto
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, Pieve Emanuele-Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | - Alessandro Villaschi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, Pieve Emanuele-Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | - Jorge Sanz-Sánchez
- Hospital Universitario y Politecnico La Fe, Valencia, Spain.,Centro de Investigación Biomedica en Red (CIBERCV), Madrid, Spain
| | - Fabio Fazzari
- IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | | | | | | | | | | | - Gianluigi Condorelli
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, Pieve Emanuele-Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | - Giulio G Stefanini
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 4, Pieve Emanuele-Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
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27
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Bay K, Gustafsson F, Maiborg M, Bagger‐Bahnsen A, Strand AM, Pilgaard T, Poulsen SH. Suspicion, screening, and diagnosis of wild-type transthyretin amyloid cardiomyopathy: a systematic literature review. ESC Heart Fail 2022; 9:1524-1541. [PMID: 35343098 PMCID: PMC9065854 DOI: 10.1002/ehf2.13884] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 02/11/2022] [Accepted: 02/25/2022] [Indexed: 01/15/2023] Open
Abstract
Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non-invasive diagnosis by bone scintigraphy, and the development of disease-modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at-risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light-chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at-risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high-quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at-risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.
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Affiliation(s)
- Katrine Bay
- Bay WritingCopenhagenDenmark
- Pfizer DenmarkBallerupDenmark
| | - Finn Gustafsson
- The Heart CenterCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
| | - Michael Maiborg
- Odense Amyloidosis Center & Department of CardiologyOdense University HospitalOdenseDenmark
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28
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Andrews JPM, Trivieri MG, Everett R, Spath N, MacNaught G, Moss AJ, Doris MK, Pawade T, van Beek EJR, Lucatelli C, Newby DE, Robson P, Fayad ZA, Dweck MR. 18F-fluoride PET/MR in cardiac amyloid: A comparison study with aortic stenosis and age- and sex-matched controls. J Nucl Cardiol 2022; 29:741-749. [PMID: 33000405 PMCID: PMC8993737 DOI: 10.1007/s12350-020-02356-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 08/19/2020] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls. METHODS In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging. Standardized volumes of interest were drawn in the septum and areas of late gadolinium enhancement to derive myocardial standardized uptake values (SUV) and tissue-to-background ratio (TBRMEAN) after correction for blood pool activity in the right atrium. RESULTS 53 patients were scanned: 18 with cardiac amyloid (10 ATTR and 8 AL), 13 controls, and 22 with aortic stenosis. No differences in myocardial TBR values were observed between participants scanned in Edinburgh and New York. Mean myocardial TBRMEAN values in ATTR amyloid (1.13 ± 0.16) were higher than controls (0.84 ± 0.11, P = .0006), aortic stenosis (0.73 ± 0.12, P < .0001), and those with AL amyloid (0.96 ± 0.08, P = .01). TBRMEAN values within areas of late gadolinium enhancement provided discrimination between patients with ATTR (1.36 ± 0.23) and all other groups (e.g., AL [1.06 ± 0.07, P = .003]). A TBRMEAN threshold >1.14 in areas of LGE demonstrated 100% sensitivity (CI 72.25 to 100%) and 100% specificity (CI 67.56 to 100%) for ATTR compared to AL amyloid (AUC 1, P = .0004). CONCLUSION Quantitative 18F-fluoride PET/MR imaging can distinguish ATTR amyloid from other similar phenotypes and holds promise in improving the diagnosis of this condition.
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Affiliation(s)
- Jack P M Andrews
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK.
| | - Maria Giovanni Trivieri
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- BioMedical Engineering and Imaging Institute, New York, NY, USA
| | - Russell Everett
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK
| | - Nicholas Spath
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK
| | - Gillian MacNaught
- Edinburgh Imaging, Queen's Medical Research Institute University of Edinburgh, Edinburgh, UK
| | - Alastair J Moss
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK
| | - Mhairi K Doris
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK
| | - Tania Pawade
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK
| | - Edwin J R van Beek
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK
- Edinburgh Imaging, Queen's Medical Research Institute University of Edinburgh, Edinburgh, UK
| | - Christophe Lucatelli
- Edinburgh Imaging, Queen's Medical Research Institute University of Edinburgh, Edinburgh, UK
| | - David E Newby
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK
| | - Philip Robson
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- BioMedical Engineering and Imaging Institute, New York, NY, USA
| | - Zahi A Fayad
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
- BioMedical Engineering and Imaging Institute, New York, NY, USA
| | - Marc R Dweck
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Room SU.305, Chancellor's building, 51 Little France Crescent, Edinburgh, EH16 4SB, UK
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Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis. Nat Commun 2021; 12:7112. [PMID: 34876572 PMCID: PMC8651690 DOI: 10.1038/s41467-021-27416-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 11/19/2021] [Indexed: 02/07/2023] Open
Abstract
Cardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments. ATTR amyloidosis causes heart failure through the accumulation of misfolded transthyretin in cardiac muscle. Here the authors report a mouse model of ATTR amyloidosis and demonstrate the involvement of protease activity in ATTR amyloid deposition.
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30
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Tahara N, Lairez O, Endo J, Okada A, Ueda M, Ishii T, Kitano Y, Lee HE, Russo E, Kubo T. 99m Technetium-pyrophosphate scintigraphy: a practical guide for early diagnosis of transthyretin amyloid cardiomyopathy. ESC Heart Fail 2021; 9:251-262. [PMID: 34841715 PMCID: PMC8788016 DOI: 10.1002/ehf2.13693] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 09/16/2021] [Accepted: 10/25/2021] [Indexed: 01/15/2023] Open
Abstract
Transthyretin amyloid cardiomyopathy (ATTR‐CM) is caused by the cardiac deposition of insoluble amyloid fibrils formed by misfolded transthyretin proteins and is associated with various cardiac symptoms, such as progressive heart failure, conduction disturbance, and arrhythmia. The implementation of 99mtechnetium (99mTc)‐labelled bone radiotracer scintigraphy for diagnosing ATTR‐CM has enabled accurate diagnosis of the disease with high sensitivity and specificity and positioned this diagnostic modality as an integral part of disease diagnostic algorithms. In 2020, 99mTc‐pyrophosphate scintigraphy received exceptional approval for Japanese national health insurance reimbursement as a diagnostic method of ATTR‐CM. Nevertheless, the utility of 99mTc‐labelled bone radiotracer scintigraphy and the importance of an early diagnosis of suspected ATTR‐CM using this technique have yet to be internalized as common practice by general cardiologists, and guidance on daily clinical scenarios to consider this technique for a diagnosis of suspected ATTR‐CM is warranted. In this review, we discuss the utility of 99mTc‐labelled bone radiotracer scintigraphy for the early diagnosis of ATTR‐CM based on published literature and the outcomes of an advisory board meeting. This review also discusses clinical scenarios that could support early diagnosis of suspected ATTR‐CM as well as common pitfalls, correct implementation, and future perspectives of 99mTc‐labelled bone radiotracer scintigraphy in daily clinical practice. The clinical scenarios to consider 99mTc‐labelled bone radiotracer scintigraphy in daily practice may include, but are not limited to, patients with a family history of the hereditary type of disease; elderly patients (aged ≥60 years) with unexplained cardiac findings (e.g. cardiac hypertrophy associated with abnormalities on an electrocardiogram, heart failure with preserved ejection fraction associated with unexplained left ventricular hypertrophy, and heart failure with reduced ejection fraction associated with atrial fibrillation and left ventricular hypertrophy); and patients with cardiac hypertrophy associated with diastolic dysfunction, right ventricular/interatrial septum/valve thickness, left ventricular sparkling, or apical sparing. Cardiac hypertrophy and persistent elevation in cardiac troponin in elderly patients are also suggestive of ATTR‐CM. 99mTc‐labelled bone radiotracer scintigraphy is also recommended in patients with characteristic cardiac magnetic resonance findings (e.g. diffuse subendocardial late gadolinium enhancement patterns, native T1 increase, and increase in extracellular volume) or patients with cardiac hypertrophy and bilateral carpal tunnel syndrome.
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Affiliation(s)
- Nobuhiro Tahara
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0001, Japan
| | - Olivier Lairez
- Centre Hospitalier Universitaire de Toulouse, Toulouse, France
| | - Jin Endo
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
| | - Atsushi Okada
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Mitsuharu Ueda
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | | | | | | | | | - Toru Kubo
- Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University, Kochi, Japan
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31
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Lioncino M, Monda E, Palmiero G, Caiazza M, Vetrano E, Rubino M, Esposito A, Salerno G, Dongiglio F, D'Onofrio B, Verrillo F, Cerciello G, Manganelli F, Pacileo G, Bossone E, Golino P, Calabrò P, Limongelli G. Cardiovascular Involvement in Transthyretin Cardiac Amyloidosis. Heart Fail Clin 2021; 18:73-87. [PMID: 34776085 DOI: 10.1016/j.hfc.2021.07.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Transthyretin cardiac amyloidosis (ATTR-CA) is a systemic disorder resulting from the extracellular deposition of amyloid fibrils of misfolded transthyretin protein in the heart. ATTR-CA is a life-threatening disease, which can be caused by progressive deposition of wild type transthyretin (wtATTR) or by aggregation of an inherited mutated variant of transthyretin (mATTR). mATTR Is a rare condition transmitted in an autosomal dominant manner with incomplete penetrance, causing heterogenous phenotypes which can range from predominant neuropathic involvement, predominant cardiomyopathy, or mixed. Diagnosis of ATTR-CA is complex and requires integration of different imaging tools (echocardiography, bone scintigraphy, magnetic resonance) with genetics, clinical signs, laboratory tests, and histology. In recent years, new therapeutic agents have shown good efficacy and impact on survival and quality of life in this subset of patients, nevertheless patients affected by ATTR-CA may still carry an unfavorable prognosis, thus highlighting the need for new therapies. This review aims to assess cardiovascular involvement, diagnosis, and management of patients affected by ATTR-CA.
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Affiliation(s)
- Michele Lioncino
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Emanuele Monda
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Giuseppe Palmiero
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Martina Caiazza
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Erica Vetrano
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy; Internal Medicine Unit, Department of Translational Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Marta Rubino
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Augusto Esposito
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Gemma Salerno
- Vanvitelli Cardiology Unit, Monaldi Hospital, Naples 80131, Italy
| | - Francesca Dongiglio
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Barbara D'Onofrio
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Federica Verrillo
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Giuseppe Cerciello
- Haematology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Fiore Manganelli
- Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples 'Federico II', Via Pansini, 5, Naples 81025, Italy
| | - Giuseppe Pacileo
- Heart Failure and Cardiac Rehabilitation Unit, Department of Cardiology, AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Eduardo Bossone
- Division of Cardiology, "Antonio Cardarelli" Hospital, Naples 80131, Italy
| | - Paolo Golino
- Vanvitelli Cardiology Unit, Monaldi Hospital, Naples 80131, Italy; Department of Translational Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Paolo Calabrò
- Department of Translational Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; Division of Cardiology, A.O.R.N. "Sant'Anna & San Sebastiano", Caserta I-81100, Italy
| | - Giuseppe Limongelli
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy; Institute of Cardiovascular Sciences, University College of London and St. Bartholomew's Hospital, London WC1E 6DD, UK.
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Griffin JM, Rosenthal JL, Grodin JL, Maurer MS, Grogan M, Cheng RK. ATTR Amyloidosis: Current and Emerging Management Strategies: JACC: CardioOncology State-of-the-Art Review. JACC: CARDIOONCOLOGY 2021; 3:488-505. [PMID: 34729521 PMCID: PMC8543085 DOI: 10.1016/j.jaccao.2021.06.006] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/02/2021] [Accepted: 06/04/2021] [Indexed: 12/15/2022]
Abstract
Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly diagnosed owing to the emergence of noninvasive imaging and improved awareness. Clinical penetrance of pathogenic alleles is not complete and therefore there is a large cohort of asymptomatic transthyretin variant carriers. Screening strategies, monitoring, and treatment of subclinical ATTR-CA requires further study. Perhaps the most important translational triumph has been the development of effective therapies that have emerged from a biological understanding of ATTR-CA pathophysiology. These include recently proven strategies of transthyretin protein stabilization and silencing of transthyretin production. Data on neurohormonal blockade in ATTR-CA are limited, with the primary focus of medical therapy on judicious fluid management. Atrial fibrillation is common and requires anticoagulation owing to the propensity for thrombus formation. Although conduction disease and ventricular arrhythmias frequently occur, little is known regarding optimal management. Finally, aortic stenosis and ATTR-CA frequently coexist, and transcatheter valve replacement is the preferred treatment approach.
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Key Words
- 6MWT, 6-minute walk test
- AF, atrial fibrillation
- AL, light chain amyloid
- AS, aortic stenosis
- ASO, antisense oligonucleotide
- ATTR-CA, transthyretin cardiac amyloidosis
- ATTRv, variant transthyretin cardiac amyloidosis
- ATTRwt, wild-type transthyretin cardiac amyloidosis
- CMR, cardiac magnetic resonance
- DCCV, direct current cardioversion
- HF, heart failure
- LVEF, left ventricular ejection fraction
- NT-proBNP, N-terminal pro–B-type natriuretic peptide
- SAP, serum amyloid P component
- TAVR, transcatheter aortic valve replacement
- amyloidosis
- cardiomyopathy
- heart failure
- siRNA, small interfering RNA
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Affiliation(s)
- Jan M Griffin
- Columbia University Irving Medical Center, New York, New York, USA
| | | | - Justin L Grodin
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Mathew S Maurer
- Columbia University Irving Medical Center, New York, New York, USA
| | | | - Richard K Cheng
- University of Washington Medical Center, Seattle, Washington, USA
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33
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Bajwa F, O'Connor R, Ananthasubramaniam K. Epidemiology and clinical manifestations of cardiac amyloidosis. Heart Fail Rev 2021; 27:1471-1484. [PMID: 34694575 DOI: 10.1007/s10741-021-10162-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/17/2021] [Indexed: 11/29/2022]
Abstract
Cardiac amyloidosis, once considered a rare disease, has garnered significant attention over the last few years due to three key reasons: first, increased recognition of this disease in conjunction with various common cardiac conditions such as heart failure with preserved ejection fraction and aortic stenosis; second, due to the advent of promising new therapies for light chain disease (AL), transthyretin (ATTR) cardiomyopathy, and amyloid neuropathy; finally, the advancements in cardiac imaging including echocardiography, magnetic resonance imaging, and nuclear cardiac scintigraphy aid in non-biopsy diagnosis of ATTR cardiac amyloidosis. The hereditary forms of ATTR have further come into importance with the availability of genetic testing and increased prevalence of certain mutations in African Americans. Recognition of non-cardiac clues to this disease has gained importance and reiterates that high clinical suspicion, detailed patient history, and examination with appropriate use of imaging are vital to confirm the diagnosis.
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Affiliation(s)
- Farhan Bajwa
- Department of Cardiology, University of Rochester Medical Center, Rochester, NY, USA
| | - Ryan O'Connor
- Department of Cardiology, University of Rochester Medical Center, Rochester, NY, USA
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Fabbri G, Serenelli M, Cantone A, Sanguettoli F, Rapezzi C. Transthyretin amyloidosis in aortic stenosis: clinical and therapeutic implications. Eur Heart J Suppl 2021; 23:E128-E132. [PMID: 34650371 PMCID: PMC8503413 DOI: 10.1093/eurheartj/suab107] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
About one in seven elderly patients with severe calcific aortic stenosis (AS) also have ATTR amyloid cardiomyopathy (AC-TTR). The reasons for this close association are not fully known, but the two entities are not only related by common epidemiology. For example, it is possible to hypothesize that an amyloidotic infiltration of the aortic valve, even partial, can act as a trigger for the development of endothelial damage and subsequent calcification. Another hypothesis is the increased myocardial strain induced by AS may locally favour the process of amyloidogenesis and tissue infiltration. In a patient with AS, the coexistence of AC-TTR can be suspected by careful analysis of the echocardiogram and the ECG, especially if a clinical history of carpal tunnel syndrome coexists. Bone tracer scintigraphy allows a diagnosis of certainty. Recently, several studies have evaluated the prognostic implications of the coexistence of the two entities in candidates for percutaneous aortic valve replacement, showing how amyloidosis would not significantly impact the results of the procedure, but would only be associated with a greater risk of distant heart failure. In patients with AS associated with AC-TTR, valve replacement should not be ruled out in the presence of the usual clinical-haemodynamic indications.
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Affiliation(s)
- Gioele Fabbri
- Centro Cardiologico, Università di Ferrara, via Aldo Moro 8, Cona, 44124 Ferrara, Italy
| | - Matteo Serenelli
- Centro Cardiologico, Università di Ferrara, via Aldo Moro 8, Cona, 44124 Ferrara, Italy
| | - Anna Cantone
- Centro Cardiologico, Università di Ferrara, via Aldo Moro 8, Cona, 44124 Ferrara, Italy
| | - Federico Sanguettoli
- Centro Cardiologico, Università di Ferrara, via Aldo Moro 8, Cona, 44124 Ferrara, Italy
| | - Claudio Rapezzi
- Centro Cardiologico, Università di Ferrara, via Aldo Moro 8, Cona, 44124 Ferrara, Italy.,Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy
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35
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Affiliation(s)
- Richard Cheng
- Division of Cardiology, University of Washington Medical Center, Seattle, Washington, USA
| | - Jan Griffin
- Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA
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36
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Singal AK, Bansal R, Singh A, Dorbala S, Sharma G, Gupta K, Saxena A, Bhargava B, Karthikeyan G, Ramakrishnan S, Bisoi AK, Hote MP, Rajashekar P, Chowdhury UK, Devagourou V, Patel C, Ray R, Arawa SK, Mishra S. Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population: A Pilot Study. JACC CardioOncol 2021; 3:565-576. [PMID: 34746852 PMCID: PMC8551518 DOI: 10.1016/j.jaccao.2021.08.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 08/15/2021] [Accepted: 08/18/2021] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Prevalence of both degenerative severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CA) increases with age. Dual disease (AS+myocardial ATTR-CA) occurs in significant proportion of patients undergoing surgical aortic valve replacement (SAVR). OBJECTIVES This study aimed to determine the prevalence of ATTR-CA in severe AS in the Indian population, identify noninvasive predictors of its diagnosis, and understand its impact on prognosis. METHODS Symptomatic severe AS patients aged ≥65 years undergoing SAVR were enrolled. ATTR-CA diagnosis was based on preoperative 99m-technetium pyrophosphate (PYP) scan and intraoperatively obtained basal interventricular septum biopsy for myocardial ATTR-CA, and excised native aortic valve for isolated valvular ATTR-CA. Primary amyloidosis was excluded by serum/urine protein electrophoresis with serum immunofixation. RESULTS SAVR was performed in 46 AS patients (age 70 ± 5 years, 70% men). PYP scan was performed for 32 patients, with significant PYP uptake in 3 (n = 3 of 32, 9.4%), suggestive of myocardial ATTR-CA. On histopathological examination, none of the interventricular septum biopsy specimens had amyloid deposits, whereas 33 (71.7%) native aortic valves showed amyloid deposits, of which 19 (57.6%) had transthyretin deposition suggestive of isolated valvular amyloidosis. Noninvasive markers of dual disease included low myocardial contraction fraction (median [interquartile range], 28.8% [23.8% to 39.1%] vs 15.3% [9.3% to 16.1%]; P = 0.006), deceleration time (215 [144 to 236] ms vs 88 [60 to 106] ms; P = 0.009) and global longitudinal strain (-18.7% [-21.1% to -16.9%] vs -14.2% [-17.0% to -9.7%]; P = 0.030). At 1-year follow-up, 2 patients died (4.3%); 1 each in myocardial ATTR-CA negative and positive groups (3.4% vs 33.3%; P = 0.477). CONCLUSIONS Dual disease is not uncommon in India. Isolated valvular amyloidosis in severe AS is much more common.
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Key Words
- 99m-technetium pyrophosphate scan
- 99mTc-PYP, 99m-technetium pyrophosphate
- AL-CA, light chain cardiac amyloidosis
- AS, aortic stenosis
- ATTR-CA, transthyretin cardiac amyloidosis
- EMB, endomyocardial biopsy
- GLS, global longitudinal strain
- IHC, immunohistochemistry
- LfLg AS, low-flow, low-gradient aortic stenosis
- SAVR, surgical aortic valve replacement
- TAVR, transcatheter aortic valve replacement
- TTR, transthyretin
- dual aortic stenosis transthyretin cardiac amyloidosis
- severe aortic stenosis
- transthyretin cardiac amyloidosis
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Affiliation(s)
| | | | - Avinainder Singh
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Sharmila Dorbala
- Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | - Kartik Gupta
- Department of Medicine, Henry Ford Hospital, Detroit, Michigan, USA
| | - Anita Saxena
- Department of Cardiology, AIIMS, New Delhi, India
| | - Balram Bhargava
- Department of Cardiology, AIIMS, New Delhi, India
- Indian Council of Medical Research, New Delhi, India, and Department of Health Research (Ministry of Health and Family Welfare), Government of India, New Delhi, India
| | | | | | | | | | | | | | | | - Chetan Patel
- Department of Nuclear Medicine, AIIMS, New Delhi, India
| | - Ruma Ray
- Department of Pathology, AIIMS, New Delhi, India
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37
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Bonelli A, Paris S, Nardi M, Henein MY, Agricola E, Troise G, Faggiano P. Aortic Valve Stenosis and Cardiac Amyloidosis: A Misleading Association. J Clin Med 2021; 10:4234. [PMID: 34575344 PMCID: PMC8471197 DOI: 10.3390/jcm10184234] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/13/2021] [Accepted: 09/13/2021] [Indexed: 01/15/2023] Open
Abstract
The association between aortic stenosis (AS) and cardiac amyloidosis (CA) is more frequent than expected. Albeit rare, CA, particularly the transthyretin (ATTR) form, is commonly found in elderly people. ATTR-CA is also the most prevalent form in patients with AS. These conditions share pathophysiological, clinical and imaging findings, making the diagnostic process very challenging. To date, a multiparametric evaluation is suggested in order to detect patients with both AS and CA and choose the best therapeutic option. Given the accuracy of modern non-invasive techniques (i.e., bone scintigraphy), early diagnosis of CA is possible. Flow-charts with the main CA findings which may help clinicians in the diagnostic process have been proposed. The prognostic impact of the combination of AS and CA is not fully known; however, new available specific treatments of ATTR-CA have changed the natural history of the disease and have some impact on the decision-making process for the management of AS. Hence the relevance of detecting these two conditions when simultaneously present. The specific features helping the detection of AS-CA association are discussed in this review, focusing on the shared pathophysiological characteristics and the common clinical and imaging hallmarks.
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Affiliation(s)
- Andrea Bonelli
- Cardiology Unit, Spedali Civili and University of Brescia, 25100 Brescia, Italy; (A.B.); (S.P.); (M.N.)
| | - Sara Paris
- Cardiology Unit, Spedali Civili and University of Brescia, 25100 Brescia, Italy; (A.B.); (S.P.); (M.N.)
| | - Matilde Nardi
- Cardiology Unit, Spedali Civili and University of Brescia, 25100 Brescia, Italy; (A.B.); (S.P.); (M.N.)
| | - Michael Y. Henein
- Department of Public Health and Clinical Medicine, Umea University, 90187 Umea, Sweden;
| | - Eustachio Agricola
- Cardiovascular Imaging Unit, Cardio-Thoracic-Vascular Department, San Raffaele Hospital, Vita-Salute University, 20132 Milan, Italy;
| | - Giovanni Troise
- Cardiac Surgery, Cardiothoracic Department, Fondazione Poliambulanza, 25100 Brescia, Italy;
| | - Pompilio Faggiano
- Cardiology, Cardiothoracic Department, Fondazione Poliambulanza, 25100 Brescia, Italy
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38
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[Cardiac amyloidosis and aortic valve stenosis]. Herz 2021; 46:485-496. [PMID: 34487196 DOI: 10.1007/s00059-021-05054-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2021] [Indexed: 10/20/2022]
Abstract
Aortic valve stenosis in old age has become a topic of interest for cardiology and cardiac surgery after the development of transvascular and transluminal minimally invasive techniques for aortic valve implantation. The observation of amyloid deposits in surgically excised valvular material led to the diagnostics of amyloidosis of the myocardium, which was discovered in up to 20% of the patients who underwent valve implantation. Clinical signs of cardiac amyloidosis, such as carpal tunnel syndrome and ruptured distal biceps tendon should be taken into account. In addition to the electrocardiogram (ECG), echocardiogram and magnetic resonance imaging, 99mtechnetium bone scintigraphy plays a key diagnostic role. The simultaneous occurrence of severe aortic valve stenosis and amyloidosis explains the special hemodynamic situation of a low gradient with low blood flow in high-grade valve stenosis. The interventional or surgical valve implantation improves the prognosis for these patients, similarly to aortic valve stenosis alone, followed by a specific pharmaceutical treatment depending on the type of amyloidosis.
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39
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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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40
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Smith A, Balmforth D, Treibel TA, Lall K, Oo A, Ambekar S. Cardiac amyloidosis in non-transplant cardiac surgery. J Card Surg 2021; 36:2901-2910. [PMID: 33993535 DOI: 10.1111/jocs.15629] [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: 12/05/2020] [Revised: 04/14/2021] [Accepted: 04/15/2021] [Indexed: 11/30/2022]
Abstract
Cardiac amyloidosis is a rare infiltrative cardiomyopathy that portends a poor prognosis. There is a growing recognition of co-existent aortic valve stenosis and transthyretin cardiac amyloidosis, with some studies suggesting that dual pathology may be associated increased risk of complication and mortality during surgical intervention. This review aims to evaluate the available literature on non-transplant cardiac surgical interventions in patients with cardiac amyloidosis, with particular focus on diagnosis, high surgical risk and areas of uncertainty that require further research.
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Affiliation(s)
- Alex Smith
- The Department of Cardiac Surgery, St Bartholomew's Hospital, London, UK.,Queen Mary University of London, London, UK
| | - D Balmforth
- The Department of Cardiac Surgery, St Bartholomew's Hospital, London, UK
| | - T A Treibel
- The Department of Cardiac Surgery, St Bartholomew's Hospital, London, UK.,Institute for Cardiovascular Sciences, University College London, London, UK
| | - Kulvinder Lall
- The Department of Cardiac Surgery, St Bartholomew's Hospital, London, UK
| | - Aung Oo
- The Department of Cardiac Surgery, St Bartholomew's Hospital, London, UK
| | - Shirish Ambekar
- The Department of Cardiac Surgery, St Bartholomew's Hospital, London, UK
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41
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Wehbe RM, Kansal P, Holly TA. Cases from a busy nuclear cardiology laboratory: Potential pitfalls in the interpretation of cardiac scintigraphy for ATTR cardiac amyloidosis. J Nucl Cardiol 2021; 28:653-660. [PMID: 32383085 DOI: 10.1007/s12350-020-02094-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 02/24/2020] [Indexed: 01/15/2023]
Abstract
Cardiac scintigraphy has emerged as a key diagnostic test for transthyretin cardiac amyloidosis (ATTR-CA). However, there are potential limitations and pitfalls in the interpretation of cardiac scintigraphy for ATTR-CA that are worth noting. We present here a series of three cases which illustrate some of these important principles.
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Affiliation(s)
- Ramsey M Wehbe
- Division of Cardiology, Department of Medicine, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Preeti Kansal
- Division of Cardiology, Department of Medicine, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Thomas A Holly
- Division of Cardiology, Department of Medicine, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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42
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Abstract
PURPOSE OF REVIEW Cardiac amyloidosis is an underrecognized cause of heart failure. We review clinical clues to the diagnoses, a rational approach to testing, and current and emerging therapies. RECENT FINDINGS Advances in the diagnosis of amyloid cardiomyopathy include (1) use of 99mtechnetium (99mTc) bone-avid compounds which allow accurate noninvasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) in the context of a negative monoclonal light chain screen; and (2) the use of serum and urine immunofixation electrophoresis with serum free light chains as an accurate first diagnostic step for light chain cardiac amyloidosis (AL-CM). Advances in treatment include tafamidis for ATTR-CM and immunologic therapies for AL-CM. With the advent of accurate noninvasive diagnostic modalities and effective therapies, early recognition of cardiac amyloidosis is paramount to implement a diagnostic algorithm and expeditiously institute effective therapies to minimize morbidity and mortality.
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43
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Han D, Tamarappoo B, Klein E, Tyler J, Chakravarty T, Otaki Y, Miller R, Eisenberg E, Park R, Singh S, Shiota T, Siegel R, Stegic J, Salseth T, Cheng W, Dey D, Thomson L, Berman D, Makkar R, Friedman J. Computed tomography angiography-derived extracellular volume fraction predicts early recovery of left ventricular systolic function after transcatheter aortic valve replacement. Eur Heart J Cardiovasc Imaging 2021; 22:179-185. [PMID: 33324979 PMCID: PMC7822636 DOI: 10.1093/ehjci/jeaa310] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 10/30/2020] [Indexed: 01/04/2023] Open
Abstract
AIMS Recovery of left ventricular ejection fraction (LVEF) after aortic valve replacement has prognostic importance in patients with aortic stenosis (AS). The mechanism by which myocardial fibrosis impacts LVEF recovery in AS is not well characterized. We sought to evaluate the predictive value of extracellular volume fraction (ECV) quantified by cardiac CT angiography (CTA) for LVEF recovery in patients with AS after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS In 109 pre-TAVR patients with LVEF <50% at baseline echocardiography, CTA-derived ECV was calculated as the ratio of change in CT attenuation of the myocardium and the left ventricular (LV) blood pool before and after contrast administration. Early LVEF recovery was defined as an absolute increase of ≥10% in LVEF measured by post-TAVR follow-up echocardiography within 6 months of the procedure. Early LVEF recovery was observed in 39 (36%) patients. The absolute increase in LVEF was 17.6 ± 8.8% in the LVEF recovery group and 0.9 ± 5.9% in the no LVEF recovery group (P < 0.001). ECV was significantly lower in patients with LVEF recovery compared with those without LVEF recovery (29.4 ± 6.1% vs. 33.2 ± 7.7%, respectively, P = 0.009). In multivariable analysis, mean pressure gradient across the aortic valve [odds ratio (OR): 1.07, 95% confidence interval (CI): 1.03-1.11, P: 0.001], LV end-diastolic volume (OR: 0.99, 95% CI: 0.98-0.99, P: 0.035), and ECV (OR: 0.92, 95% CI: 0.86-0.99, P: 0.018) were independent predictors of early LVEF recovery. CONCLUSION Increased myocardial ECV on CTA is associated with impaired LVEF recovery post-TAVR in severe AS patients with impaired LV systolic function.
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Affiliation(s)
- Donghee Han
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Balaji Tamarappoo
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Eyal Klein
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Jeffrey Tyler
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Tarun Chakravarty
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Yuka Otaki
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Robert Miller
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Evann Eisenberg
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Rebekah Park
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Siddharth Singh
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Takahiro Shiota
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Robert Siegel
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Jasminka Stegic
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Tracy Salseth
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Wen Cheng
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Damini Dey
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
- Biomedical Imaging Research Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Louise Thomson
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Daniel Berman
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - Raj Makkar
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
- Smidt Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
| | - John Friedman
- Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA
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Nitsche C, Scully PR, Patel KP, Kammerlander AA, Koschutnik M, Dona C, Wollenweber T, Ahmed N, Thornton GD, Kelion AD, Sabharwal N, Newton JD, Ozkor M, Kennon S, Mullen M, Lloyd G, Fontana M, Hawkins PN, Pugliese F, Menezes LJ, Moon JC, Mascherbauer J, Treibel TA. Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis. J Am Coll Cardiol 2021; 77:128-139. [PMID: 33181246 PMCID: PMC7805267 DOI: 10.1016/j.jacc.2020.11.006] [Citation(s) in RCA: 225] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/26/2020] [Accepted: 11/04/2020] [Indexed: 01/15/2023]
Abstract
BACKGROUND Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR). OBJECTIVES This study identified clinical characteristics and outcomes of AS-CA compared with lone AS. METHODS Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality. RESULTS A total of 407 patients (age 83.4 ± 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n = 16]; grade 2/3: 7.9% [n = 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p < 0.001). Decisions by the heart team (DPD-blinded) resulted in TAVR (333 [81.6%]), surgical AVR (10 [2.5%]), or medical management (65 [15.9%]). After a median of 1.7 years, 23% of patients died. One-year mortality was worse in all patients with AS-CA (grade: 1 to 3) than those with lone AS (24.5% vs. 13.9%; p = 0.05). TAVR improved survival versus medical management; AS-CA survival post-TAVR did not differ from lone AS (p = 0.36). CONCLUSIONS Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA.
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Affiliation(s)
- Christian Nitsche
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Paul R Scully
- Institute of Cardiovascular Science, University College London, London, United Kingdom; Cardiology Department, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom
| | - Kush P Patel
- Institute of Cardiovascular Science, University College London, London, United Kingdom; Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
| | - Andreas A Kammerlander
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Matthias Koschutnik
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Carolina Dona
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Tim Wollenweber
- Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
| | - Nida Ahmed
- Institute of Cardiovascular Science, University College London, London, United Kingdom; Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
| | - George D Thornton
- Institute of Cardiovascular Science, University College London, London, United Kingdom; Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
| | | | | | | | - Muhiddin Ozkor
- Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
| | - Simon Kennon
- Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
| | - Michael Mullen
- Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
| | - Guy Lloyd
- Institute of Cardiovascular Science, University College London, London, United Kingdom; Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom; Queen Mary University London, London, United Kingdom
| | | | | | - Francesca Pugliese
- Institute of Cardiovascular Science, University College London, London, United Kingdom; Queen Mary University London, London, United Kingdom
| | - Leon J Menezes
- Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom; UCL/ULCH NIHR Biomedical Research Centre, London, United Kingdom
| | - James C Moon
- Institute of Cardiovascular Science, University College London, London, United Kingdom; Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
| | - Julia Mascherbauer
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Thomas A Treibel
- Institute of Cardiovascular Science, University College London, London, United Kingdom; Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom.
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Paeng JC, Choi JY. Nuclear Imaging for Cardiac Amyloidosis: Bone Scan, SPECT/CT, and Amyloid-Targeting PET. Nucl Med Mol Imaging 2021; 55:61-70. [PMID: 33968272 DOI: 10.1007/s13139-020-00681-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 12/21/2020] [Accepted: 12/29/2020] [Indexed: 02/06/2023] Open
Abstract
Cardiac amyloidosis (CA) is a type of systemic amyloidosis, in which abnormal amyloid fibril is deposited in extracellular space of myocardium. Most common subtypes of CA are amyloidosis of immunoglobulin light chain (AL) and amyloidosis of transthyretin (ATTR). With increase in incidence of CA and development of new drugs, the needs of early and accurate diagnosis of CA are increasing. In CA, bone scan and SPECT/CT have long been used for diagnosis. Currently, bone scan is included in almost all practice guidelines as one of key diagnostic examinations for ATTR CA. In some specific scenarios, bone scan can be used as even a substitute for endomyocardial biopsy. Recently, amyloid-targeting PET that is used for Alzheimer dementia has also been attempted as an imaging method for CA. Although the study results are still insufficient, amyloid-targeting has shown promising potential as an imaging method for CA, particularly in AL. Here, imaging method and clinical application and implication of bone scan, SPECT/CT, and amyloid-targeting PET/CT in CA are reviewed.
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Affiliation(s)
- Jin Chul Paeng
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, Republic of Korea
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BİÇER A, TAŞCANOV MB, TANRIVERDİ Z. Günlük pratikte tanıdan tedaviye amiloid kardiyomiyopati. CUKUROVA MEDICAL JOURNAL 2020. [DOI: 10.17826/cumj.780658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
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Rapezzi C, Giannini F, Campo G. Aortic stenosis, transcatheter aortic valve replacement and transthyretin cardiac amyloidosis: are we progressively unraveling the tangle? Eur J Heart Fail 2020; 23:259-263. [PMID: 33190343 DOI: 10.1002/ejhf.2057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 11/09/2020] [Accepted: 11/11/2020] [Indexed: 01/20/2023] Open
Affiliation(s)
- Claudio Rapezzi
- Cardiovascular Center, University of Ferrara, Ferrara, Italy.,Maria Cecilia Hospital, GVM Care & Research, Cotignola (RA), Italy
| | | | - Gianluca Campo
- Cardiovascular Center, University of Ferrara, Ferrara, Italy.,Maria Cecilia Hospital, GVM Care & Research, Cotignola (RA), Italy
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Pasqualucci D, Iacovoni A, Palmieri V, De Maria R, Iacoviello M, Battistoni I, Macera F, Olivotto I, Arbustini E, Mortara A. Epidemiology of cardiomyopathies: essential context knowledge for a tailored clinical work-up. Eur J Prev Cardiol 2020; 29:1190-1199. [PMID: 33623987 DOI: 10.1093/eurjpc/zwaa035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 07/10/2020] [Accepted: 08/01/2020] [Indexed: 12/19/2022]
Abstract
Cardiomyopathies (CMPs) are primary disorders of myocardial structure and function in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease. Knowledge of the incidence and prevalence of CMPs may help clinicians to compare their observations in clinical practice with expected cases per person-year and to avoid under-reporting in clinical context. Currently, available estimates of prevalence and incidence of CMPs are based on clinical data, collected with a wide variability in population-source, and before the genetic testing evolved as a standard diagnostic tool. This review focuses on the epidemiology of CMPs in subjects aged between 18 and 55 years. A structured up-to-date diagnostic flow-chart for CMPs diagnosis and assessment is proposed to avoid misdiagnosis of CMPs in the young population and in subjects with unexplained cardiac disorders.
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Affiliation(s)
- Daniele Pasqualucci
- Department of Cardiology, Azienda Ospedaliera Brotzu, Piazzale Ricchi 1, 09134, Cagliari, Italy
| | - Attilio Iacovoni
- Cardiovascular Department, ASST Papa Giovanni XXIII Hospital, Piazza OMS, 1, 24127, Bergamo, Italy
| | - Vittorio Palmieri
- Heart Transplantation Unit, Department of cardiac surgery and transplantation, Ospedali dei Colli ,Via L. Bianchi s.n.c. 80131 Naples, Italy
| | - Renata De Maria
- CNR Institute of Clinical Physiology, CardioThoracic and Vascular Department, ASST Great Metropolitan Hospital Niguarda, Piazza Ospedale Maggiore 3 20162, Milan, Italy
| | - Massimo Iacoviello
- Cardiology Unit of Riuniti Policlinic University Hospital, Department of Medical and Surgical Sciences, University of Foggia, ViaLuigi Pinto 1, 71122, Foggia, Italy
| | - Ilaria Battistoni
- CCU-Cardiology Department, Azienda Ospedaliero-Universitaria "Ospedali Riuniti", via Conca 71 60020, Ancona, Italy
| | - Francesca Macera
- Heart Failure and Transplant Unit, De Gasperis CardioCenter, ASST Great Metropolitan Hospital Niguarda, P.zza Ospedale Maggiore 3, 20162 Milan, Italy
| | - Iacopo Olivotto
- Cardiomiopathy Unit, Careggi University Hospital, Viale Pieraccini 1, 50134, Florence, Italy
| | - Eloisa Arbustini
- Centre for Inherited Cardiovascular Diseases, IRCCS Fondazione Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy
| | - Andrea Mortara
- Department of Clinical Cardiology, Policlinico di Monza, Via Carlo Amati, 111, 20900 Monza, Italy
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Garcia-Pavia P, Domínguez F, Gonzalez-Lopez E. Transthyretin amyloid cardiomyopathy. Med Clin (Barc) 2020; 156:126-134. [PMID: 33138983 DOI: 10.1016/j.medcli.2020.06.064] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/25/2020] [Accepted: 06/27/2020] [Indexed: 12/11/2022]
Abstract
Transthyretin (TTR) cardiac amyloidosis is a severe, progressive, infiltrative disease caused by the deposition of TTR at cardiac level. It may be due to a genetic alteration in its hereditary form (ATTRv) or as a consequence of an age-related degenerative process (ATTRwt). Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that ATTR is more frequent than traditionally considered and that it is particularly relevant in patients over 65 years with heart failure or with aortic stenosis. With the appearance of several treatment options capable of modifying the natural history of ATTR, it is necessary for clinicians to be familiar with the diagnostic process and treatment of this disease. This review will cover the clinical spectrum of presentation of ATTR, its diagnosis and treatment.
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Affiliation(s)
- Pablo Garcia-Pavia
- Unidad de Insuficiencia Cardíaca y Cardiopatías Familiares, Servicio de Cardiología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, España; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, España; Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, España.
| | - Fernando Domínguez
- Unidad de Insuficiencia Cardíaca y Cardiopatías Familiares, Servicio de Cardiología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, España; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, España
| | - Esther Gonzalez-Lopez
- Unidad de Insuficiencia Cardíaca y Cardiopatías Familiares, Servicio de Cardiología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, España; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, España
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Prognostic Value of Computed Tomography-Derived Extracellular Volume in TAVR Patients With Low-Flow Low-Gradient Aortic Stenosis. JACC Cardiovasc Imaging 2020; 13:2591-2601. [PMID: 33129731 DOI: 10.1016/j.jcmg.2020.07.045] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 07/06/2020] [Accepted: 07/09/2020] [Indexed: 01/01/2023]
Abstract
OBJECTIVES The association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND Patients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes. METHODS In 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH. RESULTS During a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p < 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p < 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p < 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p < 0.01). CONCLUSIONS In patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.
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