Portal de Periódicos da CAPES

Extreme Left Ventricular Hypertrophy in Pediatric Hypertrophic Cardiomyopathy: Good News or Bad News?

2022; Lippincott Williams & Wilkins; Volume: 15; Issue: 5 Linguagem: Inglês

10.1161/circep.122.011033

1941-3149

Utkarsh Kohli, Elizabeth V. Saarel, Maully J. Shah,

Cardiac Arrhythmias and Treatments

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 15, No. 5Extreme Left Ventricular Hypertrophy in Pediatric Hypertrophic Cardiomyopathy: Good News or Bad News? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBExtreme Left Ventricular Hypertrophy in Pediatric Hypertrophic Cardiomyopathy: Good News or Bad News? Utkarsh Kohli, Elizabeth V. Saarel and Maully Shah Utkarsh KohliUtkarsh Kohli https://orcid.org/0000-0003-3410-840X Department of Pediatrics, Division of Pediatric Cardiology, West Virginia University School of Medicine and West Virginia University Medicine Children's Hospital, Morgantown (U.K.). , Elizabeth V. SaarelElizabeth V. Saarel https://orcid.org/0000-0002-3743-465X St. Luke's Pediatric Cardiology, Meridian, ID (E.V.S.). and Maully ShahMaully Shah Correspondence to: Maully Shah, MBBS, CCDS, CEPS, Cardiac Center, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, Email E-mail Address: [email protected] https://orcid.org/0000-0002-4743-6915 Department of Pediatrics, Division of Pediatric Cardiology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia (M.S.). Originally published2 May 2022https://doi.org/10.1161/CIRCEP.122.011033Circulation: Arrhythmia and Electrophysiology. 2022;15This article is a commentary on the followingRelationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic CardiomyopathyOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: May 2, 2022: Ahead of Print See Article by Norrish et alIn contrast to adults, the risk factors for sudden cardiac death (SCD) in children with hypertrophic cardiomyopathy (HCM) are less well defined and remain an area of active investigation.1–3Although maximal left ventricular wall thickness (MLVWT) ≥30 mm is a well-known risk factor for SCD in adults with HCM, the relationship is less well defined in pediatric patients.4–6 For children, this criteria is confounded by needing to adjust for body size and growth. The most recent iteration of American Heart Association guidelines for diagnosis and treatment of patients with HCM suggest an increased risk of SCD with MLVWT Z score of ≥20 or >10 in the presence of other risk factors, such as unexplained syncope, nonsustained VT, and family history of early HCM-related SCD.4Norrish et al5 sought to describe the relationship between left ventricular hypertrophy (LVH) and observed and predicted SCD risk from a retrospective, longitudinal study of a large cohort (n=1075) of children aged 10.2±4.4 years (1–16 years) with HCM enrolled in the International Pediatric Hypertrophic Cardiomyopathy Consortium. Based on severity of LVH, the patients were divided into groups (MLVWT Z score <10; ≥10–<20; and ≥20). The MLVWT Z score was <10 in 58.1%, between 10 and 20 in 31.1%, and ≥20 in 13.3% of the pediatric cohort. Not unexpectedly, higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. Coexisting risk factors for SCD were also more common in those with more severe LVH. In patients with MLVWT Z score ≥20, 71.3% had ≥1 coexisting risk factors for SCD. Over a median follow-up of 4.9 years, 10.7% of the cohort had an SCD event with an overall incidence of 1.7/100 patient-years at risk. Freedom from SCD event at 5 years for those with MLVWT Z score <10, ≥10 to <20 and ≥20 was 95.6%, 87.4%, and 86%, respectively. The authors showed that estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, and the presence of coexisting risk factors had an additive effect on risk.5 This study also shows that for a specified change in MLVWT, there seems to be a variable change both in the magnitude and direction of SCD risk, depending on the specific risk factors.This study follows the findings of an inverted U-shaped relationship between the risk of SCD and MLVWT in adults (≥16 years) by O'Mahony et al.6 The inverted U-shape of this relation implies that the estimated risk of SCD increases with worsening hypertrophy to reach plateau and declines thereafter. O'Mahony et al6 had shown that in adult patients, the cumulative incidence of SCD risk increased with 5 mm increments in MLVWT, but beyond MLVWT ≥35 mm the risk of SCD was not greater than the baseline HCM group with MLVWT≤14 mm. Similarly, Norrish et al5 have shown that estimated risk of SCD at 5 years peaked at an MLVWT Z score of +23; beyond which no further increase in risk was seen, and instead, there was a fall in the estimated risk of SCD. While no specific MLVWT Z score threshold for the decline in estimated SCD risk was set for children in this study, it appears that similar to adult patients, risk increases with worsening hypertrophy to reach a plateau and decreases thereafter. However, the median follow-up of 4.9 years in this study may be insufficient to draw any definitive conclusions regarding prognosis and freedom from SCD.There is no clear explanation as to why extreme LVH might confer a survival advantage, but the authors draw attention to an interesting and counterintuitive phenomenon that raises several questions. What are the potential factors thatunderlie this paradox? Are there protective factors that operate at the extremes of the MLVWT spectrum thereby increasing the arrhythmia threshold? Does the genetic substrate differ from patients with lesser degrees of LVH? Do some patients with extreme MLVWT have undiagnosed metabolic disorders? Although male preponderance is common in HCM, do variations in sex hormones affect arrhythmia risk? The presence of LV outflow tract obstruction as a SCD risk factor in children has been debated and recent studies have hypothesized that LV outflow obstruction may be protective against SCD.7,8 In this study, 40% of patients with MLVWT Z score ≥20 had LV outflow tract obstruction, and its role in arrhythmia risk, if any, needs further investigation. Advanced tissue characterization techniques with cardiac magnetic resonance and positron emission tomography across the LV wall thickness spectrum may improve our understanding of the thresholds for arrhythmogenesis in HCM.9 The current study emphasizes a need for a more thorough evaluation of factors that underlie arrhythmic risk in children with extreme hypertrophy.Several other findings from this study are noteworthy. The study argues against the traditional paradigm that increases in LVH are more common in adolescence.10 In this large pediatric cohort, LVH was variable and not dependent on age. Although an MLVWT Z score of ≥20 has been suggested for SCD risk stratification in the most recent iteration of American Heart Association guidelines,4 the findings of this study show an enhanced risk of SCD at MLVWT Z score of ≥10. Moreover, clinical findings such as unexplained syncope and nonsustained ventricular tachycardia and to a lesser extent, family history of SCD conferred an additional risk for arrhythmic events and SCD. The findings of this study are consistent with the findings of prior studies in children with HCM and, therefore, reaffirm the utilization of the current risk predictors for malignant arrhythmias and SCD in children with HCM.4,6,7,11,12The authors suggest that although MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillators implantation in children. For current scientific society guidelines and clinical practice to change, larger prospective studies with long-term follow-up are needed to inform practitioners of pediatric-specific risk factors for SCD in HCM.Article InformationDisclosures None.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 301.Correspondence to: Maully Shah, MBBS, CCDS, CEPS, Cardiac Center, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, Email shahm@chop.eduReferences1. Kamp AN, Von Bergen NH, Henrikson CA, Makhoul M, Saarel EV, Lapage MJ, Russell MW, Strieper M, Yu S, Dick M, et al. Implanted defibrillators in young hypertrophic cardiomyopathy patients: a multicenter study.Pediatr Cardiol. 2013; 34:1620–1627. doi: 10.1007/s00246-013-0676-6CrossrefMedlineGoogle Scholar2. Bharucha T, Lee KJ, Daubeney PE, Nugent AW, Turner C, Sholler GF, Robertson T, Justo R, Ramsay J, Carlin JB, et al; NACCS (National Australian Childhood Cardiomyopathy Study) Investigators. Sudden death in childhood cardiomyopathy: results from a long-term national population-based study.J Am Coll Cardiol. 2015; 65:2302–2310. doi: 10.1016/j.jacc.2015.03.552CrossrefMedlineGoogle Scholar3. Moak JP, Leifer ES, Tripodi D, Mohiddin SA, Fananapazir L. Long-term follow-up of children and adolescents diagnosed with hypertrophic cardiomyopathy: risk factors for adverse arrhythmic events.Pediatr Cardiol. 2011; 32:1096–1105. doi: 10.1007/s00246-011-9967-yCrossrefMedlineGoogle Scholar4. Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: executive summary: a report of the american college of cardiology/american heart association joint committee on clinical practice guidelines.J Am Coll Cardiol. 2020; 76:3022–3055. doi: 10.1016/j.jacc.2020.08.044CrossrefMedlineGoogle Scholar5. Norrish G, Ding T, Field E, Cervi E, Ziolkowska L, Olivotto I, Khraiche D, Limongelli G, Anastasakis A, Weintraub R, et al. Relationship between maximal left ventricular wall thickness and sudden cardiac death in childhood onset hypertrophic cardiomyopathy.Circ Arrhythm Electrophysiol. 2022; 15:e010075. doi: 10.1161/CIRCEP.121.010075LinkGoogle Scholar6. O'Mahony C, Jichi F, Monserrat L, Ortiz-Genga M, Anastasakis A, Rapezzi C, Biagini E, Gimeno JR, Limongelli G, McKenna WJ, et al; Hypertrophic Cardiomyopathy Outcomes Investigators*. Inverted U-shaped relation between the risk of sudden cardiac death and maximal left ventricular wall thickness in hypertrophic cardiomyopathy.Circ Arrhythm Electrophysiol. 2016; 9:e003818. doi: 10.1161/CIRCEP.115.003818LinkGoogle Scholar7. Balaji S, DiLorenzo MP, Fish FA, Etheridge SP, Aziz PF, Russell MW, Tisma S, Pflaumer A, Sreeram N, Kubus P, et al. Risk factors for lethal arrhythmic events in children and adolescents with hypertrophic cardiomyopathy and an implantable defibrillator: An international multicenter study.Heart Rhythm. 2019; 16:1462–1467. doi: 10.1016/j.hrthm.2019.04.040CrossrefMedlineGoogle Scholar8. Norrish G, Cantarutti N, Pissaridou E, Ridout DA, Limongelli G, Elliott PM, Kaski JP. Risk factors for sudden cardiac death in childhood hypertrophic cardiomyopathy: a systematic review and meta-analysis.Eur J Prev Cardiol. 2017; 24:1220–1230. doi: 10.1177/2047487317702519CrossrefMedlineGoogle Scholar9. Windram JD, Benson LN, Dragelescu A, Yoo SJ, Mertens L, Wong D, Grosse-Wortmann L. Distribution of hypertrophy and late gadolinium enhancement in children and adolescents with hypertrophic cardiomyopathy.Congenit Heart Dis. 2015; 10:E258–67. doi: 10.1111/chd.12286. Epub 2015 Jul 20. PMID: 26193909.CrossrefMedlineGoogle Scholar10. Maron BJ, Desai MY, Nishimura RA, Spirito P, Rakowski H, Towbin JA, Rowin EJ, Maron MS, Sherrid MV. Diagnosis and evaluation of hypertrophic cardiomyopathy: JACC state-of-the-art review.J Am Coll Cardiol. 2022; 79:372–389. doi: 10.1016/j.jacc.2021.12.002CrossrefMedlineGoogle Scholar11. Miron A, Lafreniere-Roula M, Steve Fan CP, Armstrong KR, Dragulescu A, Papaz T, Manlhiot C, Kaufman B, Butts RJ, Gardin L, et al. A validated model for sudden cardiac death risk prediction in pediatric hypertrophic cardiomyopathy.Circulation. 2020; 142:217–229. doi: 10.1161/CIRCULATIONAHA.120.047235LinkGoogle Scholar12. Yetman AT, Hamilton RM, Benson LN, McCrindle BW. Long-term outcome and prognostic determinants in children with hypertrophic cardiomyopathy.J Am Coll Cardiol. 1998; 32:1943–1950. doi: 10.1016/s0735-1097(98)00493-8CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesRelationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic CardiomyopathyGabrielle Norrish, et al. Circulation: Arrhythmia and Electrophysiology. 2022;15 May 2022Vol 15, Issue 5 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.122.011033PMID: 35491875 Originally publishedMay 2, 2022 Keywordsrisk factorhypertrophyEditorialschildcardiomyopathyPDF download Advertisement SubjectsSudden Cardiac Death