Impact of Smoking on Coronary Volume-to-Myocardial Mass Ratio: An ADVANCE Registry Substudy.

Purpose To examine the relationship between smoking status and coronary volume-to-myocardial mass ratio (V/M) among individuals with coronary artery disease (CAD) undergoing CT fractional flow reserve (CT-FFR) analysis. Materials and Methods In this secondary analysis, participants from the ADVANCE registry evaluated for suspected CAD from July 15, 2015, to October 20, 2017, who were found to have coronary stenosis of 30% or greater at coronary CT angiography (CCTA) were included if they had known smoking status and underwent CT-FFR and V/M analysis. CCTA images were segmented to calculate coronary volume and myocardial mass. V/M was compared between smoking groups, and predictors of low V/M were determined. Results The sample for analysis included 503 current smokers, 1060 former smokers, and 1311 never-smokers (2874 participants; 1906 male participants). After adjustment for demographic and clinical factors, former smokers had greater coronary volume than never-smokers (former smokers, 3021.7 mm3 ± 934.0 [SD]; never-smokers, 2967.6 mm3 ± 978.0; P = .002), while current smokers had increased myocardial mass compared with never-smokers (current smokers, 127.8 g ± 32.9; never-smokers, 118.0 g ± 32.5; P = .02). However, both current and former smokers had lower V/M than never-smokers (current smokers, 24.1 mm3/g ± 7.9; former smokers, 24.9 mm3/g ± 7.1; never-smokers, 25.8 mm3/g ± 7.4; P < .001 [unadjusted] and P = .002 [unadjusted], respectively). Current smoking status (odds ratio [OR], 0.74 [95% CI: 0.59, 0.93]; P = .009), former smoking status (OR, 0.81 [95% CI: 0.68, 0.97]; P = .02), stenosis of 50% or greater (OR, 0.62 [95% CI: 0.52, 0.74]; P < .001), and diabetes (OR, 0.67 [95% CI: 0.56, 0.82]; P < .001) were independent predictors of low V/M. Conclusion Both current and former smoking status were independently associated with low V/M. Keywords: CT Angiography, Cardiac, Heart, Ischemia/Infarction Clinical trial registration no. NCT02499679 Supplemental material is available for this article. © RSNA, 2024.

Redo-TAVI with SAPIEN 3 in SAPIEN XT or SAPIEN 3 - impact of pre- and post-dilatation on final THV expansion.

BACKGROUND: When a balloon-expandable transcatheter heart valve (THV) is chosen to treat a failed balloon-expandable THV, there is a risk of underexpansion with a potential impact on performance. AIMS: We aimed to assess the impact of pre- and post-dilatation on the expansion of balloon-expandable THVs after redo-transcatheter aortic valve implantation (TAVI). METHODS: Redo-TAVI was performed on the bench with a 23 mm SAPIEN 3 (S3) implanted within a 23 mm SAPIEN XT (SXT) or a 23 mm S3, both of which served as the "failed" THVs. Pre- and/or post-dilatation was performed using a 23 mm non-compliant TRUE balloon. Expansion of the index and redo-THVs were assessed before and after pre-/post-dilatation using microcomputed tomography (micro-CT), and THV hydrodynamic testing was conducted. RESULTS: Without pre- or post-dilatation, the S3 was underexpanded, for all combinations, particularly in the mid-portion of the THV (18.6 mm and 19.7 mm representing 81% and 86% of the nominal diameter inside the SXT and S3, respectively). Pre- and post-dilatation had an additive effect on diameter expansion of the redo-THV, which remained constrained in most combinations. The only combination to achieve nominal expansion was the S3 in S3 when both pre- and post-dilatation were performed. The S3 remained underexpanded inside the SXT despite pre- and post-dilatation (93% in the mid-portion). Improved redo-THV expansion was accompanied by 2.7 mm (12%) overexpansion of the index THV. While all samples had acceptable hydrodynamic performance, the underexpanded samples had worse leaflet pinwheeling. CONCLUSIONS: When performing redo-TAVI with a 23 mm S3 inside a 23 mm SXT or S3, only the S3 in S3 with the use of pre- and post-dilatation reached full expansion. This underlines the importance of CT assessment of THV expansion and the role of pre-/post-dilatation.

Bioprosthetic Valve Remodeling in Nonfracturable Surgical Valves: Impact on THV Expansion and Hydrodynamic Performance.

BACKGROUND: There are limited data on the effect of bioprosthetic valve remodeling (BVR) on transcatheter heart valve (THV) expansion and function following valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) in a nonfracturable surgical heart valve (SHV). OBJECTIVES: This study sought to assess the impact of BVR of nonfracturable SHVs on THVs after VIV implantation. METHODS: VIV TAVR was performed using 23-mm SAPIEN3 (S3, Edwards Lifesciences) or 23/26-mm Evolut Pro (Medtronic) THVs implanted in 21/23-mm Trifecta (Abbott Structural Heart) and 21/23-mm Hancock (Medtronic) SHVs with BVR performed with a noncompliant TRUE balloon (Bard Peripheral Vascular Inc). Hydrodynamic assessment was performed, and multimodality imaging including micro-computed tomography was performed before and after BVR to assess THV and SHV expansion. RESULTS: BVR resulted in limited improvement of THV expansion. The largest gain in expansion was observed for the S3 in the 21-mm Trifecta with up to a 12.7% increase in expansion at the outflow of the valve. Minimal change was observed at the level of the sewing ring. The Hancock was less amenable to BVR with lower final expansion dimensions than the Trifecta. BVR also resulted in notable surgical post flaring of up to 17.6°, which was generally more marked with the S3 than with the Evolut Pro. Finally, BVR resulted in very limited improvement in hydrodynamic function. Severe pinwheeling was observed with the S3, which improved slightly but persisted despite BVR. CONCLUSIONS: When performing VIV TAVR inside a Trifecta and Hancock SHV, BVR had a limited impact on THV expansion and resulted in SHV post flaring with unknown consequences on coronary obstruction risk and long-term THV function.

Timing of bioprosthetic valve fracture in transcatheter valve-in-valve intervention: impact on valve durability and leaflet integrity.

BACKGROUND: Bioprosthetic valve fracture (BVF) can be used to improve transcatheter heart valve (THV) haemodynamics following a valve-in-valve (ViV) intervention. However, whether BVF should be performed before or after THV deployment and the implications on durability are unknown.  Aims: We sought to assess the impact of BVF timing on long-term THV durability. METHODS: The impact of BVF timing was assessed using small ACURATE neo (ACn) or 23 mm SAPIEN 3 (S3) THV deployed in 21 mm Mitroflow valves compared to no-BVF controls. Valves underwent accelerated wear testing up to 200 million (M) cycles (equivalent to 5 years). At 200M cycles, THV were evaluated by hydrodynamic testing, second-harmonic generation (SHG) microscopy, scanning electron microscopy (SEM) and histology. RESULTS: At 200M cycles, the regurgitant fraction (RF) and effective orifice area (EOA) for the ACn were 8.03±0.30%/1.74±0.01 cm2 (no BVF), 12.48±0.70%/1.97±0.02 cm2 (BVF before ViV) and 9.29±0.38%/2.21±0.0 cm2 (BVF after ViV), respectively. For the S3 these values were 2.63±0.51%/1.26±0.01 cm2, 2.03±0.42%/1.65±0.01 cm2, and 1.62±0.38%/2.22±0.01 cm2, respectively. Further, SHG and SEM revealed a higher degree of superficial leaflet damage when BVF was performed after ViV for the ACn and S3. However, the histological analysis revealed significantly less damage, as determined by matrix density analysis, through the entire leaflet thickness when BVF was performed after ViV with the S3 and a similar but non-significant trend with the ACn.  Conclusions: BVF performed after ViV appears to offer superior long-term EOA without increased RF. Ultrastructure leaflet analysis reveals that the timing of BVF can differentially impact leaflets, with more superficial damage but greater preservation of overall leaflet structure when BVF is performed after ViV.

Impact of sex on microvascular reactivity in a murine model of diet-induced obesity and insulin resistance.

The association of obesity with cardiovascular disease is well established. However, the interplay of obesity and vascular dysfunction in peripheral tissues such as skeletal muscle, which plays a key in role metabolic homeostasis, requires further study. In particular, there is a paucity of data with regard to sex-differences. Therefore, using a murine model (C57BL/6) of high-fat diet-induced obesity and insulin resistance, we investigated changes in vascular function in gluteus maximus muscle of female and male mice. Diet-induced obesity resulted in alterations in microvascular function. Obese male mice displayed impaired vasoconstriction in second order arterioles compared to lean, male mice, whereas arterioles of obese, female mice displayed significant impairments of both vasodilation and vasoconstrictor responses compared to lean, female mice. Overall, this study identifies distinct differences in how obesity impacts the female and male murine response to skeletal muscle vascular function. This work advances our understanding of sex-specific risk of metabolic complications of obesity and indicates the need for expansion of this study as well as detailed investigation of sex-specific differences in obesity pathology in the future.

Rural healthcare delivery: Navigating a complex ecosystem.

Clinical Practice Guidelines (CPGs) provide evidence-based recommendations for Healthcare Providers (HCPs) to utilize when making patient care decisions. Rural providers face challenges in the provision of evidence-based care, including the use of guidelines. The aim of this article is to explore the complexities of providing healthcare in rural areas. This article will focus on a specific aspect of rural maternity care with well-established CPGs, the prevention of Rhesus D factor alloimmunization. An applied health research approach, interpretive description, utilized semistructured interviews with HCPs across the vast geographic region of northern British Columbia. The study found that HCPs are aware of guidelines but face various barriers during implementation. In order to implement guidelines within practice, rural HCPs adapt processes to overcome local barriers. These process adaptations need to be identified and shared across a large health authority with a complex geography and healthcare system to ensure quality of care.

Rhesus D factor (RhD) negative women's experiences with pregnancy: An interpretive description.

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.

Anti-Inflammatory Activity of the Wild Mushroom, Echinodontium tinctorium, in RAW264.7 Macrophage Cells and Mouse Microcirculation.

The aim of this study was to investigate the anti-inflammatory activity of a previously un-studied wild mushroom, Echinodontium tinctorium, collected from the forests of north-central British Columbia. The lipopolysaccharide (LPS)-induced RAW264.7 macrophage model was used to study the in vitro anti-inflammatory activity. The crude alkaline extract demonstrated potent anti-inflammatory activity, and was further purified using a "bio-activity-guided-purification" approach. The size-exclusion and ion-exchange chromatography yielded a water-soluble anti-inflammatory polysaccharide (AIPetinc). AIPetinc has an average molecular weight of 5 kDa, and is a heteroglucan composed of mainly glucose (88.6%) with a small amount of galactose (4.0%), mannose (4.4%), fucose (0.7%), and xylose (2.3%). In in vivo settings, AIPetinc restored the histamine-induced inflammatory event in mouse gluteus maximus muscle, thus confirming its anti-inflammatory activity in an animal model. This study constitutes the first report on the bioactivity of Echinodontium tinctorium, and highlights the potential medicinal benefits of fungi from the wild forests of northern British Columbia. Furthermore, it also reiterates the need to explore natural resources for alternative treatment to modern world diseases.

Inonotus obliquus attenuates histamine-induced microvascular inflammation.

Cell-to-cell communication is a key element of microvascular blood flow control, including rapidly carrying signals through the vascular endothelium in response to local stimuli. This cell-to-cell communication is negatively impacted during inflammation through the disruption of junctional integrity. Such disruption is associated with promoting the onset of cardiovascular diseases as a result of altered microvascular blood flow regulation. Therefore, understanding the mechanisms how inflammation drives microvascular dysfunction and compounds that mitigate such inflammation and dysfunction are of great interest for development. As such we aimed to investigate extracts of mushrooms as potential novel compounds. Using intravital microscopy, the medicinal mushroom, Inonotus obliquus was observed, to attenuate histamine-induced inflammation conducted vasodilation in second-order arterioles in the gluteus maximus muscle of C57BL/6 mice. Mast cell activation by C48/80 similarly disrupted endothelial junctions and conducted vasodilation but only histamine was blocked by the histamine antagonist, pyrilamine not C48/80 suggesting the importance of mast cell activation. Data presented here supports that histamine induced inflammation is a major disruptor of junctional integrity, and highlights the important anti-inflammatory properties of Inonotus obliquus focusing future assessment of mast cells as putative target for Inonotus obliquus.

Impact of sublingual nitroglycerin dosage on FFRCT assessment and coronary luminal volume-to-myocardial mass ratio.

OBJECTIVES: Fractional flow reserve computed tomography (FFRCT) depends upon nitroglycerin (NTG) inducing maximal hyperemia. However, the impact of NTG dosages on FFRCT analysis including coronary volume-to-mass ratio (V/M) is unknown. METHODS: Eighty patients with repeat coronary CT angiograms (CCTAs) with different sublingual spray NTG doses (0.4 mg and 0.8 mg) were retrospectively analyzed with 45 patients excluded. Patient and scan demographics, post-stenosis and nadir FFRCT values, coronary volume, and coronary volume-to-mass ratio (V/M) were compared at initial CCTA (0.4 mg NTG) and follow-up CCTA (0.8 mg NTG). Differences were compared by Wilcoxon signed-rank test. RESULTS: Thirty-five patients were included (time between CCTAs, 3.9 ± 1.6 years). Segment involvement score was 2.4 ± 3.3 and 2.8 ± 3.4 at initial and repeat CCTA (0.4 and 0.8 mg NTG), respectively (p = 0.004). There was similar image quality (4.1 ± 0.7 vs 4.1 ± 0.8; p = 0.51). Nadir FFRCT values did not differ in the left (0.4 mg, 0.80 ± 0.08 vs 0.8 mg, 0.80 ± 0.03; p = 0.66), right (0.4 mg, 0.90 ± 0.04 vs 0.8 mg, 0.90 ± 0.06; p = 0.25), or circumflex coronaries (0.4 mg, 0.87 ± 0.06 vs 0.8 mg, 0.88 ± 0.06; p = 0.34). Post-stenosis FFRCT values did not differ (p = 0.65). Coronary volume increased with 0.8 mg of NTG (2639 ± 753 mm3 vs 2844.8 ± 827 mm3; p = 0.009) but V/M ratio did not (p = 0.20). CONCLUSIONS: Use of 0.8 mg versus 0.4 mg of NTG in routine clinical CCTAs significantly increased coronary volume determined from FFRCT analysis but did not alter FFRCT or V/M. Further evaluation of repeat CCTAs in a more contemporaneous fashion using varied nitrate doses and disease severity is needed. KEY POINTS: • Fractional flow reserve from computed tomography (FFRCT) is a noninvasive method for evaluating the coronary arteries and relies on nitroglycerin (NTG) to induce coronary vasodilation, but the impact of different NTG dosages is unknown. • Retrospective analysis evaluated use of different NTG doses on FFRCT. • Increased NTG dose increased coronary luminal volume on FFRCTanalysis, but did not change FFRCTvalues.

Modified Intravital Microscopy to Assess Vascular Health and T-Cell Motility.

The ability to study the microcirculation in real time is key to elucidating how the immune system and the associated microvasculature interact and influence one another within the lymph node (LN). Here, we present a method for near in-situ imaging of the inguinal LN. In particular, this method is ideal for the assessment of overall vascular health that influences immune functions and for the evaluation of T-cell motility. We focus on imaging of the microvasculature of the LN, paying particular attention to methods that ensure the study of healthy vessels, the ability to maintain imaging of viable vessels over a number of hours, quantification of vessel magnitude and vessel integrity. Modified intravital microscopy (M-IVM) of the LNs allows direct evaluation of microvascular functions as well as real-time imaging of the direct interface between immune cells, the LN, and the microcirculation. Importantly, M-IVM technique can be readily combined with many other vascular and immunological techniques such as fluorescent cell labeling and assessment of sticking and rolling time as descripted. Furthermore, it can be adapted to study vasculature of other than the inguinal LN. Overall, this chapter provides a dependable method for fundamental vascular immunological assessment of LNs that is decidedly useful in a diverse range of investigations.

Transcatheter Aortic Heart Valves: Histological Analysis Providing Insight to Leaflet Thickening and Structural Valve Degeneration.

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.

Hypertrophic Cardiomyopathy (HCM): New insights into Coronary artery remodelling and ischemia from FFRCT.

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 (FFRCT) 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. FFRCT values were calculated for the left anterior descending (LAD), left circumflex (LCx) and right coronary (RCA) arteries as well as the 3-vessel cumulative FFRCT values. RESULTS: HCM patients had significantly increased myocardial mass (176 ±â€¯84 vs. 119 ±â€¯27 g, p < 0.0001) and total coronary artery luminal volume (4112 ±â€¯1139 vs. 3290 ±â€¯924 mm3, 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 ±â€¯5.9 vs. 26.5 ±â€¯5.3 mm3/g; p = 0.026) which was further decreased when restricting V/M analysis to those HCM patients with septal hypertrophy (22.4 mm3/g, p = 0.01) that was mild-moderately predictive of HCM (AUC = 0.68). HCM patients also showed significantly lower nadir FFRCT values in the LCx (0.87 ±â€¯0.06 vs. 0.91 ±â€¯0.06, p = 0.02), and cumulative 3-vessel FFRCT values (2.58 ±â€¯0.18 vs. 2.63 ±â€¯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.

Increased nonHDL cholesterol levels cause muscle wasting and ambulatory dysfunction in the mouse model of LGMD2B.

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.

Growth-Inhibitory and Immunomodulatory Activities of Wild Mushrooms from North-Central British Columbia (Canada).

Wild mushrooms, especially from North America, have not been systematically explored for their medicinal properties. Here we report screening for the growth-inhibitory and immunomodulatory activities of 12 species collected from multiple locations in north-central British Columbia, Canada. Mushrooms were characterized using morphology and DNA sequencing, followed by chemical extraction into 4 fractions using 80% ethanol, 50% methanol, water, and 5% sodium hydroxide. Growth-inhibitory, immunostimulatory, and anti-inflammatory activities of 5 mushrooms (Leucocybe connata, Trichaptum abietinum, Hydnellum sp., Gyromitra esculenta, and Hericium coralloides) are reported here, to our knowledge for the first time. Growth-inhibitory effects were assessed using the cytotoxic MTT assay. Immunostimulatory activity was assessed by tumor necrosis factor-α production in Raw 264.7 macrophages, whereas anti-inflammatory activity was assessed based on the inhibition of lipopolysaccharide-induced tumor necrosis factor-α production. The ethanol and aqueous extracts of Hydnellum sp. were potent growth inhibitors, with a half-maximal inhibitory concentration of 0.6 mg/mL. All 5 fungi displayed strong immunostimulatory activity, whereas only L. connata and T. abietinum showed strong anti-inflammatory activity. For the 7 other fungi investigated, which included well-known medicinal species such as Inonotus obliquus, Phellinus igniarius, and Ganoderma applanatum, the remarkable similarities in the biological activities reported here, and by others for specimens collected elsewhere, suggest that mushrooms can produce similar metabolites regardless of their habitat or ecosystem. This is to our knowledge the first study to explore wild mushrooms from British Columbia for biological activities that are relevant to cancer, and the results provide an initial framework for the selection of mushroom species with the potential for discovery of novel anticancer compounds.