Circulation, Volume 150, Issue Suppl_1, Page A4143294-A4143294, November 12, 2024. Introduction:Cardiac pacing devices, including Permanent Pacemakers (PPM) and Implanted Cardioverter Defibrillators (ICD), are essential in managing various cardiac conditions. Exercise capacity in patients hinges on both cardiac function enhancement and an appropriate chronotropic response. This case report underscores the strategic use of Cardiopulmonary Exercise Testing (CPET) to determine the activation of the Rate Response to Exercise (RRE) function in a patient with Heart Failure with reduced ejection fraction (HFrEF).Case Report:Our patient is a 64-year-old male with HFrEF due to hypertensive heart disease and ICD placement. He was undergoing therapy optimization at our advanced heart diseases clinic. Initially presenting with poor functional capacity, his condition improved significantly with ongoing therapy adjustments, as reflected by his KCCQ scores. This improvement enabled a comprehensive assessment using CPET. The initial CPET trial revealed moderately reduced exercise capacity and an absent chronotropic response, with a heart rate at 65 bpm and a peak VO2 of 67% predicted, categorizing him as Weber Class B. Based on these findings, we activated the RRE function and conducted a follow-up CPET. The re-evaluation demonstrated notable improvements: extended exercise duration post-anaerobic threshold, a peak VO2 of 72% predicted, and an upgraded Weber Class A status.Summary:This case exemplifies how tailored programming of pacing devices can significantly enhance exercise capacity in HF patients. Activating the RRE function in the patient’s PPM led to marked improvements in exercise capacity and prognostic indicators derived from CPET parameters, corroborating the limited existing data on this approach. Although specific guidelines are lacking, our findings highlight the utility of CPET in customizing PPM settings, particularly for HFrEF patients. This report underscores the importance of individualized treatment and invites further research into optimizing device settings to maximize patient outcomes. Leveraging CPET in routine clinical practice could revolutionize heart failure management, offering a precise and patient-centric approach.
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Abstract 4142133: Variant-enhancer-gene mapping at the 9p21 locus in smooth muscle cells reveals new enhancer-gene pairs and mechanistic insights for coronary artery disease
Circulation, Volume 150, Issue Suppl_1, Page A4142133-A4142133, November 12, 2024. The majority of variants identified by genome-wide association studies (GWAS) that influence coronary artery disease (CAD) risk reside in noncoding regions of the genome, making it challenging to link them with the genes they regulate. The 9p21.3 locus is the most impactful genetic risk locus for CAD. Due to the complexity of this locus, the causal genes and molecular mechanisms are poorly understood. Enhancers are cell type specific, and vascular smooth muscle cells (SMC) are known to have the highest heritable risk for CAD and play a major role in the atherosclerotic plaque formation. Here, we report efforts to systematically map SMC specific enhancers to neighboring genes within the 9p21.3 locus by implementing single cell CRISPRi enhancer screens and validating single causal variants in these enhancers. First, we intersected CAD GWAS loci with human coronary artery SMC (HCASMC) ATAC-seq and H3K27ac ChIP-seq datasets to focus on the disease relevant SNPs. This analysis identified 27 SNPs in 11 enhancers, that we targeted with CRISPRi machinery and analyzed at 5- and 10-days post transduction. As target genes in the locus are lowly expressed, we employed the targeted Perturb-seq (TAP-seq) approach for library generation and sequencing. We identified several enhancer-gene -pairs, including a strong enhancer-gene connection to bothCDKN2AandCDKN2B. Additionally, we identified multiple enhancer regions that controlMTAPexpression, with smaller but significant effects. We followed up with individual validation of enhancer-gene pairs through qPCR. Furthermore, these results are consistent with chromosomal interaction data obtained from our previous HiChIP. Notably, enhancers 5 and 6 were strong regulators of CDNK2B and CDKN2A expression, so we investigated how variants in these enhancers might directly disrupt transcription factor (TF) binding. By using luciferase enhancer assays, CHIPseq and phenotypic in vitro assays we linked this variation with TFs that drive vascular calcification in SMCs. Our results identify new variant to gene links and suggest how the genetic risk in 9p21 is mediated in the vascular wall, providing mechanistic understanding of vascular calcification and genetic risk of CAD and suggesting a novel mechanism of how 9p21.3 mediates disease risk.
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.
Abstract 4146475: Impact of Cancer on Atherosclerotic Burden and Coronary Anatomical Complexity in the Presence of Acute Coronary Syndromes: A Comparative Analysis from the BRAVADO Registry
Circulation, Volume 150, Issue Suppl_1, Page A4146475-A4146475, November 12, 2024. Background:The interaction between cancer and coronary artery disease (CAD) significantly impacts cardiovascular outcomes and disease progression. However, the impact of cancer on atherosclerotic plaque burden and coronary lesion complexity in acute coronary syndrome (ACS) have not yet been studied.Objective:The aim of this study is to correlates the presence of cancer e atherosclerotic plaque burdenMethods:This is a multicenter, ambispective, observational study, based on the analysis of coronary angiographies. Data was collected between September 2016 to December 2022. Patients were categorized into three study groups: ACSC (ACS with a history of cancer), ACSNC (ACS without a history of cancer), and CCAD (chronic coronary artery disease). Patients with ACS were consecutively included while those with CCAD were randomly included. Propensity score matching between ACSC and ACSNC groups was performed.Results:618 patients were included, and 3,752 coronary lesions were analyzed. The mean age of the patients was 68 years, with more than 74% diagnosed with hypertension. The most common types of cancer were prostate, hematological, and colorectal cancer (Figure 1). Patients with acute presentations had more eccentric and ulcerated lesions, with lumen obstructions greater than 90%, involving bifurcations and resulting in worse SYNTAX and Leaman scores compared to chronic coronary artery disease (p values < 0.01 for all). Post-matching, 234 ACSC and ACSNC patients were compared, revealing heightened atherosclerotic burden in ACSC, evidenced by elevated SYNTAX scores and complex lesions (p < 0.01). This group also showed a higher prevalence of complex lesions in the proximal thirds of the vessels, with statistical correlation (p = 0.003), as shown onFigure 2.Conclusion:Cancer was associated with a greater atherosclerotic burden and greater complexity of coronary lesions in patients with ACS when compared to those without history of cancer. These findings underscore the impact of cancer on exacerbating cardiovascular complexity in ACS individuals, emphasizing the need for comprehensive management strategies in this population.
Abstract 4146512: Modifiability of Post-Exercise Oxygen Uptake Recovery Patterns: A Substudy of the SEQUOIA-HCM Randomized Trial
Circulation, Volume 150, Issue Suppl_1, Page A4146512-A4146512, November 12, 2024. Background:Recent heart failure studies show that post-exercise VO2recovery (VO2Rec) patterns track closely with exercise cardiac output and outcomes, but not with peripheral oxygen (O2) extraction. In patients with obstructive hypertrophic cardiomyopathy (oHCM), studies of VO2Rec changes with effective cardio-specific interventions are lacking. We hypothesized that treatment with aficamten, a next-in-class cardiac myosin inhibitor, would shorten VO2Rec in patients with oHCM.Methods:SEQUOIA-HCM is the pivotal phase 3 trial of aficamten in symptomatic patients with oHCM (New York Heart Association functional class [NYHA FC] II-III, peak VO2[pVO2] ≤90% predicted, respiratory exchange ratio ≥1.05). Patients were randomized 1:1 to aficamten or placebo for 24 weeks with the primary endpoint of change from baseline (BL) in pVO2. For this analysis, VO2Rec was measured as the time taken after exercise cessation for VO2to decline by 12.5% (t12.5%), 25%, or 50% of pVO2. Response rates for achieving clinically meaningful threshold reductions ( >15 seconds) in t12.5%, and correlations with changes in cardiac function (echocardiographic parameters/cardiac biomarkers) were assessed.Results:Among 282 randomized patients (mean age 59.1±12.9 years, 115 female [41%]), 263 (93%) had CPETs at BL and W24 with VO2Rec values as shown (Table). At W24, t12.5%improved by 8sec (95% CI, -12, -5sec, p
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 4135723: Efficacy and Safety of Ticagrelor with Aspirin vs Ticagrelor Monotherapy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Circulation, Volume 150, Issue Suppl_1, Page A4135723-A4135723, November 12, 2024. Background:Dual antiplatelet therapy (DAPT) consisting of ticagrelor, a P2Y12inhibitor, and aspirin, is the recommended treatment of acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI). However, recently ticagrelor monotherapy has been shown to preserve ischemic protection while reducing bleeding risk in ACS patients. We aimed to compare the clinical outcomes of DAPT and ticagrelor monotherapy in ACS patients undergoing PCI.Methods:MEDLINE, Scopus, and EMBASE were queried up to May 2024 for randomized controlled trials (RCTs) comparing ticagrelor monotherapy after 1 to 3 months of DAPT versus continued DAPT for 12 months in ACS patients. The primary outcomes were all-cause death, net adverse clinical events (NACE) and Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. Key secondary endpoints included BARC 3 or 5 bleeding, myocardial infarction (MI), hemorrhagic and ischemic stroke, and target vessel revascularization (TVR). A random-effects meta-analysis was performed to derive risk ratios (RR) and corresponding 95% confidence intervals (CI).Results:Six RCTs including 28,526 patients, with a mean age of 63.5 years, were included. DAPT was associated with a significantly higher risk of all-cause death (RR: 1.32, 95% CI: 1.05-1.64, P=0.02), NACE (RR: 1.20, 95% CI: 1.01-1.42, P=0.04), and BARC 2, 3, or 5 bleeding (RR: 1.96, 95% CI: 1.71-2.26, P
Abstract 4143356: Validation of a High Bleeding Risk Definition in Cancer Patients Undergoing Percutaneous Coronary Intervention
Circulation, Volume 150, Issue Suppl_1, Page A4143356-A4143356, November 12, 2024. Background:Currently, there are no validated tools to stratify bleeding risk in cancer patients undergoing percutaneous coronary intervention (PCI). The presence of cancer itself is considered a major high bleeding risk (HBR) feature according to the Academic Research Consortium (ARC) definition. However, cancer creates a hypercoagulable state and predisposes patients to thrombotic complications as well as bleeding.Hypothesis:A dedicated HBR definition for cancer patients undergoing PCI could be useful to identify subjects at higher risk of adverse events.Aims:To validate an adapted version of the ARC-HBR criteria in patients with cancer undergoing PCI.Methods:Consecutive patients with a history of cancer undergoing PCI between 2012 and 2022 at a tertiary care center (Mount Sinai Hospital, New York, US) were included. According to our adapted definition, patients were considered at HBR if they met at least one of the major ARC-HBR criteria (other than cancer) or two minor criteria.The primary endpoint was a composite of periprocedural in-hospital or post-discharge bleeding at 1 year. The key secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE) consisting of death, myocardial infarction, or stroke.Results:Of the 2,007 cancer patients included in this study, 1,142 (56.9%) were classified as HBR. Moderate to severe anemia was the most prevalent major HBR criterion (Figure 1).At 1 year, the incidence of bleeding was significantly higher in HBR compared to non-HBR patients (10.9% vs. 3.9%, adj. HR: 2.10, 95% CI: 1.39-3.18, p
Abstract 4145440: Simultaneous Percutaneous Ventricular Septal Closure and Mitral Valve Repair in Postinfarction Ventricular Septal Rupture and Papillary Muscle Rupture Complicated by Cardiogenic Shock
Circulation, Volume 150, Issue Suppl_1, Page A4145440-A4145440, November 12, 2024. Introduction:Post-infarction (post-MI) ventricular septal rupture (VSR) and papillary muscle rupture (PMR) are usually lethal complications of acute STEMI that have decreased in the fibrinolytic era and with rapid STEMI response teams. Delayed correction is preferred for recovery from MI and healing of the edges of the VSD but like emergent repair, delayed treatment is also associated with high mortality. We present a case of concomitant post-MI VSR and PMR successfully corrected by simultaneous percutaneous intervention.Case presentation:A 76-yo female with hypertension, obesity and asthma presented with progressively worsening dyspnea and mild substernal chest pain for 4 days. She appeared pale, diaphoretic, and hypoxic, with troponin of 22ng/mL and lactate of 9mmol/L. ECG showed Q waves with STE
Abstract 4141366: Teamwork Makes the Dream Work: Self-care and Depressive Symptoms in Rural Heart Failure Dyads
Circulation, Volume 150, Issue Suppl_1, Page A4141366-A4141366, November 12, 2024. Introduction:Managing heart failure (HF) in the home is stressful and complex for rural dyads who experience unique challenges and barriers to optimal HF self-care (SC). Innovative, tailored, dyadic problem-solving interventions are needed which support teamwork in managing HF SC problems in the home to enhance dyadic HF SC and reduce depressive symptoms.Research Question:Will participation in a 3-month dyadic, telephone-based problem-solving intervention focused on dyadic HF SC problems experienced in the home improve patient and care partner-contributed HF SC and reduce depressive symptoms in rural dyads living with HF?Methods:Using a dyadic single-group repeated-measures design, 41 rural dyads (patient-informal care partner) living with HF participated in 8 telephone sessions with a registered nurse to identify and develop management strategies for dyadic HF SC problems experienced in the home. Data were collected at baseline and 5-, 9-, and 13-weeks post baseline using the Self-care of HF Index (SCHFI), Caregiver Contribution to the SCHFI, and the Center for Epidemiological Studies – Depression Scale. HF patients were mostly female (59%), married (66.7%) Caucasians (69.2%), with 2-3 comorbidities (53.8%) and Class 2 NYHA HF (69.2%). Care partners were primarily female (58.5%), married (75.6%) Caucasians (70.7%), and spouses of the HF patient (68.3%), with 0-1 comorbidities (58.6%), and had been providing care for ≥ 5 years (46.3%). Descriptive statistics were used to examine dyad characteristics and outcome variables at each time point. Changes in patients’ and care partners’ outcomes were analyzed using dyadic Growth Curve Modeling within the Multilevel Modeling framework.Results:Across time, patient scores improved for depressive symptoms (b= -1.81,p= .002) and SC maintenance (b= 2.29,p< .001). SC confidence increased in both patients (b= 2.51,p< .001) and care partners (b= 2.26,p= .01). Increases in patient SC management across time was noted but non-significant (b= 1.46,p= .133 for patients;b= 0.60,p= .561 for care partners).Conclusions:Problem-solving interventions in rural dyads living with HF may be helpful in addressing HF SC issues and depressive symptoms in the home, especially in HF patients. However, more research is needed to examine this promising intervention in a larger clinical trial.
Abstract 4142875: Beyond Static Cold storage: Partial freezing for extending heart preservation and improving recovery
Circulation, Volume 150, Issue Suppl_1, Page A4142875-A4142875, November 12, 2024. Background:Cardiovascular diseases, the leading cause of mortality with 17.9 million deaths annually (WHO), often necessitate heart transplants for end-stage organ failure. However, donor heart demand far exceeds supply. Traditional organ preservation methods like static cold storage (SCS) offer a limited 4-6 hour window, while machine perfusion (MP) extends this by circulating an oxygen-rich solution but faces challenges with nutrient depletion and metabolic imbalances. Our “partial freezing” method offers a novel approach to organ preservation using cryoprotectants (CPAs), by achieving a stable frozen state while maintaining an unfrozen fraction to limit ice damage and dehydrationHypothesis:Partial freezing (PF) method can effectively extend the storage duration of rodent hearts while maintaining their viability and function.Methods:The PF of the heart entails six major steps: (1) Procuring hearts (N=3) from adult male Lewis rats (2) Preloading of CPAs (DMSO, glycerol, raffinose, mannitol, and proline) during hypothermic Langendorff mode perfusion for 30 min (3) Freezing the hearts at a controlled rate of 0.3°C/min to -6°C (4) Storage at -6°C for 18 hours (5) Gradual thawing and unloading of CPAs (6) Recovery of hearts during NMP (normothermic machine perfusion) with antioxidant-supplemented Tyrode solution, followed by viability assessment using metabolic, hemodynamic, and molecular parameters. Two control groups were also included in the study: (1) Fresh hearts (N=3) functionally recovered in Tyrode solution, and (2) SCS hearts (N=3), perfused with cold University of Wisconsin (UW) solution and stored in the UW solution for 18 hours at 4°C, then recovered in same solution as the PF hearts.Results:NMP assessments revealed promising outcomes for PF hearts, with histology, TTC (Triphenyltetrazolium chloride) and Connexin-43 immunostaining profiles comparable to fresh controls and superior to SCS hearts. Although PF hearts exhibited lower beating rates, they demonstrated comparable metabolic parameters (lactate and oxygen consumption) and tissue edema compared to fresh controls, indicating preserved cardiac performance post-recovery.Conclusion:Our study shows the potential of the PF method to extend storage to 18 hours while maintaining viability and molecular function similar to fresh controls and superior to SCS hearts. This exploratory study suggests PF as a promising method to extend heart preservation times, addressing current limitations.
Abstract 4145869: Predictive Value of Dipeptidyl Peptidase 3 Plasma Levels for Cardiogenic Shock and Mortality in Acute Coronary Syndromes
Circulation, Volume 150, Issue Suppl_1, Page A4145869-A4145869, November 12, 2024. Introduction:Dipeptidyl amino-peptidase 3 (DPP3) is an aminopeptidase released into the bloodstream following cell death. Studies have demonstrated that in patients experiencing cardiogenic shock (CS), there’s an elevation in circulating DPP3 (cDPP3) plasma concentration, which is associated with a heightened risk of mortality. This research investigated the connection between serum DPP3 levels, CS occurrence, and mortality in individuals diagnosed with acute coronary syndromes (ACS).Methods and Materials:In this prospective, multicentric study, consecutive patients with acute coronary syndrome diagnosis were enrolled, and their plasma levels of DPP3 were evaluated at both baseline and 12-24 hours post-presentation. The ORBI risk score was used to classify patients with a higher risk of cardiogenic shock.Results:Elevated circulating levels of DPP3 were linked to in-hospital cardiogenic shock, even when considering established risk factors such as the ORBI risk score (with a hazard ratio of 2.17 per log-2 increase, 95% confidence interval 0.94–1.97, and a P-value
Abstract 4135852: Safety and Post-operative Complications of Endovascular Versus Surgical Versus Follow-up and Medical Treatment for Patients with Vertebrobasilar Artery Stenosis: Propensity Score Weighting and a Machine Learning Driven Analysis
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.
Abstract 4145275: Demonstrating Pulmonary Hypertension Reversibility Before Heart Transplantation: A Novel Bedside Technique Using Postural Change
Circulation, Volume 150, Issue Suppl_1, Page A4145275-A4145275, November 12, 2024. Introduction:Pre-transplant pulmonary hypertension (PH) increases the risk of post-heart transplant right ventricular failure and as a result, morbidity, and mortality. Irreversible pulmonary hypertension is a contraindication to heart-only transplantation. Invasive and non-invasive methods to show PH reversibility include temporary and durable mechanical circulatory support (MCS), pulmonary vasodilators, diuretics, and inotropes. We herein describe a novel bedside technique to show PH reversibility and discuss its potential implications.Case:A 58-year-old female with advanced nonischemic cardiomyopathy was evaluated for heart transplant. There was no history of diabetes or dysautonomia. Supine right heart catheterization showed significant PH with the following data: PA 70/37 mmHg (48 mmHg); PCWP 25 mmHg; CO 4.03 L/min; PVR 5.7 WU. Diuretic therapy and sodium nitroprusside (SNP) were started, however due to hypotension SNP was stopped, and milrinone was initiated. Incidentally, we noticed that while seated in a chair her pulmonary hemodynamics dramatically improved without additional intervention: BP 111/73 (85) mmHg; PA 36/20 (25 mmHg); CO 3.91L/min. Once back in the supine position, the PA pressures returned to baseline. The findings were reproducible (Figure).Management:The patient continued IV diuretic and milrinone. SNP was not reintroduced, and IABP unloading was avoided as we felt reassured that the postural change in PA pressure was equivalent to vasodilator associated PH reversibility and identified a favorable phenotype for transplant. The patient underwent heart transplant and did not require an RVAD, or prolonged inotrope wean.Conclusion:To our knowledge this is the first case to describe the utility and predictive value of postural reversibility in PH in heart transplant. This is a simple bedside technique that can be performed at no extra cost using gravity to change cardiac loading conditions and may be as effective as more expensive and invasive treatments. Implications include the use of lower body negative pressure (LBNP) to prevent PH while supine during sleep or in bed. LBNP decreases venous return, leading to reduced preload and afterload, and thus reduces PH and in theory may avoid the need for durable MCS to treat PH in those needing heart transplant. We encourage further studies to determine the cost-effectiveness, clinical utility, and predictability of this novel technique for both RV failure post heart transplant and post-LVAD.
Abstract 4147797: Clinical Correlations with Longitudinal Echocardiography and Global Longitudinal Strain in the First and Second Genetically Modified Porcine to Human Cardiac Xenotransplantation
Circulation, Volume 150, Issue Suppl_1, Page A4147797-A4147797, November 12, 2024. Background:Our institution performed the first and second genetically modified porcine cardiac xenotransplantation in a human in the world. Our laboratory performed serial and longitudinal transthoracic echocardiograms (TTE) with global longitudinal strain (GLS) for both patients for clinical surveillance and to identify any evidence of xenograft failure. For both recipients, marked myocardial hypertrophy with worsening GLS were noted at the time of graft failure.Study Aim:The aim of this study is to identify noninvasive measurements which may help predict early graft failure and mortality in cardiac xenotransplantation. We hypothesize that a ratio of papillary muscle measurement (PPM) to end diastolic diameter (EDD) measured on TTE with GLS may predict xenotransplant graft failure and mortality.Methods:Echocardiographic measurements were made in both xenotransplanted patients, which included PPM, EDD, and GLS. Serial echocardiographic measurements and ratios were subsequently compared to endomyocardial biopsies (EMBx) and clinical correlation, including terminal graft failure and death.Results:From post-operative day (POD) 1 of xenotransplant to end-of-life for both recipients, PPM thickness increased by 84.5% (CI 78.8-95.2%) while EDD decreased by 40.2% (CI 20.3-64.1%). For the first recipient, PPM/EDD progressively increased from 0.23 (POD 1) to 0.57 (POD 58), when the xenotransplant terminally failed from a restrictive myopathy (LVEF 55%, GLS -7.7) confirmed by EMBx. For the second recipient, PPM/EDD progressively increased from 0.26 (POD 1) to 1.00 (POD 40) (Figure 1), when the graft terminally failed due to combined systolic and diastolic dysfunction (LVEF 25%, GLS -7.6), also confirmed by EMBx. For both xenografts, the global longitudinal strain (GLS) worsened (more positive) by an average of 42.3% (CI 42.2 – 42.4%) when the PPM/EDD ratio reached between 0.5 and 0.6.Conclusion:Increased ratio of PPM to EDD is associated with worsening GLS, cardiac xenotransplant graft failure, and recipient mortality. TTE with GLS provided real-time clinical and noninvasive histological correlation in the first and second transgenic cardiac xenotransplants. Given the interest in cardiac xenotransplantation, serial noninvasive measurements identifying early graft failure will be important for future monitoring and management.
Abstract 4146286: Embolization of an Amplatzer Amulet Through a MitraClip Causing Torsades and LVOT Obstruction: A Case Report
Circulation, Volume 150, Issue Suppl_1, Page A4146286-A4146286, November 12, 2024. Introduction:The morphology and blood stasis of the left atrial appendage (LAA) in tandem with disorganized conduction in atrial fibrillation (AF) creates favorable conditions for thrombus formation. Left atrial appendage occlusion (LAAO) devices have become increasingly utilized for stroke prevention in select patients with AF who have contraindications to oral anticoagulation (OAC). We present a unique case of an embolized Amplatzer Amulet LAAO device through a MitraClip into the LV causing polymorphic VT and obstructive shock.Case Presentation:An 80-year-old man with AF and mitral valve prolapse status post MitraClip presented to the hospital for difficulty breathing and palpitations two days after implantation of a 31mm Amplatzer Amulet LAAO device. Notably, he underwent failed attempt at Watchman LAAO implantation due to peridevice leak one year prior. On arrival, he was hypotensive with numerous episodes of polymorphic VT, requiring cardioversion, vasopressors, and mechanical ventilation. TTE located the Amulet within the LV outflow tract (LVOT) creating LVOT obstruction and revealed single-leaflet attachment of the MitraClip. He was evaluated for device retrieval and mechanical support but was deemed not a surgical candidate due to severe thrombocytopenia and guarded prognosis. Despite ongoing resuscitative efforts, the patient became increasingly unstable and died in the cardiac ICU.Discussion:In patients who are unable to tolerate OAC, occlusion of the LAA for stroke prevention has garnered growing interest; however, these devices are not without complication and do not guarantee full occlusion of the LAA. Despite our patient’s history of failing Watchman deployment, he was discharged on the same day after implant of the Amulet device without post-procedure TTE. We postulate that the Amulet device dislodged shortly after deployment and was held within the left atrium by the MitraClip until detachment, allowing for device embolization and severe MR. To our knowledge this is the first documented instance of Amulet device migration into the LV in a patient with a MitraClip. This case highlights the need for heightened post-procedure monitoring, surveillance, and imaging in select patients.