Michelle Noga

Long-Term Treatment With Oral Sildenafil Is Safe and Improves Functional Capacity and Hemodynamics in Patients With Pulmonary Arterial Hypertension

Background—The prognosis and functional capacity of patients with pulmonary arterial hypertension (PAH) is poor, and there is a need for safe, effective, inexpensive oral treatments. A single dose of sildenafil, an oral phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown. Methods and Results—We hypothesized that 3 months of sildenafil (50 mg orally every 8 hours) added to standard treatment would be safe and improve functional capacity and hemodynamics in PAH patients. We studied 5 consecutive patients (4 with primary pulmonary hypertension, 1 with Eisenmenger’s syndrome; New York Heart Association class II to III). Functional class improved by ≥1 class in all patients. Pretreatment versus posttreatment values (mean±SEM) were as follows: 6-minute walk, 376±30 versus 504±27 m, P <0.0001; mean PA pressure, 70±3 versus 52±3 mm Hg, P <0.007; pulmonary vascular resistance index 1702±151 versus 996±92 dyne · s · cm−5 · m−2, P <0.006. The systemic arterial pressure was unchanged, and no adverse effects occurred. Sildenafil also reduced right ventricular mass measured by MRI. In 7 human PAs (6 cardiac transplant donors and 1 patient with PAH on autopsy), we showed that PD-5 is present in PA smooth muscle cells and that sildenafil causes relaxation by activating large-conductance, calcium-activated potassium channels. Conclusion—This small pilot study suggests that long-term sildenafil therapy might be a safe and effective treatment for PAH. At a monthly cost of

Takayasu’s arteritis progression on anti-TNF biologics: a case series

492 Canadian, sildenafil is more affordable than most approved PAH therapies. A large multicenter trial is indicated to directly compare sildenafil with existing PAH treatments.

Deposition of Inhaled Ultrafine Aerosols in Replicas of Nasal Airways of Infants

Takayasu’s arteritis (TA) is a rare granulomatous vasculitic disease that affects the aorta and its major branches. Recent studies have suggested that anti-TNFα biological therapies are highly effective in treating TA refractory to conventional immunosuppressive therapy. We describe two patients with TA: one with progressive TA despite management with two different anti-TNFα agents, infliximab and adalimumab, and another who developed TA while treated with infliximab for the management of pre-existing Crohn’s disease. From our observations, we believe that a multicentered randomized study should be designed to assess the extent of resistance to these agents when different therapeutic doses are employed for managing TA.

Navigator-gated three-dimensional MR angiography of the pulmonary arteries using steady-state free precession.

Experimentally measured deposition of ultrafine particles, ranging from 13–100 nm in diameter, in nasal airway replicas of ten infants aged 3–18 months is presented. The replicas included the face, nostrils, and nasal airways including the upper trachea. A differential mobility analyzer (DMA) and a condensation particle counter (CPC) were used to quantify the nasal deposition by comparing the number of polydisperse sodium chloride particles, generated by evaporation from a Collison atomizer, at the inlet and outlet of the replicas. Particles were individually classified in size by DMA and subsequently were counted one size bin at a time by CPC upstream and downstream of each replica. Since in vivo data is not available for infants to compare to, we validated our experimental procedure instead by comparing deposition in nasal airway replicas of six adults with in vivo measurements reported in literature. In the infant replicas, tidal inhalation was simulated at two physiologically compatible flow rates and the effect of flow rate on deposition was found to be small. Deposition obtained at constant flow rates is lower than with tidal breathing, indicating the importance of unsteadiness, in contrast to similar data in adults where unsteadiness is known to be unimportant. An empirical equation, containing geometrical features of the nasal airways in the form of related non-dimensional dynamical parameters (Reynolds, Schmidt, and Womersley numbers), was best fitted to the infant data. This equation may be useful for a priori prediction of nasal deposition and intersubject variability during exposure of infants to ultrafine aerosols.

Right ventricular segmentation in cardiac MRI with moving mesh correspondences.

To assess the quality of a navigator‐gated, free breathing, steady‐state free precession (SSFP) technique in comparison to a single breathhold for pulmonary artery imaging in normal volunteers.

The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study

This study investigates automatic propagation of the right ventricle (RV) endocardial and epicardial boundaries in 4D (3D+time) magnetic resonance imaging (MRI) sequences. Based on a moving mesh (or grid generation) framework, the proposed algorithm detects the endocardium and epicardium within each cardiac phase via point-to-point correspondences. The proposed method has the following advantages over prior RV segmentation works: (1) it removes the need for a time-consuming, manually built training set; (2) it does not make prior assumptions as to the intensity distributions or shape; (3) it provides a sequence of corresponding points over time, a comprehensive input that can be very useful in cardiac applications other than segmentation, e.g., regional wall motion analysis; and (4) it is more flexible for congenital heart disease where the RV undergoes high variations in shape. Furthermore, the proposed method allows comprehensive RV volumetric analysis over the complete cardiac cycle as well as automatic detections of end-systolic and end-diastolic phases because it provides a segmentation for each time step. Evaluated quantitatively over the 48-subject data set of the MICCAI 2012 RV segmentation challenge, the proposed method yielded an average Dice score of 0.84±0.11 for the epicardium and 0.79±0.17 for the endocardium. Further, quantitative evaluations of the proposed approach in comparisons to manual contours over 23 infant hypoplastic left heart syndrome patients yielded a Dice score of 0.82±0.14, which demonstrates the robustness of the algorithm.

Safety and Efficacy of Gadobutrol-Enhanced MRI in Patients Aged Under 2 Years—A Single-Center, Observational Study

BackgroundNationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs

Toward automated classification of acetabular shape in ultrasound for diagnosis of DDH

3 billion in hospital costs annually and the global burden is expected to double in the next 1–2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition.Methods/DesignThe objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years.DiscussionAlberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure.Trial registrationClinicalTrials.gov NCT02052804.

A case of Sotos syndrome with neuroblastoma.

Gadobutrol is a 1-molar gadolinium-based contrast agent with well-characterized safety and efficacy for magnetic resonance imaging (MRI) in adults and children ≥ 2 years old. This observational study assessed gadobutrol-enhanced MRI in children < 2 years of age. Sixty infants (mean age 11.1 months) underwent MRI using gadobutrol at standard dose of 0.1 mL/kg (0.1 mmol/kg) body weight. MRI examinations included brain, spine, and neck (n = 24), subcutaneous soft tissues (n = 14), chest, abdomen, and pelvis (n = 12), musculoskeletal system (n = 7) and vascular system (n = 3). No patients experienced adverse events related to gadobutrol injection. In 57 patients with confirmed diagnoses, gadobutrol-enhanced MRI provided findings consistent with confirmed pathologies. This study indicates that gadobutrol at a standard dose for MRI is safe in patients aged < 2 years and provides diagnostic information for multiple pathologies.

Topical contrast agents to improve soft-tissue contrast in the upper airway using cone beam CT: a pilot study

BACKGROUND AND OBJECTIVES The diagnosis of Developmental Dysplasia of the Hip (DDH) in infants is currently made primarily by ultrasound. However, two-dimensional ultrasound (2DUS) images capture only an incomplete portion of the acetabular shape, and the alpha and beta angles measured on 2DUS for the Graf classification technique show high inter-scan and inter-observer variability. This variability relates partly to the manual determination of the apex point separating the acetabular roof from the ilium during index measurement. This study proposes a new 2DUS image processing technique for semi-automated tracing of the bony surface followed by automatic calculation of two indices: a contour-based alpha angle (αA), and a new modality-independent quantitative rounding index (M). The new index M is independent of the apex point, and can be directly extended to 3D surface models. METHODS We tested the proposed indices on a dataset of 114 2DUS scans of infant hips aged between 4 and 183 days scanned using a 12MHz linear transducer. We calculated the manual alpha angle (αM), coverage, contour-based alpha angle and rounding index for each of the recordings and statistically evaluated these indices based on regression analysis, area under the receiver operating characteristic curve (AUC) and analysis of variance (ANOVA). RESULTS Processing time for calculating αA and M was similar to manual alpha angle measurement, ∼30s per image. Reliability of the new indices was high, with inter-observer intraclass correlation coefficients (ICC) 0.90 for αA and 0.89 for M. For a diagnostic test classifying hips as normal or dysplastic, AUC was 93.0% for αA vs. 92.7% for αM, 91.6% for M alone, and up to 95.7% for combination of M with αM, αA or coverage. CONCLUSIONS The rounding index provides complimentary information to conventional indices such as alpha angle and coverage. Calculation of the contour-based alpha angle and rounding index is rapid, shows potential to improve the reliability and accuracy of DDH diagnosis from 2DUS, and could be extended to 3D ultrasound in future.