Genetic family screening following the detection of a pathogenic or likely pathogenic variant in a proband with dilated cardiomyopathy (DCM) remains one of the main applications of genetic testing. While cardiac screening is recommended for all first-degree relatives, the a priori risk among family members varies. Consequently, screening regimens should be tailored according to both genetic and clinical information at the individual and familial level. This clinical consensus statement provides tools to help with the risk assessment and follow-up of screening for family members and discusses the utility for integration of genotype-specific information, cardiac imaging, and electrocardiogram findings to personalize cardiac screening regimens, which in conjunction will likely improve individualized risk prediction. Early phenotypic detection of DCM in family members remains an active area of research and innovation. In addition, data are starting to accrue on the utility of early therapeutic intervention in family members with very mild phenotypes that may inform future management in addition to screening. A systematic strategy is proposed to determine the a priori risk of developing DCM for a family member, and the potential of integrating genotype-phenotype knowledge towards family management. Lastly, there is a focus on the current knowledge gaps and ongoing and future opportunities to improve risk prediction, early disease detection, and treatment of family members of patients with DCM.

2nd Department of Medicine Department of Cardiovascular Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Aberdeen Cardiovascular and Diabetes Centre University of Aberdeen Aberdeen UK

Barts Heart Centre St Bartholomew's Hospital London UK

Cardiothoracovascular Department Azienda Sanitaria Universitaria Giuliano Isontina Center for Cardiomyopathies University of Trieste Trieste Italy

Cardiovascular and GEbonics Research Institute City St George's University of London London UK

Cardiovascular Clinical Academic Group St George's University Hospitals NHS Foundation Trust London UK

Centre for Inherited Cardiovascular Diseases Great Ormond Street Hospital London UK

Centre for Paediatric Inherited and Rare Cardiovascular Disease Institute of Cardiovascular Science University College London London UK

Centro Nacional de Investigaciones Cardiovasculares Melchor Fernández Almagro 3 28029 Madrid Spain

CIBER Cardiovascular Instituto de Salud Carlos 3 Av Monforte de Lemos 3 5 28029 Madrid Spain

CRY Cardiovascular Pathology Unit Cardiovascular and Genetic Research Institute St George's University of London London UK

Department of Cardiology Amsterdam Cardiovascular Sciences Amsterdam University Medical Centre University of Amsterdam Amsterdam The Netherlands

Department of Cardiology Cardiovascular Research Institute Maastricht Maastricht University Universiteitssingel 50 6229 ER Maastricht The Netherlands

Department of Cardiology Deutsches Herzzentrum München Universitätsklinikum der Technischen Universität München Munich Germany

Department of Cardiology Karolinska University Hospital Stockholm Sweden

Department of Cardiology Oslo University Hospital Oslo Norway

Department of Cardiology Serbian Academy of Sciences and Arts and Faculty of Medicine University of Belgrade Belgrade Serbia

Department of Cardiovascular Sciences Centre for Molecular and Vascular Biology University of Leuven Belgium

Department of Clinical Genetics Maastricht University Medical Center P Debyelaan 25 6229HX Maastricht The Netherlands

Department of Genetics University Medical Center Utrecht Utrecht The Netherlands

Department of Molecular Medicine University of Pavia Pavia Italy

Deutsches Zentrum für Herz und Kreislauferkrankungen Partner Site Munich Heart Alliance Munich Germany

Filière Nationale de Santé CARDIOGEN Paris France

Genetics and Cardiology Departments APHP Sorbonne Université INSERM 1166 Institute of Cardiology and ICAN Institute for Cardiometabolism and Nutrition Pitié Salpêtrière Hospital Paris France

Heart Failure and Inherited Cardiac Diseases Unit Department of Cardiology Hospital Universitario Puerta de Hierro IDIPHISA Manuel de Falla 2 Madrid 28222 Spain

Institute of Cardiovascular Science University College London London UK

Institute of Health Informatics University College London London UK

Medical Department Dilemma Solutions A Coruña Spain

Molecular Cardiology Unit IRCCS Istituti Clinici Scientifici Maugeri Pavia Italy

Royal Brompton and Harefield Hospitals London UK

The National Institute for Health Research University College London Hospitals Biomedical Research Centre University College London London UK

Zobrazit více v PubMed

Arbelo  E, Protonotarios  A, Gimeno  JR, Arbustini  E, Barriales-Villa  R, Basso  C, et al.  2023 ESC guidelines for the management of cardiomyopathies. Eur Heart J  2023;44:3503–626. doi: 10.1093/eurheartj/ehad194 PubMed DOI

Verdonschot  JAJ, Hazebroek  MR, Krapels  IPC, Henkens  M, Raafs  A, Wang  P, et al.  Implications of genetic testing in dilated cardiomyopathy. Circ Genom Precis Med  2020;13:476–87. doi: 10.1161/CIRCGEN.120.003031 PubMed DOI

Pinto  YM, Elliott  PM, Arbustini  E, Adler  Y, Anastasakis  A, Bohm  M, et al.  Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J  2016;37:1850–8. doi: 10.1093/eurheartj/ehv727 PubMed DOI

Wilde  AAM, Semsarian  C, Márquez  MF, Shamloo  AS, Ackerman  MJ, Ashley  EA, et al.  European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases. Europace  2022;24:1307–67. doi: 10.1093/europace/euac030 PubMed DOI PMC

Jordan  E, Peterson  L, Ai  T, Asatryan  B, Bronicki  L, Brown  E, et al.  Evidence-based assessment of genes in dilated cardiomyopathy. Circulation  2021;144:7–19. doi: 10.1161/circulationaha.120.053033 PubMed DOI PMC

Mazzarotto  F, Tayal  U, Buchan  RJ, Midwinter  W, Wilk  A, Whiffin  N, et al.  Reevaluating the genetic contribution of monogenic dilated cardiomyopathy. Circulation  2020;141:387–98. doi: 10.1161/CIRCULATIONAHA.119.037661 PubMed DOI PMC

Stroeks  S, Hellebrekers  D, Claes  GRF, Tayal  U, Krapels  IPC, Vanhoutte  EK, et al.  Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy. Genet Med  2021;23:2186–93. doi: 10.1038/s41436-021-01255-1 PubMed DOI PMC

Domínguez  F, Lalaguna  L, Martínez-Martín  I, Piqueras-Flores  J, Rasmussen  TB, Zorio  E, et al.  Titin missense variants as a cause of familial dilated cardiomyopathy. Circulation  2023;147:1711–3. doi: 10.1161/circulationaha.122.062833 PubMed DOI

Richards  S, Aziz  N, Bale  S, Bick  D, Das  S, Gastier-Foster  J, et al.  Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med  2015;17:405–24. doi: 10.1038/gim.2015.30 PubMed DOI PMC

Kääb  S, Bondue  A. An update on the ESC Council on Cardiovascular Genomics: out from the niche into the open. Eur Heart J  2025;46:1784–6. doi: 10.1093/eurheartj/ehaf068 PubMed DOI

Mahon  NG, Murphy  RT, MacRae  CA, Caforio  AL, Elliott  PM, McKenna  WJ. Echocardiographic evaluation in asymptomatic relatives of patients with dilated cardiomyopathy reveals preclinical disease. Ann Intern Med  2005;143:108–15. doi: 10.7326/0003-4819-143-2-200507190-00009 PubMed DOI

Edwards  A, Gray  J, Clarke  A, Dundon  J, Elwyn  G, Gaff  C, et al.  Interventions to improve risk communication in clinical genetics: systematic review. Patient Educ Couns  2008;71:4–25. doi: 10.1016/j.pec.2007.11.026 PubMed DOI

Austin  J, Semaka  A, Hadjipavlou  G. Conceptualizing genetic counseling as psychotherapy in the era of genomic medicine. J Genet Couns  2014;23:903–9. doi: 10.1007/s10897-014-9728-1 PubMed DOI PMC

Schoonvelde  SAC, Ruijmbeek  CWB, Hirsch  A, van Slegtenhorst  MA, Wessels  MW, von der Thüsen  JH, et al.  Phenotypic variability of filamin C-related cardiomyopathy: insights from a novel Dutch founder variant. Heart Rhythm  2023;20:1512–21. doi: 10.1016/j.hrthm.2023.08.003 PubMed DOI

Jacobs  J, Van Aelst  L, Breckpot  J, Corveleyn  A, Kuiperi  C, Dupont  M, et al.  Tools to differentiate between filamin C and titin truncating variant carriers: value of MRI. Eur J Hum Genet  2023;31:1323–32. doi: 10.1038/s41431-023-01357-1 PubMed DOI PMC

Stroeks  S, Verdonschot  JAJ. The next step toward personalized recommendations for genetic cardiomyopathies. Eur J Hum Genet  2023;31:1201–3. doi: 10.1038/s41431-023-01394-w PubMed DOI PMC

Te Rijdt  WP, Ten Sande  JN, Gorter  TM, van der Zwaag  PA, van Rijsingen  IA, Boekholdt  SM, et al.  Myocardial fibrosis as an early feature in phospholamban p.Arg14del mutation carriers: phenotypic insights from cardiovascular magnetic resonance imaging. Eur Heart J Cardiovasc Imaging  2019;20:92–100. doi: 10.1093/ehjci/jey047 PubMed DOI

Fontana  M, Barison  A, Botto  N, Panchetti  L, Ricci  G, Milanesi  M, et al.  CMR-verified interstitial myocardial fibrosis as a marker of subclinical cardiac involvement in LMNA mutation carriers. JACC Cardiovasc Imaging  2013;6:124–6. doi: 10.1016/j.jcmg.2012.06.013 PubMed DOI

Cabrera-Romero  E, Ochoa  JP, Barriales-Villa  R, Bermúdez-Jiménez  FJ, Climent-Payá  V, Zorio  E, et al.  Penetrance of dilated cardiomyopathy in genotype-positive relatives. J Am Coll Cardiol  2024;83:1640–51. doi: 10.1016/j.jacc.2024.02.036 PubMed DOI

de Frutos  F, Ochoa  JP, Fernández  AI, Gallego-Delgado  M, Navarro-Peñalver  M, Casas  G, et al.  Late gadolinium enhancement distribution patterns in non-ischemic dilated cardiomyopathy: genotype–phenotype correlation. Eur Heart J Cardiovasc Imaging  2023;25:75–85. doi: 10.1093/ehjci/jead184 PubMed DOI PMC

Akhtar  MM, Lorenzini  M, Cicerchia  M, Ochoa  JP, Hey  TM, Molina  MS, et al.  Clinical phenotypes and prognosis of dilated cardiomyopathy caused by truncating variants in the TTN gene. Circ Heart Fail  2020;13:e006832. doi: 10.1161/CIRCHEARTFAILURE.119.006832 PubMed DOI

Hasselberg  NE, Haland  TF, Saberniak  J, Brekke  PH, Berge  KE, Leren  TP, et al.  Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation. Eur Heart J  2018;39:853–60. doi: 10.1093/eurheartj/ehx596 PubMed DOI PMC

de Frutos  F, Ochoa  JP, Navarro-Peñalver  M, Baas  A, Bjerre  JV, Zorio  E, et al.  Natural history of MYH7-related dilated cardiomyopathy. J Am Coll Cardiol  2022;80:1447–61. doi: 10.1016/j.jacc.2022.07.023 PubMed DOI

Jansen  M, de Brouwer  R, Hassanzada  F, Schoemaker  AE, Schmidt  AF, Kooijman-Reumerman  MD, et al.  Penetrance and prognosis of MYH7 variant-associated cardiomyopathies: results from a Dutch multicenter cohort study. JACC Heart Fail  2024;12:134–47. doi: 10.1016/j.jchf.2023.07.007 PubMed DOI

Carrick  RT, Gasperetti  A, Protonotarios  A, Murray  B, Laredo  M, van der Schaaf  I, et al.  A novel tool for arrhythmic risk stratification in desmoplakin gene variant carriers. Eur Heart J  2024;45:2968–79. doi: 10.1093/eurheartj/ehae409 PubMed DOI PMC

Verstraelen  TE, van Lint  FHM, Bosman  LP, de Brouwer  R, Proost  VM, Abeln  BGS, et al.  Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers-reaching the frontiers of individual risk prediction. Eur Heart J  2021;42:2842–50. doi: 10.1093/eurheartj/ehab294 PubMed DOI PMC

Domínguez  F, Cuenca  S, Bilińska  Z, Toro  R, Villard  E, Barriales-Villa  R, et al.  Dilated cardiomyopathy due to BLC2-associated athanogene 3 (BAG3) mutations. J Am Coll Cardiol  2018;72:2471–81. doi: 10.1016/j.jacc.2018.08.2181 PubMed DOI PMC

Cannie  DE, Protonotarios  A, Bakalakos  A, Syrris  P, Lorenzini  M, De Stavola  B, et al.  Risks of ventricular arrhythmia and heart failure in carriers of RBM20 variants. Circ Genom Precis Med  2023;16:434–41. doi: 10.1161/circgen.123.004059 PubMed DOI PMC

Akhtar  MM, Lorenzini  M, Pavlou  M, Ochoa  JP, O'Mahony  C, Restrepo-Cordoba  MA, et al.  Association of left ventricular systolic dysfunction among carriers of truncating variants in filamin C with frequent ventricular arrhythmia and end-stage heart failure. JAMA Cardiol  2021;6:891–901. 10.1001/jamacardio.2021.1106. PubMed DOI PMC

Ni  H, Jordan  E, Kinnamon  DD, Cao  J, Haas  GJ, Hofmeyer  M, et al.  Screening for dilated cardiomyopathy in at-risk first-degree relatives. J Am Coll Cardiol  2023;81:2059–71. doi: 10.1016/j.jacc.2023.03.419 PubMed DOI PMC

Vissing  CR, Espersen  K, Mills  HL, Bartels  ED, Jurlander  R, Skriver  SV, et al.  Family screening in dilated cardiomyopathy: prevalence, incidence, and potential for limiting follow-up. JACC Heart Fail  2022;10:792–803. doi: 10.1016/j.jchf.2022.07.009 PubMed DOI

Huggins  GS, Kinnamon  DD, Haas  GJ, Jordan  E, Hofmeyer  M, Kransdorf  E, et al.  Prevalence and cumulative risk of familial idiopathic dilated cardiomyopathy. JAMA  2022;327:454–63. doi: 10.1001/jama.2021.24674 PubMed DOI PMC

Hey  TM, Rasmussen  TB, Madsen  T, Aagaard  MM, Harbo  M, Mølgaard  H, et al.  Clinical and genetic investigations of 109 index patients with dilated cardiomyopathy and 445 of their relatives. Circ Heart Fail  2020;13:e006701. doi: 10.1161/circheartfailure.119.006701 PubMed DOI

Gigli  M, Merlo  M, Graw  SL, Barbati  G, Rowland  TJ, Slavov  DB, et al.  Genetic risk of arrhythmic phenotypes in patients with dilated cardiomyopathy. J Am Coll Cardiol  2019;74:1480–90. doi: 10.1016/j.jacc.2019.06.072 PubMed DOI PMC

Escobar-Lopez  L, Ochoa  JP, Mirelis  JG, Espinosa  M, Navarro  M, Gallego-Delgado  M, et al.  Association of genetic variants with outcomes in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol  2021;78:1682–99. doi: 10.1016/j.jacc.2021.08.039 PubMed DOI

Verdonschot  JAJ, Hazebroek  MR, Wang  P, Sanders-van Wijk  S, Merken  JJ, Adriaansen  YA, et al.  Clinical phenotype and genotype associations with improvement in left ventricular function in dilated cardiomyopathy. Circ Heart Fail  2018;11:e005220. doi: 10.1161/circheartfailure.118.005220 PubMed DOI

Zeppenfeld  K, Tfelt-Hansen  J, de Riva  M, Winkel  BG, Behr  ER, Blom  NA, et al.  2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J  2022;43:3997–4126. doi: 10.1093/eurheartj/ehac262 PubMed DOI

Paldino  A, Dal Ferro  M, Stolfo  D, Gandin  I, Medo  K, Graw  S, et al.  Prognostic prediction of genotype vs phenotype in genetic cardiomyopathies. J Am Coll Cardiol  2022;80:1981–94. doi: 10.1016/j.jacc.2022.08.804 PubMed DOI PMC

Wenger  BM, Patel  N, Lui  M, Moscati  A, Do  R, Stewart  DR, et al.  A genotype-first approach to exploring Mendelian cardiovascular traits with clear external manifestations. Genet Med  2021;23:94–102. doi: 10.1038/s41436-020-00973-2 PubMed DOI PMC

Kumar  S, Baldinger  SH, Gandjbakhch  E, Maury  P, Sellal  JM, Androulakis  AF, et al.  Long-term arrhythmic and nonarrhythmic outcomes of lamin A/C mutation carriers. J Am Coll Cardiol  2016;68:2299–307. doi: 10.1016/j.jacc.2016.08.058 PubMed DOI

Wahbi  K, Ben Yaou  R, Gandjbakhch  E, Anselme  F, Gossios  T, Lakdawala  NK, et al.  Development and validation of a new risk prediction score for life-threatening ventricular tachyarrhythmias in laminopathies. Circulation  2019;140:293–302. doi: 10.1161/CIRCULATIONAHA.118.039410 PubMed DOI

Virk  ZM, El-Harasis  MA, Yoneda  ZT, Anderson  KC, Sun  L, Quintana  JA, et al.  Clinical characteristics and outcomes in patients with atrial fibrillation and pathogenic TTN variants. JACC Clin Electrophysiol  2024;10:2445–57. doi: 10.1016/j.jacep.2024.07.029 PubMed DOI

Gigli  M, Stolfo  D, Graw  SL, Merlo  M, Gregorio  C, Nee Chen  S, et al.  Phenotypic expression, natural history, and risk stratification of cardiomyopathy caused by filamin C truncating variants. Circulation  2021;144:1600–11. doi: 10.1161/circulationaha.121.053521 PubMed DOI PMC

Smith  ED, Lakdawala  NK, Papoutsidakis  N, Aubert  G, Mazzanti  A, McCanta  AC, et al.  Desmoplakin cardiomyopathy, a fibrotic and inflammatory form of cardiomyopathy distinct from typical dilated or arrhythmogenic right ventricular cardiomyopathy. Circulation  2020;141:1872–84. doi: 10.1161/circulationaha.119.044934 PubMed DOI PMC

van der Zwaag  PA, van Rijsingen  IA, Asimaki  A, Jongbloed  JD, van Veldhuisen  DJ, Wiesfeld  AC, et al.  Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. Eur J Heart Fail  2012;14:1199–207. doi: 10.1093/eurjhf/hfs119 PubMed DOI PMC

Dominguez  F, Zorio  E, Jimenez-Jaimez  J, Salguero-Bodes  R, Zwart  R, Gonzalez-Lopez  E, et al.  Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. Heart Rhythm  2020;17:945–54. doi: 10.1016/j.hrthm.2020.01.035 PubMed DOI

Cannie  DE, Syrris  P, Protonotarios  A, Bakalakos  A, Pruny  JF, Ditaranto  R, et al.  Emery–Dreifuss muscular dystrophy 1 is associated with high risk of malignant ventricular arrhythmias and end-stage heart failure. Eur Heart J  2023;44:5064–73. doi: 10.1093/eurheartj/ehad561 PubMed DOI PMC

Bermudez-Jimenez  FJ, Protonotarios  A, García-Hernández  S, Pérez Asensio  A, Rampazzo  A, Zorio  E, et al.  Phenotype and clinical outcomes in desmin-related arrhythmogenic cardiomyopathy. JACC Clin Electrophysiol  2024;10:1178–90. doi: 10.1016/j.jacep.2024.02.031 PubMed DOI

Parikh  VN, Caleshu  C, Reuter  C, Lazzeroni  LC, Ingles  J, Garcia  J, et al.  Regional variation in RBM20 causes a highly penetrant arrhythmogenic cardiomyopathy. Circ Heart Fail  2019;12:e005371. doi: 10.1161/circheartfailure.118.005371 PubMed DOI PMC

Corrado  D, van Tintelen  PJ, McKenna  WJ, Hauer  RNW, Anastastakis  A, Asimaki  A, et al.  Arrhythmogenic right ventricular cardiomyopathy: evaluation of the current diagnostic criteria and differential diagnosis. Eur Heart J  2020;41:1414–29. doi: 10.1093/eurheartj/ehz669 PubMed DOI PMC

Muser  D, Nucifora  G, Muser  D, Nucifora  G, Pieroni  M, Castro  SA, et al.  Prognostic value of nonischemic ringlike left ventricular scar in patients with apparently idiopathic nonsustained ventricular arrhythmias. Circulation  2021;143:1359–73. doi: 10.1161/circulationaha.120.047640 PubMed DOI

Di Marco  A, Anguera  I, Schmitt  M, Klem  I, Neilan  TG, White  JA, et al.  Late gadolinium enhancement and the risk for ventricular arrhythmias or sudden death in dilated cardiomyopathy: systematic review and meta-analysis. JACC Heart Fail  2017;5:28–38. 10.1016/j.jchf.2016.09.017 PubMed DOI

Mirelis  JG, Escobar-Lopez  L, Ochoa  JP, Espinosa  M, Villacorta  E, Navarro  M, et al.  Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non-ischaemic dilated cardiomyopathy. Eur J Heart Fail  2022;24:1183–96. doi: 10.1002/ejhf.2514 PubMed DOI PMC

Bariani  R, Rigato  I, Cipriani  A, Bueno Marinas  M, Celeghin  R, Basso  C, et al.  Myocarditis-like episodes in patients with arrhythmogenic cardiomyopathy: a systematic review on the so-called hot-phase of the disease. Biomolecules  2022;12:1324. doi: 10.3390/biom12091324 PubMed DOI PMC

Wang  W, Murray  B, Tichnell  C, Gilotra  NA, Zimmerman  SL, Gasperetti  A, et al.  Clinical characteristics and risk stratification of desmoplakin cardiomyopathy. Europace  2022;24:268–77. doi: 10.1093/europace/euab183 PubMed DOI PMC

McDonagh  TA, Metra  M, Adamo  M, Gardner  RS, Baumbach  A, Böhm  M, et al.  2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J  2021;42:3599–726. doi: 10.1093/eurheartj/ehab368 PubMed DOI

Catchpool  M, Ramchand  J, Martyn  M, Hare  DL, James  PA, Trainer  AH, et al.  A cost-effectiveness model of genetic testing and periodical clinical screening for the evaluation of families with dilated cardiomyopathy. Genet Med  2019;21:2815–22. doi: 10.1038/s41436-019-0582-2 PubMed DOI PMC

Verdonschot  JAJ, Hazebroek  MR, Derks  KWJ, Aizpurua  AB, Merken  JJ, Wang  P, et al.  Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias. Eur Heart J  2018;39:864–73. doi: 10.1093/eurheartj/ehx808 PubMed DOI

Ortiz-Genga  MF, Cuenca  S, Dal Ferro  M, Zorio  E, Salgado-Aranda  R, Climent  V, et al.  Truncating FLNC mutations are associated with high-risk dilated and arrhythmogenic cardiomyopathies. J Am Coll Cardiol  2016;68:2440–51. doi: 10.1016/j.jacc.2016.09.927 PubMed DOI

van Rijsingen  IA, van der Zwaag  PA, Groeneweg  JA, Nannenberg  EA, Jongbloed  JD, Zwinderman  AH, et al.  Outcome in phospholamban R14del carriers: results of a large multicentre cohort study. Circ Cardiovasc Genet  2014;7:455–65. doi: 10.1161/circgenetics.113.000374 PubMed DOI

de Brouwer  R, Te Rijdt  WP, Hoorntje  ET, Amin  A, Asselbergs  FW, Cox  M, et al.  A randomized controlled trial of eplerenone in asymptomatic phospholamban p.Arg14del carriers. Eur Heart J  2023;44:4284–7. doi: 10.1093/eurheartj/ehad292 PubMed DOI PMC

Lee  A, Mavaddat  N, Wilcox  AN, Cunningham  AP, Carver  T, Hartley  S, et al.  BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors. Genet Med  2019;21:1708–18. doi: 10.1038/s41436-018-0406-9 PubMed DOI PMC

van de Leur  RR, Taha  K, Bos  MN, van der Heijden  JF, Gupta  D, Cramer  MJ, et al.  Discovering and visualizing disease-specific electrocardiogram features using deep learning: proof-of-concept in phospholamban gene mutation carriers. Circ Arrhythm Electrophysiol  2021;14:e009056. doi: 10.1161/circep.120.009056 PubMed DOI PMC

Verbrugge  FH, Reddy  YNV, Attia  ZI, Friedman  PA, Noseworthy  PA, Lopez-Jimenez  F, et al.  Detection of left atrial myopathy using artificial intelligence-enabled electrocardiography. Circ Heart Fail  2022;15:e008176. doi: 10.1161/circheartfailure.120.008176 PubMed DOI PMC

Khurshid  S, Friedman  S, Pirruccello  JP, Di Achille  P, Diamant  N, Anderson  CD, et al.  Deep learning to predict cardiac magnetic resonance-derived left ventricular mass and hypertrophy from 12-lead ECGs. Circ Cardiovasc Imaging  2021;14:e012281. doi: 10.1161/circimaging.120.012281 PubMed DOI PMC

Kwon  JM, Jeon  KH, Kim  HM, Kim  MJ, Lim  SM, Kim  KH, et al.  Comparing the performance of artificial intelligence and conventional diagnosis criteria for detecting left ventricular hypertrophy using electrocardiography. Europace  2020;22:412–9. doi: 10.1093/europace/euz324 PubMed DOI

Vaid  A, Johnson  KW, Badgeley  MA, Somani  SS, Bicak  M, Landi  I, et al.  Using deep-learning algorithms to simultaneously identify right and left ventricular dysfunction from the electrocardiogram. JACC Cardiovasc Imaging  2022;15:395–410. doi: 10.1016/j.jcmg.2021.08.004 PubMed DOI PMC

Lee  Y, Choi  B, Lee  MS, Jin  U, Yoon  S, Jo  YY, et al.  An artificial intelligence electrocardiogram analysis for detecting cardiomyopathy in the peripartum period. Int J Cardiol  2022;352:72–7. doi: 10.1016/j.ijcard.2022.01.064 PubMed DOI

Khunte  A, Sangha  V, Oikonomou  EK, Dhingra  LS, Aminorroaya  A, Mortazavi  BJ, et al.  Detection of left ventricular systolic dysfunction from single-lead electrocardiography adapted for portable and wearable devices. NPJ Digit Med  2023;6:124. doi: 10.1038/s41746-023-00869-w PubMed DOI PMC

Taha  K, Kirkels  FP, Teske  AJ, Asselbergs  FW, van Tintelen  JP, Doevendans  PA, et al.  Echocardiographic deformation imaging for early detection of genetic cardiomyopathies: JACC review topic of the week. J Am Coll Cardiol  2022;79:594–608. doi: 10.1016/j.jacc.2021.11.045 PubMed DOI

Verdonschot  JAJ, Merken  JJ, Brunner-La Rocca  HP, Hazebroek  MR, Eurlings  C, Thijssen  E, et al.  Value of speckle tracking-based deformation analysis in screening relatives of patients with asymptomatic dilated cardiomyopathy. JACC Cardiovasc Imaging  2020;13:549–58. doi: 10.1016/j.jcmg.2019.02.032 PubMed DOI

Baudry  G, Mansencal  N, Reynaud  A, Richard  P, Dubourg  O, Komajda  M, et al.  Global and regional echocardiographic strain to assess the early phase of hypertrophic cardiomyopathy due to sarcomeric mutations. Eur Heart J Cardiovasc Imaging  2020;21:291–8. doi: 10.1093/ehjci/jez084 PubMed DOI

Caenen  A, Bézy  S, Pernot  M, Nightingale  KR, Vos  HJ, Voigt  JU, et al.  Ultrasound shear wave elastography in cardiology. JACC Cardiovasc Imaging  2024;17:314–29. doi: 10.1016/j.jcmg.2023.12.007 PubMed DOI

Pugh  TJ, Kelly  MA, Gowrisankar  S, Hynes  E, Seidman  MA, Baxter  SM, et al.  The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med  2014;16:601–8. doi: 10.1038/gim.2013.204 PubMed DOI

Verdonschot  JAJ, Heymans  SRB. Dilated cardiomyopathy: second hits knock-down the heart. Eur Heart J  2024;45:500–1. doi: 10.1093/eurheartj/ehad778 PubMed DOI

Pirruccello  JP, Bick  A, Wang  M, Chaffin  M, Friedman  S, Yao  J, et al.  Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy. Nat Commun  2020;11:2254. doi: 10.1038/s41467-020-15823-7 PubMed DOI PMC

Garnier  S, Harakalova  M, Weiss  S, Mokry  M, Regitz-Zagrosek  V, Hengstenberg  C, et al.  Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23. Eur Heart J  2021;42:2000–11. doi: 10.1093/eurheartj/ehab030 PubMed DOI PMC

Lee  DS, Pencina  MJ, Benjamin  EJ, Wang  TJ, Levy  D, O'Donnell  CJ, et al.  Association of parental heart failure with risk of heart failure in offspring. N Engl J Med  2006;355:138–47. doi: 10.1056/NEJMoa052948 PubMed DOI

Tadros  R, Francis  C, Xu  X, Vermeer  AMC, Harper  AR, Huurman  R, et al.  Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect. Nat Genet  2021;53:128–34. doi: 10.1038/s41588-020-00762-2 PubMed DOI PMC

Pelliccia  A, Sharma  S, Gati  S, Bäck  M, Börjesson  M, Caselli  S, et al.  2020 ESC guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J  2021;42:17–96. doi: 10.1093/eurheartj/ehaa605 PubMed DOI

van Lint  FHM, Hassanzada  F, Verstraelen  TE, Wang  W, Bosman  LP, van der Zwaag  PA, et al.  Exercise does not influence development of phenotype in PLN p.(Arg14del) cardiomyopathy. Neth Heart J  2023;31:291–9. doi: 10.1007/s12471-023-01800-4 PubMed DOI PMC

Restrepo-Córdoba  MA, Chmielewski  P, Truszkowska  G, Peña-Peña  ML, Kubánek  M, Krebsová  A, et al.  Pregnancy in women with dilated cardiomyopathy genetic variants. Rev Esp Cardiol (Engl Ed)  2025;78:2–9. doi: 10.1016/j.rec.2024.04.002 PubMed DOI

Castrini  AI, Skjølsvik  E, Estensen  ME, Almaas  VM, Skulstad  H, Lyseggen  E, et al.  Pregnancy and progression of cardiomyopathy in women with LMNA genotype-positive. J Am Heart Assoc  2022;11:e024960. doi: 10.1161/jaha.121.024960 PubMed DOI PMC

Ware  JS, Li  J, Mazaika  E, Yasso  CM, DeSouza  T, Cappola  TP, et al.  Shared genetic predisposition in peripartum and dilated cardiomyopathies. N Engl J Med  2016;374:233–41. doi: 10.1056/NEJMoa1505517 PubMed DOI PMC

van Spaendonck-Zwarts  KY, Posafalvi  A, van den Berg  MP, Hilfiker-Kleiner  D, Bollen  IA, Sliwa  K, et al.  Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy. Eur Heart J  2014;35:2165–73. doi: 10.1093/eurheartj/ehu050 PubMed DOI

Ware  JS, Amor-Salamanca  A, Tayal  U, Govind  R, Serrano  I, Salazar-Mendiguchia  J, et al.  Genetic etiology for alcohol-induced cardiac toxicity. J Am Coll Cardiol  2018;71:2293–302. doi: 10.1016/j.jacc.2018.03.462 PubMed DOI PMC

Gulati  G, Heck  SL, Ree  AH, Hoffmann  P, Schulz-Menger  J, Fagerland  MW, et al.  Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2  ×  2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J  2016;37:1671–80. doi: 10.1093/eurheartj/ehw022 DOI

Brown  SA, Okwuosa  TM, Barac  A, Volgman  AS. The role of angiotensin-converting enzyme inhibitors and β-blockers in primary prevention of cardiac dysfunction in breast cancer patients. J Am Heart Assoc  2020;9:e015327. doi: 10.1161/jaha.119.015327 PubMed DOI PMC

Odagiri  F, Inoue  H, Sugihara  M, Suzuki  T, Murayama  T, Shioya  T, et al.  Effects of candesartan on electrical remodeling in the hearts of inherited dilated cardiomyopathy model mice. PLoS One  2014;9:e101838. doi: 10.1371/journal.pone.0101838 PubMed DOI PMC

Domínguez  F, Lalaguna  L, López-Olañeta  M, Villalba-Orero  M, Padrón-Barthe  L, Román  M, et al.  Early preventive treatment with enalapril improves cardiac function and delays mortality in mice with arrhythmogenic right ventricular cardiomyopathy type 5. Circ Heart Fail  2021;14:e007616. doi: 10.1161/circheartfailure.120.007616 PubMed DOI

Duboc  D, Meune  C, Lerebours  G, Devaux  JY, Vaksmann  G, Bécane  HM. Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol  2005;45:855–7. doi: 10.1016/j.jacc.2004.09.078 PubMed DOI

Raman  SV, Hor  KN, Mazur  W, Halnon  NJ, Kissel  JT, He  X, et al.  Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol  2015;14:153–61. doi: 10.1016/s1474-4422(14)70318-7 PubMed DOI PMC