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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

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.

Antiplatelet therapy plays a central role in the management of ischaemic heart disease [1]. While poor inhibition of P2Y12 receptor has been linked to higher incidence of ischaemic events, enhanced...

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.

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 …

Introduction Hepatocyte growth factor (HGF) acts via the tyrosine kinase receptor, c-MET, on endothelial and epithelial cells. It has angiogenic, mitogenic, motogenic and anti-apoptotic effects. Administration of HGF has been shown to ameliorate pulmonary arterial hypertension (PAH) in the monocrotaline rat model.1,2 Little is known regarding circulating HGF levels in human disease. Methods 47 incident, treatment naive patients with PAH in association with connective tissue disease (CTD-PAH) had blood sampling at or within 1 day of diagnostic right heart catheterisation. Plasma HGF concentrations were measured using Bio-Plex bead array. A proportion of patients also had NT-proBNP measured and underwent cardiac MRI. Results Baseline characteristics were (mean, sd): Age 64(10)yrs, mean right atrial pressure (mRAP) 9.6(11.7)mmHg, mean pulmonary arterial pressure (mPAP) 40.6(13)mmHg, pulmonary arterial wedge pressure 10.5(4.5)mmHg, cardiac index (CI) 2.97(0.7)L/min, pulmonary vascular resistance (PVR) 531(350)dyns. HGF levels correlated positively with mRAP (0.6, r < 0.001), mPAP (r = 0.68, p < 0.001: [fig 1][1]), PVR (r = 0.51, p = 0.001) and negatively with CI (r = -0.43, p = 0.008) and right ventricular ejection fraction measured by MRI (r = -0.53, p = 0.034). N-terminal pro B-type natriuretic peptide (NT-proBNP) measured in approximately 50% of patients correlated more strongly with CI (r = -0.72, p < 0.001) and PVR (r = 0.61, p = 0.003) but did not correlate with mPAP. A small proportion (7) of patients underwent repeat right heart catheterisation (RHC) following therapy with Bosentan (n = 6) or sildenafil (n = 1). Interestingly, improvement in CI at repeat RHC correlated positively with a further increase in HGF levels (r = 0.8, p = 0.03). ![Abstract P157 Figure 1.][2] Abstract P157 Figure 1. Conclusion Plasma HGF concentrations correlate with haemodynamic severity in CTD-PAH. Further work to determine whether high levels of HGF are involved in the pathogenesis of PAH or are instead elevated in a reparative response to underlying pulmonary vascular remodelling is required. References 1. Ono M et al . Circulation 2004;110:2896–92 2. Hiramine K et al . Int J Molec Med 2011;27:497–502 [1]: #F1 [2]: pending:yes

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.

Background Percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) measurement is superior to visual angiographic assessment alone. We have developed a workflow that takes a single rotational angiogram (RoCA), reconstructs the 3-dimensional arterial tree and applies computational fluid dynamics (CFD) to calculate the FFR without the need to induce hyperaemia or perform invasive pressure measurements. Methods 20 patients, scheduled for elective PCI underwent RoCA. The FFR was measured with a Combowire (Volcano), under resting and hyperaemic conditions. Physiologically significant lesions were stented and the measurements repeated. The arterial anatomy was reconstructed on a Philips 3DCA workstation. Generic boundary conditions for CFD were derived from the measured data. The calculated (“virtual”) and measured FFR values were then compared. Results There were 11 right coronary artery (RCA) cases (6 stented) and 12 left coronary artery (LCA) cases (8 stented). The anatomy was reconstructed, and the FFR computed in each case (pre- and post-stenting). The CFD model accurately predicted which lesions were physiologically significant (FFR 0.8) in all cases. The virtual FFR values deviated from the measured by ±6% (SD=6%) for both RCA and LCA cases. Conclusion We have developed a novel, user-friendly workflow, which has the potential to predict FFR without the need for invasive measurements or inducing hyperaemic conditions. Our model identified lesions requiring intervention in all cases. Further work will optimise and refine the model by better characterising the downstream generic boundary conditions. We aim to improve the accuracy of the optimised model with more complex patients and lesions.

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.

Introduction: Chronic total coronary artery occlusion (CTO) in man remains a significant challenge for percutaneous coronary intervention (PCI) and a common reason for coronary artery bypass surgery, as often the CTO cannot be crossed. This study investigated whether a potential angiogenic treatment, the prolyl-4-hydroxylase inhibitor, di-methyl oxalyl glycine (DMOG), would increase collateral vessel formation and myocardial perfusion without opening the CTO in a porcine model of coronary CTO. Methods: We assessed the effect of DMOG upon tube formation of HUVEC in a matrigel assay in vitro. DMOG was loaded onto a polymer-coated coronary stent. Copper-coated stents were used to produce a coronary CTO in 20 pigs. DMOG-loaded or control stents were implanted in an alternating, blinded manner at day 28, proximal to the CTO. Angiographic and physiological flow data were collected at day 56, when the animals were sacrificed and the collateral vessels counted. Results: DMOG increased tubule formation in vitro by 77% compared with control (p