Risultati per: Uso dei test del DNA tumorale circolante per i pazienti con cancro

Circulation, Volume 150, Issue Suppl_1, Page A4143506-A4143506, November 12, 2024. Background:Anatomic burden of coronary artery disease (CAD) has been considered a consistent prognostic marker. Inflammation also increases the cardiovascular risk and plays a significant role in the evolution of atherosclerosis. The progression of CAD impacts the responses to exercise, reducing functional capacity. Despite this knowledge, the specific interplay between inflammation and atherosclerotic burden in influencing submaximal exercise capacity, particularly oxygen uptake (VO2) kinetics, remains underexplored in CAD. This study aims to investigate how these factors correlate with VO2on-kinetics in the Six-minute Walk Test (6MWT) in patients with CAD.METHODS:Patients with obstructive CAD, confirmed by coronary angiography, underwent a 6MWT using a mobile telemetric cardiopulmonary monitoring to assess functional capacity and the VO2on-kinetics through the mean response time corrected by work (wMRT). Inflammatory markers were analyzed by dosage of high-sensitivity C-reactive protein, interferon-gama, tumor necrosis factor alpha and interleukins (IL), IL-6, IL-8 and IL-10. Coronary atherosclerotic burden was evaluated by the Grading Scale for Anatomic Burden of Disease from COURAGE Trial. Correlation analyses were performed according to the symmetric distribution of data, using Pearson’s (r) or Spearman’s rank correlation coefficients(rs).RESULTS:A total of thirty-four patients aged between 60.3±8.0 years were enrolled, presenting body mass index of 26.0±3.7kg/cm2, left ventricular ejection fraction of 0.50±0.14, walking distance of 443±66m, VO2at steady-state (VO2SS) of 896±240ml/min and wMRT of 1.64×10-3± 1.00×10-3min2/ml. Although correlated with distance and VO2SS(r=-0.472;p=0.002 and r=-0.434;p=0.015, respectively), atherosclerotic burden was not associated with wMRT (p=0.17). High-sensitivity C-reactive protein and IL-8 were negatively associated with both distance and VO2SS(rs=-0.428;p=0.001/ rs=-0.543;p=0.001 and rs=-0.438;p=0.014/ rs=-0.407;p=0.019) and positively correlated with wMRT (rs=0.412;p=0.022/ rs=0.505;p=0.003).CONCLUSION:In contrast to anatomic burden, inflammatory markers were associated with both walking intensity and VO2kinetics. Therefore, inflammation may be more crucial to exercise response mechanisms than coronary stenosis, suggesting a paradigm shift in our understanding of clinical repercussions of obstructive CAD. Actions able to attenuate the inflammatory profile may improve exercise capacity and prognosis.

Circulation, Volume 150, Issue Suppl_1, Page A4118724-A4118724, November 12, 2024. Background:The New York Heart Association (NYHA) classification is a subjective tool that is commonly used in clinical practice to assess symptoms and functional capacity of patients with heart failure (HF). Correct assignment of NYHA is essential to facilitate evidence-based management.Research Question:What is the validity of the CLASS-HF Guide compared to the 6-minute walk test (6MWT)?Purpose:To examine the validity of the new investigator-developed CLASS-HF guide to assist in appropriate assignment of NYHA Class relative to the 6MWT.Methods:A multi-site, cross-sectional study in three cardiology clinical sites (two specializing in HF) recruited 103 patients in various classes and stages of HF. Providers assigned patients their NYHA Classification using the CLASS-HF guide. Patients then performed the 6MWT with test staff blinded to the assigned NYHA class. Exertion, dyspnea, and walk distance were captured post-test. The validity of the guide-assisted classification was then examined for convergent validity with 6MWT outcomes. Data analysis was performed with correlations, ANOVA, and multivariable regression.Results:Of the 103 total participants, 65.1% were male, 18.4% were non-White, with an average age of 66.0 ± 15.5 years old. A little less than one-third (30.1%) had HFpEF (LVEF ≥ 50%). Provider-assigned NYHA Class was 22.3% I, 38.8% II, 35.0% III and 3.9% IV. The average distance walked during the 6MWT by class was: 367.1 ± 85.6 m for I, 343.7 ± 104.7 m for II, 261.6 ± 73.9 m for III, and 184.6 ± 114.0 m for IV. Convergent validity of NYHA class with Borg exertion (Spearman’sr= .546,p< .001) and dyspnea (r= .504,p< .001) was strong. A statistically significant inverse correlation was found between NYHA assigned class and meters walked during the 6MWT (r= -.469,p< .001), with significant mean differences (ANOVAF(3,99) = 10.72,p< .001) in distance walked for: NYHA Class I vs. III (md= 105.5 m), I vs. IV (md= 182.6 m), II vs. III (md= 82.1 m), II vs. IV (md= 159.2 m). Increasing NYHA class remained significantly associated with lower 6MWT distance (F(3,90)=5.22,p= .002) in multivariable regression (Adj.R-squared= .575) controlling for age, sex, race/ethnicity, diagnosis, site, Borg exertion and dyspnea, and 6MWT stopping/pausing.Conclusion:Validity evidence was found for NYHA class assignment after use of the CLASS-HF guide with respect to 6MWT distance and post-test perceived exertion and dyspnea.

Circulation, Volume 150, Issue Suppl_1, Page A4117646-A4117646, November 12, 2024. Introduction:The HeartMate 3 (HM3) LVAD, was shown to have a higher survival free of hemocompatibility related adverse events (HRAE) compared to its predecessors (HM2, HVAD). Superior HM3 outcomes are attributed to wide blood flow pathways coupled with frictionless movement and intrinsic pulsatility, reducing shear stress and blood stasis. It is unknown if improved hemocompatibility can withstand pump restart after prolonged shutdown. We herein report a case of HM3 pump stoppage without subsequent HRAE.Case Presentation:A 41-year-old male underwent HVAD implant in 2019 for advanced non-ischemic cardiomyopathy. This was exchanged to HM3 for recurrent neurological events despite therapeutic anticoagulation. Ten months after exchange, he awakened one morning to find his LVAD had been off for an unknown period but had not heard any device alarms (85dB if on battery power, 165dB if on wall power). Since he felt well he changed to battery power resulting in immediate pump restart. Log file analysis showed pump stoppage 2 am – 10 am, without preceding low flow alarms or power elevations.Management and Outcomes:In the ER INR was 1.5 (2.8 one week prior) and systemic heparin was started. Evaluation included: 1) CT brain without acute infarcts 2) echocardiogram without intracardiac thrombus 3) CT Angiography with patency of the inflow cannula and outflow graft 4) stable serial LDH measurements. The controller was exchanged, and analysis noted normal function. 1-year later the patient is maintained on warfarin and aspirin 325mg without further HRAE. Given the patient’s neurologic history and pump stoppage event, we did not invoke ARIES trial guidance and thus continued aspirin.Conclusion:Pump stoppage occurs when there is complete battery depletion, disconnection of both power leads, or the percutaneous lead from system controller. Our case is unique in that the duration of pump shutdown was 8 hours and INR subtherapeutic, without HRAE in the background of neurologic events on HVAD support. It has been previously reported that complete outflow graft thrombosis can occur shortly after LVAD decommissioning. The HM3 User Manual recommends restarting the pump immediately if off for a few minutes and using clinical judgment for longer durations due to increased risk for thromboembolic events. Our case adds to the paucity of existing data on improved hemocompatibility of the HM3 during rare circumstances of the ultimate test in hemocompatibility: complete pump shut down.

Circulation, Volume 150, Issue Suppl_1, Page A4144019-A4144019, November 12, 2024. Introduction:Donor fraction (DF) cell-free DNA (cfDNA) is an emerging tool for non-invasive rejection surveillance in heart transplantation (HTx). Little is known about the significance of DF and/or total cfDNA (TcfDNA) in the first month post HTx. We explored the relationship between early cfDNA results and later clinical events in adult and pediatric HTx recipients.Aims:1. Explore the relationship between early cfDNA levels and late events after HTx 2. Describe the decline in DF during the first month post HTxMethods:Retrospective data from the multicenter prospective blinded DTRT study (DNA-based transplant rejection test) was used. DF and TcfDNA results from samples drawn post HTx day 1 (35d to 1 year post HTx. Captured events include cardiac arrest, mechanical circulatory support or death. Exclusions included absent TcfDNA, multiorgan Tx, any PTLD, or other cancer in previous 2 yrs. Cell-free DNA values were compared across event groups and time windows using GEE (generalized estimating equation) with Max Likelihood Estimation.Results:190 subjects had 566 samples drawn < 35 days post HTx. Median age was 17.8 yrs with a range of 26 days - 73.4 yrs; 51.8% were pediatric. 16 subjects (8.4%) had events bridging or following day 35 post HTx; 23 with events prior to day 35 were included as non-event subjects. TcfDNA was significantly higher in event subjects on days 4, 7 and 28 post HTx. [Fig 1]. There was no difference in DF between event and non-event subjects. Median (IQR) DF at 14 days was 0.26% (0.20, 0.39) and 0.19% (0.13, 0.29) at 28 days.Conclusions:Elevated TcfDNA, even in the setting of normal DF, may be a useful early marker to identify patients at risk for later events in the first year post HTx. The majority of patients reach low DF levels by 28 days post HTx suggesting an opportunity to incorporate cfDNA earlier into rejection surveillance protocols.

Circulation, Volume 150, Issue Suppl_1, Page A4143940-A4143940, November 12, 2024. Introduction:Ischemia/reperfusion (I/R) injury occurs after coronary revascularization, contributing to infarct size. Circulating mitochondrial DNA (mtDNA) levels are elevated in acute myocardial infarction (MI) patients, and act as Damage Associated Molecular Patterns (mtDNA DAMP), which are recognized by the Toll-like receptor 9 (TLR9), initiating pro-inflammatory responses. Prior studies have shown that loss of TLR9 prevents I/R injury in isolated mouse hearts. However, mtDNA DAMP levels have not been measured in ST-elevation MI (STEMI) patients, and whether blocking TLR9 in mice can reduce I/R injury remains unknown.Hypothesis:MtDNA DAMP levels serve as markers of STEMI related cardiac injury. Blocking the activation of TLR9 will decrease cardiac I/R injury.Methods:MtDNA DAMP levels in serum were measured pre- and 24 hours post- PCI in 55 STEMI patients and 37 healthy controls by qPCR. To evaluate the role of TLR9 on I/R injury, ODN2088 was used to block TLR9 receptor, wild type and TLR9 germline KO mice were subjected to close-chest I/R surgery with minimal systemic inflammation. The cardiac systolic function and infarct size were assessed. Immune cells were isolated from the injured left ventricle and spleens and detected by flow cytometry.Results:Pre- PCI mtDNA DAMP levels were increased ~200 folds in STEMI patients compared to healthy controls. After PCI, the elevated mtDNA DAMP levels reduced significantly, while the troponin T levels increased, suggesting mtDNA is an early marker of MI. Compared with negative ODN, ODN2088 treatment at reperfusion reduced infarct size and total leukocytes, myeloid cells, neutrophils and TNF-α+cells, and a trend of reduced IL-1β+cells, and there was no difference in IL-6+cells, total macrophages and residential macrophages. Loss of TLR9 in male and female mice significantly reduced infarct size by ~40% and preserved the systolic function. Meanwhile, there is no difference between genders.Conclusions:Circulating mtDNA DAMP level is an early marker of STEMI and may predict the success of PCI. Blocking the mtDNA DAMP-TLR9 signaling pathway during reperfusion significantly reduces I/R injury, indicating it is a viable therapy to mitigate cardiac I/R injury after prompt coronary revascularization.

Circulation, Volume 150, Issue Suppl_1, Page A4146883-A4146883, November 12, 2024. Introduction:Peripheral arterial disease (PAD) is caused by a lack of blood flow to the musculature relative to its metabolism which results in pain. PAD impacts up to 20% of patients around the world. PAD involves macrovascular and microvascular dysfunction. Near-infrared spectroscopy (NIRS) measures muscle oxygenation levels and assesses microvascular function. The standard of care for diagnosing PAD is the ankle-brachial index (ABI), which assesses macrovascular disease, and the 6-minute walk test (6MWT), which measures gait speed and claudication. NIRS has the potential to monitor progression of PAD.Hypothesis:NIRS measurement of muscle oxygenation, during a standard test of vascular occlusion and post-occlusive hyperemia, the vascular occlusion test (VOT), is predictive of PAD severity as determined by ABI and 6MWT.Methods:We studied 24 patients diagnosed with PAD. The mean age of the patients was 71.3 years, including 54% (n=13) males and 46% (n=11) females. The VOT consisted of rest, occlusion, and reperfusion phases each lasting 5 min (15 min total). Muscle oxygen saturation levels were recorded at 2 hertz. For every patient, 6 features were extracted from the VOT data using computational methods. The VOT features from 15 patients were used to train function-fitting neural network models to predict ABI and 6MWT Continuous Distance. The models were then used to predict ABI and 6MWT Continuous Distance from the VOT features of 9 test patients not used in the training,Results:For patients in the test set, the ABI and 6MWT Continuous Distance predicted by the models differed from the actual measurements by 14%±13% and 15%±17%, respectively (Figure 1). For patients in the training set, the ABI and 6MWT Continuous Distance predicted by the models differed from the actual measurements by 0±0% and 12%±11%, respectively (Figure 1).Conclusion:The VOT has the potential to predict the ABI and 6MWT Continuous Distance of patients diagnosed with PAD, suggesting that the VOT can be automated and used to monitor the severity of PAD. With more data from both healthy patients and PAD patients, and improvement of the model, we anticipate that the VOT will complement ABI and 6MWT in the diagnosis and monitoring of PAD.

Circulation, Volume 150, Issue Suppl_1, Page A4143732-A4143732, November 12, 2024. Background:Variants of mitochondrial DNA (mtDNA) may exist in heteroplasmy and have been associated with increased risk of mortality and cancer. While variation in mtDNA has been associated with cardiomyopathy in mitochondrial disease, the association between mtDNA heteroplasmy and cardiovascular disease (CVD) in the general population has not been well studied.Methods:We quantified mtDNA heteroplasmy from whole genome sequencing data in 476,434 participants in the UK Biobank. We defined a variant allele frequency of 5–95% as heteroplasmic. We functionally characterized mtDNA single nucleotide variants using a constraint-based score, mitochondrial local constraint score sum (MSS). We evaluated the associations of MSS and incident CVD, defined as fatal or non-fatal myocardial infarction (MI) or ischemic stroke (IS), using Cox proportional hazards models adjusted for demographic, lifestyle, and clinical factors in 463,705 participants free of CVD. We further tested the interactions with clonal hematopoiesis of indeterminant potential (CHIP) and leukocyte telomere length (LTL) in the association between heteroplasmy and CVD. We performed additional analysis stratified by MSS for each complex/region in the mtDNA, and subgroup analysis by sex and C-reactive protein (CRP; ≥3mg/L). Lastly, we performed analysis separately for MI and IS.Results:During a median (1stand 3rdquartiles) follow-up of 13.6 (13.1–14.5) years, there were 24,723 incident CVD events (16,959 MI and 9671 IS cases). 28.3% of the study population had 1 or more heteroplasmies. We found that higher MSS was associated with CVD (adjusted hazard ratio [aHR] for a 1-unit increase in MSS 1.08; 95% confidence interval 1.00–1.17). In particular, a higher MSS was associated with MI (aHR 1.13; 1.02–1.24) but not with IS (aHR 1.03; 0.90–1.17). The association between MSS and MI was stronger for fatal MI (aHR 1.52; 1.10–2.10) than for non-fatal MI (aHR 1.10; 0.99–1.21). When stratified by complex/region, higher MSS in Complex I increased the risk of MI by 27% (aHR 1.27; 1.06–1.53) but not in other complexes/regions. Although LTL was inversely associated with CVD outcomes, there were no associations with CHIP. Furthermore, there was no interactions by LTL, CHIP, sex, and CRP in the association between MSS and CVD outcomes.Conclusion:These results indicate that mitochondria may have a functional role in the development of CVD, particularly MI, and MSS may serve as a biomarker for CVD risk.

Circulation, Volume 150, Issue Suppl_1, Page A4140642-A4140642, November 12, 2024. Background:The diagnosis of VVS largely relies on clinical history and simple diagnostic tools (e.g., electrocardiogram) to rule out dangerous differential diagnoses. However, using the head-up tilt test (HUTT) has become controversial among clinicians. This retrospective study aims to evaluate whether the prodromal symptoms experienced during HUTT are consistent with those experienced during spontaneous syncope.Methods:This study utilized data from the HUTT registry at the Syncope Unit of the tertiary Heart Center, focusing on adults aged 18 and older diagnosed with VVS. Diagnoses were based on clinical histories, physical examinations, and the latest syncope guidelines. Out of 1914 patients with HUTT results, 764 patients with positive tests were analyzed for mutual prodromal symptoms during HUTT and spontaneous syncope.Results:The McNemar test revealed significant differences for several symptoms, including palpitation (X2 = 30.59, P < 0.001), nausea (X2 = 16.13, P < 0.001), chest pain (X2 = 24.32, P < 0.001), abdominal discomfort (X2 = 22.33, P < 0.001), flushing (X2 = 10.87, P < 0.001), and aura (X2 = 19.86, P < 0.001), indicating discrepancies in the occurrence of these symptoms. Cohen's Kappa values ranged from 0.06 to 0.32, signifying slight to fair agreement. Specifically, diaphoresis (k = 0.32), palpitation (k = 0.27), and vertigo (k = 0.25) demonstrated fair agreement, whereas nausea, aura, chest pain, abdominal discomfort, and flushing exhibited slight agreement. Among the 640 patients who experienced prodrome during spontaneous syncope, 110 (17.19%) had no symptoms. Conversely, among the 123 patients who did not experience prodrome, 96 (78.05%) experienced at least one symptom during the tilt test (Figure).Conclusion:The assessment of prodromal symptoms during HUTT compared to spontaneous syncope showed significant differences for several symptoms and overall low levels of agreement. Also, tilt cannot differentiate patients with or without prodrome during their spontaneous spells.

Oncologi, disagio psicologico per il 64% portatori di geni Brca

Perrone (Aiom) ,rischio concreto di un ulteriore aumento dei costi a carico dei malati

Il 13 novembre giornata dedicata a salute e prevenzione giovani

Chi ne consuma molti ha rischio ridotto di avere vari tumori

Chi ne consuma molti ha rischio ridotto di avere vari tumori

Colpiti 537 milioni nel mondo e 4 in Italia, tendenza in aumento

Il numero 1 al mondo per l’iniziativa ‘Un ace per la ricerca’

Obiettivo ridurre la spesa privata a carico dei cittadini