Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

The Impact of Acute Kidney Injury on Chronic Kidney Disease After Cardiac Surgery: A Systematic Review and Meta-analysis.

OBJECTIVES: To evaluate the impact of acute kidney injury on transition to chronic kidney disease (CKD) after cardiac surgery and to determine frequency of incident CKD in these patients. DESIGN: A systematic review and meta-analysis of observational studies. SETTING: Electronic databases Medline and Embase were systematically searched from 1974 to February 6, 2023. PARTICIPANTS: Eligible studies were original observational studies on adult cardiac surgery patients, written in the English language, and with clear kidney disease definitions. Exclusion criteria were studies with previously transplanted populations, populations with preoperative kidney impairment, ventricular assist device procedures, endovascular procedures, a kidney follow-up period of <90 days, and studies not presenting necessary data for effect size calculations. INTERVENTIONS: Patients developing postoperative acute kidney injury after cardiac surgery were compared with patients who did not develop acute kidney injury. MEASUREMENTS AND MAIN RESULTS: The search identified 4,329 unique studies, 87 underwent full-text review, and 12 were included for analysis. Mean acute kidney injury occurrence across studies was 16% (minimum-maximum: 8-50), while mean occurrence of CKD was 24% (minimum-maximum: 3-35), with high variability depending on definitions and follow-up time. Acute kidney injury was associated with increased odds of CKD in all individual studies. The pooled odds ratio across studies was 5.67 (95% confidence interval, 3.34-9.64; p < 0.0001). CONCLUSIONS: Acute kidney injury after cardiac surgery was associated with a more than 5-fold increased odds of developing CKD. New-onset CKD occurred in almost 1 in 4 patients in the years after surgery.

Early healing after treatment of coronary lesions by thin strut everolimus, or thicker strut biolimus eluting bioabsorbable polymer stents: The SORT-OUT VIII OCT study.

AIMS: Early healing after drug-eluting stent (DES) implantation may reduce the risk of stent thrombosis. The aim of this study was to compare patterns of early healing after implantation of the thin strut everolimus-eluting Synergy DES (Boston Scientific) or the biolimus-eluting Biomatix Neoflex DES (Biosensors). METHODS AND RESULTS: A total of 160 patients with the chronic or acute coronary syndrome were randomized 1:1 to Synergy or Biomatrix DES. Optical coherence tomography (OCT) was performed at baseline and at either 1- or 3-month follow-up. The primary endpoint was a coronary stent healing index (CSHI), a weighted index of strut coverage, neointimal hyperplasia, malapposition, and extrastent lumen. A total of 133 cases had OCT follow-up and 119 qualified for matched OCT analysis. The median CSHI score did neither differ significantly between the groups at 1 month: Synergy 8.0 (interquartile range [IQR]: 3.0; 14.0) versus Biomatrix 8.5 (IQR: 4.0; 15.0) (p = 0.47) nor at 3 months: Synergy 6.5 (IQR: 2.0; 13.0) versus Biomatrix 6.0 (IQR: 4.0; 11.0) (p = 0.83). Strut coverage was 84.6% (IQR: 72.0; 97.9) for Synergy versus 77.6% (IQR: 70.1; 90.3) for Biomatrix (p = 0.15) at 1 month and 90.3% (IQR 79.0; 98.8) (Synergy) versus 83.9% (IQR: 77.5; 92.6) (Biomatrix) (p = 0.068) at 3 months. Pooled 1- and 3-month coverage was 88.6% (IQR: 74.4; 98.4) for Synergy compared with 80.7% (IQR: 73.2; 90.8) for Biomatrix (p = 0.02). CONCLUSIONS: The early healing response after treatment with the Synergy or Biomatrix DES did not differ significantly as determined by a healing index. The Synergy DES showed overall better early stent strut coverage.

Bifurcation left main stenting with or without intracoronary imaging: Outcomes from the EBC MAIN trial.

BACKGROUND: The impact of intracoronary imaging on outcomes, after provisional versus dual-stenting for bifurcation left main (LM) lesions, is unknown. OBJECTIVES: We investigated the effect of intracoronary imaging in the EBC MAIN trial (European Bifurcation Club LM Coronary Stent study). METHODS: Four hundred and sixty-seven patients were randomized to dual-stenting or a stepwise provisional strategy. Four hundred and fifty-five patients were included. Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was undertaken at the operator's discretion. The primary endpoint was death, myocardial infarction or target vessel revascularization at 1-year. RESULTS: Intracoronary imaging was undertaken in 179 patients (39%; IVUS = 151, OCT = 28). As a result of IVUS findings, operators reintervened in 42 procedures. The primary outcome did not differ with intracoronary imaging versus angiographic-guidance (17% vs. 16%; odds ratio [OR]: 0.92 (95% confidence interval [CI]: 0.51-1.63) p = 0.767), nor for reintervention based on IVUS versus none (14% vs. 16%; OR: 0.88 [95% CI: 0.32-2.43] p = 0.803), adjusted for syntax score, lesion calcification and ischemic symptoms. With angiographic-guidance, primary outcome events were more frequent with dual versus provisional stenting (21% vs. 10%; adjusted OR: 2.11 [95% CI: 1.04-4.30] p = 0.039). With intracoronary imaging, there were numerically fewer primary outcome events with dual versus provisional stenting (13% vs. 21%; adjusted OR: 0.56 [95% CI: 0.22-1.46] p = 0.220). CONCLUSIONS: In EBC MAIN, the primary outcome did not differ with intracoronary imaging versus none. However, in patients with angiographic-guidance, outcomes were worse with a dual-stent than provisional strategy When intracoronary imaging was used, there was a trend toward better outcomes with the dual-stent than provisional strategy.

Impact of technique on bifurcation stent outcomes in the European Bifurcation Club Left Main Coronary Trial.

BACKGROUND: Techniques for provisional and dual-stent left main bifurcation stenting require optimization. AIM: To identify technical variables influencing procedural outcomes and periprocedural myocardial infarction following left main bifurcation intervention. METHODS: Procedural and outcome data were analyzed in 438 patients from the per-protocol cohort of the European Bifurcation Club Left Main Trial (EBC MAIN). These patients were randomized to the provisional strategy or a compatible dual-stent extension (T, T-and-protrude, or culotte). RESULTS: Mean age was 71 years and 37.4% presented with an acute coronary syndrome. Transient reduction of side vessel thrombolysis in myocardial infarction flow occurred after initial stent placement in 5% of procedures but was not associated with periprocedural myocardial infarction. Failure to rewire a jailed vessel during any strategy was more common when jailed wires were not used (9.5% vs. 2.5%, odds ratio [OR]: 6.4, p = 0.002). In the provisional cohort, the use of the proximal optimization technique was associated with less subsequent side vessel intervention (23.3% vs. 41.9%, OR: 0.4, p = 0.048). Side vessel stenting was predominantly required for dissection, which occurred more often following side vessel preparation (15.3% vs. 4.4%, OR: 3.1, p = 0.040). Exclusive use of noncompliant balloons for kissing balloon inflation was associated with reduced need for side vessel intervention in provisional cases (20.5% vs. 38.5%, OR: 0.4, p = 0.013), and a reduced risk of periprocedural myocardial infarction across all strategies (2.9% vs. 7.7%, OR: 0.2, p = 0.020). CONCLUSION: When performing provisional or compatible dual-stent left main bifurcation intervention, jailed wire use is associated with successful jailed vessel rewiring. Side vessel preparation in provisional patients is linked to increased side vessel dissection requiring stenting. Use of the proximal optimization technique may reduce the need for additional side vessel intervention, and noncompliant balloon use for kissing balloon inflation is associated with a reduction in both side vessel stenting and periprocedural myocardial infarction. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02497014.

The European bifurcation club Left Main Coronary Stent study: a randomized comparison of stepwise provisional vs. systematic dual stenting strategies (EBC MAIN).

BACKGROUND: Patients with non-left-main coronary bifurcation lesions are usually best treated with a stepwise provisional approach. However, patients with true left main stem bifurcation lesions have been shown in one dedicated randomized study to benefit from systematic dual stent implantation. METHODS AND RESULTS: Four hundred and sixty-seven patients with true left main stem bifurcation lesions requiring intervention were recruited to the EBC MAIN study in 11 European countries. Patients were aged 71 ± 10 years; 77% were male. Patients were randomly allocated to a stepwise layered provisional strategy (n = 230) or a systematic dual stent approach (n = 237). The primary endpoint (a composite of death, myocardial infarction, and target lesion revascularization at 12 months) occurred in 14.7% of the stepwise provisional group vs. 17.7% of the systematic dual stent group (hazard ratio 0.8, 95% confidence interval 0.5-1.3; P = 0.34). Secondary endpoints were death (3.0% vs. 4.2%, P = 0.48), myocardial infarction (10.0% vs. 10.1%, P = 0.91), target lesion revascularization (6.1% vs. 9.3%, P = 0.16), and stent thrombosis (1.7% vs. 1.3%, P = 0.90), respectively. Procedure time, X-ray dose and consumables favoured the stepwise provisional approach. Symptomatic improvement was excellent and equal in each group. CONCLUSIONS: Among patients with true bifurcation left main stem stenosis requiring intervention, fewer major adverse cardiac events occurred with a stepwise layered provisional approach than with planned dual stenting, although the difference was not statistically significant. The stepwise provisional strategy should remain the default for distal left main stem bifurcation intervention. STUDY REGISTRATION: http://clinicaltrials.gov NCT02497014.

Magnesium(II)-ATP Complexes in 1-Ethyl-3-Methylimidazolium Acetate Solutions Characterized by 31 Mg ß-Radiation-Detected NMR Spectroscopy.

The complexation of MgII with adenosine 5'-triphosphate (ATP) is omnipresent in biochemical energy conversion, but is difficult to interrogate directly. Here we use the spin- 1/2 ß-emitter 31 Mg to study MgII -ATP complexation in 1-ethyl-3-methylimidazolium acetate (EMIM-Ac) solutions using ß-radiation-detected nuclear magnetic resonance (ß-NMR). We demonstrate that (nuclear) spin-polarized 31 Mg, following ion-implantation from an accelerator beamline into EMIM-Ac, binds to ATP within its radioactive lifetime before depolarizing. The evolution of the spectra with solute concentration indicates that the implanted 31 Mg initially bind to the solvent acetate anions, whereafter they undergo dynamic exchange and form either a mono- (31 Mg-ATP) or di-nuclear (31 MgMg-ATP) complex. The chemical shift of 31 Mg-ATP is observed up-field of 31 MgMg-ATP, in accord with quantum chemical calculations. These observations constitute a crucial advance towards using ß-NMR to probe chemistry and biochemistry in solution.

Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention: The SORT OUT IX Trial.

BACKGROUND: In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021. RESULTS: Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; Pnoninferiority=0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66-4.62]; P<0.0001). CONCLUSIONS: The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02623140.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial. METHODS: The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 [95% CI 1·24-2·01]); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 [95% CI 0·74-1·59]; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 [95% CI 1·66-5·39]; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 [95% CI 1·25-2·40]; p=0·0009). INTERPRETATION: In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation. FUNDING: Biosensors.

Coronary Artery Healing Process after Bioresorbable Scaffold in Patients with Non-ST-Segment Elevation Myocardial Infarction: Rationale, Design, and Methodology of the HONEST Study.

BACKGROUND: Bioresorbable scaffolds (BRSs) is a relatively new approach in treating coronary artery stenosis. The initial results of the first commercially available scaffolds consisting of a backbone of poly-L-lactide raised safety concerns related to delayed resorption and healing. The magnesium alloy-based scaffold degrades via bio-corrosion within months, whereas it often takes several years for polymer scaffolds to degrade. The aim of the study was to assess the healing stage by optical coherence tomography (OCT) after 6 months in patients with non-ST-segment elevation myocardial infarct (NSTEMI) randomized to OCT or angiography-guided percutaneous coronary intervention with implantation of a magnesium sirolimus-eluting Magmaris scaffold (Magmaris; Biotronik, Bülach, Switzerland). METHODS: We analyzed the healing process by comparing OCT at baseline and after 6 months. Five stages of healing were defined with stage 1 being the least healed and stage 5 demonstrating complete resorption and healing with no visible scaffold/remnant. The primary end point is a calculated healing score that is based on 5 subtypes of healing stage: (1) malapposed, (2) uncovered with no detection of smooth surface tissue on top of struts or remnants, (3) covered protruding, (4) covered embedded, and (5) complete healing with a smooth neointimal surface and no sign of struts or visible remnants assessed by OCT 6 months after the index procedure. RESULTS: The impact of OCT-guided compared to angiography-guided scaffold implantation will be illuminated. CONCLUSION: The present study will provide new information on midterm healing properties of the magnesium BRS in patients with NSTEMI.

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

European Bifurcation Club white paper on stenting techniques for patients with bifurcated coronary artery lesions.

BACKGROUND: Defining the optimal conduction of percutaneous-coronary-intervention (PCI) to treat bifurcation lesions has been the subject of many clinical studies showing that the applied stenting technique may influence clinical outcome. Accordingly, bifurcation stenting classifications and technical sequences should be standardized to allow proper reporting and comparison. METHODS: The European Bifurcation Club (EBC) is a multidisciplinary group dedicated to optimize the treatment of bifurcations and previously created a classification of bifurcation stenting techniques that is based on the first stent implantation site. Since some techniques have been abandoned, others have been refined and dedicated devices became available, EBC promoted an international task force aimed at updating the classification of bifurcation stenting techniques as well as at highlighting the best practices for most popular techniques. Original descriptive images obtained by drawings, bench tests and micro-computed-tomographic reconstructions have been created in order to serve as tutorials in both procedure reporting and clinical practice. RESULTS: An updated Main-Across-Distal-Side (MADS)-2, classification of bifurcation stenting techniques has been realized and is reported in the present article allowing standardized procedure reporting in both clinical practice and scientific studies. The EBC-promoted task force deeply discussed, agreed on and described (using original drawings and bench tests) the optimal steps for the following major bifurcation stenting techniques: (a) 1-stent techniques ("provisional" and "inverted provisional") and (b) 2-stent techniques ("T/TAP," "culotte," and "DK-crush"). CONCLUSIONS: The present EBC-promoted paper is intended to facilitate technique selection, reporting and performance for PCI on bifurcated lesions during daily clinical practice.

The association between self-reported health status and adverse events: a comparison among coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI).

PURPOSE: While several studies have investigated clinical outcomes following coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI), studies investigating self-reported health and the association with adverse outcomes are limited. Thus, the aim was to investigate differences in health-related quality of life (HRQoL), anxiety and depression at discharge and the association with a composite endpoint of the first event of acute cardiac readmission, revascularisation or 1-year mortality among patients undergoing CABG vs. PCI. METHODS: Data from the national cohort study, DenHeart, were used, including measures of HRQoL; EuroQoL-5D-5L (EQ-5D Index Score and VAS) and HeartQoL (Global, Physical and Emotional), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and register-based follow-up. A total of 7000 patients were included (CABG n = 652, PCI n = 6348) (median age 65, 75% men). Cox Proportional Hazard models were performed among a propensity-matched population of responders (n = 520). RESULTS: HRQoL was significantly better among patients undergoing PCI vs. CABG, but with no differences in time to readmission or revascularisation. HRQoL, anxiety and depression were significantly associated with the risk of the composite endpoint among the PCI group (Hazard Ratio, HR (95% confidence intervals, CI) [EQ-5D index score 3.07 (1.67-5.67), EQ-5D VAS 0.97 (0.96-0.99), HeartQol Global 0.61 (0.38-0.95), HeartQol Emotional 0.56 (0.39-0.80), HADS-D ≥ 8 3.12 (1.61-6.01), HADS-A ≥ 8 2.08 (1.14-3.80)]. CONCLUSION: Patients undergoing PCI reported better HRQoL at discharge compared with patients undergoing CABG, whereas readmission rates were similar. Self-reported health was associated with the risk of adverse events among patients undergoing PCI, but not among patients undergoing CABG. CLINICAL TRIAL REGISTRATION: NCT01926145.

Comparison of the polymer-free biolimus-coated BioFreedom stent with the thin-strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population treated with percutaneous coronary intervention: Rationale and design of the randomized SORT OUT IX trial.

BACKGROUND: In patients with increased bleeding risk during dual antiplatelet therapy, the biolimus A9-coated BioFreedom, a stainless steel drug-coated stent devoid of polymer, has shown superiority compared to a bare-metal stent. The aim of this study was to investigate whether the polymer-free biolimus A9-coated BioFreedom is noninferior to a modern thin-strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The multicenter SORT OUT IX trial (NCT02623140) randomly assigned all-comers patients to treatment with the BioFreedom drug-coated stent or the biodegradable polymer Orsiro stent in 4 Danish University Hospitals. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection based on Danish registries will be used and continue through 5 years. Assuming an event rate of 4.2% in each stent group, 1,563 patients in each treatment arm will provide 90% power to detect noninferiority of the drug-coated BioFreedom stent with a noninferiority margin of 2.1%. RESULTS: A total of 3,150 patients have been randomized and enrolled in the study. CONCLUSIONS: The SORT OUT IX trial will determine whether the drug-coated BioFreedom stent is noninferior to a modern biodegradable polymer Orsiro stent.

Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial.

OBJECTIVE: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM. BACKGROUND: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population. METHODS: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested. RESULTS: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding. CONCLUSIONS: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

Diabetes and risk of peripheral artery disease in patients undergoing first-time coronary angiography between 2000 and 2012 - a nationwide study.

BACKGROUND: The risk of peripheral artery disease (PAD) in patients with diabetes mellitus (DM) and coronary artery disease (CAD) is an important and inadequately addressed issue. Our aim is to examine the impact of DM on risk of PAD in patients with different degrees of CAD characterized by coronary angiography (CAG). METHODS: Using nationwide registers we identified all patients aged ≥18 years, undergoing first time CAG between 2000 and 2012. Patients were categorized into DM/Non-DM group, and further classified into categories according to the degree of CAD i.e., no-vessel disease, single-vessel disease, double-vessel disease, triple-vessel disease, and diffuse disease. Risk of PAD was estimated by 5-year cumulative-incidence and adjusted multivariable Cox-regression models. RESULTS: We identified 116,491 patients undergoing first-time CAG. Among these, a total of 23.969 (20.58%) had DM. Cumulative-incidence of PAD among DM patients vs. non-DM were 8.8% vs. 4.9% for no-vessel disease, 8.2% vs. 4.8% for single-vessel disease, 10.2% vs. 6.0% for double-vessel disease, 13.0% vs. 8.4% for triple-vessel disease, and 6.8% vs. 6.1% for diffuse disease, respectively. For all patients with DM, the cox-regression analysis yielded significantly higher hazards of PAD compared with non-DM patients with HR 1.70 (no-vessel disease), 1.96 (single-vessel disease), 2.35 (double-vessel disease), 2.87 (triple-vessel disease), and 1.46 (diffuse disease), respectively (interaction-p 0.042). CONCLUSION: DM appears to be associated with increased risk of PAD in patients with and without established CAD, with increasing risk in more extensive CAD. This observation indicates awareness on PAD risk in patients with DM, especially among patients with advanced CAD.

Thrombus aspiration and prehospital ticagrelor administration in ST-elevation myocardial infarction: Findings from the ATLANTIC trial.

BACKGROUND: The potential interactions between prehospital (pre-H) ticagrelor administration and thrombus aspiration (TA) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) have never been studied. Therefore, we evaluated the potential benefit of TA and pre-H ticagrelor treatment in patients enrolled in the ATLANTIC trial (NCT01347580). METHODS: This analysis included 1,630 patients who underwent primary PCI. Multivariate analysis was used to explore the potential association of TA and pre-H treatment to clinical outcomes. Potential interactions between TA and pre-H ticagrelor were also explored. RESULTS: A total of 941 (57.7%) patients underwent TA. In adjusted multivariate logistic model, pre-H ticagrelor treatment was significantly associated with less frequent new MI or definite stent *thrombosis (ST) (odds ratio [OR] 0.43, 95% CI 0.20-0.92, P=.031), or definite ST (OR 0.26, 95% CI 0.07-0.91, P=.036) at 30 days. Patients treated with TA had higher frequency of Thrombolysis in Myocardial Infarction (TIMI) flow 0-1 compared with no-TA group (80.7% vs 51.9%, P<.0001). TA when also adjusted for TIMI flow 0-1 showed significant association only for higher bailout use of glycoprotein IIb/IIIa inhibitors (OR 1.72, 95% CI 1.18-2.50, P=.004) and more frequent 30-day TIMI major bleeding (OR 2.92, 95% CI 1.10-7.76, P=.032). No significant interactions between TA and pre-H ticagrelor were present for the explored end points. CONCLUSIONS: TA when left to physicians' discretion was used in high-risk patients, was associated with bailout use of glycoprotein IIb/IIIa inhibitors and TIMI major bleeding, and had no impact on 30-day clinical outcomes. Conversely, pre-H ticagrelor treatment predicted lower 30-day rates of ST or new MI without interaction with TA.

Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study.

BACKGROUND: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. METHODS: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. RESULTS: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P < .001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P < .001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all < .001). CONCLUSIONS: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.

Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study.

BACKGROUND: Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration. METHODS: In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre- versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [≤1 hour (n = 773), >1 to ≤3 hours (n = 772), and >3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome. RESULTS: Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC >3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 2.9% vs. >1 to ≤3 hours, 3.6% vs. >3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 1.3% vs. >1 hour to ≤3 hours, 0.7% vs. >3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95%CI 1.20-2.97, P < .01), but not post-PCI ST-segment resolution (P = .41). CONCLUSIONS: The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

Integrated prediction of lesion-specific ischaemia from quantitative coronary CT angiography using machine learning: a multicentre study.

OBJECTIVES: We aimed to investigate if lesion-specific ischaemia by invasive fractional flow reserve (FFR) can be predicted by an integrated machine learning (ML) ischaemia risk score from quantitative plaque measures from coronary computed tomography angiography (CTA). METHODS: In a multicentre trial of 254 patients, CTA and invasive coronary angiography were performed, with FFR in 484 vessels. CTA data sets were analysed by semi-automated software to quantify stenosis and non-calcified (NCP), low-density NCP (LD-NCP, < 30 HU), calcified and total plaque volumes, contrast density difference (CDD, maximum difference in luminal attenuation per unit area) and plaque length. ML integration included automated feature selection and model building from quantitative CTA with a boosted ensemble algorithm, and tenfold stratified cross-validation. RESULTS: Eighty patients had ischaemia by FFR (FFR ≤ 0.80) in 100 vessels. Information gain for predicting ischaemia was highest for CDD (0.172), followed by LD-NCP (0.125), NCP (0.097), and total plaque volumes (0.092). ML exhibited higher area-under-the-curve (0.84) than individual CTA measures, including stenosis (0.76), LD-NCP volume (0.77), total plaque volume (0.74) and pre-test likelihood of coronary artery disease (CAD) (0.63); p < 0.006. CONCLUSIONS: Integrated ML ischaemia risk score improved the prediction of lesion-specific ischaemia by invasive FFR, over stenosis, plaque measures and pre-test likelihood of CAD. KEY POINTS: • Integrated ischaemia risk score improved prediction of ischaemia over quantitative plaque measures • Integrated ischaemia risk score showed higher prediction of ischaemia than standard approach • Contrast density difference had the highest information gain to identify lesion-specific ischaemia.