Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy

Circulation Arrhythmia and Electrophysiology, vol. 15, pp. e010075

Abstract

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. Methods: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1–16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). Results: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3–9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Authors 59

1. Gabrielle Norrish

   Great Ormond Street Hospital · University College London

   Affiliation as printed

   Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (G.N., E.F., E.C., J.P.K.)

   Institute of Cardiovascular Sciences (G.N., C.O., P.M.E., J.P.K.), University College London, United Kingdom

   Gabrielle Norrish Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (G.N., E.F., E.C., J.P.K.). Institute of Cardiovascular Sciences (G.N., C.O., P.M.E., J.P.K.), University College London, United Kingdom

2. Tao Ding

   University College London

   Affiliation as printed

   Department of Statistical Science (T.D., R.Z.O.), University College London, United Kingdom

   Tao Ding Department of Statistical Science (T.D., R.Z.O.), University College London, United Kingdom

3. Ella Field

   Great Ormond Street Hospital

   Affiliation as printed

   Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (G.N., E.F., E.C., J.P.K.)

   Ella Field https://orcid.org/0000-0002-0808-2763 Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (G.N., E.F., E.C., J.P.K.)

4. Elena Cervi

   Great Ormond Street Hospital

   Affiliation as printed

   Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (G.N., E.F., E.C., J.P.K.)

   Elena Cervi https://orcid.org/0000-0003-2612-1014 Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (G.N., E.F., E.C., J.P.K.)

5. Lidia Ziółkowska

   Children's Memorial Health Institute

   Affiliation as printed

   The Children’s Memorial Health Institute, Warsaw, Poland (L.Z.)

6. Iacopo Olivotto

   Azienda Ospedaliero-Universitaria Careggi

   Affiliation as printed

   Careggi University Hopsital, Florence, Italy (I.O.)

   Iacopo Olivotto https://orcid.org/0000-0003-1751-9266 Careggi University Hopsital, Florence, Italy (I.O.)

7. Diala Khraiche

   Hôpital Necker-Enfants Malades · Institut Necker Enfants Malades

   Affiliation as printed

   Necker–Enfants Malades Hospital, Paris, France (D.K.)

8. Giuseppe Limongelli

   Ospedale Monaldi

   Affiliation as printed

   Monaldi Hospital, Naples, Italy (G.L.)

   Giuseppe Limongelli https://orcid.org/0000-0002-8291-9517 Monaldi Hospital, Naples, Italy (G.L.)

9. Aris Anastasakis

   Onassis Cardiac Surgery Center

   Affiliation as printed

   Onassis Cardiac Surgery Center, Athens, Greece (A.A.)

   Aris Anastasakis Onassis Cardiac Surgery Center, Athens, Greece (A.A.)

10. Robert Gideon Weintraub

    Royal Children's Hospital

    Affiliation as printed

    Royal Children’s Hospital, Melbourne, Australia (R.W.)

    Robert Weintraub https://orcid.org/0000-0001-7324-8697 Royal Children's Hospital, Melbourne, Australia (R.W.)

11. Elena Biagini

    IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola

    Affiliation as printed

    Cardiology Unit, S. Orsola-Malpighi Hospital, IRCCS Azienda Ospedalierao-Universitaria di Bologna, Italy (E.B., L.R.)

    Elena Biagini https://orcid.org/0000-0003-0295-0440 Cardiology Unit, S. Orsola-Malpighi Hospital, IRCCS Azienda Ospedalierao-Universitaria di Bologna, Italy (E.B., L.R.)

12. Luca Ragni

    IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola · University of Bologna

    Affiliation as printed

    Cardiology Unit, S. Orsola-Malpighi Hospital, IRCCS Azienda Ospedalierao-Universitaria di Bologna, Italy (E.B., L.R.)

    Luca Ragni Cardiology Unit, S. Orsola-Malpighi Hospital, IRCCS Azienda Ospedalierao-Universitaria di Bologna, Italy (E.B., L.R.)

13. Terrence Prendiville

    Children's Health Ireland at Crumlin

    Affiliation as printed

    Our Lady’s Children’s Hospital, Dublin, Ireland (T.P., S.D.)

    Terrence Prendiville https://orcid.org/0000-0002-3824-636X Our Lady's Children's Hospital, Dublin, Ireland (T.P., S.D.)

14. Sophie M. Duignan

    Royal Hospital for Children

    Affiliation as printed

    Royal Hospital for Children, Glasgow, United Kingdom (K.M., M.I.)

    Sophie Duignan https://orcid.org/0000-0002-0384-1193 Royal Hospital for Children, Glasgow, United Kingdom (K.M., M.I.)

15. KAREN A. McLEOD

    Royal Hospital for Children

    Affiliation as printed

    Royal Hospital for Children, Glasgow, United Kingdom (K.M., M.I.)

    Karen McLeod Royal Hospital for Children, Glasgow, United Kingdom (K.M., M.I.)

16. Maria V. Ilina

    Royal Hospital for Children

    Affiliation as printed

    Royal Hospital for Children, Glasgow, United Kingdom (K.M., M.I.)

    Maria Ilina https://orcid.org/0000-0002-6930-9343 Royal Hospital for Children, Glasgow, United Kingdom (K.M., M.I.)

17. Adrián Fernández

    Favaloro University · Fundacion Favaloro Hospital Universitario

    Affiliation as printed

    Fundación Favaloro University Hospital, Buenos Aires, Argentina (A.F.)

18. Chiara Marrone

    Ospedale Papa Giovanni XXIII

    Affiliation as printed

    Papa Giovanni XXIII Hospital, Bergamo (C.M.)

    Chiara Marrone Papa Giovanni XXIII Hospital, Bergamo (C.M.)

19. Regina Bökenkamp Aachen

    Leiden University Medical Center

    Affiliation as printed

    Leiden University Medical Center, the Netherlands (R.B.)

20. Anwar Baban

    Bambino Gesù Children's Hospital

    Affiliation as printed

    Bambino Gesu Hospital, Rome, Italy (A.B.)

    Anwar Baban https://orcid.org/0000-0002-9428-4934 Bambino Gesu Hospital, Rome, Italy (A.B.)

21. Peter Kubuš

    University Hospital in Motol

    Affiliation as printed

    University Hospital Motol, Prague, Czech Republic (P.K.)

    Peter Kubus University Hospital Motol, Prague, Czech Republic (P.K.)

22. Piers E.F. Daubeney

    Royal Brompton & Harefield NHS Foundation Trust · Harefield Hospital

    Affiliation as printed

    Royal Brompton and Harefield NHS Trust, London, United Kingdom (P.E.F.D.)

    Piers E.F. Daubeney Royal Brompton and Harefield NHS Trust, London, United Kingdom (P.E.F.D.)

23. Georgia Sarquella‐Brugada
    Affiliation as printed

    Sant Joan de Deu, Barcelona, Spain (G.S.-B., S.C.)

    Georgia Sarquella-Brugada https://orcid.org/0000-0002-6857-8904 Sant Joan de Deu, Barcelona, Spain (G.S.-B., S.C.)

24. Sergi César
    Affiliation as printed

    Sant Joan de Deu, Barcelona, Spain (G.S.-B., S.C.)

    Sergi Cesar https://orcid.org/0000-0002-2798-1756 Sant Joan de Deu, Barcelona, Spain (G.S.-B., S.C.)

25. Sabine Klaassen

    Max Delbrück Center · German Centre for Cardiovascular Research · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Department of Pediatric Cardiology (S.K.), Charite–Universitatsmedizin Berlin, Germany

    Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück-Center for Molecular Medicine (S.K.), Charite–Universitatsmedizin Berlin, Germany

    German Centre for Cardiovascular Research, Partner Site Berlin, Germany (S.K.)

26. Tiina H. Ojala

    University of Helsinki

    Affiliation as printed

    Department of Pediatric Cardiology, Pediatric Research Center, New Children’s Hospital, University of Helsinki, Finland (T.H.O.)

    Tiina H. Ojala https://orcid.org/0000-0001-9092-7763 Department of Pediatric Cardiology, Pediatric Research Center, New Children's Hospital, University of Helsinki, Finland (T.H.O.)

27. Vinay Bhole

    Birmingham Children's Hospital

    Affiliation as printed

    Birmingham Children’s Hospital, United Kingdom (V.B.)

    Vinay Bhole Birmingham Children's Hospital, United Kingdom (V.B.)

28. Constancio Medrano

    Hospital General Universitario Gregorio Marañón · Fondazione Toscana Gabriele Monasterio

    Affiliation as printed

    Fondazione Toscana G. Monasterio, Massa-Pisa, Italy (C.M.)

    Hospital General Universitario Gregorio Marañón, Madrid, Spain (C.M.)

29. Orhan Uzun

    University Hospital of Wales

    Affiliation as printed

    University Hospital of Wales, Cardiff (O.U.)

    Orhan Uzun https://orcid.org/0000-0002-0565-9627 University Hospital of Wales, Cardiff (O.U.)

30. Elspeth Brown

    Leeds General Infirmary

    Affiliation as printed

    Leeds General Infirmary, United Kingdom (E.B.)

    Elspeth Brown https://orcid.org/0000-0002-7229-7881 Leeds General Infirmary, United Kingdom (E.B.)

31. Ferrán Gran

    Vall d'Hebron Hospital Universitari

    Affiliation as printed

    Val d’Hebron University Hospital, Barcelona, Spain (F.G.)

    Ferran Gran https://orcid.org/0000-0001-9076-241X Val d'Hebron University Hospital, Barcelona, Spain (F.G.)

32. Gianfranco Sinagra

    University of Trieste

    Affiliation as printed

    Heart Muscle Disease Registry Trieste, University of Trieste, Italy (G.S.)

    Gianfranco Sinagra https://orcid.org/0000-0003-2700-8478 Heart Muscle Disease Registry Trieste, University of Trieste, Italy (G.S.)

33. Francisco José Castro

    Hospital Universitario Virgen de la Arrixaca

    Affiliation as printed

    University Hospital Virgen de la Arrixaca, Murcia, Spain (F.J.C.)

    Francisco J. Castro https://orcid.org/0000-0003-2862-0749 University Hospital Virgen de la Arrixaca, Murcia, Spain (F.J.C.)

34. Graham Stuart

    Bristol Royal Hospital for Children

    Affiliation as printed

    Bristol Royal Hospital for Children, United Kingdom (G.S.)

    Graham Stuart https://orcid.org/0000-0003-2789-2216 Bristol Royal Hospital for Children, United Kingdom (G.S.)

35. Gabriele Vignati

    Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

    Affiliation as printed

    Niguarda Hospital, Milan, Italy (G.V.)

    Gabriele Vignati https://orcid.org/0000-0002-9654-4226 Niguarda Hospital, Milan, Italy (G.V.)

36. Hirokuni Yamazawa

    Hokkaido University · Hokkaido University Hospital

    Affiliation as printed

    Department of Pediatrics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Hospital, Sapporo, Japan (H.Y.)

    Hirokuni Yamazawa https://orcid.org/0000-0002-9257-5623 Department of Pediatrics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Hospital, Sapporo, Japan (H.Y.)

37. Roberto Barriales Villa

    Centro de Investigación en Red en Enfermedades Cardiovasculares · Complexo Hospitalario Universitario A Coruña · Instituto de Investigación Biomédica de A Coruña

    Affiliation as printed

    Complexo Hospitalario Universitario A Coruna, INIBIC, CIBERCV, Spain (R.B.-V.)

    Roberto Barriales-Villa https://orcid.org/0000-0002-6721-3487 Complexo Hospitalario Universitario A Coruna, INIBIC, CIBERCV, Spain (R.B.-V.)

38. Luis Garcı́a-Guereta

    Hospital Universitario La Paz

    Affiliation as printed

    University Hospital La Paz, Madrid, Spain (L.G.-G.)

    Luis Garcia-Guereta https://orcid.org/0000-0003-4675-365X University Hospital La Paz, Madrid, Spain (L.G.-G.)

39. Satish Adwani

    John Radcliffe Hospital

    Affiliation as printed

    John Radcliffe Hospital, Oxford (S.A.)

    Satish Adwani https://orcid.org/0000-0002-4693-5309 John Radcliffe Hospital, Oxford (S.A.)

40. Katie Linter

    Glenfield Hospital

    Affiliation as printed

    Glenfield Hospital, Leicester (K.L.)

    Katie Linter Glenfield Hospital, Leicester (K.L.)

41. Tara Bharucha

    Southampton General Hospital

    Affiliation as printed

    Southampton General Hospital, Southampton, United Kingdom (T.B.)

    Tara Bharucha https://orcid.org/0000-0003-2713-8125 Southampton General Hospital, Southampton, United Kingdom (T.B.)

42. Pablo García‐Pavía

    Hospital Universitario Puerta de Hierro Majadahonda

    Affiliation as printed

    Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain (P.G.-P., A.S.)

    Pablo Garcia-Pavia Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain (P.G.-P., A.S.)

43. Ana Siles

    Hospital Universitario Puerta de Hierro Majadahonda

    Affiliation as printed

    Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain (P.G.-P., A.S.)

    Ana Siles https://orcid.org/0000-0002-7122-2132 Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain (P.G.-P., A.S.)

44. Torsten B. Rasmussen

    Aarhus University Hospital

    Affiliation as printed

    Aarhus University Hospital, Denmark (T.B.R.)

    Torsten B. Rasmussen https://orcid.org/0000-0003-1468-7248 Aarhus University Hospital, Denmark (T.B.R.)

45. Margherita Maria Calcagnino

    Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Affiliation as printed

    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, Dept di Medicina Interna, UOC Cardiologica, Milano, Italy (M.C.)

    Margherita Calcagnino https://orcid.org/0000-0001-9781-0031 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Dept di Medicina Interna, UOC Cardiologica, Milano, Italy (M.C.)

46. Caroline B. Jones

    Alder Hey Children's Hospital

    Affiliation as printed

    Alder Hey Children’s Hospital, Liverpool, United Kingdom (C.B.J.)

    Caroline B. Jones https://orcid.org/0000-0002-5105-6384 Alder Hey Children's Hospital, Liverpool, United Kingdom (C.B.J.)

47. Hans De Wilde

    Ghent University Hospital

    Affiliation as printed

    Ghent University Hospital, Belgium (H.D.W.)

    Hans De Wilde https://orcid.org/0000-0003-0284-6889 Ghent University Hospital, Belgium (H.D.W.)

48. Toru Kubo

    Kochi Medical School Hospital

    Affiliation as printed

    Kochi Medical School Hospital, Japan (T.K.)

    Toru Kubo https://orcid.org/0000-0001-5681-8854 Kochi Medical School Hospital, Japan (T.K.)

49. Tiziana Felice

    Mater Dei Hospital

    Affiliation as printed

    Mater Dei Hospital, Malta (T.F.)

    Tiziana Felice https://orcid.org/0000-0002-8220-5848 Mater Dei Hospital, Malta (T.F.)

50. Anca Popoiu

    Victor Babeș University of Medicine and Pharmacy Timișoara · Spitalul Clinic Dr. Victor Babes

    Affiliation as printed

    Department of Pediatrics, University of Medicine and Pharmacy “Victor Babes” Timisoara, Children’s Hospital ‘Louis Turcanu,’ Romania (A.P.)

    Anca Popoiu https://orcid.org/0000-0002-8029-5472 Department of Pediatrics, University of Medicine and Pharmacy "Victor Babes" Timisoara, Children's Hospital 'Louis Turcanu,' Romania (A.P.)

51. Jens Mogensen

    Aalborg University Hospital

    Affiliation as printed

    Aalborg University Hospital, Denmark (J.M.)

    Jens Mogensen https://orcid.org/0000-0002-8813-573X Aalborg University Hospital, Denmark (J.M.)

52. Sujeev Mathur

    Evelina London Children's Healthcare

    Affiliation as printed

    Evelina Children’s Hospital, London, United Kingdom (S.M.)

    Sujeev Mathur Evelina Children's Hospital, London, United Kingdom (S.M.)

53. Fernando Centeno-Malfaz

    Hospital Universitario Río Hortega

    Affiliation as printed

    Rio Hortega University Hospital, Valladolid, Spain (F.C.)

    Fernando Centeno https://orcid.org/0000-0002-4816-7649 Rio Hortega University Hospital, Valladolid, Spain (F.C.)

54. Zdenka Reinhardt

    Freeman Hospital

    Affiliation as printed

    The Freeman Hospital, Newcastle, United Kingdom (Z.R.)

    Zdenka Reinhardt https://orcid.org/0000-0002-4446-1138 The Freeman Hospital, Newcastle, United Kingdom (Z.R.)

55. Sylvie Schouvey

    Hôpital Saint Joseph

    Affiliation as printed

    Hospital Saint Joseph, Marseille, France (S.S.)

    Sylvie Schouvey Hospital Saint Joseph, Marseille, France (S.S.)

56. Costas O’Mahony

    St Bartholomew's Hospital · University College London

    Affiliation as printed

    Institute of Cardiovascular Sciences (G.N., C.O., P.M.E., J.P.K.), University College London, United Kingdom

    St Bartholomew’s Centre for Inherited Cardiovascular Diseases, St Bartholomew’s Hospital, West Smithfield, London, United Kingdom (C.O., P.M.E.)

    Costas O'Mahony Institute of Cardiovascular Sciences (G.N., C.O., P.M.E., J.P.K.), University College London, United Kingdom. St Bartholomew's Centre for Inherited Cardiovascular Diseases, St Bartholomew's Hospital, West Smithfield, London, United Kingdom (C.O., P.M.E.)

57. Rumana Omar

    University College London

    Affiliation as printed

    Department of Statistical Science (T.D., R.Z.O.), University College London, United Kingdom

    Rumana Z. Omar https://orcid.org/0000-0003-1483-1932 Department of Statistical Science (T.D., R.Z.O.), University College London, United Kingdom

58. Perry Mark Elliott

    St Bartholomew's Hospital · University College London

    Affiliation as printed

    Institute of Cardiovascular Sciences (G.N., C.O., P.M.E., J.P.K.), University College London, United Kingdom

    St Bartholomew’s Centre for Inherited Cardiovascular Diseases, St Bartholomew’s Hospital, West Smithfield, London, United Kingdom (C.O., P.M.E.)

    Perry M. Elliott https://orcid.org/0000-0003-3383-3984 Institute of Cardiovascular Sciences (G.N., C.O., P.M.E., J.P.K.), University College London, United Kingdom. St Bartholomew's Centre for Inherited Cardiovascular Diseases, St Bartholomew's Hospital, West Smithfield, London, United Kingdom (C.O., P.M.E.)

59. Juan Pablo Kaski corresponding

    Great Ormond Street Hospital · University College London

    Affiliation as printed

    Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (G.N., E.F., E.C., J.P.K.)

    Institute of Cardiovascular Sciences (G.N., C.O., P.M.E., J.P.K.), University College London, United Kingdom

    (Res), Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London WC1N 3JH, United Kingdom