A streamlined pathway for transcatheter aortic valve implantation: the BENCHMARK study.

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

Risk assessment-based verification of the CertiPURTM limit values for toluene diamine and methylene dianiline in flexible polyurethane foam.

Flexible polyurethane foams (PUF) are used in many consumer products. PUF may contain trace levels of aromatic diamine impurities that could represent a potential health risk. The risk associated with sleeping on a PUF mattress was evaluated. Toxicity benchmarks for sensitization and non-cancer endpoints were derived from the respective points-of-departure using standard assessment factors. For the cancer endpoints, toxicity benchmarks were derived from the 25th-percentile values of animal studies. Recently published emission and migration data allowed to link exposure with the CertiPURTM voluntary quality limits of ≤5 mg.kg-1 for 2,4-toluene diamine and 4,4'-methylene dianiline in PUF. Using conservative exposure scenarios, lifetime-average daily internal doses from the combined inhalation and dermal exposures were calculated. Margins of safety for non-cancer and sensitization endpoints were >104. The theoretical excess cancer risk was ≤1.5 × 10-7. It is concluded that sleeping on a mattress that satisfies the CertiPUR limit value does not pose undue risk to consumers.

Assessment of hemodynamic indices of conjunctival microvascular function in patients with coronary microvascular dysfunction.

OBJECTIVE: Coronary microvascular dysfunction (CMD) is a cause of ischaemia with non-obstructive coronary arteries (INOCA). It is notoriously underdiagnosed due to the need for invasive microvascular function testing. We hypothesized that systemic microvascular dysfunction could be demonstrated non-invasively in the microcirculation of the bulbar conjunctiva in patients with CMD. METHODS: Patients undergoing coronary angiography for the investigation of chest pain or dyspnoea, with physiologically insignificant epicardial disease (fractional flow reserve ≥0.80) were recruited. All patients underwent invasive coronary microvascular function testing. We compared a cohort of patients with evidence of CMD (IMR ≥25 or CFR <2.0); to a group of controls (IMR <25 and CFR ≥2.0). Conjunctival imaging was performed using a previously validated combination of a smartphone and slit-lamp biomicroscope. This technique allows measurement of vessel diameter and other indices of microvascular function by tracking erythrocyte motion. RESULTS: A total of 111 patients were included (43 CMD and 68 controls). There were no differences in baseline demographics, co-morbidities or epicardial coronary disease severity. The mean number of vessel segments analysed per patient was 21.0 ± 12.8 (3.2 ± 3.5 arterioles and 14.8 ± 10.8 venules). In the CMD cohort, significant reductions were observed in axial/cross-sectional velocity, blood flow, wall shear rate and stress. CONCLUSION: The changes in microvascular function linked to CMD can be observed non-invasively in the bulbar conjunctiva. Conjunctival vascular imaging may have utility as a non-invasive tool to both diagnose CMD and augment conventional cardiovascular risk assessment.

Long-term durability of self-expanding and balloon-expandable transcatheter aortic valve prostheses: UK TAVI registry.

BACKGROUND: With expansion of transcatheter aortic valve implantation (TAVI) into younger patients, valve durability is critically important. AIMS: We aimed to evaluate long-term valve function and incidence of severe structural valve deterioration (SVD) among patients ≥ 10-years post-TAVI and with echocardiographic follow-up at least 5-years postprocedure. METHODS: Data on patients who underwent TAVI from 2007 to 2011 were obtained from the UK TAVI registry. Patients with paired echocardiograms postprocedure and ≥5-years post-TAVI were included. Severe SVD was determined according to European task force guidelines. RESULTS: 221 patients (79.4 ± 7.3 years; 53% male) were included with median echocardiographic follow-up 7.0 years (range 5-13 years). Follow-up exceeded 10 years in 43 patients (19.5%). Valve types were the supra-annular self-expanding CoreValve (SEV; n = 143, 67%), balloon-expandable SAPIEN/XT (BEV; n = 67, 31%), Portico (n = 4, 5%) and unknown (n = 7, 3%). There was no difference between postprocedure and follow-up peak gradient in the overall cohort (19.3 vs. 18.4 mmHg; p = NS) or in those with ≥10-years follow-up (21.1 vs. 21.1 mmHg; p = NS). Severe SVD occurred in 13 patients (5.9%; median 7.8-years post-TAVI). Three cases (23.1%) were due to regurgitation and 10 (76.9%) to stenosis. Valve-related reintervention/death occurred in 5 patients (2.3%). Severe SVD was more frequent with BEV than SEV (11.9% vs. 3.5%; p = 0.02), driven by a difference in patients treated with small valves (BEV 28.6% vs. SEV 3.0%; p < 0.01). CONCLUSIONS: Hemodynamic function of transcatheter heart valves remains stable up to more than 10 years post-TAVI. Severe SVD occurred in 5.9%, and valve-related death/reintervention in 2.3%. Severe SVD was more common with BEV than SEV.

Impact of technique on bifurcation stent outcomes in the European Bifurcation Club Left Main Coronary Trial.

BACKGROUND: Techniques for provisional and dual-stent left main bifurcation stenting require optimization. AIM: To identify technical variables influencing procedural outcomes and periprocedural myocardial infarction following left main bifurcation intervention. METHODS: Procedural and outcome data were analyzed in 438 patients from the per-protocol cohort of the European Bifurcation Club Left Main Trial (EBC MAIN). These patients were randomized to the provisional strategy or a compatible dual-stent extension (T, T-and-protrude, or culotte). RESULTS: Mean age was 71 years and 37.4% presented with an acute coronary syndrome. Transient reduction of side vessel thrombolysis in myocardial infarction flow occurred after initial stent placement in 5% of procedures but was not associated with periprocedural myocardial infarction. Failure to rewire a jailed vessel during any strategy was more common when jailed wires were not used (9.5% vs. 2.5%, odds ratio [OR]: 6.4, p = 0.002). In the provisional cohort, the use of the proximal optimization technique was associated with less subsequent side vessel intervention (23.3% vs. 41.9%, OR: 0.4, p = 0.048). Side vessel stenting was predominantly required for dissection, which occurred more often following side vessel preparation (15.3% vs. 4.4%, OR: 3.1, p = 0.040). Exclusive use of noncompliant balloons for kissing balloon inflation was associated with reduced need for side vessel intervention in provisional cases (20.5% vs. 38.5%, OR: 0.4, p = 0.013), and a reduced risk of periprocedural myocardial infarction across all strategies (2.9% vs. 7.7%, OR: 0.2, p = 0.020). CONCLUSION: When performing provisional or compatible dual-stent left main bifurcation intervention, jailed wire use is associated with successful jailed vessel rewiring. Side vessel preparation in provisional patients is linked to increased side vessel dissection requiring stenting. Use of the proximal optimization technique may reduce the need for additional side vessel intervention, and noncompliant balloon use for kissing balloon inflation is associated with a reduction in both side vessel stenting and periprocedural myocardial infarction. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02497014.

Glu298Asp variant of the endothelial nitric oxide synthase gene and acute coronary syndrome or premature coronary artery disease: A systematic review and meta-analysis.

INTRODUCTION: Several published studies have reported an association between the Glu298Asp polymorphism (rs1799983), residing in the endothelial nitric oxide synthase (NOS3) gene, and lower levels of circulating nitric oxide, as well as an increased risk of coronary artery disease (CAD). However, association status of this genetic variant with acute coronary syndrome (ACS) or premature CAD (PCAD) is still unclear. Against this background, we conducted a systematic review and study level meta-analysis to assess the association of the NOS3 Glu298Asp polymorphism with ACS or PCAD. MATERIALS AND METHODS: A comprehensive online search to identify relevant studies was performed on several databases including PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science. The identified studies were stratified into two ancestral subgroups: 'European ancestry' and 'All other ancestries combined'. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random/fixed effects employing a Z test. RESULTS: Out of a total of 195 distinct records identified through online search, 37 articles with 39 different studies, with a total sample size of 27,441 (11,516 cases/15,925 controls) were included for quantitative synthesis. Pooled results suggested significant associations of the NOS3 Glu298Asp polymorphism with ACS or PCAD through dominant as well as allelic genetic models (p ≤ 0.002), primarily driven by the 'All other ancestries combined' subgroup. The 'All other ancestries combined' subgroup demonstrated an additional risk of 36% for ACS or PCAD, through both dominant and allelic genetic models (OR = 1.36, 95%CI = 1.13, 1.63, p = 0.001 and OR = 1.36, 95%CI = 1.14, 1.61, p = 0.0005 respectively). On the other hand, the 'European ancestry' subgroup did not show any significant associations. Sensitivity analysis and a sub-analysis for the myocardial infarction endpoint further supported these observed associations. CONCLUSIONS: This meta-analysis indicates towards an association between the NOS3 Glu298Asp polymorphism and ACS or PCAD, predominantly driven by 'All other ancestries combined' subgroup. In contrast, the 'European ancestry' subgroup did not demonstrate any significant association. Further large-scale investigations are required to confirm our derived results.

Emission and time-resolved migration rates of aromatic diamines from two flexible polyurethane foams.

Performing risk assessments (RA) on household use of flexible polyurethane (PU) foams requires access to reliable data about emission and migration of potential diamine impurities. A toluene diisocyanate (TDI) and a methylene diphenyl diisocyanate (MDI) based foam were thermally treated to enable measurements on samples with defined concentrations of the corresponding diamines, toluene diamine (TDA), and methylene dianiline (MDA). The thermally treated foams used for emission testing contained up to 15 mg.kg-1 of TDA and 27 mg.kg-1 of MDA. Those used for migration testing contained 5.1 mg.kg-1 of TDA and 14.1 mg.kg-1 of MDA. Stability of the thermally generated diamines was sufficient for testing over a 37-day period. Analytical techniques that did not decompose the polymer matrix were applied. Emission rates for TDA and MDA isomers were less than the limit of quantitation (LOQ) of 0.008-0.07 µg.m-2.h-1. Migration was studied using samples of the same thermally treated foams over a 35-day period. Quantifiable migration of MDA from the MDI-based foam was only observed on Days 1 and 2. From Day 3 onward, migration rates were less than the LOQ. Quantifiable migration of TDA from the TDI-based foam rapidly decreased with time and was only observed on Days 1 thru 3. From Day 4 onward, migration rates were less than the LOQ. Theoretically, the migration rate should be inversely proportional to the square root of time (t) as t-0.5. This relationship was confirmed by the experimental data and enables extrapolating migration values to more extended time periods to conduct RAs.

Methylene diphenyl diisocyanate occupational exposure data in industry (1998-2020): A descriptive summary from an industrial hygiene perspective.

This paper provides an overview of airborne methylene diphenyl diisocyanate (MDI) concentrations in workplaces across North America and Europe. A total of 7649 samples were collected between 1998 and 2020 by producers of MDI during product stewardship activities at customer sites, primarily using validated OSHA or ISO sampling and analysis techniques. As would be expected from the low vapor pressure of MDI, 80% of the concentrations were less than 0.01 mg/m3 (1 ppb) and 93% were less than 0.05 mg/m3 (5 ppb). Respiratory protection is an integral part of Industrial Hygiene practices; therefore, its use was studied and summarized. While covering a variety of MDI applications, a large number of samples was obtained from composite wood manufacturing facilities, offering specific insight into potential exposures associated with different process sections and job types in this industry sector. Given the potential presence in industrial processes of MDI-containing dust or aerosols, future work should place increased emphasis on also investigating dermal exposure. The data reported in this paper provide valuable information for product stewardship and industrial hygiene purposes throughout the MDI-processing industry.

Redo aortic valve replacement versus valve-in-valve trans-catheter aortic valve implantation: a UK propensity-matched analysis.

This study sought to compare the morbidity and mortality of redo aortic valve replacement (redo-AVR) versus valve-in-valve trans-catheter aortic valve implantation (valve-in-valve TAVI) for patients with a failing bioprosthetic valve. A multicenter UK retrospective study of redo-AVR or valve-in-valve TAVI for patients referred for redo aortic valve intervention due to a degenerated aortic bioprosthesis. Propensity score matching was performed for confounding factors. From July 2005 to April 2021, 911 patients underwent redo-AVR and 411 patients underwent valve-in-valve TAVI. There were 125 pairs for analysis after propensity score matching. The mean age was 75.2±8.5 years. In-hospital mortality was 7.2% (n=9) for redo-AVR versus 0 for valve-in-valve TAVI, p=0.002. Surgical patients suffered more post-operative complications, including intra-aortic balloon pump support (p=0.02), early re-operation (p<0.001), arrhythmias (p<0.001), respiratory and neurological complications (p=0.02 and p=0.03) and multi-organ failure (p=0.01). The valve-in-valve TAVI group had a shorter intensive care unit and hospital stay (p<0.001 for both). However, moderate aortic regurgitation at discharge and higher post-procedural gradients were more common after valve-in-valve TAVI (p<0.001 for both). Survival probabilities in patients who were successfully discharged from the hospital were similar after valve-in-valve TAVI and redo-AVR over the 6-year follow-up (log-rank p=0.26). In elderly patients with a degenerated aortic bioprosthesis, valve-in-valve TAVI provides better early outcomes as opposed to redo-AVR, although there was no difference in mid-term survival in patients successfully discharged from the hospital.

The impact of learning-curve-experience on transcatheter aortic valve replacement outcomes: Insights from the United Kingdom and Ireland all-comers second-generation ACURATE neo™ transcatheter aortic heart valve registry.

BACKGROUND: The ACURATE neo™ is a novel, second-generation self-expanding supra-annular transcatheter heart valve (THV). The objective of this multi-centre registry is to assess the safety, clinical utility, and impact of 'learning-curve-experience' (LCE) on transcatheter aortic valve replacement outcomes in the United Kingdom (UK) and Ireland. METHODS: We prospectively collected data from seven ACURATE neo™ THV implanting centres (n = 484) between February 2016 and November 2020. We compared mortality rates and outcomes in the LCE group (n = 120) compared to next successive 120 cases. RESULTS: The mean age of the cohort was 81.9(SD: 6.1) years and the majority were in the moderate risk category (EuroSCORE-II):3.3(SD: 3). The 97.5% of cases were performed under local anesthetic. The valve was successfully deployed in 98.8% of cases. The survival rate at 30 days was 97.9%. The incidence of stroke was 2.5%. Life threatening bleeding occurred in 0.6% of cases and vascular access complications occurred in 21 (4.3%) patients. Implantation-related conduction abnormalities occurred in 8.3% but only 5.6% required a PPM. The successful valve deployment occurred in 96% of the patients in the LCE group compared to 100% in the other group (p = 0.04; OR-2[CI 1.7-2.3]). The mortality rates at 30 days (1.7% vs. 1.7%) and 1 year (1.9% vs. 2.7%) were comparable between the two groups. CONCLUSIONS: This study represents the largest published UK and Ireland real-world experience of the ACURATE neo™ valve. The procedural success rates and safety outcomes were excellent and endorse its utility in clinical practice. The LCE appears to have an impact on the successful valve deployment but without translating into short-term or long-term outcomes.

A brief overview of properties and reactions of diisocyanates.

By way of introduction to the special issue on diisocyanates and their corresponding diamines, this brief overview presents, for the most commonly used diisocyanate monomers, a selection of physical-chemical properties that are relevant to exposure in the workplace and in the general environment, as well as a concise overview of diisocyanate reactions and some of their toxicological implications.

Exploring structure/property relationships to health and environmental hazards of polymeric polyisocyanate prepolymer substances-1. Design of experiments, aquatic exposure, and acute aquatic toxicity.

Polymeric polyisocyanate prepolymer substances are reactive intermediates used in the manufacture of various polyurethane products. Knowledge of their occupational and environmental hazard properties is essential for product stewardship and industrial hygiene purposes. This work reports on the systematic design of a program to explore how structural features (i.e., types of polymeric polyol and diisocyanate reactants, functionality) and physical-chemical properties (i.e., octanol-water partition coefficient [log Kow], viscosity, molecular weight) of a group of 10 toluene diisocyanate (TDI)- and methylene diphenyl diisocyanate (MDI)-based monomer-depleted prepolymer substances can be related to their exposure and hazard potentials. The revelation of trends or thresholds in such relationships could form a basis for regulatory screening of existing or new prepolymer substances, while also informing the design of substances having reduced exposure and/or hazard profiles. As a first step, the aquatic exposure and hazard potentials of these 10 substances were investigated. The results of this investigation showed that yields of dissolved reaction products (derived from non-purgeable organic carbon measurements and carbon contents of the parent prepolymers) were inversely correlated with the calculated log Kow of the substances. For prepolymer loading rates of both 100 and 1000 mg/L in water, the average dissolved reaction product yields ranged from ≤1% to 32% and from ≤0.1% to 25%, respectively, over calculated log Kow values ranging from -4.8 to 45. For both loading rates, dissolved reaction products were not quantifiable where the calculated log Kow value was >10. Yet, none of the 10 prepolymers and tested loading rates exhibited acute adverse effects on the aquatic invertebrate, Daphnia magna, in the 48-h acute immobilization test. From a product stewardship perspective, polymeric prepolymers of TDI and MDI within the investigated domain and concentration range are not expected to be hazardous in the aquatic environment.

Toluene diisocyanate occupational exposure data in the polyurethane industry (2005-2020): A descriptive summary from an industrial hygiene perspective.

This article provides an overview of toluene diisocyanate (TDI) workplace air concentration data. Data were collected between 2005-2020 in workplaces across the United States, Canada, and the European Union by a number of different organizations, primarily using the sampling procedures published in OSHA Methods 42 and 5002. The data were then collated and organized by the International Isocyanate Institute. Air samples were collected from several market segments, with a large portion of the data (87%) from the flexible foam industry. The air samples (2534 in total) were categorized into "area" or "personal," and the personal samples were subcategorized into "task," "short term," and "long term." Most of the air sample concentrations (87%) were less than 5 ppb. However, the presence of airborne TDI greater than 5 ppb indicated the importance of respiratory protection in some situations; therefore, respirator use patterns were studied and summarized. Additionally, this article provides a summary of air sample concentrations at different flexible foam manufacturing job roles. The information on air sampling concentrations and respiratory protection during TDI applications collected in this paper could be useful for product stewardship and industrial hygiene purposes in the industries studied.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial. METHODS: The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 [95% CI 1·24-2·01]); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 [95% CI 0·74-1·59]; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 [95% CI 1·66-5·39]; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 [95% CI 1·25-2·40]; p=0·0009). INTERPRETATION: In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation. FUNDING: Biosensors.

Sex-based difference in fractional flow reserve and its impact on clinical outcomes.

BACKGROUND: Obesity is a real public health problem and is of growing concern. People are resorting to surgical or endoscopic means to fight against overweight and obesity. In recent years, there has been a marked increase in the use of these means and in particular the insertion of a gastric balloon which seems to present less risk than surgical methods. Renal complications from intragastric balloon placement are extremely rare. We report here the case of compression of the left renal vein revealed by lumbar pain and hematuria in an overweight 39-year-old woman who benefited from the balloon gastric placement one month before symptoms. The scanner made the diagnosis and showed a good evolution after the withdrawal of the balloon. METHODS: This was a prespecified and retrospective analysis of all consecutive patients who underwent FFR assessment for intermediate coronary lesions between January 2014 and December 2015. The primary endpoint was defined as the 1-year composite of cardiac death, vessel-related myocardial infarction, and clinically-driven target vessel revascularization. RESULTS: In 1554 lesions (23% in women), FFR was lower in men [0.83 ±0.09 vs 0.85 ±0.08, P = .004] driven by LAD values (for LAD P < .001, LCx or RCA P> .40). In proximal lesions (PLs), FFR was lower in men [0.83 ±0.10 vs 0.85 ±0.08, P = .004] with comparable values in non-PLs [0.84 ±0.09 vs 0.85 ±0.08, P = .36]. In PLs, the primary endpoint was higher in women [HR(adjusted) 3.18 (1.08-9.37), P = .035] with comparable outcomes in non-PLs (P = .032 for interaction). In deferred lesions, the primary endpoint was higher in women [HR(adjusted) 2.73 (1.10-6.74), P = .03] with no differences in revascularized lesions across sex (P = .02 for interaction). Results were consistent when using propensity score matching analysis. CONCLUSIONS: There is a sex-based difference in FFR, particularly in stenoses subtending large myocardium, and more evident in deferred lesions.

Assessment of the conjunctival microcirculation in adult patients with cyanotic congenital heart disease compared to healthy controls.

PURPOSE: Congenital heart disease (CHD) is the most common live birth defect and a proportion of these patients have chronic hypoxia. Chronic hypoxia leads to secondary erythrocytosis resulting in microvascular dysfunction and increased thrombosis risk. The conjunctival microcirculation is easily accessible for imaging and quantitative assessment. It has not previously been studied in adult CHD patients with cyanosis (CCHD). METHODS: We assessed the conjunctival microcirculation and compared CCHD patients and matched healthy controls to determine if there were differences in measured microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. The axial velocity was estimated by applying the 1D + T continuous wavelet transform (CWT). Results are for all vessels as they were not sub-classified into arterioles or venules. RESULTS: 11 CCHD patients and 14 healthy controls were recruited to the study. CCHD patients were markedly more hypoxic compared to the healthy controls (84% vs 98%, p = 0.001). A total of 736 vessels (292 vs 444) were suitable for analysis. Mean microvessel diameter (D) did not significantly differ between the CCHD patients and controls (20.4 ± 2.7 µm vs 20.2 ± 2.6 µm, p = 0.86). Axial velocity (Va) was lower in the CCHD patients (0.47 ± 0.06 mm/s vs 0.53 ± 0.05 mm/s, p = 0.03). Blood volume flow (Q) was lower for CCHD patients (121 ± 30pl/s vs 145 ± 50pl/s, p = 0.65) with the greatest differences observed in vessels >22 µm diameter (216 ± 121pl/s vs 258 ± 154pl/s, p = 0.001). Wall shear rate (WSR) was significantly lower for the CCHD group (153 ± 27 s-1 vs 174 ± 22 s-1, p = 0.04). CONCLUSIONS: This iPhone and slit-lamp combination assessment of conjunctival vessels found lower axial velocity, wall shear rate and in the largest vessel group, lower blood volume flow in chronically hypoxic patients with congenital heart disease. With further study this assessment method may have utility in the evaluation of patients with chronic hypoxia.

Age-Stratified Outcome in Treatment of Left Main Coronary Artery Stenosis: A NOBLE Trial Substudy.

BACKGROUND: In the treatment of left main coronary artery (LMCA) disease, patients' age may affect the clinical outcome after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study stratified the clinical outcome according to the age of patients treated for LMCA stenosis with PCI or CABG in the Nordic-Baltic-British Left Main Revascularization (NOBLE) study. METHODS: Patients with LMCA disease were enrolled in 36 centers in northern Europe and randomized 1:1 to treatment by PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST elevation myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCEs), a composite of all-cause mortality, nonprocedural myocardial infarction, any repeat coronary revascularization, and stroke. Age-stratified analysis was performed for the groups younger and older than 67 years and for patients older than 80 years. RESULTS: For patients ≥67 years, the 5-year MACCEs were 35.7 versus 22.3% (hazard ratio [HR] 1.72 [95% confidence interval [CI] 1.27-2.33], p = 0.0004) for PCI versus CABG. The difference in MACCEs was driven by more myocardial infarctions (10.8 vs. 3.8% HR 3.01 [95% CI 1.52-5.96], p = 0.0009) and more repeat revascularizations (19.5 vs. 10.0% HR 2.01 [95% CI 1.29-3.12], p = 0.002). In patients younger than 67 years, MACCE was 20.5 versus 15.3% (HR 1.38 [95% CI 0.93-2.06], p = 0.11 for PCI versus CABG. All-cause mortality was similar after PCI and CABG in both age-groups. On multivariate analysis, age was a predictor of MACCE, along with PCI, diabetes, and SYNTAX score. CONCLUSIONS: As the overall NOBLE results show revascularization of LMCA disease, age of 67 years or older was associated with lower 5-year MACCE after CABG compared to PCI. Clinical outcomes were not significantly different in the subgroup younger than 67 years, although no significant interaction was present between age and treatment. Mortality was similar for all subgroups (ClinicalTrials.gov identifier: NCT01496651).

Initial experience of a self-expanding transcatheter aortic valve with an outer pericardial wrap: The United Kingdom and Ireland Implanters' registry.

OBJECTIVES: The United Kingdom and Ireland Implanters' registry is a multicenter registry which reports on real-world experience with new transcatheter heart valves. BACKGROUND: The Evolut PRO (Medtronic, Minneapolis, MN) transcatheter aortic valve is a self-expanding transcatheter aortic valve with an outer pericardial wrap, designed to minimize paravalvular regurgitation. METHODS: Between July 2017 and December 2018, clinical, procedural, and 30-day outcome data were prospectively collected from all patients receiving the Evolut PRO valve across nine participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2 (VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 317 patients underwent implantation. Mean age was 81.8 ± 6.4 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.5 ± 1.8%. Iliofemoral access was used in 99.1% of patients. Device success was 91.2%. Mean gradient was 7.6 ± 4.7 mmHg and effective orifice area 1.9 ± 0.7 cm2 . The incidence of moderate paravalvular regurgitation was 1.7% and there was no severe paravalvular regurgitation. A new permanent pacemaker was implanted in 17.8% of patients without a pacemaker at baseline. Early safety was demonstrated in 92.7%. At 30 days, all-cause mortality was 0.6%, stroke 3.8%, and major vascular complication 2.8%. CONCLUSIONS: Real-world experience of the Evolut PRO transcatheter aortic valve demonstrated favorable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

Aspirin Discontinuation in Patients Requiring Oral Anticoagulation Undergoing Percutaneous Coronary Intervention, The Role of Procedural Complexity.

BACKGROUND: The prognostic role of procedural complexity when discontinuing aspirin in patients on oral anticoagulation undergoing percutaneous coronary intervention (PCI) has never been studied. METHODS: Ischaemic events were compared in 256 consecutive patients according to procedural complexity and aspirin on discharge. PCI complexity was defined according to the high-risk features for ischaemic events in the current guidelines RESULTS: Forty percent patients had stable presentation. In patients with complex PCI, ischaemic events were significantly higher when discharged without aspirin (adjusted HR 3.66, (95% CI 1.07 to 12.47), P = 0.038). This was driven from both target vessel failure and de-novo coronary lesions. Ischaemic events were comparable between patients with complex PCI on aspirin and those who underwent non-complex PCI. CONCLUSIONS: Procedural complexity in patients with indication for oral anticoagulation undergoing PCI should be factored in when deciding optimal antithrombotic therapies. Aspirin discontinuation in patients with high-risk PCI features should be discouraged.

Practical learnings from an epidemiology study on TDI-related occupational asthma: Part I-Cumulative exposure is not a good indicator of risk.

The anonymized data of an epidemiology study on incidence of toluene diisocyanate (TDI)-related occupational asthma in three US-based TDI production facilities have been reanalyzed to identify where to best focus exposure reduction efforts in industrial practice to reduce the risk of sensitization to TDI. Since the induction of sensitization has sometimes been attributed to cumulative exposure, this relationship was examined first. Gross cumulative exposure values (i.e. not taking into account whether respiratory protection was used or not) and net cumulative exposure values (i.e. accounting for the use of respiratory protection) per participant were calculated based on the duration of their study participation and the average time-weighted average value of the exposure group to which they belonged. These two sets of cumulative exposure data were compared with asthma incidence using logistic regression. Incidence was zero among workers who rarely come into contact with open plant systems (e.g. during maintenance or spills). Notwithstanding, no statistically significant relationship between asthma incidence and either gross or net cumulative exposure could be determined. This is shown to be consistent with the results of several other epidemiology studies on TDI-related occupational asthma. In conclusion, cumulative exposure values are not a good indicator of the risk of developing TDI-related occupational asthma.