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.

Storied Lessons: Learning from Anger in Childhood by Narrating.

We evaluated whether narrating anger-provoking events promoted learning from those events, as compared with other responses to anger, and whether the effectiveness of narrative depended on age. In addition, we tested relations between anger-reduction and learning and in a subset of participants, between narrative quality and learning. 248 youth (8 to 17 years old) recalled an anger-provoking experience, and were randomly assigned to one of four activities: recalling the event a second time, narrating the event, and distraction (via video game play or conversation). Youth then recalled the event one last time, and rated the extent to which they had learned from that event. Younger children reported more learning when they had narrated their experience. Older youth reported more learning when they had narrated the event more frequently prior to participation. Stronger reductions in anger following regulation were associated with greater self-reported learning. Finally, more elaborative and less resolved narratives were associated with greater self-reported learning.

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.

Modelling the Impact of Atherosclerosis on Drug Release and Distribution from Coronary Stents.

Although drug-eluting stents (DES) are now widely used for the treatment of coronary heart disease, there remains considerable scope for the development of enhanced designs which address some of the limitations of existing devices. The drug release profile is a key element governing the overall performance of DES. The use of in vitro, in vivo, ex vivo, in silico and mathematical models has enhanced understanding of the factors which govern drug uptake and distribution from DES. Such work has identified the physical phenomena determining the transport of drug from the stent and through tissue, and has highlighted the importance of stent coatings and drug physical properties to this process. However, there is limited information regarding the precise role that the atherosclerotic lesion has in determining the uptake and distribution of drug. In this review, we start by discussing the various models that have been used in this research area, highlighting the different types of information they can provide. We then go on to describe more recent methods that incorporate the impact of atherosclerotic lesions.

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.

Attenuation of exercise induced ST elevation in non-obstructive coronary disease--a case for calcium channel blockade?

A male smoker already on atenolol therapy, presented with chest pain and dramatic exercise induced ST segment elevation. Coronary angiography demonstrated non-obstructive disease and treatment with diltiazem abolished ST segment elevation on subsequent exercise testing.

Secondhand smoke exposure and survival following acute coronary syndrome: prospective cohort study of 1261 consecutive admissions among never-smokers.

OBJECTIVE: To determine whether exposure to secondhand smoke is associated with early prognosis following acute coronary syndrome. DESIGN, SETTING AND PARTICIPANTS: We interviewed consecutive patients admitted to nine Scottish hospitals over 23 months. Information was obtained, via questionnaire, on age, sex, smoking status, postcode of residence and admission serum cotinine concentration was measured. Follow-up data were obtained from routine hospital admission and death databases. RESULTS: Of the 5815 participants, 1261 were never-smokers. Within 30 days, 50 (4%) had died and 35 (3%) had a non-fatal myocardial infarction. All-cause deaths increased from 10 (2.1%) in those with cotinine < or =0.1 ng/ml to 22 (7.5%) in those with cotinine >0.9 ng/ml (chi(2) test for trend p<0.001). This persisted after adjustment for potential confounders (cotinine >0.9 ng/ml: adjusted OR 4.80, 95% CI 1.95 to 11.83, p = 0.003). The same dose response was observed for cardiovascular deaths and death or myocardial infarction. CONCLUSIONS: Secondhand smoke exposure is associated with worse early prognosis following acute coronary syndrome. Non-smokers need to be protected from the harmful effects of secondhand smoke.

Current issues in coronary stent technology.

Coronary artery stents have become the medical device of choice for the treatment of coronary artery disease. Since their introduction in 1987, significant advances in stent technology have taken place. A major objective of these developments was the reduction of in-stent restenosis, the formation of neointimal tissue inside the stent triggered by vessel injury and the inflammatory response, which results in renarrowing of the coronary artery. Improvements in strut configuration, thickness, and materials have enhanced deliverability and reduced vessel damage. Currently available drug-eluting stents release drugs that reduce neointimal formation through the arrest of cell proliferation. Drug-eluting stents have significantly reduced rates of in-stent restenosis. However, concerns have been raised with respect to their long-term safety, particularly in relation to the occurrence of late thrombosis. The post-procedural monitoring of stent-related complications is also of interest, including the relative suitability of invasive techniques such as angiography and intravascular ultrasound, and non-invasive techniques such as computed tomography and magnetic resonance imaging scanning. This paper reviews the current issues in stent technology.

Drug-eluting stents: a review of current evidence on clinical effectiveness and late complications.

Drug-eluting stent (DES) use has increased greatly as a result of early trial evidence of a reduction in restenosis. However, thet are expensive and do not improve patient survival. Therefore their use has been rationed in some countries. There is a paucity of clinical evidence for some patient groups such as non-ST elevation myocardial infarction and multi-vessel disease. Recent studies suggest that the early benefits of drug-eluting stents may be offset by an increased risk in late stent thrombosis which is a potentially fatal complication. However, the absolute risk appears low and, as yet, there is no evidence of an increased risk of stent-thrombosis related myocardial infarction or death in patients studied in randomised clinical trials. Long-term use of anti-platelet therapy may protect against the risk of late stent thrombosis but the optimal treatment strategy is currently unclear. The aim of this paper is to provide an up-to-date review of the current evidence on DES; including clinical effectiveness, the limitations of existing trials, the emerging evidence on late stent thrombosis and the potential role of clopidogrel.

Magnetic resonance myocardial perfusion imaging: a new era in the detection of reversible myocardial ischaemia.

In due course, magnetic resonance myocardial perfusion imaging will probably replace SPECT as the most widely used non-invasive method for detecting reversible myocardial ischaemia.

Hospital volume of throughput and periprocedural and medium-term adverse events after percutaneous coronary intervention: retrospective cohort study of all 17,417 procedures undertaken in Scotland, 1997-2003.

OBJECTIVE: To determine whether percutaneous coronary intervention (PCI) hospital volume of throughput is associated with periprocedural and medium-term events, and whether any associations are independent of differences in case mix. DESIGN: Retrospective cohort study of all PCIs undertaken in Scottish National Health Service hospitals over a six-year period. METHODS: All PCIs in Scotland during 1997-2003 were examined. Linkage to administrative databases identified events over two years' follow up. The risk of events by hospital volume at 30 days and two years was compared by using logistic regression and Cox proportional hazards models. RESULTS: Of the 17,417 PCIs, 4900 (28%) were in low-volume hospitals and 3242 (19%) in high-volume hospitals. After adjustment for case mix, there were no significant differences in risk of death or myocardial infarction. Patients treated in high-volume hospitals were less likely to require emergency surgery (adjusted odds ratio 0.18, 95% confidence interval (CI) 0.07 to 0.54, p = 0.002). Over two years, patients in high-volume hospitals were less likely to undergo surgery (adjusted hazard ratio 0.52, 95% CI 0.35 to 0.75, p = 0.001), but this was offset by an increased likelihood of further PCI. There was no net difference in coronary revascularisation or in overall events. CONCLUSION: Death and myocardial infarction were infrequent complications of PCI and did not differ significantly by volume. Emergency surgery was less common in high-volume hospitals. Over two years, patients treated in high-volume centres were as likely to undergo some form of revascularisation but less likely to undergo surgery.

Anaesthetic considerations in a parturient with critical coronary artery disease and a drug-eluting stent presenting for caesarean section.

A parturient presented with her first symptoms of coronary artery disease at 18 weeks' gestation. Following an angiogram, a drug-eluting stent was inserted, resulting in resolution of her symptoms. The patient was prescribed anti-platelet medication including clopidogrel. She was delivered by elective caesarean section at 35 weeks under general anaesthesia. The anaesthetic management is discussed and a review of the literature presented.

Relation between coronary pressure derived collateral flow, myocardial perfusion grade, and outcome in left ventricular function after rescue percutaneous coronary intervention.

OBJECTIVE: To evaluate the relation between pressure derived coronary collateral flow (PDCF) index and angiographic TIMI (thrombolysis in myocardial infarction) myocardial perfusion (TMP) grade, angiographic collateral grade, and subsequent recovery of left ventricular function after rescue percutaneous coronary intervention (PCI) for failed reperfusion in acute myocardial infarction. METHODS: The pressure wire was used as the guidewire in 38 consecutive patients who underwent rescue PCI between December 2000 and March 2002. Follow up angiography was performed at six months. Baseline and follow up single plane ventriculograms were analysed off line by an automated edge detection technique. A linear model was fitted to assess the relation between 0.1 unit increase in PDCF and change in left ventricular regional wall motion. RESULTS: Patients with TMP 0 grade had significantly higher mean (SD) PDCF than patients with TMP 1-3 (0.30 (0.11) v 0.15 (0.07), p < 0.0001, r = -0.5). A similar relation was observed between TMP grade and coronary wedge pressure (mean (SD) 28 (16) mm Hg with TMP 0 v 9 (7) mm Hg with TMP 1-3, p = 0.001, r = -0.4). Higher PDCF was associated with increased left ventricular end diastolic pressures (0.28 (0.14) with end diastolic pressure > 20 mm Hg v 0.22 (0.09) with end diastolic pressure < 20 mm Hg, p = 0.08, r = 0.2). No correlation was observed between PDCF and Rentrops collateral grade (0.26 (0.13) with grade 0 v 0.25 (0.11) with grades 1-3, p = 0.4, r = -0.06). No linear relation existed between changes in PDCF and changes in left ventricular regional wall motion. CONCLUSION: PDCF in the setting of rescue PCI for failed reperfusion after thrombolysis does not predict improvement in left ventricular function. Increased PDCF and coronary wedge pressure in acute myocardial infarction reflect a dysfunctional microcirculation rather than good collateral protection.

Comparison of survival following coronary artery bypass grafting vs. percutaneous coronary intervention in diabetic and non-diabetic patients: retrospective cohort study of 6320 procedures.

AIM: To determine whether mortality following percutaneous coronary intervention vs. coronary bypass grafting varies according to whether or not patients have diabetes. METHODS: We used the Scottish Coronary Revascularization Register to identify all patients undergoing revascularization in Scottish NHS hospitals since 1997. We excluded single-vessel disease, left main stem stenosis, and bypass grafting performed at the same time as other operations. We used death certificate data from the Registrar General to identify all subsequent deaths. RESULTS: Of the 6320 eligible procedures, 5042 (80%) were bypass grafts and 1278 (20%) angioplasties. Overall 831 (13%) patients had diabetes with no significant difference by procedure (13% vs. 12%). A total of 382 deaths occurred over a mean follow-up of 2.3 years. Diabetic patients had a poorer prognosis following both surgery (adjusted hazards ratio (HR) 1.43, 95% confidence interval (CI) 1.08, 1.89) and percutaneous intervention (adjusted HR 2.58, 95% CI 1.43, 4.63). Among non-diabetic patients, no significant differences in mortality were detected between the two procedures. Among diabetic patients, no significant difference was detected in those with two-vessel disease. In those with impaired left ventricular function and triple-vessel disease, angioplasty was associated with a significantly higher risk of death (adjusted HR 3.58, 95% CI 1.40, 9.19). CONCLUSIONS: This is the first study to demonstrate statistically significant results that support the BARI trial findings. Our study demonstrated a significant difference for triple-vessel disease but not two-vessel disease. The former may be due to incomplete revascularization using percutaneous intervention. Our results require corroboration from randomized trials.

Recovery of normal diurnal variation of blood pressure following renal artery stenting.

Renal artery stenting is a therapeutic option in patients with functionally significant atherosclerotic renovascular disease. Improved control of blood pressure (BP) and preservation of renal function may be achieved following intervention. We present a case in which renal artery stenting was followed by recovery of the normal diurnal variation in BP.