Brent J. Barber

Validation of the Myocardial Performance Index by Echocardiography in Mice: A Noninvasive Measure of Left Ventricular Function

BACKGROUND The myocardial performance index (MPI) is a Doppler-based measure of left ventricular (LV) function. It is noninvasive, independent of LV shape, and does not require dimensional measurements. However, it has never been validated in mice. METHODS A total of 29 anesthetized mice with LV pressure catheters underwent echocardiography (2-dimensional, M-mode, and Doppler) at baseline and during manipulations of beta-adrenergic tone, temperature, preload, and afterload. The maximum derivative of LV pressure with respect to time (dP/dt(max)) was compared with MPI, fractional shortening (FS), mean velocity of circumferential fiber shortening, and the FS/MPI ratio. RESULTS MPI (baseline 0.44 +/- 0.07) correlated strongly with dP/dt(max) (R = -.779, P <.001), as did FS and mean velocity of circumferential fiber shortening. MPI differed significantly with contractility, preload, and afterload manipulation. FS/MPI showed the best correlation with dP/dt(max). CONCLUSIONS MPI strongly correlates with dP/dt(max) over a range of hemodynamic conditions in mice. It can be used as a noninvasive index of LV function in this species.

Oral Corticosteroids and Onset of Cardiomyopathy in Duchenne Muscular Dystrophy

OBJECTIVE To estimate the age when cardiomyopathy develops in boys with Duchenne muscular dystrophy (DMD) and to analyze the effect of corticosteroid treatment on the age of cardiomyopathy onset. STUDY DESIGN We identified a population-based sample of 462 boys with DMD, born between 1982 and 2005, in 5 surveillance sites in the US. Echocardiographic and corticosteroid treatment data were collected. Cardiomyopathy was defined by a reduced fractional shortening (<28%) or ejection fraction (<55%). The age of cardiomyopathy onset was determined. Survival analysis was performed to determine the effects of corticosteroid treatment on cardiomyopathy onset. RESULTS The mean (SD) age of cardiomyopathy onset was 14.3 (4.2) years for the entire population and 15.2 (3.4) years in corticosteroid-treated vs 13.1 (4.8) in non-treated boys. Survival analysis described a significant delay of cardiomyopathy onset for boys treated with corticosteroids (P < .02). By 14.3 years of age, 63% of non-treated boys had developed cardiomyopathy vs only 36% of those treated. Among boys treated with corticosteroids, there is a significant positive effect of duration of corticosteroid treatment on cardiomyopathy onset (P < .0001). For every year of corticosteroid treatment, the probability of developing cardiomyopathy decreased by 4%. CONCLUSIONS Oral corticosteroid treatment was associated with delayed cardiomyopathy onset. The duration of corticosteroid treatment also correlated positively with delayed cardiomyopathy onset. Our analysis suggests that a boy with DMD treated for 5 years with corticosteroids might experience a 20% decrease in the likelihood of developing cardiomyopathy compared with untreated boys.

Resolution of Plastic Bronchitis with Atrial Pacing in a Patient with Fontan Physiology

We describe a 5-year-old boy with Fontan physiology and a ventricular pacemaker who developed severe plastic bronchitis. Evaluation by cardiac catheterization revealed profoundly altered hemodynamics, which improved with atrial pacing. Following implantation of an atrial pacemaker, which restored atrioventricular (A-V) synchrony, the patient’s hemodynamics greatly improved and his plastic bronchitis resolved.

Recovery of dilated cardiomyopathies in infants and children using left ventricular assist devices.

Most infants and children implanted with left ventricular assist devices (LVADs) are bridged to cardiac transplantation. Prioritizing recovery may decrease this trend. Patients were treated with LVAD ventricular decompression, medical heart failure therapy, and bolus therapy with a beta-agonist before weaning trials. Devices were removed if adequate function was observed. Eleven patients with a mean age of 1.7 years presented for LVAD implantation. The mean Z score for left ventricular end diastolic diameter (LVEDD) was +5.5 (+1.6 to +7.3), and the mean fractional shortening was 9% (5%–14%). They were on maximal medical therapy and inotropic support. Duration of device support ranged from 6 to 22 days (mean: 13 days). There were three deaths, one from preimplant anoxic brain damage and two from thromboembolism. Eight patients (73%) recovered, were explanted, and are alive 0.6–6 years with hearts that have a mean Z score for LVEDD of 1.0 (0.09–3.7) and fractional shortening of 23%–36%. Left ventricular assist device decompression of dilated left ventricles in infants and children led to long-term survival in 73%. Ventricular size was significantly reduced and contractility significantly increased. None of these patients required transplantation.

Outpatient continuous inotrope infusion as an adjunct to heart failure therapy in Duchenne muscular dystrophy

We report the use of continuous intravenous inotrope infusion as a palliative management strategy for the treatment of symptomatic, refractory, end stage cardiac dysfunction in patients with Duchenne muscular dystrophy. Milrinone and/or dobutamine administered by continuous intravenous infusion provided symptomatic and objective cardiovascular improvement up to 30 months in 3 individuals with Duchenne muscular dystrophy and severe dilated cardiomyopathy. Continuous inotrope infusion should be considered a practical treatment strategy for end stage cardiac dysfunction in Duchenne muscular dystrophy patients when cardiac transplantation is not a viable option.

Left ventricular assist device support as a bridge to recovery in young children.

OBJECTIVE Left ventricular assist device (LVAD) experience and follow-up data in children are limited. We report the deployment and successful weaning from LVAD in young children with severe heart failure (HF). DESIGN From 2004--2009, 13 children suffering from HF were placed on LVAD. All presented with a dilated left ventricle (LV) with severely reduced contractility, secondary to myocarditis, atrial arrhythmia or idiopathic HF. This study reports their outcomes and longitudinal follow-up. RESULTS Of 13 young children with HF (ages 1 month--6 years; mean 19.2 months) placed on LVAD: eight weaned to recovery and successful hospital discharge, one was transplanted and four died. Echo follow-up in the weaned patients (mean age 22.1 months) revealed significant improvements from pre-LVAD measurements: LV end-diastolic dimension (LVED) mean z-score decreased from +4.8 to +0.95 (P < .001); fractional shortening (FS %) improved from a mean of 9.3% to 33% (P < .001); and the degree of mitral regurgitation (MR) significantly improved (P < .05). Time to LVAD deployment from HF diagnosis was more likely to be less than 30 days in the successfully weaned patients (100%) than patients who died or were transplanted (20%); P = .007. CONCLUSIONS LVAD support can be utilized as a bridge to recovery in young children with HF. Following LVAD weaning, children sustain improvements in LV size, function and degree of MR. LVAD deployment less than 30 days from HF diagnosis improves the likelihood of successful weaning and illustrates that children with acute etiologies of HF are more likely to achieve recovery.

The Night Vision Threshold Test (NVTT) : A simple instrument for testing dark adaptation in young children

It is estimated that 41 per cent of the population aged under 5 in the developing world has an inadequate vitamin A dietary intake resulting in increased morbidity and mortality. Half a million children go blind each year as a result of vitamin A deficiency. Thirteen and a half million have night blindness, the first sign of vitamin A deficiency. Unfortunately, there is no simple, sensitive and inexpensive means to identify the child who has marginal levels of vitamin A and thus institute means to prevent their development of severe deficiency. A low cost, simple, easy-to-use instrument designed to detect a young childs ability to adapt to darkness was tested in children admitted to the Mwanamugimu Nutrition Unit at Makerere Medical School in Kampala, Uganda. Despite the severe degree of malnutrition found in these children, Night Vision Threshold Test results and serum retinol levels were related (r = 0.41, p < 0.05). Further efficacy trials for this instrument are planned at community sites in Nepal.

Remote Diagnosis of Congenital Heart Disease in Southern Arizona: Comparison Between Tele-echocardiography and Videotapes

OBJECTIVE We report our experience with tele-echocardiography and echocardiograms recorded digitally or on videotape (recorded-echos) at The University of Arizona from August 2006 to December 2010 and compare their quality and diagnostic accuracy. MATERIALS AND METHODS Tele-echocardiograms (tele-echos) were transmitted from the Yuma Regional Medical Center to The University of Arizona via a T-1 and aT-3 line at a bandwidth of 768 kilobits per second. Recorded-echos were shipped for interpretation to The University of Arizona by overnight mail. Diagnostic accuracy was assessed by comparing tele- and recorded-echos with electrocardiograms performed by a pediatric cardiologist (PedsCard-echos). RESULTS Three hundred forty-six tele-echos in 260 patients and 455 recorded-echos in 406 patients were performed (median age, 6 and 8 days, respectively). Indications included possible congenital heart disease (CHD), patent ductus arteriosus (PDA), and persistent pulmonary hypertension of the newborn. Diagnostic categories included complex CHD, non-critical disease, PDA, and other. PedsCard-echos were available for 27% of the tele-echo and 30% of the recorded-echo patients. Comparisons between tele- and PedsCard-echo yielded no discrepancies in 12 (23%), expected resolution of condition in 26 (49%), and minor in 14 (26%). One (2%) major discrepancy was detected. Comparisons between recorded- and PedsCard-echo showed no discrepancies in 28 (40%), expected resolution of condition in 14 (20%), and minor discrepancies in 28 (40%) patients. No significant difference with respect to discrepancies was detected between tele- and recorded-echos. There was significant (p<0.01) improvement in tele- and recorded-echo study quality by 2010. CONCLUSIONS (1) Tele-echocardiography can be performed successfully with excellent accuracy. (2) The quality of tele- and recorded-echo studies improved toward the end of the analysis period. (3) Although initially tele-echo studies were more accurate than recorded-echo studies, there was no difference between these two types of studies by the fourth year of the study. (4) Both tele- and recorded-echos were indispensible in the remote diagnosis of CHD.

The perfect storm: Torsades de Pointes in a child with leukemia.

Torsades de Pointes (TdP) is a life‐threatening ventricular arrhythmia that can be associated with metabolic abnormalities, exposure to arrhythmogenic medications, and congenital long‐QT syndrome. This report describes a patient with ALL and multiple complications of therapy who developed TdP. The patient had no evidence of congenital long‐QT syndrome, but a constellation of factors appears to have led to QT prolongation, ventricular ectopy, and TdP. Although the patient suffered cardiac arrest, rapid recognition of TdP and prompt defibrillation resulted in an excellent outcome. Pediatr Blood Cancer 2007;49:996–999.

Associations between timing of corticosteroid treatment initiation and clinical outcomes in Duchenne muscular dystrophy

The long-term efficacy of corticosteroid treatment and timing of treatment initiation among Duchenne muscular dystrophy (DMD) patients is not well-understood. We used data from a longitudinal, population-based DMD surveillance program to examine associations between timing of treatment initiation (early childhood [before or at age 5 years], late childhood [after age 5 years], and naïve [not treated]) and five clinical outcomes (age at loss of ambulation; ages at onset of cardiomyopathy, scoliosis, and first fracture; and pulmonary function). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using survival analysis. DMD patients who initiated corticosteroid treatment in early childhood had a higher risk of earlier onset cardiomyopathy compared to cases who initiated treatment in late childhood (HR = 2.0, 95% CI = [1.2, 3.4]) or treatment naïve patients (HR = 1.9, 95% CI = [1.1, 3.2]), and higher risk of suffering a fracture (HR = 2.3, 95% CI = [1.4, 3.7] and HR = 2.6, 95% CI = [1.6, 4.2], respectively). Patients with early childhood treatment had slightly decreased respiratory function compared with those with late childhood treatment. Ages at loss of ambulation or scoliosis diagnosis did not differ statistically among treatment groups. We caution that the results from our study are subject to several limitations, as they were based on data abstracted from medical records. Further investigations using improved reporting of disease onset and outcomes are warranted to obtain a more definitive assessment of the association between the timing of corticosteroid treatment and disease severity.