Inter- and intra-observer reliability and agreement of O2Pulse inflection during cardiopulmonary exercise testing: A comparison of subjective and novel objective methodology.

Cardiopulmonary exercise testing (CPET) is the 'gold standard' method for evaluating functional capacity, with oxygen pulse (O2Pulse) inflections serving as a potential indicator of myocardial ischaemia. However, the reliability and agreement of identifying these inflections have not been thoroughly investigated. This study aimed to assess the inter- and intra-observer reliability and agreement of a subjective quantification method for identifying O2Pulse inflections during CPET, and to propose a more robust and objective novel algorithm as an alternative methodology. A retrospective analysis was conducted using baseline data from the HIIT or MISS UK trial. The O2Pulse curves were visually inspected by two independent examiners, and compared against an objective algorithm. Fleiss' Kappa was used to determine the reliability of agreement between the three groups of observations. The results showed almost perfect agreement between the algorithm and both examiners, with a Fleiss' Kappa statistic of 0.89. The algorithm also demonstrated excellent inter-rater reliability (ICC) when compared to both examiners (0.92-0.98). However, a significant level (P ≤0.05) of systematic bias was observed in Bland-Altman analysis for comparisons involving the novice examiner. In conclusion, this study provides evidence for the reliability of both subjective and novel objective methods for identifying inflections in O2Pulse during CPET. These findings suggest that further research into the clinical significance of O2Pulse inflections is warranted, and that the adoption of a novel objective means of quantification may be preferable to ensure equality of outcome for patients.

Prospective cohort study of elderly patients with coronary artery disease: impact of frailty on quality of life and outcome.

BACKGROUND: Elderly, frail patients are often excluded from clinical trials so there is lack of data regarding optimal management when they present with symptomatic coronary artery disease (CAD). OBJECTIVE: The aim of this observational study was to evaluate an unselected elderly population with CAD for the occurrence of frailty, and its association with quality of life (QoL) and clinical outcomes. METHODS: Consecutive patients aged ≥80 years presenting with CAD were prospectively assessed for frailty (Fried frailty phenotype (FFP), Edmonton frailty scale (EFS)), QoL (Short form survey (SF-12)) and comorbidity (Charlson Comorbidity Index (CCI)). Patients were re-assessed at 4 months to determine any change in frailty and QoL status as well as the clinical outcome. RESULTS: One hundred fifty consecutive patients with symptomatic CAD were recruited in the study. The mean age was 83.7±3.2 years, 99 (66.0%) were men. The clinical presentation was stable angina in 68 (45.3%), the remainder admitted with an acute coronary syndrome including 21 (14.0%) with ST-elevation myocardial infarction. Frailty was present in 28% and 26% by FFP and EFS, respectively, and was associated with a significantly higher CCI (7.5±2.4 in frail, 6.2±2.2 in prefrail, 5.9±1.6 in those without frailty, p=0.005). FFP was significantly related to the physical composite score for QoL, while EFS was significantly related to the mental composite score for QoL (p=0.003). Treatment was determined by the cardiologist: percutaneous coronary intervention in 51 (34%), coronary artery bypass graft surgery in 15 (10%) and medical therapy in 84 (56%). At 4 months, 14 (9.3%) had died. Frail participants had the lowest survival. Cardiovascular symptom status and the mental composite score of QoL significantly improved (52.7±11.5 at baseline vs 55.1±10.6 at follow-up, p=0.04). However, overall frailty status did not significantly change, nor the physical health composite score of QoL (37.2±11.0 at baseline vs 38.5±11.3 at follow-up, p=0.27). CONCLUSIONS: In patients referred to hospital with CAD, frailty is associated with impaired QoL and a high coexistence of comorbidities. Following cardiac treatment, patients had improvement in cardiovascular symptoms and mental component of QoL.

No-reflow phenomenon and comparison to the normal-flow population postprimary percutaneous coronary intervention for ST elevation myocardial infarction: case-control study (NORM PPCI).

INTRODUCTION: No-reflow (NR) phenomenon is characterised by the failure of myocardial reperfusion despite the absence of mechanical coronary obstruction. NR negatively affects patient outcomes, emphasising the importance of prediction and management. The objective was to evaluate the incidence and independent predictors of NR in patients presenting with ST-elevation myocardial infarction (STEMI). METHODS: This was a single-centre prospective case-control study. Cases were subjects who suffered NR, and the control comparators were those who did not. Clinical outcomes were documented. Salient variables relating to the patients and their presentation, history and angiographical findings were compared using one-way analysis of variance or χ2 test. Multiple regression determined the independent predictors, and a risk score was established based on the ß coefficient. RESULTS: Of 173 consecutive patients, 24 (13.9%) suffered from NR, with 46% occurring post stent implantation. Patients with NR had increased risk of in-hospital death (OR 7.0, 95% CI 1.3 to 36.7, p=0.022). From baseline variables available prior to percutaneous coronary intervention, the independent predictors of NR were increased lesion complexity, admission systolic hypertension, weight of <78 kg and history of hypertension. Continuous data were transformed into best-fit binary variables, and a risk score was defined. Significant difference was demonstrated between the risk score of patients with NR (4.1±1) compared with controls (2.6±1) (p<0.001), and the risk score was considered a good test (area under the curve=0.823). A score of ≥4 had 75% sensitivity and 76.5% specificity. CONCLUSION: Patients with NR have a higher rate of mortality following STEMI. Predictors of NR include lesion complexity, systolic hypertension and low weight. Further validation of this risk model is required.

Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia: Secondary Analysis of the ISCHEMIA Randomized Clinical Trial.

Importance: While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization. Objective: To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants. Design, Setting, and Participants: This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018. Interventions: CCTA and angina assessment. Main Outcomes and Measures: Sex differences in stress test, CCTA findings, and symptom severity. Results: Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76). Conclusions and Relevance: Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease. Trial Registration: ClinicalTrials.gov Identifier: NCT01471522.

Exercise Training as a Mediator for Enhancing Coronary Collateral Circulation: A Review of the Evidence.

Coronary collateral vessels supply blood to areas of myocardium at risk after arterial occlusion. Flow through these channels is driven by a pressure gradient between the donor and the occluded artery. Concomitant with increased collateral flow is an increase in shear force, a potent stimulus for collateral development (arteriogenesis). Arteriogenesis is self-limiting, often ceasing prematurely when the pressure gradient is reduced by the expanding lumen of the collateral vessel. After the collateral has reached its self-limited maximal conductance, the only way to drive further increases is to re-establish the pressure gradient. During exercise, the myocardial oxygen demand is increased, subsequently increasing coronary flow. Therefore, exercise may represent a means of driving augmented arteriogenesis in patients with stable coronary artery disease. Studies investigating the ability of exercise to drive collateral development in humans are inconsistent. However, these inconsistencies may be due to the heterogeneity of assessment methods used to quantify change. This article summarises current evidence pertaining to the role of exercise in the development of coronary collaterals, highlighting areas of future research.

Multi-disciplinary palliative care is effective in people with symptomatic heart failure: A systematic review and narrative synthesis.

BACKGROUND: Despite recommendations, people with heart failure have poor access to palliative care. AIM: To identify the evidence in relation to palliative care for people with symptomatic heart failure. DESIGN: Systematic review and narrative synthesis. (PROSPERO CRD42016029911). DATA SOURCES: Databases (Medline, Cochrane database, CINAHL, PsycINFO, HMIC, CareSearch Grey Literature), reference lists and citations were searched and experts contacted. Two independent reviewers screened titles and abstracts and retrieved papers against inclusion criteria. Data were extracted from included papers and studies were critically assessed using a risk of bias tool according to design. RESULTS: Thirteen interventional and 10 observational studies were included. Studies were heterogeneous in terms of population, intervention, comparator, outcomes and design rendering combination inappropriate. The evaluation phase studies, with lower risk of bias, using a multi-disciplinary specialist palliative care intervention showed statistically significant benefit for patient-reported outcomes (symptom burden, depression, functional status, quality of life), resource use and costs of care. Benefit was not seen in studies with a single component/discipline intervention or with higher risk of bias. Possible contamination in some studies may have caused under-estimation of effect and missing data may have introduced bias. There was no apparent effect on survival. CONCLUSION: Overall, the results support the use of multi-disciplinary palliative care in people with advanced heart failure but trials do not identify who would benefit most from specialist palliative referral. There are no sufficiently robust multi-centre evaluation phase trials to provide generalisable findings. Use of common population, intervention and outcomes in future research would allow meta-analysis.

Outcomes After Percutaneous Coronary Intervention in Women: Are There Differences When Compared with Men?

Despite advances in the diagnosis and treatment of coronary artery disease, there remains evidence of a disparity in the outcomes for women when compared with men. This article provides a review of the evidence for this discrepancy and discusses some of the potential contributing factors.

Safety and efficacy of a sirolimus-eluting coronary stent with ultra-thin strut for treatment of atherosclerotic lesions (TALENT): a prospective multicentre randomised controlled trial.

BACKGROUND: Supraflex is a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts. We aimed to compare Supraflex with the standard of care, Xience, an everolimus-eluting stent with a durable polymer coating, regarding clinical outcomes with a randomised trial in an all-comer population. METHODS: We did a prospective, randomised, single-blind, multicentre study (TALENT) across 23 centres in Europe (the Netherlands, Poland, the UK, Spain, Bulgaria, Hungary, and Italy). Eligible participants were aged 18 years or older, had one or more coronary artery stenosis of 50% or greater in a native coronary artery, saphenous venous graft, or arterial bypass conduit, and had a reference vessel diameter of 2·25-4·50 mm. Patients underwent percutaneous coronary intervention in an all-comer manner. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts (Supraflex) or an everolimus-eluting stent with a durable polymer coating (Xience). Randomisation was done by local investigators by use of a web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between groups at 12 months after the procedure, assessed in an intention-to-treat population. On assumption of 1-year composite endpoint prevalence of 8·3%, a margin of 4·0% was defined for non-inferiority of the Supraflex group compared with the Xience group. This trial is registered with ClinicalTrials.gov, number NCT02870140. FINDINGS: Between Oct 21, 2016, and July 3, 2017, 1435 patients with 1046 lesions were randomly assigned to Supraflex, of whom 720 received the index procedure, and 715 patients with 1030 lesions were assigned to Xience, all receiving the index procedure. At 12 months, the primary endpoint had occurred in 35 patients (4·9 %) in the Supraflex group and in 37 patients (5·3%) in the Xience group (absolute difference -0·3% [one-sided 95% upper confidence bound 1·6%], pnon-inferiority<0·0001). Definite or probable stent thrombosis prevalence, a safety indicator, was low in both groups and did not differ between them. INTERPRETATION: The Supraflex stent was non-inferior to the Xience stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. Supraflex seems a safe and effective alternative drug-eluting stent to other stents in clinical practice. FUNDING: European Cardiovascular Research Institute.

Is there Sex-related Outcome Difference According to oral P2Y12 Inhibitors in Patients with Acute Coronary Syndromes? A Systematic Review and Meta-Analysis of 107,126 Patients.

BACKGROUND AND OBJECTIVES: The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes. METHODS: Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel. RESULTS: Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men. CONCLUSION: In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.

The HF-CGM Study: An Analysis of Cardiogoniometric Axes in Patients With Cardiac Resynchronization Therapy.

GOAL: The HF-CGM is a proof-of-principle study to investigate whether cardiogoniometry (CGM), a three-dimensional electrocardiographic method, can differentiate between pacing modes in patients with cardiac resynchronization therapy (CRT). METHODS: At a tertiary cardiology center, CGM recordings were performed using four pacing modes: no pacing; right ventricular (RV) pacing; left ventricular (LV) pacing, and biventricular (BIV) pacing. Three orthogonal CGM planes orientated to the long axis (XY), the frontal plane (YZ), and the short axis (XZ) of the heart were constructed, and the direction of the QRS-axis was calculated for each pacing mode in each plane. During BIV pacing, the direction of CGM QRS-axis was compared between patients with optimal and nonoptimal 12-lead pacing variables. RESULTS: Twenty-two participants (aged 71.5 ± 10.8; 77.3% male, LVEF 29 ± 7%) were consecutively recruited. Only QRS-axis measured in the XY plane could significantly distinguish between all three pacing modes versus no pacing. Mean QRS-axis in the XY plane with pacing off and during RV pacing was leftward and basal; LV pacing was apical; and BIV pacing was rightward and basal. There was a statistically significant difference in the direction of the QRS-axis between patients with optimal versus nonoptimal paced QRS morphology in the XY plane (rightward and basal versus inconsistent). SIGNIFICANCE: CGM recorded in the XY plane can accurately detect differences between ventricular pacing sites. It may also be able to identify patients with a CRT device in situ who have optimal response.

Cardiogoniometry Compared to Fractional Flow Reserve at Identifying Physiologically Significant Coronary Stenosis: The CARDIOFLOW Study.

Cardiogoniometry (CGM) is method of 3-dimensional electrocardiographic assessment which has been shown to identify patients with angiographically defined, stable coronary artery disease (CAD). However, angiographic evidence of CAD, does not always correlate to physiologically significant disease. The aim of our study was to assess the ability of CGM to detect physiologically significant coronary stenosis defined by fractional flow reserve (FFR). In a tertiary cardiology centre, elective patients with single vessel CAD were enrolled into a prospective double blinded observational study. A baseline CGM recording was performed at rest. A second CGM recording was performed during the FFR procedure, at the time of adenosine induced maximal hyperaemia. A significant CGM result was defined as an automatically calculated ischaemia score < 0 and a significant FFR ratio was defined as < 0.80. Measures of diagnostic performance (including sensitivity and specificity) were calculated for CGM at rest and during maximal hyperaemia. Forty-five patients were included (aged 61.1 ± 11.0; 60.0% male), of which eighteen (40%) were found to have significant CAD when assessed by FFR. At rest, CGM yielded a sensitivity of 33.3% and specificity of 63.0%. At maximal hyperaemia the sensitivity and specificity of CGM was 71.4 and 50.0% respectively. The diagnostic performance of CGM to detect physiologically significant stable CAD is poor at rest. Although, the diagnostic performance of CGM improves substantially during maximal hyperaemia, it does not reach sufficient levels of accuracy to be used routinely in clinical practice.

Proprotein Convertase Subtilisin/kexin type 9 Inhibition in Cardiovascular Prevention.

Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly associated with increased risk for atherosclerotic cardiovascular and cerebrovascular events. Statins have been used to control serum LDLC and this has translated into reduction in cardiovascular and cerebrovascular events. However, despite high dose statin therapy, LDL-C control may remain inadequate in some patients, particularly those with familial hypercholesterolemia. A new therapeutic approach has emerged in recent years with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In this review, we describe the development and the use of this new class of drugs.

The Proximal Optimisation Technique for Intervention of Coronary Bifurcations.

The proximal optimisation technique (POT) has been proposed as a strategy to improve the results of stent scaffolding of bifurcation lesions. It is a straightforward technique whereby a short, appropriately-sized balloon is inflated in the main vessel just proximal to the carina. The technique has several advantages: it reduces the risk of side branch compromise related to shifting of the carina, it improves stent apposition in the proximal main vessel, and it facilitates side branch access after main vessel stent implantation. When treating bifurcations, final kissing balloon dilation (KBD) has traditionally been used routinely to optimise angiographic results. However, recent clinical data have questioned this philosophy and bench models have demonstrated several shortcomings of KBD. Instead, the optimal strategy may centre on performing POT, followed by side branch dilation, and completed with a final (re)-POT. The following review article describes how to perform POT and presents the evidence to support its' routine use.

Percutaneous Device Closure of Paravalvular Leak: Combined Experience From the United Kingdom and Ireland.

BACKGROUND: Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery. METHODS: All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up. RESULTS: Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004-2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure (P<0.001) and was none (33.3%), mild (41.4%), moderate (18.6%), or severe (6.7%) at last follow-up. Mean New York Heart Association class improved from 2.7±0.8 preprocedure to 1.6±0.8 (P<0.001) after a median follow-up of 110 (7-452) days. Hospital mortality was 2.9% (elective), 6.8% (in-hospital urgent), and 50% (emergency) (P<0.001). MACE during follow-up included death (16%), valve surgery (6%), late device embolization (0.4%), and new hemolysis requiring transfusion (1.6%). Mitral PVL was associated with higher MACE (hazard ratio [HR], 1.83; P=0.011). Factors independently associated with death were the degree of persisting leak (HR, 2.87; P=0.037), New York Heart Association class (HR, 2.00; P=0.015) at follow-up and baseline creatinine (HR, 8.19; P=0.001). The only factor independently associated with MACE was the degree of persisting leak at follow-up (HR, 3.01; P=0.002). CONCLUSION: Percutaneous closure of PVL is an effective procedure that improves PVL severity and symptoms. Severity of persisting leak at follow-up is independently associated with both MACE and death. Percutaneous closure should be considered as an alternative to repeat surgery.

Dedicated Bifurcation Stent for the Treatment of Bifurcation Lesions Involving Large Side Branches: Outcomes From the Tryton Confirmatory Study.

OBJECTIVES: The aim of this study was to prospectively study and confirm the safety and efficacy of the Tryton Side Branch Stent in the treatment of coronary artery bifurcations involving large side branches (SBs). BACKGROUND: The TRYTON Pivotal randomized controlled trial (RCT) was designed to compare the Tryton stent with standard provisional SB stenting in large vessels. The trial inadvertently enrolled patients with too small SBs (<2.25 mm). The overall trial did not meet its primary endpoint, because of an increased rate of periprocedural myocardial infarction in the Tryton stent arm. A post hoc analysis restricted to the intended population showed that the trial would have met its endpoint if only patients with SBs ≥2.25 mm in diameter (by core laboratory quantitative coronary angiography) had been enrolled. METHODS: The Tryton Confirmatory Study was a prospective, single-arm extension of the TRYTON Pivotal RCT that enrolled an additional 133 patients treated with the Tryton Side Branch Stent. It was designed to confirm the results of the post hoc analysis and emphasized the inclusion of appropriately sized SBs. The primary endpoint was noninferiority with regard to periprocedural myocardial infarction (creatine kinase myocardial band 3 times the upper limit of normal) compared with a performance goal based on the TRYTON Pivotal RCT. RESULTS: Among the 133 enrolled patients, 132 (99.2%) had SBs ≥2.25 mm. Baseline clinical and angiographic parameters were similar in this study and the RCT. Periprocedural myocardial infarction occurred in 10.5% of patients, which was numerically lower than the provisional group in the TRYTON Pivotal RCT (11.9%). The 95% confidence bounds did not extend beyond the pre-defined performance goal of 17.9%, meeting the noninferiority primary endpoint. CONCLUSIONS: The Tryton Confirmatory Study, in conjunction with the post hoc analysis of the intended population in the TRYTON Pivotal RCT, supports the safety and efficacy of the Tryton Side Branch Stent for treatment of bifurcation lesions involving large SBs.

Systematic review and meta-analysis of optimal P2Y12 blockade in dual antiplatelet therapy for patients with diabetes with acute coronary syndrome.

BACKGROUND: Patients with diabetes are at increased risk of acute coronary syndromes (ACS) and their mortality and morbidity outcomes are significantly worse following ACS events, independent of other comorbidities. This systematic review sought to establish the optimum management strategy with focus on P2Y12 blockade in patients with diabetes with ACS. METHODS: MEDLINE (1946 to present) and EMBASE (1974 to present) databases, abstracts from major cardiology conferences and previously published systematic reviews were searched to June 2014. Relevant randomised control trials with clinical outcomes for P2Y12 inhibitors in adult patients with diabetes with ACS were scrutinised independently by 2 authors with applicable data was extracted for primary composite end point of cardiovascular death, myocardial infarction (MI) and stroke; enabling calculation of relative risks with 95% CI with subsequent direct and indirect comparison. RESULTS: Four studies studied clopidogrel in patients with diabetes, with two (3122 patients) having primary outcome data showing superiority of clopidogrel against placebo with RR0.84 (95% CI 0.72-0.99). Irrespective of management strategy, the newer agents prasugrel (2 studies) and ticagrelor (1 study) had a lower primary event rate compared with clopidogrel; RR 0.80 (95% CI 0.66 to 0.97) and RR 0.89 (95% CI 0.77 to 1.02), respectively. When ticagrelor was indirectly compared with prasugrel, there was a trend to an improved primary outcome with prasugrel (RR 1.11 (95% CI 0.94 to 1.31)) particularly in those managed with percutaneous coronary intervention (PCI) (RR 1.23 (95% CI 0.95 to 1.59)). Prasugrel demonstrated a statistical superiority with prevention of further MI with RR 1.48 (95% CI 1.11 to 1.97). This was not at the expense of increased major thrombolysis in MI (TIMI) bleeding rates RR 0.94 (95% CI 0.59 to 1.51). CONCLUSIONS: This meta-analysis shows the addition of a P2Y12 inhibitor is superior to placebo, with a trend favouring the use of prasugrel in patients with diabetes with ACS, particularly those undergoing PCI.

Biomarkers of coronary endothelial health: correlation with invasive measures of collateral function, flow and resistance in chronically occluded coronary arteries and the effect of recanalization.

OBJECTIVES: In the presence of a chronically occluded coronary artery, the collateral circulation matures by a process of arteriogenesis; however, there is considerable variation between individuals in the functional capacity of that collateral network. This could be explained by differences in endothelial health and function. We aimed to examine the relationship between the functional extent of collateralization and levels of biomarkers that have been shown to relate to endothelial health. METHODS: We measured four potential biomarkers of endothelial health in 34 patients with mature collateral networks who underwent a successful percutaneous coronary intervention (PCI) for a chronic total coronary occlusion (CTO) before PCI and 6-8 weeks after PCI, and examined the relationship of biomarker levels with physiological measures of collateralization. RESULTS: We did not find a significant change in the systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor 6-8 weeks after PCI. We did find an association between estimated retrograde collateral flow before CTO recanalization and lower levels of sICAM-1 (r=0.39, P=0.026), sE-selectin (r=0.48, P=0.005) and microparticles (r=0.38, P=0.03). CONCLUSION: Recanalization of a CTO and resultant regression of a mature collateral circulation do not alter systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor. The identified relationship of retrograde collateral flow with sICAM-1, sE-selectin and microparticles is likely to represent an association with an ability to develop collaterals rather than their presence and extent.