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Patients with acute STEMI were randomly assigned to undergo infarct-vessel-only PCI or preventive PCI (PCI to noninfarct arteries with stenoses). The rate of the primary outcome of cardiac death, myocardial infarction, or refractory angina was lower with preventive PCI. Patients with acute ST-segment elevation myocardial infarction (STEMI) are effectively treated with emergency angioplasty, hereafter called percutaneous coronary intervention (PCI), to restore blood flow to the coronary artery that is judged to be causing the myocardial infarction (infarct artery, also known as culprit artery). 1 – 5 These patients may have major stenoses in coronary arteries that were not responsible for the myocardial infarction, 6 but the value of performing PCI in such arteries for the prevention of future cardiac events is not known. Some physicians have taken the view that stenoses in noninfarct arteries may cause serious adverse cardiac events that could . . .

In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up. The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774. After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75–1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001). The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients. St Jude Medical, Friends of the Heart Foundation, and Medtronic.

Fractional flow reserve (FFR) is a measure of the functional significance of a coronary stenosis. In this study, the use of FFR, as compared with angiography alone, in guiding the placement of coronary stents resulted in the use of fewer stents and better clinical outcomes. The use of fractional flow reserve, as compared with coronary angiography alone, in guiding the placement of coronary stents resulted in the use of fewer stents and better clinical outcomes. The presence of myocardial ischemia is an important risk factor for an adverse clinical outcome. 1 – 3 Revascularization of stenotic coronary lesions that induce ischemia can improve a patient's functional status and outcome. 3 – 5 For stenotic lesions that do not induce ischemia, however, the benefit of revascularization is less clear, and medical therapy alone is likely to be equally effective. 6 , 7 With the introduction of drug-eluting stents, the percentage of patients with multivessel coronary artery disease in whom percutaneous coronary intervention (PCI) is performed has increased. 8 , 9 Because drug-eluting stents are expensive and are associated with potential late complications, their appropriate . . .

Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA). Our research has 2 objectives. The first is to undertake a diagnostic study, and the second is to undertake a nested, clinical trial of stratified medicine. A prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03477890) will be performed. All-comers referred for clinically indicated CTCA for investigation of suspected coronary artery disease (CAD) will be screened in 3 regional centers. Following informed consent, eligible patients with angina symptoms are enrolled before CTCA and remain eligible if CTCA excludes obstructive CAD. Diagnostic study: Invasive coronary angiography involving an interventional diagnostic procedure (IDP) to assess for disease endotypes: (1) angina due to obstructive CAD (fractional flow reserve ≤0.80); (2) microvascular angina (coronary flow reserve <2.0 and/or index of microvascular resistance >25); (3) microvascular angina due to small vessel spasm (acetylcholine); (4) vasospastic angina due to epicardial coronary spasm (acetylcholine); and (5) noncoronary etiology (normal coronary function). The IDP involves direct invasive measurements using a diagnostic coronary guidewire followed by provocation testing with intracoronary acetylcholine. The primary outcome of the diagnostic study is the reclassification of the initial CTCA diagnosis based on the IDP. Stratified medicine trial: Participants are immediately randomized 1:1 in the catheter laboratory to therapy stratified by endotype (intervention group) or not (control group). The primary outcome of the trial is the mean within-subject change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and certainty), and clinical utility (impact on treatment and investigations). Health status assessments include quality of life, illness perception, anxiety-depression score, treatment satisfaction, and physical activity. Participants who are not randomized will enter a follow-up registry. Health and economic outcomes in the longer term will be assessed using electronic patient record linkage. CorCTCA will prospectively characterize the prevalence of disease endotypes in INOCA and determine the clinical value of stratified medicine in this population. [Display omitted]

Treatment options for coronary chronic total occlusions (CTO) are limited, with low historical success rates from percutaneous coronary intervention (PCI). We report procedural outcomes of CTO PCI from 7 centres with dedicated CTO operators trained in hybrid approaches comprising antegrade/retrograde wire escalation (AWE/RWE) and dissection re-entry (ADR/RDR) techniques. Clinical and procedural data were collected from consecutive unselected patients with CTO between 2012 and 2014. Lesion complexity was graded by the Multicentre CTO Registry of Japan (J-CTO) score, with ≥2 defined as complex. Success was defined as thrombolysis in myocardial infarction 3 flow with <30% residual stenosis, subclassified as at first attempt or overall. Inhospital complications and 30-day major adverse cardiovascular events (MACEs, death/myocardial infarction/unplanned target vessel revascularisation) were recorded. 1156 patients were included. Despite high complexity (mean J-CTO score 2.5±1.3), success rates were 79% (first attempt) and 90% (overall) with 30-day MACE of 1.6%. AWE was highly effective in less complex lesions (J-CTO ≤1 94% success vs 79% in J-CTO score ≥2). ADR/RDR was used more commonly in complex lesions (J-CTO≤1 15% vs J-CTO ≥2 56%). Need for multiple approaches during each attempt increased with lesion complexity (17% J-CTO ≤1 vs 48% J-CTO ≥2). Lesion modification ('investment procedures') at the end of unsuccessful first attempts increased the chance of subsequent success (96% vs 71%). Hybrid-trained operators can achieve overall success rates of 90% in real world practice with acceptable MACE. Use of dissection re-entry and investment procedures maintains high success rates in complex lesions. The hybrid approach represents a significant advance in CTO treatment.

Post‐percutaneous coronary intervention (PCI) fractional flow reserve (FFR) ≥0.90 confers an improved cardiac prognosis. There are currently limited data available to determine how often it is possible to improve an angiographically acceptable but physiologically suboptimal result. A physiology‐guided optimization strategy can achieve a clinically meaningful increase in the proportion of patients achieving a final post‐PCI FFR ≥0.90 compared to standard care. Following angiographically successful PCI procedures, 260 patients will be randomized (1:1) to receive either a physiology‐guided incremental optimization strategy (intervention group) or blinded post‐PCI coronary physiology measurements (control group). Patients undergoing successful, standard‐of‐care PCI for either stable angina or non‐ST‐segment‐elevation myocardial infarction who meet the study's inclusion and exclusion criteria will be eligible for randomization. The primary endpoint is defined as the proportion of patients with a final post‐PCI FFR result ≥0.90. Secondary endpoints include change from baseline in Seattle Angina Questionnaire and EQ‐5D‐5L scores at 3 months and the rate of target vessel failure and its components (cardiac death, myocardial infarction, stent thrombosis, unplanned rehospitalization with target vessel revascularization) at 3 months and 1 year. 260 individual patients were successfully randomized between March 2018 and November 2019. Key baseline demographics of the study population are reported within. TARGET FFR is an investigator‐initiated, prospective, single‐center, randomized controlled trial of an FFR‐guided PCI optimization strategy. The study has completed recruitment and is now in clinical follow‐up. It is anticipated that primary results will be presented in Autumn 2020. ClinicalTrials.gov Identifier: NCT03259815. [Correction added on Apr 3 2020, after first online publication: Clinical Trials identifier added.]

Nitrogen is abundant in the earth’s atmosphere but, unlike carbon, cannot be directly assimilated by plants. The limitation this places on plant productivity has been circumvented in contemporary agriculture through the production and application of chemical fertilizers. The chemical reduction of nitrogen for this purpose consumes large amounts of energy and the reactive nitrogen released into the environment as a result of fertilizer application leads to greenhouse gas emissions, as well as widespread eutrophication of aquatic ecosystems. The environmental impacts are intensified by injudicious use of fertilizers in many parts of the world. Simultaneously, limitations in the production and supply of chemical fertilizers in other regions are leading to low agricultural productivity and malnutrition. Nitrogen can be directly fixed from the atmosphere by some bacteria and Archaea, which possess the enzyme nitrogenase. Some plant species, most notably legumes, have evolved close symbiotic associations with nitrogen-fixing bacteria. Engineering cereal crops with the capability to fix their own nitrogen could one day address the problems created by the over- and under-use of nitrogen fertilizers in agriculture. This could be achieved either by expression of a functional nitrogenase enzyme in the cells of the cereal crop or through transferring the capability to form a symbiotic association with nitrogen-fixing bacteria. While potentially transformative, these biotechnological approaches are challenging; however, with recent advances in synthetic biology they are viable long-term goals. This review discusses the possibility of these biotechnological solutions to the nitrogen problem, focusing on engineering the nitrogen symbiosis in cereals.

Guidelines recommend coronary artery bypass graft (CABG) surgery over percutaneous coronary intervention (PCI) for the treatment of 3-vessel coronary artery disease (3-VD). The inferior results of PCI demonstrated by previous large randomized trials comparing PCI and CABG might be explained by the use of suboptimal stent technology and by the lack of fractional flow reserve (FFR) guidance of PCI. The objective of this investigator-initiated, multicenter, randomized clinical trial is to investigate whether FFR-guided PCI with new-generation stents is noninferior to CABG in patients with 3-VD, not including the left main coronary artery. Eligible patients must have ≥50% coronary stenoses in all 3 major epicardial vessels or major side branches. Patients with a nondominant right coronary artery may be included only if the left anterior descending artery and left circumflex have ≥50% stenoses. Consecutive patients who meet all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to either CABG or FFR-guided PCI. Coronary artery bypass graft will be performed based on the angiogram as per clinical routine. Patients assigned to FFR-guided PCI will have FFR measured in each diseased vessel and only undergo stenting if the FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac and cerebrovascular events, including death, myocardial infarction, repeat coronary revascularization, and stroke at 1 year. Key secondary end point will be a composite of death, myocardial infarction, and stroke at 3-year follow-up. Other secondary end points include the individual adverse events, cost-effectiveness, and quality of life at 2-year, 3-year, with up to 5-year follow-up. The FAME 3 study will compare in a multicenter, randomized fashion FFR-guided PCI with contemporary drug-eluting stents to CABG in patients with 3-VD.

Influenza vaccination reduces the risk of adverse cardiovascular events.The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344).The primary endpoint wasthe composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. Thecumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion,there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccinationbut regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.

In this multicenter trial, patients in whom thrombolytic therapy for acute myocardial infarction failed were randomly assigned to repeated thrombolysis, conservative therapy, or emergency percutaneous coronary intervention (rescue PCI). Event-free survival was better among patients assigned to rescue PCI. Patients in whom thrombolytic therapy for acute myocardial infarction failed were randomly assigned to repeated thrombolysis, conservative therapy, or emergency percutaneous coronary intervention. Event-free survival was better among patients assigned to rescue PCI. Patients who have an open infarct-related artery after acute myocardial infarction with ST-segment elevation have better clinical outcomes than patients without an open artery. 1 – 4 Although primary percutaneous coronary intervention (primary PCI) is a proven therapeutic approach in this setting 5 , 6 and is used increasingly, intravenous thrombolysis remains the first-line therapy in 30 to 70 percent of cases worldwide. 7 , 8 However, thrombolysis results in a grade 3 flow, according to the Thrombolysis in Myocardial Infarction (TIMI) classification system, in only 60 percent of patients, even with current fibrin-specific agents. 9 To date, it has been unclear how best to treat the . . .