tbuckley/cabot-search huggingface dataset:
Abstract 212: Association of Glycocalyx Shedding and Outcomes in Patients After Cardiac Arrest: A Prospective Observational Study
Authors: Dan He, Chenglei Su, Xianliang Yan, Tie Xu
Journal: Circulation (2023)

Background: The glycocalyx sheds early after cardiac arrest (CA). However, the potential value of elevated serum glycocalyx components remains unknown. Methods: This prospective observational study included patients who suffered CA and survived over 24 hours in the ICU of the Affiliated Hospital of Xuzhou Medical University from September 2021 to October 2022. Serum samples were collected 24 hours post CA to assess the concentration of glycocalyx shedding, including Heparan Sulfate (HS), Hyaluronic Acid (HA) and Syndecan-1 (Sdc-1). Patients were followed for 30 days or until death after CA. Outcome measures were 30-day Cerebral Performance Categories scale (CPC≤2, good function group; CPC&gt;2, poor function group), and 30-day mortality. Logistic regression was used to assess the association of glycocalyx shedding with the 30-day CPC scale. COX regression was used to assess the association of glycocalyx shedding with 30-day mortality. Results: we included 71 patients. Compared with good function group (n=22), poor function group (n=49) had significantly higher levels of HS. Adjusted logistic regression showed that the high level of HS was associated with poor functional outcome (Figure1A, OR=0.41, 95% CI=0.21-0.79, p&lt;0.01). Compared with the survival group (n=39), non-survival group (n=32) had higher levels of HA. Adjusted Cox regression indicated that high levels of HA was associated with mortality (Figure1B,Figure2, HA: HR=1.69,95%, CI=1.13-2.56, p&lt;0.05). Conclusions: Elevated serum HS levels in the early stages post-CA have an association with poor functional outcomes. Increased levels of serum HA post-CA are associated with a higher 30-day mortality.
Abstract 12687: Evaluating a Coronary Artery Disease Polygenic Risk Score Screening Strategy in a Diverse Patient Cohort at UCLA
Authors: Kristin Boulier, Yi Ding, Vidhya Venkateswaran, Bogdan Pasaniuc
Journal: Circulation (2023)

Introduction: Recent efforts to predict and mitigate coronary artery disease (CAD) risk have incorporated polygenic risk scores (PGS). Few studies examine the clinical impact of these PGS screening strategies or quantify their performance in clinical terms. Here we estimate the number needed to screen (NNS) of a PGS screening strategy for CAD based using a diverse electronic health record (EHR) linked biobank at UCLA Health. Methods: We leveraged longitudinal EHR data to conduct a synthetic trial. We assumed PGS screening was performed on 6/1/2013 for patients established prior to 1/1/2013 or 6 months into follow time if established later. Patients with preexisting cardiovascular disease or strong statin indications (LDL &gt; 190, diabetes or already on statins) are excluded. Patients with PGS scores in the top 5% of their genetic ancestry groupings (European, East Asian, African, Hispanic) are assumed to have been started on statins for the median 6.9 years of follow up. CAD diagnosis during follow up time was determined by ICD codes. NNS to prevent one CV event is calculated from cohort size and events assuming a statin number needed to treat of 50. Results: Of 33,789 adults, 17,074 were low risk and eligible for PGS screening (35% male with a mean age of 44). NNS to detect one CAD diagnosis was 351, 359, 814, 159 in the European, Hispanic, East Asian and African ancestry groups and NNS to prevent one cardiovascular event was 17,550, 17,950, 40,700, 7,950 respectively. Conclusion: Although PGS accuracy is lower in African ancestry individuals as compared to Europeans, the clinical utility of this PGS-based screening is highest in African ancestries due to increased baseline rates of disease in the African genetic ancestry grouping. Our results demonstrate that PGS accuracy is distinct from clinical utility of PGS-based strategies. Evaluation of screening strategies rather than accuracy alone will be required before PGS screening implementation.
Abstract 17637: Lacking MicroRNA-1’s Biophysical Action Causes Heart Failure Revealed by a Newly Developed Biplane Echocardiography of Mouse Heart
Authors: Ege Kacira, Mitchell Pittman, Dandan Yang, Sarah L Sturgill, Mark T Ziolo, Yuchi Han, Isabelle Deschenes, Jidong Fu
Journal: Circulation (2023)

MicroRNA-1 (miR1) is the most abundant microRNA in the heart and plays a key role in maintaining cardiac homeostasis through a well-known RNAi mechanism. Recently, we found a novel biophysical function of miR1 to physically bind to and modulate cardiac ion channels. A human single nucleotide polymorphism-hSNP14A/G (rs776480338) of miR1, in which the 14th nucleotide “A” is mutated to “G”, specifically abolishes the biophysical modulation while maintaining the RNAi. However, the physiological significance of microRNA’s biophysical action remains unknown. To study this, we created a single-nucleotide 14A/G mutation on miR1-1 and miR1-2 genes by using CRISPR/Cas9 and developed 14G-mutated homozygous (14G-Homo, miR1-1 14G/G:miR1-2 14G/G) transgenic mice. In addition, we also developed a new echocardiography methodology that can consistently record clear 4-chamber views of mouse hearts, allowing integration of 4-chamber and long axis views for the clinically recommended Biplane Simpson’s assessment of left ventricular (LV) function. Validation via Cardiac Magnetic Resonance (CMR) revealed that the Biplane method is more accurate than M-mode analysis for precise assessments of mouse LV functional parameters. These findings were highlighted in practice by monitoring both Wild Type (WT) and 14G-Homo mice at 2, 3, and 4 months of age, in which M-mode consistently overestimated LV parameters. Moreover, the clarity of the 4 chamber images enables many cardiac analyses that were previously not feasible for the mouse heart, such as the mitral valve color doppler that revealed turbulent blood flow into the LV of 14G-Homo mice. With the 4-chamber view methodology, we also studied the right ventricular (RV) function by assessing fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) and found that cardiac functional deterioration of 14G-Homo mice most likely originated in the LV, followed by RV deteriorations and development of heart failure. In conclusion, our study demonstrated that the biophysical action of miR1 is essential to cardiac homeostasis. Additionally, our new imaging methodology enables more clinically comparable analyses which significantly improve translational implications of mouse cardiac research.
Abstract 17563: Serial ABPM, Antihypertensive Drug Treatment, and Pregnancy Outcomes in Women With Hypertension Found Early During Pregnancy
Authors: Ewa M Wojciechowska, Piotr Gryglas
Journal: Circulation (2023)

Introduction: Few data are available on serial ambulatory blood pressure monitoring (ABPM) throughout pregnancyand antihypertensive drug treatment required for good blood pressure (BP) control in hypertensivepregnant women. Hypothesis: Evaluation of BP control, antihypertensive drug treatment intensity, and pregnancy outcomes in patients with hypertension (HTN) found early during pregnancy. Methods: We studied 49 consecutive pregnant patients (mean age 33.4±4.8 years, BMI before pregnancy24.5±3.7 kg/m2) referred for office HTN found early during pregnancy who gave birth to 50 children (1 twin pregnancy) in 2011-2015. Gestational HTN was previouslydiagnosed in 39 women, and 9 women had a history of previous miscarriage or stillbirth, with multipleprevious pregnancies lost in some patients. ABPM was repeated at 5-10-15-20-25-30-33-35-37 weeksof pregnancy. We calculated overall antihypertensive treatment intensity in standard daily drug doses per patient (standard doses: labetalol 200 mg, methyldopa 750 mg, metoprolol 50 mg, nifedipine 20mg, verapamil 120 mg). Statistical analysis was performed using ANOVA. Results: All children were born alive (24 vaginal delivery, 26 cesarean section) and are well at follow-up.Gestational age was 38.0±2.5 (range 29-40) weeks, and birth weight was 3215±653g (range 955-4200). Preeclampsia/eclampsia occurred in 10/3 patients. Four patients had normal BP values by ABPM throughout pregnancy and did not receive antihypertensive drugs. Most patients were treatedwith labetalol and methyldopa. Throughout pregnancy, BP remainedwell controlled (24h mean SBP/DBP 120.3-126.0/75.3-77.1 mmHg), the number of treated patientsincreased from 25 at 5 weeks to 42 at 25-35 weeks, and the average number of daily antihypertensivedrug doses in treated pts increased from 1.82 at 5 weeks to 2.98 at 37 weeks. Conclusions: Serial ABPM-guided antihypertensive drug treatment started early during pregnancywas associated with favorable outcomes. The number of patients requiring treatment increased throughout the pregnancy. No physiological BP fall atthe end of 1 st trimester was observed. Our findings help estimate the expected treatment intensity required in pregnant patients with preexisting hypertension.
Abstract 14703: Platelet Reactivity and Long-Term Outcomes Following Acute Myocardial Infarction
Authors: Peter D Larsen, Ana S Holley, Kathryn E Hally, Scott A Harding
Journal: Circulation (2023)

Introduction: A large volume of literature demonstrates a short term (1 year) association between high on treatment platelet reactivity in patients with acute myocardial infarction treated with clopidogrel and adverse cardiovascular outcomes. There is less literature examining whether this association extends beyond the duration of clopidogrel treatment. Hypothesis: That on-treatment platelet reactivity is associated wtih 5-year death and recurrent myocardial infarction in patients with acute myocardial infarction. Methods: We measured platelet reactivity in patients presenting with AMI to Wellington Hospital between 2012 and 2015 who had been treated with clopidogrel prior to angiography using Multiplate P2Y 12 assay (Roche Diagnostics). Platelet reactivity was measured in platelet reactive units (PRU). We examined the relationship between PRU and both death and myocardial infarction at 5 years follow-up. Results: In 921 patients with acute myocardial infarction (mean age 63.2, sd 10.8, 81% NSTEMI 19% STEMI) mean PRU was 39.3 (sd 23.6) PRU, with 74 patients (8%) having a PRU greater than 47, previously described as high on treatment platelet reactivity. 5-year mortality was observed in 10.4% (96 cases) and recurrent myocardial infarction in 12.2% (122 cases). Platelet reactivity was significantly associated with 5-year mortality in Receiver Operator Curve analysis, with AUC 0.58, p=0.009. Mean PRU was 45.8 (sd 27.5) in those who died versus 38.4 (sd 23.2) in those still alive at 5 years (p=0.004, unpaired t-test). Cox regression analysis demonstrated a hazard ratio of 1.01 (95% CI 1.003-1.017, p=0.01) for each increasing unit of PRU. Recurrent MI was not significantly associated with PRU, with an AUC of 0.55, p=0.09). Conclusions: Levels of platelet reactivity were associated with long-term mortality risk in AMI patients. This may suggest platelet reactivity in the acute phase following an AMI is a marker of poor cardiovascular repair, leading to an association with long-term mortality risk
Abstract 13581: Effect of Lipoprotein(a) on Long-Term Outcomes at Different LDL-C and hs-CRP Status in Patients With Percutaneous Coronary Intervention
Authors: Jiawen Li, Kailun Yan, Yulong Li, Yuejin Yang, Jinqing Yuan, Xueyan Zhao
Journal: Circulation (2023)

Background: Although some studies have shown that the risk of adverse events associated with lipoprotein (a) [Lp(a)] are influenced by low-density lipoprotein cholesterol (LDL-C) or high-sensitivity C-reactive protein (hs-CRP) levels, results on whether hs-CRP and LDL-C jointly mediate the effect of Lp(a) on long-term outcomes are unknown. Aim: To investigate the effect of Lp(a) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) according to LDL-C levels and further hs-CRP levels. Methods: This prospective study consecutively enrolled 10,724 patients with PCI in the year 2013. The primary endpoint was all-cause death. The secondary endpoint was cardiac death. Results: There were 10,000 patients with available baseline data included in final analysis (Age 58.33±10.26 years, 77.27% Male). During a median follow-up of 5.1 years, 358 patients developed all-cause death and 217 cardiac death. After the multi-variable Cox analysis, in the overall population, Lp(a) ≥ 30 mg/dL was an independent risk factor of all-cause death and cardiac death. Further analysis showed that, in patients with LDL-C &lt; 70 mg/dL, Lp(a) ≥ 30 mg/dL was not an independent risk factor of all-cause death and cardiac death regardless of hs-CRP &lt; 2 or ≥ 2 mg/L. However, when LDL-C ≥ 70 mg/dL, in the setting of hs-CRP ≥ 2 mg/L, Lp(a) ≥ 30 mg/dL was an independent risk factor of all-cause death and cardiac death; in the setting of hs-CRP &lt; 2 mg/L, Lp(a) ≥ 30 mg/dL was only the independent risk factor of cardiac death. Conclusions: The current study first reported that LDL-C and hs-CRP jointly affected the long-term outcomes associated with Lp(a) in PCI patients. When LDL-C &lt; 70 mg/dL, Lp(a) ≥ 30 mg/dL was not associated with the risk of all-cause death and cardiac death irrespective of hs-CRP levels. Our finding may be instructive for the management and treatment of Lp(a) in the future.
Abstract 17372: Cardiac Magnetic Resonance in Takotsubo Disease: Impact on Outcomes and Resource Utilization
Authors: Aparna Narendrula, Rochell Issa, David Chen, Wai Hong W Tang, Christopher Nguyen, David Kaelber, Deborah H Kwon
Journal: Circulation (2023)

Introduction: Takotsubo cardiomyopathy (CM), characterized by transient left ventricular dysfunction, presents diagnostic and management challenges. The utility of cardiac magnetic resonance (CMR) in Takotsubo CM is uncertain. We investigate CMR's impact on outcomes and resource utilization in Takotsubo CM. Methods: A retrospective analysis was conducted with TriNetX. Two cohorts with Takotsubo CM, with and without CMR within 1 month of diagnosis, were matched for lipidemias, hypertension, diabetes, sarcoidosis, and heart diseases (n=1,422 per cohort), Risks assessed 30-day, 1- and 5-year outcomes, resource utilization, and medication/procedure usage. Results: The CMR group had 3.9% (1.5% vs 5.4%, p=0.000) lower risk of mortality within 30 days and 2.6% (4.6% vs 7.2%, p=0.003) lower risk between 1 and 5 years. Hospitalization rates were similar, while complication risks (cardiomyopathy, heart failure) were higher in the CMR group at 1 and 5 years. The CMR group had higher utilization of GDMT, with similar usage for some treatments. Risk of pacemaker or implantable defibrillator usage were 4.9% higher within 30 days (5.8% vs 0.8%, p=0.000) and 5.8% higher within 1 year (8.2% vs 2.5% p=0.000) in the CMR group. Conclusions: Takotsubo patients undergoing CMR exhibited increased risk of concomitant diagnoses of CM/heart failure/pericarditis, received treatments earlier in the disease course, and experienced lower risk of mortality. These results support utilization of CMR as a routine diagnostic imaging modality in patients with suspected Takotsubo CM for comprehensive evaluation to guide treatment decisions and improve patient prognosis.
Abstract 18811: Heart Failure in a Carrier of Danon Disease
Authors: Yasmeen Mohammad, Benjamin Brink, daniel levine
Journal: Circulation (2023)

Background: Danon Disease is a rare X-linked dominant genetic condition characterized by hypertrophic cardiomyopathy, skeletal muscle myopathy, and intellectual disability, among other serious complications. The disease is a lysosomal storage disorder in which a mutation in the LAMP-2 gene causes a defect in the lysosome membrane and an accumulation of glycogen in vital tissue including cardiac muscle cells. It occurs more commonly in males, who are also more severely affected than females with this condition. There are no specific treatments available, although studies involving gene therapy have been ongoing. Patients with Danon Disease often require heart transplantation as treatment for end-stage heart failure. Description of Case: A 37-year-old female with a known family history of Danon Disease was discovered to be a carrier of the LAMP-2 mutation after presenting to the hospital with dizziness and palpitations. An echocardiogram obtained at the time of diagnosis revealed left ventricular hypertrophy and left ventricular apical thrombus with normal ejection fraction. She was started on anticoagulation and began following closely with a heart failure clinic. Since diagnosis, she has had multiple echocardiograms which have shown a steady decline in her ejection fraction to 25% and biventricular failure. An ICD was placed, with no shocks ever administered. She has had multiple hospital admissions for exacerbations of heart failure since diagnosis. Telemetry monitoring during these admissions revealed frequent premature ventricular contractions attributed to the patient’s severe cardiomyopathy. Despite continuation of guideline-directed medical treatment, this patient’s systolic heart failure is anticipated to continue worsening. She will likely require heart transplant, for which evaluation has already been initiated. Discussion: Danon Disease is a rare lysosomal storage disorder that often involves progressively worsening cardiomyopathy. Individuals with a known family history of this condition should be referred early for genetic testing. If found to have the condition or be a carrier, they should begin following with a heart failure specialist and consideration for advanced therapies, like transplant, should be initiated.
Abstract 16532: Mosaic Loss of Y Chromosome in Leukocytes Predicts Death in Patients With Chronic Heart Failure Across the Whole Spectrum of Ejection Fraction
Authors: Sebastian Cremer, Klara Kirschbaum, Lukas Tombor, Silvia Mas-Peiro, Tina Rasper, David M Leistner, Stefanie Dimmeler, Andreas M Zeiher
Journal: Circulation (2023)

Aims: Mosaic loss of Y chromosome (LOY) in men increases with age and correlates with clonal expansion of myeloid cells. Experimental modeling demonstrated that LOY in hematopoietic cells leads to diffuse cardiac fibrosis and subsequent development of heart failure in mice. Cardiac fibrosis is an important pathogenic feature in heart failure irrespective of etiology. Therefore, we investigated the prognostic significance of LOY in men with chronic heart failure. Methods and Results: In a total of 705 male patients with chronic heart failure with reduced and preserved ejection fraction, LOY was determined by digital PCR of peripheral blood cells by assessing the 6bp sequence difference between the AMELX and AMELY genes. ROC analysis relating the extent of LOY to mortality revealed a LOY of 17% as the optimal cut-off value to predict death during follow-up. LOY &gt;17% was observed in 18.6% of all patients, increased with age and was associated with increased mortality after three years (13,7% in patients without LOY compared to 29.0% in patients with LOY, p&lt;0.001, Figure 1). LOY remained an independent predictor of death in multivariate analysis including, age, LVEF and nt-pro BNP serum levels (HR 1,67; 95% CI 1.08-2.57; p=0.017). Importantly, LOY was associated with increased mortality in patients with heart failure with reduced ejection fraction defined as LVEF &lt; 50% (p&lt;0.001) as well as in patients with preserved LVEF ≥ 50% (p=0.01). Conclusion: Among patients with heart failure, LOY in blood cells is associated with increased risk of death across the complete range of ejection fraction. Further studies are warranted to discern if LOY associates with cardiac fibrosis in men with heart failure and triggers increased profibrotic signaling. The results of this study may inform trials evaluating precision-targeted anti-fibrotic therapies in patients with chronic heart failure.
Abstract 14208: New Artificial Intelligence Algorithms of Electrocardiogram Detection for Patients With Heart Failure
Authors: Youngjun Park, Kyung Geun Kim, Sunghoon Joo, Mineok Chang, Yeha Lee
Journal: Circulation (2023)

Introduction: Heart failure (HF) is a global pandemic with an increasing prevalence. The burden of HF-related hospitalizations and costs are increasing. Artificial intelligence(AI) algorithms applied to electrocardiograms have shown promise in diagnosing HF, but they require a large amount of training data, which is scarce and costly. Transfer learning addresses this challenge by utilizing knowledge from previous tasks, resulting in superior performance with limited data compared to conventional AI algorithms Hypothesis: AI algorithms using transfer learning can be accurately diagnose heart failure with reduced ejection fraction(HFrEF) using electrocardiograms compared to conventional AI algorithms. Methods: All patients aged 18 years older from the two hospitals with at least one ECG were included in the study. Electrocardiogram, transthoracic Echocardiogram (TTE), and demographic data were collected. The AI algorithm consisted of two phases: conventional AI algorithms, pre-training with a large-scale ECG dataset and transfer learning for HFrEF detection. Performance evaluation was conducted using various metrics, including AUROC, sensitivity, specificity, accuracy, F1 score. Results: The dataset consisted of 687,911 ECGs from 259,943 patients. Testing the conventional model on the HFrEF resulted in a sensitivity of 63.8%, specificity of 96.2%, accuracy of 93.6%, area under the receiver operating curve (AUC) of 0.93 (95% CI, 0.92 - 0.94), and F1 score of 61.6%. Testing the transfer learning model on the HFrEF increased the sensitivity of 75.1%, accuracy of 93.7%, area under the receiver operating curve (AUC) of 0.952 (95% CI, 0.93 - 0.96), and F1 score of 65.6%. but lowered the specificity of 95.3% Conclusions: A New AI-enabled ECG algorithm for identifying patients with HFrEF can be more accurately diagnosed than conventional AL algorithms.