Revisiting the concept of "phenotype" in pediatric hypertrophic cardiomyopathy using myocardial stiffness and strain variations assessed by ultrafast ultrasound imaging

BackgroundPediatric hypertrophic cardiomyopathy (HCM) is associated with significant morbidity and mortality. While identified as a genetic disease mainly involving sarcomeric genes, the association between genotypical variation and phenotypic expression is not fully established. Developments in Ultrafast ultrasound imaging allows quantifying myocardial stiffness using shear waves elastography (SWE). When combined with strain measurements, myocardial work can be computed, offering new insights into phenotype myocardial properties. MethodsAn age-matched population of 20 Healthy volunteers (HVs, mean age=11.1 {+/-} 4.5years), 20 HCM (genotype- and phenotype-positive, mean age=11.6 {+/-} 5.3years) and 20 Genotype (genotype-positive, phenotype-negative, mean age=11.1 {+/-} 4.8years) were included in the study. Each participant underwent conventional echocardiography and a full cardiac-cycle exploration of the basal anteroseptal segment consisting of: (1) myocardial stiffness by SWE, (2) segmental strain and thickness, which are used to compute one-beat work, the stress-strain loop area, contributive and dissipative work. ResultsMean diastolic myocardial stiffness (DMS) and peak myocardial strain (PMS) distinguished the HCM group (DMS=23.7 {+/-} 8.7kPa; PMS= -6.64 {+/-} 5.9%) from HV group (DMS=7.2 {+/-} 0.7kPa, p<0.01; PMS= -19.9 {+/-}4.1%, p<0.01). No significant differences were observed in DMS and PMS between HVs and Genotype groups. One-beat work and stress-strain loop areas showed significant differences among all 3 groups (p<0.01) and could distinguish the Genotype group (one-beat work= 318.2 {+/-} 100.2{micro}J/mm; stress-strain loop area=33.2 {+/-} 10.6kPa.%) from HVs (one-beat work= 582.4 {+/-} 137{micro}J/mm; stress-strain loop area= 66.8 {+/-} 19.8 kPa.%), and the HCM group (one-beat work= 38.2 {+/-} 107.1{micro}J/mm, stress-strain loop area=5.8 {+/-} 6.5kPa.%), p<0.01. ConclusionCombining Ultrafast ultrasound with speckle-tracking echocardiography, we demonstrate that one-beat work and stress-strain relationship, obtained by combining myocardial stiffness, strain, and thickness have the potential to distinguish genotype-positive, phenotype-negative patients from healthy controls. Clinical outcome studies are needed to determine the prognostic value of these parameters in phenotype-positive HCM patients.