Circulation, Volume 146, Issue Suppl_1, Page A14479-A14479, November 8, 2022. Introduction:Reducing mitochondrial ROS (mito-ROS) has been a novel approach for improving cardiac function. Here, we evaluated the effect of prolonged decrease in EC-specific mito-ROS on post-acute myocardial infarction (AMI) coronary angiogenesis and cardiac function.Hypothesis:We hypothesized that a prolonged decrease in EC-specific mito-ROS contributes to mitochondrial dysfunction in coronary EC resulting in post-AMI maladaptive cardiac remodeling.Methods:We used an EC-specific, tetracycline-controlled, transgenic MnSOD overexpression (MnSOD-OE) model. After 16 weeks of MnSOD-OE, mice underwent ligation of left anterior coronary artery (AMI). 28 days post-AMI, ejection fraction (EF), fractional shortening (FS), and left ventricle (LV) mass were determined by echocardiography (n=8/group). Isolated mouse heart ECs (MHEC) were evaluated by Seahorse for mitochondrial function and by western blot for cell signaling. Data were analyzed by Student’s t test. Ap-value ≤0.05 was considered statistically significant.Results:MnSOD-OE mice showed 33% decrease (44.4±2.3 vs. 29.7±3.5) in EF and 35% decrease (21.7±1.2 vs. 14.2±1.7) in FS, compared to control. LV mass was increased by 51% (76.4±1.8 vs. 115.1±12.33 mg) in MnSOD-OE heart. LV end systolic and diastolic areas were increased in MnSOD-OE, by 2-fold (5.8±0.4 vs. 12.6±1.8) and 1.7-fold (9.8±0.5 vs. 16.8±1.6 mm2), respectively. MnSOD-OE MHEC showed a reduction in mitochondrial maximal and spare respiration capacities, and decreased activation of Akt by 25% and ERK by 23%.Conclusions:Prolonged MnSOD-OE impaired mitochondrial respiration and inhibited Akt and ERK signaling in MHEC. These changes were associated with maladaptive remodeling post-AMI, including cardiac hypertrophy, LV dilatation, and systolic dysfunction. Together, these findings suggest that prolonged decrease in mito-ROS has detrimental effects on coronary EC resulting in maladaptive post-AMI cardiac remodeling.
Risultati per: Linee Guida per le cure post-parto
Questo è quello che abbiamo trovato per te
Abstract 15008: Hydrogel-Mediated Sustained Intra-Pericardial Delivery of Endothelial Colony-Forming Cells-Derived Extracellular Vesicles Promote Cardiac Repair Post-Myocardial Infarction
Circulation, Volume 146, Issue Suppl_1, Page A15008-A15008, November 8, 2022. Introduction:Myocardial infarction (MI) is a leading cause of death worldwide. Although available treatments improve prognosis post-MI, they do not remediate cardiomyocyte death and loss of cardiac vasculature, resulting in chronic maladaptive remodeling and subsequently, heart failure. Extracellular vesicles (EVs) derived from endothelial colony-forming cells (ECFCs) show therapeutic potential, facilitating adaptive cardiac remodeling post-MI. However, ECFCs function is compromised in patients with type-2 diabetes, a common risk factor for MI, limiting the applicability of autologous cell-based therapies. Therapeutic administration is a further challenge, as current strategies present difficulties regarding invasiveness, retention, and efficacy.Hypothesis:We hypothesized that the minimally invasive intra-pericardial (IP) injection of ECFCs-EVs within a hydrogel would improve cardiac retention and promote sustained therapeutic release, facilitating cardiac repair in a murine model of MI. We anticipated that this repair would be greater with the use of EVs derived from wildtype mice than from diabetic mice.Methods:The impact of wildtype and diabetic ECFCs-EVs was evaluated on both in vitro EVs retention and angiogenesis. In a murine model of MI, the left anterior descending coronary artery was ligated while the pericardium was preserved. We evaluated whether IP injection is an effective and safe method of delivering hydrogels containing ECFCs-EVs, in addition to its long-term effects on cardiac morphology and function.Results:Our findings indicate that hydrogel use facilitates sustained EVs release. Besides that, the administration of ECFCs-EVs increased coronary endothelial cell proliferation, migration, and vascularization in vitro, and reduced maladaptive cardiac remodeling, improving cardiac contractility and function in vivo. These effects appear to be more pronounced with the administration of wildtype ECFCs-EVs.Conclusions:Collectively, our results underscore the therapeutic promise of ECFCs-EVs to improve cardiac repair after MI.
Abstract 12848: Infections Requiring Hospitalization in Patients One Year Post Heart Transplant
Circulation, Volume 146, Issue Suppl_1, Page A12848-A12848, November 8, 2022. Introduction:Immunosuppression of heart transplant (txp) recipients increases risk of infection. This study will identify the most common pathogens and characterize the most at-risk patients.Methods:We performed a single center retrospective cohort study at the University of Rochester. Demographics, pretransplant characteristics, and infections requiring rehospitalization were obtained (table 1) from electronic records of patients who received a txp from January 1, 2011 through July 1, 2020. Chi-square, t-test, and Wilcoxon rank-sum test assessed association between mortality, infection risk and other variables.Results:We identified 132 patients who received txp but excluded 4 due to incomplete data, 10 (7.6%) patients died during index admission while 12 (9.4%) more patients died in the year following their txp. Infections occurring 1 month post txp were associated with mortality (p-adj 0.026). Prior sternotomies (n=65, 50.8%) were associated with both mortality and bacterial infection (p-adj
Abstract 11319: Post-Operative Dialysis in Failing Fontan Patients Undergoing Heart Transplant: How Well Does the Pre-Transplant Creatinine Clearance Risk-Stratify Patients?
Circulation, Volume 146, Issue Suppl_1, Page A11319-A11319, November 8, 2022. Introduction:The need for dialysis early post-heart transplant (HT) can be suprisng when it occurs in the setting of purportedly normal renal function pre-HT, as has been described in failing Fontan (FF) patients.Hypothesis:We hypothesized that FF patients may have an increased incidence of post-operative dialysis (POD).Methods:The Pediatric Heart Transplant Society (PHTS) database was used to identify all children ≥2 years of age with failing Fontan (FF) physiology or cardiomyopathy (CM, benchmark lesion) who underwent isolated HT from 2005-2019. The primary endpoint was POD, defined as any form of dialysis within the first 30 days post-HT. Pre-transplant estimated glomerular filtration rate (eGFR) was calculated using the modified Schwartz formula, and a subset of patients with provided supplemental data additionally had renal function evaluated by a non-creatinine-based method.Results:Of 2003 children who met the inclusion criteria, 263 had FF (13%) and 1740 had CM (87%). Whereas the mean ages were similar (FF 11.2 vs CM 12.2 years, P=0.3), FF patients were 11% shorter (134 vs. 148, P
Abstract 10209: The Effect of the Dual SGLT1 and 2 Inhibitor Sotagliflozin on Cardiovascular Mortality and Hospital Readmission Rates for Heart Failure at 30 and 90 Days Post Discharge in Patients With Type 2 Diabetes Hospitalized for Worsening Heart Failure in the SOLOIST-WHF Trial
Circulation, Volume 146, Issue Suppl_1, Page A10209-A10209, November 8, 2022. Introduction:SGLT inhibitors demonstrate reductions in CV mortality and HHF in patients with diabetes and chronic HF. Despite therapy, patients hospitalized for worsening HF (WHF) are at high risk of death or readmission.Hypothesis:The SOLOIST-WHF trial admitted patients for their index WHF event and initiated randomized therapy during hospitalization. This study evaluated the effect of the SGLT1 and 2 inhibitor sotagliflozin on 30- and 90-day CV death and HF readmission rates after discharge.Methods:Of 1222 randomized patients with T2D, 86% were admitted for their index WHF event. Of them, 46% (n = 563) started study drug prior to or at discharge. In post hoc exploratory analyses, CV death and HF readmission (HHF or urgent visits for HF) rates were determined 30- or 90-days post discharge. Comparisons were done by Cochran-Mantel-Haenszel test stratified by region and baseline LVEF (50% for readmission for non-fatal HF-related events or the composite of CV death and readmission for HF-related events within 30 or 90 days of discharge vs placebo (Table 1). The sotagliflozin safety profile in those windows was generally consistent with the overall study duration. Incidence of adverse events (AEs) and serious AEs was similar between groups. Increased incidence of diarrhea and volume-related AEs was noted with sotagliflozin. No appreciable eGFR change from baseline occurred at 30 days, but there was lower incidence of AEs linked to acute kidney injury with sotagliflozin.Conclusions:Sotagliflozin, given to patients with T2D prior to or at hospital discharge after an episode of WHF, was well tolerated and resulted in a significant >50% reduction in CV mortality or readmission for a HF event at 30 and 90 days post-discharge.
Abstract 15841: Echocardiographic Parameters Are Correlated With Initial Infection Severity in Long-Term Post Covid-19 Patients
Circulation, Volume 146, Issue Suppl_1, Page A15841-A15841, November 8, 2022. Introduction:COVID-19 acutely affects the cardiovascular system leading to various cardiac complications. Major concerns are on the less understood long-term cardiovascular consequences of COVID-19.Hypothesis: Post COVID-19 cardiac dysfunctions could be long lasting and vary by severity of initial infection.Methods:This is an on-going prospective observational study from a multidisciplinary Post COVID-19 Research Clinic. Inclusion criteria included both RT-PCR confirmed and recovered COVID-19 patients and control subjects. After IRB approval and informed consents, 83 participants received serial transthoracic echocardiography at 3, 6 or >12 months after initial infection. Pearson’s correlation coefficients, Fisher’s exact test and one-way ANOVA was conducted to examine the association between variables, across follow-up time and severity of initial infection.Results:Proximal RVOT diastolic diameter was significantly larger at >12 months’ compared to earlier time points post COVID-19 (2.92±0.55 cm at 3 months, 2.81±0.57 cm at 6 months and 3.15±0.52 cm at >12 months). The posterior wall was significantly thicker in post COVID-19 patients with moderate or severe infection compared to patients with mild infection. The left atrium diameter was significantly larger as the initial infection severity increased. Pulmonary artery acceleration time was significantly shorter as initial infection severity increased indicating higher pulmonary arterial pressure although no significant relationship was found with follow-up time. There were no left ventricular ejection fraction, E/E’ (index of diastolic function) or valvular abnormality differences by either follow-up time or severity. Furthermore, 77% patients with severe infection had grade 1 diastolic dysfunction compared to mild (28.57%) or moderate (33.33%) patients.Conclusions:Long-term echocardiographic follow-up showed increased RV size after COVID-19 over time. Posterior wall thickness, left atrium size and pulmonary artery acceleration time, and diastolic dysfunction were correlated with initial infection severity in long-term post COVID-19 patients suggestive of possible structural changes in recovered patients from COVID-19.
Abstract 12809: Cirrhotic Cardiomyopathy Before Orthotropic Liver Transplantation is Associated With Major Adverse Cardiac Events at 13-Months Post Orthotropic Liver Transplantation
Circulation, Volume 146, Issue Suppl_1, Page A12809-A12809, November 8, 2022. Background:Major adverse cardiac events (MACE) are a leading cause of morbidity and mortality after orthotopic liver transplantation (OLT). Cirrhotic cardiomyopathy (CCM) is relatively common and a source of MACE in patients after OLT. Initial diagnostic criteria based on transthoracic echocardiogram (TTE) were described in 2005 and revised in 2019 with echocardiographic advancements (Table 1). We sought to identify CCM related predictors of MACE at 13 months post-OLT.Methods:This is a retrospective study of adult patients who underwent OLT between 2009-2019. All patients had TTE’s within one year pre-OLT and one month to 13 months post-OLT. We excluded TTE’s within one-month post-OLT to reduce contributions from stress cardiomyopathy. Patients with a left ventricular ejection fraction less than 50% pre-OLT were excluded. MACE was defined as death, MI, CHF hospitalization, or cardiac arrest. Multivariable Cox regression was used to identify independent predictors of MACE.Results:Of 568 OLT patients screened, 131 met inclusion criteria for this study. There were 103 and 23 patients who met 2005 and 2019 criteria, respectively. During the 13 month follow up period, 42 patients had MACE. Compared to those without MACE, patients with MACE had more ascites (93 vs 70%, p 0.003), hepatorenal syndrome (HRS) (17 vs 4%, p 0.019), delayed OLT >10 days after admission (19 vs 7%, p 0.033), pre-OLT CCM per 2005 criteria (90% vs 73%, p 0.023), and lower diastolic blood pressure (60.81 vs 66.88, p 0.014). There was no difference in pre-OLT CCM per 2019 criteria (19 vs 17%, p 0.758) or MELD-Na score (21.24 vs 19.40, p 0.166). In multi-variable cox regression analysis adjusted for diastolic blood pressure, HRS, ascites, and OLT timing during admission, CCM per 2005 criteria remained significant as seen in Figure 1 (Hazard Ratio = 3, p 0.038).Conclusion:CCM per 2005 criteria is an independent predictor of MACE at 13 months post-OLT while CCM per 2019 criteria is not.
Abstract 12070: Post-Cardiac Arrest Sedation Modulates Electroencephalographic Slow-Wave Activity and Promotes Neurological Recovery in a Mouse Model of Cardiac Arrest
Circulation, Volume 146, Issue Suppl_1, Page A12070-A12070, November 8, 2022. Introduction:The majority of patients resuscitated from cardiac arrest (CA) present in coma or with an altered level of consciousness. Although CA survivors are routinely sedated during targeted temperature management, the effects of sedation on CA outcomes remain to be determined.Hypothesis:Post-CA sedation would modulate cerebral physiology and improve neurological outcomes in mice.Methods:Adult C57BL/6J mice of both sexes were subjected to potassium chloride-induced CA and thereafter resuscitated with manual chest compression. Starting at return of spontaneous circulation (ROSC) or at 60 minutes after ROSC, mice received intravenous infusion of propofol at 40 mg · kg-1· h-1, dexmedetomidine at 1 μg · kg-1· h-1, or normal saline for 2 hours. Body temperature was lowered and maintained at 33°C during sedation. Cerebral blood flow was measured for 4 hours after ROSC. Telemetric electroencephalogram (EEG) was recorded in freely moving mice from 3 days before up to 7 days after CA.Results:Sedation with propofol or dexmedetomidine starting at ROSC attenuated brain injury and improved survival in hypothermia-treated post-CA mice (propofol [13/16] vs. no sedation [4/16],P= 0.008; dexmedetomidine [14/16] vs. no sedation [4/16],P= 0.002). Mice that were not sedated after ROSC exhibited cerebral hyperemia immediately after resuscitation and EEG power in all frequency bands remained less than 20% of the baseline in the first 4 hours after ROSC. Administration of propofol or dexmedetomidine starting at ROSC attenuated cerebral hyperemia and induced slow-wave (0.5-4 Hz) EEG activity that reached near baseline levels during and early after sedation. Increased EEG activity within 6 hours after ROSC was associated with improvement in neurological outcomes at 24 hours post-CA. In contrast, delayed sedation starting at 60 minutes after ROSC failed to improve outcomes, without attenuating cerebral hyperemia and inducing slow-wave EEG activity.Conclusions:Post-CA sedation with propofol or dexmedetomidine improved neurological outcomes and survival in mice resuscitated from CA and treated with hypothermia. The beneficial effects of sedation were accompanied by attenuation of the cerebral hyperemic response and induction of EEG slow-wave activity.
Abstract 12700: Post-GWAS Functional SNP Analysis to Define Genetic and Acquired Pathogenesis of Pulmonary Arterial Hypertension
Circulation, Volume 146, Issue Suppl_1, Page A12700-A12700, November 8, 2022. Introduction:Pulmonary arterial hypertension (PAH) is an enigmatic and morbid disease where insights are emerging regarding genetic susceptibility. Genome-wide Association Studies (GWAS) have identified genomic SNPs associated with increased PAH risk. It has been challenging to define the mechanisms underlying the contribution of non-coding PAH-associated functional SNPs (fSNPs) to the pathogenesis of this disease.Methods:We developed a post-GWAS functional genomics strategy to define the causative fSNPs and the associated biological mechanisms. It includes Reel-seq (Regulatory element-sequencing), an EMSA-based technique to identify fSNPs in a synthetic SNP library; SDCP-MS (SNP-specific DNA competition pulldown-mass spectrometry) to identify proteins that specifically bind to fSNPs; and AIDP-Wb (allele-imbalanced DNA pulldown-Western blot) to show allele-imbalanced binding of these proteins to fSNPs. The regulation of risk gene expression by fSNP-binding proteins and their pathogenicity were determined in human pulmonary arterial endothelial cells (PAECs) and confirmed in PAH animal models and patients.Results:An intergenic SNP rs4738801 was identified as a fSNP by Reel-seq. This non-coding fSNP resides in a remote upstream enhancer region of SOX17, an endothelial effector increasingly associated with PAH pathogenesis. Using SDCP-MS and AIDP-Wb, we found that transcription factor FUBP1 binds to rs4738801 risk allele C with lower affinity than non-risk allele G, resulting in a decrease in SOX17 expression. FUBP1 and target gene SOX17 controlled PAH-associated pathophenotypes in PAECs, including proliferation, apoptosis, and angiogenesis. Downregulated by major acquired PAH trigger hypoxia, FUBP1 and SOX17 were decreased in lungs and pulmonary ECs isolated from PAH patients and mouse models. A 3.8-fold enrichment of risk allele C was found in patients with PAH induced by hypoxia, but not in PAH associated with connective tissue disease or other etiology.CONCLUSION:Our functional genomics findings identify a novel role of FUBP1 in the functional regulation of SOX17 locus and elucidate a pathogenic mechanism that combines the acquired PAH-triggering factors and altered genetic susceptibility.
Abstract 11765: Gender Disparities in Complications Post Atrial Fibrillation Ablation
Circulation, Volume 146, Issue Suppl_1, Page A11765-A11765, November 8, 2022. Introduction:Catheter ablation therapy (CAT) is recommended for the management of symptomatic atrial fibrillation (AF). Previous real-world studies using the National Inpatient Sample (NIS) have described a disproportionately higher burden of post-CAT complications in womenHypothesis:We sought to determine whether the prior gender disparities in complications post-CAT for AF still exist. We hypothesize that with increasing CAT proficiency women would be no more likely to suffer complications compared to menMethods:We identified all percutaneous AF CAT hospitalizations in the NIS 2016-2019. We used Inverse-Probability Weighting (IPW) to create a pseudo-population where gender was independent of the following confounders: age, race/ethnicity, primary payor, median income, CHA2DS2VASc and Elixhauser scores, comorbidities including obesity, alcohol use disorder, obstructive sleep apnea, chronic pulmonary disease, and hospital characteristics-region, teaching-status, and bed-size. We compared in-hospital mortality rate, total procedural complications including pericardial (tamponade/effusion/pericarditis); cardiac (heart failure/perioperative MI/shock); respiratory (pneumothorax/respiratory failure); esophageal (perforation/injury); vascular (access-site fistulas/bleeding); and renal (acute kidney injury) between men and womenResults:Of the 5,835 AF CATs identified (representing 29,175 nationally), 43.2% were performed in women. Before IPW, women were older, and had higher proportions of comorbidities. After applying weights, baseline characters were well-balanced. In the weighted-cohort, there was no difference in mortality (0.48% vs 0.29%, p=0.52) or total complications (8.3% vs 9.6%, p=0.20). Likewise, pericardial (4.5% vs 4.1%, p=0.26); cardiac (0.3% vs 0.4%, p=0.40); vascular (3.6% vs 3.4%, p=0.37); respiratory (0.7% vs 0.8%, p=0.70); esophageal (0.5% vs 0.4%, p=0.31); and renal (1.2% vs 2.3%, p=0.38) complications, were similar across genderConclusion:In this real-world cohort, the burden of complications after CAT for AF was similar across gender. Sustained national efforts at maintaining awareness of gender disparities in complications post-AF CAT are needed to keep this new status quo
Abstract 10900: Implication of the Post-Translational Formation of Hypusine in Eif5a in Pulmonary Arterial Hypertension
Circulation, Volume 146, Issue Suppl_1, Page A10900-A10900, November 8, 2022. Pulmonary Arterial Hypertension (PAH) is characterized by progressive pulmonary arteries (PAs) obstruction leading to heart failure and death. PA smooth muscle cells (PASMCs) of PAH patients display a “cancer-like” phenotype that contributes to PA remodeling. Eukaryotic translation initiation factor 5A (eIF5A) was shown to provide cancer cells with a competitive advantage by increasing translation of mRNAs with oncogenic proprieties, many of them containing proline/glycine-rich patterns. Strikingly, eIF5A is the only protein containing the unique, polyamine-derived amino acid hypusine, which is required for its function. Hypusine formation is catalyzed by the sequential actions of deoxyhypusine synthase (DHPS) and deoxyhypusine hydrolase (DOHH). We hypothesized that increased eiF5AHypin PAH-PASMCs is required to promote translational efficiency of a set of factors conferring a higher survival and fibroproliferative capacity, leading to pulmonary vascular remodeling.Data derived from a comparative proteomic analysis (LC-MSMS) between normal and PAH-PASMCs and confirmed by Western blot indicate that DHPS and DOHH are overexpressed in PAH-PASMCs compared to controls (p
Abstract 12760: Microvascular Endothelial Dysfunction in Postural Orthostatic Tachycardia Syndrome Associated With Post-Acute Sequelae of COVID-19
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.
Abstract 10315: The Effect of Protease-Activated Receptor-1 Inhibition With Vorapaxar in Post-mi and Nstemi Patients on Selected Biomarkers Reflecting Endothelial Function
Circulation, Volume 146, Issue Suppl_1, Page A10315-A10315, November 8, 2022. Introduction:Biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has essentially focused on platelets. Follow-up (FU) time has been short, whereas in the current study, focus has been on endothelial function during both short- and long-term PAR-1 inhibition.Aim:To assess short- and long-term effects of vorapaxar (V) as compared to Placebo (PL) on the following biomarkers: Angiopoietin-2 (ANGPT2), Angiopoietin-like 4 (ANGPTL4), VEGF, ICAM-1, VCAM-1, E-Selectin (ESEL), von Willebrand Factor (VWF), Thrombomodulin (TM), PAI-1 and PAI-2.Methods:In an independent collective subproject performed in Norway, post-MI patients at steady state were recruited from the “Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients with Atherosclerosis” (TRA2ᵒP-TIMI 50) and NSTEMI patients were recruited from the “Thrombin Receptor Antagonist for Clinical Event Reduction in acute coronary syndrome” (TRACER) trial. Biomarkers were measured in duplicate by enzyme immunoassays (EIA) in citrated plasma at one month follow-up and at study completion (median 2.3 years) for subjects recruited from both trials.Results:Biomarkers were measured in 265 consecutive patients [age median 62.0 years (Q1-Q3: 55.0-68.0 years), males 83%] with at least one change from baseline value. Among these, biomarkers were available at both short- and long-term follow-up in 221 subjects.ANGPT2 increased significantly in V as compared to PL at 1-month follow-up in the total population (p=0.034), and in males in both post-MI (p=0.031) and NSTEMI subjects (p=0.012), respectively. ANGPTL4 increased (p=0.028) and PAI-2 decreased (p=0.025) significantly in the total population in favor of V at final FU. In the total post-MI subgroup and among males of that group, a short-term significant increase in ESEL in favor of V was observed, p=0.029 and p=0.018, respectively. Also, a transient significant increase in VWF (p=0.032) in favor of V was seen at one month in NSTEMI patients.Conclusions:Significant changes suggesting potential harmful effects in some biomarkers were observed during 1-month and long-term PAR-1 inhibition as compared to placebo in post-MI and acute coronary syndrome patients.
Abstract 12877: Investigation of the Role of Fgf23 in the Pathogenesis of Post-Splenectomy Cardiovascular Dysfunction
Circulation, Volume 146, Issue Suppl_1, Page A12877-A12877, November 8, 2022. Introduction:Splenectomy is a relatively common surgical procedure in hematologic disorders, such as thalassemia, to improve anemia. However, splenectomy is clinically indicated as a strong risk factor for the development of post-splenectomy cardiovascular dysfunction. The underlying mechanisms have not been well established. We have found elevated levels of circulating FGF23 in thalassemia mice. As a hormone mainly expressed by osteocytes in bone, FGF23 has been shown to be an independent marker for cardiovascular risk in various patient populations. In this study we sought to investigate the role of FGF23 in the pathogenesis of post-splenectomy cardiovascular dysfunction.Methods:Splenectomy was performed in thalassemia (Hbbth-3) mice at 4 weeks of age and cardiovascular functions were evaluated at 10 weeks post-splenectomy. Right ventricular maximum systolic pressure (RVSP) was measured using a closed chest right heart catheterization approach. Cardiac structure and functions were evaluated using echocardiography. Realtime RT-PCR and immunostaining were used to determine FGF23 expression in mouse tissues. Hepatocyte specific FGF23 KO thalassemia mice were generated by cross breeding albumin-Cre, Flox-Fgf23 and thalassemia mice.Results:Using a thalassemia mouse model (Hbbth-3), we found thatHbbth-3mice with surgical splenectomy developed significant cardiovascular dysfunction including biventricular cardiac hypertrophy, impaired diastolic function as well as pulmonary hypertension. We also found circulating levels of intact FGF23 were dramatically elevated in splenectomisedHbbth-3mice, along with significantly upregulated FGF23 expression in liver and bone tissues. However, FGF23 levels in plasma were not normalized in hepatocyte specific FGF23 KO mice, suggesting bone-derived FGF23 is most likely the major source account for elevated FGF23 in circulation.Conclusions:Our findings suggest bone-derived FGF23 may contribute to the development of post-splenectomy cardiovascular dysfunction in thalassemia. The role of FGF23 in post-splenectomy pathogenesis will be further investigated using global FGF23 KO and osteocyte specific FGF23 KO mouse models.
Abstract 11491: Clinical Time Course of Post-Acute Sequelae of SARS-CoV-2 Cardiovascular Syndrome
Circulation, Volume 146, Issue Suppl_1, Page A11491-A11491, November 8, 2022. Introduction:Post-acute sequelae of SARS-CoV-2 cardiovascular syndrome (PASC-CVS) is a heterogeneous disorder of post-COVID syndrome that involves a wide range of cardiovascular symptoms including palpitations, chest pain, dyspnea and dizziness. The clinical time-course of PASC-CVS is not well characterized. We sought to understand predictors of time to symptom improvement for patients with PASC-CVS.Methods:Patients with PASC-CVS undergoing evaluation in a dedicated post-COVID cardiology clinic were recruited after informed consent. Information was obtained from chart review and included demographics, comorbidities, symptoms, time of infection to time of presentation to the clinic and time to improvement in symptoms. A multivariate linear regression model was used to determine predictors of time to improvement.Results:A total of 144 consecutive patients were included that had complete records available for review. Average age was 46 years, 74% were female and 94% were Caucasian. Comorbities included obesity (49%), mental health disorder (25%), hypertension (24%), hyperlipidemia (24%), pulmonary disease (18%), type II diabetes (9%), atrial arrhythmia (5%) and coronary artery disease (3%). Time from infection to presentation (p
Abstract 14602: Does Cancer Treatment Break Your Heart? A Linked Health Data Analysis of Thecharacteristics and Survival of Patients Who Have Developed Cardiovascular Disease Post Cancer Treatment
Circulation, Volume 146, Issue Suppl_1, Page A14602-A14602, November 8, 2022. Background:Cancer treatment induced cardiotoxicity, can be a devastating outcome of cancer therapy. It is possible that a patient can survive cancer but develop cardiovascular disease (CVD).Aim:to determine whether there are differences in the characteristics of cancer patients who received potentially cardiotoxic cancer therapy and subsequently developed CVD and those who did not.Methods:This epidemiological study will comprise a retrospective analysis of de-identified linked health data sets, including the Integrated Activity Collection (ISAAC) of Hospital Separations, South Australian Cancer Registry (SACR), Northern Territory Cancer Registry (NTCR) and mortality (Births Deaths and Marriage Registry Data) and NT Hospital Separation data. The total population will be segregated in two distinct groups namely ‘Cancer with no HF’ and ‘Cancer with HF’ to compare the between group differences by demographic factors and medical history.Results:Of the (n=17,389) patients who received chemotherapy cancer treatment between July 2001-June 2017, 49% (8,530) were diagnosed with HF post cancer treatment( median age at cancer diagnosis 65 years; 58% male); crude mortality was 73% within the HF and cancer group; cause of death within this group was HF related 14%; cancer related 63%; other 22% compared to the non HF and cancer group ( median age at cancer diagnosis 58 years; 53% male) who had a mortality rate of 46%; 6.2% CVD related; 68.8% cancer related and 25% other.Conclusion:After adjusting for age, sex, tumour grade, cancer site and CVD admissions prior to cancer diagnosis patients with CVD and cancer had poorer outcomes.