Complete revascularization in stable multivessel coronary artery disease: A real world analysis from the British Columbia Cardiac Registry.

BACKGROUND: More than half of patients undergoing percutaneous coronary intervention (PCI) have multivessel disease (MVD). The prognostic significance of PCI in stable patients has recently been debated, but little data exists about the potential benefit of complete revascularization (CR) in stable MVD. We investigated the prognostic benefit of CR in patients undergoing PCI for stable disease. METHODS: We compared CR versus incomplete revascularization (IR) in 8,436 patients with MVD. The primary outcome was all-cause mortality at 5 years. RESULTS: A total of 1,399 patients (17%) underwent CR during the index PCI procedure for stable disease. CR was associated with lower mortality (6.2 vs. 10.7%, p < .001) and lower repeat revascularization at 5 years (12.7 vs. 18.4%, p < .001). Multivariable-adjusted analyses indicated that CR was associated with lower mortality (HR = 0.73, 95% CI: 0.58-0.91, p = .005) and repeat revascularization at 5 years (HR = 0.78, 95% CI: 0.66-0.93, p = .005). These findings were also confirmed in propensity-matched cohorts. Subgroup analyses indicated that CR conferred survival in older patients, male patients, absence of renal disease, greater angina (CCS Class III-IV) and heart failure (NYHA Class III-IV) symptoms, and greater burden of coronary disease. In sensitivity analyses where patients with subsequent repeat revascularization events were excluded, CR remained a strong predictor for lower mortality (HR = 0.69, 95% CI: 0.54-0.89, p = .004). CONCLUSIONS: In this study of stable patients with MVD, CR was an independent predictor of long-term survival. This benefit was specifically seen in higher risk patient groups and indicates that CR may benefit selected stable patients with MVD.

The Impact of Pre-Procedural Renal Impairment on Outcomes Following Percutaneous Coronary Intervention: An Analysis of 45,287 Patients From the British Columbia Cardiac Registry.

BACKGROUND: Renal disease confers a strong independent risk for morbidity and mortality after percutaneous coronary intervention (PCI). We evaluated the relationship between baseline pre-procedural renal function and outcomes following PCI. METHODS: We examined 45,287 patients who underwent PCI in British Columbia. We evaluated all-cause mortality and target vessel revascularisation (TVR) at 2 years. Pre-procedural renal impairment was categorised by creatinine clearance (CrCl, mL/min): CrCl≥90 (n=14,876), 90>CrCl≥60 (n=10,219), 60>CrCl≥30 (n=14,876), 30>CrCl≥0 (n=2,594) and dialysis (n=579). RESULTS: Declining CrCl values less than 60 mL/min were progressively associated with greater mortality: 60>eGFR≥30 (HR=2.01, 95% CI 1.71-2.37, p<0.001); 30>eGFR≥0 (HR=4.10, 95% CI 3.39-4.95, p<0.001); and dialysis (HR=6.22, 95% CI 5.07-7.63, p<0.001). A reduction in eGFR was not associated with TVR in non-dialysis patients. However, dialysis was a strong independent predictor for TVR (HR=1.69, 95% CI 1.37-2.08, p<0.001). This was confirmed in propensity-matched analyses where, dialysis was strongly associated with TVR (HR=1.53, 95% CI 1.24-1.89, p<0.001). This association was consistently seen in stratified analyses for diabetic versus non-diabetic patients; stent length >30 mm versus <30 mm; stent diameter >3 mm versus <3 mm; and receipt of bare metal stents versus drug-eluting stents. CONCLUSIONS: This study indicates the association with declining renal function and mortality in patients undergoing PCI. Whilst renal disease was not associated with increased TVR in non-dialysis patients, dialysis-dependence was a strong independent predictor for increased TVR.

The prognostic impact of revascularization strategy in acute myocardial infarction and cardiogenic shock: Insights from the British Columbia Cardiac Registry.

BACKGROUND: In patients with acute myocardial infarction (AMI) and cardiogenic shock (CS), percutaneous coronary intervention (PCI) of the culprit vessel is associated with improved outcomes. A large majority of these patients have multivessel disease (MVD). Whether or not PCI of non-culprit disease in the acute setting improves outcomes continues to be debated. We evaluated the prognostic impact of revascularization strategy for patients presenting with AMI and CS. METHODS: We compared culprit vessel intervention (CVI) versus multivessel intervention in 649 patients with AMI, CS, and MVD enrolled in the British Columbia Cardiac Registry. We evaluated mortality at 30 days and 1 year. RESULTS: CVI was associated with lower mortality at 30 days (23.7% vs. 34.5%, P = 0.004) and 1 year (32.6% vs. 44.3%, P = 0.003). CVI was an independent predictor for survival at 30 days (HR = 0.63, 95% CI: 0.45-0.88, P = 0.009) and 1 year (HR = 0.72, 95% CI: 0.54-0.96, P = 0.027). These findings were confirmed in propensity-matched cohorts. Subgroup analyses indicated that CVI was associated with lower mortality in patients aged <80 years; non-diabetics; and those presenting with ST-elevation MI. When analyzing non-culprit anatomy, PCI of non-culprit LAD disease was associated with higher 1-year mortality (HR = 1.51, 95% CI: 1.13-2.01, P = 0.006), primarily with non-culprit proximal LAD disease (HR = 1.82, 95% CI: 1.20-2.76, P = 0.005). However, PCI of non-culprit non-proximal LAD, LCx, and RCA disease was not associated with mortality. CONCLUSIONS: In patients with AMI and CS, a strategy of CVI appears to be associated with lower mortality. These findings are consistent with recently published randomized-controlled trial data.

Variation in practice and concordance with guideline criteria for length of stay after elective percutaneous coronary intervention.

BACKGROUND: Considerable variability remains as regards the appropriate and safe length of stay after elective PCI. We performed a survey of interventional cardiologists to identify current views on appropriate and safe length of stay after PCI. METHODS: We created an online survey using the commercially available SurveyMonkey application. This was sent to interventional cardiologists in the US, Canada and the UK with the assistance of the national interventional cardiology societies (SCAI, CAIC/CCS, BCIS/BCS) as well as being made available on the theheart.org website. RESULTS: 505 interventional cardiologists responded, of which 237 were practicing in the US. Of those from the US, 52% were not aware of any guidelines for length of stay and 48% reported that their unit did not have a standard practice for length of stay. Same-day discharge after PCI was practiced as routine by 14% of cardiologists in the US versus 32% of cardiologists from Canada (P = 0.003) and 57% (P < 0.0001) from the UK. Amongst respondents, there was significant variation between respondents and divergence from published SCAI guidelines regarding appropriate length of stay for patient specific and procedural related clinical factors. CONCLUSIONS: There is considerable variation in practice patterns regarding length of stay after PCI. Whilst most cardiologists practice overnight observation, a significant minority utilize same-day discharge. There is also lack of familiarity with published guidelines. This variation and knowledge gap confirms an urgent need for updated guidelines and a concerted effort to educate cardiologists on appropriate post-PCI length of stay. © 2017 Wiley Periodicals, Inc.

Embolic protection device use and its association with procedural safety and long-term outcomes following saphenous vein graft intervention: An analysis from the British Columbia Cardiac registry.

BACKGROUND: Embolic protection devices (EPDs) have been designed and introduced to reduce distal embolization and peri-procedural myocardial infarction during saphenous vein graft (SVG) intervention. Current guidelines give a class I recommendation to EPD use during SVG intervention when technically feasible. However, the routine use of these devices has recently been debated. METHODS: We analyzed 1,359 patients undergoing isolated SVG intervention between 2008 and 2013 in the British Columbia Cardiac Registry. We analyzed (a) post-procedural TIMI flow; and (b) target vessel revascularization (TVR) and mortality at 1 and 2 years. RESULTS: EPD use was an independent predictor of post-procedural TIMI 2/3 flow (OR = 2.38, 95% CI: 1.51-3.74, P < 0.001). At 1 year, EPD use was an independent predictor for lower TVR (HR = 0.35, 95% CI: 0.14-0.85, P = 0.021) and a trend towards lower mortality (HR = 0.45, 95% CI: 0.18-1.10, P = 0.082). These associations were lost at 2 years where EPD use was not predictive of mortality (HR = 0.62, 95% CI: 0.33-1.17, P = 0.144) or TVR (HR = 0.70, 95% CI: 0.41-1.17, P = 0.176). These findings were confirmed in propensity-matched and inverse probability treatment weighted analyses. CONCLUSIONS: In this analysis of patients undergoing SVG intervention, EPD use was a strong predictor for improved post-procedural TIMI flow. Whilst EPD use was associated with lower TVR and a trend for lower mortality at 1 year, these associations were lost at 2 years. These findings would appear to support the use of EPD for SVG intervention. © 2015 Wiley Periodicals, Inc.

Long-term outcomes following drug-eluting stents versus bare metal stents for primary percutaneous coronary intervention: A real-world analysis of 11,181 patients from the british columbia cardiac registry.

BACKGROUND: Drug eluting stents (DES) are associated with reduced risk of restenosis when compared with bare metal stents (BMS). Their use in ST-elevation myocardial infarction (STEMI) is debated, owing to concerns about stent thrombosis. There are limited real-world data comparing DES versus BMS in STEMI. We conducted an observational analysis in this setting and rigorously adjusted for treatment selection bias. METHODS: We analyzed 11,181 consecutive patients with acute STEMI who received either DES or BMS during 2008-2014 in the British Columbia Cardiac Registry. We analyzed target vessel revascularization (TVR) and mortality at 2 years. RESULTS: Multivariable-adjusted, propensity-matched and inverse probability-treatment weighted analyses found DES to be associated with early and late survival up to 2 years but not TVR. However, when adjusting for measured and unmeasured confounders, instrumental variable (IV) analyses demonstrated that DES use was associated with reduced TVR up to 2 years (Δ = -6.7%, 95% CI: -10.0%, -3.4%, P < 0.001). DES use was not associated with mortality at 1 year (Δ = -2.3%, 95% CI: -5.0%, 0.4%, P = 0.100) but associated with reduced mortality at 2 years (Δ = -5.4%, 95% CI: -8.3%, -2.5%, P < 0.001). Stratified IV analyses indicated that this long-term survival benefit was largely attributable to the second generation DES. CONCLUSIONS: In this study of patients with STEMI, when adjusting for measured and unmeasured factors, DES use was associated with reduced TVR and long-term survival beyond 1 year. This long-term survival was largely attributable to the second generation DES. These real-world data are reassuring and support the use of DES for STEMI. © 2016 Wiley Periodicals, Inc.

Radial artery pseudoaneurysms after transradial cardiac catheterisation.

BACKGROUND: Although uncommon, radial artery access site complications are likely to become more frequent with the increased adoption of transradial cardiac catheterisation. There is a lack of data regarding the incidence and clinical features of radial artery pseudoaneuryms. We aimed to describe the incidence, clinical features and management of radial artery pseudoaneurysms in a high-volume transradial cardiac catheterisation centre. PATIENTS AND METHODS: We performed a search of the Vancouver Island Health Authority medical imaging database from 1st Jan 2008 to April 2012 looking for all radial and femoral artery pseudoaneuryms occurring after cardiac catheterisation. Hospital charts were reviewed to determine patient and procedural characteristics as well as management and outcome. RESULTS: There were a total of 14,968 coronary procedures performed over the four year search period, of which 13,216 (88%) were trans-radial. The incidence of radial artery pseudoaneurysm after cardiac catheterisation was 0.08%, and did not differ between transradial diagnostic angiography and PCI (0.07% vs 0.08%; P = 0.90). In contrast, the incidence of femoral artery pseudoaneurysm was higher, at 1.4% (P < 0.0001). Patients with radial pseudoaneurysms were generally elderly, with a median age of 77 years, and there were no gender differences. Only one patient had received a glycoprotein IIb/IIIa inhibitor, whilst two received warfarin post-procedure. The majority of cases (80%) were treated with surgical repair. CONCLUSIONS: We have demonstrated that radial artery pseudoaneuryms are a rare but important complication of transradial cardiac catheterisation, with patients generally requiring surgical repair. Most patients were elderly, but surprisingly only a minority were anti-coagulated with warfarin.

Cardiac MRI of myocardial salvage at the peri-infarct border zones after primary coronary intervention.

The purpose of this study was to use cardiac MRI to define the morphology of the reversibly injured peri-infarct border zone in patients treated with primary percutaneous coronary intervention (PPCI) for acute ST elevation myocardial infarction. In 15 patients, T2-weighted myocardial edema imaging was used to identify the ischemic bed or area at risk (AAR), and late gadolinium enhancement imaging was used to measure infarct size. Images were coregistered, and the boundaries of edema and necrosis were defined using an edge-detection methodology. We observed that infarction always involved the subendocardium but showed variable transmural extension within the AAR. The mean infarct size was 22 +/- 19% (range: 8-48%), and the mean AAR was 34 +/- 12% (range: 20-57%). The infarcted myocardium was always smaller than the ischemic AAR and involved between 34% and 99% (mean 72 +/- 21%) of the ischemic bed primarily due to variation in transmural infarct extension. Although a lateral border zone of potentially viable myocardium was often present, its extent was limited (range: 0-11 mm, mean: 5 +/- 4 mm). As a result of this, infarcts occupied the majority (range: 70-100%, mean: 82 +/- 13%) of the width of the AAR. The mean fractional wall thickening in the infarcted, peri-infarcted, and remote myocardium was 3.6 +/- 16.0%, 40.5 +/- 26.4%, and 88.2 +/- 39.3%, respectively. These findings demonstrate that myocardial salvage is largely determined by epicardial limitation of the infarct within the ischemic AAR after PPCI. The lateral boundaries of necrosis approximate to the lateral extent of the ischemic bed and systolic wall motion abnormalities extend well beyond the infarct border zone.

Reperfusion hemorrhage following acute myocardial infarction: assessment with T2* mapping and effect on measuring the area at risk.

Research ethics committee approval and informed consent were obtained. The purpose of this study was to assess the feasibility of multiecho T2* mapping of the heart for detecting reperfusion hemorrhage following percutaneous primary coronary intervention (PPCI) for acute myocardial infarction, and to measure the effect of hemorrhage on quantifying the ischemic area at risk (IAR) on T2-weighted magnetic resonance images. Fifteen patients (mean age, 59 years; 13 men, two women) were imaged a mean of 3.2 days following PPCI. The mean area of hemorrhage, indicated by a T2* decay constant of less than 20 msec, was 5.0% +/- 4.9 (standard deviation) at the level of the infarct and this correlated with the infarct (r(2) = 0.76, P < .01) and microvascular obstruction (r(2) = 0.75, P < .01) volumes. When 5% or less hemorrhage was present, the IAR was underestimated by 50% at a standard deviation threshold level of five, compared with a boundary detection tool (21.8% vs 44.0%, P < .05). T2* mapping is feasible for quantifying post-reperfusion hemorrhage and boundary detection is required to accurately assess the IAR when hemorrhage is present.

Coronary Angiography and Revascularization Following Coronary Artery Bypass Grafting in British Columbia: Incidence, Predictors and Longer-term Outcomes.

BACKGROUND: Coronary artery bypass grafting (CABG) is established treatment for subsets of coronary artery disease (CAD). Observational data have characterised significant progression of native coronary as well as graft vessel disease during longer-term follow-up, potentially reducing the benefit of CABG. We sought to assess longer-term outcomes following CABG by determining rates of repeat coronary angiography, revascularization procedures, and survival. METHODS: Data for all patients undergoing isolated CABG in British Columbia between 2001 and 2009 inclusive, and with follow-up until the end of 2013, were retrieved from the British Columbia Cardiac Registry. Cox proportional hazard regression and competing risk regression were performed for survival and subsequent cardiac procedures (coronary angiography, percutaneous coronary intervention [PCI] or repeat CABG). RESULTS: Data were available from 17,316 patients with a mean age at index CABG of 65.7 ± 9.8 years. At a median follow-up of 8.5 (range 4.0 to 12.9) years, 3185 patients (18.4%) had died, 3135 (18.1%) underwent repeat coronary angiography with or without PCI or repeat CABG, and 11,557 (66.7%) had survived without additional procedures. Of those who underwent angiography, 1459 patients (46.5%) underwent further revascularization. In multivariate analysis, the strongest predictors of long-term mortality were dialysis dependency and age >75, whereas left internal mammary artery utilization and aspirin therapy were protective. Repeat revascularization predicted survival (adjusted hazard ratio 0.76; 95% confidence interval, 0.63-0.92; P = 0.004), whereas angiography alone did not. CONCLUSIONS: Following CABG, patients frequently undergo repeat coronary angiography. Although only a minority of patients receive further revascularization, this appears to be associated with longer-term survival.

Proinflammatory activation of macrophages by basic calcium phosphate crystals via protein kinase C and MAP kinase pathways: a vicious cycle of inflammation and arterial calcification?

Basic calcium phosphate (BCP) crystal deposition underlies the development of arterial calcification. Inflammatory macrophages colocalize with BCP deposits in developing atherosclerotic lesions and in vitro can promote calcification through the release of TNF alpha. Here we have investigated whether BCP crystals can elicit a proinflammatory response from monocyte-macrophages. BCP microcrystals were internalized into vacuoles of human monocyte-derived macrophages in vitro. This was associated with secretion of proinflammatory cytokines (TNFalpha, IL-1beta and IL-8) capable of activating cultured endothelial cells and promoting capture of flowing leukocytes under shear flow. Critical roles for PKC, ERK1/2, JNK, but not p38 intracellular signaling pathways were identified in the secretion of TNF alpha, with activation of ERK1/2 but not JNK being dependent on upstream activation of PKC. Using confocal microscopy and adenoviral transfection approaches, we determined a specific role for the PKC-alpha isozyme. The response of macrophages to BCP crystals suggests that pathological calcification is not merely a passive consequence of chronic inflammatory disease but may lead to a positive feed-back loop of calcification and inflammation driving disease progression.

Culprit Vessel Versus Multivessel Versus In-Hospital Staged Intervention for Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease: Stratified Analyses in High-Risk Patient Groups and Anatomic Subsets of Nonculprit Disease.

OBJECTIVES: This study evaluated revascularization strategies for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. BACKGROUND: In patients with STEMI and multivessel disease, it is unclear whether multivessel intervention (MVI), culprit vessel intervention (CVI) only (CVI-O) or CVI with staged revascularization (CVI-S) is associated with improved outcomes. Whether MVI at primary percutaneous coronary intervention may benefit specific patient groups is unclear. METHODS: We compared revascularization strategies (MVI, CVI-O, and CVI-S) in 6,503 patients with STEMI and multivessel disease enrolled in the British Columbia Cardiac Registry (2008 to 2014). We evaluated all-cause mortality and repeat revascularization at 2 years. RESULTS: Compared with MVI, CVI-O (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.64 to 0.97; p = 0.023) and CVI-S (HR: 0.55; 95% CI: 0.36 to 0.82; p = 0.004) were associated with lower mortality. Comparing CVI-O with CVI-S, CVI-S was associated with lower mortality (HR: 0.65; 95% CI: 0.47 to 0.91; p = 0.013). Compared with MVI, CVI-O was associated with increased repeat revascularization (HR: 1.25; 95% CI: 1.02 to 1.54; p = 0.036). Comparing CVI-O versus CVI-S, CVI-S was associated with lower repeat revascularization (HR: 0.64; 95% CI: 0.46 to 0.90; p = 0.012). CVI was associated with lower mortality in the presence of nonculprit left circumflex artery disease (HR: 0.63; 95% CI: 0.45 to 0.89; p = 0.011) and right coronary artery disease (HR: 0.66; 95% CI: 0.44 to 0.99; p = 0.050), but not nonculprit left anterior descending artery disease (HR: 0.83; 95% CI: 0.54 to 1.28; p = 0.399). CONCLUSIONS: In patients with STEMI undergoing primary percutaneous coronary intervention, a strategy of CVI-S seems to be associated with lower mortality and repeat revascularization rates. However, MVI may be considered in selected patients and in the setting of nonculprit left anterior descending artery disease. These findings warrant prospective evaluation in large adequately powered randomized controlled trials.

Intra-Aortic Balloon Pump Counterpulsation during Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction and Cardiogenic Shock: Insights from the British Columbia Cardiac Registry.

BACKGROUND: Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non-randomized studies may remain biased. METHODS: We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008-2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods. RESULTS: A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20-2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84-1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Δ = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non-diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis. CONCLUSIONS: In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data.

Prognostic Significance of Polymer Coatings in Zotarolimus-Eluting Stents.

Polymer coatings on drug-eluting stents (DES) serve as a vehicle for delivery of antirestenotic drugs. Whether they influence outcomes for contemporary DES is unknown. The evolution of polymer coatings for zotarolimus-eluting stents (ZES) provides a natural experiment that facilitates such analysis. The Resolute ZES (R-ZES) uses the same antirestenotic drug as the Endeavor ZES (E-ZES) but has a more biocompatible polymer with enhanced drug release kinetics. However, there are limited data on the real-world comparative efficacy of R-ZES and the preceding E-ZES. Thus, we analyzed 17,643 patients who received either E-ZES or R-ZES from 2008 to 2014 from the British Columbia Cardiac Registry. A total of 9,869 patients (56%) received E-ZES and 7,774 patients (44%) received R-ZES. Compared with E-ZES, R-ZES was associated with lower 2-year mortality (4.1% vs 6.4%, p <0.001) and 2-year target vessel revascularization (TVR; 6.8% vs 10.7%, p <0.001). R-ZES use was an independent predictor of lower mortality rate and TVR. This was confirmed in propensity-matched analyses for 2-year mortality (hazard ratio [HR] 0.59, 95% CI 0.49 to 0.71, p <0.001) and 2-year TVR (HR 0.86, 95% CI 0.75 to 0.98, p = 0.032). Instrumental variable analyses demonstrated R-ZES to be associated with lower 2-year mortality (Δ = -2.2%, 95% CI -4.3% to -0.2%, p = 0.032) and 2-year TVR (Δ = -3.3% to 95% CI -6.1% to -0.7%, p = 0.015). Acknowledging the limitations of observational analyses, this study has shown that R-ZES was associated with lower long-term TVR and mortality. These data are reassuring for the newer R-ZES and demonstrate how polymer coatings may influence the clinical performance of DES with wider implications for future DES development and design.

The effect of coronary artery disease defined by quantitative coronary angiography and SYNTAX score upon outcome after transcatheter aortic valve implantation (TAVI) using the Edwards bioprosthesis.

AIMS: We sought to evaluate the effects of significant coronary artery disease (CAD) upon outcome after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: We performed a retrospective study of 271 consecutive patients undergoing TAVI using either the Edwards SAPIEN or Edwards SAPIEN XT valve. Pre-procedural coronary angiograms were analysed by quantitative coronary angiography (defining significant CAD as a stenosis of ≥70% or ≥50% if in the left main stem or a vein graft). Ninety-three out of 271 patients had significant CAD. There was no difference in mortality at 30 days or 12 months between the two groups (6.7% vs. 7.5% and 21.5% vs. 23.7%; log-rank p=0.805). A secondary analysis using the SYNTAX algorithm of coronary anatomy complexity was performed on 189 patients. Those in the high SYNTAX score (>33) group had higher mortality at 30 days and 12 months (14.3% and 57.1%) than the low (5.2% and 23.3%) and intermediate-risk groups (11.1% and 22.2%; log-rank p=0.007). ROC analysis identified a SYNTAX score of >9 at the time of TAVI as the optimal cut-off, with an independent association with mortality (HR 1.95 [95% CI: 1.21-3.13]; p=0.006). Patients with a SYNTAX score >9 had greater 30-day, 12-month and overall mortalities than those with a SYNTAX score <9 (3.7% vs. 11.3% and 20.7% vs. 34.3%; log-rank p=0.005). CONCLUSIONS: Significant CAD, as defined using "real-world" QCA margins, did not have a significant effect upon mortality after TAVI for severe aortic stenosis. However, higher-risk SYNTAX groups, including those with a score >9, had increased mortality.

Anti-inflammatory haemoglobin scavenging monocytes are induced following coronary artery bypass surgery.

OBJECTIVE: Circulating monocytes may counter systemic pro-inflammatory and haemolytic insults through the expression and shedding of the haemoglobin scavenger receptor (CD163). This prospective study aims to assess the effects of coronary artery bypass grafting with and without cardiopulmonary bypass (CPB) on haemoglobin scavenging and anti-inflammatory monocyte behaviour. METHODS: Forty consecutive patients underwent coronary surgery using CPB (n=20) and off-pump (n=20) techniques. Peri-operative blood samples were taken until the fifth day following surgery and statistical comparison performed to baseline using group- and subject-based analysis. Monocyte receptor expression and plasma concentrations of anti-inflammatory molecules were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Monocyte CD163 expression was significantly elevated post-operatively in both surgical groups with (p=0.001) and without CPB (p=0.000) at 24-48h. By contrast, shed CD163 (p=0.02) and haemoglobin-haptoglobin complexes (p=0.000) in plasma were only significantly elevated in the on-pump group at 2-4h. Subject-based analysis demonstrated that CPB is an independent predictor of monocyte CD163 (p=0.002) and plasma sCD163 (p=0.01) concentration adjusting for the measurement timing. Significant downregulation of the monocyte major histocompatibility complex II receptor was observed in both surgical groups, whereas lipopolysaccharide receptor (CD14) expression only declined following on-pump surgery. The anti-inflammatory cytokine interleukin (IL)-10 was elevated post-operatively in both surgical groups peaking earlier in the on-pump group (2h) versus off-pump group (4h). The immunoregulatory IL-6 cytokine was significantly upregulated at 4h in both groups. CONCLUSION: Coronary artery bypass surgery induces monocyte-associated anti-inflammatory and immunoregulatory responses. There was no significant difference in haemolysis although the effect on monocyte CD163 and plasma sCD163 concentration was significantly different between the two groups. Compensation for varying pro-inflammatory and haemolytic insults may explain the differences observed. Therapeutic strategies for inducing such desirable circulating monocytes may potentially improve surgical outcome and patient recovery.

Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages.

Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.