Disopyramide use in infants and children with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy has a range of clinical severity in children. Treatment options are limited, mainly on account of small patient size. Disopyramide is a sodium channel blocker with negative inotropic properties that effectively reduces left ventricular outflow tract gradients in adults with hypertrophic cardiomyopathy, but its efficacy in children is uncertain. A retrospective chart review of patients ⩽21 years of age with hypertrophic cardiomyopathy at our institution and treated with disopyramide was performed. Left ventricular outflow tract Doppler gradients before and after disopyramide initiation were compared as the primary outcome measure. Nine patients received disopyramide, with a median age of 5.6 years (range 6 days-12.9 years). The median left ventricular outflow tract Doppler gradient before initiation of disopyramide was 81 mmHg (range 30-132 mmHg); eight patients had post-initiation echocardiograms, in which the median lowest recorded Doppler gradient was 43 mmHg (range 15-100 mmHg), for a median % reduction of 58.2% (p=0.002). With median follow-up of 2.5 years, eight of nine patients were still alive, although disopyramide had been discontinued in six of the nine patients. Reasons for discontinuation included septal myomectomy (four patients), heart transplantation (one patient), and side effects (one patient). Disopyramide was effective for the relief of left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy, although longer-term data suggest that its efficacy is not sustained. In general, it was well tolerated. Further study in larger patient populations is warranted.

Home Is Where the HeartWare Is: Preparing Pediatric Patients and Caregivers for Discharge to Home and Integration Into the Community.

The Cardiac Center at The Children's Hospital of Philadelphia has cared for patients with implanted ventricular assist device (VAD) technology since 1998. Historically, patients requiring VAD support were managed exclusively in the Cardiac Intensive Care Unit with the first medically stable transition to the Cardiac Care Unit (step-down) taking place in 2001. Patient management was confined to the inpatient setting, as the primary device used at the time was paracorporeal and not suitable for home use. Continuous-flow devices, such as the HeartWare HVAD, have gained popularity because of miniaturized size and lower profiles of side effects and adverse events, making them more suitable for home use. This article describes a single-center experience with transitioning the VAD-supported pediatric patient to the outpatient setting, highlighting outcomes, strategies, and lessons learned in order to support VAD patients and their caregivers in the hospital and community setting.

Systemic Atrioventricular Valve Excision and Ventricular Assist Devices in Pediatric Patients.

BACKGROUND: Continuous-flow ventricular assist devices (CF VADs) designed for adults are increasingly used in pediatric patients. However, there is greater risk of device inflow obstruction as a result of size and anatomy. METHODS: We reviewed all cases of systemic atrioventricular valve (AVV) excision with HeartWare HVAD (HeartWare, Framingham, MA) implantation in the systemic ventricle performed at our institution from November 2015 to May 2016. RESULTS: AVV excision with CF VAD implantation was undertaken in 3 patients. Patient 1 was palliated in infancy, resulting in biventricular physiology with a systemic right ventricle, and presented at age 15 years with worsening ventricular dysfunction. After CF VAD implantation in the systemic ventricle and discharge to home, tricuspid valve obstruction to VAD inflow developed, and the patient and underwent tricuspid valve excision on postoperative day 52. Patients 2 and 3 were aged younger than 4 years, with a body surface area of 0.62 m2 and 0.58 m2, respectively, and had undergone Fontan palliation, with subsequent systemic ventricular dysfunction and AVV regurgitation. In both Fontan patients, the CF VAD was implanted in the right atrium with simultaneous excision of the AVV. None have had evidence of elevated atrial pressures or recalcitrant pulmonary edema. At a mean follow-up of 359 days (range, 304 to 422 days), there have been no concerns for inflow obstruction or low flow. CONCLUSIONS: CF VAD implantation with AVV excision can successfully support complex pediatric patients in a wide range of size and anatomy (small chambers, systemic right ventricles). This technique may allow for CF VAD implantation in patients previously deemed too small for such support.

A Preliminary Study of Left Ventricular Rotational Mechanics in Children with Noncompaction Cardiomyopathy: Do They Influence Ventricular Function?

BACKGROUND: Current diagnostic criteria for noncompaction cardiomyopathy (NCC) lack specificity, and the disease lacks prognostic indicators. Reverse apical rotation (RAR) with abnormal rotation of the cardiac apex in the same clockwise direction as the base has been described in adults with NCC. The aim of this study was to test the hypothesis that RAR might differentiate between symptomatic NCC and benign hypertrabeculations and might be associated with ventricular dysfunction. METHODS: Echocardiograms from 28 children with NCC without cardiac malformations were prospectively compared with those from 29 age-matched normal control subjects. A chart review was performed to identify the patients' histories and clinical characteristics. Speckle-tracking was used to measure longitudinal strain, circumferential strain, and rotation. RESULTS: RAR occurred in 39% of patients with NCC. History of left ventricular (LV) dysfunction or arrhythmia was universal in, but not exclusive to, patients with RAR. Patients with RAR had lower LV longitudinal strain but similar ejection fractions compared with patients without RAR (median, -15.6% [interquartile range, -12.9% to -19.3%] vs -19% [interquartile range, -14.5% to -21.9%], P < .01; 53% [interquartile range, 43% to 68%] vs 61% [interquartile range, 58% to 67%], P = .08). Only a pattern of contraction with RAR, early arrest of twisting by mid-systole, and premature untwisting was associated with lower ejection fraction (46%; interquartile range, 43% to 52%; P = .006). CONCLUSIONS: RAR is not a sensitive but is a specific indicator of complications in children with NCC. Therefore, RAR may have prognostic rather than diagnostic value. Premature untwisting of the left ventricle during ejection may be an even more worrisome indicator of LV dysfunction.

Transient ALT activation protects human primary cells from chromosome instability induced by low chronic oxidative stress.

Cells are often subjected to the effect of reactive oxygen species (ROS) as a result of both intracellular metabolism and exposure to exogenous factors. ROS-dependent oxidative stress can induce 8-oxodG within the GGG triplet found in the G-rich human telomeric sequence (TTAGGG), making telomeres highly susceptible to ROS-induced oxidative damage. Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes and their dysfunction is believed to affect a wide range of cellular and/or organismal processes. Acute oxidative stress was shown to affect telomere integrity, but how prolonged low level oxidative stress, which may be more physiologically relevant, affects telomeres is still poorly investigated. Here, we explored this issue by chronically exposing human primary fibroblasts to a low dose of hydrogen peroxide. We observed fluctuating changes in telomere length and fluctuations in the rates of chromosome instability phenotypes, such that when telomeres shortened, chromosome instability increased and when telomeres lengthened, chromosome instability decreased. We found that telomere length fluctuation is associated with transient activation of an alternative lengthening of telomere (ALT) pathway, but found no evidence of cell death, impaired proliferation, or cell cycle arrest, suggesting that ALT activation may prevent oxidative damage from reaching levels that threaten cell survival.

Phototropism and gravitropism in lateral roots of Arabidopsis.

Gravitropism and, to a lesser extent, phototropism have been characterized in primary roots, but little is known about structural/functional aspects of these tropisms in lateral roots. Therefore, in this study, we report on tropistic responses in lateral roots of Arabidopsis thaliana. Lateral roots initially are plagiogravitropic, but when they reach a length of approximately 10 mm, these roots grow downward and exhibit positive orthogravitropism. Light and electron microscopic studies demonstrate a correlation between positive gravitropism and development of columella cells with large, sedimented amyloplasts in wild-type plants. Lateral roots display negative phototropism in response to white and blue light and positive phototropism in response to red light. As is the case with primary roots, the photoresponse is weak relative to the graviresponse, but phototropism is readily apparent in starchless mutant plants, which are impaired in gravitropism. To our knowledge, this is the first report of phototropism of lateral roots in any plant species.

Analysis of the ability of spirochete species associated with relapsing fever, avian borreliosis, and epizootic bovine abortion to bind factor H and cleave c3b.

Some Borrelia species associated with Lyme disease bind the complement-regulatory protein factor H (fH), a process that may aid in immune evasion. In this report we demonstrate that some Borrelia species associated with relapsing fever bind fH, but not those associated with avian borreliosis and epizootic bovine abortion. Cell-bound fH was also found to mediate cleavage of exogenously supplied human C3b, demonstrating the biological relevance of fH binding and its possible importance in the pathogenesis of the relapsing-fever spirochetes.