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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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Ahmad S, Ahsan MJ, Newlun M, Sand M, Rmilah AA, Yousaf A, Shabbir MA, Malik SA, Goldsweig AM. Outcomes of aortic stenosis in patients with cardiac amyloidosis: A systematic review and meta-analysis. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2025:S1553-8389(25)00047-8. [PMID: 39955158 DOI: 10.1016/j.carrev.2025.02.005] [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: 12/07/2024] [Revised: 02/02/2025] [Accepted: 02/06/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND Cardiac amyloidosis (CA) results from the deposition of abnormally folded protein fibrils, leading to restrictive cardiomyopathy, valvular heart disease, and arrhythmias. Up to 15 % of patients with severe aortic stenosis (AS) have concomitant CA (AS-CA). We conducted this systematic review and meta-analysis to compare medical management, transcatheter aortic valve replacement (TAVR), and surgical AVR (SAVR) in AS-CA. METHODS A comprehensive literature search was conducted for relevant studies from inception through January 20, 2024. Studies exploring outcomes in adult AS patients with and without CA receiving medical therapy, TAVR, or SAVR were included in this analysis. RESULTS Fifteen studies including 253,334 patients (AS-CA 6704; AS alone 246,630) were identified. AS-CA patients had significantly higher all-cause mortality (RR = 2.60, 95 % CI 1.48-4.57, P = 0.0009) compared to AS alone. Among patients with AS-CA, TAVR was associated with lower all-cause mortality compared to both medical therapy (RR = 0.50, 95 % CI 0.29-0.89, P = 0.02) and SAVR (RR = 0.41, 95 % CI 0.22-0.78, P = 0.007). AS-CA patients undergoing TAVR were more likely to have paradoxical low-flow, low-gradient AS (RR = 1.56, 95 % CI 1.15-2.12, P = 0.04) at baseline and had a higher risk of post-TAVR acute kidney injury (RR = 1.95, 95 % CI 1.35-2.80, P = 0.0003) compared to patients undergoing TAVR for AS alone. There were similar risks of other post-TAVR complications, including major bleeding, vascular complications, stroke, and new pacemaker implantation between AS-CA and AS alone. CONCLUSION CA is associated with a higher mortality in patients with severe AS. In patients with concomitant AS and CA, TAVR is safe and associated with better survival than medical therapy or SAVR. SOCIAL MEDIA ABSTRACT: #Meta-Analysis: Cardiac amyloidosis is associated with increased mortality in severe AS. #TAVR is safe in amyloidosis & improves survival more than medical therapy or SAVR.
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Affiliation(s)
- Soban Ahmad
- Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
| | - Muhammad Junaid Ahsan
- Department of Cardiovascular Medicine, Baylor University Medical Center, Dallas, TX, USA
| | - Morgan Newlun
- Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Mitchell Sand
- Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Anan Abu Rmilah
- Department of Medicine, Magnolia Regional Health Center, Corinth, MS, USA
| | - Amman Yousaf
- Department of Medicine, McLaren Flint-Michigan State University, Flint, MI, USA
| | - Muhammad Asim Shabbir
- Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Shahbaz A Malik
- Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Andrew M Goldsweig
- Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Department of Cardiovascular Medicine, Baystate Medical Center and University of Massachusetts-Baystate, Springfield, MA, USA. https://twitter.com/AGoldsweig
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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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Shchendrygina A, Mewton N, Niederseer D, Kida K, Guidetti F, Duval AJ, Milinkovic I, Oerlemans MIFJ, Zaleska-Kociecka M, de Gracia SG, Palacio MI, Giverts I, Komarova I, Rustamova Y, Bahouth F, Mežnar AZ, Mapelli M, Suvorov A, Dyachuk I, Shutov M, Sitnikova V, Garnier-Crussard A, Barasa A, Loncar G, Tokmakova M, Skouri H, Ruschitzka F, Saldarriaga C. Cardiac Amyloidosis Screening and Management in Patients With Heart Failure With Preserved Ejection Fraction: An International Survey. Am J Cardiol 2025; 236:42-48. [PMID: 39481586 DOI: 10.1016/j.amjcard.2024.10.009] [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: 08/31/2024] [Revised: 09/30/2024] [Accepted: 10/14/2024] [Indexed: 11/02/2024]
Abstract
Cardiac amyloidosis (CA) is still an underdiagnosed cause of heart failure (HF) and early disease recognition and timely disease-modifying therapy (DMT) administration translate to better outcomes. We aimed to assess CA screening and management approaches for patients with HF preserved ejection fraction (HFpEF) among physicians worldwide. An independent academic web-based survey was distributed worldwide between May 2023 and July 2023. Overall, 1,460 physicians (61% were men, median age was 42 [34 to 49] years) from 95 countries completed the survey. A total of 2/3 of respondents had experience diagnosing CA and reported having 10% of patients with CA in patients with HFpEF. Systematic screening for CA of all patients with HFpEF was performed by 10% of responders, whereas 24% did not consider the screening. Most responders (39%) used left ventricular hypertrophy as a screening criterion. Serum protein electrophoresis with immunofixation of free light chain and urine protein electrophoresis or cardiac magnetic resonance were selected by half of the responders as a first-line diagnostic tool. The combination of serum protein electrophoresis with immunofixation free light chain, urine protein electrophoresis, and bone scintigraphy was considered by 32% of the participants. CA DMT was available for 48% of the physicians. About 82% of responders would administrate HF to patients with HFpEF with CA, with the most preferable drugs being diuretics, sodium-glucose cotransporter-2 inhibitors, and renin-angiotensin-aldosterone system inhibitors. In conclusion, the results reveal the uncertainties among physicians worldwide regarding the need for CA screening of patients with HFpEF. CA remains a disease with very heterogeneous management, particularly, in the screening and diagnostic workup. The HF community should aim to educate on CA and improve access to DMT.
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Affiliation(s)
- Anastasia Shchendrygina
- Department of Hospital Therapy 2, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.
| | - Nathan Mewton
- Heart Failure Department and Clinical Investigation Center, Hôpital Cardiovasculaire Louis Pradel Hospices Civils de Lyon Heart Failure Department Clinical Investigation Center Inserm 1407 CarMeN Inserm 1060, University Claude Bernard Lyon, Bron, France
| | - David Niederseer
- Department of Cardiology, Hochgebirgsklinik Davos, Medicine Campus Davos, Davos, Switzerland; Department of Cardiology, Center for Translational and Experimental Cardiology (CTEC), University Hospital Zurich, University of Zurich, Zurich, Switzerland; Christine Kühne - Center of Allergy Research and Education (CK-CARE), Medicine Campus Davos, Davos, Switzerland
| | - Keisuke Kida
- Department of Pharmacology, St Marianna University School of Medicine, Kawasaki, Japan
| | - Federica Guidetti
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Antoine Jobbe Duval
- Heart Failure Department and Clinical Investigation Center, Hôpital Cardiovasculaire Louis Pradel Hospices Civils de Lyon Heart Failure Department Clinical Investigation Center Inserm 1407 CarMeN Inserm 1060, University Claude Bernard Lyon, Bron, France
| | - Ivan Milinkovic
- Department of Cardiology, University Clinical Centre of Serbia, Belgrade, Serbia; Faculty of Medicine, Belgrade University, Belgrade, Serbia
| | - Marish I F J Oerlemans
- Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands; Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart(1), Amsterdam, The Netherlands
| | - Marta Zaleska-Kociecka
- Department of Heart Failure and Transplantology, Mechanical Circulatory Support and Transplantology Unit, National Institute of Cardiology, Warsaw, Poland
| | | | - Maria Isabel Palacio
- Cardiovid Clinic, Pontificia Bolivariana, University of Antioquia, Medellin, Colombia
| | - Ilya Giverts
- Department of Internal Medicine, Maimonides Medical Center, Brooklyn, New York; The Cardiovascular Research Center, Massachusetts General Center, 55 Fruit street, Boston, MA 02114, USA
| | - Irina Komarova
- Department of Hospital Therapy 2, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Yasmin Rustamova
- Department of Internal Medicine, Educational-Surgery Clinic, Azerbaijan Medical University, Baku, Azerbaijan
| | - Fadel Bahouth
- Intensive Cardiac Care Unit, EMMS Nazareth Hospital, Faculty of Medicine, Bar-Ilan University, Israel
| | - Anja Zupan Mežnar
- Department of Cardiology, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Massimo Mapelli
- Heart Failure Unit, Centro Cardiologico Monzino IRCCs, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Alexandr Suvorov
- Department of Internal Medicine, Educational-Surgery Clinic, Azerbaijan Medical University, Baku, Azerbaijan; World-Class Research Center "Digital biodesign and personalized healthcare," Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Irina Dyachuk
- Cardiology Department, City Clinical Hospital named after S. S. Yudin, Moscow, Russian Federation
| | - Michail Shutov
- Cardiology Department, City Polyclinic №64, Moscow, Russian Federation
| | - Violetta Sitnikova
- Department of Hospital Therapy 2, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Antoine Garnier-Crussard
- Clinical and Research Memory Centre of Lyon, Lyon Institute for Aging, Charpennes Hospital, Hospices Civils de Lyon, Clinical Research Center Ageing-Brain-Frailty, Inserm 1237, University Claude Bernard Lyon 1, Villeurbanne, France
| | - Anders Barasa
- Department of Cardiology, Amager Hvidovre Hospital, University of Copenhagen, Denmark
| | - Goran Loncar
- Dedinje Cardiovascular Institute, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Serbia
| | - Mariya Tokmakova
- Devision of Cardiology, First Department of Internal Diseases, Medical University of Plovdiv, Clinic of Cardiology, UMHAT "Sv. Georgi" EAD Plovdiv, Bulgaria
| | - Hadi Skouri
- Cardiology Division, Sheikh Shakhbout Medical City, Abu-Dhabi, United Arab Emirates
| | - Frank Ruschitzka
- Department of Cardiology, Center for Translational and Experimental Cardiology (CTEC), University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Clara Saldarriaga
- Cardiovid Clinic, Pontificia Bolivariana, University of Antioquia, Medellin, Colombia
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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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7
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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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8
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Delgado D, Dabbous F, Shivappa N, Mazhar F, Wittbrodt E, Shridharmurthy D, Järbrink K. Epidemiology of transthyretin (ATTR) amyloidosis: a systematic literature review. Orphanet J Rare Dis 2025; 20:29. [PMID: 39819351 PMCID: PMC11740649 DOI: 10.1186/s13023-025-03547-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 01/07/2025] [Indexed: 01/19/2025] Open
Abstract
INTRODUCTION Significant advances in the treatment of transthyretin (ATTR) amyloidosis has led to an evolving understanding of the epidemiology of this condition. This systematic literature review (SLR) aims to synthesize current evidence on epidemiology and mortality outcomes in ATTR amyloidosis, addressing the need for a comprehensive understanding of its current global impact. METHODS An SLR of the literature from January 2018 to April 2023 was conducted using the Medline and Embase databases. The review followed the PRISMA guidelines. Studies evaluating populations with genotypes and phenotypes of ATTR amyloidosis (variant and wild-type cardiomyopathy, polyneuropathy, and mixed) were included. Observational studies, systematic reviews, and meta-analyses were eligible, while reports, commentaries, clinical trials, and non-ATTR amyloidosis studies were excluded. Extracted data included prevalence, incidence, and mortality rates. RESULTS Of the 1,458 studies identified, 113 met the inclusion criteria. Forty-nine studies reported on epidemiology, while 64 focused on mortality rates in cohorts of patients with ATTR amyloidosis from Europe (n = 16), North America (n = 26), Asia (n = 5), and Australia (n = 2). No studies were found that exclusively focused on ATTR amyloidosis in Africa or South America. ATTR prevalence ranged from 6.1/million in the US to 232/million in Portugal with very limited data on ATTR-PN. The 2-year mortality risk ranged from 10 to 30% among wild-type ATTR-CM and from 10 to 50% for variant type of ATTR-CM. CONCLUSIONS This SLR demonstrated heterogeneity in ATTR epidemiology and mortality rates across global regions. Further investigation is needed to address knowledge gaps of the epidemiology and burden of ATTR, which may improve early diagnosis and management.
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Affiliation(s)
- Diego Delgado
- Division of Cardiology and Transplant, UHN, Toronto, ON, Canada
| | - Firas Dabbous
- Data Analytics - Real World Evidence, Evidera, Bethesda, MD, USA
| | - Nitin Shivappa
- Cardiovascular, Renal and Metabolism (CVRM) Evidence, BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA.
| | - Faizan Mazhar
- Real-World Evidence, Data Analytics, Evidera, Stockholm, Sweden
| | - Eric Wittbrodt
- Cardiovascular, Renal and Metabolism (CVRM) Evidence, BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA
| | | | - Krister Järbrink
- Cardiovascular, Renal and Metabolism (CVRM) Evidence, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden
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Lee CY, Nabeshima Y, Kitano T, Yang LT, Takeuchi M. Diagnostic Accuracy and Prognostic Value of Relative Apical Sparing in Cardiac Amyloidosis - Systematic Review and Meta-Analysis. Circ J 2024; 89:16-23. [PMID: 39496393 DOI: 10.1253/circj.cj-24-0472] [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: 11/06/2024]
Abstract
BACKGROUND Although the relative apical sparing (RAPS) pattern of left ventricular (LV) longitudinal strain is a hallmark of cardiac amyloidosis, recent studies have raised concerns about its accuracy. The aim of this systematic review was to investigate diagnostic test accuracy (DTA) and prognostic impact of RAPS in cardiac amyloidosis. METHODS AND RESULTS We searched PubMed, Embase, and Scopus for manuscripts that could potentially be used in the DTA arm and prognosis arm. Thirty-seven studies were used for DTA analysis. The pooled sensitivity, specificity, and diagnostic odds ratio were 61% (95% confidence interval [CI] 54-68%), 83% (95% CI 80-86%), and 8.9 (95% CI 6.1-13.1), respectively. These values did not differ regardless of the presence of aortic stenosis, but the diagnostic odds ratio differed significantly among analytical software packages. For the prognosis arm, 6 studies were dichotomously assessed for RAPS, and 5 were assessed quantitatively. The pooled proportion of RAPS was 49% and the pooled estimate of the RAPS ratio was 1.40. Although RAPS was associated with outcome (hazard ratio [HR] 1.87; 95% CI 1.15-3.04; P=0.011), its significance disappeared after trim and fill analysis (HR 1.42; 95% CI 0.85-2.38; P=0.184). CONCLUSIONS RAPS has a modest DTA with a significant vendor dependency and does not provide robust prognostic information.
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Affiliation(s)
| | | | - Tetsuji Kitano
- Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine
| | - Li-Tan Yang
- Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital
| | - Masaaki Takeuchi
- Department of Laboratory and Transfusion Medicine, Hospital of University of Occupational and Environmental Health
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10
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Collins C, Cios TJ, Walker J. RNA Interference in Amyloid: What's New From HELIOS-B? J Cardiothorac Vasc Anesth 2024:S1053-0770(24)00993-5. [PMID: 39799050 DOI: 10.1053/j.jvca.2024.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Accepted: 12/16/2024] [Indexed: 01/15/2025]
Affiliation(s)
- Christopher Collins
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S Hershey Medical Center, Hershey, PA
| | - Theodore J Cios
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S Hershey Medical Center, Hershey, PA.
| | - Justin Walker
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S Hershey Medical Center, Hershey, PA
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11
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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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12
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Chauhan A, Greason KL, Borgeson DD, Todd A, Stulak JM, Daly RC, Crestanello JA, Schaff HV. A propensity-matched analysis of cardiac operation in patients with and without cardiac amyloidosis. JTCVS OPEN 2024; 22:235-243. [PMID: 39780801 PMCID: PMC11704520 DOI: 10.1016/j.xjon.2024.07.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 07/31/2024] [Indexed: 01/11/2025]
Abstract
Objective There are limited data on the outcome of routine cardiac operations in patients with cardiac amyloidosis. This study studied the impact of amyloidosis on early and late results of cardiac operations. Methods This was a retrospective, propensity-matched, case-control study of patients with cardiac amyloidosis undergoing cardiac surgery. Heart transplantation and ventricular assist implantation were excluded. Controls were patients without known cardiac amyloidosis matched on baseline patient characteristics, echocardiographic findings, and type of operation. Outcomes included operative complications and survival. Results In total, 42 patients with cardiac amyloidosis (amyloid group [AG]) were matched with 168 controls (CON group). The median left ventricular ejection fraction was 63% in the AG group (vs 64% CON). Aortic valve replacement and septal myectomy were the most common operations. Cardiopulmonary bypass (P = .374) and crossclamp (P = .185) times were similar in the 2 groups. Complication rates were similar in the 2 groups, including the need for mechanical circulatory support (n = 1 AG group vs n = 1 CON; P = .361) and intra-aortic balloon pump use (n = 3 AG group vs n = 13 CON; P = 1.000). There were no operative deaths. Survival was similar in the 2 groups at 1 year (AG 93% vs 89% CON; P = .1) but was worse in the AG at 5 years (59% vs 68% CON; P = .1). Conclusions Early procedural outcomes and 1-year survival are similar in patients with and without cardiac amyloidosis with preserved cardiac function. Diagnosis of amyloidosis should not be a contraindication to cardiac surgery.
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Affiliation(s)
- Akshay Chauhan
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn
| | - Kevin L. Greason
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn
| | | | - Austin Todd
- Department of Clinical Trials & Biostatistics, Mayo Clinic, Rochester, Minn
| | - John M. Stulak
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn
| | - Richard C. Daly
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn
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13
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Nies RJ, Ney S, Kindermann I, Bewarder Y, Zimmer A, Knebel F, Hahn K, Spethmann S, Luedike P, Michel L, Rassaf T, Papathanasiou M, Störk S, Cejka V, Polzin A, Voss F, Kelm M, Unsöld B, Meindl C, Paulus M, Yilmaz A, Chamling B, Morbach C, Pfister R. Real-world characteristics and treatment of cardiac transthyretin amyloidosis: A multicentre, observational study. ESC Heart Fail 2024. [PMID: 39505353 DOI: 10.1002/ehf2.15126] [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: 06/24/2024] [Revised: 09/03/2024] [Accepted: 10/03/2024] [Indexed: 11/08/2024] Open
Abstract
AIMS Data on the clinical profiles of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) in the post-approval era of tafamidis 61 mg are lacking. Study aims were characterization of contemporary ATTR-CM patients, analysis of potential eligibility for the 'Transthyretin Amyloidosis Cardiomyopathy Clinical Trial' (ATTR-ACT) and identification of factors associated with the decision on tafamidis 61 mg treatment. METHODS AND RESULTS This retrospective study analysed ATTR-CM patients seen at eight University Hospitals in the first year after approval of tafamidis 61 mg for ATTR-CM in Germany (April 2020 to March 2021). The cohort comprised 366 patients (median age 79 [74; 82] years, 84% male), with 47% and 45% of the cohort being in National Amyloidosis Centre ATTR stage ≥ II and NYHA class ≥ III, respectively. Sixty-four per cent of patients met key eligibility criteria of the pivotal ATTR-ACT. In recently diagnosed patients (58% with diagnosis ≤6 months), the rate of variant ATTR was significantly lower than in patients diagnosed more than 6 months ago (9.3% vs. 19.7%). Of the 293 patients without prior ATTR specific treatment, tafamidis 61 mg was newly initiated in 77%. Patients with tafamidis 61 mg treatment were significantly younger, were more often eligible for ATTR-ACT, had lower NYHA class and higher serum albumin levels. These variables explained 16% of the variance of treatment decision. Unadjusted survival was higher in patients with than those without treatment (1-year survival 98.6% vs. 87.3%, P < 0.001). CONCLUSIONS Wild-type ATTR was the primary aetiology amongst contemporary ATTR-CM patients and almost two-thirds of patients were in an advanced disease stage. Clinical profiles of 64% of patients in routine care matched those of the ATTR-ACT. Further effort is needed to detect patients at an earlier disease stage and to validate criteria justifying treatment initiation.
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Affiliation(s)
- Richard J Nies
- Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne, Cologne, Germany
| | - Svenja Ney
- Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne, Cologne, Germany
| | - Ingrid Kindermann
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg, Germany
| | - Yvonne Bewarder
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg, Germany
| | - Angela Zimmer
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg, Germany
| | - Fabian Knebel
- Sana Klinikum Berlin Lichtenberg, Berlin, Germany
- Klinik für Kardiologie, Angiologie und Intensivmedizin, Deutsches Herzzentrum der Charité, Berlin, Germany
| | - Katrin Hahn
- Klinik für Kardiologie, Angiologie und Intensivmedizin, Deutsches Herzzentrum der Charité, Berlin, Germany
- Klinik für Neurologie mit Experimenteller Neurologie, Charité Universitätsmedizin Berlin, Berlin, Germany
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Sebastian Spethmann
- Klinik für Kardiologie, Angiologie und Intensivmedizin, Deutsches Herzzentrum der Charité, Berlin, Germany
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Amyloidosis Center Charité Berlin (ACCB), Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Peter Luedike
- West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Lars Michel
- West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Tienush Rassaf
- West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Maria Papathanasiou
- West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Department of Cardiology, University Hospital Frankfurt, Frankfurt, Germany
| | - Stefan Störk
- Department of Clinical Research and Epidemiology, Department of Medicine I, Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany
| | - Vladimir Cejka
- Department of Clinical Research and Epidemiology, Department of Medicine I, Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany
| | - Amin Polzin
- Division of Cardiology, Pulmonology, and Vascular Medicine, University Duesseldorf, Medical Faculty, Cardiovascular Research Institute Düsseldorf (CARID), Duesseldorf, Germany
| | - Fabian Voss
- Division of Cardiology, Pulmonology, and Vascular Medicine, University Duesseldorf, Medical Faculty, Cardiovascular Research Institute Düsseldorf (CARID), Duesseldorf, Germany
| | - Malte Kelm
- Division of Cardiology, Pulmonology, and Vascular Medicine, University Duesseldorf, Medical Faculty, Cardiovascular Research Institute Düsseldorf (CARID), Duesseldorf, Germany
| | - Bernhard Unsöld
- Medical Clinic I, Cardiology and Angiology, Justus-Liebig-University Giessen, Giessen, Germany
- Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany
| | - Christine Meindl
- Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany
| | - Michael Paulus
- Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany
| | - Ali Yilmaz
- Klinik für Kardiologie I, Sektion für Herzbildgebung, Universitätsklinikum Münster, Münster, Germany
| | - Bishwas Chamling
- Klinik für Kardiologie I, Sektion für Herzbildgebung, Universitätsklinikum Münster, Münster, Germany
- Department of Internal Medicine B, University Medicine Greifswald and DZHK (German Centre for Cardiovascular Research) partner site Greifswald, Greifswald, Germany
| | - Caroline Morbach
- Department of Clinical Research and Epidemiology, Department of Medicine I, Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany
| | - Roman Pfister
- Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne, Cologne, Germany
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14
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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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15
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Hara J, Ishii S, Kobiyama H, Fukushima K, Kawamoto N, Yamakuni R, Suenaga H, Muto Y, Sugawara S, Sato A, Oikawa M, Takeishi Y, Ito H. A Quantitative Diagnostic Method Using 99mTc-pyrophosphate Lateral Planar Images to Distinguish Between Transthyretin Amyloid Cardiomyopathy and False-Positive Images Due to Blood Pools. ANNALS OF NUCLEAR CARDIOLOGY 2024; 10:23-28. [PMID: 39635326 PMCID: PMC11612392 DOI: 10.17996/anc.24-00001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/04/2024] [Accepted: 04/01/2024] [Indexed: 12/07/2024]
Abstract
Background: This study investigated the feasibility of using a quantitative diagnostic method based on 99mTc-pyrophosphate scintigraphy (PYP) lateral planar images to differentiate between PYP-positive (myocardial uptake) and false-positive (blood pool uptake) scans. Methods: The study included 93 consecutive patients with suspected transthyretin amyloid cardiomyopathy (ATTR-CM) who underwent PYP between April 2022 and December 2023. Patients were categorized using planar anterior PYP images according to the Perugini visual grading system; patients with grades ≥ 2 were analyzed. Whether the uptake of the ventricle was in the blood pool or the myocardium was confirmed by transaxial single-photon emission tomography (SPECT). The heart-to-mediastinum ratios (H/M ratio) of the left lateral planar images at 1- and 3-h were calculated by placing a circular region of interest in the heart and cephalodorsal side of the heart to determine optimal cut-off values. Results: Among the PYP images, the study analyzed 15 positives diagnosed as ATTR-CM and 10 false positives. Significant differences were observed in the H/M ratio at 1- and 3-h (both p<0.01), with 100% sensitivity and specificity using cut-off values of 1.22 and 1.21 at 1- and 3-h, respectively. The interclass correlation coefficients (2, 1) between the two readers were 0.919 and 0.958 for the 1- and 3-h H/M ratios, respectively. Conclusions: Lateral planar PYP imaging can exclude PYP false-positive cases caused by blood pools in a simple and quantitative manner using only a 1-h planar image, possibly obviating the need for SPECT imaging.
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Affiliation(s)
- Junko Hara
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
| | - Shiro Ishii
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
| | - Honami Kobiyama
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
| | - Kenji Fukushima
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
| | - Natsumi Kawamoto
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
| | - Ryo Yamakuni
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
| | - Hiroki Suenaga
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
| | - Yuuki Muto
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Shigeyasu Sugawara
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
| | - Akihiko Sato
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Masayoshi Oikawa
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Yasuchika Takeishi
- Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan
| | - Hiroshi Ito
- Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan
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16
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Dicorato MM, Basile P, Muscogiuri G, Carella MC, Naccarati ML, Dentamaro I, Guglielmo M, Baggiano A, Mushtaq S, Fusini L, Pontone G, Forleo C, Ciccone MM, Guaricci AI. Novel Insights into Non-Invasive Diagnostic Techniques for Cardiac Amyloidosis: A Critical Review. Diagnostics (Basel) 2024; 14:2249. [PMID: 39410653 PMCID: PMC11475987 DOI: 10.3390/diagnostics14192249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/03/2024] [Accepted: 10/07/2024] [Indexed: 10/20/2024] Open
Abstract
Cardiac amyloidosis (CA) is a cardiac storage disease caused by the progressive extracellular deposition of misfolded proteins in the myocardium. Despite the increasing interest in this pathology, it remains an underdiagnosed condition. Non-invasive diagnostic techniques play a central role in the suspicion and detection of CA, also thanks to the continuous scientific and technological advances in these tools. The 12-lead electrocardiography is an inexpensive and reproducible test with a diagnostic accuracy that, in some cases, exceeds that of imaging techniques, as recent studies have shown. Echocardiography is the first-line imaging modality, although none of its parameters are pathognomonic. According to the 2023 ESC Guidelines, a left ventricular wall thickness ≥ 12 mm is mandatory for the suspicion of CA, making this technique crucial. Cardiac magnetic resonance provides high-resolution images associated with tissue characterization. The use of contrast and non-contrast sequences enhances the diagnostic power of this imaging modality. Nuclear imaging techniques, including bone scintigraphy and positron emission tomography, allow the detection of amyloid deposition in the heart, and their role is also central in assessing the prognosis and response to therapy. The role of computed tomography was recently evaluated by several studies, above in population affected by aortic stenosis undergoing transcatheter aortic valve replacement, with promising results. Finally, machine learning and artificial intelligence-derived algorithms are gaining ground in this scenario and provide the basis for future research. Understanding the new insights into non-invasive diagnostic techniques is critical to better diagnose and manage patients with CA and improve their survival.
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Affiliation(s)
- Marco Maria Dicorato
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Paolo Basile
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Giuseppe Muscogiuri
- Department of Radiology, IRCCS Istituto Auxologico Italiano, San Luca Hospital, 20149 Milan, Italy
| | - Maria Cristina Carella
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Maria Ludovica Naccarati
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Ilaria Dentamaro
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Marco Guglielmo
- Department of Cardiology, Division of Heart and Lungs, Utrecht University, Utrecht University Medical Center, 3584 Utrecht, The Netherlands;
- Department of Cardiology, Haga Teaching Hospital, 2545 The Hague, The Netherlands
| | - Andrea Baggiano
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; (A.B.); (S.M.); (L.F.); (G.P.)
| | - Saima Mushtaq
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; (A.B.); (S.M.); (L.F.); (G.P.)
| | - Laura Fusini
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; (A.B.); (S.M.); (L.F.); (G.P.)
| | - Gianluca Pontone
- Department of Perioperative Cardiology and Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; (A.B.); (S.M.); (L.F.); (G.P.)
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
| | - Cinzia Forleo
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Marco Matteo Ciccone
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
| | - Andrea Igoren Guaricci
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, Polyclinic University Hospital, 70124 Bari, Italy; (M.M.D.); (P.B.); (M.C.C.); (M.L.N.); (I.D.); (C.F.); (M.M.C.); (A.I.G.)
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17
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Pereira T, Fernandes RM, Mata E, Azevedo O, Bento D, Jesus I, Lourenço A. Transthyretin amyloid cardiomyopathy in severe aortic stenosis submitted to valve replacement: a multicenter study. Future Cardiol 2024; 20:419-430. [PMID: 39229685 PMCID: PMC11457626 DOI: 10.1080/14796678.2024.2393031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 08/13/2024] [Indexed: 09/05/2024] Open
Abstract
Aim: To evaluate the prevalence of TTR amyloid cardiomyopathy (ATTR-CM) in severe aortic stenosis (SAS) patients, and to determine the independent predictors of major adverse events (MAE).Patients & methods: 91 SAS patients >65 years with an interventricular septum thickness ≥12.5 mm were referred for aortic valve replacement (AVR). 99mTc-DPD scintigraphy was applied to diagnose ATTR-CM, in the absence of monoclonal protein.Results: ATTR-CM was found in 11%. 78% of patients underwent AVR, but only 2 had ATTR-CM. There were no significant differences in the composite of all cause-mortality or cardiovascular hospitalizations. Lower left ventricle ejection fraction and not performing AVR were independent predictors of MAE.Conclusion: Not performing AVR was an independent predictor of MAE, regardless the ATTR-CM diagnosis.
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Affiliation(s)
- Tamara Pereira
- Cardiology Department, Hospital Senhora da Oliveira – Guimarães, Guimarães, 4835-044, Portugal
| | - Raquel Menezes Fernandes
- Cardiology Department, Unidade Local de Saúde do Algarve – Hospital de Faro, Faro, 8000-386, Portugal
| | - Emídio Mata
- Cardiology Department, Hospital Senhora da Oliveira – Guimarães, Guimarães, 4835-044, Portugal
| | - Olga Azevedo
- Cardiology Department, Hospital Senhora da Oliveira – Guimarães, Guimarães, 4835-044, Portugal
- Reference Center of Lysosomal Storage Disorders, Hospital Senhora da Oliveira – Guimarães, Guimarães, 4835-044, Portugal
| | - Dina Bento
- Cardiology Department, Unidade Local de Saúde do Algarve – Hospital de Faro, Faro, 8000-386, Portugal
| | - Ilídio Jesus
- Cardiology Department, Unidade Local de Saúde do Algarve – Hospital de Faro, Faro, 8000-386, Portugal
| | - António Lourenço
- Cardiology Department, Hospital Senhora da Oliveira – Guimarães, Guimarães, 4835-044, Portugal
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18
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Papathanasiou M, Schlender LS, Johnson VL, Wakili R. [Arrhythmias and amyloidosis]. Herzschrittmacherther Elektrophysiol 2024; 35:199-204. [PMID: 38740607 DOI: 10.1007/s00399-024-01016-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 04/14/2024] [Indexed: 05/16/2024]
Abstract
Cardiac amyloidosis is an infiltrative cardiomyopathy characterized by the extracellular deposition of amyloid fibrils within the myocardium. Beyond heart failure, patients with cardiac amyloidosis commonly present with arrhythmias and conduction system disorders. Atrial fibrillation is observed in up to 80% of patients at the time of diagnosis, with patients typically maintaining normal heart rates due to concurrent atrioventricular nodal disease. The thromboembolic risk is particularly high in patients with cardiac amyloidosis, and left atrial thrombi have been observed even in the absence of atrial fibrillation. Conduction system diseases are also highly prevalent, often necessitating permanent pacemaker implantation. The use of implantable defibrillators in this population remains controversial. This overview of published data and therapeutic strategies related to arrhythmias and conduction system disorders aims to assist readers in decision-making in complex clinical scenarios.
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Affiliation(s)
- Maria Papathanasiou
- Medizinische Klinik 3-Kardiologie/Angiologie, Department of Cardiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt, Deutschland.
| | - Lara S Schlender
- Medizinische Klinik 3-Kardiologie/Angiologie, Department of Cardiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt, Deutschland
| | - Victoria Louise Johnson
- Medizinische Klinik 3-Kardiologie/Angiologie, Department of Cardiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt, Deutschland
| | - Reza Wakili
- Medizinische Klinik 3-Kardiologie/Angiologie, Department of Cardiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt, Deutschland
- German Center for Cardiovascular Research (DZHK), Partner Site Rhein-Main, 60596, Frankfurt, Deutschland
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19
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Magalhães GCM, Bezerra LC, Binensztok B, Vilela MR, das Neves Braga EF, de Brito ASX, Camargo GC, Camillis LF, Rey HCV, Weksler C. Challenges in the approach to a patient with aortic stenosis and cardiac amyloidosis with ATTR mutation associated with negative scintigraphy - A case report. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 45:100444. [PMID: 39282010 PMCID: PMC11395716 DOI: 10.1016/j.ahjo.2024.100444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 08/08/2024] [Accepted: 08/12/2024] [Indexed: 09/18/2024]
Abstract
Introduction Cardiac amyloidosis (CA) poses significant diagnostic and therapeutic challenges. In this case report, we detail a patient with CA due to a rare transthyretin (CA-TTR) mutation, manifesting with negative myocardial scintigraphy and requiring genetic testing for diagnosis. The patient also had severe aortic stenosis (AS), necessitating discussion with a heart team to determine the optimal treatment strategy. Case report A 70-year-old male with a family history of sudden death was previously diagnosed with third-degree atrioventricular block and treated with a pacemaker. He presented with worsening exertional dyspnoea, and examination revealed a third heart sound, a systolic murmur indicative of AS and bilateral muscular atrophy in the thenar region. Transthoracic echocardiography indicated severe AS and moderate left ventricular dysfunction, with images suggesting infiltrative disease. Pyrophosphate scintigraphy revealed no abnormal cardiac tracer uptake. Cardiac magnetic resonance imaging (MRI) revealed extensive, heterogeneous, subendocardial late gadolinium enhancement in both the atria and ventricles, which was consistent with CA. Genetic testing identified the Phe84Leu mutation in the TTR gene. Following heart team discussions, the patient underwent successful transcatheter aortic valve implantation (TAVI) and remained asymptomatic in follow-up, being monitored at an outpatient clinic specializing in CA and using tafamidis. Discussion CA-TTR can be an autosomal dominant disease with variable penetrance involving abnormal amyloid protein deposition in tissues and can often be diagnosed noninvasively via myocardial scintigraphy. However, some TTR mutations do not affect scintigraphy results, necessitating genetic testing when clinical suspicion is high, potentially avoiding endomyocardial biopsy. Moreover, AS occurs in up to 16 % of TTR amyloidosis patients, with the conditions mutually exacerbating each other. Recent consensus suggests that TAVI reduces mortality in patients with severe AS and amyloidosis. Conclusions Various diagnostic algorithms emphasize the use of myocardial scintigraphy for suspected CA-TTR. Genetic testing is crucial when scintigraphy results are negative, but clinical suspicion remains high, potentially circumventing invasive procedures. Compared with medical management alone, TAVI has been shown to improve quality of life and survival in patients with concurrent severe AS and CA.
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20
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Cianci V, Cianci A, Sapienza D, Cracò A, Germanà A, Ieni A, Gualniera P, Asmundo A, Mondello C. Epidemiological Changes in Transthyretin Cardiac Amyloidosis: Evidence from In Vivo Data and Autoptic Series. J Clin Med 2024; 13:5140. [PMID: 39274353 PMCID: PMC11396392 DOI: 10.3390/jcm13175140] [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: 08/05/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 09/16/2024] Open
Abstract
Cardiac amyloidosis is an infiltrative disease that causes progressive myocardial impairment secondary to amyloid fibril deposition in the extracellular space of the myocardium. Many amyloid precursors, including transthyretin protein, are known to determine cardiac damage by aggregating and precipitating in cardiac tissue. Transthyretin cardiac amyloidosis may be either caused by rare genetic mutations of the transthyretin gene in the hereditary variant, or may arise as a consequence of age-related mechanisms in the acquired form. Although it has been labeled as a rare disease, in recent years, transthyretin cardiac amyloidosis has stood out as an emerging cause of aortic stenosis, unexplained left ventricular hypertrophy and heart failure with preserved ejection fraction, particularly in the elderly. Indeed, the integration of data deriving from both in vivo imaging techniques (whose advancement in the last years has allowed to achieve an easier and more accessible non-invasive diagnosis) and forensic studies (showing a prevalence of amyloid deposition in cardiac tissue of elderly patients up to 29%) suggests that cardiac amyloidosis is a more common disease than traditionally considered. Thanks to all the improvements in non-invasive diagnostic techniques, along with the development of efficacious therapies offering improvements in survival rates, transthyretin cardiac amyloidosis has been transformed from an incurable and infrequent condition to a relatively more diffuse and treatable disease, which physicians should take into consideration in the differential diagnostic processes in daily clinical practice.
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Affiliation(s)
- Vincenzo Cianci
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Legal Medicine, University of Messina, Via Consolare Valeria, 1, 98125 Messina, Italy
| | - Alessio Cianci
- Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
| | - Daniela Sapienza
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Legal Medicine, University of Messina, Via Consolare Valeria, 1, 98125 Messina, Italy
| | - Annalisa Cracò
- Department of Biomedical Sciences and Morphological and Functional Imaging, Diagnostic and Interventional Radiology Unit, University Hospital Messina, 98168 Messina, Italy
| | - Antonino Germanà
- Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, Via Palatucci snc, University of Messina, 98168 Messina, Italy
| | - Antonio Ieni
- Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Pathology, University of Messina, 98125 Messina, Italy
| | - Patrizia Gualniera
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Legal Medicine, University of Messina, Via Consolare Valeria, 1, 98125 Messina, Italy
| | - Alessio Asmundo
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Legal Medicine, University of Messina, Via Consolare Valeria, 1, 98125 Messina, Italy
| | - Cristina Mondello
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Section of Legal Medicine, University of Messina, Via Consolare Valeria, 1, 98125 Messina, Italy
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21
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Costa J, El-Ali A, Morland D, Dejust S, Papathanassiou D, Nazeyrollas P, Metz D. Cardiac amyloidosis prevalence and 1-year outcome in patients with aortic stenosis undergoing transaortic valve implantation: Findings from the CAMPOS-TAVI study. Arch Cardiovasc Dis 2024; 117:461-469. [PMID: 39153878 DOI: 10.1016/j.acvd.2024.04.007] [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: 12/28/2023] [Revised: 04/22/2024] [Accepted: 04/24/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND Transthyretin amyloid cardiomyopathy (ATTR-CM) can manifest as rhythm disorders, heart failure, but also valvular degeneration. Despite aortic stenosis (AS) being prevalent among the elderly, data on ATTR-CM prevalence and outcome in patients with AS undergoing transaortic valve implantation (TAVI) remain scarce. AIM To determine ATTR-CM prevalence and evaluate 1-year survival in patients undergoing TAVI. METHODS Between December 2020 and September 2021, 100 consecutive patients underwent TAVI and were screened prospectively for ATTR-CM using bone scintigraphy (BS). Monoclonal gammopathy was ruled out in case of cardiac uptake on BS. All patients were followed prospectively for 1year after TAVI. RESULTS The proportion of patients aged≥75years or with a EuroSCORE II>8% and possible femoral access was 99%. The abnormal cardiac uptake rate on BS was 7% (95% confidence interval: 2-12%); 86% of these patients were male. The RAISE (remodelling, age, injury, system and electrical) score, indicative of ATTR-CM risk, was higher in case of positive BS (P=0.04). Patients with positive BS were older and exhibited wider QRS complexes on electrocardiography (P=0.003), a higher frequency of reduced LVEF (57% vs. 17%), impaired basal LV strain (P=0.02) and a lower voltage/mass ratio (P=0.01). History of pacemaker implantation before TAVI was higher in the positive BS group (P=0.0004) and remained the only statistically significant factor after adjustment using the Holm-Bonferroni method. One-year survival of patients with positive BS did not differ from that of patients with isolated AS. CONCLUSIONS Prevalence of ATTR-CM in patients treated with TAVI, underscoring the need for continued surveillance for potential development of ATTR-CM after TAVI. Caution is warranted regarding the 1-year survival because of the lack of study power. Further investigations are needed to define long-term prognosis of AS with ATTR-CM.
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Affiliation(s)
- Jérôme Costa
- Cardiology Department, University Hospital of Reims, rue du Général-Koenig, 51100 Reims, France.
| | - Ahmed El-Ali
- Cardiology Department, University Hospital of Reims, rue du Général-Koenig, 51100 Reims, France
| | - David Morland
- Service de Médecine Nucléaire, Institut Godinot, 51100 Reims, France; Laboratoire de Biophysique, UFR de Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, France; CReSTIC UR 3804, Université de Reims Champagne-Ardenne, Reims, France
| | - Sebastien Dejust
- Service de Médecine Nucléaire, Institut Godinot, 51100 Reims, France
| | - Dimitri Papathanassiou
- Service de Médecine Nucléaire, Institut Godinot, 51100 Reims, France; Laboratoire de Biophysique, UFR de Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, France; CReSTIC UR 3804, Université de Reims Champagne-Ardenne, Reims, France
| | - Pierre Nazeyrollas
- Cardiology Department, University Hospital of Reims, rue du Général-Koenig, 51100 Reims, France; Laboratoire de recherche en Santé Publique, Vieillissement, Qualité de vie et Réadaptation des Sujets Fragiles, EA 3797, Université de Reims Champagne-Ardenne, Reims, France
| | - Damien Metz
- Cardiology Department, University Hospital of Reims, rue du Général-Koenig, 51100 Reims, France
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22
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Gaznabi S, Miranda J, Lorenzatti D, Piña P, Balasubramanian SS, Desai D, Desai A, Ho EC, Scotti A, Gongora CA, Schenone AL, Garcia MJ, Latib A, Parwani P, Slipczuk L. Multimodality Imaging in Aortic Stenosis: Beyond the Valve - Focusing on the Myocardium. Cardiol Clin 2024; 42:433-446. [PMID: 38910026 DOI: 10.1016/j.ccl.2024.04.002] [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: 06/25/2024]
Abstract
Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.
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Affiliation(s)
- Safwan Gaznabi
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, University of Chicago at Northshore University Health System, 1000 Central Street, Evanston, IL 60201, USA
| | - Jeirym Miranda
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, Mount Sinai Morningside. 419 West 114th Street, NY 10025, USA
| | - Daniel Lorenzatti
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Pamela Piña
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, CEDIMAT. Arturo Logroño, Plaza de la Salud, Dr. Juan Manuel Taveras Rodríguez, C. Pepillo Salcedo esq. Santo Domingo, Dominican Republic
| | - Senthil S Balasubramanian
- Division of Cardiology, University of Chicago at Northshore University Health System, 1000 Central Street, Evanston, IL 60201, USA
| | - Darshi Desai
- Department of Internal Medicine, University of California Riverside School of Medicine. 900 University Avenue, Riverside, CA 92521, USA
| | - Aditya Desai
- Department of Internal Medicine, University of California Riverside School of Medicine. 900 University Avenue, Riverside, CA 92521, USA
| | - Edwin C Ho
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Andrea Scotti
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Carlos A Gongora
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Aldo L Schenone
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Mario J Garcia
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Azeem Latib
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Purvi Parwani
- Division of Cardiology, Department of Medicine, Loma Linda University Health, 11234 Anderson Street, Loma Linda, CA 92354, USA
| | - Leandro Slipczuk
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA.
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23
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Beuthner BE, Elkenani M, Evert K, Mustroph J, Jacob CF, Paul NB, Beißbarth T, Zeisberg EM, Schnelle M, Puls M, Hasenfuß G, Toischer K. Histological assessment of cardiac amyloidosis in patients undergoing transcatheter aortic valve replacement. ESC Heart Fail 2024; 11:1636-1646. [PMID: 38407567 PMCID: PMC11098657 DOI: 10.1002/ehf2.14709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 11/28/2023] [Accepted: 01/19/2024] [Indexed: 02/27/2024] Open
Abstract
AIMS Studies have reported a strongly varying co-prevalence of aortic stenosis (AS) and cardiac amyloidosis (CA). We sought to histologically determine the co-prevalence of AS and CA in patients undergoing transcatheter aortic valve replacement (TAVR). Consequently, we aimed to derive an algorithm to identify cases in which to suspect the co-prevalence of AS and CA. METHODS AND RESULTS In this prospective, monocentric study, endomyocardial biopsies of 162 patients undergoing TAVR between January 2017 and March 2021 at the University Medical Centre Göttingen were analysed by one pathologist blinded to clinical data using haematoxylin-eosin staining, Elastica van Gieson staining, and Congo red staining of endomyocardial biopsies. CA was identified in only eight patients (4.9%). CA patients had significantly higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (4356.20 vs. 1938.00 ng/L, P = 0.034), a lower voltage-to-mass ratio (0.73 vs. 1.46 × 10-2 mVm2/g, P = 0.022), and lower transaortic gradients (Pmean 17.5 vs. 38.0 mmHg, P = 0.004) than AS patients. Concomitant CA was associated with a higher prevalence of post-procedural acute kidney injury (50.0% vs. 13.1%, P = 0.018) and sudden cardiac death [SCD; P (log-rank test) = 0.017]. Following propensity score matching, 184 proteins were analysed to identify serum biomarkers of concomitant CA. CA patients expressed lower levels of chymotrypsin (P = 0.018) and carboxypeptidase 1 (P = 0.027). We propose an algorithm using commonly documented parameters-stroke volume index, ejection fraction, NT-proBNP levels, posterior wall thickness, and QRS voltage-to-mass ratio-to screen for CA in AS patients, reaching a sensitivity of 66.6% with a specificity of 98.1%. CONCLUSIONS The co-prevalence of AS and CA was lower than expected, at 4.9%. Despite excellent 1 year mortality, AS + CA patients died significantly more often from SCD. We propose a multimodal algorithm to facilitate more effective screening for CA containing parameters commonly documented during clinical routine. Proteomic biomarkers may yield additional information in the future.
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Affiliation(s)
- Bo Eric Beuthner
- Department of Cardiology and PneumologyUniversity Medical Centre Göttingen, Georg August University of GöttingenRobert‐Koch‐Straße 4037075GöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Manar Elkenani
- Department of Cardiology and PneumologyUniversity Medical Centre Göttingen, Georg August University of GöttingenRobert‐Koch‐Straße 4037075GöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Katja Evert
- Institute of PathologyUniversity of RegensburgRegensburgGermany
| | - Julian Mustroph
- Department of Internal Medicine IIUniversity Medical Centre RegensburgRegensburgGermany
| | - Christoph Friedemann Jacob
- Department of Cardiology and PneumologyUniversity Medical Centre Göttingen, Georg August University of GöttingenRobert‐Koch‐Straße 4037075GöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Niels Benjamin Paul
- Department of Cardiology and PneumologyUniversity Medical Centre Göttingen, Georg August University of GöttingenRobert‐Koch‐Straße 4037075GöttingenGermany
- Department of Medical BioinformaticsUniversity Medical Centre Göttingen, Georg August University of GöttingenGöttingenGermany
| | - Tim Beißbarth
- Department of Medical BioinformaticsUniversity Medical Centre Göttingen, Georg August University of GöttingenGöttingenGermany
| | - Elisabeth Maria Zeisberg
- Department of Cardiology and PneumologyUniversity Medical Centre Göttingen, Georg August University of GöttingenRobert‐Koch‐Straße 4037075GöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Moritz Schnelle
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
- Department of Clinical ChemistryUniversity Medical Centre Göttingen, Georg August University of GöttingenGöttingenGermany
| | - Miriam Puls
- Department of Cardiology and PneumologyUniversity Medical Centre Göttingen, Georg August University of GöttingenRobert‐Koch‐Straße 4037075GöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Gerd Hasenfuß
- Department of Cardiology and PneumologyUniversity Medical Centre Göttingen, Georg August University of GöttingenRobert‐Koch‐Straße 4037075GöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Karl Toischer
- Department of Cardiology and PneumologyUniversity Medical Centre Göttingen, Georg August University of GöttingenRobert‐Koch‐Straße 4037075GöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
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24
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Yun S, Casado J, Pérez-Silvestre J, Salamanca P, Llàcer P, Quirós R, Ruiz-Hueso R, Méndez M, Manzano L, Formiga F. Clinical suspicion, diagnosis and management of cardiac amyloidosis: update document and executive summary. Rev Clin Esp 2024; 224:288-299. [PMID: 38614320 DOI: 10.1016/j.rceng.2024.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 03/22/2024] [Indexed: 04/15/2024]
Abstract
In recent years, the interest in cardiac amyloidosis has grown exponentially. However, there is a need to improve our understanding of amyloidosis in order to optimise early detection systems. Therefore, it is crucial to incorporate solutions to improve the suspicion, diagnosis and follow-up of cardiac amyloidosis. In this sense, we designed a tool following the different phases to reach the diagnosis of cardiac amyloidosis, as well as an optimal follow-up: a) clinical suspicion, where the importance of the "red flags" to suspect it and activate the diagnostic process is highlighted; 2) diagnosis, where the diagnostic algorithm is mainly outlined; and 3) follow-up of confirmed patients. This is a practical resource that will be of great use to all professionals caring for patients with suspected or confirmed cardiac amyloidosis, to improve its early detection, as well as to optimise its accurate diagnosis and optimal follow-up.
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Affiliation(s)
- S Yun
- Bio-Heart Cardiovascular Diseases Research Group, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Programa de Atención a la Insuficiencia Cardíaca Comunitaria, Servicios de Cardiología y Medicina Interna, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Servicio de Medicina Interna, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - J Casado
- Servicio de Medicina Interna, Hospital Universitario de Getafe, Madrid, Spain; Universidad Europea de Madrid, Madrid, Spain
| | - J Pérez-Silvestre
- Servicio de Medicina Interna, UMIPIC, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
| | - P Salamanca
- Servicio de Medicina Interna, Hospital Universitario Virgen Macarena, Sevilla, Spain; Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain
| | - P Llàcer
- Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain; Departamento de Medicina y Especialidades Médicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Madrid, Spain
| | - R Quirós
- Servicio de Medicina Interna, Hospital Costa del Sol, Marbella, Spain; RICAPPS, Red de Investigación en Cronicidad, Atención Primaria y Prevención y Promoción de la Salud, Spain
| | - R Ruiz-Hueso
- Servicio de Medicina Interna, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | - M Méndez
- Servicio de Medicina Interna, Hospital Clínico San Carlos, Facultad de Medicina, Universidad Complutense, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - L Manzano
- Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain; Departamento de Medicina y Especialidades Médicas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Madrid, Spain
| | - F Formiga
- Servicio de Medicina Interna, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Instituto de Investigación Biomédica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
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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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26
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Göbel S, Braun AS, Hahad O, von Henning U, Brandt M, Keller K, Gaida MM, Gori T, Schultheiss HP, Escher F, Münzel T, Wenzel P. Etiologies and predictors of mortality in an all-comer population of patients with non-ischemic heart failure. Clin Res Cardiol 2024; 113:737-749. [PMID: 38224373 PMCID: PMC11026225 DOI: 10.1007/s00392-023-02354-6] [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: 03/23/2023] [Accepted: 11/29/2023] [Indexed: 01/16/2024]
Abstract
BACKGROUND Despite progress in diagnosis and therapy of heart failure (HF), etiology and risk stratification remain elusive in many patients. METHODS The My Biopsy HF Study (German clinical trials register number: DRKS22178) is a retrospective monocentric study investigating an all-comer population of patients with unexplained HF based on a thorough workup including endomyocardial biopsy (EMB). RESULTS 655 patients (70.9% men, median age 55 [45/66] years) with non-ischemic, non-valvular HF were included in the analyses. 489 patients were diagnosed with HF with reduced ejection fraction (HFrEF), 52 patients with HF with mildly reduced ejection fraction (HFmrEF) and 114 patients with HF with preserved ejection fraction (HFpEF). After a median follow-up of 4.6 (2.5/6.6) years, 94 deaths were enumerated (HFrEF: 68; HFmrEF: 8; HFpEF: 18), equating to mortality rates of 3.3% and 11.6% for patients with HFrEF, 7.7% and 15.4% for patients with HFmrEF and 5.3% and 11.4% for patients with HFpEF after 1 and 5 years, respectively. In EMB, we detected a variety of putative etiologies of HF, including incidental cardiac amyloidosis (CA, 5.8%). In multivariate logistic regression analysis adjusting for age, sex and comorbidities only CA, age and NYHA functional class III + IV remained independently associated with all-cause mortality (CA: HRperui 3.13, 95% CI 1.5-6.51; p = 0.002). CONCLUSIONS In an all-comer population of patients presenting with HF of unknown etiology, incidental finding of CA stands out to be independently associated with all-cause mortality. Our findings suggest that prospective trials would be helpful to test the added value of a systematic and holistic work-up of HF of unknown etiology.
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Affiliation(s)
- S Göbel
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany
| | - A S Braun
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany
| | - O Hahad
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany
| | - U von Henning
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany
| | - M Brandt
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany
| | - K Keller
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany
| | - M M Gaida
- Institute of Pathology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Mainz, Germany
- TRON, Translational Oncology at the University Medical Center Mainz, Mainz, Germany
| | - T Gori
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany
| | - H P Schultheiss
- Institute of Cardiac Diagnostics and Therapy (IKDT), Berlin, Germany
| | - F Escher
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Virchow Klinikum, Berlin, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
| | - T Münzel
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany
| | - P Wenzel
- Cardiology I - Department of Cardiology, University Medical Center Mainz (Johannes Gutenberg University Mainz), Langenbeckstr. 1, 55131, Mainz, Germany.
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany.
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz (Johannes Gutenberg-University Mainz), Mainz, Germany.
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Westin OM, Clemmensen TS, Hansen AT, Gustafsson F, Poulsen SH. Familial occurrences of cardiac wild-type transthyretin amyloidosis: a case series. Eur Heart J Case Rep 2024; 8:ytae199. [PMID: 38765770 PMCID: PMC11099943 DOI: 10.1093/ehjcr/ytae199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 04/09/2024] [Accepted: 04/16/2024] [Indexed: 05/22/2024]
Abstract
Background Cardiomyopathy caused by aggregation and deposition of transthyretin amyloid fibrils in the heart (ATTR-CM) is divided into a hereditary (ATTRv) and a wild-type (ATTRwt) forms. While ATTR-CM has been considered a rare disease, recent studies suggest that it is severely underdiagnosed and an important cause of heart failure in elderly patients. Familial occurrence is implicit in ATTRv, but it is not expected in ATTRwt. Case summary We report a case series of two unrelated families each with two brothers diagnosed with ATTRwt. Genetic testing did not reveal mutations in the transthyretin gene. Family screening with electrocardiogram, echocardiography, and genetic testing did not raise any suspicion of ATTR in first-line family members. Discussion Familial occurrence of a rare, non-hereditary disease is statistically unlikely. Two siblings in two different families diagnosed with ATTRwt highlight that the aetiology of ATTRwt is poorly understood, and that genetic factors distinct from mutations in the transthyretin gene, as well as environmental factors, might contribute to the pathogenesis. Identifying such factors might reveal new therapeutic targets. To investigate this further, clinicians need to be aware of the possibility of familial occurrence of ATTRwt.
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Affiliation(s)
- Oscar M Westin
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Tor S Clemmensen
- Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark
| | - Anne Tybjærg Hansen
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Finn Gustafsson
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Steen Hvitfeldt Poulsen
- Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark
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Bart NK, Fatkin D, Gunton J, Hare JL, Korczyk D, Kwok F, Lam K, Russell D, Sidiqi H, Sutton T, Gibbs SDJ, Mollee P, Thomas L. 2024 Australia-New Zealand Expert Consensus Statement on Cardiac Amyloidosis. Heart Lung Circ 2024; 33:420-442. [PMID: 38570258 DOI: 10.1016/j.hlc.2023.11.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 11/17/2023] [Indexed: 04/05/2024]
Abstract
Over the past 5 years, early diagnosis of and new treatments for cardiac amyloidosis (CA) have emerged that hold promise for early intervention. These include non-invasive diagnostic tests and disease modifying therapies. Recently, CA has been one of the first types of cardiomyopathy to be treated with gene editing techniques. Although these therapies are not yet widely available to patients in Australia and New Zealand, this may change in the near future. Given the rapid pace with which this field is evolving, it is important to view these advances within the Australian and New Zealand context. This Consensus Statement aims to update the Australian and New Zealand general physician and cardiologist with regards to the diagnosis, investigations, and management of CA.
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Affiliation(s)
- Nicole K Bart
- Department of Cardiology, St Vincent's Hospital, Sydney; School of Clinical Medicine, Faculty of Health and Medicine, The University of New South Wales, Sydney, and The Victor Chang Cardiac Research Institute, Sydney, NSW, Australia. http://www.twitter.com/drnikkibart
| | - Diane Fatkin
- Department of Cardiology, St Vincent's Hospital, Sydney; School of Clinical Medicine, Faculty of Health and Medicine, The University of New South Wales, Sydney, and The Victor Chang Cardiac Research Institute, Sydney, NSW, Australia
| | - James Gunton
- Department of Cardiology, Flinders Medical Centre, Adelaide, SA, Australia
| | - James L Hare
- Department of Cardiology, Alfred Health, Melbourne, and Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic, Australia
| | - Dariusz Korczyk
- Department of Cardiology, The Princess Alexandra Hospital, Brisbane, Qld, Australia
| | - Fiona Kwok
- Department of Haematology, Westmead Hospital, Sydney, NSW, Australia
| | - Kaitlyn Lam
- Department of Cardiology, Western Australia Advanced Heart Failure and Cardiac Transplant Service, Perth, WA, Australia
| | - David Russell
- Department of Cardiology, Royal Hobart Hospital, Hobart, Tas, Australia
| | - Hasib Sidiqi
- Department of Haematology, Fiona Stanley Hospital, Perth, WA, Australia
| | - Tim Sutton
- Te Whatu Ora Counties Manukau, Auckland; and Department of Cardiology, Auckland, Aotearoa, New Zealand
| | - Simon D J Gibbs
- Department of Haematology, Eastern Health; Epworth Freemasons; and Monash University, Melbourne, Vic, Australia
| | - Peter Mollee
- Queensland Amyloidosis Centre, The Princess Alexandra Hospital, Brisbane; and, School of Medicine, University of Queensland, Brisbane, Qld, Australia
| | - Liza Thomas
- Department of Cardiology, Westmead Hospital, Sydney; Westmead Clinical School, University of Sydney, Sydney; and, South West Clinical School, University of New South Wales, Sydney, NSW, Australia.
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Mir T, Uddin M, Ulbeh TM, Perveiz E, Lohia P, Sattar Y, Abohashem S, Ullah W, Maganti K, Qureshi WT, Lakis N. Clinical Outcomes of Aortic Stenosis in Amyloidosis: A United States National Cohort Study. Heart Lung Circ 2024; 33:443-449. [PMID: 38036372 DOI: 10.1016/j.hlc.2023.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 07/21/2023] [Accepted: 09/21/2023] [Indexed: 12/02/2023]
Abstract
BACKGROUND Literature regarding outcomes associated with surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) among amyloidosis (AM) with aortic stenosis (AS) is limited. OBJECTIVES We aim to study the mortality and in-hospital clinical outcomes among AM with AS associated with SAVR or TAVR. METHODS We performed a retrospective study of all hospitalisation encounters associated with a diagnosis of AM with AS, using the Nationwide Readmissions Database for the years 2012-2019. Primary outcomes were in-hospital mortality, and 30-day readmissions. RESULTS A total of 4,820 index hospitalisations of AS (mean age 78.35±10.11 years; female 37.76%) among AM were reported. Total 464 patients had mechanical intervention, 251 patients (54.1%) TAVR and 213 patients (45.9%) SAVR. A total of 317 patients (6.77%) with AS died; TAVR 4.4%, SAVR 11.9% (p=0.01) and 6.66% died among the subgroup who did not have any mechanical intervention. Higher complication rates were observed among patients who had SAVR than those who had TAVR including acute kidney injury (39.8% vs 22.4%; p=0.01), septic shock (12.1% vs 4.4%; p=0.05) and cardiogenic shock (22% vs 4.4%; p<0.001). Acute heart failure was higher among patients who had TAVR (40.2% vs 27.5%; p=0.04) than those who had SAVR. All conduction block and ischaemic stroke were similar between the two groups (p=0.09 and p=0.1). The overall 30-day readmission rate among AM with AS encounters was 16.82%, higher among TAVR compared to SAVR subgroups (21.25% vs 11.17%; p=0.001). CONCLUSIONS Among AM with AS hospitalisations, TAVR had mortality benefits compared to SAVR and non-mechanical intervention subgroups. Moreover, higher 30-day mortality rate were observed among SAVR subgroup, which may suggest that TAVR should be strongly considered in AM patients complicated by AS.
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Affiliation(s)
- Tanveer Mir
- Internal Medicine, Wayne State University, Detroit, MI, USA; Internal Medicine, Baptist Health System, Montgomery, AL, USA.
| | - Mohammed Uddin
- Internal Medicine, Wayne State University, Detroit, MI, USA
| | | | - Eskara Perveiz
- Internal Medicine, Baptist Health System, Montgomery, AL, USA
| | - Prateek Lohia
- Internal Medicine, Wayne State University, Detroit, MI, USA
| | - Yasar Sattar
- Cardiology Division, University of Virginia, Charlottesville, VA, USA
| | - Shady Abohashem
- Cardiology Division, Harvard Medical School Massachusetts General Hospital, Boston, MA, USA
| | - Waqas Ullah
- Cardiology Division, Thomas Jefferson University, PA, USA
| | | | - Waqas T Qureshi
- Cardiology Division, University of Massachusetts, Amherst, MA, USA
| | - Nasser Lakis
- Internal Medicine, Wayne State University, Detroit, MI, USA
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30
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Ruberg FL, Maurer MS. Cardiac Amyloidosis Due to Transthyretin Protein: A Review. JAMA 2024; 331:778-791. [PMID: 38441582 PMCID: PMC11167454 DOI: 10.1001/jama.2024.0442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/07/2024]
Abstract
Importance Systemic amyloidosis from transthyretin (ATTR) protein is the most common type of amyloidosis that causes cardiomyopathy. Observations Transthyretin (TTR) protein transports thyroxine (thyroid hormone) and retinol (vitamin A) and is synthesized predominantly by the liver. When the TTR protein misfolds, it can form amyloid fibrils that deposit in the heart causing heart failure, heart conduction block, or arrhythmia such as atrial fibrillation. The biological processes by which amyloid fibrils form are incompletely understood but are associated with aging and, in some patients, affected by inherited variants in the TTR genetic sequence. ATTR amyloidosis results from misfolded TTR protein deposition. ATTR can occur in association with normal TTR genetic sequence (wild-type ATTR) or with abnormal TTR genetic sequence (variant ATTR). Wild-type ATTR primarily manifests as cardiomyopathy while ATTR due to a genetic variant manifests as cardiomyopathy and/or polyneuropathy. Approximately 50 000 to 150 000 people in the US have heart failure due to ATTR amyloidosis. Without treatment, heart failure due to ATTR amyloidosis is associated with a median survival of approximately 5 years. More than 130 different inherited genetic variants in TTR exist. The most common genetic variant is Val122Ile (pV142I), an allele with an origin in West African countries, that is present in 3.4% of African American individuals in the US or approximately 1.5 million persons. The diagnosis can be made using serum free light chain assay and immunofixation electrophoresis to exclude light chain amyloidosis combined with cardiac nuclear scintigraphy to detect radiotracer uptake in a pattern consistent with amyloidosis. Loop diuretics, such as furosemide, torsemide, and bumetanide, are the primary treatment for fluid overload and symptomatic relief of patients with ATTR heart failure. An ATTR-directed therapy that inhibited misfolding of the TTR protein (tafamidis, a protein stabilizer), compared with placebo, reduced mortality from 42.9% to 29.5%, reduced hospitalizations from 0.7/year to 0.48/year, and was most effective when administered early in disease course. Conclusions and Relevance ATTR amyloidosis causes cardiomyopathy in up to approximately 150 000 people in the US and tafamidis is the only currently approved therapy. Tafamidis slowed progression of ATTR amyloidosis and improved survival and prevented hospitalization, compared with placebo, in people with ATTR-associated cardiomyopathy.
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Affiliation(s)
- Frederick L Ruberg
- Section of Cardiovascular Medicine, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, Massachusetts
- Amyloidosis Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts
| | - Mathew S Maurer
- Cardiac Amyloidosis Program, Seymour, Paul, and Gloria Milstein Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, and NewYork-Presbyterian Hospital, New York
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Hayashi H, Oda S, Kidoh M, Yamaguchi S, Yoshimura F, Takashio S, Usuku H, Nagayama Y, Nakaura T, Ueda M, Tsujita K, Hirai T. Myocardial extracellular volume quantification in cardiac amyloidosis: a comparative study between cardiac computed tomography and magnetic resonance imaging. Eur Radiol 2024; 34:1016-1025. [PMID: 37597032 DOI: 10.1007/s00330-023-10129-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 06/27/2023] [Accepted: 07/04/2023] [Indexed: 08/21/2023]
Abstract
OBJECTIVES Myocardial extracellular volume (ECV) on computed tomography (CT), an alternative to cardiac magnetic resonance (CMR), has significant practical clinical advantages. However, the consistency between ECVs quantified via CT and CMR in cardiac amyloidosis (CA) has not been investigated sufficiently. Therefore, the current study investigated the application of CT-ECV in CA with CMR-ECV as the reference standard. METHODS We retrospectively evaluated 31 patients with CA who underwent cardiac CT and CMR. Pearson correlation analysis was performed to investigate correlations between CT-ECV and CMR-ECV at each segment. Further, correlations between ECV and clinical parameters were assessed. RESULTS There were no significant differences in the mean global ECVs between CT scan and CMR (51.3% ± 10.2% vs 50.0% ± 10.5%). CT-ECV was correlated with CMR-ECV at the septal (r = 0.88), lateral (r = 0.80), inferior (r = 0.79), anterior (r = 0.77) segments, and global (r = 0.87). In both CT and CMR, the ECV had a weak to strong correlation with high-sensitivity cardiac troponin T level, a moderate correlation with global longitudinal strain, and an inverse correlation with left ventricular ejection fraction. Further, the septal ECV and global ECV had a slightly higher correlation with the clinical parameters. CONCLUSIONS Cardiac CT can quantify myocardial ECV and yield results comparable to CMR in patients with CA. Moreover, a significant correlation between CT-ECV and clinical parameters was observed. Thus, CT-ECV can be an imaging biomarker and alternative to CMR-ECV. CLINICAL RELEVANCE STATEMENT Cardiac CT can quantify myocardial ECV and yield results comparable to CMR in patients with CA, and CT-ECV can be used clinically as an imaging biomarker and alternative to CMR-ECV. KEY POINTS • A significant correlation was found between CT myocardial extracellular volume and cardiac MR myocardial extracellular volume in patients with cardiac amyloidosis. • In CT and cardiac MR, the myocardial extracellular volume correlated well with high-sensitivity cardiac troponin T level, global longitudinal strain, and left ventricular ejection fraction. • CT myocardial extracellular volume can be an imaging biomarker and alternative to cardiac MR myocardial extracellular volume.
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Affiliation(s)
- Hidetaka Hayashi
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Seitaro Oda
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan.
| | - Masafumi Kidoh
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Shinpei Yamaguchi
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
- Department of Radiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
| | - Fumihiro Yoshimura
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Seiji Takashio
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiroki Usuku
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yasunori Nagayama
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Takeshi Nakaura
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Mitsuharu Ueda
- Department of Neurology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Toshinori Hirai
- Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
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Jakstaite AM, Vogel JK, Luedike P, Jánosi RA, Carpinteiro A, Rischpler C, Herrmann K, Rassaf T, Papathanasiou M. Screening for Occult Transthyretin Amyloidosis in Patients with Severe Aortic Stenosis and Amyloid Red Flags. J Clin Med 2024; 13:671. [PMID: 38337363 PMCID: PMC10856049 DOI: 10.3390/jcm13030671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 01/02/2024] [Accepted: 01/22/2024] [Indexed: 02/12/2024] Open
Abstract
AIMS The optimal strategy to identify transthyretin-type cardiac amyloidosis (ATTR-CA) in patients with aortic stenosis (AS) is still unclear. This study aimed to investigate if targeted screening for ATTR-CA in patients with severe AS and amyloid red flags is associated with higher detection rates. METHODS The study prospectively enrolled patients ≥65 years with severe AS. Patients who fulfilled ≥1 major (carpal tunnel syndrome (CTS), ruptured biceps tendon, spinal stenosis, N-terminal pro B-type natriuretic peptide ≥1000 pg/mL, cardiac troponin >99th percentile) or ≥2 minor criteria (diastolic dysfunction ≥2 grade/lateral e' <10 cm/s, atrial fibrillation, atrioventricular conduction disease/pacemaker) received bone scintigraphy and biochemical analysis for light chain amyloidosis. Hypertensive patients (>140/90 mmHg) and those with interventricular septal thickness (IVSd) ≤13 mm were excluded. RESULTS Overall, 264 patients were screened, of whom 85 were included in the analysis. Tracer uptake Perugini grade ≥1 was detected in nine patients (11%). An endomyocardial biopsy was additionally performed in four of nine patients, yielding a prevalence of 7% (n = 6). All patients with dual AS-ATTR were male. Syncope was more commonly reported in AS-ATTR patients (50% vs. 6%, p = 0.010), who also tended to have more severe hypertrophy (IVSd of 18 vs. 16 mm, p = 0.075). Pericardial effusion and CTS were more common in patients with dual pathology (67% vs. 8%, p < 0.001, and 83% vs. 24%, p = 0.003, respectively). CONCLUSION Targeted screening for ATTR-CA in patients with AS and amyloid red flags does not yield higher detection rates than those reported previously in all comers with AS.
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Affiliation(s)
- Aiste Monika Jakstaite
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Julia Kirsten Vogel
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Peter Luedike
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Rolf Alexander Jánosi
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Alexander Carpinteiro
- Department of Hematology and Stem Cell Transplantation, West German Tumor Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
- Institute of Molecular Biology, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Christoph Rischpler
- Department of Nuclear Medicine, Klinikum Stuttgart, Kriegsbergstrasse 60, 70174 Stuttgart, Germany
| | - Ken Herrmann
- Department of Nuclear Medicine, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Tienush Rassaf
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Maria Papathanasiou
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
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Lahoud RN, Abadie B. Editorial: STOP or YIELD sign at the intersection of TAVR and amyloidosis? CARDIOVASCULAR REVASCULARIZATION MEDICINE 2024; 58:43-44. [PMID: 37690931 DOI: 10.1016/j.carrev.2023.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 08/24/2023] [Indexed: 09/12/2023]
Affiliation(s)
- Rony N Lahoud
- University of Vermont Larner College of Medicine, Burlington, VT, USA.
| | - Bryan Abadie
- Division of Cardiovascular Medicine, Cleveland Clinic Foundation, USA
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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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Ismayl M, Abbasi M, Al-Abcha A, El-Am E, Alkhouli M, Guerrero M, Dispenzieri A, Nkomo VT, Abou Ezzeddine OF, Grogan M, Anavekar NS. Outcomes of transcatheter aortic valve replacement in patients with and without amyloidosis: A nationwide analysis from the United States. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2024; 58:34-42. [PMID: 37468384 DOI: 10.1016/j.carrev.2023.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/18/2023] [Accepted: 07/10/2023] [Indexed: 07/21/2023]
Abstract
BACKGROUND Amyloidosis is a common comorbidity in elderly patients with aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR). This study aims to assess the impact of amyloidosis on the clinical outcomes of TAVR. METHODS This is a retrospective study of the National Inpatient Sample database that identified adult patients (≥18 years) with AS hospitalized for TAVR from 2016 through 2020 to compare outcomes in those with versus without amyloidosis. Our primary outcome was in-hospital mortality. Secondary outcomes included procedural complications, hospital length of stay (LOS), and total costs. TAVR trends in both cohorts were also evaluated. RESULTS The total cohort included 304,710 patients with AS undergoing TAVR, of whom 410 had amyloidosis. Over the study period, TAVR trends increased significantly in patients with and without amyloidosis (both ptrend < 0.01). Patients with amyloidosis were more likely to be older males with atrial fibrillation/flutter, congestive heart failure, renal disease, and dementia compared to non-amyloidosis patients. After adjustment for baseline characteristics, patients with amyloidosis had similar odds of in-hospital mortality (adjusted odds ratio [aOR] 1.66, 95 % confidence interval [CI] 0.34-3.63), heart block (aOR 1.33, 95 % CI 0.84-2.10), permanent pacemaker insertion (aOR 0.67, 95 % CI 0.27-1.66), stroke (aOR 0.90, 95 % CI 0.32-3.13), acute kidney injury, major bleeding, blood transfusion, vascular complications, in addition to similar LOS (p = 0.21) and total costs (p = 0.18) compared to patients without amyloidosis. CONCLUSION In patients with AS undergoing TAVR, comorbid amyloidosis is associated with similar in-hospital mortality and procedural complications compared to patients without amyloidosis.
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Affiliation(s)
- Mahmoud Ismayl
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA.
| | - Muhannad Abbasi
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Abdullah Al-Abcha
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Edward El-Am
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Mohamad Alkhouli
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Mayra Guerrero
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Angela Dispenzieri
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Vuyisile T Nkomo
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Omar F Abou Ezzeddine
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Martha Grogan
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Nandan S Anavekar
- Department of Cardiovascular Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
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Gaznabi S, Miranda J, Lorenzatti D, Piña P, Balasubramanian SS, Desai D, Desai A, Ho EC, Scotti A, Gongora CA, Schenone AL, Garcia MJ, Latib A, Parwani P, Slipczuk L. Multimodality Imaging in Aortic Stenosis: Beyond the Valve - Focusing on the Myocardium. Interv Cardiol Clin 2024; 13:101-114. [PMID: 37980060 DOI: 10.1016/j.iccl.2023.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2023]
Abstract
Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.
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Affiliation(s)
- Safwan Gaznabi
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, University of Chicago at Northshore University Health System, 1000 Central Street, Evanston, IL 60201, USA
| | - Jeirym Miranda
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, Mount Sinai Morningside. 419 West 114th Street, NY 10025, USA
| | - Daniel Lorenzatti
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Pamela Piña
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, CEDIMAT. Arturo Logroño, Plaza de la Salud, Dr. Juan Manuel Taveras Rodríguez, C. Pepillo Salcedo esq. Santo Domingo, Dominican Republic
| | - Senthil S Balasubramanian
- Division of Cardiology, University of Chicago at Northshore University Health System, 1000 Central Street, Evanston, IL 60201, USA
| | - Darshi Desai
- Department of Internal Medicine, University of California Riverside School of Medicine. 900 University Avenue, Riverside, CA 92521, USA
| | - Aditya Desai
- Department of Internal Medicine, University of California Riverside School of Medicine. 900 University Avenue, Riverside, CA 92521, USA
| | - Edwin C Ho
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Andrea Scotti
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Carlos A Gongora
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Aldo L Schenone
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Mario J Garcia
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Azeem Latib
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Purvi Parwani
- Division of Cardiology, Department of Medicine, Loma Linda University Health, 11234 Anderson Street, Loma Linda, CA 92354, USA
| | - Leandro Slipczuk
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA.
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37
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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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38
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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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39
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Aimo A, Fabiani I, Maccarana A, Vergaro G, Chubuchny V, Pasanisi EM, Petersen C, Poggianti E, Giannoni A, Spini V, Taddei C, Castiglione V, Passino C, Fontana M, Emdin M, Venneri L. Valve disease in cardiac amyloidosis: an echocardiographic score. Int J Cardiovasc Imaging 2023; 39:1873-1887. [PMID: 37341947 PMCID: PMC10589146 DOI: 10.1007/s10554-023-02901-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 06/14/2023] [Indexed: 06/22/2023]
Abstract
Cardiac amyloidosis (CA) may affect all cardiac structures, including the valves. From 423 patients undergoing a diagnostic workup for CA we selected 2 samples of 20 patients with amyloid transthyretin (ATTR-) or light-chain (AL-) CA, and age- and sex-matched controls. We chose 31 echocardiographic items related to the mitral, aortic and tricuspid valves, giving a value of 1 to each abnormal item. Patients with ATTR-CA displayed more often a shortened/hidden and restricted posterior mitral valve leaflet (PMVL), thickened mitral chordae tendineae and aortic stenosis than those with AL-CA, and less frequent PMVL calcification than matched controls. Score values were 15.8 (13.6-17.4) in ATTR-CA, 11.0 (9.3-14.9) in AL-CA, 12.8 (11.1-14.4) in ATTR-CA controls, and 11.0 (9.1-13.0) in AL-CA controls (p = 0.004 for ATTR- vs. AL-CA, 0.009 for ATTR-CA vs. their controls, and 0.461 for AL-CA vs. controls). Area under the curve values to diagnose ATTR-CA were 0.782 in patients with ATTR-CA or matched controls, and 0.773 in patients with LV hypertrophy. Patients with ATTR-CA have a prominent impairment of mitral valve structure and function, and higher score values. The valve score may help identify patients with ATTR-CA among patients with CA or unexplained hypertrophy.
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Affiliation(s)
- Alberto Aimo
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy.
| | - Iacopo Fabiani
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Agnese Maccarana
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy
| | - Giuseppe Vergaro
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy
| | | | | | - Christina Petersen
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Elisa Poggianti
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Alberto Giannoni
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy
| | - Valentina Spini
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Claudia Taddei
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Vincenzo Castiglione
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy
| | - Claudio Passino
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy
| | - Marianna Fontana
- National Amyloidosis Centre, University College London, Royal Free Campus, London, UK
| | - Michele Emdin
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124, Pisa, Italy
| | - Lucia Venneri
- National Amyloidosis Centre, University College London, Royal Free Campus, London, UK
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40
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Gaznabi S, Miranda J, Lorenzatti D, Piña P, Balasubramanian SS, Desai D, Desai A, Ho EC, Scotti A, Gongora CA, Schenone AL, Garcia MJ, Latib A, Parwani P, Slipczuk L. Multimodality Imaging in Aortic Stenosis: Beyond the Valve - Focusing on the Myocardium. Heart Fail Clin 2023; 19:491-504. [PMID: 37714589 DOI: 10.1016/j.hfc.2023.05.010] [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: 09/17/2023]
Abstract
Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.
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Affiliation(s)
- Safwan Gaznabi
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, University of Chicago at Northshore University Health System, 1000 Central Street, Evanston, IL 60201, USA
| | - Jeirym Miranda
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, Mount Sinai Morningside. 419 West 114th Street, NY 10025, USA
| | - Daniel Lorenzatti
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Pamela Piña
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA; Division of Cardiology, CEDIMAT. Arturo Logroño, Plaza de la Salud, Dr. Juan Manuel Taveras Rodríguez, C. Pepillo Salcedo esq. Santo Domingo, Dominican Republic
| | - Senthil S Balasubramanian
- Division of Cardiology, University of Chicago at Northshore University Health System, 1000 Central Street, Evanston, IL 60201, USA
| | - Darshi Desai
- Department of Internal Medicine, University of California Riverside School of Medicine. 900 University Avenue, Riverside, CA 92521, USA
| | - Aditya Desai
- Department of Internal Medicine, University of California Riverside School of Medicine. 900 University Avenue, Riverside, CA 92521, USA
| | - Edwin C Ho
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Andrea Scotti
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Carlos A Gongora
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Aldo L Schenone
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Mario J Garcia
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Azeem Latib
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA
| | - Purvi Parwani
- Division of Cardiology, Department of Medicine, Loma Linda University Health, 11234 Anderson Street, Loma Linda, CA 92354, USA
| | - Leandro Slipczuk
- Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th street, Bronx, NY 10467, USA.
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41
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Jaiswal V, Joshi A, Ishak A, Nataraj M, Ang SP, Khan N, Daneshvar F, Aguilera-Alvarez VH, Verma D, Shrestha AB, Sharma P. Meta-analysis of post-transcatheter aortic valve replacement outcomes in patients with cardiac amyloidosis and aortic stenosis. Int J Surg 2023; 109:2872-2874. [PMID: 37300891 PMCID: PMC10498851 DOI: 10.1097/js9.0000000000000532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023]
Affiliation(s)
| | - Amey Joshi
- Vydehi Institute of Medical Sciences and Research Centre, Bangalore, India
| | - Angela Ishak
- European University Cyprus, School of Medicine, Nicosia, Cyprus
| | - Megha Nataraj
- Cardio-Pulmonary Physiotherapist and Research, Manipal, Karnataka, India
| | - Song P. Ang
- Division of Internal Medicine, Rutgers Health/Community Medical Center, New Jersey, USA
| | - Nida Khan
- Jinnah Sindh Medical University, Karachi, Pakistan
| | | | | | | | - Abhigan B. Shrestha
- Department of Internal Medicine, M Abdur Rahim Medical College, Dinajpur, Bangladesh
| | - Prachi Sharma
- Division of Cardiology, Department of Internal Medicine, King George's Medical University, India
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42
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Czepluch F. [Transthyretin amyloid cardiomyopathy]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2023; 64:823-829. [PMID: 37540258 DOI: 10.1007/s00108-023-01569-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/17/2023] [Indexed: 08/05/2023]
Abstract
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure and arrhythmia. This differential diagnosis should particularly be considered in older patients with left ventricular hypertrophy (LVH) who are also suffering from heart failure with preserved ejection fraction (HFpEF) or aortic valve stenosis. ATTR-CM is caused either by a genetic variation or by aging processes. The extracellular accumulation of amyloid fibrils in the heart causes a restrictive cardiomyopathy, which leads to typical heart failure symptoms as well as cardiac conduction and repolarization disturbances. Extracardiac problems such as a carpal tunnel syndrome can also be indicative for ATTR-CM. The disease can be diagnosed either by a myocardial biopsy or alternatively by a positive bone scintigraphy with the simultaneous exclusion of monoclonal proteins in blood and urine. Besides a symptomatic treatment, the transthyretin (TTR) stabilizer tafamidis is now available, which can significantly delay the disease progress. In the coming years, the approval of further drugs for the treatment of ATTR-CM is to be expected.
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Affiliation(s)
- Frauke Czepluch
- Klinik für Kardiologie und Pneumologie, Universitätsmedizin Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Deutschland.
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43
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Tore D, Faletti R, Gaetani C, Bozzo E, Biondo A, Carisio A, Menchini F, Miccolis M, Papa FP, Trovato M, Fonio P, Gatti M. Cardiac magnetic resonance of hypertrophic heart phenotype: A review. Heliyon 2023; 9:e17336. [PMID: 37441401 PMCID: PMC10333467 DOI: 10.1016/j.heliyon.2023.e17336] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 06/05/2023] [Accepted: 06/14/2023] [Indexed: 07/15/2023] Open
Abstract
Hypertrophic heart phenotype is characterized by an abnormal left ventricular (LV) thickening. A hypertrophic phenotype can develop as adaptive response in many different conditions such as aortic stenosis, hypertension, athletic training, infiltrative heart muscle diseases, storage disorders and metabolic disorders. Hypertrophic cardiomyopathy (HCM) is the most frequent primary cardiomyopathy (CMP) and a genetical cause of cardiac hypertrophy. It requires the exclusion of any other cause of LV hypertrophy. Cardiac magnetic resonance (CMR) is a comprehensive imaging technique that allows a detailed evaluation of myocardial diseases. It provides reproducible measurements and myocardial tissue characterization. In clinical practice CMR is increasingly used to confirm the presence of ventricular hypertrophy, to detect the underlying cause of the phenotype and more recently as an efficient prognostic tool. This article aims to provide a detailed overview of the applications of CMR in the setting of hypertrophic heart phenotype and its role in the diagnostic workflow of such condition.
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Affiliation(s)
- Davide Tore
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Riccardo Faletti
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Clara Gaetani
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Elena Bozzo
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Andrea Biondo
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Andrea Carisio
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Francesca Menchini
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Maria Miccolis
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Francesco Pio Papa
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Martina Trovato
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Paolo Fonio
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Marco Gatti
- Radiology Unit, Department of Surgical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
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Bahadormanesh N, Tomka B, Abdelkhalek M, Khodaei S, Maftoon N, Keshavarz-Motamed Z. A Doppler-exclusive non-invasive computational diagnostic framework for personalized transcatheter aortic valve replacement. Sci Rep 2023; 13:8033. [PMID: 37198194 PMCID: PMC10192526 DOI: 10.1038/s41598-023-33511-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 04/13/2023] [Indexed: 05/19/2023] Open
Abstract
Given the associated risks with transcatheter aortic valve replacement (TAVR), it is crucial to determine how the implant will affect the valve dynamics and cardiac function, and if TAVR will improve or worsen the outcome of the patient. Effective treatment strategies, indeed, rely heavily on the complete understanding of the valve dynamics. We developed an innovative Doppler-exclusive non-invasive computational framework that can function as a diagnostic tool to assess valve dynamics in patients with aortic stenosis in both pre- and post-TAVR status. Clinical Doppler pressure was reduced by TAVR (52.2 ± 20.4 vs. 17.3 ± 13.8 [mmHg], p < 0.001), but it was not always accompanied by improvements in valve dynamics and left ventricle (LV) hemodynamics metrics. TAVR had no effect on LV workload in 4 patients, and LV workload post-TAVR significantly rose in 4 other patients. Despite the group level improvements in maximum LV pressure (166.4 ± 32.2 vs 131.4 ± 16.9 [mmHg], p < 0.05), only 5 of the 12 patients (41%) had a decrease in LV pressure. Moreover, TAVR did not always improve valve dynamics. TAVR did not necessarily result in a decrease (in 9 out of 12 patients investigated in this study) in major principal stress on the aortic valve leaflets which is one of the main contributors in valve degeneration and, consequently, failure of heart valves. Diastolic stresses increased significantly post-TAVR (34%, 109% and 81%, p < 0.001) for each left, right and non-coronary leaflets respectively. Moreover, we quantified the stiffness and material properties of aortic valve leaflets which correspond with the reduced calcified region average stiffness among leaflets (66%, 74% and 62%; p < 0.001; N = 12). Valve dynamics post-intervention should be quantified and monitored to ensure the improvement of patient conditions and prevent any further complications. Improper evaluation of biomechanical valve features pre-intervention as well as post-intervention may result in harmful effects post-TAVR in patients including paravalvular leaks, valve degeneration, failure of TAVR and heart failure.
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Affiliation(s)
- Nikrouz Bahadormanesh
- Department of Mechanical Engineering, McMaster University, JHE-310, Hamilton, ON, L8S 4L7, Canada
| | - Benjamin Tomka
- Department of Mechanical Engineering, McMaster University, JHE-310, Hamilton, ON, L8S 4L7, Canada
| | | | - Seyedvahid Khodaei
- Department of Mechanical Engineering, McMaster University, JHE-310, Hamilton, ON, L8S 4L7, Canada
| | - Nima Maftoon
- Department of Systems Design Engineering, University of Waterloo, Waterloo, ON, Canada
- Centre for Bioengineering and Biotechnology, University of Waterloo, Waterloo, ON, Canada
| | - Zahra Keshavarz-Motamed
- Department of Mechanical Engineering, McMaster University, JHE-310, Hamilton, ON, L8S 4L7, Canada.
- School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.
- School of Computational Science and Engineering, McMaster University, Hamilton, ON, Canada.
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45
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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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46
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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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47
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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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48
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Ricci F, Cipriani A, Khanji MY. Amyloidosis and Risk of Stroke After Transcatheter Aortic Valve Replacement: It Takes Two to Tango? JACC. ADVANCES 2023; 2:100256. [PMID: 38938317 PMCID: PMC11198413 DOI: 10.1016/j.jacadv.2023.100256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
Affiliation(s)
- Fabrizio Ricci
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti-Pescara, Chieti, Italy
- Department of Clinical Sciences, Lund University, Malmö, Sweden
- Fondazione Villaserena per la Ricerca, Città Sant’Angelo, Italy
| | - Alberto Cipriani
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Mohammed Y. Khanji
- Newham University Hospital, Barts Health NHS Trust, London, United Kingdom
- Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom
- NIHR Barts Biomedical Research Centre, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
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49
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Khor YM, Cuddy SAM, Singh V, Falk RH, Di Carli MF, Dorbala S. 99mTc Bone-Avid Tracer Cardiac Scintigraphy: Role in Noninvasive Diagnosis of Transthyretin Cardiac Amyloidosis. Radiology 2023; 306:e221082. [PMID: 36537896 PMCID: PMC9885342 DOI: 10.1148/radiol.221082] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 08/11/2022] [Accepted: 09/15/2022] [Indexed: 12/24/2022]
Abstract
Transthyretin cardiac amyloidosis (ATTR-CA) is an overlooked cause of heart failure, with substantial morbidity and mortality. The emergence of several novel therapies has fueled the interest in early and accurate diagnosis of ATTR-CA so that potentially life-saving pharmacologic therapy can be administered in a timely manner. The most promising imaging modality and biomarker is SPECT imaging with technetium 99m (99mTc)-radiolabeled bone-seeking tracers, which have high specificity in the diagnosis of ATTR-CA, potentially obviating biopsy. In this article, the authors provide a focused review on the use of 99mTc pyrophosphate (PYP), 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), and hydroxymethylene diphosphonate (HMDP) for diagnosis of ATTR-CA, present a systematic approach to interpretation of the scans, and highlight several common pitfalls to illustrate important diagnostic principles for accurate interpretation of these images. The authors indicate when to use endomyocardial biopsy for the diagnosis of cardiac amyloidosis and conclude with a section on quantitation of 99mTc-PYP/DPD/HMDP imaging.
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Affiliation(s)
- Yiu Ming Khor
- From the Department of Nuclear Medicine and Molecular Imaging,
Singapore General Hospital, Singapore (Y.M.K.); Division of Nuclear Medicine and
Molecular Imaging, Department of Radiology (Y.M.K., V.S., M.F.D.C., S.D.),
Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine
(S.A.M.C., R.H.F., S.D.), and CV Imaging Program, Cardiovascular Division and
Department of Radiology (S.A.M.C., V.S., M.F.D.C., S.D.), Brigham and
Women’s Hospital and Harvard Medical School, 70 Francis St, Boston, MA
02115; and Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas
City, Mo (V.S.)
| | - Sarah A. M. Cuddy
- From the Department of Nuclear Medicine and Molecular Imaging,
Singapore General Hospital, Singapore (Y.M.K.); Division of Nuclear Medicine and
Molecular Imaging, Department of Radiology (Y.M.K., V.S., M.F.D.C., S.D.),
Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine
(S.A.M.C., R.H.F., S.D.), and CV Imaging Program, Cardiovascular Division and
Department of Radiology (S.A.M.C., V.S., M.F.D.C., S.D.), Brigham and
Women’s Hospital and Harvard Medical School, 70 Francis St, Boston, MA
02115; and Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas
City, Mo (V.S.)
| | - Vasvi Singh
- From the Department of Nuclear Medicine and Molecular Imaging,
Singapore General Hospital, Singapore (Y.M.K.); Division of Nuclear Medicine and
Molecular Imaging, Department of Radiology (Y.M.K., V.S., M.F.D.C., S.D.),
Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine
(S.A.M.C., R.H.F., S.D.), and CV Imaging Program, Cardiovascular Division and
Department of Radiology (S.A.M.C., V.S., M.F.D.C., S.D.), Brigham and
Women’s Hospital and Harvard Medical School, 70 Francis St, Boston, MA
02115; and Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas
City, Mo (V.S.)
| | - Rodney H. Falk
- From the Department of Nuclear Medicine and Molecular Imaging,
Singapore General Hospital, Singapore (Y.M.K.); Division of Nuclear Medicine and
Molecular Imaging, Department of Radiology (Y.M.K., V.S., M.F.D.C., S.D.),
Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine
(S.A.M.C., R.H.F., S.D.), and CV Imaging Program, Cardiovascular Division and
Department of Radiology (S.A.M.C., V.S., M.F.D.C., S.D.), Brigham and
Women’s Hospital and Harvard Medical School, 70 Francis St, Boston, MA
02115; and Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas
City, Mo (V.S.)
| | - Marcelo F. Di Carli
- From the Department of Nuclear Medicine and Molecular Imaging,
Singapore General Hospital, Singapore (Y.M.K.); Division of Nuclear Medicine and
Molecular Imaging, Department of Radiology (Y.M.K., V.S., M.F.D.C., S.D.),
Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine
(S.A.M.C., R.H.F., S.D.), and CV Imaging Program, Cardiovascular Division and
Department of Radiology (S.A.M.C., V.S., M.F.D.C., S.D.), Brigham and
Women’s Hospital and Harvard Medical School, 70 Francis St, Boston, MA
02115; and Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas
City, Mo (V.S.)
| | - Sharmila Dorbala
- From the Department of Nuclear Medicine and Molecular Imaging,
Singapore General Hospital, Singapore (Y.M.K.); Division of Nuclear Medicine and
Molecular Imaging, Department of Radiology (Y.M.K., V.S., M.F.D.C., S.D.),
Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine
(S.A.M.C., R.H.F., S.D.), and CV Imaging Program, Cardiovascular Division and
Department of Radiology (S.A.M.C., V.S., M.F.D.C., S.D.), Brigham and
Women’s Hospital and Harvard Medical School, 70 Francis St, Boston, MA
02115; and Midwest Heart and Vascular Specialists, HCA Midwest Health, Kansas
City, Mo (V.S.)
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50
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Ajmone Marsan N, Delgado V, Shah DJ, Pellikka P, Bax JJ, Treibel T, Cavalcante JL. Valvular heart disease: shifting the focus to the myocardium. Eur Heart J 2023; 44:28-40. [PMID: 36167923 PMCID: PMC9805407 DOI: 10.1093/eurheartj/ehac504] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 07/12/2022] [Accepted: 08/26/2022] [Indexed: 01/05/2023] Open
Abstract
Adverse cardiac remodelling is the main determinant of patient prognosis in degenerative valvular heart disease (VHD). However, to give an indication for valvular intervention, current guidelines include parameters of cardiac chamber dilatation or function which are subject to variability, do not directly reflect myocardial structural changes, and, more importantly, seem to be not sensitive enough in depicting early signs of myocardial dysfunction before irreversible myocardial damage has occurred. To avoid irreversible myocardial dysfunction, novel biomarkers are advocated to help refining indications for intervention and risk stratification. Advanced echocardiographic modalities, including strain analysis, and magnetic resonance imaging have shown to be promising in providing new tools to depict the important switch from adaptive to maladaptive myocardial changes in response to severe VHD. This review, therefore, summarizes the current available evidence on the role of these new imaging biomarkers in degenerative VHD, aiming at shifting the clinical perspective from a valve-centred to a myocardium-focused approach for patient management and therapeutic decision-making.
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Affiliation(s)
- Nina Ajmone Marsan
- Department of Cardiology, Leiden Univesity Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands
| | - Victoria Delgado
- Department of Cardiology, Leiden Univesity Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands
- Department of Cardiology, Germans Trias i Pujol Hospital, Carretera de Canyet s/n. 08916 Badalona, Barcelona, Spain
| | - Dipan J Shah
- Division of Cardiovascular Imaging, Weill Cornell Medical College, Houston Methodist DeBakey Heart & Vascular Center, 6565 Fannin St, Houston, TX 77030, USA
| | - Patricia Pellikka
- Department of Cardiovascular Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA
| | - Jeroen J Bax
- Department of Cardiology, Leiden Univesity Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands
| | - Thomas Treibel
- Department of Cardiology, Barts Heart Centre and University College London, West Smithfield, London EC1A 7BE, UK
| | - João L Cavalcante
- Department of Cardiology, Minneapolis Heart Institute at Abbott Northwestern Hospital, 800 E 28th St, Minneapolis, MN 55407, USA
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