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.

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.

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.

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.

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.

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.

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.

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.

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.

Influence of hyperkalaemia and ischaemia on non-receptor-mediated cardiac electrophysiological effects of naloxone.

OBJECTIVE: The aim was to investigate the cardiac electrophysiological effects of the opioid receptor antagonist naloxone and examine whether hyperkalaemia and ischaemia influence these effects. METHODS: The cardiac electrophysiological effects of racemic naloxone, nalmafene, and morphine were examined in superfused rabbit papillary muscles under normal conditions and in the case of naloxone under conditions of hyperkalaemia. The electrophysiological effects of racemic naloxone and d-naloxone were examined in arterially perfused rabbit interventricular septa before and during 30 min global zero flow ischaemia; the rate of rise of extracellular K+ concentration was also measured. RESULTS: Naloxone, nalmafene and morphine all prolonged action potential duration and effective refractory period in superfused papillary muscles (class III effects), suggesting that these effects are not receptor mediated. During hyperkalaemia, naloxone increased the depressant effect on the maximum upstroke velocity of the action potential and enhanced post-repolarisation refractoriness, further suggesting a class I effect. Both racemic naloxone (active at opioid receptors) and d-naloxone (inactive) prolonged action potential duration and effective refractory period in septa, again suggesting non-receptor-mediated effects. During myocardial ischaemia the class III effects of both compounds were gradually lost in such a way that post-repolarisation refractoriness developed. Both compounds reduced the rate of rise of extracellular K+ concentration and preserved resting membrane potential, but the fall in maximum upstroke velocity was enhanced, again suggesting that naloxone has an additional class I effect in partially depolarised ventricular myocardium. CONCLUSIONS: The antiarrhythmic activity of naloxone in models of myocardial ischaemia/reperfusion can be explained by non-opioid receptor mediated effects on the duration and maximum upstroke velocity of the action potential and on extracellular potassium accumulation during ischaemia.

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.

Probucol reduces plasma lipid peroxides in man.

Although primarily used as a lipid lowering drug, probucol also possesses anti-oxidant activity and has been shown in animal models to inhibit or delay the progression of atherosclerosis. It has been suggested that this anti-atherosclerotic effect may occur through inhibition of free radical oxidation of low density lipoprotein. The aim of this study was to investigate the effects of probucol on free radical activity in hyperlipidaemic patients. Plasma lipid peroxides were measured before probucol treatment, at 4 and 12 weeks treatment and then 4 weeks after stopping probucol. Lipid peroxide concentrations were significantly reduced during and 4 weeks after stopping treatment with probucol, when compared with baseline values. There were no changes in plasma vitamin E concentrations. The results of this study indicate that probucol reduces lipid peroxidation in patients, an effect which may occur through a free radical scavenging action.

Open multicentre study of the P2T receptor antagonist AR-C69931MX assessing safety, tolerability and activity in patients with acute coronary syndromes.

Platelet aggregation is the central process in the pathophysiology of acute coronary syndromes. ADP contributes to thrombosis by activating platelets, and AR-C69931MX is a specific antagonist of this process acting at the P2T receptor. At 5 hospitals, 39 patients with unstable angina or non-Q wave myocardial infarction, who were receiving aspirin and heparin, were administered intravenous AR-C69931MX with stepped dose increments over 3 h to a plateau of either 2 microg/kg/min for 21 h (Part 1; n = 12) or up to 69 h (Part 2; n = 13) or 4 microg/kg/min for up to 69 h (Part 3: n = 14). Safety parameters, platelet aggregation (PA) induced by ADP 3 micromol/L (impedance aggregometry), bleeding time (BT) and plasma concentrations of AR-C69931XX were assessed. AR-C69931MX was well tolerated. 33 patients completed the study. There were no deaths at 30 days and no serious adverse events attributed to AR-C69931MX. Trivial bleeding (56%) was common. At 24 h, mean inhibition of PA was 96.0 +/- 8.6, 94.9 +/- 14.4 and 98.7 +/- 2.1% and BT was 9.5 +/- 8.4, 14.0 +/- 9.7 and 16.0 +/- 11.1 min for Parts 1, 2 and 3 respectively. At 1 h post-infusion, mean inhibition of PA was 36.2 +/- 39.2, 20.7 +/- 25.9 and 40.7 +/- 36.7% respectively. 90% patients had a plasma half-life for AR-C69931XX of <9 min. In conclusion, AR-C69931MX is a potent, short-acting platelet ADP receptor antagonist suitable for further studies as an antithrombotic agent.

Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction.

In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Bradykinin and endothelial-cardiac myocyte interactions in ischemic preconditioning.

Myocardial ischemia results in the release of a variety of vasoactive substances from coronary vascular endothelial cells and/or from cardiac myocytes. Some of these substances appear to be protective and include nitric oxide and bradykinin. One hypothesis for the pronounced antiarrhythmic effects of preconditioning involves the early generation of bradykinin and, subsequently, nitric oxide. Evidence for early bradykinin release has come from clinical studies involving patients undergoing coronary angioplasty where, in 4 of 5 patients, there was evidence for elevated kinin levels in coronary sinus blood either during balloon inflation (i.e., ischemia) or deflation (reperfusion). The levels reached are sometimes considerable (increases 10-20 fold). The second piece of evidence comes from dogs subjected to a preconditioning stimulus (2 x 5 min periods of ischemia), followed 20 min later by occlusion of the same artery for a 25-min period. This preconditioning procedure markedly reduces ischemia-induced ventricular arrhythmias and, although under resting conditions there was little difference between arterial and coronary sinus bradykinin levels (125 +/- 22 and 157 +/- 41 pg/mL, respectively), there was a marked increase in coronary sinus levels in preconditioned dogs before the prolonged occlusion (637 +/- 293 pg/mL compared with 114 +/- 18 pg/mL in nonpreconditioned dogs); levels at the end of the prolonged occlusion in the preconditioned dogs were also higher (577 +/- 305 pg/mL compared with 162 +/- 34 pg/mL in control dogs). Other evidence for the involvement of bradykinin and nitric oxide comes from studies in which the generation, or effects, of these mediators have been suppressed (e.g., with the bradykinin B2 receptor blocking agent icatibant, with inhibitors of the L-arginine-nitric oxide pathway, and by methylene blue). The conclusion is that early bradykinin release is protective under conditions of ischemia, is presumably enhanced during therapy with angiotensin-converting enzyme (ACE) inhibitors and is suppressed under conditions of endothelial dysfunction.

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.

Dissecting aneurysm of a right-sided descending aorta with a left-sided aortic arch.

A 66-year-old man presented with myocardial infarction. Chest X-ray showed a large mediastinal mass. Aortic dissection was suggested by a past history of chest trauma, but the mass was in a very atypical site. Dissection of an abnormally placed right-sided descending aorta was confirmed by computed tomography. The aortic arch lay on the left side. This rare combination of congenital and acquired heart disease led to diagnostic difficulty.

Pacing termination of spontaneous ventricular tachycardia in the coronary care unit.

We reviewed our experience with the use of pacing techniques in the acute treatment of spontaneous ventricular tachycardia occurring outside the context of acute myocardial ischaemia. Over a consecutive 18 month period 23 patients (20 male, aged 38-76 yr) admitted to our coronary care unit experienced a total of 75 episodes of haemodynamically tolerated sustained ventricular tachycardia. Pace termination was attempted in 18 patients in a total of 58 episodes of ventricular tachycardia using a standard temporary external pacemaker. Pacing was successful in 32/58 (55%) attempts vs 13/49 (27%) with intravenous antiarrhythmic drug therapy p = 0.003. The superior success rate of pacing was apparent whether or not patients were receiving chronic antiarrhythmic drug therapy. Pace termination should be considered in the treatment of haemodynamically tolerated spontaneous ventricular tachycardias.

A clinical and in vitro study on the possible interaction of intravenous nitrates with heparin anticoagulation.

It has been reported that intravenous nitrates inhibit the anticoagulant effect of heparin. This possible interaction has potentially serious implications for the management of patients with acute coronary ischemic syndromes. This possible interaction was assessed prospectively in a clinical and in an in vitro study involving 24 patients receiving both drugs for the management of unstable angina pectoris. There was a small inhibitory effect of intravenous glyceryl trinitrate or isosorbide dinitrate on the anticoagulant effect of heparin in 3 of 24 cases in vivo, as assessed by activated partial thromboplastin time measurements. Nitrates or propylene glycol had no effect on heparin activity in vitro. It was concluded that there may be an inhibitory effect of nitrates on anticoagulation in a small minority of patients, but close attention to detail in monitoring heparin anticoagulation is far more important.

Cardiac catheterisation by the Judkins technique as an outpatient procedure.

OBJECTIVE: To assess the safety and cost benefit of left heart catheterisation by a modified Judkins technique performed as a day patient procedure. DESIGN: Review study of case notes of consecutive patients examined by the procedure over three years (January 1984 to December 1986). SETTING: Outpatient referrals in a regional cardiac centre within a district general hospital. PATIENTS: Nine hundred patients aged 18-76 (mean 54) selected at a previous clinic as suitable for the procedure. MAIN RESULTS: Eight hundred and fifty patients (94.4%) were discharged home on the day of the procedure. Forty others (4.4%) could not be discharged owing to complications during or just after the procedure. Of these patients, two died (0.2%), six suffered a myocardial infarction (0.7%), and two had major vascular complications. The remaining 30 patients were admitted because of chest pain without infarction (10 cases), minor vascular incidents (six), haemorrhage at the puncture site (five), arrhythmia (four), pulmonary oedema (three), and contrast reaction (two). Ten patients were admitted for either urgent coronary artery bypass grafting or social reasons. CONCLUSIONS: Cardiac catheterisation is safe as an outpatient procedure in most cases. Beds are spared and roughly 35,000 pounds is saved for every 500 procedures performed.