Three-dimensional speckle tracking echocardiography for left atrial and left ventricular function in hypertrophic cardiomyopathy mutation carriers

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disorder and is the leading cause of sudden cardiac death in young individuals and athletes. It is caused by mutations in genes that encode for sarcomere proteins and is characterized by unexplained left ventricular (LV) hypertrophy (LVH). However, the penetrance of LVH is incomplete, highly variable, and age dependent. Recent reports have suggested that HCM mutation carriers without overt LVH frequently have risk factors for sudden cardiac death. Genetic testing provides a certain diagnosis for HCM mutation carriers before development of LVH, though it is hampered by being complex and unfeasible in up to 50% of HCM family members as genetic mutations are only identified in 40–60% of HCM patients. Therefore, an alternative family screening approach for early diagnosis of HCM patients is required. LV diastolic dysfunction as the first marker of disease in preclinical HCM mutation carriers has been previously detected by tissue Doppler imaging (TDI). However, the reported sensitivity and specificity were highly variable. Other imaging tools for the early identification of myocardial systolic dysfunction and myocardial structural alteration such as two–dimensional speckle tracking echocardiography (2DSTE) and integrated backscatter echocardiography, respectively were also investigated albeit with mixed results. Recently, cardiac magnetic resonance (CMR) imaging with its high spatial resolution has displayed subtle myocardial structural changes but also intramyocardial crypts in these mainly asymptomatic patients. However the availability of CMR is limited and the analysis is time consuming. Quantification of LA size and function is a good diagnostic tool for LV diastolic function as well as a predictor of therapy response and major cardiovascular outcomes in various cardiac patients including HCM patients. The assessment of left atrial (LA) longitudinal strain using 2DSTE has recently been shown as a feasible and reproducible marker of LA function. Three–dimensional speckle tracking echocardiography (3DSTE) is an emerging tool building on the strengths of 2DSTE for better quantification of myocardial volumes and mechanics including assessment of dyssynchrony in one fast analysis. In this study, we tested the ability of 3DSTE to distinguish HCM mutation carriers from normal subjects primarily by detecting subtle abnormalities in LA size and longitudinal strain as surrogate markers of early LV dysfunction. Likewise, we evaluated the magnitude and timing of systolic myocardial deformation to detect any abnormalities that can define early systolic dysfunction in these subjects. Methods and results: A total of 80 subjects with normal LV ejection fraction (EF) were divided into 3 groups: HCM mutation carriers (n = 23), manifest HCM patients (n = 28), and normal controls (n = 29). They prospectively underwent 3DSTE for left atrial (LA) and LV strain analysis. HCM mutation carriers showed significantly higher LA minimum volume (ml/m2) (17 ± 6 vs. 14 ± 4, respectively, P = 0.03) and a significantly lower peak atrial longitudinal strain (PALS) (%), (27 ± 5 vs. 31 ± 7, respectively, P = 0.02) when compared to controls. However, no differences were found in global or regional LV systolic myocardial deformation between carriers and normal controls. Manifest HCM patients, compared to carriers showed significantly higher LA minimum (27 ± 10 vs. 17 ± 6, respectively, P< 0.001) and maximum volume (42 ± 14 vs. 32 ± 8, respectively, P = 0.007) as well as lower LA EF (%) (35 ± 8 vs. 47 ± 9, respectively, P< 0.001) and PALS (17 ± 5 vs. 27 ± 5, respectively, P< 0.001). Comparing LV strain, HCM patients showed reduced global longitudinal (−11 ± 4 vs. −16 ± 3, respectively, P < 0.001) and area strain (−35 ± 6 vs. −40 ± 5, respectively, P = 0.005). In addition, there was higher mechanical dyssynchrony (SDI) in the long-axis motion (13.6 ± 10 vs. 8.3 ± 4, respectively, P = 0.007). Conclusion: HCM mutation carriers could be distinguished from healthy subjects using 3DSTE through detection of LA dysfunction that might indicate subtle LV dysfunction. No differences were found in LV systolic myocardial deformation between both groups. The exact clinical value of 3DSTE in family screening for HCM needs to be further evaluated