Huon Gray

Guidelines on the management of stable angina pectoris: executive summary

We thank the authors for raising the interesting discussion regarding the treatment of hypertension in patients with concomitant coronary disease. The J-shaped association between on-treatment blood pressure and risk has been described in longitudinal cohorts of patients with treated hypertension as well as in clinical trial populations, both in on-treatment and control arms. However, it is not absolutely clear that the association is treatmentrelated; in fact, one meta-analysis of seven randomized controlled trials including data on more than 40 000 patients has shown that the J-shaped relationship between blood pressure and mortality was not related to antihypertensive treatment. In this meta-analysis, noncardiovascular death was inversely related to blood pressure (both systolic and diastolic) in contrast to the J-shaped relationships for cardiovascular and total mortality, leading the authors to hypothesize that poor health conditions leading to low blood pressure and an increased risk of death might in part explain the J-shaped curve. Secondly, as discussed in the full-text version of the guidelines, there is accumulating evidence that blood pressure lowering in the ‘normal’ range is associated with improved cardiovascular outcomes in the population with known coronary disease. In the CAMELOT study, patients with coronary disease and mean blood pressure of 129/78 were randomized to enalapril, amlodipine, or placebo. Blood pressure reductions were similar (5/2 mm) in both treatment groups and associated with similar relative reductions in the composite endpoint of cardiovascular death, MI, and stroke, although not statistically significant in either group because of the small sample size. An intravascular ultrasound substudy demonstrated a significant inverse correlation between progression of atherosclerosis and blood pressure reduction even in this normal blood pressure range, with the greatest benefit observed in patients whose blood pressure fell below 120/80. Thus, the task force has felt it important, in the absence of unequivocal evidence to the contrary, to preserve consistency between guidelines on prevention and angina with regard to targets for institution of therapy for hypertension in the presence of coronary disease. No lower limit has yet been identified as a definite cutoff beyond which blood pressure should not be lowered further, although, clearly, symptomatic hypotension or postural hypotension will limit aggressive blood pressure lowering in the lower range.

Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: the U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry.

OBJECTIVES The objective was to define the characteristics of a real-world patient population treated with transcatheter aortic valve implantation (TAVI), regardless of technology or access route, and to evaluate their clinical outcome over the mid to long term. BACKGROUND Although a substantial body of data exists in relation to early clinical outcomes after TAVI, there are few data on outcomes beyond 1 year in any notable number of patients. METHODS The U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry was established to report outcomes of all TAVI procedures performed within the United Kingdom. Data were collected prospectively on 870 patients undergoing 877 TAVI procedures up until December 31, 2009. Mortality tracking was achieved in 100% of patients with mortality status reported as of December 2010. RESULTS Survival at 30 days was 92.9%, and it was 78.6% and 73.7% at 1 year and 2 years, respectively. There was a marked attrition in survival between 30 days and 1 year. In a univariate model, survival was significantly adversely affected by renal dysfunction, the presence of coronary artery disease, and a nontransfemoral approach; whereas left ventricular function (ejection fraction <30%), the presence of moderate/severe aortic regurgitation, and chronic obstructive pulmonary disease remained the only independent predictors of mortality in the multivariate model. CONCLUSIONS Midterm to long-term survival after TAVI was encouraging in this high-risk patient population, although a substantial proportion of patients died within the first year.

Transcatheter Aortic Valve Implantation in the United Kingdom Temporal Trends, Predictors of Outcome, and 6-Year Follow-Up: A Report From the UK Transcatheter Aortic Valve Implantation (TAVI) Registry, 2007 to 2012

Background— We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality. Methods and Results— Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007–2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 μmol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P <0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome. Conclusions— We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors. # CLINICAL PERSPECTIVE {#article-title-29}Background— We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality. Methods and Results— Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007–2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 &mgr;mol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P<0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome. Conclusions— We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors.

Pulmonary embolectomy for acute massive pulmonary embolism: an analysis of 71 cases.

Between 1964 and 1986 a total of 71 pulmonary embolectomies were performed for acute massive pulmonary embolism. All patients were severely compromised haemodynamically. Sixteen (64%) of 25 patients who had sustained significant periods of cardiac arrest before operation died. The principal cause of death in this group was severe neurological damage. Five (11%) of the 46 who had not had a cardiac arrest died. The 50 (70%) patients who survived did so largely without morbidity during their hospital admission and in the follow up period. Most were not treated with long term anticoagulants and only two had another embolism. When a patient with acute massive pulmonary embolism is too ill to be given thrombolytic treatment, or when thrombolysis is either contraindicated or too slow in producing benefit, pulmonary embolectomy remains an effective alternative treatment with an acceptable mortality.

Public access defibrillation remains out of reach for most victims of out-of-hospital sudden cardiac arrest

Introduction Public access defibrillation (PAD) prior to ambulance arrival is a key determinant of survival from out-of-hospital (OOH) cardiac arrest. Implementation of PAD has been underway in the UK for the past 12 years, and its importance in strengthening the chain of survival has been recognised in the governments recent ‘Cardiovascular Disease Outcomes Strategy’. The extent of use of PAD in OOH cardiac arrests in the UK is unknown. We surveyed all OOH cardiac arrests in Hampshire over a 12-month period to ascertain the availability and effective use of PAD. Methods A retrospective review of all patients with OOH cardiac arrest attended by South Central Ambulance Service (SCAS) in Hampshire during a 1-year period (1 September 2011 to 31 August 2012) was undertaken. Emergency calls were reviewed to establish the known presence of a PAD. Additionally, a review of all known PAD locations in Hampshire was undertaken, together with a survey of public areas where a PAD may be expected to be located. Results The current population of Hampshire is estimated to be 1.76 million. During the study period, 673 known PADs were located in 278 Hampshire locations. Of all calls confirmed as cardiac arrest (n=1035), the caller reported access to an automated external defibrillator (AED) on 44 occasions (4.25%), successfully retrieving and using the AED before arrival of the ambulance on only 18 occasions (1.74%). Conclusions Despite several campaigns to raise public awareness and make PADs more available, many public areas have no recorded AED available, and in those where an AED was available it was only used in a minority of cases by members of the public before arrival of the ambulance. Overall, a PAD was only deployed successfully in 1.74% OOH cardiac arrests. This weak link in the chain of survival contributes to the poor survival rate from OOH cardiac arrest and needs strengthening.

Percutaneous coronary intervention: recommendations for good practice and training

EXECUTIVE SUMMARY: Cardiologists undertaking percutaneous coronary intervention (PCI) are excited by the combination of patient and physician satisfaction and technological advance occurring on the background of the necessary manual dexterity. Progress and applicability of percutaneous techniques since their inception in 1977 have been remarkable; a sound evidence base coupled with the enthusiasm and ingenuity of the medical device industry has resulted in a sea change in the treatment of coronary heart disease (CHD), which continues to evolve at breakneck speed. This is the third set of guidelines produced by the British Cardiovascular Intervention Society and the British Cardiac Society.1,2 Following the last set of guidelines published in 2000, we have seen PCI activity in the UK increase from 33 652 to 62 780 (87% in four years) such that the PCI to coronary artery bypass grafting ratio has increased to 2.5:1. The impact of drug eluting stents has been profound, and the Department of Health is investigating the feasibility of primary PCI for acute myocardial infarction. Nevertheless, the changes in the structure of National Health Service funding are likely to focus our attention on cost effective treatments and will require physician engagement and sensitive handling if we are to continue the rapid and appropriate growth in our chosen field.3 It is important with this burgeoning development now occurring on a broad front (in both regional centres and district general hospitals) that we maintain our vigilance on audit and outcome measures so that standards are maintained for both operators and institutions alike. This set of guidelines includes new sections on training, informed consent, and a core evidence base, which we hope you will find useful and informative. Keith D Dawkins: President, British Cardiovascular Intervention Society (2000–2004) Huon H Gray: President, British Cardiac Society (2003–2005)

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.

Early management of unstable angina and non-ST-segment elevation myocardial infarction: summary of NICE guidance

Acute coronary syndromes are due to rupture or erosion of an atherosclerotic coronary artery plaque with superimposed platelet aggregation and coronary thrombosis. Complete thrombotic occlusion of a coronary artery generally causes acute ST-elevation myocardial infarction (STEMI), whereas incomplete occlusion will usually cause some myocardial necrosis (as shown by a rise in a cardiac-specific serum biomarker such as troponin) and is termed ‘non-ST elevation myocardial infarction’ (NSTEMI). When myocardial ischaemia is present without evidence of myocardial necrosis the clinical syndrome is described as unstable angina (UA). Hospital Episodes Statistics data for England suggest that there may be as many as 100 000–150 000 admissions with UA or NSTEMI per year (Green S, Personal communication, 2010). Although very early mortality (first few days) is lower for NSTEMI than for STEMI, over a longer period (6 months) their risk of death is comparable.1 The recently published NICE clinical guideline on the early management of UA and NSTEMI (CG94) examines selected aspects of in-hospital management, including risk assessment and its impact on patient management, antiplatelet and antithrombin therapy, the role of coronary angiography, revascularisation and intra-aortic balloon counterpulsation, testing for myocardial ischaemia and left ventricular function, specialist versus non-specialist care, rehabilitation and discharge planning. Detailed discussion of the evidence for the guideline can be found in the full version (http://guidance.nice.org.uk/CG94/Guidance/pdf/English, accessed August 2010), and this article summarises the most important conclusions. CG94 assumes that a firm diagnosis of UA or NSTEMI has already been established, and the differentiation of cardiac from non-cardiac chest pain is dealt with in separate NICE guidance (http://guidance.nice.org.uk/CG95/Guidance/pdf/English, accessed August 2010). An appreciation of an individuals risk of an adverse outcome following UA or NSTEMI is important when assessing which treatment strategies are most appropriate. For instance, antithrombotic agents may reduce further ischaemic events, but increase bleeding complications, and this …

Engaging with the clinical data transparency initiative: a view from the National Institute for Cardiovascular Outcomes Research (NICOR)

The availability of centrally analysed, comprehensive outcome data from cardiovascular audits has underpinned the success of the National Service Framework (NSF) for coronary heart disease1 in achieving a substantial reduction in morbidity and mortality from cardiovascular (CV) disease in the UK.2 The UK Government is now intending to implement ‘transparency initiatives’ within the National Health Service (NHS)—reporting outcomes for General Practice, hospital complaints and satisfaction surveys and healthcare team performance.3 Routine (‘raw’) clinical data will be made publicly and commercially available, so that independent parties will have open access to anonymised data relating to all recorded components contributing to the quality of CV care. The coalition Government has promised ‘an openness about results that we have never experienced before’, in an attempt to ‘reform public services, foster innovation and empower citizens’.3 While there is likely to be little opposition to policies aimed at improving quality of care for patients with CV disease, strategies for managing national clinical data present a number of challenges if they are to impact on the drive towards further reducing the burden from CV disease in the UK. The National Institute for Cardiovascular Outcomes Research (NICOR) runs a programme that engages with aspects of the Governments agenda. It addresses the particular challenges of managing large complex clinical datasets, while minimising any unintended consequences of releasing raw data into the public domain. NICOR is an umbrella organisation for a number of national registries created by professional CV societies. It is based at University College London (UCL), importantly offering linkage of national cardiovascular databases and the potential for increased international comparative data analysis. Established by Professor Sir Bruce Keogh, in 2006, it is currently led by Professors Sir Roger Boyle and John Deanfield, …