Determinants of excess mortality following unprotected left main stem percutaneous coronary intervention.

OBJECTIVE: For percutaneous coronary intervention (PCI) to the unprotected left main stem (UPLMS), there are limited long-term outcome data. We evaluated 5-year survival for UPLMS PCI cases taking into account background population mortality. METHODS: A population-based registry of 10 682 cases of chronic stable angina (CSA), non-ST-segment elevation acute coronary syndrome (NSTEACS), ST-segment elevation myocardial infarction with (STEMI+CS) and without cardiogenic shock (STEMI-CS) who received UPLMS PCI from 2005 to 2014 were matched by age, sex, year of procedure and country to death data for the UK populace of 56.6 million people. Relative survival and excess mortality were estimated. RESULTS: Over 26 105 person-years follow-up, crude 5-year relative survival was 93.8% for CSA, 73.1% for NSTEACS, 77.5% for STEMI-CS and 28.5% for STEMI+CS. The strongest predictor of excess mortality among CSA was renal failure (EMRR 6.73, 95% CI 4.06 to 11.15), and for NSTEACS and STEMI-CS was preprocedural ventilation (6.25, 5.05 to 7.75 and 6.92, 4.25 to 11.26, respectively). For STEMI+CS, the strongest predictor of excess mortality was preprocedural thrombolysis in myocardial infarction (TIMI) 0 flow (2.78, 1.87 to 4.13), whereas multivessel PCI was associated with improved survival (0.74, 0.61 to 0.90). CONCLUSIONS: Long-term survival following UPLMS PCI for CSA was high, approached that of the background populace and was significantly predicted by co-morbidity. For NSTEACS and STEMI-CS, the requirement for preprocedural ventilation was the strongest determinant of excess mortality. By contrast, among STEMI+CS, in whom survival was poor, the strongest determinant was preprocedural TIMI flow. Future cardiovascular cohort studies of long-term mortality should consider the impact of non-cardiovascular deaths.

Does the response to aspirin and clopidogrel vary over 6 months in patients with ischemic heart disease?

BACKGROUND: Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor, mostly clopidogrel, is the default therapy in both acute coronary syndrome (ACS) and after intracoronary stents. It is well established that responses to antiplatelet therapy (APT), particularly clopidogrel, are subject to considerable interindividual variability. OBJECTIVES: We investigated whether responses to APT in individuals vary significantly over time. METHODS: Simultaneous assay with VerifyNow(™) and short thrombelastography (s-TEG) was performed before and at four time points over 6 months after hospital discharge in 40 patients receiving DAPT. Serum thromboxane B2 levels were also measured. RESULTS: While aspirin response units (ARU) by VerifyNow(™) and serum thromboxane B2 levels remained stable over time, arachidonic acid (AA)-mediated platelet aggregation with s-TEG (i.e. area under the curve at 15 min in AA channel, AUC15AA ) increased at 1 week compared with predischarge (P < 0.008). In addition, platelet reactivity units (PRU) by VerifyNow(™) (P = 0.046) and adenosine diphosphate (ADP)-mediated platelet aggregation with s-TEG (i.e. AUC15ADP ) also increased at 1 week compared with predischarge (P = 0.026). There were no significant changes in either platelet reactivity or rates of high on-treatment platelet reactivity while receiving clopidogrel beyond 1 week. CONCLUSIONS: This study demonstrates important variability in responses to APT within individuals between predischarge and 1 week but not thereafter. The use of a single early (predischarge) platelet function assay as an indicator of future response may therefore be flawed. The design of future strategies to assess individual responses for tailored therapy needs to take this into account.

Transapical perfusion for peri-arrest salvage during transcutaneous aortic valve implantation.

An 80-year-old man developed severe haemodynamic instability during a transapical aortic valve implantation. He was not suitable for a conventional surgical approach due to comorbidities and patent aortocoronary bypass grafts also limited further stabilizing actions. As a bail-out procedure, we demonstrate the feasibility of transapical arterial cannulation by crossing a newly implanted TAVI valve in order to establish an emergency bypass circuit.

Troponin-positive chest pain with unobstructed coronary arteries: definitive differential diagnosis using cardiac MRI.

OBJECTIVE: The purpose of this study was to assess the outcome of cardiac MRI (CMRI) with late gadolinium enhancement (LGE) at outpatient follow-up in a consecutive series of patients with troponin-positive chest pain but unobstructed coronary arteries at the index admission. METHODS: The study group comprised 91 consecutive patients who presented to our institution with cardiac chest pain, elevated troponin I and unobstructed coronary arteries on coronary angiography. All patients underwent an outpatient CMRI with LGE imaging in order to establish a definitive diagnosis. RESULTS: The average time from coronary angiography to LGE-CMRI was 2 months. 73% of patients had no abnormality on their LGE-CMRI, 16% of patients had patchy late enhancement consistent with myocarditis and 11% had focal subendocardial or full thickness late enhancement consistent with myocardial infarction. There were no deaths in this cohort during a mean follow-up of 21 months. CONCLUSION: LGE-CMRI is a useful tool for establishing whether such patients have definitive evidence of non-ST-segment elevation myocardial infarction (NSTEMI), and can make an important contribution to the long-term management strategy of these patients as an inappropriate diagnosis of NSTEMI carries important medical, social and financial implications.

Individualised assessment of response to clopidogrel in patients presenting with acute coronary syndromes: a role for short thrombelastography?

INTRODUCTION: There is considerable interindividual variation in response to the antiplatelet agent clopidogrel. Hyporesponse predicts negative outcomes in patients presenting with a variety of ischemic cardiac conditions and following intracoronary stent placement. Many tests of clopidogrel activity are time consuming and complex. Short thromboelastography (s-TEG) allows rapid measurement of platelet clopidogrel response. AIMS: We initiated this study to investigate the utility of s-TEG in assessing the response to clopidogrel in patients presenting with acute coronary syndromes (ACS) and to compare these results with established clopidogrel monitoring techniques. METHODS: Patients admitted with unstable angina (UA) or Non ST elevation myocardial infarction (NSTEMI) undergoing coronary angiography were recruited. After routine loading with clopidogrel, all patients were tested with s-TEG and Accumetrics Verify-Now rapid platelet function analyzer (VN-RPFA). We used the modified TEG technique of measuring area under the curve at 15 min (AUC15), which allows a rapid estimation of antiplatelet response. Vasodilator-stimulated phosphoprotein phosphorylation (VASP) was also tested in a subgroup of patients. Clinical follow-up was obtained at 1 year. s-TEG results were correlated with VN-RPFA and VASP findings. RESULTS: A total of 49 patients (33 male, mean age 63) were recruited and tested with s-TEG and VN-RPFA and a total of 39 patients were also assessed with VASP. s-TEG readings correlated well with VN-RPFA (r(2)= 0.54, P < 0.0001) and VASP (r(2)= 0.26, P= 0.001). CONCLUSION: s-TEG provides timely results which compare to current tests of clopidogrel activity. This technique can also be used to measure a variety of other clotting parameters and as such could develop into a valuable near patient test for the interventional cardiologist.

Is there evidence for prognostic benefit following PCI in stable patients? COURAGE and its implications: an interventionalist's view.

The COURAGE study has stimulated intensive discussion about the optimal approach to treatment of patients with stable angina. To some, the study implied that PCI has no clinical benefit versus optimal medical therapy but this is open to alternative considered interpretation. To the interventionalist who deploys optimal medical therapy responsibly, the study highlights the importance of the concept of an ischaemia driven approach. The availability of the pressure wire has provided cardiologists with an important additional tool with which to tailor the delivery of revascularisation to not just the ischaemic patient but also to the ischaemic lesion. Such a strategy applied to COURAGE (and perhaps also to SYNTAX) might provide a very different comparative outcome.

Coronary spasm induced by capecitabine mimicks ST elevation myocardial infarction.

Capecitabine is a chemotherapeutic prodrug that is metabolised to 5-fluorouracil. Supported by the National Institute for Health and Clinical Excellence guidance it is now first-line adjuvant treatment for metastatic colorectal cancer in the UK. Although cardiac chest pain and myocardial ischaemia are well recognised side effects of 5-fluorouracil, their association with capecitabine is not widely appreciated. Two cases are described of coronary spasm secondary to capecitabine in patients referred for emergency invasive treatment of presumed ST elevation myocardial infarction (STEMI). The contemporary treatment of acute coronary syndromes involves aggressive antiplatelet therapy, anticoagulation and cardiac catheterisation. This treatment, although beneficial in most patients, is associated with a small but significant risk of bleeding complications. A wider appreciation of the potential for capecitabine to induce spasm mimicking STEMI is important in order to reduce the risk of the administration of thrombolytics and other potentially dangerous drugs and have a higher threshold for referral for emergency angiography.

Antiplatelet effects of licking an aspirin tablet can be detected by thrombelastography.

Aspirin is a cornerstone of treatment in cardiovascular disease. However, individual responses vary and hyporesponsiveness has been associated with poor outcomes following percutaneous intervention. Point of care assays for detecting the effects of aspirin in individual patients would therefore be useful. Thrombelastography has been shown to correlate with optical aggregation in the assessment of antiplatelet therapies and is suitable for use as a point of care assay. We demonstrate the ability of thrombelastography to detect the profound effects of even the tiny doses of aspirin obtained by licking an aspirin tablet.

Atherogenesis: the role of inflammation and infection.

Atherosclerosis is no longer considered a disorder of lipid accumulation, but a disease process characterized by the dynamic interaction between endothelial dysfunction, subendothelial inflammation and the 'wound healing response' of the vascular smooth muscle cells. Prospective epidemiological studies have unequivocally demonstrated increased vascular risk in individuals with elevated levels of (i) cytokines such as interleukin-6 and tumour necrosis factor-alpha, (ii) cell adhesion molecules such as intercellular adhesion molecule-1 and P-selectin, and (iii) acute-phase proteins such as C-reactive protein, fibrinogen and serum amyloid A. Furthermore, evidence from clinical trials have demonstrated that risk reduction achieved with anti-inflammatory agents such as statins is significantly greater in patients with evidence of inflammation. A number of risk factors for atherogenesis, including infectious agents, have been shown to exert their influence via inflammatory mechanisms. However, despite compelling experimental evidence, clinical studies looking at the role of infection in atherogenesis have lacked consistency. The clinical product of this dynamic process is variable and unpredictable between individuals, even those with apparently similar risk profiles.

Thrombelastography: current clinical applications and its potential role in interventional cardiology.

Thrombelastography is a bedside blood test used to assess patients' haemostatic status. It has a well-established role in hepatobiliary and cardiac surgery and is also used in obstetrics and trauma medicine to assess coagulation and identify the causes of post-operative bleeding. It is not routinely used in the diagnosis or treatment of thrombosis although recently it has been shown to predict thrombotic events post-operatively and after percutaneous intervention (PCI). In cardiovascular medicine the importance of the platelet in the pathophysiology of vascular events is increasingly apparent. As a result antiplatelet therapy is a cornerstone of the treatment for coronary disease, particularly in the setting of acute coronary syndromes. The increasing utilization of stents, particularly drug-eluting devices, in PCI has also necessitated widespread use of antiplatelet agents to minimize the risk of stent thrombosis. A quick, accurate and reliable test to measure the effect of platelet inhibition by antiplatelet agents on clotting in an individual patient would be of profound clinical value. The results from such a test could provide prognostic information, allow treatment with antiplatelet agents to be tailored to the individual and identify resistance to one or more of these agents. Optimization and tailoring of anti-platelet therapy in patients with cardiovascular disease, particularly those undergoing PCI, using such a test may reduce morbidity and mortality from thrombotic and haemorrhagic complications. Current methods of assessing platelet activity measure platelet count and function in isolation. Optical aggregation is the most widely used method for assessing platelet function but it is relatively time consuming, measures platelet function in isolation rather than in the context of clot formation and is not a bedside test. By contrast the modified thrombelastograph platelet mapping kit marketed by Haemoscope can be used to assess the effects of antiplatelet agents on ex vivo blood clotting, thus giving a measurement more relevant to in vivo responses. This represents a potentially powerful tool to assess response of individual patients to antiplatelet therapy, particularly in the context of PCI.

Thromboelastography: potential bedside tool to assess the effects of antiplatelet therapy?

Modified thrombelastography (TEG) is a simple point of care test that provides an overall assessment of ex vivo clot formation and currently has limited clinical application. We evaluated the ability of TEG to assess the effects of antiplatelet therapy on clot formation using a novel assessment parameter (the area under curve). Forty healthy volunteers were divided into four groups of 10. Group A took aspirin 75 mg once daily for 7 days followed by aspirin 75 mg and clopidogrel 75 mg once daily in combination for 7 more days. Blood samples were taken for analysis at day 0 and days 7 and 14. Group B took a single 300 mg dose of aspirin. Group C took 600 mg of clopidogrel only. Group D took 300 mg of aspirin and 600 mg of clopidogrel at the same time. For groups B, C and D blood was taken prior to drug administration and at 2, 6 and 24 h afterwards. Each sample was tested by TEG in four channels following activation using (1) kaolin, (2) activator F (Act F), a direct activator of fibrin, (3) Act F + arachidonic acid (AA) and (4) Act F + adenosine diphosphate (ADP). Parameters measured included the maximum amplitude (MA) of the clot and the area under the TEG-generated curve at 1 h. Significant, time-dependent reductions in MA and area were seen in the AA-activated samples following administration of aspirin in all groups as compared to baseline. By contrast, there were no significant differences in MA or area in the AA-activated samples with clopidogrel alone. Significant reductions were also seen in MA and area in ADP-activated samples from volunteers treated with clopidogrel as compared to baseline. Three out of 10 subjects receiving 600 mg clopidogrel had a reduction in their responses of 30% or less, thus identifying them as relatively resistant to the drug. This study identifies a rapid, reliable method for assessing the time-dependent effects of antiplatelet therapy on clotting using a novel parameter of area of the TEG trace, which could have an important clinical application as a point of care test of efficacy, particularly in the context of acute coronary syndromes and percutaneous coronary intervention.

Reducing transfer times for coronary angiography in patients with acute coronary syndromes: one solution to a national problem.

BACKGROUND: Patients with acute coronary syndrome (ACS) are at high risk of further cardiac events and benefit from early intervention, as reflected by international guidelines recommending early transfer to interventional centres. The current average waiting time of up to 21 days contravenes evidence based early intervention, creates geographical inequity of access, wastes bed days, and is unsatisfactory for patients. METHODS: A regional transfer unit (RTU) was created to expatriate access of ACS patients referred from other centres to the revascularisation service. By redesigning the care pathway patients arriving on the RTU undergo angiography within 24 hours, and then leave the RTU the following day, allowing other ACS patients to be treated. RESULTS: During the first six months of the RTU, the mean waiting time from referral to procedure decreased from 20 (SD 15) days (range 0-51) to 8 (SD 3) days (range 0-21) for 365 patients transferred from a district general hospital. Ninety seven per cent of patients underwent angiography within 24 hours, 61% having undergone percutaneous coronary intervention at the same sitting, and 78% were discharged home within 24 hours. CONCLUSIONS: Delivering standards laid out in the National Service Framework, reducing inequalities of care across the region, and facilitating evidence based strategies of care represents a challenging and complex issue. For high risk patients suffering ACS who need early invasive investigation, a coordinated network wide approach together with the creation of an RTU resulted in a 62% reduction in waiting times for no extra resources. Further improvements can be expected through increased capacity of this verified strategy.

The limitations of coronary angiography: identification of a critical coronary stenosis using intravascular ultrasound.

Coronary angiography is considered the gold standard method of imaging coronary stenoses. Quantitative coronary angiography (QCA) has helped to provide information about the degree of stenosis which is used as a surrogate to indicate impaired flow in a coronary bed. QCA however can underestimate disease severity. In this case intravascular ultrasound identifies a critical coronary stenosis not seen on angiography.

What is the role for revascularisation in patients being considered for ICD therapy?

Patients being considered for ICD therapy are a heterogeneous group.For the vast majority, who have significant left ventricular impairment, it has become common practice to assess their coronary artery anatomy as a surrogate for ischaemia and/or viability. Such patients are therefore frequently under the care of both electrophysiologists and interventionists. The coronary anatomy often raises the dilemma about whether such patients should undergo revascularisation. If the patients present with angina or in the context of an acute myocardial infarct then this decision is clear cut. By contrast, however, a significant proportion of them have no history to suggest ongoing ischaemia or of recent MI. In conventional practice, therefore, there would be no decisive mandate to offer them revascularisation, especially PCI, in the absence of further objective evidence of ischaemia or viability. A review of the literature in our paper does not resolve this dilemma.Further observational data are required to help guide cardiologists as to which of these patients will benefit from revascularisation, since in many cases the coronary anatomy is no surrogate for the presence of ischaemia or viability.

Patients undergoing coronary revascularisation: a missed opportunity for secondary prevention?

BACKGROUND: This study tested the hypothesis that the opportunity to start secondary prevention therapy before discharge after coronary revascularisation is being missed. The study assessed current prescribing practice and identified discrepancies in prescribing for patients managed by surgeons (especially) and cardiologists. METHODS: 200 consecutive patients from the Manchester Heart Centre percutaneous coronary intervention (PCI) and coronary artery bypass (CABG) registries were identified (100 from each registry) and the notes analysed. All had undergone coronary revascularisation from February 2002 to March 2002. Data were analysed using SPSS for Windows, version 10.1. RESULTS: After exclusion of two patients with contraindications, 100% (98 of 98) of PCI patients and 92% (90 of 98) CABG patients were prescribed aspirin at discharge. Eight two per cent of eligible PCI patients and 70% of eligible CABG patients were prescribed beta blockers at discharge. Ninety six per cent (96 of 100) of PCI patients and 73% (73 of 100) of CABG patients were prescribed statins of any dose at discharge, (p<0.001). Sixty five per cent of PCI but only 26% of CABG patients were discharged prescribed ACE inhibitors (eligible patients based on HOPE, heart outcomes prevention evaluation trial), (p<0.001). CONCLUSIONS: Secondary prevention prescription after coronary revascularisation remains suboptimal in all but aspirin use. Patients in the PCI group were statistically more likely to be discharged prescribed a statin or an ACE inhibitor, or both, than patients after CABG. Both interventional cardiologists and (especially) cardiac surgeons must improve their use of secondary prevention therapy.