tbuckley/cabot-search huggingface dataset:
Abstract 4127891: Value of Left Ventricular and Left Atrial Strains in Loeffler Endocarditis and Hypereosinophilic Syndrome
Authors: Yuichiro Okushi, Matthew Reeder, Saberio LoPresti Vega, Richard Grimm, Brian Griffin, Bo Xu
Journal: Circulation (2024)

Background: Hypereosinophilic syndrome (HES) is a rare disease that causes organ damage and thrombosis due to sustained eosinophilia of the blood or tissues. Loeffler endocarditis (LE) is defined as cardiac involvement in the setting of HES. There are limited data on the diagnostic and prognostic impact of strain imaging on LE. Methods: A single-center retrospective cohort study was performed. Patients with eosinophilia between January 2000 and January 2023 were identified. We included patients who met the current diagnostic criteria for HES and underwent echocardiography prior to treatment. LE was defined as the presence of eosinophils in the myocardium by an endomyocardial biopsy, endocardial thickening, or left ventricular thrombus due to HES. We evaluated the composite events defined as CV death and stroke at diagnosis and during follow-up. Results: Of 1,664 patients with eosinophilia, 34 patients with HES were included (10 with LE and 24 without LE). In the entire cohort, the mean age was 57 ± 16 years and 41% were male. The median follow-up duration was 85 months (25th -75th percentile: 41-145 months). The composite events occurred in 6 patients. Left ventricular ejection fraction (LVEF) was similar in both groups (60% vs. 61%, p = 0.691). Patients with LE had significantly lower left ventricular global longitudinal strain (LV-GLS) (-9.7% vs. -15.5%, p = 0.001), left atrial (LA) reservoir strain (21.0% vs. 32.1%, p = 0.021) and LA conduit strain (-9.7% vs. -19.2%, p &lt;0.001), compared to patients without LE. There were no significant differences in LA booster strain (-11.3% vs. -12.8%, p = 0.606) and right ventricular free wall strain (-17.5% vs. -23.4%, p = 0.083). All LE patients and half of non-LE patients had LV-GLS worse than -16 %. There was a significant difference in the compsoite events for patients with LV-GLS worse than -16% (28.6% vs. 0.0%, p = 0.049). Conclusions: LE was associated with significantly worse LV-GLS and left atrial strain compared to patients without LE. Worse LV-GLS was associated with a higher frequency of the composite events.
Abstract 4128590: Identical Twins, Non-Identical Results: Genetic Testing for Cardiomyopathy
Authors: Noah Newman, Mariana Garcia, Abhishek Singh, Robert Coyne, Kunal Bhatt, Michael Burke
Journal: Circulation (2024)

Case: A 58-year-old male (Twin A) with no medical history presented with syncope while playing paddle ball. TTE showed LVEF 15-20%. Cardiac MRI (CMR) identified transmural late gadolinium enhancement (LGE) in the inferolateral wall of the LV, but angiography showed non-obstructive CAD. Four years later, his monozygotic twin (Twin B), also with no medical history, suffered cardiac arrest while playing paddle ball. TTE showed LVEF 5-10%. CMR revealed inferolateral LGE (Figure 1) with angiography showing non-obstructive CAD. Genetic testing was performed by different companies. Twin A was found to be heterozygous for myosin light chain kinase 3 ( MYLK3 ) p.R380H (c.1139C&gt;A), a variant of uncertain significance (VUS). While rare (gnomAD allele frequency 2.7e -4 ), MYLK3 p.R380H is not conserved across species, exchanges amino acids with similar biochemical properties, and is predicted to be benign by in silico pathogenicity tools. Notably, MYLK3 was not sequenced in Twin B, who was instead found to be heterozygous for desmoplakin ( DSP ) p.R1002W (c.3004C&gt;T). DSP p.R1002W is highly conserved, exchanges amino acids with dissimilar properties, and is very rare (gnomAD allele frequency 2.8e -5 ). In silico testing yielded conflicting results with some tools predicting it to be damaging to protein function. Interestingly, the variant was present in both twins but was classified differently by each company: likely benign for Twin A (and therefore not reported) and VUS for Twin B. First degree relatives are advised to undergo clinical screening and cascade genetic testing for DSP p.R1002W. Discussion: The presentation described is consistent with arrhythmogenic cardiomyopathy (ACM) and the family history strongly supports a genetic etiology. DSP is a causal gene for ACM with unique clinical features that are strikingly similar to those observed herein. The differences in genes tested and variant adjudication between companies has left diagnostic uncertainty; hence, definitive pathogenicity cannot be attributed to either variant without cosegregation analysis, which is ongoing. In summary, this case illustrates the challenges of variant interpretation, and the impact that this can have on genetic counseling and family screening.
Abstract 4128201: Reducing Blood Product Waste in a Pediatric Cardiac Catheterization Laboratory – A Quality Improvement Initiative
Authors: Jacqueline Morrison, Jacqueline Zedalis, Benjamin Parrish, Eduardo Goenaga Diaz, Friedman David, Jaleah Hawkins, Farzana Shah, Sharna Basu, Edith Ryan, Jie Tang, Christopher Smith, Ryan Callahan, MATTHEW GILLESPIE, Jonathan Rome, David Hehir, Michael O'byrne
Journal: Circulation (2024)

Background/Aim: Transfusion can be a life-saving intervention, however routine pre-procedural blood products frequently go unused. Recent national blood product shortages highlight the importance of blood product stewardship. In our pediatric cardiac catheterization laboratory (PCCL), packed red blood cells (pRBCs) were ordered prior to all cases. These units are rarely transfused and sometimes cannot be reallocated, resulting in waste. As a quality improvement project, we set a primary aim to reduce the percentage of monthly pRBC waste from a baseline mean of 7.4% to &lt;5% over 12 months. Methods: Baseline data on all cardiac catheterization cases, excluding electrophysiology, lymphatic, and hybrid cases, were collected from 1/1/2022 to 2/28/2023. Interventions (Table 1) were implemented and outcomes measured from 3/1/2023 to 3/31/2024. Primary outcome measures were monthly percentage of blood wasted, and percent of unused pRBC orders. Emergency blood product activation was measured as a balancing metric. Statistical process control charts were used to display and analyze data. Results: During the intervention period 1,318 cases were performed of which 32% met low-risk criteria for pRBC order de-implementation. The percent of blood that was subsequently wasted was reduced from 7.4% to 5.5% (Figure 1A), primarily driven by the reduction in the anecdotal practice of pRBC unit splitting in patients &lt;1 year old (Figure 1B). The percent of unused pRBC orders was reduced from 97% to 79% with sustained improvement following two cycles of routine blood order de-implementation for low-risk cases. No emergency blood activation occurred (0%, 97.5% CI: 0-0.28%). Conclusion: De-implementation of default pRBC orders for low-risk catheterization procedures and reduction in unit splitting reduced the percent of blood wasted in our PCCL, saving time and cost without compromising patient safety. A data-driven approach to blood stewardship may be broadly applicable across procedural areas.
Abstract 4131439: Routine Social Isolation Screening Among Adults with Cardiovascular Disease: A Survival Analysis
Authors: Kathleen Galper, Matthew Nudy, Lawrence SINOWAY, Emily Brignone
Journal: Circulation (2024)

Background: Evidence linking social isolation to cardiovascular disease morbidity and mortality has grown in recent years. Still, information on how this may manifest in real world settings and its implications for screening practices is limited. In 2019, our large national integrated health care system implemented screening for social isolation as part of a broader universal social risk assessment. This repository of screening data was joined to administrative claims to test these associations in real world data and explore differences by demographic and medical factors. Methods: Social isolation responses recorded from 2019-2022 were included for a cohort of adult health plan members with documented atherosclerotic cardiovascular disease (ASCVD). We selected a single random assessment for each member and retained any other responses for sensitivity analyses. Cohort members had at least 10 months of enrollment surrounding assessment date for use as the baseline period and were followed for 365 days. We used cox proportional hazards regression with right censoring for coverage gaps to estimate the risk of all-cause mortality conferred by social isolation. We used Poisson regression to model the rate of inpatient stays. Results: There were 881 deaths among 7,484 members (18% of those with social isolation; 11% of those without). The isolated group skewed less male (54% vs. 65%, p &lt;0.001) and older (68.4 [SD 12.7] vs. 67.5 [SD 12.6] years, p &lt;0.05) than those not isolated. At baseline, the isolated group had higher rates of mean inpatient stays (2.3 [SD 1.9] vs. 1.9 [SD 1.6], p &lt;0.001), ED visits (1.2 [SD 1.9] vs. 0.9 [SD 1.6], p &lt; 0.001), and smoking (50% vs. 44%, p &lt; 0.05), and a higher mean Charlson Comorbidity Index (CCI) (3.6 [SD 2.6] vs. 3.0 [SD 2.4], p &lt; 0.001). Adjusted survival models suggested an independent 33% increase in all-cause mortality risk among those screening positive for social isolation (1.33 HR 95% CI 1.10, 1.62). Adjusted Poisson models found a similar increase in inpatient stays (1.36 IRR 95% CI 1.14, 1.62). Conclusions: Our findings corroborate the association between social isolation and morbidity and mortality among those with known ASCVD. The effect for social isolation was similar in magnitude to clinical comorbidities and smoking, suggesting that routine screening for social isolation may provide valuable information for assessing and managing the risk of death among patients with ASCVD.
Abstract 4132249: Preoperative identification of respiratory viral genomes in the trachea but not in the nasopharynx is a risk factor for postoperative pulmonary hypertension in patients with congenital cardiac communications
Authors: KELLY CRISTINA DE OLIVEIRA ABUD, Lucy Vilas Boas, Nair Maeda, Maria Souza, Eloisa Carvalho, Antonio Lopes
Journal: Circulation (2024)

Introduction: Pulmonary vascular remodeling is a key determinant of outcomes in patients undergoing surgery for congenital cardiac communications (CCCs). Respiratory epithelial cells infected by viruses express cytokines and growth factors with potential impact on airway and vascular remodeling. Hypothesis: Preoperative exposure to respiratory viruses renders CCC patients susceptible to postoperative pulmonary hypertension. Aims: To investigate if asymptomatic patients carrying respiratory viral genomes (RVGs) in the airways are at risk for pulmonary hypertension following cardiac surgery. To analyze the role of postoperative inflammatory reaction. Methods: The study comprised patients with unrestrictive CCCs undergoing surgery under cardiopulmonary bypass (CPB). In the absence of any signs of recent infection, RVGs were searched for in nasopharyngeal aspirates 2-3 days before surgery, and in tracheal aspirates collected in the operating room (RT-PCR, panel for 19 viruses). Serum levels of 36 inflammatory proteins were measured by chemiluminescence preoperatively and 4 hours post CPB. Pulmonary/systemic mean arterial pressure ratio (PAP/SAP) computed during the first 12 hours postoperatively (invasive assessment) was defined as the study outcome. A cutoff level was set at 0.40. Results: Sixty patients were enrolled (age 11 [7-16] months, median with interquartile range). Preoperative PAP/SAP was 0.78 (0.63-0.88). RVGs were present in nasopharyngeal and tracheal aspirates in 64% and 38% of patients, respectively. The presence of RVGs in tracheal aspirates was associated with an upward shift of postoperative PAP/SAP curve (p=0.006). The same was not observed for positive tests in nasopharyngeal aspirates (p=0.343). Of all factors analyzed as possible predictors of postoperative PAP/SAP &gt;0.40, only preoperative peripheral oxygen saturation and the presence of RVGs in the trachea were selected at multivariate analysis (respective OR with 95% CI, 0.40 [0.23-0.72] and 4.42 [1.17-16.78]. Heightened post-CPB levels of interleukin-1 receptor antagonist and chemokines MIF and MCP-1 were found to increase the risk of having a PAP/SAP &gt;0.40 in RVG carriers (respective OR with 95% CI, 2.04 [1.09-3.81], 2.34 [1.15-4.74] and 2.18 [1.07-4.43]. Conclusion: The observed relation of postoperative hemodynamics to respiratory viruses and post-CPB inflammatory reaction may have pathophysiological and therapeutic implications in pulmonary hypertension associated with congenital heart disease.
Abstract 4131736: Myocardial Work in Patients with Systemic Arterial Hypertension: Correlation with Left Ventricular Mass and Aortic Strain Lidia Capotosto <sup>1,2</sup> , Enrico Mangieri <sup>2</sup> , Gaetano Tanzilli <sup>2</sup> , Giuseppe Placanica <sup>2</sup> , Attilio Placanica <sup>2</sup> , Fabio Miraldi <sup>2</sup> , Antonio Vitarelli <sup>1,21</sup> Department of Echocardiography, Cardiodiagnostica CS, Rome, Italy, <sup>2</sup> Department of Cardiology and Cardiac Surgery, …
Authors: Lidia Capotosto, Enrico Mangieri, Gaetano Tanzilli, Giuseppe Placanica, Attilio Placanica, Fabio Miraldi, Antonio Vitarelli
Journal: Circulation (2024)

Background: Myocardial work (MW) is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure-strain loops and has been validated against invasively derived pressure-volume measurements. The purpose of the present study was to analyze whether systemic arterial hypertension is associated with abnormal left ventricular (LV) function assessed by myocardial work and how these changes are related to left ventricular hypertrophy (LVH) and aortic strain. Methods: We examined 86 hypertensive (mean age, 66±14 years, 51% male) and 86 sex- and age-matched healthy controls (mean age, 64±15 years, 53% male). Hypertensive patients were divided into two groups: patients without LVH (group-A) and patients with LVH (group-B, LVMI&gt;115g/m2 men, LVMI&gt;95g/m2 women). All of them had preserved LV ejection fraction. Global LV longitudinal strain (GLS) was calculated by speckle tracking echocardiography. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Corrected circumferential aortic strain (Ao-S) was calculated in the ascending aorta by two-dimensional speckle tracking echocardiography as global aortic strain /pulse pressure. Data analysis was performed offline (GE EchoPAC). Results: GWI and GCW were increased in group-A compared to controls (p&lt;0.05) and decreased in group-B (p=0.04). GWW was increased in group-A(p=0.02) and group-B(p&lt;0.001). GWE was decreased in group-A(p&lt;0.01) and group-B(p&lt;0.005). There was a positive correlation between GWE and Ao-S(r=0.51,p=0.03). GWE was independently associated with GLS(β=0.26,p=0.034), LV mass(β=0.31,p=0.02) and Ao-S(β=0.37,p=0.01) in the whole hypertensive population. At the receiver operating characteristic (ROC) analysis, optimal cutoff values of GWI, GLS, Ao-S, GWE and (GWE+Ao-S) discriminating LV hypertrophy were 0.7329, 0.7613, 0.8011, 0.8442 and 0.8986, respectively. Conclusions: Decreased GWE in systemic hypertension was related to aortic strain and occurred even in the absence of LV hypertrophy. Additional assessment of aortic strain improved the ability of myocardial work variables to differentiate patients with LVH, patients without LVH, and control subjects.
Abstract 4128606: Detailed Measurements of Surgical Mitral Valves: Implications for Transcatheter Mitral Valve-in-Valve Interventions
Authors: Joseph Kassab, Nour Mohammed, Nour Lababede, Abdel Hadi El Hajjar, Karl West, Shinya Unai, Samir Kapadia, Serge Harb
Journal: Circulation (2024)

Background: With the increasing prevalence of transcatheter mitral valve-in-valve interventions (V-in-V), a detailed understanding of the surgical valves (SV) is of paramount importance. Left ventricular outflow tract obstruction (LVOTO) is a feared complication and is typically caused by the anterior displacement of the LVOT-facing surgical leaflet, which, along with the surgical post at that level, forms a fixed obstruction. Traditionally, the risk is estimated using computed tomography software by simulating a valve that extends to the surgical post height of the implanted SV. However, this does not account for the actual leaflet length and post width at the level of the leaflet tip, which could differ significantly from the surgical post height but accurately estimate LVOTO risk. Methods: We conducted detailed measurements of three different sizes of two commonly used surgical mitral valves: the Biocor EPIC ( Abbott ) in sizes 27 mm, 31 mm, and 33 mm, and the Mosaic ( Medtronic ) in sizes 25 mm, 31 mm, and 33 mm. Using a digital caliper and height gauge, we measured several key parameters for each valve, including leaflet height, post height, leaflet width, post width at the level of the leaflet tip, maximal post width, and valve inner diameter. Results: The results, presented in Table 1, show significant differences in leaflet height and post widths across manufacturers and sizes. Leaflet height was consistently shorter than post height in both Abbott and Medtronic valves, with this discrepancy more pronounced in larger valves and Medtronic valves. The post width at the leaflet tip also varied considerably. Conclusions: Given the substantial differences between leaflet and post heights—with the leaflet typically much shorter—an accurate assessment of LVOTO risk should account for both the leaflet height and the width of the post at that level to avoid overestimating the risk of LVOTO.
Abstract 4128189: CD44 Knockdown Attenuates the Abnormal Cellular Phenotype of BMPR2-Deficient Primary Human Pulmonary Artery Endothelial Cells
Authors: Md Abdul Hai Siddique, Li-Yuan Chen, Keytam S. Awad, Shuibang Wang, Robert Danner, Jason Elinoff
Journal: Circulation (2024)

Background: BMPR2 gene silencing in primary human pulmonary artery endothelial cells (PAECs) produces a proliferative, hypermigratory PAH-like cellular phenotype. Genome-wide expression profiling in BMPR2 -silenced cells uncovered CD44 , a cancer stem cell marker associated with tumor progression and metastasis, among the top upregulated transcripts. Therapeutic strategies that block CD44 or reduce its expression are currently in various stages of development for cancer. Thus, mechanistic studies investigating the contribution of CD44 to vascular remodeling in PAH may reveal new therapeutic targets. Hypothesis: Upregulation of CD44 contributes to the abnormal phenotype of BMPR2-deficient PAECs and thus may contribute to vascular remodeling in PAH. Aims: Determine the effect of CD44 -silencing on gene expression and cell proliferation in BMPR2-deficient PAECs. Methods: Commercially available primary, human PAECs were transfected with scrambled control (siCTRL) or gene specific siRNA(s). PAH patient-derived (N=24) and failed donor-derived (N=11) PAECs were obtained from the PHBI. mRNA and protein expression were determined by quantitative RT-PCR and Western blotting, respectively. Cell proliferation was assessed by BrdU incorporation 96h after siRNA transfection. Data was analyzed using t-tests or ANOVA with post hoc pairwise comparisons. Results: Consistent with our previous findings, CD44 protein expression was increased 4-fold in BMPR2 -silenced PAECs 48h following siRNA transfection (P&lt;0.0001 vs siCTRL; N=10 unique donors). Genes involved in endothelial-mesenchymal transition and cell proliferation were also increased in BMPR2 -silenced PAECs including HMGA1 , ID1 , SNAI1, and SNAI2 (P&lt;0.01 for all vs siCTRL; N=5 independent experiments) and co-silencing CD44 attenuated their upregulation (P&lt;0.05 for all vs siBMPR2 alone). Importantly, CD44 knockdown reduced PAEC proliferation in the absence (P=0.01 vs siCTRL) and presence of BMPR2 deficiency (P=0.002 vs siBMPR2 alone). Like BMPR2 -silenced PAECs, CD44 mRNA levels were higher in PAH patient-derived versus failed donor control PAECs (P=0.07). Conclusions: CD44 knockdown corrected aberrant gene expression associated with endothelial-mesenchymal transition and reduced cellular proliferation in BMPR2-deficient PAECs. Thus, endothelial CD44 upregulation may contribute to pathologic vascular remodeling in PAH and represents an unexplored therapeutic target.
Abstract 4127919: Disease-associated variants in <i>DSP</i> -encoded desmoplakin are common, yet low penetrant alleles associated with development of myocarditis and cardiomyopathy at a population level
Authors: Manasa Gurumoorthi, Ghaith Sharaf Dabbagh, Kerrick Hesse, Rachel Wolfe, Ravi Shah, Leonie Kurzlechner, Babken Asatryan, Anwar Chahal, Andrew Landstrom
Journal: Circulation (2024)

Intro: DSP- encoded desmoplakin is implicated in a distinct form of arrhythmic cardiomyopathy (ACM), often involving the LV and characterized by myocardial inflammation. Conventional ACM diagnostic criteria has poor sensitivity for DSP -associated ACM, thus highlighting the need to identify the full spectrum of phenotypic risk associated with disease-associated DSP variants. Objective: To analyze the genotypic and phenotypic spectrum of DSP -mediated disease at a large population level. Methods: UK Biobank participants with exome sequencing (ES) were included. Variants were filtered by gene evidence category, yielding 3 groups: predicted deleterious (pDel); subset with predicted loss of function (LOF); and ultra-filtered subset by ClinVar 2* pathogenic/likely pathogenic (P/LP). Phenotypic penetrance was analyzed with DSP -neg individuals as control. Variant location analysis assessed LOFs by susceptibility to nonsense mediated decay region and missenses by amino acid sequence to identify mutational hotspots where P/LPs localize. Results: Out of 200,580 with ES, 1407 DSP carriers had pDel, 168 with LOF, and 44 with ClinVar 2* P/LP. DSP carriers had higher burden of myocarditis, cardiomyopathy (CM), and heart failure. A progressive enrichment in myocarditis and CM was observed by more stringent variant filtering in DSP carriers compared to control. A higher proportion of DSP carriers had myocarditis – 0.28% (4) of the pDels, 1.8% (3) of LOFs, and 4.5% (2) compared to control 0.07% (p&lt;0.05). A parallel trend noted the proportion of DSP carriers with CM growing from 1.4% (19) to 5.4% (9) and 6.8% (3) in the pDel, LOF, and ClinVar 2* P/LPs respectively compared to 0.6% in the control group (p&lt;0.01). Location analysis of missense variants revealed that P/LPs localized in higher proportions (74%) to key domains compared to non-P/LPs (50%; p&lt;0.001), highlighting prognostic value of predicting pathogenicity of missense DSP variants by mutation hotspots. Conclusions: While DSP variants are relatively common in the population, variant presence is associated with low penetrance. Enhancing clinical penetrance with increasingly stringent filtering of DSP variants emphasizes the importance of variant evaluation in clinical risk assessment. This first-in-kind population study of DSP provides insights into novel risk prediction factors, allowing us to predict pathogenicity by type and location of mutation and using variant filtering strategy to better assess phenotypic penetrance.