Circulation, Volume 150, Issue Suppl_1, Page A4139235-A4139235, November 12, 2024. Background:Colorectal cancer (CRC) risk is elevated in solid organ transplant recipients. However, data on CRC risk in heart transplant (HT) patients are limited. Also, screening recommendations for CRC in the HT population, especially patients under age 45, are lacking. Previous studies have been constrained by single-center designs, outdated cohorts, and lack of competing mortality analysis.Objectives:We aimed to assess competing-risk incidence of post-HT CRC, with focus on the effect of age, to inform CRC screening recommendations.Methods:We identified patients ≥18 years old at the time of HT in the TriNetX Research Network, which encompasses healthcare records from over 80 systems in the US, using CPT codes for HT (33945) and combined lung-HT (33935). CRC was identified from ICD-10 CM codes (C18, C19&C20). Because mortality is significantly higher than CRC risk in this population, we used the Fine and Gray competing-risks framework to estimate CRC incidence for the entire cohort and subgroups of interest.Results:We identified 4791 patients with HT or lung-HT between 1996 and 2024. After excluding 275 patients because of missing (N=266) or too short (N=9) follow-up, 4516 patients were included (Table 1). After a median follow up of 3.6 years (25th– 75thpercentile, 1.4 – 6.7), 48 patients developed CRC. The median time from HT to CRC was 4.5 years (0.7 – 8.0) and the median age at CRC was 65 (55 – 71). The cumulative incidence, adjusting for competing mortality, was 0.68% (95%CI: 0.45%, 1.0%) at 5 years and 1.7% (95%CI: 1.2%, 2.4%) at 10 years (Figure 1), corresponding to an incidence rate of 170 cases per 100,000 patient-years, and did not differ between men and women (180 vs. 120; P=0.7). In comparison, all-cause mortality was 20% at 5 years and 38% at 10 years. Age at HT was not significantly associated with CRC risk (P=0.22); patients age
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Abstract 4139977: Aggressive LDL cholesterol lowering post ACS with triple combination therapy: Insights from the multicentric LAI-REACT study
Circulation, Volume 150, Issue Suppl_1, Page A4139977-A4139977, November 12, 2024. Background:Patients with acute coronary syndrome (ACS) face a high risk of recurrent events in the early post ACS period. Rapid reduction of low-density lipoprotein cholesterol (LDL-C) is crucial, but high-intensity statins (HIS) alone often fall short of goals.Research Hypothesis:Early use of triple combination therapy of HIS with non-statin drugs: ezetimibe and bempedoic acid (BA) is likely to help achieving the target goals rapidly.Aim:The LAI-REACT (Lipid Association of India Recommended Early and aggressive lipid lowering in ACS with triple Combination Therapy) study evaluated the LDL-C lowering efficacy of a novel triple combination REB (40 mg rosuvastatin, 10 mg ezetimibe, and 180 mg bempedoic acid daily), in patients with ACS.Methods:The multicentric LAI-REACT study enrolled 369 statin-naïve ACS patients across five Indian centers. All received the triple REB combination upon admission. Lipid profiles were assessed at baseline and weeks 1, 2, 4, and 6.Results:The mean age of the study population was 56.3 ± 11.3 years. The mean LDL-C at admission was 119.2 ± 37.1 mg/dL, which significantly decreased to 49.4 ± 19.3 mg/dL at week 1, 44.7 ± 17.4 mg/dL at week 2, 44.6 ± 16.6 mg/dL at week 4, and 46.7 ± 18.3 mg/dL at week 6. The percentage reductions in LDL-C at weeks 1, 2, 4, and 6 were 58.6%, 62.5%, 62.6%, and 60.8% respectively (repeated measures ANOVA, p
Abstract 4141532: Time-Restricted Eating Improves Heart Rate, Symptoms, and Quality of Life Metrics in Patients With Postural Orthostatic Tachycardia Syndrome
Circulation, Volume 150, Issue Suppl_1, Page A4141532-A4141532, November 12, 2024. Introduction/Hypothesis:Time-restricted eating (TRE) is a lifestyle intervention in which there is an extended fasting period overnight of about 14 hours with a 10-hour eating window. Clinical and animal studies have shown that TRE decreases inflammation, and improves immune autonomic and mitochondrial function and cardiometabolic parameters. Patients with POTS have derangements in many of these parameters resulting in the hypothesis that TRE could be beneficial for patients with POTS.Methods/Approach:20 participants aged 18-70 (M=36 years ±11.79), all on pharmacological therapy for POTS, met inclusion criteria: ≥12-hour dietary window and established POTS diagnosis (≥30 bpm increase in upright heart rate). After a 2-week baseline period of monitoring via myCircadianClock App, to ensure baseline eating window was ≥12 hours, participants entered a 12-week TRE intervention, consuming calories within an 8-10 hour eating window. Pre/post-intervention assessments included a 10-minute stand test and QOL questionnaires (SF-36 and MALMO POTS).Results/Data:Orthostatic assessments comparing pre and post-intervention standing tests revealed reduction in heart rate increase. 19 of the 20 participants experienced this improvement, with the mean decrease in heart rate change (Figure 1A) averaging approximately 11 bpm (p < 0.001). Additionally, outcomes from the MALMO POTS Symptom Score Survey (MALMO) (Figure 1B) and the Short Form (36) Health Survey (SF-36) showcased substantial enhancements in participants' QOL. These improvements were evidenced by reductions in POTS symptom severity (p < 0.0001) and notable enhancements in physical functioning (p = 0.015) and energy/fatigue levels (p < 0.01).Conclusion:In this pilot study, TRE improved heart rate, symptoms and QOL in patients with POTS, who are on background medical therapy, suggesting this lifestyle intervention could be beneficial for patients with POTS.
Abstract 4145292: DERIVATION OF AN ARTIFICIAL INTELLIGENCE – BASED ELECTROCARDIOGRAPHIC MODEL FOR THE DETECTION OF ACUTE CORONARY OCCLUSIVE MYOCARDIAL INFARCTION
Circulation, Volume 150, Issue Suppl_1, Page A4145292-A4145292, November 12, 2024. INTRODUCTION:Current ACS guidelines suggest classifying patients according to the presence of persistent ST segment elevation, as a finding suggestive of acute thrombotic coronary occlusion. However, large series have documented that up to 15% of patients initially classified as NSTEMI will show evidence of total coronary occlusion on index angiography, increasing the length of stay, use of hospital resources, and short-term and long-term mortality. Therefore, prompt detection of Acute Coronary Occlusion Myocardial Infarction (ACOMI) is paramount.AIMS:We aimed to assess the performance of an AI-ECG based model capable of detecting ACOMI in the setting of patients with ACS.Methods:This is a prospective study based on the development of an AI-ECG based model capable of detecting ACOMI. A publicly available dataset (PTB-XL ECG) of 21,837 12-lead ECGs was used for training in recognizing ST-segment elevation. Regarding the detection of ACOMI, 12-lead ECGs from 361 patients who presented to the ED with an ACS (2017-2023) at our center were digitized with phone cameras of varying quality. ECGs were independently evaluated by two expert cardiologists blinded to clinical outcomes; each was asked to determine a) whether the patient had an STEMI, based on universal criteria or b) if STEMI criteria was not met, to identify any other ECG finding suggestive of ACOMI. ACOMI was defined as the presence of one of the following: TIMI V thrombus, TIMI thrombus grade 2 or higher + TIMI grade flow 1 or less, or the presence of a subocclusive ( >90%) lesion. Patients were classified into four groups: STEMI + ACOMI, NSTEMI + ACOMI, STEMI + non-ACOMI and NSTEMI + non-ACOMI. Performance of the AI model was evaluated using a comparison of multiple areas under the receiver operating characteristic curve (AUC-ROC). Sensitivity, specificity, positive and negative (PPV, NPV) predictive values and F1-score were also calculated.Results:The AI model accomplished an AUC of 0.8667 in identifying ACOMI, outperforming ECG experts (AUC: 0.3333) and the use of universal STEMI criteria (AUC: 0.5095). It also accomplished a sensitivity of 1, specificity of 0.733, a PPV of 0.846, an NPV of 1 and an F1-score of 0.92.Conclusion:Our AI-ECG model demonstrated a higher diagnostic precision for the detection of ACOMI compared with experts and use of STEMI criteria. Further research and external validation is needed to understand the role of AI-based models in the setting of ACS.:
Abstract 4141423: Bridging the Divide: Evaluating Outcomes Between the Sexes for Transcatheter Aortic Valve Replacement
Circulation, Volume 150, Issue Suppl_1, Page A4141423-A4141423, November 12, 2024. Introduction:Sex-related short-term outcomes following transcatheter aortic valve replacement (TAVR) are known. There is less data comparing the long-term differences in outcomes between sexes. Studies suggest women are less likely to be referred for TAVR and have higher mortality. This study investigated the differences between genders and races on outcomes in the following 6 and 12 months post-TAVR.Questions:Are there differences in outcomes between males and females who undergo TAVR? Are there differences in outcomes between females of different races undergoing TAVR?Methods:We performed a retrospective cohort study among 252 patients undergoing TAVR between 2018 and 2023 at a major academic medical center in Chicago, Illinois. Primary outcomes included composite major adverse cardiac events (MACE) (CVA, MI and/or CVA) and all-cause death. Outcomes were analyzed at 6 and 12 months following TAVR. T and Chi square tests were used to analyze continuous/categorical variables respectively.Results:Among the 252 patients studied, 27.4% were female, 27.5% white, 47.8% black, 10.1% Hispanic/Latino, 14.45% other. Average age of females and males were 77 ± 1 years and 75 ± 0.74 years (p=0.2967), respectively. Males were more likely to be former smokers (p=0.000) and to drink more than 8 alcoholic beverages per week (p=0.023). No significant differences were seen between genders for MACE, all-cause death, CVA or MI at 6 or 12 months (Table 1). There were also no significant differences were found between females of different races for MACE, all-cause death, CVA, or MI at 6 or 12 months. There was a significant difference by race for development of conduction abnormalities found at 6-month follow-up (p=0.02).Conclusion:This study shows females appeared to have similar outcomes at 6 and 12 months following TAVR when compared to males. However, the possible causes leading to increased development of conduction abnormalities found at 6 months follow up between female racial groups needs to be further studied.
Abstract 4140361: Evaluating Inflammatory Tone Following Consumption of Full-fat or Non-fat Yogurt: Peripheral Blood Mononuclear Cell Inflammatory Response
Circulation, Volume 150, Issue Suppl_1, Page A4140361-A4140361, November 12, 2024. Inflammation is vital to maintaining homeostasis and immune defense, yet chronic, low-grade inflammation is a hallmark of many cardiometabolic diseases. Due to the high saturated fatty acid content in full-fat dairy foods, national dietary guidance recommends consuming low- or non-fat dairy foods to decrease cardiometabolic disease risk. However, many unique fatty acids found in dairy fat may elicit beneficial effects on chronic low-grade inflammation and the effect of dairy fat within its food matrix remains unclear. Thus, our research question centered on the effect of full-fat dairy foods on inflammatory tone. We hypothesized that short-term consumption of three daily servings of full-fat yogurt would beneficially affect inflammatory tone. The aim of the project was to compare the inflammatory response of individuals with prediabetes after a diet with and without dairy fat. An eight-week randomized controlled clinical trial was conducted comprising two, three-week experimental diet periods, differentiated by the daily consumption of either full-fat yogurt (3.25% fat) or non-fat yogurt. Each experimental diet was preceded by a one-week control diet. Following each diet period, peripheral blood mononuclear cells were isolated from whole blood and incubated in media with or without lipopolysaccharide stimulus. After a 24-hour incubation, cell supernatants were analyzed for interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α concentrations. Under unstimulated conditions, the concentration of IL-1β present in the cell supernatant was lower as a result of the full-fat yogurt diet, compared to the non-fat yogurt diet (0.1 pg/mL compared to 24 pg/mL, respectively;P< 0.01), but there were no differences between diets in IL-1β concentrations at 1, 10, or 100 ng/mL lipopolysaccharide stimulation. Diet did not affect supernatant concentrations of IL-6, IL-8, IL-10, or tumor necrosis factor-α in the unstimulated and stimulated conditions. In conclusion, only minimal differences were observed between diets with three daily servings of full-fat or non-fat yogurt indicating that short-term consumption of dairy fat may not impact inflammation via peripheral blood mononuclear cell cytokine secretion.Funding for this project was provided by the National Dairy Council, Vermont Dairy Promotion Board, USDA National Institute of Food and Agriculture, and UVM Food Systems Research Center.
Abstract 4145771: Association Between Sleep Quality Parameters and Risk of Stroke: A Meta-Analysis of Mendelian Randomization Studies
Circulation, Volume 150, Issue Suppl_1, Page A4145771-A4145771, November 12, 2024. Background:Sleep quality has emerged as a potential contributor to ischemic stroke risk, and genetic associations have been increasingly investigated for this association. Our analysis aims to elucidate the current understanding of the genetic basis linking sleep quality parameters to ischemic stroke through four distinct exposure groups: short sleep duration, long sleep duration, total sleep duration, and the presence of insomnia.Method:The PubMed database was searched to find Mendelian randomization studies reporting the association between ischemic stroke and associated sleep durations and parameters using title abstract keywords and medical subject headings. The initial search yielded 76 results, of which 62 underwent title abstract screening, and nine studies were identified for full-text screening. Eight studies were included in the final analysis. The random effects model was used to pool binary outcomes as odds ratios (OR) with 95% confidence intervals (CI), and the results were presented on forest plots. P value < 0.05 was considered for statistical significance.Results:Our pooled analysis revealed a statistically significant association between insomnia and higher odds of ischemic stroke (1.11 [95% CI 1.01-1.22, p=0.03]). However, this finding was limited by high heterogeneity (I2 = 77%, p
Abstract 4141398: Relationship between Gut Microbial Butyrate and Hypertension
Circulation, Volume 150, Issue Suppl_1, Page A4141398-A4141398, November 12, 2024. Background:Hypertension is the most common cardiovascular disease risk factor of which African Americans have a greater burden. Gut microbial production of short chain fatty acids (SCFA) has been associated with blood pressure status in animals, with limited evidence in humans. The complex and diverse gut microbial ecosystem contributes to synthesizing the SCFA butyrate. Aim: The goal of the study is to determine if butyrate production in the gut is associated with hypertension and how the microbial composition differs in normal and hypertensive participants.Methods:Fecal samples from 20 participants diagnosed with normal (n = 10) or high (n = 10) blood pressure were sequenced via the 16S rRNA gene. Inference-based modeling generated functional (PICRUSt2) and metabolic (MICOM) models of microbial communities focusing on carbohydrate fermentation pathways. Supervised learning was conducted to identify significant (p < 0.05) differences in predicted functional genes and microbial communities.Results:Microbial dominance was inversely correlated with increasing systolic blood pressure (Pearson, p < 0.05, R = -0.44); however, no significant correlation was measured for beta diversity between the two groups. More importantly, inference modeling showed differences in microbial function and metabolism between groups. Functional pathways associated with carbohydrate fermentation were significantly (ANOVA, p < 0.05) lower for hypertensive compared to normal participants. Carbohydrate fermentation accounted for only 8.05% of the predicted functions of the identified pathways. Within this subset, pyruvate fermentation to isobutanol was the most abundant pathway (12.6%), followed by starch degradation (9.6%) and glycolysis III (9.34%). Additionally, metabolic flux models revealedCatenibacterium, Subdoligranulum, andRoseburiawere predicted as butyrate producers.CatenibacteriumandSubdoligranulumproduced 51% and 44% butyrate, respectively, in the normal group. In contrast, a different distribution was observed in the hypertensive group, withCatenibacteriumaccounting for 97% andRoseburiacontributing 3% of the butyrate production.Conclusion:Our preliminary investigation elucidates the potential relationship between SCFA producers (as well as butyrate producers) and blood pressure status among minority participants, providing insights into how gut microbiota may influence or be influenced by blood pressure.
Abstract 4143160: Serotonin Norepinephrine Reuptake Inhibitor is Associated with Lower Mortality Among Patients Presenting with Takotsubo Cardiomyopathy
Circulation, Volume 150, Issue Suppl_1, Page A4143160-A4143160, November 12, 2024. Background:Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic reuptake of serotonin and norepinephrine and are widely used in the treatment of depression and neuropathic pain. Some studies suggest that the use of SNRIs may play a role in the etiology of takotsubo cardiomyopathy.Objectives:We aim to evaluate the impact of serotonin-norepinephrine reuptake inhibitors on the clinical outcomes of patients with takotsubo cardiomyopathy.Method:The authors retrospectively analyzed the deidentified patient data from TriNetX research network. Patients aged ≥18 years with a principal diagnosis of takotsubo cardiomyopathy were identified from January 1, 2003, to December 31, 2023. Patients with a history of myocarditis, pheochromocytoma, acute myocardial infarction, cocaine-related disorders, opioid-related disorders, and patients on with an active prescription for 5-fluorouracil, capecitabine, gemcitabine, and trastuzumab were excluded. Additionally, patients on selective serotonin reuptake inhibitors, tricyclic antidepressants, modafinil, armodafinil, methylphenidate, bupropion and atomoxetine were excluded. We used propensity score matching to adjust for potential confounders. The final study population was divided into two cohorts: Patients on SNRIs (duloxetine, venlafaxine, and desvenlafaxine) and patients not on SNRIs. The primary outcome was all-cause mortality, and the secondary outcome was takotsubo cardiomyopathy-related complications.Results:A total of 16,853 patients with a diagnosis of takotsubo cardiomyopathy were identified, of which 2,482 (14.7%) were on SNRIs at the time of diagnosis. The SNRIs cohort was slightly older (mean age 64.1 vs. 63.4 years). Patients on SNRI had a higher proportion of Whites (76.2% vs. 66.5%). After propensity score matching, patients on SNRI had lower 7-day mortality (OR, 0.59; 95% CI, 0.41 – 0.84, p
Abstract 4138674: Long-acting CRF2 receptor agonist, COR-1389, improves cardiopulmonary function in the rat model of Sugen plus hypoxia-induced pulmonary hypertension and right heart failure
Circulation, Volume 150, Issue Suppl_1, Page A4138674-A4138674, November 12, 2024. Introduction:Urocortin-2 (UCN-2), a peptide which is part of the corticotropin-releasing factor (CRF) family, functions as an autocrine and paracrine factor, exerting its effects on cardiac and pulmonary function through agonism of CRF2 receptors. Although acute administration of UCN-2 has shown promise by improving heart and lung function in conditions like heart failure (HF) and pulmonary hypertension (PH), its limited stability impedes its chronic therapeutic use.Hypothesis:In this study, we explored the efficacy of COR-1389, a potent, selective and long-acting CRF2 agonist peptide, in the Sugen 5416 (VEGFR2 inhibitor, Su) combined with hypoxia (Hx) rat model of PH and right heart failure (RHF).Methods:To this aim, male adult Sprague Dawley rats were divided into three groups: Control rats (normoxia) were compared with rats injected subcutaneously with 20 mg/kg Sugen 5416 and exposed to chronic hypoxia for 3 weeks, followed by 2 weeks of normoxia. At 5 weeks, control rats and one SuHx group received subcutaneously vehicle (control and SuHx), while the third group received COR-1389 at a dose of 100 μg/kg every 4 days subcutaneously for 3 weeks (SuHx + COR-1389). At 8 weeks, cardiac and pulmonary hemodynamic functions of the three groups were evaluated using echocardiography and right heart catheterization, and heart and lung tissue were evaluated by histology and immunohistochemistry.Results:Compared to controls (n=10), SuHx exhibited increased mean pulmonary arterial pressure (mPAP), right ventricle (RV) hypertrophy (Fulton Index/body weight), muscularization of distal pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy, alongside reduced RV systolic function (Tricuspid Annular Plane Systolic Excursion, TAPSE) and cardiac output (CO). Conversely, compared to the SuHx + vehicle group (n=11), curative treatment with COR-1389 for 3 weeks in SuHx rats (n=13) led to enhanced RV systolic function (TAPSE) and CO, together with reductions in mPAP, RV hypertrophy, muscularization of pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy. Systolic blood pressure remained unchanged across all groups.Conclusion:These findings indicate that COR-1389 ameliorates the deteriorating cardiopulmonary parameters observed in the SuHx model and represents a promising approach for the treatment of PH and RHF.
Abstract 4145138: Use of Cardiac Magnetic Resonance Imaging to Assess Response to Oral Treprostinil Therapy in Pediatric Pulmonary Hypertension Patients1
Circulation, Volume 150, Issue Suppl_1, Page A4145138-A4145138, November 12, 2024. Background:Pulmonary hypertension (PH) contributes to significant morbidity and mortality in pediatric patients. Cardiac catheterization remains standard of care for diagnosis and serial monitoring in PH patients despite its significant risk of morbidity and mortality. Cardiac magnetic resonance (CMR) imaging provides critical information about the right ventricle (RV) and left ventricle (LV) and may have significant prognostic power. We aim to use CMR to demonstrate response to oral Treprostinil in pediatric PH patients.Methods:This is a retrospective, multi-center study of 9 PH patients who underwent a baseline CMR study, as well as a follow up study 24 weeks following transitioning to oral Treprostinil from intravenous/inhaled formulations. Feature-tracking (Qstrain, Medis) was performed on short/long-axis cines to assess RV global longitudinal strain (GLS), LV GLS, and LV global circumferentialstrain (GCS). Volumetric data and conventional functional parameters were also compared, pre and post initiation of oral Treprostinil therapy.Results:Eighteen CMR studies from 9 patients were analyzed. Average baseline RV ejection fraction (EF) was 48.1% compared to post therapy RV EF 51.9% (p = 0.188). Average baseline RV GLS was -20.5% compared to post therapy RV GLS -23.3% (p = 0.025), Figure 1. Overall, there was no significant difference in LV EF, LV GLS, and LV GCS after transitioning to oral therapy. Increased RV EF post initiation of oral Treprostinil therapy correlated with increased magnitude LV GCS (r = 0.701, p = 0.036), reflecting critical interventricular interaction in the disease process.Conclusion:Assessment of RV strain is more sensitive in detecting improvement in cardiac performance following initiation of oral Treprostinil in pediatric PH patients compared to ejection fraction. Future studies should focus on the development of novel CMR biomarkers in place of cardiac catheterization in assessing cardiac performance in PH patients.1. This abstract was written by one of ISS investigators, Dr. Truong, who is using data from TDE-PH-206 (pediatric oral Treprostinil study) to investigate cMRI parameters.
Abstract 4139216: The tolerability, safety, pharmacokinetics, and pharmacodynamics of TX000045, a long-acting Fc-relaxin fusion protein after single doses in healthy volunteers
Circulation, Volume 150, Issue Suppl_1, Page A4139216-A4139216, November 12, 2024. Introduction:TX000045 (TX45) is a long-acting Fc-relaxin fusion protein with vasodilatory, anti-fibrotic and anti-inflammatory activity due to selective agonism of the G protein-coupled relaxin family peptide receptor 1 (RXFP1). It is being developed for Group 2 pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF). This first-in-human study evaluated the safety/tolerability, pharmacokinetic and pharmacodynamic profile of TX45 in healthy volunteers after single doses.Methods:This phase 1a, randomized, double-blind, placebo-controlled single ascending dose study was performed in seven cohorts of healthy volunteers. Six cohorts consisted of eight patients receiving intravenously (IV) or subcutaneously (SC) one of several doses of TX45 (n=6 on treatment) or placebo (n=2), including 0.3 mg/kg IV, 1 mg/kg IV, 3 mg/kg IV, 150 mg SC (x2 cohorts), and 300 mg SC. One cohort consisted of seven patients receiving 600 mg SC TX45 (n=5 patients) or placebo (n=2 patients). The goals of the study were to assess the tolerability and safety, immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD = renal plasma flow, RPF) properties of TX45 in healthy volunteers after single doses. RPF was determined by analysis of steady-state para-aminohippurate (PAH) blood levels in response to a PAH IV infusion.Results:55 healthy volunteers were randomized. TX45 was well tolerated. Most adverse events were mild to moderate in intensity. The most common treatment emergent adverse event was transient orthostatic tachycardia, not associated with hypotension. TX45 demonstrated linear pharmacokinetics across the dose range with a terminal half-life estimated to be 13-23 days. Treatment with TX45, across dose levels, increased renal plasma flow by 16-42%, consistent with known relaxin effects. Leveraging repeated measures of renal plasma flow post dose, TX45 demonstrated prolonged maintenance of a pharmacodynamic effect. There was no evidence of immune mediated clearance of TX45.Conclusions:TX45 was generally well tolerated with a safety, pharmacokinetic and pharmacodynamic profile to support further clinical development. Its maximum effect on RPF is similar to previously described effects of native relaxin. Its half-life will support a prolonged dosing interval. These findings support further evaluation of TX45 in patients with Group 2 pulmonary hypertension associated with HFpEF.
Abstract 4145408: The Unexpected Heart Stopper: A Case of Ketamine-Induced Stress Cardiomyopathy Requiring Mechanical Circulatory Support
Circulation, Volume 150, Issue Suppl_1, Page A4145408-A4145408, November 12, 2024. Background:Stress cardiomyopathy (SCM) is rarely triggered by ketamine and seldom leads to cardiogenic shock. Ketamine-induced catecholaminergic surge can lead to myocardial stunning with transient ischemia and subsequent reversible heart failure. Mechanical circulatory support can be successfully leveraged in SCM-associated cardiogenic shock while awaiting myocardial recovery.Case Presentation:A 28-year-old female with chronic pain was admitted for failure to thrive secondary to opioid-induced gastroparesis. The patient was weaned off opiates while on ketamine over 4 days. After halting ketamine, the patient had a cardiac arrest with eventual return of spontaneous circulation. After being extubated, she developed chest pain, hypotension, and ventricular tachycardia with anterolateral ST elevations, troponin leak, and lactic acidosis. TTE revealed an EF
Abstract 4147575: Outcomes of Utilizing Sodium Glucose Transporter Inhibitors Following Acute Myocardial Infarction: A Comprehensive Meta-Analysis
Circulation, Volume 150, Issue Suppl_1, Page A4147575-A4147575, November 12, 2024. Introduction:Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. In the quest for improved therapeutic strategies, the addition of Sodium Glucose Transporter Inhibitors (SGLTis) to the treatment regimen has garnered considerable attention. This meta-analysis endeavors to shed light on the efficacy of SGLTis in short-term cardio-renal protection post-AMI. By synthesizing evidence from diverse studies.Methods:Adhering to the PRISMA guidelines, a meticulous systematic review and meta-analysis were conducted. Comprehensive literature searches across PubMed, Web of Science, Scopes, and Google Scholar were performed. Inclusion criteria comprised four Randomized Controlled Trials (RCTs), one retrospective cohort, and one observational study, investigating the effects of SGLTis versus placebo on AMI patients, irrespective of diabetic status. Our analysis included the following outcomes: acute kidney injury, all-cause death, cardiovascular mortality, cardiac death, composite of cardiovascular death/hospitalization for heart failure, and NT-proBNP levels.Results:Our analysis encompassed six scientific articles involving 7238 patients. SGLTIs exhibited a notable favorable effect solely on acute kidney injury (P value=0.001, 95% CI [0.46-0.82]). Conversely, no significant benefit was observed in other short-term outcomes, including all-cause death, cardiovascular mortality, cardiac death, composite of cardiovascular death/hospitalization for heart failure, and NT-proBNP levels. These results align with previous studies suggesting the renal protective effects of SGLTIs but highlight the need for further research to clarify their overall cardiovascular benefits in AMI patients.Conclusion:Incorporating SGLTis into the therapeutic armamentarium of AMI patients, irrespective of diabetic status, demonstrated a discernible advantage solely concerning acute kidney injury. However, no appreciable benefit was discerned across other assessed metrics. These findings underscore the need for further exploration and tailored therapeutic strategies in the management of post-AMI patients.
Abstract 4142374: The Impacts of Achieved Blood Pressure During the First 12 hours on Clinical Outcomes in Patients with Out-of-hospital Cardiac Arrest
Circulation, Volume 150, Issue Suppl_1, Page A4142374-A4142374, November 12, 2024. Background:Out-of-hospital cardiac arrest (OHCA) typically results in low survival rates and undesirable neurological outcome. There is a significant correlation between mean arterial pressure (MAP) levels after the return of spontaneous circulation (ROSC) and the outcomes of OHCA patients, yet the optimal blood pressure target remains unclear. This study explores how achieved blood pressure within the initial 12 hours after ROSC impacts the clinical outcomes of OHCA patients.Methods:We conducted a retrospective analysis of patients who experienced OHCA and achieved ROSC. Patients were divided into three tertiles based on the distribution of patient numbers, with each tertile defined as follows: MAP < 80 mmHg, 80 mmHg ≤ MAP < 95 mmHg, and MAP ≥ 95 mmHg. MAP levels were measured within the first 12 hours. Mortality and cerebral performance category (CPC) were utilized in the study to assess the clinical outcomes at 30 days post-OHCA event.Results:A total of 231 non-traumatic OHCA patients who survived for 12 hours after ROSC were enrolled. Among the three tertiles (n = 77 in each), significant difference in mortality and CPC score were found between tertile 1 and the remaining two tertiles, but no notable difference were observed between tertile 2 and 3. Higher MAP level, specifically target MAP ≥ 80 mmHg (hazard ratio [HR]: 0.960, 95% confidence interval [CI]: 0.949-0.971, P < 0.001) was associated with lower 30-day mortality. Additionally, a higher MAP level with target MAP ≥ 80 mmHg within the first 12 hours was correlated with better neurological outcomes (odd ratio [OR]: 0.370, 95% CI: 0.147-0.935, P = 0.035).Conclusions:MAP levels within the initial 12 hours after ROSC is a practical predictor of 30-day mortality and neurological outcomes among OHCA patients. Maintaining MAP levels above 80mmHg exhibits strong correlation with short-term outcomes improvement in the early post-arrest period.
Abstract 4138799: SGK1 inhibition shortens action potential duration in LQT3 mice and LQT2 rabbits via inhibition of late sodium current
Circulation, Volume 150, Issue Suppl_1, Page A4138799-A4138799, November 12, 2024. Background:Serum and glucocorticoid regulated kinase 1 (SGK1) activation during pathological conditions has been shown to increase late sodium current, prolong action potential duration (APD), and induce ventricular arrhythmias, thus recapitulating a long QT syndrome (LQTS) phenotype. Hence, pharmacological SGK1 inhibition may be a novel therapeutic approach in inherited LQTS.Aim:We aimed to investigate potential effects of SGK1 inhibition in animal models of different LQTS subtypes, and the potential involvement of late INainhibition.Methods:Cardiomyocytes (CMs) isolated from wild-type (WT) and LQT3 mice (Scn5a-1798insD) as well as from WT, LQT1 (KCNQ1-Y315S) and LQT2 (KCNH2-G628S) rabbits, were incubated for 3-5 hours with SGK1-inhibitor (SGK1-inh, 300 nM-3 μM) or DMSO (vehicle). Patch-clamp experiments were performed to assess AP properties, short-term variability (STV) of APD and late INa.Result:SGK1-inh incubation significantly shortened the prolonged APD90in LQT3 CMs by 23% and in LQT2 CMs by 25% (restoring them towards the WT level), without affecting other AP properties. In contrast, in WT and LQT1 CMs, no effect of SGK1-inh on APD90was observed. Furthermore, short-term-variability (STV) of APD, a measure of pro-arrhythmia, was pathologically increased in LQT3 (5.6±0.2 ms vs WT 2.7±0.3 ms, p