Simon Corbett

Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain? The RIPCORD Study

Background—The use of coronary angiography (CA) for diagnosis and management of chest pain (CP) has several flaws. The assessment of coronary artery disease using fractional flow reserve (FFR) is a well-validated technique for describing lesion-level ischemia and improves clinical outcome in the context of percutaneous coronary intervention. The impact of routine FFR at the time of diagnostic CA on patient management has not been determined. Methods and Results—Two hundred patients with stable CP underwent CA for clinical indications. The supervising cardiologist (S.C.) made a management plan based on CA (optimal medical therapy alone, percutaneous coronary intervention, coronary artery bypass grafting, or more information required) and also recorded which stenoses were significant. An interventional cardiologist then measured FFR in all patent coronary arteries of stentable diameter (≥2.25 mm). S.C. was then asked to make a second management plan when FFR results were disclosed. Overall, after disclosure of FFR data, management plan based on CA alone was changed in 26% of patients, and the number and localization of functional stenoses changed in 32%. Specifically, of 72 cases in which optimal medical therapy was recommended after CA, 9 (13%) were actually referred for revascularization with FFR data. By contrast, of 89 cases in whom management plan was optimal medical therapy based on FFR, revascularization would have been recommended in 25 (28%) based on CA. Conclusions—Routine measurement of FFR at CA has important influence both on which coronary arteries have significant stenoses and on patient management. These findings could have important implications for clinical practice. Clinical Trial Registration—URL: http://www.clinicaltrial.gov. Unique identifier: NCT01070771.

Personalised antiplatelet therapy in stent thrombosis: observations from the Clopidogrel Resistance in Stent Thrombosis (CREST) registry

Objective Previous studies have demonstrated significant heterogeneity in responses to antiplatelet therapy (APT), and high residual platelet reactivity is associated with the risk of ischaemic events, including stent thrombosis (ST). The prevalence of APT hyporesponsiveness in a ‘real world’ registry of ST patients and the feasibility of personalising APT are reported. Patients and setting 39 consecutive patients admitted to a single regional cardiothoracic centre with definite ST were prospectively evaluated. Interventions Response to aspirin and clopidogrel was measured following discharge using short thrombelastography (TEG), a rapid, well validated near patient platelet function test. Treatment modification in hyporesponders comprised an increase in aspirin dose and/or changing clopidogrel to prasugrel or ticagrelor. Short TEG was repeated following treatment modification to ensure an adequate response had been achieved. Results 12 (31%) patients had an adequate response to both aspirin and clopidogrel, 16 (41%) were hyporesponsive to clopidogrel alone, one (3%) was hyporesponsive to aspirin alone and 10 (26%) were hyporesponsive to both aspirin and clopidogrel. Following treatment modification, an adequate response to aspirin and P2Y12 agent was achieved in 10 (91%) and 22 (85%) patients, respectively. None has presented with a further ST episode. Conclusions There is a high prevalence of hyporesponsiveness to APT in patients with ST. Improved APT efficacy can be achieved by tailored therapy. Short TEG is a plausible platelet function test that can be used to deliver point of care personalised APT.

Effect of clopidogrel withdrawal on platelet reactivity and vascular inflammatory biomarkers 1 year after drug-eluting stent implantation: results of the prospective, single-centre CESSATION study

Background The optimal duration of clopidogrel treatment, particularly following drug-eluting stent (DES) implantation, remains contentious. Previous studies have observed a clustering of adverse events following clopidogrel cessation 1 year after DES, the aetiology of which is poorly understood. Objective To investigate, in the prospective CESSATION study, the effect of clopidogrel withdrawal at 1 year after DES implantation on (i) arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation, and (ii) biomarkers of vascular inflammation, including soluble CD40 ligand (sCD40L), high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6). Methods and results The prospective CESSATION study was undertaken in 33 patients receiving aspirin and due to discontinue clopidogrel 1 year after DES. Platetet reactivity was measured using short thromboelastography, and compliance with aspirin determined from serum thromboxane B2 (TXB2) levels. Venesection was performed at 4 weeks and 24 h before, and at 24 h, 48 h, 1, 2 and 4 weeks after, clopidogrel cessation. Following clopidogrel withdrawal, there was (i) a predictable increase in ADP-induced platelet aggregation (ii) an unexpected significant increase in AA-induced platelet aggregation (iii) a decline in IL-6 and hsCRP at 1 week and 4 weeks respectively; and (iv) a non-significant increase in sCD40L at 4 weeks TXB2 levels were consistently suppressed, indicating complete inhibition of cyclo-oxygenase-1 by aspirin. Conclusion An aspirin-independent, time-dependent increase in AA-induced platelet activation following clopidogrel withdrawal in patients with a DES has been described. New insights into a potential mechanism for the observed clustering of adverse events that occur early after clopidogrel cessation have been provided. These findings raise the question as to whether AA-induced clotting is an appropriate test of aspirin sensitivity.

Detection of transient regional myocardial ischemia using body surface Delta map in patients referred for myocardial perfusion imaging--a pilot study.

BACKGROUND The diagnosis of transient regional myocardial ischemia (TRMI) in patients presenting with stable chest pain is a challenge. Exercise Tolerance Test (ETT) is no longer recommended in most cases due to its flaws. Alternative tests are more expensive and less readily available. The BSM Delta map is an intuitive color display of digitally subtracted ST-segment shift derived from two 80-electrode BSM recordings at baseline and at peak stress, and has shown promise as a tool for detection of TRMI. OBJECTIVES The purpose of this pilot study was to assess the feasibility of BSM Delta map as a tool to detect TRMI using dobutamine stress ECG gated single-photon emission computed tomography myocardial perfusion imaging (MPI) as a reference. METHOD Forty consecutive patients were recruited who were referred for MPI with a history of angina-like symptoms. The BSM Delta map was derived from two 80-electrode body surface mapping system recordings carried out simultaneously with MPI at (a) baseline and (b) peak dobutamine stress. Standard 12-lead ECGs were also recorded at the same time points. RESULTS The mean patient age was 68±7.1years, and 52% (21/40) were female. Using MPI as the reference the sensitivity of BSM Delta map was 82% (9/11) and specificity was 86% (25/29) (95% CI 0.688-0.992), positive likelihood ratio 5.93 (95% CI 2.29-15), negative likelihood ratio 0.21 (95% CI 0.06-0.75). The sensitive of the 12-lead ECG was 36% (4/11) and specificity was 76% (22/29) (95% CI 0.356-0.767), positive likelihood ratio 1.51 (95% CI 0.55-4.15), negative likelihood ratio 0.84 (95% CI 0.51-1.37). BSM Delta map is more sensitive and specific (McNemars chi-square test p=0.03 (95% CI, 0.448-0.924). The PPV and NPV for BSM Delta map were 69% (9/13) and 93% (25/27) respectively, compared with 36% (4/11) and 76% (22/29) for 12-lead ECG. CONCLUSION This pilot study confirms the feasibility of using Delta map in this context and suggests that it has promising diagnostic accuracy and is superior to the 12-lead ECG. It could potentially represent a clinically suitable screening tool for TRMI in patients presenting with stable chest pain, since it is near patient and requires little specialist training for acquisition and interpretation. A larger clinical study is now required.

NICE recommendations for the management of hyperglycaemia in acute coronary syndrome

It is well established that hyperglycaemia is common in patients admitted to the hospital with acute coronary syndrome (ACS), and is an an independent risk factor for adverse outcome.1 ,2 A significant proportion of these patients with ACS and hyperglycaemia will not previously have been diagnosed with diabetes mellitus, and not all of them will automatically turn out to be diabetic in the long term.2 It is therefore unsurprising that a number of studies have tried to evaluate the best way to manage hyperglycaemia in ACS.3–6 However, the results have been mixed, contradictory on occasion, and even identified for potential for harm. The waters are muddied further by significant heterogeneity between studies across important factors, such as: the patient populations studied (eg, hyperglycaemic ACS patients,3 versus intensive insulin therapy in unselected ACS patients with or without hyperglycaemia6); and the nature and efficacy of intensive insulin therapy under evaluation (eg, the patients treated with an intensive insulin regimen in DIGAMI-2 did not achieve as good a glycaemic control as intended4). There is a correspondingly wide variation in practice, and it is for this reason that NICE was asked to evaluate the evidence and produce a clinical guideline to guide contemporary practice in this area in England and Wales.7 The guideline was produced in accordance with NICEs short clinical guideline process using the methodology set out in the NICE Guideline Manual (2009).8 For those without experience of developing NICE guidance, a brief review of this process may help in understanding not only how NICE produces its recommendations, but also why they are drafted the way they are, particularly if the guidance may be considered controversial. The guideline topic is referred to NICE by the Department of Health. National organisations representing patients and carers, …

Screening for Atrial Fibrillation Using Economical and Accurate Technology (From the SAFETY Study)

The prevalence of atrial fibrillation (AF) is estimated at more than 3% in the adult population and there has been increased interest in screening for AF. In the SAFETY trial we chose to evaluate if inexpensive, wearable, consumer electrocardiography (ECG) sensing devices (Polar-H7 [PH7] and Firstbeat Bodyguard 2 [BG2]), could be used to detect AF accurately. We undertook a case-control study of 418 participants aged >65 (82 with AF and/or flutter at the study visit and 336 without) attending 3 general practice surgeries in Hampshire, UK for a single screening visit. The PH7 and BG2 devices were tested alongside 2 established AF detection devices (AliveCor and WatchBP) in random order and the diagnosis of AF was confirmed by 12-Lead ECG interpreted by a panel of cardiologists. The sensitivity (95% confidence interval [CI] range), specificity (95% CI range), and overall accuracy (95% CI range) of the 4 devices were: AliveCor: 87.8% (78.7% to 94.0%), 98.8% (97.0% to 99.7%), 96.7% (94.4% to 98.2%); WatchBP: 96.3% (89.7% to 99.2%), 93.5% (90.3% to 95.9%), 94.0% (91.3% to 96.1%): PH7: 96.3% (89.7% to 99.2%), 98.2% (96.2% to 99.3%), 97.9% (96.0% to 99.0%). BG2: 96.3% (89.7% to 99.2%), 98.5% (96.6% to 99.5%), 98.1% (96.3% to 99.2%). The PH7 and BG2 devices were highly reliable (the devices acquired sufficient data and obtained a diagnostic result in all but 1 participant on the first attempt). In conclusion, inexpensive, consumer heart rate monitoring devices (PH7 and BG2) can be used to detect AF accurately with sensitivity and specificity >95%. The consumer devices performed as well or better than WatchBP and AliveCor and have the capability to store or transmit ECG data which could be used to confirm AF.

20 What happens to platelet function and vascular inflammation when clopidogrel is withdrawn? Insights using short thrombelastography

Introduction A clustering of adverse events, in particular stent thrombosis (ST) has been observed following clopidogrel cessation 1-year after drug-eluting stenting (DES), the aetiology of which is poorly understood. We investigated the effect of withdrawing clopidogrel in DES patients using a simple, rapid, reproducible near-patient platelet function test known as short Thrombelastography (s-TEG) that has been developed and validated by this group. Methods 33 patients on aspirin and due to stop clopidogrel at 1 year following DES were investigated. Venesection was performed at (i) 4 weeks and 24 h pre clopidogrel cessation (ii) 24 h, 48 h, 1, 2 and 4 weeks post clopidogrel cessation. At all time-points, platelet reactivity was determined using s-TEG and thromboxane (TX) B2, IL-6, CD40 ligand and high sensitivity CRP were measured. Results Clopidogrel cessation produced (i) a predictable increase in ADP-induced platelet aggregation, and (ii) an unexpected and significant rise in AA-induced platelet aggregation. TXB2 was consistently suppressed confirming inhibition of COX by aspirin.Abstract 20 Figure 1 Conclusion We have described for the first time an aspirin-independent increase in AA-induced clotting following clopidogrel withdrawal in DES patients. As well as potentially helping to explain the observed clustering of ST events early after clopidogrel withdrawal, these findings raise the question as to whether AA-induced clotting is an appropriate test of aspirin sensitivity. Our results also confirm s-TEG as a plausible candidate for near-patient platelet function testing in this field.