Risultati per: Sindromi coronariche acute

Circulation, Volume 146, Issue Suppl_1, Page A15880-A15880, November 8, 2022. Acute pulmonary embolism classically presents with dyspnea, tachypnea, and hypoxia, but self-recognition of symptoms and clinical findings is often challenging. This is particularly true in elder patients or those with cognitive impairments. Digital health technologies offer opportunities to remotely detect pre-symptomatic illness. We present a prodrome of an acute pulmonary embolism as it emerges in the home during continuous respiratory monitoring using a non-contact adherence-independent home bed sensor. The patient is an 85-year-old woman who is morbidly obese, has limited mobility, and multiple comorbidities including a recent diagnosis of atrial fibrillation for which she was prescribed anticoagulation but has not yet initiated. As part of an observational study, nocturnal respiratory rates (NRR) were longitudinally monitored in her home bed using a non-contact, adherence-independent bed sensor. Eight days prior to admission, increasing NRR prompted a patient call to family who noted no acute symptomatic changes. During the call it was discovered she had not been started on apixaban. On subsequent days, persistently elevated NRR prompted a second phone call 4 days prior to admission (PTA), where again no acute symptoms were noted. Anticoagulation still had not been started at that time. NRR worsened further on days following the second call prompting a home visit by an RN who found the patient dyspneic, tachypneic in the high 20s, and hypoxic with oxygen saturations in the 80s, prompting a transfer to the emergency department for further evaluation. She was eventually diagnosed with an acute pulmonary embolism. After a week-long hospitalization, the patient was discharged on adequate anticoagulation therapy.This case suggests that adherence-independent home bed monitoring of nocturnal respiratory rate may enable early detection of chronic volume overload and acute pulmonary embolism, potentially facilitating early intervention.

Circulation, Volume 146, Issue Suppl_1, Page A15758-A15758, November 8, 2022. Background:Socioeconomic, racial, and regional disparities have been associated with worse clinical outcomes among patients with coronary disease. We evaluated the association of income, race, and geographic variation and in-hospital mortality among acute myocardial infarction (AMI) admissions in the United States.Methods:We conducted a retrospective cohort study using the Nationwide Inpatient Sample from 2015 to 2019. A multi-level logistic regression model was used (with sampling weights) to investigate the association between in-hospital mortality and income quartiles by patient’s ZIP code, race, and hospital regions, while adjusting for hospital clustering, lifestyle factors, clinical history, and hospital-level factors.Results:A total of 2,798,225 hospitalizations (≥18 years) with a principal diagnosis of AMI were identified. In multivariable analysis, compared with the highest income quartile, residents in the lowest income quartile (OR=1.10 [1.08–1.13]P

Circulation, Volume 146, Issue Suppl_1, Page A12075-A12075, November 8, 2022. Introduction:Acute decompensation is associated with increased long-term mortality in patients with heart failure (HF). Biomarkers of acute HF that are dynamic during decongestion may provide physiologic insight for this observation. We hypothesized that long-noncoding RNAs (lncRNAs) and mRNAs in extracellular vesicles (EVs) not only mark different types of HF, but also may be dynamically altered with decongestion across physiologically important pathways.Methods:RNA sequencing was performed on plasma-derived EVs in acute HF patients (7 HFpEF; 7 HFrEF) at hospital admission (V1) and at discharge (V2) along with 9 controls without HF. Differential expression analysis was performed using DESeq2 across groups and time-points. Transcripts were prioritized by fold change (±1.5) and statistical significance (

Circulation, Volume 146, Issue Suppl_1, Page A10170-A10170, November 8, 2022. Introduction:Previous studies have compared Impella to intra-aortic balloon pump (IABP) in patients with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI) but did not include a cohort of patients receiving vasopressors alone. We assessed the hypothesis that there would be a difference in clinical outcomes in patients with AMI-CS undergoing PCI who received Impella alone, IABP alone, and vasopressor therapy without MCS.Methods:We queried the National Inpatient Sample inclusive of 2015 to 2018 and created three propensity-matched cohorts (Impella alone vs IABP alone, Impella alone vs vasopressors without MCS, and IABP alone vs vasopressors without MCS). We performed propensity matching by adjusting for 21 clinical variables including age, comorbidities, and presence of lactic acidosis. Patients receiving both MCS and vasopressors were excluded, in order to best isolate the effect of each intervention.Results:Among 17,762 hospitalized patients with AMI-CS undergoing PCI, Impella use was associated with significantly higher in-hospital mortality (40.6% vs 27.4%; p=0.003), major bleeding (29.3% vs 13.5%; p < 0.001), acute kidney injury (56.4% vs 45.9%; p=0.04), and hospital charges compared to IABP use (p

Circulation, Volume 146, Issue Suppl_1, Page A15830-A15830, November 8, 2022. Introduction:Obesity is approaching epidemic status in the United States and is strongly associated with a higher risk of heart failure after myocardial infarction (MI), a major cause of morbidity and mortality in obese individuals. However, the mechanisms underlying obesity-associated heart failure are poorly understood. Lysophosphatidic acid (LPA), produced by autotaxin (ATX), is highly expressed in adipose tissue with increased levels in obesity and has been shown to mediate post-MI inflammation.Methods:3-week aged male C57BL/6J mice were randomly assigned to low-fat (LFD-10%) or high-fat (HFD-60%) diet based on the percentage of calories from fat. HFD-fed mice were randomly assigned to receive the specific ATX inhibitor, PF-8380 at 10 mg/kg twice daily. 2 months after initiating the diet, mice were randomized to undergo MI surgery (permanent ligation of the left anterior descending artery) or sham surgery.Results:MI was associated with an increased number of circulating inflammatory monocytes (CD45+/Ly6C+/CD115+), as well as cardiac total and pro-inflammatory macrophages (CD45+/F4-80+/CD11b+/CD86+), as assessed by flow cytometry (Fig. 1A). This effect was exacerbated in HFD-fed mice but significantly attenuated in HFD+PF8380 treated mice with effective ATX inhibition. Changes in circulating and cardiac immune cells were reflective of increased proliferation of bone marrow progenitors, a phenomenon that was blunted by ATX inhibition (Fig. 1B). Moreover, HFD was associated with larger scar size (Fig. 1C) and worse cardiac functional recovery (Fig. 1D) 30 days after MI. The obesity-asscoiated heart failure could be rescued by ATX inhibition.Conclusion:ATX/LPA plays an important role in modulating inflammation and could be a therapeutic target for obesity-related coronary heart diseases.

Circulation, Volume 146, Issue Suppl_1, Page A12760-A12760, November 8, 2022. Introduction:Post-acute sequelae of COVID-19 (PASC) is a novel clinical syndrome. We have previously reported that PASC patients can develop postural orthostatic tachycardia syndrome (POTS) and that COVID-19 induce microvascular endothelial dysfunction in acutely ill, hospitalized patients, that persist up to four months post discharge. Whether microvascular endothelial dysfunction contributes to POTS pathophysiology in PASC remains unclear.Hypothesis:Patients with PACS combined with POTS have impaired microvascular endothelial function.Methods:PASC patients (n=44) with mild SARS-CoV-2 infection (not hospitalized) were recruited from the post-COVID multidisciplinary clinic at Karolinska University Hospital. PASC diagnosis was based on the WHO PASC criteria. POTS was diagnosed in 21 patients (PASC + POTS) while 23 had a negative head-up tilt test (PASC – POTS). Age- and gender-matched healthy subjects (n=15) served as controls. Microvascular endothelial function was quantified as reactive hyperemia index (RHI) determined from the changes in pulse amplitude tonometry before and after a 5 min episode of arterial occlusion. Stress-perfusion cardiac magnetic resonance imaging (cMRI) with adenosine was performed in a subset of patients.Results:Mean age was 42±11 years and 95 % were women among PACS patients. Time from COVID-19 symptom onset to study inclusion was 18±3 months. RHI was significantly lower in PASC + POTS than in healthy controls and PASC – POTS (Figure 1). The prevalence of cardiac microvascular dysfunction on cMRI did not differ between the PASC groups (8% in PASC + POTS vs. 13% in PASC – POTS, p=1.00). All subjects with microvascular dysfunction on cMRI except one had a RHI below the cutoff (1.67) indicating microvascular dysfunction.Conclusions:Microvascular endothelial dysfunction is common in patients with PACS-associated POTS and may cause stress-induced myocardial ischemia up to 18 months after a mild primary infection.

Circulation, Volume 146, Issue Suppl_1, Page A10172-A10172, November 8, 2022. Introduction:Acute kidney injury (AKI) is a serious complication after cardiovascular surgery requiring circulatory arrest and hypothermia has been used for organ protection. We recently reported that mice can be induced into a hibernation-like hypometabolic state by the stimulation of a specific neuron producing pyroglutamylated RFamide peptide (QRFP) located at hypothalamus (Q neurons-induced hypometabolism; QIH). Here, we investigated the efficacy of QIH for the amelioration of AKI in an experimental circulatory arrest under normal and reduced body temperature using a transgenic mouse model in which QIH can be induced.Methods:We genetically prepared mice in which Q neurons specifically express iCre, a Cre recombinase (QrfpiCremice), from male C57/B6J mice. To prepare QIH-ready mice, we intracranially injected AAV8-hSyn-DIO-hM3-mCherry targeting hypothalamus for specific expression of hM3Dq in which QIH can be induced by intraperitoneal injection (i.p.) of clozapine-N-oxide (CNO), an agonist of hM3Dq. For the control, we injected AAV8-hSyn-DIO-mCherry. Mice were divided into 4 groups (n=6 for each): QIH-ready; normothermia (QN), QIH-ready; hypothermia (QH), control; normothermia (CN), and control; hypothermia (CH). At 3 hours after CNO i.p., left thoracotomy and 15-minutes descending aorta cross-clamping were conducted. After re-perfusion, we collected kidneys and evaluated histological changes and serum biochemical markers, neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C indicating early kidney injury.Results:Normothermia showed higher tubular injury scores than those in hypothermia (QN vs QH: p=0.0021, CN vs CH: p

Circulation, Volume 146, Issue Suppl_1, Page A11310-A11310, November 8, 2022. Introduction:The aim of this study was to evaluate malperfusion in patients presenting with acute type A dissection (ATAD) and correlate with mortality based on organ system involved.Methods:A registry of all patients who underwent ATAD repair at our tertiary referral center between 2002 and 2018 was retrospectively queried. Patients with type B aortic dissection and chronic type A aortic dissections (time from presentation > 14 days) were excluded. Malperfusion syndromes at presentation including central nervous system (brain and spinal cord), visceral renal, and lower extremity (LE) were documented. Preoperative and intraoperative variables were analyzed, and post-operative outcomes were correlated with the malperfused organ system.Results:From 2002 to 2018, 378 patients underwent ATAD repair at our tertiary referral center. The average age was 57 years, 68% were male, and 51% were white. Approximately 70% of the cohort were transferred from an outside hospital. A total of 124 patients (33%) presented with malperfusion of at least one organ: 16% (N=62) LE, 8% (N=31) brain, 8% (N=30) renal, 3% (N=11) with visceral malperfusion, and 2% (N=8) with spinal cord malperfusion. On multivariate analysis, 30-day mortality was significantly increased in patients presenting with visceral ischemia (OR=3.7, P=0.04). The average follow-up was 2.3 years. Kaplan Meier survival curves showed a significant decrease in long term survival in patients presenting with brain (P=0.01), visceral (P=0.002), and renal ischemia (P

Circulation, Volume 146, Issue Suppl_1, Page A15810-A15810, November 8, 2022. Establishment of mechanical thrombectomy as the standard of care provides a unique opportunity to refine stroke subtype mechanism by studying thrombus retrieved from stroke patients. Using traditional pathologic methods, researchers have described the form and structure of cerebral thrombi. These methods do not spatially resolve tissues and cell populations with functional segmentation. We applied next generation genomic tools to determine the spatially resolved transcriptome within cerebral thrombus.Methods:Cerebral thrombus was retrieved under sterile conditions. Tissue was formalin-fixed and paraffin embedded in standard fashion. Using the GeoMx Digital Spatial Profiling platform, morphology marker antibodies and WTA RNA probes coupled to photocleavable oligonucleotide tags were applied to the slide. After hybridization of the probes to tissue sections, 24 regions of interest (ROIs) were selected, and oligonucleotide tags were released from the discrete regions of the tissue via UV exposure. Released tags were quantitated using next generation sequencing and counts were mapped back to tissue location, yielding a spatially-resolved digital profile of analyte abundance.Results:Sequencing quality was inspected for sufficient saturation and data normalized to the third quartile to account for differences in cellularity. 18,676 genes were assayed across the 24 ROI. Of these, 4,590 genes were expressed in 10% of ROI and 1,127 genes were expressed in 50% of ROI.Conclusion:Significant transcriptional activity is seen within cerebral thrombus and preliminary analysis shows feasibility for a novel application of spatial transcriptomics. Further evaluation of expressed genes provides information about the microenvironment of thrombus origin and mechanistic insight to stroke subtype etiology.Figure.Number of genes detected across increasing % of ROIs.

Circulation, Volume 146, Issue Suppl_1, Page A10933-A10933, November 8, 2022. Introduction:Feasibility of automated volume-derived cardiac functional evaluation has successfully been demonstrated using cardiovascular magnetic resonance (CMR) imaging. Notwithstanding, strain assessment has proven incremental value for cardiovascular risk stratification. Since introduction of deformation imaging to clinical practice has been complicated by time-consuming post-processing, we sought to investigate automation respectively.Methods:CMR data (n=1095 patients) from two prospectively recruited acute myocardial infarction (AMI) populations with ST-elevation (STEMI) (AIDA STEMI n=759) and non-STEMI (TATORT-NSTEMI n=336) were analysed fully automated and manually on conventional cine sequences. LV function assessment included global longitudinal, circumferential, and radial strains (GLS/GCS/GRS). Agreements were assessed between automated and manual strain assessments. The former were assessed for major adverse cardiac event (MACE) prediction within 12 months following AMI.Results:Manual and automated derived GLS showed the best and excellent agreement with an intraclass correlation coefficient (ICC) of 0.81. Agreement was good for GCS and poor for GRS. Amongst automated analyses, GLS (HR 1.12, 95% CI 1.08-1.16, p

Circulation, Volume 146, Issue Suppl_1, Page A12855-A12855, November 8, 2022. Introduction:Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. NAFLD patients have an increased risk of cardiovascular disease. Matrin-3 is a DNA- and RNA-binding protein, and its mutation causes amyotrophic lateral sclerosis in humans. Among these patients, 76% have hepatic steatosis. However, the role of matrin-3 in NAFLD has not been previously studied.Methods and Results:We found that matrin-3 expression is induced in fatty livers of humans and mice. Matrin-3 liver specific knockout mice (LKO) displayed increased levels of plasma triglycerides compared with matrin-3 floxed mice, while the body weights of the two groups of mice are similar after 16-week high-fat diet. Moreover, histological staining and triglyceride assay revealed that LKO mice had a 1.57- and 1.58-fold increase in hepatic lipid area and triglyceride levels, respectively, which associate with an increased liver/body weight ratio. Transcriptome and bioinformatics analysis identified 622 differentially expressed genes in LKO livers. Among them, 142 are target genes of constitutive androstane receptor (CAR), a transcription factor controlling the expression of many genes involved in xenobiotic and lipid metabolism. We also found that the expression of CAR and many CAR target genes was reduced in LKO livers. These data suggest that matrin-3 is important in CAR expression and matrin-3 knockout impairs CAR signaling. Interestingly, matrin-3 LKO mice had increased acute phase response and levels of phosphorylated Stat3 in the livers, indicating increased liver injury and inflammation. Mechanistically, impaired CAR signaling reversed the suppression of Plin2, Plin3, and Plin5 proteins that stabilize lipid droplet and inhibit lipolysis, and it reversed the suppression of interleukin 1 receptor type 1 that activates Stat3 signaling in LKO livers. Lastly, CAR expression positively correlates with matrin-3 expression in human livers (r=0.85,P=0.0002, n=13).Conclusion:matrin-3-CAR axis is an important mechanism to maintain lipid homeostasis and limit acute phase response in fatty livers. It can be potentially targeted to ameliorate hepatic steatosis and inflammation and reduce the risk of cardiovascular disease in NAFLD patients.

Circulation, Volume 146, Issue Suppl_1, Page A12001-A12001, November 8, 2022. BACKGROUND:Acute pericarditis is the most common disorder affecting the pericardium. It accounts for less than 1% of patients who are admitted to the hospital for non-ischemic chest pain and 5% who present to the emergency department with non-ischemic chest pain. The most common etiology of acute pericarditis in developed countries is idiopathic although a pre-disposing viral illness has also been recognized as a common cause. Infectious etiologies in developed countries have been seen with commonly occurring viruses such as coxsackievirus, echovirus, adenovirus and less frequently EBV.CASE:We present a 41-year-old man who came in with fevers, rigors, shortness of breath and chest pain. Transthoracic echocardiogram was (TTE) demonstrated a large pericardial effusion without evidence of tamponade. He underwent a diagnostic pericardiocentesis followed by a pericardial window during his initial hospitalization without any complications and was discharged home on NSAIDs and colchicine. Serology results demonstrated positive EBV IgG and Nuclear Antigen, concerning for active EBV pericarditis. Pathology resulted as necrotizing pericardial tissue with diffuse inflammation. The patient was readmitted within 48 hours with worsening shortness of breath and leg edema. Repeat TTE revealed a large recurrent pericardial effusion with right ventricular collapse concerning for tamponade. The patient was ultimately transferred to a tertiary care center for pericardiectomy evaluation.DISCUSSION:Ebstein-Barr virus is rarely an etiology of acute pericarditis, much less necrotizing pericarditis. When identified it should raise concern for long term complications such as recurrent pericarditis and tamponade. We believe patients who have evidence of necrotizing pericarditis are at a high risk for constrictive pericarditis and should not only have closer follow while maintaining a low clinical threshold for definitive treatment with pericardiectomy.

Circulation, Volume 146, Issue Suppl_1, Page A13194-A13194, November 8, 2022. SARS-CoV2 (CoV2) infection causes both acute and long-term health effects via damaging multiple organs including lung. The endothelial dysfunction associated with the infection may contribute to pathogenesis of acute COVID-19 and long COVID. However, the mechanisms underlying the endothelial dysfunction remain elusive. Development of mouse models for these diseases will help us better dissect these mechanisms and facilitate the development of therapeutics for treatment of the disease. Previously, we developed an acute COVID model by infecting human ACE2 transgenic (K18) mice with a lethal CoV2 dose. K18 mice developed severe COVID-19, including progressive body weight loss and fatality at days 7 post infection (DPI), severe lung interstitial inflammation, edema, hemorrhage, perivascular inflammation, systemic lymphocytopenia, and eosinopenia. We detected CoV2 in capillary endothelial cells, activation and adhesion of platelets and immune cells to the vascular wall of the alveolar septa, and increased complement deposition in the lungs in this model. These results indicate that CoV2 infection and infection-mediated immune activation caused endothelial dysfunction, which contributes to the pathogenesis of severe COVID-19. To further develop a model for long COVID, we infected K18 mice with sub lethal CoV2 dose, monitored the body weight and survival rate and characterized the lung and brain histological changes at 21 and 45 DPI. The infected mice progressively lost body weights from 5 to 7 DPI and started to rebound from 8 DPI and then returned to baseline at 13 DPI. Mice had extensive patchy inflammation in the lungs associated with collagen deposition and smooth muscle action expression. We also found moderate levels of total viral RNA in the lung but not brain while viral subgenomic RNA (a correlate of viral replication) was undetectable in lung or brain by qRT-PCR assay. Fluorescence staining showed co-localization of CoV2 spike protein and CD206 in lungs, suggesting macrophage engulfment CoV2 at late time points. Together, we have successfully established long-term COVID mouse models, which will be useful tools for further defining the role of endothelial dysfunction in pathogeneses of CoV2-related acute and long COVID.

Circulation, Volume 146, Issue Suppl_1, Page A13993-A13993, November 8, 2022. Introduction:Women have a higher incidence of heart failure (HF) hospitalizations than men following acute myocardial infarction (AMI). The extent to which differential cardiac remodeling between men and women might account for this higher risk in women is poorly understood.Hypothesis:Women and men have differences in cardiac remodeling after AMI that are predictive of clinical outcomes.Methods:The Prospective ARNI versus ACE inhibitor trial to Determine Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial randomized patients within 0.5 to 7 days of AMI complicated by left ventricular (LV) dysfunction, pulmonary congestion, or both to sacubitril/valsartan or ramipril. In the pre-specified echocardiographic sub-study, 544 participants were enrolled to undergo protocol echocardiography at the time of randomization and after 8 months.Results:At baseline, women (n=142, 26%) were older, more likely to have a history of hypertension, and less likely to have a history of MI. Women had a higher LV ejection fraction (LVEF), lower LV end-diastolic index (LVEDVi) and end-systolic volume index (LVESVi), and LV mass index, but no difference in left atrium (LA) volume index compared with men (Table). Women had better diastolic function compared with men. The absolute and relative changes in these echocardiographic parameters from baseline to 8 months were not significantly different between women and men. In univariate analyses, baseline LVEF, LVEDVi, LVESVi, LA dimensions and diastolic measurements are associated with primary outcome (Table).Conclusion:In PARADISE-MI, women have higher LVEF and lower indexed LV and LA chamber sizes compared to men following high-risk MI. The changes between baseline and 8-month in LVEF, LV and LA dimensions did not differ significantly between men and women, suggesting that differential cardiac remodeling post-MI may not account for the increased HF risk in women compared with men.

Circulation, Volume 146, Issue Suppl_1, Page A13239-A13239, November 8, 2022. Introduction:The variation in medical cost by risk stratification using history, electrocardiogram, age, risk factors and troponin (HEART), after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS), is not well understood.Hypothesis:We hypothesized that annual total all cause cost will increase significantly with increasing HEART score and the primary driver of the total cost will be cardiovascular disease (CVD) related care.Methods:This was a retrospective cohort study of adults (age ≥18) with chest pain and complete data for HEART score, presenting at EDs within the Kaiser Permanente Southern California health system from 1/2016-12/2018. We analyzed direct medical cost associated with medical office visits, hospital facility and ED visits, pharmacy utilization, hospice stays, skilled nursing stays, home health, dialysis, laboratory, and radiology utilization during the 1-year following the index ED visit. Stratified by HEART score categories, we used one part and two part generalized linear models (log link & gamma family distribution) adjusted for socio-demographics, cardiovascular disease (CVD) history and treatment and non-CVD comorbidities, to estimate average adjusted total all cause expenditure as well as subgroups of utilization.Results:The cohort included 33,990 patients (60% Low risk; 37% intermediate risk and 3% high risk). The adjusted annual total cost varied from $6,544 (95% CI $6,228 to $6,860) in the low risk to $21,210 ($19,458 to $22,962) in the high-risk group (Table 1). In each group, the primary driver of total cost was CVD related care accounting for 41% to 46% of total cost. CVD care provided in a hospital setting accounted for 44%-76% of CVD total cost.Conclusions:Increased follow-up medical office visits, improved medications and lifestyle management may reduce the near exponential increase in cost driven by catastrophic hospital utilization, in higher HEART risk stratified patients.

Circulation, Volume 146, Issue Suppl_1, Page A15868-A15868, November 8, 2022. Introduction:In the US, there are approximately 84 million cases of COVID-19 accounting for 1 million deaths. Though there are not many studies, acute myocardial infarction (AMI) is one of the most lethal complications of COVID-19. In this study, we looked for occurrence of AMI and its effects on hospital outcomes among COVID-19 patients.Hypothesis:AMI among COVID-19 hospitalizations could worsen the levels of adverse in-hospital outcomes.Methods:Data from the 2020 California State Inpatient Database was used retrospectively. All COVID-19 hospitalizations with age ≥18 years were included in the analyses. Adverse hospital outcomes included in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and ICU admission. Prolonged length of stay included any hospital length of stay ≥75th percentile. We explored for differences in adverse hospital outcomes between those with and without AMI. Multivariate logistic regression analyses were used to understand the strength of these associations after adjusting for cofactors.Results:Our analysis had a total of 94,114 COVID-19 hospitalizations and 1548 (1.6%) had AMI. Adverse hospital outcomes such as mortality (43.2% versus 10.8%, P