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Background: The optimal management of patients with ST-segment elevation myocardial infarction (STEMI) presenting late->12 hours following symptom onset-is still under debate.Objectives: The purpose of this study was to describe characteristics, temporal trends, and impact of revascularization in a large population of latecomer STEMI patients.Methods: The authors analyzed the data of 3 nationwide observational studies from the FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) program, conducted over a 1-month period in 2005, 2010, and 2015. Patients presenting between 12 and 48 hours after symptom onset were classified as latecomers.Results: A total of 6,273 STEMI patients were included in the 3 cohorts, 1,169 (18.6%) of whom were latecomers. After exclusion of patients treated with fibrinolysis and patients deceased within 2 days after admission, 1,077 patients were analyzed, of whom 729 (67.7%) were revascularized within 48 hours after hospital admission. At 30-day follow-up, all-cause death rate was significantly lower among revascularized latecomers (2.1% vs 7.2%; P < 0.001). After a median follow-up of 58 months, the rate of all-cause death was 30.4 (95% CI: 25.7-35.9) per 1,000 patient-years in the revascularized latecomers group vs 78.7 (95% CI: 67.2-92.3) per 1,000 patient-years in the nonrevascularized latecomers group (P < 0.001). In multivariate analysis, revascularization of latecomer STEMI patients was independently associated with a significant reduction of mortality occurrence during follow-up (HR: 0.65 [95% CI: 0.50-0.84]; P = 0.001).Conclusions: Coronary revascularization of latecomer STEMI patients is associated with better short and long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Treatment of locally advanced rectal cancer with chemoradiotherapy, surgery, and adjuvant chemotherapy controls local disease, but distant metastases remain common. We aimed to assess whether administering neoadjuvant chemotherapy before preoperative chemoradiotherapy could reduce the risk of distant recurrences.Methods: We did a phase 3, open-label, multicentre, randomised trial at 35 hospitals in France. Eligible patients were adults aged 18-75 years and had newly diagnosed, biopsy-proven, rectal adenocarcinoma staged cT3 or cT4 M0, with a WHO performance status of 0-1. Patients were randomly assigned (1:1) to either the neoadjuvant chemotherapy group or standard-of-care group, using an independent web-based system by minimisation method stratified by centre, extramural extension of the tumour into perirectal fat according to MRI, tumour location, and stage. Investigators and participants were not masked to treatment allocation. The neoadjuvant chemotherapy group received neoadjuvant chemotherapy with FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 intravenously every 14 days for 6 cycles), chemoradiotherapy (50 Gy during 5 weeks and 800 mg/m2 concurrent oral capecitabine twice daily for 5 days per week), total mesorectal excision, and adjuvant chemotherapy (3 months of modified FOLFOX6 [intravenous oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2, followed by intravenous 400 mg/m2 fluorouracil bolus and then continuous infusion at a dose of 2400 mg/m2 over 46 h every 14 days for six cycles] or capecitabine [1250 mg/m2 orally twice daily on days 1-14 every 21 days]). The standard-of-care group received chemoradiotherapy, total mesorectal excision, and adjuvant chemotherapy (for 6 months). The primary endpoint was disease-free survival assessed in the intention-to-treat population at 3 years. Safety analyses were done on treated patients. This trial was registered with EudraCT (2011-004406-25) and ClinicalTrials.gov (NCT01804790) and is now complete.Findings: Between June 5, 2012, and June 26, 2017, 461 patients were randomly assigned to either the neoadjuvant chemotherapy group (n=231) or the standard-of-care group (n=230). At a median follow-up of 46·5 months (IQR 35·4-61·6), 3-year disease-free survival rates were 76% (95% CI 69-81) in the neoadjuvant chemotherapy group and 69% (62-74) in the standard-of-care group (stratified hazard ratio 0·69, 95% CI 0·49-0·97; p=0·034). During neoadjuvant chemotherapy, the most common grade 3-4 adverse events were neutropenia (38 [17%] of 225 patients) and diarrhoea (25 [11%] of 226). During chemoradiotherapy, the most common grade 3-4 adverse event was lymphopenia (59 [28%] of 212 in the neoadjuvant chemotherapy group vs 67 [30%] of 226 patients in the standard-of-care group). During adjuvant chemotherapy, the most common grade 3-4 adverse events were lymphopenia (18 [11%] of 161 in the neoadjuvant chemotherapy group vs 42 [27%] of 155 in the standard-of-care group), neutropenia (nine [6%] of 161 vs 28 [18%] of 155), and peripheral sensory neuropathy (19 [12%] of 162 vs 32 [21%] of 155). Serious adverse events occurred in 63 (27%) of 231 participants in the neoadjuvant chemotherapy group and 50 (22%) of 230 patients in the standard-of-care group (p=0·167), during the whole treatment period. During adjuvant therapy, serious adverse events occurred in 18 (11%) of 163 participants in the neoadjuvant chemotherapy group and 36 (23%) of 158 patients in the standard-of-care group (p=0·0049). Treatment-related deaths occurred in one (<1%) of 226 patients in the neoadjuvant chemotherapy group (sudden death) and two (1%) of 227 patients in the standard-of-care group (one sudden death and one myocardial infarction).Interpretation: Intensification of chemotherapy using FOLFIRINOX before preoperative chemoradiotherapy significantly improved outcomes compared with preoperative chemoradiotherapy in patients with cT3 or cT4 M0 rectal cancer. The significantly improved disease-free survival in the neoadjuvant chemotherapy group and the decreased neurotoxicity indicates that the perioperative approach is more efficient and better tolerated than adjuvant chemotherapy. Therefore, the PRODIGE 23 results might change clinical practice.Funding: Institut National du Cancer, Ligue Nationale Contre le Cancer, and R&D Unicancer. [ABSTRACT FROM AUTHOR]

Background: Contemporary data are lacking regarding the prognosis and management of left ventricular thrombus (LVT).Objectives: The purpose of this study was to quantify the effect of anticoagulation therapy on LVT evolution using sequential imaging and to determine the impact of LVT regression on the incidence of thromboembolism, bleeding, and mortality.Methods: From January 2011 to January 2018, a comprehensive computerized search of LVT was conducted using 90,065 consecutive echocardiogram reports. Only patients with a confirmed LVT were included after imaging review by 2 independent experts. Major adverse cardiovascular events (MACE), which included death, stroke, myocardial infarction, or acute peripheral artery emboli, were determined as well as major bleeding events (BARC ≥3) and all-cause mortality rates.Results: There were 159 patients with a confirmed LVT. Patients were treated with vitamin K antagonists (48.4%), parenteral heparins (27.7%), and direct oral anticoagulants (22.6%). Antiplatelet therapy was used in 67.9% of the population. A reduction of the LVT area from baseline was observed in 121 patients (76.1%), and total LVT regression occurred in 99 patients (62.3%) within a median time of 103 days (interquartile range: 32 to 392 days). The independent correlates of LVT regression were a nonischemic cardiomyopathy (hazard ratio [HR]: 2.74; 95% confidence interval [CI]: 1.43 to 5.26; p = 0.002) and a smaller baseline thrombus area (HR: 0.66; 95% CI: 0.45 to 0.96; p = 0.031). The frequency of MACE was 37.1%; mortality 18.9%; stroke 13.3%; and major bleeding 13.2% during a median follow-up of 632 days (interquartile range: 187 to 1,126 days). MACE occurred in 35.4% and 40.0% of patients with total LVT regression and those with persistent LVT (p = 0.203). A reduced risk of mortality was observed among patients with total LVT regression (HR: 0.48; 95% CI: 0.23 to 0.98; p = 0.039), whereas an increased major bleeding risk was observed among patients with persistent LVT (9.1% vs. 12%; HR 0.34; 95% CI: 0.14 to 0.82; p = 0.011). A left ventricular ejection fraction ≥35% (HR: 0.46; 95% CI: 0.23 to 0.93; p = 0.029) and anticoagulation therapy >3 months (HR: 0.42; 95% CI: 0.20 to 0.88; p = 0.021) were independently associated with less MACE.Conclusions: The presence of LVT was associated with a very high risk of MACE and mortality. Total LVT regression, obtained with different anticoagulant regimens, was associated with reduced mortality. [ABSTRACT FROM AUTHOR]

Background: Current data are lacking for incidence, correlates, and prognosis associated with incident myocardial infarction (MI) in patients with stable coronary artery disease (CAD). Furthermore, the contribution of very late stent thrombosis (VLST) to these events remains poorly understood.Objectives: This study aimed to analyze the residual risk of MI, together with relevant associated factors, and related mortality in stable CAD outpatients.Methods: The multicenter CORONOR (Suivi d'une cohorte de patients COROnariens stables en region NORd-Pas-de-Calais) study enrolled 4,184 unselected outpatients with stable CAD (i.e., MI or coronary revascularization >1 year previously). Five-year follow-up was achieved for 4,094 patients (98%).Results: We identified a linear risk of incident MI (0.8% annually), with ST-segment elevation MI constituting one-third of all cases. Current smoking, low-density lipoprotein cholesterol, multivessel CAD, diabetes with glycosylated hemoglobin >7%, and persistent angina were all associated with increased risk, and prior bypass surgery was associated with decreased risk. When used as a time-dependent variable, incident MI was associated with an increased risk of death (hazard ratio: 2.05; p < 0.0001). Among patients with prior stent implantation, VLST was causal in 20% of MI cases and presented more often as ST-segment elevation MI versus MI not related to a stented site (59% vs. 26%, p = 0.001). Adjusted mortality was 4 times higher in patients with VLST than in MI not related to a stented site.Conclusions: In stable CAD outpatients, incident MI occurs at a stable rate of 0.8% annually, is related to VLST in one-fifth of cases, and is associated with an increased mortality risk, especially for VLST. Multivessel CAD and residual uncontrolled risk factors are strongly associated with MI. [ABSTRACT FROM AUTHOR]

Background: Pulse pressure (PP) provides valuable prognostic information in specific populations, but few studies have assessed its value on cardiovascular outcomes in a broad, worldwide population.Objectives: The aim of this study was to determine whether PP is associated with major adverse cardiovascular outcomes, independently of mean arterial pressure.Methods: Participants from the international REACH (Reduction of Atherothrombosis for Continued Health) registry, which evaluates subjects with clinical atherothrombotic disease or risk factors for its development, were examined. Those with incomplete 4-year follow-up or PP data (final n = 45,087) were excluded. Univariate and multivariate regression analyses were performed to determine the association between PP and cardiovascular outcomes, including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, all myocardial infarction, all stroke, cardiovascular hospitalization, and a combined outcome. PP was analyzed as a continuous and categorical (i.e., by quartile) variable.Results: The mean age of the cohort was 68 ± 10 years, 35% were women, and 81% were treated for hypertension. The mean blood pressure was 138 ± 19/79 ± 11 mm Hg, rendering a mean PP of 49 ± 16 mm Hg. On univariate analysis, increasing PP quartile was associated with worse outcomes (p < 0.05 for all comparisons). After adjusting for sex, age, current smoking status, history of hypercholesterolemia, history of diabetes, aspirin use, statin use, blood pressure medication use, and mean arterial pressure, PP quartile was still associated with all outcomes except all stroke and cardiovascular death (p < 0.05 for all comparisons). Analysis of PP as a continuous variable yielded similar results.Conclusions: In an international cohort of high-risk subjects, PP, a readily available hemodynamic parameter, is associated with multiple adverse cardiovascular outcomes and provides prognostic utility beyond that of mean arterial pressure. [ABSTRACT FROM AUTHOR]