Prognostic significance of left atrial strain in sarcomere gene variant carriers without hypertrophic cardiomyopathy

Background Genetic testing of relatives of hypertrophic cardiomyopathy (HCM) patients has led to a large group of genotype-positive, phenotype-negative (G+/Ph-) subjects. Prediction of progression to overt HCM in these subjects is challenging. While left atrial (LA) strain is reduced in HCM patients it is currently unknown whether this parameter can be used to predict HCM phenotype progression. Methods This study includes 91 G+/Ph- subjects and 115 controls. Standard echocardiographic parameters as well as left ventricular global longitudinal strain (LV GLS) and LA reservoir strain (LASr) were assessed for each patient. Logistic and Cox proportional hazard regression analyses were used to investigate predictors of G+/Ph- status and HCM during follow-up. Results Independent predictors of G+ status included pathological Q waves (OR 1.60 [1.15-2.23], p < .01), maximal wall thickness (MWT: OR 1.10 [1.07-1.14], p < .001), mitral inflow E wave (OR 1.06 [1.02-1.10, p = .001), A wave (OR 1.06 [1.03-1.10], p < .001), LV GLS (OR .96 [.94-.98], p < .001), and LASr (OR .99 [.97-.99], p = .03). In univariable Cox regression analysis, male sex (HR 2.78 [1.06-7.29], p = .04), MWT (HR 1.72 [1.14-2.57], p = .009) and posterior wall thickness (HR 1.65 [1.17-2.30], p = .004) predicted HCM during a median follow-up of 5.9 [3.2-8.6] years, whereas LASr did not (HR .95 [.89-1.02], p = .14). There were no significant predictors of HCM after multivariable adjustment. Conclusion LASr is significantly impaired in G+/Ph- subjects and is an independent predictor of G+/Ph- status, but did not predict HCM development during follow-up.