Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation.

BACKGROUND: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. STUDY DESIGN: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding. CONCLUSIONS: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF. CLINICAL TRIAL REGISTRATION: NCT04394546.

Rationale and design of the AngeLmed for Early Recognition and Treatment of STEMI trial: a randomized, prospective clinical investigation.

Significant improvements in door-to-balloon times have led to a reduction in mortality in ST-segment elevation myocardial infarction; however, mean symptom-to-door times remain at 2 to 3 hours. An intracardiac electrogram monitoring device may be beneficial in high-risk patients by alerting them to rapidly progressive ST-segment changes indicative of acute coronary occlusion. The Cardiosaver and DETECT phase I clinical studies demonstrated the safety, feasibility, and potential benefit of using an intracardiac electrogram monitoring device to alert the patient to seek medical attention. The goal of the randomized, prospective ALERTS Trial (Clinicaltrials.gov no. NCT00781118) is to evaluate the efficacy of an implantable monitoring device (IMD) in reducing the composite of either cardiac or unexplained death, new Q-wave myocardial infarction, or symptom-to-door time of >2 hours for confirmed thrombotic events. The IMD alerts the patient in real time when ST-segment deviation from a personalized baseline exceeds the trigger threshold. The trial is designed to enroll high-risk post-acute coronary syndrome patients or patients with previous multivessel coronary artery bypass surgery. All patients have the IMD implanted, with 1:1 unblinded randomization to the alerting feature being either turned on versus turned off for the first 6 months. Randomization occurs at the first follow-up visit, 7 to 14 days after the implantation of the IMD. Subjects then return for follow-up visits at months 1, 3, and 6 and thereafter every 6 months until closure of the investigational device exemption. Subjects who cannot be implanted successfully or who have the device explanted are removed from the study and followed up for a minimum of 30 days post-procedure. If a subject experiences a device-related complication and/or adverse experience, the subject is followed up until resolution or until the condition becomes stable and no further change is anticipated.

Impact of time-to-treatment on myocardial perfusion after primary percutaneous coronary intervention with Gp IIb-IIIa inhibitors.

BACKGROUND: Primary angioplasty has been shown to be superior to thrombolysis. However, previous reports have shown a negative impact of longer time-to-treatment on myocardial perfusion and survival even with mechanical reperfusion. However, these deleterious effects might potentially be overcome by an extensive use of glycoprotein (Gp) IIb-IIIa inhibitors. Thus, the aim of the current study was to evaluate the prognostic role of the interval from symptoms onset to reperfusion in a large cohort of patients undergoing primary angioplasty with Gp IIb-IIIa inhibitors. METHODS: Our population is represented by 1560 patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (STEMI) included in the EGYPT (Early Glycoprotein IIb-IIIa Inhibitors in Primary Angiography) database. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak creatine kinase and creatine kinase-MB (CK-MB). Follow-up data were collected between 30 days and 1 year after primary angioplasty. RESULTS: Time-to-treatment was significantly associated with age and female sex, diabetes and previous myocardial infarction (MI), but inversely related to smoking. Time-to-treatment affected the rate of postprocedural thrombolysis in myocardial infarction (TIMI) 3 flow (P < 0.0001), myocardial blush grade 2-3 (P = 0.052), complete ST-resolution (P < 0.0001) and distal embolization (P = 0.038). This relationship was confirmed after correction for baseline confounding factors for postprocedural TIMI 3 flow (P = 0.008) and complete ST-segment resolution (P = 0.003). Furthermore, time-to-treatment significantly affected enzymatic infarct size, even after correction for baseline confounding factors [odds ratio (OR) 95% confidence interval (95% CI) = 1.002 (1.001-1.003), P = 0.004]. At 208 ±â€Š160 days follow-up, time-to-treatment was associated with a significantly higher mortality (P = 0.006). The impact was confirmed when time-to-treatment was evaluated as a continuous variable (P < 0.001), even after correction for baseline confounding factors [age, sex, diabetes, smoking, hypertension, previous myocardial infarction (MI), preprocedural TIMI 3 flow, multivessel disease, coronary stenting and early Gp IIb-IIIa inhibitors] (P = 0.001). CONCLUSION: This study showed that time-to-treatment is a major determinant of mortality in ST-segment elevation myocardial infarction patients undergoing primary angioplasty. Impaired epicardial and myocardial perfusion and larger infarct size associated with longer ischemia time contribute to explain this finding.

Does aspirin use prevent acute coronary syndrome in patients with pneumonia: multicenter prospective randomized trial.

OBJECTIVES: The aim of this study was to test the hypothesis that aspirin would reduce the risk for acute coronary syndromes (ACSs) in patients with pneumonia. BACKGROUNDS: Pooled data suggest that pneumonia may trigger an ACS as a result of inflammatory reactions and the prothrombotic changes in patients with pneumonia. Hypothetically considering its antiaggregating and anti-inflammatory effects, aspirin might also be beneficial for the primary prevention of ACS in patients with pneumonia. METHODS: One hundred and eighty-five patients with pneumonia who had more than one risk factor for cardiovascular disease were randomized to an aspirin group (n=91) or a control group (n=94). The patients in the aspirin group received 300 mg of aspirin daily for 1 month. ECGs were recorded on admission and 48 h and 30 days after admission to assess silent ischemia. The level of high-sensitivity cardiac troponin T was measured on admission and 48 h after admission. The primary endpoint was the development of ACS within 1 month. The secondary endpoints included cardiovascular death and death from any cause within 1 month. RESULTS: The χ-test showed that the rates of ACS at 1 month were 1.1% (n=1) in the aspirin group and 10.6% (n=10) in the control group (relative risk, 0.103; 95% confidence interval 0.005-0.746; P=0.015). Aspirin therapy was associated with a 9% absolute reduction in the risk for ACS. There was no significant decrease in the risk of death from any cause (P=0.151), but the aspirin group had a decreased risk of cardiovascular death (risk reduction: 0.04, P=0.044). CONCLUSION: This randomized open-label study shows that acetyl salicylic acid is beneficial in the reduction of ACS and cardiovascular mortality among patients with pneumonia.

Prognostic value of neutrophil/lymphocyte ratio in patients with ST-elevated myocardial infarction undergoing primary coronary intervention: a prospective, multicenter study.

OBJECTIVE: The pre-procedural neutrophil to lymphocyte ratio (N/L) is associated with adverse outcomes among patients with coronary artery disease but its prognostic value in ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. This study evaluated the relations between pre-procedural N/L ratio and the in-hospital and long-term outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 682 STEMI patients presented within the first 6h of symptom onset were enrolled and stratified according to tertiles of N/L ratio based on the blood samples obtained in the emergency room upon admission. RESULTS: The mean follow-up period was 43.3 months (1-131 months). In-hospital in-stent thrombosis, non-fatal myocardial infarction, and cardiovascular mortality increased as the N/L tertile ratio increased (p<0.001, p<0.001, p=0.003, respectively). Long-term in-stent thrombosis, non-fatal myocardial infarction and cardiovascular mortality also increased as the N/L ratio increased (p<0.001, p<0.001, p=0.002, respectively). On multivariate analysis, N/L ratio remained an independent predictor for both in-hospital (OR 1.189, 95% CI 1.000-1.339; p<0.001) and long-term major (OR 1.228, 95% CI 1.136-1.328; p<0.001) adverse cardiac events. CONCLUSION: The N/L ratio was an independent predictor of both in-hospital and long-term adverse outcomes among STEMI patients undergoing primary PCI. Our findings suggest that this inexpensive, universally available hematological marker may be incorporated into the current established risk assessment model for STEMI.

Temporal changes in TIMI myocardial perfusion grade in relation to epicardial flow, ST-resolution and left ventricular function after primary percutaneous coronary intervention.

BACKGROUND: Myocardial perfusion at the end of reperfusion therapy assessed angiographically with thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG) has been associated with recovery of left ventricular (LV) function and survival. The aim of this analysis was to study the evolution of TMPG within the first week following primary percutaneous coronary intervention (PCI) and its association with ECG-derived ST-segment resolution (STRES) and recovery of LV function. METHODS: A total of 76 patients with acute myocardial infarction were pretreated with enoxaparine and abciximab and subjected to primary PCI within a prospective study and evaluated with TMPG assessed on coronary angiography at the end of the procedure and after 5-7 days. STRES was evaluated at 120 min post inclusion and global LV function was assessed by echocardiography after 30 days. RESULTS: Reperfusion (TIMI flow 2-3) was reached in all patients. Forty one percent had 'open myocardium' (i.e. TMPG 2 or 3) after PCI, a number that increased to 61% after 5-7 days (P=0.003). STRES >50% was reached in 73% of the patients and there was a good correlation between TMPG and STRES. Furthermore, those who improved from 'closed' to 'open myocardium' had higher STRES (and similar to those with 'open myocardium' already post-PCI) than those who had 'closed myocardium' at both occasions (80 vs. 52%, P=0.012). CONCLUSION: A significant increase was found in the number of patients with 'open myocardium' within the first week post-primary PCI and STRES seems to predict this improvement.

Angiographic and clinical outcomes in elderly subjects treated with percutaneous coronary intervention following fibrinolytic administration for ST-elevation myocardial infarction / 老年心脏病学杂志（英文版）

Background Prior studies have demonstrated that the achievement of faster coronary artery flow following reperfusion therapies is associated with improved outcomes among ST-elevation myocardial infarction (STEMI) patients. The association of patient age with angiographic characteristics of flow and perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) following the administration of fibrinolytic therapy has not been previously investigated. Objectives and Methods We examined the association between age (≥ 70 years or ＜ 70years)and clinical and angiographic outcomes in 1472 STEMI patients who underwent rescue/adjunctive PCI following fibrinolytic therapy in 7 TIMI trials. We hypothesized that elderly patients would have slower post-PCI epicardial flow and worsened outcomes compared to younger patients. Results The 218 patients aged ≥ 70 years (14.8%) had more comorbidities than younger patients. Although these patients had significant angiographic improvement in TIMI frame counts and rates of TIMI Grade 3 flow following rescue/adjunctive PCI, elderly patients had higher (slower)post-PCI TIMI frame counts compared to the younger cohort (25 vs 22 frames, P = 0.039), and less often achieved post-PCI TIMI Grade 3 flow (80.1 vs 86.4%, P = 0.017). The association between age ( ≥70 years) and slower post-PCI flow was independent of gender, time to treatment, left anterior descending (LAD) lesion location, and pulse and blood pressure on admission. Elderly patients also had 4-fold higher mortality at 30 days (12.0 vs 2.7%,P = 0. 001 ). Conclusions This study suggests one possible mechanism underlying worsened outcomes among elderly STEMI patients insofar as advanced chronological age was associated with higher TIMI frame counts and less frequent TIMI Grade 3 flow after rescue/adjunctive PCI.