Sex-based outcomes on unguided de-escalation from ticagrelor to clopidogrel in stabilized patients with acute myocardial infarction undergoing percutaneous coronary intervention: a post-hoc analysis of the TALOS-AMI.

Background: The TALOS-AMI study highlighted the effectiveness of a de-escalation strategy shifting from ticagrelor to clopidogrel 1 month after percutaneous coronary intervention (PCI), resulting in significant reduction in clinical events, primarily attributed to a substantial decrease in bleeding events. Nevertheless, the impact of this strategy on outcomes based on sex remains unclear. Methods: This was a post-hoc analysis of the TALOS-AMI study. At 1 month after PCI, patients who remained adherent to aspirin and ticagrelor without experiencing major adverse events were randomized into either the de-escalation group (clopidogrel plus aspirin) or the active control group (ticagrelor plus aspirin) for an additional 12 months. The primary endpoint encompassed a composite of cardiovascular death, myocardial infarction, stroke, and Bleeding Academic Research Consortium bleeding type 2 or greater at 12 months after randomization. Results: Among the 2,697 patients included in this study, 454 (16.8%) were women. Women, characterized by older age and a higher prevalence of hypertension, diabetes, impaired renal function, and non-ST-segment myocardial infarction, exhibited a lower primary endpoint at 12 months compared to men [adjusted hazards ratio (HR), 0.60; 95% confidence interval (CI), 0.37-0.95; P = 0.03]. Compare to the active control group, the de-escalation group demonstrated a reduced risk of the primary endpoint in both women (adjusted HR, 0.38; 95% CI, 0.15-0.95; P = 0.039) and men (adjusted HR, 0.56; 95% CI, 0.40-0.79; P = 0.001) (interaction P = 0.46). Conclusions: In stabilized patients post-PCI with drug-eluting stents for acute myocardial infarction, the primary endpoint was lower among women compared to men. In this cohort, the benefits of an unguided de-escalation strategy from ticagrelor to clopidogrel were comparable in women and men.

Optimal timing of percutaneous coronary intervention for non-ST elevated myocardial infarction with congestive heart failure.

OBJECTIVES: This study investigated the optimal timing for percutaneous coronary intervention (PCI) in patients with NSTEMI complicated by heart failure (HF). METHODS: In total, 762 patients with NSTEMI and HF in a multicenter, prospective registry in South Korea were classified according to the Killip classification (Killip class 2, n = 414 and Killip class 3, n = 348) and underwent early (within 24 h) and delayed (after 24 h) PCI. The primary outcome was all-cause mortality which was further analyzed with landmark analysis with two months as a cut-off. Secondary outcomes were cardiovascular death, in-hospital cardiogenic shock (CS), readmission due to HF, and acute myocardial infarction during follow-up. RESULTS: Delayed PCI was associated with lower rates of 2-month mortality (6.1 % vs. 15.8 %, p = 0.007) and in-hospital CS (4.3 % vs. 14.1 %, p = 0.003), along with lower risks of 2-month mortality (hazard ratio [HR] = 0.38, 95 % confidence interval [CI] = 0.18-0.83, p = 0.014), in-hospital CS (HR = 0.29, 95 % CI = 0.12-0.71, p = 0.006) in multivariate Cox models of Killip class 3 patients. There was no statistical difference of incidence and risk of all predefined outcomes according to varying timing of PCI in Killip 2 patients. CONCLUSIONS: Based on these results, the timing of PCI in patients with NSTEMI complicated by HF should be determined based on HF severity. Delayed PCI should be considered in patients with NSTEMI and more severe HF.

Clinical Impact of Dyspnea after Ticagrelor Treatment and the Effect of Switching to Clopidogrel in Patients with Myocardial Infarction.

BACKGROUND: Dyspnea is frequent during ticagrelor-based dual antiplatelet therapy (DAPT) for acute myocardial infarction (AMI). However, its clinical characteristics or management strategy remains uncertain. METHODS: The study assessed 2,617 AMI patients from the Ticagrelor versus Clopidogrel in Stabilized Patients with AMI (TALOS-AMI) trial. Dyspnea during 1-month ticagrelor-based DAPT and following DAPT strategies with continued ticagrelor or de-escalation to clopidogrel from 1 to 12 months were evaluated for drug adherence, subsequent dyspnea, major adverse cardiovascular events (MACE), and bleeding events. RESULTS: Dyspnea was reported by 538 patients (20.6%) during 1 month of ticagrelor-based DAPT. Adherence to allocated DAPT over the study period was lower in the continued ticagrelor arm than the de-escalation to clopidogrel, particularly among the dyspneic population (81.1% vs. 91.5%, p < 0.001). Among ticagrelor-treated patients with dyspnea, those switched to clopidogrel at 1 month had a lower frequency of dyspnea at 3 months (34.3% vs. 51.7%, p < 0.001) and 6 months (25.5% vs. 38.4%, p = 0.002) than those continued with ticagrelor. In patients with dyspnea in their 1-month ticagrelor-based DAPT, de-escalation was not associated with increased MACE (1.3% vs. 3.9%, hazard ratio [HR]: 0.31, 95% confidence interval [CI]: 0.08-1.11, p = 0.07) or clinically relevant bleeding (3.2% vs. 6.2%, HR: 0.51, 95% CI: 0.22-1.19, p = 0.12) at 1 year. CONCLUSION: Dyspnea is a common side effect among ticagrelor-based DAPTs in AMI patients. Switching from ticagrelor to clopidogrel after 1 month in AMI patients may provide a reasonable option to alleviate subsequent dyspnea in ticagrelor-relevant dyspneic patients, without increasing the risk of ischemic events (NCT02018055).

Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stent.

BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.

Balloon-Expandable Versus Self-Expandable Valve in Transcatheter Aortic Valve Replacement: A Nation-Wide Study.

A few studies have reported comparative analysis of clinical outcomes between balloon-expandable valve (BEV) and self-expandable valve (SEV) after transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis using newer-generation devices. However, those reports were mostly limited to short-term outcomes and Western populations. In the present study, data of patients with severe aortic stenosis who underwent TAVR between March 2016 and December 2018 were obtained from the National Health Insurance Service in Korea. The primary end point, defined as all-cause mortality, was compared in BEV (SAPIEN 3, Edwards Lifesciences, Irvine, California) and SEV (Evolut R, Medtronic, Minneapolis, MN) groups using a propensity-score matching analysis. Cumulative event rates of ischemic stroke, repeat procedures, and permanent pacemaker insertion (PPI) were evaluated as secondary outcomes. All events were followed up to a maximum of 3 years. A total of 1,172 patients underwent transfemoral TAVR, of whom 707 (60.3%) were treated with BEV and 452 (38.6%) with SEV. After 1:1 propensity-score matching, the BEV group showed lower all-cause mortality after a median follow-up of 12.0 months (mean: 13.1 ± 9.3 months) based on Cox proportional hazard model analysis (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.45 to 0.99, p = 0.04). Cumulative incidence of ischemic stroke was not statistically different between the 2 groups (HR 0.68, 95% CI 0.29 to 1.59, p = 0.37). PPI occurred less frequently in the BEV group (HR 0.4, 95% CI 0.25 to 0.64, p < 0.01). Repeat procedures were rare (1 patient in BEV and 2 patients in SEV group). In conclusion, Korean nation-wide data analysis showed that BEV was associated with less all-cause death and incidence of PPI after TAVR than was SEV using a newer-generation device.

Dual Antiplatelet Therapy De-Escalation in Stabilized Myocardial Infarction With High Ischemic Risk: Post Hoc Analysis of the TALOS-AMI Randomized Clinical Trial.

Importance: In patients with acute myocardial infarction (AMI) who have high ischemic risk, data on the efficacy and safety of the de-escalation strategy of switching from ticagrelor to clopidogrel are lacking. Objective: To evaluate the outcomes of the de-escalation strategy compared with dual antiplatelet therapy (DAPT) with ticagrelor in stabilized patients with AMI and high ischemic risk following percutaneous coronary intervention (PCI). Design, Setting, and Participants: This was a post hoc analysis of the Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction (TALOS-AMI) trial, an open-label, assessor-blinded, multicenter, randomized clinical trial. Patients with AMI who had no event during 1 month of ticagrelor-based DAPT after PCI were included. High ischemic risk was defined as having a history of diabetes or chronic kidney disease, multivessel PCI, at least 3 lesions treated, total stent length greater than 60 mm, at least 3 stents implanted, left main PCI, or bifurcation PCI with at least 2 stents. Data were collected from February 14, 2014, to January 21, 2021, and analyzed from December 1, 2021, to June 30, 2022. Intervention: Patients were randomly assigned to either de-escalation from ticagrelor to clopidogrel or ticagrelor-based DAPT. Main Outcomes and Measures: Ischemic outcomes (composite of cardiovascular death, myocardial infarction, ischemic stroke, ischemia-driven revascularization, or stent thrombosis) and bleeding outcomes (Bleeding Academic Research Consortium type 2, 3, or 5 bleeding) were evaluated. Results: Of 2697 patients with AMI (mean [SD] age, 60.0 [11.4] years; 454 [16.8%] female), 1371 (50.8%; 684 assigned to de-escalation and 687 assigned to ticagrelor-based DAPT) had high ischemic risk features and a significantly higher risk of ischemic outcomes than those without high ischemic risk (1326 patients [49.2%], including 665 assigned to de-escalation and 661 assigned to ticagrelor-based DAPT) (hazard ratio [HR], 1.74; 95% CI, 1.15-2.63; P = .01). De-escalation to clopidogrel, compared with ticagrelor-based DAPT, showed no significant difference in ischemic risk across the high ischemic risk group (HR, 0.88; 95% CI, 0.54-1.45; P = .62) and the non-high ischemic risk group (HR, 0.65; 95% CI, 0.33-1.28; P = .21), without heterogeneity (P for interaction = .47). The bleeding risk of the de-escalation group was consistent in both the high ischemic risk group (HR, 0.64; 95% CI, 0.37-1.11; P = .11) and the non-high ischemic risk group (HR, 0.42; 95% CI, 0.24-0.75; P = .003), without heterogeneity (P for interaction = .32). Conclusions and Relevance: In stabilized patients with AMI, the ischemic and bleeding outcomes of an unguided de-escalation strategy with clopidogrel compared with a ticagrelor-based DAPT strategy were consistent without significant interaction, regardless of the presence of high ischemic risk.

Predictors for early cardiac death after discharge from successfully treated acute myocardial infarction.

Background: The use of a cardioverter defibrillator for the primary prevention of sudden cardiac death is not recommended within 40 days after acute myocardial infarction (AMI). We investigated the predictors for early cardiac death among patients who were admitted for AMI and successfully discharged. Methods: Consecutive patients with AMI were enrolled in a multicenter prospective registry. Among 10,719 patients with AMI, 554 patients with in-hospital death and 62 patients with early non-cardiac death were excluded. Early cardiac death was defined as a cardiac death within 90 days after index AMI. Results: Early cardiac death after discharge occurred in 168/10,103 (1.7%) patients. A defibrillator was not implanted in all patients with early cardiac death. Killip class ≥3, chronic kidney disease stage ≥4, severe anemia, cardiopulmonary support usage, no dual antiplatelet therapy at discharge, and left ventricular ejection fraction (LVEF) ≤35% were independent predictors for early cardiac death. The incidence of early cardiac death according to the number of factors added to LVEF criteria in each patient was 3.03% for 0 factor, 8.11% for 1 factor, and 9.16% for ≥2 factors. Each model that sequentially added the factors in the presence of LVEF criteria showed a significant gradual increase in predictive accuracy and an improvement in reclassification capability. A model with all factors showed C-index 0.742 [95% CI 0.702-0.781], p < 0.001; IDI 0.024 [95% CI 0.015-0.033], p < 0.001; and NRI 0.644 [95% CI 0.492-0.795], p < 0.001. Conclusion: We identified six predictors for early cardiac death after discharge from AMI. These predictors would help to discriminate high-risk patients over current LVEF criteria and to provide an individualized therapeutic approach in the subacute stage of AMI.

Office-Visit Heart Rate and Long-Term Cardiovascular Events in Patients with Acute Myocardial Infarction.

An elevated heart rate at admission or discharge is known to be associated with poor cardiovascular outcomes in patients with acute myocardial infarction (AMI). The association between post-discharge average office-visit heart rate and cardiovascular outcomes in patients with AMI has rarely been studied. We analyzed data for 7840 patients from the COREA-AMI registry who had their heart rates measured at least three times after hospital discharge. The office-visit heart rates were averaged and categorized into four groups by quartiles (<68, 68-74, 74-80, and >80 beats per minute). The primary end point was a composite of cardiovascular death, myocardial infarction, and ischemic stroke. During a median of 5.7 years of follow-up, major adverse cardiovascular events (MACE) affected 1357 (17.3%) patients. An average heart rate higher than 80 bpm was associated with an increased incidence of MACE compared to the reference average heart rate of 68-74 bpm. When dichotomized into <74 or ≥74 bpm, a lower average heart rate was not associated with MACE in patients with LV systolic dysfunction, in contrast to those without LV systolic dysfunction. An elevated average heart rate at office visits after AMI was associated with an increased risk of cardiovascular outcomes. Heart rate monitoring at office visits after discharge provides an important predictor related to cardiovascular events.

Role of Statins after Endovascular Repair of Abdominal Aortic Aneurysms: A Nationwide Population-Based Study.

The role of statins after endovascular abdominal aortic aneurysm repair (EVAR) has not been well established in an Asian context. In this study, the use of statins and their association with long-term health outcomes were evaluated in patients undergoing EVAR using the Korean National Health Insurance Service database. Among the 8893 patients who underwent EVAR from 2008 to 2018, 3386 (38.1%) were on statins prior to the procedure. Patients using statins had a higher prevalence of comorbidities, such as hypertension (88.4% vs. 71.5%), diabetes mellitus (24.5% vs. 14.1%), and heart failure (21.6% vs. 13.1%), compared with non-users (all p < 0.001). After propensity score matching, statin use prior to EVAR was associated with a lower risk of all-cause mortality (HR 0.85, 95% CI 0.78-0.92, p < 0.001) and cardiovascular mortality (HR 0.66, 95% CI 0.51-0.86, p = 0.002). Statin use following EVAR was associated with a lower risk of adverse events, but not significantly so. Patients on statins both preceding and following EVAR had a lower risk of all-cause mortality (HR 0.82, 95% CI 0.73-0.91, p < 0.001) and cardiovascular mortality (HR 0.62, 95% CI 0.44-0.87, p = 0.007), compared with statin non-users. Among Korean patients undergoing EVAR, the persistent use of statins prior to and after the procedure was associated with a lower risk of mortality, compared with non-statin users.

Case report: Constrictive pericarditis after coronary artery perforation during percutaneous coronary intervention.

A 77-year-old man underwent percutaneous coronary intervention (PCI) at the right coronary artery, which was complicated by coronary artery perforation (CAP). After prolonged balloon tamponade proximal to the CAP there was no more contrast extravasation, and the CAP was thought to have resolved. Computed tomography (CT) and echocardiography the following day did not find evidence of continued bleeding, and the patient was discharged. Echocardiograms and chest CT scans obtained one week and two months after PCI detected no remarkable interval change. The patient complained of progressive dyspnea and abdominal distension seven months after PCI however, and echocardiography found an increased amount of pericardial effusion and constrictive physiology. The patient underwent pericardiectomy due to congestive hepatopathy, and progressive dyspnea. The pericardium was thickened and adhesive, and a dark bloody effusion was found. Pathology was unremarkable except for thick fibrosis. After the operation the patient made full recovery, and is stable three years after surgery.

Real-World Comparison of Transcatheter Versus Surgical Aortic Valve Replacement in the Era of Current-Generation Devices.

Few studies have reported comparisons of out-of-hospital clinical outcomes after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) in the era of current-generation valves that reflect the real-world situation. Data on patients with severe AS aged 65 years or older who underwent TAVR or SAVR between 2015 and 2018 were obtained from the National Health Insurance Service in Korea and clinical event rate was analyzed. The primary endpoint was all-cause death at 1 year. The cohort included a total of 4623 patients over 65 years of age, of whom 1269 (27.4%) were treated with TAVR. After 1:1 propensity score matching, 2120 patients were included in the study. TAVR was associated with reduced 1-year mortality (hazard ratio (HR): 0.55; 95% confidence interval (CI): 0.42−0.70; p < 0.001). There was no difference between the groups in the incidence of ischemic stroke (HR: 0.72, 95% CI: 0.43−1.20; p = 0.21) and intracranial hemorrhage (HR: 1.10; p = 0.74). Permanent pacemaker insertion was observed more frequently in the TAVR cohort (9.4% vs. 2.5%, HR: 3.95, 95% CI: 2.57−6.09; p < 0.001), whereas repeat procedures were rare in both treatments (0.5% vs. 0.3%, p = 0.499). In the nation-wide real-world data analysis, TAVR with current-generation devices showed significantly lower 1-year mortality compared to SAVR in severe AS patients.

Impact of the risk of malnutrition on bleeding, mortality, and ischemic events in patients with acute myocardial infarction.

BACKGROUND & AIMS: Data regarding the relationship between malnutrition and clinical outcomes of acute myocardial infarction (AMI) is limited. The study aims to evaluate the clinical impact of malnutrition in AMI patients after percutaneous coronary intervention (PCI). METHODS AND RESULTS: The COREA-AMI registries identified 10,161 AMI patients who underwent PCI from January 2004 to August 2014. Patients with geriatric nutritional risk index (GNRI) scores of <82, 82 to <92, 92 to <98, and ≥98 were categorized as having severe, moderate, mild malnutrition risk, and absence of risk, respectively. Associations of GNRI with Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding, all-cause death, and major cardiovascular events (MACEs; a composite of cardiovascular death, myocardial infarction, or ischemic stroke) were evaluated. Over 50% of AMI patients were malnourished, with 25.0%, 22.7%, and 4.9% having mild, moderate, and severe malnutrition risks, respectively. Over a median 4.9-year follow-up, patients with malnutrition risk had higher risks of BARC 3 or 5 bleeding (adjusted hazard ratios [aHRs], 1.27, 1.55, and 2.02 for mild, moderate, and severe, respectively; p < 0.001), all-cause death (aHRs, 1.26, 1.46, and 1.85 for mild, moderate, and severe, respectively; p < 0.001), and MACEs (aHRs, 1.14, 1.32, and 1.67 for mild, moderate, and severe, respectively; p < 0.001) than patients without risk. CONCLUSION: Elevated malnutrition risk was common among AMI patients undergoing PCI and was strongly associated with a higher risk of major bleeding, all-cause death, and major ischemic events.

Clinical benefit of long-term use of dual antiplatelet therapy for acute myocardial infarction patients with the PEGASUS-TIMI 54 criteria.

Background: We evaluated the effectiveness of extended dual antiplatelet therapy (DAPT) usage after 2nd-generation drug elution stent implantation in acute myocardial infarction (AMI) survivors with high ischemic risk characteristics who had no major bleeding for 24 months under at least 1 year of DAPT maintenance. Materials and methods: The primary ischemic and bleeding endpoints were the risk of mortality and the risk of BARC 3 or 5 (major) bleeding. We investigated the event rates for 2-5 years after the index procedure. Results: Of 3382 post-AMI survivors who met the PEGASUS-TIMI 54 (PEGASUS) criteria and without major bleeding until 2 years, 2281 (67.4%) maintained DAPT over 24 months, and 1101 (32.5%) switched DAPT to a single antiplatelet agent. The >24 M DAPT group showed a lower risk of mortality than the 12-24 M DAPT group (7.2 vs. 9.2%; adjusted hazard ratio: 0.648; 95% confidence interval: 0.595-0.976; p < 0.001). The mortality risk was significantly greater as the number of PEGASUS criteria increased (p < 0.001). DAPT > 24 months was not significantly associated with a decreased risk for major bleeding in the population meeting the PEGASUS criteria (2.0 vs. 1.1%; p = 0.093). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences. Conclusion: Extended DAPT over 24 months was associated with a lower risk of mortality without increasing the risk of major bleeding among 2 years survivors after AMI who met the PEGASUS criteria and had no major bleeding events before 24 months.

Prognosis and the Effect of De-Escalation of Antiplatelet Therapy After Nuisance Bleeding in Patients With Myocardial Infarction.

BACKGROUND: Data regarding prognosis and management after nuisance bleeding (NB) is limited. The purpose was to examine the prognostic significance of NB in patients receiving potent dual antiplatelet treatment (DAPT) after acute myocardial infarction and the impact of de-escalation of DAPT on clinical outcomes thereafter. METHODS: From the TALOS-AMI trial (Ticagrelor Versus Clopidogrel in Stabilized Patients With Acute Myocardial Infarction)' 2583 patients were used to investigate the clinical impact of NB (defined as Bleeding Academic Research Consortium [BARC] 1 bleeding) during 1-month treatment with ticagrelor-based DAPT after acute myocardial infarction. We assessed the associations between NB within 1 month and BARC 2, 3, or 5 bleeding and major adverse cardiovascular event (a composite of cardiovascular death, myocardial infarction, stroke) from 1 to 12 months. We also evaluated the effect of de-escalation to clopidogrel in patients with or without NB. RESULTS: NB occurred in 416 patients (16.7%) after 1 month of ticagrelor-based DAPT. At 1 year, NB was not associated with increase in BARC 2, 3, or 5 bleeding (hazard ratio [HR]' 1.29 [95% CI' 0.7-2.14]) and major adverse cardiovascular event (HR' 1.72 [95% CI' 0.87-3.39]). However, patients with NB had an increased risk of BARC 2, 3, or 5 bleeding at 6 months (HR, 1.94 [95% CI, 1.08-3.48]; P=0.026), which diminished over the next 6 months. De-escalation from ticagrelor to clopidogrel reduced the incidence of BARC 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in NB (HR' 0.31 [95% CI' 0.10-0.92]) and non-NB patients (HR' 0.58 [95% CI' 0.37-0.90]) without heterogeneity (P interaction=0.291). There was no increase in major adverse cardiovascular event after DAPT de-escalation, irrespective of NB. CONCLUSIONS: NB was frequent in patients with acute myocardial infarction on 1-month ticagrelor-based DAPT and was associated with an early increase of bleeding. DAPT de-escalation after NB may reduce bleeding without increasing ischemic events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02018055.

Association Between Bleeding and New Cancer Detection and the Prognosis in Patients With Myocardial Infarction.

Background Antithrombotic agents to treat patients with acute myocardial infarction can cause bleeding, which may reveal undiagnosed cancer. However, the relationship between bleeding and new cancer diagnosis and the prognostic impact is still unclear. Methods and Results We analyzed the new cancer diagnosis, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and all-cause death of 10 364 patients with acute myocardial infarction without a history of previous cancer in a multicenter acute myocardial infarction registry. During a median of 4.9 years, 1109 patients (10.7%) experienced Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and 338 patients (3.3%) were newly diagnosed with cancer. Bleeding Academic Research Consortium 2, 3, or 5 bleeding was associated with an increased risk of new cancer diagnosis (subdistribution hazard ratio [sHR] 3.29 [95% CI, 2.50-4.32]). In particular, there were robust associations between gastrointestinal bleeding and new gastrointestinal cancer diagnosis (sHR, 19.96 [95% CI, 11.30-29.94]) and between genitourinary bleeding and new genitourinary cancer diagnosis (sHR, 28.95 [95% CI, 14.69-57.07]). The risk of all-cause death was not lower in patients diagnosed with new gastrointestinal cancer after gastrointestinal bleeding (hazard ratio [HR], 4.05 [95% CI, 2.04-8.02]) and diagnosed with new genitourinary cancer after genitourinary bleeding (HR, 2.79 [95% CI, 0.81-9.56]) than in patients newly diagnosed with cancer without previous bleeding. Conclusions Clinically significant bleeding, especially gastrointestinal and genitourinary bleeding, in patients with AMI was associated with an increased risk of new cancer diagnoses. However, the bleeding preceding new cancer detection was not associated with better survival. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385682 and NCT02806102.

High Uric Acid Levels in Acute Myocardial Infarction Provide Better Long-Term Prognosis Predictive Power When Combined with Traditional Risk Factors.

The current study aimed to investigate the association between serum UA levels and the mortality rate of AMI patients. We analyzed 5888 patients with successfully revascularized AMI (mean age: 64.0 ± 12.7 years). The subjects were divided into the high UA group (uric acid >6.5 mg/dL for males, >5.8 mg/dL for females) or the normal UA group based on initial serum UA level measured at admission. The primary outcome was all-cause mortality. A total of 4141 (70.3%) and 1747 (29.7%) patients were classified into the normal UA group and high UA groups, respectively. Over a median follow-up of 5.02 (3.07, 7.55) years, 929 (21.5%) and 532 (34.1%) patients died in each group. Cox regression analysis identified high UA levels as an independent predictor of all-cause mortality (unadjusted hazard ratio (HR) 1.69 [95% CI 1.52−1.88]; p < 0.001, adjusted HR 1.18 [95% CI: 1.05−1.32]; p = 0.005). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences. The predictive accuracies of conventional clinical factor discrimination and reclassification were significantly improved upon the addition of hyperuricemia (C-index 0.788 [95% CI 0.775−0.801]; p = 0.005, IDI 0.004 [95% CI 0.002−0.006]; p < 0.001, NRI 0.263 [95% CI 0.208−0.318]; p < 0.001).

Prognostic Impact of the HFA-PEFF Score in Patients with Acute Myocardial Infarction and an Intermediate to High HFA-PEFF Score.

This study aimed to investigate the efficacy of the HFA-PEFF score in predicting the long-term risks in patients with acute myocardial infarction (AMI) and an HFA-PEFF score ≥ 2. The subjects were divided according to their HFA-PEFF score into intermediate (2−3 points) and high (4−6 points) score groups. The primary outcome was all-cause mortality. Of 1018 patients with AMI and an HFA-PEFF score of ≥2, 712 (69.9%) and 306 (30.1%) were classified into the intermediate and high score groups, respectively. Over a median follow-up of 4.8 (3.2, 6.5) years, 114 (16.0%) and 87 (28.4%) patients died in each group. Multivariate Cox regression identified a high HFA-PEFF score as an independent predictor of all-cause mortality [hazard ratio (HR): 1.53, 95% CI: 1.15−2.04, p = 0.004]. The predictive accuracies for the discrimination and reclassification were significantly improved (C-index 0.750 [95% CI 0.712−0.789]; p = 0.049 and NRI 0.330 [95% CI 0.180−0.479]; p < 0.001) upon the addition of a high HFA-PEFF score to clinical risk factors. The model was better at predicting combined events of all-cause mortality and heart failure readmission (C-index 0.754 [95% CI 0.716−0.791]; p = 0.033, NRI 0.372 [95% CI 0.227−0.518]; p < 0.001). In the AMI cohort, the HFA-PEFF score can effectively predict the prognosis of patients with an HFA-PEFF score of ≥2.

Independent Clinical Impacts of Procedural Complexity on Ischemic and Bleeding Events in Patients with Acute Myocardial Infarction: Long-Term Clinical Study.

This study aimed to investigate the relationship between a complex percutaneous coronary intervention (C-PCI) and long-term clinical outcomes in the AMI cohort. A total of 10,329 patients were categorized into the C-PCI and non-C-PCI groups. The primary ischemic endpoint was a composite of major adverse cardiac events (MACEs, cardiac death, myocardial infarction, stent thrombosis and revascularization). The primary bleeding endpoint was the risk of overt bleeding (BARC 2, 3 or 5). The median follow-up duration was 4.9 (2.97, 7.16) years. The risks of MACEs and bleeding were significantly higher in the C-PCI group (hazard ratio (HR): 1.72; 95% confidence interval (CI): 1.60 to 1.85; p < 0.001; and HR: 1.32; 95% CI: 1.17 to 1.50; p < 0.001, respectively). After propensity score matching, compared to the non-C-PCI group, the adjusted MACE rate in C-PCI remained significantly higher (p < 0.001), but no significant interaction (p = 0.273) was observed for bleeding. Significant differences in overt bleeding were observed only within the first three months (p = 0.024). The MACEs were consistently higher in the C-PCI group with or without severe comorbid conditions (p < 0.001 for both). Patients with AMI who undergo C-PCI experience worse long-term ischemic outcomes after successful PCI, regardless of the presence of severe comorbidities.

Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts.

Heart failure (HF) is a frequent consequence of myocardial infarction (MI). Identification of the precise, time-dependent composition of inflammatory cells may provide clues for the establishment of new biomarkers and therapeutic approaches targeting post-MI HF. Here, we investigate the spatiotemporal dynamics of MI-associated immune cells in a mouse model of MI using spatial transcriptomics and single-cell RNA-sequencing (scRNA-seq). We identify twelve major immune cell populations; their proportions dynamically change after MI. Macrophages are the most abundant population at all-time points (>60%), except for day 1 post-MI. Trajectory inference analysis shows upregulation of Trem2 expression in macrophages during the late phase post-MI. In vivo injection of soluble Trem2 leads to significant functional and structural improvements in infarcted hearts. Our data contribute to a better understanding of MI-driven immune responses and further investigation to determine the regulatory factors of the Trem2 signaling pathway will aid the development of novel therapeutic strategies for post-MI HF.

Long-Term Clinical Outcomes and Its Predictors Between the 1- and 2-Stent Strategy in Coronary Bifurcation Lesions　- A Baseline Clinical and Lesion Characteristic-Matched Analysis.

BACKGROUND: Differences in the impact of the 1- or 2-stent strategy in similar coronary bifurcation lesion conditions are not well understood. This study investigated the clinical outcomes and its predictors between 1 or 2 stents in propensity score-matched (PSM) complex bifurcation lesions.Methods and Results: We analyzed the data of patients with bifurcation lesions, obtained from a multicenter registry of 2,648 patients (median follow up, 53 months). The patients were treated by second generation drug-eluting stents (DESs). The primary outcome was target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TVMI), and ischemia-driven target lesion revascularization (TLR). PSM was performed to balance baseline clinical and angiographic discrepancies between 1 and 2 stents. After PSM (N=333 from each group), the 2-stent group had more TLRs (hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.42-6.97, P=0.005) and fewer hard endpoints (composite of cardiac death and TVMI; HR 0.44, 95% CI 0.19-1.01, P=0.054), which resulted in a similar TLF rate (HR 1.40, 95% CI 0.83-2.37, P=0.209) compared to the 1-stent group. Compared with 1-stent, the 2-stent technique was more frequently associated with less TLF in the presence of main vessel (pinteraction=0.008) and side branch calcification (pinteraction=0.010). CONCLUSIONS: The 2-stent strategy should be considered to reduce hard clinical endpoints in complex bifurcation lesions, particularly those with calcifications.