tbuckley/cabot-search huggingface dataset:
Abstract 11050: Sex Differences in Culprit Plaque Characteristics in Acute Coronary Syndromes
Authors: Lena M Seegers, Makoto Araki, Akihiro Nakajima, Taishi Yonetsu, Tsunenari Soeda, osamu kurihara, Takumi Higuma, Shigeki Kimura, Yoshiyasu Minami, Junya Ako, Tom Adriaenssens, Holger Nef, Hang Lee, Iris McNulty, Tomoyo Sugiyama, Tsunekazu Kakuta, Ik-kyung Jang
Journal: Circulation (2021)

Introduction: Despite the significant decline in cardiovascular mortality in women over the past few decades, sex differences in the underlying mechanisms remain poorly understood. Previous postmortem studies have demonstrated differences between men and women in coronary plaque characteristics with a higher prevalence of plaque erosion in young women, but more plaque rupture (PR) in older women after menopause. However, in vivo data are limited. Methods: This study included 1368 patients with acute coronary syndrome undergoing pre-intervention optical coherence tomography (OCT) imaging from a multicenter international registry. The culprit plaque was categorized as plaque rupture, plaque erosion or calcified plaque, and stratified by age. Plaque microstructures at culprit lesion were also analyzed. Results: Sex differences were found in the underlying mechanisms of the culprit lesion: In women a significant ascending trend with age (P&lt;0.001) was observed in PR and plaque vulnerability with lipid rich plaque (P&lt;0.001) and thin cap fibroatheroma (TCFA) (P=0.005), whereas this trend was not obvious in men. In multivariate analysis, age was identified as an independent predictor for PR (odds ratio (OR) 1.039; 95% CI, 1.015-1.062, P &lt;0.001) and for lipid rich plaque (OR 1.054; 95% CI 1.030-1.079, P&lt;0.001) in women. Conclusions: An increasing trend in the prevalence of PR and plaque vulnerability with age was observed only in women but not in men.
Abstract 13034: Endothelial Exosomal miR-24 Predicts Cerebrovascular Events in COVID-19 Patients
Authors: Jessica Gambardella, Stanislovas Jankauskas, Xujun Wang, ANTONIETTA COPPOLA, Raffaele Izzo, anna annunziata, giuseppe fiorentino, Alessandro Matarese, Bruno Trimarco, Gaetano Santulli
Journal: Circulation (2021)

Introduction: Neuropilin-1 has been recently identified as a co-factor needed for the entry of SARS-CoV-2 in host cells and has been linked to neurologic symptoms of COVID-19 (Science 2020). Emerging evidence indicates that exosomal microRNAs (miRNAs) are involved in a number of physiologic and pathologic processes. However, to our knowledge, exosomal miRNAs have not been hitherto investigated in COVID-19. Hypothesis: Since we have recently demonstrated that miR-24 targets the 3’UTR of the gene encoding for Neuropilin-1 and this miRNA is expressed in human brain endothelial cells, we hypothesized an association between plasma levels of CD31 + extracellular vesicles (EVs) enriched in miR-24 and the risk of cerebrovascular manifestations in patients hospitalized for COVID-19. Methods and Results: We obtained plasma from &gt;300 COVID-19 patients; as control COVID-19 negative populations, we obtained plasma from healthy donors and patients hospitalized for cerebrovascular disorders. CD31 + EVs were isolated from plasma on hospital admission, and miR-24 levels were quantified. When comparing patients with vs without cerebrovascular disorders, we found that plasma levels of CD31 + EV miR-24 were significantly different between these populations. We did not find any significant difference among groups when assessing circulating free levels of miR-24. Using a multiple regression analysis, adjusting for age, hypertension, and diabetes, the association between EV miR-24 and cerebrovascular complications in COVID-19 patients was confirmed (P&lt;0.05). Conclusions: This is the first study showing a significant association between EV non-coding RNAs and clinical outcome in COVID-19 patients. Our results are relevant for basic researchers, because we identified an unprecedented significant association between EV miR-24 and cerebrovascular disorders, which could be helpful to better understand the molecular mechanisms underlying the pathophysiology of cerebrovascular events in COVID-19, as well as for clinicians, inasmuch as this association may help healthcare professionals in identifying COVID-19 patients who are at high risk of developing cerebrovascular disease.
Abstract 13478: Cardiac Magnetic Resonance Imaging Identifies Cardiac Disease in Limb-Girdle Muscular Dystrophy in Previously Low Risk Mutations
Authors: Selina Vickery, Jerry R Mendell, Kelly Lehman, Kan N Hor
Journal: Circulation (2021)

Introduction: Limb-Girdle Muscular Dystrophies (LGMD) are an inheritable group of genetic disorders primarily involving progressive weakening and atrophy of the pelvic or shoulder girdle musculature with potential cardiac dysfunction. Prior reports stratified frequency of cardiac disease based on genetic mutations. The general incidence of cardiac muscle involvement in LGMD is variable depending on genetic factors and carry important indications for clinical management. Cardiac magnetic resonance imaging (CMR) is increasingly used in dystrophinopathies and determining management. There is limited CMR data in adult LGMD patients and fewer reports in younger patients. Hypothesis: Therefore, we sought to determine the extent of cardiac involvement based on genetic risk of cardiomyopathy. Methods: This is a retrospective review of LGMD patients followed at our institution who underwent CMR assessment. Patients stratified into Group A (high incidence of cardiomyopathy; LGMDs 1B, 2E, 2F and 2I) and Group B (rare or no reported cardiomyopathy; LGMDs 1A, 1C, 2A, 2B, 2C, 2D, 2G, 2H, 2J) with CMR studies were assessed for presence of cardiac scar defined as late gadolinium enhancement (LGE) and LVEF for each subject. Results: 41 subjects were identified with average age of 21.3±11.5 years (range 6-50) with normal LVEF 58±12.1% and 12/41 (29.3%) with LGE with the youngest patient age 12.4 years. Group A included 14/41 (34%) and 27/41 (66%) were in Group B. Group A had higher incidence of LGE 6/14(42.9%) with preserved LVEF of 58.2±11% compared to Group B with 6/27 (22.2%) with no difference in LVEF of 55.7±16.4% (p = 0.5). When stratified by LGE status, the LGE-positive group was older at 26.4±11.9 years and had preserved LVEF of 61.9±11.1% versus LGE-negative group of 19.1±10.9 years (p = 0.03) with abnormal LVEF of 49.4±9.5% (p =0.0008). Conclusions: This is the largest study of CMR in LGMD patients, confirming presence of cardiac disease by LGE in the high risk group. Surprisingly, nearly 25% of the low risk mutations have evidence of LGE. Abnormal LGE predicted abnormalities in LVEF in both Group A and Group B. Management of LGMD patients should include CMR even in low risk population. Ongoing data collection may reveal disease cluster in previous low risk groups.
Abstract P174: The Role of Kidney Function in the Effectiveness of Lifestyle Modifications for Hypertension: Results From the ENCORE Trial
Authors: Crystal C Tyson
Journal: Circulation (2016)

Background: Kidney function plays a major role in determining BP and may influence the effectiveness of lifestyle modifications on hypertension. We examined the role of kidney function on BP response to weight loss and dietary changes in the ENCORE trial. Methods: The ENCORE trial was a randomized controlled trial that compared the DASH diet alone or in combination with a weight management program in sedentary overweight or obese adults with above normal BP and preserved kidney function. Clinic and 24-hour ambulatory BP, body weight, diet intake, and 24-hour urine sodium were assessed at baseline and 4 months. Kidney function was assessed at baseline. The relationships between changes in BP and lifestyle behavior change (weight, DASH diet adherence, and urine sodium) were assessed using adjusted multivariable linear regression. Interactions between behavior changes and eGFR (“HI group”: ≥90 or “LO group”: &lt;90 ml/min/1.73m2) were assessed. Results: Of 144 participants included in our analysis: women = 67%, mean age =52 years, mean clinic BP =138/86 mmHg, mean ambulatory BP =137/82 mmHg, median eGFR =90 (range 53-146 ml/min/1.73m2). Seventy-four participants were in the HI group and 70 were in the LO group. Improvements in clinic and ambulatory BP were significantly correlated with improvements in weight and DASH adherence (Ps&lt;.05), but not with urine sodium excretion. Participants in the LO group experienced greater BP reductions from weight loss than those in HI group (Ps&lt;.05) (Figure 1), while only participants in the HI group experienced a BP benefit from reduction in urine sodium (P=0.01). BP changes related to DASH adherence did not vary by eGFR. Conclusions: Among overweight and obese adults with above normal BP and preserved kidney function, baseline eGFR was observed to influence the magnitude of BP reduction from weight loss and sodium reduction. These findings suggest that certain lifestyle modifications may more favorably lower BP across different levels of kidney function.
LGG-25. A PHASE 2 STUDY OF TRAMETINIB FOR PATIENTS WITH PEDIATRIC GLIOMA WITH ACTIVATION OF THE MAPK/ERK PATHWAY. TRAM-01
Authors: Sébastien Perreault, Valérie Larouche, Uri Tabori, Cynthia Hawkins, Sarah Lippé, Benjamin Ellezam, Jean-Claude Décarie, Yves Théoret, Marie-Élaine Métras, Serge Sultan, Édith Cantin, Marie-Ève Routhier, Maxime Caru, Geneviève Legault, Eric Bouffet, Lucie Lafay-Cousin, Juliette Hukin, Craig Erker, Nada Jabado
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. It is now known that the majority of PLGG have activation of the MAPK/ERK pathway. We hypothesize that we will observe responses in recurrent/refractory PLGG treated with trametinib. METHODS This is a multicenter phase II including three progressing/refractory PLGG groups: NF1 patients, KIAA1549-BRAF fusion patients and patients with other activation of the MAPK/ERK pathway (excluding V600E). Patients will receive daily oral trametinib for a total of 18 cycles of 28 days. A total of 104 patients will be enrolled in seven Canadian centers. Secondary objectives include the assessment of progression-free survival, tolerability of trametinib, serum levels of trametinib and evaluation of quality of life during treatment. RESULTS As of January 7 2020, 28 patients have been enrolled (NF1: 6 patients, KIAA1549-BRAF fusion: 17, other: 5 including 3 patients FGFR1 alteration). Median age is 8.5 years (range 2.5–25.4 years). Median follow-up is currently 4.6 months (range 0.16–14.7 months). Twenty patients are currently evaluable. Best response includes: 1 complete response (5%), 3 partial response (15%), 4 minor response (20%), 8 stable disease (40%), 4 progressive disease (20%). 8 patients (28,5%) discontinued treatment: 4 for progressive disease, 3 adverse event (alanine aminotransferase increase), 1 withdrew. CONCLUSION Trametinib is potential effective targeted therapy for patients with recurrent/refractory PLGG. Overall treatment is well tolerated. This ongoing trial will continue to gather data on response rate, duration of response and safety of trametinib for PLGG.
Abstract 12599: Pushing the Boundaries of Heart Transplantation in a Patient With Giant Cell Myocarditis and Pulmonary Embolism
Authors: Lauren S Ranard, Michael Brener, Amirali Masoumi, Yuji Kaku, Koji Takeda, Justin A Fried, Nir Uriel, Jan Griffin
Journal: Circulation (2021)

A 47-year-old woman with a remote history of hormone receptor positive breast cancer presented to our hospital with dyspnea and malaise. She was hypotensive and had an S3 gallop with cool extremities. Electrocardiogram demonstrated atrioventricular dissociation with a wide underlying ventricular escape. Transthoracic echocardiography revealed a left ventricular ejection fraction of 15% and severely depressed right ventricular function with normal biventricular dimensions.She emergently went for temporary transvenous pacemaker placement and a right heart catheterization with endomyocardial biopsy. This revealed elevated biventricular filling pressures (central venous pressure = 16 mmHg; pulmonary capillary wedge pressure = 19 mmHg) and a low cardiac index (2.0 L/min/kg 2 ).Her hemodynamics deteriorated despite inotropes and an intra-aortic balloon pump, prompting escalation to veno-arterial extracorporeal membrane oxygenation. She was initiated on pulse dose steroids for 3 days, followed by a slow taper. Over the course of 24 hours, she had worsening right ventricular function and developed episodic ventricular tachyarrhythmias requiring recurrent defibrillation. She was escalated to CentriMag biventricular support. The endomyocardial biopsy revealed severe giant cell myocarditis with &gt;25% destruction of the sampled myocardium. After an expedited transplant committee review, the patient was listed for heart transplantation (HT).Three days after HT listing, she developed acute hypoxemia and profound hypotension. CT angiography of the chest identified multiple pulmonary emboli (PE), including a centrally located thrombus causing partial obstruction of the right pulmonary artery. Despite this complication, the patient proceeded to a combined pulmonary embolectomy and HT. She was discharged home from the hospital post HT and at 10-week follow-up demonstrated excellent functional rehabilitation.Although PE is a relative contraindication for heart transplantation, the reversible nature of her pathology and the benefit of avoiding time-dependent pulmonary vascular remodeling favored early transplantation. PE in HT recipients is far less well characterized and has important implications for management and prognosis.
Promotion of right ventricular outflow tract reconstruction using a novel cardiac patch incorporated with hypoxia-pretreated urine-derived stem cells
Authors: Long-Mei Zhao, Long Wang, Wen-Qian Zhang, Rui Wang, Xiu-Zhen Zhang, Xiong-Xin Lei, Yan Liang, Yu-Ting Song, Qing-Yi Zhang, Ke Lin, Hui-Qi Xie
Journal: Bioactive Materials (2021)

Approximately 25% of patients with congenital heart disease require implantation of patches to repair. However, most of the currently available patches are made of inert materials with unmatched electrical conductivity and mechanical properties, which may lead to an increased risk for arrhythmia and heart failure. In this study, we have developed a novel Polyurethane/Small intestinal submucosa patch (PSP) with mechanical and electrical properties similar to those of the native myocardial tissue, and assessed its feasibility for the reconstruction of right ventricular outflow tract. A right ventricular outflow tract reconstruction model was constructed in 40 rabbits. Compared with commercially available bovine pericardium patch, the PSP patch has shown better histocompatibility and biodegradability, in addition with significantly improved cardiac function. To tackle the significant fibrosis and relatively poor vascularization during tissue remodeling, we have further developed a bioactive patch by incorporating the PSP composites with urine-derived stem cells (USCs) which were pretreated with hypoxia. The results showed that the hypoxia-pretreated bioactive patch could significantly inhibit fibrosis and promote vascularization and muscularization, resulting in better right heart function. Our findings suggested that the PSP patch combined with hypoxia-pretreated USCs may provide a better strategy for the treatment of congenital heart disease.
COVID-19 considerations and strategy for a safe return to international football competitions: an African perspective
Authors: Maurice Douryang, Yagaï Bouba, Eméline Zogning Makemjio, Andrillene Laure Deutou Wondeu, Lervasen Pillay
Journal: British Journal of Sports Medicine (2021)

The COVID-19 pandemic has affected many aspects of life worldwide—educational, economic, cultural, social and sporting.1 To limit the spread of COVID-19, initial containment strategies included proper mask wearing, respiratory and hand hygiene, social/physical distancing and different levels of lockdown to limit social interaction.2 While competitive sport has also been impacted by these measures, risk mitigation protocols have allowed competitions at the national, international and professional levels to resume in some countries around the world.3–5 However, additional barriers exist on the African continent to safely resume sport that may not exist elsewhere. These include cost and resource limitations to facilitate player and staff education, safe team transport, hotel and club sanitisation, regular COVID-19 PCR testing with short result turnaround times and access to vaccinations.6 7 This commentary outlines practical recommendations for a scientifically valid COVID-19 risk mitigating strategy to enhance safety for teams and spectators at African football competitions that accommodate regional challenges. ### Design a guideline The success of COVID-19 prevention during football competitions must involve a scientifically based risk mitigation plan that can evolve as new evidence and interventions emerge. This plan must be accepted by all stakeholders, including stadium management, National Federations, and executive committees of leagues and individual teams. A well-designed guideline on COVID-19 risk mitigation should be practical, concise and consider the following8:
Abstract 11091: Failure of Right Ventricular Adaptation to Pressure Overload Due to a Profound Deficiency in Adenylate Kinase 1 and Impaired Ventricular Energetics
Authors: Jason Zelt, Virgilio Cadete, Yupu Deng, Rafael Godoy, Alexanne Cuillerier, Katelynn Rowe, Mohammad Abdul-Ghani, Lynn Megeney, Yan Burelle, Antonio Giulivi, Alexandre F STEWART, Steeve Provencher, Sandra Breuils-bonnet, sébastien bonnet, Robert deKemp, Rob S Beanlands, Lisa Mielniczuk, Duncan J Stewart
Journal: Circulation (2021)

Introduction: Interindividual heterogeneity in the ability of the right ventricular (RV) to adapt to pressure overload in pulmonary hypertension (PH) is likely influenced by genetic determinants. We took advantage of strain-dependent, maladaptive RV remodeling in Fischer compared to Sprague-Dawley (SD) rats to define the molecular and genetic mechanisms that predispose to development of RV failure in PH. Methods/Results: In the SU5416/hypoxia(SUHx) PH model, Fischer rats exhibited RV failure and 100% mortality by 5-weeks, whereas SD rats showed preserved RV function and 88% survival beyond 9 weeks (p&lt;0.0001). In vivo oxidative metabolism, assessed by [ 11 C]acetate PET, was increased in Fischer rats at 4 weeks (p&lt;0.05), associated with impaired RV efficiency compared to SD (work metabolic index: 58±12 vs 102±20 mmHg·mL/cm 2 , respectively; p&lt;0.001), but no differences were observed in mitochondrial complex activity in permeabilized RV cardiac fibers. Adenylate Kinase 1 (AK1) was among the top ten differentially expressed genes between Fischer and SD rats by unbiased transcriptomic analysis, with markedly lower expression in the RV of Fischer rats (FC:3.36, P&lt;0.05). Profound AK1 deficiency was confirmed by proteomics and validated by Western blotting (&gt;10-fold reduction, P&lt;0.001). Fischer rats also exhibited evidence of hemolysis, recapitulating the hemolytic phenotype seen in patients with rare AK1 coding region mutations. While whole genome sequencing failed to reveal any coding region mutations in Fischer rats, there was a unique variant in a highly conserved upstream flanking region. AK1 levels were also reduced in the RV of PH patients with decompensated RV function and right heart failure. Conclusion: Fischer rats with AK1 deficiency have inefficient energetics likely related to reduced ATP shuttling from the mitochondria to the contractile fibers, which represents a novel mechanism for RV failure in response to chronic increases in afterload.
Abstract 13561: Does the Use of Advanced Therapies Improve Outcomes During Pregnancy and Post Partum Period in Patients With Group I Pulmonary Hypertension
Authors: Sanjay Polisetty, Ignacio Zepeda, Jesus R Quispe, Cynthia C Taub
Journal: Circulation (2021)

Introduction: Poor outcomes have been reported in Pregnant patients with WHO Group I Pulmonary Hypertension (PH) before the advent of PH targeted therapies. We performed a systematic review and meta-analysis with the goal of evaluating the association between mortality rates and PH targeted therapies in pregnant women with WHO group 1 PH. Methods: PubMed Database was searched with keywords “pulmonary hypertension”, “pregnancy” from inception to December 2020. Inclusion criteria: &gt;10 pregnancies, maternal mortality reported and WHO Classification available. A meta-analysis was performed to evaluate the association between maternal death and treatment with PH targeted therapies in patients with WHO group 1 PH. All other WHO groups were excluded. Results: Seven studies, published between 1992 and 2016, including 91 patients with WHO group 1 PH met inclusion criteria and were analyzed. (Table 1) Most common etiologies were Idiopathic PH and Congenital Heart Disease. Mortality ranged from 8.3% to 36.3%. Use of PH targeted therapies ranged from 25% to 100%. There was a trend towards survival benefit with PH targeted therapies compared with no therapy. This trend was not statistically significant. Of all deaths reported (n=18), thirteen (72.2%) occurred postpartum. Conclusions: Mortality in pregnant patients with WHO group I PH remains high; most deaths were due to PH crisis and occurred postpartum. Increased monitoring in the postpartum period is likely warranted. Studies were retrospective with small sample sizes. Larger and higher quality studies are needed to determine if PH targeted therapies improve mortality in pregnant patients with WHO group I PH.
Polycythemia Vera and Cardiac Arrhythmias: Association and Outcomes- a Propensity Matched Analysis in Hospitalized Patients
Authors: Shivani Dalal, Krunalkumar Patel, Akash Patel, Daniel Tran, Thanh Nguyen, Umang Patel, Venkataraman Rajagopalan
Journal: Blood (2021)