tbuckley/cabot-search huggingface dataset:
Abstract 16709: Metabolic Clusters and Their Association With Progression of Coronary Artery Calcification (From the ELSA-Brasil)
Authors: Fernando Y Cesena, Giuliano Generoso, Marcio Bittencourt, Alexandre Pereira, Raul D Santos, Paulo A Lotufo, Isabela M Bensenor
Journal: Circulation (2023)

Introduction: Metabolic risk factors for CVD tend to cluster. However, the association between metabolic clusters considering lipoprotein subclasses and subclinical atherosclerosis is not well understood. This study aimed to characterize metabolic clusters and determine their association with CAC progression. Methods: We included individuals with available lipid profiles assessed by NMR spectroscopy and excluded those taking lipid-lowering medications. Hierarchical clustering was performed using BMI, fasting glycemia, HbA1c, HOMA-IR, LDL-c, HDL-c, TG, and subclasses of LDLs, HDLs, and TG-rich lipoproteins (TRLs). CAC was evaluated in a subset of participants with two cardiac CT measurements and no prior history of ASCVD. The association between clusters and CAC progression (evaluated by the Berry method) was assessed using logistic regression. Results: The study included 4328 participants (55% females, mean age 50.6 ± 8.7 years), among whom 4 metabolic clusters were identified (Table). HOMA-IR, BMI, glycemia, HbA1c, TG, and hsCRP increased from Cluster 1 to Cluster 4. Compared to Cluster 1, Clusters 3 and 4 were significantly associated with CAC progression (OR 1.59 [95% CI 1.21; 2.09], p &lt;0.001 and OR 2.79 [95% CI 1.43; 5.45], p=0.003, respectively). The Figure demonstrates that individuals with lower calculated CVD risk but more pronounced metabolic abnormalities may have a probability of CAC progression as high as those with higher calculated CVD risk but fewer metabolic alterations. Conclusions: Metabolic clustering around insulin resistance can help identify individuals at higher risk of CAC progression, regardless of calculated CVD risk and baseline CAC.
Abstract 14561: Utility of TAPSE/RVSP Ratio in Predicting Severity of Pulmonary Hypertension and Survival in the PVDOMICS Cohort
Authors: Ambreen F Ali, Zackary D Goff, Shilin Yu, Miriam Jacob, Deborah H Kwon, Robert Frantz, Christine L Jellis
Journal: Circulation (2023)

Introduction: The right ventricle [RV] adapts to pulmonary hypertension [PH] by increasing contractility to maintain RV-PA coupling. With increased afterload, RV contractility cannot compensate, resulting in RV failure. TAPSE/RVSP ratio is a non-invasive measure of RV-PA coupling. We aim to assess TAPSE/RVSP ratio for predicting PH severity and survival across a spectrum of PH in the PVDOMICS cohort. Methods: PVDOMICS subjects from the 5 World Symposium PH groups and comparators were evaluated. TAPSE/RVSP ratio, in mm/mmHg, was derived for each group. PH subjects were stratified by TAPSE/RVSP ratio into low &lt; 0.19, intermediate ≥ 0.19 to &lt; 0.32, and high ratio &gt; 0.32. The relationship between the ratio and RHC parameters (mean PA pressure [mPAP] and pulmonary vascular resistance [PVR]), and between-group differences were evaluated by one-way ANOVA. Kaplan-Meier curves and log-rank tests were used to characterize and compare survival between groups. Results: Data were available for 514 PH subjects (58 ± 15 yrs, 64% female) and 179 comparators (61 ± 13 yrs, 59% female). Mean TAPSE/RVSP ratio was 0.35 ± 0.18 in PH vs 0.63 ± 0.26 in comparators (p &lt; 0.001). Mean TAPSE/RVSP across the PH groups 1-5 were similar, 0.33 ± 0.19, 0.33 ± 0.16, 0.37 ± 0.15, 0.41 ± 0.21 and 0.43 ± 0.29 (p=NS). Within PH subjects, 99 (19.2%) had low, 173 (33.7%) had intermediate and 242 (47.1%) had high ratio. Those with low ratio had higher mPAP (53.6 ± 11.8 mmHg), compared to intermediate (44.6 ± 11.7 mmHg) and high ratio (34.1 ± 10.2 mmHg) [p &lt; 0.001]. Those with low ratio had higher PVR (10.1 ± 5.1 WU), compared to intermediate (6.8 ± 4.1 WU) and high ratio (4.1 ± 2.1 WU) [p &lt; 0.001]. Survival was significantly higher for those with high TAPSE/RVSP ratio compared to those with low ratio (p &lt; 0.001) [Figure]. Discussion: TAPSE/RVSP ratio correlates well with invasive markers to predict PH severity. This useful measure of RV-PA coupling also enables stratification for outcome, with ratio &gt; 0.32 having the best survival rates.
Abstract 12818: Clinical Significance of Myocardial Perfusion in Dilated Cardiomyopathy and Hypokinetic Non-Dilated Cardiomyopathy
Authors: Hisanori Kosuge, Shoko Hachiya, Yasuhiro Fujita, Satoshi Hida, Kazuhiro Satomi
Journal: Circulation (2023)

Introduction: Dilated cardiomyopathy (DCM) is characterized by left ventricular (LV) systolic dysfunction with LV dilatation. Hypokinetic non-dilated cardiomyopathy (HNDC) characterized by LV dysfunction without LV dilatation is proposed as a new category of DCM. Microvascular dysfunction in DCM is associated with the degree of LV dysfunction. However, the association between myocardial perfusion and clinical spectrum of DCM has not been elucidated. Hypothesis: We assessed the hypothesis that myocardial perfusion is correlated with the clinical spectrum of DCM. Methods: Thirty-six subjects (20 non-ischemic cardiomyopathy (NICM) patients and 16 control subjects, mean age: 59 ± 2 years) underwent CMR at 3T. Cine imaging, adenosine stress perfusion, T1 mapping, and late gadolinium enhancement were performed. NICM group was divided into DCM (n=10) and HNDC (n=10). Native T1 and extracellular volume fraction (ECV) were measured as an averaged values in the septum of 3 short-axis slices of base-to-apex LV myocardium. Myocardial perfusion reserve (MPR) was calculated as the ratio of stress/rest myocardial blood flow. Results: LV ejection fraction was significantly lower in NICM compared to control (29.2±1.6% vs. 56.6±1.5%, p&lt;0.001). Native T1 and ECV were significantly higher in NICM compared to control (native T1: 1296±12ms vs. 1228±8ms, p&lt;0.001, ECV: 32.9±1.7% vs. 27.3±0.62%, p&lt;0.001), but they showed no significant differences between DCM and HNDC. MPR in HNDC was significantly higher than that in DCM (2.0±0.51 vs. 1.5±0.27, p=0.026), and comparable to that in control (1.9±0.11, p=0.717, Fig 1). MPR was negatively correlated with LV end diastolic volume index (r=-0.333, p=0.047, Fig 2), but MPR showed no significant correlations with native T1 and ECV. Conclusions: HNDC showed preserved MPR in contrast to impaired MPR in DCM. Myocardial perfusion may be a promising factor for the clinical spectrum of DCM.
Abstract 17593: Betel Quid Addiction Causing Monomorphic Ventricular Tachycardia
Authors: Cali Clark, Shane Miller, Justin Wilberding
Journal: Circulation (2023)

A 44-year-old woman presented to the emergency room due to worsening shortness of breath over the past few days with accompanying dizziness, cough, and fever. Her history was significant for asthma, obstructive sleep apnea, and hypertension. Upon arrival, she was noted to be hypoxic on room air and required supplemental oxygen. Physical exam showed extensive pitting edema in the lower extremities and crackles in bilateral lung fields. Chest radiograph revealed an enlarged cardiac silhouette and increased interstitial infiltrates consistent with pulmonary edema. While in the emergency department she was noted to have frequent episodes of asymptomatic non-sustained monomorphic ventricular tachycardia. Further questioning revealed the patient had been using betel quid daily for over 20 years to improve her mood and energy levels. She had attempted to quit in the past but was unable to do so. Echocardiogram was performed which showed preserved left ventricular function and severely dilated right ventricle. BNP was elevated at 1930 pg/mL. Due to her ventricular arrhythmias and cardiomyopathy, coronary angiography was performed; this was negative for epicardial coronary artery obstruction. Case was discussed with electrophysiology who determined the arrhythmias were likely caused by the extensive betel quid consumption. She was placed on beta-blockers and betel quid cessation was strongly recommended. Betel quid is a chewing product made from of areca nut, betel leaf, slaked lime, with or without tobacco. It is commonly used in the tropical Pacific, Asia, and parts of East Africa, and is the fourth most widely consumed addictive substances in the world due to its ability to increase alertness and produce mild euphoria. Adverse effects of betel quid include tachycardia, hyperlipidemia, metabolic syndrome, hepatotoxicity, and it is a known carcinogen. The active compound is arecoline, which acts as a parasympathomimetic on muscarinic and cholinergic receptors, increasing the central sympathetic response and producing tachycardia. Betel quid has been shown to produce ventricular arrhythmias in patients with underlying cardiomyopathy, which is likely what occurred in our patient. Betel quid cessation therefore advised in these patients.
Abstract 17714: Randomized Clinical Trial Comparing Bare Metal Stents Plus Oral Colchicine versus Drug-Eluting Stents for the Prevention of Hard Clinical Outcomes. Two Years Follow-Up Results
Authors: Alfredo M Rodriguez-Granillo, Camila Correa Sadouet, Juan Mieres, MARIA VALERIA CUROTTO, JOSE MILEI, Sandra P Swieszkowski, Pablo Stutzbach, Carlos Fernandez-Pereira, Hernan Pavlovsky, Diego Ascarrunz, Adnan Kastrati, Alfredo Rodriguez
Journal: Circulation (2023)

Introduction: Percutaneous coronary intervention (PCI) for ischemic heart disease is common and stent selection. Bare metal stents (BMS) or drug-eluting stents (DES) impact outcomes. Colchicine has been shown to reduce cardiac events. The long-term efficacy of BMS plus colchicine (BMS+C) vs DES in terms of major adverse cardiovascular events (MACE) is unknown. We presented preliminary results at AHA 2022, we are reporting extended follow-up. Hypothesis: PCI with BMS+C have similar MACE compared to DES-treated patients (pts). Methods: Multicenter, randomized clinical trial (RCT) enrolled PCI pts from February 2020 to April 2022, randomly assigned to BMS+C or DES and followed at 1, 6, 12 months, and then annually until 5 years. BMS+C received 0.5 mg oral colchicine BID for 3 months. Primary endpoint (EP) compared cost and incidence of MACE, a composite of death, myocardial infarction, stroke, or ischemic-driven target vessel revascularization. Due to the cost difference between devices a non-inferiority 15% threshold level was estimated. Secondary EP included individual components of primary EP and overall costs. Drug tolerance was analyzed. Baseline and 1-month C-Reactive Protein (CRP) levels were assessed and a delta difference was compared. An IRB and local authorities approved the protocol (NCT04382443). Results: We included 205 pts in each arm. Baseline characteristics were similar, Acute Coronary Syndromes was 78% vs 74.6% (p=0.24). Syntax Score was 22.2+/-11.4 vs 21.1+/- 9.4, respectively (p=0.49). Follow-up was 25 +/- 5 months. Primary and secondary EP are presented in the table. 5% of BMS+C pts withdraw from the drug due to side effects. Delta CRP between groups showed 5.4 +/- 6.4 vs 1.6 +/- 1.7, BMS vs DES, p&lt;0.001. Conclusions: In this RCT of pts with ACS and low Syntax score, a strategy with BMS+C was non-inferior to DES in terms of long-term clinical outcomes. Colchicine diminished inflammation markers. Cumulative costs were lower in the BMS+C group. cost.
Abstract 16169: Use of Ramen in Heart Failure: Correction of Severe Hyponatremia With Salt Intake
Authors: Gabriela Narowska, Brianna Graham, Hugh Davis, Estefania Oliveros, Jean Lee
Journal: Circulation (2023)

Background Hyponatremia (Na&lt;136mmol) is the most common electrolyte imbalance in patients with heart failure (HF) and is associated with increased mortality, morbidity and rehospitalizations. The mechanisms of hyponatremia in heart failure are multifold and include an increased sympathetic tone and renin-angiotensin-aldosterone-system, salt and water retention in the proximal and distal tubules, high antidiuretic hormone coupled low glomerular filtration rate and diuretic use. We present a case highlighting the complexity of sodium balance in acute decompensated heart failure. Case Presentation A 65-year-old female with a medical history of heart failure with preserved ejection fraction (EF 60-65%), pulmonary hypertension, atrial fibrillation, and CKD presented to the Emergency Department with volume overload. We began diuresis with bumetanide on hospital day 1 (HD#), however given inadequate urine output chlorthalidone was added on HD #5 and metolazone on HD #7. On admission, her sodium was 134 and down trended to a low of 121 on HD#13. She had worsening BUN/Cr from 62/2.14 at admission to a peak 135/2.66. She developed oral intake intolerance, asterixis and encephalopathy. The management changed to halting diuretics, fluid restriction, and hypertonic saline without improvement. Urine electrolytes were used to tailor treatment, leading to cessation of hypertonic saline stopped and introducing Ramen (875 mg of Na) and salt tablets (394 mg of Na). While maintaining euvolemia, there was resolution of symptoms and improvement in Na=134, BUN 49, Cr 1.16. Discussion Treatment options for hyponatremia in HF, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. The use of high oral salt intake with close monitoring of jugular vein pressure, weight, symptoms, and urine electrolytes can help a select group of patients with hyponatremia and advance heart failure despite traditional knowledge.
Abstract 17551: Mapping the Interactome of FLNC in Restrictive Cardiomyopathy
Authors: Bryan Wang, Xiaokan Zhang, Lori Luo, Margaretha Morsink, Jenny Rao, Gordana Vunjak-Novakovic, Barry Fine
Journal: Circulation (2023)

Introduction: Filamin C (FLNC) is an actin crosslinking protein that organizes structural components of the sarcomere and signal transduction complexes. Human mutations in FLNC have been linked to dilated, hypertrophic and restrictive cardiomyopathies. The mechanism connecting mutations in FLNC to sarcomeric impairment remains undefined. We recently reported the ability to model FLNC cardiomyopathy using induced pluripotent stem cell (iPSC) derived engineered heart tissue. Here, we employ a knock-in approach to epitope tag endogenous alleles in iPSC derived cardiomyocytes to explore FLNC genotype-interactome relationships using affinity purification mass spectrometry. Methods: An iPSC line was generated from a patient with restrictive cardiomyopathy caused by an insertion deletion mutation in the ROD2 domain FLNC (c.7416_7418delGAA, p.Glu2472_Asn2473delinAsp). CRISPR-Cas9 was used to establish a corrected cell line as a wild type control. 3X-Flag motif was introduced to the N terminus of FLNC using CRISPR-Cas9. iPSCs were then differentiated into cardiomyocytes using standard techniques. Affinity purification mass spectrometry (AP-MS) was performed using the Flag epitope. Interaction data was analyzed using Perseus software. Gene ontology (GO) enrichment analysis was performed using ToppFun. Results: 3X-Flag insertion was confirmed using genomic sequencing. AP-MS identified 281 high confidence interactors of mutant FLNC and 208 interactors of wild type FLNC (FDR 0.01, log2FC &gt;1.5) when compared to IgG controls. Interestingly, 161 proteins were shared between the two genotypes. These were enriched in mitochondrial ribosomal proteins and phosphorylase kinase subunits, potentially revealing an unknown role of FLNC in mitochondria translation and metabolism. Thirty-three proteins were significantly differentially bound to mutant FLNC protein, including tropomyosin 4, caldesmon 1, and filamin A (FDR &lt;0.05, log2FC&gt;1). GO analysis of these proteins revealed enrichment of actin cytoskeleton elements, muscle contraction, and muscle system processes. Conclusions: Human mutations in FLNC lead to disruption of key protein interactions, revealing a potential mechanism for disease pathogenesis in FLNC cardiomyopathy.
Abstract 18007: Role of Interferon Lambda in Influenza-Induced Exacerbation of Atherosclerosis
Authors: Crystal Moras, Baskaran Chinnappan, Nicholas J Constantinesco, Louis De Vito, Sashwath Srikanth, John F Alcorn, Radha Gopal
Journal: Circulation (2023)

Introduction and Hypothesis: Influenza infection is a significant public health and economic threat around the world. Although pneumonia is the most common complication associated with influenza, there are several clinical reports demonstrating increased risk for cardiovascular disease. In influenza infection type I, type II and type III IFNs play an indispensable role in controlling the virus. In atherosclerosis, type I and type II IFNs promote atherosclerosis by inducing chemokines from macrophages and vascular endothelial cells. Studies have shown that the influenza infection exacerbates atherosclerosis. However, there are no studies determining the role of type III IFNs on influenza-induced exacerbation of atherosclerosis. In this study, we hypothesize that the type III IFN (IFNL3) may play a protective role in atherosclerosis. Methods: ApoE -/- mice were fed with a high-fat diet (HFD) containing 42% Kcal fat (Teklad) for 11 weeks. Mice were then infected with influenza A/PR/8/34 (H1N1) (100 pfu) and treated with recombinant IFNL3 by oropharyngeal (O/P) aspiration or intraperitoneal (I/P) injection, and weight loss, and gene expression of inflammatory cytokines and chemokines were measured. In another study, HFD-fed ApoE -/- and ApoE -/- IFNLR1 -/- mice were infected with influenza, and the disease outcomes were measured as described above. Results and Conclusions: IFNL3 treatment decreased influenza-induced weight loss in ApoE -/- mice during the early phase (4-6 days) of influenza infection. Further, IFNL3 treatment decreased gene expression levels of IL-6 and CCL2 in the aorta in influenza-infected ApoE -/- mice. Based on these findings, it seems likely that INFL3 plays a protective role in acute influenza-induced exacerbation of atherosclerosis. However, ApoE -/- IFNLR1 -/- mice recovered body weight faster than wild-type mice suggesting a detrimental role for IFNL after acute infection. These data show that IFNLR plays a protective role during the early phase of influenza infection and potentially a pathological role during the recovery phase of influenza infection.
Abstract 15913: Takotsubo Cardiomyopathy, is It Preventable?
Authors: Mohammed Abdelsalam, Falah Abu Hassan
Journal: Circulation (2023)

Introduction: Takotsubo cardiomyopathy (TCM) is a reversible type of heart failure that occurs mostly in postmenopausal women. There are no definitive preventive measures in literature for this condition. Case: A 75-year-old female with a past medical history of hypertension presented with a new intermittent pressure-like chest pain and dyspnea right after a 1000-miles road trip. she reported that she had been feeling sad after her best friend died. Physical exam showed bilateral lower lung lobes crepitation and hypoxia. Lab work up revealed troponin of 1522 ng/L trending up to 2400 ng/L on serial measurements and elevated BNP. EKG showed ST changes and inverted T wave. Chest x-ray showed pulmonary vascular congestion and small bilateral pleural effusion. TTE showed LVEF 25-30% and mid and apical LV hypokinesis. Chest CT angiography was normal. Left heart catheter showed nonoccluded coronary arteries. LV angiogram portrayed mid and apical hypokinesis. Serology and PCR of EBV, Coxsackie B virus, CMV, HSV, influenza A and B, adenovirus and parvo virus were negative. She was started on a diuretic, a Beta blocker and an ACE inhibitor. Her symptoms improved. A follow up echocardiogram after 1 month showed improved ejection fraction and resolution of LV mid and apical hypokinesis. Recent combined emotional and physical stress of driving a long distance were thought to be the cause of stress cardiomyopathy. Discussion: Approximately 1-2% of patients presenting with symptoms of MI meet the criteria for TCM. A recent systematic review by Nyman et al on triggers of TCM found that physical factors are more common than emotional factors. However, some cases had both emotional and physical stressors. This patient had combined psychological and physical stressors, which may have precipitated TCM. postmenopausal women with recent emotional stressors should be advised to avoid physical stress until emotional issues have been resolved.
Abstract 13572: Electrocardiographic Aging Derived From Artificial Intelligence is Associated With the Risk of Early- and New-Onset Atrial Fibrillation: A Multi-National Cohort Study
Authors: Seunghoon Cho, Sujeong Eom, Seng Chan You, Hee Tae Yu, BOYOUNG JOUNG
Journal: Circulation (2023)

Background: The application of artificial intelligence (AI) algorithms to ECG provides promising age prediction methods. We investigated whether the age discrepancy between AI-predicted age from ECG (AI-ECG age) and chronological age, known as the AI-ECG age gap or electrocardiographic aging (ECG-aging), could predict atrial fibrillation (AF) risk. Methods: We developed an AI-ECG age prediction model using a single-center dataset (1,533,042 ECGs from 689,639 participants) and validated it using five independent, multi-national datasets (637,177 ECGs from 230,838 participants). The AI-ECG age gap was calculated in two cohorts from South Korea and the UK. Based on this age gap, participants were classified into two study groups: Normal ECG-aging (Normal EA, age gap &lt;7 years) and Early ECG-aging (Early EA, age gap ≥7 years). We assessed the predictive capability of ECG-aging for early- and new-onset AF risk. Results: In two cohorts followed up for 5.9±3.7 and 3.0±1.6 years with 37,208 and 40,989 participants, respectively, the mean AI-ECG age with mean age gap was 47.4±12.4 (-0.1±6.0) and 68.4±7.8 (4.7±8.7) years, respectively. The early EA group was associated with increased risk of new-onset AF with HR of 1.86 (95% confidence interval, 1.46-2.38) and 1.88 (1.54-2.29), and early-onset AF with OR of 2.23 (1.79-2.77) and 1.52 (1.34-1.73), compared to the normal EA group in each cohort, respectively. Furthermore, there was an increased risk of both early- and new-onset AF with an increasing AI-ECG age gap. Conclusions: ECG-aging derived from the AI model was associated with the risk of early- and new-onset AF, indicating its potential as a risk predictor for AF in primary prevention.