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Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited.In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke.A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31).In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

Cardiac myxoma is a benign primary cardiac tumour which can present with nonspecific symptoms of right heart failure, syncope, exertional dyspnea, and pulmonary embolism. We describe a case of a right ventricular myxoma complicated with bilateral pulmonary embolism, with an incidental right coronary artery fistula but otherwise normal coronary anatomy on coronary angiogram. This case report emphasizes the importance of performing a transesophageal echo in the setting of pulmonary embolism to search for the origin of thrombus/tumour, and performing a comprehensive assessment is also necessary to rule out coronary artery disease, coronary artery fistula that may also represent a tumour blush.

Dual antiplatelet therapy consisting of clopidogrel in addition to aspirin has previously been the standard of care for patients with acute coronary syndromes (ACS) but international guidelines have been evolving over the last 4 years with the introduction of prasugrel and ticagrelor. In October 2009, prasugrel was approved in the UK by the National Institute of Health and Clinical Excellence (NICE) for use in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), diabetic patients with non-ST-elevation (NSTE) ACS undergoing PCI and patients with stent thrombosis while other ACS patients were to continue receiving clopidogrel. Ticagrelor was approved in October 2011 by NICE for use in patients with moderate-to-high risk NSTE ACS and STEMI undergoing primary PCI and was recommended in preference to clopidogrel in European guidelines. These recommendations were adopted in our region, constituting a population of 1.8 million. We studied the effect of changing patterns of P2Y12 inhibitor usage on levels of platelet inhibition during maintenance therapy. Patients admitted to Northern General Hospital, Sheffield, with NSTE ACS or STEMI managed with primary PCI were enrolled over two periods of time: May 2010 to November 2011 (T1); and October 2012 to February 2013 (T2). Venous blood samples were obtained at 1 month after the onset of ACS. Light transmittance aggregometry (LTA) was performed and maximum aggregation response to ADP 20 μM was determined. A total of 116 patients were enrolled in T1 of whom 82 were receiving clopidogrel and 34 were receiving prasugrel. Twenty-nine patients were enrolled in T2, all of whom were receiving ticagrelor. Mean LTA results according to treatment with clopidogrel, prasugrel and ticagrelor were 57 ± 18%, 41 ± 20%, and 31 ± 12%, respectively. Prasugrel was associated with significantly lower platelet aggregation responses than clopidogrel (p

Objectives The aim of this study was to develop a composite numerical model based on parameters from cardiac magnetic resonance (CMR) imaging for noninvasive estimation of the key hemodynamic measurements made at right heart catheterization (RHC). Background Diagnosis and assessment of disease severity in patients with pulmonary hypertension is reliant on hemodynamic measurements at RHC. A robust noninvasive approach that can estimate key RHC measurements is desirable. Methods A derivation cohort of 64 successive, unselected, treatment naive patients with suspected pulmonary hypertension from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) Registry, underwent RHC and CMR within 12 h. Predicted mean pulmonary arterial pressure (mPAP) was derived using multivariate regression analysis of CMR measurements. The model was tested in an independent prospective validation cohort of 64 patients with suspected pulmonary hypertension. Surrogate measures of pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were estimated by left atrial volumetry and pulmonary arterial phase contrast imaging, respectively. Noninvasive pulmonary vascular resistance (PVR) was calculated from the CMR-derived measurements, defined as: (CMR-predicted mPAP – CMR-predicted PCWP)/CMR phase contrast CO. Results The following composite statistical model of mPAP was derived: CMR-predicted mPAP = –4.6 + (interventricular septal angle × 0.23) + (ventricular mass index × 16.3). In the validation cohort a strong correlation between mPAP and MR estimated mPAP was demonstrated (R2 = 0.67). For detection of the presence of pulmonary hypertension the area under the receiver-operating characteristic (ROC) curve was 0.96 (0.92 to 1.00; p Conclusions CMR imaging can accurately estimate mean pulmonary artery pressure in patients with suspected pulmonary hypertension and calculate PVR by estimating all major pulmonary hemodynamic metrics measured at RHC.

Aims There is some evidence to suggest that incompleteness of coronary artery revascularisation after PCI is associated with inferior outcomes. The SYNTAX score was developed as a tool to quantify the extent of coronary artery disease in the SYNTAX study. We aimed to use this score to quantify the completeness of revascularisation after PCI (the "residual SYNTAX score") and to determine its impact upon mortality. Methods and results We studied 240 consecutive patients with native three-vessel disease who underwent PCI between 2003 and 2008. SYNTAX scores prior to, and after, PCI were calculated, the difference (ΔSYNTAX) being a measure of the relative completeness of revascularisation. Median follow-up was 2.6 (1.2-3.2) years; 21% of patients were surgical turndowns, and 38% were non-elective. A residual (rSYNTAX) score of zero (full revascularisation) was achieved in 40% and median rSYNTAX was 3.5 (0-10.9). At final follow-up reduced mortality was found in patients with rSYNTAX 0 vs. others (2.5 vs. 12%, respectively, p=0.003) and for those with rSYNTAX median (3 vs. 11%, p=0.003). rSYNTAX was an independent predictor of mortality in a multivariate analysis, whereas baseline SYNTAX score was not. Conclusions The residual SYNTAX score is a useful method to quantify incomplete revascularisation in patients undergoing PCI for 3VD. Complete revascularisation (rSYNTAX=0) is achieved in only a minority and, for them, the mortality rate is low.

Introduction Percutaneous revascularization of patients with multivessel and left main stem (LMS) disease may be incomplete and the impact of this is not well reported and may influence outcome. In this study we assessed the role of completeness of revascularization upon outcome after PCI for unprotected left main stem (uLMS) PCI in the “real world.” Materials and Method Consecutive patients (n = 353) with uLMS disease were treated by PCI by a single operator with a policy of maximal feasible revascularization between 2000 and 2011. The SYNTAX score was calculated before and after PCI (residual SYNTAX score) to gauge the completeness of revascularization. The endpoints were mortality and repeat revascularization. Results Mean age was 69 ± 11 years, baseline SYNTAX score was 33.4 ± 15, 53% were nonelective, 10% were in cardiogenic shock, and 45% were not surgical candidates. LMS bifurcation was involved in 74% and 2.0 ± 0.9 other vessels were diseased. Complete revascularization was achieved in 49% and was associated with reduced mortality compared with incomplete, at 30 days [5(2.9%) v 23(13%)], 1 year [9(5%) v 34(19%)], and 3 years [14(8%) v 46(26%)]; all P < 0.0001). Median rSYNTAX score was 1(0–11), 1-year survival for the lowest, middle and highest tertiles of rSYNTAX were 1.7%, 3.1% and 7.3% (P < 0.0001), respectively. In multivariate analysis postprocedure rSYNTAX score independently predicted outcome but preprocedural SYNTAX score did not. Conclusions For unselected patients with uLMS treated by PCI, completeness of revascularization is associated with superior survival. The rSYNTAX score, a novel index of completeness of revascularization, independently predicts survival. Baseline SYNTAX score does not. © 2013 Wiley Periodicals, Inc.

Objectives The aim of this study was to develop a computer model that accurately predicts myocardial fractional flow reserve (FFR) from angiographic images alone, in patients with coronary artery disease. Background Percutaneous coronary intervention (PCI) guided by FFR is superior to standard assessment alone. FFR-guided PCI results in improved clinical outcomes, a reduction in the number of stents implanted, and reduced cost. Currently FFR is used in few patients. A less invasive FFR would be a valuable tool. Methods Nineteen patients with stable coronary artery disease awaiting elective PCI were studied. They underwent rotational coronary angiography. The FFR was measured, physiologically significant lesions were stented, and angiography and FFR were repeated. Three-dimensional arterial anatomy pre- and post-stenting was reconstructed offline. Generic boundary conditions for computational fluid dynamics analysis were applied. The virtual fractional flow reserve (vFFR) and measured fractional flow reserve (mFFR) values were compared. Results Thirty-five matched anatomical and physiological datasets were obtained: 10 right coronary arteries (RCA) (5 pre- and post-stenting), and 12 left coronary arteries (LCA) (8 pre- and post-stenting). The computational fluid dynamics model predicted which lesions were physiologically significant (FFR 0.80) with accuracy, sensitivity, specificity, positive and negative predictive values of 97%, 86%, 100%, 100%, and 97% respectively. On average, the vFFR values deviated from mFFR by ±0.06 (mean delta = 0.02, SD = 0.08). The vFFR and mFFR were closely correlated (r = 0.84). Conclusions We have developed a model of intracoronary physiology based upon a rotational coronary angiogram. Significant lesions were identified with 97% accuracy. The FFR was reliably predicted without the need for invasive measurements or inducing hyperemia.

Objectives To investigate the value of rotational coronary angiography (RoCA) in the context of percutaneous coronary intervention (PCI) planning. Background As a diagnostic tool, RoCA is associated with decreased patient irradiation and contrast use compared with conventional coronary angiography (CA) and provides superior appreciation of three-dimensional anatomy. However, its value in PCI remains unknown. Methods We studied stable coronary artery disease assessment and PCI planning by interventional cardiologists. Patients underwent either RoCA or conventional CA pre-PCI for planning. These were compared with the referral CA (all conventional) in terms of quantitative lesion assessment and operator confidence. An independent panel reanalyzed all parameters. Results Six operators performed 127 procedures (60 RoCA, 60 conventional CA, and 7 crossed-over) and assessed 212 lesions. RoCA was associated with a reduction in the number of lesions judged to involve a bifurcation (23 vs. 30 lesions, P

Aims: Percutaneous coronary intervention (PCI) is increasingly being used to treat left main stem (LMS) coronary artery disease. Disease at the LMS bifurcation is technically challenging to treat, and there is no consensus as to the best method. We previously described experimental and initial clinical results with the simultaneous kissing stents (SKS) technique in a small series using drug-eluting stents (DES). We now report our results in a larger cohort with long-term follow-up. Methods and results: We treated 150 consecutive, unselected patients with unprotected bifurcation LMS with SKS using DES. The patients’ mean age was 67 years, 70% were male, 45% were non-elective and 35% were not surgical candidates. The New York Risk Score estimate of in-hospital mortality was (median) 0.7% (IQR 0.3-3.9%), logistic EuroSCORE 3.3% (1.3-11.9%) and angiographic SYNTAX score 20 (15-27). SKS were deployed in 99.3% of cases, and DES in 97%. There was no emergency CABG. The mortality rate at one year was 11.3% and at two years 12.7%. The (ischaemia-driven) target lesion revascularisation rate was 4.3% at one year and 6.2% at two years. Conclusions: The SKS technique for treating ULMS bifurcation disease is simple, feasible, effective and durable in treating “all-comers” with LMS bifurcation disease. It is a two-stent technique worthy of consideration at the LMS bifurcation.

Coronary heart disease is the leading cause of death worldwide. In the United States, approximately 1 of every 6 deaths in 2007 was caused by coronary heart disease. Clinical presentation in the acute setting is mostly due to atherosclerotic plaque rupture leading to flow limitation in the affected vessel, and myocardial ischemia and infarction. ST-segment elevation myocardial infarction is usually associated with complete occlusion of the coronary artery and carries the worst prognosis in terms of in-hospital mortality. Despite various advances in treatment options, including percutaneous coronary intervention, ischemic heart disease still carries a significant morbidity and mortality. In this article, we aim to provide a summary of a few key advances in the management of ST-segment elevation myocardial infarction.

Objectives: We studied the acute safety and feasibility of a pericardium-covered stent (PCS) in the obliteration of massive coronary thrombus. Background: Thrombus is frequently encountered in the setting of acute myocardial infarction, and conventional pharmacological and aspiration approaches are not always successful in dispersing or removing it, especially when it is very substantial. Methods: We treated nine patients (10 lesions) in the setting of an acute coronary syndrome characterized by the presence of substantial (TIMI grade 3–4) thrombus in a large caliber native coronary artery, persisting after conventional treatment, with percutaneous implantation of an equine PCS graft. Nine of 10 lesions were in large right coronary arteries. Results: Deployment was successful in nine of 10 lesions. In all nine cases, the filling defect was immediately eliminated and there was restoration or maintenance of TIMI grade 3 blood flow. There was one in-hospital stent thrombosis in a 56-year-old male, who had only received aspirin due to a coexistent stroke. This patient underwent successful repeat percutaneous intervention but died later of complications of the stroke. There were no 30-day events, and medium-term follow-up continues. Conclusions: A PCS graft is a potentially useful device to treat massive thrombus burden in the setting of acute coronary syndrome. A larger study is warranted. © 2011 Wiley Periodicals, Inc.

SummaryDelays in the onset of action of prasugrel during primary percutaneous coronary intervention (PPCI) have been reported and could be related to the effects of morphine on gastric emptying and subsequent intestinal absorption. The study objective was to determine whether morphine delays the onset of action of prasugrel in patients with a prior history of ST-elevation myocardial infarction (STEMI) treated with PPCI. This was a crossover study of 11 aspirin-treated patients with prior history of STEMI treated with PPCI, for which prasugrel and morphine had been previously administered. Patients were randomised to receive either morphine (5 mg) or saline intravenously followed by 60 mg prasugrel. Blood samples were collected before randomised treatment and over 24 hours after prasugrel administration. The inhibitory effects of prasugrel on platelets were determined using the VerifyNow P2Y12 assay and light transmission aggregometry. Plasma levels of prasugrel and prasugrel active metabolite were measured. Platelet reactivity determined by VerifyNow PRU, VerifyNow % Inhibition and LTA was significantly higher at 30–120 minutes (min) when morphine had been co-administered compared to when saline had been co-administered. Morphine, compared to saline, significantly delayed adequate platelet inhibition after prasugrel administration (158 vs 68 min; p = 0.006). Patients with delayed onset of platelet inhibition also had evidence of delayed absorption of prasugrel. In conclusion, prior administration of intravenous morphine significantly delays the onset of action of prasugrel. Intravenous drugs may be necessary to reduce the risk of acute stent thrombosis in morphine-treated STEMI patients undergoing PPCI.

Background Percutaneous vascular access for coronary intervention is currently achieved predominately via the radial route, the femoral route acting as a backup. Percutaneous trans-brachial access is no longer commonly used due to concerns about vascular complications. This study aimed to investigate the safety and feasibility of percutaneous brachial access when femoral and radial access was not possible. Methods This is a retrospective data analysis of patients who attended a single tertiary cardiology centre in the UK between 2005 and 2014 and had a coronary intervention (coronary angiogram or PCI) via the brachial route. The primary endpoints were procedural success and the occurrence of vascular complications. Results During the study period 26602 patients had a procedure (15655 underwent PCI and 10947 diagnostic angiography). Of these, 117 (0.44% of total) had their procedure performed via the brachial route. The procedure was successful in 96% (112/117) of cases. 13 (11%) patients experienced post procedural complications, of which 2 (1.7%) were serious. There were no deaths. Conclusion Percutaneous trans-brachial arterial access is feasible with a high success rate and without evidence of high complication rate in a rare group of patients in whom femoral or sometimes radial attempts have failed.

Rationale Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality. Methods Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years. Results CXCL12α concentrations were elevated in PAH groups compared to controls (P

In this paper we examine whether the structure, geometry and dimensions of coronary stents influence the occurrence of restenosis. Whilst many consider these parameters to be less important since the advent of drug-eluting stents, this view reveals a poor appreciation of the technological development of stents over the last 18 years. Early 'slotted tube' stents were completely inflexible and posed major problems for delivery; and early 'coil' stents had poor radial strength, allowing considerable tissue prolapse. Nowadays, we are used to greatly improved physical stent parameters, which provide better deliverability, visibility, procedural success and scaffolding performance. Many of these physical parameters also impact upon restenosis, even in the current era of drug-eluting stent. In this paper we examine the contribution of mode of expansion (self vs. balloon-expandable), design (coil vs. tube), length and width to restenosis. We also consider the more subtle influence of advanced slotted tube vs. modular design, percent metal coverage, strut thickness, strut shape, surface smoothness and alloy composition.

Introduction: Platelets contribute plasma microRNAs (miRNAs). Levels of platelet-related miRNAs change in plasma in response to platelet inhibition. Hypothesis: It is currently unclear how plasma miRNAs correlate to platelet function in patients with acute coronary syndrome (ACS). Methods: We measured plasma miRNAs in 125 patients with a history of ACS (STEMI, NSTEMI or unstable angina) who have undergone detailed assessment of platelet function 30 days after the acute event. Results: Using custom-made quantitative real-time polymerase chain reaction plates, 92 miRNAs were assessed in patients on different anti-platelet therapies (clopidogrel, prasugrel, aspirin). Key platelet-related miRNAs were correlated with platelet function tests, including optical aggregometry using the agonists ADP and arachidonic acid, VerifyNow P2Y12 assay and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay. Significant associations were obtained for miR-126 with the VerifyNow (rp=0.347, n=39, P=0.033) and VASP assay (rp=0.224, n=125, P=0.013). Other abundant platelet miRNAs also showed strong correlations with the VASP assay: miR-223 (rp =0.231, P=0.003), miR-191 (rp =0.243, P=0.007), miR-24 (rp =0.246, P=0.006), miR-197 (rp=0.293, P=0.008), miR-30b (rp=0.230, P=0.010) and miR-20b (rp=0.231 , P=0.010). Conclusions: Levels of platelet-related plasma miRNAs correlate with platelet function tests in ACS patients. Our findings reinforce the concept that platelets are an important contributor to the plasma miRNA pool.

There is turnover of type I collagen during tissue repair. The degradation of type I collagen by matrix metalloproteinases (MMPs) is reflected by serum ICTP and that by cathepsins by CTX-I. There is evidence for increases in ICTP after acute coronary syndromes (ACS) and in CTX-I during fracture repair. The involvement of the MMP pathway in fracture repair and cathepsins after myocardial infarction is unclear. We studied 74 men; 22 were admitted to the hospital on the day of their ACS (ST or non-ST elevation myocardial infarction) (mean age 56 years, range 39 to 82) and 9 attended hospital on the day of their tibial shaft fracture (mean age 33 years, range 21 to 79); we had 43 age-matched controls (mean age 54 years, range 20 to 82). Subjects with ACS and tibial shaft fracture were followed up for up to one year; control subjects were used to establish a reference interval. We measured serum ICTP by ELISA (reference interval 1.1 to 17.6 ng/mL) and CTX-I by chemiluminescence (reference interval 0.094 to 0.991 ng/mL). After ACS, the mean ICTP increased from 5.41 to 6.60 ng/mL within one day of admission (p

Aims: Stent thrombosis (ST) is an infrequent but potentially fatal complication of PCI. The reported incidence of ST varies from 0-5%, due to differences in definition of ST, inclusion/exclusion criteria, and the type of stent and dual antiplatelet therapy used. We aimed to examine the incidence of ST and associated risk factors in this “real-world, all-comers” study. Methods and results: All patients undergoing PCI at South Yorkshire Cardiothoracic Centre (UK) between 2007 and 2010 were included, with no exclusion criteria. ST cases were divided into definite and probable ST, according to the ARC criteria. Univariate predictors were identified using Student’s t-test and chi-square test, and entered into a Cox proportional hazards model to identify factors independently associated with ST. For 5,833 PCI patients followed up for two years, the incidence of definite and probable ST together was 1.9% (n=109); of these 73% were early, 11% late and 16% very late ST. Cardiogenic shock, ST-elevation myocardial infarction (STEMI), lack of dual antiplatelet treatment, diabetes mellitus, stent length and stent diameter were the independent predictors of ST. Conclusions: The incidence of definite/probable ST in this “real-world” registry is 1.9%. Cardiogenic shock, often excluded in clinical trials, is the strongest independent predictor of ST.

PCI (percutaneous coronary intervention) now outnumbers CABG (coronary artery bypass grafting) by more than 3:1 for the treatment of coronary heart disease. In this article, we discuss the current challenges faced by interventional cardiologists including restenosis and its treatment options and potential therapies for the future. The impact of stent geometry on restenosis and strategies to deal with challenging lesions such as bifurcations and lesions in the left main stem are also discussed.

Drug eluting stents (DES) reduce the risk of restenosis as compared to bare metal stents (BMS).1 The high cost of these stents, however, makes their use in all patients undergoing percutaneous coronary intervention (PCI) problematic. In this journal 3 years ago we argued for a policy of selective implantation of DES, restricting their use to arteries of small calibre requiring a long stent, with some extra allowance for patients with diabetes.2 We recommended DES for all lesions if they needed a 2.5 or 2.75 mm stent ⩾12 mm long or a 3 mm stent ⩾16 mm long. For diabetic patients, in addition, a DES was recommended for stent sizes 2.5×8 mm, 3×12 mm and 3.5×⩾20 mm. For all other stent sizes, BMS were appropriate. These recommendations were similar in principle to the NICE guidelines.3 We estimated that the introduction of this policy would imply DES implantation in about 30% of lesions and would reduce the clinical restenosis rate in our institution by 33%.2 The aim of this study was to test the hypothesis that a policy of selectively targeted implantation of DES would lead to a significant reduction in our overall clinical restenosis rate. DES were available to us from July 2003 onwards. In the preceding …

Background: While several endovascular techniques have been developed for treating arterial bifurcation lesions, there is, as yet, no single, widely accepted technique for treating left main stem (LMS) bifurcation lesions with stents. The simultaneous kissing stent (SCS) technique seems particularly suited for such lesions. The authors describe a consecutive cohort of patients with LMS bifurcation stenosis treated with this technique and present mechanistic insights from a porcine model. Methods: Thirty consecutive patients with LMS bifurcation stenosis ± multivessel disease were treated with SCS technique using paclitaxel-eluting stents. The technique involves simultaneous implantation of two stents (LMS-LAD and LMS-Cx) so that the proximal end of both stents lie at the same level in the body of LMS. Symptom status was recorded and follow-up angiography was performed. In addition, four pigs underwent SCS implantation of the LMS and were studied by direct examination, histology, and scanning electron microscopy. Results: The patients' mean age was 63, 26 were elective and 19 were male. Paclitaxel-eluting stents (Taxus™, Boston Scientific) were used. There was one in-hospital death in a highly unstable patient. At 6-month follow-up angiography, two patients required target lesion revascularization. At 13 ± 3 month follow-up, the remaining patients remain well, with no other major adverse cardiac events. The animals all survived with patent stents. SEM demonstrated full re-endothelialization and histology showed a thin but complete neointima covering the stent struts. Conclusion: The SCS technique for treating LMS bifurcation disease with paclitaxel-eluting stents is safe and feasible. Medium term clinical and angiographic results are good. An endothelium and a thin neointima cover the metal struts. © 2006 Wiley-Liss, Inc.

A 70-year-old man underwent elective percutaneous coronary intervention (PCI) with two stents to the left anterior descending coronary artery. The procedure was uneventful. In the recovery area he complained of difficulty breathing and collapsed. His pulse was weak and the blood pressure unrecordable. He was immediately transferred back to the catheter laboratory. Echocardiography revealed tamponade. He started to lose consciousness and became restless. In addition, he had pectus excavatum. The …

Objective: To determine the influence of IL-1 on the arterial response to experimental injury in porcine models of percutaneous coronary intervention (PCI). Methods: An intravenous (i.v.) bolus of 0.5 mg/kg followed by a subcutaneous (s.c.) infusion of 2 mg/kg/24 h of human IL-1 receptor antagonist (IL-1ra) inhibited neutrophil recruitment in response to intradermal IL-1. Using this dose regimen, five groups of pigs were studied: Group 1, oversized balloon angioplasty of 2 coronary vessels (14-day infusion, 28th day sacrifice and analysis); Groups 2, 3, 4, and 5, oversized stenting of 2 coronary vessels (Group 2: 14-day infusion, 28th day analysis; Group 3: 14-day infusion, 14th day analysis; Group 4: 28-day infusion, 28th day analysis; Group 5: 28-day infusion, 90th day analysis). Neointimal area was quantified by standard means. Results: In Group 1, IL-1ra resulted in a 23% decrease in neointimal area ( p =0.04); in Group 2, a 34% increase ( p =0.001); in Group 3, a 38% decrease ( p

A policy of selective implantation of drug eluting stents, in a minority of lesions most likely to benefit, seems to be a rational way to employ this new and currently costly technology.

Background Risk scoring is a useful tool for prognostication, decision-making and, increasingly, assessing individual and institutional performance. At the South Yorkshire Cardiothoracic Centre, we have been using the New York risk score as a clinical routine which was developed in 2002 on a large population from the state of New York. We developed a “Sheffield risk score”, originally created in 2004, validated internally in a second Sheffield population in 2007 and externally in another UK centre 3 years ago. This study aimed to assess the ability of both scores to predict 30-day mortality. Methods The data from all patients undergoing PCI at the South Yorkshire Cardiothoracic Centre from January 2009 to December 2011 were collected prospectively. The variables for the New York PCI risk score (age, sex, haemodynamic status, previous MI, congestive heart failure, left ventricular function, renal function, peripheral arterial disease and left main stem disease) and the Sheffield score (age, extent of coronary disease, urgency of the PCI and cardiogenic shock) were extracted from this database. 30-day all-cause mortality was collected from the Office of National Statistics (ONS). The predictive power of the two scores was assessed using ROC curve analysis and Hosmer-Lemeshow (HL) tests. Results 4,607 patients underwent PCIs during the study period. The age of the patients was 63 ± 12 years, 72% were males, 71% had PCI for ACS and 1.0% had cardiogenic shock. The 30-day mortality in this population was 2.5%. Both the New York score and the Sheffield score discriminated well between patients who did and did not die within 30 days (area under curve 0.84 and 0.81, respectively). The New York score did not show superior predictive power compared with the Sheffield score. However, both scores showed poor calibration and a sub-optimal fit for this population (HL statistic 54.4, p Conclusion Risk models developed from a distinct population group need not only geographical validation, but also periodic update as their value may diminish with changing patient profile and treatment options. Our findings highlight their use as a guide; clinical judgement, informed consent and multidisciplinary review remain indispensable.

Even in the era of drug eluting stents, in-stent restenosis is likely to remain a significant problem. Restenosis is caused by growth of a neointima, comprised of smooth muscle cells and intercellular matrix. The quantity of neointima is directly proportional to the amount of injury inflicted upon the artery by the stent itself.1 That injury is in the form of either a deep laceration or stretch of the arterial wall. We have previously shown that stretch is ubiquitous after stenting and, even in the absence of deep injury, is an important mediator of neointima formation.2 A few parameters of stent geometry have been shown to have an influence upon neointima formation, including smaller strut number,3 greater strut thickness,4 and increased variation in the angular burden (pointedness) of the stent cross section.5 Therefore, in this study, we aimed to examine the contribution of a wide panel of parameters of stent geometry to the development of neointima in stent sections that displayed stretch but not deep injury. In accordance with UK Home Office regulations, we deployed BiodivYsio stents (3.5 × 15 mm) in 26 coronary arteries of 21 pigs; 17 in the right coronary artery (RCA) and nine in the left anterior descending (LAD). Quantitative coronary angiography identified two …

There is public concern over the long term systemic health effects of metal released from hip replacement prostheses that use large-diameter metal-on-metal bearings. However, to date there has been no systematic study to determine which organs may be at risk, or the magnitude of any effect. We undertook a detailed cross-sectional health screen at a mean of 8 years after surgery in 35 asymptomatic patients who had previously received a metal-on-metal hip resurfacing (MoMHR) versus 35 individually age and sex matched asymptomatic patients who had received a conventional hip replacement. Total body bone mineral density was 5% higher (mean difference 0.05 g/cm², P = 0.02) and bone turnover was 14% lower (TRAP 5b, mean difference -0.56IU/L, P = 0.006; osteocalcin, mean difference -3.08 ng/mL, P = 0.03) in the hip resurfacing versus conventional hip replacement group. Cardiac ejection fraction was 7% lower (mean absolute difference -5%, P = 0.04) and left ventricular end-diastolic diameter was 6% larger (mean difference 2.7 mm, P = 0.007) in the hip resurfacing group versus those patients who received a conventional hip replacement. The urinary fractional excretion of metal was low (cobalt 5%, chromium 1.5%) in patients with MoMHR, but creatinine clearance was normal. Diuretic prescription was associated with a 40% increase in the fractional excretion of chromium (mean difference 0.5%, P = 0.03). There was no evidence of difference in neuropsychological, renal tubular, hepatic or endocrine function between groups (P>0.05). Our findings of differences in bone and cardiac function between patient groups suggest that chronic exposure to low elevated metal concentrations in patients with well-functioning MoMHR prostheses may have systemic effects. Long-term epidemiological studies in patients with well-functioning metal on metal hip prostheses should include musculoskeletal and cardiac endpoints to quantitate the risk of clinical disease.

Just as a single antibiotic cannot treat all infections, it may be that a variety of agents utilised in drug eluting stents will be necessary to treat restenosis With the introduction of drug eluting stents (DES) into routine percutaneous coronary intervention (PCI), many consider the battle against restenosis won. A more realistic viewpoint, perhaps, is that these are merely the early engagements in what will eventually turn out to be a longer war. The evidence base for sirolimus and paclitaxel eluting stents is impressive, with target vessel revascularisation < 5% at nine months in selected patients and lesions.12 One area of uncertainty is whether these two agents alone are sufficient to treat the wide variety of lesions found in day-to-day practice; just as a single antibiotic cannot treat all infections, it may be that a variety of agents will be necessary to treat restenosis. Another question is whether there will be room to further lower the restenosis rate (ideally to zero) in the “real world” where complex coronary artery lesions (long, diffuse, calcific, etc) are the norm rather than the exception. Is there room for more troops on the restenosis “field of battle”? In this issue of Heart , Huang and colleagues describe the effects of methotrexate contained in a new biological polymer coating (SAE) upon in-stent stenosis in a porcine model of coronary artery stent implantation.3 Methotrexate is a folate antagonist and is widely used in the treatment of proliferative diseases such as Crohn’s disease, cancer, rheumatoid arthritis, and psoriasis. Folates are essential for the synthesis of purine nucleotides and thymidylate that, in turn, are essential for DNA synthesis and cell division. In order to act as coenzymes, folates must be reduced to tetrahydrofolate. Methotrexate exerts its cytotoxic effects by inhibiting dihydrofolate reductase and depleting intracellular …

Aims To assess the impact of completeness of revascularisation upon outcome after PCI for unprotected left main stem (LMS) PCI in the “real world”. Methods and Results We studied 348 consecutive patients with LMS disease treated by PCI by a single operator with a policy of maximal feasible revascularisation between 2000 and 2011. The SYNTAX score was calculated before and after PCI (the residual SYNTAX (rSYNTAX) score) to gauge the completeness of revascularisation. The endpoint was mortality and repeat revascularisation. Average age was 68±10 years, baseline SYNTAX score was 33.6±15.2, 51% were non-elective, 10% were in cardiogenic shock and 49% were not surgical candidates. The LMS bifurcation was involved in 73% and 2.0±0.9 other vessels were diseased. Complete revascularisation was achieved in 49% and was associated with reduced mortality compared with incomplete, at 30 days, 1 year and 3 years (2.9% vs 13%, 5% vs 19%, 8% vs 26%; all p Conclusions In this single centre, “real world” series of patients with LMS disease treated by PCI, complete revascularisation was associated with superior survival vs incomplete. The rSYNTAX score, a novel index of completeness of revascularisation, independently predicted survival and the baseline SYNTAX score did not.

Methaemoglobinaemia is rare. Acute myocardial infarction (AMI) is common. The authors present a unique case of methaemaglobinaemia masquerading as an AMI. A middle-aged male was urgently referred to a tertiary cardiac centre for primary percutaneous coronary intervention with acute chest pain, cyanosis and tachycardia. However, on arrival, his ECG was felt to be within normal limits. Similarly unremarkable, were his echocardiogram and routine blood tests. Arterial blood gas analysis revealed a methaemaglobinaemia of 28.5% which normalised spontaneously. This was thought to be secondary to the use of smelling salts, inhaled earlier that day in the gymnasium. This is the first reported case of smelling salts inducing methaemaglobinaemia and of methaemaglobinaemia mimicking an AMI.

Purpose microRNAs (miRs) are non-coding RNAs that silence mRNA translation and influence many biological processes. Peripheral blood miR expression patterns may provide mechanistic insight and novel biomarkers in Acute Coronary Syndromes (ACS). Our objective is to characterise whole blood miR expression following ACS and correlate this with miR target gene expression. Methods 10 patients with Unstable Angina (UA) served as a reference group to which 20 patients with Myocardial Infarction (MI) were compared. miR were extracted from peripheral whole blood, expression of 754 species quantified by RT-qPCR and analysed using the Relative Quantification method. mRNA was hybridised on microarrays and gene expression analysis performed using probabilistic models. Results Principal component analysis of whole genome microarray data showed clear discrimination between UA and MI groups at 7 and 30 days. Of particular interest is the differential expression of miR-20a between groups. Belonging to the miR-17-92 cluster, miR-20a is an endothelial derived miR involved in cardiovascular disease which has a regulatory role in smooth muscle cell proliferation. To assess possible involvement of miR-20a in endothelial dysfunction we compared its expression with miR-126. Comparison of expression showed correlation between miR and mRNA of putative targets. Conclusions We have shown that it is possible to classify and differentiate ACS events using transcriptional profiling of miRs and mRNA in whole blood. We have identified a group of 9 miRs that discriminate UA and MI at 30 days. The correlation of miR126 and miR20a suggests a possible role for miR-20a in quantifying endothelial dysfunction post MI.

Background Inflammatory mechanisms are involved in both coronary atherogenesis and its presentation as acute coronary syndromes (ACS). To date, drugs used at the time of ACS, or for primary and secondary prevention have not primarily targeted inflammatory mechanisms. Studies with aspirin and statin drugs indicate that anti-inflammatory properties of these compounds may contribute to their beneficial effects. Pre-clinical studies from our group have indicated that the pro-inflammatory cytokine IL-1 drives a number of vascular events relevant to coronary artery disease and ACS. IL-1 can be inhibited by IL-1 receptor antagonist (IL-1ra, Anakinra, Amgen) which is licensed for the treatment of rheumatoid arthritis. Aims To investigate the effects of interleukin-1 receptor antagonist (IL-1ra) on inflammatory biomarkers in patients with ACS Design and methods The UK MRC ILA-HEART study is an investigator-initiated, non-industry sponsored, phase 2, multi-centre, placebo-controlled trial, comparing the IL-1ra (100 mg) with matching placebo given as a single, daily subcutaneous injection over 2 weeks. The primary outcome of the study was area under the curve (AUC) of high sensitivity CRP (hs-CRP) over the first 7 days of treatment, and the main secondary outcomes are AUC of troponin and safety and compliance of trial treatment. Patients were encouraged to self-administer trial treatment, and underwent daily assessment of hs-CRP, troponin, von Willebrand factor and other biomarkers up to 7 days, and again at 2 weeks and 30 days. Patients were followed up to 12 months for safety (Abstract 15 table 1). Results Five UK centres randomised 182 patients with non-ST elevation (NSTEMI) ACS to IL-1ra or placebo. Enrolment completed in March 2010. Mean age was 61 years, 32% female, 28% prior MI, 15% diabetes, 90% were receiving a statin at the time of randomisation and 64% had early PCI or CABG. Compliance was good with 85% of patients receiving daily injections during the first 7 days, and 70% of patients were able to self-administer the injections. Injection site reactions reported as adverse events occurred in 14% of patients. There was no significant difference in area under the curve for hsCRP between active and placebo groups. The MACE and serious adverse event rates are shown in Abstract 15 table 2. Discussion NSTEMI ACS treated with all the current evidenced-based therapies still has significant recurrent events. MRC ILA-HEART is the first study to evaluate the effects of the anti-inflammatory IL-1ra in ACS. The data indicates that despite encouraging pre-clinical evidence, the inflammatory driver for NSTEMI-ACS is not IL-1 mediated.

Background Despite data showing excellent results for revascularisation of patients with LMS disease by PCI in a randomised trial vs CABG, there is still a need for PCI outcome data in ‘real world’ patients, many of whom are not suitable for CABG. Objective We assessed the results of left main stem (LMS) PCI in a ‘real world’ cohort of 302 consecutive patients. Methods A retrospective analysis was made of prospectively collected data on every patient undergoing PCI to the LMS performed by a single operator between 2000 and 2009 including patients who were not candidates for coronary artery bypass surgery, those treated as an emergency and those in cardiogenic shock. Clinical and angiographic data and logistic New York PCI Risk Scores (NYRSs) and EuroSCOREs were recorded. The endpoint was long-term mortality and repeat revascularisation, short term mortality was modelled on risk adjusted funnel plots. Results We treated 302 consecutive, unselected, patients with LMS disease±multi-vessel disease. The mean age was 67±10, 72% were male, 41% were non-elective, 10% were in cardiogenic shock, 21.5% required IABP and 46% were not surgical candidates. The NYRS was median 0.6% (IQR 0.32–4.2) and EuroSCORE 3.9 (1.82–11.4). Apart from the LMS, 2.1±0.9 vessels were diseased, 69% of the LMS lesions involved the bifurcation. Technical success was achieved in 99% LMS lesions, 1.7±0.8 other vessels were successfully treated and 57% LMS lesions were treated with drug-eluting stents; single stent being used in 44% and simultaneous kissing stents in 50%. The in-hospital, 30 day, 1 year and 3 year mortality rates of the whole group were 5%, 7.6%, 13.9% and 20.8%. For elective vs non-elective patients, the equivalent figures were 1% vs 4%, 1.3% vs 6.3%, 4% vs 10% and 8% vs 12.8%. The ischaemia-driven target lesion revascularisation rate at 1, 2 and 3 y was 12% (3%LMS), 15% (3.5% LMS) and 15.5% (4%LMS). There was 1% emergency CABG. The 30-day mortality rate was 7.6%, as compared with 6.2% predicted by NYRS (abstract 101 figure 1) and 10.1% predicted by EuroSCORE. Incomplete revascularisation was associated with an increased mortality at follow-up (1 yr 20.2% vs 10.3%, 3 yr 29.3% vs 16%; p Conclusions PCI is applicable to a wide variety of patients with CHD involving the LMS, with very few patients being unsuitable. Excellent results can be achieved for a typical, mixed population of patients requiring revascularisation over a wide range of risk profiles, in terms of both mortality and repeat revascularisation, to 3 years. Mortality risk is strongly influenced by clinical factors rather than disease pattern or procedural details.

Background Acute Coronary Syndromes account for 15% of deaths in the UK, and patients remain at significant risk of re-admission for future complications and death. Pathologically the underlying process of atherosclerosis is driven by inflammatory mechanisms, which are activated in ACS patients. Previous studies have investigated the role of inflammatory markers in this process, including interleukin 1 (IL-1) and C Reactive Protein (CRP). Pre-clinical studies indicate that IL-1 may be a primary driver of ACS and that the naturally occurring interleukin-1 receptor antagonist (IL-1ra) may inhibit the atherosclerotic process. This study will investigate the effects of IL-1ra on inflammatory markers in man. Methods/design Three centres in the UK are planning to recruit 186 Non-ST elevation myocardial infarction patients to receive either interleukin-1 receptor antagonist (Anakinra) or matching placebo. Patients will receive a daily subcutaneous injection of either study drug or placebo over a 14 day period. The primary outcome is area under the curve of high sensitivity C-Reactive Protein (CRP) over the first 7 days. Discussion The MRC-ILA-HEART Study is a proof of concept clinical trial investigating the effects of IL-1ra upon markers of inflammation in patients with Non-ST elevation myocardial infarction. It is hoped this will provide new and exciting information in relation to an "anti-inflammatory" strategy for patients with acute coronary syndrome. Trial registration ISRCTN89369318