Search Results for: FDA approva un nuovo trattamento per l’emicrania

Circulation, Volume 150, Issue Suppl_1, Page A4147683-A4147683, November 12, 2024. Background:Midodrine, an FDA-approved peripheral alpha1-adrenergic agonist for treating orthostatic hypotension, is also used off-label to manage hypotension in patients with advanced heart failure (HF). Hypotension, whether due to HF itself or as a side effect of its treatment, often restricts the optimization of medical therapy in these patients. By increasing baseline blood pressure, midodrine can enhance the tolerance of HF medications, potentially improving patient outcomes. The use of midodrine is limited due to the risk of supine hypertension, making it crucial to investigate its effects in this patient population.Methods:This study utilized data from the US Collaborative Network, focusing on heart failure patients with a Left Ventricular Ejection Fraction (LVEF) of less than 50%. It compared outcomes between patients treated with midodrine (22,178 patients) and those not treated (376,686 patients). After Propensity Score Matching (PSM), each group consisted of 21,893 matched patients. The outcomes measured included emergency department visits, mortality, shock, and CHF exacerbation, aiming to assess the impact of midodrine on these aspects of heart failure management.Results:Midodrine treatment was associated with significant improvements in key outcomes for heart failure patients: it reduced emergency department visits (OR: 0.68, 95% CI: 0.57-0.81, p

Circulation, Volume 150, Issue Suppl_1, Page A4139340-A4139340, November 12, 2024. Introduction:Studies on the natural history of coronary artery disease have traditionally evaluated the progression of the disease in the presence of MACE, risk factors or risk modifying interventions including pharmacological and non-pharmacological treatment. It is not known how atherosclerotic plaque progresses over the time in the absence of MACE, risk factors or risk modifying interventions.Aim:To evaluate the natural history of atherosclerosis in healthy populations on serial CCTA.Methods:NATURE-CT retrospectively selected 205 participants from two sites in Los Angeles. Subjects underwent at least two CCTA scans, the initial scan showing CAC ≤100, absence of MACE, not placed on lipid modifying therapy in the first and last scan, and at least 2 years apart. Patients with diabetes, familial hypercholesterolemia or chronic kidney disease were excluded. FDA cleared automated software Cleerly Labs (Cleerly.Inc, NY, NY) quantified plaque and stenosis. Primary outcome will be the observed annualized rate of change in the atherosclerotic plaque during the observation period.Results:At baseline visit, the mean age of the cohort was 54.9±10.2 (years), 72% (147) being white males, 0% had DM, 0% had lipid modifying therapy, 24% (49) had hypertension, 28% (57) reported hyperlipidemia and 15% (30) were ever smokers. Mean LDL was 111.6±32.0 mg/dl and the average time between CCTA scans was 4.9±2.2 years. Over half (54%) of the cohort had a CAC=0 at the baseline visit. At baseline, total non-calcified plaque volume was (median and IQR in mm3) [27.5 (10.1, 55.5)] versus at follow-up [53.5 (24.0, 97.9)], with a calculated annualized median change of [4.9 (1.4, 9.6)] in non-calcified plaque. Total calcified plaque volume was [0.3 (0.0, 5.7)] and at follow-up [3.2 (0.1, 18.2)], with a calculated annualized median change of [0.4 (0.0, 2.4)] in calcified plaque. At baseline, 9% (19 subjects) had low attenuation plaque greater than zero, and at follow-up, 23% (48 subjects). 6 subjects had annual change in PAV >=1% (3%) and 23 subjects had annual change in PAV >=0.59% (11%).Conclusions:Atherosclerotic plaque in the absence of MACE, risk factors or risk modifying interventions progresses overtime. The burden of non-calcified plaque has greater progression than calcified plaque. In healthy subjects, the presence of low attenuation plaque is infrequent. When observed, its progression is present overtime. Rapid plaque progression is present in some healthy subjects.

Circulation, Volume 150, Issue Suppl_1, Page A4147650-A4147650, November 12, 2024. Background:Invasive hemodynamics are the gold standard for diagnosis of heart failure with preserved ejection fraction (HFpEF). A novel, FDA-approved artificial intelligence (AI) technology that uses a single, 4-chamber transthoracic echocardiogram (TTE) image to screen patients for HFpEF shows promise as a non-invasive tool to assist in diagnosis. Development of right ventricular (RV) dysfunction is a sign of a more advanced HFpEF. Advanced RV hemodynamic parameters, beyond pulmonary arterial pressures (PAP), have not been well studied in HFpEF. We sought to correlate advanced RV hemodynamic parameters in patients screened for HFpEF with this AI screening tool.Method:We retrospectively evaluated two cohorts of patients with suspected HFpEF that underwent TTE and RHC at our institution. The most recent TTE for each patient was screened using the AI-based analysis tool and was reported as either “suggestive” or “non-suggestive” of HFpEF – labeled as “positive” or “negative,” respectively. Mean PAP, pulmonary vascular resistance (PVR), pulmonary artery pulsatility index (PAPI), RV cardiac power output (RV-CPO), RV myocardial performance score (RV-MPS), and right atrial pressure to pulmonary capillary wedge pressure ratio (RA:PCWP) were calculated using invasive hemodynamic parameters at rest, and exercise when available. RV-CPO was calculated as [(mean PAP-RAP) x cardiac output] /451, and RV-MPS was calculated as (RV-CPO x PAP)x1.5. Median values were calculated. AI positive and negative groups were compared using Student’s t-test.Results:A total of 47 patients (82% women, 79% Black, average EF 62%) were included, with 23 undergoing subsequent exercise RHC. There were 18 (38%) that screened positive for HFpEF, and 29 (62%) screened negative by TTE AI software. Positive patients had a significantly higher mean PAP (median 31 vs 23 mmHg, p=0.01), PVR (2.1 vs 1.3 WU, p=0.02), and RV-CPO (0.26 vs. 0.17, p=0.04) than patients who were screened negative. There were no significant differences in PAPI, RV-MPS, and RA:PCWP at rest. There were no significant differences in mean PAP, PVR, PAPI RV-CPO, RV-MPS, or RA:PCWP with exercise.Conclusion:Patients screened positive for HFpEF by a novel AI TTE software had significantly higher PAP and RV-CPO at rest, but no differences in PAPI, RV-MPS, or RA:PCWP ratio. This tool may help identify more advanced HFpEF.

Circulation, Volume 150, Issue Suppl_1, Page A4125667-A4125667, November 12, 2024. Background:Renal denervation (RDN) has been shown in randomized trials to improve blood pressure compared with a sham procedure. Currently, there are two FDA-approved RDN devices in the United States (US). While nearly half of the US population has hypertension (HTN), the number of patients who may benefit from RDN therapy remains uncertain. In this study, we used a nationally representative dataset to approximate the proportion of patients with HTN who may be eligible for consideration of RDN based on selective criteria.Methods:All adult patients with HTN who participated in the National Health and Nutrition Examination Survey (NHANES) between the years 2009-2020 were identified. We characterized the proportion of these participants that met eligibility criteria based on 1) the FDA indication, 2) the SCAI 2023 RDN position statement, and 3) enrollment criteria from the RDN on-medication randomized trials. National estimates were obtained utilizing survey weighting from the NHANES multistage probability survey design.Results:In total, we identified 16,677 patients with HTN in the US, representing a weighted total of 113,786,149 patients (Table). Using the FDA indication, 31.6% (95% CI, 30.7%-32.6%) of patients meet eligibility criteria for RDN, corresponding to 35,988,870 US adults. By the SCAI 2023 position statement selection criteria, 21.5% (95% CI, 20.7%-22.3%) of patients are eligible for consideration of RDN. Based on enrollment criteria from the RDN on-medication randomized trials, 2.05% (95% CI, 1.81%-2.33%) of US adults meet eligibility for consideration of RDN (Figure).Conclusions:Our findings indicate that nearly one third of US adults with HTN are eligible for consideration of RDN based on the FDA indication; however, a smaller proportion of patients would be eligible based upon society recommendations and randomized trial inclusion criteria. Future studies are needed to further inform which patients will best benefit from this intervention.

Circulation, Volume 150, Issue Suppl_1, Page A4147545-A4147545, November 12, 2024. Introduction:Pulsed field ablation (PFA) is an adaptation of direct current ablation first used for catheter ablation in the 1980s. Expectations of a reduced risk profile led to the current resurgence in investment and interest in the technology as a potential alternative energy source for ablations to treat atrial fibrillation (AF). However, reports of adverse events, including new risks, are increasing.Research Question:How many adverse effects are reported with the use of newly available PFA systems?Aims:Quantify and describe the adverse events from PFA reported to date in the Food and Drug Administration’s (FDA) Manufacturer and User Facility Device Experience (MAUDE) database.Methods:We searched the U.S. FDA’s MAUDE database for all reports filed with the code “QZI”, which is the product code for PFA systems created with the first FDA approvals in February 2024. All reports from inception through April 2024 (a total of 3 months) were included in this review. Per manufacturer presentation in May 2024, approximately 1000 cases utilizing PFA had been captured in a post-market registry of the predominant commercially used technology, but the exact number of cases can not be determined from MAUDE data.Results:A total of 217 adverse events were reported over the first 3 months of US approval, with 91 of these considered patient injuries. These injuries included 10 cases of cardiac tamponade, 7 reports of postoperative arrhythmia, 6 instances of device-related tissue entrapment, 5 cases of hemolysis with impaired renal function, 5 cases of stroke or TIA, including both embolic and hemorrhagic, 3 cases of intraoperative heart block, 2 coronary spasms, and 2 cases of intraoperative ST elevation.(Figure)Of the 91 reported patient safety events, 46 required hospitalization, 13 cases required temporary pacing, 11 required pericardiocentesis, 4 required dialysis, 4 required cardiothoracic surgery, and 2 required cardioversion.Conclusions:A number of adverse events have been reported to the MAUDE database in the first 3 months of FDA approval of PFA. The cardiac electrophysiology community should remain vigilant to ensure that the benefit-risk profile remains acceptable for patient safety.

Circulation, Volume 150, Issue Suppl_1, Page A4143175-A4143175, November 12, 2024. Background:Mavacamten was approved by the US Food and Drug Administration (FDA) in April 2022 for the treatment of adults with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (HCM). Few studies have reported on the long-term real-world effectiveness and safety of mavacamten. We evaluated clinical outcomes in patients on mavacamten in multiple health centers across the United States.Research Questions:This study assessed the real-world effectiveness and safety of mavacamten in patients with symptomatic obstructive HCM.Methods:In this multi-center observational study, we evaluated patient characteristics at baseline, NYHA class, left ventricular outflow tract gradients (LVOTg) at rest and Valsalva, and left ventricular ejection fraction (LVEF) in patients with symptomatic obstructive HCM treated with mavacamten for up to 72 weeks.Results:Mavacamten was initiated in 172 patients across 4 US centers (UCSF, Mayo Arizona, Stanford, and Atlantic Health System/Morristown Medical Center). Baseline characteristics included: 56% female, mean age 64 (standard deviation ±13) years, 47% NYHA class III, mean resting LVOTg of 47 mmHg and mean Valsalva LVOTg of 89 mmHg, and 23% non-White. Comorbidities included hypertension (56%) and atrial fibrillation (25%) at baseline (Table). Patients experienced a notable early response to mavacamten in resting and Valsalva gradients by week 4, which was sustained through week 72 (Figure A). No patients were NYHA class III at week 72, compared to 47% at baseline (Figure B). Mean LVEF did not change substantially between baseline and week 72. No patients experienced an LVEF of

Circulation, Volume 150, Issue Suppl_1, Page A4145249-A4145249, November 12, 2024. Introduction:Droxidopa (DD) is the second FDA approved drug after midodrine for neurogenic orthostatic hypotension (nOH). Isaacon et al reported that 19 (5.4%) of total 350 patients on droxidopa had 25 cardiac events, most commonly atrial fibrillation in a mean duration of 363 days. Currently, limited long term cardiovascular safety data is available. We encountered a patient with nOH on DD, who developed symptomatic frequent premature ventricular contractions (PVCs) and severe cardiomyopathy (CM).Case:A 52-year-old woman with a long-standing nOH had persistent lightheadedness, dizziness, presyncope and hypotension despite midodrine, fludrocortisone, and non-pharmacological measures. Her past medical history was significant for nodular lymphocyte dominant Hodgkin lymphoma status post AVBD chemotherapy in 2001, with recurrence in 2012, which was treated with autologous stem cell transplantation.Patient was switched to DD from midodrine for nOH and responded well. However, she developed frequent PVCs(13%), left bundle branch block(QRS 127 ms), with new onset CM approximately 2 years later. The ischemic work-up with coronary angiography was normal and cardiac MRI showed no late gadolinium enhancement. DD was stopped and patient was started on GDMT for HFrEF with subsequent improvement in PVC burden(1%). GDMT uptitration was limited due to hypotension. Without EF recovery up to 2 years, she received CRT-D placement.Discussion:CM after anthracycline therapy is rare after 5 years. Our patient’s last exposure to doxorubincin was 17 years before the onset of CM. Serial echocardiograms showed normal cardiac function over years. A potential association of developing takotsubo cardiomyopathy was suggested in patients on DD by Sato et al, the potential mechanism being the increased adrenergic drive. The rapid development of non-ischemic, non-infiltrative CM and cardiac arrythmia, which subsequently improved by stopping the DD, is alarming for DD’s potential side effect.Conclusion:Caution should be taken in prescribing DD in patients with nOH, who are at higher risk for development of cardiac arrythmia and cardiomyopathy. Further studies and data are needed in identifying or excluding the potential cardiovascular side effects.

Circulation, Volume 150, Issue Suppl_1, Page A4147674-A4147674, November 12, 2024. Background:Leadless pacemaker (LP) is a novel pacemaker offering an innovative approach to bradyarrhythmia treatment. Aveir LP and Micra LP are the two leadless pacing systems available in the United States. Aveir LP was approved by the Food and Drug Administration (FDA) in April 2022. Data regarding the adverse events (AE) following implantation of Aveir LP is scarce, largely limited to single centers, and no real-world comparative analyses were done previously.Methods:We queried the FDA Manufacturer and User Facility Device Experience (MAUDE) database between April 2022 and December 2023 to assess the safety and AE following implantation of Aveir LP. “AVIER” and “MICRA” were the key terms used to search the MAUDE database. The event types “death” and “injury” were included in our search to capture major clinical events related to the patient. Disproportionality analysis was performed using the reporting odds ratio (ROR) to compare the adverse events of Aveir LP with Micra LP. A signal to noise ratio was considered to be significant if the confidence interval (CI) did not cross the number “one”.Results:Our search resulted in 207 event reports for Aveir LP and 1969 event reports for Micra LP. Major device related adverse events with Aveir LP were capturing problem (33.8%) followed by dislodgement (16.9%), and sensing problem (7.2%). Most encountered device related AE with Micra LP were capturing problem (37.8%), pacing problem (11.5%), and sensing problem (9.3%). Frequencies of all the analyzed AE are shown in Figure 1. The reporting of pericardial effusion (ROR 2.84, 95% CI 2.18-3.71), and dislodgment (ROR 1.85, 95% CI 1.26-2.73) were significantly higher with Aveir, whereas cardiac arrest (ROR 0.18, 95% CI 0.04-0.74) was disproportionately lower. Overall, patient related AE were significantly higher (ROR 1.53, 95% CI 1.20-1.95) and device related events were significantly lower (ROR 0.65, 95% CI 0.51-0.83) with Aveir LP compared to Micra LP (Figure 2).Conclusion:This is the first real-world comparative analysis of two leadless pacing systems available in the United States. Our analysis showed that, when compared to Micra LP, the newer Aveir LP had lower device related events but higher patient related events, largely driven by pericardial effusion. These events could be attributed to the operator learning curve and long-term data are needed to further verify these findings.

Circulation, Volume 150, Issue Suppl_1, Page A4141717-A4141717, November 12, 2024. Introduction:Although 14-day patch-based long-term continuous ambulatory ECG monitoring (LTCM) has shown greater diagnostic yield and lower retest rates compared to other rhythm monitoring modalities, wear can still be limited by factors related to patient comfort and acceptance. Rather than data from small, non-generalizable focus groups, patient survey data at point of care offered to all patients may be valuable in collecting quality improvement data on product experience and satisfaction. We assessed the feasibility of this approach to compare patient satisfaction associated with the prior generation LTCM to that of a new generation, FDA-cleared LTCM product designed with patient-centered features, including a more breathable adhesive, waterproof housing, thinner profile, and lighter weight.Methods:Starting in March 2018, we implemented a survey provided to all patients prescribed Zio® XT LTCM (iRhythm Technologies, San Francisco, CA) to complete and return at end of wear. The survey was completed via paper card or digitally via a web address printed on the card. The survey included questions regarding ease of use, comfort, ability for normal activity, and willingness to wear the device again. Scores of 4 or 5 (i.e., Agree or Strongly Agree) on a Likert scale were considered affirmative responses. Beginning in April 2022, the new Zio® Monitor device was launched for use and the same survey method was used. We compared survey responses for Monitor and XT between Jan 1 and Dec 31, 2023.Results:Among 334,054 respondents, the new LTCM was associated with a greater proportion of affirmative responses across all survey categories (Table 1), with the largest gains in comfort of wear (79.1% vs. 64.7%; p

Circulation, Volume 150, Issue Suppl_1, Page A4146364-A4146364, November 12, 2024. Background:According to the European Guidelines, “low-risk” pulmonary arterial hypertension (PAH) patients is defined as a risk of death < 5% within a year and represents a treatment-goal. However, the impact of morbidity (e.g. hospitalization and clinical worsening), were not included in this definition.Research Questions:Can REVEAL 2.0 risk score further identify low-risk PAH patients for both morbidity and mortality?Aims:Using the REVEAL 2.0 risk score, to propose a modified definition of “low-risk” to include the risk of both morbidity and mortality at 1- and 3-years, respectively.Methods:A harmonized dataset from 8 PAH randomized controlled trials from the FDA was used for this analysis and REVEAL 2.0 risk score was calculated for each patient. Modified low-risk was a priori defined by “risk of death ≤ 5% at 3-years and risk of clinical worsening ≤10% at 1-year”. Clinical worsening was defined as any of the following: lung transplantation or hospitalization due to PAH worsening, initiation of prostanoids/chronic oxygen, 15% decrease in 6-MWD from baseline, a worsening of NYHA, addition of a new PAH medication.Results:A total of 4,122 PAH patients were included: median age 49 (36, 62) yo, mPAP 50 (40, 60) mmHg, PVR 10 (7, 14) WU, 6MWD 375 (306, 423) m, NTproBNP 884 (230, 3010) pg/mL. Patients with a REVEAL 2.0 risk score ≤ 4 had a 1-year clinical worsening free-survival and 3-year survival rate of 92% and 95% (Figure 1). The 3-years survival was significantly better in patients with a REVEAL 2.0 ≤ 4 compared to 5-6: HR=0.47, 95%CI[0.27-0.84], p=0.01. Compared to patients with REVEAL 2.0 risk score of 5-6 (“classical” low-risk), those with a REVEAL 2.0 risk score ≤ 4 (“refined low-risk”) had a better clinical, biological, hemodynamic presentation, and outcomes (Table 1).Conclusion:This study is the first embedding both morbidity and mortality within the definition of low risk for PAH patients and suggests that PAH patients with REVEAL 2.0 risk score ≤ 4 meet this definition. This definition may be a promising new treatment-goal strategy in future randomized controlled trials but also for daily clinical practice.

Circulation, Volume 150, Issue Suppl_1, Page A4140424-A4140424, November 12, 2024. Introduction:Mavacamten is a first-in-class cardiac myosin inhibitor initially approved in the US for treating obstructive hypertrophic cardiomyopathy (oHCM) under the FDA-mandated Risk Evaluation Mitigation Strategy (REMS). Subsequently, mavacamten was approved in Canada with less restrictions. A patient support program (PSP) was implemented, offering a unique opportunity to generate data on mavacamten utilization in the Canadian population.Aims:The objective of the study was to obtain real-world insights into the demographic and clinical characteristics, including dosing and treatment duration of patients treated with mavacamten for oHCM in Canada.Methods:This was an observational retrospective study of 683 adult patients with symptomatic oHCM enrolled in the Canadian mavacamten PSP between January 4, 2023 to April 12, 2024. Baseline demographic and clinical data were collected for age, gender, NYHA class, vLVOT gradient, LVEF and change in mavacamten dose.Results:The baseline clinical characteristics of the 683 patients are summarized in Table 1. Patients were distributed across several provinces with a median age of 65 years and a similar distribution between the male and female populations. The majority (N=458: 67.1%) were classified as NYHA class II. Nearly all patients were initiated at 5 mg of mavacamten as per the Canadian product monograph. Most (63.7%) of patients were on β-blockers alone (Table 1). The median follow-up time was 27.4 weeks (range 1.6-70.1). Notably, at the time of data cut off, 13.2% of patients were receiving mavacamten alone compared to 10.5% at initiation. The median treatment duration was 24.6 weeks, censored at data cut-off, with a discontinuation rate of 7.9%, primarily due to adverse events (2.5%) and lack of efficacy (0.9%).Conclusions:Mavacamten has been widely adopted across Canada with low discontinuation rates indicating good tolerability. The current risk management strategies in Canada are sufficient and obviate the need for a stricter approach. These early results provide the largest dataset on mavacamten utilization in the Canadian HCM population, adding to the accruing evidence of its safe and effective use in the real world.

Circulation, Volume 150, Issue Suppl_1, Page A4142154-A4142154, November 12, 2024. Introduction:With the increasing popularity of glucagon-like peptide 1 receptor agonists (GLP1-RAs), numerous safety concerns arose pertaining to suicide, hair loss, and aspiration risks. We attempted to validate these concerns.Methods:We queried the FDA Adverse Event Reporting System (FAERS) database; a post-marketing pharmacovigilance database, from Q4/2003 till Q3/2023 to analyze public reports of these adverse events with GLP1-RAs and other diabetes medications, including sodium-glucose transporter 2 inhibitors (SGLT2is), dipeptidyl peptidase 4 inhibitors (DPP4is), sulfonylureas, metformin, and insulin. OpenVigil 2.1 is an online tool that was utilized to perform disproportionality analysis. A positive signal signifying disproportionate reporting was detected if the proportional reporting ratio (PRR) > 2 and chi-squared (χ2) > 4 for any drug-event pair. The studied medications were arranged in descending order according to the corresponding reporting odds ratio (ROR), which is a measure of the likelihood of reporting a certain event with a certain drug in comparison to all other drugs in the database.Results:No positive signals were observed between GLP1-RAs and either suicide, hair loss, or aspiration events. Semaglutide [ROR= 0.601 (95% CI 0.51 – 0.71)] and liraglutide [ROR= 0.282 (95% CI 0.228 – 0.35)] had higher suicidal events than DPP4is and SGLT2is. GLP1-RAs were the most reported class with hair loss [ROR= 0.605 (95% CI 0.6 – 0.64)], and semaglutide, liraglutide, and dulaglutide were the three leading medications. GLP1-RAs ranked lower with aspiration events, which were led by sitagliptin and DPP4i as a group. Only metformin and glyburide generated positive signals with suicide risk.Conclusion:GLP1-RAs exhibit higher reporting of suicide, hair loss, and aspiration events when compared to several other antidiabetic medications, despite not meeting the criteria for positive signals yet. This warrants intensive monitoring and reporting.

Circulation, Volume 150, Issue Suppl_1, Page A4143977-A4143977, November 12, 2024. Introduction:Chimeric Antigen Receptor T-cell therapy (CAR-T) has revolutionized the treatment of relapsed refractory multiple myeloma (RRMM) and lymphoma over the past decade. Our objective is to examine the incidence, patterns, and outcomes of cardiac events in patients with RRMM and lymphoma who are receiving CAR-T therapy, utilizing the FDA Adverse Event Reporting System (FAERS) database.Methods:We employed the FDA Adverse Event Reporting System (FAERS) database and the Medical Dictionary for Regulatory Activities (MEDRA) to conduct a retrospective post-marketing pharmacovigilance inquiry. We analyzed the incidence of cardiac events associated with six CAR-T products, namely Idecabtagene vicleucel, Cilitacabtagene autoleucel, Axicabtagene ciloleucel, Tisagenlecleucel, Lisocabtagene maraleucel, and Brexucabtagene autoleucel, since their FDA approval (accessed 05/01/2024). We assessed the cardiotoxicities such as coronary artery disease (CAD), myocardial infarction (MI), arrhythmia, heart failure, and hypotension.Results:A total of 12,949 adverse events, including Axicabtagene ciloleucel (n=6222, 48%), Brexucabtagene autoleucel (n=1127, 8.7%), Tisagenlecleucel (n=3290, 25.4%), Lisocabtagene maraleucel (n=463, 3.5%), Idecabtagene vicleucel (n=722, 5.5%), and Cilitacabtagene autoleucel (n=1125, 8.6%). Of those, 675 cases (5.2% of the total) that were related to cardiac events, regardless of their severity. The cardiotoxicity incidence was highest in Brexucabtagene autoleucel (n=85,7.5%), followed by Idecabtagene vicleucel (n=50,6.9%), Tisagenlecleucel (n=208,6.3%), Axicabtagene ciloleucel (n=278,4.5%), Lisocabtagene maraleucel (n=17,3.6%), and Ciltacabtagene autoleucel (n=37,3.2%).Cytokine release syndrome (CRS) is linked to nearly 440 cardiac events,accounting for 65% of all cardiac events.The most prevalent cardiotoxic event was Atrial Fibrillation (122), followed by the development of heart failure (113), Ventricular arrhythmia (108), hypotension (87), and Brady arrhythmia (41).The recipients of Brexucabtagene autoleucel had the highest mortality rate (n = 26,2.3%), followed by those receiving Tisagenlecleucel (n = 71,2.1%) and Lisocabtagene maraleucel (n = 10,2.1%).Conclusion:The cardiotoxic properties of CAR-T therapy can lead to fatal adverse events. Improving outcomes and preventing mortality in these populations can be achieved through timely monitoring.

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 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 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