Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy
Authors: Norrish Gabrielle , Ding Tao , Field Ella , Cervi Elena , Ziółkowska Lidia , Olivotto Iacopo , Khraiche Diala , Limongelli Giuseppe , Anastasakis Aris , Weintraub Robert , Biagini Elena , Ragni Luca , Prendiville Terrence , Duignan Sophie , McLeod Karen , Ilina Maria , Fernández Adrián , Marrone Chiara , Bökenkamp Regina , Baban Anwar , Kubus Peter , Daubeney Piers E.F. , Sarquella-Brugada Georgia , Cesar Sergi , Klaassen Sabine , Ojala Tiina H. , Bhole Vinay , Medrano Constancio , Uzun Orhan , Brown Elspeth , Gran Ferran , Sinagra Gianfranco , Castro Francisco J. , Stuart Graham , Vignati Gabriele , Yamazawa Hirokuni , Barriales-Villa Roberto , Garcia-Guereta Luis , Adwani Satish , Linter Katie , Bharucha Tara , Garcia-Pavia Pablo , Siles Ana , Rasmussen Torsten B. , Calcagnino Margherita , Jones Caroline B. , De Wilde Hans , Kubo Toru , Felice Tiziana , Popoiu Anca , Mogensen Jens , Mathur Sujeev , Centeno Fernando , Reinhardt Zdenka , Schouvey Sylvie , O’Mahony Costas , Omar Rumana Z. , Elliott Perry M. , Kaski Juan Pablo 
Published: May 2022

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.