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
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Abstract 14991: Local Prolongation of Repolarization Prevents Post Myocardial Infarction Ventricular Tachycardia
Circulation, Volume 146, Issue Suppl_1, Page A14991-A14991, November 8, 2022. Introduction:Reentry is the predominant mechanism underlying ventricular arrhythmias in chronic myocardial infarction patients. Reentry can be prevented by prolonging effective refractory period, thereby blocking reexcitation of recently activated tissue. This is currently achieved with systemically administered class III antiarrhythmic drugs. These therapies are limited by their risk of provoking ventricular arrhythmias by off-target effects.Hypothesis:Local prolongation of repolarization in healthy myocardium adjacent to the exit site attenuates reentry and postinfarction arrhythmias.Method and results:We used a pig model and generated myocardial infarction by balloon occlusion of the left anterior descending coronary artery and performed epicardial mapping 6 weeks later during Langendorff-perfusion. Programmed stimulation induced reentry leading to ventricular premature beats and sustained ventricular tachycardia (VT). Local injection of Sotalol adjacent to the infarcted myocardium prolonged repolarization and prevented VT after programmed stimulation. To translate these experimental findings to the patient situation we used a virtual heart based on data from a patient suffering from postmyocardial infarction VTs. The patient underwent pre-ablation cardiac late gadolinium enhanced- magnetic resonance imaging followed by geometrical reconstruction of the left ventricle and computational electrophysiological modelling of VT induction. We used a rapid pacing protocol to induce VT and determined the site where the activation front exited the infarct zone and reactivated the adjacent normal myocardium. Next, we prolonged repolarization of the normal myocardium adjacent to the exit site with 50 ms and performed rapid pacing to induce VT. This only resulted in a single premature ventricular beat after which sinus rhythm restored.Conclusion:Our experimental andin silicofindings show the potential of local prolongation of repolarization a novel potentially genetic anti-arrhythmic therapy in post-infarction patients.
Abstract 14979: MicroRNA-342-3p Regulates Post-Ischemic Angiogenesis in Diabetic Mice
Circulation, Volume 146, Issue Suppl_1, Page A14979-A14979, November 8, 2022. Introduction:Diabetic patients are more likely to suffer from adverse cardiovascular events such as myocardial infarction (MI) compared to non-diabetics. Angiogenesis is crucial to limiting infarct size. However, this angiogenic response is blunted in patients with diabetes. MicroRNAs (miRNAs) have been shown to affect both physiological and pathological angiogenesis. However, the role of miRNAs in MI-associated angiogenesis in diabetes remains poorly defined. Here, we describe a novel role of miRNA-342-3p in angiogenesis following ischemic injury to the myocardium.Methods:We performed RNA sequencing on cardiac endothelial cells of Ldlr-deficient mice on either chow or high fat sucrose containing (HFSC) diet at 0-, 3-, 7- and 14-days post-MI. Gain and loss of function studies, functional assays, RNA-seq, bioinformatics, RNA-FISH, and light-sheet microscopy were used to ascertain the function and mechanism of this miRNA.Results:miR-342-3p was upregulated in cardiac ECs during the vascular remodeling phase post-MI in chow-fed mice compared to the HFSC-fed group. Overexpression of miR-342-3p promotes the number of endothelial sprouts (140% vs control), cumulative sprout length (311% vs control) and scratch closure (AUC 83% vs control, p
Abstract 13040: Insulin-Like Growth Factor-1 Upregulates Larp6 via Translational and Post-Translational Mechanisms in Vascular Smooth Muscle Cells, Leading to Elevated Collagen Production
Circulation, Volume 146, Issue Suppl_1, Page A13040-A13040, November 8, 2022. Introduction:Collagen content in atherosclerotic plaque is a hallmark of plaque stability. We have shown that insulin-like growth factor-1 (IGF1) increased collagen content in atherosclerotic plaques of Apoe-/-mice. We have identified LARP6 (La Ribonucleoprotein Domain Family, Member 6), a type I collagen mRNA-binding protein, as a mediator of IGF1-dependent type I collagen upregulation and increased mature fibril formation by smooth muscle cells (SMC), however specific mechanism has not been elucidated yet.Methods and Results:Micro-RNAs, including miR-1976 have been shown to bind to LARP6 mRNA. We found that SMC treatment with IGF1 significantly downregulated miR-1976 by 41±5% after 3h (P<0.05), consistent with the IGF1-induced LARP6 upregulation. In fact, miR-1976 mimic (20 nM) decreased LARP6 by 67% (P<0.05) and reduced type I procollagen protein levels by 85% (P<0.05). MiR-1976 mimic inhibits IGF1-induced LARP6 upregulation showing miR-1976 involvement in IGF1 effect on LARP6. It has been reported that LARP6-mediated promotion of procollagen synthesis may be regulated by phosphorylation of LARP6, therefore we investigated whether IGF1 induces LARP6 phosphorylation in cultured human aortic SMCs. For this experiment, SMCs were serum-starved and treated for 0-48h with 10 ng/mL IGF1. LARP6 protein was detected by immunoblots as a single 67kDa band in untreated SMC. However, after 6h of IGF1 treatment there was additional phosphorylated LARP6 band detected at 70 kDa. The levels of 70kDa LARP6 time-dependently increased up to 18h of treatment, with a concomitant increase of type I procollagen and collagen expression levels.Conclusions:In summary, our data suggests that (i) IGF1 downregulates miR-1976, thereby increasing LARP6 expression levels and (ii) IGF1 induces phosphorylation of LARP6, thereby promoting LARP6 activity. Our study revealed novel mechanisms underlying IGF1-induced type I collagen upregulation in vascular SMC and potentially in atherosclerotic plaques.
Abstract 12333: Therapeutic Window of Low-Dose Prasugrel for Platelet Reactivity in the Chronic Phase of Post-Percutaneous Coronary Intervention: The Chaperon Study
Circulation, Volume 146, Issue Suppl_1, Page A12333-A12333, November 8, 2022. Introduction:There are many reports on the effects of on-treatment platelet reactivity using P2Y12reaction units (PRU) on the ischemic or bleeding risk in patients who underwent percutaneous coronary intervention (PCI). However, there was little report including low-dose prasugrel (2.5mg).Hypothesis:We assumed that low-dose prasugrel use may contribute to the effectiveness and safety in the chronic phase of PCI in Japanese patients.Methods:This prospective observational study included 398 patients who underwent PCI between 2017 and 2018 (mean age: 68±11 years, male: 83%). Serial PRU measurements were performed; the baseline was at 6 to 12 months after PCI, and the follow-up was after 6 months later. The PRU was measured by the VerifyNow® P2Y12assay, and we assessed the distribution of PRU in each P2Y12inhibitor, after defined PRU 86 to 238 as therapeutic window.Results:Among 398 patients, the follow-up PRU was obtained in 360 patients (90%), and 80 patients (22%) were taking prasugrel 2.5mg. The baseline PRUs of clopidogrel 75mg, prasugrel 3.75mg, and prasugrel 2.5mg were 175±64, 147±55, and 154±66, respectively (p
Abstract 11044: Neither Peak Donor Troponin Nor Donor Troponin Trends Adversely Impact Post-Transplant Outcomes in Pediatric Heart Transplantation
Circulation, Volume 146, Issue Suppl_1, Page A11044-A11044, November 8, 2022. Introduction:Cardiac troponin is utilized in decision making when considering a suitable donor for heart transplant (HT). To date, no pediatric study has assessed the impact of peak donor troponin or donor troponin trends on post-HT survival.Methods:All children in the Organ Procurement and Transplantation Network database undergoing HT in the U.S. from 2007 – 2020 and with donor troponin I levels recorded were included. Donors were divided into groups based on peak troponin value:Low(0-20% increase,Persistently high:initial and final troponin high;Persistentlylow:initial and final troponin normal;Decreasing: >20% decrease. Donor characteristics were compared and effects of donor troponin on graft survival were evaluated both unadjusted and after multivariable adjustment using Cox proportional hazards model.Results:Of 5569 HT, troponin levels were available for 4572 (82%) recipients. Compared to donors withLowandMediumtroponin values, donors withHightroponin values were older (median age 3 vs. 7 vs. 13 years), male (59.2 vs. 59.5 vs. 64.7%), White (50.3 vs. 52.4 vs. 55.5%), died from anoxia (33.5 vs. 41.1 vs. 48.9%), with ejection fraction ≤55% (4.2 vs. 6.4 vs. 8.7%) and receive cardiopulmonary resuscitation [CPR] (44.3 vs. 53.7 vs. 63.3%) (p
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.
Abstract 9737: Association of Endogenous Sex Hormone Levels and Myocardial Fibrosis in Men and Post-menopausal Women: The Multi-Ethnic Study of Atherosclerosis
Circulation, Volume 146, Issue Suppl_1, Page A9737-A9737, November 8, 2022. Introduction:Endogenous sex hormone(ESH) imbalances have been linked to a higher risk of heart failure in men and post-menopausal women(PMW). However, experimental studies have found conflicting results regarding ESH’ response to myocardial fibrosis(MF).Hypothesis:We hypothesize that at baseline, men and PMW with abnormal ESH profiles will have higher rates of MF measured by CMR T1 mapping and higher rates of myocardial scar detected by CMR during a ten-year follow up.Methods:A total of 1,276 men and 1,048 PMW were included in the MESA with ESH measured at baseline and had undergone CMR 10 years later. All analyses were stratified by sex and age groups (Table1A-B). Multivariable linear regression models were constructed to assess the associations of baseline ESH, ECV, and nativeT1 time. Multivariable logistic regression models were built to determine the associations of baseline ESH and myocardial scar among men.Results:Each 1-SD increment higher free and bioavailable testosterone in older men (≥65) was associated with 2.5% (p=0.008) and 1.0%(p=0.08) lower ECV, respectively, and 21.5%(p=0.03) and13.4%lower native T1(p=0.02). A 1-SD increment greater SHBG level was associated with 2%(p=0.01) higher ECV and 12% higher native T1 (p=0.08)(Table1A). Among post-menopausal women of 44-54 years, a 1-SD increment higher free testosterone was associated with 14% greater native T1 only; however, those between 55-64 years, a 1-SD increment higher total testosterone was associated with 9% lower native T1 (Table1B). Higher levels of estradiol in older men (≥65 years) were independently associated with a significantly higher odds of having a myocardial scar (OR:4.10,95%CI:1.35-12.40;p=0.01).Conclusions:Among older men, lower free testosterone and higher levels of estradiol were independently associated with CMR-defined interstitial MF and replacement fibrosis, respectively. There was no consistent association between ESH and interstitial MF among PMW.
Abstract 126: The Association Of Higher Or Lower Mean Arterial Pressure On Kidney Function After Cardiac Arrest: A Post-hoc Analysis Of The Comacare And Neuroprotect Trials
Circulation, Volume 146, Issue Suppl_1, Page A126-A126, November 8, 2022. Introduction:Acute kidney injury (AKI) denotes a sudden reduction in kidney function manifested by a rise in S-creatine levels and reduced urine output. Studies have suggested an association between AKI severity and outcomes after OHCA. Various criteria have been used to define AKI, the Kidney Disease Improving Global Outcomes (KDIGO) published in 2012 being the currently used tool. AKI is a feature of post-cardiac arrest syndrome.During post-CA syndrome, possible causes of renal damage are direct renal ischaemic-reperfusion injury and indirect renal damage characterized by the activation of inflammatory and coagulation pathways. Although the overall mortality rate after CA mainly relates to hypoxic-ischaemic brain injury, damage to other organs also has prognostic implications.Methods:Pooled post-hoc analysis of the COMACARE (NCT02698917) and NEUROPROTECT (NCT02541591) trials that randomized patients to lower (MAP 65-70 mmHg) or higher (MAP 80-100 mmHg) targets for the first 36 hours of post-CA intensive care. Kidney function was categorised using the KDIGO classification during the first five days after OHCA. We used Cox regression analysis to identify factors associated with AKI after OHCA.Results:A total of 227 patients were included: 115 in the high MAP group and 112 in the low MAP group. Eighty-six (38%) patients developed AKI during the first five days; 40 (47%) patients had AKI in the high MAP group and 46 (54%) in the low MAP group (p = 0.51). The mean creatinine and mean daily diuresis were 104 (95% CI 94-115) μmol/l and 1989 (95% CI 1829-2150) mL/day in the high MAP group and 111 (95% CI 99-122) μmol/l and 1677 (95% CI 1530-1824) mL/day in the low MAP group. In a Cox regression model, independent AKI predictors were previous hypertension (HR 1.72; 95% CI 1.07-2.78; p = 0.03), bystander cardiopulmonary resuscitation (hazard ratio [HR] 0.46; 95% CI 0.29-0.73; p < 0.01), shockable initial rhythm (HR 0.36; 95% CI 0.21-0.61; p ≤ 0.01), and time to ROSC (HR 1.04; 95% CI 1.02-1.06; p < 0.01) whereas high/low MAP was not an independent predictor of AKI.Conclusions:KDIGO1-staged AKI is common after CA and is associated with previous hypertension and CA factors. Targeting higher MAP after CA does not appear to influence the development of AKI.
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.
Abstract 15633: Differences in Atrial Fibrillation Symptoms Post-Ablation by Age
Circulation, Volume 146, Issue Suppl_1, Page A15633-A15633, November 8, 2022. Introduction:The prevalence of atrial fibrillation (AF) increases with age. Although catheter ablation is a recommended treatment for AF and is safe and effective in older adults, symptom outcomes post-ablation have not been well studied among older adults. The objective of this study was to investigate differences in the prevalence of symptoms post-ablation and the need for repeat ablation by age group.Methods:From electronic health records, we used International Classification of Diseases billion codes to identify all patients with an admitting diagnosis of paroxysmal AF who were treated at NewYork-Presbyterian Hospital between 2010 and 2020. We then used Current Procedural Terminology Codes to identify patients who underwent catheter ablation. We extracted age, gender, race, ethnicity, and prevalence of repeat ablations using structured queries. We extracted symptoms post-ablation from unstructured clinical notes using natural language processing. We separated patients into five age groups and evaluated associations between demographics, symptoms, repeat ablations and age group using Chi-square tests.Results:Of the 1,414 patients studied, 34.4% were female and 58.6% were white, and 4.1% were Hispanic or Latino. Significantly more female patients were age 61-80, and significantly more non-White participants were age 51-70, compared to other age groups. There was a clinically but not statistically significant difference in the prevalence of repeat ablations by age, with nearly half of those with repeat ablations being age 61-70. There were no significant differences in symptom prevalence 6 and 12 months post-ablation.Conclusion:A greater proportion of female and non-White patients undergoing ablation are older adults compared to younger or much older ( >80 years) patients. There were no differences in repeat post-ablation symptoms by age, suggesting older adults may experience similar symptom reduction following ablations as younger adults.
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.
Abstract 107: Systemic Allogeneic Mesenchymal Stem Cell Administration Does Not Attenuate Early Post-resuscitation Brain Injury Or Inflammation In A Porcine Model Of Cardiac Arrest
Circulation, Volume 146, Issue Suppl_1, Page A107-A107, November 8, 2022. Introduction:Based on emerging evidence that systemic inflammation exacerbates post-resuscitation organ injury, we recently tested the efficacy of allogeneic mesenchymal stem cell (MSC) administration early after return of spontaneous circulation (ROSC) in a porcine model of cardiac arrest (CA). Initial results indicate that MSCs attenuate post-ROSC cardiac dysfunction, but it is unclear if these protective effects extend to the brain. Accordingly, we aimed to determine if systemic allogeneic MSCs reduce early post-ROSC brain injury and inflammation in swine.Methods:Swine (n=33) were subjected to 10 min CA followed by mechanical CPR with defibrillation and epinephrine (EPI; 0.015 mg/kg iv). Animals that achieved ROSC (n=19) were blindly randomized to intra-arterial saline (n=9) or allogeneic bone marrow-derived MSCs (55±2 x 106; n=10) 30 min post-ROSC. Blood sampling was performed for 4 hours post-ROSC to quantify serum neurofilament light chain (NFL) levels, after which brain tissue was collected for post-mortem quantification of regional neuronal injury (H&E), activated microglia (IBA-1), and inflammatory gene expression (PCR) vs. healthy control swine (n=8).Results:Animals resuscitated from CA exhibited a significant increase in neuronal injury throughout the brain vs. controls that was not affected by MSC treatment (A). Similarly, the post-ROSC rise in serum NFL was not different between saline-treated and MSC-treated animals (2.5±0.6 vs. 2.5±0.8 fold-change vs. baseline; p=0.94). A significant increase in activated microglia (B) and inflammatory gene expression (C) was observed throughout the brain in both CA groups vs. healthy controls, with particularly prominent changes in the striatum but no notable differences between treatment groups.Conclusions:Despite favorable effects on the heart, systemic allogeneic MSC therapy after ROSC does not significantly affect early markers of brain injury and inflammation in a porcine model of CA.
Abstract 13551: Non-Invasive Assessment of Systemic Microvascular Function in Patients With Severe Aortic Stenosis Pre- and Post- Transcatheter Aortic Valve Intervention
Circulation, Volume 146, Issue Suppl_1, Page A13551-A13551, November 8, 2022. Background:Aortic stenosis (AS) is associated with pathophysiological changes in both left ventricular and coronary microvascular structure and function. The treatment of AS with transcatheter aortic valve replacement (TAVR) has been associated with improvements in invasive indices of coronary microvascular function. This study sought to address whether systemic microvascular dysfunction was present in patients with AS and if microvascular function was altered by treatment of aortic stenosis with TAVR. The conjunctival microcirculation was used as the site for the non-invasive assessment of systemic microvascular function.Methods:Patients undergoing TAVR for the treatment of severe AS were compared to a cohort of age- and sex-matched controls without valvular heart disease. Conjunctival vascular imaging was performed in all subjects using a previously validated combination of a smartphone and slit-lamp biomicroscope. This technique allowed measurement of vessel diameter and other indices of microvascular function by tracking erythrocyte motion. Conjunctival hemodynamics were compared pre- and post-TAVR, in addition to between the severe AS and control cohorts.Results:A total of 165 patients were included (90 severe AS and 75 controls). Baseline characteristics were well matched between groups. In comparison to the control cohort, arteriole axial (Va) and cross-sectional velocity (Vcs) were significantly lower in females with AS (Va severe AS 0.53 ± 0.11mm/s vs control 0.59 ± 0.12mm/s, p=0.047; Vcs severe AS 0.38 ± 0.07mm/s vs control 0.41 ± 0.08mm/s, p=0.043), but not in males (Va severe AS 0.61 ± 0.11mm/s vs control 0.58 ± 0.10mm/s, p=0.19; Vcs severe AS 0.43 ± 0.08mm/s vs control 0.41 ± 0.07mm/s, p=0.20). Arteriole Va and Vcs significantly increased following TAVR in females (Va Pre-TAVR 0.52 ± 0.16mm/s vs post-TAVR 0.59 ± 0.15mm/s, p
Abstract 10824: Pulsatile Ventricular Assist Device Prior to Pediatric Heart Transplantation is Associated With Favorable Post-Transplant Hemodynamics
Circulation, Volume 146, Issue Suppl_1, Page A10824-A10824, November 8, 2022. Background:Ventricular assist device (VAD) support is increasingly used in end-stage pediatric heart failure management. The effects of pulsatile VAD (PVAD) and continuous-flow VAD (CVAD) support on hemodynamics (HDS) after pediatric heart transplant (HT) are unknown. We compared the difference in post-HT HDS between patients supported with PVAD vs CVAD.Methods:We collected measures of pulmonary vascular resistance index (PVRi), cardiac index (CI), and pulmonary wedge pressure (PCWP) in the 1styear post-HT among patients that underwent HT at our institution between 2013-2020. We defined normal HDS as a PVRi < 3Wu/m2, CI > 2.5L/min/m2, and PCWP < 12mmHg. Linear regression analysis and Cox regression were performed to compare differences in HDS post-HT.Results:Demographics/clinical features of the patients supported with PVAD (n=18) and CVAD (n=41)are described in Table 1. PVR, CI, and PCWP are plotted in Figure 1. Accounting for confounders, the mean PCWP over the 1styear is lower in the PVAD group (-0.83 [-1.72-0.07], p=0.07) while the mean CI and mean PVR are similar. In the PVAD cohort, 16 (89%) had normalized HDS in the 1st year vs 17 (42%) in the CVAD group (Log Rank: p
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.