Hemodynamic Forces Assessment Identifies Preclinical Abnormalities in Hypertrophic Cardiomyopathy Mutation Carriers (RF_TH_196)

Individuals with preclinical hypertrophic cardiomyopathy (HCM), defined as those carrying sarcomere mutations without left ventricular (LV) hypertrophy, are at a higher risk of progressing to overt HCM. However, the phenotypic characteristics of preclinical HCM remain poorly understood. The objective of this study was to evaluate early abnormalities in preclinical HCM through comprehensive assessment using cardiovascular magnetic resonance (CMR)-derived multimodal imaging.

Methods:

Family members of patients diagnosed with HCM who carried the same sarcomere gene mutations as the proband but without LV hypertrophy during family screening were enrolled and classified as participants with preclinical HCM. All participants underwent a comprehensive evaluation utilizing CMR-derived multimodal imaging, which included assessments of LV structure, function, strain, pressure-volume loop characteristics, hemodynamic forces (HDF), and tissue characteristics. The effectiveness of various parameters in distinguishing preclinical HCM from normal conditions was assessed using receiver operating characteristic curves and logistic regression analysis.

Results:

A total of 40 participants were enrolled, comprising 20 participants with preclinical HCM and 20 age- and gender-matched normal controls. Among the participants with preclinical HCM, mutations were identified in 15 (75%) of MYBPC3, 3 (15%) of MYH7, and 2 (10%) of TNNI3. In comparison to the normal controls, participants with preclinical HCM had similar mean regional LV wall thickness; however, the variability in basal LV wall thickness was significantly greater in the preclinical HCM group (1.73 ± 0.82 mm vs. 1.13 ± 0.34 mm, P = 0.006). The mean global and regional strains in participants with preclinical HCM were comparable to those observed in the normal controls, but the circumferential transmural strain difference was significantly larger (22.24 ± 5.59% vs. 18.08 ± 3.82%, P = 0.010). Additionally, participants with preclinical HCM demonstrated lower total HDF in the longitudinal direction, as well as during systole (systolic peak, systolic impulse, and systolic deceleration) and early diastole (diastolic deceleration). In the stepwise regression analysis, variability in basal LV wall thickness and total HDF in the longitudinal direction were identified as significant predictors (adjusted odds ratio: 12.61 (1.97-80.59), P = 0.007; 0.74 (0.6-0.9), P = 0.003, respectively).

Conclusion:

Increased variability of LV wall thickness and abnormal HDF are the important characteristics of preclinical HCM.