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Physical activity (PA) has been demonstrated to have a powerful role in reducing cardiovascular risk and is therefore universally recommended by international guidelines. Although there is a dose-dependent risk reduction with increasing levels of PA, there is some concern that extreme levels of PA can result in adverse cardiovascular outcomes. It is important to adapt PA advice to each individual, and in particular to note that there are conditions that are not compatible with competitive sport because of increased cardiovascular risk. Exercise also has an key role in the assessment of patients presenting with symptoms that could potentially result from cardiovascular disease, both as a measure of the impact of the disease and as a diagnostic tool.

This was an observational study of the 1-year outcomes of the 20,000 patients included in the original CHARIOT study. The aim of the study was to assess the association between high sensitivity troponin I (hs-cTnI) concentration and 1 year mortality in this cohort. The original CHARIOT study included a consecutive cohort of in- and out-patients undergoing blood tests for any reason. Hs-cTnI concentrations were measured regardless of whether the clinician requested them. These results were nested and not revealed to the team unless requested for clinical reasons. One year mortality data was obtained from NHS Digital as originally planned. Overall, 1782 (8.9%) patients had died at 1 year. Multivariable Cox regression analysis showed that a hs-cTnI concentration above the upper limit of normal was independently associated with the hazard of mortality (HR 2.23; 95% confidence intervals 1.97 to 2.52). Furthermore, the log (10) hs-cTnI concentration was independently associated with the hazard of 1 year mortality (HR 1.77; 95% confidence intervals 1.64 to 1.91). In conclusion, in a large, unselected hospital population of both in- and out-patients, in 18,282 (91.4%) of whom there was no clinical indication for testing, hs-cTnI concentration was associated with 1 year mortality.

Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS.This study aimed to detail the role of GCS and GRS in ICI myocarditis.In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n=42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P< 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P< 0.001). Over a median follow-up of 30days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95%CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95%CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95%CI: 0.70-0.91]) and GRS (AUC: 0.76 [95%CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95%CI: 0.58-0.82]), LVEF (AUC: 0.69 [95%CI: 0.56-0.81]), and age (AUC: 0.54 [95%CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002).GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.

Approximately 50% of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease (CAD). A number of randomized studies ( Table 1 ) have all shown that complete revascularization (CR), either at the time of primary percutaneous coronary revascularization (PPCI) or within 45 days of the index admission, is safe and reduces the risk of repeat coronary revascularization and myocardial infarction (MI), particularly in the non-infarct related artery (NIRA). Despite consistently showing clinical benefit for CR, the results from the trials show variations in what drives this effect. Specifically, no study to date has provided a mechanistic insight as to how complete revascularization of chronic bystander disease may lead to the observed clinical benefit. Indeed, the randomized studies, through the variable nature of their results (reduction in MI versus revascularization etc.), have suggested the possibility that there are differing mechanisms for the observed benefit. In this review, we summarize the evidence base, highlight the limitations, and make the case that we need to understand the mechanism(s) underpinning the advantage of revascularization of NIRA in order to establish which patients are most likely to benefit. Without this insight, the current “one size fits all” approach may lead us in the wrong direction.

BACKGROUND Data comparing plaque characteristics and wire-free physiological assessment in the target vessel in patients with stable angina versus acute coronary syndrome are sparse. Therefore, we investigated the difference in plaque distribution between stable angina and non-ST-elevation myocardial infarction (NSTEMI) and explored the relationship between target vessel vulnerability by optical coherence tomography (OCT) and wire-free functional assessment with quantitative flow ratio (QFR). METHODS Patients with stable angina (n = 25) and NSTEMI (n = 24) were in the final prospective study cohort from the DECODE study (ClinicalTrials.gov, NCT02335086). All 5480 OCT frames in the region of interest were analyzed to study plaque morphology in the target vessel. QFR was analyzed from baseline coronary angiography before percutaneous coronary intervention. Vulnerable vessel score (VVS) was calculated from each plaque, and vessel QFR was then compared. RESULTS Out of all frames, thin-cap fibroatheroma was common with NSTEMI compared to stable angina (10.9 versus 6.3%, P

Introduction: Myocarditis is as a major immune-related adverse event following the use of immune checkpoint inhibitors (ICI). Global radial strain (GRS) reflects both longitudinal and circumferential fiber shortening but no data exist regarding its utility for diagnosis and risk stratification of ICI-myocarditis. Hypothesis: We hypothesized that GRS from echocardiography data would be reduced in patients with ICI-myocarditis and its reduction would have prognostic implications. Methods: Leveraging a multicenter international registry, we measured GRS from 76 patients with myocarditis and 49 ICI treated patients with no myocarditis. Pre-ICI GRS values were available for 10 cases and 38 controls. Measures were performed in a central laboratory blinded to group and time (TomTec, Germany). Major adverse cardiac event was a composite of cardiogenic shock, cardiac arrest, complete heart block and cardiac death. Results: Groups had similar age (66±15 vs. 63±12 years; p=0.20), sex distribution (male: 72% vs. 61%; p= 0.27) and cancer type (p=0.07). Pre-ICI GRS values were similar between cases and controls (47.4±2.9 vs. 45.4±6.0; p=0.12). A total of 57% of myocarditis patients had LVEF of >50% at presentation. The GRS was lower in patients with myocarditis compared with controls (28.6±6.7 vs. 47±7.4; p Conclusions: Global radial strain is lower in ICI- myocarditis and the magnitude of the reduction is associated with a higher rate of events.

Background Immune checkpoint inhibitor (ICI)-associated myocarditis is associated with a markedly increased risk of morbidity and mortality. The occurrence of ventricular arrhythmias (VA) in patients with ICI-associated myocarditis has not been well characterized. Purpose The aim of this study was to determine the characteristics and risk factors for severe VA in patients with ICI myocarditis. Methods The cohort consisted of 202 patients with ICI myocarditis. Ventricular arrhythmias were defined as a composite of sustained ventricular tachycardia and ventricular fibrillation. We used a multivariable logistic regression model to test the association between clinical variables and the development of VA. Results From a cohort of 202 patients with ICI myocarditis (67±13 years, 35% female, 60% hypertension, 23% diabetes mellitus), 41 (20.3%) developed VA, of which, 33 had VT and 8 had VF. The median time from admission to VF was 144 hours and to VT was 72 hours. A VA occurred in 17.5% of patients with a normal LVEF, and 25% of patients with reduced LVEF. On univariate analysis, a QRS duration >110ms (OR 2.88, 95% CI 1.40 to 6.16, P=0.005) and a QTc duration >470ms were associated with an increased probability of VA (OR 2.58, 95% CI 1.23, 5.41, P=0.012). The association remained significant after adjustment for age and gender. Additionally, a longer time from admission to initiation of corticosteroids was associated with a higher probability of VA (OR 1.06, 95% CI 1.01 to 1.13, P=0.027). The association between the time from admission to administration of corticosteroids and probability of VA remained significant after adjustment for age, gender, and LVEF on admission (OR, 1.06, 95% CI 1.00, 1.13, P=0.037) where each 6-hour delay in the initiation of corticosteroids was associated with a 4% increase in the risk for VA. Conclusions Ventricular arrhythmias are common in the setting of ICI myocarditis and are observed in patients presenting with both a preserved and a reduced LVEF. Wider QRS and longer QT at presentation and longer time from admission to initiation of corticosteroids were associated with an increased risk of VA. Funding Acknowledgement Type of funding sources: None.

Myocardial ischemia/reperfusion-related oxidative stress as a result of cardiopulmonary bypass is thought to contribute to the adverse clinical outcomes following surgical aortic valve replacement (SAVR). Although the acute response following this procedure has been well characterized, much less is known about the nature and extent of oxidative stress induced by the transcatheter aortic valve replacement (TAVR) procedure. We therefore sought to examine and directly compare the oxidative stress response in patients undergoing TAVR and SAVR. A total of 60 patients were prospectively enrolled in this exploratory study, 38 patients undergoing TAVR and 22 patients SAVR. Reduced and oxidized glutathione (GSH, GSSG) in red blood cells as well as the ferric-reducing ability of plasma (FRAP) and plasma concentrations of 8-isoprostanes were measured at baseline (S1), during early reperfusion (S2), and 6-8 hours (S3) following aortic valve replacement (AVR). TAVR and SAVR were successful in all patients. Patients undergoing TAVR were older (79.3±9.5 vs. 74.2±4.1 years; P<0.01) and had a higher mean STS risk score (6.6±4.8 vs. 3.2±3.0; P<0.001) than patients undergoing SAVR. At baseline, FRAP and 8-isoprostane plasma concentrations were similar between the two groups, but erythrocytic GSH concentrations were significantly lower in the TAVR group. After AVR, FRAP was markedly higher in the TAVR group, whereas 8-isoprostane concentrations were significantly elevated in the SAVR group. In conclusion, TAVR appears not to cause acute oxidative stress and may even improve the antioxidant capacity in the extracellular compartment.

Objective The aim of this study was to examine DNA ligase activity and expression of DNA damage response pathway (DDR) genes in patients with stable angina (SA) and non-ST elevation myocardial infarction (NSTEMI) and determine whether they correlate with plaque morphology. Background Patients with coronary artery disease (CAD) have evidence of deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs). It is unclear whether this represents excess damage or defective DNA repair activity. Methods DNA ligase activity and the expression of 22 DDR genes were measured in PBMCs of patients (both SA (n = 47) and NSTEMI (n = 42)) and in age and gender-matched controls (n = 35). Target lesion anatomical assessment was undertaken with frequency domain optical coherent tomography. Results DNA ligase activity was different across the three groups of patients (control = 119 ± 53, NSTEMI = 115.6 ± 85.1, SA = 81 ± 55.7 units/g of nuclear protein; ANOVA p = 0.023). Pair wise comparison demonstrated that this significance is due to differences between the control and SA patients (p = 0.046). Genes involved in double strand break repair and nucleotide excision repair pathways were differentially expressed in patients with SA and NSTEMI. In SA patients, fibrocalcific plaques were strongly associated with GTSE1, DDB1, MLH3 and ERCC1 expression. By contrast, in NSTEMI patients the strongest association was observed between fibrous plaques and ATM and XPA expression. Conclusion PBMCs from patients with CAD exhibit differences in DNA ligase activity and expression of DDR genes. Expression levels of certain DDR genes are strongly associated with plaque morphology and may play a role in plaque development and progression.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Oxford Biomedical Research Centre Introduction Non-contact charge density mapping allows visualisation of whole chamber propagation during atrial fibrillation (AF). The identification of regions with repetitive or, conversely, more complex patterns of wavefront propagation may provide clues to mechanisms responsible for AF maintenance and lead to improved outcomes from catheter ablation. Our novel mapping approach based on signal recurrence plots has never been applied to whole chamber, bi-atrial recording of atrial fibrillation. Purpose To apply recurrence analysis to characterise whole chamber bi-atrial AF propagation. Methods Non-contact dipole signals from left and right atrial maps were obtained during simultaneous bi-atrial charge density mapping of AF. Signals were converted to phase and mean phase coherence calculated for the generation of recurrence distance matrices for the whole chamber and each anatomical region (6x LA and 4x RA) over the 30-second recording duration, where a value of 1 (purple, see figure panel A) represents uniform repetitive conduction, and 0 (red), irregular, non-repetitive activity. Whole chamber and regional mean recurrence values were calculated and correlated with the frequency of wavefronts of localised irregular activation patterns. Results Maps were obtained prior to ablation in 21 patients (5 paroxysmal (pAF), 16 persistent AF (persAF)) undergoing de-novo catheter ablation procedures. Whole chamber recurrence was higher in patients with pAF (0.40 ± 0.08) than persAF (0.34 ± 0.05), p Conclusion Use of recurrence distance matrices characterises global AF propagation phenotypes. Regional values are inversely correlated with the frequency of localised irregular activation patterns identified demonstrating an anatomic dependence in the level of AF propagation complexity, greatest in the anterior LA and septal RA. Comparison of strategies targeting regions with maximal vs. minimal values during catheter ablation may define an optimal approach to treatment of persistent AF. Abstract Figure. Recurrence abstract figure

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Oxford Biomedical Research Centre Introduction Early evidence of pulmonary vein triggers initiating AF has led to focus on the left atrium (LA). Little work has been done to characterise the role of the right atrium (RA) in AF maintenance. Purpose To characterise the relative roles of the LA and RA in maintenance of atrial fibrillation and explore mechanisms of AF propagation. Methods Simultaneous bi-atrial mapping was carried out in patients undergoing first time catheter ablation using 2 linked non-contact charge density mapping systems to obtain 30-second recordings during AF. The predominant channel of communication between chambers was identified and the time difference across this channel measured (see figure). The proportion of signals earlier in each chamber was calculated and a dominant chamber identified if preceding the opposite chamber for ≥60% of the recording. AF was characterised in each chamber according to frequency of specific propagation patterns (localised rotational activation (LRA) and focal firing (FF)). The difference in AF characteristics in the LA and RA according to acute procedural outcome (termination with ablation vs. DCCV) was measured using 2-way ANOVA and predictors of AF termination identified using binomial logistic regression. Results Twenty-one patients were included (16 persistent AF, 5 paroxysmal AF, 11 in sinus rhythm at baseline) with 41 maps obtained prior to ablation. A dominant chamber was identified in 11 maps (in 9 patients). Of these, 5 maps (in 4 patients) were LA dominant, and 6 maps (in 5 patients) were RA dominant. The remainder showed balanced interatrial propagation. For patients with persistent AF, in the RA, those needing DCCV had more LRA than those with termination with ablation (79 activations, (95% CI 65-93) vs. 51 (30-71); p = 0.025). There was no difference in the LA in the two groups (77 vs 59, p = 0.541). There were fewer FFs in the RA vs LA in patients needing DCCV (123 (106-140) vs. 155 (137-172), p = 0.012)(see panel F). No differences in distribution of LIA were observed. The frequency of LRA (p = 0.003) and FF (p = 0.004) in the RA, and RA AFCL (p = 0.041), were predictors of acute procedural outcome. Conclusions Our novel approach of simultaneous bi-atrial mapping revealed that mechanisms responsible for AF maintenance were evenly distributed between atria whilst acute AF termination with left atrial ablation was dependent on the contribution of right atrial substrate. Strategies incorporating right atrial mechanisms may result in improved outcomes from AF ablation. Abstract Figure.

Background Charge density mapping of atrial fibrillation (AF) reveals dynamic localised rotational activation (LRA), irregular activation (LIA) and focal firing (FF). Their spatial stability, conduction characteristics and the optimal duration of mapping required to reveal these phenomena and has not been explored. Methods Bi-atrial mapping of AF propagation was undertaken using AcQMap (Acutus Medical) and variability of activation patterns quantified up to a duration of 30-seconds(s). The frequency of each pattern was quantified at each unique point of the chamber over 2 separate 30s recordings prior to ablation and R2 calculated to quantify spatial stability. Regions with the highest frequency were identified at increasing time durations and compared to the result over 30s using Cohen's kappa. Properties of regions with the most stable patterns were assessed during sinus rhythm and extrastimulus pacing. Results In twenty-one patients, 62 paired LA and RA maps were obtained. LIA was highly spatially stable with R2 between maps of 0.83(0.71-0.88) compared to 0.39(0.24-0.57) and 0.64(0.54-0.73) for LRA and FF, respectively. LIA was most temporally stable with a kappa of >0.8 reached by 12s. LRA showed greatest variability with kappa>0.8 only after 22s. Regions of LIA were of normal voltage amplitude (1.09mv) but showed increased conduction heterogeneity during extrastimulus pacing (p=0.0480). Conclusion Irregular activation patterns characterised by changing wavefront direction are temporally and spatially stable in contrast with LRA that is transient with least spatial stability. Focal activation appears of intermediate stability. Regions of LIA show increased heterogeneity following extrastimulus pacing and may represent fixed anatomical substrate. This article is protected by copyright. All rights reserved.

International audience; BACKGROUND Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.OBJECTIVES This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.METHODS In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.RESULTS Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 +/- 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction

BackgroundMyocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis.MethodsFrom an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested.ResultsBoth the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, pConclusionsThe QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.

Background Contemporary sensitivity troponin (cs-cTn) concentrations above the upper limit of normal (ULN) are seen in a wide range of clinical conditions and evidence is growing that suggests cs-cTn may be a biomarker of future morbidity and mortality. Objectives Our aim was to test the hypothesis that cs-cTn, measured in the emergency department, may be a biomarker for 30-day mortality, irrespective of the patient9s presentation. Method In all 5,708 consecutive cases, contemporary sensitivity troponin I (cs-cTnI) was measured either as requested by the clinical team or as part of the study, in which case both the clinical team and the patient were unaware of the result. Basic demographics were available from the original study and 30-day mortality was derived from NHS Digital data. Results In patients whose cs-cTnI test was requested solely as part of the study, 30-day mortality increased with increasing cs-cTnI concentrations (0% with undetectable concentrations to 14.7% with concentrations above the ULN). Multivariable Cox regression analysis showed that log(10)cs-cTnI concentration was independently associated with 30-day mortality. Conclusion Increasing cs-cTnI concentrations are associated with higher short-term mortality as well as length of stay. As such, cs-cTnI measurements may provide useful prognostic information.

Introduction The introduction of high-sensitivity troponin assays has facilitated pathways to rapidly exclude myocardial infarction (MI) in patients presenting to the emergency department (ED) with chest pain. However, hs-cTn concentrations above the manufacturer-supplied upper limit of normal (ULN) are frequently detected in patients presenting to ED, despite only a small proportion having a type 1 MI. Furthermore, there is also increasing evidence that hs-cTn concentrations may act as a biomarker of cardiovascular risk in patients outside the context of acute coronary syndrome. In the current study, we report the distribution of hs-cTn in the subpopulation of CHARIOT who attended ED, in whom the assay was taken regardless of whether there was a clinical indication. Our aim was to test the hypothesis that hs-cTn may be a biomarker for in-hospital mortality, irrespective of the indication for its measurement. Method The study included 5708 consecutive patients attending ED in a single centre. In all cases hs-cTnI was measured either as requested by the clinical team, or as part of the study, in which case both the clinical team and the patient were unaware of the test. Basic demographics were available from the original CHARIOT study and both the electronic clinical record and coding data were interrogated to ascertain the clinical outcome. Results 491 (8.6%) patients had hs-cTnI concentrations above the manufacturer’s ULN. There were 4157 (72.8%) patients in whom the hs-cTnI was performed solely as part of the study, with 309 (7.4%) of these above the ULN. Five patients died in ED. Of the remaining patients, 3603 (63.2%) were admitted to hospital. The rate of admission increased with rising hs-cTnI concentrations (table 1). A cardiovascular diagnosis was the most frequent discharge diagnosis in those with a hs-cTnI above the ULN. However, a neurological condition was most common in the patients in whom the test was only performed as part of the study. Increasing hs-cTnI concentrations were associated with increasing in hospital mortality regardless of whether the hs-cTnI was requested for clinical reasons or not (figures 1 & 2). Furthermore, hs-cTnI demonstrated good discriminative ability for in-patient mortality (area under receiver operator curve 0.834). Hs-cTnI above the ULN remained an independent predictor of mortality on multivariate analysis. The median length of stay was also associated with increasing hs-cTnI concentrations. Conclusion In consecutive patients presenting to ED, hs-cTnI elevation is common. Furthermore, increasing hs-cTnI concentrations are associated with increased admission rates from ED, longer in-patient stays and higher in-hospital mortality. Hs-cTnI may therefore represent a biomarker for in hospital outcomes in these patients. Conflict of Interest Unrestricted research grant from Beckman Coulter (who had no role in the design, analysis, interpretation of the study)

Introduction: myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). While corticosteroids are the cornerstones of the treatment, there are no data to guide the dose and timing. Methods: from an international registry of patients with ICI myocarditis diagnosed between 2013 and 2019, data on the type, dose (in methylprednisolone equivalent dose) and timing of steroids were extracted. Major cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically-significant complete heart block. Results: in total, 143 ICI myocarditis patients (67±13 years old, 29% women) were included. Among them, 125 received corticosteroids (87%), with the initial agent being either methylprednisolone (95, 76%), prednisone (25, 20%), hydrocortisone (2, 1.6%) or dexamethasone (3, 2.4%). The rates of overall MACE (by admission time tertile 1: 45.8%, tertile 2: 43.8%, tertile 3: 38.3%, P=0.746) and individual elements of MACE were unchanged from 2013 to 2019. The initial corticosteroid dose was categorized as low (500mg). There was an inverse relationship between the occurrence of MACE and initial dose of corticosteroid, where MACE declined with increasing doses (low 61.9%, intermediate 54.6%, high 20.4%, P72 hours (85.7%, P

Introduction Interatrial propagation has been widely studied in anatomical specimens and electrophysiological studies during sinus rhythm or pacing. However, pathways of conduction during atrial fibrillation (AF) are poorly characterised in vivo. Purpose We sought to develop a method of identifying the dominant channel of communication between atria during AF with a view to characterising the role of localised mechanisms in maintaining AF between both chambers. Methods 10 patients undergoing simultaneous bi-atrial non-contact charge density mapping before and following pulmonary vein isolation (PVI) were analysed. Simultaneous 30s recordings during AF were obtained. Virtual electrograms from every vertex of the reconstructed left and right atrial (LA, RA) anatomies were exported and phase calculated using a method of sinusoidal recomposition and Hilbert transform. For each vertex, coherence between a sequence of activations between this point and every other point on the opposing chamber was calculated using mean phase coherence (MPC). The maximum of all MPC values was assigned to this local point to estimate the degree of coherence between activity at a given point and the entire opposing chamber. The regions with highest MPC value represent the channel of communication. Each activation of this zone is then evaluated and difference in local activation time between LA and RA determined (figure). Communication between atria is determined where a normal distribution of timing shift within this channel can be demonstrated (as opposed to a uniform histogram in the case of a lack of any correlation between electrograms). If seen to be preceding the opposite chamber for ≥60% of the recording then the chamber was deemed to be leading. Results A total of 18 maps were obtained (pre-PVI only in 2). A clear channel of interatrial propagation could be seen in 17 maps (MPC value 0.48 ± 0.16) with communication within this channel demonstrated in 13 of these (MPC 0.52 ± 0.16). In the RA the most common site was in the posterior inter-caval zone (in 13) and on the posterior septum of the LA (in 14). The LA was leading in 4 maps and the RA in 2 with balanced propagation in 7. Conclusion The method of average MPC identifies channels of inter-atrial communication during AF which appear to predominantly involve posterior interatrial connections. Further application of this technique to characterise interatrial propagation may help to define patient specific phenotypes of AF and guide targeted therapy. Abstract Figure 1

Introduction Non-contact charge density mapping identifies complex wavefront propagation including localised rotational activation (LRA), localised irregular activation (LIA) and focal firing (FF). However, the duration of mapping required to reveal underlying patterns and their temporal stability is unknown. Purpose We sought to evaluate the variability in propagation patterns over increasing durations of recordings up to 30 seconds and examine the stability of these patterns between 2 separate maps with the aim of identifying the minimum duration required to reveal underlying patterns and how they represent the stable arrhythmia substrate. Methods Patients undergoing first time AcQMap guided catheter ablation were studied. 30s recordings of left atrial propagation were analysed. LIA, LRA, and FF were quantified for frequency, percentage time present and percentage surface area affected (for FF only frequency was assessed) at increasing durations up to 30s in 1s increments. At each incremental recording duration the percentage change in each variable was calculated. For occurrence frequency the results for every possible combination of maps of increasing duration within the 30s recording were compared whilst for occurrence time and surface area a 5s moving average at 1s increments was calculated. The point at which variability was seen to plateau represents the minimum optimal mapping duration. Spatial stability was assessed by correlating the frequency of patterns at each vertex of the anatomy over 2 separate 30s recordings. Stability of regions with the most repetitive patterns were compared using Cohen’s kappa statistic. Results 15 patients were analysed (age 63 ± 9, 10 male, BMI 30 ± 5, CHA2DS2Vasc 1 ± 1.3, ejection fraction 54 ± 12%, left atrial diameter 46 ± 7mm, paroxysmal 1, persistent 14) with 11 included in the spatial stability analysis due to availability of recordings of sufficient duration. LRA demonstrated most variability followed by LIA and FF. Variability in LIA, LRA and FF decrease at increasing durations. LIA and FF variability plateau by 13 and 17s respectively. LRA plateaus at 23s. Variability of LIA demonstrated the greatest stability with average R2 of 0.76 ± 0.14 (figure). Average R2 for LRA and FF were 0.45 ± 0.16 and 0.47 ± 0.12. Low frequency focal firings were widely distributed across the atrial surface. For FF occurring at a frequency ≥10 over the 30s, average R2 value was 0.65 ± 0.14. Cohen kappa statistic was 0.70 for LIA and 0.45 for LRA. Conclusion Mapping durations of ≥23s are required to identify all temporally variable propagation patterns although shorter durations will identify less variable LIA and FF. LIA demonstrates high spatiotemporal stability and may best reflect disrupted conduction caused by the underlying atrial substrate and tissue architecture. Regions of high frequency FF are temporally stable and may represent important targets for ablation. Abstract Figure 1

Author(s): Zhang, Lili; Awadalla, Magid; Mahmood, Syed S; Nohria, Anju; Hassan, Malek Z O; Thuny, Franck; Zlotoff, Daniel A; Murphy, Sean P; Stone, James R; Golden, Doll Lauren Alexandra; Alvi, Raza M; Rokicki, Adam; Jones-O'Connor, Maeve; Cohen, Justine V; Heinzerling, Lucie M; Mulligan, Connor; Armanious, Merna; Barac, Ana; Forrestal, Brian J; Sullivan, Ryan J; Kwong, Raymond Y; Yang, Eric H; Damrongwatanasuk, Rongras; Chen, Carol L; Gupta, Dipti; Kirchberger, Michael C; Moslehi, Javid J; Coelho-Filho, Otavio R; Ganatra, Sarju; Rizvi, Muhammad A; Sahni, Gagan; Tocchetti, Carlo G; Mercurio, Valentina; Mahmoudi, Michael; Lawrence, Donald P; Reynolds, Kerry L; Weinsaft, Jonathan W; Baksi, A John; Ederhy, Stephane; Groarke, John D; Lyon, Alexander R; Fradley, Michael G; Thavendiranathan, Paaladinesh; Neilan, Tomas G | Abstract: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Heart failure (HF) and ischaemic heart disease (IHD) are among the leading causes of death globally [1,2]. Despite improvements in the prevention and management of IHD, it remains the commonest cause of HF [2,3]. The prognosis, once a diagnosis of HF is established, is limited with only 50% surviving to 5 years and 10% to 10 years [2]. It is therefore critical that interventional cardiologists not only focus on appropriate revascularisation strategies but also optimal medical therapy to prevent and/or treat HF. Spironolactone, the first available mineralocorticoid receptor antagonist (MRA), has been available for over 50 years when it was used solely in states of hyperaldosteronism [4]. Since then the class has expanded and their role in the medical management and prevention of HF has been firmly established [4]. However, despite the recommendations of both the European Society of Cardiology (ESC) and the American Heart Association (AHA) to initiate eplerenone early after acute myocardial infarction (AMI) associated with left ventricular systolic dysfunction, there are concerns that there is a mismatch between the evidence base behind these recommendations and contemporary management of patients with AMI particularly with regard to revascularisation and speed of discharge [5–7].

Deoxyribonucleic acid (DNA) damage and repair signaling cascades are related to the development of atherosclerosis. Pathological studies have demonstrated that healed coronary plaque rupture (HCPR) contributes to plaque progression and predisposes to sudden ischemic cardiac death. The objective of this study is to investigate the relationship between HCPR detected by optical coherence tomography (OCT) and DNA ligase. Forty-two patients with both OCT and DNA ligase were prospectively enrolled. The population included patients with stable angina pectoris (SA) and non-ST-elevation myocardial infarction (NSTEMI). It was found that the prevalence of HCPR was greater in subjects with higher DNA ligase activity (correlation coefficient 0.36, p = 0.019). The presence of HCPR in patients with NSTEMI was greater than in patients with SA per OCT analysis; however, there was no statistical difference in this limited population (22.53% versus 12.83%, respectively, p = 0.116). DNA repair activity by DNA ligase was associated with HCPR in advanced coronary artery plaque by OCT.

Introduction: Troponin is considered to be the gold standard biomarker for ruling out MI. There has been a drive to improve the diagnostic speed, and as such the high sensitivity cardiac troponin (hs-cTn) assays have been introduced into clinical practice and are now part of international guidelines. Their novel value in clinical practice more generally is becoming apparent.Areas covered: In this review we will evaluate the evidence for the use of hs-cTn assays in clinical practice, the issues with the assay and how the hs-cTn can be utilized in the future as a biomarker of cardiovascular risk.Expert commentary: The use of the hs-cTn assays as a ‘rule out’ test for MI is compelling, as a ‘rule in’ there are significant issues relating the specificity of the assay for MI. The future of the assay may lie in population screening and risk modeling.

Background Fractional flow reserve measurement based on computed tomography (FFRCT) is a novel, well validated, non-invasive method for determining the presence and extent of coronary artery disease (CAD) combined with a physiological assessment of vessel-specific ischemia in patients with chest pain. Previous studies indicate that FFRCT reduces the uptake of invasive angiography that shows no significant CAD, without compromising patient safety. The clinical effectiveness and economic impact of using FFRCT instead of other tests in the initial evaluation of patients with stable chest pain has not been tested in a randomized trial. Methods The FORECAST trial will randomise 1400 patients with stable chest pain to receive either FFRCT or routine clinical assessment as directed by the National Institute for Health and Care Excellence (NICE) CG95 guideline for Chest Pain of Recent Onset. The primary endpoint will be resource utilisation over the subsequent nine months, including non-invasive cardiac investigations, invasive coronary angiography, coronary revascularization, hospitalization for cardiac events, and the use of cardiac medications. Key pre-specified secondary endpoints will be major adverse cardiac events, angina severity, quality of life, patient satisfaction, time to definitive management plan, time to completion of initial evaluation, number of hospital attendances, and working days lost in patients who are in employment. Conclusion The FORECAST randomized trial will assess the clinical and economic outcomes of using FFRCT as the primary test to evaluate patients presenting with stable chest pain.

Background The use of high-sensitivity troponin (hs-cTn) is established in guideline-directed clinical practice to facilitate the diagnosis or exclusion of myocardial infarction (MI). The manufacturer provided 99th percentile for this assay is derived from a small population of relatively healthy individuals but is used as an “upper limit of normal” (ULN) in routine hospital practice. This raises the question: does this ULN actually represent the 99th centile of the distribution of the assay in an all comers hospital population, in most of whom there is no clinical suspicion of an MI? Methods Twenty thousand consecutive patients attending this large University Teaching Trust who had biochemistry tests for any clinical reason, either as in- or outpatient had an hs-cTn assay as part of this study. In those patients in whom hs-cTn was not requested by their supervising clinician, the result of the assay was nested, and never revealed to doctor or patient. Ethical approval for this method required special permission from the national Confidentiality Advisory Group following support from the British Cardiac Patients Association. The Beckman Coulter Access AccuTnI+3 assay was used throughout. These data were combined with the source location for the blood test, as well as the presence of coded co-morbidity since the year 2000. Results There were 18171 patients left once patients discharged with a diagnosis of MI (122) and those suspected of MI (1707) by the clinical team were excluded. There were 4759 inpatients, 9280 outpatients and 4132 patients in the emergency department with 7.3%, 2.0% and 7.4% of these having an hs-cTn level above the manufacturer-provided ULN respectively. Table 1 demonstrates the prevalence of hs-cTn levels above the ULN in hospitalised patients by speciality. In terms of outpatients; cardiothoracic, renal and oncology/haematology patients were the most likely to have an hs-cTn above the ULN with 7.4%, 4.9% and 2.6% respectively above this level. There were 4265 (46%) outpatients in whom there was at least one coded co-morbidity present. These patients were more likely to have an hs-cTn above the ULN than those without a coded co-morbidity (2.8% versus 1.2%, P Conclusion These data suggest that application of a manufacturer-derived 99th centile for hs-cTn assay to a hospital population may be flawed, particularly if any assumption is made that a result above this level may represent acute MI in patients without a classical history. Caution and a good understanding of the assay is imperative for accurate diagnosis and management of hospital patients with an apparently elevated level, but these results also raise interesting questions about what the levels actually indicate in patients in whom the suspicion f acute Mi is low. More data are required. Conflict of Interest Educational support from BAYER

ObjectiveTo determine the distribution, and specifically the true 99th centile, of high sensitivity cardiac troponin I (hs-cTnI) for a whole hospital population by applying the hs-cTnI assay currently used routinely at a large teaching hospital.DesignProspective, observational cohort study.SettingUniversity Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, between 29 June 2017 and 24 August 2017.Participants20 000 consecutive inpatients and outpatients undergoing blood tests for any clinical reason. Hs-cTnI concentrations were measured in all study participants and nested for analysis except when the supervising doctor had requested hs-cTnI for clinical reasons.Main outcome measuresDistribution of hs-cTnI concentrations of all study participants and specifically the 99th centile.ResultsThe 99th centile of hs-cTnI for the whole population was 296 ng/L compared with the manufacturer’s quoted level of 40 ng/L (currently used clinically as the upper limit of normal; ULN). Hs-cTnI concentrations were greater than 40 ng/L in one in 20 (5.4%, n=1080) of the total population. After excluding participants diagnosed as having acute myocardial infarction (n=122) and those in whom hs-cTnI was requested for clinical reasons (n=1707), the 99th centile was 189 ng/L for the remainder (n=18 171). The 99th centile was 563 ng/L for inpatients (n=4759) and 65 ng/L for outpatients (n=9280). Patients from the emergency department (n=3706) had a 99th centile of 215 ng/L, with 6.07% (n=225) greater than the recommended ULN. 39.02% (n=48) of all patients from the critical care units (n=123) and 14.16% (n=67) of all medical inpatients had an hs-cTnI concentration greater than the recommended ULN.ConclusionsOf 20 000 consecutive patients undergoing a blood test for any clinical reason at our hospital, one in 20 had an hs-cTnI greater than the recommended ULN. These data highlight the need for clinical staff to interpret hs-cTnI concentrations carefully, particularly when applying the recommended ULN to diagnose acute myocardial infarction, in order to avoid misdiagnosis in the absence of an appropriate clinical presentation.Trial registrationClinicaltrials.govNCT03047785.

Objectives: To compare UK Cardiovascular Disease Deaths (CDD) with twenty Other Western Countries (OWC). Design: Population-controlled-based study using WHO data on CDD people aged 55-74 and Age-Standardised-Death-Rates (ASDR) rates per million (pm) contrasts UK and OWC outcomes between 1989-2015 and World Bank % GDP Expenditure-on-Health (%GDPEH) data. Setting: Twenty-one Western Countries. Participants: National populations. Outcome measures: Reduced CDD for people aged 55-74 and ASDR confidence intervals determines statistical differences between UK and OWC over the period. Result: All countries substantially reduced CDD 55-74, highest current rates America at 3440pm, Finland 3197pm, Greece 3173 to lowest, France 1522pm, Australia 1634pm and Japan 1866pm. Previously UK was 4th highest but fell to 8th at 2524pm, significantly reducing CDD more than 15 OWC, though three had greater falls than Britain. ASDR fell substantially everywhere but the UK had second biggest reduction, significantly reducing total CDD deaths more than 15 OWC. Highest 1980-2015 average %GDPEH was USA at 12.7%, UK’s 7.6% was lowest suggesting British cardiac services achieved more with proportionately less. Conclusion: Improvements in primary and secondary prevention of cardiovascular disease occurred in every country, we speculate whether the UK success might be attributable to the Pan UK public health innovations, the National Service Framework (2000) to reduce myocardial infarction, and, National Framework for long term conditions (2005) but further research is required to identify the effective mechanisms. These results should be a morale boost for patients and their families and or all in the cardiac services, especially in the UK.

Background Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs. Methods Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death. Results The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002). Conclusion The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV. Electronic supplementary material The online version of this article (10.1186/s40425-019-0535-y) contains supplementary material, which is available to authorized users.

Significant left main coronary artery disease (LMCAD) occurs in 5–7% of patients undergoing coronary angiography. Patients with LMCAD have a 50% 3-year mortality despite optimal medical therapy. As such, coronary artery bypass grafting (CABG) emerged as the gold standard therapy for the treatment of patients with LMCAD either in isolation or in association with disease elsewhere in the coronary circulation. Advances in stent and adjunctive intracoronary imaging as well as pharmacotherapy has enabled percutaneous coronary intervention (PCI) to challenge CABG in such patients, with a host of randomized and observational studies comparing the safety and efficacy of PCI with CABG. This chapter covers historical data on CABG in LMCAD, compares various PCI techniques with CABG, and finally evaluates the differences in efficacy and safety.

Coronary heart disease is the single most common cause of death in the UK and in Europe, although death rates are declining in most European countries. Hospital mortality rates between non-ST elevation acute coronary syndrome and ST-elevation myocardial infarction are compared, with an examination of the pathophysiology, clinical syndromes, and trials of conservative versus early invasive strategy throughout the chapter. Finally, special subgroups are considered, including those with anaemia and diabetes mellitus.

INTRODUCTION: There is potential value in testing individual response to P2Y12 inhibitors to predict ischemic and bleeding risk in patients undergoing percutaneous coronary intervention. The aims of this study were: (1) to validate the ability of a novel point of care (POC) assay, thrombelastography (TEG) 6s, to detect changes in adenosine diphosphate (ADP)-induced whole blood clotting in volunteers and patients given clopidogrel using TEG 5000 as a reference and (2) to compare a novel, rapid parameter, area under the curve at 15 minutes (AUC15), with the traditional maximum clot amplitude (MA) in TEG 6s.METHODS: A total of 25 participants were included in whom ADP-induced clotting was measured at 4 time points: (1) 12 healthy volunteers given 600 mg of clopidogrel; (2) 12 patients with ACS given 600 mg of clopidogrel; (3) 1 healthy volunteer given 600 mg of clopidogrel on 5 separate occasions. All samples were tested using conventional TEG 5000 and the new POC TEG 6S, and a new parameter called AUC15 was compared with MA in TEG 6s.RESULTS: (1) TEG 5000 and TEG 6s both detected changes in ADP-induced platelet activation. Bland-Altman analysis demonstrated a good level of agreement between them. (2) For TEG 6S, correlation between MA and the novel AUC15 was strong for both thrombin and ADP channels (R2 = 0.867, R = .936, P < .001), and the AUC15 result was available on average 13.3 minutes earlier.CONCLUSIONS: Thrombelastography 6s is a rapid, easy to use and accurate test of ADP-induced clotting using TEG 5000 as a reference. A novel parameter, AUC15, is a viable, time-saving option for this test and has potential value in personalized P2Y12 inhibitor therapy.

A 48-year-old man was admitted as a Level 1 trauma after attempting suicide by jumping 28 m into a river. He was haemodynamically stable with unremarkable physical examination except for bilateral periorbital bruising. Trauma-protocol CT demonstrated an isolated T5 vertebral fracture. Despite being pain free, serial ECGs showed dynamic anterior ST-elevation. Review of the trauma CT identified a subtle perfusion defect in the left anterior descending artery (LAD) territory in keeping with a recent infarct, but motion artefact made assessment of the aortic root challenging. In view these findings, …

Objective MicroRNAs (miRNAs) may serve as potential biomarkers in a variety of pathologies. The aim of this study was to determine whether miRNAs could serve as blood-based markers of isolated coronary artery calcification (CAC) defined as CAC in the absence of an underlying metabolic abnormality. Methods 24 age-matched and sex-matched patients who had been referred for elective CT coronary calcium score and angiography as part of investigation for cardiac chest pain were recruited. Peripheral venesection was performed and an Agatston calcium score was derived from the CT coronary angiogram using default software. RNA was extracted using the LeukoLOCK Total RNA Isolation System for Toray’s microarray analysis and quantitative reverse transcription PCR (qRT-PCR). Results The patients were well matched for age, sex and conventional risk factors for coronary artery disease. Microarray analysis identified lower expression of miRNA-138-2-3p, miRNA-1181, miRNA-6816-3p and miRNA-8059 in patients with coronary artery calcium score (CACS)=0 vs CACS>100. qRT-PCR confirmed significant downregulation of miRNA-8059 in patients with CACS>100 (CACS=0 vs CACS>100; P=0.03). Conclusion miRNA-8059 may serve as a peripheral blood-based biomarker for the presence of CAC, as well as provide a platform for studying the pathophysiological basis of isolated CAC. Trial registration number NCT01992848; Results.

Objective To compare the clinical outcomes of patients undergoing percutaneous intervention for stent thrombosis (ST) or saphenous vein graft (SVG) occlusion. Background Patients presenting with ST or SVG occlusion are at increased risk of adverse outcomes. There is limited literature comparing the outcome of such patients. Methods A cohort of 415 consecutive patients presenting to the MedStar Washington Hospital Center undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome secondary to ST (n=136) or SVG occlusion (n=279) was studied. The SVG group was subdivided into patients who underwent PCI in the occluded SVG (SVG-PCI: n=75) or in the subtended native coronary artery (NC-PCI: n=204). The analyzed clinical parameters were in-hospital complications as well as 30-day and 1-year major adverse cardiac events (MACE). MACE was defined as all-cause mortality, Q-wave myocardial infarction, or target vessel revascularization. Results The rates of death, major bleeding, and length of hospital stay were significantly different between the ST and NC-PCI groups. The SVG-PCI group had a shorter hospital stay. The 30-day MACE rate was significantly different in the ST and NC-PCI groups (18.9% vs. 7.5%; risk ratio=0.40, 95% CI=0.20–0.81, p=0.03) but not in the ST and SVG-PCI groups (18.9% vs. 15.1%; p=0.55, risk ratio=0.80, 95% CI=0.38–1.68). There were no differences in the 1-year MACE rate. Conclusions As compared to patients undergoing NC-PCI, patients with ST have greater rates of in-hospital mortality and major bleeding as well as 30-day MACE rate. The 1-year MACE rate is similar in patients with ST and SVG occlusion who undergo PCI.

Background The influence of age upon the use of drug-eluting stents (DES) in patients aged ≥ 65 years is uncertain. The aim of this study is to investigate the impact of age increase in patients aged ≥ 65 years in the use of DES in patients undergoing percutaneous coronary intervention (PCI). Method The study cohort comprised 8,598 patients ≥ 65 years of age who underwent stent implantation from April 2003 to March 2014. We defined the first DES era as the period April 2003 to July 2008 and the second DES era as the period July 2008 to March 2014. Multivariable logistic regression was performed for both eras to assess the impact of age increase and analyze independent factors associated with DES implantation. Results In the first DES era cohort, the two groups of patients differed in their risk factor profile with lower rates of male sex, diabetes, smokers, and hypercholesterolemia in those aged ≥ 75 years. There were more Caucasian and less African-Americans in this age group. Furthermore, patients aged ≥ 75 years had lower left ventricular ejection fraction (LVEF) and baseline haematocrit concentration were more likely to present with an acute myocardial infarction (MI) than stable or unstable angina and had higher rates of a previous history for congestive heart failure (CHF), chronic renal insufficiency (CRI), and peripheral vascular disease (PVD). These differences were broadly similar for patients in the second DES era except for similarities in LVEF, presentation with unstable angina, and PVD, as well as a lower rate for previous PCI. DES use was reduced with increasing age in both the first (OR=0.78; 95% CI=0.69–0.89) and second DES era (OR=0.53; 95% CI=0.47–0.58). In both eras, DES use was less likely in current smokers, patients presenting with acute MI and cardiogenic shock, and those with a previous history of CHF. Conclusion In patients aged ≥ 65 years, the use of DES decreased with increasing age. This observation was apparent in both the first and second DES era. © 2015 Wiley Periodicals, Inc.

The global burden of cardiovascular disease is increasing despite therapeutic advances in medication and interventional technologies. Accumulated deoxyribonucleic acid (DNA) damage and subsequent repair pathways are now increasingly recognised as a causal factor in the initiation and progression of atherosclerosis. These molecular alterations have been shown to occur within affected vasculature, plaque microenvironment as well as in circulating cells. The DNA damage response (DDR) pathway is reliant on post-translational modification of sensing proteins which activate a signalling cascade to repair, if possible, DNA damaged sites in response to various environmental and physiological insults. This review summarises the current evidence for DNA damage in atherosclerosis, the key steps involved in the DDR pathway, DNA repair and their subsequent effects on atherosclerotic plaques, as well as the therapeutic options in managing DNA damage-induced atherosclerosis.

BACKGROUND: There is paucity of data regarding the clinical outcome of second generation drug- eluting stents (DES) post rotational atherectomy (RA) for heavily calcified coronary lesions (HCCL). METHODOLOGY: The study cohort comprised 99 (116 lesions) consecutive patients who underwent RA for HCCL at our institution and received either a first generation DES (40 patients, 53 lesions) or a second generation DES (59 patients, 63 lesions). The analyzed clinical parameters were the 12-month rates of death (all cause and cardiac), Q-wave MI, target lesion revascularization (TLR), definite stent thrombosis (ST) and major adverse cardiac events (MACE) defined as the composite of death, Q-wave MI, or TLR. RESULTS: The two groups were well matched for their baseline characteristics except for a lower left ventricular ejection fraction in the second generation DES group (46.0±23.0% vs. 55.0±9.0%; p=0.02). The group receiving second generation DES had more type C lesions (81.0% vs. 58.8%; p=0.01), shorter stent length (19.9±6.1 mm vs. 22.7±7.3 mm; p=0.04) and was more likely to undergo stent postdilatation (52.4% vs. 23.1%; p=0.001). The 1-year analyzed clinical parameters were similar in the two groups: all cause death (8.5% vs. 10.3%; p=1.0), cardiac death (8.5% vs. 2.5%; p=0.40), Q-wave MI (0% vs. 0%), TLR (3.6% vs. 2.7%; p=1.0), ST (0% vs. 0%), and MACE (11.9% vs. 12.8%; p=1.0). The 1-year MACE-free survival rate was also similar in the two cohorts. CONCLUSION: The use of second generation DES, following RA for HCCL, is associated with similar short and long-term clinical outcomes to first generation DES.

The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels. The aim of this study was to assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in patients on aspirin before, during, and after major vascular surgery, which represents a model of on/off vascular inflammation. Firstly, we hypothesised, that in association with this inflammatory episode AA-, ADP- and thrombin-induced clotting would change in a dynamic manner. Secondly, that AA-induced clotting will be modified despite complete suppression of platelet TXB2 production by aspirin throughout the periprocedural period, possibly via a lipoxygenase-mediated mechanism. Fourty patients underwent major vascular surgery (open abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of aspirin prior to and throughout the perioperative period and received 5000 units of unfractionated heparin intraoperatively. AA-, ADP- and thrombin- induced clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12- HETE)) and inflammatory markers (CRP, IL-6, TNF-α and CD40) were measured preprocedure and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and thrombin- induced platelet reactivity was assessed using thrombelastography. TxB2, 12- HETE, IL-6, TNF-α, CD40 were determined using the sequential competitive binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an immune-turbidimetric test on human serum. There was a transient rise in inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3 to 5 days pThrombin at 48 hours p=0.001 and 3 to 5 days pAA and MAADP p=0.001 at 2 hours). At 3 months, the level of AA- and ADP-induced clotting was significantly higher than at baseline (p=0.008 for MAAA and p=0.002 for MAADP), hence demonstrating a rebound effect. These data demonstrate a novel dynamic variation in platelet aggregation with acute vascular inflammation, including AA-induced whole blood clotting which is apparently COX-1 independent.

The introduction of the highly sensitive troponin (hs-trop) assays into clinical practice has allowed for the more rapid diagnosis or exclusion of type 1 myocardial infarctions (T1MI) by clinicians, in addition type 2 myocardial infarctions (T2MI) are now more frequently detected. Tachyarrhythmias are one of the common causes of T2MI, the medium and long term outcome for this cohort of T2MI is yet to be clarified.Retrospective review of consecutive patients admitted with a diagnosis of either (a) non ST-elevation myocardial infarction (NSTEMI) or (b) tachyarrhythmia was performed. Data were collected on patient demographics and investigations. Patient mortality status was recorded through the Personal Demographics Service (PDS) via NHS Digital.A total of 704 patients were eligible for inclusion to the study. 264 patients were included in the study with a final discharge diagnosis of NSTEMI and 440 patients with a final discharge diagnosis of tachyarrhythmia. There was a significantly higher peak troponin in NSTEMI patients compared to the tachyarrhythmia troponin positive group (4552ng/L vs 571ng/L, p0.001). Mortality was significantly higher in the troponin positive tachyarrhythmia patients than the troponin negative patients (54 vs 34, 26.2% vs 14.5%, log rank p=0.003), furthermore, the mortality of NSTEMI and troponin positive tachyarrhythmia patients was similar (55 vs 54, 20.8% vs 26.2%, log rank p=0.416). Only one patient (0.14%) was given a formal diagnosis of T2MI.These data suggest that troponin positive tachyarrhythmia is not a benign diagnosis, and has a mortality rate similar to NSTEMI. Formal labeling as T2MI is rare in real life practice. More investigation into the detection and management of T2MI and troponin positive arrhythmia patients is now warranted.

Background\ud The assessment of patients presenting with angina using invasive angiography alone is imperfect. By contrast, fractional flow reserve (FFR) allows for assessment of lesion-specific ischemia, which is predictive of clinical outcome. A series of studies has demonstrated that the availability of FFR data at the time of diagnostic angiography leads to significant differences in the management of those patients.\ud \ud Hypothesis: The objective of this paper is to assess the consistency in the difference in management resulting from an FFR-directed versus and angiogram-directed strategy in appropriate observational and randomized trials.\ud \ud Methods\ud A methodical search was made using MEDLINE, Current Contents Connect, Google Scholar, EMBASE, Cochrane library, PubMed, Science Direct, and Web of Science.\ud \ud Results\ud Eight studies were identified using the eligibility criteria. A total of 2468 patients were recommended to have optimal medical therapy (OMT) alone after initial angiographic assessment but, after FFR results were available, a total of 716 (29.0%) were referred for revascularization (PCI 626 patients [25.36%]; CABG 90 patients [3.64%]). Similarly, 3766 patients were originally committed to PCI after initial angiography: of these 1454 patients (38.61%) were reconsidered to be suitable for OMT alone and 71 individuals (1.8%) were deemed suitable for CABG after FFR data were available. Further, of 366 patients referred for CABG based on angiographic data, the availability of FFR data changed the final decision to OMT alone in 65 patients (17.76%) and PCI in 51 patients (13.9%). Overall, the angiogram-derived management was changed in 22%–48% of these study populations when FFR data were available.\ud \ud Conclusions\ud Some use of FFR during coronary angiography alters the angiogram-directed management in a remarkably consistent manner. These data suggest that routine use of FFR at the diagnostic angiogram would improve patient care.