Risultati per: AGA: linee guida sulla de-prescrizione degli inibitori della pompa protonica

The American Gastroenterological Association (AGA) maintains a strong history of creating and sustaining impactful programming to support diversity and inclusion for physicians and scientists in gastroenterology (GI) and hepatology. After the inception of its Diversity Committee in 1993 (formerly the Underrepresented Minority Committee), AGA expanded its commitment to diversity, equity, inclusion, and justice in 2020 with the Equity Project. This 3-year equity strategic plan more concretely and systematically operationalizes the organization’s diversity policy throughout the organization, identifying opportunities for greater impact by means of leveraging all levels and stakeholders in the society to be invested in the success of the project, extending beyond the scope of the Diversity Committee alone.

Objective
We aimed to increase the understanding of the scaling of de-implementation strategies by identifying the determinants of the process and developing a determinant framework.

Design and methods
This study has a mixed-methods design. First, we performed an integrative review to build a literature-based framework describing the determinants of the scaling of healthcare innovations and interventions. PubMed and EMBASE were searched for relevant studies from 1995 to December 2020. We systematically extracted the determinants of the scaling of interventions and developed a literature-based framework. Subsequently, this framework was discussed in four focus groups with national and international de-implementation experts. The literature-based framework was complemented by the findings of the focus group meetings and adapted for the scaling of de-implementation strategies.

Results
The literature search resulted in 42 articles that discussed the determinants of the scaling of innovations and interventions. No articles described determinants specifically for de-implementation strategies. During the focus groups, all participants agreed on the relevance of the extracted determinants for the scaling of de-implementation strategies. The experts emphasised that while the determinants are relevant for various countries, the implications differ due to different contexts, cultures and histories. The analyses of the focus groups resulted in additional topics and determinants, namely, medical training, professional networks, interests of stakeholders, clinical guidelines and patients’ perspectives. The results of the focus group meetings were combined with the literature framework, which together formed the supporting the scaling of de-implementation strategies (SPREAD) framework. The SPREAD framework includes determinants from four domains: (1) scaling plan, (2) external context, (3) de-implementation strategy and (4) adopters.

Conclusions
The SPREAD framework describes the determinants of the scaling of de-implementation strategies. These determinants are potential targets for various parties to facilitate the scaling of de-implementation strategies. Future research should validate these determinants of the scaling of de-implementation strategies.

Circulation, Volume 146, Issue Suppl_1, Page A15718-A15718, November 8, 2022. Introduction:Heart failure cardiogenic shock (HF-CS) constitutes a heterogenous population and has been identified as the leading type of shock among contemporary intensive care units. The in-hospital trajectory of shock severity and its association with mortality and transition to heart replacement therapy (HRT) or native heart survival (NHS) based on HF-CS phenotype has not been well described.Methods:The Cardiogenic Shock Working Group (CSWG) registry includes patients from 17 hospitals between 2016 and 2021. For this analysis, HF-CS patients were sub-classified as havingde novoHF-CS or acute-on-chronic (ACHF) CS. In-hospital trajectories were assessed using baseline and maximum Society for Cardiovascular Angiography and Interventions (SCAI) stages and clinical outcomes were analyzed.Results:A total of 1,767 patients with HF-CS were included. Of these, 349 hadde novoHF-CS (19.8%) and 1,371 (77.6%) had ACHF-CS. Overall, patients withde novoHF-CS had greater in-hospital death (32% vs 22%), NHS (58% vs 45%) and less HRT (33% vs 10%) when compared to ACHF-CS (all p

Circulation, Volume 146, Issue Suppl_1, Page A12086-A12086, November 8, 2022. Introduction:Current guidelines recommend the use of implantable cardioverter-defibrillators (ICDs) for primary prevention of arrhythmia in patients with reduced ejection fraction cardiomyopathy. Little is known about the long-term outcomes of patients with ICDs in clinical practice.Objective:To develop a risk prediction model for 10-year survival after ICD implantation for primary prevention.Methods:In this population-based registry of all ICD patients across 18 centers in Ontario, CA, 5097 patients receiving ICD implant for primary prevention from February 2007 to March 2011 were followed for up to 10 years. Patients were randomly split 2:1 into derivation and internal validation cohorts to develop and validate a prognostic model using Cox regression and predictors measured at initial ICD evaluation.Results:Mean age was 65.3 years (SD 11.0), 664 patients were female (19.5%) and 2344 patients (69.0%) had ischemic cardiomyopathy for primary disease indication. 10-year survival was 45.7% (95% CI 44.0%-47.4%).The final prediction model included age, sex, disease indication, comorbidities and biomarkers at the time of ICD assessment (Table 1). This model had good discrimination in derivation (AUC 0.80; 95% CI 0.78-0.81) and validation samples (0.79, 95% CI 0.77-0.81) and good calibration. Sensitivity analyses showed that the addition of device type, provider factors (implantation site, implanter volume, physician main specialty), sex-related interaction terms, and frailty scores did not significantly improve the prediction model.Conclusion:A combination of demographic and patient factors determined at baseline device evaluation enabled the prediction of 10-year survival in patients undergoing ICD for primary prevention in the clinical practice. Our findings may help identify and monitor individuals at risk of long-term mortality and may be useful in targeting future prevention strategies to enhance longevity in this high-risk population.

Circulation, Volume 146, Issue Suppl_1, Page A12107-A12107, November 8, 2022. Background:Short-term (

Circulation, Volume 146, Issue Suppl_1, Page A9694-A9694, November 8, 2022. Introduction:TdP is a polymorphic VT that occurs with prolonged QT interval and can cause sudden cardiac death. Trends in incidence and outcomes of TdP during the COVID-19 pandemic are not well-established. We aim to report incidence of intrahospital TdP and VT, baseline characteristics of patients with TdP, and trends in post-TdP recovery and mortality before and during the COVID-19 pandemic.Methods:Patients with diagnoses of VT and TdP from 2016-2020 at our institution were included. The diagnosis was confirmed after analysis of the patients’ ECGs. Demographics, medical history, and hospital course data were collected. Chi-square/Fisher’s exact, one-way ANOVA, and logistic regression analyses were conducted.Results:Seventy-four patients were included in the analysis. Average age was 60 ± 17, and 57% were male. Fifty-two (70%) patients were in the ICU at time of TdP. Co-morbidities included hypertension (53%), atrial fibrillation/flutter (41%), diabetes mellitus (34%), CAD (26%), and CKD (22%). Average LVEF was 39 ± 19%. Forty-two (57%) underwent emergent defibrillation, 19 (26%) required transvenous pacing, and 7 (10%) were administered isoproterenol for acute management of TdP. Median recovery time of QTc interval to

Circulation, Volume 146, Issue Suppl_1, Page A11472-A11472, November 8, 2022. Background:Recent randomized controlled trials (RCTs) have demonstrated the superiority of treating patients with acute coronary syndrome (ACS) with dual antiplatelet therapy (DAPT) uniform de-escalation strategy (i.e., switching from potent P2Y12inhibitors to clopidogrel one month after the event). However, it remains unclear if this strategy would be effective in elderly patients. We aimed to assess the efficacy of the available DAPT strategies, including the uniform de-escalation strategy, in ACS patients older than 65.Methods:We searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to December 2021 for RCTs or subgroup analyses investigating DAPT strategies for elderly ACS patients (age ≥65 years) and conducted a network meta-analysis. The endpoint was net clinical benefit outcome, defined as a composite of major adverse cardiovascular events and bleeding. The P-score was used to rank the treatments.Results:Seven RCTs with 5,079 patients were included. The uniform de-escalation strategy was associated with a better net clinical benefit outcome (hazard ratio: 0.62; 95% confidence interval [0.41-0.92]) compared with DAPT using potent P2Y12inhibitors, and it was similarly effective compared with other DAPT strategies. There was no significant heterogeneity (I2=0%;p=0.82) or inconsistency (p=0.40). The uniform de-escalation strategy was ranked as the most effective strategy (by P score) superior to DAPT using clopidogrel or low-dose prasugrel.Conclusions:The uniform de-escalation strategy was an effective strategy for older ACS patients. Compared with conventional DAPT using potent P2Y12inhibitors, this strategy decreased the composite of major adverse cardiovascular events and bleeding events.

Circulation, Volume 146, Issue Suppl_1, Page A15753-A15753, November 8, 2022. Epigenetic regulation is critical for cardiac electrophysiology and pathology. Epigenetic modulators, such as histone deacetylases (HDACs) and histone acetyltransferases (HATs) are known master regulators of gene expression. Recently, novel pharmacological agents, HDAC inhibitors, have been developed as treatments for cancer and immune diseases. The effects of HDAC inhibitors on cardiac ion channels (ICs) are of great interest. To exert specific gene modulation, we used small interfering RNAs against the known HDACs, including sirtuins, and deployed them in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Follow-up RNAseq data (n = 61) were compared to identically processed and normalized RNAseq data from human left ventricle (LV) from the GTEx database (n = 84). Gene expression of cardiac ICs displayed similar patterns, with some differences. For example, hiPSC-CMs showed upregulatedCACNA1C, SLC8A1and downregulatedKCNJ2andRYR2compared to the adult LV, most of which are known distinctions (Fig. 1A). Correlative analysis (Fig. 1B) and partial least square regression models helped visualize links between HDACs/HATs, key transcription factors (TFs) and cardiac ICs. Powerful TFs, includingMEF2A, GATA4, 6exerted positive effect on ICs in hiPSC-CM and the adult LV. In the hiPSC-CMs,HDAC1, HDAC10andSIRT6were found to be the strongest predictors of the expression of individual cardiac ICs, as revealed by permutation importance. Further studies will involve determination of the role of different cell types using single-cell sequencing data from the adult LV. Our analysis offers new insights about the role of epigenetic modifiers on cardiac electrophysiology and informs the utility of hiPSC-CM as a scalable, experimental model for cardiotoxicity testing of HDAC inhibitors.

Circulation, Volume 146, Issue Suppl_1, Page A11327-A11327, November 8, 2022. A 24-year-old male, with no past medical history, presented to the ER with a 15-day history of insidious abdominal pain and distention, associated with progressive dyspnea on exertion and bilateral lower extremity pitting edema. In the previous 48 hours before his hospital admission, patient began presenting orthopnea and paroxysmal nocturnal dyspnea.On presentation patient was normotensive and tachycardic, with low oxygen saturation on pulse oximetry. On auscultation a loud early diastolic decrescendo murmur was heard at the parasternal border, with and audible S3 gallop. Characteristic Marfanoid habitus was observed. Patient underwent TTE were there was a notable aortic root dilation, mainly at the level of the sinuses of Valsalva, which had a diameter of 85 mm and 62 mm at the sinotubular junction. Ascending and descending aorta had a normal diameter. An eccentric jet of severe aortic regurgitation was also noted, which collided with the anterior mitral valve leaflet causing an Austin Flint phenomenon. Left ventricular ejection fraction was estimated at 24%, severe dilation was noted on all chambers. There were no echocardiographic signs of aortic dissection. Patient underwent genetic testing and ophthalmic evaluation, confirming the diagnosis of Marfan’s syndrome. A contrast enhanced CT angiogram confirmed the presence of severe aortic root dilation without dissection. Patient underwent Bentall procedure and began treatment for HFrEF at discharge. Marfan Syndrome is an autosomal dominant connective tissue disorder, due to mutations mostly in theFBN1gene. Most cardiovascular symptoms are related to dilation of the aortic root and subsequent aortic regurgitation due to aortic annulus dilation. In patients with Marfan’s syndrome, all aortic root aneurysms ≥5.0 mm should undergo surgical repair regardless of symptoms.

Circulation, Volume 146, Issue Suppl_1, Page A13311-A13311, November 8, 2022. Introduction:Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced proarrhythmia. It is unknown whether patients with HF with preserved ejection fraction (HFpEF) are also at increased risk.Hypothesis:The risk of drug-associated ventricular tachycardia (VT) and sudden cardiac arrest (SCA) is increased in patients with HFpEF.Methods:Using Medicare enrollment in fee-for-service medical and pharmacy benefits (2014 to 2016) and ICD-9/10 codes, we identified patients taking drugs known to cause torsades de pointes (TdP drugs; www.crediblemeds.org) and non-TdP drug users among three groups: HFrEF (n=31,422), HFpEF (n=40,012), and no HF (n=633,558). Multinomial propensity score-matching was performed to minimize baseline differences in covariates (patient demographics, comorbidities, health care utilization and drug history). Cochran-Mantel-Haenszel statistics and standardized differences were used to compare baseline characteristics. A generalized Cox proportional hazards model was used to estimate hazard ratios (HRs) and test the association of VT and SCA among TdP drug users with HFpEF, HFrEF, and no HF.Results:Of 23,910 TdP drug users with HFrEF, VT and SCA occurred in 4,263 (17.8%) and 493 (2.1%) patients, respectively. In comparison, among 31,359 TdP drug users with HFpEF, VT and SCA occurred in 1,570 (5.0%) and 340 (1.1%) patients. VT and SCA occurred in 3,154 (0.8%) and 528 (0.1%) of 384,824 TdP drug users without HF. The overall risk of both VT and SCA was increased in patients with HFrEF and in those with HFpEF (Table). The risk of VT associated with TdP drugs was increased across the overall population. Use of TdP drugs significantly increased the risk of VT and SCA in patients with HFrEF, but not in patients with HFpEF.Conclusions:The risk of VT and SCA associated with drugs known to cause TdP was increased in patients with HFrEF but not in those with HFpEF.

Circulation, Volume 146, Issue Suppl_1, Page A11858-A11858, November 8, 2022. Aims:Disturbed flow at arterial bifurcations and curvatures of blood vessels, combining with other atherosclerotic risk factors, promotes endothelial cell (EC) DNA damage and the subsequent EC death, compromises the integrity of the endothelial barrier and ultimately leads to the formation of atherosclerotic lesions. ECs reprogram their metabolism to protect them from atherogenic injury induced by disturbed flow.De novopurine synthesis (DNPS) has been reported to regulate DNA repair and cell proliferation in cancer cells, however, its role in atherosclerosis has not been determined. 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC) is the enzyme that catalyzes last two steps of DNPS. We investigated the role of ATIC-driven DNPS in flow-induced EC metabolic reprogramming and in the development of atherosclerosis.Methods and Results:The expression of DNPS and DNA damage associated genes in ECs exposed to disturbed flow were assessed by analyzing the published RNA-Seq datasets. ATIC protein expression and DNA damage were examined in the endothelium at atheroprone regions of mouse aortas. Mice with EC-specificAticknockout were utilized to investigate the role of endothelial ATIC in atherosclerosis. ATIC-mediated DNPS were increased in ECs exposed to disturbed flow bothin vitroandin vivo, which was highly associated with the increased DNA damage response. EC-specificAticknockout enhanced DNA damage of ECs, EC apoptosis, EC permeability and the subsequent formation of atherosclerotic lesions.Conclusion:Enhanced ATIC-mediated DNPS in ECs exposed to disturbed flow supplies purine nucleotides to repair DNA damage and to preserve EC barrier integrity in vulnerable atheroprone regions, and ultimately protects against the development and progression of atherosclerosis.