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This randomized clinical trial compares the effectiveness of resuscitative endovascular balloon occlusion of the aorta and standard care in the emergency department vs standard care alone on mortality in trauma patients with exsanguinating hemorrhage.
Circulation, Volume 148, Issue Suppl_1, Page A12986-A12986, November 6, 2023. Introduction:Thoracic aortic disease is an important cause of morbidity and mortality in the US, and aortic diameter is a heritable contributor to risk.Question:Could a polygenic prediction of ascending aortic diameter improve detection of aortic aneurysm?Methods:We used deep learning to measure ascending thoracic aortic diameter in 56,556 UK Biobank participants and conducted a genome-wide association study (GWAS) in 39,524. We built a 1.1-million SNP polygenic score usingPRScs. In 4,896 non-GWAS participants (“training set”), we built linear models from clinical variables and the polygenic score (“AORTA Gene”) and simpler comparators. The models were assessed in the remaining 4,962 unrelated UK Biobank participants with imaging (“test set”). The models were externally validated inAll Of Usparticipants over the age of 40.Results:In the test set, the AORTA Gene model explained 39.9% (95% CI 37.8-42.0%) of the variance in thoracic aortic diameter compared to 29.2% for the clinical model (95% CI 27.1-31.4%). For diameter ≥ 4cm, the area under the receiver operating characteristic curve (AUROC) was 0.834 for AORTA Gene, superior to the clinical model (0.765, P=7.3E-10). Thresholding at the top 10% of the score, AORTA Gene had a sensitivity of 52% and a specificity of 91.2% (F1: 0.197) for detecting the 113 participants with diameter ≥ 4. For the clinical score, the respective values were 36.3%, 90.9%, and 0.137.In 610All Of Usparticipants with genetic data and aortic measurements, the AORTA Gene model had a correlation of 0.591 (95% CI 0.537-0.640) with aortic diametervs0.538 (95% CI 0.479-0.592) for the clinical model (P=2.2E-13 against a null hypothesis of the genetics being uninformative beyond clinical factors). It had an AUROC of 0.827 for identifying diameter ≥4cmvs0.791 for the clinical model (P=7.8E-03). AORTA Gene also had a higher AUROC for prevalent thoracic aneurysm diagnoses (0.760vs0.739 for the clinical score, N=1,904 cases, P=2.4E-16) and incident diagnoses (0.748vs0.729, N=1,632 events, P=9.5E-10).Conclusions:Genetic information improved prediction of thoracic aortic diameter and aneurysm when added to clinical risk factors. Larger and more diverse samples will be needed to develop more powerful scores.
Circulation, Volume 148, Issue Suppl_1, Page A18241-A18241, November 6, 2023. Introduction:CoA’s complex hemodynamics may lead to post-repair complications such as pseudoaneurysms. Understanding the effects of beta-blockers, successful in adult heart failure and potentially beneficial for children, is critical. We used a high-resolution image-based CFD model to study these effects on aortic WSS and turbulence in CoA patients.Hypothesis:Beta-blocker therapy may favorably influence hemodynamic turbulence stresses.Methods:Patient-specific CT scans informed 3D CoA aorta models. Large eddy simulations were conducted at neonatal heart rates of 100, 120, and 160 bpm. Aortic segments were divided into front and back regions based on jet flow impact.Results:Despite heart rate-induced turbulence, WSS distributions remained consistent across rates. Lower rates notably decreased maximal systolic WSS distal to the coarctation site but reduced localized WSS and its variability(6.49 +/- 3.29Pa). Both front and back segments showed unique WSS patterns and peak systolic WSS increases with heart rate(0.1Pa per 10BPM & 0.07Pa/ per 10BPM, P >0.05). Significantly higher stress was experienced by the front region(max: 95.2%, min: 70.4%).Conclusions:Heart rate changes impact WSS values, indicating heart rate-lowering drugs like beta-blockers may alleviate hemodynamic stress. Despite overall lower WSS, the front region is more susceptible to shear stress at lower rates. This could guide beta-blocker therapy decisions and identify potential beneficiaries.
Circulation, Volume 148, Issue Suppl_1, Page A14746-A14746, November 6, 2023. Introduction:Left atrial (LA) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) predominates near the aorta(AO); however, LGE does not equate fibrosis and may be artifactual or indicate expanded interstituim.Hypothesis:We sought to examine the association of LA LGE with proximity to the descending and ascending AO and use regional impedance and voltage measurements to dissect the mechanism of LGE .Methods:The retrospective cohort included consecutive patients who underwent pre-procedural CMR and atrial fibrillation (AF) ablation between January 2016 – 2021. The association of voltage amplitude, impedance, and image intensity ratio (IIR) at each electroanatomic map point with distance from the nearest AO point was examined after adjustment for age, sex, AF type, AO stenosis, LA volume, and AO diameter.Results:Included 63 patients (age 65.5±8.8 years, 33% female). Among 42 ablation naive patients, distance from AO was unassociated with bipolar and unipolar voltage amplitudes, but associated with impedance (+0.04 ohm/mm, P=0.011) and IIR (-0.03 /mm, P
Circulation, Volume 148, Issue Suppl_1, Page A11914-A11914, November 6, 2023. Introduction:The relative diagnostic and prognostic performance of left ventricular global longitudinal strain (LVGLS) as compared to LV ejection fraction (LVEF), and the role of LVGLS for detecting early stages of LV systolic dysfunction in adults with repaired coarctation of aorta (COA) is unknown.Objective:The purpose of this study was to address these knowledge gaps.Methods:Retrospective cohort study of adults with repaired COA that underwent transthoracic echocardiogram (2003-2020). LV systolic function was assessed using LVEF (derived from volumetric analysis) and LVGLS (derived from speckle-tracking echocardiography).Results:Of the 795 patients (age 36±14 years), mean LVEF and LVGLS were 62±11%, and 21±4%, respectively. The prevalence of LV systolic dysfunction was higher when assessed using LVGLS as compared to LVEF (20% versus 6%, p
Circulation, Volume 148, Issue Suppl_1, Page A11913-A11913, November 6, 2023. Introduction:Right ventricular (RV) systolic dysfunction and pulmonary hypertension is present in 20% of adults with repaired coarctation of aorta (COA). However, the prognostic value of RV to pulmonary artery (RV-PA) coupling in this population is unknown.Objective:The purpose of this study was to assess the relationship between RV-PA coupling and clinical outcomes (heart failure hospitalization and all-cause mortality) in this population.Methods:Retrospective cohort study of adults with repaired COA and normal RV systolic function defined as RV-free wall strain ≥-24%. RV-PA coupling was assessed using tricuspid annular plane systolic excursion/ RV systolic pressure (TAPSE/RVSP) ratio.Results:Of 509 patients (median age 32 [20-45] years; men 290 [57%]), the average TAPSE and RVSP were 22±5 mm and 33±9 mmHg, respectively, and TAPSE/RVSP ratio was 0.78 (0.56-0.96) mm/mmHg. Of 509 patients, 51 (10%) died and 43 (8%) were hospitalized for heart failure. TAPSE/RVSP was associated with all-cause mortality (hazard ratio 0.82, 95% confidence interval 0.78-0.86, per 0.1 mm/mmHg), and heart failure hospitalization (hazard ratio 0.86, 95% confidence interval 0.79-0.83, per 0.1 mm/mmHg) after adjustment for anatomic lesions, cardiovascular interventions, comorbidities, and echocardiographic indices. The inclusion of TAPSE/RVSP ratio in the risk models improved the prognostic power of the models to predict all-cause mortality (C-statistics difference 0.046, p
Circulation, Volume 148, Issue Suppl_1, Page A18373-A18373, November 6, 2023. Introduction:The serum and glucocorticoid inducible kinase-1 (SGK-1) can contribute to matrix remodeling in murine models of hypertension (HTN) and abdominal aortic aneurysm (AAA), a potential biomechanical link between these aortopathies. Utilizing aortic stiffness as a marker of pathologic remodeling.Hypothesis:We hypothesize that HTN causes an SGK-1 dependent increase in aortic stiffness to amplify AAA growth.Methods:AngiotensinII (AngII) infusion induced HTN in C57Bl/6 mice (WT;1.46mg/kg/day) with subset groups treated + periadventitial CaCl2 to induce AAA and + infusion of the specific SGK-1 inhibitor EMD638683 (2.5mg/kg/day;n=2-4 each). Abdominal aortic ultrasound was conducted on Day 0 and Day 21 to measure stiffness parameters (radial strain(RS), distensibility(D), pulse propagation velocity(PPV)). Aortic diameter (AoD) was obtained by ultrasound and systolic blood pressures (SBP) were measured by Coda tail cuff.Results:This HTN model has consistently resulted in >30% increase in SBP and AAA induction did not effect SBP. Although the WT+AngII+AAA mice had 66+8% increase in AoD, dilation was not amplified beyond that of the WT+AAA mice (72+7%, p=NS). Treatment with EMD had no impact on SBP, but did significantly reduce AAA growth (WT+AAA+EMD=29+5%; WT+AngII+AAA+EMD= 24+3%), therefore despite ongoing mechanical tension, SGK-1 inhibition abrogated a pathway necessary for degenerative remodeling. Accordingly, aortic stiffness was differentially altered in HTN versus AAA. As indictors of increased stiffness, D decreased with HTN (p
Circulation, Volume 148, Issue Suppl_1, Page A16628-A16628, November 6, 2023. Introduction:Ascending aortic diameter (AAoD) is commonly monitored to manage patients at risk of aortic dissection. Z-scores have also been proposed to identify at risk aortas, adjusting AAo for age, gender, and body surface area (BSA). Despite improved imaging and proven association of AAoD with age, sex and BSA, cutoff remains at 4.5 cm for monitoring and 5.5 cm for surgery in guidelines. However, studies like International Registry of Acute Aortic Dissection found that most aortic dissection had AAoD4.5 cm and compared them with Z >2 cutoff value that might require imaging follow-up for managing their dilated aortas.Results:AAoD diameter was calculated for 44,799 participants (22,983 females and 21,816 males). Common demographics in both groups are listed in the Table. Average AAoD was 3.15±0.32 cm in females and 3.44±0.35 cm in males. Diameter cutoff of 4.5 cm identified 15 females and 110 males with dilated aortas. On the other hand, Z-HAS classified 862 females and 674 males, while Z-BAS classified 583 females and 405 males (orange dots in the top and bottom panels of Figure, respectively) with higher aortic diameter that might require regular follow-up imaging.Conclusion:Z-Score might identify more people at dilated aortas as compared to the hard cutoff. Future work is needed to define whether Z scores are more sensitive means of identifying patients who might be at increased risk of aortic dissection.
Circulation, Volume 148, Issue Suppl_1, Page A15340-A15340, November 6, 2023. Atherosclerosis is a complex process characterized by chronic systemic inflammation, endothelial dysfunction, retention of lipoproteins, plaque formation in large and medium-sized arteries, and has become one of the most common causes of death in the elderly nowadays. Octacosanol, a very long chain (C28) aliphatic alcohol, is believed to be the main active ingredient in the Policosanol, which is extracted from plants, such as sugar cane and wheat germ. Policosanol has been used as a potential diet supplementary to improve fatigue, obesity and lipid metabolism. Previous animal studies have shown that both Policosanol and Octacosanol can significantly ameliorate formation of atherosclerotic lesion. To further explore the possible mechanism of Octacosanol on the formation of atherosclerosis, we examined the anti-inflammatory effects of Octacosanol on HAEC treated with LPS at 100ng/ml FBS-free cell culture medium. LPS treatment significantly enhanced human monocyte (THP1) adherence to HAEC cells in time-dependent and dose-dependent style, but Octacosanol at 1.25 or 2.5 μM markedly blocked the adhesion of THP1 to HAEC. ELISA showed that LPS can significantly increase the expression of inflammatory cytokines and adhesion molecules by HAEC at 100ng/ml within 4 hours. LPS stimulated more than 3-fold of release of IL-6, IL-8, MCP-1 at 4 hours. By flow cytometry and ELISA, LPS dramatically increase the expression of PE-Selectin and VCAM-1. When HAEC were pretreated with Octacosanol (1.25μM or 2.5μM), it significantly reduced the release of inflammatory cytokines, MCP-1(p
Circulation, Volume 148, Issue Suppl_1, Page A13729-A13729, November 6, 2023. Introduction:Upper extremity atherosclerosis is typically localized in the subclavian arteries, although it is less prevalent and less often symptomatic than in the lower extremities. Subclavian artery calcification (SAC) is a metabolic consequence of subclavian artery atherosclerosis.Hypothesis:SAC is different in gender and in different ethnicties.Aim:We studied SAC, in comparison with coronary artery calcification (CAC) and descending thoracic aorta calcification (TAC) in the MESA study population.Methods:We quantified SAC, TAC, and CAC in MESA participants who had a chest CT in 2016-18 (N = 2756, mean age 68.3±9.2 years, 48% male, 27% Black, 13% Chinese, 22% Hispanic, 38% White). We characterized the distributions of SAC and TAC, relative to CAC, and examined their associations with age, race/ethnicity, and sex. Race and sex differences were studied separately using logistic regression, adjusted for age, for each vascular bed.Results:Prevalence of any SAC was 62%, TAC 60%, and CAC 69%. Among those with any calcification, N, median and 90th percentiles were SAC: 1704, 76, 534; TAC: 1655, 152, 2011; CAC 1896, 135, 1118. Pairwise correlations [ln(Agatston score + 1)] were SAC – TAC: 0.61, SAC – CAC: 0.48, TAC – CAC: 0.48. Correlations with age were 0.46 for SAC, 0.58 for TAC and 0.40 for CAC. SAC and TAC prevalences were similar for males and females, but CAC was more common in males (Table, p
Circulation, Volume 148, Issue Suppl_1, Page A375-A375, November 6, 2023. Background:Recently, the resuscitative endovascular balloon occlusion of the aorta (REBOA) has become widespread in hemorrhagic shock (HS). It temporarily increases the proximal blood pressure (pBP); but sacrifices the distal blood flow to the visceral organs, causing ischemic injury. We previously reported that hydrogen (H2) gas inhalation mitigated ischemic injury and improved survival in rats with HS; however, during REBOA use, the H2gas was not delivered to the ischemic organs as it is distributed via the bloodstream. Therefore, we hypothesized that intra-aortic irrigation of H2-containing solution into the downstream of REBOA would mitigate ischemic injury.Methods:Herein, a swine liver injury with volume-regulated HS model was used. The female swine (around 40 kg, n = 16) were divided into two groups; a H2-containing solution irrigation (H2group) and saline irrigation (C group). After HS induction (20% of estimated total blood volume), the liver injury was initiated (20% of total liver volume). The REBOA was inflated during predefined time (60 min and 90 min) and intra-aortic irrigation to downstream of REBOA was started. The hemodynamic parameters, blood samples, and pathological changes were evaluated.Results:The elevation in lactate, interleukin 6, and syndecan levels were significantly suppressed over time in the H2group than in C group (p < 0.05). The pBP tended to decrease during REBOA in the C group; however, it remained higher in H2group (p < 0.05). Pathologically, the ischemic changes, such as liver sinusoidal enlargement and intestinal villi flattening and inflammatory infiltration were identified in the C group but not in H2group.Conclusion:The REBOA with downstream intra-aortic irrigation using H2-containing solution for liver injury with HS stabilizes hemodynamics, suppresses cellular injury, and mitigates organ damages. These results in large animals can be immediately applied to clinical use in humans.
Circulation, Volume 148, Issue Suppl_1, Page A200-A200, November 6, 2023. Background:The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) for hemorrhagic shock (HS) has grown in popularity. However, REBOA has a risk of complications related to blocking the blood flow downstream to the visceral organs. Several drugs have been reported so far to mitigate ischemia, including hydrogen gas (H2); however, they could not reach the downstream of REBOA as they are distributed through the bloodstream. This study aimed to develop a system to deliver drugs to the ischemic organs where REBOA blocks the bloodstream.Methods:Herein, a female 40-kg swine volume-regulated HS model was used. In addition to the REBOA in zone 1, a catheter was inserted for drug delivery retrograde into the right femoral artery. The top tip of the catheter was positioned distal to the REBOA balloon. After HS induction (20% of the total blood volume), drug delivery capability was evaluated in three REBOA use patterns, such as controlled HS in normal time of full inflation , uncontrolled HS with liver injury in extended time of full inflation, and partial inflation. Simultaneously with the REBOA inflation, the intra-aortic irrigation of a drug-containing solution, H2-dissolved saline, was initiated.Results:The occlusion by the REBOA was achieved in all cases after shock induction (approximately 40 mmHg). In all patterns, the concentration of H2in the portal vein, which represents the concentration of outflow from the intestine and inflow to the liver, increased immediately after the irrigation. A full inflation setting required 30 mL/min of irrigation speed to obtain the minimum effective concentration of H2(1%), whereas a partial inflation setting required 2 mL/min.Conclusion:A drug delivery system combined with the REBOA was developed, which enabled the drugs to be administered downstream of REBOA. The newly developed system can potentially overcome the major limitations of REBOA.
Giudice (Ospedale San Giovanni): “E’ fatale senza l’intervento”
Autore/Fonte: Techniques and Innovations in Gastrointestinal Endoscopy
La nuova variante EG.5 diventerà dominante ma non evade il sistema immunitario
Indicato anche il controllo nelle acque e fra gli animali
