2023 ESC Guidelines for Cardiomyopathies PDF

European Heart Journal (2023) 44, 3503–3626 ESC GUIDELINES https://doi.org/10.1093/eurheartj/ehad194 2023 ESC Guidelines for the management of cardiomy...

European Heart Journal (2023) 44, 3503–3626 ESC GUIDELINES https://doi.org/10.1093/eurheartj/ehad194 2023 ESC Guidelines for the management of cardiomyopathies Developed by the task force on the management of cardiomyopathies of the European Society of Cardiology (ESC) Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 Authors/Task Force Members: Elena Arbelo *†, (Chairperson) (Spain), Alexandros Protonotarios ‡, (Task Force Co-ordinator) (United Kingdom), Juan R. Gimeno ‡, (Task Force Co-ordinator) (Spain), Eloisa Arbustini (Italy), Roberto Barriales-Villa (Spain), Cristina Basso (Italy), Connie R. Bezzina 1 (Netherlands), Elena Biagini (Italy), Nico A. Blom (Netherlands), Rudolf A. de Boer (Netherlands), Tim De Winter (Belgium), Perry M. Elliott (United Kingdom), Marcus Flather (United Kingdom), Pablo Garcia-Pavia (Spain), Kristina H. Haugaa (Sweden), Jodie Ingles (Australia), Ruxandra Oana Jurcut (Romania), Sabine Klaassen (Germany), 2 Giuseppe Limongelli (Italy), Bart Loeys (Belgium), Jens Mogensen (Denmark), Iacopo Olivotto (Italy), Antonis Pantazis (United Kingdom), Sanjay Sharma (United Kingdom), J. Peter Van Tintelen (Netherlands), † James S. Ware (United Kingdom), Juan Pablo Kaski * , (Chairperson) (United Kingdom), and ESC Scientific Document Group * Corresponding authors: Elena Arbelo, Arrhythmia Section, Cardiology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain, IDIBAPS, Institut d’Investigació August Pi i Sunyer (IDIBAPS), Barcelona, Spain, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain, and European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart, ERN GUARD-Heart, Barcelona, Spain. Tel: +34 93 22 75 55 11, E-mail: [email protected]; and Juan Pablo Kaski, Centre for Paediatric Inherited and Rare Cardiovascular Disease, University College London, Institute of Cardiovascular Science, London, United Kingdom and Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom. Tel: +44 78 29 88 39, E-mail: [email protected] † The two Chairpersons contributed equally to the document and are joint corresponding authors. ‡ The two Task Force Co-ordinators contributed equally to the document. Author/Task Force Member affiliations are listed in author information. 1 Representing the Association for European Paediatric and Congenital Cardiology (AEPC) 2 Representing the European Society of Human Genetics (ESHG) ESC Clinical Practice Guidelines (CPG) Committee: listed in the Appendix. ESC subspecialty communities having participated in the development of this document: Associations: Association of Cardiovascular Nursing & Allied Professions (ACNAP), European Association of Cardiovascular Imaging (EACVI), European Association of Preventive Cardiology (EAPC), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA). Councils: Council on Cardiovascular Genomics. Working Groups: Development Anatomy and Pathology, Myocardial and Pericardial Diseases. Patient Forum The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal, and the party authorized to handle such permissions on behalf of the ESC ([email protected]). Disclaimer. The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription. © The European Society of Cardiology 2023. All rights reserved. For permissions please email: [email protected]. 3504 ESC Guidelines Document Reviewers: Philippe Charron, (CPG Review Co-ordinator) (France), Massimo Imazio, (CPG Review Co-ordinator) (Italy), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Michael Arad (Israel), Folkert W. Asselbergs (Netherlands), Riccardo Asteggiano (Italy), Zofia Bilinska (Poland), Damien Bonnet (France), Henning Bundgaard (Denmark), Nuno Miguel Cardim (Portugal), Jelena Čelutkienė (Lithuania), Maja Cikes (Croatia), Gaetano Maria De Ferrari (Italy), Veronica Dusi (Italy), Volkmar Falk (Germany), Laurent Fauchier (France), Estelle Gandjbakhch (France), Tiina Heliö (Finland), Konstantinos Koskinas (Switzerland), Dipak Kotecha (United Kingdom), Ulf Landmesser (Germany), George Lazaros (Greece), Basil S. Lewis (Israel), Ales Linhart (Czechia), Maja-Lisa Løchen (Norway), Benjamin Meder (Germany), Richard Mindham (United Kingdom), James Moon (United Kingdom), Jens Cosedis Nielsen (Denmark), Steffen Petersen (United Kingdom), Eva Prescott (Denmark), Mary N. Sheppard (United Kingdom), Gianfranco Sinagra (Italy), Marta Sitges (Spain), Jacob Tfelt-Hansen (Denmark), Rhian Touyz (Canada), Rogier Veltrop (Netherlands), Josef Veselka (Czechia), Karim Wahbi (France), Arthur Wilde (Netherlands), and Katja Zeppenfeld (Netherlands) Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the guidelines. The report is also available on the ESC website www.escardio.org/Guidelines See the European Heart Journal online for supplementary documents that include background information and evidence tables. Keywords Guidelines Arrhythmia Arrhythmogenic right ventricular cardiomyopathy Cardiomyopathies Diagnosis Dilated cardiomyopathy Genetics Genetic counselling Genetic testing Hypertrophic cardiomyopathy Implantable cardioverter defibrillator Management Multimodality imaging Non-dilated left ventricular cardiomyopathy Pregnancy Restrictive cardiomyopathy Risk stratification Screening Sports Sudden cardiac death 6. The patient pathway....................................................................................... 3519 Table of contents 6.1. Clinical presentation............................................................................. 3520 1. Preamble.............................................................................................................. 3509 6.2. Initial work-up.......................................................................................... 3520 2. Introduction....................................................................................................... 3511 6.3. Systematic approach to diagnosis of cardiomyopathy........... 3520 3. Phenotypic approach to cardiomyopathies.......................................... 3511 6.4. History and physical examination................................................... 3520 3.1. Definitions................................................................................................. 3514 6.5. Resting and ambulatory electrocardiography............................ 3521 3.2. Cardiomyopathy phenotypes............................................................ 3514 6.6. Laboratory tests...................................................................................... 3524 3.2.1. Hypertrophic cardiomyopathy................................................. 3514 6.7. Multimodality imaging........................................................................... 3524 3.2.2. Dilated cardiomyopathy.............................................................. 3514 6.7.1. General considerations................................................................ 3524 3.2.3. Non-dilated left ventricular cardiomyopathy..................... 3514 6.7.2. Echocardiography........................................................................... 3524 3.2.4. Arrhythmogenic right ventricular cardiomyopathy......... 3516 6.7.3. Cardiac magnetic resonance...................................................... 3525 3.2.5. Restrictive cardiomyopathy........................................................ 3517 6.7.3.1. Special considerations.......................................................... 3525 3.3. Other traits and syndromes associated with cardiomyopathy 6.7.4. Computed tomography and nuclear medicine phenotypes........................................................................................................ 3517 techniques...................................................................................................... 3528 3.3.1. Left ventricular hypertrabeculation (left ventricular non- 6.7.5. Endomyocardial biopsy................................................................ 3528 compaction).................................................................................................. 3517 6.8. Genetic testing and counselling........................................................ 3529 3.3.2. Takotsubo syndrome.................................................................... 3517 6.8.1. Genetic architecture..................................................................... 3529 4. Epidemiology...................................................................................................... 3517 6.8.2. Genetic testing................................................................................. 3529 4.1. Special populations................................................................................ 3518 6.8.2.1. Non-Mendelian cardiomyopathies and implications 5. Integrated patient management................................................................. 3518 for genetic testing.................................................................................. 3534 5.1. Multidisciplinary cardiomyopathy teams...................................... 3518 6.8.2.2. Genetic test reports and variant interpretation....... 3534 5.2. Co-ordination between different levels of care........................ 3518 6.8.3. Genetic counselling........................................................................ 3534 ESC Guidelines 3505 6.8.3.1. Genetic counselling in children........................................ 3534 7.1.5.6. Prevention of sudden cardiac death.............................. 3560 6.8.3.2. Pre- and post-test genetic counselling (proband).... 3535 7.2. Dilated cardiomyopathy...................................................................... 3562 6.8.3.3. Genetic counselling for cascade testing........................ 3535 7.2.1. Diagnosis............................................................................................ 3562 6.8.3.4. Pre-natal or pre-implantation genetic diagnosis....... 3536 7.2.1.1. Index case.................................................................................. 3562 6.9. Diagnostic approach to paediatric patients................................ 3537 7.2.1.2. Relatives..................................................................................... 3562 6.9.1. Infantile and early childhood-onset cardiomyopathy...... 3538 7.2.1.3. Diagnostic work-up............................................................... 3562 6.10. General principles in the management of patients with 7.2.1.4. Echocardiography................................................................... 3562 cardiomyopathy............................................................................................... 3539 7.2.1.5. Cardiac magnetic resonance............................................. 3563 6.10.1. Assessment of symptoms......................................................... 3539 7.2.1.6. Nuclear medicine................................................................... 3563 6.10.2. Heart failure management........................................................ 3539 7.2.2. Genetic testing and family screening...................................... 3563 6.10.2.1. Preventive heart failure medical therapy of 7.2.2.1. Genetic testing........................................................................ 3563 asymptomatic carriers/early disease expression....................... 3540 7.2.3. Assessment of symptoms........................................................... 3564 6.10.2.2. Cardiac transplantation..................................................... 3540 7.2.4. Management...................................................................................... 3564 Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 6.10.2.3. Left ventricular assist devices......................................... 3540 7.2.5. Sudden cardiac death prevention in dilated 6.10.3. Management of atrial arrhythmias........................................ 3541 cardiomyopathy........................................................................................... 3564 6.10.3.1. Anticoagulation..................................................................... 3541 7.2.5.1. Secondary prevention of sudden cardiac death....... 3564 6.10.3.2. Rate control........................................................................... 3541 7.2.5.2. Primary prevention of sudden cardiac death............. 3564 6.10.3.3. Rhythm control.................................................................... 3543 7.3. Non-dilated left ventricular cardiomyopathy............................. 3566 6.10.3.4. Comorbidities and risk factor management............ 3543 7.3.1. Diagnosis............................................................................................ 3566 6.10.4. Management of ventricular arrhythmias............................ 3544 7.3.1.1. Index case.................................................................................. 3566 6.10.5. Device therapy: implantable cardioverter defibrillator 3544 7.3.1.2. Relatives..................................................................................... 3566 6.10.6. Routine follow-up of patients with cardiomyopathy... 3546 7.3.1.3. Diagnostic work-up............................................................... 3566 6.11. Family screening and follow-up evaluation of relatives....... 3546 7.3.1.4. Electrocardiographic features........................................... 3567 6.11.1. Special considerations in family screening......................... 3547 7.3.1.5. Echocardiography................................................................... 3567 6.12. Psychological support in cardiomyopathy patients and family 7.3.1.6. Cardiac magnetic resonance............................................. 3567 members............................................................................................................. 3548 7.3.1.7. Nuclear medicine................................................................... 3567 6.13. The patient pathway.......................................................................... 3549 7.3.1.8. Endomyocardial biopsy........................................................ 3567 7. Specific cardiomyopathy phenotypes...................................................... 3549 7.3.2. Genetic testing................................................................................. 3567 7.1. Hypertrophic cardiomyopathy......................................................... 3549 7.3.3. Assessment of symptoms........................................................... 3567 7.1.1. Diagnosis............................................................................................ 3549 7.3.4. Management...................................................................................... 3567 7.1.1.1. Diagnostic criteria.................................................................. 3549 7.3.5. Sudden cardiac death prevention in non-dilated left 7.1.1.2. Diagnostic work-up............................................................... 3549 ventricular cardiomyopathy.................................................................... 3568 7.1.1.3. Echocardiography................................................................... 3549 7.3.5.1. Secondary prevention of sudden cardiac death....... 3568 7.1.1.4. Cardiac magnetic resonance............................................. 3550 7.3.5.2. Primary prevention of sudden cardiac death............. 3568 7.1.1.5. Nuclear imaging...................................................................... 3551 7.4. Arrhythmogenic right ventricular cardiomyopathy................. 3569 7.1.2. Genetic testing and family screening...................................... 3551 7.4.1. Diagnosis............................................................................................ 3569 7.1.3. Assessment of symptoms........................................................... 3552 7.4.1.1. Index case.................................................................................. 3569 7.1.4. Management of symptoms and complications................... 3552 7.4.1.2. Relatives..................................................................................... 3569 7.1.4.1. Management of left ventricular outflow tract 7.4.1.3. Diagnostic work-up............................................................... 3569 obstruction............................................................................................... 3553 7.4.1.4. Electrocardiography and Holter monitoring.............. 3569 7.1.4.1.1. General measures.......................................................... 3553 7.4.1.5. Echocardiography and cardiac magnetic resonance 3569 7.1.4.1.2. Drug therapy................................................................... 3553 7.4.1.6. Endomyocardial biopsy........................................................ 3569 7.1.4.1.3. Invasive treatment of left ventricular outflow 7.4.1.7. Nuclear medicine................................................................... 3569 tract (septal reduction therapy)................................................. 3555 7.4.1.8. Arrhythmogenic right ventricular cardiomyopathy 7.1.4.2. Management of symptoms in patients without left phenocopies............................................................................................. 3570 ventricular outflow tract obstruction........................................... 3557 7.4.2. Genetic testing and family screening...................................... 3570 7.1.4.2.1. Heart failure and chest pain...................................... 3557 7.4.3. Assessment of symptoms........................................................... 3570 7.1.4.2.2. Cardiac resynchronization therapy........................ 3557 7.4.4. Management...................................................................................... 3570 7.1.5. Sudden cardiac death prevention in hypertrophic 7.4.4.1. Antiarrhythmic therapy....................................................... 3570 cardiomyopathy........................................................................................... 3558 7.4.5. Sudden cardiac death prevention in arrhythmogenic right 7.1.5.1. Left ventricular apical aneurysms.................................... 3559 ventricular cardiomyopathy.................................................................... 3570 7.1.5.2. Left ventricular systolic dysfunction............................... 3559 7.4.5.1. Secondary prevention of sudden cardiac death....... 3571 7.1.5.3. Late gadolinium enhancement on cardiac magnetic 7.4.5.2. Primary prevention of sudden cardiac death............. 3571 resonance imaging................................................................................. 3559 7.5. Restrictive cardiomyopathy............................................................... 3572 7.1.5.4. Abnormal exercise blood pressure response............ 3559 7.5.1. Diagnosis............................................................................................ 3572 7.1.5.5. Sarcomeric variants............................................................... 3560 7.5.2. Genetic testing................................................................................. 3572 3506 ESC Guidelines 7.5.3. Assessment of symptoms........................................................... 3573 12.1. Cardiovascular risk factors.............................................................. 3587 7.5.4. Management...................................................................................... 3573 12.2. Dilated cardiomyopathy................................................................... 3588 7.6. Syndromic and metabolic cardiomyopathies............................. 3574 12.3. Hypertrophic cardiomyopathy...................................................... 3588 7.6.1. Anderson–Fabry disease.............................................................. 3574 12.4. Arrhythmogenic right ventricular cardiomyopathy.............. 3588 7.6.1.1. Definition................................................................................... 3574 13. Coronavirus disease (COVID-19) and cardiomyopathies........... 3588 7.6.1.2. Diagnosis, clinical work-up, and differential diagnosis 3574 14. Key messages.................................................................................................. 3588 7.6.1.3. Clinical course, outcome, and risk stratification....... 3574 15. Gaps in evidence............................................................................................ 3589 7.6.1.4. Management............................................................................. 3577 16. ‘What to do’ and ‘What not to do’ messages from the 7.6.2. RASopathies...................................................................................... 3577 Guidelines................................................................................................................. 3591 7.6.2.1. Definition................................................................................... 3577 17. Supplementary data...................................................................................... 3595 7.6.2.2. Diagnosis, clinical work-up, and differential diagnosis 3577 18. Data availability statement......................................................................... 3595 7.6.2.3. Clinical course, management, and sudden death risk 19. Author information...................................................................................... 3595 stratification.............................................................................................. 3577 20. Appendix........................................................................................................... 3596 Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 7.6.2.4. Management............................................................................. 3577 21. Acknowledgements...................................................................................... 3597 7.6.3. Friedreich ataxia.............................................................................. 3578 22. References........................................................................................................ 3597 7.6.3.1. Definition................................................................................... 3578 7.6.3.2. Diagnosis, clinical work-up, and differential diagnosis 3578 7.6.3.3. Clinical course, management, and risk stratification 3579 Tables of Recommendations 7.6.3.4. Management............................................................................. 3579 7.6.4. Glycogen storage disorders....................................................... 3579 Recommendation Table 1 — Recommendations for the provision of service of multidisciplinary cardiomyopathy teams................................ 3519 7.6.4.1. Definition................................................................................... 3579 Recommendation Table 2 — Recommendations for diagnostic 7.6.4.2. Diagnosis, clinical work-up, and differential diagnosis 3579 work-up in cardiomyopathies.......................................................................... 3520 7.6.4.3. Clinical course, management, and risk stratification 3579 Recommendation Table 3 — Recommendations for laboratory 7.6.4.4. Management............................................................................. 3579 tests in the diagnosis of cardiomyopathies................................................ 3524 7.7. Amyloidosis............................................................................................... 3579 Recommendation Table 4 — Recommendation for 7.7.1. Definition........................................................................................... 3579 echocardiographic evaluation in patients with cardiomyopathy...... 3524 7.7.2. Diagnosis, clinical work-up, and differential diagnosis..... 3579 Recommendation Table 5 — Recommendations for cardiac 7.7.3. Clinical course and risk stratification..................................... 3580 magnetic resonance indication in patients with cardiomyopathy.... 3526 7.7.4. Management...................................................................................... 3580 Recommendation Table 6 — Recommendations for computed 7.7.4.1. Specific therapies.................................................................... 3581 tomography and nuclear imaging................................................................... 3528 8. Other recommendations.............................................................................. 3581 Recommendation Table 7 — Recommendation for endomyocardial 8.1. Sports.......................................................................................................... 3581 biopsy in patients with cardiomyopathy..................................................... 3528 8.1.1. Cardiovascular benefits of exercise........................................ 3581 Recommendation Table 8 — Recommendations for genetic 8.1.2. Exercise-related sudden cardiac death and historical counselling and testing in cardiomyopathies............................................. 3537 exercise recommendations for patients with cardiomyopathy 3582 Recommendation Table 9 — Recommendations for cardiac 8.1.3. Exercise recommendations in hypertrophic transplantation in patients with cardiomyopathy................................... 3540 cardiomyopathy........................................................................................... 3582 Recommendation Table 10 — Recommendation for left ventricular 8.1.4. Exercise recommendations in arrhythmogenic right assist device therapy in patients with cardiomyopathy........................ 3540 ventricular cardiomyopathy.................................................................... 3582 Recommendation Table 11 — Recommendations for management of 8.1.5. Exercise recommendations in dilated cardiomyopathy atrial fibrillation and atrial flutter in patients with cardiomyopathy.... 3543 and non-dilated left ventricular cardiomyopathy.......................... 3582 Recommendation Table 12 — Recommendations for implantable 8.2. Reproductive issues............................................................................... 3583 cardioverter defibrillator in patients with cardiomyopathy................ 3545 8.2.1. Contraception, in vitro fertilization, and hormonal Recommendation Table 13 — Recommendations for routine follow-up of patients with cardiomyopathy.............................................. 3546 treatment........................................................................................................ 3583 Recommendation Table 14 — Recommendations for family 8.2.2. Pregnancy management............................................................... 3583 screening and follow-up evaluation of relatives....................................... 3546 8.2.2.1. Pre-pregnancy.......................................................................... 3583 Recommendation Table 15 — Recommendations for psychological 8.2.2.2. Pregnancy.................................................................................. 3583 support in patients and family members with cardiomyopathies.... 3549 8.2.2.3. Timing and mode of delivery............................................ 3584 Recommendation Table 16 — Recommendation for evaluation of 8.2.2.4. Post-partum.............................................................................. 3584 left ventricular outflow tract obstruction.................................................. 3549 8.2.2.5. Pharmacological treatment: general aspects.............. 3584 Recommendation Table 17 — Additional recommendation for 8.2.2.6. Specific cardiomyopathies.................................................. 3584 cardiovascular magnetic resonance evaluation in hypertrophic 8.2.2.7. Peripartum cardiomyopathy............................................. 3585 cardiomyopathy..................................................................................................... 3550 8.3. Recommendations for non-cardiac surgery............................... 3585 Recommendation Table 18 — Recommendations for treatment of 9. Requirements for specialized cardiomyopathy units........................ 3586 left ventricular outflow tract obstruction (general measures).......... 3553 10. Living with cardiomyopathy: advice for patients............................. 3586 Recommendation Table 19 — Recommendations for medical 11. Sex differences in cardiomyopathies..................................................... 3587 treatment of left ventricular outflow tract obstruction....................... 3554 12. Comorbidities and cardiovascular risk factors in Recommendation Table 20 — Recommendations for septal cardiomyopathies.................................................................................................. 3587 reduction therapy................................................................................................. 3556 ESC Guidelines 3507 Recommendation Table 21 — Recommendations for indications for Table 10 Overview of genes associated with monogenic, cardiac pacing in patients with obstruction............................................... 3557 non-syndromic cardiomyopathies, and their relative contributions Recommendation Table 22 — Recommendations for chest pain on to different cardiomyopathic phenotypes.................................................. 3530 exertion in patients without left ventricular outflow tract Table 11 Utility of genetic testing in cardiomyopathies....................... 3533 obstruction.............................................................................................................. 3557 Table 12 Specific issues to consider when counselling children....... 3534 Recommendation Table 23 — Additional recommendations for Table 13 Key discussion points of pre- and post-test genetic prevention of sudden cardiac death in patients with hypertrophic counselling................................................................................................................ 3536 cardiomyopathy..................................................................................................... 3561 Table 14 Pre-natal and pre-implantation options and implications 3536 Recommendation Table 24 — Recommendations for an implantable Table 15 Atrial fibrillation burden and management in cardioverter defibrillator in patients with dilated cardiomyopathy 3566 cardiomyopathies.................................................................................................. 3542 Recommendation Table 25 — Recommendation for resting and Table 16 Psychological considerations......................................................... 3548 ambulatory electrocardiogram monitoring in patients with Table 17 Imaging evaluation in hypertrophic cardiomyopathy......... 3550 non-dilated left ventricular cardiomyopathy............................................. 3567 Table 18 Echocardiographic features that suggest specific aetiologies Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 Recommendation Table 26 — Recommendations for an implantable in hypertrophic cardiomyopathy.................................................................... 3551 cardioverter defibrillator in patients with non-dilated left ventricular Table 19 Major clinical features associated with an increased risk of cardiomyopathy..................................................................................................... 3568 sudden cardiac death........................................................................................... 3558 Recommendation Table 27 — Recommendation for resting and Table 20 Non-genetic causes of dilated cardiomyopathy....................... 3563 ambulatory electrocardiogram monitoring in patients with Table 21 High-risk genotypes and associated predictors of sudden arrhythmogenic right ventricular cardiomyopathy................................. 3569 cardiac death........................................................................................................... 3566 Recommendation Table 28 — Recommendations for the Table 22 Clinical features and management of syndromic and antiarrhythmic management of patients with arrhythmogenic right metabolic cardiomyopathies............................................................................ 3575 ventricular cardiomyopathy.............................................................................. 3570 Table 23 Anderson–Fabry disease red flags.............................................. 3577 Recommendation Table 29 — Recommendations for sudden Table 24 General guidance for daily activity for patients with cardiac death prevention in patients with arrhythmogenic right cardiomyopathies.................................................................................................. 3586 ventricular cardiomyopathy.............................................................................. 3571 Table 25 Modulators of the phenotypic expression of Recommendation Table 30 — Recommendations for the cardiomyopathies.................................................................................................. 3588 management of patients with restrictive cardiomyopathy................. 3574 Recommendation Table 31 — Exercise recommendations for patients with cardiomyopathy......................................................................... 3582 List of figures Recommendation Table 32 — Recommendations for reproductive Figure 1 Central illustration.............................................................................. 3512 issues in patients with cardiomyopathy...................................................... 3585 Figure 2 Clinical diagnostic workflow of cardiomyopathy.................. 3513 Recommendation Table 33 — Recommendations for non-cardiac Figure 3 Examples of non-dilated left ventricular cardiomyopathy surgery in patients with cardiomyopathy................................................... 3585 phenotypes and their aetiological correlates............................................ 3515 Recommendation Table 34 — Recommendation for management Figure 4 Worked example of the non-dilated left ventricular of cardiovascular risk factors in patients with cardiomyopathy....... 3588 cardiomyopathy phenotype............................................................................. 3516 Figure 5 Multidisciplinary care of cardiomyopathies.............................. 3519 Figure 6 Multimodality imaging process in cardiomyopathies........... 3526 List of tables Figure 7 Examples of cardiac magnetic resonance imaging tissue Table 1 Classes for recommendations........................................................ 3510 characterization features that should raise the suspicion of specific Table 2 Levels of evidence................................................................................ 3510 aetiologies, grouped according to cardiomyopathy phenotype....... 3527 Table 3 Morphological and functional traits used to describe Figure 8 The genetic architecture of the cardiomyopathies.............. 3533 cardiomyopathy phenotypes............................................................................ 3514 Figure 9 A patient-centred approach to cascade genetic testing of Table 4 Key epidemiological metrics in adults and children for the children...................................................................................................................... 3535 different cardiomyopathy phenotypes......................................................... 3517 Figure 10 Clinical approach to infantile and childhood Table 5 Examples of inheritance patterns that should raise the cardiomyopathy..................................................................................................... 3538 suspicion of specific genetic aetiologies, grouped according to Figure 11 Algorithm for the approach to family screening and cardiomyopathy phenotype............................................................................. 3521 follow-up of family members........................................................................... 3547 Table 6 Examples of signs and symptoms that should raise the Figure 12 Protocol for the assessment and treatment of left suspicion of specific aetiologies, grouped according to ventricular outflow tract obstruction.......................................................... 3551 cardiomyopathy phenotype............................................................................. 3522 Figure 13 Algorithm for the treatment of heart failure in Table 7 Examples of electrocardiographic features that should raise hypertrophic cardiomyopathy......................................................................... 3552 the suspicion of specific aetiologies, grouped according to Figure 14 Flow chart on the management of left ventricular outflow cardiomyopathy phenotype............................................................................. 3523 tract obstruction................................................................................................... 3554 Table 8 First-level (to be performed in each patient) and Figure 15 Pre-assessment checklist for patients being considered for second-level (to be performed in selected patients following invasive septal reduction therapies................................................................ 3555 specialist evaluation to identify specific aetiologies) laboratory tests, Figure 16 Flow chart for implantation of an implantable cardioverter grouped by cardiomyopathy phenotype.................................................... 3525 defibrillator in patients with hypertrophic cardiomyopathy.............. 3561 Table 9 Frequently encountered actionable results on multimodality Figure 17 Implantation of implantable cardioverter defibrillators in imaging....................................................................................................................... 3528 patients with dilated cardiomyopathy or non-dilated left ventricular cardiomyopathy flowchart................................................................................ 3565 3508 ESC Guidelines Figure 18 Algorithm to approach implantable cardioverter CPR Cardio-pulmonary resuscitation defibrillator decision-making in patients with arrhythmogenic right CRT Cardiac resynchronization therapy ventricular cardiomyopathy.............................................................................. 3572 CrCl Creatinine clearance Figure 19 Spectrum of restrictive heart diseases.................................... 3573 CT Computed tomography Figure 20 Anderson–Fabry disease diagnostic algorithm..................... 3578 CTCA Computed tomography coronary angiography Figure 21 Screening for cardiac amyloidosis............................................. 3580 DBS Deep brain stimulation Figure 22 Diagnosis of cardiac amyloidosis............................................... 3581 DCM Dilated cardiomyopathy DES Desmin DMD Duchenne muscular dystrophy Abbreviations and acronyms DOAC Direct-acting oral anticoagulant 18F-FDG 18F-fluorodeoxyglucose DPD 3,3-diphosphono-1,2-propanodicarboxylic acid 2D Two-dimensional DSP Desmoplakin 3D Three-dimensional EAST-AFNET Early Treatment of Atrial Fibrillation for Stroke Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 99m 99m Tc Technetium Prevention Trial AAD Antiarrhythmic drug ECG Electrocardiogram ABC Atrial Fibrillation Better Care approach ECHO Echocardiogram ACE Angiotensin-converting enzyme ECV Extracellular volume ACE-I Angiotensin-converting enzyme inhibitor EF Ejection fraction ACM Arrhythmogenic cardiomyopathy EHRA European Heart Rhythm Association AD Autosomal dominant EMB Endomyocardial biopsy AED Automated external defibrillator EMF Endomyocardial fibrosis AF Atrial fibrillation EORP EURObservational Research Programme AFD Anderson–Fabry disease ERN European Reference Network AHA/ACC American Heart Association/American College of ERT Enzyme replacement therapy Cardiology FLNC Filamin C AL Monoclonal immunoglobulin light chain amyloidosis FRA Friedreich ataxia ALCAPA Anomalous left coronary artery from the pulmonary FTX Frataxin artery Gb3 Globotriaosylceramide ALT Alanine aminotransferase GDMT Guideline-directed medical therapy ALVC Arrhythmogenic left ventricular cardiomyopathy GSD Glycogen storage disorder APHRS Asia Pacific Heart Rhythm Society GWAS Genome-wide association study AR Autosomal recessive HbA1c Haemoglobin A1C ARB Angiotensin receptor blocker HBP His-Bundle pacing ARNI Angiotensin receptor neprilysin inhibitor HCM Hypertrophic cardiomyopathy ARVC Arrhythmogenic right ventricular cardiomyopathy HCMR Hypertrophic Cardiomyopathy Registry ASA Alcohol septal ablation HF Heart failure AST Aspartate transaminase HFmrEF Heart failure with mildly reduced ejection fraction ATPase Adenosine triphosphatase HFpEF Heart failure with preserved ejection fraction ATTR Transthyretin amyloidosis HFrEF Heart failure with reduced ejection fraction ATTR-CA Transthyretin cardiac amyloidosis HMDP Hydroxymethylene diphosphonate ATTR-CM Transthyretin amyloid cardiomyopathy HR Hazard ratio ATTRv Hereditary transthyretin amyloidosis HRS Heart Rhythm Society ATTRwt Wild-type OR Acquired transthyretin amyloidosis hs-cTnT High-sensitivity cardiac troponin T AV Atrioventricular ICD Implantable cardioverter defibrillator b.p.m. Beats per minute INR International normalized ratio BAG3 BAG cochaperone-3 ITFC International Task Force Consensus statement BNP Brain natriuretic peptide IVF In vitro fertilization CAD Coronary artery disease LA Left atrium CCB Calcium channel blocker LAHRS Latin American Heart Rhythm Society CHA2DS2-VASc Congestive heart failure or left ventricular LBBB Left bundle branch block dysfunction, hypertension, age ≥75 (doubled), LGE Late gadolinium enhancement diabetes, stroke (doubled)-vascular disease, age 65– LMNA Lamin A/C 74, sex category (female) (score) LMWH Low-molecular-weight heparin CHD Congenital heart disease LSD Lysosomal storage disease CK Creatinine kinase LV Left ventricular CMR Cardiac magnetic resonance LVAD LV assist device COVID-19 Severe acute respiratory syndrome coronavirus 2 LVEDV Left ventricular end-diastolic volume (SARS-CoV-2) infection LVEF Left ventricular ejection fraction CPET Cardio-pulmonary exercise testing LVH Left ventricular hypertrophy ESC Guidelines 3509 LVNC Left ventricular non-compaction TRED-HF Therapy withdrawal in REcovered Dilated LVOT Left ventricular outflow tract cardiomyopathy—Heart Failure LVSD Left ventricular systolic dysfunction TTE Transthoracic echocardiography LVOTO Left ventricular outflow tract obstruction TTN Titin MCS Mechanical circulatory support TTNtv Titin gene truncating variants MELAS Mitochondrial encephalomyopathy, lactic acidosis, TTR Transthyretin and stroke-like episodes (syndrome) TWI T wave inversion MERRF Mitochondrial epilepsy with ragged-red fibres UFH Unfractionated heparin MGUS Monoclonal gammopathy of undetermined VALOR-HCM A Study to Evaluate Mavacamten in Adults With significance Symptomatic Obstructive HCM Who Are Eligible MICONOS Mitochondrial Protection with Idebenone in Cardiac for Septal Reduction Therapy or Neurological Outcome (study group) VE Ventricular extrasystole MLVWT Maximum left ventricular wall thickness VF Ventricular fibrillation Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 MRA Mineralocorticoid receptor antagonist VKA Vitamin K antagonist MRI Magnetic resonance imaging VT Ventricular tachycardia MV Mitral valve VUS Variant of unknown significance mWHO Modified World Health Organization WHO World Health Organization (classification) NCS Non-cardiac surgery NDLVC Non-dilated left ventricular cardiomyopathy 1. Preamble NGS Next-generation sequencing Guidelines evaluate and summarize available evidence with the aim of NSML Noonan syndrome with multiple lentigines assisting health professionals in proposing the best diagnostic or thera­ NSVT Non-sustained ventricular tachycardia peutic approach for an individual patient with a given condition. NT-proBNP N-terminal pro-brain natriuretic peptide Guidelines are intended for use by health professionals and the NYHA New York Heart Association European Society of Cardiology (ESC) makes its Guidelines freely OMT Optimal medical therapy available. P/LP Pathogenic/likely pathogenic ESC Guidelines do not override the individual responsibility of health PES Programmed electrical stimulation professionals to make appropriate and accurate decisions in consider­ PET Positron emission tomography ation of each patient’s health condition and in consultation with that pa­ PKP2 Plakophilin 2 tient or the patient’s caregiver where appropriate and/or necessary. It is PLN Phospholamban also the health professional’s responsibility to verify the rules and reg­ PPCM Peripartum cardiomyopathy ulations applicable in each country to drugs and devices at the time of PRKAG2 Protein kinase AMP-activated non-catalytic subunit prescription, and, where appropriate, to respect the ethical rules of gamma 2 their profession. PRS Polygenic risk scores ESC Guidelines represent the official position of the ESC on a given PTH Parathyroid hormone topic and are regularly updated. ESC Policies and Procedures for for­ PVR Pulmonary vascular resistance mulating and issuing ESC Guidelines can be found on the ESC website PYP Pyrophosphate (https://www.escardio.org/Guidelines). QoL Quality of life The Members of this Task Force were selected by the ESC to re­ QRS Q, R, and S waves of an ECG present professionals involved with the medical care of patients with RAS-HCM RASopathy-associated HCM this pathology. The selection procedure aimed to include members RBBB Right bundle branch block from across the whole of the ESC region and from relevant ESC RBM20 RNA binding motif protein Subspecialty Communities. Consideration was given to diversity and in­ RCM Restrictive cardiomyopathy clusion, notably with respect to gender and country of origin. The Task RCT Randomized controlled trial Force performed a critical evaluation of diagnostic and therapeutic ap­ RV Right ventricular proaches, including assessment of the risk-benefit ratio. The strength of RVEF Right ventricular ejection fraction every recommendation and the level of evidence supporting them were RVOTO Right ventricular outflow tract obstruction weighed and scored according to predefined scales as outlined below. RWMA Regional wall motion abnormality The Task Force followed ESC voting procedures, and all approved re­ SAECG Signal-averaged electrocardiogram commendations were subject to a vote and achieved at least 75% SAM Systolic anterior motion agreement among voting members. SCD Sudden cardiac death The experts of the writing and reviewing panels provided declaration SGLT2i Sodium–glucose co-transporter 2 inhibitor of interest forms for all relationships that might be perceived as real or SMVT Sustained monomorphic ventricular tachycardia potential sources of conflicts of interest. Their declarations of interest SPECT Single-photon emission computed tomography were reviewed according to the ESC declaration of interest rules and SRT Septal reduction therapy can be found on the ESC website (http://www.escardio.org/ TIA Transient ischaemic attack Guidelines) and have been compiled in a report published in a supple­ TMEM43 transmembrane protein 43 mentary document with the guidelines. The Task Force received its 3510 ESC Guidelines Table 1 Classes for recommendations Definition Wording to use Classes of recommendations Class I Evidence and/or general agreement Is recommended or is indicated that a given treatment or procedure is beneficial, useful, effective. Class II Conflicting evidence and/or a divergence of opinion about the usefulness/ efficacy of the given treatment or procedure. Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 Class IIa Weight of evidence/opinion is in Should be considered favour of usefulness/efficacy. Class IIb Usefulness/efficacy is less well May be considered established by evidence/opinion. Class III Evidence or general agreement that the Is not recommended given treatment or procedure is not ©ESC 2023 useful/effective, and in some cases © ESC 2023 may be harmful. Table 2 Levels of evidence Level of Data derived from multiple randomized clinical trials evidence A or meta-analyses. Level of Data derived from a single randomized clinical trial evidence B or large non-randomized studies. Level of Consensus of opinion of the experts and/or small studies, evidence C retrospective studies, registries. ©ESC 2023 © ESC 2023 ESC Guidelines 3511 entire financial support from the ESC without any involvement from recommendations for each individual cardiomyopathy phenotype; in­ the healthcare industry. stead, the aim is to provide a guide to the diagnostic approach to car­ The ESC Clinical Practice Guidelines (CPG) Committee supervises diomyopathies, highlight general evaluation and management issues, and co-ordinates the preparation of new guidelines and is responsible and signpost the reader to the relevant evidence base for the for the approval process. ESC Guidelines undergo extensive review recommendations. by the CPG Committee and external experts, including members Adoption of morphological and functional disease definitions means from across the whole of the ESC region and from relevant ESC that the number of possible aetiologies is considerable, particularly in Subspecialty Communities and National Cardiac Societies. After appro­ young children. As it is impractical to provide an exhaustive compen­ priate revisions, the guidelines are signed off by all the experts involved dium of all possible causes of cardiomyopathy, the guideline focuses in the Task Force. The finalized document is signed off by the CPG on the most common disease phenotypes, but additional references Committee for publication in the European Heart Journal. The guidelines for less common disorders are also provided. Similarly, treatment re­ were developed after careful consideration of the scientific and medical commendations focus largely on generic management issues but refer knowledge and the evidence available at the time of their writing. Tables to specific rare diseases when appropriate. The central illustration Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 of evidence summarizing the findings of studies informing development (Figure 1) highlights key aspects in the evaluation and management of of the guidelines are included. The ESC warns readers that the technical cardiomyopathies addressed in this guideline. language may be misinterpreted and declines any responsibility in this This is the first major international guideline to address cardiomyop­ respect. athies other than HCM. Other major innovations include: Off-label use of medication may be presented in this guideline if a suf­ A new phenotypic description of cardiomyopathies, including up­ ficient level of evidence shows that it can be considered medically ap­ dated descriptions of dilated and non-dilated left ventricular (LV) car­ propriate for a given condition. diomyopathy phenotypes, and highlighting the key role of ventricular However, the final decisions concerning an individual patient must be myocardial scar assessment using cardiac magnetic resonance (CMR) made by the responsible health professional giving special consideration imaging. to: A focus on the patient pathway, from presentation, through initial as­ The specific situation of the patient. Unless otherwise provided for sessment and diagnosis, to management, highlighting the importance by national regulations, off-label use of medication should be limited of considering cardiomyopathy as a cause of common clinical presen­ to situations where it is in the patient’s interest, with regard to the tations (e.g. heart failure, arrhythmia) and the importance of utilizing a quality, safety, and efficacy of care, and only after the patient has multiparametric approach following the identification of the present­ been informed and has provided consent. ing phenotype to arrive at an aetiological diagnosis. Country-specific health regulations, indications by governmental Updated recommendations for clinical and genetic cascade screening drug regulatory agencies, and the ethical rules to which health profes­ for relatives of individuals with cardiomyopathies. sionals are subject, where applicable. A focus on cardiomyopathies across the life course, from paediatric to adult age (including transition), and considering the different clin­ ical phases (e.g. concealed, overt, end stage). 2. Introduction New recommendations on sudden cardiac death (SCD) risk stratifi­ cation for different cardiomyopathy phenotypes, including in child­ The objective of this European Society of Cardiology (ESC) Guideline is hood, and highlighting the important role of genotype in the to help healthcare professionals diagnose and manage patients with car­ assessment of sudden death risk. diomyopathies according to the best available evidence. Uniquely for Updated recommendations for the management of left ventricular relatively common cardiovascular diseases, there are very few rando­ outflow tract obstruction (LVOTO) in HCM. mized controlled clinical trials in patients with cardiomyopathies. For A multidisciplinary approach to cardiomyopathies that has the pa­ this reason, the majority of the recommendations in this guideline are tient and their family at its heart. based on observational cohort studies and expert consensus opinion. The aim is to provide healthcare professionals with a practical diagnos­ tic and treatment framework for patients of all ages and, as an increasing 3. Phenotypic approach to number of patients have a known genetic basis for their disease, the guideline also considers the implications of a diagnosis for families cardiomyopathies and provides advice on reproduction and contraception. As cardio­ In medicine, classification systems are used to standardize disease no­ myopathies can present at any age and can affect individuals and families menclature by grouping disorders according to shared characteristics. across the entire life course, this guideline follows the principle of con­ In 2008, the ESC promoted a pragmatic system for the clinical descrip­ sidering cardiomyopathies in all age groups as single disease entities, tion of cardiomyopathies in which a historical focus on ventricular with recommendations applicable to children and adults with cardio­ morphology and function was maintained, while signposting aetiological myopathy throughout, while accepting that the evidence base for diversity through subdivision into genetic and non-genetic subtypes.2 many of the recommendations is significantly more limited for children. Since then, knowledge of cardiomyopathies has increased substantially Age-related differences are specifically highlighted. through the application of new imaging and molecular technologies. This is a new guideline, not an update of existing guidelines, with the In this guideline, the Task Force took a number of considerations into exception of the section on hypertrophic cardiomyopathy (HCM), in account when deciding its approach to disease description. These in­ which we have provided a focused update to the 2014 ESC Guidelines cluded: (i) a historical legacy which, while still useful, has led to contra­ on diagnosis and management of hypertrophic cardiomyopathy.1 As such, dictory and confusing terminology in many situations; (ii) the evolving most of the recommendations in this guideline are new. It is beyond nature of cardiomyopathies over a lifetime; (iii) aetiological complexity the scope of this guideline to provide detailed descriptions and with multiple disease processes contributing to disease phenotypes; 3512 ESC Guidelines 1 Clinical scenario Symptoms Incidental findings Family screening 2 3 Morphological/functional Additional traits characterization Arrhythmias/conduction Extracardiac Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 Ventricular morphology/ disease involvement function Pedigree analysis Laboratory markers Ventricular scar and tissue characterization Genetic testing Pathology 4 5 6 General Phenotype- Phenotype management principles specific management Symptom management LVOTO management HCM SCD risk prediction Drug therapy Mechanical circulatory support/transplantation GDMT for HF symptoms DCM Family screening and Aetiology-specific SCD genetic risk to relatives risk prediction Genetic testing and counselling Family screening and monitoring GDMT for HF symptoms NDLVC Aetiology-specific SCD Prevention of disease- risk prediction related complications SCD ICD Stroke thromboembolic prophylaxis Antiarrhythmic therapy ARVC SCD risk prediction Lifestyle Exercise recommendations GDMT for HF symptoms Pregnancy RCM PVR study to guide timing of School, employment, transplantation psychological support Figure 1 Central illustration. Key aspects in the evaluation and management of cardiomyopathies. ARVC, arrhythmogenic right ventricular cardiomyop­ athy; CMR, cardiac magnetic resonance; DCM, dilated cardiomyopathy; GDMT, guideline-directed medical therapy; HCM, hypertrophic cardiomyopathy; HF, heart failure ICD, implantable cardioverter defibrillator; LVOTO, left ventricular outflow tract obstruction; MCS, mechanical circulatory support; NDLVC, non-dilated left ventricular cardiomyopathy; PVR, pulmonary vascular resistance; RCM, restrictive cardiomyopathy; SCD, sudden cardiac death.Image %: ESC Guidelines 3513 Symptoms Incidental findings Family screening Dyspnoea Chest pain Abnormal ECG 1st degree relative Clinical Palpitation Murmur with CMP Syncope/presyncope Arrhythmia Family history of scenario sudden death Cardiac arrest Suspected cardiomyopathy Ventricular morphology/function Ventricular scar/fatty replacement Downloaded from https://academic.oup.com/eurheartj/article/44/37/3503/7246608 by guest on 05 June 2024 Morphological/ Hypertrophy Non-ischaemic ventricular scar on functional CMR/pathological examination Dilatation Other tissue characterization characterization Systolic/diastolic function parameters on CMR HCM DCM ARVC Phenotype RCM NDLVC Arrhythmias/conduction disease (atrial, ventricular, atrioventricular block) Pedigree analysis Genetic testing Extracardiac involvement Additional traits Laboratory markers Pathology Phenotype-based integrated aetiological diagnosis Figure 2 Clinical diagnostic workflow of cardiomyopathy. ARVC, arrhythmogenic right ventricular cardiomyopathy; CMP, cardiomyopathy; CMR, cardiac magnetic resonance; DCM, dilated cardiomyopathy; ECG, electrocardiogram; HCM, hypertrophic cardiomyopathy; NDLVC, non-dilated left ventricular car­ diomyopathy; RCM, restrictive cardiomyopathy. (iv) differential disease expression in families; and (v) emerging phenotypic descriptions and to simplify terminology, while simultan­ aetiology-focused therapies. eously providing a conceptual framework for diagnosis and treatment. The Task Force concluded that a single classification system that em­ This nomenclature prompts clinicians to consider cardiomyopathy as braces all possible causes of disease and every clinical scenario remains the cause of several clinical presentations (e.g. arrhythmia, heart failure), an aspiration that is outside the scope of this clinical guideline. Instead, and focuses on morphological and functional characteristics of the the Task Force updated the existing clinical classification to include new myocardium (Figure 2). It is important to recognize that different 3514 ESC Guidelines cardiomyopathy phenotypes may coexist in the same family, and that Table 3 Morphological and functional traits used to de­ disease progression in an individual patient can include evolution scribe cardiomyopathy phenotypes from one cardiomyopathy phenotype to another. Nevertheless, the Morphological traits Task Force recommends an approach to disease nomenclature and diagnosis that is based on the predominant cardiac phenotype at Ventricular hypertrophy: left and/or right presentation.