tbuckley/cabot-search huggingface dataset:
Abstract 4122543: Can We Diagnose Ticagrelor-induced Dyspnea After Urgent Percutaneous Coronary Intervention with Cardiopulmonary Exercise Testing?
Authors: Ilya Giverts, Denis Andreev, Saumya Nanda
Journal: Circulation (2024)

Background: Ticagrelor has been reported to cause shortness of breath (SOB) in 6 to 9 % of patients. Precise mechanisms are not enirely understood. We hypothesize that cardiopulmonary exercise testing (CPET) may be helpful in clinical assessment of patients reporting SOB on ticagrelor. Case presentation: 66-yo female with history of arterial hypertension, DM type 2 and prior MI presented with STEMI and successfully underwent urgent PCI of RCA and LAD. The patient received ticagrelor in loading dose followed by 90 mg b.i.d plus low-dose aspirin. Just after PCI she developed SOB with no evidence of acute cardiac or respiratory compromise. After discharge the patient continued to experience SOB impairing daily activities. In 6 months she was re-assessed. Clinical investigation (physical exam, blood tests, echo, CXR, spirometry) showed no abnormalities that could explain SOB. CPET despite good effort showed low VO 2 peak (7,8 ml*min/kg; 49% from predicted), undetectable anaerobic threshold (AT), severely impaired ventilatory efficacy (VE/VCO 2 =50,1) and marked hyperventilation (resting RER=1,0; PetCO 2 =18,0 mmHg at rest and 22,4 mmHg at peak load). Exercise EKG, blood pressure response, SpO 2 and breathing reserve were normal. Once the patient was switched from ticagrelor to clopidogrel she reported significant improvement. CPET one week after showed increase in VO 2 peak up to 12,5 ml/kg/min., AT of 11,1 ml*min/kg, better ventilatory efficacy (VE/VCO 2 =37,1) and less hyperventilation (PetCO 2 28,1 mmHg at rest and 28,8 mmHg at peak load). CPET performed one month later showed further improvement in VO 2 peak to 13,2 ml*min/kg, normal VE/VCO 2 and no signs of hyperventilation. Discussion: it is believed that ticagrelor-induced dyspnea can be driven by 2 potential mechanisms, first related to inhibition of adenosine reuptake, second - to sensory neuron P2Y12 inhibition. It occurs early after starting the medication and is not associated with structural cardiopulmonary abnormalities. Previous small data showed evidence of Cheyne-Stokes respiration during both night and day related to ticagrelor. Symptoms usually are dose-dependent and disappear after discontinuation of ticagrelor. In our case the patient demonstrated reversible hyperventilation and reduced exercise capacity associated with ticagrelor that was confirmed with CPET. Conclusion: CPET allows differentiating SOB in patients treated with ticagrelor. Further investigations are required to confirm this hypothesis.
Abstract 4122256: Health Status Outcomes of Nicorandil in Patients With Angina Pectoris: A Prospective, Multicenter, Registry-Based Study
Authors: Yong Zeng, xiliang zhao
Journal: Circulation (2024)

Background: Coronary artery disease (CAD) exerts a considerable impact on mortality from cardiovascular disease. Approximately half of patients with CAD initially present with angina pectoris. The GREAT study is designed to establish a large cohort of Chinese patients with angina pectoris and compare the effectiveness of different anti-angina regimens, using the Seattle Angina Questionnaire. Method: The GREAT (reGistRy study of medical thErapy in patients with Angina pecToris) Registry is a multicenter, prospective, observational, cohort study that enrolled 1556 adult CAD patients with angina pectoris from nine hospitals in China. The study included patients currently receiving or eligible to receive oral anti-anginal regimens. The cohort was classified into nicorandil and non-nicorandil groups based on the treatment therapies. The primary outcome was the Seattle Angina Questionnaire summary score (SAQ-SS) changes from baseline to 12 months. The SAQ-SS averages the domains of physical limitation, angina frequency, and quality-of-life scores. Results: From September 2021 to May 2022, a total of 1575 patients were screened, of whom 1556 met the inclusion criteria and were included ( Figure 1 ). Among the patients at the full analysis set (FAS, N=1528), 28.5% were women, and the median age was 61 years. Baseline variables were well balanced after propensity score matching, with both groups containing 450 patients. In the nicorandil group, patients showed a significantly greater increase in mean SAQ-SS score at Month 12 compared to the non-nicorandil group (17.6±14.0 vs 15.1±13.0; difference: 0.19; 95% CI, 0.05-0.32; p=0.003). In addition, patients in the nicorandil versus the non-nicorandil group reported a significantly greater mean improvement in the SAQ-QoL domain (18.9±21.4 vs 16.3±20.4; p=0.042) and SAQ-PL domain (11.7±16.9 vs 10.0±17.0; p=0.001). Over 12 months, a higher proportion of patients in the nicorandil group, compared to the non-nicorandil group, reported substantial improvements in SAQ-SS, with 24.1% experiencing large improvements (20-29 points) and 18.2% reporting very large improvements (≥30 points) versus 20.7% and 12.0%, respectively (p=0.005 across all categories) ( Figure 2 ). Conclusion: This real-world data indicates that nicorandil-based anti-angina regimens are associated with a greater health status outcome improvement compared to those not using nicorandil in CAD patients.
Abstract 4120966: Outcomes Following Balloon Angioplasty with Drug Coated Versus Uncoated Balloons in Patients with Coronary In-Stent Restenosis: A Systematic Review and Meta-Analysis
Authors: Mohammad Rehman, Burhan Khalid, Muhammad Haris Khan, Muhammad Waseem, Nohela Rehman, Zain Ul Abideen, Muhamamd Jamil, Muhammad Hamza, Malaika Nasir, Abdullah Afridi, Simel Masood, Hamza Shahram, Sajeel Saeed, Tehseen Haider, Jawad Basit, Usman Akbar, Ahmad Iftikhar
Journal: Circulation (2024)

Background &lt;div&gt; &lt;/div&gt; &lt;div&gt;The development of in-stent restenosis (ISR) has emerged as a substantial barrier to interventional treatment for coronary heart disease. Drug-coated balloon (DCB) is an efficacious interventional technique for the management of ISR. This meta-analysis compares the efficacy of DCB in the treatment of ISR with that of an uncoated balloon (UCB).&lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt;Methods&lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt;We comprehensively searched literature on MEDLINE, Embase, Cochrane, and clinicaltrials.gov using MeSH terms and relevant keywords for “Balloon Angioplasty” and “in-stent Restenosis” from inception to June 1, 2024, followed by a meta-analysis of all randomized controlled trials (RCTs) to assess both strategies for treatment of ISR. Random effects model was used to aggregate the risk ratios (RR) for dichotomous and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).&lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt;Results&lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt;The search strategy retrieved 2330 studies. Duplicates and irrelevant articles were removed and data from seven RCTs (1,408 patients) was extracted. The mean age ranged from 64 to 74 years. The mean clinical follow-up ranged from 1 to 10 years. DCB was found to be superior to UCB at latest follow up in terms of target lesion revascularization (TLR) (RR 0.34, 95% CI 0.19-0.58; p 0.0001; I2 79%), major adverse cardiovascular events (MACE) (RR 0.41, 95% CI 0.23-0.73; p 0.003; I2 84%), late lumen loss (LLL) (MD -0.46 mm, 95% CI -0.64- -0.28]; p &lt;0.00001; I2 64%), and target vessel revascularization (TVR) (RR 0.45, 95% CI 0.29-0.70; p 0.0003; I2 67%). The two groups were comparable at latest follow up in terms of mortality (RR 0.87, 95% CI 0.65-1.16; p 0.35; I2 0%), cardiac death (RR 0.89, 95% CI 0.66-1.19; p 0.43; I2 0%), myocardial infarction (MI) (RR 0.70, 95% CI 0.39-1.24; p 0.22; I2 28%) and stent thrombosis (RR 0.22, 95% CI 0.04-1.10; p 0.06; I2 46%).&lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt;Conclusion&lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt;DCB showed promising results in the treatment of patients with coronary ISR. DCB outperformed UCB in significantly reducing TLR, MACE, LLL and TVR risks. The risk of mortality, cardiac death, MI, and stent thrombosis was similar between DCB and UCB.&lt;/div&gt; &lt;div&gt; &lt;/div&gt; &lt;div&gt; &lt;/div&gt;
Abstract 4120749: GPR39 Orchestrates the Myogenic Response in Coronary Autoregulation
Authors: Dai-Trang Le, Masaki Kajimoto, Yan Zhao, Sanjiv Kaul
Journal: Circulation (2024)

Background: Coronary autoregulation is the ability of a normal heart to maintain constant coronary blood flow (CBF) over a wide range of coronary driving pressures (CDPs) provided cardiac work remains constant. It is based on the myogenic response, the molecular mechanism of which is unknown. We recently described the presence of a G-protein coupled receptor (GPR39) in the vascular smooth muscle cells (VSMCs) of coronary arterioles in the mouse heart. We showed that endogenous eicosanoids, the vasoconstrictor 15-hydroxyeicosatetraenoic acid (15-HETE) and the vasodilator 14,15-epoxyeicosatrienoic acid (14,15 EET). act through this receptor to maintain coronary vascular tone. Hypothesis: We, therefore, hypothesized that GPR39 is the molecular switch responsible for the coronary myogenic response and autoregulation. Methods: We studied 6 anesthetized dogs at baseline and after administration of VC-108, a specific, potent GPR39 antagonist. Both during baseline and drug administration multiple coronary stenoses were created on the left anterior descending coronary artery (LAD). At each stage, heart rate, mean aortic pressure, distal LAD pressure, and right atrial pressure (RAP) were measured, as was CBF. Stenosis severity was defined by the CDP (LAD pressure minus RAP). Results: Mean basal coronary hyperemic response was 3.0 in all anesthetized animals indicating normal vasomotor function. Systemic hemodynamics did not differ between baseline and drug stages. Figure 1 is an example from a single dog where, at baseline, CBF remained constant over a CDP of 40-90 mm Hg indicating intact autoregulation. As expected, CBF declined when CDP fell below the autoregulatory range. After VC-108 administration CBF correlated linearly with CDP, indicating abolishment of the myogenic response. Baseline CDP vs. CBF data from all 6 animals within the autoregulatory range is depicted in Figure 2. No relation is noted between the two indicating intact autoregulation. In contrast, CDP vs. CBF relation is linear in all animals after VC108 is administered over the entire range of CDP’s measured, indicating abolishment of autoregulation (Figure 3). Conclusions: Our results indicate that GPR39 is a potential molecular switch for the regulation of the myogenic response underlying coronary autoregulation. Pharmacological blockage of GPR39 abolishes the myogenic tone. These novel findings set the stage for development of novel pharmacological agents for treatment of coronary artery disease.
Abstract 4122249: Deletion of macrophage dynamin-related protein 1 exacerbates left ventricular remodeling after myocardial infarction by impairing mitochondrial quality maintenance machinery
Authors: Yuki Kondo, Junichiro Koga, Nasanbadrakh Orkhonselenge, Yosuke Nishimura, Masatoshi Nomura, Masaharu Kataoka
Journal: Circulation (2024)

Background: Macrophage-mediated inflammation plays an important role in the healing process after myocardial infarction (MI). We have previously reported in macrophages that inhibition of dynamin-related protein 1 (Drp1), which induces mitochondrial fission, restrains skewing toward inflammatory phenotype. It is, however, obscure whether macrophage Drp1 promotes left ventricular (LV) remodeling after MI. Aims: The aim of this study is to elucidate the role of macrophage Drp1 in the mechanisms of LV remodeling after MI. Methods: C57Bl/6J mice specifically deficient Drp1 in Lysozyme-M + macrophages (Drp1KO) were created by Cre/loxP technology and underwent ligation of the left anterior descending coronary artery at 8 to 12 weeks of age. Results: Deletion of macrophage Drp1 decreased LV ejection fraction (38±14 vs. 23±9% at day 28. N=9, p&lt;0.05) and increased LV diameter (LVDd/Ds 5.7±0.4/4.8±0.3 vs. 4.6±0.2/3.7±0.3mm at day 28, N=9, p&lt;0.05) (Figure). Survival rates until 28 days after MI were significantly lower in Drp1KO mice (25 vs. 64%. N=24 and 33, p&lt;0.05). Deletion of Drp1 led to sustained macrophage accumulation and fibrosis of infarcted tissues. TEM revealed that mitophagosomes are decreased in Drp1-deficient macrophages in infarcted hearts. In ex vivo cultured macrophages, siRNA-mediated knockdown of Drp1 impaired mitochondrial fission and LC3-dependent mitophagy. In these macrophages, inhibition of Drp1 by Mdivi-1 for 96 hr, but not for 24 hr, induced mitochondrial DNA (mtDNA) leakage to the cytosol accompanied by increased expression of inflammatory cytokines. Hypoxia and starvation, in addition to Mdivi-1, induced leakage of mtDNA and expression of inflammatory cytokines at 24 hr. These results suggest that impairment of mitochondrial quality maintenance machinery causes leakage of mtDNA that induces inflammation. Conclusions: Macrophage Drp1 protects the heart from sustained inflammation and adverse cardiac remodeling after MI. Drp1-LC3-mediated mitophagy could be a mechanism that maintains mitochondrial quality and prevents excessive inflammation after MI.
Abstract 4121733: Comprehensive Plasma Proteomics Profiling Identifies Circulating Biomarkers to Distinguish Hypertrophic Cardiomyopathy from Other Cardiomyopathies with Left Ventricular Hypertrophy
Authors: Keitaro Akita, Mathew Maurer, Albree Tower Rader, Michael Fifer, Muredach Reilly, Yuichi Shimada
Journal: Circulation (2024)

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. It is sometimes challenging to distinguish HCM from other cardiomyopathies that cause left ventricular hypertrophy (LVH) such as hypertensive LVH, transthyretin cardiac amyloidosis (ATTR-CA), and aortic stenosis (AS). We aimed to identify a set of plasma protein biomarkers that distinguishes HCM from the other cardiomyopathies with LVH. Methods: In this multi-center case-control study, we conducted plasma proteomics profiling of 4,979 proteins in cases with HCM (n=879) and controls with hypertensive LVH (n=331), ATTR-CA (n=169), and AS (n=36). We identified clinical parameters that were significantly (univariable P&lt;0.05) different between HCM and hypertensive LVH. We then specified proteins that were significantly (multivariable P&lt;0.001) upregulated or downregulated in HCM compared to hypertensive LVH by performing multivariable logistic regression analysis on each protein adjusting for the identified clinical parameters (comparison #1). We performed the same analysis between HCM and ATTR-CA (comparison #2) as well as between HCM and AS (comparison #3). We identified proteins that were upregulated in HCM in all 3 comparisons. We also specified proteins downregulated in HCM throughout all 3 comparisons. Finally, using these proteins, we constructed a logistic regression model to distinguish HCM from all 3 control groups combined, and calculated an area under the receiver-operating-characteristics curve (AUROC). Results: Eight clinical parameters listed in Image 1 were significantly different between HCM and the controls and adjusted for in the multivariable logistic regression analyses. In the comparison between HCM and hypertensive LVH, 444 proteins were upregulated and 267 downregulated with multivariable P&lt;0.001 ( Image 1 ). There were 226 upregulated and 170 downregulated proteins comparing HCM with ATTR-CA, and 57 upregulated and 74 downregulated proteins when comparing HCM with AS ( Image 1 ). Among these proteins, 4 were upregulated in all 3 comparisons with multivariable P&lt;0.001 and 5 were downregulated ( Image 2 ). The logistic regression model with these 9 proteins had AUROC of 0.86 (95% confidence interval 0.84-0.88, Image 3 ). Conclusions: This study serves as the first to apply comprehensive proteomics profiling to identify circulating biomarkers that distinguish HCM from other cardiomyopathies with LVH independently from potential confounders.
Abstract 4120246: PFO Device Complications: Literature Review and Possible Implications for Echocardiographic Follow-up
Authors: Kaitlyn Foreman, Elizabeth Lyman, Sara Conroy, Arash Salavitabar, Clifford Cua
Journal: Circulation (2024)

Introduction: Transthoracic (TTE) guidelines after PFO device closure are vague. Goal: To perform a literature search to characterize the type, frequency, and timing of complications that occur after PFO device placement to determine the utility of routine TTE in post-device patients. Methods: A search was performed in Medline (PubMed) with English language and publication date (2000-2023) filters applied. Studies were included if they reported on PFO device closures. If a study included both PFO and ASD device closures with no distinction between the groups, it was included. Studies were excluded if it only reported on ASD device closures, were meta-analysis/review papers, or did not report any outcomes for the PFO device procedure. Results: Total of 305 articles met criteria. Incidence of complications was 6.9% (3358/48348). Maximum range of follow-up was 0 – 17 years. Types and timing of complications presented in Tables 1 and 2. Majority of complications occurred &lt; 6 months (57.8%, 1941/3358) with only 0.8% (27/3358) occurring &gt; 5 years post-device. All patients with complications &gt; 5 years device placement presented with clinical symptoms related to their complications. Conclusion: Incidence of complications after PFO device placement appeared to significantly decrease 5 years post-procedure. Late complications were all preceded by clinical symptoms. Routine use of TTE &lt; 5 years post-device may be reasonable, but &gt; 5 years, TTE may only be needed if clinical symptoms occur.
Abstract 4121148: A functional survey of postnatal heart maturation with <i>in vivo</i> Perturb-seq in spatial and temporal resolution
Authors: Haofei Wang, Yanhan Dong, Huitong Shi, Marazzano Colon, Xingyan Liu, Gregory Farber, Yunzhe Qian, Nicholas Anthony, Li Qian, Jiandong Liu
Journal: Circulation (2024)

Background: Cardiomyocyte maturation is a crucial process that involves intricate molecular and structural changes necessary for more vigorous and efficient heart function after birth. Understanding the regulatory mechanisms of this process is essential for leveraging these insights to develop advanced therapies for heart disease. Despite recent advancements, the limitations of current in vivo genetic and single-cell approaches - such as the low throughput of in vivo genetics, lack of spatial information in single-cell RNA-seq, and, most importantly, the lack of high-throughput combined use of both approaches - hinder the construction of a comprehensive regulatory network of cardiomyocyte maturation. Methods: Here, we established an experimental pipeline combining time-course single-nucleus RNA sequencing and spatial transcriptomics with our optimized in vivo Perturb-seq platform to establish the regulatory network underlying heart maturation. Results: Our current study has generated a postnatal murine heart atlas with 67,000 nuclei from postnatal heart. Temporal analysis of the cardiomyocyte transcriptome dynamics identifies Ankrd1+ cardiomyocyte as a transient state between proliferative and matured cardiomyocytes. We constructed a regulatory network consisting of 35 known and novel regulators for cardiomyocyte maturation. Our analysis of postnatal cardiomyocyte interactome elucidated signaling pathways’ stage-specific contribution to cardiomyocyte maturation. With the spatial transcriptomic data, we further identified signaling pathways that played unique roles in the maturation of chamber-specific cardiomyocytes. Using fixed RNA in vivo Perturb-seq established in this study, we have validated 21 novel regulators of postnatal cardiomyocyte maturation out of 53 candidate regulators from previous temporal and spatial analyses. Conclusions: We have not only created a single-cell-resolution temporal and spatial atlas during postnatal heart development but also established an in vivo Perturb-seq platform to allow the functional interrogation of key regulatory genes in a physiologically relevant context. Importantly, the proposed working model unlocks new possibilities for research, no longer limiting to a single gene or pathway, but allowing for the exploration of a network of genes. This high-resolution, high-throughput in vivo mapping and screening platform has the potential to revolutionize the way we study organogenesis and disease progression in the heart.
Abstract 4121359: Heart Disease and Heart Failure: Trends and Disparities in Mortality Rates in the United States from 2000 to 2020
Authors: Christian Akem Dimala, Christopher Reggio, Anthony Donato, Wissam Khalife
Journal: Circulation (2024)

Background: The remarkable decline in the overall prevalence and mortality rates of cardiovascular diseases (CVD) in the United States (US) over the past few decades has not been consistent across all age groups, sexes, races, and types of cardiovascular diseases. Heart disease (HD) and heart failure (HF) still pose a significant burden to the healthcare system. Objectives: This study sought to describe the age, sex and racial disparities in the trends in mortality rates for these two outcomes in the US over the past two decades. Methods: This was an ecological study with trend analysis of the mortality from heart disease and heart failure in the US between 2000 and 2020. Data on CVD was obtained from the National Centers for Disease Control and Prevention (CDC) surveillance databases and analyzed. Binomial regression models were used to evaluate trends in outcomes. Statistical significance was considered for p-values &lt; 0.05. Results: There was a significant decrease in the age-standardized mortality for HD over the past two decades (from 343.5 per 100,000 cases to 215.1 per 100,000 cases (p&lt;0.001)). Mortality rates were significantly higher in males (p&lt;0.001, R2 = 0.92), non-Hispanic blacks (p&lt;0.001) and non-Hispanic whites (p&lt;0.001) compared to Hispanics, (R2 = 0.94) and in adults aged 65+ (p&lt;0.001) and 75+ (p&lt;0.001) (R2 = 0.98). There was no significant decrease in the age-standardized mortality for HF (from 26.9 per 100,000 cases to 25.7 per 100,000 cases (p=0.706)) due to a reversal in the trend after 2011. Though the rates were significantly lower in males overall (p=0.001, R2 = 0.27), these rates became higher in males and in non-Hispanic Blacks compared to non-Hispanic Whites beyond 2016. Mortality rates due to HF were highest in the 65+ and 75+ age groups. Conclusions: This study on national trends in heart disease and heart failure across age groups, sexes and races over the past two decades confirmed a significant reduction in heart disease mortality rates over this period, but with persistent disparities between males and females, non-Hispanic Blacks and other races and the older age groups. This study also highlights important reversals of heart failure mortality rates trends in more recent years in males and females, and non-Hispanic Blacks and Whites, the reasons for which are amenable to further research.