Feasibility and Reproducibility of Echocardiographic Measures in Children with Muscular Dystrophies.

BACKGROUND: Cardiac disease is a major cause of death in patients with muscular dystrophies. The use of feasible and reproducible echocardiographic measures of cardiac function is critical to advance the field of therapeutics for dystrophic cardiomyopathy. METHODS: Participants aged 8 to 18 years with genetically confirmed Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, or limb-girdle muscular dystrophy were enrolled at five centers, and standardized echocardiographic examinations were performed. Measures of systolic and diastolic function and speckle-tracking echocardiography-derived cardiac strain were reviewed independently by two central readers. Furthermore, echocardiographic measures from participants with DMD were compared with those from retrospective age-matched control subjects from a single site to assess measures of myocardial function. RESULTS: Forty-eight participants (mean age, 13.3 ± 2.7 years) were enrolled. Shortening fraction had a greater interobserver correlation (intraclass correlation coefficient [ICC] = 0.63) compared with ejection fraction (ICC = 0.49). One reader could measure ejection fraction in only 53% of participants. Myocardial performance index measured by pulse-wave Doppler and Doppler tissue imaging showed similar ICCs (0.55 and 0.54). Speckle-tracking echocardiography showed a high ICC (0.96). Focusing on participants with DMD (n = 33), significantly increased mitral A-wave velocities, lower E/A ratios, and lower Doppler tissue imaging mitral lateral E' velocities were observed compared with age-matched control subjects. Speckle-tracking echocardiography demonstrated subclinical myocardial dysfunction with decreased average circumferential and longitudinal strain in three distinct subgroups: participants with DMD with normal shortening fractions, participants with DMD aged < 13 years, and participants with DMD with myocardial performance index scores < 0.40 compared with control subjects. CONCLUSIONS: In a muscular dystrophy cohort, assessment of cardiac function is feasible and reproducible using shortening fraction, diastolic measures, and myocardial performance index. Cardiac strain measures identified early myocardial disease in patients with DMD.

Noninvasive measurement of cardiac output during exercise in children with tetralogy of Fallot.

In patients with surgically repaired tetralogy of Fallot (TOF), reported peak oxygen consumption (VO(2)) is decreased compared with control subjects. The measurement of exercise cardiac output (CO) could be a useful adjunct for assessing cardiovascular fitness. There are few data assessing noninvasive CO, cardiac index (CI), and stroke volume (SV) during exercise for these patients. This study sought to measure noninvasive CI and SV during rest and exercise in children with repaired TOF. The authors compared 21 asymptomatic children with repaired TOF ages 11-17 years during rest and exercise and 42 gender- and age-matched healthy control children without structural heart disease. Using a Bruce exercise protocol, exercise data were measured noninvasively by a novel inert gas rebreathing technique including peak duration and heart rate, as well as VO(2), CO, CI, and SV measured at 90 % of peak predicted theoretical heart rate (90 % ppHR). Statistical correlation between peak VO(2) and CI was performed. At baseline, there was no statistically significant difference in any of the measures between the groups. At 90 % ppHR, there was an increase in CI during exercise of 140 % in the TOF children and 180 % in the control children. During exercise, SV changed minimally in the patient group, whereas it increased more than 30 % in the control children. At 90 % ppHR, the patient group showed an increase in VO(2) during exercise similar to that of their healthy peers. The patients had a significantly shorter peak exercise duration than normal control subjects. The patients had a lower CI during exercise because they were less able to increase SV. Therefore, at similar heart rates, patients who have had TOF repair must rely on increased peripheral muscle extraction, with a higher arteriovenous oxygen difference (SaO(2)-MvO(2)) during exercise, which may limit peak exercise capacity. In this cohort of TOF patients, noninvasive CI measurement was feasible, and correlation with VO(2) was good.

Assessment of ventilatory sensitivity to carbon dioxide changes during orthostasis.

Investigators have anecdotally reported changes in respiratory pattern preceding symptoms of orthostatic intolerance for several years. Evidence from recent studies support these observations, and show that alterations in respiration often precede pre-syncope during orthostasis. These observations suggest the possibility that changes in interaction between the chemo and baro-reflex control systems may produce phasic or dynamic changes in respiratory and hemodynamic parameters such that these changes are important in orthostasis intolerance. Our objective in the present study was to develop a method to obtain a quantitative index of ventilatory sensitivity to changes in inspired during orthostasis. Based on an approach previously developed by one of the authors (EB), we used, during supine and 70 degrees head up tilt, pseudo-random binary changes in inspired CO2 to quantify ventilatory sensitivity to CO2 disturbances. A pneumotach was used to measure airflow. From these recordings, we used a prediction error based systems identification algorithm to quantify ventilatory impulse response to CO2 stimulus. Results from 7 subjects showed that the integrated ventilatory response (area under impulse response curve) to CO2 was larger during tilt than that during supine (mean [std] 5.3 [2.6] Vs 3.0 [1.6] ml/min/0.01LCO2). These results suggest that the changes in ventilation due to disturbances in CO2 are likely to be larger during orthostasis than those during supine. Such an elevated response would indicate that the role of chemo-reflex control of breathing in cardiovascular instability culminating in orthostatic intolerance is likely to be important and should be further investigated.

Clinical Validation of Digital Image Compression Levels for Fetal Echocardiograms for Telemedicine.

BACKGROUND: Digital telephone transmission of dynamic fetal echocardiographic sequences requires wide bandwidths. To reduce the transmission of nonessential information present in echocardiographic images, compression algorithms have been used and validated for adult echocardiography. The level of compression that retains all diagnostic clinical information must be determined and validated for fetal echocardiographic studies. The purpose of this study was to validate levels of image compression that are diagnostic for fetal echocardiography. METHODS: Twenty previously recorded fetal echocardiograms representing two normal and 18 congenitally abnormal hearts were looped, digitized, and compressed at differing ratios. Images were reviewed in a blinded manner by four experts. Images were scored for diagnosis, diagnostic quality, and technical quality. RESULTS: Forty-four images were viewed. Experts correctly diagnosed 87% of images. There were no images of unacceptable diagnostic quality at a compression ratio of 300 (0%) and 2% at compression ratio of 600:1. CONCLUSIONS: Digital image compression of 300:1 was diagnostic for fetal congenital heart diseases with a variety of defects using cine-looped images. These data support the use of compressed fetal images for telephone transmission with a low bandwidth.