Circulation, Volume 150, Issue Suppl_1, Page A4135852-A4135852, November 12, 2024. Background:Vertebrobasilar artery stenosis (VBAS) can cause posterior circulation strokes (PCS). Optimal management is controversial, with options including medical therapy (MT), endovascular stenting (ES), and surgical revascularization (SR). This study compares outcomes of these treatments and evaluates the correlation between clinical features and medical history with 30-day outcome.Methods:Patients with VBAS were identified from the 2017-2018 National Inpatient Sample (NIS). Propensity scores adjusted for baseline differences. Outcomes included mortality, neurological complications (NC), discharge destination (DD), length of stay (LOS), total charges (TC), and procedural complications (PC). Predictive ability of clinical variables was assessed using logistic regression (LR) and machine learning techniques (MLT).Results:Of 1,343 patients, 1,061 (79.0%) received NI, 234 (17.4%) underwent ES, and 24 (1.8%) had SR. Mean age was 69.45 years, with 64.1% male. Demographics: 69.8% White, 14.9% Black, 10.0% Hispanic, and 5.3% other races. Hypertension (HTN, 85.4%) and diabetes (DM, 18.9%) were prevalent. After propensity weighting, ES was associated with higher odds of mortality, surgical/medical complications (SMC), and device/graft complications (DGC) compared to NI. SR showed a non-significant trend toward higher non-home discharges (NHD). ES and SR groups had higher resource utilization with longer LOS and greater TC. Clinical variables alone were weak predictors, with AUC values ranging from 0.454 to 0.71 across different outcomes and models.Conclusion:ES of VBAS was associated with higher mortality and complication rates compared to MT alone, with inconsistent benefits for NC. SR also carried elevated risks without clear advantages over MT. These results support that current clinical independent variables from the NIS are weak predictors. This highlights the limitation of the database in relying solely on clinical and medical history, and suggests that future use of radiological and anatomical features can improve predictions of outcomes and determination of subgroups that can benefit from certain treatment. More studies should be conducted, including post hoc analyses based on radiological and anatomical features, to better inform treatment decisions and determine subgroups that can benefit from intervention or surgery. These findings suggest a need for judicious patient selection and reinforce the role of optimal MT.
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Abstract 4146283: Infrequent Cognitive Assessments in CABG Trials (from 2005-2023) Highlight Need for Improved Strategies for Cognitive Screening post-coronary bypass grafting (CABG) surgery
Circulation, Volume 150, Issue Suppl_1, Page A4146283-A4146283, November 12, 2024. Objective:The incidence of cognitive decline following coronary artery bypass grafting (CABG) is well-documented, significantly impacting patient morbidity, mortality, and quality of life. We conducted a systematic review that examines cognitive outcomes in CABG randomized controlled trials (RCTs) to identify which cognitive assessments were used, their administration frequency, attrition rates, and their effectiveness in detecting perioperative cognitive changes in control groups.Methods:We conducted a search of MEDLINE, EMBASE, Cochrane Library, and PsycINFO for CABG RCTs that included cognitive assessments, from January 2005 to December 2023. Descriptive statistics were used to summarize the frequency, domains, and attrition rates of each cognitive task. For tasks assessed both pre- and post-operatively in at least three RCTs, control group scores and standard deviations were reported.Results:Out of 3337 screened studies, 2163 were CABG RCTs, and only 69 (3.2%) included cognitive evaluations (Figure 1). These trials involved 15,839 subjects (79% male, mean age 64.4, median follow-up time 90 days) and used 145 unique cognitive tasks. The Trailmaking Test Part B (40/69; 58.0%) and Part A (38/69; 55.0%) were the most frequently used. Only 7 tasks had means and standard deviations reported before and after surgery in more than three RCTs, and none detected significant pre- to post-operative changes. Attrition rates averaged 19.3%, with a wide range from 0% to 62%. Figure 2 demonstrates the decline in cognitive assessments in CABG trials over the years, with a sharp decline after 2014. Trials that assessed cogntion after 2014 tended to favor screening tasks (MMSE/MoCA) alone.Conclusion:Cognitive assessments are infrequent in CABG trials, and existing tests fail to consistently detect cognitive changes. To effectively evaluate and address cognitive impact after CABG, new assessment strategies that are resilient to attrition and practical for use in diverse trial settings are needed.
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 4136346: A Comparative Analysis of Esophageal Cooling for Preventing Esophageal Injury Post Atrial Fibrillation Catheter Ablation: A Systematic Review and Meta-analysis
Circulation, Volume 150, Issue Suppl_1, Page A4136346-A4136346, November 12, 2024. Introduction:Thermal injury following atrial fibrillation catheter ablation is a rare but fatal complication. We aim to assess the safety profile of different forms of esophageal cooling methods versus standards of care.Methods:We searched PubMed, Cochrane Library, Scopus, and Web of Science databases for randomized controlled trials and cohort studies comparing esophageal cooling to Luminal esophageal temperature (LET) monitoring regarding esophageal thermal lesions (ETL) post atrial fibrillation ablation. Case reports, case series, reviews, conference abstracts and animal studies were excluded. Review manager software (version 5.4) was used to perform the meta-analysis.Results:We included 10 studies with 25662 patients in total: 14515 patients in the esophageal cooling group and 11147 patients in the LET group. Overall esophageal lesion analysis demonstrated no statistically significant difference between the esophageal cooling group and LET (RR = 0.72, 95% CI = 0.35 to 1.49, p-value = 0.38). Subgroup analysis showed no statistically significant difference for mild/moderate lesions (RR = 1.52, 95% CI = 0.80 to 2.90, p-value = 0.20). However, the subgroup analysis showed a statistically significant association between esophageal cooling and decreased severity of esophageal lesions compared with LET (RR = 0.29, 95% CI = 0.12 to 0.71, p-value = 0.007). Regarding AF recurrence, the pooled analysis showed no statistically significant difference between esophageal cooling group and LET (RR = 1.24, 95% CI = 0.95 to 1.61, p-value = 0.11).Conclusion:In patients undergoing AF catheter ablation, the implementation of esophageal cooling showed statistical significance in decreasing the severity of esophageal lesions compared to the LET group. Also, esophageal cooling demonstrated non-inferiority in AF recurrence compared to LET. Future research should focus on assessing the long-term effects of esophageal cooling during AF catheter ablation.
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 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 4141719: Gender Differences in Bleeding Risk and Mortality Following Dual Antiplatelet Therapy Post-Percutaneous Coronary Intervention: A Meta-Analysis
Circulation, Volume 150, Issue Suppl_1, Page A4141719-A4141719, November 12, 2024. Background:Dual antiplatelet therapy (DAPT) is widely used following percutaneous coronary intervention (PCI), but it can be associated with bleeding events and adverse outcomes during therapy. This study aims to perform a gender-based analysis of the bleeding risk and mortality associated with DAPT following PCI.Methods:On May 15, 2024, we searched the following databases: PubMed, Embase and Cochrane. Our inclusion criteria included any trial or cohort that performed a gender-based analysis of bleeding and mortality outcomes in patients taking DAPT post-PCI. Our outcomes were all-cause mortality, cardiac mortality, and bleeding risk. Bleeding risk was assessed using the Bleeding Academic Research Consortium (BARC) classification, and Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria. We used RevMan with a random-effects model to calculate the effect size, using odds ratios (OR) with a 95% confidence interval.Results:Out of the 1,865 articles searched, only 26 papers were eligible for inclusion and analysis. Nine were randomized controlled trials, and 17 were observational cohorts. The total number of patients was 267,986, of which 203,524 were male and 64,436 were female. There was no significant difference in cardiac mortality between males and females; the OR was 0.88 (95% CI: 0.71-1.08, P=0.22). All-cause mortality was reduced in males compared to females, with an OR of 0.81 (95% CI 0.71-0.92, p=0.002). The BRAC 2-5 classification was less likely in males compared to females, with an OR of 0.81 (95% CI: 0.70-0.94, p=0.005). Similarly, in the BRAC 3-5 classification, there was a significant lower probability of bleeding in male compared to female (OR 0.65, 95% CI: 0.52-0.82, p=0.0002). TIMI major bleeding classification was lower in males compared to females, with an OR of 0.61 (95% CI: 0.42-0.88, p = 0.009). This indicates higher rates of major bleeding in females compared to males; and Similar findings were also observed with TIMI minor (OR 0.65, 95% CI: 0.46-0.92, p=0.01).Conclusions:These findings highlight the disparities in clinical outcomes of dual antiplatelet therapy following PCI. Females had higher rates of significant bleeding events and all-cause mortality compared to males. This underscores the necessity of investigating the underlying mechanisms driving this gap, emphasizing the need for further research in order to understand and address these differences.
Abstract 4142740: O2-independent photodynamic neuroimmune modulation for prevention and treatment of malignant arrhythmia post myocardial infarction
Circulation, Volume 150, Issue Suppl_1, Page A4142740-A4142740, November 12, 2024. Background:Hyperactivation of the left stellate ganglion (LSG) is a key link in the occurrence of ventricular arrhythmias after myocardial infarction (MI). It is reported that neuroimmune interaction based on the depleting of macrophages modulated the overactive neural activity. However, exogenous macrophage scavengers, which is the common depletion strategy in animal models, are hardly capable of depleting the target cells selectively in certain tissues and transient control performance. Consequently, a degradable nanocomposite (PPSM@CS/DSS) were fabricatedto deplete M1 macrophages selectively in LSG and further inhibit the overactive LSG neural activity after myocardial infarction.Hypothesis:In this study, we constructed a degradable nanocomposite with dual functions of targeting M1 macrophages and oxygen-independent PDT-mediated neuroimmune modulation, which isanticipated to deplete M1 macrophages selectively in LSG and further inhibit the overactive LSG neural activity after myocardial infarctionfor prevention and treatment of ventricular arrhythmias post MI.Methods:The prepared nanocomposite material, which is capable of targeting M1 macrophages and oxygen-independent PDT-mediated neuroimmune modulation, was slowly microinjected into LSG of Beagle dogs. The effectiveness and safety of this method based on apoptosisof M1 macrophagesby oxidizing active species was explored and the mechanism of prevention as well as treatment of malignant arrhythmias were discussed. M1 macrophages were selectively apoptotic in the LSG after myocardial infarction under the irradiation of near infrared light.Results:PPSM@CS/DSS is a core-shell structure with a particle size of about 50nm. The PPSM@CS/DSS nanocomposites exhibits band adsorption between 200-900 nm with a pronounced peaks at 650 nm.Cell experiments showed that PPSM@CS/DS was targeted and mainly induced apoptosis of M1 macrophages under 650nm near-red light, but did not significantly increase apoptosis of neuronal cells. PPSM@CS/DSS significantly reduced LSG activity and the incidence of malignant arrhythmias after MI in Beagle dogs under the action of 650nm light.Conclusion:An innovative nanomaterial for regulating LSG through depletion M1 macrophages selectively in LSG is developed to prevent and treat malignant arrhythmias after myocardial infarction.The implementation of this work will provide a novel neural modulation strategy for preventing ventricular arrhythmias.
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 4140204: Relationship of Oxidized Phospholipids and Lp(a) to Outcomes after Acute Coronary Syndrome: A Post Hoc Analysis of the ODYSSEY OUTCOMES Trial
Circulation, Volume 150, Issue Suppl_1, Page A4140204-A4140204, November 12, 2024. Background:Oxidized phospholipids (OxPL) are preferentially carried by and contribute to the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPL can be quantitated on all apolipoprotein B-100 containing lipoproteins (OxPL-apoB), a dominant proportion of which are present on Lp(a) particles.Objectives:To assess the effect of PCSK9 inhibition by alirocumab on plasma levels of OxPL-apoB, and the relationship to Lp(a) and major adverse cardiovascular events (MACE) in patients with a recent acute coronary syndrome (ACS) on optimized statin treatment.Methods:OxPL-apoB (Diazyme, Inc) and Lp(a) (TinaQuant, Roche Diagnostics) were measured at baseline (1-12 months after ACS) in a subset of participants in the ODYSSEY OUTCOMES trial with samples available at baseline (prior to randomization to alirocumab or placebo, n=11,630) and log2-transformed. Proportional hazards models adjusted for 12 baseline covariates evaluated the association of predictor variables (OxPL-apoB and Lp(a)) with MACE (coronary heart disease death, non-fatal MI, ischemic stroke, and hospitalized unstable angina) and all-cause death, with HRs for doubling of the predictor variable.Results:Baseline OxPL-apoB correlated with Lp(a) (r=0.68, p
Abstract 4145409: Detection and Significance of Nonsustained Ventricular Tachycardia in a Post-stroke Population
Circulation, Volume 150, Issue Suppl_1, Page A4145409-A4145409, November 12, 2024. Introduction / Background:Clinical guidelines emphasize cardiac rhythm monitoring in post-stroke patients (pts) for detecting atrial fibrillation. Limited studies have evaluated other arrhythmias in this population.Objective:We sought to assess the prevalence and significance of nonsustained ventricular tachycardia (NSVT) in pts who have had an ischemic stroke or TIA. We hypothesize that pts who have NSVT will have a higher risk of cardiovascular events and recurrent stroke than those who do not have NSVT on monitoring.Methods:In a large, quaternary academic health system, we evaluated 563 consecutive, post-stroke pts, who did not have a history of MI or heart failure (HF) and underwent routine, mobile cardiac outpatient monitoring (MCOT, Phillips Biotelemetry, Malvern, PA) between 2019 and 2023. We evaluated all episodes of NSVT, defined as a ventricular rhythm with a wide QRS complex for at least 3 beats and a rate faster than 100 beats per minute. We collected all NSVT episodes during the wear period. For each episode, we also collected the total duration and maximum heart rate. We also calculated the NSVT burden by summing the duration of NSVT episodes and dividing by the total monitoring time. The electronic health record was utilized to identify incident MI, heart failure and/or recurrent stroke. Cox proportional hazard models were used to determine the risk of developing a cardiovascular event across the follow-up period.Results:Of 563 patients, the mean duration of MCOT monitoring was 19±7 days. NSVT was observed in 113 pts (mean 1.8±2.5 episodes per patient). Compared to pts who did not have NSVT, those with NSVT were older, more likely to be male, and more likely to smoke. No differences were observed in the prevalence of hypertension, diabetes, or hyperlipidemia. After a median follow-up of 920 days [IQR 844], there were 123 cardiovascular events. Patients with NSVT had higher risk of incident HF (HR 4.7, 95% CI [1.8, 12.1]; p = 0.002), incident MI (HR 4.2, 95% CI [1.8, 10.0]; p = 0.001) or recurrent stroke (HR 2.1, 95% CI [1.2, 3.7]; p = 0.007). Among those with NSVT, a higher NSVT burden was associated with a greater risk of cardiovascular events (p=0.004).Conclusion:In post-stroke patients, the presence and burden of NSVT are associated with a higher risk of incident cardiovascular events and recurrent stroke. Future studies should evaluate whether NSVT is a modifiable marker of cardiovascular risk in these pts.
Abstract 4145096: Postural Orthostatic Tachycardia Syndrome and Inappropriate Sinus Tachycardia – Two Distinct Phenotypes in Post-COVID-19 Cardiovascular Dysautonomia: Prevalence, Overlap and Clinical Characteristics
Circulation, Volume 150, Issue Suppl_1, Page A4145096-A4145096, November 12, 2024. Introduction:Postural orthostatic tachycardia syndrome (POTS) and Inappropriate sinus tachycardia (IST) are common manifestations of cardiovascular dysautonomia (CVAD) in patients with post-COVID-19 syndrome. Studies regarding differences between post-COVID-19 POTS and post-COVID-19 IST have been sparse and based on small patient series.Aims:To examine clinical differences between POTS and IST in patients with post-COVID-19 syndrome.Methods:A cross-sectional observational study based on a dataset of patients diagnosed with post-COVID-19 syndrome and POTS/IST, at Karolinska University Hospital, Stockholm in 2020-2023, was performed. Data was retrieved using patients’ medical records. ANOVA, chi-square tests and Fisher’s exact tests were used for analysis.Results:A total of 200 patients diagnosed with post-COVID POTS/IST (ICD-10 codes, I.498 + U.099) were included (female, 85%) and divided into a POTS-group (n=110) and IST-group (n=90). Sixty-one patients (31%) met the diagnostic criteria of both and were included in the IST-group. The mean ages were 38 years for the POTS-group and 42 years for the IST-group (p=0.027). Hypertension was more common within the IST-group (p
Abstract 4148133: Association between small pre-implant left ventricular end diastolic diameter and post left ventricular assist device implantation all-cause mortality: A systematic review and meta-analysis
Circulation, Volume 150, Issue Suppl_1, Page A4148133-A4148133, November 12, 2024. Background:Left ventricular assist devices (LVADs) are crucial for the management of advanced heart failure patients acting, both as a bridge to heart transplant or destination therapy. Existing studies revealed mixed results on the impact of pre-implant left ventricular end-diastolic diameter (LVEDD) on post-LVAD mortality. Some studies found smaller LVEDD increases mortality, while others revealed no significant impact. Due to the limited evidence, this meta-analysis aims to determine the association between pre-LVEDD and post-LVAD implantation mortality through a systematic review and meta-analysis.Method:We systematically reviewed articles until May 2024 examining the association between pre-implant LVEDD and post-LVAD implantation mortality using PubMed, Google Scholar, Embase, and Scopus. A random effects model was used to calculate the pooled adjusted odds ratio (aOR). We used I2statistics to determine the heterogeneity of studies. Leave-one-out sensitivity analysis was done to evaluate each study’s effect on the overall estimate, with statistical significance set at p
Abstract 4138268: The Use of Mavacamten for Management of Post TAVR Obstruction: A Novel Approach to Treatment
Circulation, Volume 150, Issue Suppl_1, Page A4138268-A4138268, November 12, 2024. Background:Treatment of left ventricular outflow tract (LVOT) obstruction involves a combination of negative inotropic agents. However, these therapies have limitations which may result in insufficient control of symptoms, leading to more invasive options such as surgical septal myectomy or septal alcohol ablation. Mavacamten, a cardiac myosin inhibitor, is currently approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). We present a case of a patient treated with mavacamten in addition to β-blockers (BB) for management of post-TAVR LVOT obstruction.Case:A 76 year old female with a past medical history of hypertension, severe aortic stenosis, and coronary artery disease underwent a Medtronic Evolut TAVR in March 2022. Her TTE post TAVR showed LVOT peak gradient greater than 100 mm Hg, LVEF 75% and severe eccentric mitral regurgitation secondary to systolic anterior motion (SAM) of the mitral valve (MV). After multidisciplinary discussion, the patient was discharged on maximally tolerated BB therapy. Follow up TTE showed persistent obstruction and gradients, so diltiazem was added to her regimen. Her subsequent TTE showed a peak LVOT > 100 mmHg at rest, and severe MR. Given persistent findings, she was started on mavacamten, continued on metoprolol, and tapered off of diltiazem. Her TTE two months after initiation of mavacamten revealed resolution of LVOT gradients, reduction of MR to mild and normal LV and TAVR function. She tolerated the therapy well and endorsed ongoing symptomatic improvement on subsequent follow up.Discussion:With the increasing use of TAVR therapy, there has been a corresponding rise in cases of post-TAVR obstruction that must be managed. As demonstrated by this case, management with BB therapy alone may be suboptimal. Although mavacamten is currently approved in patients with HCM, the obstruction in post-TAVR patients is functionally similar. Thus, this medication was trialed as a supplemental treatment in this patient and yielded positive results. This case highlights the potential benefit of extending use of mavacamten alongside β-blocker therapy for this patient population and suggests the need for future studies.
Abstract 4119613: Evaluation of Gender, Racial and Ethnic Differences in Time to PCI in the Pre and Post Covid-19 Era
Circulation, Volume 150, Issue Suppl_1, Page A4119613-A4119613, November 12, 2024. Introduction:Percutaneous Coronary Intervention (PCI) is recommended for reperfusion of patients presenting with ST-segment myocardial infarction (STEMI) within 90 minutes. In this study, we sought to identify differences in PCI timing based on gender, race and ethnicity in the pre- and post-COVID era.Methods:We collected retrospective data on 760 patients admitted with STEMI at our quaternary academic medical center from 2018-2022. We defined our binary outcome as time to PCI less than 90 minutes, and adjusted for transfers from outside hospitals. We utilized univariate logistic regression analysis to analyze the association of demographic, clinical, and cardiac catheterization details on our outcome. We then utilized multivariate logistic regression analysis to determine the association of our covariates of interests with time to PCI. The logistic regression model was adjusted for collinearity which were deemed not significant.Results:Among our study population, COVID did not significantly impact whether or not a patient had a diagnostic cardiac catheterization on univariate analysis (OR 2.68, 95% CI 0.61-18.40, p=0.23). However, the post-COVID era was significantly associated with a delayed time to PCI on multivariate analysis [OR 1.62, 95% CI 1.04-2.55, p=0.035) [Figure 1]. In addition, females were 1.8x more likely to have a delayed PCI than males on multivariate regression [OR 1.80, 95% CI 1.10-2.95, p= 0.019) [Figure 1]. Interestingly, on multivariate analysis, females were more likely to have delayed reperfusion in the pre-COVID era (OR 2.92, 1.29-6.77,p= 0.01) but not the post-COVID era (OR 1.54, 0.78-3.06,p=0.2134). Patients in the post-COVID era had increased risk of having their culprit coronary not revascularized on multivariate analysis (OR 2.85, 1.2-8.03, p= 0.03).Conclusions:At our center, COVID did not significantly impact cardiac catheterization rates. However, COVID was significantly associated with delayed reperfusion timing and not revascularizing culprit vessels. Females were much more likely to have a delayed PCI than males in the pre-COVID era which was not seen following COVID-19.
Abstract 4139404: Post-Translational Regulation of Larp6 by IGF-1 Modulates Collagen Synthesis in Smooth Muscle Cells
Circulation, Volume 150, Issue Suppl_1, Page A4139404-A4139404, November 12, 2024. Introduction:Vascular smooth muscle cells (SMCs) play a crucial role in atherosclerosis, contributing to plaque stability by forming the main cellular component of the fibrous cap and synthesizing extracellular matrix. We previously showed that insulin-like growth factor-1 (IGF-1) increases expression of the collagen mRNA binding protein La ribonucleoprotein domain family member 6 (Larp6) and of collagen in atherosclerotic plaques. However, molecular mechanisms remain unclear.Hypothesis:We hypothesized that IGF-1 increases collagen synthesis via a post-translational regulation mechanism of Larp6.Methods:An SMC-specific Larp6 overexpression mouse model (SMC-Larp6) was generated using the Myh11 promoter. Entire aortas and aortic roots were isolated for plaque analysis. IGF-1 was injected in WT mice at a dosage of 1.5 mg/kg. For in vitro assays, human aortic SMCs were transduced with an adenoviral vector to overexpress Larp6 and treated with 50 ng/mL IGF-1 for 18 h.Results:SMC-Larp6 mice had no significant change in plaque collagen content. Additionally, IGF-1 increased Larp6 protein but not mRNA levels suggesting that IGF-1 likely regulated Larp6 via a post-transcriptional mechanism. Western blotting identified two major Larp6 bands at 67 kDa and 70 kDa. We observed a clear band shift from the lower to the upper band after IGF-1 treatment, with a concomitant increase in Procollagen I, suggesting that IGF-1 enhances Larp6’s role in promoting collagen through post-translational modification. Mass spectrometry analysis revealed multiple phosphorylation sites on the LaM and LSA domains of Larp6, including S451, which is phosphorylated by the IGF-1/PI3K/AKT axis. We also observed this protein modification pattern in mouse aortic tissue lysates following IGF-1 injection.Conclusions:IGF-1 regulates Larp6 phosphorylation in SMC, thereby likely playing an important role in IGF-1 induced collagen synthesis. This study provides insight into molecular mechanisms underlying collagen production in SMCs and could inform therapeutic strategies for plaque stabilization.