A meta-analysis of effects of 3-nitrooxypropanol on methane production, yield, and intensity in dairy cattle.

Ruminants, particularly dairy and beef cattle, contribute to climate change through mostly enteric methane emissions. Several mitigating options have been proposed, including the feed additive 3-nitrooxypropanol (3-NOP). The objectives of this study were to explain the variability in the mitigating effect of 3-NOP and to investigate the interaction between diet composition and 3-NOP dose, using meta-analytical approaches. Data from 13 articles (14 experiments) met the selection criteria for inclusion in the meta-analysis, and 48 treatment means were used for the analysis. Mean differences were calculated as 3-NOP treatment mean minus control treatment mean and then expressed as a percentage of the control mean. Three types of models were developed: (1) one including 3-NOP dose, overall mean, and individual covariate; (2) a combination of neutral detergent fiber (NDF), 3-NOP dose, and overall mean; and (3) one selected model from all combinations of up to 5 covariates, which were compared using a leave-one-out cross validation method. Models including only 3-NOP dose resulted in a significant reduction of 32.7%, 30.9%, and 32.6% for CH4 production (g/d), yield (g/kg dry matter intake), and intensity (g/kg energy-corrected milk), respectively, at an average 3-NOP dose of 70.5 mg/kg dry matter (DM). The greater the NDF content in the diet, the lower the reduction efficiency for a given 3-NOP dose. For 10 g/kg DM increase in NDF content from its mean (329 g of NDF/kg of DM) the 3-NOP effect on CH4 production was impaired by 0.633%, the 3-NOP effect on CH4 yield by 0.647%, and the 3-NOP effect on CH4 intensity by 0.723%. The analysis based on leave-one-out cross validation showed an increase in NDF and crude fat content reduces efficacy of 3-NOP and an increase in 3-NOP dose increases efficacy. A 1% (10 g/kg) DM decrease in dietary NDF content from its mean may increase the efficacy of 3-NOP in reducing CH4 production by 0.915%. A 1% (10 g/kg DM) decrease in dietary crude fat content from its mean enhances the efficacy of 3-NOP on CH4 production by 3.080% at a given dose and NDF level. For CH4 yield, next to 3-NOP dose, dietary NDF content and dietary crude fat content were included in the selected model, but also dietary starch content with an opposite direction to NDF and crude fat. The effect of 3-NOP dose on CH4 intensity was similar to its effect on CH4 production, whereas the effect of dietary NDF content was slightly lower. Expanding the previously published models with the newly available data published from trials since then improved model performance, hence demonstrating the value of regularly updating meta-analyses if a wider range of data becomes available.

Assessment of residual thrombus burden in patients with ST-segment elevation myocardial infarction undergoing bivalirudin versus unfractionated heparin infusion: The MATRIX (minimizing adverse hemorrhagic events by transradial access site and angioX) OCT study.

BACKGROUND: Residual stent strut thrombosis after primary percutaneous coronary intervention (PCI), negatively affects myocardial perfusion, may increase stent thrombosis risk, and it is associated with neointima hyperplasia at follow-up. OBJECTIVES: To study the effectiveness of any bivalirudin infusion versus unfractionated heparin (UFH) infusion in reducing residual stent strut thrombosis in patients with ST-elevation myocardial infarction (STEMI). METHODS: Multi-vessel STEMI patients undergoing primary PCI and requiring staged intervention were selected among those randomly allocated to two different bivalirudin infusion regimens in the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) Treatment-Duration study. Those receiving heparin only were enrolled into a registry arm. Optical coherence tomography (OCT) of the infarct-related artery was performed at the end of primary PCI and 3-5 days thereafter during a staged intervention. The primary endpoint was the change in minimum flow area (ΔMinFA) defined as (stent area + incomplete stent apposition [ISA] area) - (intraluminal defect + tissue prolapsed area) between the index and staged PCI. RESULTS: 123 patients in bivalirudin arm and 28 patients in the UFH arm were included. Mean stent area, percentage of malapposed struts, and mean percent thrombotic area were comparable after index or staged PCI. The ΔMinFA in the bivalirudin group was 0.25 versus 0.05 mm2 in the UFH group, which resulted in a between-group significant difference of 0.36 [95% CI: (0.05, 0.71); p = .02]. This was mostly related to a decrease in tissue protrusion in the bivalirudin group (p = .03). There was a trend towards more patients in the bivalirudin group who achieved a 5% difference in the percentage of OCT frames with the area >5% (p = .057). CONCLUSIONS: The administration of bivalirudin after primary PCI significantly reduces residual stent strut thrombosis when compared to UFH. This observation should be considered hypothesis-generating since the heparin-treated patients were not randomly allocated.

Safety of Algal Oil Containing EPA and DHA in cats during gestation, lactation and growth.

Algal Oil Containing EPA and DHA (AOCED) at approximately 50% was developed as a sustainable n-3 fatty acid source. AOCED was incorporated in diets at dose levels of 0%, 0.75%, 1.5% and 3.0% (w/w) and administered to healthy domestic shorthair female cats starting two weeks before mating, then during mating, gestation, lactation and to their kittens until they reached 32 weeks of age. The diets were made isocaloric and met the Association of American Feed Control Officials (AAFCO) nutrient requirements of cats for growth and reproduction. Dietary AOCED treatment did not affect the overall health, physiological parameters, food consumption and body weights of the queens and their kittens. No AOCED-related changes in haematology, coagulation or clinical chemistry parameters were observed in either generation when compared to control cats. Plasma levels of EPA and DHA were dose-dependently increased in both generations, demonstrating bioavailability of the fatty acids. In this study, safety of AOCED at levels up to 3.0% in the diet was demonstrated in cats with administration starting in utero and until kittens reached 32 weeks of age. Bioavailability of EPA and DHA in cats supports use of AOCED as a source of EPA and DHA for feline growth and reproduction.

Effects of dietary supplementation with 3-nitrooxypropanol on enteric methane production, rumen fermentation, and performance in young growing beef cattle offered a 50:50 forage:concentrate diet.

There is an urgent requirement internationally to reduce enteric methane (CH4) emissions from ruminants to meet greenhouse gas emissions reduction targets. Dietary supplementation with feed additives is one possible strategy under investigation as an effective solution. The effects of the CH4 inhibitor 3-nitrooxypropanol (3-NOP) at reducing CH4 emissions in beef have been shown mainly in adult cattle consuming backgrounding and high-energy finishing diets. In this study, the effects of dietary supplementation of young growing (≤6 mo) beef cattle with 3-NOP were examined in a 50:50 forage:concentrate diet. A total of 68 Dairy × Beef (Aberdeen Angus and Hereford dairy cross) male calves (≤6 mo of age at the start of experiment, body weight: 147 ±â€…38 kg) underwent a 3-wk acclimatization period and were then assigned to one of two treatments in a completely randomized block design. Dietary treatments were (1) control, placebo (no 3-NOP), and (2) 3-NOP applied at 150 mg kg-1 DM. Calves were fed a partial mixed ration for 12 wk. Body weight was recorded weekly and feed intake daily using the Calan Broadbent feeding system. Methane and hydrogen emissions were measured using the GreenFeed system. Total weight gained, dry matter intake (DMI), and average daily gain were not affected by 3-NOP (P > 0.05) supplementation. On average, the inclusion of 3-NOP decreased (P < 0.001) CH4 emissions: g d-1; g kg-1 DMI; by 30.6% and 27.2%, respectively, during the study with a greater reduction occurring over time. Incorporating 3-NOP into beef cattle diets is an efficient solution to decrease CH4 emissions during indoor feeding and when offered 50:50 forage:concentrate diet.

Enteric methane (CH4) is a by-product from the fermentation of feed in the digestive tract of cattle. The production of CH4 is responsible for the loss of 2% to 12% of the animal's gross energy intake. A potent greenhouse gas, CH4 from ruminant systems accounts for 30% of international anthropogenic CH4 emissions. As a result, a significant effort has been made internationally to reduce CH4 emissions from ruminants in order to achieve reductions in global greenhouse gas emissions. The supplementation of additives in the feed has been demonstrated to be an effective strategy in reducing CH4 emitted from livestock. The purpose of this research was to investigate the effects of supplementing young growing cattle with the CH4 inhibitor, 3-nitrooxypropanol (3-NOP), consuming a 50:50 forage:concentrate diet. A total of 68 Dairy × Beef (Aberdeen Angus and Hereford dairy cross) male calves (≤6 mo of age at the start of the experiment) were assigned to one of two treatments: control (no 3-NOP) and 3-NOP. Animals received their diets for 12 wk. Animal performance was recorded weekly, with CH4 and hydrogen (H2) emissions recorded daily. Dry matter intake and animal performance were not affected by the inclusion of 3-NOP. Over the duration of this study, the inclusion of 3-NOP decreased daily CH4 emissions by 30.6%, with a 227% increase in daily H2 emissions.

Self-reported non-adherence to P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: Application of the medication non-adherence academic research consortium classification.

AIMS: The Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Using a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (<30 days) in 21%, late (30-180 days) in 45%, and very late (>180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE. CONCLUSIONS: In real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts. CLINICALTRIALS.GOV IDENTIFIER: NCT02241291.

Correction: Safety of a novel feed ingredient, Algal Oil containing EPA and DHA, in a gestation-lactation-growth feeding study in Beagle dogs.

[This corrects the article DOI: 10.1371/journal.pone.0217794.].

Relationship between arterial remodelling and serial changes in coronary atherosclerosis by intravascular ultrasound: an analysis of the IBIS-4 study.

AIMS: Arterial remodelling is an important determinant of coronary atherosclerosis. Assessment of the remodelling index, comparing a lesion to a local reference site, is a suboptimal correlate of serial vascular changes. We assessed a novel approach which, unlike the local-reference approach, uses the entire artery's global remodelling as reference. METHODS AND RESULTS: Serial (baseline and 13 months) intravascular ultrasound was performed in 146 non-infarct-related arteries of 82 patients treated with high-intensity statin. Arteries were divided into 3-mm segments (n = 1479), and focal remodelling was characterized in individual segments at both timepoints applying the global arterial reference approach. First, we compared preceding vascular changes in relation to follow-up remodelling. Second, we examined whether baseline remodelling predicts subsequent plaque progression/regression. At follow-up, segments with constrictive vs. compensatory or expansive remodelling had greater preceding reduction of vessel area (-0.67 vs. -0.38 vs. -0.002 mm2; P < 0.001) and lumen area (-0.82 vs. -0.09 vs. 0.40 mm2; P < 0.001). Overall, we found significant regression in percent atheroma volume (PAV) [-0.80% (-1.41 to -0.19)]. Segments with constrictive remodelling at baseline had greater subsequent PAV regression vs. modest regression in the compensatory, and PAV progression in the expansive remodelling group (-6.14% vs. -0.71% vs. 2.26%; P < 0.001). Lesion-level analyses (n = 118) showed no differences when remodelling was defined by the local reference approach at baseline or follow-up. CONCLUSION: Remodelling assessment using a global arterial reference approach, but not the commonly used, local reference site approach, correlated reasonably well with serial changes in arterial dimensions and identified arterial segments with subsequent PAV progression despite intensive statin treatment and overall atheroma regression.

Discordance in the diagnostic assessment of vulnerable plaques between radiofrequency intravascular ultrasound versus optical coherence tomography among patients with acute myocardial infarction: insights from the IBIS-4 study.

We aimed to evaluate the diagnostic agreement between radiofrequency (RF) intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for thin-cap fibroatheroma (TCFA) in non-infarct-related coronary arteries (non-IRA) in patients with ST-segment elevation myocardial infarction (STEMI). In the Integrated Biomarker Imaging Study (IBIS-4), 103 STEMI patients underwent OCT and RF-IVUS imaging of non-IRA after successful primary percutaneous coronary intervention and at 13-month follow-up. A coronary lesion was defined as a segment with ≥ 3 consecutive frames (≈1.2 mm) with plaque burden ≥ 40% as assessed by grayscale IVUS. RF-IVUS-derived TCFA was defined as a lesion with > 10% confluent necrotic core abutting to the lumen in > 10% of the circumference. OCT-TCFA was defined by a minimum cap thickness < 65 µm. The two modalities were matched based on anatomical landmarks using a dedicated matching software. Using grayscale IVUS, we identified 276 lesions at baseline (N = 146) and follow-up (N = 130). Using RF-IVUS, 208 lesions (75.4%) were classified as TCFA. Among them, OCT identified 14 (6.7%) TCFA, 60 (28.8%) thick-cap fibroatheroma (ThCFA), and 134 (64.4%) non-fibroatheroma. All OCT-TCFA (n = 14) were confirmed as RF-TCFA. The concordance rate between RF-IVUS and OCT for TCFA diagnosis was 29.7%. The reasons for discordance were: OCT-ThCFA (25.8%); OCT-fibrous plaque (34.0%); attenuation due to calcium (23.2%); attenuation due to macrophage (10.3%); no significant attenuation (6.7%). There was a notable discordance in the diagnostic assessment of TCFA between RF-IVUS and OCT. The majority of RF-derived TCFA were not categorized as fibroatheroma using OCT, while all OCT-TCFA were classified as TCFA by RF-IVUS.ClinicalTrials.gov Identifier NCT00962416.

Ultra-Short Term Evaluation of Coronary Vessel Wall Changes in Reference Segments Adjacent to Culprit Lesions in ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Culprit lesions of ST-segment elevation myocardial infarction (STEMI) patients are friable, soft, and prone to disruption during primary percutaneous coronary intervention (pPCI). The presence of dissections in reference vessel segments (RVSs), adjacent to stented culprit lesions, and dynamic luminal changes in proximal or distal RVSs have not yet been investigated. We therefore sought to assess the healing patterns of edge dissections and the changes of lumen area at RVSs within 1 week post stent implantation in patients with STEMI. METHODS: In the MATRIX trial (ClinicalTrials.gov NCT01433627), optical coherence tomography (OCT) was performed at the end of pPCI and within 1 week during staged PCI. The RVS dissection was defined as: type 1 = flap; type 2 = cavity; type 3 = double barrel; and type 4 = fissure. We compared separately the fate of residual dissection and luminal area/dimension by OCT in the target vessel between pPCI and staged PCI, including 1-year clinical outcomes. RESULTS: Out of 151 patients, 46 patients had dissections in 50 RVSs and did not experience worse clinical outcome. Dissections were 44% type 1, 28% type 2, 12% type 3, and 16% type 4. Overall, 18% of the dissections healed. The mean lumen area of the RVS enlarged in 82 patients (59%) from pPCI to staged PCI. Compared with the proximal RVS, there was a significant increase in the lumen diameter at the distal RVS (0.06 ± 0.25 mm vs -0.01 ± 0.21 mm; P=.01). CONCLUSION: Dissections occur frequently after pPCI. One-fifth of them heal within 1 week and do not seem to negatively impact clinical outcomes. Distal RVS lumen area increased compared with proximal RVS, likely reflecting a different vasoconstriction pattern over time.

Impact of optical coherence tomography findings on clinical outcomes in ST-segment elevation myocardial infarction patients: a MATRIX (Minimizing Adverse Hemorrhagic Events by Trans-radial Access Site and angioX) OCT sub-study.

PURPOSE: To investigate the association of the degree of stent expansion, as assessed by optical coherence tomography (OCT), following stent implantation, and clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients. METHODS: STEMI patients from the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) OCT study were selected; Clinical outcomes were collected through 1 year. Stent expansion index is a minimum stent area (MSA) divided by average lumen area (average of proximal and distal reference lumen area). The following variables were measured: MSA (< 4.5mm2), dissection (> 200 µm in width and < 5 mm from stent segment), malapposition (> 200 µm distance of stent from vessel wall), a thrombus (area > 5% of lumen area) were compared. RESULTS: A total of 151 patients were included; after excluding patients with suboptimal OCT quality, the population with available OCT was classified into 2 groups: under-expanded < 90% (N = 72, 51%) and well-expanded ≥ 90% (N = 67, 49%). In the well-expanded group, a significant number of the proximal vessels had a lumen area < 4.5mm2 (16.1%, p < 0.001) and a greater thrombus burden within stent (56.7%, p = 0.042). The overall 30 day and 1 year major adverse cardiovascular event (MACE) rates were 5% and 6.1%, respectively. CONCLUSION: Irrespective of the degree of stent expansion, the OCT findings, in STEMI patients, and the MACE at 30 days and one year follow up was low; further, well-expanded stents led to a more significant residual thrombotic burden within the stent but seemed to have insignificant clinical impact. Acknowledged stent optimization criteria, traditionally related to worse outcomes in stable patients, do not seem to be associated with worse outcomes in this STEMI population.

Randomized Comparison of Optical Coherence Tomography Versus Angiography to Guide Bioresorbable Vascular Scaffold Implantation: The OPTICO BVS Study.

PURPOSE: We investigated whether optical coherence tomography (OCT)-guided bioresorbable vascular scaffolds (BVS) implantation can improve in-scaffold minimal lumen area (MLA) at 6-month compared with angiography guidance. METHODS: The OPTICO BVS was a randomized, international multicenter, assessor blind, superiority trial comparing OCT- versus angiography-guided percutaneous coronary intervention (PCI) (1:1 allocation) in patients with coronary artery disease undergoing Absorb BVS 1.1 implantation. The primary endpoint was in-scaffold MLA at 6-month. RESULTS: The trial was prematurely stopped on May 31, 2017 after enrollment of 38 of 270 planned patients (14%) following the retraction of the device in Europe. Patients were randomly assigned to OCT- (n = 19) or angiography-guided PCI (n = 19). Scaffold diameter (OCT 3.0 ± 0.3 mm vs. angiography 3.1 ± 0.3 mm, P = .333) and length (28.8 ± 13.6 mm vs. 23.8 ± 12.3 mm, P = .223) were comparable. There was no significant difference in in-scaffold MLA at 6 months (4.47mm2 vs. 5.08mm2, P = .692). Scaffold expansion at 6-month was significantly higher in the OCT-guided PCI as compared with angiography-guided PCI (84.5% vs. 76.5%, P = .010). There was no significant difference in clinical outcomes. CONCLUSIONS: Although in-scaffold MLA at 6-month did not differ between groups, scaffold expansion was improved following OCT- as compared with angiography-guided PCI. The findings of this study must be interpreted in view of the premature termination with inclusion of 14% of the initially planned study sample.

Shear Stress Estimated by Quantitative Coronary Angiography Predicts Plaques Prone to Progress and Cause Events.

OBJECTIVES: This study examined the value of endothelial shear stress (ESS) estimated in 3-dimensional quantitative coronary angiography (3D-QCA) models in detecting plaques that are likely to progress and cause events. BACKGROUND: Cumulative evidence has shown that plaque characteristics and ESS derived from intravascular ultrasound (IVUS)-based reconstructions enable prediction of lesions that will cause cardiovascular events. However, the prognostic value of ESS estimated by 3D-QCA in nonflow limiting lesions is yet unclear. METHODS: This study analyzed baseline virtual histology (VH)-IVUS and angiographic data from 28 lipid-rich lesions (i.e., fibroatheromas) that caused major adverse cardiovascular events or required revascularization (MACE-R) at 5-year follow-up and 119 lipid-rich plaques from a control group that remained quiescent. The segments studied by VH-IVUS at baseline were reconstructed using 3D-QCA software. In the obtained geometries, blood flow simulation was performed, and the pressure gradient across the lipid-rich plaque and the mean ESS values in 3-mm segments were estimated. The additive value of these hemodynamic indexes in predicting MACE-R beyond plaque characteristics was examined. RESULTS: MACE-R lesions were longer, had smaller minimum lumen area, increased plaque burden (PB), were exposed to higher ESS, and exhibited a higher pressure gradient. In multivariable analysis, PB (hazard ratio: 1.08; p = 0.004) and the maximum 3-mm ESS value (hazard ratio: 1.11; p = 0.001) were independent predictors of MACE-R. Lesions exposed to high ESS (>4.95 Pa) with a high-risk anatomy (minimal lumen area <4 mm2 and PB >70%) had a higher MACE-R rate (53.8%) than those with a low-risk anatomy exposed to high ESS (31.6%) or those exposed to low ESS who had high- (20.0%) or low-risk anatomy (7.1%; p < 0.001). CONCLUSIONS: In the present study, 3D-QCA-derived local hemodynamic variables provided useful prognostic information, and, in combination with lesion anatomy, enabled more accurate identification of MACE-R lesions.

Predictive value of the QFR in detecting vulnerable plaques in non-flow limiting lesions: a combined analysis of the PROSPECT and IBIS-4 study.

Studies have shown that the quantitative flow ratio (QFR), recently introduced to assess lesion severity from coronary angiography, provides useful prognostic information; however the additive value of this technique over intravascular imaging in detecting lesions that are likely to cause events is yet unclear. We analysed data acquired in the PROSPECT and IBIS-4 studies, in particular the baseline virtual histology-intravascular ultrasound (VH-IVUS) and angiographic data from 17 non-culprit lesions with a presumable vulnerable phenotype (i.e., thin or thick cap fibroatheroma) that caused major adverse cardiac events or required revascularization (MACE) at 5-year follow-up and from a group of 78 vulnerable plaques that remained quiescent. The segments studied by VH-IVUS were identified in coronary angiography and the QFR was estimated. The additive value of 3-dimensional quantitative coronary angiography (3D-QCA) and of the QFR in predicting MACE at 5 year follow-up beyond plaque characteristics was examined. It was found that MACE lesions had a greater plaque burden (PB) and smaller minimum lumen area (MLA) on VH-IVUS, a longer length and a smaller minimum lumen diameter (MLD) on 3D-QCA and a lower QFR compared with lesions that remained quiescent. By univariate analysis MLA, PB, MLD, lesion length on 3D-QCA and QFR were predictors of MACE. In multivariate analysis a low but normal QFR (> 0.80 to < 0.97) was the only independent prediction of MACE (HR 3.53, 95% CI 1.16-10.75; P = 0.027). In non-flow limiting lesions with a vulnerable phenotype, QFR may provide additional prognostic information beyond plaque morphology for predicting MACE throughout 5 years.

Utility of Multimodality Intravascular Imaging and the Local Hemodynamic Forces to Predict Atherosclerotic Disease Progression.

OBJECTIVES: This study sought to examine the utility of multimodality intravascular imaging and of the endothelial shear stress (ESS) distribution to predict atherosclerotic evolution. BACKGROUND: There is robust evidence that intravascular ultrasound (IVUS)-derived plaque characteristics and ESS distribution can predict, with however limited accuracy, atherosclerotic evolution; nevertheless, it is yet unclear whether multimodality imaging and ESS mapping enable more accurate prediction of coronary plaque progression. METHODS: A total of 44 patients admitted with a myocardial infarction that had successful revascularization and 3-vessel IVUS and optical coherence tomography (OCT) imaging at baseline and 13-month follow-up were included in the study. The IVUS data acquired at baseline in the nonculprit vessels were fused with x-ray angiography to reconstruct coronary anatomy and in the obtained models blood flow simulation was performed and the ESS was estimated. The baseline plaque characteristics and ESS distribution were used to identify predictors of disease progression: defined as a lumen reduction and an increase in plaque burden at follow-up. RESULTS: Seventy-three vessels were included in the final analysis. Baseline ESS and the IVUS-derived but not the OCT-derived plaque characteristics were independently associated with a decrease in lumen area and an increase in plaque burden. Low ESS (odds ratio: 0.45; 95% confidence interval: 0.28 to 0.71; p < 0.001) and plaque burden (odds ratio: 0.73; 95% confidence interval: 0.54 to 0.97; p = 0.030) were the only independent predictors of disease progression at follow-up. The accuracy of the IVUS-derived plaque characteristics in predicting disease progression did not improve when ESS (AUC: 0.824 vs. 0.847; p = 0.127) or when OCT variables and ESS (AUC: 0.842; p = 0.611) were added into the model. CONCLUSIONS: ESS and OCT-derived variables did not improve the efficacy of IVUS in predicting disease progression. Further research is required to investigate whether multimodality imaging combined with ESS mapping will allow more reliable vulnerable plaque detection. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416).

Safety of a novel feed ingredient, Algal Oil containing EPA and DHA, in a gestation-lactation-growth feeding study in Beagle dogs.

An Algal Oil Containing EPA and DHA (AOCED) at ~50% was developed as a sustainable source of omega-3 fatty acids. AOCED was incorporated into extruded dry foods for dogs at 0, 0.75%, 1.5% and 3.0% levels (equivalent to 0, 7.5, 15 and 30 g/kg diet) on dry matter basis at the expense of chicken fat and fed to healthy female Beagle dogs starting at mating and throughout gestation and lactation. The offspring were fed their maternal corresponding diets for 26 weeks after weaning. AOCED-enriched diets were well tolerated by dogs in both generations and did not affect their overall health, physiological parameters, food consumption, body weights and body weight gains. There were no changes in hematology, clinical chemistry, and coagulation parameters in both generations of dogs fed the AOCED diets when compared to those in the control group. Plasma levels of DHA and EPA increased significantly and generally dose-dependently in both generations. The study demonstrated the safety of AOCED in dogs during gestation, lactation, and growth periods at dietary levels up to 3.0wt%, equivalent to 30 g/kg diet. AOCED's bioavailability as a source of DHA and EPA in dogs was demonstrated by the increased plasma concentrations of these nutritional lipids.

Ischemia and Bleeding in Cancer Patients Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: The purpose of this study was to evaluate ischemic and bleeding outcomes of unselected cancer patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: The number of cancer patients undergoing PCI is increasing despite concerns regarding ischemic and bleeding risks. METHODS: Between 2009 and 2017, consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Cancer-specific data including type, date of initial diagnosis, and health status at index PCI were collected. We performed propensity score matching to adjust for baseline differences between patients with and without cancer. The primary ischemic endpoint was the device-oriented composite endpoint (cardiac death, target vessel myocardial infarction, target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 2 to 5 at 1 year. RESULTS: Among 13,647 patients, 1,368 (10.0%) had an established diagnosis of cancer. The 3 leading cancer types were prostate (n = 294), gastrointestinal tract (n = 188), and hematopoietic (n = 177). At index PCI, 179 (13.1%) patients were receiving active cancer treatment. In matched analysis, there was no significant difference in device-oriented composite endpoint (11.5% vs. 10.2%; p = 0.251), whereas cardiac death and BARC 2 to 5 bleeding occurred more frequently among patients with cancer compared with those without cancer (6.8% vs. 4.5%; p = 0.010 and 8.0% vs. 6.0%; p = 0.026, respectively). Cancer diagnosis within 1 year before PCI emerged as an independent predictor for cardiac death and BARC 2 to 5 bleeding at 1 year. CONCLUSIONS: Cancer patients carry an increased risk of cardiac mortality that was not associated with stent-related ischemic events among patients undergoing PCI in routine clinical practice. Higher risk of bleeding in cancer patients undergoing PCI deserves particular attention. (CARDIOBASE Bern PCI Registry; NCT02241291).

Implications of the local haemodynamic forces on the phenotype of coronary plaques.

AIM: To examine the effect of endothelial shear stress (ESS) on the dynamic changes in plaque phenotype. METHODS: Patients with myocardial infarction that had intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT) at baseline and 13-month follow-up were studied. The IVUS-VH data were used to reconstruct the nonculprit vessels, and in the obtained models the ESS was estimated in 3 mm segments. Plaque morphology was derived in each segment from IVUS-VH and OCT. Disease progression was defined as the presence of ≥2 out of the following criteria: reduction in lumen area, increase in plaque burden and change of plaque morphology to a more vulnerable phenotype. Linear mixed effects models were used to assess the effect of ESS in different phenotypes. RESULTS: Sixty-eight vessels were included in the analysis. Low ESS was associated with plaque progression in all phenotypes. The effect of ESS on plaque burden (p for interaction=0.467) and phenotype (p for interaction=0.188) was similar in all plaque types, whereas the effect of ESS on the changes in lumen dimensions was more prominent in disease-free (ß=0.70, p<0.001) than fibrotic/fibrocalcific (ß=0.28, p<0.001) or lipid-rich plaques (ß=0.15, p=0.015). Standalone IVUS-VH misclassified plaque morphology in one-third of the cases leading to erroneous estimations about the effect of ESS on plaque evolution in different phenotypes. CONCLUSIONS: The effect of ESS on plaque progression is similar in all phenotypes and cannot be accurately assessed by standalone IVUS-VH which often misclassifies plaque morphology. Therefore, multimodality imaging should be considered to examine the implications of ESS on plaque evolution. CLINICAL TRIAL REGISTRATION: NCT00962416; Post-results.

Validation of High-Risk Features for Stent-Related Ischemic Events as Endorsed by the 2017 DAPT Guidelines.

OBJECTIVES: This study sought to validate European Society of Cardiology guideline-endorsed high-risk features of stent-related recurrent ischemic events for the prediction of ischemic and bleeding outcomes including a stratification according to the PRECISE-DAPT score estimated bleeding risk. BACKGROUND: The 2017 European Society of Cardiology-focused update on dual-antiplatelet therapy endorsed high-risk features of stent-related recurrent ischemic events. Because patients with high ischemic risk also have an increased bleeding risk, appropriate risk stratification for ischemic and bleeding events is crucial. METHODS: Between January 2009 and December 2015, a total of 10,236 consecutive patients undergoing clinically indicated percutaneous coronary intervention were prospectively included in the Bern PCI Registry. Guideline-endorsed high-risk features were retrospectively assessed. The primary ischemic endpoint was device-oriented composite endpoint (DOCE) (cardiac death, target-vessel myocardial infarction, and target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 3-5 at 1 year. RESULTS: A total of 5,323 (52.0%) patients had at least 1 high-risk feature. Among patients with high-risk features, DOCE (12.3% vs. 5.5%; p < 0.001) and BARC 3-5 bleeding (4.9% vs. 2.2%; p < 0.001) occurred more frequently compared with those without. There was a graded risk increase for DOCE (0: 5.5%; 1 to 2: 11.3%; and ≥3: 16.7%; p < 0.001) and BARC 3-5 bleeding (0: 2.2%; 1 to 2: 4.5%; and ≥3: 6.6%; p < 0.001) as the number of high-risk features increased. High-PRECISE-DAPT score (≥25) was associated with an increased risk of DOCE and BARC 3-5 bleeding, irrespective of number of high-risk features. CONCLUSIONS: The European Society of Cardiology guideline-endorsed high-risk features were associated with increased ischemic and bleeding risks following percutaneous coronary intervention in routine clinical practice. (CARDIOBASE Bern PCI Registry; NCT02241291).

Angiographic derived endothelial shear stress: a new predictor of atherosclerotic disease progression.

AIMS: To examine the efficacy of angiography derived endothelial shear stress (ESS) in predicting atherosclerotic disease progression. METHODS AND RESULTS: Thirty-five patients admitted with ST-elevation myocardial infarction that had three-vessel intravascular ultrasound (IVUS) immediately after revascularization and at 13 months follow-up were included. Three dimensional (3D) reconstruction of the non-culprit vessels were performed using (i) quantitative coronary angiography (QCA) and (ii) methodology involving fusion of IVUS and biplane angiography. In both models, blood flow simulation was performed and the minimum predominant ESS was estimated in 3 mm segments. Baseline plaque characteristics and ESS were used to identify predictors of atherosclerotic disease progression defied as plaque area increase and lumen reduction at follow-up. Fifty-four vessels were included in the final analysis. A moderate correlation was noted between ESS estimated in the 3D QCA and the IVUS-derived models (r = 0.588, P < 0.001); 3D QCA accurately identified segments exposed to low (<1 Pa) ESS in the IVUS-based reconstructions (AUC: 0.793, P < 0.001). Low 3D QCA-derived ESS (<1.75 Pa) was associated with an increase in plaque area, burden, and necrotic core at follow-up. In multivariate analysis, low ESS estimated either in 3D QCA [odds ratio (OR): 2.07, 95% confidence interval (CI): 1.17-3.67; P = 0.012) or in IVUS (<1 Pa; OR: 2.23, 95% CI: 1.23-4.03; P = 0.008) models, and plaque burden were independent predictors of atherosclerotic disease progression; 3D QCA and IVUS-derived models had a similar accuracy in predicting disease progression (AUC: 0.826 vs. 0.827, P = 0.907). CONCLUSIONS: 3D QCA-derived ESS can predict disease progression. Further research is required to examine its value in detecting vulnerable plaques.