Risultati per: Nuovi farmaci per il danno renale acuto (Acute kidney injury – AKI)

Circulation, Volume 150, Issue Suppl_1, Page A4142908-A4142908, November 12, 2024. Background:Extracorporeal membrane oxygenation(ECMO) is a critical intervention for treating critically ill patients, Kidney injury is a common occurrence during ECMO therapy, and studies indicate that Veno-Arterial ECMO (VA-ECMO) is linked to more severe kidney damage compared to Veno-Venous ECMO (VV-ECMO). This study aims to compare the impact of VV-ECMO and VA-ECMO on the kidneys and explore their potential underlying mechanisms.Methods:Based on our prior research, we established rat models for both VV-ECMO and VA-ECMO. Subsequently, we conducted a comparative analysis to assess the impact of VV-ECMO and VA-ECMO on renal injury. This analysis involved the examination of various data points such as blood urea nitrogen (BUN), creatinine (CR), cystatin C, and Kidney Injury Molecule-1 (KIM-1). Histopathological analysis using HE staining was performed to evaluate the extent of pathological damage. Additionally, we placed particular emphasis on monitoring the pulsatility index in both groups.Furthermore, we employed RNA-Seq on both the VV-ECMO and VA-ECMO rat groups to investigate potential underlying mechanisms.Results:The study demonstrated lower levels of renal injury indicators (e.g., BUN, CR, cystatin C, KIM-1) in the VV-ECMO group compared to the VA-ECMO group. Furthermore, HE staining revealed less severe pathological damage in the VV-ECMO group. VV-ECMO also displayed a higher pulsatility index. Transcriptomic analysis highlighted differentially expressed genes between the VV-ECMO and VA-ECMO groups, primarily associated with angiotensin II. Concurrently, the omics data indicated a milder inflammatory response in the VV-ECMO group. We further validated the more pronounced inflammatory response of VA-ECMO through Western blot and RT-PCR experiments. This suggests that VA-ECMO might activate angiotensin II, inducing inflammation due to the absence of cardiac pulsation.Conclusion:Compared to VA-ECMO, VV-ECMO demonstrates a more favorable effect in mitigating renal injury. The potential mechanism may involve the rhythmic cardiac pulsation provided by VV-ECMO, effectively suppressing angiotensin II and thereby reducing inflammatory responses. This study offers crucial insights for developing rational strategies in the clinical selection of combined cardiopulmonary support systems.

Circulation, Volume 150, Issue Suppl_1, Page A4121234-A4121234, November 12, 2024. Background:Ischemia-related ventricular arrhythmia is the leading cause of death in patients after acute myocardial infarction (AMI). Although the therapeutic potential of renal denervation (RDN) for ventricular arrhythmias has been reported, RDN-induced adverse complications partially limit its use in the clinic. Since neuroinflammation has recently emerged as a key factor for sympathetic overactivation in the central and peripheral nervous systems, this study aims to test if macrophage activation in renal sympathetic postganglionic (RSP) neurons located in the aorticorenal ganglion (ARG) contributes to renal sympathetic overactivation-related ventricular arrhythmogenesis post-AMI.Methods and Results:AMI was induced by surgical ligation of the left anterior descending artery in rats. Data from immunofluorescence staining showed that the expression of Iba1, TNF-α, and IL-1β was increased in ARGs at 3 days post-AMI rats compared with sham rats, suggesting that macrophage activation and neuroinflammation occurred in the ARG at an early stage after AMI. Direct recording of renal sympathetic nerve activity (RSNA) found that the RSNA was much higher in the 3 days post-AMI rats than in sham rats. To validate the contribution of macrophage activation to AMI-elevated RSNA, we depleted macrophages in ARGs by local microinjection of clodronate liposomes (CL) into ARGs. Immunofluorescence staining data showed that microinjection of CL into ARGs attenuated the AMI-induced macrophage activation (Iba1) and neuroinflammation (TNF-α and IL-1β) in ARGs. Flow cytometry data also confirmed that macrophage depletion in ARGs reduced the AMI-elevated macrophage infiltration in ARGs, which was accompanied by a significant decrease in RSNA in CL-treated AMI rats. To test the ventricular arrhythmogenesis post-AMI, we measured ventricular tachycardia/fibrillation (VT/VF) from 24-hour telemetry ECG recording in conscious rats. Our data showed that macrophage depletion in ARGs alleviated AMI-induced ventricular arrhythmogenesis, as evidenced by a significant reduction in the occurrence of VT/VF in CL-treated AMI rats.Conclusion:These data suggest that macrophage activation and neuroinflammation in the ARG might be critical factors responsible for the renal sympathetic overactivation-related ventricular arrhythmia post-AMI. Inhibiting macrophage activation and neuroinflammation in the ARG could be an effective strategy to achieve the antiarrhythmic effect of RDN after AMI.

Circulation, Volume 150, Issue Suppl_1, Page A4119428-A4119428, November 12, 2024. Background:Stroke remains a leading cause of mortality and disability. The narrow temporal window and limited availability of, and eligibility for thrombolytic therapy or endovascular thrombectomy are major therapeutic limitations in treating stroke. Neuroprotective therapies that could be given early to replace or augment these existing therapies are needed to improve stroke outcomes. We showed that monosialoganglioside (GM1) containing nanoliposomes composed of phosphatidylcholine, cholesterol and GM1 (70/25/5% molar ratios, NLGM1) protect against hypoxic injury likely through Nrf2-dependent upregulation of antoxidant enzymes.Aims:To test if post-occlusion NLGM1 treatment could reduce 1) acute stroke injury following middle cerebral artery occlusion (MCAO) and 2) chronic injury following photothrombotic (PT) stroke injury.Methods:20 week old C57BL/6 mice underwent MCAO for 60 minutes and then injected with saline or NLGM1 (1 or 2 mg IV) prior to reperfusion. Neurologic deficit score and brain infarct % area were measured the next day. Separately, mice underwent PT injury followed by injection of saline or NLGM1 (1 or 2 mg immediately and 2 hours post-injury) and cognitive/behavior tests done 1-90 days post injury.Results:Following MCAO, there was reduced neurologic impairment, infarct volume and brain edema with NLGM1 versus saline control (Fig. 1). Following PT injury, there was reduced neurologic, cognitive and motor impairment from Day 2-90 post-injury with NLGM1 versus saline control (Fig. 2). In both stroke models, there was no difference in efficacy between 1 and 2 mg NLGM1 doses.Conclusions:Treatment of mice with NLGM1 following MCAO or PT stroke injury resulted in improved structural (infarct size, edema) and functional (cognitive, behavior, motor) outcomes in the acute (MCAO) and chronic (PT) timeframes. NLGM1 is a potential novel therapeutic agent for stroke.

Circulation, Volume 150, Issue Suppl_1, Page A4140204-A4140204, November 12, 2024. Background:Oxidized phospholipids (OxPL) are preferentially carried by and contribute to the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPL can be quantitated on all apolipoprotein B-100 containing lipoproteins (OxPL-apoB), a dominant proportion of which are present on Lp(a) particles.Objectives:To assess the effect of PCSK9 inhibition by alirocumab on plasma levels of OxPL-apoB, and the relationship to Lp(a) and major adverse cardiovascular events (MACE) in patients with a recent acute coronary syndrome (ACS) on optimized statin treatment.Methods:OxPL-apoB (Diazyme, Inc) and Lp(a) (TinaQuant, Roche Diagnostics) were measured at baseline (1-12 months after ACS) in a subset of participants in the ODYSSEY OUTCOMES trial with samples available at baseline (prior to randomization to alirocumab or placebo, n=11,630) and log2-transformed. Proportional hazards models adjusted for 12 baseline covariates evaluated the association of predictor variables (OxPL-apoB and Lp(a)) with MACE (coronary heart disease death, non-fatal MI, ischemic stroke, and hospitalized unstable angina) and all-cause death, with HRs for doubling of the predictor variable.Results:Baseline OxPL-apoB correlated with Lp(a) (r=0.68, p

Circulation, Volume 150, Issue Suppl_1, Page A4139204-A4139204, November 12, 2024. Background:Emergency department (ED) overcrowding is a significant healthcare challenge that continues to strain medical facilities internationally. The need to assess myocardial injury in the ED is thought to be common, accounting for greater than 13 million visits annually. Therefore, we sought to assess the frequency and impact of myocardial injury assessment on the intermediates to ED overcrowding – ED disposition distribution and time to disposition – at an urban ED.Methods:In this single-center, retrospective cohort study from February 1, 2023, to January 31, 2024, the disposition distribution and median time to disposition were recorded for ED patient encounters. The study population was divided into encounters resulting in ED assessment for myocardial injury with conventional troponin measurement (ED-Tn group) and all other encounters without ED assessment for myocardial injury (control group). Pearson test was used for analyzing disposition distribution and Wilcoxon test for comparing time to disposition between the two defined groups.Results:66,984 patient encounters resulted in a disposition of discharge or admission during the study period. 15,918 (23.8%) were categorized into ED-Tn group, while 51,066 (76.2%) were categorized into control group. The ED-Tn group had a significantly lower discharge frequency of 51% compared to the control group with 59.1% (p

Circulation, Volume 150, Issue Suppl_1, Page A4147790-A4147790, November 12, 2024. Background:Anticoagulation therapy (ACT) remains the cornerstone of acute pulmonary embolism (PE) management and reduces the mortality risk to

Circulation, Volume 150, Issue Suppl_1, Page A4146347-A4146347, November 12, 2024. Background:Acute ischemic stroke (AIS) is a leading cause of mortality and disability globally, disproportionately affecting Black and Latinx populations who experience increased morbidity and mortality compared to their white counterparts. At one month, roughly 50% of AIS survivors experience mood disturbances (e.g., anger, irritability, and aggression) and exhibit a lower health-related quality of life (HRQOL) compared to pre-AIS levels. Downstream biomarkers of mitochondrial dysfunction such as oxidative stress may be important pathophysiological mechanisms underlying mood disturbance symptoms, stroke severity, and long-term functional recovery.Purpose:To examine associations among early and late peripheral plasma lipid levels, mood disturbance symptoms (e.g., anger, irritability), and HRQOL outcome over 3 months (baseline/study day 5, and months 1, 3) in persons following AIS.Methods:The pilot study is a non-probability, convenience sample of adult subjects ( > 18 years of age) with a diagnosis of AIS. Lipidomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS) of untargeted lipids. The Agilent 6545 LC/Q-TOF platform was used to determine the absolute concentration of lipid species from peripheral plasma samples collected days 1, 3, 5 and months 1 and 3 post-AIS. General linear mixed models were used to test the predictive association of lipidomic biomarker mean value of peripheral plasma lipid levels and symptoms and outcomes over time (baseline and months 1 and 3).Results:We analyzed 82 subjects (age = 64 ± 12.1, 52% male, 78% Black, and 94% with hypertension). Elevated oxidative stress biomarkers (e.g., lipoxygenases, arachidonic acid, glycosylphosphatidylinositol) were associated with higher severity of anger and irritability symptoms, and a poorer HRQOL from baseline to 1- and 3-months post-AIS (p=0.04).Conclusion:An untargeted LC-MS lipidomics approach was used to identify lipids following AIS. Because oxidative stress plays a key regulatory role in complex downstream cellular function, these findings may be of great significance in understanding AIS pathophysiology that has the potential to inform personalized preventive strategies.

Circulation, Volume 150, Issue Suppl_1, Page A4144657-A4144657, November 12, 2024. Introduction:Seasonal variations, particularly cold weather, can increase the risk of acute coronary syndrome, as evidenced by various studies over the years. On the other hand, hot weather can cause dehydration, electrolyte imbalances, and thermoregulatory strain on the heart, leading to adverse cardiac events. In recent years with rising concerns about global warming, we aim to study the impact of climate changes during the summer on outcomes among people hospitalized with ACS.Methods:We used the National Inpatient Sample from 2016 to 2020 to identify young adults hospitalized with ACS using appropriate ICD-10 codes. Patients were categorized into two cohorts: summer (hospitalizations during June, July, and August) and non-summer (hospitalizations during other months). The outcomes studied were ACS hospitalizations and in-hospital mortality. Pearson chi-square tests and the Mann-Whitney U test were used for cohort comparisons.Results:Of 230,555 ACS hospitalizations, 26.2% (n=60,340) occurred during the summer months, with a median age of 40 years. White individuals had higher hospitalization rates compared to others (57.8% vs. 58%), and those from lower socioeconomic statuses had higher ACS hospitalizations in both cohorts (37.5% vs. 38.1%). Comorbidities like hypertension, diabetes, and hyperlipidemia were lower in the summer cohort (all p

Circulation, Volume 150, Issue Suppl_1, Page A4142116-A4142116, November 12, 2024. Introduction:The measurement of Urinary Sodium Concentration (UNa) is a pivotal biomarker in managing Acute Heart Failure (AHF), offering a non-invasive and readily accessible means to evaluate diuretic response. This systematic review and meta-analysis is designed to investigate the correlation between UNa levels and patient-centric outcomes in AHF, aiming to validate the evidence base and refine clinical practice.Methods:This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. We systematically searched PubMed, Cochrane Central, Scopus, Google Scholar, and ClinicalTrials.gov from their inception to May 2024. Our search included randomized controlled trials (RCTs) and observational studies comparing outcomes between acute heart failure (AHF) patients with high urinary sodium concentration (UNa) and those with low UNa.Results:The analysis included 12 studies comprising 5 RCTs and 7 observational studies, incorporating a total of 8,743 AHF patients. In the high UNa group, pooled data demonstrated significantly higher urinary output (MD 534.49 ml, 95% CI 348.48 to 720.49; P < 0.00001) and increased weight loss (MD 1.15 kg, 95% CI 0.45 to 1.85; P < 0.001). Additionally, there was a lower risk of renal function decline (OR 0.48, 95% CI 0.24 to 0.97; P < 0.04). Patients with high urinary sodium had a shorter mean hospital stay of 7.6 days compared to 8.8 days for those with low UNa, with an overall reduction in length of stay (MD -1.38 days, 95% CI -2.44 to -0.32; P < 0.01). Mortality was also lower in the high UNa group, particularly over longer follow-up periods: at 1-month follow-up (OR 0.40, 95% CI 0.21 to 0.78; P = 0.007), at 6-month follow-up (OR 0.45, 95% CI 0.29 to 0.72; P = 0.0007), and at 12-month follow-up (OR 0.16, 95% CI 0.16 to 0.26; P < 0.00001). Furthermore, the high UNa group exhibited a lower risk of worsening heart failure requiring inotropes (OR 0.40, 95% CI 0.23 to 0.70; P = 0.002) and a reduced incidence of heart failure rehospitalization (OR 0.42, 95% CI 0.20 to 0.89; P = 0.02).Conclusion:High urinary sodium concentration is strongly associated with improved clinical outcomes in acute heart failure, including greater urinary output, increased weight loss, shorter hospital stays, and reduced risks of renal function decline, mortality, worsening heart failure, and rehospitalization.

Circulation, Volume 150, Issue Suppl_1, Page A4146431-A4146431, November 12, 2024. The growing adoption of advanced imaging modalities, such as transesophageal echocardiography (TEE), has led to more frequent detection of cardiac structural abnormalities. While intracardiac cardiac tumors and shunts are infrequent and typically asymptomatic, their existence can precipitate severe outcomes, including stroke, myocardial infarction and sudden death.Case Description:A 69-year-old female presented with left sided facial droop, slurred speech and left arm weakness. A computed tomography angiography revealed focal occlusion of the distal right middle cerebral artery. She was initiated on thrombolytic therapy and experienced resolution of symptoms. Transthoracic echocardiogram revealed right to left shunting consistent with a patent foramen ovale (PFO). Further workup with TEE confirmed the presence of a PFO but also detected a mobile echogenic mass on the aortic valve leaflet, indicative of papillary fibroelastoma (PFE). Cerebral infarction was attributed to an embolic event, with the PFO and PFE being likely culprits.Discussion:Current guidelines give a conditional recommendation, low certainty of evidence, for PFO closure in adults older than 60 years, although some observational studies have shown some risk reduction in older patients. The key trials showing clinical benefit of PFO closure were in adults younger than the age of 60. For left sided cardiac tumors, such as PFE, guidelines give a 2A recommendation for resection. Addressing the risk for recurrent stroke in this 69-year-old patient was an essential part of stroke care, as such, a multi-disciplinary team of experts including cardiology, neurology, and cardiothoracic surgery was conveyed. The decision was to proceed with surgical intervention in addition to antiplatelet therapy to achieve optimal risk reduction. The patient subsequently underwent successful surgical removal of the PFE with native valve preservation and PFO closure.Conclusion:Cardiac PFEs and PFOs can be associated with increased stroke risk. Employing appropriate imaging techniques and timely interventions are of utmost importance in stroke management.

Circulation, Volume 150, Issue Suppl_1, Page A4117085-A4117085, November 12, 2024. Background:Etripamil nasal spray (NS) is a fast acting, self-administered calcium channel blocker in development for the termination of AV-nodal-dependent supraventricular tachycardia (SVT). Prior randomized, placebo-controlled and open-label studies have demonstrated favorable safety and efficacy of etripamil in converting paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm (SR) self-administered without direct medical supervision.Research Question/Hypothesis:To assess patterns and annualized PSVT episode frequency among patients opting to self-administer acute treatment with etripamil.Methods:NODE-303 was an event-driven, multi-center, open-label Phase 3 study, conducted in North and South America to evaluate the safety and efficacy of etripamil in patients with documented PSVT over multiple episodes. Test dosing was not performed prior to at-home use. Enrolled patients, upon perceiving symptoms of PSVT: applied an ambulatory ECG monitor, performed a previously trained vagal maneuver and, if symptoms persisted, self-administered etripamil NS 70 mg. During the study, the protocol was amended to allow a repeat dose (70 mg) if symptoms persisted 10 min after the first dose. Each patient could self-treat up to 4 episodes.Results:Of 1,116 enrolled patients, 503 (45.1%) treated ≥1 perceived PSVT episode (safety population). Etripamil achieved conversion to SR in 60% of patients by 30 minutes and 70% by 60 minutes. A total of 220, 118, 62, and 103 patients completed the study with 1, 2, 3, and 4 etripamil-treated perceived episodes of PSVT, respectively, with an average time on study of 440 days. Among these patients, the average number of annualized etripamil-treated PSVT episodes was 3.2 (standard deviation 3.8). Annualized use: etripamil was self-administered for 0-2 PSVT episodes per year, 2-6 episodes, 6-12 episodes, and >12 episodes, in 54%, 32%, 10%, and 4% of patients, respectively(Figure).Conclusions:This analysis aimed to assess the annualized use of etripamil NS in a real-world setting, by analyzing how often patients would self-administer the drug for PSVT episodes. Of patients that self-administered etripamil (n=503), the majority treated >1 episode and the annualized frequency of episodes treated with etripamil was 3.2 episodes/yr.

Circulation, Volume 150, Issue Suppl_1, Page A4147592-A4147592, November 12, 2024. Introduction:Adderall, the brand name for a combination of dextroamphetamine and amphetamine salts, is used to treat attention deficit disorder and narcolepsy, but is widely abused for improving cognitive function and alertness in absence of a medical indication. While little is known of its acute cardiovascular (CV) physiologic effects, Adderall has been linked to acute CV events (myocardial infarction, tachyarrhythmias, heart failure, Takotsubo cardiomyopathy and sudden death) and to long term CV consequences including hypertension and arterial disease.Aim:To examine the acute CV responses to Adderall in healthy subjects not on stimulant therapy in a randomized double-blind placebo-controlled crossover study. (CT.gov NCT02979327)Methods:Thirty subjects were randomized to 25 mg Adderall versus placebo. We measured supine resting blood pressure (BP), heart rate (HR), and plasma catecholamines, before and 3 hours after consuming Adderall or placebo.Results:Twenty-nine subjects (16 females; aged 25±5 yrs) completed both Adderall and placebo conditions, with a median of 10 days between visits. Systolic BP (SBP) increased from 112±10 mmHg to 127±11 mmHg after use of Adderall but was unchanged before vs after placebo drug intake (112±8 mmHg and 112±9 mmHg respectively; group by time interaction p

Circulation, Volume 150, Issue Suppl_1, Page A4145932-A4145932, November 12, 2024. Background:A new ESC guidelines in 2023, the International Lipid Expert Panel (ILEP) 2021 recommendations, and a subsequent statement by EAS have been published based on recent advances in lipid lowering treatments. However, real world data are lacking regarding the implementation among the community of French cardiologists.Objective:To determine the current approach and therapeutic strategies concerning lipid lowering treatments post-acute coronary syndromes in France.Methods:This national survey was performed during October and November 2023 in France with an online questionnaire on the websites of 2 national French Societies of Cardiologists.Four mailings were sent to cardiologists to invite them to answer to the questionnaire. A total of 400 answers of cardiologists were collected during this 2-month period.Results:For ASCVD patients, cardiologists agreed with an LDL-C goal below 55 mg/dL (1.4 mmol/L) in 69%, below 70 mg/dL (1.8 mmol/L) in 16.5%, and 14.5% between 70 mg/dL and 100 mg/dL (1.8-2.5 mmol/L). An upfront lipid lowering combination strategy using fixed dose combination (FDC) of statins and ezetimibe was prescribed in less than 5% of patients, whereas high-intensity statins were prescribed in more than 90% of patients. No significant differences were observed in terms of sex of patients, geographical area, or strategies followed by male and female cardiologists (p > 0.05). A combination of statins and ezetimibe was prescribed only for a minority of patients, especially as an early upfront strategy. The use of PCSK9i remains marginal and the interval between the ACS and initiation of these medicines remains high.Conclusion:In this contemporary national survey, we report an excellent agreement of lipid goals in secondary prevention by cardiologists. Despite the declared consensus recommending a low LDL-C target in ACS patients, lipid lowering strategies are suboptimal, mainly consisting of high intensity statins. The lack of recommended use of ezetimibe and PCSK9i to lower LDL-C levels highlights the importance of better implementation of intensive and early upfront strategies to reduce recurrent ischemic events.

Circulation, Volume 150, Issue Suppl_1, Page A4145703-A4145703, November 12, 2024. Introduction:Acute coronary syndrome (ACS) is a leading cause of cardiovascular (CV) death. Sickle cell disease (SCD) is the most common inherited blood disorder in the United States and is associated with coronary microvascular dysfunction and impaired myocardial perfusion reserve. However, data on post-ACS outcomes in patients with SCD are scarce.Methods:Patients admitted with ACS from 2014-2020 with and without SCD were identified using the National Readmissions Database. In-hospital outcomes were death, major bleeding, stroke or arterial thromboembolism, and venous thromboembolism (VTE). Ninety-day readmission outcomes were CV-related, heart failure (HF) related, bleeding-related, and all-cause. Multivariable logistic or Cox proportional hazards were utilized with age, sex, chronic kidney disease, prior MI, prior stroke, prior VTE, pulmonary hypertension, STEMI, cardiogenic shock, revascularization, anemia, mechanical circulatory support use, hospital size and teaching status in addition to social factors as co-variables.Results:A total of 2,190,358 patients with ACS were included, of whom 1,471 (0.067%) had SCD. After multivariable adjustment, there was no difference in in-hospital mortality (OR 0.92; 95% CI 0.68-1.26) or major bleeding (OR 1.03; 95% CI 0.82-1.28) between patients with and without SCD. There was no significant difference in 90-day CV-related (HR 1.11; 95% CI 0.94-1.3) or bleeding-related (HR 0.86; 95% CI 0.49-1.52) readmissions between patients with and without SCD. However, SCD was associated with a higher rate of HF-related (HR 1.25; 95% CI, 1.04-1.52) and all-cause 90-day readmissions (HR 1.17; 95% CI, 1.04-1.32).Conclusion:Among patients admitted with ACS, SCD was not associated with increased risk of in-hospital outcomes though there was an association of increased HF-related and all-cause 90-day readmissions with SCD. Further investigation is needed to better characterize and improve outcomes of patients with SCD and ACS.

Circulation, Volume 150, Issue Suppl_1, Page A4146327-A4146327, November 12, 2024. Background:Despite advances in treatment strategies for out-of-hospital cardiac arrest (OHCA), prognosis remains poor. The MIRACLE2 score is an established risk stratification tool for cardiogenic OHCA, but its utility in acute coronary syndrome (ACS), a leading OHCA etiology, is unclear.Aims:To validate the prognostic performance of the MIRACLE2 score in OHCA patients with ACS undergoing urgent/emergent percutaneous coronary intervention (PCI).Methods:We conducted a single-center, observational study (COEDO-CPA registry) of consecutive cardiogenic OHCA patients from 2018-2024. Patients with OHCA due to ACS who underwent urgent/emergent PCI were stratified into high-risk (MIRACLE2 score >5), medium-risk (3-4), and low-risk (0-2) groups based on their MIRACLE2 scores. The primary endpoint was 30-day all-cause mortality, compared among risk groups using Kaplan-Meier analysis.Results:Of 124 cardiogenic OHCA patients, 80 with ACS-related OHCA undergoing PCI were analyzed (mean age 64.7 years, 89% male). The mean MIRACLE2 score was 3.2, with 18 high-risk, 30 medium-risk, and 32 low-risk patients. Mechanical circulatory support was used in 58%. The high-risk group tended to be older with higher lactate levels, worse renal function, elevated D-dimer, and longer cardiopulmonary resuscitation duration compared to lower-risk groups. Kaplan-Meier analysis demonstrated a graded increase in 30-day mortality across risk groups, with effective risk stratification by the MIRACLE2 score (log-rank p=0.003).Conclusion:Among OHCA patients with ACS undergoing PCI, the MIRACLE2 score effectively stratified short-term mortality risk. This validated risk stratification tool could guide treatment strategies and resource allocation in this critically ill population. Incorporating the MIRACLE2 score into OHCA management pathways may optimize care for ACS-related OHCA.

Circulation, Volume 150, Issue Suppl_1, Page A4144815-A4144815, November 12, 2024. Background:Natriuretic peptides (NP) are frequently employed in diagnosing heart failure (HF); however, their effectiveness in guiding HF treatment lacks sufficient evidence. To address this gap, we conducted an updated meta-analysis assessing the efficacy of NP-guided therapy versus usual care in decompensated HF.Methods:PubMed, Embase and Cochrane database were searched for randomized controlled trials (RCTs) that compared NP-guided treatment to usual care for patients with acute decompensated heart failure. The reported outcomes were (1) all-cause mortality; (2) cardiovascular death; and a (3) composite of all-cause mortality and HF hospitalizations. Heterogeneity was examined with I2statistics. A random-effects model was used for outcomes with high heterogeneity. Statistical analysis was done using R Studio 4.3.2.Results:We included 10 RCTs with 4122 patients, of whom 2072 (50.3%) underwent NP-guided treatment. Mean follow-up was 14.8 months. All-cause mortality (HR 1.03; 95% CI 0.81-1.32; p=0.79; figure 1A), cardiovascular death (HR 1.33; 95% CI 0.72-2.47; p=0.36; figure 1B), and the composite outcome of HF hospitalization or cardiovascular death (HR 0.92; 95% CI 0.77-1.11; p=0.4; figure 1C) were not significantly different between groups.Conclusion:These findings suggest that NP-guided therapy does not reduce mortality and heart failure readmissions in the management of patients with acute decompensated heart failure.