Search Results for: La FDA approva il sistema di riabilitazione dell’ictus

Circulation, Volume 150, Issue Suppl_1, Page A4137177-A4137177, November 12, 2024. Background:Arrhythmia is always a concern in oncological treatments. The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, enhancing the immune system’s ability to combat malignancies. They are being more frequently used, revealing a range of immune-related adverse events (irAEs). This study aims to investigate the incidence of cardiac arrhythmias in patients receiving Pembrolizumab.Methods:We conducted a retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database, focusing on reports submitted between 2006 to 2024. Cases involving patients treated with ICs were identified, and information related to cardiac arrhythmias was extracted using the Medical Dictionary for Regulatory Activities (MedDRA). Patients ≥ 18 years of age treated with ICIs were included in this study. A disproportionality analysis was conducted to identify arrhythmia events associated with pembrolizumab by comparing it with other immune checkpoint inhibitors (nivolumab, ipilimumab, and atezolizumab) and the entire FAERS database using the reporting odds ratio (ROR) and information component (IC).Results:A comprehensive analysis of 61,236 reported cases of pembrolizumab use revealed a total of 3,901 cases with cardiac complications. Among these, 672 cases (17.22 %) of arrhythmias were reported, with 452 individuals (67.26%) requiring hospitalization and 172 cases (25.59%) resulting in fatalities.Atrial fibrillation emerged as the most prevalent arrhythmia (49.7%). The occurrence of ventricular tachycardia with an ROR of 1.67 (1.18–2.35) and an IC of 0.44 (0.01–1.46) and complete atrio-ventricular block with an ROR of 1.57 (1.19–2.08) and an IC of 0.40 (0.04–1.24) were statistically significant. The reported arrhythmias associated with pembrolizumab are tabulated inTable 1. The majority of events were reported in males, as shown inFigure 1.Conclusion:This research offers significant insights into the connection between ICIs and cardiac arrhythmias, utilizing real-world data from the FAERS database. Healthcare providers should monitor cardiac events in patients receiving ICIs and aim to achieve a balance between anticancer effectiveness and cardiovascular safety. Further investigation is necessary to better understand the underlying mechanisms of arrhythmia and enhance risk stratification strategies for this specific patient group.

Circulation, Volume 150, Issue Suppl_1, Page A4140535-A4140535, November 12, 2024. Introduction:Programmed cell removal, or efferocytosis, has been proposed as a method to dispose of unwanted cells that accumulate to promote diseases such as cancer, infection, and atherosclerosis. The defective efferocytosis process in advanced atherosclerotic plaque causes secondary necrosis and contributes to plaque vulnerability. Blockade of ‘don’t eat me’ molecules such as CD47 induces favorable vascular effects, but can induce the clearance of some healthy tissue such as RBCs. Accordingly, we conducted a high-throughput screen of about 3000 FDA-approved drugs and compounds, to identify new pro-efferocytic therapies that may have translational potential.Methods&Results:Using flow cytometry-based phagocytosis assays with RAW 264.7 murine macrophages, we identified 8 candidate compounds that reproducibly increased efferocytosis. Subsequent validation assays using Incucyte live-cell imaging assay in RAW cells, primary cultured murine macrophages, and human macrophages allowed us to identify the atypical antipsychotic drug, thiothixene, as a promising candidate for clinical translation, which induced cellular clearance without changing macrophage apoptosis, migration or proliferation. Leveraging thiothixene’s known inhibitory effects on a wide range of neurotransmitters and catecholamines, we found that dopamine has a potent inhibitory effect on efferocytosis, which thiothixene could partially offset. Thiothixene induced macrophage polarization and Arginase1 upregulation, promoting continual efferocytosis. Mechanistically, RNA-sequencing revealed that thiothixene upregulated Stra6L, a receptor for retinol-binding protein that mediates cellular uptake of retinol. Retinol and all-trans retinoic acid upregulated Arginase1 expression and promoted efferocytosis, which could be reversed via knockdown of Stra6l.Conclusion:This unbiased screen identified unanticipated anti-efferocytic properties of dopamine, while highlighting the translational potential of a generic, FDA-approved anti-psychotic drug. This therapy may represent a novel method for promoting continual efferocytosis and the disposal of unwanted cells that otherwise can promote a range of clinical disorders including atherosclerosis.

Circulation, Volume 150, Issue Suppl_1, Page A4135178-A4135178, November 12, 2024. Background:Tricuspid regurgitation (TR) is no longer considered forgotten. Transcatheter tricuspid valve repair/replacement (TVRR) has become widely accepted as gauged by clinical outcomes. FDA approved two tricuspid valve devices for the purpose of improving quality of life and not necessarily to improve TR severity. We aim to support evidence-based use of TVRR, by summarizing the latest evidence on the clinical effectiveness in terms of post-procedural length of hospital stay, readmissions for heart failure and procedure success if an Intracardiac device is present.Methods:We searched Pubmed, Embase and Cochrane databases and performed a meta-analysis of the included cohort studies using a fixed-effects model. Studies were excluded if they did not present an outcome in each intervention group or did not have enough information required for continuous data comparison. We performed a meta-analysis of hazard ratio (HR) for two outcomes and odds ratio (OR) for one outcome using the random effects model to remove inconsistency and compared the results with fixed effects model. The compared findings of both methods were similar. The variables used for analysis were number of events in exposure group and total amount of events. All data analyses were performed using MedCalc® Statistical Software version 22.023.Results:Of 161 potentially relevant studies, 8 retrospective studies with a total of 1,717 patients were included in the meta-analysis. Procedure (TVRR) success was associated with fewer readmissions for heart failure in all three studies included in the analysis of pooled HR (HR = 0.46, 95% confidence interval [CI]: 0.33 – 0.63, p

Circulation, Volume 150, Issue Suppl_1, Page A4144040-A4144040, November 12, 2024. Background:Coronary heart disease (CHD) remains the primary cause of mortality and morbidity in the USA. Although rodents are widely used to explore mechanisms, they have major biological differences with humans. Pigs develop CHD similar to humans, and pigs are the FDA-preferred species for testing anti-atherosclerotic drugs. Pigs with familial hypercholesterolemia (FH pigs) are known to develop advanced atheromas containing thin fibrous caps, and large necrotic cores. However, little is known about the porcine plaque phenotype and whether pigs develop a full range of coronary plaques similar to humans.Aims:To quantify the distribution of porcine coronary plaque types, assess plaque morphology and cellular composition to obtain insights into mechanisms of atherosclerosis in a large animal model and to facilitate development of new therapies.Methods:Right coronary and left anterior descending arteries were dissected from FH pig hearts (n=9), each artery split into 6 fragments and a total of 108 vascular fragments were used to obtain cross-sections. The sections were stained with Trichrome to quantify intima/media thickness ratio (IMT), medial and necrotic core areas. The sections were also used for immunohistochemistry with cell marker antibodies (to measure % plaque smooth muscle cells (SMC), macrophages (MF), and endothelial cells (EC)). Cell apoptosis was assessed by TUNEL assay.Results:All vascular fragments were classified into 4 groups based on IMT (from A to D). Increase in IMT significantly correlated with elevation in total vessel area (A: 3.8mm2to D: 7.2mm2), increase in necrotic core area (B: 13.8% to D: 30.7%), elevation in plaque MF (A: 16.7% to D: 22.5%), increase in plaque cell apoptosis (A: 5.2% to D: 17.4% apoptotic cells) and with thinning of vascular media (A:1.3mm2to D: 0.74mm2), decrease in number of plaque SMC (A: 62.5% to D:17.9%) and plaque EC (A:3.21% to D:1.48%). We assigned each porcine plaque group to the corresponding type of human plaque: A, human type III, early lesions, 28% of all coronary plaques; B, type III/IV, fibrous plaque, 43%; C, type V, fibroatheroma, 16%; D, type VI, complicated lesions, 13%.Conclusions:Like humans, pigs develop plaques that range from early lesions to advanced atheromas resembling type III-type VI lesions. These findings provide a rationale to use FH pigs to test the effect of novel anti-atherosclerotic drugs on the full range of coronary plaques mimicking human settings.

Circulation, Volume 150, Issue Suppl_1, Page A4144021-A4144021, November 12, 2024. Background:β-3 adrenoceptor (AR) activation is antiarrhythmic in a canine model of ventricular arrhythmia. Na-K ATPase (NKA) expression is higher in female than male rats and is stimulated by β-3 agonist due to an inhibitory oxidative modification.Objective:To test the hypothesis that mirabegron, a β-3 agonist approved by the FDA for treating overactive bladder, has more anti-fibrillatory effects in females than in male rabbit ventricles due to NKA stimulation.Methods:We performed optical mapping studies in 6 male and 6 female Langendorff-perfused rabbit hearts at baseline, then sequentially after adding mirabegron (500 and 1000 nM), followed by ouabain (500 nM), a specific NKA blocker. All hearts underwent 10 attempts of ventricular fibrillation (VF) induction with a ventricular burst pacing (20 Hz for 10 s) at each stage of the experiment.Results:Ashows phase maps during VF. Triangles indicate PSs. Mirabegron 1000 nM significantly decreased VF inducibility (number of VF induced in the 10 attempts) from 4.8±3.2 to 2.2±2.9 (p=0.034) in females but not in males (from 4.5±2.6 to 5.0±2.8, p=0.656) (B). Consistent with our previous reports, Mirabegron 1000 nM decreased PSs/VF (number of phase singularity per VF episode) in females (from 10.5±2.7 to 2.9±3.3, p=0.010) but not in males (from 11.3±2.3 to 9.7±2.6, p=0.167). Adding ouabain did not reverse mirabegron’s effects on PSs/VF (2.4±3.9, p=0.706) in females. However, it decreased PSs/VF significantly in males (3.4±4.0, p=0.038). Mirabegron decreased conduction velocity (CV, activation time-1, /s) in both males (from 40.3±6.5 to 30.4±5.3, p

Circulation, Volume 150, Issue Suppl_1, Page A4141921-A4141921, November 12, 2024. Previous studies have highlighted the risk of acute kidney injury (AKI) development, underlining the need for strategies to mitigate this complication.We analyzed 208 consecutive patients who underwent pulsed field ablation (PFA) for post-FDA approval. All patients received pulmonary vein isolation. Ablation of extra-PV sites was performed per the operator’s choice, with no contrast agents . Serum creatinine was measured in all patients at baseline and 24 after ablation.The aim of our study was to evaluate the impact of hydration timing and the amount of fluids on incidence of AKI in patients undergoing PFA.Group means for continuous variables were compared using the Student t-test. Categorical variables were compared using the Chi-square test. A ROC analysis was done to evaluate the predictive model of PFA applications to evaluate AKI. All tests were two-tailed and conducted at an α level of 0.05.We divided patients into two groups:Group 1(n=102) received either one liter of saline pre-procedure or one liter pre-procedure followed by a liter post-procedure;Group 2(n=106) was preemptively hydrated with two liters of saline before the procedure, followed by additional 500cc if the patient had received more than 100 PF applications. Baseline Characteristics of population are described inFig.1a.In the comparative analysis of the two groups, there was no significant difference regarding the number of PFA applications administered.None of the patients in Group 2 experienced AKI, while Group 1 AKI occurred in 9 patients. (0/106 vs 9/102, p-value=0.0034).The ROC analysis yielded an area under the curve of 0.709 ± 0.107 with a 95% confidence interval ranging from 0.498 to 0.919 (p-value=0.035). An optimal PF application cutoff point of 105.50 was determined, associating a higher probability of AKI with PFA applications exceeding this threshold (sensitivity:0.667, specificity:0.735, Youden’s index:0.402) (Fig.1b).Among the 9 patients who developed AKI, we observed that 7 received more than 100PF applications; the remaining 2 patients, each with baseline stage 3 chronic kidney disease and prior episodes of AKI following surgeries, received 54 and 50PF applications, respectively.In this series of patients, pre-procedural hydration with two liters of fluids eliminated the risk of AKI even in patients who received a high number of PFA applications.

Circulation, Volume 150, Issue Suppl_1, Page A4147246-A4147246, November 12, 2024. Introduction:Non-invasivesurveillance of cardiac allograft health has included biomarkers such as NT-proBNP, and donor-derived cell-free DNA (dd-cfDNA). It has previously been shown that these biomarkers when elevated, indicate graft complications such as rejection, coronary artery vasculopathy, or donor-specific antibody production. As xenotransplantation enters the arena as a potential option for those with advanced heart failure, noninvasive monitoring techniques need to be investigated. Our institution performed the second porcine to human cardiac xenotransplant with a 10 gene edited porcine cardiac xenograft under FDA compassionate use authorization. After requiring perioperative transfusions, by post operative day (POD) 13, endomyocardial biopsy (EMB) revealed antibody and complement deposition without damage. Hemodynamic decompensation on POD 29 prompted EMB, revealing antibody mediated rejection (AMR).Research Questions/Goals:The authors sought to investigate if NT-proBNP and dd-cfDNA positively correlate in the patient with cardiac xenograft.Methods/Approach:NT-proBNP was checked periodically and dd-cfDNA was assessed once to twice weekly post-transplant. A retrospective review was completed including Pearson’s correlation coefficient analysis.Results/Data:There was a weak negative correlation between the NT-proBNP and dd-cfDNA (r=-0.28). After the initial spike in the perioperative period, NT ProBNP levels declined. NT Pro-BNP did not rise as dd-cfDNA did at the time of biopsy proven antibody mediated rejection (AMR). See the graphic below for detailsConclusion:Noninvasive surveillance of cardiac xenografts needs further investigation. Biomarkers such as NT-proBNP negatively correlated with dd-cfDNA, which increased as expected at the time of biopsy proven antibody mediated rejection. Porcine xenografts are accustomed to a low-pressure circulatory system in contrast to the human recipient milieu. Despite this increased load to the xenograft, NT-proBNP levels decreased significantly after the initial postoperative phase. The NT proBNP values could have been lower than expected due to the effects of continuous renal replacement therapy. It is interesting to also note that the human assay detected xeno NT-proBNP.

Circulation, Volume 150, Issue Suppl_1, Page A4145631-A4145631, November 12, 2024. Description of Case:A 64-year-old male with complex medical history, including infective endocarditis of the aortic valve requiring surgical replacement with a bioprosthetic valve and recurrent infective endocarditis of the bioprosthetic valve, presented with two hours of crushing chest pain and found to have ST elevations. Urgent angiography revealed complete occlusion with thrombus of the proximal left anterior descending (LAD) coronary artery. The patient underwent aspiration thrombectomy, followed by intracoronary vasodilators, without improvement of flow. Due to ongoing shock despite initial mechanical support, the patient was escalated to an Impella CP device after a transthoracic echo confirmed no left ventricle thrombus. Once stabilized, intravascular ultrasound showed significant thrombus and plaque in the LAD. This was treated with a drug-eluting stent, but TIMI 3 flow was not achieved. The patient was placed on an integrilin drip with plans to reevaluate in 24 hours. While preparing for transport to the cardiac ICU, the Impella device malfunctioned, and function could not be restored. With ongoing hemodynamic collapse, a second Impella device was placed, but it malfunctioned almost immediately, and the patient suffered a pulseless electrical activity arrest. Advanced Cardiac Life Support was initiated, but the patient ultimately expired. Abiomed’s investigation following the case identified an unknown biological material obstructing both Impella devices. In light of a leukocytosis of 14,000 and a recent urine sample positive for E. coli, there is a high suspicion that the patient suffered from recurrent infective endocarditis causing septic embolization and subsequent Impella device failure from aspiration of bacterial vegetations.Discussion:This is the first known reported case of Impella device failure resulting from the aspiration of vegetation in a patient with infective endocarditis of a bioprosthetic aortic valve. The case highlights the challenges of diagnosing endocarditis in bioprosthetic valves and emphasizes the importance of transesophageal echo in cases with high clinical suspicion. Additionally, considering the recent FDA recall of Impella devices in patients who have had transcatheter aortic valve replacement (TAVR) procedures due to the risk of motor damage after contact with TAVR stents, this case calls attention to a need for further research of the use and safety of Impella devices in patients with non-native aortic valves.

Circulation, Volume 150, Issue Suppl_1, Page A4125893-A4125893, November 12, 2024. Introduction:Drug combinations offer increased therapeutic efficacy and reduced toxicity and plays a vital role in treating chronic complex diseases. Understanding a drug combination’s mechanism of action (MoA) can provide important insights into its therapeutic efficacy. The MoA of many FDA-approved drugs, however, often remains unclear.Methods:In this study, we investigated the combination of a statin [atorvastatin (ATO) or simvastatin (SIM) plus ezetimibe (EZE)] and utilized drug-treated RNA-seq transcriptome data from SOAT2-only-HepG2 cells (treated with ATO 5 umol/L, EZE, 25 umol/L, their combination or vehicle) and from liver biopsies of patients with uncomplicated cholesterol gallstone disease in the Stockholm Study (a single-blind, randomized trial with SIM 80 mg daily, EZE 10 mg daily, their combination, or placebo) to decipher the underlying molecular mechanisms of the drug combination. We proposed a Boolean logical modeling framework to simulate the MoA of a drug combination. Specifically, fourteen two-variable Boolean models were used to describe the combinatory relationships of ATO/SIM and EZE. Thereafter, a pattern matching approach was applied to associate drug-induced differentially expressed genes with the idealized differential expression templates derived from Boolean models.Results:We found 1,560 and 594 genes differentially expressed in at least one treatment condition in SOAT2-only-HepG2 cells and liver biopsies, respectively. Our analysis revealed both expected and novel combinatorial modes of ATO/SIM and EZE. For example, ATO independently activates downstream genes (i.e. B4(ATO,EZE)=ATO), and ATO and EZE synergistically inhibits downstream genes (i.e. B15(ATO,EZE)=NOT (ATO AND EZE)) , as the two most prevalent MoAs in SOAT2-only-HepG2 cells (Figure 1). Similarly, the combination of SIM and EZE synergistically inhibiting downstream genes was also the most prevalent MoA in the liver biopsies. We mapped the downstream genes of each combinatorial mode to the human interactome and obtained underlying subnetworks, which are important for understanding the therapeutic effects of the drug combination. Functional enrichment and disease-association analyses of the downstream suggest the additional therapeutic indications of the drugs.Conclusion:Drug-induced transcriptomes are informative in deciphering the MoA of drug combinations using Boolean logical modeling. This framework can be easily extended to the combinations of three drugs.

Circulation, Volume 150, Issue Suppl_1, Page A4135497-A4135497, November 12, 2024. Digoxin is commonly used in infants with single ventricle heart disease (SVD) and may decrease mortality in the interstage period. While labeled for the treatment of heart failure in infants, dosing recommendations do not account for alterations in drug disposition in SVD. We aimed to characterize digoxin pharmacokinetics (PK) in interstage infants with SVD.Infants 2mg/dL or on extracorporeal support at enrollment were excluded. PK samples were prospectively collected and digoxin plasma concentrations quantitated by HPLC/MS/MS assay validated per FDA guidance. Population PK analysis was performed in NONMEM. Effects of covariates on PK parameters were evaluated. Dosing simulations were conducted in a virtual cohort of infants with SVD that optimized dosing to achieve trough concentrations of 0.5-2 ng/mL, the label-endorsed reference range for heart failure.Across 10 sites, 50 infants contributed 207 PK samples.Table 1shows cohort characteristics. A 2-compartment model with transit compartment absorption and linear elimination best described the data. Renal function and weight were significant covariates. Infants with SVD had lower apparent clearance than previously reported in infants without SVD. Current labeled dosing resulted in simulated exposures above the reference range (Figure 1). A new dosing regimen for infants with SVD is proposed.Digoxin PK is altered in infants with SVD. Dosing should account for renal function, age, and weight.

Circulation, Volume 150, Issue Suppl_1, Page A4141811-A4141811, November 12, 2024. Background:Ambulatory ECG (AECG) enables heart rhythm monitoring during daily activities, with a focus on arrythmia detection. Detection and quantification of sleep and activity patterns during monitoring may provide insights into lifestyle and aid in contextualizing arrhythmia events.Aims:We developed an AI algorithm to classify sleep, activity, and inactivity periods using a novel AECG patch with embedded accelerometry. We assessed algorithm performance and compared it to FDA-cleared actigraphy and consumer devices, which have shown 93-99% sensitivity (SE) and 39-54% specificity (SP) in classifying sleep vs. polysomnography (PSG).Methods:We conducted a prospective study of 81 participants at 3 sites who wore the Zio®monitor AECG patch (iRhythm Technologies, San Francisco, CA) and Actigraph wGT3X (Pensacola, FL) simultaneously for 14 days. Sleep disordered breathing was excluded. Participants underwent a 6-minute walk test at the beginning of wear and in-clinic overnight PSG sleep testing at 7±3 days.Data were split into training (n=40) and validation (n=41) sets. Feature and model selection utilized five-fold cross-validation on the training set, focusing on total activity and body angle. The final machine model was trained on selected features using the entire training set. In validation, SE and SP for sleep were assessed based on 1-minute epochs vs. PSG and also vs. a 24-hour reference (combined PSG and actigraphy-wake labeling). SE and SP for activity were assessed vs. actigraphy over 8 minutes sampled per subject (4min walk test, 4min PSG wake periods).Results:The study population was diverse (age 43±14 years, 57% female, 64% White, 25% Black, 20% Hispanic). In the validation set, average sleep and wake times were 5.9 and 1.2 hours, respectively, during PSG. SE and SP were 88.8% and 54.0%, respectively, in sleep detection vs. PSG, or 88.8% SE and 95.6% SP vs. the 24-hour reference (Table 1). SE and SP for activity detection were 97.0% and 100%, respectively.Conclusion:Assessment of sleep and activity during AECG is feasible, with performance comparable to FDA-cleared actigraphy. This feature offers insights into patient wellness patterns, highlighting its potential for personalized healthcare monitoring.

Circulation, Volume 150, Issue Suppl_1, Page A4143757-A4143757, November 12, 2024. Background:Cardiac contractility modulation (CCM) is a device-based heart failure therapy that augments cardiac contractility. One CCM device – the Optimizer Smart Mini System [Impulse Dynamics, Marlton, NJ] – is approved by the Food and Drug Administration (FDA) for clinical use.Research Question:What are real-world and long-term outcomes of the Optimizer Smart Mini CCM system?Objective:We reviewed the United States FDA Manufacturer and User Facility Device Experience (MAUDE) database for adverse events and outcomes associated with the Optimizer Smart Mini System CCM.Methods:On June 3rd, 2024, we performed a MAUDE database search for all reports of CCM devices from January 2019 – when the first pre-market implantation was noted – to the present. Duplicates were removed, and outcomes were noted.Results:A total of 34 total reports were found. The majority of events were reported since 2023. 58.8% (n=20) of events were classified as device malfunctions. This occurred most often due to a computer software problem (35.3%, n=12), failure to charge (14.7%, n=5), and an adverse event without an identified problem (14.7%, n=5). Commonly, error code A09 – a charging error due to incorrect interpretation of a high current during a routine safety self-check – occurred in 38.2% (n=13) of all cases, even in patients without a reported software problem, and was solved by resetting the device in 47.1% (n=16) of cases. This is a known problem. Injury occurred in 35.3% (n=12) of cases due to implant failure (52.9%, n=18) as the most common patient problem. There was a 5.9% (n=2) rate of mortality.Conclusions:Real-world CCM implantation appears to have low device-related adverse risks but suffers from computer software issues that may be solved by resetting the device. Continued monitoring and accurate adverse event reporting are needed with increased use to assess long-term risks.

Circulation, Volume 150, Issue Suppl_1, Page A4141001-A4141001, November 12, 2024. Background:Pulsed field ablation (PFA) has emerged as a safe and effective alternative to thermal ablation modalities for treatment of paroxysmal and persistent AF in a de novo procedure.Research Questions:Since the FaraPulse system (Boston Scientific) was approved by FDA, no data was reported on whether PFA can be used in redo procedures.Aims:We reported our initial experience with PFA in patients with recurrent atrial tachyarrhythmias (ATs) who failed at least one thermal ablation of AF.Methods:Consecutive patients receiving redo ablation using PFA (FaraPulse) for recurrent ATs were enrolled. ICE and fluoroscopy were used to guide the placement of FaraWave catheter. Voltage and activation mapping of LA were performed in all patients before ablation using Orion high density mapping catheter and Rhythmia system. Ablation strategy included PV re-isolation as needed, LA posterior wall (PW) isolation if low voltage zone was identified, and ablation of any organized ATs. Procedural endpoints were PVs and LAPW isolation, non-inducibility for ATs and bidirectional block for linear ablation.Results:15 patients (12 male; age 66.3±10.3 years) were included. The median number of prior RF ablations was 2; 2 patients also received one cryoballoon ablation. Patients presented with persistent (80%) AF or paroxysmal (20%) AF with/without documented organized ATs. By using PFA, LAPW isolation was performed and achieved in all patients, while 11 (73.3%) patients required reisolation of at least one PV (Figure). Organized ATs were present/induced in 7 (46.7%) patients including 3 peri-mitral AFL, 3 LA roof-dependent AFL, 3 CTI AFL and 3 atrial tachycardias from LA roof, LA septum and RA roof respectively. RF ablation was required in 2 patients (2/7, 28.5%) to eliminate CTI AFL. Per case total PFA applications number were 48.7±24.4 (46, 22-90); total fluoroscopy time was 6.8±5.6 mins. No major peri-procedural complication was observed except for one case (90 PFA applications) of hemolysis and acute renal failure that completely recovered.Conclusion:PFA of recurrent ATs after failed thermal ablation is feasible and safe acutely if limited the applications. The long-term outcome of this strategy warrants further investigation.

Circulation, Volume 150, Issue Suppl_1, Page A4142327-A4142327, November 12, 2024. Background:Apixaban and rivaroxaban are common agents used for anticoagulation to treat and prevent blood clots and to prevent stroke in people with atrial fibrillation.Research question:As anticoagulants, there is a risk of bleeding occurring. The question is, which of these two medications has a higher risk of bleeding from various organ systems.Goals:Using the FAERS database to calculate the reporting odds ratio (ROR) for the risk of ocular, cerebral, gastrointestinal, rectal, and renal hemorrhage in addition to epistaxis and hemoptysis of these medications.Methods:We manually extracted data from the FAERS database owned by the FDA on hemorrhagic events related to Apixaban and Rivaroxaban from January 2012 to March 2024. We calculated the reported odds ratio for both drugs to compare their respective hemorrhagic outcomes.Results:The total AE reported for apixaban and rivaroxaban from 2012 to March 2024 was 87490 and 88026, respectively. Rivaroxaban has an increased risk for cerebral (ROR 1.73, 95% CI 1.60 to 1.86), gastrointestinal (ROR 5.91, 95% CI 5.61 to 6.22), rectal (ROR 4.64, 95% CI 4.21 to 5.12), renal (ROR 3.83, 95% CI 2.87 to 5.11), epistaxis (ROR 2.06, 95% CI 1.93 to 2.20) and hemoptysis (ROR 3.20, 95% CI 2.80 to 3.66) compared to apixaban with a significant p-value. There was no statistical significance in reported cases of ocular hemorrhage in apixaban versus rivaroxaban.Conclusion:Apixaban and rivaroxaban are common medications used in the treatment of people with atrial fibrillation to reduce the risk of clots and stroke. The FAERs database compared the risk of ocular, cerebral, gastrointestinal, rectal, and renal hemorrhage and epistaxis and hemoptysis of these medications. There was no statistical significance in reported cases of ocular hemorrhage in apixaban versus rivaroxaban. Rivaroxaban overall has a significantly higher risk of bleeding in multiple organ systems, especially cerebral, gastrointestinal, rectal, and renal hemorrhage, as well as epistaxis and hemoptysis. Apixaban would be a better option for people at risk for or with a history of these complications.

Circulation, Volume 150, Issue Suppl_1, Page A4147915-A4147915, November 12, 2024. Introduction:Endothelin receptor antagonists (ERAs) are the mainstay therapy for pulmonary arterial hypertension (PAH). However, there is limited data on cardiac adverse drug events (ADEs) associated with ERA medications. We performed a pharmacovigilance study comparing bosentan and ambrisentan using the FDA Adverse Event Reporting System (FAERS) data.Methods:Cardiac ADE data for bosentan and ambrisentan from January 1, 2004, to December 31, 2023, in the FAERS database were retrieved. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) aligned with p-values. The following cardiac ADEs were included: atrial fibrillation (AF), right ventricular failure (RVF), and cardiac arrest (CA).Results:For adults ≥ 18 years, a total of 12,058 cardiac ADEs were reported for both bosentan (38%) and ambrisentan (62%). Among the selected cardiac ADEs, AF was more frequently reported with bosentan (ROR 3.99, 95% CI: 3.62-4.40) than ambrisentan (ROR 1.91, 95% CI: 1.77-2.07). RVF showed a significantly higher ROR for bosentan (73.60, 95% CI: 66.68-81.25) than ambrisentan (23.11, 95% CI: 20.99-25.46). CA was also more commonly associated with bosentan (ROR 2.25, 95% CI: 1.98-2.55) than with ambrisentan (ROR 0.69, 95% CI: 0.61-0.78), with all comparisons showing p-values < 0.001.Conclusion:Our study identifies a significantly higher frequency of cardiac ADEs, particularly AF, RVF, and CA, in patients treated with bosentan compared to ambrisentan. This finding corroborates previous literature that has suggested differential safety profiles among ERAs, emphasizing the need for vigilant cardiac monitoring. Clinicians should integrate these insights into their practice, potentially favoring ambrisentan in patients with elevated cardiac risk, thus optimizing the management of PAH and improving patient outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4142273-A4142273, November 12, 2024. Background:GLP-1 Receptor Agonists have become widely used for treating Diabetes Mellitus Type 2 and weight loss in patients across the United States. However, new data reports increasing cases of pancreatitis, acute kidney injury, increased Hba1c, and thyroid malignancy.Research question:Like many medications, GLP-1 receptor antagonists have a risk of side effects. The question is which medication, Semaglutide or Tirzepatide, has the highest risk of developing the above mentioned side effects.Goals:Using the FAERS database to calculate the reporting odds ratio (ROR) for the risk of pancreatitis, acute kidney injury, increased HgA1c, and thyroid malignancy.Methods:The FDA’s FAERS system gathers information on adverse events and medication errors. The data shows that both Semaglutide and Tirzepatide have been linked to pancreatitis, acute kidney injury, elevation in HbA1c, and various types of thyroid malignancies. For consistent analysis, this data covers the period from 2022 to 2024 for both drugs.Results:January 2022- March 2024 data showed that Semaglutide and Tirzepatide had 11584 AE and 29453 AE, respectively. Semaglutide had a higher risk of developing pancreatitis, elevation of HbA1c, and thyroid malignancy compared to Tirzepatide (ROR 2.62, 95% CI 2.21-3.10) (ROR 1.72, 95% CI 1.38 to 2.15), (ROR 4.32, 95%CI 2.66 to 7.01) respectively. However, Semaglutide had 72% fewer reported cases of AKI than Semaglutide (ROR 0.28, 95% CI= 0.20 to 0.37).Conclusion:Lately, the popularity of GLP-1 Agonists is soaring mainly due to their role in facilitating weight loss and providing additional cardiovascular benefits. To the best of our knowledge, this is the first study comparing the likelihood of these four AEs with Semaglutideand Tirzepatide, using the FAERS Database. Being the newer agent, Tirzepatide is significantly less strongly associated with three AEs than AKI. Additional studies are needed to investigate further the epidemiology and pathophysiology of AKI with Tirzepatide use. In the meantime, Tirzepatide should be the drug of choice in patients who are at high risk for pancreatitis, thyroid cancer, and poorly controlled DM. Semaglutide might be considered in chronic kidney disease patients.