tbuckley/cabot-search huggingface dataset:
Abstract 16199: Postsurgical Takotsubos Complicated by Clot Burden in the Setting of Heterozygous Prothrombin Gene Mutation
Authors: Rohan Umrani, Mansoor Choudhry
Journal: Circulation (2023)

Introduction: Postsurgical Takotsubo cardiomyopathy (TCM) is associated with acute stress secondary to catecholamine release causing reversible left ventricular (LV) failure. We present a diagnostically challenging presentation of postsurgical TCM with underlying prothrombin gene mutation. Case Presentation: A 53 year old female underwent laparoscopic hysterectomy 2 days prior to presentation with chest pain and shortness of breath. Vitals were unremarkable, labs showed elevated troponin and EKG consistent with NSTEMI. CTA chest demonstrated significant clot burden to the ascending and descending aorta. Echocardiogram revealed a reduced ejection fraction (EF) of 25-30% with apical ballooning and thrombus. She was admitted on heparin drip and completed an infusion of eptifibatide for 24 hours. Repeat CTA chest demonstrated mildly reduced clot burden. Left heart catheterization (LHC) was precluded due to aortic arch clot. Coronary CTA revealed no CAD with a calcium score of 0. Coagulopathy workup showed heterozygous prothrombin G20210A variant. She was discharged on warfarin. Repeat echocardiography 1 month later showed improved EF to 40-45%. Discussion: TCM accounts for 1-3% of cases of acute coronary syndromes (ACS) and affects women at a rate of 90%. Studies have shown that TCM with apical ballooning is minimally associated with LV thrombus . The presence of heterozygous prothrombin gene mutation increases risk of clot formation by 2 to 3 times. Surgery can cause this risk to dramatically increase. Coronary CTA was the best noninvasive approach to make the diagnosis as the risk of LHC was too great given the anatomic challenge of the aortic arch clot. We advocate for hypercoagulable workups to inform management of anticoagulation in patients with clotting events without known risk factors for thrombus formation.
Abstract 14975: SIRT1 Ameliorates Cardiac Dysfunction Caused by Lamin A/C Deficiency via Mitochondrial Bioenergetics Improvement
Authors: Zunhui Du, Yanting Zhou, Yuan Xie, Tong Yin, Yucai Xie
Journal: Circulation (2023)

Background: The LMNA gene encodes lamin A/C and is the second most frequently mutated gene associated with dilated cardiomyopathy (DCM) but lacks effective therapeutic options. Recent transcriptomic studies have shown that mutation of LMNA leads to abnormal expression of genes related to mitochondrial function, however, the mechanisms have not been investigated further. Hypothesis: LMNA protects against cardiac dysfunction via mitochondrial bioenergetics maintenance. Aims To decipher the mechanism by which LMNA mediates mitochondrial bioenergetics and DCM phenotype. Methods: Proteomics was performed to decipher the pathogenesis of DCM in Lmna -/- mice. Neonatal rat ventricular myocytes (NRVMs) were used to dissect molecular mechanisms. Adenovirus and adeno-associated virus (AAV) were constructed to overexpress SIRT1 in vitro and in vivo , respectively. Results: Lmna -/- mice at 1 month of age showed obvious cardiac dysfunction, while 2-week-old Lmna -/- mice showed no obvious cardiac phenotype. Proteomics revealed downregulated mitochondrial function-related pathways in Lmna -/- hearts. Early injured mitochondria with decreased cristae density were detected and the only reduced mitochondrial biogenesis regulator SIRT1 was found in 2 week-old Lmna -/- hearts. Overexpression of SIRT1 in lamin A/C knockdown NRVMs effectively improved mitochondrial oxidative respiration capacity. AAV-SIRT1 injection significantly alleviated mitochondrial injury, DCM phenotype of Lmna -/- mice, and prolonged lifespan (Figure 1). Mechanistically, LMNA maintains mitochondrial bioenergetics through SIRT1-PARKIN axis. Conclusions: Lamin A/C deficiency leads to mitochondrial damage in cardiomyocytes and promotes the development of DCM through SIRT1 downregulation. Targeting SIRT1 ameliorates mitochondrial injury and DCM phenotype in Lmna -/- mice, which may provide a novel therapeutic strategy for LMNA mutation-associated DCM.
Abstract 12025: Utility of Intracardiac Echocardiography for Prosthetic Valve Infective Endocarditis and Cardiovascular Device-Related Infection: A Contemporary Systematic Review
Authors: Alejandro Sanchez-Nadales, Juan Cedeño, Alice Sonnino, Abdullah Sarkar, Craig R Asher, Bo Xu
Journal: Circulation (2023)

Introduction: Infective endocarditis (IE), particularly prosthetic valve endocarditis (PVE) and cardiac device-related endocarditis (CDIE), presents significant diagnostic challenges. The efficacy of intra-cardiac echocardiography (ICE) for diagnosing IE and assessing intra-cardiac infections when transesophageal echocardiography (TEE) is contraindicated, is not extensively studied. Methods: We searched six databases, including PubMed, Embase, Scopus, Ovid, Science Direct, and Web of Science, for articles published between September 2002 and November 2022, related to the utility of ICE in IE. Eligibility screening followed the search. Results: From the 12 identified studies discussing ICE for IE diagnosis, ten cases of IE were highlighted in nine reports, and three cohort studies included 236 patients without individual patient details. ICE was not used in any native valve IE case. Predominantly male patients (90%) had a median age of 42 years, developing endocarditis 2.5 years post initial cardiac procedure. The most common microorganisms identified were Staphylococcus species. ICE proved beneficial in various scenarios, particularly PVE and CDIE, especially when echocardiography studies were inconclusive or contraindicated. As an alternative to TEE, ICE offers clear visualization of right heart structure, guiding interventions such as pacemaker lead extractions. It excels in detecting device lead abnormalities and small vegetations in CDIE cases, supporting risk stratification and preparation for infected device extraction. Notably, all PVE cases involved bioprosthetic valves, affecting various heart structures and valves. Conclusion: This systematic review highlights ICE as an adjunct imaging modality in IE, especially in PVE and CDIE when TEE is contraindicated. Preliminary data suggest its valuable role during intracardiac lead extractions.
Abstract 13031: Real World Outcomes of Prognostic Value of Platelet Function Testing for Five-Year Ischemic Events in Patients Undergoing Percutaneous Coronary Intervention: A Large-Scale Cohort Study
Authors: Yulong Li, Jiawen Li, Kailun Yan, Yuejin Yang, Jinqing Yuan, Xueyan Zhao
Journal: Circulation (2023)

Introduction: Individualized antithrombotic therapy guided by platelet function testing is a hot topic in current study. However, the prognostic value of platelet function testing for long-term ischemic events in percutaneous coronary intervention (PCI) population is still unknown. Objective: To investigate whether platelet function testing (reflected by adenosine diphosphate-induced platelet maximum amplitude [MA ADP ] based on thromboelastogram) is associated with five-year ischemic events in patients undergoing PCI. Methods: 10,724 consecutive patients undergoing PCI in 2013 were enrolled. The traditional cut-off point of MA ADP (47) and the optimal cut-off point of MA ADP (41.8) according to receiver operating curve were selected. The primary endpoint was cardiovascular death. The secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction, ischemic revascularization, and stroke. Results: A total of 6,290 patients (mean age, 58.27 ± 10.30; male, 77.5%) who had both MA ADP results and completed follow-up were finally included. After five-year follow-up, 143 (2.3%) cardiovascular death and 1,410 (22.4%) MACCE occurred. According to the traditional cut-off point, multivariate COX regression analysis (Figure 1) showed no prognostic value of MA ADP for both cardiovascular death and MACCE (all P &gt;0.05). As for the optimal cut-off point, multivariate COX regression analysis (Figure 2) showed that MA ADP ≥ 41.8 was independently associated with cardiovascular death (HR=1.484, 95% CI: 1.043-2.111, P =0.028) and MACCE (HR=1.138, 95% CI: 1.018-1.272, P =0.023). Conclusions: Our study is the first to report that platelet function testing can help identify individuals at high risk of long-term ischemic events. We proposed a new cut-off point of MA ADP to assess the prognosis of ischemic events, and demonstrated that MA ADP ≥ 41.8 was associated with five-year cardiovascular death and MACCE.
Abstract 15161: Prediction of Decompensated Heart Failure Using an Implanted Cardiac Device Risk Analysis
Authors: Archana Ganapathy, Brian Li, Samantha Langley, Rebecca Clark, Anthony Dimarco, Rossella Barbagallo, Jason Dungu, Henry Oluwasefunmi Savage
Journal: Circulation (2023)

Introduction: TriageHF is a Heart Failure Risk Status (HFRS) diagnostic tool available on Medtronic implantable cardiac devices which reports dynamic statuses of risk of Heart Failure related Hospitalization (HFH) within the next 30 day, as high, medium or low. We investigated the accuracy of TriageHF in predicting 30-day HFH for patients attending a tertiary heart failure clinic. Methods: We retrospectively recorded HFRS between November 2021 and May 2023, from patients implanted with Medtronic Cardiac Resynchronization Therapy (CRT) or Internal Cardioverter Defibrillator (ICD) devices. We then correlated HFRS with HHF within 30 days of these alerts. Two thresholds were tested: T1 where High &amp; Medium HFRS were considered a positive alert and Low HFRS a negative alert and T2 where High HFRS was considered a positive alert and Medium &amp; Low HFRS a negative alert. The sensitivity and specificity of each threshold in predicting 30-day HFH was tested in a contingency table. Results: Over 18-months, we recorded 135 consecutive alerts from 32 patients. Median age was 72 years, 25% were female and 56% had an ischaemic substrate. 36, 88 and 11 alerts were high, medium, and low risk respectively. 0% of low HFRS and 19% of the high HFRS resulted in a 30-day HHF. 10 high HFRS alerts led to clinical interventions which was associated with a higher rate of HHF, compared to 26 high HFRS alerts where no contact was made (HHF 40% vs 11% p=0.05). The sensitivity and specificity of TriageHF in predicting 30-day HFH was 46.7% and 76.03% respectively for T1 and 100% and 9.1% respectively for T2. Conclusions: This real-world analysis suggests that TriageHF risk prediction using T2 correctly predicted HHF at 30 days with the caveat of a high false positive rate. The potential exists for viable clinical use, however research into the amalgamation of clinical data may improve it and consequently lead to better utilisation of limited clinical resources.
Abstract 16586: Differences in Medical Care Across the Left Ventricular Ejection Fraction Spectrum Following New Heart Failure Diagnosis in a US Healthcare System
Authors: Gregory A Nichols, Bettina J Kraus, Qing Qiao
Journal: Circulation (2023)

Introduction: Heart failure (HF) is a major public health concern with increasing prevalence and burden on healthcare systems. HF is aggravated by type 2 diabetes (T2D) and chronic kidney disease (CKD). Research Question: Understanding how HF is treated after new diagnosis could improve care. Aim: Describe treatment of patients with newly diagnosed HF. Methods: Observational, longitudinal study using electronic medical record data from 24,340 adults (≥18 years) in the US between 2005-2019 with new diagnosis of HF, defined as no HF identified at least 12 months prior to index diagnosis. Outcomes were stratified by HF type (reduced ejection fraction [HFrEF; LVEF ≤40%], preserved ejection fraction [HFpEF; LVEF ≥50%]) and presence of CKD and T2D. Results: For the 24,340 incident HF cases, mean age was 72.1±13.4 years. 51.1% had HFpEF and 10.0% HFrEF; 38.6% also had CKD, 39.7% had T2D and 40.3% had neither. Most patients were diagnosed in hospital (41.7%), Emergency Department (23.3%) or Primary Care (16.9%). First visit after HF diagnosis was most commonly with Primary Care (34.0%) or other specialties (39.6%), with only 10.7% with a cardiologist, regardless of comorbid CKD or T2D. Within the first year, those with HFpEF vs HFrEF were less likely to be seen by a cardiologist (51.7% vs 79.6%). Hospitalization rates within the first year were higher in patients with HF and both comorbidities (49.6%). All-cause mortality was slightly higher in HFpEF (15.3%) compared to HFrEF (13.9%), particularly in those with HFpEF and CKD (19.2%). At time of diagnosis, patients were likely to use any HF medication. Patients with HFpEF were more likely than those with HFrEF to be treated with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB; 46.1% vs 40.7%), β-blockers (BB; 53.2% vs 41.3%) and diuretics (41.0% vs 26.5%). Within 90 days of diagnosis, fewer patients with HFpEF vs HFrEF initiated ACEi/ARB (42.8% vs 70.4%), BB (35.4% vs 56.2%) and diuretics (47.8% vs 65.2%). Conclusion: Primary care plays a major role in early HF care. Comorbid CKD and T2D increased hospitalization and mortality rates but not cardiology care. However, patients with HFpEF were less likely to be seen by a cardiologist or initiate medication following diagnosis vs those with HFrEF.
Abstract 16533: Non-Invasive Insulin Resistance Evaluation Using Carotid Pressure Waveforms in Framingham Heart Study
Authors: Jing Liu, Soha Niroumandi, Danny Petrasek, Niema M Pahlevan
Journal: Circulation (2023)

Introduction: Insulin resistance (IR) and the resultant hyperinsulinemia not only lead to the onset of diabetes but also are shown to elevate the risk of heart failure and underlie a spectrum of cardio-metabolic pathologies in both diabetic and non-diabetes patients. Measuring IR is challenging owing to reliance on an invasive and time-consuming procedure called a glucose clamp study, which is known as the gold standard method of assessing IR. However, this method is not routinely available in most clinical settings. The Homeostasis Model Assessment of IR (HOMA-IR) is a validated tool for evaluating IR calculated based on fasting glucose and insulin concentrations obtained from fasting blood samples. Determining optimal cut-off values for HOMA-IR has been challenging since its distribution varies across different demographic characteristics and populations. Aim: This study aims to facilitate the screening of HOMA-IR by introducing a new method that utilizes a non-invasive carotid pressure waveform to assess HOMA-IR. Methods: We extracted Intrinsic Frequency Analysis-derived features from carotid pressure waveform to detect HOMA-IR using machine learning. A non-diabetic cohort from Framingham Heart Study (FHS) (n=5427, 53% female, age range 19-90) was used to develop and test the proposed method. The method was developed on 80% of the data and blindly tested on 20% . Results: Using thresholds of 0.5 and 3 for the low (carefree) and high (alarming) zones of HOMA-IR in FHS dataset, respectively, the performance of detecting high HOMA achieved an area under curve (AUC) of 0.82 on the blind test set data (n=1085) (Fig.1; ROC: receiver operating characteristic curve). Conclusion: The non-invasive nature of the proposed method facilitates the screening of metabolic disease risks based on HOMA-IR level inferences from noninvasive carotid pressure waveforms, which can be implemented in routine clinical practice using inexpensive standard hand-held tonometry devices.
Abstract 18614: Growth Hormone Releasing Hormone Agonists Reverse the Cardiometabolic Heart Failure With Preserved Ejection Fraction Phenotype via the Hypoxia-Inducible Factor 1 Alpha
Authors: Rosemeire M Kanashiro-Takeuchi, Lauro M Takeuchi, Wayne Balkan, Raul A Dulce, Katarzyna Kazmierczak, Shathiyah Kulandavelu, Renzhi Cai, wei sha, Andrew Schally, Joshua M Hare
Journal: Circulation (2023)

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) treatment is limited due in large part to lack of understanding of the underlying mechanisms involved. Recently, we showed that growth hormone-releasing hormone-agonist (GHRH-agonist) has cardioprotective effects in a cardiometabolic HFpEF model; however, the mechanism of these therapeutic effects is still unclear. Here, we hypothesize that the anti-HFpEF properties of GHRH-receptor activation are mediated by hypoxia-induced factor (HIF)-1α pathway. Methods: Wild-type (WT) and HIF-1α cardiomyocyte knockout (HIF-1α CM KO) mice received a high-fat diet (HFD) plus the nitric oxide synthase inhibitor (L-NAME) for 9 weeks. After 5 weeks of HFD+L-NAME regimen, animals receive daily injections of GHRH-agonist, MR-356, or placebo during a 4-week period. Control animals received no HFD+L-NAME or MR-356 treatment. Echocardiography, blood pressure, glucose tolerance test, and hemodynamic measurements were evaluated. Results: The HFD+L-NAME diet produced a HFpEF phenotype, which was reversed in mice with intact HIF-1α treated with MR-356 (Figure 1 A-E). In contrast, following cardiac-specific deletion of HIF-1α CM , MR-356 no longer reversed (A) the elevated isovolumetric relaxation time (IVRT), (B) increased E/E’ ratio and (C) reduced global longitudinal strain (GLS). EF was preserved (D) while the slope of the end-diastolic pressure-volume relationship (EDPVR, E) was increased in the placebo group and restored by MR-356 in WT mice but not HIF-1α CM KO mice. Figure 1F shows representative pressure-volume loops from WT placebo, HIF-1α CM treated with placebo or MR-356. Conclusions: Our findings show that cardiac-specific HIF-1α deletion blocks cardioprotective effects of MR-356 suggesting that HIF-1α is necessary for its anti-HFpEF effects.
Abstract 14302: Heart Logic Directed Uptitration of Guideline Directed Medical Therapy Improves EF Across All Device Categories
Authors: Robert A Pickett, Elizabeth Shannon, Daniel W Kaiser, Jonathan Gandhi, Ricardo M Lugo
Journal: Circulation (2023)

Introduction: Historically data for CHF management in ICD patients had been for adjustments in diuretics. GDMT changes are often limited due to BP, renal function, or concerns for hypotension. Hypothesis: Using the Heart Logic score on Boston Scientific ICDs we could up-titrate GDMT in a safe reliable fashion which would allow for further improvement in LVEF and avoid complications. Methods: 30 patients with either a new implant or generator change (single, dual, or resynchronization) with a compatible ICD were enrolled. The alert threshold was lowered from the standard of 16 to 10. The goal was to identify patients before congestion occurred. All patients were followed with remote monitoring. When an alert occurred, a single class of GDMT was increased. If alert did not go back to zero on repeat transmission, then a second class of medicine was up-titrated, changed, or added. The patients were followed for one year with yearly echo. Results: 30 patients were enrolled. 2 died during the year follow-up from end stage CHF after being turned down for transplant or MCS. 1 patient did not have a one year follow-up echo. A total of 47 medicine changes or up-titrations were made. The average EF improved from baseline 27.5% to 37.2%. There were no syncopal events, worsening renal function, or hyperkalemia reported. The only subjective complaints were transient dizziness. Conclusions: Heart Logic based medication management allows a safe mechanism for increase or change in GDMT in the CHF population. Up-titration is necessary for better outcomes in CHF care but is also often limited to subjective concerns regarding potential complications.
Abstract 13041: Effects of Parity on Arterial Stiffness Persists Into Old Age, Independent of Chronological Ageing
Authors: Keerthana Thangaraja, Gayathri Basker, Fei Gao, Ru S Tan, Gina S Lee, Charmaine Cheng, Loon Yee Teo, See H Ewe, Ling-Jun Li, Angela S Koh
Journal: Circulation (2023)

Introduction: Persistent effects of reproductive factors on vascular ageing, over chronological ageing, as examined through objective measurements of arterial stiffness, are rarely studied. Hypothesis: We hypothesized that the effects of parity and maternal age at first birth (AFB) on vascular ageing will persist over time independent of chronological ageing, in older Asian women. Methods: Among a community-based cohort of older Asian adults without cardiovascular disease, we prospectively studied demographics, parity, AFB, and cardiovascular risk factors, at baseline and 5-year examination timepoints. Arterial stiffness was measured through pulse wave velocity (PWV) using a cuff-based auscultatoric oscillometric pulse wave analysis machine. Results: 170 women (baseline mean age 60.76±13.75 years) were included. Parity ranged from 0 to 8 (mean parity 2±1.3). AFB ranged from 18 to 44 (mean age 28±4.4) years. By regression, univariate determinants of 5-year PWV were parity (β=0.491, p=&lt;.001), αFB (β=-0.107, p=.011), baseline age (β=3.884, p=&lt;.001), body mass index (βμΙ) (β=0.147, p=.006), waist circumference (β=0.076, p=&lt;.001), diabetes (β=1.681, p=&lt;.004), hypertension (β=2.383, p=&lt;.001), dyslipidemia (β=2.220, p=&lt;.001), 5-year age (β=3.886, p=&lt;.001),waist circumference (β=0.085, p=&lt;.001), diabetes (β=1.723, p=.001), hypertension (β=2.485, p=&lt;.001). Based on multivariate regression, parity (β=0.345, 95% CI 0.105, 0.586, p=.005), but not AFB, was independently associated with 5-year PWV, independent of age. Conclusions: Parity and AFB correlated with PWV, a marker of arterial stiffness, in old age in Asian women. Accounting for chronological ageing and clinical factors across 5 years, parity exerted a persistent independent effect on arterial stiffness in older women. Other biological factors surrounding parity in these women apart from traditional cardiovascular risk factors may explain these observations.
Abstract 13628: Methicillin-Resistant Staphylococcus Aureus Associated Pericardial Empyema: A Lethal Threat to the Heart
Authors: Mohammad Hazique, Sara Ahmed
Journal: Circulation (2023)

Introduction: A highly uncommon but potentially life-threatening condition called Pericardial empyema is a rare but rapidly fatal condition, and in more than half the cases, the diagnosis is postmortem. The most common causal microorganism is Staphylococcus aureus. Case Presentation: A 73-year-old male with a past medical history of type 2 diabetes mellitus and hypothyroidism presented with chills, fever, and a non-healing skin infection on his arm for the last two weeks. Wound and blood cultures were positive for Methicillin-resistant Staphylococcus aureus (MRSA). He was started on intravenous Vancomycin. On day 3 of admission, he suddenly developed chest pain. On examination, he had muffled heart sounds with jugular venous distension. Electrocardiogram showed sinus tachycardia with diffuse ST elevation. Laboratory investigations were significant for marked leukocytosis of 28,000/ul, Troponin was 0.056 ng/ml. Bedside transthoracic echocardiography (TTE) showed a large pericardial effusion (Figure 1A). An emergent pericardiocentesis was performed, yielding 250 ml of cloudy serosanguinous fluid. A pericardial window with 28 F drain placement was carried out. A right radial arterial line was placed for further hemodynamic monitoring. The next day, there was a clot in the drain, which after removal, yielded 1000 ml of bloody fluid. Immediate bedside TTE showed no significant effusion or rupture of the myocardium (Figure 1B). The patient suddenly became dyspneic and developed pulseless electrical activity. Code blue was initiated. The patient passed away from cardiopulmonary collapse. Later, the pericardial fluid was positive for MRSA. Conclusions: This case illustrates the importance of timely diagnosis and management of pericardial empyema. Due to its high mortality rate, we encourage professionals to be more aware of this phenomenon's presence as well as its ambiguous clinical outcome.