Risultati per: Epidemiologia e classificazione del Low Back Pain

Circulation, Volume 150, Issue Suppl_1, Page A4124369-A4124369, November 12, 2024. Background:Several clinical trials have demonstrated non-inferiority of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) and low to intermediate surgical risk. However, mid-term results are still contentious.Question:Is TAVR superior to SAVR in the mid-term in terms of mortality outcomes or adverse cardiovascular events?Methods:We searched Embase, Pubmed and Cochrane databases for RCTs that compared TAVR with SAVR in patients with symptomatic severe AS with a follow-up of at least 4 years. Outcomes of interest were all-cause mortality and disabling stroke.Results:We included six RCTs involving 6,444 patients with severe AS, of whom 3,282 (50.9%) underwent TAVR. There was no difference in mortality from all causes (RR 1.08; 95%CI 0.94-1.25; p=0.30; I2=45%) and disabling stroke (RR 0.95; 95%CI 0.75-1.21; p=0.67; I2=9%) between groups. In the subgroup analysis, 5-year mortality (RR 1.28; 95%CI 1.10-1.49; I2=0%) was higher in the TAVI group. The new pacemaker implantation rate was higher in the TAVI group (RR 2.22; 95%CI 1.42-3.45; p=0.0004 ; I2=91%). However, new atrial fibrillation rate was higher in the SAVR group (RR 0.42; 95%CI 0.37-0.49; p=0.00001; I2=62%).Conclusion:Mid-term mortality and disabling stroke of patients with severe AS treated with TAVR or SAVR were similar.

Circulation, Volume 150, Issue Suppl_1, Page A4144964-A4144964, November 12, 2024. Major adverse cardiovascular (CV) events (MACE) occur in a substantioal percentage of individuals following acute coronary syndromes (ACS), primarily driven by residual vascular inflammation. Anti-inflammatory drugs have improved CV outcomes but their use is limited by significant side-effects. Low-dose interleukin 2 (IL2) increases regulatory T (Treg) cells, which are powerful endogenous regulators of the immune response, and could provide a new, targeted anti-inflammatory strategy in high-risk ACS patients. In IVORY, we hypothesised that treatment with low-dose IL2 would reduce arterial inflammation measured by18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), compared to placebo. In IVORY FINALE we hypothesised that low dose IL2 could reduce MACE compared to placebo at follow up (up to 5 years.)IVORY was a double-blind, placebo-controlled, Phase IIb trial randomising ACS patients with high-sensitivity CRP levels ≧ 2mg/L to receive either 1.5×106IU IL2 or placebo (1:1). Dosing consisted of a daily induction (5 days) and a weekly maintenance phase (7 weeks).18F-FDG-PET/CT imaging of the ascending aorta and carotid arteries was performed before and after treatment. The primary outcome was the difference in the mean maximum target-to-background ratio (TBRmax) in the index vessel on follow-up imaging between the groups.60 patients (IL2:placebo, n=31:29) completed the trial. Arterial inflammation in the index vessel was lower at the end of treatment in the IL2 group than in placebo (TBRmax = -0.171[-7.7%], 95% CI -0.308 to -0.034, p=0.015)[Fig1]. In more inflamed areas with a mean TBRmax ≧ 2 (active slices), the difference between the groups was greater (-0.185 [-8.3%], P=0.009, 95% CI -0.323 to -0.0478). Overall, the additive treatment effect of low-dose IL2 was greater at higher baseline inflammation [Fig 2]. Low-dose IL2 significantly increased circulating Tregs compared to placebo (p

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 A4125419-A4125419, November 12, 2024. Introduction:Metabolic syndrome (MS) is an important predisposing factor for atrial fibrillation, and is highly related to the autonomic nervous system. Triglyceride-rich very-low-density lipoprotein (VLDL) has specific VLDL receptors (VLDLR), which are abundantly expressed in cardiomyocytes.Hypothesis:VLDL affects neuronal growth through cardiomyocyte-secreted exosomes in metabolic syndrome.Goals/Aims:To determine whether exosomes from VLDL-incubated cardiomyocytes can alter neuronal proliferation.Methods/ Approach:HL-1 cardiomyocytes were incubated with VLDL isolated from human subjects with MS, and exosomes were extracted at the end of the incubation period. VLDLR knockdown HL-1 cells were used to determine the role of VLDLR in exosome secretion. The molecular contents of exosomes were determined by mass spectrometry, which identified neurotropic proteins only detected in the exosomes of MS VLDL-incubated cardiomyocytes. We selected transmembrane protein 14B (TMEM14B) to investigate its effect on neuronal proliferation in P19 cells.Results:Regardless of the knockdown or overexpression of VLDLR in HL-1 cardiomyocytes, exosomes isolated from after VLDL incubation were shown to cause 2.062-fold and 2.084-fold expression of tyrosine hydroxylase (TH) in P19 cells, relative to P19 cells induced by non-VLDL-treated HL-1 cardiomyocyte-secreted exosomes. A similar trend could be seen with HL-1 cardiomyocytes without VLDLR editing, as VLDL-incubated HL-1 cardiomyocytes produced exosomes that could cause 1.926-fold increase in P19 TH expression, relative to treatment by exosomes from HL-1 cardiomyocytes without VLDL-incubation. The P19 cells incubated with TMEM14B demonstrated increased neurite length, with an average of 2.342-fold neurite length when compared with that of control cells.Conclusions:VLDL in MS induced HL-1 cardiomyocytes to secrete exosomes containing neurotrophic molecules and increased dendritic growth of neuronal cells. This effect was VLDLR-independent and was partially caused by TMEM14B in the exosomes.

Circulation, Volume 150, Issue Suppl_1, Page A4140363-A4140363, November 12, 2024. Introduction:An estimated 23-85% of adults with chronic heart failure (HF) experience comorbid chronic pain, yet no comprehensive theoretical models have been developed or tested that completely capture the salient variables which affect pain. The aim of this study was to construct a preliminary theoretical model of pain in HF and evaluate the associations between identified variables in the model with pain presence.Methods:In this cross-sectional study, baseline data were obtained from the Cognitive Intervention to Improve Memory in Heart Failure Patients study (MEMOIR-HF) (n = 235). The Biopsychosocial Model of Chronic Pain was adapted for an HF-specific population. The dependent variable was pain presence (yes/no), which was measured using the Health Utilities Index Mark-3 (HUI-3). Independent variables were identified for the model using previous literature and univariate analyses comparing patients with vs. without pain in MEMOIR-HF. Logistic regression was used to test for differences between patients with pain present and not present.Results:Demographics were 45.5% men, 54.5% women, 86.4% White, 13.6% Black, mean age 66.39 (SD 12.04) years. Of 235 patients, 159 (67.66%) reported pain on the HUI-3 items.The variables that were included following univariate analysis and literature review were age, self-reported race and gender, comorbid conditions, sleep disturbances, HF severity, B-type natriuretic peptide, brain-derived neurotrophic factor, body mass index, and depression. Patients with pain were more likely to have worse HF severity (NYHA Class II or III compared with Class I) (Class II: OR 5.09 [1.71 – 15.08], p = .003, Class III: 5.05 [1.73 – 14.71], p = .003), more severe depression (OR 1.14 [1.06 – 1.23], p = .001), and worsened daytime sleepiness (OR 0.90 [0.83 – 0.98], p = .017), see Table 1.Conclusions:We believe this study is one of the first to construct and test a preliminary comprehensive model of pain in HF. Complete characterization of pain in HF is needed before treatments can be improved. Future research is needed to explore variables that were not available in the MEMOIR-HF dataset. More robust pain measures are needed to adequately test all variables.

Circulation, Volume 150, Issue Suppl_1, Page A4139970-A4139970, November 12, 2024. Introduction:Anticoagulation (AC) is the mainstay of thromboprophylaxis for stroke prevention in atrial fibrillation (AF) and is recommended. Gastrointestinal bleeding (GIB) is a common complication with varied severity and often poses a challenge for cardiologists and gastroenterologists. The decision of whether to continue anticoagulation, when to resume and at what dose is often the challenge. Our study assesses the safety and efficacy of low-dose apixaban compared to a full-dose in patients with AF who had GIB over the course of 5 years.Methods:We queried the US Collaborative Network (which contains 63 healthcare organizations) of TriNetX deidentified research database. Patients with atrial fibrillation who have history of gastrointestinal bleed who received apixaban were identified and divided into two cohorts; patients on low dose of 2.5mg and those on full dose of 5mg. We excluded patients with serum creatinine ≥ 1.5 mg/dL and patients with body weight ≤ 132 lbs.Two well-matched cohorts were created using a 1:1 propensity-score matching (PSM) model using patients’ baseline characteristics and comorbidities. PSM components were age, gender, race, PPI use, anti-platelets, hypertension, coronary artery disease, heart failure, COPD, and CKD. We compared the risk of stroke, GIB, and mortality in 5 years.Results:A total of 19,427 patients with UGIB who have AFIB received oral apixaban were identified. Of those, 19% (n=3,701) were on low dose of 2.5mg and 81% (n=15,726) were on full dose of 5mg of apixaban. After PSM, each cohort included 3,701 patients. There was no statistically significant difference in the risk of stroke in 5 years between the patients on low dose compared to those on full dose (10.9% vs 11.9%, p=0.3). However, patients on low dose had a statistically significant lower risk of GIB compared to those on full dose (30.4% vs 35.3%, p

Circulation, Volume 150, Issue Suppl_1, Page A4142085-A4142085, November 12, 2024. Background:Highly precise definition of high-risk features associated with HFpEF may guide targeted treatments and inform biological studies. The aim of this two-step study is to 1) define a high risk HFpEF cluster with unsupervised machine learning approach using cardiac magnetic resonance (CMR), 2) define novel pulmonary vascular mechanics at rest and with exercise in low- vs. high-risk phenotypes. Vascular mechanics defines vessel- and cardiac cycle-specific flow dynamics in pulmonary circulation.Methods:48 HFpEF participants underwent CMR and invasive cardiopulmonary exercise testing. With unsupervised K-means clustering analyses using CMR data, two specific clusters were identified with different survival outcomes at 12-months (mortality and heart failure hospitalizations): HR=5.4 (CI:1.7-17.4), log-rank p

Circulation, Volume 150, Issue Suppl_1, Page A4141389-A4141389, November 12, 2024. Introduction:Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent form of heart failure (HF) in the US today. Our prior work revealed low albumin at first hospitalization for HF exacerbation with underlying HFpEF to be an independent predictor of all-cause mortality in a small cohort of patients. We now sought to confirm our earlier findings across a larger and more diverse patient population.Methods:Seven thousand, eight hundred and forty patients had a first admission to Mayo Clinic for HF exacerbation with an echo-confirmed left ventricular ejection fraction >50% between 2010 and 2020. Patient baseline demographics, co-morbidities, admission laboratory values, echocardiographic parameters, discharge medications, and outcomes were obtained from chart abstraction. To validate our previous model, patients were grouped based on the number of risk factors as previously defined: age >80 years, serum albumin level

Circulation, Volume 150, Issue Suppl_1, Page A4144944-A4144944, November 12, 2024. Background:The American Heart Association’s (AHA) Life’s Essential 8 (LE8) concept serves as a quantitative framework for assessing cardiovascular health (CVH). Post-operative coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) patients are at high-risk for subsequent cardiovascular events (CVE). However, LE8 scores for post-procedural CABG or PCI patients remain unknown.Methods:Isolated post-operative CABG (n=208) or PCI (n=739) non-institutionalized patients from the National Institutes of Health’s (NIH) All of Us (AoU) Research Program (2017-2022) were included. LE8 scores (range 0-100, higher = better CVH; excluding diet metric) were calculated using methods recommended by the AHA. Physical activity and sleep metrics were derived from patients’ Fitbit data, while all other metrics were sourced from electronic health records (EHR).Results:Overall LE8 scores for post-operative CABG (57.9 [95% CI: 56.6-59.2]) and PCI patients (55.3 [54.4-56.1]) were significantly lower than that of the general population (65.9 [65.1-66.7] (p

Circulation, Volume 150, Issue Suppl_1, Page A4140382-A4140382, November 12, 2024. Introduction:Although an estimated 54% of patients with heart failure (HF) and chronic pain report high symptom-associated distress, it is unclear whether pain predicts reduced physical function, cognitive function, independent activities of daily living (IADL) or health-related quality of life (HRQL) over time. The aims were to evaluate baseline pain presence as a predictor of physical function, cognitive function, IADL, and HRQL at baseline, 10 weeks, 4 months, and 8 months after baseline.Methods:In a retrospective longitudinal secondary analysis, data were analyzed from 237 participants with HF enrolled in the Cognitive Intervention to Improve Memory in Heart Failure Patients study. Pain presence was measured with the Health Utilities Index Mark-3 Questionnaire (HUI-3), physical function was measured by the Timed Up and Go (TUG), cognitive function was measured with the Montreal Cognitive Assessment (MoCA), IADL was measured by the Everyday Problems Test (EPT), and HRQL was measured by the Minnesota Living with Heart Failure Questionnaire (LHFQ). Descriptive statistics, independent t-tests, and linear mixed models were used to achieve the aims while controlling for gender.Results:The demographics were mean age 66.31 ± 12.02 years, gender 46% men, 54% women, race 13.5% Black, 85.7% White, 0.8% Other, NYHA class I: 9.7% II: 37.6% III: 52.7%, average LVEF: 48.9%. A total of 160 (67.51%) reported pain.In independent t-tests, patients with pain experienced significantly longer (i.e., worse) TUG scores at all timepoints except 10 weeks, and significantly higher (i.e., worse) LHFQ scores at all timepoints (see Table 1). However, in linear mixed models, pain at baseline did not predict TUG scores (F = 1.239, p = .298), MoCA scores (F = 0.148, p = .931), EPT scores, (F = 0.522, p = .668), or LHFQ scores (F = 0.364, p = .779) over time – see Table 1.Conclusions:Patients with HF and pain experienced significantly worse LHFQ and TUG scores at multiple timepoints. However, pain did not significantly predict cognitive function, physical function, IADL, or HRQL over time. Future prospective studies are needed to examine other outcomes associated with pain in this population and utilize more robust pain instruments.

Circulation, Volume 150, Issue Suppl_1, Page A4129733-A4129733, November 12, 2024. Background:The impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on lipid components is unclear. The objective of this study was to measure the lipid-lowering effect of GLP-1RAs.Methods:A thorough database search was performed to identify placebo-controlled randomized controlled trials (RCTs) on GLP-1RA therapy through January 2023. From these trials, data was extracted and a robust statistical analysis was performed using a random effects model to determine outcomes with weighted mean difference (MD) in milligrams per deciliter (mg/dL) and 95% confidence intervals (CIs). The primary outcome was the mean difference in low-density lipoprotein cholesterol (LDL-C). Secondary outcomes were mean differences in total cholesterol (TC), triglycerides, high-density lipoprotein-C (HLD-C), and very low-density lipoprotein-C (VLDL-C). To account for covariates, subgroup analyses and meta-regression were performed.Results:A total of 33 studies were included in the final meta-analysis carried out between 2008 and 2023, which were conducted in 26 countries. Of the 5,918 participants, the study population comprised 2,603 (44%) males and 3,315 (56%) females, aged between 33.7 and 65.9 years. GLP-1RAs significantly reduced LDL-C compared to placebo (MD -2.93, 95% CI (-5.01, -0.85), P=0.01). Treatment effect was consistent regardless of duration of treatment;12 weeks or less MD: -5.39, 95% CI (-10.36, -0.42), P=0.03 vs >12 weeks MD: -2.39, 95% CI (-4.70, -0.007), P=0.04, P interaction 0.28). In our analysis, GLP-1RA reduced TC by ~7 mg/dl. There was no significant reduction in triglycerides (MD = -7.19, 95% CI (- 15.01, 0.62], P=0.07) and VLDL-C ~4 mg/dl (MD = -3.99, 95%, CI (-8.73, 0.75), P=0.10). Furthermore, GLP-1RA did not increase HDL-C (MD = -0.12, 95% CI (-0.73, 0.49], P=0.69. Regression analysis determined that weight loss did not affect the treatment effect on LDL-C (tau2=28.38, I2=99.83, R2=0.0, p=0.67), and total cholesterol (tau2=93.6, I2=99.86, R2=0.0, p=0.92).Conclusion:Patients on GLP-1RA experienced modest LDL-C and TC lowering compared to placebo. GLP-1RA did not decrease triglycerides and VLDL-C. GLP-1RA did not increase HDL-C.

Circulation, Volume 150, Issue Suppl_1, Page A4138733-A4138733, November 12, 2024. Introduction:Identifying low-voltage areas (LVAs) within left atrium (LA) is crucial for predicting atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Animal studies have shown that the parasympathetic neurotransmitter vasoactive intestinal peptide (VIP) affects atrial electrophysiological remodeling.Hypothesis:Thus, we hypothesized that elevated serum VIP levels might contribute to the development of LVAs and that serum VIP concentrations could serve as a biomarker for LVA presence in AF patients.Aims:The aim of this study is to investigate the relationship between the blood levels of VIP and the presence of LVAs in AF patients with electroanatomical mapping (EAM).Methods:We conducted an observational, prospective cross-sectional study on AF patients undergoing PVI between 2021 and 2023. Blood samples for VIP were collected before atrial septal puncture, and EAM was performed using CARTO 3® before PVI. VIP concentrations were measured using an enzyme-linked immunosorbent assay kit. Patients were divided into two groups based on LVA presence (≥5% or

Circulation, Volume 150, Issue Suppl_1, Page A4134364-A4134364, November 12, 2024. Introduction:Inclisiran, an siRNA, targeting PCSK9 mRNA, reduces LDL-c levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower cardiovascular (CV) events in virtual patients with atherosclerotic cardiovascular disease (ASCVD).Research question:This analysis predicted the potential efficacy of inclisiran on CV outcomes in virtual patients with or without prior ischemic stroke (IS).Methods:The SIRIUS trial was conducted using a calibrated and validated knowledge-based mechanistic computational model of ASCVD applied to a virtual population with LDL-C ≥ 70 mg/dL. Each virtual patient was its own control. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statin with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal IS over 5 years in patients with or without prior IS. Occurrence of fatal and non-fatal (IS) was also individually assessed in time-to-first-event analyses.Results:Among 204,691 virtual SIRIUS ASCVD patients, 39 371 (19%) had prior IS. At 5 years, the predicted mean percentage reduction in LDL-C with inclisiran as compared to placebo was –49.17% and –49.88% in patients with or without prior IS respectively. Patients with prior IS were at higher risk of 3P-MACE than patients without IS both with placebo and inclisiran (17.01% vs 14.41% with placebo and 13.44% vs 10.83% with inclisiran). However, the predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm for both prior IS and no prior IS (HR 0.78 medium uncertainty and 0.74 low uncertainty respectively). Compared to placebo, inclisiran was also predicted to consistently reduce fatal and non-fatal IS in patients with or without prior IS (5.45% vs 7.22%; HR: 0.75 medium uncertainty and 1.87% vs 2.54%; HR: 0.73 medium uncertainty respectively).Conclusion:SIRIUS provides insights into the potential efficacy of inclisiran on CV events suggesting a substantial 3P-MACE and fatal and non-fatal IS reduction in ASCVD patients including those with prior IS, several years before the availability of results from ongoing outcomes trials (ORION-4, VICTORION-2P).

Circulation, Volume 150, Issue Suppl_1, Page A4139384-A4139384, November 12, 2024. Background:Recent evidence suggests a therapeutic role for ketosis in patients with heart failure (HF). However, little is known regarding the safety and effectiveness of a low carbohydrate ketogenic diet (LCKD) in patients with overweight or obesity and HF.Purpose:To examine the safety and effectiveness of a LCKD in patients with overweight or obesity and HF.Methods:A retrospective review from 2006-2024 was conducted of all patients with overweight or obesity and HF who followed a LCKD with clinical oversight for at least one year in a university health system. Changes in metabolic outcomes, echocardiographic measures, and medication use were assessed. Heart failure hospitalization (HFH) rates and rate ratios (RR) and all-cause mortality rates were calculated and stratified by HF classification.Results:A total of 125 patients met inclusion criteria, including 59 patients with HF with reduced ejection fraction (HFrEF) and 66 patients with HF with preserved ejection fraction (HFpEF). Patients lost a median (interquartile range) of 11.2 kg (-19.5, 4.4;p

Circulation, Volume 150, Issue Suppl_1, Page A4139036-A4139036, November 12, 2024. Background:Patients with low-flow low-gradient (LFLG) aortic stenosis (AS) are at risk of worse outcomes following transcatheter aortic valve replacement (TAVR). Flow is known to improve after TAVR, however the clinical and echocardiographic characteristics correlating with flow improvement in patients with LFLG AS are still unclear.Hypothesis:Some baseline and discharge clinical and echocardiographic characteristics correlate with flow improvement in patients with LFLG AS post-TAVR.Aims:The present study sought to explore the clinical and echocardiographic characteristics correlating with flow improvement in patients with LFLG AS post-TAVR.Methods:This is a retrospective cohort of patients >18 years of age who underwent TAVR at Cleveland Clinic between 2016 and 2020. Only patients with aortic valve (AV) area

Circulation, Volume 150, Issue Suppl_1, Page A4136136-A4136136, November 12, 2024. Background:The optimal clinical management and timing of intervention are less well defined in paradoxical low-flow, low-gradient severe aortic stenosis (PLFLG AS). Left ventricular global longitudinal strain (LV-GLS) has been shown to predict outcomes in high flow severe AS, but there is lack of data in patients with PLFLG AS. Given the exaggerated LV hypertrophy and remodeling pattern in PLFLG AS, LV-GLS may be a mechanistic imaging marker for worse outcomes.Hypothesis:In patients with PLFLG AS, LV-GLS is associated with adverse clinical outcomes by detecting subclinical myocardial fibrosis resulting from myocardial remodeling due to LV pressure overload.Methods:We examined patients with PLFLG AS defined as AVA