Skip to main content
SpringerLink
Log in

High ECG Risk-Scores Predict Late Gadolinium Enhancement on Magnetic Resonance Imaging in HCM in the Young

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

An ECG risk-score has been described that predicts high risk of subsequent cardiac arrest in young patients with hypertrophic cardiomyopathy (HCM). Myocardial fibrosis measured by cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) also affects prognosis. We assessed whether an ECG risk-score could be used as an indicator of myocardial fibrosis or perfusion deficit on CMR in HCM. In total 42 individuals (7–31 years); 26 HCM patients, seven genotype-positive, phenotype-negative individuals at risk of HCM (first-degree relatives) and nine healthy volunteers, underwent CMR to identify, and grade extent of, myocardial fibrosis and perfusion defect. 12-lead ECG was used for calculating the ECG risk-score (grading 0–14p). High-risk ECG (risk-score > 5p) occurred only in the HCM group (9/26), and the proportion was significantly higher vs mutation carriers combined with healthy volunteers (0/16, p = 0.008). Extent of LGE correlated to the ECG-score (R2 = 0.47, p = 0.001) in sarcomeric mutations. In low-risk ECG-score patients (0–2p), median percent of myocardium showing LGE (LGE%LVM) were: 0% [interquartile range, IQR, 0–0%], in intermediate-risk (3–5p): 5.4% [IQR 0–13.5%] and in high-risk (6–14p): 10.9% [IQR 4.2–12.3%]. ECG-score > 2p had a sensitivity and specificity of 79% and 84% to detect positive LGE on CMR and 77% vs. 75% to detect perfusion defects in sarcomeric mutations carriers. In patients with myocardial fibrosis as identified by LGE, median ECG risk-score was 8p [range 3–10p]. In conclusions, ECG risk-score > 2 p could be used as a cut-off for screening of myocardial fibrosis. Thus ECG risk-score is an inexpensive complementary tool in risk stratification of HCM in the young.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data Availability

Data and material are available after contacting the corresponding author.

Code Availability

Microsoft Office, SPSS and MedCalc (https://www.medcalc.org/calc/diagnostic_test.php).

References

  1. Maron BJ, Maron MS (2013) Hypertrophic cardiomyopathy. Lancet 381(9862):242–255. https://doi.org/10.1016/S0140-6736(12)60397-3

    Article  PubMed  Google Scholar 

  2. Moak JP, Kaski JP (2012) Hypertrophic cardiomyopathy in children. Heart 98(14):1044–1054. https://doi.org/10.1136/heartjnl-2011-300531

    Article  PubMed  Google Scholar 

  3. Basso C, Thiene G, Corrado D, Buja G, Melacini P, Nava A (2000) Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia. Hum Pathol 31(8):988–998. https://doi.org/10.1053/hupa.2000.16659

    Article  CAS  PubMed  Google Scholar 

  4. Gyllenhammar T, Fernlund E, Jablonowski R, Jogi J, Engblom H, Liuba P, Arheden H, Carlsson M (2014) Young patients with hypertrophic cardiomyopathy, but not subjects at risk, show decreased myocardial perfusion reserve quantified with CMR. Eur Heart J Cardiovasc Imaging 15(12):1350–1357. https://doi.org/10.1093/ehjci/jeu137

    Article  PubMed  Google Scholar 

  5. Camaioni C, Knott KD, Augusto JB, Seraphim A, Rosmini S, Ricci F, Boubertakh R, Xue H, Hughes R, Captur G, Lopes LR, Brown LAE, Manisty C, Petersen SE, Plein S, Kellman P, Mohiddin SA, Moon JC (2019) Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy. Heart. https://doi.org/10.1136/heartjnl-2019-315848

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jablonowski R, Fernlund E, Aletras AH, Engblom H, Heiberg E, Liuba P, Arheden H, Carlsson M (2015) Regional stress-induced ischemia in non-fibrotic hypertrophied myocardium in young HCM patients. PediatrCardiol 36(8):1662–1669. https://doi.org/10.1007/s00246-015-1214-5

    Article  Google Scholar 

  7. Bravo PE, Zimmerman SL, Luo HC, Pozios I, Rajaram M, Pinheiro A, Steenbergen C, Kamel IR, Wahl RL, Bluemke DA, Bengel FM, Abraham MR, Abraham TP (2013) Relationship of delayed enhancement by magnetic resonance to myocardial perfusion by positron emission tomography in hypertrophic cardiomyopathy. CircCardiovasc Imaging 6(2):210–217. https://doi.org/10.1161/CIRCIMAGING.112.000110

    Article  Google Scholar 

  8. Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ (2000) Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Heart 84(5):476–482. https://doi.org/10.1136/heart.84.5.476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Moon JC, McKenna WJ, McCrohon JA, Elliott PM, Smith GC, Pennell DJ (2003) Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance. J Am CollCardiol 41(9):1561–1567. https://doi.org/10.1016/s0735-1097(03)00189-x

    Article  Google Scholar 

  10. O’Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R, Webb J, Kulkarni M, Dawson D, Sulaibeekh L, Chandrasekaran B, Bucciarelli-Ducci C, Pasquale F, Cowie MR, McKenna WJ, Sheppard MN, Elliott PM, Pennell DJ, Prasad SK (2010) Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am CollCardiol 56(11):867–874. https://doi.org/10.1016/j.jacc.2010.05.010

    Article  Google Scholar 

  11. Adabag AS, Maron BJ, Appelbaum E, Harrigan CJ, Buros JL, Gibson CM, Lesser JR, Hanna CA, Udelson JE, Manning WJ, Maron MS (2008) Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance. J Am CollCardiol 51(14):1369–1374. https://doi.org/10.1016/j.jacc.2007.11.071

    Article  Google Scholar 

  12. Neubauer S, Kolm P, Ho CY, Kwong RY, Desai MY, Dolman SF, Appelbaum E, Desvigne-Nickens P, DiMarco JP, Friedrich MG, Geller N, Harper AR, Jarolim P, Jerosch-Herold M, Kim DY, Maron MS, Schulz-Menger J, Piechnik SK, Thomson K, Zhang C, Watkins H, Weintraub WS, Kramer CM, Investigators H (2019) Distinct subgroups in hypertrophic cardiomyopathy in the NHLBI HCM registry. J Am CollCardiol 74(19):2333–2345. https://doi.org/10.1016/j.jacc.2019.08.1057

    Article  CAS  Google Scholar 

  13. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW, American College of Cardiology Foundation/American Heart Association Task Force on Practice G (2011) 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am CollCardiol 58(25):e212-260. https://doi.org/10.1016/j.jacc.2011.06.011

    Article  CAS  Google Scholar 

  14. Authors/Task Force m, Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H (2014) 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 35(39):2733–2779. https://doi.org/10.1093/eurheartj/ehu284

    Article  Google Scholar 

  15. Ostman-Smith I, Wisten A, Nylander E, Bratt EL, Granelli A, Oulhaj A, Ljungstrom E (2010) Electrocardiographic amplitudes: a new risk factor for sudden death in hypertrophic cardiomyopathy. Eur Heart J 31(4):439–449. https://doi.org/10.1093/eurheartj/ehp443

    Article  PubMed  Google Scholar 

  16. Ostman-Smith I, Sjoberg G, Rydberg A, Larsson P, Fernlund E (2017) Predictors of risk for sudden death in childhood hypertrophic cardiomyopathy: the importance of the ECG risk score. Open Heart 4(2):e000658. https://doi.org/10.1136/openhrt-2017-000658

    Article  PubMed  PubMed Central  Google Scholar 

  17. McLeod CJ, Ackerman MJ, Nishimura RA, Tajik AJ, Gersh BJ, Ommen SR (2009) Outcome of patients with hypertrophic cardiomyopathy and a normal electrocardiogram. J Am CollCardiol 54(3):229–233. https://doi.org/10.1016/j.jacc.2009.02.071

    Article  Google Scholar 

  18. O’Mahony C, Jichi F, Pavlou M, Monserrat L, Anastasakis A, Rapezzi C, Biagini E, Gimeno JR, Limongelli G, McKenna WJ, Omar RZ, Elliott PM, Hypertrophic Cardiomyopathy Outcomes I (2014) A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur Heart J 35(30):2010–2020. https://doi.org/10.1093/eurheartj/eht439

    Article  PubMed  Google Scholar 

  19. Norrish G, Ding T, Field E, Ziolkowska L, Olivotto I, Limongelli G, Anastasakis A, Weintraub R, Biagini E, Ragni L, Prendiville T, Duignan S, McLeod K, Ilina M, Fernandez A, Bokenkamp R, Baban A, Kubus P, Daubeney PEF, Sarquella-Brugada G, Cesar S, Marrone C, Bhole V, Medrano C, Uzun O, Brown E, Gran F, Castro FJ, Stuart G, Vignati G, Barriales-Villa R, Guereta LG, Adwani S, Linter K, Bharucha T, Garcia-Pavia P, Rasmussen TB, Calcagnino MM, Jones CB, De Wilde H, Toru-Kubo J, Felice T, Mogensen J, Mathur S, Reinhardt Z, O’Mahony C, Elliott PM, Omar RZ, Kaski JP (2019) Development of a novel risk prediction model for sudden cardiac death in childhood hypertrophic cardiomyopathy (HCM risk-kids). JAMA Cardiol. https://doi.org/10.1001/jamacardio.2019.2861

    Article  PubMed  PubMed Central  Google Scholar 

  20. Miron A, Lafreniere-Roula M, Steve Fan CP, Armstrong KR, Dragulescu A, Papaz T, Manlhiot C, Kaufman B, Butts RJ, Gardin L, Stephenson EA, Howard TS, Aziz PF, Balaji S, Ladouceur VB, Benson LN, Colan SD, Godown J, Henderson HT, Ingles J, Jeewa A, Jefferies JL, Lal AK, Mathew J, Jean-St-Michel E, Michels M, Nakano SJ, Olivotto I, Parent JJ, Pereira AC, Semsarian C, Whitehill RD, Wittekind SG, Russell MW, Conway J, Richmond ME, Villa C, Weintraub RG, Rossano JW, Kantor PF, Ho CY, Mital S (2020) A validated model for sudden cardiac death risk prediction in pediatric hypertrophic cardiomyopathy. Circulation 142(3):217–229. https://doi.org/10.1161/CIRCULATIONAHA.120.047235

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pettersen MD, Du W, Skeens ME, Humes RA (2008) Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study. J Am SocEchocardiogr 21(8):922–934. https://doi.org/10.1016/j.echo.2008.02.006

    Article  Google Scholar 

  22. Ostman-Smith I (2010) Hypertrophic cardiomyopathy in childhood and adolescence—strategies to prevent sudden death. FundamClinPharmacol 24(5):637–652. https://doi.org/10.1111/j.1472-8206.2010.00869.x

    Article  CAS  Google Scholar 

  23. Heiberg E, Sjogren J, Ugander M, Carlsson M, Engblom H, Arheden H (2010) Design and validation of Segment–freely available software for cardiovascular image analysis. BMC Med Imaging 10:1. https://doi.org/10.1186/1471-2342-10-1

    Article  PubMed  PubMed Central  Google Scholar 

  24. Engblom H, Tufvesson J, Jablonowski R, Carlsson M, Aletras AH, Hoffmann P, Jacquier A, Kober F, Metzler B, Erlinge D, Atar D, Arheden H, Heiberg E (2016) A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data. J CardiovascMagnReson 18(1):27. https://doi.org/10.1186/s12968-016-0242-5

    Article  Google Scholar 

  25. Crilley JG, Boehm EA, Blair E, Rajagopalan B, Blamire AM, Styles P, McKenna WJ, Ostman-Smith I, Clarke K, Watkins H (2003) Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J Am CollCardiol 41(10):1776–1782. https://doi.org/10.1016/s0735-1097(02)03009-7

    Article  CAS  Google Scholar 

  26. Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG, Seidman CE (2002) Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 109(3):357–362. https://doi.org/10.1172/JCI14571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Banankhah P, Fishbein GA, Dota A, Ardehali R (2018) Cardiac manifestations of PRKAG2 mutation. BMC Med Genet 19(1):1. https://doi.org/10.1186/s12881-017-0512-6

    Article  PubMed  PubMed Central  Google Scholar 

  28. Park CH, Chung H, Kim Y, Kim JY, Min PK, Lee KA, Yoon YW, Kim TH, Lee BK, Hong BK, Rim SJ, Kwon HM, Choi EY (2018) Electrocardiography based prediction of hypertrophy pattern and fibrosis amount in hypertrophic cardiomyopathy: comparative study with cardiac magnetic resonance imaging. Int J Cardiovasc Imaging 34(10):1619–1628. https://doi.org/10.1007/s10554-018-1365-6

    Article  PubMed  Google Scholar 

  29. Delcre SD, Di Donna P, Leuzzi S, Miceli S, Bisi M, Scaglione M, Caponi D, Conte MR, Cecchi F, Olivotto I, Gaita F (2013) Relationship of ECG findings to phenotypic expression in patients with hypertrophic cardiomyopathy: a cardiac magnetic resonance study. Int J Cardiol 167(3):1038–1045. https://doi.org/10.1016/j.ijcard.2012.03.074

    Article  PubMed  Google Scholar 

  30. Chen X, Zhao T, Lu M, Yin G, Xiangli W, Jiang S, Prasad S, Zhao S (2014) The relationship between electrocardiographic changes and CMR features in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. Int J Cardiovasc Imaging 30(Suppl 1):55–63. https://doi.org/10.1007/s10554-014-0416-x

    Article  PubMed  Google Scholar 

  31. Morimoto Y, Miyazaki A, Tsuda E, Hayama Y, Negishi J, Ohuchi H (2020) Electrocardiographic changes and long-term prognosis of children diagnosed with hypertrophic cardiomyopathy by the school screening program for heart disease in Japan. J Cardiol 75(5):571–577. https://doi.org/10.1016/j.jjcc.2019.10.008

    Article  PubMed  Google Scholar 

  32. Grall S, Biere L, Clerfond G, Mateus V, Prunier F, Furber A (2014) ECG characteristics according to the presence of late gadolinium enhancement on cardiac MRI in hypertrophic cardiomyopathy. Open Heart 1(1):e000101. https://doi.org/10.1136/openhrt-2014-000101

    Article  PubMed  PubMed Central  Google Scholar 

  33. Axelsson Raja A, Farhad H, Valente AM, Couce JP, Jefferies JL, Bundgaard H, Zahka K, Lever H, Murphy AM, Ashley E, Day SM, Sherrid MV, Shi L, Bluemke DA, Canter CE, Colan SD, Ho CY (2018) Prevalence and progression of late gadolinium enhancement in children and adolescents with hypertrophic cardiomyopathy. Circulation 138(8):782–792. https://doi.org/10.1161/CIRCULATIONAHA.117.032966

    Article  PubMed  Google Scholar 

  34. Rubinshtein R, Glockner JF, Ommen SR, Araoz PA, Ackerman MJ, Sorajja P, Bos JM, Tajik AJ, Valeti US, Nishimura RA, Gersh BJ (2010) Characteristics and clinical significance of late gadolinium enhancement by contrast-enhanced magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Circ Heart Fail 3(1):51–58. https://doi.org/10.1161/CIRCHEARTFAILURE.109.854026

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are deeply grateful to the support from the study participants during the study. The authors would like to thank the technicians Ann-Helen Arvidsson and Christel Carlander for their help with CMR data acquisition. Special thanks to research nurse Annika Maxedius for excellent support in the study.

Funding

This study has been possible by support and grants from Region Ostergotland (ALF and the Office for Trainee and Fellowship programs), the Strategic Research Area in Forensic Science, Schelins Foundation and FORSS (Medical Research Council of Southeast Sweden).

Author information

Authors and Affiliations

  1. Crown Princess Victoria Children’s Hospital, Department of Biomedical and Clinical Sciences, Department of Pediatrics, Linköping University, 581 85, Linköping, Sweden

    Anna Wålinder Österberg & Eva Fernlund

  2. Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Ingegerd Östman-Smith

  3. Clinical Physiology, Department of Clinical Sciences, Lund University, Lund, Sweden

    Robert Jablonowski & Marcus Carlsson

  4. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden

    Henrik Green

  5. Division of Drug Research, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden

    Henrik Green

  6. Department of Clinical Genetics, Department of Biomedical and Clinical Sciences, Centre for Rare Diseases in South East Region of Sweden, Linköping University, Linköping, Sweden

    Cecilia Gunnarsson

  7. Pediatric Heart Centre, Skåne University Hospital and Department of Clinical Sciences, Lund University, Lund, Sweden

    Petru Liuba & Eva Fernlund

Authors
  1. Anna Wålinder Österberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ingegerd Östman-Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Jablonowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcus Carlsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henrik Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cecilia Gunnarsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Petru Liuba
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eva Fernlund
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by AWÖ, RJ, MC, and EF. Analysis was performed by AWÖ with support from all other authors. The first draft of the manuscript was written by AWÖ and all authors commented on previous versions of the manuscript. All authors have read and approved the final manuscript. All the above authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Corresponding author

Correspondence to Eva Fernlund.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical Approval

The study was approved by the Regional Ethical Review Board in Lund, Sweden, H15 2009/616 and 2011/668. The study conforms to the ethical guidelines of the 1975 Declaration of Helsinki.

Informed Consent

An informed consent was obtained from all participants or their legal guardians (for participants < 18 years of age).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 262 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Österberg, A.W., Östman-Smith, I., Jablonowski, R. et al. High ECG Risk-Scores Predict Late Gadolinium Enhancement on Magnetic Resonance Imaging in HCM in the Young. Pediatr Cardiol 42, 492–500 (2021). https://doi.org/10.1007/s00246-020-02506-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-020-02506-9

Keywords

Search

Navigation