Myocardial Strain and Association With Clinical Outcomes in Danon Disease: A Model for Monitoring Progression of Genetic Cardiomyopathies.

Background Myocardial strain can identify subclinical left ventricular dysfunction in various cardiac diseases, but its association with clinical outcomes in genetic cardiomyopathies remains unknown. Herein, we assessed myocardial strain in patients with Danon disease (DD), a rare X-linked autophagic disorder that causes severe cardiac manifestations. Methods and Results Echocardiographic images were reviewed and used to calculate myocardial strain from a retrospective, international registry of patients with DD. Regression analyses were performed to evaluate for an association of global longitudinal strain (GLS) and ejection fraction with the composite outcome (death, ventricular assist device, heart transplantation, and implantable cardioverter defibrillator for secondary prevention). A total of 22 patients with DD (male 14 [63.6%], median age 16.5 years) had sufficient echocardiograms for analysis. Absolute GLS was reduced with a mean of 12.2% with an apical-sparing pattern observed. Univariable regression for GLS and composite outcome showed an odds ratio of 1.32 (95% CI, 1.02-1.71) with P=0.03. For receiver operating characteristic analysis, the areas under the curve for GLS and ejection fraction 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 of 85.7% and false positive rate of 13.3%. Conclusions In this cohort of patients with DD, GLS may be a useful assessment of myocardial function and may predict clinical outcomes. This study highlights the potential use of myocardial strain phenotyping to monitor disease progression and potentially to predict clinical outcomes in DD and other genetic cardiomyopathies.

Intraventricular Flow Patterns in Patients Treated with Left Ventricular Assist Devices.

The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV). We used echo-CDV and custom postprocessing methods to map blood flow inside the LV in patients with ongoing LVAD support (Heartmate II, N = 7). We compared it to healthy controls (N = 20) and patients with dilated cardiomyopathy (DCM, N = 20). We also analyzed intraventricular flow changes during LVAD ramp tests (baseline ± 400 rpm). LVAD support reversed the increase in blood stasis associated with DCM, but it did not reduce intraventricular shear exposure. Within the narrow range studied, the ventricular flow was mostly insensitive to changes in pump speed. Patients with significant aortic insufficiency showed abnormalities in blood stasis and shear indices. Overall, this study suggests that noninvasive flow imaging could potentially be used in combination with standard clinical methods for adjusting LVAD settings to optimize flow transport and minimize stasis on an individual basis.

Systematic Assessment of the Impact of Ultrasound-Enhancing Agents upon Measurements of Cardiac Size and Function by Echocardiography.

BACKGROUND: Echocardiography with an ultrasound-enhancing contrast agent (CON) is a powerful tool for identifying the endocardial border. However, the precise relationship of measurements obtained from CON to the reference values of two-dimensional unenhanced echocardiography (BASL) remains undefined, especially regarding wall thickness. The aim of this study was to systematically determine the differences between unenhanced and enhanced images for a broad range of left ventricular (LV) measurements and to define reference values for the relationship between the two methods. METHODS: We examined the echocardiograms of 624 consecutive patients in whom CON was performed for clinical indications. We excluded 192 patients in whom studies were technically difficult for measurement by either or both methods. Echocardiograms were from standard parasternal and apical views according to American Society of Echocardiography guidelines. Recordings were measured for wall thickness and chamber dimension in 343 patients and for LV volumes and ejection fraction in 212 patients. RESULTS: LV wall thickness measurements were systematically reduced with a bias of 0.2 cm with limits of agreement (LOA) from -0.5 to 0.16 cm in interventricular septal thickness, and from -0.46 to 0.13 cm in posterior wall thickness in CON. LV dimensions and volumes systematically increased with a bias of 0.2 cm (LOA, -0.19 to 0.58 cm) and 14 to 16 mL (LOA, -11.9 to 42.8 mL), respectively. LV ejection fraction systematically decreased with a bias of 3.4% (LOA, -13.5% to 6.8%) in CON compared to BASL. All differences showed normal distribution in the Kolmogorov-Smirnov test. CONCLUSION: CON yields significantly different measurements of cardiac size and function compared to unenhanced imaging. These data define the systematic differences in measurements between CON and BASL images; the range of differences is narrow. These differences may influence management when the measurement value is a borderline.

Accuracy of left ventricular ejection fraction determined by automated analysis of handheld echocardiograms: A comparison of experienced and novice examiners.

BACKGROUND: Handheld ultrasound devices have been developed that facilitate imaging in new clinical settings. However, quantitative assessment has been difficult. Software algorithms have recently been developed with the aim of providing rapid measurements of left ventricular ejection fraction (LVEF) with minimal operator input. METHODS: We prospectively enrolled a cohort of 70 patients scheduled to undergo echocardiography at the University of California, San Diego. Each patient underwent a standard echocardiography examination by an experienced sonographer as well as a handheld ultrasound with automated software by both the sonographer and an inexperienced resident. RESULTS: There was a positive correlation between the LVEFs obtained from the standard transthoracic echocardiogram and handheld device in the hands of a novice (r = 0.62; 95% CI 0.45-0.75) and experienced sonographer (r = 0.69; 95% CI 0.54-0.80). The sensitivity and specificity to detect a reduced LVEF (<50%) were 69% and 96% for the novice and 64% and 98% for the experienced sonographer. The sensitivity and specificity to detect a severely reduced LVEF (<35%) were 67% and 97% for the novice and 56% and 93% for the experienced sonographer, but when limited to recordings of at least adequate quality, improved to 100% and 100% for the novice and 100% and 98% for the experienced sonographer, respectively. CONCLUSION: These data demonstrate that the handheld ultrasound device paired with novel software can provide a clinically useful estimate of LVEF when the images are of adequate quality and yield results by novice examiners that are similar to experienced sonographers.