Association Of Myocardial Strain With Clinical Outcomes In Danon Disease

Abstract

Background Ejection fraction (EF) has been the gold standard for assessing cardiac function, but does not directly measure myocardial contractility and has limited efficacy in predicting outcomes. Myocardial strain has become increasing used in identifying subclinical left ventricular dysfunction in various cardiac diseases. Therefore, we evaluated myocardial strain in a cohort of patients with Danon Disease (DD), a rare X-linked autophagic disorder that causes severe cardiac manifestations. Methods Echocardiograms were reviewed from a retrospective, international registry of DD patients. Traditional echo and myocardial strain parameters were obtained from images available. Regression analyses and receiver operating curve (ROC) were performed to evaluate for relationships between global longitudinal strain (GLS) and ejection fraction (EF) with the composite outcome (death, ventricular assist device, heart transplantation and implantable cardioverter-defibrillator for secondary prevention). Results Twenty-two patients with DD (male 14 [63.6%], median age 16.5 years) were included in the study. Notable echo and strain parameters included a median EF 60.0%, intraventricular septal diameter 12.8 mm, LV mass 228.3 g, LA volume index 21.2 mL/m2 and mean GLS of 12.2%. Univariate and multivariate logistic regression for GLS and composite outcome showed an odds ratio (OR) of 1.32 with p = 0.03 and OR 1.42 with p = 0.05, respectively. Mean GLS differed by presence of the composite outcome (8.43 vs 13.9%, p = 0.016). For ROC analysis, the area under the curve for GLS and EF with the composite outcome were 0.810 (p = 0.02) and 0.605 (p = 0.44), respectively. An absolute GLS cutoff of 10.0% yielded a true positive rate 85.7% and false positive rate of 13.3%. Conclusion In this cohort of DD patients, GLS may be superior to EF in predicting clinical outcomes. This study suggests that myocardial strain can be used to monitor disease progression and to predict clinical outcomes in DD and other genetic or acquired cardiomyopathies. Ejection fraction (EF) has been the gold standard for assessing cardiac function, but does not directly measure myocardial contractility and has limited efficacy in predicting outcomes. Myocardial strain has become increasing used in identifying subclinical left ventricular dysfunction in various cardiac diseases. Therefore, we evaluated myocardial strain in a cohort of patients with Danon Disease (DD), a rare X-linked autophagic disorder that causes severe cardiac manifestations. Echocardiograms were reviewed from a retrospective, international registry of DD patients. Traditional echo and myocardial strain parameters were obtained from images available. Regression analyses and receiver operating curve (ROC) were performed to evaluate for relationships between global longitudinal strain (GLS) and ejection fraction (EF) with the composite outcome (death, ventricular assist device, heart transplantation and implantable cardioverter-defibrillator for secondary prevention). Twenty-two patients with DD (male 14 [63.6%], median age 16.5 years) were included in the study. Notable echo and strain parameters included a median EF 60.0%, intraventricular septal diameter 12.8 mm, LV mass 228.3 g, LA volume index 21.2 mL/m2 and mean GLS of 12.2%. Univariate and multivariate logistic regression for GLS and composite outcome showed an odds ratio (OR) of 1.32 with p = 0.03 and OR 1.42 with p = 0.05, respectively. Mean GLS differed by presence of the composite outcome (8.43 vs 13.9%, p = 0.016). For ROC analysis, the area under the curve for GLS and EF with the composite outcome were 0.810 (p = 0.02) and 0.605 (p = 0.44), respectively. An absolute GLS cutoff of 10.0% yielded a true positive rate 85.7% and false positive rate of 13.3%. In this cohort of DD patients, GLS may be superior to EF in predicting clinical outcomes. This study suggests that myocardial strain can be used to monitor disease progression and to predict clinical outcomes in DD and other genetic or acquired cardiomyopathies.