Risultati per: Short Acting Opioid

Circulation, Volume 150, Issue 22, Page 1815-1817, November 26, 2024.

The American Academy of Pediatrics (AAP) released its first clinical guidance on prescribing opioids for outpatient acute pain management to youth. Although it cautions against the dangers of rising opioid use disorder among children and teens, it also notes that a decrease in opioid prescription rates may leave some youth with pain that is not adequately treated.

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…

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…

Objective
In patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse ( >6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy).

Design
In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE).

Results
In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76–0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66–0.68 vs 0.61 vs 0.52 vs 0.59, respectively).

Conclusion
In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.

Trial registration number
NCT00571337 and NCT02177071.

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…

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 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 A4147011-A4147011, November 12, 2024. Introduction:Guidelines recommend dual antiplatelet therapy (DAPT) for 12 months following percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). However, prolonged DAPT may increase bleeding risk. Monotherapy with the potent P2Y12 inhibitor ticagrelor after short DAPT offers a promising strategy to balance thrombotic and bleeding risks.Objective:To compare outcomes of short DAPT (≤3 months) followed by ticagrelor monotherapy until 12 months vs. 12-month DAPT in patients undergoing PCI for ACS.Methods:We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing short DAPT followed by ticagrelor monotherapy vs. 12-month DAPT following PCI. Outcomes of interest included net adverse clinical events (NACE), major adverse cardiovascular/cerebrovascular events (MACCE), and any bleeding at 12 months post-PCI. Statistical analysis was done using R software. Random effects models were used to generate risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2statistics. Analysis followed the PRISMA guideline.Results:The systematic review identified 4 randomized controlled trials including 5,293 patients. Ticagrelor monotherapy was used in 2,667 (50.38%) patients. At 12 months, NACE (RR 0.81; 95%CI 0.57-1.14; p=0.227; I2=45%), MACCE (RR 1.11; 95%CI 0.86-1.42; p=0.415; I2=3%), and any bleeding (RR 0.68; 95%CI 0.46-1.01; p=0.055; I2=34%) were comparable between the two groups.Conclusion:After PCI for STEMI, short DAPT for ≤3 months followed by ticagrelor monotherapy was non-inferior to 12-month DAPT in terms of NACE, MACCE, and bleeding. Ticagrelor monotherapy following short DAPT may be considered for STEMI patients after PCI.

Circulation, Volume 150, Issue Suppl_1, Page A4117180-A4117180, November 12, 2024. Introduction:Patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi) are at increased risk of developing hyperkalemia (HK). Sodium zirconium cyclosilicate (SZC) is used to treat HK, but the impact of duration of SZC on healthcare resource utilization (HRU) in RAASi users is unknown. The GALVANIZE Outcome study compared HK-related HRU among RAASi users between long-term and short-term SZC users.Methods:Adults with ≥1 outpatient prescription for SZC (index date) and ≥1 RAASi prescription spanning the index date were identified from a large US insurance claims database (7/2018-12/2022) and were stratified based on duration of SZC use. Long-term SZC users ( >90 days) and short-term SZC users (≤30 days) were exactly and propensity score matched on key baseline characteristics. Rates of HK-related hospitalizations or emergency department (ED) visits, HK-related ED visits, and HK-related hospitalizations were compared during follow-up from index to the earliest of 6 months post-index, end of data availability, other potassium binder use, or re-initiation of SZC post-discontinuation.Results:Among 1,586 matched pairs, the mean age was 65.5 years, 41.0% of patients were female, and most patients had any stage chronic kidney disease (91.9%), hypertension (90.8%), and diabetes (73.4%). Also, 30.0% of patients had heart failure. The most used RAASi therapies at index were angiotensin-converting enzyme inhibitors (57.3%) and angiotensin-receptor blockers (56.3%). Patients with long-term SZC use had a 44% lower rate of HK-related hospitalizations or ED visits, a 41% lower rate of HK-related hospitalizations and a 52% lower rate of HK-related ED visits than patients with short-term SZC use during follow-up (all p

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 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 A4144700-A4144700, November 12, 2024. Background:Long term right ventricular apex pacing has been reported to affect myocardial metabolism and perfusion to lead to impaired left ventricular function. However, there is little information available on the effect on fatty acid metabolism, myocardial perfusion and function in RV septal or His bundle pacing.Methods and Results:We studied 94 patients (mean age 77±11 years, male 40%, AV block 71%) admitted for pacemaker implantation in our prospective cohort study, excluding patients with coronary artery disease who had past histories of coronary arterial revascularization and severe stenosis in coronary CT or coronary angiography. Forty-five patients had right ventricular apex pacing (RVA; n=10) or right ventricular septal pacing (RVS; n=35), 17 had selective or non-selective His bundle pacing (HIS) and, as a control, 32 had right atrial pacing (RA). The patients underwent 123I-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) SPECT imaging and Tc-99m- methoxyisobutylisonitrile (MIBI) SPECT imaging between 3 months and 1 year after implantation. The uptakes of both tracers were displayed on a polar map, which was divided into 17 segments. Regional tracer activity at each segment was quantified as %uptake. Left ventricular ejection fraction (LVEF) was also obtained in MIBI imaging.There were no significant differences in baseline characteristics such as age, gender, or underlying heart disease between the four groups. LVEF in MIBI rest imaging in RVA group was significantly lower than RA group (58.3±2.1% vs 64.9±1.2%, p=0.013), while there was no significant difference in LVEF among RVS, HIS and RA groups, with non-significantly (p=0.25) lower LVEF in RVS (62.5±1.1%) than HIS (65.3±1.6%) groups. The average of BMIPP %uptake in 17 segments significantly correlated with LVEF (r=-0.259, p=0.01). BMIPP and MIBI (stress and rest) %uptake were significantly lower in RVA group and RVS group than RA group in the septal or anterolateral area. Especially, BMIPP %uptake in RVA group was significantly lower at the broad area. On the other hand, BMIPP and MIBI (stress and rest) %uptake in HIS group were almost similar to those in RA group.Conclusion:His bundle pacing, but not RV septal pacing, maintains myocardial metabolism, perfusion and function.

Circulation, Volume 150, Issue Suppl_1, Page A4145933-A4145933, November 12, 2024. Introduction:Cardiogenic shock (CS) remains a clinical challenge with a high mortality rate. An escalation strategy from intra-aortic balloon pump (IABP) to Impella has been proposed for patients with CS refractory to IABP therapy, but clinical data on this approach are lacking. This study aimed to elucidate the short-term clinical outcomes after IABP-Impella escalation in patients with CS.Methods and Results:From the Japanese nationwide registry of Impella (J-PVAD) database between 2020 and 2022, a total of 2,578 patients with CS who received Impella support were classified into the IABP-Impella group (n=189) or the Primary Impella group (n=2,389). We applied a 1:3 propensity score matching, selecting 180 patients in the IABP-Impella group and 540 patients in the Primary Impella group. Before matching, the IABP-Impella group presented significantly longer shock-to-Impella time, worse laboratory data indicating multiorgan damage, and more frequent inotrope use compared to the Primary Impella group. After matching, the baseline characteristics were well-balanced between the two groups. The clinical outcomes within 30 days after the initiation of Impella were compared between the matched groups. The IABP-Impella group showed a significantly higher rate of additional mechanical circulatory support (MCS) use than the Primary Impella group (33.9% vs. 25.6%, p=0.034). Although the incidence of mortality was similar between the two groups (30.6% vs. 30.9%, p >0.99), the incidence of major complications (a composite of bleeding, hemolysis, infection, stroke, myocardial infarction, limb ischemia, and vascular injury) tended to be higher in the IABP-Impella group (43.0% vs. 36.3%, p=0.053). Notably, the incidence of infection was significantly higher in the IABP-Impella group than in the Primary Impella group (10.0% vs. 4.8%, p=0.018). Kaplan-Meier estimates revealed that infection occurred more frequently in the IABP-Impella group during the 30-day follow-up period (log-rank p=0.016).Conclusions:Patients undergoing the IABP-Impella escalation strategy showed poorer baseline clinical conditions in baseline and were associated with a higher likelihood of further MCS upgrade and an increased risk of infection.

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.