The road to a transcatheter edge-to-edge repair: patient experiences leading up to the procedure and in the early recovery period.

AIMS: Mitral valve transcatheter edge-to-edge repair (TEER) is a minimally invasive treatment option for patients with severe symptomatic mitral regurgitation who are at increased risk for cardiac surgery and are receiving optimal medical therapy. Little is known about patients' perspectives on their journey of care, including their experiences leading up to treatment and their early recovery period. The aim of this study was to explore patients' experiences of their journey to TEER and their perspectives on early recovery. METHODS AND RESULTS: We conducted a qualitative study using interpretive description. A purposive sample of 12 patients from a purposive sample, 3-6 monthspost-TEER procedure, were recruited from a tertiary hospital. The median age of the patients was 79 years, with seven males and five females. Data collection included semi-structured interviews over the phone. Data analysis followed an iterative process and utilized thematic analysis. There were four central themes highlighting the experiences of the patients leading up to their procedure: (i) escalating challenges with everyday life; (ii) plummeting losses; (iii) choosing and readiness to proceed with TEER; and (iv) the long and uncertain waiting time. The theme-improved health status highlights the experiences of patients in their early recovery. CONCLUSION: Patients' experiences of waiting for TEER are complex and involve multifaceted challenges related to their worsening cardiac symptoms and navigating the healthcare system. Therefore, care pathways must be put in place to provide continuity of care and support.

Predictors of perforation during lead extraction: Results of the Canadian Lead ExtrAction Risk (CLEAR) study.

BACKGROUND: Transvenous lead extraction can have serious adverse events, such as cardiac or vascular perforation. Risk factors have not been well characterized. OBJECTIVE: The purpose of this study was to identify factors associated with perforation and death, and to characterize lead extraction in a large contemporary population. METHODS: We performed a retrospective multicenter study examining patients undergoing lead extraction at 8 Canadian institutions from 1996 through 2016. Demographic and clinical data were used to identify variables associated with perforation and mortality using logistic regression modeling. RESULTS: A total of 2325 consecutive patients (age 61.9 ±16.5 years) underwent extraction of 4527 leads. Perforation rate was 2.7% (63/2325) and 30-day mortality was 1.6% (38/2325), with mortality of 0.4% due to perforation (10/2325). Variables associated with perforation included no previous cardiac surgery (odds ratio [OR] 3.33; 95% confidence interval [CI] 1.54-7.19; P = .002), female sex (OR 3.27; 95% CI 1.91-5.60; P <.001); left ventricular ejection fraction ≥40% (OR 2.81; 95% CI 1.28-6.14; P = .010); lead age >8 years (OR 2.64; 95% CI 1.52-4.60; P <.001); ≥2 leads extracted (OR 2.49; 95% CI 1.23-5.04; P = .011); and diabetes (OR 2.12; 95% CI 1.16-3.86; P = .014). Variables associated with death included infection as indication for extraction (OR 3.85; 95% CI 1.38-10.73; P = .010); anemia (OR 3.14; 95% CI 1.38-6.61; P = .003), and patient age (OR 1.04; 95% CI 1.01-1.07; P = .012). CONCLUSION: Risk factors associated with perforation in lead extraction include no history of cardiac surgery, female sex, preserved left ventricular ejection fraction, lead age >8 years, ≥2 leads extracted, and diabetes.

Examining Coronary Revascularization Practice Patterns for Diabetics: Perceived Barriers, Facilitators, and Implications for Knowledge Translation.

BACKGROUND: The FREEDOM trial provided robust evidence that coronary artery bypass grafting (CABG) was superior to percutaneous coronary intervention (PCI) for coronary revascularization in patients with diabetes mellitus (DM) and multivessel coronary artery disease (MV-CAD). The present study examined practice pattern changes and perceived barriers and facilitators to implementing FREEDOM trial evidence in British Columbia (BC). METHODS: Using a population-based database of cardiac procedures in BC, PCI:CABG ratios from 2007-2014 were compared before and after publication of the FREEDOM trial in the 4 tertiary cardiac centres that provided both CABG and PCI. Surveys of barriers and facilitators to implementation of evidence in practice were completed by 57 health care providers (HCPs) attending educational outreach sessions conducted in 2016-17 at 5 tertiary cardiac centres in BC. RESULTS: The overall PCI:CABG ratio declined from 1.59 (95% confidence interval [CI] 1.48-1.70, range 1.16-1.86) before publication to 0.88 (95% CI 0.75-1.01, range 0.56-0.82) after publication (P < 0.01). This decline from before to after publication was significant in 3 centres, but not in the fourth centre (from 1.62 to 1.49; P = 0.61). Barriers were identified at the levels of evidence (applicability, credibility), HCP (awareness/knowledge, practice behaviours), patient (knowledge/misconceptions, preferences), and systems (siloing of care, financial disincentives, resource limitations, geography). Facilitators were additional studies/guidelines, education/dissemination, shared decision making, a heart team approach, changes to remuneration models, and increased resources. CONCLUSIONS: Following publication of the FREEDOM trial, the proportion of patients with DM and MV-CAD undergoing CABG increased in BC; however, practice patterns varied across cardiac centres. HCPs attributed these practice variations to multilevel barriers and facilitators. Future knowledge translation strategies should be multifaceted and tailored to identified determinants.

"The ABCs of AD": A prospective evaluation of the efficacy of an educational intervention to increase knowledge of autonomic dysreflexia management among emergency health care professionals.

CONTEXT/OBJECTIVE: Despite the availability of consensus-based resources, first responders and emergency room (ER) health care professionals (HCPs) have limited knowledge regarding autonomic dysreflexia (AD) recognition and treatment. The purpose of this study was to assess the efficacy of "The ABCs of AD" educational seminar for improving HCPs' short- and long-term knowledge of AD recognition, diagnosis, and management. DESIGN: Multi-center prospective pre, post, and follow-up questionnaire study. SETTING: Level I trauma centers with emergency departments in British Columbia, Manitoba, and Ontario. METHODS: ER professionals completed measures immediately before and after (n = 108), as well as 3-months following (n = 23), attendance at "The ABCs of AD" seminar. OUTCOME MEASURES: AD knowledge test; seminar feedback. RESULTS: Following the seminar, participants had higher ratings of their AD knowledge and had significantly higher AD knowledge test scores (M ± SD pre = 11.85 ± 3.88, M ± SD post = 18.95 ± 2.39, out of 22; P < 0.001, d = 2.21). Most participants believed the seminar changed their AD knowledge, and rated the seminar information as having the potential to influence and change their practice. AD knowledge test scores significantly decreased between post-seminar and 3-month follow-up (M ± SD 3mo = 17.04 ± 3.28; P = 0.004, d = -0.70); however, 3-month scores remained significantly higher than baseline. CONCLUSION: "The ABCs of AD" seminar improves HCPs' perceived and actual AD knowledge in the short-term. To enhance knowledge retention in both the short- and long-term, the inclusion of additional active learning strategies and follow-up activities are recommended. The seminar is being translated into an online training module to enhance the dissemination of the AD clinical practice guidelines among first responders, ER staff, and SCI practitioners.

Massage impairs postexercise muscle blood flow and "lactic acid" removal.

PURPOSE: This study tested the hypothesis that one of the ways sports massage aids muscle recovery from exercise is by increasing muscle blood flow to improve "lactic acid" removal. METHODS: Twelve subjects performed 2 min of strenuous isometric handgrip (IHG) exercise at 40% maximum voluntary contraction to elevate forearm muscle lactic acid. Forearm blood flow (FBF; Doppler and Echo ultrasound of the brachial artery) and deep venous forearm blood lactate and H+ concentration ([La-], [H+]) were measured every minute for 10 min post-IHG under three conditions: passive (passive rest), active (rhythmic exercise at 10% maximum voluntary contraction), and massage (effleurage and pétrissage). Arterialized [La-] and [H+] from a superficial heated hand vein was measured at baseline. RESULTS: Data are presented as mean +/- SE. Venoarterial [La-] difference ([La-]v-a) at 30 s of post-IHG was the same across conditions (passive = 6.1 +/- 0.6 mmol x L(-1), active = 5.7 +/- 0.6 mmol x L(-1), massage = 5.5 +/- 0.6 mmol x L(-1), NS), whereas FBF was greater in passive (766 +/- 101 mL x min(-1)) versus active (614 +/- 62 mL x min(-1), P = 0.003) versus massage (540 +/- 60 mL x min(-1), P < 0.0001). Total FBF area under the curve (AUC) for 10 min after handgrip was significantly higher in passive versus massage (4203 +/- 531 vs 3178 +/- 304 mL, P = 0.024) but not versus active (3584 +/- 284 mL, P = 0.217). La(-)- efflux (FBF x [La-]v-a) AUC mirrored FBF AUC (passive = 20.5 +/- 2.8 mmol vs massage = 14.7 +/- 1.6 mmol, P = 0.03, vs active = 15.4 +/- 1.9 mmol, P = 0.064). H+ efflux (FBF x [H+]v-a) was greater in passive versus massage at 30 s (2.2 +/- 0.4e(-5) vs 1.3 +/- 0.2e(-5) mmol, P < 0.001) and 1.5 min (1.0 +/- 0.2e(-5) vs 0.6 +/- 0.09e(-5) mmol, P = 0.003) after IHG. CONCLUSIONS: Massage impairs La(-) and H+ removal from muscle after strenuous exercise by mechanically impeding blood flow.

Cowpox virus exploits the endoplasmic reticulum retention pathway to inhibit MHC class I transport to the cell surface.

Major histocompatibility complex (MHC) class I molecules assemble with peptides in the ER lumen and are transported via Golgi to the plasma membrane for recognition by T cells. Inhibiting MHC assembly, transport, and surface expression are common viral strategies of evading immune recognition. Cowpox virus, a clinically relevant orthopoxvirus, downregulates MHC class I expression on infected cells. However, the viral protein(s) and mechanisms responsible are unknown. We identify CPXV203 as a cowpox virus protein that associates with fully assembled MHC class I molecules and blocks their transport through the Golgi. A C-terminal KTEL motif in CPXV203 closely resembles the canonical ER retention motif KDEL and is required for CPXV203 function, indicating that a physiologic pathway is exploited to retain MHC class I in the ER. This viral mechanism for MHC class I downregulation may explain virulence differences between clinical isolates of orthopoxviruses.

A mycobacterial operon essential for virulence in vivo and invasion and intracellular persistence in macrophages.

The ability to invade and grow in macrophages is necessary for Mycobacterium tuberculosis to cause disease. We have found a Mycobacterium marinum locus of two genes that is required for both invasion and intracellular survival in macrophages. The genes were designated iipA (mycobacterial invasion and intracellular persistence) and iipB. The iip mutant, which was created by insertion of a kanamycin resistance gene cassette at the 5' region of iipA, was completely avirulent to zebra fish. Expression of the M. tuberculosis orthologue of iipA, Rv1477, fully complemented the iip mutant for infectivity in vivo, as well as for invasion and intracellular persistence in macrophages. In contrast, the iipB orthologue, Rv1478, only partially complemented the iip mutant in vivo and restored invasion but not intracellular growth in macrophages. While IipA and IipB differ at their N termini, they are highly similar throughout their C-terminal NLPC_p60 domains. The p60 domain of Rv1478 is fully functional to replace that of Rv1477, suggesting that the N-terminal sequence of Rv1477 is required for full virulence in vivo and in macrophages. Further mutations demonstrated that both Arg-Gly-Asp (RGD) and Asp-Cys-Ser-Gly (DCSG) sequences in the p60 domain are required for function. The iip mutant exhibited increased susceptibility to antibiotics and lysozyme and failed to fully separate daughter cells in liquid culture, suggesting a role for iip genes in cell wall structure and function. Altogether, these studies demonstrate an essential role for a p60-containing protein, IipA, in the pathogenesis of M. marinum infection.

Role of the WASP family proteins for Mycobacterium marinum actin tail formation.

Mycobacterium marinum, a natural pathogen of fish and frogs and an occasional pathogen of humans, is capable of inducing actin tail formation within the cytoplasm of macrophages, leading to actin-based motility and intercellular spread. Actin tail formation by M. marinum is markedly reduced in macrophages deficient in the Wiskott-Aldrich syndrome protein (WASP), which still contain the closely related and ubiquitously expressed protein N-WASP (neuronal WASP). In fibroblasts lacking both WASP and N-WASP, M. marinum is incapable of efficient actin polymerization and of intercellular spread. By reconstituting these cells, we find that M. marinum is able to use either WASP or N-WASP to induce actin polymerization. Inhibition or genetic deletion of tyrosine phosphorylation, Nck, WASP-interacting protein, and Cdc42 does not affect M. marinum actin tail formation, excluding the participation of these molecules as upstream activators of N-WASP in the initiation of actin-based motility. In contrast, deletion of the phosphatidylinositol 4,5-bisphosphate-binding basic motif in N-WASP eliminates M. marinum actin tail formation. Together, these data demonstrate that M. marinum subversion of host actin polymerization is most similar to distantly related Gram-negative organisms but that its mechanism for activating WASP family proteins is unique.