1-year Events Research Articles

Dose-finding and efficacy confirmation trial of the superselective intra-arterial infusion of cisplatin and concomitant radiation therapy for locally advanced maxillary sinus cancer (JCOG1212): final analysis.

JCOG1212 is a dose-finding and efficacy confirmatory study of concurrent superselective intra-arterial infusion of cisplatin and radiotherapy (RADPLAT) for locally advanced primary squamous cell carcinoma of the maxillary sinus (cT4a,bN0M0). In this study, we report the results of the final analysis of the efficacy confirmation phase for the T4a cohort with 5-year follow-up data to evaluate the late adverse events and long-term efficacy. Based on the results of the dose-finding phase, the efficacy confirmation phase consisted of seven weekly intra-arterial infusions of cisplatin 100mg/m2 combined with radiotherapy (70Gy). The 5-year prognosis and late adverse events were evaluated. Between April 2014 and August 2018, 64 patients were included in the analysis (one ineligible patient was excluded); 31 patients were treated with three-dimensional conformal radiation therapy (3D-CRT) and 33 with intensity modulated radiation therapy (IMRT). The 5-year overall survival, event-free survival, and local event-free survival was 71.9, 54.7, and 57.5%, respectively. In terms of late adverse events, grade 3 or higher non-hematologic toxicity was observed in 42.9% of 63 patients (retinopathy: 12, cataract: 10, osteonecrosis of mandible: 4, etc.). Grade 3 and 4 cataracts of affected side appeared in 22.6% (7/31) of the 3D-CRT group compared to 3.1% (1/32) in the IMRT group. Twenty-one patients had died, with 15 from the primary disease, 5 from other causes, and 1 from treatment-related cause. The prognosis of RADPLAT was favorable after 5-year follow-up with acceptable late adverse events and low proportion of treatment related death.

Development and Validation of Risk Stratification for Heart Failure After Acute Coronary Syndrome Based on Dynamic S100A8/A9 Levels.

The early assessment of heart failure (HF) risk in patients with acute coronary syndrome (ACS) can help reduce mortality. S100A8/A9 is not only rapidly released after myocardial ischemia, but is also involved in reperfusion injury, which is an important predictor of HF after ACS. We attempted to construct a reliable HF risk stratification tool for evaluating patients with ACS after reperfusion therapy based on S100A8/A9 dynamic changes. This prospective study included 3 independent cohorts of patients with ACS who received reperfusion therapy. The discovery cohort was divided into 2 subgroups: the longitudinal subgroup (n=264) with serum S100A8/A9 levels measured at admission and on days 1, 2, 3, and 4 postadmission, respectively, and the 2-point subgroup (n=798) with S100A8/A9 levels measured at admission and on day 1 postadmission, respectively. Validation cohorts 1 (n=1399) and 2 (n=1183) both had S100A8/A9 levels measured on day 1 postadmission. HF events included in-hospital HF events after the initial presentation and long-term HF events after discharge. The median follow-up for the discovery cohort, validation cohort 1, and validation cohort 2 was 4.2, 2.6, and 1.8 years, respectively. In the discovery cohort, S100A8/A9's predictive ability at day 1 surpassed other time points. Through the S100A8/A9-guided risk stratification, patients deemed high risk (>7900 ng/mL) exhibited a higher 1-year HF event rate (46% versus 2%, 38% versus 5%) than patients at low risk (<2100 ng/mL) in both validation cohorts. Among patients without left ventricular dysfunction after ACS, β-blocker therapy correlated with reduced 1-year HF events in intermediate-to- high-risk patients but not in low-risk patients. S100A8/A9 levels on day 1 accurately classified patients at varying risks of HF, serving as a robust tool for HF risk prediction and treatment guidance. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03752515.

Comparative Effectiveness of Rosuvastatin Versus Atorvastatin in Acute Ischemic Stroke Treatment.

Research specifically addressing the efficacy of rosuvastatin versus atorvastatin in patients with ischemic stroke is insufficient. Using a large stroke registry, we investigated whether 2 commonly used statins, rosuvastatin and atorvastatin, differ in their effectiveness in reducing the risk of vascular events in patients with acute ischemic stroke. We analyzed data from a nationwide stroke registry in South Korea between January 2011 and April 2022. Patients with acute ischemic stroke within 7 days of onset who were prescribed either atorvastatin or rosuvastatin at discharge were included. The primary outcome was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause mortality within 1 year. A total of 43 512 patients (age, 69.2±12.5 years; male, 59.8%) were analyzed in this study. Atorvastatin was used in 84.8% (n=36 903), and rosuvastatin was used in 15.2% (n=6609). The 1-year cumulative event rate of the composite of recurrent stroke, myocardial infarction, and all-cause mortality was significantly lower in the rosuvastatin group than in the atorvastatin group (9.7% [95% CI, 9.0-10.5] versus 10.7% [95% CI, 10.4-11.0]; P=0.049). Cox proportional hazards analysis revealed that rosuvastatin, compared with atorvastatin, was significantly associated with less risk of 1-year composite of recurrent stroke, myocardial infarction, and all-cause mortality, with an absolute risk reduction of 1% [95% CI, -1.8 to -0.2] and a relative risk reduction of 11% (hazard ratio, 0.89 [95% CI, 0.82-0.97]). However, there were discrepancies in the statistical significance of the results between the propensity score matching and stabilized inverse probability of treatment weighting analysis. The results of this analysis of a large cohort of patients with ischemic stroke suggested that, compared with atorvastatin, rosuvastatin was significantly associated with a reduced risk of a 1-year composite of recurrent stroke, myocardial infarction, and all-cause mortality in patients with acute ischemic stroke. However, in real clinical practice, rosuvastatin is used less than one-fifth as frequently as atorvastatin in patients with acute ischemic stroke. This study serves as a hypothesis-generating function.

Mid-Regional Pro-Adrenomedullin Is Associated with Adverse Cardiovascular Outcomes After Cardiac Surgery

Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that mirrors cardiac function and fibrosis. Therefore, we aimed to investigate the prognostic potential of MR-proADM in patients undergoing elective cardiac surgery. Methods: Patients undergoing elective cardiac bypass and/or valve surgery were prospectively enrolled between May 2013 and August 2018. The primary endpoint was the composite of hospitalization for heart failure (HHF) or cardiovascular (CV) mortality. Results: In total, 500 patients (146 female [29.2%]; median age 69.8 years (IQR 60.6–75.5 years) were included. Individuals were stratified into risk categories based on their MR-proADM values (Low Risk ≤ 0.63 nmol/L, Intermediate Risk &gt; 0.63 and ≤0.84, High Risk &gt; 0.84). A significant increase in 5-year event rates for HHF/CV mortality in patients in the high-risk category (Low Risk 8.6% vs. High Risk 37.7%, p &lt; 0.001) was observed. MR-pro ADM showed an independent association with HHF/ CV mortality (adjusted HR of 3.43, 95% CI 1.83–6.42; p &lt; 0.001 comparing the High-Risk group to the Low-Risk group). Conclusions: MR-pro ADM was found to be a strong and independent predictor for HHF/CV mortality in patients undergoing elective cardiac surgery. Considering a personalized diagnostic and prognostic work-up, a standardized preoperative evaluation of MR-proADM levels might help to identify patients at risk for major adverse events and early re-hospitalization.

Long-Term Clinical Impact of Paravalvular Leak Following Transcatheter Aortic Valve Implantation.

Background: Paravalvular leak (PVL) was initially recognized as one of the most common complications after transcatheter aortic valve implantation (TAVI) and has been linked to adverse clinical outcomes, including mortality. This study aims to assess the long-term clinical effects of PVL in patients undergoing TAVI with the latest generation of transcatheter aortic valves, as part of the national observational prospective multicenter study OBSERVANT II. Methods: OBSERVANT II included all consecutive patients with severe aortic stenosis who underwent TAVI across 28 Italian centers from December 2016 to September 2018. A total of 2125 patients were included in this analysis and stratified according to the presence of moderate-to-severe PVL (significant PVL, n = 155) versus no/trace-to-mild PVL (no significant PVL, n = 1970). The primary endpoint was 5-year major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, stroke, myocardial infarction, and coronary revascularization. Five-year all cause death and re-hospitalization for heart failure (HF) were the secondary endpoints. Results: In our cohort, the incidence of moderate-to-severe PVL was 7%. Age, aortic anulus perimeter, and self-expandable valves were determinants of PVL. The risk of MACCE, all-cause death, and re-hospitalization for HF at the 5-year follow-up were not different between the study groups [HR = 1.07 (95% CI: 0.85-1.34) p = 0.571; HR = 1.10 (95% CI: 0.87-1.39) p = 0.435; HR = 1.20 (95% CI: 0.88-1.62) p = 0.245, respectively]. Conclusions: In this analysis of the OBSERVANT II study, moderate/severe PVL was not associated with a higher incidence of MACCE and re-hospitalization for heart failure at the 5-year follow-up.

Development and Validation of a Nomogram for Predicting Long-Term Net Adverse Clinical Events in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention.

Patients with a high risk of bleeding undergoing percutaneous coronary intervention (PCI-HBR) were provided consensus-based criteria by the Academic Research Consortium for High Bleeding Risk (ARC-HBR). However, the prognostic predictors in this group of patients have yet to be fully explored. Thus, an effective prognostic prediction model for PCI-HBR patients is required. We prospectively enrolled PCI-HBR patients from May 2022 to April 2024 at West China Hospital of Sichuan University. The cohort was randomly divided into training and internal validation sets in a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) regression algorithm was employed to select variables in the training set. Subsequently, a prediction model for 1-year net adverse clinical events (NACEs)-free survival was developed using a multivariable Cox regression model, and a nomogram was constructed. The outcome of the NACEs is defined as a composite endpoint that includes death, myocardial infarction, ischemic stroke, and Bleeding Academic Research Consortium (BARC) grade 3-5 major bleeding. Validation was conducted exclusively using the internal validation cohort, assessing the discrimination, calibration, and clinical utility of the nomogram. This study included 1512 patients with PCI-HBR, including 1058 in the derivation cohort and 454 in the validation cohort. We revealed five risk factors after LASSO regression, Cox regression, and clinical significance screening. These were then utilized to construct a prognostic prediction nomogram, including chronic kidney disease, left main stem lesion, multivessel disease, triglycerides (TG), and creatine kinase-myocardial band (CK-MB). The nomogram exhibited strong predictive ability (the area under the curve (AUC) to predict 1-year NACE-free survival was 0.728), displaying favorable levels of accuracy, discrimination, and clinical usefulness in the internal validation cohort. This study presents a nomogram to predict 1-year NACE outcomes in PCI-HBR patients. Internal validation showed strong predictive capability and clinical utility. Future research should validate the nomogram in diverse populations and explore new predictors for improved accuracy. The data for this study were obtained from the PPP-PCI registry, NCT05369442 (https://clinicaltrials.gov/study/NCT05369442).

Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct.

After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI. We identified participants with lacunar stroke and MRI-confirmed RSSI from 3 prospective studies. At baseline, we collected risk factors, RSSI characteristics, small vessel disease (SVD) features, and microstructural integrity on diffusion imaging. Over 1-year, we repeated MRI and recorded 'caps/tracks' blinded to other data. We evaluated predictors of 'caps/tracks', and their association with 1-year functional (modified Rankin Scale score ≥2), mobility (Timed Up-and-Go), cognitive outcomes (Montreal Cognitive Assessment [MoCA] score <26), and recurrent cerebrovascular events (stroke/transient ischemic attack/incident infarct) using multivariable regression. Among 185 participants, 93 (50.3%) developed 'caps/tracks' first detected at median 198 days after stroke. 'Caps/tracks' were independently predicted by baseline factors: larger RSSI, RSSI located in white matter, higher SVD score, and higher mean diffusivity in normal-appearing white matter (odds ratio [OR] [95% confidence interval {CI}], 1.15 [1.07-1.25], 6.01 [2.80-13.57], 1.77 [1.31-2.44], 1.42 [1.01-2.03]). At 1 year, 'cap/track' formation was associated with worse functional outcome (OR: 3.17, 95% CI: 1.28-8.22), slower gait speed (β: 0.13, 95% CI: 0.01-0.25), and recurrent cerebrovascular events (hazard ratio [HR]: 2.05, 95% CI: 1.05-4.02), but not with cognitive impairment. 'Caps/tracks' after RSSI are associated with worse clinical outcomes, and may reflect vulnerability to progressive SVD-related injury. Reducing 'caps/tracks' may offer early efficacy markers in trials aiming to improve outcome after lacunar stroke. ANN NEUROL 2025.

High-resolution assessment of climate change impacts on the surface energy and water balance in the glaciated Naryn River basin, Central Asia.

Mountain regions of Central Asia are experiencing strong influences from climate change, with significant reductions in snow cover and glacial reserves. A comprehensive assessment of the potential consequences under the worst-case climate scenario is vital for adaptation measures throughout the region. Water balance analysis in the Naryn River basin was conducted for the baseline period of 1981-2000 including potential changes under the worst-case SSP5-8.5 scenario for 2077-2096 by combining high-resolution (5km) regional climate projections with fully distributed glacio-hydrological (1km) modeling. Results showed that with the complete degradation of glaciers and increase in evapotranspiration, the overall runoff will decrease by 16%, and in the upper basins, the reduction will exceed 40%. The maximum snow water equivalent (SWE) is projected to decrease by 17%, and the seasonal peak of SWE will occur one month earlier. The transition from snow to rain will significantly affect lower regions, increasing extremes in peak runoff and causing 10-year recurrence interval events to occur every 3-4 years. Moreover, extreme runoff in high mountainous areas will increase due to intensified snowmelt and increased rainfall extremes. Additionally, a gradient of surface soil temperature change of 0.1°C per 100m elevation gain was observed, suggesting a potential snow-albedo feedback effect that could further amplify the warming, especially at higher altitudes. This study provides a robust analytical framework to assess the complex responses of mountain ecosystems to the impacts of climate change, with the potential of widespread application for addressing the challenges facing these critical regions.

Preoperative Neutrophil-to-Lymphocyte Ratio as a Predictor of Clinical Outcomes in Patients Undergoing Femoral Endarterectomy.

Background/Objectives: This study aimed to evaluate the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with peripheral arterial disease (PAD) undergoing femoral endarterectomy. Methods: We performed a retrospective analysis of our institutional data, evaluating consecutive patients with PAD who underwent femoral endarterectomy between January 2013 and March 2023. The main objective was to assess the prognostic value of preoperative NLR for 5-year mortality. Additionally, we examined its relationship with perioperative clinicopathological features and 5-year major adverse limb events (MALEs). Results: During the study period, 200 consecutive patients underwent femoral endarterectomy. Of these, 128 patients with available NLR values within 30 days prior to surgery were analyzed. According to the receiver operating characteristic curve, the cut-off value of NLR was 4.0. Eighty-seven patients (68.0%) were assigned to the low-NLR group, and 41 patients (32.0%) to the high-NLR group. The frequency of postoperative complications did not differ significantly between the two groups. Freedom from MALEs up to five years was significantly lower in the high-NLR group (66.0% vs. 46.5%, p = 0.006). The overall survival rates were significantly lower in the high-NLR group (p < 0.001). At 1, 3, and 5 years, the survival rates in the low-NLR group were 96.4%, 91.6%, and 84.5%, respectively, while those in the high-NLR group were 84.2%, 59.5%, and 42.5%. Univariate analysis showed that cerebrovascular disease, end-stage renal disease, Rutherford category ≥ 4, a low albumin concentration (<3.5 g/dL), and a high NLR were significantly associated with 5-year mortality. Multivariate analysis indicated that a high NLR was the only independent factor associated with 5-year mortality. Conclusions: Preoperative NLR > 4.0 was significantly associated with 5-year rates of MALE and mortality in patients with symptomatic CFA occlusive disease who underwent femoral endarterectomy.

Impact of White Blood Cell Count After Percutaneous Coronary Intervention on Long-Term Prognosis in Patients with Unstable Angina Pectoris: A Single-Center Retrospective Observational Cohort Study.

An association between white blood cell count (WBC-C) before percutaneous coronary intervention (PCI) and prognosis has been established in patients undergoing PCI. However, the effect of WBC-C after PCI on the long-term prognosis of patients with unstable angina pectoris (UA) is unclear. A retrospective cohort study was conducted in 1811 consecutive patients with UA. The changes of WBC and subgroup counts before and in the early postoperative stages after PCI were observed by paired Wilcoxon signed-rank test. The Kaplan-Meier method and COX proportional regression model were used to evaluate the association between the incidence of 5-year endpoint events and post-PCI leukocytosis. Leukocytosis and neutrocytosis within 24hours after PCI were observed in majority of patients with UA, while lymphocyte count significantly decreased after PCI in those patients. There were no significant differences in 5-year all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) between patients in the post-PCI leukocytosis and the control group. However, the 5-year incidence of major adverse cardiovascular events (MACE) was significantly increased in the post-PCI leukocytosis group (p = 0.017, Log rank test). Leukocytosis after PCI was independently associated with the occurrence of MACE (hazard ratio: 1.36; 95% confidence interval: 1.06-1.75; p = 0.015). Peripheral WBC and neutrophil counts within 24hours after PCI significantly increased in response to PCI in patients with UA, while lymphocyte count significantly decreased after PCI in those patients. The post-PCI leukocytosis offered predictive value for an increased risk of MACE for up to 5 years in patients with UA.

Impact of high bleeding risk and associated risk factors on major adverse cardiovascular or cerebrovascular events in primary percutaneous coronary intervention treated ST-elevation myocardial infarction.

After percutaneous coronary intervention (PCI), patients at high bleeding risk (HBR) according to The Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria have increased risk for ischemic complications. The underlying cause is not well documented. The aim of this study was to assess the ischemic risk among ST-elevation myocardial infarction (STEMI) patients classified as HBR according to the ARC-HBR and to identify individual risk factors. Consecutive STEMI patients treated with primary PCI in a Finnish tertiary hospital between 2016 and 2022 were identified using a database search. Data was collected by reviewing electronic patient records. Bleeding risk was assessed according to the ARC-HBR criteria. The primary endpoint was 1-year major adverse cardiovascular or cerebrovascular event (MACCE). In total, 1367 STEMI patients were included. Cumulative incidence of MACCE was 19.5 % among HBR and 6.32 % among non-HBR. From the ARC-HBR criteria, multivariable competing risk analysis identified use of non-steroidal anti-inflammatory drugs or steroids and active malignancy as risk factors for MACCE. Diabetes and left ventricular ejection fraction <35 % were MACCE predictors and both were more prevalent among HBR patients. Dual antiplatelet therapy duration of ≥3 months significantly reduced risk of MACCE and was less prevalent among HBR. The higher observed ischemic risk among HBR patients might not be explained by bleeding risk status itself but rather with some of its components and other underlying comorbidities and management strategies. These findings may be useful when evaluating the balance of ischemic and bleeding risks based on patient-specific risk factors.

Prognostic Implication of Computational Angiography-Derived Fractional Flow Reserve in Patients With Nonobstructive Coronary Artery Disease.

Risk stratification of patients with symptomatic nonobstructive coronary artery disease remains uncertain. Our study assessed the clinical value of single-vessel, multivessel, and 3-vessel computational angiography-derived fractional flow reserve (caFFR) measurement in patients with nonobstructive coronary artery disease. We enrolled patients with ≤50% stenosis with a caFFR value ≥0.8 in all 3 coronary arteries on coronary angiography. The sum of caFFR values in the 3 vessels was computed for each patient. Patient stratification was based on the median value of the following criteria: single-vessel analysis, multivessel analysis, and 3-vessel analysis. The primary end point of this study was major adverse cardiac events at 5 years, defined as a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. A total of 490 patients were included. The 5-year major adverse cardiac event rates in single-vessel analysis were statistically insignificant between low- and high-caFFR groups (left anterior descending artery [P=0.163]; left circumflex artery [P=0.797]; right coronary artery [P=0.127]). In multivessel analysis, patients in the multiple-vessel low-caFFR group (with 2-3 vessels lower than median value of all coronary arteries) showed an increased risk of 5-year major adverse cardiac events compared with patients in the single-vessel low-caFFR group (0-1 vessel) (hazard ratio [HR], 2.648 [95% CI, 1.141-6.145]; P=0.023). In 3-vessel analysis, patients in the low 3-vessel caFFR group demonstrated a greater 5-year major adverse cardiac event risk than the high 3-vessel caFFR group (HR, 2.43 [95% CI, 1.087-5.433]; P=0.031). We demonstrated that both multiple-vessel and 3-vessel caFFR measurements serve as valuable prognostic indicators for risk assessment in patients with nonobstructive coronary artery disease.

Comparing moderate-severe and severe mitral regurgitation in transcatheter aortic valve replacement on 1-year survival: insights from a Japanese Nationwide Registry.

This study aims to compare 1-year outcomes after transcatheter aortic valve replacement (TAVR) between patients with moderate-severe MR and severe MR preoperatively using the Japan Transcatheter Valve Therapy (J-TVT) registry. Patients undergoing TAVR for aortic stenosis between August 2013 and December 2019 with preoperative mitral regurgitation of moderate-severe (group MR3) or severe (group MR4) were included. Patients with a history of valve surgery and dialysis patients were excluded. A total of 2017 patients were included, and 1-year follow-up data were obtained from the registry (follow-up rate 98.5%). Propensity-score matching between MR3 and MR4 groups was performed. All-cause mortality and the composite outcome of death and/or heart failure events were compared. Crude data showed that 1-year survival was significantly higher in the MR 3 (89.8%) than MR 4 (84.7%) groups, and freedom from 1-year mortality and heart failure events was also higher in the MR 3 (87.1%) than MR 4 (80.5%) groups (p = 0.0001). After propensity-score matching, 452 cases (226 cases each in MR 3 group and MR 4 group) were extracted. Cox regression model showed no statistical difference in the 1-year survival rate between MR 3 group (84.5%) and MR 4 group (85.5%) (p = 0.84), nor in freedom from 1-year death and/or heart failure events between MR 3 group (80.2%) and MR 4 group (81.6%) (p = 0.72). The 1-year survival rate and freedom from death and/or heart failure events were found to be similar between patients undergoing TAVR with MR grade 3 and MR grade 4.

Comparison of invasive and non-invasive gradients before and after TAVI and their implications on clinical outcomes.

Transcatheter aortic valve implantation (TAVI) is recommended for treatment of high-risk aortic stenosis patients. While measuring mean transaortic valve gradient (MG) is crucial in evaluating procedural success, echocardiographic measurements often overestimate direct invasive measurements. This study aimed to examine the discordance between echocardiographic and invasive MGs in TAVI patients and assess their prognostic value on long-term outcomes. This prospective registry included consecutive TAVI patients at a tertiary university hospital. Transthoracic or transoesophageal echocardiography was performed pre-TAVI, at discharge, 1month, 1, and 5years with invasive MG measurements obtained peri-procedurally. The primary endpoints were 5-year all-cause mortality and major adverse cardiac events. Among 1353 patients from 2011 to 2023, non-invasive MGs exceeded invasive MGs pre- and post-implantation (43 [36, 52] mmHg vs. 40 [30, 50] mmHg, p < 0.001; 9 [6, 12] mmHg vs. 4 [2, 7] mmHg, p < 0.001) Pre-procedural MGs correlated better than post-procedural MGs (r = 0.70, p < 0.001 vs. r = 0.23, p < 0.001), particularly in self-expandable valves and smaller sinus of Valsalva diameter (SOVd) (r = 0.33, p < 0.001; r = 0.46, p < 0.001 vs R = 0.06, p = 0.701). Non-invasive MG remained stable from discharge (9 [6, 12] mmHg) to 5years (9 [7, 12] mmHg). While structural valve deterioration and patient-prosthesis mismatch showed no impact, extreme invasive MGs (< 3 or > 6mmHg) predicted worse outcomes (mortality hazard: 1.25 [1.06, 1.88] and 0.85 [0.8, 0.95], respectively), unlike non-invasive measurements. In conclusion, invasive as compared with non-invasive MGs correlated better before than after valve implantation, whereas invasive MGs were always lower than non-invasive MGs. Lower invasive MGs after TAVI appeared to be associated with favourable long-term outcomes.

Outcomes Based on Histological Tumor Necrosis and Predictive Clinical and Laboratory Parameters for Necrosis in Children With Osteosarcoma Treated on a Non-High Dose Methotrexate-Based Chemotherapy Backbone.

Histopathological response to neoadjuvant chemotherapy (NACT) measured as tumor necrosis (TN) has been reported to be prognostic post-high-dose methotrexate (HDMTX)-based chemotherapy. We studied this on a non-HDMTX chemotherapy backbone. Children ≤15years, with osteosarcoma treated on OGS-2012 protocol and surgery post NACT from January 2013 to December 2020 were retrospectively analyzed. TN was expressed as percentage. Outcomes based on different TN cutoffs (used in a dichotomized manner dividing the cohort into two groups of less than/greater than the particular cutoff) and clinical-laboratory parameters predictive of TN were studied. Analysis was done in 258 patients. Amputation was performed in 20.1%. Median TN was 94%. At a median follow-up of 38months (range: 34-45months), 3-year event free survival (EFS) and overall survival (OS) of the whole cohort were 56.1% (SE: 3.3%) and 87.8% (SE: 2.4%). For entire cohort, TN-70% (29.3% vs. 60.7%), 90% (38.7% vs. 69.0%), 100% (50.8% vs. 84.1%), were prognostic for EFS (p = 0.0001), while TN-90% (80.3% vs. 92.9%, p = 0.006) and 100% (85.5% vs. 97.7%, p = 0.023) were prognostic for OS. For localized disease, TN-70% (35.4% vs. 66.4%), 90% (41.6% vs. 77.0%), 100% (54.8% vs. 96.2%) were prognostic for EFS (p = 0.0001) and OS (p = 0.0001). For metastatic disease, TN-70% was prognostic for EFS (16.6% vs. 50.1%, p = 0.0047). Receiver-operator curve derived cutoff of 85.5% TN for EFS, 83.5% TN for OS prognosticated whole and localized cohorts the best. For metastatic cohort, 84.5% TN best prognosticated EFS. Among clinical-laboratory parameters, male gender (OR: 1.9, p = 0.01) and amputation (OR: 2.1, p = 0.014) had a higher risk of less than 90% TN. Tumor necrosis at 90% cutoff in localized disease is prognostic of survival even on a non-HDMTX-based backbone, but exploring other cutoffs for survival predictive and prognostic value could guide future treatment modification strategies and resource allocation in LMICs. Amputation, male gender predicts poor histological necrosis.

Effect of LDL-C/HDL-C ratio on severity of coronary artery disease and 2-year long-term prognosis in elderly patients with coronary heart disease

Objective: To explore the effect of low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio on the severity of coronary artery disease and 2-year adverse events in elderly patients with coronary heart disease. Methods: This prospective, multicenter, observational cohort study was from the prospective observational multicenter cohort for ischemic and hemorrhage risk in coronary artery disease patients (PROMISE) study, in which 18 701 patients with coronary heart disease (CHD) were included from January 2015 to May 2019. Among them, 6 770 elderly patients with CHD were enrolled in the current study. According to the median of LDL-C/HDL-C ratio (2.1), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.1, n=3 346) and high LDL-C/HDL-C group (LDL-C/HDL-C2.1, n=3 424). Baseline data and 2-year outcomes (including death, myocardial infarction, revascularization, stroke) were collected and analyzed in order to found the differences of elderly CHD patients with different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and prognosis using Cox multivariate regression analysis. Results: Patients in the low LDL-C/HDL-C group were older [(71.9±5.5) vs (71.5±5.4) years old, P=0.003], and there was no statistically significant difference in the proportion of males between the two groups (61.9% vs 63.4%,P=0.208). The indicators reflecting the severity of coronary artery lesions, including the number of target lesions, the number of coronary artery disease, preoperative SNYTAX score, and the proportion of triple-vessel disease (1.01±0.81 vs 0.88±0.78, 2.28±0.81 vs 2.14±0.83, 16.05±10.67 vs 13.59±9.49, 49.0% vs 41.0%, respectively, all P0.05) were higher in the high LDL-C/HDL-C group. The 2-year follow-up showed that there was no statistically significant difference in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), all-cause mortality, cardiac death, myocardial infarction, and revascularization between the high LDL-C/HDL-C ratio group and the low LDL-C/HDL-C ratio group. Compared by gender, the incidence of all-cause death and cardiac death in the high LDL-C/HDL-C group of female patients were higher than the low LDL-C/HDL-C group (6.9% vs 4.8%, 5.3% vs 3.7%, both P0.05, respectively); There was no statistically difference in the incidence of adverse events between the two groups of male patients. Cox multivariate regression analysis showed that, regardless of gender, the LDL-C/HDL-C ratio was not a risk factor for 2-year MACCE in elderly patients with CHD (male: HR=1.21, 95%CI: 0.87-1.69; female: HR=0.96, 95%CI: 0.65-1.43;total: HR=1.09, 95%CI: 0.85-1.39,all P0.05). Conclusions: The severity of coronary artery disease is higher in elderly patients with high LDL-C/HDL-C ratio than in those with low LDL-C/HDL-C ratio. The LDL-C/HDL-C ratio is not a risk factor for 2-year adverse cardiovascular and cerebrovascular events in elderly patients with coronary heart disease. However, the incidences of 2-year adverse cardiovascular events of female patients with high LDL-C/HDL-C ratio are higher than patients with low LDL-C/HDL-C ratio.

Intraprocedural 3D-vena contracta area predicts survival after transcatheter edge-to-edge repair: results from MITRA-PRO registry.

The MITRA-PRO registry revealed residual mitral regurgitation (MR) to be an important predictor of survival following transcatheter edge-to-edge repair (TEER). Intraprocedural MR assessment using 3D-Vena Contracta Area (VCA) might be a feasible tool to guide mitral TEER procedures. The study aimed to assess the impact of residual MR assessed by 3D-VCA on 1-year mortality. 823 patients with residual MR quantification using 3D-VCA in the MITRA-PRO registry, were included in this study. 1-year mortality, NYHA classification and major adverse events were assessed 1-year after mitral TEER. Patients with trace residual MR after mitral TEER were allocated to the 3D-VCA < 0.1 cm2 group (27.8%), while a 3D-VCA ≥ 0.1 < 0.3 cm2 (55.4%) was considered as mild and a 3D-VCA ≥ 0.3 cm2 (16.8%) as relevant residual MR. One-year mortality was significantly lower in patients with non-relevant residual MR (3D-VCA < 0.1 cm2: 10.5%; ≥ 0.1 < 0.3 cm2: 16.0%; ≥ 0.3: 24.8%, p = 0.003). An increasing 3D-VCA post mitral TEER was associated with a higher 1-year mortality. At a 3D-VCA of 0.07 cm2 mortality increased significantly (1-year mortality 3D-VCA post mitral TEER ≥ 0.07 cm2: 16.5% vs. < 0.07 cm2: 7.8%; p = 0.005) indicating a 3D-VCA of 0.07 cm2 to be a cut-off value for survival in daily practice. Residual MR assessed by 3D-VCA after TEER is associated with 1-year mortality. Therefore, 3D-VCA is a valuable echocardiographic tool for intraprocedural MR assessment during mitral TEER and achieving a lower 3D-VCA improve patient survival. (German Clinical Trials Register: DRKS00012288). DRKS00012288.

Prediction of Major Adverse Limb Events in Females with Peripheral Artery Disease using Blood-Based Biomarkers and Clinical Features.

The objective of this study wasto identify a female-specific prognostic biomarker for peripheral artery disease (PAD) and develop a prediction model for 2-year major adverse limb events (MALE). Patients with/without PAD were recruited (n=461). Plasma concentrations of 68 circulating proteins were measured and patients were followed for 2 years. The primary outcome was MALE (composite of vascular intervention, major amputation, or acute/chronic limb threatening ischemia). We trained a random forest model using: 1) clinical characteristics, 2) female-specific PAD biomarker, and 3) clinical characteristics and female-specific PAD biomarker. Galectin-9 was the only protein to be significantly elevated in females compared to males in the discovery/validation analyses. The random forest model achieved the following AUROC's: 0.72 (clinical features), 0.83 (Galectin-9), and 0.86 (clinical features + Galectin-9). We identified Galectin-9 as a female-specific PAD biomarker and developed an accurate prognostic model for 2-year MALE using a combination of clinical features and plasma Galectin-9 levels.

A systematic review of the accuracy of prognostic tests and scoring systems for use in the Global Vascular Guidelines' PLAN concept for the treatment of chronic limb threatening ischemia.

The 2019 Global Vascular Guidelines recommend risk assessment for evidence based revascularization based on the acronym PLAN: Patient risk, Limb severity and ANatomical complexity of disease. This meta-analysis compares a multitude of prognostic tests within these categories. A systematic review and meta-analysis of tests that estimated 1-year major event (amputation-free survival and major adverse limb events) probability. Individual patient data were reconstructed from survival estimate curves. With presence or absence of major events, sensitivity, specificity, and area under receiver operating characteristics curves (AUC) were computed. Tests with an AUC ≥70%, or that correlated with revascularization feasibility were included. Practical application of tests was assessed to make a recommendation on PLAN implementation. Ninety-six studies describing 77 unique predictive techniques were included, of which thirteen were sufficient. These 13 tests were divided in four Patient risk (5 studies), three Limb severity (3 studies), and six ANatomical complexity of disease (9 studies). Patient risk: Three tests were included: biochemical assessment of calprotectin and C-reactive protein, radiologic measurement of sarcopenia, and predictive score with the GermanVasc chronic limb-threatening ischemia (CLTI) score. These tests scored AUCs of 82.0%, 72.7%, and 71.8%, respectively, of which the GermanVasc CLTI score was deemed most applicable in clinical practice. Limb severity: The adjusted Wound Ischemia foot Infection score (WIfI) resulted as best predictive score (AUC, 78.8%), but due to the lack of external validation, the original WIfI score was deemed best applicable. ANatomical complexity of disease: No test surpassed 70% AUC for 1-year event estimation, and was correlated with feasibility of revascularization, the latter only being served by the Global Limb Anatomic Staging System. In evidence-based revascularization in patients with CLTI according to the PLAN concept, we recommend to use GermanVasc, WIfI, and the Global Limb Anatomic Staging System.

Stratification of Early Arrhythmic Risk in Patients Admitted for Acute Coronary Syndrome: The Role of the Machine Learning-Derived "PRAISE Score".

The PRAISE (PRedicting with Artificial Intelligence riSk aftEr acute coronary syndrome) score is a machine learning-based model for predicting 1-year adverse cardiovascular or bleeding events in patients with acute coronary syndrome (ACS). Its role in predicting arrhythmic complications in ACS remains unknown. Atrial fibrillation (AF) and ventricular arrhythmias (VA) were recorded by continuous electrocardiographic monitoring until discharge in a cohort of 365 participants with ACS prospectively enrolled. We considered two separate timeframes for VA occurrence: ≤ 48 and > 48 h. The objective was to evaluate the ability of the PRAISE score to identify ACS patients at higher risk of in-hospital arrhythmic complications. ROC curve analysis indicated a significant association between PRAISE score and risk of both AF (AUC 0.89, p = 0.0001; optimal cut-off 5.77%) and VA (AUC 0.69, p = 0.0001; optimal cut-off 2.17%). Based on these thresholds, high/low AF PRAISE score groups and high/low VA PRAISE score groups were created, respectively. Patients with a high AF PRAISE score more frequently developed in-hospital AF (19% vs. 1%). Multivariate analysis showed a high AF PRAISE score risk as an independent predictor of AF (HR 4.30, p = 0.016). Patients with high VA PRAISE scores more frequently developed in-hospital VA (25% vs. 8% for VA ≤ 48 h; 33% vs. 3% for VA > 48 h). Multivariate analysis demonstrated a high VA PRAISE score risk as an independent predictor of both VA ≤ 48 h (HR 2.48, p = 0.032) and VA > 48 h (HR 4.93, p = 0.014). The PRAISE score has a comprehensive ability to identify with high specificity those patients at risk for arrhythmic events during hospitalization for ACS.