tbuckley/cabot-search huggingface dataset:
Abstract 4141061: Predicting Mortality Risk In patients With Heart Failure Using Respiratory Polygraphy And Esophageal Pressure During Sleep
Authors: Hamza Nahoui, Henrik Schirmer, Harald Hrubos-Stroem
Journal: Circulation (2024)

Background: Expansion of thorax and abdomen during normal respiration generates negative intrathoracic pressure that affects organs like the heart and esophagus. Upper airway collapse during sleep increases respiratory effort. Measuring esophageal pressure (PES) is the gold standard for estimating this effort. Heart failure is highly associated with obstructive sleep apnea (OSA). Abrupt swing in thoracic pressure and nocturnal hypoxemia during apnea are two mechanisms that can lead to heart failure. Hypothesis: PES and traditional sleep metrics: apnea hypopnea index (AHI), oxygen desaturation index (ODI), and mean-spO2 are associated with increased mortality risk in patients with heart failure and OSA. Methods: 174 patients with heart failure identified in the local heart failure registry in Akershus university hospital. All patients underwent respiratory polygraphy and esophageal manometry during sleep. Observation time 2003-2024. AHI, ODI, mean-spO2 and sleeping time with elevated esophageal pressure above different cmH2O, PES, were measured. Initial proBNP were also analyzed. Cox proportional hazard models were used to analyze the risk. Results were adjusted to age, sex, body mass index (BMI), and comorbidities. Results: Mean age 66 years (SD 12.019). 34 (20%) of observed cases were females. 70 (40%) patients died during observation time. Mean time to event (death) from first proBNP 3,5 years. Mean time to event from baseline polygraphy 8,2 years. First proBNP predicted all-cause mortality (HR 1.108 [95% CI 1.052-1.167], p&lt;0,001). AHI&gt;15, ODI and mean-spO2 during sleep predicted all-cause mortality, but not sleep time with elevated esophageal pressure above 15 cmH2O. Sleep time with higher pressure degrees (above 80 cm H2O) did predict mortality. Adding first proBNP to our prediction model did not affect the predictive value of mean-spO2 (HR 0.828 [95% CI 0.752 -0.912], p&lt;0.001), or sleep time with PES above 80 cmH2O (HR 1.127 [95% CI 1.003-1.1.265], p 0.043). Conclusion: Nocturnal mean-spO2, and PES above 80 cmH2o predicted mortality in patients with heart failure and sleep apnea independent of first proBNP values. Our results might explain why treatment with positive airway pressure is more effective in patients with severe OSA, and that oxygen therapy during sleep could represent a treatment choice for patients with HF and OSA. Sleep studies may offer prognostic value for heart failure patients several years before first proBNP is obtained.
Abstract 4141300: Sympathetic Response to Dynamic Exercise Predicts the Exercise Capacity of Patients with Heart Failure with Preserved Ejection Fraction
Authors: Mark Badrov, Tomoyuki Tobushi, Catherine Notarius, Evan Keys, Massimo Nardone, David Cherney, Susanna Mak, John Floras
Journal: Circulation (2024)

Background: In heart failure, sympathetic excess and exercise intolerance impair quality of life. In HFrEF, muscle sympathetic nerve activity (MSNA) is augmented at rest and in response to exercise, of which the latter relates inversely to peak oxygen uptake (VO 2peak ). Aims: To determine, in HFpEF: 1) if resting MSNA is elevated, independent of its accompanying comorbidities; and 2) if MSNA responses to exercise are also increased and relate inversely to exercise capacity. Methods: In 13 HFpEF patients (70±6 yrs; LVEF: 63±6%; NTproBNP: 658±610 pg/ml), 17 co-morbid controls (CMC; 67±8 yrs), matched for medication and presence of comorbidities, and 18 healthy controls (HC; 65±8 yrs), we measured, in the seated position, heart rate, blood pressure, and MSNA (microneurography) during: i) 7 min baseline; ii) 2 min isometric (IHG; 40% maximal voluntary contraction [MVC]) or rhythmic handgrip (RHG; 50% and 30% MVC) exercise, followed by 2 min post-HG ischemia (PHGI); and iii) 4 min 1-leg cycling (2 min each at mild and moderate intensity). VO 2peak was obtained by open circuit spirometry. Results: Resting MSNA was higher in HFpEF (48±14 bursts/min) vs. CMC (36±9 bursts/min; P=0.02) and HC (34±12 bursts/min; P&lt;0.01). In HFpEF, relative VO 2peak (16±5 ml/kg/min) was lower vs. CMC (25±7 ml/kg/min; P=0.02) and HC (29±9 ml/kg/min; P&lt;0.001). During HG, MSNA responses were similar in magnitude in all groups (P&lt;0.05), resulting in higher absolute values in HFpEF vs. CMC and HC during HG and PHGI at 40% IHG (P&lt;0.05) and HG only at 50% and 30% RHG (P&lt;0.05). During cycling, MSNA decreased during mild (−4±4 bursts/min; P=0.01) and moderate (−8±6 bursts/min; P&lt;0.001) cycling in HC, was unchanged during mild (+1±6 bursts/min; P=0.42) and moderate (+2±8 bursts/min; P=0.28) cycling in CMC, yet increased in HFpEF during both mild (+8±8 bursts/min; P&lt;0.001) and moderate (+9±10 bursts/min; P&lt;0.001) cycling. In HFpEF, the change in MSNA elicited by moderate cycling related inversely to relative VO 2peak (R 2 =0.51; P&lt;0.01). No such relationship existed in either CMC or HC (P&gt;0.05). Conclusion: In contrast to comorbidity-matched controls, HFpEF patients exhibit augmented MSNA at rest and during exercise. As with HFrEF, the magnitude of such ‘paradoxical’ sympathoexcitation during dynamic exercise related inversely to exercise capacity, observations consistent with the concept of a peripheral neurogenic, vasoconstrictor limit on exercise in all with heart failure, regardless of LVEF.
Abstract 4140771: Utility of Non-obstructive General Angioscopy-Derived Plaque Evaluation and LDL Cholesterol Levels in Identifying CCs from High-Risk Plaques in the Aorta
Authors: Yudai Tanaka, Keisuke Kojima, Yuta Hotsubo, Yuki Nakajima, SHOHEI MIGITA, Saki Mizobuchi, Katsunori Fukumoto, Riku Arai, Yasunari Ebuchi, Tomoyuki Morikawa, Takashi Mineki, Mitsumasa Sudo, Daisuke Kitano, Yasuo Okumura
Journal: Circulation (2024)

Introduction: Severe atherosclerosis of the aorta poses a significant risk of embolism to peripheral organs. Non-obstructive general angioscopy (NOGA) offers detailed observation of atherosclerosis in the aorta. Cholesterol crystals (CCs) can disperse into the blood from ruptured plaques (RPs) and cause inflammation. However, the relationship between LDL cholesterol levels and the detection rate of CCs from RPs has not been fully elucidated. Aims: This study aims to evaluate the utility of NOGA in identifying high-risk aortic plaques for CCs detection and to examine the influence of LDL cholesterol levels on this detection rate. Methods: We investigated 105 consecutive patients with coronary artery disease who underwent NOGA between September 2021 and November 2023. Blood samples were taken from a total of 248 NOGA-derived atheromatous plaques in the infrarenal abdominal aorta. The presence of CCs was assessed using polarized light microscopy and the filter paper rinse method. The CCs detection rates were analyzed by stratifying patients based on LDL cholesterol levels (divided at 100 mg/dL) and the presence of RPs. Results: The mean age was 67 years; 82.9% were male, 41.0% had diabetes, 99.1% had dyslipidemia, and 78.1% had hypertension. RPs accounted for 52.8％ of the sampling sites, thrombi for 13.3%, yellow plaque for 21.0%, and ulcer and fissure for 12.9%. The overall CCs detection rate was 22.6% (n = 56/248). The detection rates were 1.7% (n = 2/117) in plaques without RPs and 41.2% (n = 54/131) in plaques with RPs (p &lt; 0.001). Among those with LDL levels &lt; 100 mg/dL, the detection rate was 19.3% (n = 41/213), whereas it was 42.9% (n = 15/35) in those with LDL levels ≥ 100 mg/dL (p = 0.039). Specifically, the detection rates were 1.9% (n = 2/104) in plaques without RPs and LDL &lt; 100 mg/dL, 9.1% (n = 1/11) in plaques without RPs and LDL ≥ 100 mg/dL, 36.8% (n = 39/106) in plaques with RPs and LDL &lt; 100 mg/dL, and 58.3% (n = 14/24) in plaques with RPs and LDL ≥ 100 mg/dL (p &lt; 0.001). Conclusions: Identifying plaque types using NOGA, combined with LDL cholesterol levels, is useful for detecting high-risk aortic plaques prone to CCs. The combination significantly enhances the predictive capability for CCs detection.
Abstract 4141127: Combined use of cardioprotective glucose-lowering drugs and statins in individuals with type 2 diabetes is associated with the lowest risk of all-cause mortality
Authors: Tummas Ternhamar, Mia Johansen, Borge Nordestgaard, Shoaib Afzal
Journal: Circulation (2024)

Introduction: Cardioprotective glucose-lowering drugs including sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, and lipid-lowering statins are both aimed at preventing morbidity and mortality in individuals with type 2 diabetes. The importance of combining cardioprotective glucose-lowering drugs and statins in a real-world setting is unknown, and this was never tested in a 2-by-2 randomized trial. Hypotheses: We tested the hypothesis that combination of cardioprotective glucose-lowering drug and statin is associated with lower risk of all-cause mortality than using either drug alone. Aims: We investigated the association with all-cause mortality of combined treatment of cardioprotective glucose-lowering drug with statin versus either drug alone versus no drugs, in a nationwide real-world setting. Methods: From January 2013 through December 2021, we identified all individuals with type 2 diabetes living in Denmark. We categorized four groups according to treatment status: i) both cardioprotective glucose-lowering drug and statin, ii) cardioprotective glucose-lowering drug alone, iii) statin alone, and iv) neither cardioprotective glucose-lowering drug nor statin. First, using a simple cohort design, we followed 197,507 individuals with type 2 diabetes from January 2015 through December 2021. Second, using a time-varying cohort design, we followed all 354,979 individuals with type 2 diabetes and updated their treatment and covariate status annually from 2013 through 2021. All-cause mortality was assessed from the nationwide Danish Central Person Registry, which is 100% complete. Results: During mean follow-ups of 6.1 and 6.0 years, 50,571 and 80,712 individuals died in the simple and time-varying cohorts. Compared with nonusers of cardioprotective glucose-lowering drug or statin, the multivariable adjusted hazard ratios of all-cause mortality were 0.60 (95% confidence interval: 0.57–0.63) for combined use of cardioprotective glucose-lowering drug and statin, 0.76 (0.74–0.77) for treatment with statin alone, and 0.76 (0.70–0.82) for treatment with cardioprotective glucose-lowering drug alone. Corresponding values in the time-varying cohort were 0.43 (0.42-0.45), 0.63 (0.62-0.64), and 0.61 (0.58-0.64), respectively. Conclusions: In individuals with type 2 diabetes, treatment with a cardioprotective glucose-lowering drug and statin in combination was associated with a lower risk of all-cause mortality than using either drug alone.
Abstract 4140758: Down-regulated Suv39h1 Alleviates Heart Aging by restoring mitochondrial autophagy through SIRT1-related pathways
Authors: Jian Yang, Li Liu
Journal: Circulation (2024)

Introduction: Cardiac aging is the main risk factor for cardiovascular disease, and the basis for maintaining cardiovascular system homeostasis and delaying cardiac aging is increasing mitophagy to promote the clearance of damaged mitochondria. Suv39h1 is a histone lysine methyltransferase closely associated with aging, but it is not yet clear whether Suv39h1 is associated with cardiac aging. Hypothesis: Whether downregulating Suv39h1 signaling improves cardiac aging, and if so to further explore underlying mechanism. Methods: H9C2 cardiomyocytes were stimulated with 0.1μmol doxorubicin for 24h to induce aging. Recombinant Suv39h1 lentivirus was infected with H9C2 cells to overexpress or knock down Suv39h1. The aging-associated phenotypes of cardiomyocytes was detected by western blot and β-galactosidase staining. Mitochondrial membrane potential was detected by JC-1 staining. The effect of Suv39h1 on aging phenotype was detected by β-galactosidase staining. Mitochondrial autophagy markers were detected by western blot. Results: Compared with the control group, the expression of aging marker P21 and positive staining of SA-β-gal were significantly increased in Doxorubicin induced subacute senescent cardiomyocytes. The expressions of Suv39h1 and H3K9me3 were also significantly increased in aging cardiomyocytes.Compared with sh-Con group, mitochondrial membrane potential of cardiomyocytes increased significantly in sh-Suv39h1group,indicating that down-regulated Suv39h1 reversed doxorubicin- induced mitochondrial membrane potential decline of cardiomyocytes. β-galactosidase staining showed that the positive rate of SA-β-gal in sh-Suv39h1 group was significantly lower than that in sh-Con group, indicating that cell senescence was inhibited. However, overexpression of Suv39h1 showed the opposite result.Mechanistically,down-regulation of Suv39h1 can relieve transcriptional inhibition of H3K9me3 on SIRT1, and promote mitochondrial autophagy through activation of Pink1/Parkin axis, delaying cardiac aging. Conclusions: Targeted down-regulation of Suv39h1 can relieve the transcriptional inhibition of H3K9me3 on SIRT1, promote myocardial mitochondrial autophagy and alleviate cardiac aging.
Abstract 4140774: Pharmaceutically Manufactured Cannabidiol Demonstrates Clinically Relevant Reductions in Pericarditis Pain and C-Reactive Protein in Patients with Recurrent Pericarditis – the MAvERIC-Pilot Study
Authors: Sushil Luis, Allan Klein, Paul Cremer, Antonio Abbate, Jonathan Salik, Georgia Thomas, Syed Waqas Haider, Tracy Hagerty, David Lin, Thomas Waggoner, Stephen Nicholls, Andrea Parker, Andrew Hamer
Journal: Circulation (2024)

Background: Recurrent pericarditis results from inflammasome activation and is associated with significant morbidity. Cannabidiol has been shown to block numerous inflammasome signaling pathways, including reducing transcription of pro-IL-1β and NLRP3, and inhibiting secretion of IL-1β and IL-6. Aim: To assess the impact of oral pharmaceutically manufactured (P-)cannabidiol in recurrent pericarditis patients (pts). Methods: Adult pts (≥18 years) with symptomatic, recurrent pericarditis (≥2 recurrences) were eligible for this open-label, multicenter study. Eligible pts had pericarditis chest pain with a numerical rating scale (NRS) pain score ≥4 within 7 days prior to enrollment, together with either elevated (≥1.0 mg/dL) C-reactive protein (CRP) within the prior 7 days or prior pericardial late gadolinium enhancement (LGE) on cardiac imaging. Pts had to be on chronic treatment with NSAIDs, colchicine or corticosteroids (any combination) with stable baseline (BL) doses. Oral P-cannabidiol was uptitrated to 10 mg/kg twice daily (BID), or maximum tolerated dose. The primary efficacy endpoint was improvement in NRS pain score at week 8 (WK8). A secondary efficacy endpoint among pts with elevated BL CRP was the percentage of pts with CRP normalization (≤0.5 mg/dL) at WK8. Results: 27 pts, mean age of 53 years (range 24-77), 18 of female sex, with a median of 3 prior pericarditis episodes were enrolled. CRP was ≥1.0 mg/dL in 10 pts (37%) at BL. Prior evidence of LGE was present in 21 pts (78%). At BL, 41% of pts were receiving corticosteroid therapy. The highest tolerated study medication dose was BID 10 mg/kg in 20 pts (74.1%), 7.5 mg/kg in 4 pts (14.8%), and 5 mg/kg in 3 pts (11.1%). All 27 pts (100%) completed the WK8 visit. Mean NRS score decreased by 3.7, from 5.8 at BL to 2.1 at WK8. In those with CRP elevation at BL, CRP normalized in 8 pts (80%) by WK8, with mean CRP decreasing from 5.71 to 0.31 mg/dL. Study medication was discontinued due to AEs in 2 pts (7.4%). 24 pts (89%) tolerated P-cannabidiol with a treatment response and proceeded into the 18-week extension period (EP) where background therapy is weaned. Conclusions: Among pts with symptomatic pericarditis recurrence, oral administration of P-cannabidiol led to a clinically relevant reduction in pericarditis chest pain (measured by NRS score) and in CRP. P-cannabidiol was shown to be safe and generally well tolerated, with the majority of pts reaching the target dose and continuing into the study EP.
Abstract 4141352: Can quantifiable aortic or coronary artery calcifications in the standard of care baseline CT or PET-CT scan of patients with Hodgkin or non-Hodgkin lymphoma serve as a predictor of Major Adverse Cardiovascular Events?
Authors: MARIA F. GOMEZ ARDILA, Andres Daryanani, JUAN GARZON, Eduardo Tellez Garcia, Thomas E Witzig, Thomas Habermann, James Cerhan, Thomas Foley, Hector Villarraga
Journal: Circulation (2024)

Background: Major adverse cardiovascular events (MACE), including myocardial infarction, acute coronary syndrome, ischemic heart disease requiring revascularization, stroke, and heart failure, have been documented as significant contributors to mortality in cancer survivors. Coronary artery calcium (CAC) can predict MACE in non-cancer populations, while calcium in the aorta (CA) has not been evaluated as a prognostic marker. Every patient diagnosed with cancer undergoes a standard-of-care Positron Emission Tomography-Computed Tomography (PET-CT) or a chest CT before the initiation of chemotherapy. Hypothesis: To determine whether the CAC or CA of patients with Hodgkin's or non-Hodgkin's lymphoma, derived from standard-of-care PET-CT/chest CT, can predict the incidence of MACE. Methods: Patients treated with anthracycline-based chemotherapy, diagnosed and followed from January 1, 2013, through June 30, 2023, were included. Patients who did not undergo a PET-CT or CT, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CAC, CA, or CAC-CA was associated with the development of MACE. Calcium was retrospectively quantified using TeraRecon software (Durham NC) and categorized as: 0, 1-99, and &gt;100. Outcome analyses was estimated using the Kaplan-Meier method. Results: 326 patients were included, mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was found in 89 patients and CA in 140. In the univariate regression model, a statistically significant association was found with values &gt;100 for CA, CAC and CAC-CA with the risk of MACE. (Fig 1a/b/c). CAC equal to 0 demonstrated a significant protective effect against MACE. (Fig 1a). In the multivariable analysis, these associations persisted even after adjusting for comorbidities. (Table 1). Conclusion: CAC, CA and CAC/CA &gt;100 in the standard-of-care CT/PET CT are predictors of MACE in lymphoma patients undergoing anthracycline treatment, a CAC equal to 0 has protective effect, these relationships remained statistically significant after adjusting for comorbidities.
Abstract 4140939: Platelet-to-Lymphocyte Ratio (PLR) as a Predictor of In-Hospital Mortality in Patients with First-Ever Acute Ischemic Stroke: A cross-sectional study from Ecuador.
Authors: Hans Mautong, Emilio Martinez, Akshat Banga, Carlos Noboa, Juan Zevallos
Journal: Circulation (2024)

Background: In-hospital mortality from acute ischemic stroke (AIS) remains a major concern in developing countries where access to thrombectomy or fibrinolytics is limited. Platelet-to-lymphocyte ratio (PLR) has been suggested as an inflammatory marker associated with poor outcomes in AIS. Therefore, we aim to evaluate the value of PLR as a predictor of in-hospital mortality in first-ever AIS. Methods: We evaluated the records of 293 patients with a first-ever AIS from a third-level hospital in Ecuador from 2016-2022. Immunocompromised patients, those who had active infections, autoimmune diseases, or malignancies were excluded. The PLR was calculated by dividing platelet by lymphocyte count. Participants were classified into low or high PLR groups based on the median. Univariate and multivariate logistic analyses were used to determine predictors of in-hospital mortality. A ROC curve analysis was performed to identify the optimal cutoff value of PLR for predicting the outcome. Results: 140 patients were eligible for the study. Most patients were male (67.1%) and the median age was 63 years. The median length of hospitalization was 11 days (6-19), and 35% of patients required ICU admission. In-hospital mortality was 20%. Deceased patients were significantly older and had higher rates of ICU admission and NIHSS than survivors. A high PLR was associated with an increased risk of in-hospital mortality (OR =8.30; p= 0.001) in the univariate model. After adjusting for potential confounders, only high PLR (OR =6.02; p= 0.022), ICU admission, and NIHSS remained statistically significant. The ROC curve showed that the optimal cutoff value of PLR for predicting in-hospital mortality was 159.44, with an AUC of 0.799 (Sensitivity: 85.7%, Specificity:77.7%). Conclusion: Our results suggest that PLR is an independent predictor for in-hospital mortality in patients with a first-ever AIS. This biomarker could be useful in developing countries where stroke mortality is still high.
Abstract 4141147: Age at Menarche Associated with Longitudinal Increases in Blood Pressure in Postmenopausal Indian Women: Data from the Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) study
Authors: Wilhemina Quarpong, Suchitra Chandrasekaran, Puja Mehta, K Narayan, Nikhil Tandon, Usha Ramakrishnan, Shivani Patel
Journal: Circulation (2024)

Background and research questions: Data suggest that South Asian women exhibit earlier development of cardiovascular disease and that they may also experience menarche and menopause at younger ages than other ethnic groups. We investigated whether the timing of menarche and menopause impacts the trajectories of blood pressure in postmenopausal women in India. Methods: Data were from 1,689 postmenopausal women free of cardiovascular disease at baseline in the Delhi and Chennai sites of the Centre for cArdiometabolic Risk Reduction in South-Asia (CARRS) surveillance Cohort. Women underwent blood pressure examinations at their homes in 2010-2012, 2013-2014, and 2016-2017. We assessed associations of ages at menarche (tertiles: 9-13, 14, and 15-22 years) and menopause (four categories: &lt;40, 40-44, 45-49, and ≥50 years), separately, with baseline systolic blood pressure (SBP) and trajectories of SBP change from baseline to the last available examination round. Associations were assessed using multilevel modeling, controlling for age, education, employment status, religion, body mass index, and hypertension diagnosis and/or use of antihypertensive medication at baseline. Results: Women had a median age of 54 years (IQR: 48-60) at baseline and median follow-up time was 4.8 years (IQR: 4.1-5.2). Median age at menarche was 14 years (IQR: 13-15) and median age at menopause was 45 years (IQR: 40-48). Adjusted models showed no association between age at menarche and baseline SBP. Longitudinally, the percent change in SBP per year was higher for those who had menarche before age 14 (0.83, 95% CI: 0.53-1.14) and after age 14 (0.70, 95% CI: 0.38-1.04) compared to menarche at 14 years (0.25, 95% CI: -0.06-0.55). There were no statistically significant associations of age at menopause with baseline SBP or change in SBP. Conclusions: The timing of menarche, but not menopause, was associated with blood pressure trajectories among postmenopausal Indian women. Further work to understand the mechanisms linking reproductive milestones and blood pressure trajectories as well as their implications for cardiovascular outcomes in South Asian women is needed.