Risultati per: Short Acting Opioid

We appreciate the constructive dialogue from Cheng on our study’s findings.1 We agree that any clinical database study has limitations that necessitate careful interpretation of results. Manual medical records review is a logical next step to mitigate these shortcomings and allow a more thorough examination of each patient’s course. Nevertheless, we re-analysed our data in response to points raised. The analyses in our original paper suggest an elevated risk of undergoing an esophagogastroduodenoscopy (EGD) in patients treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA) compared with control. As mentioned in our prior reply,2 we recognise that there is a potential diagnostic bias from this observation. We re-ran our cohorts and found that the rate of undergoing an EGD in the propensity-score matched cohort receiving short-acting GLP-1 RA was 6.13% compared with 5.22% in the matched control cohort (OR 1.185; 95% CI 1.131 to 1.241), reflecting the…

We write in response to the Letter to the Editor by van den Berg et al1 commenting on our recent article ‘Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis’.2 We greatly appreciate the interest in our work and are grateful to clarify some aspects of the study. The primary endpoint of our study investigated whether microbial compositions can be employed as early predictors for severity of acute pancreatitis (AP). Patients with revised Atlanta classification III (RAC III) showed highly significant microbial differences compared with RAC I and RAC II. Further analysis revealed a higher abundance of species that are known producers of short-chain fatty acids (SCFA) in severe AP. Van den Berg et al mention the lack of a healthy control cohort, however, it is already known from previous studies that the microbial composition in stool samples of patients with AP…

With great interest, we read the paper by Ammer-Hermenau et al, which features a multicentre microbiome study that included buccal and rectal samples taken at admission from 450 patients with acute pancreatitis.1 Severe acute pancreatitis was post hoc defined as persistent organ failure and/or collections that required drainage. These patients were propensity score matched with patients with mild acute pancreatitis. Remarkedly, over-representation of 10 known short-chain fatty acid (SCFA)-producing bacteria was found in the severe group. The authors conclude that SCFAs might be associated with worse outcomes and speculate that the increased mortality that was observed in the intervention group of the Probiotics in Pancreatitis Trial (PROPATRIA) could be explained by SCFA producers in the probiotics formula.2 There are, however, some limitations to this study, and we believe the author’s statements are in need of nuance. First, the authors did not include a control group…

Circulation, Volume 150, Issue Suppl_1, Page A4145819-A4145819, November 12, 2024. Introduction:Despite early mitigation efforts, the opioid pandemic in the United States has persisted and affected many Americans. A public health emergency was declared urging all prescribers to use caution in prescribing opioids. Alternative approaches to postoperative pain management during transvenous cardiac device implants (TCDI) in adults have not been described.Methods:We report a single-center retrospective analysis of 612 consecutive patients that underwent TCDI between January 2021 and January 2024 with ultrasound guided pectoral nerve block (PNB) using liposomal bupivacaine prior to implant for postoperative pain management. Pain scores (0-10) were recorded systematically in the postoperative period, at discharge, and at wound check follow-up. Any need for opioid use in the postoperative period was recorded as well.Results:A total of 612 patients were evaluated, 50% female with a mean age of 71.2 years. All patients received PNB successfully with no device site infection or hematomas. The mean Visualized Analog Scale (VAS) pain scores at 1, 3, and 5 hours after the procedure, at discharge, and at the follow-up visit were 1.93, 1.22, 1.10, 1.05, and 0.13 respectively. During follow-up, no patients required opioids for pain control throughout the entire postoperative period of 14 days.Conclusion:Pectoral nerve block with liposomal bupivacaine can be performed safely preoperatively during TCDI and provides adequate pain control without need for opioid use postoperatively. Further research is needed to assess broad scale implications of this approach to larger patient populations.

Circulation, Volume 150, Issue Suppl_1, Page A4136932-A4136932, November 12, 2024. Introduction:Annually, over 500,000 Americans are hospitalized due to heart failure (HF), marking it as a major contributor to morbidity and mortality. It also poses a significant financial burden and leads to considerable losses in productivity.Objective:This study investigates the predictive accuracy of different socioeconomic metrics on the risk and outcomes of HF in Maryland.Methodology:A retrospective analysis of the Maryland State Inpatient Database (2016-2020) was conducted to assess the predictive accuracy of race/ethnicity, insurance status, household median income, and neighborhood poverty level (measured by the Distressed Communities Index) on the risk of heart failure-related hospital admissions and outcomes. Multivariate logistic regression models were also used to adjust for confounders.Result:During the study period, a total of 389,220 cases of HF were reported in the Maryland SID. The majority of these patients were white (56.8%) and female (51.1%), with a median age of 73 years (interquartile range [IQR] 62-82 years). The in-hospital mortality rate was 5.1%, while rates of atrial fibrillation, cardiac arrest and prolonged hospital stay were 34.4%, 0.3%, and 48.4%, respectively. Multivariate analysis revealed a substantial area under the ROC curve (AUC) indicating good model performance: 0.88 for predicting HF, 0.64 for atrial fibrillation, 0.64 for cardiac arrest 0.57 for prolonged hospital stays, 0.63 for mortality. Subgroup analyses showed variable predictiveness by race (AUC = 0.4378), payment method (AUC = 0.5754), income quartile (AUC = 0.5202), and deprivation composite score (AUC = 0.4751). Patients with private insurance had the highest risk of stress cardiomyopathy (odds ratio [OR] = 1.98; 95% confidence interval [CI] 1.70-2.29). Socioeconomic metrics, including neighborhood distress, showed varying predictive accuracy for the HF-related admissions and selected short-term outcomes, with the highest predictive accuracy for neighborhood distress on the risk of HF (AUC = 0.50, std: 0.006), atrial fibrillation (AUC = 0.48, std: 0.0007), cardiac arrest (AUC = 0.51, std: 0.007), and prolonged hospital stays (AUC = 0.53, std: 0.0005) and mortality (AUC = 0.50, std: 0.0015).Conclusion:Neighborhood poverty level demonstrates significant predictive power for assessing the risk of HF-related hospital admissions and the short-term outcomes among Maryland residents, exceeding factors like insurance and race/ethnicity.

Circulation, Volume 150, Issue Suppl_1, Page A4145961-A4145961, November 12, 2024. Introduction:Approximately 20% of ischemic strokes are linked to a cardioembolic source, with 80% of cardioembolic strokes being attributed to atrial fibrillation. This study aimed to investigate the impact of non-valvular atrial fibrillation (NVAF) on mortality and recurrent stroke following a minor stroke event, considering AF as the most prevalent sustained cardiac rhythm disorder associated with stroke.Methods and Materials:Consecutive patients experiencing minor acute ischemic stroke (NIHSS

Circulation, Volume 150, Issue Suppl_1, Page A4123826-A4123826, November 12, 2024. Introduction:It has been reported that day-to-day blood pressure (BP) variability (BPV) is associated with major adverse cardiac and cerebrovascular events (MACCE) in patients with heart failure (HF). However, the clinical significance of beat-to-beat BPV is unclear.Methods and Results:We recruited data on patients with HF who underwent nighttime pulse transit time (PTT)-based continuous beat-to-beat BP measurement (n = 379, median age 71, male sex 53.6%). Standard deviation (SD) of PTT-based BP was considered as BPV. The primary outcome was MACCE defined as coronary artery disease, stroke, or death due to HF, acute coronary syndrome or ventricular fibrillation. Median values (25th and 75th percentiles) of SD of PTT-based systolic, diastolic, and mean BP were 4.2 (3.5, 5.3), 3.3 (2.7, 4.1), and 3.4 (2.8, 4.1) mmHg, respectively. During the follow-up period of median 1,083 days after BPV evaluation, 43 patients experienced MACCE. When patients were divided into three tertiles based on the systolic, diastolic, and mean BPV, MACCE occurred more frequently in those with higher tertiles of BPV (Figure). In the Cox proportional hazard analysis, systolic, diastolic, and mean BPV as continuous variables were associated with MACCE (hazard ratio, 1.191, 1.228, and 1.243, respectively).Conclusion:Beat-to-beat BPV was associated with MACCE in patients with HF.

Circulation, Volume 150, Issue Suppl_1, Page A4136013-A4136013, November 12, 2024. Introduction:The use of Transcatheter Aortic Valve Replacement(TAVR) has provided a safer alternative to open surgical approaches. The introduction of frailty scoring systems has proven effective in improving healthcare approaches and outcomes in various aspects of medicine. As there is a paucity of data on the impact of frailty among TAVR patients, we aim to conduct a retrospective study to investigate further.Methods:Our study analyzed adult cases with a primary procedural code for TAVR among hospitalizations between 2016 and 2021 through the National Inpatient Sample(NIS). Frailty status was explored through the criteria of Gilbert’s frailty index. Multivariable regression models helped evaluate differences in short-term outcomes and complications between them.Results:Our study involved 374200 cases of TAVR that were divided into LFR(285425 cases, 76.3%), IFR(86005 cases, 23.0%), and HFR(2770 cases, 0.7%). Compared to patients with LFR, patients with MFR and HFR showed higher odds of several complications, including cardiogenic shock(MFR: aOR 6.933, p

Circulation, Volume 150, Issue Suppl_1, Page A4139216-A4139216, November 12, 2024. Introduction:TX000045 (TX45) is a long-acting Fc-relaxin fusion protein with vasodilatory, anti-fibrotic and anti-inflammatory activity due to selective agonism of the G protein-coupled relaxin family peptide receptor 1 (RXFP1). It is being developed for Group 2 pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF). This first-in-human study evaluated the safety/tolerability, pharmacokinetic and pharmacodynamic profile of TX45 in healthy volunteers after single doses.Methods:This phase 1a, randomized, double-blind, placebo-controlled single ascending dose study was performed in seven cohorts of healthy volunteers. Six cohorts consisted of eight patients receiving intravenously (IV) or subcutaneously (SC) one of several doses of TX45 (n=6 on treatment) or placebo (n=2), including 0.3 mg/kg IV, 1 mg/kg IV, 3 mg/kg IV, 150 mg SC (x2 cohorts), and 300 mg SC. One cohort consisted of seven patients receiving 600 mg SC TX45 (n=5 patients) or placebo (n=2 patients). The goals of the study were to assess the tolerability and safety, immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD = renal plasma flow, RPF) properties of TX45 in healthy volunteers after single doses. RPF was determined by analysis of steady-state para-aminohippurate (PAH) blood levels in response to a PAH IV infusion.Results:55 healthy volunteers were randomized. TX45 was well tolerated. Most adverse events were mild to moderate in intensity. The most common treatment emergent adverse event was transient orthostatic tachycardia, not associated with hypotension. TX45 demonstrated linear pharmacokinetics across the dose range with a terminal half-life estimated to be 13-23 days. Treatment with TX45, across dose levels, increased renal plasma flow by 16-42%, consistent with known relaxin effects. Leveraging repeated measures of renal plasma flow post dose, TX45 demonstrated prolonged maintenance of a pharmacodynamic effect. There was no evidence of immune mediated clearance of TX45.Conclusions:TX45 was generally well tolerated with a safety, pharmacokinetic and pharmacodynamic profile to support further clinical development. Its maximum effect on RPF is similar to previously described effects of native relaxin. Its half-life will support a prolonged dosing interval. These findings support further evaluation of TX45 in patients with Group 2 pulmonary hypertension associated with HFpEF.

Circulation, Volume 150, Issue Suppl_1, Page A4124506-A4124506, November 12, 2024. Background:ATTR-CM has an age dependent prevalence and is a disorder that almost exclusively affects older adults. Objective evaluations of function are critical to assessing and managing ATTR-CM in older adults. The short physical performance battery (SPPB) is a valid measure of functional capacity that predicts morbidity and mortality in older adults but its utility in ATTR-CM remains unknown.Aims/hypothesis:To establish SPPB as a useful marker of disease severity and predictor of outcomes in ATTR-CM. We hypothesized that SPPB scores would correlate with validated markers of ATTR-CM severity and improve clinical prediction.Methods:This is a retrospective analysis of patients referred to the Columbia University Cardiac Amyloid Program. Patients were stratified into low (SPPB 0-6), moderate (7-9), and high (10-12) cohorts based on initial SPPB score and baseline characteristics were compared between groups. Cox proportional hazard models and Kaplan Meier (KM) curves were generated to assess associations with mortality as well as a composite of death and cardiovascular (CV) hospitalization in follow-up.Results:A total of 263 patients, age 78 years (IQR 73, 84), 86% male, 22% with ATTRv (variant) and 78% with ATTRwt (wild type) were studied. SPPB showed no limitation in 59%, mild limitation in 33%, and severe limitation in 8%. Lower SPPB was associated (p

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 A4139976-A4139976, November 12, 2024. Introduction:In pulmonary vein isolation (PVI), the carina is often refractory to ablation and require linear ablation, and some patients have epicardial connections.Hypothesis:High-power Shor-duration (HP-SD) ablation can prevent gap formation, and high unipolar-voltage-area (HUV), defined >2.7 mV, will identify the epicardial connection site.Aims:To investigate the impact of HP-SD ablation on durable PVI and the efficacy of HUV for the prediction of epicardial connection site.Methods:Ninety-three atrial fibrillation (AF) patients who underwent successful PVI were enrolled. Forty-one patients underwent HP-SD ablation, while fifty-two patients underwent conventional ablation. First pass isolation was achieved in 66 patients, while the remaining 27 patients needed carina ablation. The epicardial conduction gap (EG) of the PVI line was defined as the continuous propagation pattern across the PVI line under the high right atrial pacing. The epicardial connection (EC) was defined that the propagation pattern was defined as a centrifugal pattern with the earliest site located around the mid-carina, more than 5 mm far from PVI line.Results:Carina ablation following PVI was needed more frequently in conventional ablation group than in HP-SD group (38% vs. 17%, P = 0.020). However, there was no statistical difference in EC between HP-SD and conventional ablation groups ［2 of 41 (4.8%) in HP-SD vs. 3 of 52 (5.7%) in conventional, P = 0.852］. This suggests that HP-SD ablation could suppress EG formation more effectively. Among the 5 patients with EC, 4 patients (80%) had HUV adjacent to the earliest activation site at the mid-carina (3 in right and 1 in left). Notably, the EC was eliminated by ablation at the HUV but not at the earliest activation site. During a one-year follow-up, 7 patients experienced AF recurrence. Patients who underwent HP-SD ablation showed lower tendency for recurrence compared to those with conventional ablation (4.8% vs 13.4%, P = 0.126). Notably, no patients who underwent EC ablation in the HP-SD ablation group experienced recurrence, whereas all patients in the conventional ablation group experienced recurrence (0% vs 100%). Among patients requiring carina ablation, 1 of 2 in the HP-SD group and 6 of 7 in the conventional group experienced recurrence (50% vs. 85.7%).Conclusion:HP-SD ablation was effective to prevent EG and EC, and HUV was useful indicator of epicardial breakthrough site to endocardium.

Circulation, Volume 150, Issue Suppl_1, Page A4138674-A4138674, November 12, 2024. Introduction:Urocortin-2 (UCN-2), a peptide which is part of the corticotropin-releasing factor (CRF) family, functions as an autocrine and paracrine factor, exerting its effects on cardiac and pulmonary function through agonism of CRF2 receptors. Although acute administration of UCN-2 has shown promise by improving heart and lung function in conditions like heart failure (HF) and pulmonary hypertension (PH), its limited stability impedes its chronic therapeutic use.Hypothesis:In this study, we explored the efficacy of COR-1389, a potent, selective and long-acting CRF2 agonist peptide, in the Sugen 5416 (VEGFR2 inhibitor, Su) combined with hypoxia (Hx) rat model of PH and right heart failure (RHF).Methods:To this aim, male adult Sprague Dawley rats were divided into three groups: Control rats (normoxia) were compared with rats injected subcutaneously with 20 mg/kg Sugen 5416 and exposed to chronic hypoxia for 3 weeks, followed by 2 weeks of normoxia. At 5 weeks, control rats and one SuHx group received subcutaneously vehicle (control and SuHx), while the third group received COR-1389 at a dose of 100 μg/kg every 4 days subcutaneously for 3 weeks (SuHx + COR-1389). At 8 weeks, cardiac and pulmonary hemodynamic functions of the three groups were evaluated using echocardiography and right heart catheterization, and heart and lung tissue were evaluated by histology and immunohistochemistry.Results:Compared to controls (n=10), SuHx exhibited increased mean pulmonary arterial pressure (mPAP), right ventricle (RV) hypertrophy (Fulton Index/body weight), muscularization of distal pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy, alongside reduced RV systolic function (Tricuspid Annular Plane Systolic Excursion, TAPSE) and cardiac output (CO). Conversely, compared to the SuHx + vehicle group (n=11), curative treatment with COR-1389 for 3 weeks in SuHx rats (n=13) led to enhanced RV systolic function (TAPSE) and CO, together with reductions in mPAP, RV hypertrophy, muscularization of pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy. Systolic blood pressure remained unchanged across all groups.Conclusion:These findings indicate that COR-1389 ameliorates the deteriorating cardiopulmonary parameters observed in the SuHx model and represents a promising approach for the treatment of PH and RHF.

Circulation, Volume 150, Issue Suppl_1, Page A4146434-A4146434, November 12, 2024. Background:PET/CT stress test may be performed to risk stratify patients including those without known coronary artery disease (CAD) who may be at risk for short-term adverse cardiac events. In patients with low- to moderate (LTM) risk for short-term MACE and without a known history of CAD, a small percentage of these patients will undergo a coronary angiogram within 90-days, of which some will be diagnosed with high-grade stenosis. The purpose of this study is to determine factors associated with this approach and findings.Methods:Patients without a history of known CAD (n=43,271) undergoing a PET/CT from 2018-2023 at Intermountain Health, with scan interpreted clinically as LTM short-term risk for adverse cardiac events, and ischemic burden 70% stenosis in any vessel), an a priori list of clinical data and PET/CT results were examined.Results:Within 90 days of the LTM risk PET/CT, 3,163 (8.2%) had a coronary angiogram. Of these, 806 (25.5% of angiograms and 2.1% of total LTM) had high-grade CAD. The PET/CT ancillary findings were associated with the largest odds of performing an angiogram and the presence of high-grade CAD (Tables). Factors most likely to be associated with performing an angiogram were an ischemic burden of 7.5-10% (adjusted-OR [adj. OR]=11.54), coronary artery calcification (CAC) score of >300 (adj.-OR =1.62), and myocardial blood flow (MBF) of MBF 2.3). Other clinical parameters associated, after adjustment, with an angiogram were age, male sex, hypertension, elevated troponin, and inpatient status. Many of the same factors were found to be associated with the identification of high-grade CAD. However, being an inpatient was associated with increased odds of angiogram but a decrease in odds of high-grade CAD.Conclusions:In patients without a known history of CAD who underwent PET/CT clinically adjudicated as LTM short-term risk and ischemic burden

Circulation, Volume 150, Issue Suppl_1, Page A4118341-A4118341, November 12, 2024. Background:Opioid use has increased significantly in the past few decades, impacting cardiac and non-cardiac patients. As heart failure with preserved ejection fraction (HFpEF) comprises half of all heart failure cases, understanding its management and effect on outcomes is crucial. This study aims to evaluate the outcomes of chronic opioid therapy on HFpEF patients.Methods:Studying the National Inpatient Sample (2016-2020), we identified adult HFpEF patients using the appropriate ICD-10 codes -after excluding patients with end-stage renal disease (ESRD)- and compared outcomes between chronic opioid users and non-users. Multivariate logistic and linear regression analyses were performed, adjusting for multiple patient and hospital confounders. The primary outcome was all-cause in-hospital mortality while secondary outcomes included acute kidney injury/hemodialysis (AKI/HD), cardiogenic shock, cardiac arrest, mechanical ventilation, length of stay, and total charges.Results:Among 1,557,344 HFpEF patients, 21,655 (1.4%) were on opioids chronically. Inpatient mortality was not significantly different between patients who were on opioids and those who were not. (adjusted odds ratio [aOR] 1.01, 95% CI 0.85 – 1.2, p=0.89). There was a non-significant increased risk of cardiogenic shock (aOR 1.14, 95% CI 0.87 – 1.5, p=0.35) and cardiac arrest (aOR 1.05, 95% CI 0.8 – 1.36, p=0.74) in patients on chronic opioids. Chronic opioids were associated with increased risk of AKI/HD (aOR 1.12, 95% CI 1.04 – 1.2, p=0.002) and mechanical ventilation (aOR 1.29, 95% CI 1.16 – 1.43, p< 0.001). Opioid use was also associated with longer hospital stay (adjusted MD [aMD] 1.07 days, 95% CI 0.75 - 1.39, p

Circulation, Volume 150, Issue Suppl_1, Page A4114970-A4114970, November 12, 2024. Background:Pulsed field ablation (PFA) and high-power short-duration radiofrequency ablation (HPSD) are emerging techniques for treating atrial fibrillation (AF), offering promising results compared to cryoballoon ablation (CBA). This network meta-analysis aims to evaluates the efficacy and safety of PFA, HPSD, and CBA.Method:PubMed, Embase, Cochrane Central Register of Controlled Trials, and EBSCO Information Services were systematically searched for relevant studies until April 2024. The primary outcome is freedom from atrial arrhythmia. A random-effects model was used for data synthesis, and P-scores were employed for outcome ranking. Point estimation (odd ratios) was calculated for comparisons.Results:Fifteen studies were included in our network meta-analysis, involving 5,093 atrial fibrillation patients: 812 (16%), 2,659 (52%), and 1,622 (32%) patients underwent PFA, CBA, and HPSD, respectively. PFA demonstrated the highest efficacy (P-scores 99.3%). Point estimation between PFA and HPSD, and PFA and CBA, were 1.394 (95% CI: 1.047-1.858) and 1.479 (95% CI: 1.134–1.929), respectively. PFA had higher complications compared to HPSD (OR=4.44, 95% CI: 1.405-14.031) and CBA (OR=2.581, 95% CI: 0.992–6.720). HPSD had the shortest fluoroscopic time (P-scores 100%), while CBA had the longest (P-scores 0%). PFA had the shortest procedural time compared to CBA and HPSD with P-scores of 100% 50% and 0%, respectively.Conclusion:PFA showed higher efficacy but higher complication risk than HPSD and CBA. HPSD and CBA demonstrated similar efficacy and safety.