Stratified medicine using invasive coronary function testing in angina: A cost-effectiveness analysis of the British Heart Foundation CorMicA trial.

AIM: Coronary angiography is indicated in many patients with known or suspected angina for the investigation of coronary artery disease (CAD). However, up to half of patients with symptoms of ischaemia have no obstructive coronary arteries (INOCA). This large subgroup includes patients with suspected microvascular angina (MVA) and/or vasospastic angina (VSA). Clinical guidelines relating to the management of patients with INOCA are limited. Uncertainty regarding the diagnosis of patients with INOCA presents a health economic challenge, both in terms of healthcare resource utilisation and of quality-of-life impact on patients. METHODS: A cost-effectiveness analysis of the introduction of stratified medicine into the invasive management of INOCA, based on clinical and resource-use data obtained in the CorMicA trial, from a UK NHS perspective. The intervention included an invasive diagnostic procedure (IDP) of coronary vascular function during coronary angiography to define clinical endotypes to target with linked medical therapy. Outcomes of interest were mean total cost and QALY gain between treatment groups, and the incremental cost-effectiveness ratio. We undertook probabilistic sensitivity and scenario analyses. RESULTS: The incremental cost per QALY gained at 12 months was £4500 (£2937, £33264). Compared with a willingness-to-pay (WTP) threshold of £20,000 per QALY, the use of the IDP test is cost-effective. At this WTP threshold there is a 96% probability of the IDP being cost-effective, based on the uncertainty described by bootstrap analysis. CONCLUSIONS: The burden of INOCA, particularly in women, is known to be significant. These findings provided new evidence to inform this unmet clinical need.

Treating the troponin: adverse consequences of over-treatment of elevated troponin in non-coronary presentations.

BACKGROUND AND AIMS: Anti-platelet and anti-thrombotic therapy are well-established treatments in acute coronary syndromes. Highly sensitive assays have diminished the positive predictive value of troponin in acute coronary syndromes and increased the importance of the clinical assessment in interpreting positive results. This cohort study sought to investigate over-treatment of non-coronary troponin rises and associated adverse outcomes. METHODS AND RESULTS: We reviewed 223 consecutive patients presenting to Queen Elizabeth University Hospital, Glasgow, with suspected acute coronary syndromes over a six-week period. Of these, 27 (12%) met our 'inappropriate therapy' criteria. This group had a low ischaemic risk (HEART score: 4.2 ± 1.4) (GRACE score: 117 ± 30.8) but an intermediate-high bleeding risk (CRUSADE score: 34 ± 14.5). Approximately half of the patients (14/27, 52%) reported chest pain, with only 4/27 (15%) having ischaemic ECG changes. There were three intracranial haemorrhages, each after the patient had received a single dose of aspirin, ticagrelor and fondaparinux. CONCLUSION: The combination of injudicious high-sensitivity troponin testing with potent anti-platelet and anti-thrombotic therapy was associated with possible over-treatment of patients and associated harm. Emphasis on interpretation of troponin in the context of clinical presentation and improved awareness of type 2 myocardial infarction are essential to limit iatrogenic pharmacological harm.

The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease.

BACKGROUND: Remote ischaemic preconditioning (RIPC) is a cardioprotective intervention invoking intermittent periods of ischaemia in a tissue or organ remote from the heart. The mechanisms of this effect are incompletely understood. We hypothesised that RIPC might enhance coronary vasodilatation by an endothelium-dependent mechanism. METHODS: We performed a prospective, randomised, sham-controlled, blinded clinical trial. Patients with stable coronary artery disease (CAD) undergoing elective invasive management were prospectively enrolled, and randomised to RIPC or sham (1:1) prior to angiography. Endothelial-dependent vasodilator function was assessed in a non-target coronary artery with intracoronary infusion of incremental acetylcholine doses (10-6, 10-5, 10-4mol/l). Venous blood was sampled pre- and post-RIPC or sham, and analysed for circulating markers of endothelial function. Coronary luminal diameter was assessed by quantitative coronary angiography. The primary outcome was the between-group difference in the mean percentage change in coronary luminal diameter following the maximal acetylcholine dose (Clinicaltrials.gov identifier: NCT02666235). RESULTS: 75 patients were enrolled. Following angiography, 60 patients (mean±SD age 57.5±8.5years; 80% male) were eligible and completed the protocol (n=30 RIPC, n=30 sham). The mean percentage change in coronary luminal diameter was -13.3±22.3% and -2.0±17.2% in the sham and RIPC groups respectively (difference 11.32%, 95%CI: 1.2- 21.4, p=0.032). This remained significant when age and sex were included as covariates (difference 11.01%, 95%CI: 1.01- 21.0, p=0.035). There were no between-group differences in endothelial-independent vasodilation, ECG parameters or circulating markers of endothelial function. CONCLUSIONS: RIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This endothelium-dependent mechanism may contribute to the cardioprotective effects of RIPC.

One-year outcomes after successful chronic total occlusion percutaneous coronary intervention: The impact of dissection re-entry techniques.

We aimed to determine clinical outcomes 1 year after successful chronic total occlusion (CTO) PCI and, in particular, whether use of dissection and re-entry strategies affects clinical outcomes. Hybrid approaches have increased the procedural success of CTO percutaneous coronary intervention (PCI) but longer-term outcomes are unknown, particularly in relation to dissection and re-entry techniques. Data were collected for consecutive CTO PCIs performed by hybrid-trained operators from 7 United Kingdom (UK) centres between 2012 and 2014. The primary endpoint (death, myocardial infarction, unplanned target vessel revascularization) was measured at 12 months along with angina status. One-year follow up data were available for 96% of successful cases (n = 805). In total, 85% of patients had a CCS angina class of 2-4 prior to CTO PCI. Final successful procedural strategy was antegrade wire escalation 48%; antegrade dissection and re-entry (ADR) 21%; retrograde wire escalation 5%; retrograde dissection and re-entry (RDR) 26%. Overall, 47% of CTOs were recanalized using dissection and re-entry strategies. During a mean follow up of 11.5 ± 3.8 months, the primary endpoint occurred in 8.6% (n = 69) of patients (10.3% (n = 39/375) in DART group and 7.0% (n = 30/430) in wire-based cases). The majority of patients (88%) had no or minimal angina (CCS class 0 or 1). ADR and RDR were used more frequently in more complex cases with greater disease burden, however, the only independent predictor of the primary endpoint was lesion length. CTO PCI in complex lesions using the hybrid approach is safe, effective and has a low one-year adverse event rate. The method used to recanalize arteries was not associated with adverse outcomes. © 2017 Wiley Periodicals, Inc.

Hybrid approach improves success of chronic total occlusion angioplasty.

OBJECTIVES: Treatment options for coronary chronic total occlusions (CTO) are limited, with low historical success rates from percutaneous coronary intervention (PCI). We report procedural outcomes of CTO PCI from 7 centres with dedicated CTO operators trained in hybrid approaches comprising antegrade/retrograde wire escalation (AWE/RWE) and dissection re-entry (ADR/RDR) techniques. METHODS: Clinical and procedural data were collected from consecutive unselected patients with CTO between 2012 and 2014. Lesion complexity was graded by the Multicentre CTO Registry of Japan (J-CTO) score, with ≥2 defined as complex. Success was defined as thrombolysis in myocardial infarction 3 flow with <30% residual stenosis, subclassified as at first attempt or overall. Inhospital complications and 30-day major adverse cardiovascular events (MACEs, death/myocardial infarction/unplanned target vessel revascularisation) were recorded. RESULTS: 1156 patients were included. Despite high complexity (mean J-CTO score 2.5±1.3), success rates were 79% (first attempt) and 90% (overall) with 30-day MACE of 1.6%. AWE was highly effective in less complex lesions (J-CTO ≤1 94% success vs 79% in J-CTO score ≥2). ADR/RDR was used more commonly in complex lesions (J-CTO≤1 15% vs J-CTO ≥2 56%). Need for multiple approaches during each attempt increased with lesion complexity (17% J-CTO ≤1 vs 48% J-CTO ≥2). Lesion modification ('investment procedures') at the end of unsuccessful first attempts increased the chance of subsequent success (96% vs 71%). CONCLUSIONS: Hybrid-trained operators can achieve overall success rates of 90% in real world practice with acceptable MACE. Use of dissection re-entry and investment procedures maintains high success rates in complex lesions. The hybrid approach represents a significant advance in CTO treatment.

Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions.

OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in six UK centres. METHODS: We retrospectively analysed 587 CTO procedures from six UK centres and compared success rates of operators who had received proctorship with success rates of the same operators before proctorship (pre-proctored) and operators in the same institutions who had not been proctored (non-proctored). There were 232 patients in the pre-proctored/non-proctored group and 355 patients in the post-proctored group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for each case. RESULTS: CTO PCI success was greater in the post-proctored compared with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more complex cases where JCTO≥2, the difference in success was greater (70.7% vs 49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the proportion of very difficult cases with JCTO score ≥3 increased from 15.3% (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an increase in procedural success for CTO PCI, an increase in complex CTO PCI and an increase in total CTO PCI activity. Proctoring may be a valuable way to improve access to CTO PCI and the likelihood of procedural success.

Sheffield medium for cultivation of Haemophilus ducreyi.

Our interest in the role of Haemophilus ducreyi in genital ulceration led us to examine the various media commonly used for the cultivation of the organism. We describe an improved medium for the routine isolation of H ducreyi. In comparative studies using 50 test strains originally isolated in the United Kingdom, Canada, the United States of America, and Kenya, the new medium proved superior to three standard media in requiring a shorter incubation period to first visible growth, giving larger colonies in the same period, and making possible a starch aggregation test which we have found helpful in the presumptive identification of H ducreyi from clinical material.

Pathogenic microbial flora of genital ulcers in Sheffield with particular reference to herpes simplex virus and Haemophilus ducreyi.

The pathogenic microbial flora of genital ulcers in 161 (80 men and 81 women) unselected patients was studied prospectively. In only one case was Treponema pallidum responsible whereas herpes simplex virus was considered to be the cause of 130 (80.8%) genital ulcers. H ducreyi was isolated from 46 (28.6%) patients, most commonly as a secondary pathogen in herpetic lesions. Two or more pathogens were isolated from the ulcers in 67 (41.6%) patients, and in 21 (13%) patients no pathogens were isolated. Our results indicate an urgent need for antiviral treatment to reduce the local reservoir of genital herpes, challenge traditional concepts about the prevalence of H ducreyi in Britain, and call for a reappraisal of its role in the causation of genital ulcers.

Haemophilus ducreyi infections--time for reappraisal.

As the literature on Haemophilus ducreyi and clinical chancroid is reviewed, it becomes obvious that many significant findings have been forgotten over the years. As a result, from the time of Ducrey's original description of the organism in 1890 until about 1977, both clinical and laboratory experts in the United Kingdom believed that H. ducreyi infections were rare, generally acquired abroad, and almost impossible to confirm in the routine laboratory! In consequence it was a common view that it was not worth looking for H. ducreyi until all other possible causes of genital ulceration had been excluded. Moreover, the search for such an infection stopped as soon as any other cause for the patient's lesions had been found. A decision to ignore this 'rule' in Sheffield led to our looking for H. ducreyi in specimens from an unselected series of patients with genital ulceration including a number with herpes genitalis infections. The surprise finding of H. ducreyi in circumstances suggesting that it was a secondary invader made us re-examine the whole question of H. ducreyi infections and chancroid and wonder if the same organism can act as a primary pathogen and as a secondary invader. An account of the media and methods we used and of the characteristics of the organism is presented. In an attempt to find out more about the characteristic coherent colonies of H. ducreyi we studied them with the scanning electron microscope. It is clear that the whole subject of H. ducreyi infections has been neglected in the United Kingdom, but we believe that interest has now been aroused and progress will surely follow. Some areas for further investigation are suggested.

Chancroid in Sheffield. A report of 22 cases diagnosed by isolating Haemophilus ducreyi in a modified medium.

The causative organism of chancroid, Haemophilus ducreyi, is generally considered to be very fastidious and its isolation, maintenance, and detailed study very demanding. In this study a modified medium was developed, which allowed the organism to be isolated more frequently than previously would have been expected. Twenty-two cases of chancroid were confirmed by the isolation of H ducreyi in 160 patients with genital ulceration examined over a one-year period. The cases were apparently unrelated, and in only five was there a history of recent sexual contact abroad. Concurrent infection with other sexually transmitted diseases was present in 18 (81.8%) patients, and in 14 (63.6%) both H ducreyi and herpes simplex virus were isolated form the same genital ulcers. Thus, these findings indicate that chancroid is underdiagnosed in England and that H ducreyi may frequently occur as a secondary invader of damaged genital skin and mucosa.