tbuckley/cabot-search huggingface dataset:
Abstract 4138640: Learning Curve for Left Bundle Branch Area Pacing Lead Implantation
Authors: Maci Clark, Hannah Zerr, Benjamin Ose, David Fritz, Caroline Trupp, Amulya Gupta, Ahmed Shahab, Amit Noheria, Seth Sheldon
Journal: Circulation (2024)

Background: Left bundle branch area pacing (LBBAP) has shown promising outcomes at experienced centers, but less is known about the learning curve with new adoption of LBBAP. We conducted a retrospective analysis (2020-2023) of the learning curve for LBBAP at our center. Methods: Procedural success and complications in adult patients undergoing LBBAP by operators with &gt;5-years’ experience in device implantation were compared between operators’ experience ≤10th (LBBAP inexp ) vs. &gt;10th (LBBAP exp ) LBBAP implant. Successful LBBAP was defined as left ventricular activation time (LVAT) ≤80 ms. Results: Seven operators implanted LBBAP in 288 patients (age 73±11 years, 38% women): 68 (24%) in LBBAP inexp vs. 220 (76%) patients in LBBAP exp groups with similar baseline characteristics (all p &gt;0.05). The median number of implants per operator was 22 (range 8-83). Table 1 shows the procedural characteristics and ECG results. Post-implant LVAT ≤80 ms was less frequent in LBBAP inexp compared to LBBAP exp (56.9% vs 72.4%, p=0.04, Figure 1 ). There were no differences in paced QRS duration ≤130 ms (75.9% vs. 76.1 %, p=1.0) or operator self-identified success (85% vs. 91%, p=0.2). With new single-/dual-chamber device implants, there was no difference in implant duration (103.4±31.8 vs. 101.6±38.5 minutes, p=0.3) but there was longer fluoroscopy in LBBAP inexp (12.6±10.1 vs. 8.2±8.0 minutes, p&lt;0.0001, Figure 1 ). The average number of attempts at LBBAP was lower in LBBAP inexp vs. LBBAP exp (2.0 ± 1.5 vs. 2.9 ± 2.9, p=0.03). There was no difference in complications between the 2 groups ( Table 2 ). Conclusion: Operators use less fluoroscopy, make more attempts at LBBAP and more frequently achieve LVAT ≤80 ms after their first 10 implants.
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
Authors: Mark Kowala, Christophe Guignabert, Marie-Laure Ozoux, Francesca Lawson, Philip Janiak
Journal: Circulation (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 4138661: Targeting Arginase I Alleviates Cardiomyopathy
Authors: Lin Di, Natalie Hong, Lauren Switala, Andrei Maiseyeu
Journal: Circulation (2024)

Introduction: Emerging data have shown that pathological cardiac fibrosis and heart failure is driven by recruitment of CD4 + T cells to injured heart tissue. Systemic deletion of CD4 + T cells or splenectomy has been shown to attenuate CD4 + T cell heart infiltration and inflammation. We engineered cargo-less nanoparticles using a biocompatible and biodegradable polymer that target splenic macrophages to overexpress arginase I, leading to local depletion of L-arginine, an amino acid crucial for CD4 + T cell activation and expansion. Hypothesis: Cargo-less nanoparticles attenuate CD4 + T cell activation, expansion, and heart infiltration in experimental models of cardiomyopathy by regulating cross talk between macrophages and CD4 + T cells via L-arginine depletion in the spleen. Methods: Spleen-targeting, cargo-less nanoparticles were synthesized from poly(L-lactide-co-glycolide) (PLLGA) and administered to murine and human macrophages in vitro. Arginase I expression and activity were assessed via Western blotting and arginase activity assay. Epigenetic modulation was analyzed using Western blotting and CHIP-seq. Conditioned media was collected to culture CFSE-labeled T cells to assess proliferation. The nanoparticles were administered to mouse heart failure models induced by isoproterenol or angiotensin II and phenylephrine. Immune cell composition in mouse spleens and hearts was investigated by flow cytometry. Cardiac function was assessed by echocardiography and heart fibrosis was examined via immunohistochemistry and Western blotting. Results: Primary murine macrophages treated with our nanoparticles exhibited a dose-dependent T cell suppression in vitro. This effect was abrogated when an arginase inhibitor was administered together with the nanoparticles. The nanoparticles upregulated arginase I protein expression and arginase activity by increasing histone lactylation. In vivo testing with mouse heart injury models showed that the nanoparticles restored levels of effector and regulatory T cells in injured mice to non-injured levels. Additionally, the nanoparticles reduced cardiac fibrosis and restored ejection fraction. Furthermore, Western blotting of heart tissue lysate revealed that the nanoparticles downregulated the TGFb and p-SMAD signaling pathway. Conclusion: Collectively, these findings highlight a novel therapeutic strategy for heart failure, addressing the gap of fibrosis treatment by targeting upstream immunological pathways.
Abstract 4138570: The Hidden Killer in Patients with Sepsis Spectra Disorders: Systolic Heart Failure
Authors: Nadim Jaafar, Rahul Sharma, Kenan Rahima, Siddartha Guru, Nisha Strobos
Journal: Circulation (2024)

Introduction: Sepsis and systolic heart failure (sHF) often prompt hospitalization and require near diametrically opposite treatment strategies. We, therefore, studied whether sHF would impact outcomes in patients with sepsis spectra. Methods: We examined the National Inpatient Sample 2021 for adults admitted with sepsis spectra (sepsis, severe sepsis, and septic shock). We compared patients with sHF vs those without. STATA 18 th edition was used for analyses. Age, gender, race, hypertension, diabetes, obesity, dyslipidemia, and Elixhauser comorbidity index were identified as confounders by univariate analyses and tested further with multivariate logistic regression models. The primary outcome was mortality. Secondary outcomes were the need for intubation, cardiac arrest, length of stay (LOS), and total hospital charges. Results: In 2021, nationwide, 3,030,351 adults were admitted for sepsis spectra, and 209,134 (6.9%) had concomitant sHF. Patients with sHF and sepsis spectra (as compared to those without sHF) were less likely female (35.5% vs. 48%), had a substantially higher likelihood of a prior MI, and nearly 50% were diabetic and hyperlipidemic with a higher comorbidity index. Baseline characteristics are in the Table. Sepsis and sHF resulted in substantially higher mortality (22.7%) as compared to patients with sepsis alone (14.9%) adjusted odds ratio (aOR) of 1.11 (CI 1.08-1.14; p-value &lt; 0.001). Patients with sepsis and sHF were more likely to require intubation 22.2% vs. 14.0% aOR 1.21 (CI 1.18-1.25; p-value &lt; 0.001), had more cardiac arrest 7.7% vs. 4.0% aOR 1.38 (CI 1.32-1.44; p-value &lt; 0.001), and a longer LOS (11.9 vs 9.4 days adjusted incidence rate ratio (aIRR) 1.06; CI 1.05 – 1.08; p-value &lt; 0.001). Consequently, total hospital charges were also higher, $189,415 vs $133,720, aIRR 1.15 (CI 1.13-1.18; p-value &lt; 0.001). Conclusion: In 2021, nationwide, sepsis spectra remain a major cause of in-patient mortality. We demonstrate that the coexistence of systolic heart failure and sepsis dramatically worsens complications, mortality, and total hospital costs. This study is a call to action for the in-depth analyses of this very high-risk group of patients.
Abstract 4138498: Sex Differences in Plasma Acylcarnitines in Patients with STEMI undergoing Primary PCI
Authors: Jenny Namkoong, Aleksandra Stamenkovic, Arun Surendran, Amir Ravandi
Journal: Circulation (2024)

Background: Rapid coronary reperfusion using primary PCI is the corner stone therapy for patients presenting with STEMI that restores blood flow and limits infarct size. But paradoxically, the reperfusion process itself can induce additional myocardial injury. Females have increased rates of cardiovascular death compared with males following MI, and it is unclear whether this is related to differences in presentation or reperfusion injury. Given these differences, we aim to better understand the sex differences in the lipidome shift post PCI. METHODS&amp;RESULTS: 126 patients(97 males, 29 females) undergoing PCI for STEMI in a tertiary centre underwent venous blood sampling and semi-targeted Liquid Chromatography Tandem Mass Spectrometry(LC/MS/MS) to determine 291 lipid species. Samples were taken pre-PCI(T0), and 2 hours post PCI(T1) with successful reperfusion. Each lipid class and species were compared between males and females at each time point using statistical analysis, to determine the similarities and differences in plasma lipidome shifts in ACS between sexes. Whilst most lipid classes decrease following reperfusion in STEMI (T0 vs T1), Acylcarnitines increase (20%, adjusted p=0.003) in both sexes. There is a clear sex difference with a greater increase in females (39% increase, adjusted p=0.03), as compared with males (13% increase, adjusted p=0.048). In both sexes this is primarily driven by OctadecanoylCarnitine (C8), which is a medium-chained acylcarnitine. Notably, there was no significant difference in C8 between the sexes in the control group, nor the pre-PCI group(adjusted p=0.48, at T0). At T0, total free fatty acids(FFA) and total phosphatidylinositol were significantly elevated in females compared with males(adjusted p=0.012, p=0.018 respectively). Conclusion: Our analysis suggests there are differences in lipidomics shift between males and females in response to myocardial reperfusion. The higher levels of circulating FFA in ischemic females pre-PCI(T0), followed by a parallel increase of acylcarnitine with reperfusion(T0vsT1), suggest differences between the sexes in myocardial metabolic response to reperfusion injury. C8 has been associated with elevated risk of cardiovascular death in stable CAD, but its clinical impact during reperfusion is still unknown. Detailed understanding of sex specific lipidomics shifts during reperfusion injury will allow us to better understand the mechanistic differences in clinical outcome between males and females.
Abstract 4138609: Patient Care Experience Worsens After Private Equity Acquisition of US Hospitals: Implications for Cardiovascular Outcomes
Authors: Anjali Bhatla, Victoria Bartlett, Michael Liu, ZhaoNian Zheng, Rishi Wadhera
Journal: Circulation (2024)

Background: Patient care experience is strongly associated with outcomes among individuals with cardiovascular disease. There is growing concern that the recent and precipitous rise in private equity acquisitions of US hospitals may worsen patient-centered care, and ultimately, cardiovascular outcomes. However, little is known about how private equity acquisitions of hospitals impact patient care experience. Research Question: To evaluate whether the acquisition of US hospitals by private equity firms was associated with changes in measures of patient-reported experience compared with matched control hospitals (not acquired by private equity) between 2007-2019. Methods: This cohort study identified 74 US acute care hospitals newly acquired by private equity firms and 298 matched control (non-acquired) hospitals from 2007 to 2019. CMS Hospital Compare files were used to obtain patient experience measure scores for each hospital from Hospital Consumer Assessment of Healthcare Providers and Systems (HCAPHS) survey results. A quasi-experimental difference-in-differences design was used to evaluate changes in patient experience measures at private-equity acquired hospitals compared with matched control hospitals 3 years before vs 3 years after acquisition. Results: The percentage of patients rating hospitals as a 9 or 10 out of 10 at private equity acquired hospitals and control hospitals is shown in the Figure. There was a differential decrease in patient ratings (of 9 or 10 out of 10) at hospitals acquired by private equity firms compared with control hospitals (-2.4 percentage points [95% CI -3.9, -0.9]). A similar trend was seen in the percentage of patients that would definitely recommend the hospital, with a differential decrease at private equity-acquired hospitals relative to control hospitals (-2.2 percentage points [95% CI -3.6, -0.7]). For both measures, the relative decrease in patient care experience at private equity hospitals compared with control hospitals steadily grew with each subsequent year after acquisition. Conclusion: In this national study, patient-reported care experience worsened after private equity acquisition of US hospitals, which has important implications for cardiovascular care and outcomes.
Abstract 4138663: Peak nocturnal home blood pressure as an early and strong novel risk factor for stroke: the practitioner-based nationwide J-HOP Nocturnal BP study
Authors: Kazuomi Kario, Yukie Okawara, Hiroshi Kanegae, Naoko Tomitani, Satoshi Hoshide
Journal: Circulation (2024)

Background: Clinical implications of high peak nighttime home blood pressure (BP) are currently unknown. This analysis investigated the association between peak nighttime home systolic BP (SBP) and cardiovascular events in individuals with ≥1 cardiovascular risk factor. Methods: In the Japan Morning Surge-Home Blood Pressure (J-HOP) study, nighttime home BP was automatically measured three times every night for 14 days at baseline using a nighttime home BP monitoring device (HEM-5001, Omron Healthcare). Peak nighttime home SBP was defined as average of the highest three values over the 14-night measurement period. Occurrence of cardiovascular events (stroke, coronary artery disease, heart failure, aortic dissection) was determined over a mean 7.1 years’ follow-up. Results: This analysis included 2545 individuals (mean age 63.3±10.3 years, 49% male). After adjustment for covariates (including age, sex, and average office, morning, evening, and nighttime home SBP), stroke risk was significantly higher in individuals with peak nighttime home SBP in the highest (Q5, ≥149.0 mmHg) versus lowest quintile (Q1, &lt;119.3 mmHg) (hazard ratio [HR] 4.24, 95% confidence interval [CI] 1.07–16.77; p=0.039 overall and 8.92, 1.49–53.43; p=0.017 in the subgroup with ≥6 nighttime home SBP measurements). This increased stroke risk remained significant after controlling for day-by-day average real variability of nighttime BP. The average peak nighttime home SBP cut-off value for predicting an increased risk of incident stroke was 136 mmHg. Conclusions: We propose exaggerated peak nighttime home SBP determined from ≥6 measurements as a novel risk factor for stroke, independent of conventional office and home BP values.
Abstract 4138528: Clinical Characteristics of Five Different Endotypes from Coronary Reactivity Testing, and the Emergence of Sex Patterns in Coronary Microvascular Dysfunction
Authors: Jenny Namkoong, Mary McCarthy, Olga Toleva, Lynne Nield, Stephane Rinfret, Steven Miner
Journal: Circulation (2024)

Background: The common preconception is that non-obstructive coronary artery disease(NOCAD) predominantly affects females with little to no cardiac risk factors. However, it is unclear whether there is a significant difference in baseline characteristics between those with a positive vs negative coronary reactivity testing(CRT) result. Furthermore, CRT explores multiple pathophysiological mechanisms which make a positive result nuanced. This study identifies 5 different endotypes based on CRT results, aiming to identify phenotypic characteristics that correlate with these endotypes. METHODS: 409 patients were included in a cohort study, representing all patients referred for CRT to a tertiary referral centre for NOCAD, between 2016-2024. Patients underwent protocol CRT of coronary flow reserve(CFR) and index of microvascular resistance(IMR) measurements following adenosine infusion(140mcg/kg/min) and bolus acetylcholine(100mcg). Results were compared by positive vs negative CRT, normal vs abnormal CFR/IMR, and by 5 different endotypes identified from CRT result combinations. RESULTS: There was no significant difference in clinical characteristics between the positive vs negative CRT result groups. However, with further stratification, there were significant sex differences and cardiac risk profile differences in CFR and IMR results. There was a greater proportion of females in the abnormal (low) CFR group(p&lt;0.001), and higher burden of cardiac risk factors in the abnormal (high) IMR group(p&lt;0.001). The highest burden of cardiac risk factors was seen in the 'Traditional Coronary Microvascular Dysfunction (CMD)' endotype, defined as those with abnormal(low) CFR and abnormal(high) IMR. The 'Functional CMD' endotype was characterised by younger females, whilst the 'Compensated CMD' and 'Coronary spasm' endotype showed no sex difference. The normal CFR and normal IMR endotype reflected the referred population(Figure 1). CONCLUSION: There is an emergence of clinical phenotypes according to the five coronary reactivity testing endotypes. Lower CFR appears to be a more “female pattern” of microvascular dysfunction. Endotypes reflect underlying pathology and may provide mechanistic explanations for sex differences in the microvascular dysfunction types of NOCAD, whilst explaining the lack of sex differences in other types. Further detailed understanding of CRT endotypes will allow us to understand the mechanistic differences in cardiovascular outcomes between males and females.
Abstract 4138558: The effect of pulsatile vs. non-pulsatile perfusion on hospital stay, ICU stay, and intubation time in patients undergoing cardiopulmonary bypass: A meta-analysis randomized controlled trials.
Authors: Abdelrahman Mahmoud, Mohamed Ramadan, Ahmed Mazen Amin, Hazem Mohamed Salamah, Ali Ashraf Salah Ahmed, abdallah Saeed, Mohamed Ahmed Ali, Salem Elshenawy, Dina Ayman, Hassan Alshaker, Basant Katamesh, Abdul Rhman Hassan, Majd M. AlBarakat, Mohamad Alsaed, Basel Abdelazeem
Journal: Circulation (2024)

Background: Pulsatile perfusion is a developing technique that attempts to mimic the natural pulsatile flow of blood during cardiopulmonary bypass (CBP). Purpose: Our meta-analysis was done to evaluate the effects of pulsatile perfusion in CPB compared to non-pulsatile on hospital stay, ICU stay, and intubation time. Methods: Randomized control trials that evaluated the implementation of pulsatile perfusion during CPB were identified by a literature search of the following databases (PubMed, Web of Science, Scopus, Central, and Embase) up to February 2024. Results: Our search yielded 33 trials with 3174 patients, the analysis showed that pulsatile perfusion led to a significant decrease in hospital stay [MD = -1.38, 95% CI (-2.51, -0.25), P = 0.016], ICU stay [MD = -0.47, 95% CI (-0.82, -0.13), P = 0.007], intubation time [MD = -3.73, 95% CI (-5.42, -2.04), P &lt; 0.001]. However, no significant difference between the two regimens was detected in the adult subgroup when we performed sungroup analysis based on the age for hospital stay and ICU stay outcomes [MD = -0.31, 95% CI (-0.95, 0.33), P = 0.334] and [MD = -3.73, 95% CI (-5.42, -2.04), P &lt; 0.001] respectively. Conclusion: Pulsatile perfusion showed positive effects on hospital stay, ICU stay, and intubation time. However, there was no difference between the two methods on hospital and ICU stay in the adult’s subgroup. Also, the outcomes showed significant heterogeneity, which requires more robust RCTs to be conducted to increase the quality and the certainty of evidence.
Abstract 4138472: Bioactive Oxylipins Predict Coronary Artery Calcification Severity in Heart Failure with Preserved Ejection Fraction
Authors: Vaishnavi Aradhyula, Anas Fares, John Vergis, Prabhatchandra Dube, Alborz Sherafati, Alex Kloster, XBellaX XKhatib-ShahidiX, Ahmed Elzanaty, Omar Sajdeya, Sareeta Manandhar, Pamela Brewster, Krishna Rao Maddipati, Robert Smith, Steven Haller, David Kennedy, Samer Khouri, Rajesh Gupta
Journal: Circulation (2024)

Background: Inflammation is a common underlying cause in atherosclerosis and heart failure with preserved ejection fraction (HFpEF). Recent data have highlighted the critical role of circulating bioactive polyunsaturated fatty acid oxidized lipids, or oxylipins, in initiating and resolving inflammation. We sought to study the role of oxylipins in predicting coronary artery calcification (CAC) in HFpEF. Hypothesis: We hypothesize that oxylipins can predict and distinguish CAC severity in HFpEF patients. Methods: We collected venous blood samples during right heart catheterization from 71 HFpEF patients. We categorized patients by CT-based CAC severity: none (control; n=16), mild (&lt;25% CAC, n=7), moderate (26-50% CAC, n=22), and severe (&gt;50% CAC, n=26). We measured 143 oxylipins in all study participants using mass spectrometry. Along with unpaired T-tests, machine learning analysis was used to determine lipid permutation importance and evaluate predictive accuracy for CAC severity. Results: Demographic variables showed no significant differences between groups. Increased total cholesterol (p=0.031) and low HDL (p=0.011) were associated with CAC severity. Pro-inflammatory 12(S)-HHTrE (a degradation product of TxA2) levels were elevated in severe CAC vs control (p=0.031). The inactivated anti-inflammatory 5,6 DiHETrE levels were higher in moderate CAC vs control (p=0.032) and severe CAC vs control (p=0.021). Out of 143 oxylipins, the panel of LTB5, 11(R)-HEDE, 20-HETE, 5-HEPE, 11(12)-EpETrE, 14(15)-EpETE, 19,20-DiHDoPE, PD1, and 5-oxoETE were the most significant predictors of severe vs non-severe (none, mild, moderate) CAC, with 88.88% predictive accuracy. Conclusion: In HFpEF patients, CAC severity can be predicted by a novel panel of circulating, bioactive venous oxylipins.