|
1
|
Argirò A, Zampieri M, Mazzoni C, Fumagalli C, Baccini M, Mattei A, Cipriani A, De Michieli L, Porcari A, Sinagra G, Merlo M, Tini G, Musumeci B, Russo D, Vianello PF, Canepa M, Licordari R, di Bella G, Rapezzi C, Perfetto F, Cappelli F. Progression and prognostic significance of electrocardiographic findings in patients with cardiac amyloidosis. ESC Heart Fail 2025; 12:809-818. [PMID: 39665521 PMCID: PMC11911618 DOI: 10.1002/ehf2.14684] [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: 05/07/2023] [Revised: 11/21/2023] [Accepted: 12/31/2023] [Indexed: 12/13/2024] Open
Abstract
AIMS This study aimed to evaluate the change of the main electrocardiographic (ECG) characteristics and their prognostic role across the main subtypes of cardiac amyloidosis [light-chain amyloidosis (AL) and hereditary (ATTRv) and wild-type transthyretin amyloidosis (ATTRwt)]. METHODS AND RESULTS This multicentre, retrospective study was performed in six referral centres for cardiac amyloidosis. Clinical and ECG data were collected at the first and last evaluations. Three hundred fifty-six patients were included (AL, n = 105; ATTRv, n = 50; ATTRwt, n = 201). The median age was 76 (67-81) years, and 271 (74%) were men. At baseline, patients with ATTRwt showed a higher prevalence of conduction abnormalities compared with those with AL [first-degree atrioventricular block, n = 51 (40%) vs. n = 13 (34%), P < 0.01; left bundle branch block, n = 23 (11%) vs. n = 2 (2%), P < 0.01], and patients with AL more often had low QRS voltage [n = 58 (55%); in ATTRv, n = 17 (34%); in ATTRwt, n = 67 (33%), P value < 0.01] and T wave inversion compared with those with ATTR [n = 39 (37%); in ATTRv, n = 9 (18%); in ATTRwt, n = 37 (18%)]. After a median follow-up of 15 (8-26) months, the adjusted differences in mean PR, QRS interval, total, peripheral, and precordial QRS scores were similar across subtypes of amyloidosis (P value for linear regression > 0.05). The adjusted odds ratios for the development of right bundle branch block were higher in AL compared with ATTRwt [odds ratio 4.7 (95% confidence interval 1.5-15), P < 0.05]. QRS duration at baseline remained independently associated with patient survival in the overall population even after adjustment for relevant clinical variables [hazard ratio 1.78 (95% confidence interval 1.13-2.8), P < 0.01]. CONCLUSIONS The progression of the ECG abnormalities seems similar across amyloidosis subtypes. QRS duration could be a marker of more advanced disease.
Collapse
Affiliation(s)
- Alessia Argirò
- Tuscan Regional Amyloidosis CentreCareggi University HospitalFlorenceItaly
- Cardiomyopathy UnitCareggi University Hospital, University of FlorenceLargo Brambilla 3FlorenceItaly
| | - Mattia Zampieri
- Tuscan Regional Amyloidosis CentreCareggi University HospitalFlorenceItaly
- Cardiomyopathy UnitCareggi University Hospital, University of FlorenceLargo Brambilla 3FlorenceItaly
| | - Carlotta Mazzoni
- Tuscan Regional Amyloidosis CentreCareggi University HospitalFlorenceItaly
- Cardiomyopathy UnitCareggi University Hospital, University of FlorenceLargo Brambilla 3FlorenceItaly
| | - Carlo Fumagalli
- Tuscan Regional Amyloidosis CentreCareggi University HospitalFlorenceItaly
- Cardiomyopathy UnitCareggi University Hospital, University of FlorenceLargo Brambilla 3FlorenceItaly
| | - Michela Baccini
- Department of Statistics, Computer Science, Applications (DISIA)University of FlorenceFlorenceItaly
| | - Alessandra Mattei
- Department of Statistics, Computer Science, Applications (DISIA)University of FlorenceFlorenceItaly
| | - Alberto Cipriani
- Department of Cardiac, Thoracic and Vascular Sciences and Public HealthUniversity of PaduaPaduaItaly
| | - Laura De Michieli
- Department of Cardiac, Thoracic and Vascular Sciences and Public HealthUniversity of PaduaPaduaItaly
| | - Aldostefano Porcari
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular DepartmentAzienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of TriesteTriesteItaly
| | - Gianfranco Sinagra
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular DepartmentAzienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of TriesteTriesteItaly
| | - Marco Merlo
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular DepartmentAzienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of TriesteTriesteItaly
| | - Giacomo Tini
- Department of Clinical and Molecular MedicineSapienza UniversityRomeItaly
| | - Beatrice Musumeci
- Department of Clinical and Molecular MedicineSapienza UniversityRomeItaly
| | - Domitilla Russo
- Department of Clinical and Molecular MedicineSapienza UniversityRomeItaly
| | - Pier Filippo Vianello
- Cardiovascular Unit, Department of Internal MedicineUniversity of Genova, Ospedale Policlinico San Martino IRCCSGenoaItaly
| | - Marco Canepa
- Cardiovascular Unit, Department of Internal MedicineUniversity of Genova, Ospedale Policlinico San Martino IRCCSGenoaItaly
| | | | | | - Claudio Rapezzi
- Cardiothoracic DepartmentUniversity of FerraraFerraraItaly
- Maria Cecilia Hospital, GVM Care & Research, CotignolaRavennaItaly
| | - Federico Perfetto
- Tuscan Regional Amyloidosis CentreCareggi University HospitalFlorenceItaly
| | - Francesco Cappelli
- Tuscan Regional Amyloidosis CentreCareggi University HospitalFlorenceItaly
- Cardiomyopathy UnitCareggi University Hospital, University of FlorenceLargo Brambilla 3FlorenceItaly
| |
Collapse
|
|
2
|
Lellouche N, Defaye P, Algalarrondo V, Gandjbakhch E, Fauchier L, Champ-Rigot L, Delsarte L, Extramiana F, Marijon E, Martins R, Probst V, Garcia R, Combes S, Taieb J, Ait Said M, Mette C, Piot O, Boveda S, Klug D, Guenancia C, Sacher F, Maury P. Management of conduction disease and arrhythmias in patients with cardiac amyloidosis: A position paper from the Working Group of Cardiac Pacing and Electrophysiology of the French Society of Cardiology. Arch Cardiovasc Dis 2025; 118:63-74. [PMID: 39613699 DOI: 10.1016/j.acvd.2024.10.323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 10/16/2024] [Accepted: 10/21/2024] [Indexed: 12/01/2024]
Affiliation(s)
- Nicolas Lellouche
- Cardiology Department, Hôpital Henri-Mondor, AP-HP, 94000 Créteil, France.
| | - Pascal Defaye
- Cardiology Department, CHU de Grenoble-Alpes, Grenoble-Alpes University, 38043 Grenoble, France
| | - Vincent Algalarrondo
- Cardiology Department, Hôpital Bichat, AP-HP, Université Paris Cité, 75018 Paris, France
| | - Estelle Gandjbakhch
- Cardiology Department, Pitié-Salpêtrière University Hospital, AP-HP, ICAN, Sorbonne Université, 75013 Paris, France
| | - Laurent Fauchier
- Faculté de Médecine, Université François-Rabelais, 37032 Tours, France
| | | | - Laura Delsarte
- Cardiology Department, CHU de Montpellier, 34295 Montpellier, France
| | - Fabrice Extramiana
- Cardiology Department, Hôpital Bichat, AP-HP, Université Paris Cité, 75018 Paris, France
| | - Eloi Marijon
- Cardiology Department, Hôpital Européen Georges-Pompidou, AP-HP, 75015 Paris, France
| | - Raphael Martins
- Inserm, LTSI-UMR 1099, CHU de Rennes, Université de Rennes, 35000 Rennes, France
| | - Vincent Probst
- Institut du Thorax, CHU de Nantes, Inserm, CNRS, Université de Nantes, 44000 Nantes, France
| | - Rodrigue Garcia
- Cardiology Department, Centre d'Investigation Clinique CIC14-02, CHU de Poitiers, 86000 Poitiers, France
| | - Stephane Combes
- Heart Rhythm Management Department, Clinique Pasteur, 31076 Toulouse, France
| | - Jerome Taieb
- Cardiology Department, Centre Hospitalier du Pays d'Aix, 13100 Aix-en-Provence, France
| | | | - Carole Mette
- Centre Cardiologique du Nord Saint-Denis, 93207 Saint-Denis, France
| | - Olivier Piot
- Centre Cardiologique du Nord Saint-Denis, 93207 Saint-Denis, France
| | - Serge Boveda
- Heart Rhythm Management Department, Clinique Pasteur, 31076 Toulouse, France; Vrije Universiteit Brussel (VUB), 1090 Jette, Belgium; Inserm U970, 75908 Paris, France
| | - Didier Klug
- Cardiology Department, CHU de Lille, 59000 Lille, France
| | | | - Frederic Sacher
- Cardiac Arrhythmia Department, CHU de Bordeaux, 33000 Bordeaux, France; Inserm U1045, IHU Liryc, CRCTB, Bordeaux University, 33000 Bordeaux, France
| | - Philippe Maury
- Cardiology Department, Hôpital Rangueil, CHU de Toulouse, 31400 Toulouse, France; Inserm UMR 1297, I2MC, 31432 Toulouse, France
| |
Collapse
|
|
3
|
Sehrawat O, Swain WH, Alcantara HP, Tan NY, Abou Ezzeddine OF, Grogan M, Dispenzieri A, Lin G, Noseworthy PA, Siontis KC. Prognosis of patients with wild-type transthyretin cardiac amyloidosis and non-sustained ventricular tachycardia. J Cardiovasc Electrophysiol 2025; 36:124-134. [PMID: 39506467 DOI: 10.1111/jce.16470] [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: 07/09/2024] [Revised: 09/13/2024] [Accepted: 10/06/2024] [Indexed: 11/08/2024]
Abstract
INTRODUCTION Little is known regarding the prevalence and prognostic implications of non-sustained ventricular tachycardia (NSVT) in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). We aimed to investigate the prevalence of NSVT in patients with ATTRwr-CA, and the association of NSVT with sustained ventricular arrhythmias (VA) and all-cause mortality. METHODS In a cohort of ATTRwt-CA patients from 2011 to 2022 without prior sustained VA, we ascertained the presence and characteristics of NSVT during clinically indicated ambulatory Holter monitoring. Patients were stratified based on the presence of NSVT at baseline. The primary and secondary endpoints of sustained VA and all-cause mortality, respectively, were assessed during follow-up. RESULTS The cohort included 217 patients with ATTRwt-CA (95% males, median age 75 years; median NYHA class 2). Baseline Holter monitoring demonstrated NSVT in 116 (53%) patients. During a median follow-up of 27 months (IQR 16-45) after the index Holter monitor, 11 (5.1%) patients reached the primary endpoint of sustained VA (incidence 1.8 per 100 person-years, all monomorphic VT), and 46 (21%) patients died. In univariable Cox proportional hazard model, NYHA class 3 or 4 heart failure (p = .048), the presence of NSVT (p = .04), the duration of longest NSVT run (p = .029), and the percentage of ventricular ectopy (p < .001) were associated with the primary outcome. When adjusting for age and NYHA class 3 or 4 heart failure, the presence of NSVT remained associated with the primary outcome (p = .03). All-cause mortality was not significantly different between patients with and without NSVT. A cutoff for ventricular ectopy burden of 0.5%, the median for all patients in this study, was associated with increased risk in sustained VA (log-rank p = .004) and mortality (log-rank p = .02). CONCLUSION NSVT is highly prevalent among ATTRwt-CA patients undergoing clinically indicated Holter monitoring and may confer an increased risk of incident sustained VA.
Collapse
MESH Headings
- Humans
- Male
- Female
- Tachycardia, Ventricular/physiopathology
- Tachycardia, Ventricular/diagnosis
- Tachycardia, Ventricular/mortality
- Aged
- Electrocardiography, Ambulatory
- Amyloid Neuropathies, Familial/mortality
- Amyloid Neuropathies, Familial/diagnosis
- Amyloid Neuropathies, Familial/physiopathology
- Amyloid Neuropathies, Familial/genetics
- Amyloid Neuropathies, Familial/complications
- Risk Factors
- Prevalence
- Prognosis
- Time Factors
- Aged, 80 and over
- Risk Assessment
- Middle Aged
- Cardiomyopathies/mortality
- Cardiomyopathies/diagnosis
- Cardiomyopathies/physiopathology
- Retrospective Studies
- Incidence
- Heart Rate
- Action Potentials
Collapse
Affiliation(s)
- Ojasav Sehrawat
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - William H Swain
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Nicholas Y Tan
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Martha Grogan
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Angela Dispenzieri
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Grace Lin
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Peter A Noseworthy
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | |
Collapse
|
|
4
|
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.
Collapse
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.)
| |
Collapse
|
|
5
|
Teresi L, Trimarchi G, Liotta P, Restelli D, Licordari R, Carciotto G, Francesco C, Crea P, Dattilo G, Micari A, Emdin M, Berruezo A, Di Bella G. Electrocardiographic Patterns and Arrhythmias in Cardiac Amyloidosis: From Diagnosis to Therapeutic Management-A Narrative Review. J Clin Med 2024; 13:5588. [PMID: 39337075 PMCID: PMC11432666 DOI: 10.3390/jcm13185588] [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: 08/13/2024] [Revised: 09/06/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
Electrophysiological aspects of cardiac amyloidosis (CA) are still poorly explored compared to other aspects of the disease. However, electrocardiogram (ECG) abnormalities play an important role in CA diagnosis and prognosis and the management of arrhythmias is a crucial part of CA treatment. Low voltages and a pseudonecrosis pattern with poor R-wave progression in precordial leads are especially common findings. These are useful for CA diagnosis and risk stratification, especially when combined with clinical or echocardiographic findings. Both ventricular and supraventricular arrhythmias are common in CA, especially in transthyretin amyloidosis (ATTR), and their prevalence is related to disease progression. Sustained and non-sustained ventricular tachycardias' prognostic role is still debated, and, to date, there is a lack of specific indications for implantable cardiac defibrillator (ICD). On the other hand, atrial fibrillation (AF) is the most common supraventricular arrhythmia with a prevalence of up to 88% of ATTR patients. Anticoagulation should be considered irrespective of CHADsVA score. Furthermore, even if AF seems to not be an independent prognostic factor in CA, its treatment for symptom control is still crucial. Finally, conduction disturbances and bradyarrhythmias are also common, requiring pacemaker implantation in up to 40% of patients.
Collapse
Affiliation(s)
- Lucio Teresi
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
- Heart Institute, Teknon Medical Centre, 08022 Barcelona, Spain
| | - Giancarlo Trimarchi
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
- Health Science Interdisciplinary Center, Scuola Superiore Sant’Anna, 56127 Pisa, Italy
| | - Paolo Liotta
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
| | - Davide Restelli
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
| | - Roberto Licordari
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
| | - Gabriele Carciotto
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
| | - Costa Francesco
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
- Departamento de Medicina UMA, Área del Corazón, Hospital Universitario Virgen de la Victoria, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), IBIMA Plataforma BIONAND, 29010 Malaga, Spain
| | - Pasquale Crea
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
| | - Giuseppe Dattilo
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
| | - Antonio Micari
- Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98100 Messina, Italy
| | - Michele Emdin
- Health Science Interdisciplinary Center, Scuola Superiore Sant’Anna, 56127 Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy
| | | | - Gianluca Di Bella
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
| |
Collapse
|
|
6
|
Vogel J, Carpinteiro A, Luedike P, Buehning F, Wernhart S, Rassaf T, Michel L. Current Therapies and Future Horizons in Cardiac Amyloidosis Treatment. Curr Heart Fail Rep 2024; 21:305-321. [PMID: 38809394 PMCID: PMC11333534 DOI: 10.1007/s11897-024-00669-7] [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] [Accepted: 05/20/2024] [Indexed: 05/30/2024]
Abstract
PURPOSE OF REVIEW Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid. RECENT FINDINGS The current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial fibrillation and valvular disease remains a challenge in CA, driven by technical difficulties and uncertain outcomes. Tafamidis is the first ATTR-stabilizer approved with a rapidly growing rate of clinical use. In parallel, various new therapeutic classes are in late-stage clinical trials including silencers, antibodies and genetic therapy. Managing CA is a critical challenge for future heart failure care. This review delineates the current standard-of-care and scientific landscape of CA therapy.
Collapse
Affiliation(s)
- Julia Vogel
- 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 Cancer 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
| | - Florian Buehning
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany
| | - Simon Wernhart
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, 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
| | - Lars Michel
- Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Hufelandstraße 55, 45147, Essen, Germany.
| |
Collapse
|
|
7
|
Kourek C, Briasoulis A, Magouliotis DE, Georgoulias P, Giamouzis G, Triposkiadis F, Skoularigis J, Xanthopoulos A. Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis. World J Cardiol 2024; 16:370-379. [PMID: 39086890 PMCID: PMC11287460 DOI: 10.4330/wjc.v16.i7.370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 06/06/2024] [Accepted: 06/25/2024] [Indexed: 07/23/2024] Open
Abstract
Cardiac amyloidosis is a progressive disease characterized by the buildup of amyloid fibrils in the extracellular space of the heart. It is divided in 2 main types, immunoglobulin light chain amyloidosis and transthyretin amyloidosis (ATTR), and ATTR amyloidosis is further divided in 2 subtypes, non-hereditary wild type ATTR and hereditary mutant variant amyloidosis. Incidence and prevalence of ATTR cardiac amyloidosis is increasing over the last years due to the improvements in diagnostic methods. Survival rates are improving due to the development of novel therapeutic strategies. Tafamidis is the only disease-modifying approved therapy in ATTR amyloidosis so far. However, the most recent advances in medical therapies have added more options with the potential to become part of the therapeutic armamentarium of the disease. Agents including acoramidis, eplontersen, vutrisiran, patisiran and anti-monoclonal antibody NI006 are being investigated on cardiac function in large, multicenter controlled trials which are expected to be completed within the next 2-3 years, providing promising results in patients with ATTR cardiac amyloidosis. However, further and ongoing research is required in order to improve diagnostic methods that could provide an early diagnosis, as well as survival and quality of life of these patients.
Collapse
Affiliation(s)
- Christos Kourek
- Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1 Critical Care Medicine Department, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens 10676, Greece
| | - Alexandros Briasoulis
- Department of Clinical Therapeutics, Alexandra Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens 11528, Greece
| | - Dimitrios E Magouliotis
- Department of Cardiothoracic Surgery, University of Thessaly, Larissa Biopolis, Larissa 41110, Greece
| | | | - Grigorios Giamouzis
- Department of Cardiology, School of Medicine, University Hospital of Larissa, Larissa 41110, Greece
| | - Filippos Triposkiadis
- Department of Cardiology, School of Medicine, University Hospital of Larissa, Larissa 41110, Greece
| | - John Skoularigis
- Department of Cardiology, School of Medicine, University Hospital of Larissa, Larissa 41110, Greece
| | - Andrew Xanthopoulos
- Department of Cardiology, School of Medicine, University Hospital of Larissa, Larissa 41110, Greece.
| |
Collapse
|
|
8
|
Scirpa R, Follesa F, De Fazio L, Cittadini E, Francia P, Tini G, Autore C, Barbato E, Musumeci B. Arrhythmic Stratification of Cardiac Amyloidosis: State of the Art. Heart Fail Clin 2024; 20:e33-e44. [PMID: 40082014 DOI: 10.1016/j.hfc.2024.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
Cardiac amyloidosis is an infiltrative myocardial disease whose prevalence significantly increased in recent years. Its clinical history is changing due to the advent of novel therapies, and careful risk stratification has become impelling. Arrhythmias, frequently found during the course of the disease, include conduction system disease, atrial fibrillation (AF), and ventricular arrhythmias (VAs). Arrhythmic risk stratification is a key to identify those patients at higher risk to develop advanced atrioventricular blocks, asymptomatic AFs, or major VAs. This carries significant clinical implications concerning the indication and timing of implantable cardiac devices, as well as the initiation of anticoagulation therapy.
Collapse
Affiliation(s)
- Riccardo Scirpa
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy
| | - Federico Follesa
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy
| | - Ludovica De Fazio
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy
| | - Edoardo Cittadini
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy
| | - Pietro Francia
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy
| | - Giacomo Tini
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy
| | - Camillo Autore
- IRCSS San Raffele Pisana, Via Della Pisana; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy
| | - Emanuele Barbato
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy
| | - Beatrice Musumeci
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome (Lazio) 00185, Italy.
| |
Collapse
|
|
9
|
Holcman K, Ząbek A, Boczar K, Podolec P, Kostkiewicz M. Management of Arrhythmias and Conduction Disorders in Amyloid Cardiomyopathy. J Clin Med 2024; 13:3088. [PMID: 38892799 PMCID: PMC11172576 DOI: 10.3390/jcm13113088] [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: 04/26/2024] [Revised: 05/19/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open
Abstract
Cardiac amyloidosis, a condition characterized by abnormal protein deposition in the heart, leads to restrictive cardiomyopathy and is notably associated with an increased risk of arrhythmias and conduction disorders. This article reviews the current understanding and management strategies for these cardiac complications, with a focus on recent advancements and clinical challenges. The prevalence and impact of atrial arrhythmias, particularly atrial fibrillation, are examined, along with considerations for stroke risk and anticoagulation therapy. The article also addresses the complexities of managing rate and rhythm control, outlining the utility and limitations of pharmacological agents and interventions such as catheter ablation. Furthermore, it reviews the challenges in the treatment of ventricular arrhythmias, including the contentious use of implantable cardioverter-defibrillators for primary and secondary prevention. Individualized approaches, considering the unique characteristics of cardiac amyloidosis, are paramount. Continuous research and clinical exploration are essential to refine treatment strategies and improve outcomes in this challenging patient population.
Collapse
Affiliation(s)
- Katarzyna Holcman
- Department of Nuclear Medicine, John Paul II Hospital, 31-202 Krakow, Poland;
- Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, John Paul II Hospital, 31-202 Krakow, Poland;
| | - Andrzej Ząbek
- Department of Electrocardiology, Jagiellonian University Medical College, John Paul II Hospital, 31-202 Krakow, Poland; (A.Z.); (K.B.)
| | - Krzysztof Boczar
- Department of Electrocardiology, Jagiellonian University Medical College, John Paul II Hospital, 31-202 Krakow, Poland; (A.Z.); (K.B.)
| | - Piotr Podolec
- Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, John Paul II Hospital, 31-202 Krakow, Poland;
| | - Magdalena Kostkiewicz
- Department of Nuclear Medicine, John Paul II Hospital, 31-202 Krakow, Poland;
- Department of Cardiac and Vascular Diseases, Jagiellonian University Medical College, John Paul II Hospital, 31-202 Krakow, Poland;
| |
Collapse
|
|
10
|
Martini N, Sinigiani G, De Michieli L, Mussinelli R, Perazzolo Marra M, Iliceto S, Zorzi A, Perlini S, Corrado D, Cipriani A. Electrocardiographic features and rhythm disorders in cardiac amyloidosis. Trends Cardiovasc Med 2024; 34:257-264. [PMID: 36841466 DOI: 10.1016/j.tcm.2023.02.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 02/16/2023] [Accepted: 02/18/2023] [Indexed: 02/27/2023]
Abstract
Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular deposition of amyloid fibrils, mainly derived from transthyretin, either wild-type or hereditary variants, or immunoglobulin light chains misfolding. It is characterized by an increased left ventricular (LV) mass and diastolic dysfunction, which can lead to heart failure with preserved ejection fraction and/or conduction disturbances. The diagnosis is based on invasive pathology demonstration of amyloid deposits, or non-invasive criteria using advanced cardiovascular imaging techniques. Nevertheless, 12-lead electrocardiogram (ECG) remains of crucial importance in the assessment of patients with CA, since they can manifest peculiar features such as low QRS voltages, in discordance with the LV hypertrophy, but also pseudo-infarction patterns, sinus node dysfunction, atrioventricular blocks, premature supraventricular and ventricular beats, which support the presence of a myocardial disease. Great awareness of these common ECG characteristics of CA is needed to increase diagnostic performance and improve patient's outcome. In the present review, we discuss the current role of the ECG in the diagnosis and management of CA, focusing on the most common ECG abnormalities and rhythm disorders.
Collapse
Affiliation(s)
- Nicolò Martini
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, Padua 35128, Italy
| | - Giulio Sinigiani
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, Padua 35128, Italy
| | - Laura De Michieli
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, Padua 35128, Italy
| | - Roberta Mussinelli
- Amyloidosis Research and Treatment Center, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Martina Perazzolo Marra
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, Padua 35128, Italy
| | - Sabino Iliceto
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, Padua 35128, Italy
| | - Alessandro Zorzi
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, Padua 35128, Italy
| | - Stefano Perlini
- Amyloidosis Research and Treatment Center, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy; Emergency Medicine, Vascular and Metabolic Disease Unit, Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Domenico Corrado
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, Padua 35128, Italy
| | - Alberto Cipriani
- Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, Padua 35128, Italy.
| |
Collapse
|
|
11
|
Alfieri M, Guerra F, Lofiego C, Fogante M, Ciliberti G, Vagnarelli F, Barbarossa A, Principi S, Stronati G, Volpato G, Compagnucci P, Valeri Y, Tofoni P, Brugiatelli L, Capodaglio I, Esposto Pirani P, Argalia G, Schicchi N, Messano L, Centanni M, Giovagnoni A, Perna GP, Dello Russo A, Casella M. A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:613. [PMID: 38674259 PMCID: PMC11051713 DOI: 10.3390/medicina60040613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/29/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024]
Abstract
Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.
Collapse
Affiliation(s)
- Michele Alfieri
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Federico Guerra
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
- Department of Biomedical Sciences and Public Health, Marche Polytechnic University, 60121 Ancona, Italy
| | - Carla Lofiego
- Division of Cardiology, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy
| | - Marco Fogante
- Cardiovascular Radiological Diagnostics, Department of Radiological Sciences, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy; (M.F.)
| | - Giuseppe Ciliberti
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Fabio Vagnarelli
- Division of Cardiology, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy
| | - Alessandro Barbarossa
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Samuele Principi
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Giulia Stronati
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Giovanni Volpato
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Paolo Compagnucci
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Yari Valeri
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Paolo Tofoni
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Leonardo Brugiatelli
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Irene Capodaglio
- Division of Cardiology, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy
| | - Paolo Esposto Pirani
- Cardiovascular Radiological Diagnostics, Department of Radiological Sciences, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy; (M.F.)
| | - Giulio Argalia
- Cardiovascular Radiological Diagnostics, Department of Radiological Sciences, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy; (M.F.)
| | - Nicolò Schicchi
- Cardiovascular Radiological Diagnostics, Department of Radiological Sciences, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy; (M.F.)
| | - Loredana Messano
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Maurizio Centanni
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
| | - Andrea Giovagnoni
- Cardiovascular Radiological Diagnostics, Department of Radiological Sciences, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy; (M.F.)
- Department of Clinical, Special and Dental Sciences, Marche Polytechnic University, 60121 Ancona, Italy
| | - Gian Piero Perna
- Division of Cardiology, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy
| | - Antonio Dello Russo
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
- Department of Biomedical Sciences and Public Health, Marche Polytechnic University, 60121 Ancona, Italy
| | - Michela Casella
- Cardiology and Arrhythmology Clinic, University Hospital “Azienda Ospedaliero-Universitaria delle Marche”, Via Conca 71, 60126 Ancona, Italy (G.C.); (P.C.); (Y.V.); (P.T.); (L.B.)
- Department of Clinical, Special and Dental Sciences, Marche Polytechnic University, 60121 Ancona, Italy
| |
Collapse
|
|
12
|
Pagura L, Porcari A, Cameli M, Biagini E, Canepa M, Crotti L, Imazio M, Forleo C, Pavasini R, Limongelli G, Perlini S, Metra M, Boriani G, Emdin M, Sinagra G, Merlo M. ECG/echo indexes in the diagnostic approach to amyloid cardiomyopathy: A head-to-head comparison from the AC-TIVE study. Eur J Intern Med 2024; 122:68-77. [PMID: 37858441 DOI: 10.1016/j.ejim.2023.09.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 09/22/2023] [Accepted: 09/25/2023] [Indexed: 10/21/2023]
Abstract
BACKGROUND AND AIMS The discordance between QRS voltages on electrocardiogram (ECG) and left ventricle (LV) wall thickness (LVWT) on echocardiogram (echo) is a recognized red flag (RF) of amyloid cardiomyopathy (AC) and can be measured by specific indexes. No head-to-head comparison of different ECG/echo indexes among subjects with echocardiographic suspicion of AC has yet been undertaken. The study aimed at evaluating the performance and the incremental diagnostic value of different ECG/echo indexes in this subset of patients. METHODS Electrocardiograms of subjects with LV hypertrophy, preserved ejection fraction and ≥ 1 echocardiographic RF of AC participating in the AC-TIVE study, an Italian prospective multicenter study, were independently analyzed by two cardiologists. Low QRS voltages and 8 different ECG/echo indexes were evaluated. Cohort specific cut-offs were computed. RESULTS Among 170 patients, 55 (32 %) were diagnosed with AC. Combination of low QRS voltages with interventricular septum ≥ 1,6 cm was the most specific (specificity 100 %, positive predictive value 100 %) ECG/echo index, while the ratio between the sum of all QRS voltages and LVWT <7,8 was the most sensitive and accurate (sensitivity 94 %, negative predictive value 97 %, accuracy 82 %). When the latter index was added to a model using easily-accessible clinical variables, the diagnostic accuracy for AC greatly increased (AUC from 0,84 to 0,95; p = 0,007). CONCLUSIONS Among patients with non-dilated hypertrophic ventricles with normal ejection fraction and echocardiographic RF of AC, easily-measurable ECG/echo indexes, mainly when added to few clinical variables, can help the physician orient second level investigations. External validation of the results is warranted.
Collapse
Affiliation(s)
- Linda Pagura
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI) and University of Trieste, Via P. Valdoni 7, Trieste 34100, Italy; Cardiac Surgery, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), Trieste, Italy
| | - Aldostefano Porcari
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI) and University of Trieste, Via P. Valdoni 7, Trieste 34100, Italy
| | - Matteo Cameli
- Department of Medical Biotechnologies, Division of Cardiology, University of Siena, Siena, Italy
| | - Elena Biagini
- Cardiology Unit, St. Orsola Hospital, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marco Canepa
- Department of Internal Medicine, University of Genoa, Genoa, Italy; Cardiovascular Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Lia Crotti
- Department of Cardiology, Istituto Auxologico Italiano, IRCCS, Milan, Italy; Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy
| | - Massimo Imazio
- Cardiology and Cardiothoracic Department, University Hospital "Santa Maria della Misericordia", ASUFC, Udine and Department of Medicine, University of Udine, Italy; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza di Torino Hospital, University of Turin, Turin, Italy
| | - Cinzia Forleo
- University Cardiology Unit, Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Polyclinic University Hospital, Bari, Italy
| | - Rita Pavasini
- Cardiology Unit, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy
| | - Giuseppe Limongelli
- Department of Translational Medical Sciences, Inherited and Rare Heart Disease, Vanvitelli Cardiology, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Stefano Perlini
- Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Marco Metra
- Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, Italy University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy
| | - Michele Emdin
- Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, Pisa
| | - Gianfranco Sinagra
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI) and University of Trieste, Via P. Valdoni 7, Trieste 34100, Italy
| | - Marco Merlo
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI) and University of Trieste, Via P. Valdoni 7, Trieste 34100, Italy.
| |
Collapse
|
|
13
|
Gallo-Fernández I, López-Aguilera J, González-Manzanares R, Pericet-Rodriguez C, Carmona-Rico MJ, Perea-Armijo J, Castillo-Domínguez JC, Anguita-Sánchez M. [Clinical differences between transthyretin cardiac amyloidosis and hypertensive heart disease]. Med Clin (Barc) 2024; 162:205-212. [PMID: 38044190 DOI: 10.1016/j.medcli.2023.10.006] [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: 05/15/2023] [Revised: 10/08/2023] [Accepted: 10/10/2023] [Indexed: 12/05/2023]
Abstract
INTRODUCTION A significant percentage of patients eventually diagnosed with cardiac transthyretin amyloidosis (TTRA) was previously diagnosed with hypertensive heart disease (HHD), since both conditions usually present with heart failure (HF) with preserved ejection fraction (HFpEF) and ventricular hypertrophy. Our objectives were to evaluate the clinical, electrocardiographic and echocardiographic differences, and to analyse whether there exists a differential prognosis between these two nosological entities. MATERIALS AND METHODS We retrospectively included all patients with HHD for whom a cardiac scintigraphy with 99mTc-diphosphonate (GDPD) and a free light chains test in blood and urine were ordered for ATTR screening in our centre, in the period between 2016 and 2021. Those diagnosed with other types of amyloidosis were excluded from the analysis. RESULTS A total of 72 patients were analyzed: 33 were finally diagnosed with TTRA and 39 with CHTA. Patients with TTRA had higher levels of ultrasensitive troponin I (TnI-US) and N-terminal brain natriuretic propeptide (NT-ProBNP); in electrocardiography (ECG) they presented a pseudo-infarction pattern more frequently as well as conduction disturbances; in echocardiography (TTE) they presented a higher degree of ventricular hypertrophy, left ventricular dysfunction and worse diastolic function parameters, with elevated filling pressures. In the 4-year follow-up, the ATTR group showed greater need for pacemaker (PCM), with no evidence regarding mortality, development of atrial fibrillation (AF), or more admissions for heart failure (HF). CONCLUSIONS In our series, patients with TTRA showed clinical, electrocardiographic and echocardiographic differences compared to patients with HHD, with increased risk of need for PCM.
Collapse
Affiliation(s)
- Ignacio Gallo-Fernández
- Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, España; Instituto de Investigación Biomédica de Córdoba, IMIBIC, Córdoba, España
| | - José López-Aguilera
- Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, España; Instituto de Investigación Biomédica de Córdoba, IMIBIC, Córdoba, España.
| | - Rafael González-Manzanares
- Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, España; Instituto de Investigación Biomédica de Córdoba, IMIBIC, Córdoba, España
| | - Cristina Pericet-Rodriguez
- Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, España; Instituto de Investigación Biomédica de Córdoba, IMIBIC, Córdoba, España
| | | | - Jorge Perea-Armijo
- Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, España; Instituto de Investigación Biomédica de Córdoba, IMIBIC, Córdoba, España; Universidad de Córdoba, Córdoba, España
| | - Juan Carlos Castillo-Domínguez
- Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, España; Instituto de Investigación Biomédica de Córdoba, IMIBIC, Córdoba, España
| | - Manuel Anguita-Sánchez
- Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitario Reina Sofía, Córdoba, España; Instituto de Investigación Biomédica de Córdoba, IMIBIC, Córdoba, España
| |
Collapse
|
|
14
|
Ali GMS, Seme WAE, Dudhat K. Examining the Difficulties in Identifying and Handling Cardiac Amyloidosis; Acquiring Important Knowledge and Robust Treatment Methods. Cardiovasc Hematol Disord Drug Targets 2024; 24:65-82. [PMID: 39075963 DOI: 10.2174/011871529x301954240715041558] [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: 03/09/2024] [Revised: 06/20/2024] [Accepted: 07/04/2024] [Indexed: 07/31/2024]
Abstract
Systemic amyloidosis is a rare protein misfolding and deposition condition that causes slow organ failure. Each of the more than 15 exclusive sorts of systemic amyloidosis, which encourage amyloid production and tissue deposition, is introduced by a unique precursor protein. Amyloidosis can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin, and soft tissues. It can either be acquired or hereditary. Insidious and doubtful signs often cause a put-off in diagnosis. In the closing decade, noteworthy progressions have been made in the identity, prediction, and handling of amyloidosis. Shotgun proteomics based on mass spectrometry has revolutionized amyloid typing and enabled the identification of novel amyloid forms. It is critical to correctly identify the precursor protein implicated in amyloidosis because the kind of protein influences the proper treatment strategy. Cardiac amyloidosis is a disorder characterized by the systemic accumulation of amyloid protein in the myocardium's extracellular space, which causes a variety of symptoms. The buildup of amyloid aggregates precipitates myocardial thickening and stiffening, culminating in diastolic dysfunction and, in due course, heart failure. We examine every kind of systemic amyloidosis in this text to offer practitioners beneficial equipment for diagnosing and treating those unusual diseases. This review presents a comprehensive analysis of cardiac amyloidosis and consolidates current methods for screening, diagnosis, evaluation, and treatment alternatives.
Collapse
Affiliation(s)
| | | | - Kiran Dudhat
- School of Pharmacy, RK University, Kasturbadham, Rajkot, Gujarat, 360020, India
| |
Collapse
|
|
15
|
Russo D, Cappelli F, Di Bella G, Tini G, Porcari A, Cipriani A, Canepa M, Merlo M, Licordari R, Vianello PF, Zampieri M, De Michieli L, Scirpa R, Perfetto F, Sinagra G, Autore C, Rapezzi C, Musumeci MB. Electrocardiographic heterogeneity of patients with variant transthyretin amyloid cardiomyopathy: Genotype-phenotype correlations. Int J Cardiol 2023; 393:131354. [PMID: 37696363 DOI: 10.1016/j.ijcard.2023.131354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 04/17/2023] [Accepted: 09/08/2023] [Indexed: 09/13/2023]
Abstract
BACKGORUND Hereditary transthyretin(vATTR) cardiac amyloidosis has extremely different features according to the type of transthyretin(TTR) mutation. Data about electrocardiographic findings(ECG) in vATTR are limited and not informative of genotype correlation. Aim of this study is to analyze ECG characteristics and their correlation to clinical and echocardiographic aspects in patients with vATTR, focusing on different TTR mutations. METHODS AND RESULTS This is a multicentric, retrospective, observational study performed in six Italian referral centres. We divided patients in two groups, according to the previously described phenotypic manifestations of the TTR mutation. Of 64 patients with vATTR, 23(36%) had prevalent cardiac(PC) TTR mutations and 41(64%) patients had a prevalent neurological(PN) TTR mutations. Patients with PC mutations were more frequently males and older, with advanced NAC staging. At baseline ECG, atrial fibrillation was more common in patients with PC, while pacemaker induced rhythm in PN mutations. PQ and QRS durations were longer and voltage to mass ratio was lower in PC mutations. Different TTR mutations tend to have distinctive ECG features. CONCLUSIONS ECG in vATTR is extremely heterogeneous and the specific mutations are associated with distinct instrumental and clinical features. The differences between PN and PC vATTR are only partially explained by the different degree of cardiac infiltration.
Collapse
Affiliation(s)
- Domitilla Russo
- Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
| | - Francesco Cappelli
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy
| | - Gianluca Di Bella
- Clinical and Experimental Department of Medicine and Pharmacology, University of Messina, Italy
| | - Giacomo Tini
- Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
| | - Aldostefano Porcari
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Trieste, Italy
| | - Alberto Cipriani
- Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Italy
| | - Marco Canepa
- Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy; IRCCS Italian Cardiovascular Network & Department of Internal Medicine, University of Genova, Genova, Italy
| | - Marco Merlo
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Trieste, Italy
| | - Roberto Licordari
- Clinical and Experimental Department of Medicine and Pharmacology, University of Messina, Italy
| | | | - Mattia Zampieri
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy
| | - Laura De Michieli
- Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Italy
| | - Riccardo Scirpa
- Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
| | - Federico Perfetto
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy
| | - Gianfranco Sinagra
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Trieste, Italy
| | - Camillo Autore
- Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
| | - Claudio Rapezzi
- Centro Cardiologico Universitario di Ferrara, University of Ferrara, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola (RA), Italy
| | - Maria Beatrice Musumeci
- Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy.
| |
Collapse
|
|
16
|
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.
Collapse
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
| |
Collapse
|
|
17
|
Bukhari S, Kasi A, Khan B. Bradyarrhythmias in Cardiac Amyloidosis and Role of Pacemaker. Curr Probl Cardiol 2023; 48:101912. [PMID: 37392977 DOI: 10.1016/j.cpcardiol.2023.101912] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 06/27/2023] [Indexed: 07/03/2023]
Abstract
Cardiac amyloidosis (CA) is an underdiagnosed disease that is caused by deposition of misfolded transthyretin (ATTR) or immunoglobulin light chain (AL) fibrils in the myocardium. Bradyarrhythmias are commonly seen in CA, due to disruption of conducting system by amyloid fibrils. Atrioventricular conduction defect is more common than sinus node dysfunction. Bradyarrhythmias are most prevalent in wtATTR, followed by hATTR and AL. Pacemaker implantation, when indicated, can help provide symptomatic relief but does not confer mortality benefit. Progression of conduction system disease is common and often leads to increased right ventricular pacing burden with time. Therefore, cardiac resynchronizing therapy (biventricular therapy) is often considered as a better and safer option in these patients. Finally, the role of prophylactic pacemaker implantation is controversial, and current guidelines do not recommend prophylactic pacemaker insertion in CA patients.
Collapse
Affiliation(s)
- Syed Bukhari
- Department of Medicine, Temple University Hospital, Philadelphia, PA.
| | - Amail Kasi
- Department of Internal Medicine, National Hospital Quetta, Balochistan, Pakistan
| | - Bilal Khan
- Department of Medicine, Temple University Hospital-Jeanes Campus, Philadelphia, PA
| |
Collapse
|
|
18
|
Briasoulis A, Kourek C, Papamichail A, Loritis K, Bampatsias D, Repasos E, Xanthopoulos A, Tsougos E, Paraskevaidis I. Arrhythmias in Patients with Cardiac Amyloidosis: A Comprehensive Review on Clinical Management and Devices. J Cardiovasc Dev Dis 2023; 10:337. [PMID: 37623350 PMCID: PMC10455774 DOI: 10.3390/jcdd10080337] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/01/2023] [Accepted: 08/03/2023] [Indexed: 08/26/2023] Open
Abstract
Cardiac amyloidosis (CA) is a rare but potentially life-threatening disease in which misfolded proteins accumulate in the cardiac wall tissue. Heart rhythm disorders in CA, including supraventricular arrhythmias, conduction system disturbances, or ventricular arrhythmias, play a major role in CA morbidity and mortality, and thus require supplementary management. Among them, AF is the most frequent arrhythmia during CA hospitalizations and is associated with significantly higher mortality, while ventricular arrhythmias are also common and are usually associated with poor prognosis. Early diagnosis of potential arrythmias could be performed through ECG, Holter monitoring, and/or electrophysiology study. Clinical management of these patients is quite significant, and it usually includes initiation of amiodarone and/or digoxin in patients with AF, potential electrical cardioversion, or ablation in specific patients with indication, as well as initiation of anticoagulants in all patients, independent of AF and CHADS-VASc score, for potential intracardiac thrombus. Moreover, identification of patients with conduction disorders that could benefit from prophylactic pacemaker implantation and/or CRT as well as identification of patients with life-threatening ventricular arrythmias that could benefit from ICD could both increase the survival rates of these patients and improve their quality of life.
Collapse
Affiliation(s)
- Alexandros Briasoulis
- Medical School of Athens, National and Kapodistrian University of Athens, 15772 Athens, Greece; (C.K.); (A.P.); (K.L.); (D.B.); (E.R.); (I.P.)
| | - Christos Kourek
- Medical School of Athens, National and Kapodistrian University of Athens, 15772 Athens, Greece; (C.K.); (A.P.); (K.L.); (D.B.); (E.R.); (I.P.)
| | - Adamantia Papamichail
- Medical School of Athens, National and Kapodistrian University of Athens, 15772 Athens, Greece; (C.K.); (A.P.); (K.L.); (D.B.); (E.R.); (I.P.)
| | - Konstantinos Loritis
- Medical School of Athens, National and Kapodistrian University of Athens, 15772 Athens, Greece; (C.K.); (A.P.); (K.L.); (D.B.); (E.R.); (I.P.)
| | - Dimitrios Bampatsias
- Medical School of Athens, National and Kapodistrian University of Athens, 15772 Athens, Greece; (C.K.); (A.P.); (K.L.); (D.B.); (E.R.); (I.P.)
| | - Evangelos Repasos
- Medical School of Athens, National and Kapodistrian University of Athens, 15772 Athens, Greece; (C.K.); (A.P.); (K.L.); (D.B.); (E.R.); (I.P.)
| | - Andrew Xanthopoulos
- Department of Cardiology, University Hospital of Larissa, 41110 Larissa, Greece;
| | - Elias Tsougos
- Department of Cardiology, Hygeia Hospital, 15123 Athens, Greece;
| | - Ioannis Paraskevaidis
- Medical School of Athens, National and Kapodistrian University of Athens, 15772 Athens, Greece; (C.K.); (A.P.); (K.L.); (D.B.); (E.R.); (I.P.)
| |
Collapse
|
|
19
|
Knoll K, Fuchs P, Weidmann I, Altunkas F, Voss S, Lennerz C, Kolb C, Kessler T, Schunkert H, Reinhard W, Groß S, Trenkwalder T. Incidence and Predictors of Ventricular Arrhythmias in Transthyretin Amyloid Cardiomyopathy. J Clin Med 2023; 12:4624. [PMID: 37510739 PMCID: PMC10380522 DOI: 10.3390/jcm12144624] [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: 06/18/2023] [Revised: 06/29/2023] [Accepted: 07/03/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is characterized by heart failure, conduction abnormalities and arrhythmias. The incidence of ventricular arrhythmias, particularly ventricular tachycardias (VTs), in wtATTR-CM is unclear. With the development of targeted therapies and improved overall prognosis, there is an unmet need to identify patients at high risk for VTs who might benefit from ICD therapy. METHODS Between 2017 and 2022, 72 patients diagnosed with wtATTR-CM were prospectively evaluated for the presence of ventricular arrhythmias using a Holter ECG. VTs were defined as >3 consecutive beats with a heart rate > 100 beats per minute originating from a ventricle. RESULTS The incidence of VTs was 44% (n = 32/72) in unselected wtATTR-CM patients. Patients with VT showed significantly more severe left ventricular (LV) hypertrophy (septum diameter 21 ± 2.6 vs. 19 ± 3.0 mm, p = 0.006), reduced LV ejection fraction (47 ± 8 vs. 52 ± 8%, p = 0.014) and larger left atria (32 ± 7 vs. 28 ± 6 mm2, p = 0.020), but no differences in cardiac markers such as NTproBNP and troponin. In a multivariable model, LV hypertrophy (LV mass indexed, OR = 1.02 [1.00-1.03], p = 0.031), LV end-diastolic diameter (OR = 0.85 [0.74-0.98], p = 0.021) and LV end-systolic diameter (OR = 1.19 [1.03-1.349], p = 0.092) were predictive for VT occurrence with an area under the receiver operating characteristic of 0.76 [0.65-0.87]. CONCLUSIONS The incidence of ventricular arrhythmia in wtATTR-CM is high and is associated with an advanced stage of left ventricular disease. Further studies are needed evaluating the role of VTs in predicting sudden cardiac death and the benefit of ICD therapy in wtATTR-CM.
Collapse
Affiliation(s)
- Katharina Knoll
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336 Munich, Germany
| | - Patrick Fuchs
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336 Munich, Germany
| | - Isabel Weidmann
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
| | - Fatih Altunkas
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
| | - Stephanie Voss
- German Heart Centre Munich, Department of Cardiovascular Surgery, Technical University of Munich, 80636 Munich, Germany
| | - Carsten Lennerz
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336 Munich, Germany
| | - Christof Kolb
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
| | - Thorsten Kessler
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336 Munich, Germany
| | - Heribert Schunkert
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336 Munich, Germany
| | - Wibke Reinhard
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
| | - Stefan Groß
- DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, Germany
- Department of Internal Medicine B, University Medicine Greifswald, 17475 Greifswald, Germany
| | - Teresa Trenkwalder
- German Heart Centre Munich, Department of Cardiology, Technical University of Munich, 80333 Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336 Munich, Germany
| |
Collapse
|
|
20
|
Miyamoto M, Nakamura K, Nakagawa K, Nishii N, Kawada S, Ueoka A, Asada S, Watanabe A, Morita H, Ito H. Prevalence and Treatment of Arrhythmias in Patients With Transthyretin and Light-Chain Cardiac Amyloidosis. Circ Rep 2023; 5:298-305. [PMID: 37431518 PMCID: PMC10329899 DOI: 10.1253/circrep.cr-23-0022] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/22/2023] [Accepted: 05/29/2023] [Indexed: 07/12/2023] Open
Abstract
Background: Various types of arrhythmia are observed in patients with cardiac amyloidosis, but the prevalence of arrhythmia has not been fully investigated. This study investigated the prevalence and treatment of arrhythmias in patients with cardiac amyloidosis before the introduction of new agents for amyloidosis, such as tafamidis. Methods and Results: Of 53 patients who were histologically diagnosed with cardiac amyloidosis at 10 centers in western Japan between 2009 and 2021, 43 who were diagnosed on the basis of immunohistochemical staining were evaluated in this study. Of these 43 patients, 13 had immunoglobulin light-chain (AL) amyloidosis and 30 had transthyretin (ATTR) amyloidosis; further, 27 had atrial tachyarrhythmia, 13 had ventricular tachyarrhythmia, and 17 had bradyarrhythmia. Atrial fibrillation (AF) was the most common arrhythmia in patients with cardiac amyloidosis (n=24; 55.8%), especially among those with ATTR amyloidosis (70.0% of ATTR vs. 23.1% of AL). Eleven (25.6%) patients were treated with a cardiac implantable device. All 3 patients with pacemakers were alive at the last follow-up (median 76.7 months; interquartile range [IQR] 4.8-146.4 months). Of the 8 patients who underwent AF ablation, there was no recurrence in 6 (75%) after a median of 39.3 months (IQR 19.8-59.3 months). Conclusions: The prevalence of various arrhythmias was high in patients with cardiac amyloidosis. AF occurred most frequently in patients with cardiac amyloidosis, especially among patients with ATTR.
Collapse
Affiliation(s)
- Masakazu Miyamoto
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| | - Kazufumi Nakamura
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| | - Koji Nakagawa
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| | - Nobuhiro Nishii
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
- Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| | - Satoshi Kawada
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| | - Akira Ueoka
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| | - Saori Asada
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| | - Atsuyuki Watanabe
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
- Department of Cardiology, National Hospital Organization Okayama Medical Center Okayama Japan
| | - Hiroshi Morita
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
- Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| | - Hiroshi Ito
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan
| |
Collapse
|
|
21
|
Silvetti E, Lanza O, Romeo F, Martino A, Fedele E, Lanzillo C, Crescenzi C, Fanisio F, Calò L. The pivotal role of ECG in cardiomyopathies. Front Cardiovasc Med 2023; 10:1178163. [PMID: 37404739 PMCID: PMC10315483 DOI: 10.3389/fcvm.2023.1178163] [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: 03/02/2023] [Accepted: 05/15/2023] [Indexed: 07/06/2023] Open
Abstract
Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Recent technological advances in cardiovascular imaging offer an opportunity for deep phenotypic and etiological definition. Electrocardiogram (ECG) is the first-line diagnostic tool in the evaluation of both asymptomatic and symptomatic individuals. Some electrocardiographic signs are pathognomonic or fall within validated diagnostic criteria of individual cardiomyopathy such as the inverted T waves in right precordial leads (V1-V3) or beyond in individuals with complete pubertal development in the absence of complete right bundle branch block for the diagnosis of arrhythmogenic cardiomyopathy of the right ventricle (ARVC) or the presence of low voltages typically seen in more than 60% of patients with amyloidosis. Most other electrocardiographic findings such as the presence of depolarization changes including QRS fragmentation, the presence of epsilon wave, the presence of reduced or increased voltages as well as alterations in the repolarization phase including the negative T waves in the lateral leads, or the profound inversion of the T waves or downsloping of the ST tract are more non-specific signs which can however raise the clinical suspicion of cardiomyopathy in order to initiate a diagnostic procedure especially using imaging techniques for diagnostic confirmation. Such electrocardiographic alterations not only have a counterpart in imaging investigations such as evidence of late gadolinium enhancement on magnetic resonance imaging, but may also have an important prognostic value once a definite diagnosis has been made. In addition, the presence of electrical stimulus conduction disturbances or advanced atrioventricular blocks that can be seen especially in conditions such as cardiac amyloidosis or sarcoidosis, or the presence of left bundle branch block or posterior fascicular block in dilated or arrhythmogenic left ventricular cardiomyopathies are recognized as a possible expression of advanced pathology. Similarly, the presence of ventricular arrhythmias with typical patterns such as non-sustained or sustained ventricular tachycardia of LBBB morphology in ARVC or non-sustained or sustained ventricular tachycardia with an RBBB morphology (excluding the "fascicular pattern") in arrhythmogenic left ventricle cardiomyopathy could have a significant impact on the course of each disease. It is therefore clear that a learned and careful interpretation of ECG features can raise suspicion of the presence of a cardiomyopathy, identify diagnostic "red flags" useful for orienting the diagnosis toward specific forms, and provide useful tools for risk stratification. The purpose of this review is to emphasize the important role of the ECG in the diagnostic workup, describing the main ECG findings of different cardiomyopathies.
Collapse
|
|
22
|
Laptseva N, Rossi VA, Sudano I, Schwotzer R, Ruschitzka F, Flammer AJ, Duru F. Arrhythmic Manifestations of Cardiac Amyloidosis: Challenges in Risk Stratification and Clinical Management. J Clin Med 2023; 12:jcm12072581. [PMID: 37048664 PMCID: PMC10095126 DOI: 10.3390/jcm12072581] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/23/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023] Open
Abstract
Amylodiosis is a systemic disease characterized by extracellular deposits of insoluble amyloid in various tissues and organs. Cardiac amyloidosis is a frequent feature of the disease, causing a progressive, restrictive type of cardiomyopathy, and is associated with adverse clinical outcomes and increased mortality. The typical clinical presentation in patients with cardiac amyloidosis is heart failure (HF) with preserved ejection fraction. Most patients present with typical symptoms and signs of HF, such as exertional dyspnea, pretibial edema, pleural effusions and angina pectoris due to microcirculatory dysfunction. However, patients may also frequently encounter various arrhythmias, such as atrioventricular nodal block, atrial fibrillation and ventricular tachyarrhythmias. The management of arrhythmias in cardiac amyloidosis patients with drugs and devices is often a clinical challenge. Moreover, predictors of life-threatening arrhythmic events are not well defined. This review intends to give a deepened insight into the arrhythmic features of cardiac amyloidosis by discussing the pathogenesis of these arrhythmias, addressing the challenges in risk stratification and strategies for management in these patients.
Collapse
|
|
23
|
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.
Collapse
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
| |
Collapse
|
|
24
|
Bukhari S, Khan B. Prevalence of ventricular arrhythmias and role of implantable cardioverter-defibrillator in cardiac amyloidosis. J Cardiol 2023; 81:429-433. [PMID: 36894119 DOI: 10.1016/j.jjcc.2023.02.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 02/27/2023] [Accepted: 02/28/2023] [Indexed: 03/09/2023]
Abstract
Cardiac amyloidosis is an underdiagnosed disease that is caused by myocardial deposition of misfolded light chain (AL) or transthyretin (ATTR) amyloid fibrils, leading to restrictive cardiomyopathy and eventually death if untreated. Ventricular arrhythmias are common in cardiac amyloidosis, and the prevalence is higher in AL than ATTR. There are multiple suspected pathogenic mechanisms for ventricular arrhythmia including activation of inflammatory cascade from direct amyloid deposition, and electro-mechanical as well as autonomic dysfunction due to systemic amyloid deposition. Cardiac amyloidosis is associated with an increased risk of sudden cardiac death, and the risk is higher in AL than ATTR. Finally, the role of implantable cardioverter-defibrillators in cardiac amyloidosis is controversial, and while successful termination of life-threatening ventricular arrhythmias has been reported in few studies, there has been no evidence of improvement in outcomes when used for primary prevention in patients with cardiac amyloidosis.
Collapse
Affiliation(s)
- Syed Bukhari
- Department of Medicine, Temple University Hospital-Jeanes Campus, Philadelphia, PA, USA.
| | - Bilal Khan
- Department of Medicine, Temple University Hospital-Jeanes Campus, Philadelphia, PA, USA
| |
Collapse
|
|
25
|
Abdelghany M, Abdelhamid M, Allam A, El Etriby A, Hafez S, Ragy H, Sobhy M. Detection and Diagnosis of Cardiac Amyloidosis in Egypt. Cardiol Ther 2023; 12:197-213. [PMID: 36611101 PMCID: PMC9986164 DOI: 10.1007/s40119-022-00299-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 12/16/2022] [Indexed: 01/09/2023] Open
Abstract
Cardiac amyloidosis is a life-threatening disease that occurs when amyloid proteins, most commonly immunoglobulin light chain or transthyretin, mutate or become unstable, misfold, deposit as amyloid fibrils, and accumulate in the myocardium. Early diagnosis of cardiac amyloidosis is hindered by insufficient awareness, specifically regarding clinical red flags and diagnostic pathways. Cardiac amyloidosis diagnosis comprises two important phases, clinical suspicion (phase one) followed by definitive diagnosis (phase two). Each phase is associated with specific clinical techniques. For example, clinical features, electrocardiography, echocardiography, and cardiac magnetic resonance imaging serve to raise suspicion of cardiac amyloidosis and facilitate early diagnosis, whereas laboratory tests (i.e., blood or urine electrophoresis with immunofixation), biopsy, scintigraphy-based nuclear imaging, and genetic testing provide a definitive diagnosis of cardiac amyloidosis. In Egypt, both the lack of cardiac amyloidosis awareness amongst healthcare providers and the unavailability of clinical expertise for the use of diagnostic techniques must be overcome to improve the prognosis of cardiac amyloidosis in the region. Previously published diagnostic algorithms for cardiac amyloidosis have amalgamated techniques that can raise clinical suspicions of cardiac amyloidosis with those that definitively diagnose cardiac amyloidosis. Though such algorithms have been successful in developed countries, diagnostic tools like echocardiography, scintigraphy, and cardiac magnetic resonance imaging are not ubiquitously available across Egyptian facilities. This review presents the current state of knowledge regarding cardiac amyloidosis in Egypt and outlines a new diagnostic algorithm which leverages regional nuclear imaging expertise. Importantly, the proposed diagnostic algorithm guides accurate amyloid-typing to mitigate misdiagnosis and erroneous treatment selection and improve the cardiac amyloidosis diagnostic accuracy in Egypt.
Collapse
Affiliation(s)
- Mohamed Abdelghany
- Department of Cardiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Magdy Abdelhamid
- Department of Cardiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Adel Allam
- Department of Cardiology, Faculty of Medicine, Azhar University, Cairo, Egypt
| | - Adel El Etriby
- Department of Cardiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | - Hany Ragy
- National Heart Institute, Giza, Egypt.
| | - Mohamed Sobhy
- Department of Cardiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| |
Collapse
|
|
26
|
Dzhioeva ON. [Functional methods of amyloid cardiomyopathy diagnostic in practice and in expert centers: A review]. TERAPEVT ARKH 2023; 95:96-102. [PMID: 37167121 DOI: 10.26442/00403660.2023.01.202081] [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: 02/24/2023] [Accepted: 02/24/2023] [Indexed: 05/13/2023]
Abstract
The article is a set of recommendations for the interpretation of electrocardiography and echocardiography data in patients with suspected amyloidosis of the heart. Amyloid cardiomyopathy is a progressive disease characterized by a detailed picture of congestive heart failure, poor quality of life and poor prognosis. Currently, medications have appeared that can improve the prognosis in patients with amyloidosis of the heart. Therefore, raising awareness of specialists about specific instrumental signs of the disease is an important and urgent task.
Collapse
Affiliation(s)
- O N Dzhioeva
- National Research Center for Therapy and Preventive Medicine
- Yevdokimov Moscow State University of Medicine and Dentistry
| |
Collapse
|
|
27
|
Wang H, Liu S, Zhang X, Zheng J, Lu F, Lip GYH, Bai Y. Prevalence and Impact of Arrhythmia on Outcomes in Restrictive Cardiomyopathy-A Report from the Beijing Municipal Health Commission Information Center (BMHCIC) Database. J Clin Med 2023; 12:jcm12031236. [PMID: 36769884 PMCID: PMC9917641 DOI: 10.3390/jcm12031236] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/28/2023] [Accepted: 01/31/2023] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Data on the outcomes of restrictive cardiomyopathy (RCM) are limited, when the condition is complicated with arrhythmia. This study was designed to investigate the prevalence of atrial fibrillation (AF), ventricular tachycardia (VT) and bradycardia (BC) and their impact on adverse outcomes (intra-cardiac thrombus, stroke and systematic embolism [SSE], heart failure and death) of RCM. METHODS AND RESULTS The retrospective cohort study used data collected from the Beijing Municipal Health Commission Information Center (BMHCIC) database from 1 January 2010 to 31 December 2020. There were 745 (64.9%) patients with AF, 117 (10.2%) patients with VT and 311 (27.1%) patients with bradycardia. The presence of AF was associated with an increased risk of SSE (adjusted HR:1.37, 95%CI:1.02-1.83, p = 0.04) and heart failure (aHR:1.36, 95%CI:1.17-1.58, p < 0.001). VT was associated with an increased risk of intracardiac thrombus (aHR:2.34, 95%CI:1.36-4.01, p = 0.002) and death (aHR:2.07, 95%CI:1.19-3.59, p = 0.01). Bradycardia did not increase the adverse outcomes in RCM. The results remained consistent and steady when AF, VT and bradycardia were adjusted as competing factors. CONCLUSIONS Cardiac arrhythmia are highly prevalent and associated with adverse outcomes in patients with RCM. AF and VT are more likely to be associated with intracardiac thrombosis, and the presence of AF increased the risk of SSE and HF. The presence of VT increased the risk of death.
Collapse
Affiliation(s)
- Haiyan Wang
- Department of Neurology and Psychiatry, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Sitong Liu
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100051, China
| | - Xilin Zhang
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100051, China
| | - Jianpeng Zheng
- Beijing Municipal Health Commission Information Center, Beijing 100034, China
| | - Feng Lu
- Beijing Municipal Health Commission Information Center, Beijing 100034, China
| | - Gregory Y. H. Lip
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, Liverpool Heart & Chest Hospital, Liverpool L14 3PE, UK
- Department of Clinical Medicine, Aalborg University, DK-9100 Aalborg, Denmark
| | - Ying Bai
- Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100051, China
- Correspondence:
| |
Collapse
|
|
28
|
Arshad S, Goldberg YH, Bhopalwala H, Dewaswala N, Miceli NS, Birks EJ, Vaidya GN. High Prevalence of Cardiac Amyloidosis in Clinically Significant Aortic Stenosis: A Meta-Analysis. Cardiol Res 2022; 13:357-371. [PMID: 36660066 PMCID: PMC9822671 DOI: 10.14740/cr1436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 10/28/2022] [Indexed: 12/23/2022] Open
Abstract
Background There is growing evidence of coexistence of aortic stenosis (AS) and transthyretin cardiac amyloidosis (CA). Not screening AS patients at the time of hospital/clinic visit for CA represents a lost opportunity. Methods We surveyed studies that reported the prevalence of CA among AS patients. Studies that compared patients with aortic stenosis with cardiac amyloidosis (AS-CA) and AS alone were further analyzed, and meta-regression was performed. Results We identified nine studies with 1,321 patients of AS, of which 131 patients had concomitant CA, with a prevalence of 11%. When compared to AS-alone, the patients with AS-CA were older, more likely to be males, had higher prevalence of carpal tunnel syndrome, right bundle branch block. On echocardiogram, patients with AS-CA had thicker interventricular septum, higher left ventricular mass index (LVMI), lower myocardial contraction fraction, and lower stroke volume index. Classical low-flow low-gradient (LFLG) physiology was more common among patients with AS-CA. Patients with AS-CA had higher all-cause mortality than patients with AS alone (33% vs. 22%, P = 0.02) in a follow-up period of at least 1 year. Conclusions CA has a high prevalence in patients with AS and is associated with worse clinical, imaging, and biochemical parameters than patients with AS alone.
Collapse
Affiliation(s)
- Samiullah Arshad
- Department of Medicine, University of Kentucky, Lexington, KY, USA,Corresponding Author: Samiullah Arshad, Department of Medicine, University of Kentucky, Lexington, KY, USA.
| | | | - Huzefa Bhopalwala
- Department of Medicine, Appalachian Regional Healthcare, Whitesburg, KY, USA
| | - Nakeya Dewaswala
- Division of Cardiology (Advanced Heart Failure and Transplantation), Gill Heart and Vascular Institute, University of Kentucky, Lexington KY, USA
| | - Nicholas S. Miceli
- College of Management, School of Business, Park University, Parkville, MO, USA
| | - Emma J. Birks
- Division of Cardiology (Advanced Heart Failure and Transplantation), Gill Heart and Vascular Institute, University of Kentucky, Lexington KY, USA
| | - Gaurang N. Vaidya
- Division of Cardiology (Advanced Heart Failure and Transplantation), Gill Heart and Vascular Institute, University of Kentucky, Lexington KY, USA
| |
Collapse
|
|
29
|
Argirò A, Del Franco A, Mazzoni C, Allinovi M, Tomberli A, Tarquini R, Di Mario C, Perfetto F, Cappelli F, Zampieri M. Arrhythmic Burden in Cardiac Amyloidosis: What We Know and What We Do Not. Biomedicines 2022; 10:2888. [PMID: 36359408 PMCID: PMC9687719 DOI: 10.3390/biomedicines10112888] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 10/31/2022] [Accepted: 11/08/2022] [Indexed: 08/26/2023] Open
Abstract
Cardiac amyloidosis (CA), caused by the deposition of insoluble amyloid fibrils, impairs different cardiac structures, altering not only left ventricle (LV) systo-diastolic function but also atrial function and the conduction system. The consequences of the involvement of the cardiac electrical system deserve more attention, as well as the study of the underlying molecular mechanisms. This is an issue of considerable interest, given the conflicting data on the effectiveness of conventional antiarrhythmic strategies. Therefore, this review aims at summarizing the arrhythmic burden related to CA and the available evidence on antiarrhythmic treatment in this population.
Collapse
Affiliation(s)
- Alessia Argirò
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, 50134 Florence, Italy
| | - Annamaria Del Franco
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, 50134 Florence, Italy
| | - Carlotta Mazzoni
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, 50134 Florence, Italy
| | - Marco Allinovi
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, 50134 Florence, Italy
| | - Alessia Tomberli
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, 50134 Florence, Italy
| | - Roberto Tarquini
- Department of Internal Medicine I, San Giuseppe Hospital, 50053 Empoli, Italy
| | - Carlo Di Mario
- Structural Interventional Cardiology Department, Careggi University Hospital, 50134 Florence, Italy
| | - Federico Perfetto
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, 50134 Florence, Italy
| | - Francesco Cappelli
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, 50134 Florence, Italy
| | - Mattia Zampieri
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, 50134 Florence, Italy
| |
Collapse
|
|
30
|
Beyond Sarcomeric Hypertrophic Cardiomyopathy: How to Diagnose and Manage Phenocopies. Curr Cardiol Rep 2022; 24:1567-1585. [PMID: 36053410 DOI: 10.1007/s11886-022-01778-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/20/2022] [Indexed: 01/11/2023]
Abstract
PURPOSE OF REVIEW We describe the most common phenocopies of hypertrophic cardiomyopathy, their pathogenesis, and clinical presentation highlighting similarities and differences. We also suggest a step-by-step diagnostic work-up that can guide in differential diagnosis and management. RECENT FINDINGS In the last years, a wider application of genetic testing and the advances in cardiac imaging have significantly changed the diagnostic approach to HCM phenocopies. Different prognosis and management, with an increasing availability of disease-specific therapies, make differential diagnosis mandatory. The HCM phenotype can be the cardiac manifestation of different inherited and acquired disorders presenting different etiology, prognosis, and treatment. Differential diagnosis requires a cardiomyopathic mindset allowing to recognize red flags throughout the diagnostic work-up starting from clinical and family history and ending with advanced imaging and genetic testing. Different prognosis and management, with an increasing availability of disease-specific therapies make differential diagnosis mandatory.
Collapse
|
|
31
|
Isotani Y, Amiya E, Ishida J, Komuro I. Summation of Precordial R Wave Amplitudes, a Clinical Parameter for Detecting Early TTR Amyloidosis Cardiac Involvement. J Cardiovasc Dev Dis 2022; 9:jcdd9100348. [PMID: 36286300 PMCID: PMC9604937 DOI: 10.3390/jcdd9100348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/05/2022] [Accepted: 10/10/2022] [Indexed: 11/06/2022] Open
Abstract
There have been several reports on the identification of the stage of transthyretin amyloid cardiomyopathy (ATTR-CM); however, a staging system for ATTR-CM has not yet been established. An 83-year-old woman was referred to our department about ten years ago. Recently, she was diagnosed with ATTR-CM. The electrocardiogram showed characteristic changes that take place over the duration of ATTR-CM progression. Among these, the precordial R amplitudes abruptly decreased before the development of increased ventricular thickness. This case suggested that the decrease in the precordial R wave amplitudes may represent a new diagnostic clue reflecting early myocardial damage due to ATTR-CM.
Collapse
Affiliation(s)
- Yoshitaka Isotani
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Eisuke Amiya
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
- Department of Therapeutic Strategy for Heart Failure, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
- Correspondence: ; Tel.: +81-3-3815-5411 or +81-3-5800-9595
| | - Junichi Ishida
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Issei Komuro
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
| |
Collapse
|
|
32
|
Ramsell S, Arias Bermudez C, Takem Baiyee CAM, Rodgers B, Parikh S, Almaani S, Sharma N, LoRusso S, Freimer M, Redder E, Bumma N, Vallkati A, Efebera Y, Kahwash R, Campbell CM. Beta-Adrenergic Antagonist Tolerance in Amyloid Cardiomyopathy. Front Cardiovasc Med 2022; 9:907597. [PMID: 35898273 PMCID: PMC9309481 DOI: 10.3389/fcvm.2022.907597] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 06/17/2022] [Indexed: 11/24/2022] Open
Abstract
Background: Beta-adrenergic antagonists or blockers (BB) are a cornerstone of cardiac therapy for multiple indications. However, BB are considered relatively contraindicated in amyloid cardiomyopathy due to poor tolerance. This intolerance is hypothesized to be due to concomitant neuropathy and significant restrictive cardiomyopathy. This study analyzes the incidence and characteristics of BB tolerance in patients with amyloid cardiomyopathy. Methods Through a single-center retrospective chart review, patients with amyloid cardiomyopathy, confirmed by endomyocardial biopsy or technetium-99 pyrophosphate scan, were identified and clinical data was collected. Statistical methods included Chi-square test and two sample t-tests. Results Of 135 cardiac amyloidosis patients, 27 patients (20.0%) had no BB use, 56 patients (41.5%) were current BB users, and 52 patients (38.5%) were prior BB users. The most frequent indications for BB use were heart failure, hypertension, coronary artery disease, and arrhythmia. The most common reason for stopping BB therapy was hypotension (62.8%) followed by fatigue, bradycardia, and orthostasis. Neurologic symptoms at the initial BB prescription or most recent evaluation were not significantly different between current and prior BB users. Their cardiovascular profiles were similar by ejection fraction, wall thickness, troponin I, and brain natriuretic peptide. There was no association for BB discontinuation based on amyloid subtype, sex, or race. Conclusion The majority of patients with amyloid cardiomyopathy were prescribed BB, and over half of these patients still tolerated BB therapy. Current and prior BB users had similar profiles from a cardiovascular and neurologic perspective, with no association identified to predict BB discontinuation.
Collapse
Affiliation(s)
- Stuart Ramsell
- College of Medicine, The Ohio State University, Columbus, OH, United States
| | | | | | - Brandon Rodgers
- College of Medicine, The Ohio State University, Columbus, OH, United States
| | - Samir Parikh
- Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Salem Almaani
- Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Nidhi Sharma
- Division of Hematology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Samantha LoRusso
- Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Miriam Freimer
- Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Elyse Redder
- Department of Oncology Rehabilitation, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Naresh Bumma
- Division of Hematology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Ajay Vallkati
- Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Yvonne Efebera
- Division of Hematology/Oncology, OhioHealth, Columbus, OH, United States
| | - Rami Kahwash
- Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Courtney M. Campbell
- Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, OH, United States
- Cardio-Oncology Center of Excellence, Washington University in St. Louis, St. Louis, MO, United States
- *Correspondence: Courtney M. Campbell
| |
Collapse
|
|
33
|
Bay K, Gustafsson F, Maiborg M, Bagger‐Bahnsen A, Strand AM, Pilgaard T, Poulsen SH. Suspicion, screening, and diagnosis of wild-type transthyretin amyloid cardiomyopathy: a systematic literature review. ESC Heart Fail 2022; 9:1524-1541. [PMID: 35343098 PMCID: PMC9065854 DOI: 10.1002/ehf2.13884] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 02/11/2022] [Accepted: 02/25/2022] [Indexed: 01/15/2023] Open
Abstract
Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non-invasive diagnosis by bone scintigraphy, and the development of disease-modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at-risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light-chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at-risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high-quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at-risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.
Collapse
Affiliation(s)
- Katrine Bay
- Bay WritingCopenhagenDenmark
- Pfizer DenmarkBallerupDenmark
| | - Finn Gustafsson
- The Heart CenterCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
| | - Michael Maiborg
- Odense Amyloidosis Center & Department of CardiologyOdense University HospitalOdenseDenmark
| | | | | | | | | |
Collapse
|
|
34
|
Ng PLF, Lim YC, Evangelista LKM, Wong RCC, Chai P, Sia CH, Loi HY, Yeo TC, Lin W. Utility and pitfalls of the electrocardiogram in the evaluation of cardiac amyloidosis. Ann Noninvasive Electrocardiol 2022; 27:e12967. [PMID: 35567784 PMCID: PMC9296797 DOI: 10.1111/anec.12967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/25/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Cardiac amyloidosis is a protein misfolding disorder involving deposition of amyloid fibril proteins in the heart. The associated fibrosis of the conduction tissue results in conduction abnormalities and arrhythmias. "Classical" electrocardiogram (ECG) findings in cardiac amyloidosis include that of low voltage complexes with increased left ventricular wall thickness on echocardiography. However, this "classical" finding is neither sensitive nor specific. As cardiac amyloidosis is associated with a generally poor prognosis, the need for early recognition of this disease is important given the availability of new treatment options. In this review, we highlight 3 cases of patients with cardiac amyloidosis. Although presenting with typical clinical signs and symptoms, ECG for all 3 patients was not consistent with the classical findings described. They underwent further diagnostic tests which clinched the diagnosis of cardiac amyloidosis, allowing patients to receive targeted treatment. Through the review of the literature, we will highlight the different ECG patterns in patients with different types of cardiac amyloidosis and clinical scenarios, as well as the pitfalls of using ECG to identify the condition. Lastly, we also emphasize the current paradigms in diagnosing cardiac amyloidosis through the non-invasive methods of echocardiography, cardiac magnetic resonance imaging, and nuclear technetium-pyrophosphate imaging. CONCLUSIONS Electrocardiogram is often the first investigation used in evaluating many cardiac disorders, including cardiac amyloidosis. However, classical features of cardiac amyloidosis on ECG are often not present. A keen understanding on the ECG features of cardiac amyloidosis and knowledge of the diagnostic workflow is important to diagnose this condition.
Collapse
Affiliation(s)
- Perryn Lin Fei Ng
- Department of Cardiology, National University Heart Centre, Singapore, Singapore
| | - Yoke Ching Lim
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | | | - Raymond Ching Chiew Wong
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ping Chai
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ching Hui Sia
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Hoi Yin Loi
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Diagnostic Imaging, National University Hospital, Singapore, Singapore
| | - Tiong Cheng Yeo
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Weiqin Lin
- Department of Cardiology, National University Heart Centre, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| |
Collapse
|
|
35
|
A case of medical liability involving an unexpected systemic amyloidosis. Leg Med (Tokyo) 2022; 56:102049. [DOI: 10.1016/j.legalmed.2022.102049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 02/09/2022] [Accepted: 02/21/2022] [Indexed: 12/22/2022]
|
|
36
|
Electrocardiographic features and need for pacemaker in cardiac amyloidosis: Analysis of 58 cases. Med Clin (Barc) 2022; 159:78-84. [PMID: 35074177 DOI: 10.1016/j.medcli.2021.09.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 08/27/2021] [Accepted: 09/02/2021] [Indexed: 11/22/2022]
Abstract
AIM Amyloidosis is a disease in which amyloid fibrils can be deposited in different cardiac structures, and several electrocardiographic abnormalities can be produced by this phenomenon. The objective of this study was to describe the most common basal electrocardiographic alterations in patients diagnosed with cardiac amyloidosis (CA) and to determine if these abnormalities have an impact on the need of pacemaker. METHODS This retrospective study included patients who had an established diagnosis of CA [light-chain cardiac amyloidosis (LA-CA) or transthyretin cardiac amyloidosis (TTR-CA)] between January 2013 and March 2021. The baseline heart rate, the percentage of patients with a pseudo-infarct pattern, low-voltage pattern or cardiac conductions disturbances, and the impact of these factors on the need of pacemaker were analysed. RESULTS Fifty-eight patients with CA (20 with LA-CA and 38 with TTR-CA) were included, and the majority were male (69.0%). Twenty-one patients had atrial fibrillation (AF) at diagnosis. Thirty-five patients had a pseudo-infarct pattern, 35% had a low-voltage pattern, and 22% had criteria for ventricular hypertrophy. Two hirds had a conduction disorder: 18 patients with first degree atrioventricular block, 12 right bundle branch block, 3 left bundle branch block and 25 with a branch hemiblock. There were no differences between LA-CA and TTR-CA. Patients with TTR-CA had a greater need for pacemakers in the folow-up (39±40 meses). Bundle branch block was a predictor of the need for a permanent pacemaker (HR: 23.43; CI 95%: 4.09.134.09; P=.01). CONCLUSIONS Electrocardiographic abnormalities in patients diagnosed wich CA are heterogeneus. Most frecuent is the presence of conduction disorders, the pseudoinfarction pattern, followed by the low voltage pattern. Patients with any bundle branch block at the baseline electrocardiogram need more frecuent to require a pacemaker during follow-up, especially in TTR-CA.
Collapse
|
|
37
|
Cardiac Amyloidosis with Discordant QRS Voltage between Frontal and Precordial Leads. ACTA ACUST UNITED AC 2021; 57:medicina57070660. [PMID: 34199044 PMCID: PMC8306315 DOI: 10.3390/medicina57070660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/24/2021] [Accepted: 06/26/2021] [Indexed: 11/16/2022]
Abstract
Among the different types, immunoglobulin light chain (AL) cardiac amyloidosis is associated with the highest morbidity and mortality. The outcome, however, is significantly better when an early diagnosis is made and treatment initiated promptly. We present a case of cardiac amyloidosis with left ventricular hypertrophy criteria on the electrocardiogram. After 9 months of follow-up, the patient developed low voltage in the limb leads, while still maintaining the Cornell criteria for left ventricular hypertrophy as well. The relative apical sparing by the disease process, as well as decreased cancellation of the opposing left ventricular walls could be responsible for this phenomenon. The discordance between the voltage in the frontal leads and precordial leads, when present in conjunction with other findings, may be helpful in raising the clinical suspicion of cardiac amyloidosis.
Collapse
|
|
38
|
Tini G, Cappelli F, Biagini E, Musumeci B, Merlo M, Crotti L, Cameli M, Di Bella G, Cipriani A, Marzo F, Guerra F, Forleo C, Gagliardi C, Zampieri M, Carigi S, Vianello PF, Mandoli GE, Ciliberti G, Lichelli L, Mariani D, Porcari A, Russo D, Licordari R, Ponziani A, Porto I, Perfetto F, Autore C, Rapezzi C, Sinagra G, Canepa M. Current patterns of beta-blocker prescription in cardiac amyloidosis: an Italian nationwide survey. ESC Heart Fail 2021; 8:3369-3374. [PMID: 33988312 PMCID: PMC8318433 DOI: 10.1002/ehf2.13411] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 04/11/2021] [Accepted: 04/28/2021] [Indexed: 12/18/2022] Open
Abstract
Aims The use of beta‐blocker therapy in cardiac amyloidosis (CA) is debated. We aimed at describing patterns of beta‐blocker prescription through a nationwide survey. Methods and results From 11 referral centres, we retrospectively collected data of CA patients with a first evaluation after 2016 (n = 642). Clinical characteristics at first and last evaluation were collected, with a focus on medical therapy. For patients in whom beta‐blocker therapy was started, stopped, or continued between first and last evaluation, the main reason for beta‐blocker management was requested. Median age of study population was 77 years; 81% were men. Arterial hypertension was found in 58% of patients, atrial fibrillation (AF) in 57%, and coronary artery disease in 16%. Left ventricular ejection fraction was preserved in 62% of cases, and 74% of patients had advanced diastolic dysfunction. Out of the 250 CA patients on beta‐blockers at last evaluation, 215 (33%) were already taking this therapy at first evaluation, while 35 (5%) were started it, in both cases primarily because of high‐rate AF. One‐hundred‐nineteen patients (19%) who were on beta‐blocker at first evaluation had this therapy withdrawn, mainly because of intolerance in the presence of heart failure with advanced diastolic dysfunction. The remaining 273 patients (43%) had never received beta‐blocker therapy. Beta‐blockers usage was similar between CA aetiologies. Patients taking vs. not taking beta‐blockers differed only for a greater prevalence of arterial hypertension, coronary artery disease, AF, and non‐restrictive filling pattern (P < 0.01 for all) in the former group. Conclusions Beta‐blockers prescription is not infrequent in CA. Such therapy may be tolerated in the presence of co‐morbidities for which beta‐blockers are routinely used and in the absence of advanced diastolic dysfunction.
Collapse
Affiliation(s)
- Giacomo Tini
- Department of Internal Medicine, University of Genova, Viale Benedetto XV, 10, Genova, 16132, Italy.,Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
| | - Francesco Cappelli
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy
| | - Elena Biagini
- Cardiology Unit, St. Orsola Hospital, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Beatrice Musumeci
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
| | - Marco Merlo
- Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy
| | - Lia Crotti
- Department of Cardiovascular, Neural and Metabolic Sciences, University of Milano-Bicocca, Istituto Auxologico Italiano, IRCCS, Milan, Italy
| | - Matteo Cameli
- Department of Medical Biotechnologies, Section of Cardiology, University of Siena, Siena, Italy
| | - Gianluca Di Bella
- Rare Cardiac Disease Center, Cardiology Unit, University of Messina, Messina, Italy
| | - Alberto Cipriani
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | | | - Federico Guerra
- Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital "Ospedali Riuniti Umberto I -Lancisi - Salesi", Ancona, Italy
| | - Cinzia Forleo
- Cardiology Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, University Hospital Policlinico Consorziale, Bari, Italy
| | - Christian Gagliardi
- Cardiology Unit, St. Orsola Hospital, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Mattia Zampieri
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy
| | | | - Pier Filippo Vianello
- Department of Internal Medicine, University of Genova, Viale Benedetto XV, 10, Genova, 16132, Italy
| | - Giulia Elena Mandoli
- Department of Medical Biotechnologies, Section of Cardiology, University of Siena, Siena, Italy
| | - Giuseppe Ciliberti
- Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital "Ospedali Riuniti Umberto I -Lancisi - Salesi", Ancona, Italy
| | - Luca Lichelli
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Davide Mariani
- Department of Cardiovascular, Neural and Metabolic Sciences, University of Milano-Bicocca, Istituto Auxologico Italiano, IRCCS, Milan, Italy
| | - Aldostefano Porcari
- Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy
| | - Domitilla Russo
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
| | - Roberto Licordari
- Rare Cardiac Disease Center, Cardiology Unit, University of Messina, Messina, Italy
| | - Alberto Ponziani
- Cardiology Unit, St. Orsola Hospital, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Italo Porto
- Department of Internal Medicine, University of Genova, Viale Benedetto XV, 10, Genova, 16132, Italy.,Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino - IRCCS Italian Cardiovascular Network, Genova, Italy
| | - Federico Perfetto
- Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy
| | - Camillo Autore
- Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy
| | - Claudio Rapezzi
- University Cardiological Center, University of Ferrara, Ferrara, Italy.,Maria Cecilia Hospital, GVM Care & Research, Ravenna, Italy
| | - Giafranco Sinagra
- Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy
| | - Marco Canepa
- Department of Internal Medicine, University of Genova, Viale Benedetto XV, 10, Genova, 16132, Italy.,Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino - IRCCS Italian Cardiovascular Network, Genova, Italy
| |
Collapse
|
|
39
|
Khanna S, Lo P, Cho K, Subbiah R. Ventricular Arrhythmias in Cardiac Amyloidosis: A Review of Current Literature. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2020; 14:1179546820963055. [PMID: 33088185 PMCID: PMC7545745 DOI: 10.1177/1179546820963055] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 09/06/2020] [Indexed: 01/29/2023]
Abstract
Cardiac Amyloidosis is an infiltrative cardiomyopathy which occurs secondary to deposition of mis-folded protein in the myocardium, with the two most common subtypes being AL amyloidosis and TTR amyloidosis. The pathogenesis of the disease is multifaceted and involves a variety of mechanisms including an inflammatory response cascade, oxidative stress and subsequent separation of myocyte fibrils. Cardiac Amyloidosis frequently results in congestive cardiac failure and arrhythmias, from a disruption in cardiac substrate with subsequent electro-mechanical remodelling. Disease progression is usually demonstrated by development of progressive pump failure, which may be seen with a high arrhythmic burden, usually portending a poor prognosis. There is a paucity of literature on the clinical implications of ventricular arrhythmias in the context of cardiac amyloidosis. The important diagnostic investigations for these patients include transthoracic echocardiography, cardiac magnetic resonance imaging and an electrophysiology study. Whilst there are no robust management guidelines, studies have indicated benefits from contemporary pharmacological therapy and case-by-case catheter ablation. There are novel directed therapies available for TTR amyloidosis that have shown to improve overall survival. The role of ICD therapy in cardiac amyloidosis is controversial, with benefits seen predominantly in early phases of the disease process. The only definitive surgical therapy includes heart transplantation, but is largely indicated for progressive decompensated heart failure (Figure 1). Further large-scale studies are required to better outline management paradigms for treating ventricular arrhythmias in cardiac amyloidosis.
Collapse
Affiliation(s)
- Shaun Khanna
- Department of Cardiology, St Vincent's Hospital, Darlinghurst, NSW, Australia
| | - Phillip Lo
- Department of Cardiology, St Vincent's Hospital, Darlinghurst, NSW, Australia
| | - Kenneth Cho
- Department of Cardiology, St Vincent's Hospital, Darlinghurst, NSW, Australia
| | - Rajesh Subbiah
- Department of Cardiology, St Vincent's Hospital, Darlinghurst, NSW, Australia.,University of New South Wales, Kensington, Sydney, NSW, Australia.,Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
| |
Collapse
|
|
40
|
Cardiac Amyloidosis in Patients Undergoing TAVR: Why We Need to Think About It. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2020; 22:109-114. [PMID: 32571759 DOI: 10.1016/j.carrev.2020.06.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/20/2020] [Accepted: 06/03/2020] [Indexed: 01/15/2023]
Abstract
Systemic amyloidosis encompasses a variety of diseases characterized by extracellular deposition of protein-derived fibrils in different tissues and organs. Immunoglobulin light-chain (AL) and transthyretin (ATTR) amyloid are the two types that more commonly affect the heart and in both subtypes cardiac involvement is the main determinant of prognosis. Recently, several studies have suggested that Cardiac Amyloidosis (CA) and Aortic Stenosis (AS) can coexist more frequently than previously suspected with prevalence ranging from 5,6% to 16% in different cohorts. The unexpected high prevalence of CA in AS and the availability of potentially effective treatment in CA should push us to carefully investigate elderly patients with aortic valve stenosis in order to identify those with coexistent amyloidosis. While the motivation to exclude amyloidosis was in the past their exclusion from active treatment of the valve disease, judged as futile because of their poor unavoidable prognosis, the improved therapeutic options available challenges this conservative approach. Aim of this review is to identify the triggers to investigate AS patients at risk of having concomitant ATTR-CA, to propose a diagnostic path to reach diagnosis and to discuss the changes in the therapeutic strategy caused by this discovery in the era of TAVR and active pharmacological treatments to slow down disease progression.
Collapse
|