Abstract 10739: Impact of Cardiac Device Implantation in Elderly Japanese Patients With Heart Failure as Primary Prevention-A Post Hoc Analysis of the HINODE Trial

Circulation, Volume 146, Issue Suppl_1, Page A10739-A10739, November 8, 2022. Introduction:Despite increase in the incidence of chronic heart failure (HF) and sudden cardia death (SCD), the current use of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) in Japan is much lower than in Western countries. The HF Indication and SCD Prevention Trial Japan (HINODE) was designed to prospectively assess the rate of mortality, appropriately treated ventricular arrhythmias (VA) and heart failure (HF) for comparison with references from historical landmark trial MADIT-RIT in Japanese patients.Hypothesis:This sub analysis of HINODE evaluates the impact of ICD or CRT implantation in elderly Japanese patients concomitant with higher risk of heart failure.Methods:After treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (1) ICD (2) CRT with defibrillator (CRT-D) (3) standard medical therapy (‘non-device’) (4) pacing (indicated for CRT; received pacemaker or CRT pacing). We compared the all-cause mortality between elderly and non-elderly patients with elderly defined as age >70 at the time of study enrollment.Results:The HINODE study enrolled 354 patients (191 elderly) followed for 19.6 ± 6.5 months with a minimum of 12 months and an absolute death rate of 11.0%. The estimated survival rate for device recipients (n=239) through 24 months was 86.1% (97.5% LCL: 79.8%) with no significant difference for elderly vs non-elderly patients (HR 1.97, 95%CI: 0.86-4.54). Analysis within cohorts showed increased risk of all-cause mortality for elderly with an ICD compared to non-elderly with an ICD (HR 5.09 95% CI: 1.1-23.6). However, ICD cohort excluding those with CRT-D indication showed no significant difference (HR 3.70, 95% CI: 0.75-18.35). No significant difference showed in other cohorts: CRT-D (HR 1.53 95% CI: 0.34-6.84) or pacing (HR 0.84, 95%CI: 0.2-3.5). Ventricular event free rate in ICD and CRT-D patients also had no difference (HR 0.84 95% CI: 0.31-2.25)Conclusions:Although elderly patients might be associated with higher risk of mortality in general, benefit of device therapy is comparable to non-elderly patients. We might consider device therapy despite age as a standalone risk in contemporary Japanese clinical practice.

Leggi
Ottobre 2022

Abstract 11881: Association of Post-Vaccination Adverse Reactions After Influenza Vaccine With Mortality and Cardiopulmonary Outcomes in Patients With High-Risk Cardiovascular Disease: The INVESTED Trial

Circulation, Volume 146, Issue Suppl_1, Page A11881-A11881, November 8, 2022. Introduction:Influenza vaccination is associated with reduced cardiopulmonary morbidity and mortality among patients with heart failure or recent myocardial infarction. The immune response to vaccination frequently results in mild adverse reactions (AR), which leads to vaccine hesitancy. We assessed the association between vaccine-related AR and morbidity and mortality in patients with high-risk cardiovascular disease.Methods:The INVESTED trial randomized 5260 patients with recent acute myocardial infarction or heart failure hospitalization to high-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine. We examined the association between vaccine-related AR and adverse clinical outcomes in propensity-adjusted models.Results:Overall, 1968 participants (37.4%) experienced a vaccine-related AR. Compared to those without AR, post-vaccination AR, most commonly injection site pain (60.3%), were associated with lower adjusted risk for the composite of all-cause death or cardiopulmonary hospitalization, cardiopulmonary hospitalizations, all-cause death, cardiovascular hospitalizations and non-cardiopulmonary hospitalizations (Figure 1; Table 1).Conclusions:Post-vaccination reactions after influenza vaccine were associated with reduced risk of cardiopulmonary hospitalizations and all-cause mortality in patients with high-risk cardiovascular disease in propensity adjusted models, and may be a marker of a better immune response or overall health status, and should not deter future vaccinations.

Leggi
Ottobre 2022

Abstract 10623: Association of Changes in Glycemic Status and Risk of Cardiovascular Disease Among Adults With Hypertension – A Post-Hoc Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

Circulation, Volume 146, Issue Suppl_1, Page A10623-A10623, November 8, 2022. Introduction:Prediabetes (preDM) is a risk factor for diabetes mellitus (DM) and both are associated with elevated risk of cardiovascular disease (CVD). However, the association of transitions in glycemic status with cardiovascular disease (CVD) is not well established.Methods:The present study included participants with hypertension enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT) without DM at baseline. Study participants had available fasting plasma glucose (FPG) at baseline and 2-year follow-up and no primary outcome CVD event (myocardial infarction, other acute coronary syndrome, stroke, heart failure, or cardiovascular death) prior to 2 years. Euglycemia, preDM, and DM status were defined based on FPG, self-reported history, or use of glucose-lowering medication. Participants were stratified by glycemic status at baseline and 2-year follow up. The association of changes in glycemic status with CVD risk were assessed using adjusted Cox models.Results:The present study included 4,708 participants (33.6% women, 35.1% Black, 41.4% preDM). Among 2,760 participants with euglycemia at baseline, 716 (25.9%) developed preDM or DM over 2-year follow-up. Most participants with baseline preDM continued to have preDM or progressed to DM (71.3%). After the 2-year visit, 151 participants (3.2%) had a CVD event. Participants with persistent euglycemia had fewer CVD events (2.6%) compared with those with incident preDM or DM on follow-up (4.5%) (Figure 1A). In adjusted analysis, among participants with baseline euglycemia, those who developed prediabetes or diabetes had 70% higher risk of a CVD event during follow-up compared with those with persistent euglycemia (HR [95% CI], 1.70 [1.09-2.64]) (Figure 1B).Conclusions:In adults with hypertension, worsening glycemic status from euglycemia to preDM or DM was associated with higher risk for CVD. Prevention of dysglycemia may be an important target to prevent CVD in hypertension.

Leggi
Ottobre 2022

Abstract 10720: Early Growth Trajectory is Associated With Post-Traumatic Stress in Parents of Infants With Congenital Heart Disease

Circulation, Volume 146, Issue Suppl_1, Page A10720-A10720, November 8, 2022. Background:Parents of infants with congenital heart disease (CHD) have described substantial stress over infant growth. Poor growth trajectory (GT) during early infancy may be a source of traumatic stress. The purpose of this study was to determine if differences exist in parent posttraumatic stress (PTS) between parents of infants with healthy versus poor GTs from hospital discharge to 4 months post discharge.Methods:This secondary analysis of a previously reported RCT (REACH telehealth trial NCT01941667) included parents of infants with CHD with stress measures at discharge and study end (n=136). Posttraumatic Diagnostic Scale was used to measure PTS. Weights were converted to weight for age Z scores (WAZ) using World Health Organization standards. WAZ-GT classes were identified using latent class growth modeling. We used multivariate logistic regression modeling to examine associations between WAZ-GT and parental PTS over the study period, adjusting for covariates.RESULTSOne-quarter of parents (n=37, 28%) demonstrated at least moderate PTS symptom severity at discharge and one-third at study end (n=40, 31%). We identified four distinct classes of infant WAZ-GT (Figure). Among the identified GTs, two were considered healthy growth patterns: “stable around WAZ=0” (n=51, 37.5%) and “maintaining WAZ > 0” (n=12, 8.8%). Therefore, these two patterns were collapsed to serve as one reference group for the analysis. Two additional WAZ-GT classes were identified that reflected poor growth: “partially-recovered” (n=44, 32.4%) and “never-recovered” (n=29, 21.3%). Parents of infants in the “never recovered” GT were at greater risk (OR=4.58; CI=1.54-13.64) for experiencing at least moderate PTS symptom severity at end of study as well as over time from discharge to end of study (OR=3.91; CI=1.60-9.86).CONCLUSIONResults offer new insights that parents of infants with poor GT are at increased risk for persistent PTS and may need additional screening and intervention.

Leggi
Ottobre 2022

Abstract 111: Ischemic Post Conditioning After Asphyxial Arrest In A Diabetic Rat Model

Circulation, Volume 146, Issue Suppl_1, Page A111-A111, November 8, 2022. Diabetes (DM) is a pervasive disease associated with increased risk of cardiac arrest (CA) and worse survival. Diabetics display abrogation of post arrest therapies. Ischemic post-conditioning (IPoC) has been shown to improve outcomes in young healthy swine, but never in a DM model. We hypothesized that IPoC would be beneficial for survival of non-DM rats after asphyxial CA and that this benefit would be abrogated in DM. Male Wistar rats were utilized, 12 of 23 underwent induction of DM with injection of streptozotocin (30mg/kg) IP and feeding of western diet for 12 weeks. Rats were intubated, mechanically ventilated, and anesthetized with isoflurane. A non-invasive flow probe was placed on a carotid artery. An internal jugular vein and femoral artery and vein were cannulated. Electrocardiogram, echocardiogram, and arterial blood gas were analyzed. Asphyxial CA, induced by rocuronium and cessation of ventilation, proceeded for 7 min. CPR was initiated utilizing an automated chest compressor at a rate of 200/min. Animals were randomly assigned to standard CPR (S-CPR) or IPoC. IPoC was initiated 40 seconds into CPR with a 20 sec pause followed by 20 sec of compressions, 1 cycle. This cycling was performed 4 total times after which S-CPR was continued. Defibrillation and epinephrine were given, as necessary. Data were collected every 40 sec during CPR and at 15 min, 1 and 2 hr after return of spontaneous circulation (ROSC). Data were analyzed using ANOVA with pairwise comparisons. Significance set at p

Leggi
Ottobre 2022

Abstract 10465: Abnormal Post Exercise Skeletal Muscle Microvascular Response and Metabolism Correlate With Patient Reported Outcomes in Patients With Intermittent Claudication From Peripheral Artery Disease

Circulation, Volume 146, Issue Suppl_1, Page A10465-A10465, November 8, 2022. Background and Aims:Intermittent claudication (IC) in patients with peripheral artery disease (PAD) is thought to be caused by reduced lower extremity macrovascular blood flow. However, the ankle-brachial index (ABI) (a macrovascular measure) does not correlate well with patient-reported outcome measures. We aimed to study microvascular and metabolic skeletal muscle responses to exercise in patients with IC using positron emission tomography (PET).Methods:We enrolled 19 patients with IC (ABI < 0.90 and imaging/angiographic evidence of PAD) and 12 healthy controls (HCs) (normal ABI). All subjects underwent rest perfusion imaging of the legs with13N-ammonia or11C-acetate PET followed by a graded treadmill test. Subjects exercised until limited by claudication or the end of the 20-minute protocol. Subjects then underwent immediately post-exercise PET imaging of the legs. Skeletal muscle blood flow (SMBF) was quantified in each leg at rest and immediately post-exercise. Skeletal muscle oxygen utilization (SMVO2) normalized to SMBF was also quantified for patients who underwent imaging with11C-acetate. Peripheral artery questionnaire (PAQ) summary score was obtained for all subjects.Results:We found that SMBF was increased post-exercise in all subjects, and stress/rest SMBF was higher in the legs of subjects with PAD than in the legs of HCs (Figure 1A). We also found that stress SMVO2/SMBF was higher in legs of patients with PAD than in the legs of HCs (Figure 1B). There was a moderate, significant correlation between limb stress/rest SMBF and PAQ score (Figure 1C) and a strong, significant correlation between limb stress SMVO2/SMBF and PAQ score (Figure 1D).Conclusions:In conclusion, we found that SMBF increased in all subjects after treadmill exercise and paradoxically to the greatest degree in patients with IC. We also found that PET-derived markers of post-exercise microvascular perfusion and metabolism correlated with patient-reported outcomes.

Leggi
Ottobre 2022

Abstract 9901: In-Hospital and 30-day Post-Discharge Outcomes Associated With Postoperative Atrial Fibrillation: A Contemporary Analysis From the Society of Thoracic Surgeons Adult Cardiac Surgery Database

Circulation, Volume 146, Issue Suppl_1, Page A9901-A9901, November 8, 2022. Introduction:Postoperative atrial fibrillation (POAF) is associated with worse in-hospital and post-discharge morbidity and mortality. However, current estimates vary widely among published studies due to limited study centers and differing patient populations. The objective of this study was to assess the risk-adjusted in-hospital and 30-day post-discharge clinical outcomes associated with POAF in the United States.Methods:A contemporary, retrospective study was conducted using the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery database. The sample consisted of patients aged 40 to 90 who underwent open-chest coronary artery bypass and/or valvular surgery between 2011 to 2019. In-hospital and 30-day post-discharge clinical outcomes were compared between those who experienced POAF and those who did not (controls). Outcomes were risk-adjusted, where appropriate, for baseline demographics and prior medical and surgical history using a multivariable regression approach.Results:A total of 424,590 patients with a mean age of 69.3 (SD 9.2) years and 1,105,200 patients with a mean age of 64.8 (SD 10.2) years were identified in the POAF and control cohorts respectively, representing a POAF cumulative incidence of 27.8%. POAF patients experienced on average a postoperative length of stay that was 2.4 days longer (p < 0.001) and 32 additional hours (p < 0.001) in the intensive care unit compared to control patients. After risk adjustment, POAF was associated with 64% higher odds of in-hospital stroke (OR 1.64, 95% CI 1.59, 1.69), 158% higher odds of in-hospital renal failure (OR 2.58, 95% CI 2.52, 2.64), 29% higher odds of in-hospital mortality (OR 1.29, 95% CI 1.26, 1.32), 23% higher odds of 30-day readmission (OR 1.23 95% CI 1.21, 1.25), and 27% higher odds of 30-day mortality (OR 1.27, 95% CI 1.24, 1.30).Conclusions:POAF is associated with a significantly increased risk of both in-hospital and 30-days post-discharge morbidity and mortality. This study highlights the unmet need for more effective POAF prevention strategies.

Leggi
Ottobre 2022

Abstract 9801: Late Onset Phrenic Nerve Injury Post PPM Placement

Circulation, Volume 146, Issue Suppl_1, Page A9801-A9801, November 8, 2022. Background:Transient phrenic nerve paralysis is a known immediate complication of cardiac implantable electronic device implants. Proposed mechanisms include direct nerve injury during venipuncture, nerve compression from a mediastinal hematoma, or local anesthetic instillation. However, the authors present a rare case of phrenic nerve injury as a late complication of permanent pacemaker (PPM) placement after excluding other etiologies.Case Summary:A 39 year-old female with a history of hypertension and diabetes underwent dual-chamber permanent pacemaker (PPM) placement due to sinus node dysfunction. She presented a year later with a subacute onset of progressive dyspnea on exertion that worsened over the four days prior to admission. Dyspnea was associated with right neck and shoulder pain. Chest radiography at presentation showed elevated right hemidiaphragm. A fluoroscopic sniff test confirmed right hemidiaphragm paralysis. Chest computed tomography revealed no anatomic abnormalities. Magnetic resonance imaging of the cervical spine showed no spinal cord or nerve root lesions. Electromyography confirmed right phrenic nerve injury as the etiology of elevated right hemidiaphragm. She continued to experience exertional dyspnea and orthopnea. Thoracic surgery scheduled the patient for insertion of a diaphragmatic pacemaker. She was discharged pending her surgery.Discussion:Late onset diaphragmatic paralysis due to phrenic nerve injury is a rare complication of PPM insertion. The mechanism of phrenic nerve injury from PPM insertion is unclear. It may result from direct or indirect phrenic nerve micro-injury by the relatively stiff pacemaker leads or peel-away introducers, resulting in slow Wallerian degeneration of the phrenic nerve fibers. In addition, microhematomas, undetected by chest computed tomography, inflammatory or thrombotic changes of the subclavian vein or the superior vena cava may influence the adjacent phrenic nerve.

Leggi
Ottobre 2022

Abstract 13604: Sodium-Glucose-Cotransporter-2 Inhibitor (SGLT2i) Exposure in the Immediate Post-Acute Kidney Injury Period in Patients Hospitalized With Acute Heart Failure is Associated With Improved Outcomes

Circulation, Volume 146, Issue Suppl_1, Page A13604-A13604, November 8, 2022. Introduction:Sodium-Glucose Cotransporter-2 inhibitor (SGLT2i) use during or immediately following Acute Heart Failure (AHF) exacerbation has shown clinical benefit including improved symptoms, lower frequencies of re-hospitalization for heart failure and death. However, effects of SGLT2i use immediately following acute kidney injury (AKI) on mortality and renal recovery in this setting are unknown.Hypothesis:Among patients admitted with AHF who sustain in-hospital AKI, exposure to SGLT2i in the immediate post-AKI period would be associated with better outcomes.Methods:Adult patients admitted across 5 hospitals between January, 2020 and April, 2022 with acute heart failure (NT-pro-BNP >500ng/L and receipt of IV diuretic within 24 hours of admission) and KDIGO-defined AKI during hospitalization were included. Advanced CKD (eGFR ≤15 ml/min/1.72m2) and those prescribed SGLT2i > 10 days after AKI were excluded. AKI recovery and death were compared between the exposed and unexposed cohorts using a time-varying Cox-regression analysis after adjusting for potential confounders.Results:In this retrospective cohort of 3599 individuals admitted with AHF that developed AKI during hospitalization, 293 patients received SGLT2i within the 10 days post-AKI. The median (IQR) time to AKI after admission was 24 (1.41-64.48) hours. 36.52% of the SGLT2i exposed had renal recovery pre-SGLT2i exposure. For the SGLT2i-exposed (pre-renal recovery) vs. unexposed groups, rates of 14-day renal recovery were not significantly different (adj. HR 0.99, 95% CI 0.82-1.19, p=0.90). However, the post-AKI SGLT2i-exposed group had a lower risk of death at 30 days (adj. HR 0.39, 95% CI 0.19-0.79, p=0.009) after adjustment for potential confounders.Conclusion:In a retrospective cohort of patients hospitalized with AHF with in-hospital AKI, exposure to SGLT2i within 10 days post-AKI was associated with decreased mortality and no significant delay in renal recovery.

Leggi
Ottobre 2022

Abstract 15627: Inferior Vena Cava Filter Strut Fracture and Migration to the Right Ventricle in Post-COVID Patient With Intractable Cough

Circulation, Volume 146, Issue Suppl_1, Page A15627-A15627, November 8, 2022. Background:Inferior vena cava (IVC) filter fracture and migration of the fractured strut is a rare but potentially dangerous complication. We report a case of fractured IVC strut migrated to the right ventricle (RV) in a patient who was evaluated for persistent cough.Clinical Case:A 69-year-old male presented to his primary care physician for the evaluation of intractable cough and shortness of breath. Past medical history was significant for recurrent unprovoked deep vein thromboses treated with an IVC filter 15 years ago. He had COVID19 infection six months prior to current presentation. A computed tomography (CT) scan of the chest was ordered to screen for underlying pulmonary disease. CT scan showed no pulmonary process, but revealed a linear radiopaque foreign body in the RV of the heart. His cough was considered to be a sequela of his prior COIVD19 infection.Decision-making:To better characterize this foreign body in RV, a transesophageal echocardiogram was performed. This showed a prominent linear echo density on the tricuspid valve chord in the RV. On careful review of the CT scan of the chest and comparison with prior CT scans, it was found that one of the IVC filter strut at 9 o’ clock position was missing. The ‘foreign body’ in the RV had the same size as the remaining struts of the IVC filter. Given that the patient did not have any symptoms or complications from the incidentally found fractured strut, decision was made to not retrieve it with a percutaneous or surgical intervention.Conclusion:Significant variations in the intra-abdominal pressure may contribute to metal fatigue potentially leading to IVC filter strut fracture and migration to the RV. This underscores the importance of timely removal of IVC filters. Uncomplicated migrated IVC filter struts may be left unretrieved and patients can be followed clinically.

Leggi
Ottobre 2022

Abstract 15411: Life After the Valve, Analyzing Post-Procedural Anemia and Mortality in Transcatheter Aortic Valve Replacement Patients

Circulation, Volume 146, Issue Suppl_1, Page A15411-A15411, November 8, 2022. Introduction:Transcatheter Aortic Valve Replacement (TAVR) has become the primary therapeutic option for many patients with severe aortic stenosis (AS). As a result, anemia is a prevalent co-morbidity amongst the TAVR population. Recent studies have demonstrated pre-procedural anemia is associated with increased long-term mortality in TAVR patients. However, the comparison of TAVR patients’ post-procedural anemia and its effect on mortality has not been fully investigated.Methods:Retrospective analysis of electronic medical records from 2018-2021 at the University of Illinois at Chicago and Jesse Brown VA Medical Center identified TAVR patients. Primary outcomes included all-cause mortality and significant bleeding at 6-months and 12-months post-TAVR.Results:We included 160 patients in the analysis. They were 122 males, 56.88% non-white, and an average age of 73.88. At 6-months, patients who experienced all-cause mortality had an average hemoglobin of 9.85 (g/dL) compared to an average hemoglobin of 11.31 in those patients that survived (p = 0.020). There was no significant difference in major bleeding events between the two groups (p = 0.974) as well as no significant difference in past-medical history, including hypertension, hyperlipidemia (HLD), diabetes mellitus, history of stroke and history of myocardial infarction. At 12-months, patients who experienced all-cause mortality had an average hemoglobin of 10.18 compared to an average hemoglobin of 11.36 in those patients that survived (p = 0.014). There was no significant difference in major bleeding events (p = 0.753) and no significant difference in past-medical history, except for hyperlipidemia. The prevalence of HLD was 59.09% in those that experienced all-cause mortality compared to 78.72% in those that did not (p = 0.045).Conclusions:Our results suggest that patients with lower hemoglobin levels after TAVR are at a greater risk of all-cause mortality compared to those with higher hemoglobin levels. These patients may benefit from closer follow-up after the procedure.

Leggi
Ottobre 2022

Abstract 11083: Post-Infarction Cardiac Protection by Gut Butyrate-Producers

Circulation, Volume 146, Issue Suppl_1, Page A11083-A11083, November 8, 2022. BackgroundThe gut microbiota and their metabolites have been shown to contribute to the development of coronary artery diseases. However, little is known about their roles in post-injury cardiac repair. Here, we investigated the gut microbiota and plasma metabolomes distinct in patients with ST-elevation myocardial infarction (STEMI), and explored their roles on adaptive responses, using germ-free (GF) mice and nonhuman primate models.MethodsWe recruited 70 controls and 77 coronary angiogram-confirmed STEMI patients, and collected their stool and plasma. The stool and plasma of STEMI patients were collected immediately following percutaneous coronary intervention (PCI, STEMIT1) and again at 28 days after PCI (STEMIT2). We used 16S V3-V4 rRNA NGS and shotgun metagenomics to map the gut microbiota and both NMR and LC-MS metabolomics to profile the plasma metabolites. To determine therole of the gut microbiota and their metabolites on post-injury cardiac repair, we inoculated identified bacteria in GF mice and treated specific pathogen free mice with candidate metabolites. Moreover, we validated the microbiome and metabolomics findings in a nonhuman primate coronary ischemia-reperfusion (IR) injury model.ResultsThe 16S V3-V4 rRNA NGS and shotgun metagenomic analysis revealed an enrichment of butyrate-producing bacteria in STEMIT1, as compared to STEMIT2 or to control cases. Fecal microbiome transplantation of STEMI samples in GF mice deteriorated host post-injury cardiac function, showing reduced left ventricle ejection fraction and cardiac mechanics. Moreover, plasma ketogenesis increased in the STEMI patients using NMR and LC-MS metabolomics. The protective effect of butyrate was more profound with intact commensal gut flora. Furthermore, inoculation of butyrate-producers in GF mice elevated plasma ketone body and better preserved post-injury cardiac function. Agreed with the clinical finding, we observed injury-induced elevation of gut butyrate-producers and plasma ketone bodies in the nonhuman primate IR model.ConclusionThis study demonstrates the pivotal role of gut butyrate-producers and the derived ketogenesis in post-injury cardiac repair, which may lead to new prevention strategies and treatment for heart failure.

Leggi
Ottobre 2022

Abstract 10754: AMPKγ2 Deficiency Exacerbates Macrophage Recruitment and Inflammation Post-MI via Promoting YY1-CXCL16-CXCR6 Axis

Circulation, Volume 146, Issue Suppl_1, Page A10754-A10754, November 8, 2022. Background:Acute myocardial infarction (MI) has got revolutionized therapeutic strategy by applying timely reperfusion therapy in a particular increase of primary percutaneous coronary intervention. Despite this cardiac remodeling following MI are very common with high mortality. A previous study claimed that AMPK played a pivotal role in intracellular adaptation to energy stress during myocardial ischemia. However, whether AMPKγ2 subunit played an important role in MI remains poorly defined.Hypothesis:We assessed the hypothesis that AMPKγ2 played an important role in regulating MI.Methods:AMPKγ2 level in monocytes of myocardial infarction patients was tested by ELISA. Ligation of left anterior descending branch (LAD) surgery was conducted to establish MI model. Lyz2-cre AMPKγ2 and AAV carrying F4/80 promoter for macrophage-specific overexpression AMPKγ2 mice were employed to investigate the role of AMPKγ2 in macrophages derived from MI.Results:AMPKγ2 was relatively highly expressed in the spleen and macrophage. Lyz2-cre AMPKγ2 mice developed worse cardiac dysfunction post-MI by boosting macrophage infiltration and inflammation. Overexpression of AMPKγ2 in macrophages repressed its migration and inflammation and alleviated myocardial injury. Mechanistically, CXCL16-CXCR6 axis was the contributor to macrophage migration, which was alleviated by AMPKγ2 via transcriptional regulation. Further, AMPKγ2 restrained YY1 expression, a key upstream transcription factor of CXCL16, to block the migration of macrophages. AMPKγ2 promoted YY1 degradation via smurf2 mediating ubiquitin-proteasome pathway depending on AMPKα1 subunit-mediating AMPK activity. Therefore, A769662 but not Metformin alleviated AMPKγ2 deficiency-induced migration and inflammation in macrophages. Finally, IFN-γ downregulated HOXA5 to repress AMPKγ2 transcriptional activity. Consistently, AMPKγ2 was dramatically declined in monocytes of MI patients compared to the control group.Conclusion:Macrophage AMPKγ2 deficiency played an important role in cardiac dysfunction following MI by activating the YY1-CXCL16-CXCR6 axis, which can be developed as a precision therapeutic target to ameliorate cardiac remodeling post-MI.

Leggi
Ottobre 2022

Abstract 14838: Prevalence and Outcomes of Prosthetic Valve Endocarditis Post-Tavr: A Proportion Meta-Analysis

Circulation, Volume 146, Issue Suppl_1, Page A14838-A14838, November 8, 2022. Introduction:Prosthetic valve endocarditis (PVE) may occur after trans-catheter aortic valve replacement (TAVR), resulting in bio-prosthetic valve dysfunction. We aim to assess the clinical characteristics and long-term outcomes post TAVR.Methods:We performed a systematic literature search in PubMed, Scopus, and Embase for relevant articles from inception until June 01, 2022. Primary outcome was all-cause mortality. Secondary outcomes include acute kidney injury, stroke, systemic embolisation, heart failure and valve re-intervention. All endpoints were pooled using a random-effect model.Results:A total of 33 studies were included, comprising 346,094 patients who underwent TAVR. Amongst the various co-morbidities, most common were diabetes (11%), chronic kidney disease (8%) and chronic obstructive pulmonary disease (COPD) (8%).The pooled incidence of PVE was 1% [95% CI (1%-2%)]. The most common approach was trans-femoral (n=15) (88% [95% CI (79%-95%)]) followed by trans-apical (n=9) (14% [95% CI(10%-18%)]). The most common organisms isolated were staphylococcus species (n=24) (34% [95% CI (30%-38%)]), followed by streptococcal species (n=23) in 23% and enterococcus species (n=22) in 24%. The leading complications reported were acute kidney injury (AKI) (30% [95% CI (19%-44%)]) (n=7), cerebrovascular accident (10% [95% CI (7%-14%)]) (n=13), embolisation (17% [95% CI (10%-26%)]) (n=11) and patients requiring a surgical valve replacement (12% [95% CI (8%-18%)] ) (n=14). The all-cause mortality was 49% [95% CI (41%-56%)], while the in-hospital mortality was 4% [95% CI (2%-9%)].Conclusions:Incidence of IE post TAVR is low (1%), but is associated with a higher rate of mortality (49%) and morbidity. As a result, aggressive management is needed to reduce post-TAVR complications.

Leggi
Ottobre 2022

Abstract 13862: Trends in Complication Rates Post-Transcatheter Aortic Valve Replacement

Circulation, Volume 146, Issue Suppl_1, Page A13862-A13862, November 8, 2022. Introduction:Transcatheter Aortic Valve Replacement (TAVR) is a mainstay of treatment for aortic valve stenosis for patients. It is unclear if this has resulted in a significant change in post-procedural complications over time.Hypothesis:We hypothesised a reduction in major complication rates across our study period given the improvement in delivery systems.Methods:This is a nationwide temporal trends study utilizing the 2016-2019 National In Patient Sample (NIS) registry. Patients who underwent TAVR including those with major procedural complications (i.e: need for transfusion or permanent pacemaker implantation [PPMI]) were identified. The trends in overall complication rate and individual complication rates between 2016 to 2019 were analysed. Multivariate model was built to predict the factors influencing complications.Results:Between 2016-2019, 217,110 patients underwent TAVR of which 12.6% had atleast one major complication. Proportion of complications decreased significantly across the study period(see Fig 1). Overall, females had a 10% higher complication rate (aOR 1.1, p=0.002) mainly driven by bleeding with over a 50% need for transfusion (aOR 1.57, p3 having over a threefold risk (aOR 3.4, p

Leggi
Ottobre 2022

Abstract 11989: PiRNA Mined From Therapeutic Cell Extracellular Vesicles, Protects Cardiac Tissue Post-Injury Through Epigenetic Silencing of Pick1 in Circulating Macrophages

Circulation, Volume 146, Issue Suppl_1, Page A11989-A11989, November 8, 2022. Introduction:Small non-coding RNAs (snRNAs) comprise the majority of extracellular vesicle (EV) cargo. Therapeutic cells secrete EVs replete with snRNAs that repair damaged tissue through gene regulation in target cells. Piwi RNAs (piRNAs) are the most diverse class of snRNAs and a major component of EVs (called IMEX) secreted by engineered cardiosphere-derived cells. While much is known about the role of piRNAs in germline cells, little is known about their mechanism in tissue repair. Here we investigate the role of an enriched piRNA (piR-33044, we dub TEP3.4) in cardioprotection.Methods:We used ischemia/reperfusion (I/R) injury in rats to evaluate the cardioprotective effect of TEP3.4. To identify a target cell type, we exposed bone-marrow-derived macrophages (BMDMs), cardiac fibroblasts, and cardiomyocytes to TEP3.4 to assess transcriptomic changes. To identify the gene target of TEP3.4, we performed whole-genome bisulfite sequencing (WGBS) and methylation-specific sequencing. Finally, to evaluate the role of macrophages in TEP3.4 cardioprotection, we adoptively transferred BMDMs exposed to TEP3.4 in I/R injury.Results:In vivo, TEP3.4 reduced infarct size (TEP3.4: 3.45±0.43g vs vehicle: 11.41±1.32g or scramble: 11.88±2.44g) and circulating cardiac troponin I (TEP3.4: 5.79±0.83ng/ml vs vehicle: 19.16±2.81ng/ml or scramble: 17.42±2.07ng/ml). BMDMs showed more transcriptomic changes compared to cardiac fibroblasts or cardiomyocytes (5435 genes vs 4114 and 2653, respectively). Methylation analysis identified pick1 as a target of TEP3.4. Pick1 downregulation enhanced Smad3 phosphorylation and phagocytic capacity in BMDMs.In vivo,Adoptive transfer of BMDMs exposed to TEP3.4 or pick1 silencing reduced infarct size (TEP3.4: 6.55± 0.85g vs vehicle: 16.73±2.13 or scramble: 16.15±3.43g in scramble) and cardiac troponin I (TEP3.4: 7.62 ±0.83ng/ml vs vehicle: 13.27 ±3.09ng/ml or scramble:15.24 ±4.04ng/ml).Conclusions:TEP3.4 exerts cardioprotection through methylation of pick1 and enhances phagocytosis in infiltrating macrophages. Pick1 downregulation in macrophages enhances phagocytosis and potentiates tissue healing and repair.

Leggi
Ottobre 2022