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Trials suggest patients with ST-elevation myocardial infarction (STEMI) without 'standard modifiable cardiovascular risk factors' (SMuRFs) have poorer outcomes, but the role of ethnicity has not been investigated. We analyzed 118,177 STEMI patients using the Myocardial Ischaemia National Audit Project (MINAP) registry. Clinical characteristics and outcomes were analyzed using hierarchical logistic regression models; patients with ≥1 SMuRF (n = 88,055) were compared with 'SMuRFless' patients (n = 30,122), with subgroup analysis comparing outcomes of White and Ethnic minority patients. SMuRFless patients had higher incidence of major adverse cardiovascular events (MACE) (odds ratio, OR: 1.09, 95% CI 1.02-1.16) and in-hospital mortality (OR: 1.09, 95% CI 1.01-1.18) after adjusting for demographics, Killip classification, cardiac arrest, and comorbidities. When additionally adjusting for invasive coronary angiography (ICA) and revascularisation (percutaneous coronary intervention (PCI) or coronary artery bypass grafts surgery (CABG)), results for in-hospital mortality were no longer significant (OR 1.05, 95% CI .97-1.13). There were no significant differences in outcomes according to ethnicity. Ethnic minority patients were more likely to undergo revascularisation with ≥1 SMuRF (88 vs 80%, P < .001) or SMuRFless (87 vs 77%, P < .001. Ethnic minority patients were more likely undergo ICA and revascularisation regardless of SMuRF status.

Background: Biodegradable polymer drug-eluting stents were developed to improve safety and efficacy outcomes for patients undergoing percutaneous coronary intervention. However, few long-term follow-up efficacy studies are available. The study sought to investigate 5-year results from the SORT OUT VII trial (Scandinavian Organization for Randomized Trials With Clinical Outcome) comparing the biodegradable polymer ultrathin-strut sirolimus-eluting Orsiro stent (O-SES) versus the biodegradable polymer biolimus-eluting Nobori stent (N-BES). Methods: This registry-based, randomized, multicenter, single-blinded, noninferiority trial compared O-SES and N-BES in an all-comer population. The composite primary end point, target lesion failure, consisted of cardiac death, myocardial infarction related to the target lesion, or target lesion revascularization within 1 year. Follow-up was extended to 5 years. Results: Five-year follow-up was completed for 2521 patients (99.8%). Five-year target lesion failure did not differ between O-SES (12.4%) and N-BES (13.1%; rate ratio [RR], 0.94 [95% CI, 0.75–1.18]). Cardiac death (RR, 0.95 [95% CI, 0.67–1.34]), target myocardial infarction (RR, 1.14 [95% CI, 0.76–1.71]), target lesion revascularization (RR, 0.90 [95% CI, 0.67–1.21]), and definite stent thrombosis rates (RR, 0.73 [95% CI, 0.41–1.33]) did not differ significantly between the 2 stents. Within the first year, definite ST was significantly lower for O-SES (0.4%) compared to N-BES (1.2%; RR, 0.33 [95% CI, 0.12–0.92]), but no difference was from 1 through 5 years: O-SES 1.2% and N-BES 0.9% (RR, 1.28 [95% CI, 0.58–2.82]). Conclusions: Five years after treatment with biodegradable polymer stents, target lesion failure did not differ among O-SES and N-BES. Definite stent thrombosis was less often seen within the first year in the O-SES but the difference was not maintained after 5 years. Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT01879358.

OBJECTIVES: To compare the efficacy and safety of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (O-SES) in patients with and without acute coronary syndrome (ACS) included in the SORT OUT X study.BACKGROUND: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with ACS when compared to patients without ACS. Whether the results from the SORT OUT X study apply to patients with and without ACS remains unknown.METHODS: In total, 3146 patients were randomized to stent implantation with DTS (n = 1578; ACS: n = 856) or O-SES (n = 1568; ACS: n = 854). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year.RESULTS: At 1 year, the rate of TLF was higher in the DTS group compared to the O-SES group, both among patients with ACS (6.7% vs. 4.1%; incidence rate ratio: 1.65 [95% confidence interval, CI: 1.08-2.52]) and without ACS (6.0% vs. 3.2%; incidence rate ratio: 1.88 [95% CI: 1.13-3.14]). The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without ACS CONCLUSION: Compared to the O-SES, the DTS was associated with a higher risk of TLF at 12 months in patients with and without ACS. The differences were mainly explained by higher rates of TLR.

BACKGROUND: Coronary artery disease (CAD) frequently coexists with severe aortic valve stenosis (AS) in patients planned for transcatheter aortic valve implantation (TAVI). How to manage CAD in this patient population is still an unresolved question. In particular, it is still not known whether fractional flow reserve (FFR) guided revascularization with percutaneous coronary intervention (PCI) is superior to medical treatment for CAD in terms of clinical outcomes. STUDY DESIGN: The third Nordic Aortic Valve Intervention (NOTION-3) Trial is an open-label investigator-initiated, multicenter multinational trial planned to randomize 452 patients with severe AS and significant CAD to either FFR-guided PCI or medical treatment, in addition to TAVI. Patients are eligible for the study in the presence of at least 1 significant PCI-eligible coronary stenosis. A significant stenosis is defined as either FFR ≤0.80 and/or diameter stenosis >90%. The primary end point is a composite of first occurring all-cause mortality, myocardial infarction, or urgent revascularization (PCI or coronary artery bypass graft performed during unplanned hospital admission) until the last included patient have been followed for 1 year after the TAVI. SUMMARY: NOTION-3 is a multicenter, multinational randomized trial aiming at comparing FFR-guided revascularization vs medical treatment of CAD in patients with severe AS planned for TAVI. publishedVersion

Aims We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site. Methods and results We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%). Conclusion We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.

OBJECTIVES: To compare the efficacy and safety of the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (SES) in patients with and without diabetes mellitus (DM) included in the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X study.BACKGROUND: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with DM when compared to patients without DM. Thus, whether the results from the SORT OUT X study apply to patients with and without DM remains unknown.METHODS: In total 3146 patients were randomized to stent implantation with DTS (n = 1578; DM: n = 279) or SES (n = 1568; DM: n = 271). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year.RESULTS: At 1 year, the rate of TLF was increased in the DTS group compared to the SES group, both among patients with DM (9.3% vs. 4.8%; risk difference: 4.5%; incidence rate ratio: 1.99, 95% confidence interval [CI]: 1.02-3.90) and without DM (5.7% vs. 3.5%; incidence rate ratio: 1.67, 95% CI: 1.15-2.42). The differences were mainly explained by higher rates of TLR.CONCLUSION: Compared to the SES, the DTS was associated with an increased risk of TLF at 12 months in patients with and without DM. The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without DM.

The long-term cardiovascular risk for patients examined with coronary computed tomography angiography (CCTA) to rule out coronary heart disease compared with population controls remains unexplored. A nationwide register-based study including first-time CCTA-examined patients between 2007 and 2017 in Denmark alive 180 days post-CCTA was conducted. We evaluated 5-year outcomes of myocardial infarction (MI) or revascularization and all-cause mortality in 3 distinct CCTA-groups: (1) no post-CCTA preventive pharmacotherapy use (cholesterol-lowering drugs, antiplatelets, or anticoagulants); (2) post-CCTA preventive pharmacotherapy use; and (3) revascularization or MI within 180 days post-CCTA. For each patient group, population controls were matched on age, gender, and calendar year. Absolute risks standardized to the age, gender, selected co-morbidity, and anti-anginal pharmacotherapy distributions of the specific CCTA-examined patients and respective controls were obtained from multivariable Cox regression. Of 110,599 CCTA-examined patients, (1) 48,231 patients were not prescribed preventive pharmacotherapy 180 days post-CCTA; (2) 42,798 patients were prescribed preventive pharmacotherapy within 180 days post-CCTA; and (3) 19,570 patients were diagnosed with MI or revascularized within 180 days post-CCTA. For patient groups 1 to 3 versus respective controls, 5-year MI or revascularization risks were

Background Extracorporeal cardiopulmonary resuscitation (ECPR) has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). Despite growing interest in and a growing body of literature on ECPR for refractory OHCA, robust evidence on patient eligibility is still lacking. Purpose To describe the survival, neurological outcome, and adherence to the national consensus with respect to use of ECPR for OHCA, and to identify factors associated with outcome. Methods Retrospective, observational cohort study of patients who underwent ECPR for OHCA at four cardiac arrest centres. Binary logistic regression and Kaplan-Meier survival curves were performed to assess association with 30-day mortality. Results A total of 259 patients receiving ECPR for OHCA between July 2011 and December 2020 were included in the study. Thirty-day survival was 26% and a good neurological outcome Cerebral Performance Category (CPC) 1–2 was observed in 94% of patients at discharge. Strict adherence to the national consensus showed a 30-day survival rate of 30%. Adding one or more of the following criteria to the national consensus: signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow 6.8 and lactate 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had threefold higher survival rate than patients without signs of life (45% versus 13%, p Conclusion A high survival rate with a good neurological outcome was observed in this population of patients treated with ECPR for OHCA. Signs of life during CPR may aid the decision-making in the selection of appropriate candidates. Stringent patient selection for ECPR may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors, why optimization of the selection criteria is still necessary. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported by the Danish Heart Foundation [20-R142-A9498-22178]; and Health Research Foundation of Central Denmark Region [R64-A3178-B1349] Survival and adherence to consensusSigns of life during CPR

Background: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody–coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. Methods: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021. Results: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26–2.41]; P =0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37–3.61]; P =0.0012). Conclusions: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03216733.

Background Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. Methods This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan–Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. Results A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow 6.8 and lactate 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52–0.76). Conclusions A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

BackgroundIn patients with stable angina (SA), the clinical benefits of percutaneous coronary intervention (PCI) reside almost exclusively within the realm of symptomatic improvement rather than improvement in hard clinical endpoints. The benefits of PCI should always be balanced against its potential short-term and long-term risks. Common among these risks is the presence of anaemia and its interaction with poor clinical outcomes and increased morbidity; this study aims to elucidate the impact of anaemia on long-term clinical outcomes of this patient group.MethodsFrom Danish national registries, we identified patients with SA treated with PCI who had a haemoglobin measurement maximum of 90 days prior to PCI procedure. Anaemia was defined as haemoglobin ResultsOf 2837 included patients, 14.6% had anaemia prior to PCI. During follow-up, 93 patients (3.3%) had a bleeding episode, which was higher in patients with anaemia (5.8%) compared with patients without anaemia (2.8%). A total of 213 patients (7.5%) developed ACS, which was higher in patients with anaemia (10.6%) compared with patients without anaemia (7.0%). Furthermore, 185 patients (6.5%) died, with a mortality rate of 18.1% in patients with anaemia compared with 4.5% in patients without anaemia. In multivariable analyses, anaemia was associated with a significantly increased risk of bleeding (HR 1.69; 95% CI 1.04 to 2.73; P 0.033), ACS (HR 1.47; 95% CI 1.04 to 2.10; P 0.031) and all-cause mortality (HR 2.41; 95% CI 1.73 to 3.30; P ConclusionAnaemia in patients with SA was significantly associated with bleeding, ACS and all-cause mortality following PCI.

Objective: The objective of the current study is to determine the characteristics of myocardial infarction with non-obstructive coronary arteries (MINOCA) patients with and without cardiac magnetic resonance (CMR) abnormalities.Methods: We evaluated patients admitted with a presentation of acute myocardial infarction (MI) with no coronary obstruction on invasive angiography in our institution between 2012 and 2017. Patients with prior cardiac disease, myocarditis, Takotsubo cardiomyopathy and type 2 myocardial infarction were excluded. Myocardial fibrosis was determined by late gadolinium enhancement (LGE). Patients were divided into two groups based on the presence or absence of CMR abnormalities (LGE or oedema). Major adverse cardiovascular events (MACE) were defined as non-fatal MI, all-cause mortality, ventricular arrythmias or heart failure hospitalisation at follow-up.Results: Thirty-four patients fulfilling the inclusion criteria were identified. Myocardial changes with CMR were observed in 20 (59%) patients with signs of subendocardial infarct by LGE in 13 (38%) patients, transmural infarct by LGE in 6 (18%) patients and one patient had myocardial oedema. ECG and echocardiographic features were similar between patients with and without CMR abnormalities. Troponin T was significantly higher among patients with CMR abnormalities. The median duration of follow-up was 702 (IQR 456-1394) days. Two patients had MACE (both heart failure). One of them had LGE changes.Conclusions: A significant number of patients with MINOCA have ischaemic LGE changes or myocardial wall oedema. The patients with CMR abnormalities have similar ECG and echocardiographic features except higher biomarker, highlighting the role of CMR in patients with MINOCA.

Background According to Danish national guidelines, coronary computed tomography angiography (CCTA) is the preferred frontline test in patients without known coronary artery disease (CAD) and stable symptoms indicative of CAD. Over the last decade in Denmark, we have seen a steadily and considerable increase in CCTA use. Data on long-term cardiovascular risk following CCTA remains limited, in particular in comparison to background population controls. Purpose To study individual and composite five-year outcomes of mortality, myocardial infarction (MI) and revascularization in CCTA-examined patients compared to background population controls. Methods Nationwide registry-based study including 58,176 patients with an incident CCTA examination during 2007–2014 in Denmark versus 116,352 age- and sex-matched population controls. Despite no detailed information on CCTA results were available, a landmark analysis including patients and corresponding controls alive six months post-CCTA enabled us to study five patient categories: 1) 19,135 patients with no relevant medical therapy (nitrates, cholesterol-lowering, antiplatelet and/or anticoagulant drugs) before or 180 days post-CCTA; 2) 6,073 patients on relevant medical therapy prior to but not 180 days post-CCTA; 3) 5,086 patients who initiated relevant medical therapy during 180 days post-CCTA; 4) 19,809 patients on relevant medical therapy both before and during 180 days post-CCTA; and 5) 8,073 patients with myocardial infarction (MI) or treated with percutaneous intervention (PCI) or coronary artery bypass surgery (CABG) within 180 days post-CCTA. Within each CCTA patient group, two controls matched on age and sex were identified for each CCTA patient. Neither CCTA-patients nor controls had prior ischemic heart disease. Results Outcomes of MI for CCTA patient groups 1)-5) versus controls were: 0.3%, 0.6%, 0.8%, 0.7%, and 11.4% versus 0.7%, 1.1%, 1.0%, 1.1%, and 1.5%. Corresponding figures for all-cause mortality were: 2.2%, 2.0%, 4.1%, 4.9%, and 6.8%, versus 2.1%, 2.8%, 4.2%, 4.3%, and 6.4%. For composite endpoint of MI, PCI or CABG, results for CCTA patients versus controls were: 0.3%, 0.6%, 0.8%, 0.7%, and 18.2% versus 0.9%, 1.3%, 1.2%, 1.4%, and 1.9%. Lastly, for composite endpoint of MI, PCI, CABG or death, results for CCTA patients versus controls were: 2.5%, 2.6%, 4.8%, 4.9%, and 24.2% versus 3.0%, 3.9%, 5.3%, 6.1%, and 8.0%. Conclusions Only the CCTA group treated with PCI or CABG or diagnosed with MI during the first 180 days post-CCTA had substantially higher five-year MI event rates and composite endpoints of MI, PCI or CABG and MI, PCI, CABG or death. In addition, no difference in five-year all-cause mortality was seen for all CCTA patient groups when compared to their respective controls. Altogether, the majority of CCTA-examined patients were event-free at five-year follow-up suggesting a potential overutilization of CCTA and a need for refinement of CCTA referral criteria.

BACKGROUND: Clinical predictors of future ischemic events in patients with acute coronary syndrome (ACS) are also risk factors for bleeding, with patients often at high-risk of both outcomes. We aimed to define the clinical outcomes and provision of guideline-recommended care in ACS management for different combinations of ischemic and bleeding risk defined using a combined GRACE and CRUSADE score.METHODS: A retrospective observational analysis of a national ACS database was performed for patients with ACS admitted to three tertiary centres from January 2010 to March 2016. Patients were stratified into 9 groups based on possible CRUSADE-GRACE risk combinations. Multiple logistic regression was used to estimate adjusted odds ratios (ORs [95% CI]) for outcomes (in-hospital net adverse cardiac events (NACE), in-hospital all-cause mortality, 30-day mortality and treatment strategy).RESULTS: A total of 17,701 patients were included in the analysis. We observed a graded risk of mortality and adverse events in the high-risk GRACE strata (Groups 3, 6 and 9). Almost a third of patients with ACS were at a 'dual high-risk' (Group 9, 32%) and were independently associated with higher in-hospital NACE (composite of cardiac mortality, all-cause bleeding and re-infarction): aOR 6.33 [3.55, 11.29], all-cause mortality: aOR 14.17 [5.27, 38.1], all-cause bleeding: aOR 4.82 [1.96, 11.86], and 30-day mortality: aOR 10.79 [5.33, 21.81]. This group was also the least likely to be offered coronary angiography (aOR 0.24 [0.20, 0.29]) and dual anti-platelet therapy (aOR 0.26 [0.20, 0.34]).CONCLUSIONS: One in five patients presenting with an ACS are high ischemic and high bleeding risk, and these patients are more likely to experience poor clinical outcomes and reduced odds of receiving guideline-recommended therapy.

AIMS: We aimed to investigate major adverse cardiac events (MACE: defined as all-cause mortality, re-infarction, and stroke), length of hospital stays (LOS), and comorbidities following acute coronary syndrome (ACS) in a population with schizophrenia.METHODS AND RESULTS: This Danish register study included patients diagnosed with ACS in the period between 1995 and 2013 with a preceding diagnosis of schizophrenia (n = 726). Each patient was matched to a psychiatric healthy control 1:2 on sex, age, year of ACS diagnosis, and number of comorbidities (total n = 2178). After performing Cox regression and Kaplan-Meier analyses, we found that patients with schizophrenia had an increased risk of MACE [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.45-1.81], all-cause mortality (HR 2.54, 95% CI 2.22-2.90), and stroke (HR 1.51, 95% CI 1.15-1.99). No differences were found in the re-infarction rates and LOS between the populations. Patients with schizophrenia had higher prevalence's diabetes, anaemia, heart failure, cardiomyopathy, chronic obstructive lung disease, and stroke. Nonetheless, we found lower prevalence's of hypertension and hyperlipidaemia.CONCLUSION: Schizophrenia is associated with an increased risk of MACE despite a lower prevalence of some diagnosed traditional cardiac risk factors which may indicate underdiagnosing of these. Awareness of treatment bias may improve this increased risk. (Less)

Background High on treatment platelet reactivity (HTPR) is common in patients receiving clopidogrel following an acute coronary syndrome (ACS); it's also associated with increased morbidity and mortality. More potent and predictable antiplatelet drugs have addressed this issue at the expense of increased bleeding. Identification of HTPR and the targeted use of more potent antiplatelet drugs has, so far, broadly failed. We investigate this approach in terms of the timing of platelet function testing and how this can impact on the ability of these bedside tests to predict HTPR around the time of coronary intervention. Methods High risk ACS patients treated with 5 days of clopidogrel had platelet function assessed using the multiple electrode aggregometry system (MEA) pre, post and 24 h following percutaneous coronary intervention (PCI). Simultaneous detailed analysis of platelet status was undertaken with quantification of platelet bound and soluble p-selectin and mass spectrometry quantification of the eicosanoid 12-HETE. Results As assessed by MEA 40.5% of patients had HTPR pre-PCI; mean aggregation units (AU) in response to ADP were 499.1 ± 46.3 pre-PCI, 407.6 ± 37.7 post-PCI and 269.1 ± 24.6 AU 24 h post-PCI (pre to post PCI p > 0.05, pre to 24 h post-PCI p = 0.0002). This highly significant drop in platelet reactivity was contrasted with on-going expression of platelet bound p-selectin, increased soluble p-selectin and rising 12-HETE concentrations. Conclusions This study outlines significant changes in ex-vivo platelet aggregation that occur within 24 h of PCI in high risk NSTEMI patients using bedside PFT. Whilst there were no changes in antiplatelet therapy during the study period its clear that timing is crucial when assessing high on treatment residual platelet activity.

Background: Friday the 13th is described as an “unlucky” day that brings misfortune. There are few studies on the question, and none on its effect in cardiovascular patients. The recently misreported “weekend effect” has led to changes in the junior doctor contract in England, providing greater staffing levels on weekends. Should we make similar provisions for Friday the 13th? Methods: A retrospective analysis of a large database for patients admitted to hospitals in South Wales with an acute coronary syndrome (ACS) during 1999–2014. Mortality rates for 217 admission day number/name combinations and for Friday the 13th were compared in a Cox proportional hazards regression model. Results: 56 062 ACS patients were identified. There were no significant differences in 13-year mortality between most admission dates (211 of 216) and Friday the 13th. However, a statistically significant reduction in mortality was identified for five dates: Thursday the 15th (HR, 0.77; 95% CI, 0.59–0.999), Wednesday the 18th (HR, 0.76; 95% CI, 0.58–0.99), Monday the 28th (HR, 0.76; 95% CI, 0.57–0.99), Monday the 30th (HR, 0.75; 95% CI, 0.57–0.99) and Tuesday the 31st (HR, 0.71; 95% CI, 0.51–0.99). Conclusion: On most days, there was no difference in the 13-year mortality rate for patients admitted with their first ACS from that for “unlucky” Friday the 13th. However, patients admitted on five day/number combinations were 20–30% more likely to survive at 13 years. These findings could be explained by subgroup analysis inflation of the type I error, although supernatural causes merit further investigation. Our findings should be taken into account in future junior doctor contract negotiations, and may provide a case for reduced staffing levels on these lucky days.

Aim: Statins have a proven role for the secondary prevention of cardiovascular disease. Despite this, typical patient use in real life is variable. Our aim was to investigate the typical clinical use, including adherence, for statins in a sample population in South Wales (UK). Methods: We identified 2248 patients admitted to hospitals in South Wales with acute coronary syndrome using a retrospective 3-year-long longitudinal study. We performed data linkage using the Secure Anonymized Information Linkage databank. Results & conclusion: In total, 1806 (80.3%) of patients were initiated on statins at discharge, with simvastatin being most common. Only 38% of patients were on high-intensity dosage. There was minimal change in cholesterol levels, with discontinuation rates of 53.7 and 84.3% at 1- and 3-year follow-up, respectively.

BACKGROUND: Psychiatric and cardiac comorbidities form the top two budget categories for health systems in high-income countries with evidence that psychiatric pre-morbidities lead to worse outcomes in patients with acute coronary syndrome (ACS). There are no studies examining this relationship in a national multicentre population level study in the UK, and no studies examining their impact on length of in-hospital stay (LoS) in ACS. Recognizing at-risk populations and reducing LoS in ACS is an essential part of improving patient care and cost-effectiveness.METHODS: We investigated the impact of psychiatric diagnoses on morbidity, all-cause mortality and LoS amongst 57,668 ACS patients between Jan-2004 and Dec-2014 using the Secure-Anonymized-Information-Linkage (SAIL) databank. Demographics, admissions, cardiac and psychiatric comorbidities were identified using coded data.RESULTS: There were a total of 3857 out of 57,668 patients who had a pre-morbid psychiatric diagnosis. The mean LoS in patients without psychiatric comorbidities was 9.78days (95% CI: 9.66-9.91). This was higher (pCONCLUSIONS: Our results demonstrate that psychiatric comorbidities have a significant and clinically important impact on morbidity, mortality and LoS in ACS patients in Wales, UK. Clinicians' awareness and active management of psychiatric conditions amongst ACS patients is needed to reduce poor outcomes and LoS and ultimately the risk for patients and financial burden for the health-service.

Current clinical practice regarding surveillance period and length of hospital stay after an ST elevation myocardial infarction is very variable among different countries and hospitals. In general, there has been a significant reduction in length of stay overall, which is mainly due to the increasing use of primary percutaneous coronary intervention. Length of stay after a ST elevation myocardial infaction, which is a rather common event, has a major impact on health care costs and patients' quality of life. We try to evaluate how far we could push the limits.

Objectives: Determine the real-world difference\ud between 2 groups of patients with severe aortic\ud stenosis and similar baseline comorbidities: surgical\ud turn down (STD) patients, who were managed\ud medically prior to the availability of transcatheter aortic\ud valve implantation (TAVI) following formal surgical\ud outpatient assessment, and patients managed with a\ud TAVI implant.\ud Design: Retrospective cohort study from real-world\ud data.\ud Setting: Electronic patient letters were searched for\ud patients with a diagnosis of severe aortic stenosis and\ud a formal outpatient STD prior to the availability of TAVI\ud (1999–2009). The second group comprised the first 90\ud cases of TAVI in South Wales (2009 onwards). 2 years\ud prior to and 5 years following TAVI/STD were assessed.\ud Patient data were pseudoanonymised, using the Secure\ud Anonymized Information Linkage (SAIL) databank, and\ud extracted from Office National Statistics (ONS), PatientEpisode\ud Database for Wales (PEDW) and general\ud practitioner databases.\ud Population: 90 patients who had undergone TAVI in\ud South Wales, and 65 STD patients who were medically\ud managed.\ud Main outcome measures: Survival, hospital\ud admission frequency and length of stay, primary care\ud visits, and cost-effectiveness.\ud Results: TAVI patients were significantly older (81.8 vs\ud 79.2), more likely to be male (59.1% vs 49.3%),\ud baseline comorbidities were balanced. Mortality in TAVI\ud versus STD was 28% vs 70% at 1000 days follow-up.\ud There were significantly more hospital admissions per\ud year in the TAVI group prior to TAVI/STD (1.5 (IQR 1.0–\ud 2.4) vs 1.0 IQR (0.5–1.5)). Post TAVI/STD, the TAVI\ud group had significantly lower hospital admissions (0.3\ud (IQR 0.0–1.0) vs 1.2 (IQR 0.7–3.0)) and lengths of stay\ud (0.4 (IQR 0.0–13.8) vs 11.0 (IQR 2.5–28.5), p

This review outlines the priorities from cardiology and gastroenterology perspectives, resolves some of the misconceptions, and uses the evidence available to suggest strategies for optimizing management of these patients. The dual presentation of acute active gastrointestinal (GI) blood loss together with an acute coronary syndrome (NSTEACS or STEMI) is outside the remit of this review but has been previously reviewed by our group. The review covers NSTEACS together with chronic or sub-acute anemia, anemia that cannot be accounted for by chronic kidney disease, heart failure, or inflammatory disorders. Identification of a potential GI etiology of anemia is important as it allows adjustment to both GI and CV investigations and treatments that can reduce the likelihood and impact of bleeding complications.

Aortic stenosis is the most common valvular heart disease, affecting 4.6% of adults older than 75 years. Patients at high risk of surgical complication were historically treated medically. Transcatheter Aortic Valve Implantation (TAVI) allowed access to a therapy that reduced symptoms and mortality

FFR is the gold standard method of measuring stenosis-specific ischaemia and guiding revascularisation. Furthermore IMR measurement has prognostic predictive value in post STEMI patients. Both techniques are based on the presence of maximal hyperaemia, if not present there can be an underestimate of

Multiple alignment of several isozyme sequences of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase revealed conserved residues in the 2-kinase domain. Among these residues, three asparagine residues (Asn76, Asn97 and Asn133; numbering refers to the liver isozyme sequence) and three threonine residues (Thr132, Thr134 and Thr135) are located near the fructose 6-phosphate-binding site in the crystal structure of the bifunctional enzyme. The role of these residues in substrate binding and catalysis in the 6-phosphofructo-2-kinase domain has been studied by mutagenesis to alanine. Since the crystal structure of 6-phosphofructo-2-kinase does not contain fructose 6-phosphate, this substrate was docked into the putative binding site by computer modelling, and its interactions with the protein were predicted. Analysis of the mutagenesis-induced changes in kinetic properties and of the substrate-docking model revealed that all these residues are directly or indirectly involved in fructose-6-phosphate binding. All the mutants displayed an increased Km for fructose 6-phosphate (10-200-fold). We propose that Asn133 stabilises Arg138, which itself makes a direct electrostatic bond with the 6-phosphate group of fructose 6-phosphate, that Asn76 interacts with the C3 hydroxyl group of fructose 6-phosphate, that Thr132 makes a hydrogen bond with the C6 oxygen of this substrate, and that Thr134 interacts with two residues involved in fructose-6-phosphate binding, Thr132 and Tyr199. On the other hand, Asn97 and Thr135 play structural roles, by maintaining the structure of the fructose-6-phosphate-binding pocket.Multiple alignment of several isozyme sequences of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase revealed conserved residues in the 2-kinase domain. Among these residues, three asparagine residues (Asn76, Asn97 and Asn133; numbering refers to the liver isozyme sequence) and three threonine residues (Thr132, Thr134 and Thr135) are located near the fructose 6-phosphate-binding site in the crystal structure of the bifunctional enzyme. The role of these residues in substrate binding and catalysis in the 6-phosphofructo-2-kinase domain has been studied by mutagenesis to alanine. Since the crystal structure of 6-phosphofructo-2-kinase does not contain fructose 6-phosphate, this substrate was docked into the putative binding site by computer modelling, and its interactions with the protein were predicted. Analysis of the mutagenesis-induced changes in kinetic properties and of the substrate-docking model revealed that all these residues are directly or indirectly involved in fructose-6-phosphate binding. All the mutants displayed an increased Km for fructose 6-phosphate (10-200-fold). We propose that Asn133 stabilises Arg138, which itself makes a direct electrostatic bond with the 6-phosphate group of fructose 6-phosphate, that Asn76 interacts with the C3 hydroxyl group of fructose 6-phosphate, that Thr132 makes a hydrogen bond with the C6 oxygen of this substrate, and that Thr134 interacts with two residues involved in fructose-6-phosphate binding, Thr132 and Tyr199. On the other hand, Asn97 and Thr135 play structural roles, by maintaining the structure of the fructose-6-phosphate-binding pocket.

Although percutaneous coronary intervention (PCI) via radial artery access confers many advantages over the femoral artery, PCI to saphenous vein grafts (SVG) is commonly performed via the femoral route. We compared outcomes in patients undergoing SVG PCI from the radial and femoral routes.We performed a retrospective analysis of patients who underwent SVG PCI between January 2006 and December 2010 in 2 large interventional centers in the United Kingdom. All radial and femoral operators selected for this analysis performed high-volume (200 PCIs per year) procedures via either vascular route.Of 305 patients (260 males) who underwent SVG PCI, 208 (68.2%) had the procedure completed from the femoral route and 97 (32.8%) radially. There was no difference between groups in fluoroscopy time (femoral vs radial 1095 vs 1125 seconds, P nonsgnificant), but radiation doses were greater (43.87 ± 2.83 Gy/cm(2) vs 56.92 ± 4.52 Gy/cm(2), P = .012) as was body mass index in the radial group (27.99 ± 0.33 vs 29.05 ± 0.42, P = .048). Three femoral access patients had vascular access complications, whereas the radial route group had none. There were no differences in no flow/slow flow (femoral 3.86% vs radial 2.54%, P nonsignificant). The mean length of hospital stay was significantly shorter in the radial access cohort (1.09 vs 2.09 days, P.001). Three patients converted from radial to femoral artery, whereas one converted from femoral to radial after technical failure to complete the procedure.Saphenous vein graft PCI can be safely and effectively performed via radial artery access with comparable fluoroscopy times but not radiation doses. Of clinical significance, use of the radial artery access was associated with decreased hospital stay and arterial complications. These data suggest that a routine radial approach for SVG PCI is feasible and could offer clinical and economic benefits.

There is growing evidence that PCI via radial artery access confers advantages over the femoral artery. While PCI to saphenous vein grafts (SVG) is commonly performed via the femoral route because of a perception that SVG cannulation and treatment is too difficult, there is little data examining

Coronary heart disease mortality has been falling steadily over the past four to five decades. In parallel, increasing numbers of people are surviving myocardial infarction (MI) and many face the challenges of a life with heart failure. Indeed, those with substantial myocardial injury often remain symptomatically limited even with aggressive modern management including revascularisation, an optimal medication regimen and, where appropriate, resynchronisation therapy. Immediate reperfusion remains the best way to minimise left ventricular (LV) injury and subsequent dysfunction. However, despite streamlined systems of care and high profile public awareness campaigns all too many myocardial infarctions (MIs) present late or the diagnosis is missed. Thus, development and refinement of novel methodology for the repair of damaged cardiac tissue remain a major priority. One such strategy is to attempt to harness the body’s own endogenous cellular repair mechanisms. Cell populations with the potential to differentiate into mature cardiovascular cells under appropriate conditions have been identified in the bone marrow and peripheral blood of adult humans. These cells appear to participate in the maintenance of healthy cardiovascular function, although their ability to differentiate into mature cardiac myocytes that integrate into a functional myocardial syncytium remains a controversial and hotly debated issue.1 The biology of these cardiovascular progenitor cells is complex and tightly regulated and there is considerable heterogeneity between individuals in the number and quality of these cells, even for those with similar clinical conditions. These issues pose great challenges to researchers. Promising early studies in animal models and patients with MI suggest that cell therapy may attenuate LV damage and improve functional capacity, although the benefits appear modest and the exact mechanisms remain unclear at this stage.2–6 Several cell types have been studied, including unselected or specific fractions of bone marrow-derived or peripheral blood mononuclear cells (PBMCs), which …

Background: Coronary artery disease (CAD) is a major public and economic health problem. Coronary angiography is a gold standard for diagnosing CAD and is indicated in patients with 61–90% pre-test probability of the disease when the diagnosis cannot be made on clinical grounds alone and when revascularisation is being considered. The natural history of normal coronary angiogram is poorly understood. Objectives: To evaluate the progression of disease in patients with normal coronary angiography and to assess the overall survival and event-free survival from acute myocardial infarction (MI) in these patients. Methods: We interrogated the Central Cardiac Audit Database (CCAD) between November 2005 and December 2013 to identify patients with normal or ‘near-normal’ coronary angiography. Demographic, clinical and angiographic data was recorded. This database was linked with the Patient Episode Database for Wales (PEDW) and the datasets from the Office for National Statistics (for mortality) using the Secure Anonymised Information Linkage (SAIL) databank. This allowed for the extraction of information from all the sources above on the basis of the International Statistical Classification of Diseases (ICD-10) using the Structured Query Language (SQL). Results: Out of over 20,000 patients undergoing coronary angiography between November 2005 and December 2013, 5032 patients had normal coronaries and minor CAD. Of 5032 patients, 136 underwent repeat angiography, with 131 (96.3%) and 5 (3.7%) patients having two and three repeat investigations respectively. Mean time between procedures was 3.3 (±1.82) years. Of those 136 patients, at the median follow up of 6.8 years, no change in disease progression was demonstrated in 108 (79.4%) patients on the follow up studies. In the remaining 28 (20.6%) patients, normal coronaries progressed to minor CAD. No patients progressed beyond minor CAD. Patients with normal coronaries had significant better survival than patients with minor CAD (p 99.5% in both groups at the median of 5 years follow up. (p = 0.09) Conclusions: Normal coronary angiography and minor CAD is unlikely to progress to significant disease at 7 years and the incidence of MI in these patients is rare at 5 years. Therefore, repeating coronary angiography within at least 5 years is not indicated.