Circulation, Volume 150, Issue Suppl_1, Page A4144690-A4144690, November 12, 2024. Background:High-density lipoproteins (HDLs) have various potentially beneficial circulatory effects. Apolipoprotein A-1, one of the HDL mimetics, has been shown in several studies to slow the progression of atherosclerosis after an acute coronary syndrome (ACS) event.Aim:To evaluate the comparative efficacy of Apo A1 on Total Atheroma Volume (TAV), Percent Atheroma Volume (PAV), and changes in these parameters.Methods:We systematically searched articles in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase published up to June 2024. Eligible randomized controlled trials (RCTs) enrolled adults who received Apo A1 infusion, compared to placebo, within 2 weeks of an ACS event (defined as unstable angina, non-ST or ST-segment elevation myocardial infarction) or with at least one narrowing of ≥20% on coronary angiography at baseline. Apo A1 infusion preparations evaluated include ETC-216, CER-001, CSL-111, and MDCO-216. Network meta-analysis was performed.Results:A total of 5 RCTs were included in our analysis. Outcomes evaluated include PAV, TAV (measured by intravascular ultrasonography catheter), and changes in these values from baseline to follow-up. For changes in PAV, only ETC-216 45 mg was statistically significant (MD: -12.74, [-20.70; -4.78]). All other regimens were statistically insignificant: ETC-216 15 mg, ETC-216 15 and 45 mg combined, CER-001 3 mg, CER-001 6 mg, CER-001 12 mg, MDCO-216 20 mg, and CSL-111 40 or 80 mg. In addition, changes in TAV showed no significant treatment effects. PAV was lowest at follow-up in the CER-001 3 mg (MD: -1.68, [-4.73; 1.38]) and MDCO-216 20 mg (MD: 1.00, [-3.64; 5.64]) groups; all other ETC-216 and CER-001 regimens were insignificant. For TAV, only MDCO-216 20 mg (MD: -10.00, [-39.58; 19.58]) and CER-001 3 mg (MD: -2.47, [-19.84; 14.90]) showed insignificant treatment effects, while all ETC-216 regimens had no beneficial effect.Conclusion:Our analysis concludes that ETC-216, 45 mg showed a significant reduction in PAV. Other regimens were insignificant in their effect on atheroma reduction. This analysis highlights the need for further clinical trials to explore this regimen for enhancing responses in ACS patients.
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Abstract 4139469: Efficacy of Post-Procedure Voltage Mapping (PPVM) Guided Incremental Ablation Lesions in Improving 1-Year Success and Recurrence-Free Survival for Atrial Fibrillation Ablation
Circulation, Volume 150, Issue Suppl_1, Page A4139469-A4139469, November 12, 2024. Introduction:Pulmonary Vein Isolation (PVI) has become the cornerstone during ablation of Atrial Fibrillation. The primary goal of the procedure is to prevent potential arrhythmogenic triggers from accessing the main left atrial substrate. However, incomplete fibrosis leading to PV reconnection has been identified as the primary reason for AF recurrence. It is unclear whether immediate voltage mapping and additional lesions delivered to areas of residual or recovered voltages will improve the outcome. This study evaluates the 1-year success and long-term recurrence-free survival in patients who underwent post-procedure voltage mapping (PPVM) to identify residual Low-Voltage Areas (LVAs) to guide the delivery of additional ablation lesions.Methods:We analyzed 588 patients who underwent PVI from 2015 to 2023. Of these, 243 had PPVM done to determine LVAs and guide additional ablation lesions. The control arm comprised 345 patients who underwent PVI by the same operators without PPVM. The primary endpoints were 1-year success and longer-term recurrence-free survival. Secondary endpoints were the incidence of complications and the prevalence of LVAs in patients who underwent PPVM.Results:Patients who underwent remapping were older than the control arm (68.3 vs 65.6 years, p = 0.005). There were no other significant differences in baseline characteristics between the two groups. At 1-year follow-up, the success rates were 79% in the treatment arm compared to 72% in the control arm (p = 0.038). Patients in the intervention arm had a recurrence-free survival rate of 65% and 54% at 2 and 4 years, respectively, compared to 62% and 43% in the control arm (p = 0.044). The prevalence of LVAs in the treatment arm was 56.8%. Additionally, complication rates were not increased in the remapping arm (3% vs 8%, p = 0.012).Conclusion:PPVM-guided incremental ablation lesions improve the 1-year success rate and recurrence-free survival at 2 and 4 years compared to traditional PVI without increasing complications due to additional lesion delivery.
Abstract 4141782: Maladaptive alterations in the biomechanics of the post-myocardial scar as a consequence of CD8+ T-cell transfer
Circulation, Volume 150, Issue Suppl_1, Page A4141782-A4141782, November 12, 2024. CD8+T-cells are adverse regulators post myocardial infarction (MI), leading to increased mortality and impaired cardiac function. We hypothesize that CD8+T-cells impair cardiac function by altering scar composition.MI was induced by ligating the left anterior descending coronary artery in C57BL6/J (WT; 3-7 months of age, n≥2/sex) and CD8atm1makmice (CD8-/-; 3-7 months of age, n≥2/sex/treatment). CD8-/-mice were injected with either vehicle or naïve splenic CD8+T-cells (2x106cells/injection) via tail vein, 4 hours post-MI. Infarct tissue was collected post-MI Day 7 and underwent biomechanical, histological, and biochemical analyses. Effects of granzyme (Gzm) A, B, and K on collagen cleavage were tested using a fluorogenic collagen cleavage assay to examine possible mechanisms of scar alteration.Mice lacking CD8+T-cells had improved ejection fraction and decreased dilation (p
Abstract 4125636: Impaired blood pressure regulation in post-COVID-19 postural orthostatic tachycardia syndrome: novel disease mechanisms beyond sinus tachycardia
Circulation, Volume 150, Issue Suppl_1, Page A4125636-A4125636, November 12, 2024. Background:Postural orthostatic tachycardia syndrome (POTS) is a prevalent cardiovascular disorder after COVID-19 infection. Although POTS is characterized by the presence of sinus tachycardia, other hemodynamic disturbances including blood pressure (BP) regulation, remain largely unexplored.Aims:We investigated BP changes using 24-hour ambulatory-BP-monitoring in patients with new-onset POTS after COVID-19 compared with pre-pandemic healthy controls.Methods:We performed a case-control study in 100 verified COVID-19 patients with new-onset POTS (mean age 40.0±12.9 years, 85% women) diagnosed by positive head-up tilt-testing versus 100 healthy controls (mean age 45.0±14.6 years, 70% women) from a population-based cohort with negative active standing test, no history of syncope, orthostatic intolerance, or endocrine disease. We analyzed 24-hour Systolic BP (SBP) and hypotensive SBP episodes (
Abstract 4144651: Association Between Pre-Existing Chronic Total Occlusion and Post-TAVR Pacemaker Implantation: A Retrospective Propensity Matched Analysis
Circulation, Volume 150, Issue Suppl_1, Page A4144651-A4144651, November 12, 2024. Introduction:Post-transcatheter aortic valve replacement (TAVR) pacemaker (PPM) implantation is a known complication. Chronic total occlusion (CTO) of coronary arteries is common in TAVR patients and is a marker of advanced coronary calcification. Its influence on the requirement for PPM post-TAVR remains unclear. We investigated the association between pre-existing CTO and the incidence of PPM post-TAVR.Methods:A retrospective cohort study was conducted using the National Inpatient Sample database from 2018-2020 with 205,565 patients who underwent TAVR. Propensity score matching was utilized to create a matched cohort of patients with and without CTO, balancing key variables such as age, sex, elective procedure status, and comorbid conditions (heart failure, arrhythmias, pulmonary circulation disorders, peripheral vascular disorders, and complicated diabetes). Outcomes measured included the requirement for PPM implantation post-TAVR, in-hospital mortality, and major adverse cardiac events (MACE). Weighted samples were utilized and p-value
Abstract 4141358: Body weight reduction-associated and -unassociated changes in lipid profile in people with obesity, with or without T2D, treated with tirzepatide: post-hoc analysis of SURMOUNT-1 and SURMOUNT-2
Circulation, Volume 150, Issue Suppl_1, Page A4141358-A4141358, November 12, 2024. Background:Tirzepatide is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes (T2D) and obesity. This post hoc analysis evaluated the contribution of body weight reduction-associated and -unassociated effects on the lipid profile of tirzepatide-treated participants living with obesity, without and with T2D, from the SURMOUNT-1 and SURMOUNT-2 clinical trials, respectively.Methods:Participants treated with tirzepatide (pooled doses of 5, 10, 15 mg in SURMOUNT-1 [N=1765] and 10 and 15 mg in SURMOUNT-2 [N=587]) were included in this analysis. The estimated treatment effects and the body weight reduction-associated and -unassociated attribution on changes from baseline in lipid profile (total cholesterol, HDL-C, LDL-C, non-HDL-C, VLDL-C, and triglycerides) at 24 and 72 weeks were assessed via the SAS CAUSALMED procedure.Results:In SURMOUNT-1, after 24 weeks of tirzepatide treatment in participants without T2D, 69-85% of the changes in total cholesterol, HDL-C, LDL-C, and non-HDL-C, and 41-43% of the changes in VLDL-C and triglycerides occurred unassociated with body weight reduction (Table). At 72 weeks, most of the effect on the lipid profile was associated with body weight reduction. In SURMOUNT-2, after 24 weeks of tirzepatide treatment in participants with T2D, most of the changes in the lipid profile occurred unassociated with body weight reduction. At 72 weeks, changes observed in the lipid profile were predominantly associated with body weight reduction, although 43-50% of those changes also occurred unassociated with body weight reduction, except for LDL-C which was almost completely (92%) associated with body weight reduction.Conclusions:In this post hoc analysis from SURMOUNT-1 and SURMOUNT-2, changes in lipid profile were mostly unassociated with body weight reduction after 24 weeks of tirzepatide treatment and associated with of body weight reduction at 72 weeks. Body weight reduction-unassociated mechanisms responsible for the initial changes in lipid profile in participants with obesity treated with tirzepatide warrants further research studies.
Abstract 4140906: Cardiovascular Prognosis in Patients with Diabetes Mellitus Mediated by the Functional Post-revascularization Level
Circulation, Volume 150, Issue Suppl_1, Page A4140906-A4140906, November 12, 2024. Background and Aims:Functional complete revascularization (FCR) subsequent to percutaneous coronary intervention (PCI), as assessed by the residual functional SYNTAX score (rFSS), has been correlated with enhanced prognostic outcomes. This study sought to comprehensively apprehend the adverse cardiovascular prognosis within diabetic cohorts, determining what extent the association of diabetes with clinical outcomes is explained by functional revascularization.Methods:A total of 1,555 patients with available post-PCI quantitative flow ratio (QFR) were included, whose data were collected from PANDA III trial (Figure 1). FCR was defined as rFSS = 0, while anatomic complete revascularization (ACR) was defined as residual SYNTAX score (rSS) = 0. Firstly, we determined the ACR and FCR among DM and non-DM cohorts. Second, multiple cox regression was used to screen for potential mediating variables. Finally, we used structural equation modeling to analysis whether FCR explained the relationship between DM and the risk of 2-year rates of major adverse cardiac events (MACE).Results:Patients with DM had a significant lower percentage of FCR (71.9% vs 80.2%, P
Abstract 4119189: Imaging practices prior to cardioversion in patients presenting post percutaneous left atrial appendage occlusion.
Circulation, Volume 150, Issue Suppl_1, Page A4119189-A4119189, November 12, 2024. Background:Direct current cardioversion (DCCV) carries a risk for stroke in AF patients, for that reason there are guidelines for mitigating this risk in AF patients on oral anticoagulation (OAC). Meanwhile, no consensus on the best approach for cardioverting patients with an appendage occlusion device in situ. This led to a very wide variation in pre and post DCCV practices in these patients.Aims:We aim to explore different factors that might be associated with the variation seen in pre-DCCV imaging practices in patients presenting post- percutaneous LAAO.Methods:This was a multi-center retrospective cohort study of patients who received DCCV for AF or AFL during follow up after LAAO procedure within a single healthcare system from 2016-2024.Results:A total of 119 patients were included, there were more females 70 (59%), with more than half (64 (54%)) receiving a first-generation WATCHMAN™ 2.5, while the rest had WATCHMAN FLX™. Median age at presentation was 77 years (72,82), BMI of 31 kg/m2(26,37), average CHADSVASC score of 4.5 and HASBLED score of 3. A median duration of 10 months (3,21) between LAAO to presentation for DCCV . Forty-four (37%) patients had pre-DCCV imaging (imaging cohort). Number of males was significantly higher in the imaging cohort (24 (54.5%) vs 25 (33.3%), p=0.038), compared to those without imaging. There was a significant difference (p
Abstract 4146276: Conduction Delay Characteristics in the Post-operative Course of the First Porcine-to-Human Cardiac Xenotransplant Recipient
Circulation, Volume 150, Issue Suppl_1, Page A4146276-A4146276, November 12, 2024. Background:The first-ever genetically modified porcine-to-human cardiac xenotransplantation was performed in January 2022 at the University of Maryland, with the recipient surviving 60 days.Aim:Characterize trends in conduction delay observed over the 60-day post-operative course of the first-ever porcine-to-human cardiac xenotransplant recipient.Methods:Daily 12-lead ECGs were evaluated for presence and type of conduction delay. Over the post-operative period, 93 ECGs were obtained. ECGs that could not be assessed for conduction delay due to presence of significant artifact (2 ECGs) or paced rhythm (12 ECGs) were excluded from evaluation.Results:During the 60-day postoperative period, the xenotransplant exhibited alternating conduction block including nonspecific intraventricular conduction delay (NSIVCD), right bundle branch block (RBBB), incomplete RBBB, and left anterior fascicular block (LAFB). Nonspecific intraventricular conduction delay (NSIVCD) was observed on 6 days in total, occurring primarily within the first 9 post-operative days. After day 9, the conduction block alternated between bifascicular block with RBBB+LAFB, incomplete RBBB+LAFB, RBBB, and incomplete RBBB. The predominant pattern of conduction delay was bifascicular block with RBBB+LAFB, occurring over 32 days in this period. Presence of incomplete RBBB+LAFB was noted on 17 days in total. Isolated RBBB occurred on 2 days, and incomplete RBBB on 4 days. There was no evidence of high-grade atrioventricular block observed in this period.Conclusion:Ventricular conduction in the post-operative period of the first porcine-to-human xenotransplant was characterized by an alternating conduction block with NSIVCD in the early postoperative period (through day 9), followed by predominantly bifascicular block with RBBB and LAFB or incomplete RBBB and LAFB. Atrioventricular conduction remained largely intact without evidence of high-grade AV block nor dependence on back-up pacing during the majority of our patient’s post-operative course.
Abstract 4137665: Getting to the Heart of StrokeTM: A Novel American Heart Association Initiative Which Increases Identification of Stroke Etiology and Evidence-Based Post-Stroke Evaluation by Strengthening Cardiology and Neurology Collaboration
Circulation, Volume 150, Issue Suppl_1, Page A4137665-A4137665, November 12, 2024. Background:Nearly one million individuals in the U.S. experience ischemic stroke annually and one-year recurrent stroke risk may exceed 10%. American Heart Association (AHA) Get-With-The-Guidelines-Stroke® Registry (GWTG-S) data suggests that up to 40% of stroke patients are discharged with an undocumented or cryptogenic etiology which may lead to suboptimal secondary prevention. Consequently, improved cardiology and neurology collaboration and evidence-based post-stroke evaluation may help identify stroke etiology, reduce recurrent stroke risk and improve outcomes.Methods:In 2022, the AHA, in collaboration with HCA Healthcare and HCA Healthcare Foundation, designed and launched Getting to the Heart Of StrokeTM(GTTHOS) in 10 HCA Healthcare comprehensive stroke centers to improve: 1) cardiology and neurology stroke care collaboration, 2) evidence-based post-stroke diagnostic evaluation and 3) assessment of social determinants of health and barriers to care. Components included a learning collaborative model, virtual performance improvement consultations, Plan-Do-Study-Acts, multidisciplinary teams, custom and existing GWTG-S metrics and performance improvement feedback.Results:Using existing and custom GWTG-S data, GTTHOS centers increased rates of documented stroke etiology (58.06% vs. 48.63%), while decreasing cryptogenic stroke rates (31.01% vs. 34.89%) and lack of a documented stroke etiology (10.93% vs. 16.48%) (all comparisons on discharge, follow-up vs. baseline, p
Abstract 4145932: Real World Data From A Nationwide Survey: Current Approaches Post Acute Coronary Syndromes By Cardiologists
Circulation, Volume 150, Issue Suppl_1, Page A4145932-A4145932, November 12, 2024. Background:A new ESC guidelines in 2023, the International Lipid Expert Panel (ILEP) 2021 recommendations, and a subsequent statement by EAS have been published based on recent advances in lipid lowering treatments. However, real world data are lacking regarding the implementation among the community of French cardiologists.Objective:To determine the current approach and therapeutic strategies concerning lipid lowering treatments post-acute coronary syndromes in France.Methods:This national survey was performed during October and November 2023 in France with an online questionnaire on the websites of 2 national French Societies of Cardiologists.Four mailings were sent to cardiologists to invite them to answer to the questionnaire. A total of 400 answers of cardiologists were collected during this 2-month period.Results:For ASCVD patients, cardiologists agreed with an LDL-C goal below 55 mg/dL (1.4 mmol/L) in 69%, below 70 mg/dL (1.8 mmol/L) in 16.5%, and 14.5% between 70 mg/dL and 100 mg/dL (1.8-2.5 mmol/L). An upfront lipid lowering combination strategy using fixed dose combination (FDC) of statins and ezetimibe was prescribed in less than 5% of patients, whereas high-intensity statins were prescribed in more than 90% of patients. No significant differences were observed in terms of sex of patients, geographical area, or strategies followed by male and female cardiologists (p > 0.05). A combination of statins and ezetimibe was prescribed only for a minority of patients, especially as an early upfront strategy. The use of PCSK9i remains marginal and the interval between the ACS and initiation of these medicines remains high.Conclusion:In this contemporary national survey, we report an excellent agreement of lipid goals in secondary prevention by cardiologists. Despite the declared consensus recommending a low LDL-C target in ACS patients, lipid lowering strategies are suboptimal, mainly consisting of high intensity statins. The lack of recommended use of ezetimibe and PCSK9i to lower LDL-C levels highlights the importance of better implementation of intensive and early upfront strategies to reduce recurrent ischemic events.
Abstract 4145263: A Novel Multivariate Scoring System for Diagnosing Post-Myocardial Infarction Pericarditis Following Percutaneous Coronary Intervention
Circulation, Volume 150, Issue Suppl_1, Page A4145263-A4145263, November 12, 2024. Introduction:Post-myocardial infarction (MI) pericarditis, particularly after percutaneous coronary intervention (PCI), presents with distinct clinical, laboratory, and electrocardiographic features. Despite its unique presentation, no dedicated diagnostic tools exist for this condition in the post-PCI setting, highlighting the need for a tailored approach. This study aims to develop and validate the first comprehensive clinical scoring system specifically designed to accurately diagnose post-MI pericarditis following PCI, utilizing data available at admission.Methods:In this diagnostic case-control study, we compared 60 patients with confirmed post-PCI pericarditis (verified by echocardiography) from our PCI Registry with 120 control patients with various diagnoses from our hospital database. We evaluated 26 potential predictors, including clinical characteristics, chest pain descriptors, and additional diagnostic tests. Independent predictors for the scoring model were identified using stepwise logistic regression.Results:Among the 17 initial variables associated with pericarditis, five independent predictors were identified: age, chest pain exacerbation with thoracic movement, rising troponin levels, diffuse ST-segment elevation, and C-reactive protein levels. These predictors were incorporated into a scoring system based on their regression coefficients. The model demonstrated excellent discrimination, with a C-statistic of 0.97 (95% CI: 0.93-1.0). A score above 6 points yielded a sensitivity of 95% (95% CI: 85-100) and specificity of 86% (95% CI: 78-93), with positive and negative likelihood ratios of 7.2 (95% CI: 4.2-12) and 0.05 (95% CI: 0.01-0.2), respectively, Figure 1.Conclusion:We have developed the first multivariate scoring system specifically designed to identify post-MI pericarditis in patients undergoing PCI. Its promising accuracy has the potential to enhance early recognition, streamline diagnostic processes, and ultimately improve patient outcomes.
Abstract 4126893: Feasibility and Acceptability of a Nurse-Pharmacist Post-Discharge Telehealth Model of Care for Heart Failure Patients
Circulation, Volume 150, Issue Suppl_1, Page A4126893-A4126893, November 12, 2024. Background:Suboptimal medication management is common in patients with heart failure (HF), particularly during transitions-of-care. To date, there are few studies assessing the feasibility of a nurse-pharmacist post-discharge telehealth service for medication optimisation in patients with HF. We performed a feasibility study to determine service uptake and acceptability, and ability to identify medication-related issues for HF patients as they transition from hospital to home.Methods:HF patients were referred to an existing post-discharge telehealth service and offered medication reconciliation and education in addition to their usual care; a service we termed ‘MedRec’ (MR). Primary outcomes were feasibility, measured through recruitment and successful MR completion, and acceptability, measured by an investigator-developed survey. Secondary outcomes were medication-related issues detected during MR.Results:A total of 100 HF patients were offered a post-discharge MR. Mean age of patients was 68.5 ±14.2 years, and mostly male sex (62%). Pharmacist MRs were requested by 80% of patients. In total 62 MRs (77.5%) were performed; 9 patients declined MR during follow-up and an additional 9 patients were uncontactable. Mean time to MR following nurse referral was 10.98 ±9.74 days. Drug-related toxicity or adverse effect presentation was identified in 25 (40.3%) MR recipients at the time of consultation and subsequently required general practitioner follow-up. Medication compliance issues were detected by the pharmacist in 13 (20.9%) patients; forgotten doses being the most common concern. Undertreated medical conditions, such as symptomatic HF and chronic pain, were identified in 12 (19.3%) MR recipients. Medications prescribed without any apparent indication were found in 8 (12.9%) patients. Drug or disease management information was requested by 35 (56.4%) MR recipients. A total of 35 (56.5%) post-MR surveys were successfully completed. All participants who completed a post-MR survey agreed that a post-discharge telehealth MR was an acceptable form of education provision. Engagement with a pharmacist MR was perceived to ease anxiety associated with understanding medication-related changes and empowered greater medication self-management.Conclusions:A post-discharge nurse-pharmacist telehealth service is a feasible and acceptable model of care. Inclusion of a routine MR post-discharge may be an effective means of maintaining continuity of care for HF patients.
Abstract 4143985: Post-acute Sequelae of COVID-19 (PASC) is Related to Endothelial Dysfunction and Elevated Asymmetric-dimethylarginine
Circulation, Volume 150, Issue Suppl_1, Page A4143985-A4143985, November 12, 2024. Introduction:Endothelial dysfunction can trigger the development and progression of cardiovascular disease. We hypothesize that cardiovascular PASC is induced by persistent endothelial dysfunction mediated via asymmetric-dimethylarginine (ADMA, the endogenous inhibitor of endothelial nitric oxide synthase). ADMA levels rise in response to viral infections, but it is usually degraded by the enzyme DDAH1, which is inhibited by chronic inflammation and oxidative stress. This study aims to determine whether cardiovascular PASC is associated with endothelial dysfunction and to clarify the role of ADMA in this relationship.Methods:We recruited subjects who had been previously infected and developed cardiovascular symptoms (PASC+), those who had been infected but did not have PASC (PASC-), and those who had never been infected (controls) (n=20 each). Groups were matched for age, sex, and BMI and underwent blood draws and fat biopsies. Vascular function was assessedin-vivovia ultrasound imaging andex-vivoin fat-isolated arterioles.Results:Compared to PASC- and controls, PASC+ subjects exhibited 80% higher serum levels of ADMA and 40% reduced nitric oxide levels. DDAH1 activity was elevated in the PASC+, suggesting a compensatory mechanism for the elevated ADMA levels. However, PASC+ obese subjects exhibited substantially lower DDAH1 activity than non-obese subjects, which was associated with lower insulin sensitivity and higher ADMA levels. Compared to the other two groups, the PASC+ group exhibited lower brachial artery vasoreactivity, while nitroglycerin-induced dilation did not differ statistically, suggesting impaired endothelial function. In the PASC+ group, microvascular recruitment in response to reactive hyperemia was diminished, as was the ex vivo measured flow-induced arteriolar dilation and NO generation. Left ventricle (LV) dysfunction was observed in 80% of the PASC+ group, as opposed to 5% of the PASC- and controls. The LV ejection fraction and global longitudinal strain (GLS) were substantially reduced in the PASC+ group, which was correlated with higher ADMA, C-reactive protein, and troponin-1, as well as lower NO and vascular function. Obese PASC+ subjects had the highest ADMA and the lowest endothelial-dependent vasodilation and insulin sensitivity.Conclusion:Cardiovascular PASC symptoms are related to persistent endothelial dysfunction and elevated ADMA levels, which may be further exacerbated by obesity and reduced DDAH1 activity.
Abstract 4138062: Pharmacological inhibition of HDAC6 improves post-infarction cardiac function by limiting mitochondrial fission in type 2 diabetic mice
Circulation, Volume 150, Issue Suppl_1, Page A4138062-A4138062, November 12, 2024. Introduction:Histone deacetylase (HDAC) 6 functions to remove acetyl groups from lysine residues on histone and non-histone proteins. We showed that the augmented activity of HDAC6 in diabetic mice undergoing myocardial ischemia/reperfusion injury (MIRI) was associated with mitochondrial damage. However, it remains unclear how the inhibition of HDAC6 activity affects post-MIRI cardiac remodeling and function in type 2 diabetes.Hypothesis:HDAC6 inhibition suppresses adverse cardiac remodeling and improves mitochondrial dynamics and cardiac function after MIRI in type 2 diabetic mice.Methods:Type 2 diabetic db/db, db/+, and C57BL/6 mice underwent coronary artery occlusion for 20 min followed by reperfusion. Tubastatin A, a selective inhibitor of HDAC6, was injected intraperitoneally 60 min before coronary artery occlusion and once daily after surgery. Mouse hearts were evaluated with echocardiography 28 days after surgery. Myocardium was imaged using electron microscopy, and the expression of mitochondrial dynamin-related protein 1 (DRP1) and fission 1 was measured by Western blotting analysis. H9c2 cardiomyocytes were subjected to hypoxia for 3 hours followed by normoxia for 24 hours in the presence of 5.5- or 25.0-mM D-dextrose and tubastatin A or vehicle.Results:There were no significant differences in the activity of HDAC6, left ventricular diameters and fractional shortening, mitochondrial density volume and surface area, and the ratios of DRP1/GAPDH and fission 1/GAPDH between the db/+ and C57BL/6 groups. Compared to both db/+ and C57BL/6 groups, HDAC6 activity was lower, left ventricular diameters at both end diastole and end systole were longer, fractional shortening and mitochondrial surface area were smaller, and the expression of DRP1 and fission 1 was increased in the db/db group 28 days after MIRI. Interestingly, 10 mg/kg Tubastatin A significantly mitigated these effects of MIRI in db/db mice. Hypoxia/reoxygenation in the presence of 25.0-mM D-dextrose augmented HDAC6 activity and increased the expression of DRP1 and FIS1, which were blocked by Tubastatin A.Conclusions:Tubastatin A prevents post-MIRI cardiac remodeling and improves cardiac function by limiting mitochondrial fission in type 2 diabetic mice.
Abstract 4138964: Longer AF Diagnosis-to-Ablation Time is Associated with AF Inducibility Post-Pulmonary Vein Isolation
Circulation, Volume 150, Issue Suppl_1, Page A4138964-A4138964, November 12, 2024. Background:Post-ablation atrial fibrillation (AF) inducibility has been associated with AF recurrence and is often used as an endpoint for Pulmonary Vein Isolation (PVI). Little is known regarding factors affecting inducibility after PVI, as AF inducibility is common even after PV isolation. Prolonged episodes of untreated AF can result in remodeling of the atrium and the formation of new arrhythmogenic substrate, which may make treatment of AF more challenging. We hypothesized that longer diagnosis-to-ablation time (DAT) is associated with higher rates of post-PVI AF inducibility.Objective:To evaluate DATs in cases of inducible vs. non-inducible AF post ablation.Methods:A single-center, retrospective analysis of 168 consecutive patients who underwent 1sttime PVI between 1/1/2022 and 12/01/2023 was performed. Following PVI, inducibility of AF was tested by programmed stimulation using decremental pacing in 50ms windows for 10 seconds each (from 400 ms down to 200 ms or until loss of 1:1 atrial capture). Results were categorized by type of rhythm induced (non-inducible, AF) and duration (sustained, non-sustained). DAT was obtained from review of the medical records. Descriptive statistics were used to compare demographics and AF type, and parametric and non-parametric tests were used for analysis of the diagnosis-to-ablation window and its relationship to inducibility.Results:There was no difference in demographic data or AF type between the two groups. 85 patients (50.6%), had no inducible AF. 83 out of 168 cases (49.4%) had inducible sustained AF. Overall DATs ranged from 0 to 40 years. DAT was significantly higher in the inducible vs. non-inducible groups (3.810 vs. 2.906 years, p=0.023).Conclusion:Longer DAT is associated with AF inducibility post-PVI despite successful ablation. This association may reflect the increased persistence of AF as it progresses over time. Future studies are needed to evaluate the clinical implications of DAT times.