Association of MicroRNAs and YRNAs With Platelet Function.

RATIONALE: Platelets shed microRNAs (miRNAs). Plasma miRNAs change on platelet inhibition. It is unclear whether plasma miRNA levels correlate with platelet function. OBJECTIVE: To link small RNAs to platelet reactivity. METHODS AND RESULTS: Next-generation sequencing of small RNAs in plasma revealed 2 peaks at 22 to 23 and 32 to 33 nucleotides corresponding to miRNAs and YRNAs, respectively. Among YRNAs, predominantly, fragments of RNY4 and RNY5 were detected. Plasma miRNAs and YRNAs were measured in 125 patients with a history of acute coronary syndrome who had undergone detailed assessment of platelet function 30 days after the acute event. Using quantitative real-time polymerase chain reactions, 92 miRNAs were assessed in patients with acute coronary syndrome on different antiplatelet therapies. Key platelet-related miRNAs and YRNAs were correlated with platelet function tests. MiR-223 (rp=0.28; n=121; P=0.002), miR-126 (rp=0.22; n=121; P=0.016), and other abundant platelet miRNAs and YRNAs showed significant positive correlations with the vasodilator-stimulated phosphoprotein phosphorylation assay. YRNAs, miR-126, and miR-223 were also among the small RNAs showing the greatest dependency on platelets and strongly correlated with plasma levels of P-selectin, platelet factor 4, and platelet basic protein in the population-based Bruneck study (n=669). A single-nucleotide polymorphism that facilitates processing of pri-miR-126 to mature miR-126 accounted for a rise in circulating platelet activation markers. Inhibition of miR-126 in mice reduced platelet aggregation. MiR-126 directly and indirectly affects ADAM9 and P2Y12 receptor expression. CONCLUSIONS: Levels of platelet-related plasma miRNAs and YRNAs correlate with platelet function tests in patients with acute coronary syndrome and platelet activation markers in the general population. Alterations in miR-126 affect platelet reactivity.

When is rotational angiography superior to conventional single-plane angiography for planning coronary angioplasty?

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 < 0.05) and a reduction in the assessment of vessel caliber (2.8 vs. 3.0 mm, P < 0.05). RoCA improved confidence assessing lesion length (P = 0.01), percentage stenosis (P = 0.02), tortuosity (P < 0.04), and proximity to a bifurcation (P = 0.03), particularly in left coronary artery cases. X-ray dose, contrast agent volume, and procedure duration were not significantly different. CONCLUSIONS: Compared with conventional CA, RoCA augments quantitative lesion assessment, enhances confidence in the assessment of coronary artery disease and the precise details of the proposed procedure, but does not affect X-ray dose, contrast agent volume, or procedure duration.

The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study.

AIMS: Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS. METHODS AND RESULTS: A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting <48 h from onset of chest pain. Treatment was 1:1 allocation to daily, subcutaneous IL-1receptor antagonist (IL-1ra) or placebo for 14 days. Baseline characteristics were well matched. Treatment compliance was 85% at 7 days. The primary endpoint (area-under-the-curve for C-reactive protein over the first 7 days) was: IL-1ra group, 21.98 mg day/L (95%CI 16.31-29.64); placebo group, 43.5 mg day/L (31.15-60.75) (geometric mean ratio = 0.51 mg/L; 95%CI 0.32-0.79; P = 0.0028). In the IL-1ra group, 14-day achieved high-sensitive C-reactive protein (P < 0.0001) and IL-6 levels (P = 0.02) were lower than Day 1. Sixteen days after discontinuation of treatment (Day 30) high-sensitive C-reactive protein levels had risen again in the IL-1ra group [IL-1ra; 3.50 mg/L (2.65-4.62): placebo; 2.21 mg/L (1.67-2.92), P = 0.022]. MACE at Day 30 and 3 months was similar but at 1 year there was a significant excess of events in the IL-1ra group. CONCLUSION: IL-1 drives C-reactive protein elevation at the time of NSTE-ACS. Following 14 days IL-1ra treatment inflammatory markers were reduced. These results show the importance of IL-1 as a target in ACS, but also indicate the need for additional studies with anti-IL-1 therapy in ACS to assess duration and safety. CLINICAL TRIAL REGISTRATION EUCTR: 2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB.

Evolving pattern of platelet P2Y12 inhibition in patients with acute coronary syndromes.

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 < 0.001) and ticagrelor was associated with significantly lower platelet aggregation responses than both prasugrel (p = 0.015) and clopidogrel (p < 0.001). We conclude that international guidelines and NICE approval have led to increasing levels of P2Y12 inhibition in ACS patients in this UK centre between May 2010 and February 2013. Ticagrelor was associated with significantly greater P2Y12 inhibition than both clopidogrel and prasugrel during maintenance therapy.

Impact of incomplete revascularization in patients undergoing PCI for unprotected left main stem stenosis.

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.

Novel use of a pericardium-covered stent graft to treat bulky coronary artery thrombus.

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.

Interleukin-1 receptor antagonist alters the response to vessel wall injury in a porcine coronary artery model.

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<0.0001); in Group 4, a 34% decrease (p=0.0004); and in Group 5, a 41% decrease (p=0.00001). CONCLUSIONS: IL-1ra was associated with a sustained, significant reduction in neointima after vessel wall injury as long as it is given for the duration of the stimulation of the IL-1 system, in this case at least 28 days. This suggests that therapies based on the antagonism of IL-1 may modulate the coronary artery response to injury.

Antithrombotic therapy in patients with combined coronary heart disease and atrial fibrillation.

Coronary heart disease (CHD) and atrial fibrillation (AF) commonly occur together. This presents challenges for the clinician treating patients with CHD, who require antiplatelet therapy and patients with AF, who require oral anticoagulant therapy. We have reviewed PubMed and SCOPUS to identify relevant guidelines, randomised clinical trials and registry studies and clinical trials presented at international meetings, and where necessary, clinical trial protocols to identify and critically analyze all relevant trials in which combinations of oral anticoagulants and antiplatelet agents in patients with AF and CHD have been evaluated. The available evidence on the efficacy and safety of combined oral anticoagulants and anti platelet agents was reviewed for the AF patient in three clinical scenarios: 1) after percutaneous coronary intervention (PCI); 2) after an acute coronary syndrome without PCI; and 3) in stable CHD. In each the clinical scenarios evaluated, there is limited clinical trial evidence to guide clinical management. Guidelines to help the clinician choose the right combinations of warfarin, clopidogrel and aspirin and the duration of treatment have been published, but they are based on a limited evidence base. There is even less evidence to guide the use of new oral anticoagulants (NOACs) in combination with the new P2Y12 antiplatelet agents. In each clinical scenario, the risks of coronary artery or stent thrombosis in CHD and risks of stroke in AF need to be carefully balanced against the risks of bleeding. We make recommendations for management based on the evidence which is available at this time and indicate the many gaps which are currently being addressed by randomized clinical trials.

Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction.

Delays 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.

Percutaneous brachial artery access for coronary artery procedures: Feasible and safe in the current era.

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.

Stenting the stent.

BACKGROUND: Stents are constructed with predefined radial strength which, on occasion, may be insufficient to support a resistant lesion. METHODS: We prospectively assessed the need for, and safety of, implanting a second stent within the first, during the index procedure, in a consecutive series of 500 patients undergoing percutaneous coronary intervention (PCI) by a single operator in the period 1998 2001. The indication was a lesion that appeared angiographically suboptimal after full balloon/stent expansion to high pressure with appropriate sizing. Visible thrombus was an exclusion. Stents were slotted tubes or ring designs whenever possible. Clinical follow-up was > 1 year and angiographic re-study was performed when indicated. RESULTS: We identified 18 patients/lesions (3.6%) that required implantation of a stent within a stent. The appearance was due to tissue/stent prolapse in 72%, edge dissection in 17%, narrow stent inflow/outflow in 5.5% and inadvertent stent detachment in 5.5%. There were no lesion-related acute or in-hospital complications. There was no late thrombosis or death. Follow-up was 21 10 months, and revealed 11% target lesion revascularization, of which half were at the site of stent overlap. CONCLUSION: Stenting the stent, where extra support is required, is safe and effective.

Virtual fractional flow reserve from coronary angiography: modeling the significance of coronary lesions: results from the VIRTU-1 (VIRTUal Fractional Flow Reserve From Coronary Angiography) study.

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) and which were not (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.

Residual SYNTAX score after PCI for triple vessel coronary artery disease: quantifying the adverse effect of incomplete revascularisation.

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 rSYNTAXmedian (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.

Incidence and predictors of stent thrombosis: a single-centre study of 5,833 consecutive patients undergoing coronary artery stenting.

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.

Metal-on-metal hip prostheses and systemic health: a cross-sectional association study 8 years after implantation.

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.

Hirudin anticoagulation allows more rapid determination of P2Y12 inhibition by the VerifyNow P2Y12 assay.

VerifyNow (VN) P2Y12 is a point-of-care assay used to assess response to P2Y12 inhibitors. Sodium citrate (citrate) is the standard anticoagulant used for this assay but requires a pre-incubation period. Hirudin is an alternative anticoagulant for platelet function studies that maintains physiological divalent cation levels. We investigated whether hirudin anticoagulation might allow more rapid testing of P2Y12 inhibition at the time of percutaneous coronary intervention (PCI). Blood was collected from the arterial sheath of aspirin-treated patients undergoing elective, urgent or emergency coronary angiography±PCI and aliquots were anticoagulated with either citrate or hirudin. For each anticoagulant, VN P2Y12 was performed both immediately and after 20 minutes. A total of 98 patients were included in this study following pre-treatment with clopidogrel (n=88), prasugrel (n=6) or no P2Y12 inhibitor (n=4). PRU with hirudin immediately (PRU_H_Imm) and PRU with citrate 20 minutes post sampling (PRU_C_20) were very strongly correlated (R=0.95) though PRU_H_Imm tended to be lower than PRU_C_20 so that optimal correlation was estimated by the equation PRU_H_Imm=0.95xPRU_C_20 (p<0.001). Bland-Altman plots showed good agreement between PRU_H_Imm and (0.95xPRU_C_20). Platelet reactivity was more stable over the studied time course with hirudin as compared to citrate. We therefore conclude that VN P2Y12 with hirudin anticoagulation can be performed more rapidly and results are strongly correlated with delayed citrate measurements. Further studies are warranted to assess the utility of this method for improving clinical outcomes in patients undergoing PCI.

Noninvasive estimation of PA pressure, flow, and resistance with CMR imaging: derivation and prospective validation study from the ASPIRE registry.

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 (R(2) = 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 < 0.0001). CMR-estimated PVR reliably identified invasive PVR ≥3 Wood units (WU) with a high degree of accuracy, the area under the ROC curve was 0.94 (0.88 to 0.99; p < 0.0001). 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.