tbuckley/cabot-search huggingface dataset:
Abstract 17032: Association of Blood Pressure Patterns During Pregnancy With Incident Hypertension and Cardiovascular Disease Risk at 2-7 Years After Delivery: The nuMoM2b Heart Health Study
Authors: Natalie A Cameron, Xiaoning Huang, Lucia C Petito, Rebecca B McNeil, Jasmina Varagic, Janet M Catov, C Noel Bairey Merz MD, FACC, FAHA, FESC, Judith Chung, David Haas, Lisa Levine, George Saade, Robert Silver, Uma Reddy, Brian Mercer, Lynn Yee, Philip Greenland, William Grobman, Sadiya S Khan
Journal: Circulation (2023)

Introduction: Hypertensive disorders of pregnancy (HDP) are risk factors for cardiovascular disease (CVD). However, associations between subclinical blood pressure (BP) elevations in pregnancy and CVD risk are unknown. Aims: To identify BP patterns during pregnancy among individuals without HDP and determine their association with long-term CVD risk and hypertension (HTN) 2-7 years after delivery. Methods: We included nulliparous individuals from the prospective, multicenter nuMoM2b Study Heart Health Study (nuMoM2b-HHS) who had &gt; 1 BP from each trimester, and excluded those with chronic HTN or HDP. We modeled patterns using group-based trajectory analysis of the mid-BP (average of systolic and diastolic BP) during pregnancy. We selected the final number of groups based on the Bayesian Information Criteria. At 2-7 years after delivery, 30-year predicted CVD risk was estimated using the Framingham risk score; incident HTN was defined as BP &gt; 130/80. Generalized linear models estimated associations between mid-BP trajectory group and CVD risk, adjusting for sociodemographics, adverse pregnancy outcomes, and first-trimester mid-BP. Results: Of 3309 participants, mean age was 27.1 (SD 5.5) years. Five mid-BP groups were identified ( FIGURE ). Incident HTN at mean follow-up of 3.7 years after delivery was 4.2% in low-stable, 11.1% moderate-stable, 21.4% moderate-decreasing, 21.8% moderate increasing, and 44.2% in elevated-stable groups. Compared with the moderate-stable group, adjusted 30-year predicted CVD risk was significantly higher by 0.8% (0.4, 1.1), 1.6% (0.9, 2.3) and 2.6% (2.1, 3.1) in the moderate-decreasing, moderate-increasing and elevated-stable groups, respectively. Conclusions: Among people not meeting HDP criteria, but with elevated mid-BP during pregnancy, nearly half had HTN within 5 years after delivery, and long-term CVD risk was higher. Mid-BP elevations during pregnancy may inform long-term CVD risk even in the absence of HDP.
Abstract 14737: A Case of an Intracardiac Sarcoma Arising From Metastatic Spread of a Primary Phyllodes Tumor of the Breast
Authors: Donovon Allen, Kara Morton, Mustafa Ahmed, Stephen Clarkson, Jori May, Silvio Litovsky
Journal: Circulation (2023)

Background: Malignant phyllodes tumors with cardiac involvement are rare, presenting diagnostic and management challenges. The benefits of medical and surgical therapies remain unclear. Large-bore aspiration devices are currently only approved for retrieval of venous thromboemboli but may present a valid option for diagnosis and treatment of intracardiac masses in high risk patients. Case Summary: We present the case of a 57-year-old female with a malignant phyllodes tumor of the breast and bilateral pulmonary emboli who presented with an incidental complex intracardiac mass on transthoracic echocardiography (1). A follow-up transesophageal echocardiogram demonstrated masses within the superior vena cava, right atrium, and right ventricle (2a-2b). Aspiration thrombectomy was performed given clinical stability and concern for thrombi with high risk of worsening clot burden. A large-bore aspiration device was used to retrieve the masses in multiple passes (3), which were pathologically consistent with spindle cell sarcoma. A cardiac MRI was completed following aspiration, and multiple mobile masses persisted in the right ventricle (4). The patient was discharged on day nine of hospitalization with therapeutic chemotherapy planned. She had one session of chemotherapy before a fatal cardiac arrest from unknown cause three months after discharge. Discussion: Phyllodes tumors rarely metastasize to the heart, and effective modalities for their diagnosis and management are unclear. Treatment strategies include wide surgical resection of the primary tumor, however mortality remains high in the setting of metastatic spread. Current guidelines recommend following principles of soft tissue sarcomas with chemotherapy. Large-bore aspiration devices may be an effective way to resect intracardiac tumors for both diagnostic and therapeutic purposes as an alternative to invasive surgical intervention for high-risk patients.
Abstract 18593: High Prevalence of Venous Thrombosis in Cardiac Amyloidosis and the Proposed Clinical and Echocardiographic Integrated Risk Stratification Tool
Authors: Cristiane de Carvalho Singulane, Kenneth C Bilchick, Maryam E Neyestanak, Yu Wang, Jeremy A Slivnick, Karima Addetia, Deyu Sun, Roberto M Lang, Frederick H Epstein, Amit R Patel
Journal: Circulation (2023)

Introduction: The prevalence of thromboembolism (VTE) in cardiac amyloidosis (CA) is not well defined. Additionally, there is no risk stratification tool to identify CA subjects at risk for VTE to guide prophylactic treatment. We sought to identify the prevalence of VTE in CA and to develop a model to predict VTE in this population. Methods: A total of 150 subjects from two academic centers with confirmed CA (69±11years, 56% male, 58% AL-CA), and no history of VTE, atrial arrhythmia or anticoagulation use were included. The primary endpoint was DVT, pulmonary embolism or right atrial thrombi (RA). The LASSO technique was used to evaluate nearly 50 potential clinical and echocardiographic covariates in order to develop a multivariable model for predicting VTE. The subjects were randomly divided in a proportion of 70:30 into training and testing dataset. The diagnostic performance of the model was assessed by calculating the AUC of a ROC curve. Results: Thirty-two subjects (21%) developed VTE after CA diagnosis (18 DVT, 3 RA thrombus, 11 in multiple concurrent locations). The majority occurred within one year of the echocardiogram (78%). Multivariable analysis revealed four variables independently predictive of VTE (p&lt;0.05), based on the regularization parameter (lambda=0.08). VTE was more likely in the presence of liver disease or alcohol abuse, end-stage renal disease, increased LA volume and lower TAPSE. The model had excellent discrimination (AUC=0.823) (Panels A-B) and when applied to the test set an accuracy of 84.4%. The nomogram that can be used to predict the probability of VTE in CA using the covariates identified is illustrated on Panel C. Conclusions: High prevalence of VTE was identified in CA. The developed clinical and echocardiographic risk scheme is user-friendly and has the potential to identify patients with CA at high risk for VTE. It remains to be determined if pre-emptive anticoagulation in this higher risk group might be beneficial.
Abstract 17356: Recurrent Hemorrhagic Pericardial Effusion Requiring a Multimodality Imaging Approach: A Case Report
Authors: Aravind Kalluri, Marius I Chukwurah, Tom Cappola, Andrew Litwack
Journal: Circulation (2023)

Background: A 24-year-old female with no medical history presented to the ED with chest pain and dyspnea. Vitals were notable for tachycardia to 120s. Physical examination was unremarkable. Clinical Course: Initial evaluation was notable for thrombocytopenia, NT-proBNP of 151 and high sensitivity troponin T of 18. Transthoracic echocardiogram (TTE) revealed a small pericardial effusion with tamponade physiology prompting urgent pericardiocentesis. Bloody pericardial fluid was drained and fluid studies were consistent with hemorrhagic effusion with no evidence of infection or malignancy on cytology. Surveillance TTEs showed rapid reaccumulation of pericardial fluid within 72 hours of the initial intervention. Urgent pericardial window with drain placement was performed and intraoperative transesophageal echocardiogram (TEE) revealed a right atrial (RA) mass not detected on prior TTE. Cardiac MRI confirmed the presence of a large (50 mm x 31 mm) immobile and heterogeneous mass in the superior aspect of the RA suggestive of a malignant etiology with invasion to the adjacent pericardium. Positron Emission Tomography (PET) scan demonstrated hypermetabolic activity concerning for malignancy with no evidence of mediastinal, hilar adenopathy, or distant disease. She underwent mini-sternotomy and biopsy with pathology suggestive of primary cardiac angiosarcoma. Due to the high-risk nature and location of the tumor, she was unable to undergo primary surgical resection. Neoadjuvant chemotherapy was initiated with plan for subsequent surgical reassessment. Conclusion: Workup of recurrent hemorrhagic pericardial effusions require a multimodal imaging approach.
Abstract 18925: Hypertension Predicts Polycystic Kidney Disease 11 Years Ahead of Time in PKD1 and PKD2 Carriers, With a PPV of 71%
Authors: Natalie Telis, Lisa McEwen, Alexandre Bolze, Daniel Judge, Pamala Pawloski, Joseph Grzymski, Kelly Schiabor Barrett, Nicole Washington, Elizabeth Cirulli
Journal: Circulation (2023)

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the leading hereditary form of kidney disease and is characterized by the formation of fluid-filled cysts that decrease kidney function and lead to complications including cardiovascular disease, kidney failure, and other organ failure. Although causal variants in the PKD1 and PKD2 genes have been identified, penetrance, morbidity, and outcome are known to vary widely in carriers. We propose to identify early markers of disease and to characterize disease presentation at the level of biomarkers, metabolites, and comorbidity incidence. Methods: This study is based on exomes and medical information from the UK Biobank (n=470k) and 3 American cohorts (n&gt;70k) sequenced with Helix: the Healthy Nevada Project, In Our DNA SC, and myGenetics. We identified individuals with rare LoF variants in either PKD1 or PKD2. We subsequently analyzed these individuals’ medical records, blood labs, and NMR-based metabolomics data (n~120k) to characterize the detailed clinical and biomarker-level disease presentation. Results: We find that 0.05% of the general population has a relevant variant in PKD1 or PKD2 (1/2000 people). In this population-level sample, the prevalence of kidney disease in carriers with hypertension is 71% (74% for PKD1 and 66% for PKD2) compared to 12% for noncarriers with hypertension. For carriers without hypertension, the prevalence is 14% (2% for PKD1 and 30% for PKD2) vs. 1% for noncarriers without hypertension. Importantly, the hypertension diagnosis precedes the kidney disease diagnosis by a mean of 11 years in these carriers. We additionally identify a subset of carriers who are outliers for a set of metabolites that includes cystatin C, creatinine and urea. Assessed prospectively, these carriers have decreased eGFR and a number of other signs of early stage kidney disease a mean of 5 years prior to their KD diagnosis. Conclusion: Identifying PKD1 and PKD2 carriers with hypertension would allow prediction of kidney disease a mean of 11 years in advance of the disease, with a PPV of 71%. Additionally, aberrant but subclinically significant biomarkers can provide an early warning of morbidity.
Abstract 18517: Meta-Analysis of Radiation Exposure With Transradial versus Transfemoral Access for Diagnostic Coronary Angiography and Percutaneous Coronary Intervention
Authors: Farah Yasmin, Abdul Moeed, Saad Ur Rahman, Yumna Khabir, Omer Hassan, Safi U Khan, Sachin S Goel, alpesh shah
Journal: Circulation (2023)

Background: Transradial (TR) access for cardiac catheterization offers advantages over conventional transfemoral (TF) access by reducing bleeding and vascular complications. However, concerns exist regarding potential increased radiation exposure with TR access. The benefit-risk profile due to increased radiation exposure by this technique remains uncertain. We compared radiation exposure for diagnostic coronary angiograms (DCA) and percutaneous coronary interventions (PCI) between TR and TF access. Methods: We searched PubMed, Google Scholar, and Scopus through May 2023 for randomized control trials and observational studies comparing radiation parameters for TR and TF access sites. We compared fluoroscopy time (FT, min) and kerma-area product. The summary estimate was random-effects weighted mean differences (WMDs) with 95% confidence intervals. Results: A total of 33 studies (n = 89,366) were included in the analysis. TR was associated with increased FT (WMD 0.94 [0.61, 1.27] p&lt;0.01) vs. TF access, which was consistent for both DCA (WMD 0.71 [0.20, 23]) and PCI subgroups (WMD 1.09 [0.61, 1.58]) (p for interaction = 0.29). There were no significant differences for the kerma-area product (WMD -0.20 [-0.59, 0.19], p=0.32) between the two access sites, consistent for both DCA (WMD -0.04 [-0.40, 0.32]) and PCI (WMD -0.32 [-0.59, 0.19]) (p for interaction = 0.51) as shown in Figure 1 . Conclusion: TR was associated with increased FT; however, the two access sites had no significant differences concerning kerma-area products.
Abstract 17378: A Novel Strategy in the Sequencing of HFrEF Therapy: An Upfront and Prompt Approach
Authors: Silvia Prosperi, Paolo Severino, Andrea Damato, Marco Valerio Mariani, Aurora Labbro Francia, Claudia Cestiè, Vincenzo Myftari, Rosanna Germanò, Viviana Maestrini, roberto badagliacca, Francesco Fedele, Carmine Dario Vizza
Journal: Circulation (2023)

Introduction: The latest HF European guidelines recommend the use of four different classes of drugs for HFrEF. Despite advances in treatment, some gaps remain to be filled. In particular, sequencing and timing of HF therapy administration are not clarified and different strategies have been proposed. Hypothesis: An early, upfront novel approach, based on prompt administration of BB, SGLT2i, ACEi/ARNI, and MRAs may prove beneficial in terms of HF rehospitalization and CV death risk reduction. Aims: To compare early sequencing of HFrEF GDMT with the conventional, stepwise strategy. The primary endpoint was a composite of HF rehospitalization and CV death. Secondary endpoints were the single events of the primary endpoint. Methods: This prospective, observational study included consecutive patients with a HFrEF diagnosis from the Cardiology department. They were divided based on treatment strategy. Group 1 (G1) was treated with a novel GDMT sequencing (in-hospital start of BB and SGLT2i, ACE-i/ARNI, and lastly adding MRAs within 30 days from discharge). Group 2 (G2) was treated with the conventional, stepwise GDMT sequencing. Comparison between the two groups has been performed at 6-month follow up. Results: The study included a total of 302 patients. 278 patients underwent follow up: 139 in G1 group and 139 in G2 group. The two groups did not show significant differences at baseline. No significant differences have been observed for the primary composite outcome (p= 0.135) and for CV mortality (p=0.642) between the two groups. HF rehospitalization risk was significantly lower in G1 group compared to G2 group (p&lt;0.001). Conclusions: HFrEF patients treated with a novel GDMT sequencing, promptly initiated and completed within 30 days from discharge, have shown reduced risk of HF rehospitalization compared with the conventional strategy.
Abstract 17209: Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance versus Invasive Coronary Angiography: A Meta-Analysis on Diagnostic Accuracy for Cardiovascular Ischemia
Authors: Ahmed Msherghi, Ahmed BenGhatnsh, Ala Khaled, Ahmed Elfaituri, Hazem Abdelkarem Faraj, Muhammed K Elfaituri
Journal: Circulation (2023)

Introduction: Invasive Coronary Angiography (ICA) has been the gold standard for diagnosing cardiovascular ischemia, however, it carries an inherent risk due to its invasive nature. Late Gadolinium Enhancement (LGE) by Cardiovascular Magnetic Resonance (CMR) is a promising non-invasive alternative. This necessitates determining its diagnostic accuracy to inform clinical decision-making. Hypothesis: This study aims to assess the diagnostic accuracy of LGE by CMR and ICA in detecting cardiovascular ischemia. Methods: We performed a systematic review of studies until January 2023 across multiple databases, including PubMed, Embase, and the Cochrane Library, that compared the diagnostic accuracy of LGE by CMR and ICA for cardiovascular ischemia. Diagnostic performance measures, including sensitivity, specificity, false-positive rate estimates, diagnostic odds ratio, and positive and negative Likelihood Ratios (LR), were pooled using a random-effects model and presented with a 95% Confidence Interval (CI). R software (version 4.0.3) with the mada package was utilized for statistical analyses. Results: Our meta-analysis collected data from 8 studies encompassing 1,020 patients, of which 395 had confirmed ischemic imaging and 625 had confirmed non-ischemic heart imaging. The results revealed that LGE by CMR had high diagnostic accuracy for detecting cardiovascular ischemia. The sensitivity was 90.9% (95% CI: 80.2%-96.1%, I2=50.4%), the specificity was 89.3% (95% CI: 79.2%-94.8%, I2=90.5%), and the false-positive rate was 10.7% (95% CI: 5.2%-20.8%). The diagnostic odds ratio for LGE by CMR was 82.82 (95% CI: 25.2-272.5), and the positive and negative Likelihood Ratios were 8.46 (95% CI: 4.19-17.06) and 0.10 (95% CI: 0.05-0.23), respectively. Conclusions: This study demonstrates the high diagnostic accuracy of LGE by CMR for cardiovascular ischemia, as indicated by its high sensitivity, specificity, and substantial diagnostic odds ratio. These findings suggest that LGE by CMR could be a reliable non-invasive alternative to ICA, potentially improving clinical decision-making and reducing risks associated with invasive imaging. Further studies and policy reviews are needed to optimize the use of this promising diagnostic modality.
Abstract 18583: Preclinical Efficacy and Safety of Intravenously Administered LX2020 Gene Therapy for the Treatment of Arrhythmogenic Cardiomyopathy
Authors: Farah Sheikh, Jing Zhang, Erika Gutierrez Lara, Aryanne Do, Lena Nguyen, William H Bradford, Anju Nair, Nithya Selvan, Sonia Gutierrez, Ken Law, Tim Fenn, Richie Khanna
Journal: Circulation (2023)

Introduction: Arrhythmogenic cardiomyopathy (ACM) is a rare, incurable inherited cardiac disease resulting in mortality through sudden death and heart failure. ACM cases are linked to mutations in desmosomal genes, with the most frequent related to plakophilin-2 (PKP2), resulting in haploinsufficiency. LX2020 is an adeno-associated viral (AAV) based gene therapy intended to restore human PKP2 (hPKP2) protein expression. However, its efficacy in disease settings and safety has not been established. Hypothesis: LX2020 mediated hPKP2 expression is sufficient to scaffold the desmosomal complex to prevent cardiomyocyte loss and circumvent structural damage to improve cardiac electrical and mechanical function as well as promote survival, while being safe and well tolerated. Methods: LX2020 was intravenously administered to PKP2 mutant mice with severe ACM and non-human primates (NHPs) at various doses and was evaluated 12 weeks post-dose for efficacy and safety, respectively. Endpoints in mice involved effect of LX2020 on various cardiac disease-relevant phenotypes and survival, while safety, tolerability, biodistribution and expression was assessed in NHPs. Results: In ACM disease settings, LX2020 showed dose-dependent increase in hPKP2 expression that was sufficient to restore desmosomal proteins and cell-cell junctional complexes inhibiting further cardiac structural damage resulting in improved electrical and mechanical dysfunction, ultimately leading to improved survival. In NHPs, LX2020 showed dose-dependent biodistribution in various organs including the heart, with increases in cardiac hPKP2 mRNA and protein expression that were safe and well tolerated. Notably, LX2020 showed cardiac hPKP2 expression in mice and NHPs, which reached above or close to healthy human PKP2 protein levels, respectively, indicating that LX2020 could lead to therapeutic levels of PKP2 expression. Conclusions: Collectively, these data support the efficacy of LX2020 in restoring cardiac hPKP2 expression and rescuing the progressively advancing severe ACM diseae, while being safe and well tolerated. LX2020 offers a promising gene therapy that provides maximal therapeutic benefit with minimal safety risk for PKP2-ACM populations.
Abstract 17254: Myocardial Functional Recovery Following Durable Ventricular Assist Device in Children
Authors: Bhavikkumar Langanecha, Osami Honjo, Alyssa Power, Mjaye Mazwi, Oshri Zaulan, Aine Lynch, Christoph Haller, Kristen George, Linda Fazari, Andrea Maurich, David Chiasson, Aamir Jeewa
Journal: Circulation (2023)

Introduction: Ventricular Assist Device (VAD) explantation following myocardial functional recovery (MFR) for heart failure (HF) is uncommon and associated with a risk of recurrence of HF. Research Question: What are the patient characteristics and outcomes for VAD explantation in children following MFR? Methods: Retrospective, single centre study of patients who were supported with durable VADs, both intracorporeal continuous flow devices (CFD) and paracorporeal pulsatile flow devices (PFD) between 2004 to 2022. Results: A total of 75 children, of which 43 were female, underwent VAD implantation (PFD = 61 and CFD = 14) at a median (IQR) age of 5.6 (0.8, 13.5) years and with a weight of 16.2 (7.5, 40.7) kg. From this cohort, we identified 8/75 (11%) children who underwent VAD explantation for MFR after a median duration of 56 (22, 115) days. All were supported with durable PFD. Five were listed for transplantation as a part of their HF management strategy following VAD implantation and four patients had dilated cardiomyopathy (DCM). Of those, 7/8 (88%) children with MFR were under 2 years of age and 5/8 (63%) were supported for &gt; 90 days. The pathological findings on the LV core samples were variable in severity and no patient had any evidence of active inflammation (see Table). After explant, 7/8 patients remained in HF remission with no symptoms and stable LV function. One patient had a recurrence of HF following explantation after demonstrating MFR while on VAD support. This patient was 5 years old at implant and was in HF remission for ~9 months following explant before HF recurrence, requiring VAD re-implantation and eventual heart transplantation. Conclusions: MFR resulting in VAD explantation is feasible in children with chronic HF especially for those &lt; 2 years of age. Further work is needed to help better identify the features that promote MFR and maintain it after explant.
Intratumoural immunotherapy plus focal thermal ablation for localized prostate cancer
Authors: Denis Séguier, Eric S Adams, Srinath Kotamarti, Vincent D'Anniballe, Zoe D Michael, Sriram Deivasigamani, Jonathan Olivier, Arnauld Villers, Christopher Hoimes, Thomas J Polascik
Journal: Nature Reviews Urology (2023)
Unraveling the genomic underpinnings of unbalanced MYC break-apart FISH results using whole genome sequencing analysis
Authors: Marie-France Gagnon, Alan R. Penheiter, Faye Harris, Dorsay Sadeghian, Sarah H. Johnson, Giannoula Karagouga, Alexa McCune, Cinthya Zepeda-Mendoza, Patricia T. Greipp, Xinjie Xu, Rhett P. Ketterling, Ellen D. McPhail, Rebecca L. King, Jess F. Peterson, George Vasmatzis, Linda B. Baughn
Journal: Blood Cancer Journal (2023)