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Competing Interests: Funding Support and Author Disclosures Funding was received from St Paul's Foundation and the Providence Health Care Research Institute (PHCRI) Early Career Research Initiative. Dr Akodad has received research funding from Medtronic, Biotronik, MUSE Explore, and Federation Française de Cardiologie. Dr Sathananthan has received speaker fees from Edwards Lifesciences and NVT Medical; and has reported consulting for Edwards Lifesciences, Boston Scientific, and Medtronic. Dr Tzimas has reported support from the Fondation Vaudoise de Cardiologie. Dr Gulsin has reported support from a British Heart Foundation Travel Fellowship (FS/TF/21/33008). Dr Blanke has reported consulting for Edwards Lifesciences, Boston Scientific, and Neovasc; and has provided computed tomography core laboratory services for Edwards Lifesciences, Medtronic, Neovasc, Boston Scientific, and Abbott, for which no direct compensation was received. Dr Sondergaard has received consultant fees and/or institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and SMT. Dr Wood has reported consulting for and has received research funding from Edwards Lifesciences and Abbott. Dr Webb has reported consulting for Edwards Lifesciences. Dr Leipsic has reported support from a Canadian Research Chair in Advanced Cardiopulmonary Imaging; has reported consulting for MVRX, HeartFlow, and Circle Cardiovascular Imaging; and has provided computed tomography core laboratory services for Edwards Lifesciences, Medtronic, Neovasc, Boston Scientific, and Abbott, for which no direct compensation is received. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: The development of rh immune globulin (RhIG) for the prevention of Rhesus D (RhD) alloimmunization has significantly decreased the incidence of RhD alloimmunization. Despite long-standing prevention, the experiences of RhD negative women with pregnancy is absent in the literature., Aim: The purpose of this study was to explore the experiences of RhD negative women with pregnancy., Methods: Utilizing an Interpretive Description approach, semi-structured interviews were conducted with RhD negative women about their pregnancies. This study took place within the geographic context of northern British Columbia (BC). The analysis involved a two-cycle approach to identify themes within the data., Findings: Sixteen RhD negative women that live in northern BC participated in this study. The analysis identified that RhD negative women are uninformed and want to be involved in the decision-making process regarding the prevention of RhD alloimmunization. The themes that emerged from the interview data were communication, information-seeking behaviour, out of sight out of mind, choice and trust, and patient advocacy., Discussion: The participants in this study described lacking information regarding the prevention of RhD alloimmunization. They sought information to overcome the gaps in knowledge and a desire to be involved in the decision-making process., Conclusion: RhD negative women want information and to be involved in the decision-making process in the prevention of RhD alloimmunization. Working with RhD negative women to develop decision-aids and/or other educational tools to aid in the decision-making process are warranted., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study investigated processes causing leaflet thickening and structural valve degeneration (SVD)., Background: Although transcatheter aortic valve replacement (TAVR) has changed the treatment of aortic stenosis, concerns remain regarding SVD, potentially related to valve thrombosis and thickening, based on studies using computed tomography (CT). Detailed histological analyses are provided to help attain insights into these processes., Methods: Explanted transcatheter heart valves (THVs) were evaluated for thrombosis, fibrosis, and calcification for quantification of leaflet thickness. Immunohistochemical and microscopy approaches were used to investigate SVD-associated mechanisms., Results: THVs (n = 23) were obtained from 22 patients (median 81 years of age; 50% male) from 0 to 2,583 days post TAVR. Maximal leaflet thickness increased relative to implant duration (ρ = 0.427; p = 0.027). THVs explanted after >2 years were thicker than those explanted after <2 years (p = 0.007). All THVs had adherent thrombus on both aortic and ventricular sides, which beyond 60 days was seen in combination with fibrosis and beyond 4 years had calcification. Early thrombus formation (<60 days) occurred despite rapid endothelialization with an abnormal hyperplastic phenotype. Fibrosis was observed in 6 patients on both the aortic and the ventricular THV surfaces, remodeled over time, and was associated with matrix metalloproteinase-1 expression. Five THVs showed overt calcification associated with adherent thrombus and fibrosis., Conclusions: There is a time-dependent degeneration of THVs consisting of thrombus formation, endothelial hyperplasia, fibrosis, tissue remodeling, proteinase expression, and calcification. Future investigation is needed to further understand these mechanisms contributing to leaflet thickening and SVD., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Angina, myocardial ischemia, and coronary artery physiology in hypertrophic cardiomyopathy (HCM) are poorly understood. However, coronary computed tomography angiography (CCTA) with fractional flow reserve from CT (FFR CT ) analysis offers a non-invasive method for evaluation of coronary artery volume to myocardial mass ratio (V/M) that may provide insight into such mechanisms. Thus, we sought to investigate changes in V/M in HCM., Methods: A retrospective analysis was performed on 37 HCM patients and 37 controls matched for age, sex, and cardiovascular risk factors; CCTA-derived coronary artery lumen volume (V) and myocardial mass (M) were used to determine V/M. FFR CT values were calculated for the left anterior descending (LAD), left circumflex (LCx) and right coronary (RCA) arteries as well as the 3-vessel cumulative FFR CT values., Results: HCM patients had significantly increased myocardial mass (176 ± 84 vs. 119 ± 27 g, p < 0.0001) and total coronary artery luminal volume (4112 ± 1139 vs. 3290 ± 924 mm 3 , p < 0.0001) that resulted from increases in segmented luminal volumes of both the left and right coronary artery systems. However, HCM patients had significantly decreased V/M (23.8 ± 5.9 vs. 26.5 ± 5.3 mm 3 /g; p = 0.026) which was further decreased when restricting V/M analysis to those HCM patients with septal hypertrophy (22.4 mm 3 /g, p = 0.01) that was mild-moderately predictive of HCM (AUC = 0.68). HCM patients also showed significantly lower nadir FFR CT values in the LCx (0.87 ± 0.06 vs. 0.91 ± 0.06, p = 0.02), and cumulative 3-vessel FFR CT values (2.58 ± 0.18 vs. 2.63 ± 0.14, p = 0.006)., Conclusions: HCM patients demonstrate significantly greater coronary volume. Despite this, HCM patients suffer from decreased V/M. Further prospective studies evaluating the relationship between V/M, angina, and heart failure in HCM are needed., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Progressive limb and girdle muscle atrophy leading to loss of ambulation is a hallmark of dysferlinopathies, which include limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. However, animal models fail to fully reproduce the disease severity observed in humans, with dysferlin-null (Dysf -/- ) mice exhibiting minor muscle damage and weakness without dramatic ambulatory dysfunction. As we have previously reported significant Dysf expression in blood vessels, we investigated the role of vascular function in development of muscle pathology by generating a Dysf-deficient mouse model with vascular disease. This was achieved by crossing Dysf -/- mice with ApoE -/- mice, which have high levels of nonHDL-associated cholesterol. Double-knockout Dysf -/- ApoE -/- mice exhibited severe ambulatory dysfunction by 11 months of age. In limb-girdle muscles, histology confirmed dramatic muscle wasting, fibrofatty replacement, and myofiber damage in Dysf -/- ApoE -/- mice without affecting the ratio of centrally nucleated myofibers. Although there were no major changes in ex vivo diaphragm and soleus muscle function, histological analyses revealed these muscles to be untouched by damage and remodelling. In all, these data suggest that cholesterol may be deleterious to dysferlinopathic muscle and lead to ambulatory dysfunction. Moreover, differences in plasma lipid handling between mice and humans could be a key factor affecting dysferlinopathy severity., (Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.)