Impact of prior coronary artery bypass grafting in patients undergoing chronic total occlusion-percutaneous coronary intervention: Procedural and clinical outcomes from the REgistry of Crossboss and Hybrid procedures in FrAnce, the NetheRlands, BelGium, and UnitEd Kingdom (RECHARGE).

AIM: Chronic total occlusions (CTO) in patients with history of coronary artery bypass graft (CABG) show more advanced and complex atherosclerotic pathology. Aim of our study is to compare outcomes in patients undergoing CTO percutaneous coronary intervention (PCI) with previous CABG versus those without in the REgistry of Crossboss and Hybrid procedures in FrAnce the NetheRlands, BelGium and UnitEd Kingdom (RECHARGE). METHODS & RESULTS: The RECHARGE cohort (1,252 patients) was divided in two groups according to the presence of previous CABG (217) or not. We also focused, in the post-CABG group, on a comparison between CTO in previously grafted vessels versus non-grafted vessels. The CTO complexity scores were higher and the success rate (71.9% vs. 88.7%, p < .001) was lower in the CABG group, this difference was driven by higher failure rates in high-complexity-score CTO. The rate of in-hospital complications was similar. In the post-CABG group, the procedural success of CTO located in previously grafted vessels versus those in vessels not previously grafted, was comparably suboptimal (73.1% vs. 68%, p = .47). CONCLUSION: Patients undergoing CTO PCI with prior CABG have a higher prevalence of comorbidities and more complex lesion characteristics. In the post-CABG population the success rate was significantly lower, particularly in high CTO complexity scores, though complication rates were comparable. In the post-CABG population, the CTO success rate was independent of the presence of a previous graft on the CTO vessel.

Towards a contemporary, comprehensive scoring system for determining technical outcomes of hybrid percutaneous chronic total occlusion treatment: The RECHARGE score.

OBJECTIVES: This study sought to create a contemporary scoring tool to predict technical outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) from patients treated by hybrid operators with differing experience levels. BACKGROUND: Current scoring systems need regular updating to cope with the positive evolutions regarding materials, techniques, and outcomes, while at the same time being applicable for a broad range of operators. METHODS: Clinical and angiographic characteristics from 880 CTO-PCIs included in the REgistry of CrossBoss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom (RECHARGE) were analyzed by using a derivation and validation set (2:1 ratio). Variables significantly associated with technical failure in the multivariable analysis were incorporated in the score. Subsequently, the discriminatory capacity was assessed and the validation set was used to compare with the J-CTO score and PROGRESS scores. RESULTS: Technical success in the derivation and validation sets was 83% and 85%, respectively. Multivariate analysis identified six parameters associated with technical failure: blunt stump (beta coefficient (b) = 1.014); calcification (b = 0.908); tortuosity ≥45° (b = 0.964); lesion length 20 mm (b = 0.556); diseased distal landing zone (b = 0.794), and previous bypass graft on CTO vessel (b = 0.833). Score variables remained significant after bootstrapping. The RECHARGE score showed better discriminatory capacity in both sets (area-under-the-curve (AUC) = 0.783 and 0.711), compared to the J-CTO (AUC = 0.676) and PROGRESS (AUC = 0.608) scores. CONCLUSIONS: The RECHARGE score is a novel, easy-to-use tool for assessing the risk for technical failure in hybrid CTO-PCI and has the potential to perform well for a broad community of operators. © 2017 Wiley Periodicals, Inc.

Prognostic value of admission high-sensitivity troponin in patients with ST-elevation myocardial infarction.

BACKGROUND AND AIM: Although the diagnostic usefulness of high-sensitivity cardiac troponin T (hs-cTnT) is well established in ST-segment elevation myocardial infarction (STEMI), its prognostic relevance in risk stratification of patients with STEMI remains obscure. This study sought to determine the prognostic value of pre-reperfusion (admission) and post-reperfusion (12-hour) hs-cTnT in patients with STEMI treated with primary percutaneous coronary intervention (PPCI). METHODS: Retrospective observational longitudinal study including consecutive patients with STEMI treated with PPCI at a university hospital in the northeast of England. hs-cTnT was measured at admission to the catheterisation laboratory and 12 hours after PPCI. Clinical, procedural and laboratory data were prospectively collected during patient hospitalisation (June 2010-December 2014). Mortality data were obtained from the UK Office of National Statistics. The study endpoints were in-hospital and overall mortality. RESULTS: A total of 3113 patients were included. Median follow-up was 53 months. Admission hs-cTnT >515 ng/L (fourth quartile) was independently associated with in-hospital mortality (HR=2.53 per highest to lower quartiles; 95% CI: 1.32 to 4.85; p=0.005) after multivariable adjustment for a clinical model of mortality prediction. Likewise, admission hs-cTnT >515 ng/L independently predicted overall mortality (HR=1.27 per highest to lower quartiles; 95% CI: 1.02 to 1.59; p=0.029). Admission hs-cTnT correctly reclassified risk for in-hospital death (net reclassification index (NRI)=0.588, p<0.001) and overall mortality (NRI=0.178, p=0.001). Conversely, 12-hour hs-cTnT was not independently associated with mortality. CONCLUSION: Admission, but not 12-hour post-reperfusion, hs-cTnT predicts mortality and improves risk stratification in the PPCI era. These results support a prognostic role for admission hs-cTnT while challenge the cost-effectiveness of routine 12-hour hs-cTnT measurements in patients with STEMI.

Temporal management patterns and outcomes of non-ST elevation acute coronary syndromes in patients with kidney dysfunction.

AIMS: To examine: (i) the temporal changes in the management pattern; (ii) the reasons for any treatment disparities; (iii) the relationship between invasive treatment and outcome, among acute coronary syndrome (ACS) patients with vs. without kidney dysfunction. METHODS AND RESULTS: Canadian ACS I, ACS II registries and Global Registry of Acute Coronary Events (GRACE) were prospective, multi-centre, observational studies of patients with ACS. From 1999 to 2007, non-ST elevation (NSTE) ACS patients were recruited in ACS I (n = 3295; 1999-2001), ACS II (n = 1956; 2002-2003), and GRACE (n = 6491; 2004-2007) in Canada. Using the four-variable Modified Diet in Renal Disease equation, we stratified the study population (n = 11,377) into three groups based on their estimated glomerular filtration rate (eGFR), and examined their treatment and outcome. While in-hospital use of coronary angiography and revascularization increased over time in all groups (P < 0.001), patients with kidney dysfunction were less likely to undergo invasive management (P < 0.001). Unadjusted 1 year mortality was lower among patients receiving in-hospital coronary angiography within all eGFR categories (> or =60 mL/min/1.73 m(2): 2.5 vs. 7.6%, P < 0.001; 30-59 mL/min/1.73 m(2): 8.0 vs. 14.6%, P < 0.001; <30 mL/min/1.73 m(2): 27.5 vs. 41.5%, P = 0.043). In-hospital revascularization was independently associated with lower 1-year mortality (adjusted OR = 0.52, 95% CI 0.36-0.77, P = 0.001), irrespective of eGFR (P for heterogeneity = 0.39). Underestimation of patient risk was the most common barrier to an invasive treatment strategy. CONCLUSION: Despite temporal increases in invasive management of NSTE-ACS, patients with kidney dysfunction are more commonly treated conservatively, with an associated worse outcome. In-hospital revascularization was independently associated with improved survival, irrespective of eGFR. Randomized controlled trials involving patients with kidney dysfunction are needed to confirm whether more aggressive treatment will improve their poor outcome.

The "buddy-in-jail" technique-a novel method for increasing support during percutaneous coronary intervention.

The "buddy-in-jail" technique is a novel method for increasing support during percutaneous coronary intervention. We report two case-based examples of successful coronary stent delivery using the jailed buddy wire technique.

Antegrade Dissection and Reentry as Part of the Hybrid Chronic Total Occlusion Revascularization Strategy: A Subanalysis of the RECHARGE Registry (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom).

BACKGROUND: Development of the CrossBoss and Stingray devices for antegrade dissection and reentry (ADR) of chronic total occlusions has improved historically suboptimal outcomes. However, the outcomes, safety, and failure modes of the technique have to be studied in a larger patient cohort. This preplanned substudy of the RECHARGE registry (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom) aims to evaluate the value and use of ADR and determine its future position in contemporary chronic total occlusion intervention. METHODS AND RESULTS: Patients were selected if an ADR strategy was applied. Outcomes, safety, and failure modes of the technique were assessed. The ADR technique was used in 23% (n=292/1253) of the RECHARGE registry and was mainly applied for complex lesions (Japanese chronic total occlusion score=2.7±1.1). ADR was the primary strategy in 30% (n=88/292), of which 67% were successful. Bail-out ADR strategies were successful in 63% (n=133/210). The Controlled ADR (ie, combined CrossBoss-Stingray) subtype was applied most frequently (32%; n=93/292) and successfully (81%; n=75/93). Overall per-lesion success rate was 78% (n=229/292), after use of additional bail-out strategies. The inability to reach the distal target zone (n=48/100) or to reenter (n=43/100) most commonly led to failure. ADR-associated major events occurred in 3.4% (n=10/292). CONCLUSIONS: Although mostly applied as a bail-out strategy for complex lesions, the frequency, outcomes, and low complication rate of the ADR technique and its subtypes confirm the benefit and value of the technique in hybrid chronic total occlusion percutaneous coronary intervention, especially when antegrade wiring or retrograde approaches are not feasible. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02075372.

Fully Transradial Versus Transfemoral Approach for Percutaneous Intervention of Coronary Chronic Total Occlusions Applying the Hybrid Algorithm: Insights From RECHARGE Registry.

BACKGROUND: Small observational studies demonstrate the feasibility of transradial approach for chronic total occlusion (CTO) percutaneous coronary intervention. The aim of the current study is to assess technical success, complication rates, and procedural efficiency in fully transradial approach (fTRA) and transfemoral approach (TFA) in a large prospective European registry adopting the hybrid algorithm for CTO percutaneous coronary intervention (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom, RECHARGE registry). METHODS AND RESULTS: We analyzed 1253 CTO percutaneous coronary intervention procedures performed according to the hybrid protocol in 17 European centers, comparing fTRA (single or biradial access) and TFA (single or bifemoral or combined radial and femoral access). fTRA was applied in 306 (24%) and TFA in 947 (76%) cases. The average Japanese CTO score was 2.1±1.2 in fTRA and 2.3±1.1 in TFA (P=0.06). Technical success was achieved in 85% in fTRA and 86% in TFA (P=0.51). Technical success was comparable for fTRA and TFA in different Japanese CTO score subgroups after multivariable analysis and after propensity adjustment. In-hospital major adverse cardiac and cerebral events occurred in 2.0% in fTRA and 2.9% in TFA (P=0.40). Major access site bleeding occurred in 0.3% in fTRA and 0.5% in TFA (P=0.66). fTRA compared with TFA had similar procedural duration (80 minutes [54-120 minutes] versus 90 minutes [60-121 minutes]; P=0.07), similar radiation dose (dose area product 89 Gray×cm2 [52-163 Gray×cm2] versus 101 Gray×cm2 [59-171 Gray×cm2]; P=0.06), and lower contrast agent use (200 mL [150-310 mL] versus 250 mL [200-350 mL]; P<0.01). CONCLUSIONS: fTRA CTO percutaneous coronary intervention is a valid alternative to TFA with a high rate of success, low complication rates, and no decrease in procedural efficiency.

The collateral circulation of coronary chronic total occlusions.

AIMS: Despite advances in understanding the physiological role of collaterals in coronary chronic total occlusions (CTOs), collateral anatomy remains poorly defined. Our aim was to define the anatomy and interventional utility of collaterals within a large population of patients with CTOs. METHODS AND RESULTS: We studied the coronary angiograms of 481 patients with 519 CTOs at six centres in the U.K. over four years. Detailed angiographic analysis was performed by interventional cardiologists specialising in CTO percutaneous coronary intervention (PCI). All visible collaterals with a collateral connection (CC) grade ≥1 were recorded. A subgroup of CTOs (n=277) was assessed for interventional capability, defined as whether the collateral supply was able to facilitate retrograde access. We described 45 different collateral patterns: 20 in right coronary artery (RCA), 13 in left anterior descending (LAD), and 12 in circumflex artery CTOs. Septal collaterals from the LAD to the right posterior descending artery (RPDA), and from the posterior descending artery to the LAD were most common, and most often considered as having "interventional capability". CONCLUSIONS: This is the largest analysis of collateral circulation anatomy in a population of patients with CTOs. We anticipate that these data will be of significant benefit in angiographic analysis and procedure planning for CTO PCI.

The Hybrid Algorithm for Treating Chronic Total Occlusions in Europe: The RECHARGE Registry.

BACKGROUND: The hybrid algorithm for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) was developed to improve procedural outcomes. Large, prospective studies validating the algorithm in a broad multicenter setting with operators of different experience levels are lacking. OBJECTIVES: The RECHARGE (REgistry of Crossboss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom) registry aims to report achievable results using the hybrid algorithm. METHODS: Between January 2014 and October 2015, consecutive patients undergoing hybrid CTO-PCI were prospectively enrolled in 17 centers. Procedural techniques, outcomes, and in-hospital complications were analyzed. RESULTS: A total of 1,253 CTO-PCIs were performed in 1,177 patients, of which 86% were men. Mean age was 66 ± 11 years. The average Japanese CTO score was 2.0 ± 1.0, and was higher in the failure group (2.6 ± 0.6 vs. 1.9 ± 1.0; p < 0.001). Overall procedure success was 86% and major in-hospital complications occurred in 2.6%. Antegrade wire escalation was the preferred primary strategy in 77%, followed by retrograde (17%) and antegrade dissection re-entry strategies (7%). Primary strategies were successful in 60%. Consecutive strategies were applied in 34% and were successful in 74%. Antegrade dissection re-entry and retrograde strategies were the most common bailout strategies and were successful in 67% and 62%, respectively. Median procedure and fluoroscopy time were 90 (interquartile range [IQR]: 60 to 120) min and 35 (IQR: 21 to 55) min, contrast volume was 250 (IQR: 180 to 340) ml, and radiation doses (air kerma and dose area product) were 1.6 (IQR: 1.0 to 2.7) Gy and 98 (IQR: 57 to 168) Gy·cm2, respectively. CONCLUSIONS: High procedure and patient success rates, combined with a low event rate and improved procedural characteristics, support further use of the hybrid algorithm for a broad community of appropriately trained CTO operators.

Patient characteristics associated with self-presentation, treatment delay and survival following primary percutaneous coronary intervention.

BACKGROUND: Delayed arrival to a primary percutaneous coronary intervention (PPCI)-capable hospital following ST-elevation myocardial infarction (STEMI) is associated with poorer outcome. The influence of patient characteristics on delayed presentation during STEMI is unknown. METHODS AND RESULTS: This was a retrospective observational study. Patients presenting for PPCI from March 2008 to November 2011 in the north of England (Northumbria, Tyne and Wear) were included. The outcomes were self-presentation to a non-PPCI-capable hospital, symptom to first medical contact (STFMC) time, total ischaemic time and mortality during follow-up. STEMI patients included numbered 2297; 619 (26.9%) patients self-presented to a non-PPCI-capable hospital. STFMC of >30 min and total ischaemic time of >180 min was present in 1521 (70.7%) and 999 (44.9%) cases, respectively. Self-presentation was the strongest predictor of prolonged total ischaemic time (odds ratio, OR (95% confidence interval, CI): 5.05 (3.99-6.39)). Married patients (OR 1.38 (1.10-1.74)) and patients living closest to an Emergency Room self-presented more commonly (driving time (vs. ≤10 min) 11-20 min OR 0.66 (0.52-0.83), >20 minutes OR 0.46 (0.33-0.64). Unmarried females waited longest to call for help (OR vs. married males 1.89 (1.29-2.78) and experienced longer total ischaemic times (OR 1.51 (1.10-2.07)). Married patients had a borderline association with lower mortality (hazard ratio 0.75 (0.53-1.05), p=0.09). CONCLUSIONS: Unmarried female patients had the longest treatment delays. Married patients and those living closer to an Emergency Room self-present more frequently. Early and exclusive use of the ambulance service may reduce treatment delay and improve STEMI outcome.

Comparison of the efficacy of pharmacoinvasive management for ST-segment elevation myocardial infarction in smokers versus non-smokers (from the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction).

Compared with non-smokers, cigarette smokers with ST-segment elevation myocardial infarctions derive greater benefit from fibrinolytic therapy. However, it is not known whether the optimal treatment strategy after fibrinolysis differs on the basis of smoking status. The Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized patients with ST-segment elevation myocardial infarctions to a routine early invasive (pharmacoinvasive) versus a standard (early transfer only for rescue percutaneous coronary intervention or delayed angiography) strategy after fibrinolysis. The efficacy of these strategies was compared in 1,051 patients on the basis of their smoking status. Treatment heterogeneity was assessed between smokers and non-smokers, and multivariable analysis was performed to evaluate for an interaction between smoking status and treatment strategy after adjusting for baseline Global Registry of Acute Coronary Events (GRACE) risk score. Smokers (n=448) were younger, had fewer cardiovascular risk factors, and had lower GRACE risk scores. They had a lower rate of the primary composite end point of 30-day mortality, reinfarction, recurrent ischemia, heart failure, or cardiogenic shock and fewer deaths or reinfarctions at 6 months and 1 year. Smoking status was not a significant predictor of either primary or secondary end points in multivariable analysis. Pharmacoinvasive management reduced the primary end point compared with standard therapy in smokers (7.7% vs 13.6%, p=0.04) and non-smokers (13.1% vs 19.7%, p=0.03). Smoking status did not modify treatment effect on any measured outcomes (p>0.10 for all). In conclusion, compared with non-smokers, current smokers receiving either standard or early invasive management of ST-segment elevation myocardial infarction after fibrinolysis have more favorable outcomes, which is likely attributable to their better baseline risk profile. The beneficial treatment effect of a pharmacoinvasive strategy is consistent in smokers and non-smokers.

Treatment and outcomes of patients with suspected acute coronary syndromes in relation to initial diagnostic impressions (insights from the Canadian Global Registry of Acute Coronary Events [GRACE] and Canadian Registry of Acute Coronary Events [CANRACE]).

The early diagnosis of acute coronary syndrome (ACS) remains challenging, and a considerable proportion of patients are diagnosed with "possible" ACS on admission. The Global Registry of Acute Coronary Events (GRACE/GRACE(2)) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 16,618 Canadian patients with suspected ACS in 1999 to 2008. We compared the demographic and clinical characteristics, use of cardiac procedures, prognostic accuracy of the GRACE risk score, and in-hospital outcomes between patients given an admission diagnosis of "definite" versus "possible" ACS by the treating physician. Overall, 11,152 and 5,466 patients were given an initial diagnosis of "definite" ACS and "possible" ACS, respectively. Patients with a "possible" ACS had higher GRACE risk score (median 130 vs 125) and less frequently received aspirin, clopidogrel, heparin, or ß blockers within the first 24 hours of presentation and assessment of left ventricular function, stress testing, cardiac catheterization, and percutaneous coronary intervention (all p <0.05). Patients with "possible" ACS had greater rates of in-hospital myocardial infarction (9.0% vs 2.0%, p <0.05) and heart failure (12% vs 8.9%, p <0.05). The GRACE risk score demonstrated excellent discrimination for in-hospital mortality in both groups and for the entire study population. In conclusion, compared to patients with "definite" ACS on presentation, those with "possible" ACS had higher baseline GRACE risk scores but less frequently received evidence-based medical therapies within 24 hours of admission or underwent cardiac procedures during hospitalization. The GRACE risk score provided accurate risk assessment, regardless of the initial diagnostic impression.

Provision of gastroprotective medication and bleeding risk following acute coronary syndrome.

BACKGROUND: Gastrointestinal (GI) bleeding following percutaneous coronary intervention (PCI) is associated with increased mortality. ACCF/AHA/SCAI guidelines recommend prophylaxis to prevent GI bleeding in patients, with the highest GI bleeding risks taking dual-antiplatelet therapy (DAPT). The REPLACE risk score identifies factors predictive of peri-PCI bleeding from vascular access and non-access sites. We determined whether high bleeding risk acute coronary syndrome (ACS) patients taking DAPT were appropriately provided with GI prophylaxis and investigated the association between age and clinical presentation on the likelihood of receiving prophylactic therapy. METHODS: This is a retrospective analysis of all non-elective PCI patients at a single center between May and December 2008 stratified by age (<65, 65-74, and ≥ 75 years). REPLACE scores were calculated and discharge medication was obtained from case records. RESULTS: Complete discharge medication data were available for 800 patients (median age, 63 years; 45.1% with ST-elevation myocardial infarction [STEMI]). A total of 370 patients (46.3%) were high bleeding risk (REPLACE scores ≥ 10), including all patients ≥ 75 years (n = 173), 83.5% of patients 65-74 years (n = 177), and 4.8% of patients <65 years (n = 20). In total, 97.6% were discharged on DAPT. Within the high bleeding risk group, 45.1% received GI prophylaxis. Patients 65-74 years were least likely to receive prophylaxis (<65 years, 60%; 65-74 years, 38.4%; ≥ 75 years, 50.3%; P<.03). Presentation with STEMI was independently associated with a reduced likelihood of GI prophylaxis provision (odds ratio, 0.63; 95% confidence interval, 0.40-0.99; P=.045). CONCLUSIONS: Less than half of ACS patients at high bleeding risk taking DAPT are provided with GI prophylaxis. Increased use of objective bleeding risk scores may help guide risk/benefit decisions in patients taking clopidogrel and proton pump inhibitors.

Non-endothelial cell endothelin-B receptors limit neointima formation following vascular injury.

AIMS: The potent vasoconstrictor endothelin-1 (ET-1), acting on the endothelin-A (ETA) receptor, promotes intimal lesion formation following vascular injury. The endothelin-B (ETB) receptor, which mediates nitric oxide release and ET-1 clearance in endothelial cells, may moderate lesion formation, but this is less clear. We used selective ET receptor antagonists and cell-specific deletion to address the hypothesis that ETB receptors in the endothelium inhibit lesion formation following arterial injury. METHODS AND RESULTS: Neointimal proliferation was induced by wire or ligation injury to the femoral artery in mice treated with selective ETA (ABT-627) and/or ETB antagonists (A192621). Measurement of lesion formation by optical projection tomography and histology indicated that ETA blockade reduced lesion burden in both models. Although ETB blockade had little effect on ligation injury-induced lesion formation, after wire injury, blockade of the ETB receptor increased lesion burden (184% of vehicle; P < 0.05) and reversed the protective effects of an ETA antagonist. Selective deletion of ETB receptors from the endothelium, however, had no effect on neointimal lesion size. CONCLUSION: These results are consistent with ETB receptor activation playing an important role in limiting neointimal lesion formation following acute vascular injury, but indicate that this protective effect is not mediated by those ETB receptors expressed by endothelial cells. These data support the proposal that selective ETA antagonists may be preferable to mixed ETA/ETB antagonists for targeting the arterial response to injury.

Optimal medical therapy for non-ST-segment-elevation acute coronary syndromes: exploring why physicians do not prescribe evidence-based treatment and why patients discontinue medications after discharge.

BACKGROUND: Acute coronary syndrome (ACS) patients in the highest risk categories are least likely to receive evidence-based treatments (EBTs). We sought to determine why physicians do not prescribe EBTs for patients with non-ST-segment-elevation ACSs and the factors determining use of these treatments after 1 year. METHODS AND RESULTS: One thousand nine hundred fifty-six non-ST-segment-elevation ACS patients were enrolled in the prospective, multicenter Canadian ACS registry II between October 2002 and December 2003. Each patient's physician gave reasons why guideline-indicated medication(s) was not prescribed during hospitalization. Medication use and reason(s) for discontinuation after 1 year were obtained by telephone interview of the patients. The commonest reason for not prescribing EBTs was "not high-enough risk" or "no evidence/guidelines to support use." However, Global Registry of Acute Coronary Events scores of patients not treated for this reason were often similar to or higher than those of patients prescribed such treatment. After 1 year, 77% of patients not on optimal ACS treatment at discharge remained without optimal treatment, and overall antiplatelet, ß-blocker, and angiotensin-converting enzyme inhibitor use declined. Approximately one third of patients not taking EBTs had stopped their medication without instruction from their doctor. CONCLUSIONS: Nonprovision of EBTs may be due to subjective underestimation of patient risk and hence, likely treatment benefit. Oversights in care delivery were also apparent. Objective risk stratification, combined with efforts to ensure provision and adherence to EBTs, should be encouraged.

Influence of age on use of cardiac catheterization and associated outcomes in patients with non-ST-elevation acute coronary syndromes.

Randomized controlled trials support the use of an early invasive strategy in high-risk patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). Although risk increases with age, limited data are available to support this strategy in older patients. The aims of this study were to examine temporal trends in the management and outcomes of NSTE ACS in elderly patients and to explore reasons for the lower use of early angiography in the aged population. Data from 11,732 patients with NSTE ACS were collected from 3 consecutive Canadian registries (ACS I, ACS II, and Global Registry of Acute Coronary Events [GRACE]/GRACE2) from 1999 to 2007. Rates of in-hospital cardiac catheterization, revascularization, infarction or reinfarction, and death were stratified by age (<65, 65 to 74, and > or = 75 years). Although overall, rates of in-hospital catheterization and revascularization increased over time (p <0.001), the largest increase occurred in patients aged <65 years. The strongest independent negative predictor of the use of cardiac catheterization was age > or = 75 years (adjusted odds ratio 0.45, 95% confidence interval 0.37 to 0.56, p <0.001). Use of an early invasive approach was associated with a reduction in 1-year mortality across all age groups, but the absolute difference was greatest in patients aged > or = 75 years. The underestimation of risk by physicians (ascertained in ACS II) was the most common reason for choosing a conservative strategy. In conclusion, despite an overall increased use of an early invasive strategy, elderly patients with NSTE ACS remain significantly less likely to undergo cardiac catheterization and revascularization and are often erroneously perceived to be at low risk by their physicians. Future studies should determine whether more aggressive treatment of these high-risk elderly patients improves outcomes.

Deletion of endothelial cell endothelin B receptors does not affect blood pressure or sensitivity to salt.

Endothelin B receptors in different tissues regulate diverse physiological responses including vasoconstriction, vasodilatation, clearance of endothelin-1, and renal tubular sodium reabsorption. To examine the role of endothelial cell endothelin B receptors in these processes, we generated endothelial cell-specific endothelin B receptor knockout mice using a Cre-loxP approach. We have demonstrated loss of endothelial cell endothelin B receptor expression and function and preservation of nonendothelial endothelin B receptor-mediated responses through binding and functional assays. Ablation of endothelin B receptors exclusively from endothelial cells produces endothelial dysfunction in the absence of hypertension, with evidence of decreased endogenous release of NO and increased plasma endothelin-1. In contrast to models of total endothelin B receptor ablation, the blood pressure response to a high-salt diet is unchanged in endothelial cell-specific endothelin B receptor knockouts compared with control floxed mice. These findings suggest that the endothelial cell endothelin B receptor mediates a tonic vasodilator effect and that nonendothelial cell endothelin B receptors are important for the regulation of blood pressure.