tbuckley/cabot-search huggingface dataset:
Abstract 15351: Changes in Left Ventricular End-diastolic Pressure Following Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy
Authors: Courtney Kramer, Matthew C Evans, Andrew Dorsey, Chris Nielsen, VALERIAN Fernandes
Journal: Circulation (2020)

Background: LVEDP is a representation of left ventricular diastolic function. An increased LVEDP correlates to decreased compliance and increased left ventricular workload, which can be seen in HOCM. In HOCM, the interventricular septum is hypertrophied creating a LVOT obstruction and elevated LVEDP. ASA induces a targeted septal infarction to reduce the size of the septum and relieve the LVOT obstruction. Non-targeted infarction in a MI can increase LVEDP. Our study aims to determine the immediate effect of ASA on LVEDP in HOCM patients. It is hypothesized that ASA immediately reduces LVEDP. Methods: Retrospective study of 113 patients where pre and post-ablation LVEDP were compared. LVEDP was measured at the end-expiratory R wave of the ECG tracing during the procedure. LVEDP measurements were recorded at the post-“a” wave points at the immediate start of the procedure (Group A), prior to the alcohol injection under mild sedation (Group B), and at the conclusion of the successful ablation (Group C). Results: Groups A, B, and C were compared using two-tailed t-tests. We found no statistical difference between groups A and B (mean A=31.34 vs. mean B=31.54; p=0.695). LVEDP was significantly lower in group C when compared to group A (mean A=31.34 vs. mean C=25.82; p=6.525E-9). LVEDP was also significantly lower in group C when compared to group B (mean B=31.54 vs. mean C=25.82; p=4.047E-9). A linear regression model showed no significant correlation between LVEDP and LVOT gradient reduction following ASA (R 2 =0.0258, Significance F=0.0891). Conclusion: This data supports our hypothesis that ASA immediately reduces LVEDP despite inducing an infarct of the septal myometrium. There is no effect of sedation on LVEDP during the procedure. Since LVEDP reduction does not seem to correlate with LVOT gradient reduction, the reduction in LVEDP is likely related to other hemodynamics improvements including reduction in mitral regurgitation and immediate improvement in diastolic function. Future studies can include evaluating a correlation between LVEDP reduction and immediate hemodynamic changes. They could also evaluate a correlation between the immediate drop in LVEDP and long-term outcomes to predict the prognosis of HOCM patients based on their ASA outcomes.
Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine
Authors: Margaret S. Johnston, Anjela Galan, Kalman L. Watsky, Alicia J. Little
Journal: JAMA Dermatology (2021)

In response to the coronavirus disease 2019 (COVID-19) pandemic, 2 mRNA vaccines (Pfizer-BioNTech and Moderna) received emergency use authorization from the US Food and Drug Administration in December 2020. Some patients in the US have developed delayed localized cutaneous vaccine reactions that have been dubbed "COVID arm."To describe the course of localized cutaneous injection-site reactions to the Moderna COVID-19 vaccine, subsequent reactions to the second vaccine dose, and to characterize the findings of histopathologic examination of the reaction.This retrospective case series study was performed at Yale New Haven Hospital, a tertiary medical center in New Haven, Connecticut, with 16 patients referred with localized cutaneous injection-site reactions from January 20 through February 12, 2021.We collected each patient's demographic information, a brief relevant medical history, clinical course, and treatment (if any); and considered the findings of a histopathologic examination of 1 skin biopsy specimen.Of 16 patients (median [range] age, 38 [25-89] years; 13 [81%] women), 14 patients self-identified as White and 2 as Asian. The delayed localized cutaneous reactions developed in a median (range) of 7 (2-12) days after receiving the Moderna COVID-19 vaccine. These reactions occurred at or near the injection site and were described as pruritic, painful, and edematous pink plaques. None of the participants had received the Pfizer-BioNTech vaccine. Results of a skin biopsy specimen demonstrated a mild predominantly perivascular mixed infiltrate with lymphocytes and eosinophils, consistent with a dermal hypersensitivity reaction. Of participants who had a reaction to first vaccine dose (15 of 16 patients), most (11 patients) developed a similar localized injection-site reaction to the second vaccine dose; most (10 patients) also developed the second reaction sooner as compared with the first-dose reaction.Clinical and histopathologic findings of this case series study indicate that the localized injection-site reactions to the Moderna COVID-19 vaccine are a delayed hypersensitivity reaction. These reactions may occur sooner after the second dose, but they are self-limited and not associated with serious vaccine adverse effects. In contrast to immediate hypersensitivity reactions (eg, anaphylaxis, urticaria), these delayed reactions (dubbed "COVID arm") are not a contraindication to subsequent vaccination.
Abstract 17405: Chronic Treatment of Ibrutinib Reduces PI3K Activation and Causes Increased Mitochondrial Oxidative Stress Leading to Heightened AF in <i> Pitx2c <sup>+/-</sup> </i> Mice
Authors: Arvind Sridhar, ambili menon, Liang HONG, Brandon Chalazan, Meihong Zhang, Olivia T Ly, Dawood Darbar
Journal: Circulation (2020)

Background: Ibrutinib, a Bruton’s tyrosine kinase inhibitor which is currently used as first line treatment to various B-cell malignancies is known to cause proarrhythmic effects in patients thus limiting its continual use. Ibrutinib treated patients have been shown to be at a 4-fold increased risk of developing atrial fibrillation (AF), but the underlying molecular mechanisms remain unclear. Studies have shown that Pitx2 , the nearest gene to the 4q25 locus has been implicated in AF pathology and thus can serve as an experimental model for clinical AF. Objective: The goal of this study is to assess the role of the late cardiac Na current (I Na,L ), PI3K activation, and oxidative stress in mediating the increased susceptibility to AF in Pitx2c +/- mice and atrial human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to ibrutinib. Method: Pitx2c +/- mice were administered ibrutinib (30mg/kg/day IP) for 23 days after which their AF burden were assessed using transesophageal rapid pacing (TErP) along with their weight, BP, and plasma glucose. Atrial hiPSC-CMs were exposed to ibrutinib for 48 hrs. ELISA, IHC, Western blotting, cellular patch clamping and, qPCR studies were performed. Results: Pitx2c +/- mice were exposed to ibrutinib showed a graded increase in AF burden. ( Fig. 1A-C ). There was a decreased activation of the PI3K pathway and pAkt leading to overall decrease in SERCA2a expression ( Fig. 1D-F ). There was a significant increase in mitochondrial fragmentation and superoxide production in ibrutinib treated atrial hiPSC-CMs ( Fig G ) and the action potential duration at 90% repolarization and the I Na-L were markedly prolonged after ibrutinib exposure( Fig H ). Conclusion: We showed in Pitx2c +/- mice and atrial hiPSC-CMs that ibrutinib-mediated AF may in part be related to enhanced I Na-L , decreased activation of PI3K and SERCA2a and increased fibrosis leading to mitochondrial fragmentation and increased oxidative stress.
Abstract P030: Complementary Variable Selection Methods Highlight Joint Contribution Of Cystatin C And Apolipoprotein B For Cardiovascular Risk Prediction
Authors: Joshua Elliott, Matthew Whitaker, Barbara Bodinier, Paul Elliott, Ioanna Tzoulaki, Marc Chadeau-Hyam
Journal: Circulation (2021)

Introduction: Variable selection methods can provide an unbiased means of identifying informative predictors but have rarely been applied to CVD risk prediction. Hypothesis: Additional variables beyond those in pooled cohort equations may improve CVD risk prediction. Methods: Use of two complementary variable selection methods (LASSO stability selection, parametric, and survival random forests, non-parametric) to identify jointly informative sets of predictors for CVD risk and rank them in order of predictive accuracy. We used a prospective cohort (UK Biobank) of 304,839 participants aged 40-69 years at enrollment (2006—2010) without prior CVD, with follow-up to March 2017. Variables comprised those in pooled cohort equations with additional biochemistry and hematology data and polygenic risk scores for CVD. Outcomes were CVD hospitalization, procedure/operation or mortality. Data were sex-stratified and divided into independent variable selection (40%), training (30%) and test (30%) sets. Variable selection via penalized (LASSO) Cox regression with stability analysis. Variables ranked according to mean change in C statistic after variable permutation in survival random forests. Results: Mean age 55.9 years; 10,267 CVD events (6,277 men [59.0%]), median 8.1 years follow-up. The Figure summarizes results from LASSO stability selection. Jointly informative predictors for both men and women were cystatin C, apolipoprotein B, family history of coronary artery disease and polygenic risk score in addition to age, systolic blood pressure, antihypertensive use and current smoking used in pooled cohort equations. Other than variables already included in pooled cohort equations, cystatin C and apolipoprotein B ranked highest in random forests for men and for women. Conclusions: Use of two complementary data-driven variable selection methods identified variables more highly selected for CVD prediction beyond those included in pooled cohort equations.
Abstract 12969: Potential of Targeted Nanotherapy for Vascular Inflammation With Gold Nanoparticles
Authors: Hisanori Kosuge, Maki Nakamura, Ayako Oyane, Atsushi Taninaka, Hidemi Shigekawa, Taishiro Chikamori, Kazutaka Aonuma
Journal: Circulation (2020)

Introduction: Inflammation contributes to progression of both atherosclerosis and abdominal aortic aneurysms (AAA). Gold nanoparticles (GNPs) have imaging and therapeutic properties, as they can ablate cells through optical excitation. We have shown that GNPs are taken up by vascular macrophages and can be used to detect murine carotid atherosclerosis and AAA with computed tomography (CT). In this study, we evaluated GNPs for optical ablation of macrophages in vitro and ex vivo. Methods: Mouse macrophage cells were incubated with or without 100 or 200 μg/ml of GNPs (15 nm) for 24 hours. Ten million cells with or without GNPs were exposed to near-infrared (NIR) laser light (830 nm, pulse width 200 femtosecond) for 10-20 minutes at 400-437 mW. After optical excitation, cells were incubated for 24 hours, and the viability was measured by MTT assay. Male apoE-deficient mice were subject to continuous angiotensin II infusion via subcutaneously implanted osmotic mini-pumps (N=4). After 2 weeks, mice were injected with GNPs (10 mg/mouse) via tail vein. At 48 hours post-injection, aortas were excised. Excised aortas were scanned with micro-CT imaging system and exposed to the laser for 20 minutes at 364 mW. After optical ablation, the sections of aortas were stained with anti-caspase-3 antibody. Results: With the higher dose of GNPs (200 μg/ml), cell viability was significantly reduced by in vitro optical excitation for 10 minutes (Figure 1, left; p&lt;0.05). With the lower dose of GNPs (100 μg/ml), cell viability was significantly reduced by 20-minutes excitation, although 10-minutes excitation was not sufficient to reduce cell viability (Figure 1, right; p&lt;0.003). Ex vivo CT imaging showed the accumulation of GNPs in adventitia of aorta (Figure 2). Ex vivo optical excitation showed minimal apoptosis induction of macrophages in adventitia. Conclusion: Optical excitation of GNPs causes macrophage ablation and has potential for targeted nanotherapy of vascular inflammation.
Abstract 16856: Mathematical Modeling of Blood Flow to Evaluate the Hemodynamic Significance of Peripheral Vascular Lesions
Authors: Seyed Mehran Mirramezani, Paul Cimadomo, Ernie Ahsan, David Shavelle, Leonardo Clavijo, Shawn C Shadden
Journal: Circulation (2020)

Introduction: Evaluating the severity of lesions in peripheral arteries is challenging. Image-based blood flow modeling from peripheral computed tomographic angiography (pCTA) may provide a non-invasive method to determine the hemodynamic significance of lesions. The objective of this study was to evaluate the diagnostic performance of a trans-lesion pressure drop computed from pCTA-based blood flow modeling in the peripheral arteries. Methods: Ten patients undergoing digital subtraction angiography (DSA) and pCTA were included. The peripheral arteries were divided into 8 segments per extremity and stenosis severity was visually graded by DSA as non-stenosed (grade 0), mild (grade I), moderate (grade II), severe (grade III), occluded (grade IV) or non-evaluable. A functionally significant lesion was defined as grade III or IV by DSA. Independent from the DSA review, a resting pressure gradient (rPG) and exercise PG (ExPG) for each segment was calculated from pCTA-based blood flow modeling (Figure), and a functionally significant lesion was defined as having an rPG &gt; 5 mm Hg or an ExPG &gt; 20 mm Hg. Results: Mean age was 52±16 years, 4 patients (40%) were male, 8 patients (80%) presented with critical limb ischemia, mean ankle brachial index was 0.60±0.29 and 66 arterial segments were available for both assessment methods. Twenty-two segments had functionally significant lesions by DSA. For rPG, sensitivity was 80%, specificity was 85% and accuracy was 79% with DSA as the standard; for ExPG, sensitivity was 84%, specificity was 89% and accuracy was 88%. Conclusions: Use of a resting pressure gradient &gt; 5 mm Hg and an exercise pressure gradient &gt; 20 mm Hg measured by peripheral computed tomography-based blood flow modeling accurately identifies functionally significant stenosis in patients with advanced peripheral vascular disease. These results support a prospective imaging trial to further validate this novel approach.
Abstract P084: The Association Of Socioeconomic Status With Ideal Cardiovascular Health In African American Males
Authors: Rosevine A Azap, Timiya Nolan, Darrell Gray, Kiwan Lawson, John Gregory, Quinn Capers, James Odei, Joshua J Joseph
Journal: Circulation (2021)

Introduction: African American (AA) men are burdened by high cardiovascular risk and have the highest age-adjusted all-cause mortality rate in the United States of America (US). Socioeconomic status (SES) is associated with improved cardiovascular risk factors in majority populations, but there is a paucity of data in AA men. Hypothesis: We hypothesized that higher levels of socioeconomic status would be associated with higher attainment of ideal cardiovascular health in AA men. Methods: We examined the association of socioeconomic status measures including education, income, occupation, and insurance status with an ideal cardiovascular health (ICH) score which included blood pressure, glucose, cholesterol, body mass index (BMI), physical activity, and smoking in African American Male Wellness Walks (AAMWW). Six metrics of ICH were categorized into a three-tiered ICH score 0-2, 3-4, 5-6. Ordinal logistic regression modeling was performed with adjustment for age. Results: Among 1,444 men, 108 (7%) attained 5-6 ICH metrics at baseline. After adjustment for age, none of the baseline indicators of socioeconomic status were associated with attainment of ICH. Conclusion: In our community-dwelling sample of AA men, the proportion of individuals with highest scores for ICH was very low, and SES was not associated with greater attainment of ICH. Strategies to increase attainment of cardiovascular health in AA men by health care professionals and policymakers need to incorporate intentional interventions beyond the scope of SES in order to advance health equity in AA men.
Abstract MP61: Greater Late-life Physical Function Declines Among Older Adults With Higher Blood Pressure In Mid-life: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Laura Skow, J Coresh, J Deal, Rebecca F Gottesman, Jennifer Schrack, A Richey Sharrett, Priya Palta, Kunali Parimal Ghelani, Michael Griswold, Kevin Sullivan, B Gwen Windham
Journal: Circulation (2021)

Introduction: Greater late-life physical function decline is associated with incident adverse outcomes including disability and death. Hypertension is the strongest risk factor for stroke, the major cause of physical disability. Hypertension in mid-life has previously been associated with poor physical functioning in late-life; however, more evidence is needed to evaluate whether higher blood pressure in mid-life is associated with the rate of physical function decline during late-late in the absence of stroke. We hypothesized that elevated blood pressure in mid-life would be associated with greater physical function declines in late life. Methods: We studied 5,559 older adults in the ARIC Study (Visit 5; mean age: 75.8 years; range: 66.7-90.9 years; 58% women; 21% Black/79% White) without prior stroke or Parkinson disease who completed the Short Physical Performance Battery (SPPB, scored 0-12). Repeated SPPB assessments occurred at Visits 6 and 7 (median follow-up: 4.2 years). The exposure was a history of elevated blood pressure (BP) (Visit 1; mean age: 52.0 years; mean gap between mid- and late-life exams: 23.7 years). BP was modeled both categorically (hypertensive: SBP 140+ mmHg, DBP 90+ mmHg, or antihypertensive medication use; pre-hypertensive: SBP 120-139 mmHg or DBP 80-89 mmHg; else normotensive) and continuously. Random-slope, random-intercept mixed models with an independent covariance structure tested the association between BP and SPPB score change, adjusted for age, sex, race-site, BMI, education, heart disease and heart failure. Continuous analysis also adjusted for antihypertensive medication use. Results: SPPB scores declined an average of 1.60 points per 10 years (95% CI: -1.75, -1.46; p&lt;0.001) among older adults who were normotensive in mid-life. Older adults with a previous measurement of hypertension declined an additional 0.94 points per 10 years (95% CI: -1.27, -0.60; p&lt;0.001). Prehypertension was not statistically significantly associated with additional decline compared to mid-life normotension (estimate: -0.19 SPPB points/10 years; 95% CI: -0.53, 0.16; p=0.293). In the continuous analysis, each additional 10 mmHg higher mid-life systolic blood pressure above 120 mmHg was associated with an additional 0.24 point decline in SPPB per 10 years in late-life (95% CI: -0.31,-0.14; p&lt;0.001). Conclusions: Elevated BP in mid-life provides insight into the rate of physical function decline decades later, with higher mid-life systolic blood pressure corresponding with steeper declines in late-life physical function even in the absence of stroke. Future research should investigate whether elevated blood pressure at multiple points in mid-life further informs the association.
Does Health Inequity Begin at Home?
Authors: Edward P. Havranek
Journal: JAMA Cardiology (2021)

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Blood Pressure Difference between Medium-sized and Large Artery in Association with Age: Invasive Study
Authors: Kim Eung Ju, Park Chang Gyu, Kim Ji Hun, Shin Seung Yong, Ju Hyung Jun, Suh Soon Yong, Park Mi Young, Choi Cheol Ung, Kim Jin Won, Lim Hong Euy, Rha Seung Woon, Ahn Jeong Cheon, Song Woo Hyuk, Seo Hong Seog, Oh Dong Joo
Journal: Circulation (2007)
Abstract 17051: Bromocriptine Improves Central Aortic Stiffness in Adolescents With Type 1 Diabetes Mellitus: Arterial Health Results From the BCQR-T1D Study
Authors: Michal Schafer, Lorna Browne, Uyen Truong, Petter M Bjornstad, Amy Baumgartner, Alexander J Barker, Kendall Hunter, Shoshana Tell, Janet Snell-bergeon, Jane E Reusch, Irene Shauer, Kristen Nadeau
Journal: Circulation (2020)

Introduction: The presence of global vascular dysfunction is a well-recognized feature in youth with type 1 diabetes (T1D). This predisposes young patients to the life-long exposure and increased incidence of cardiovascular events. Therapeutic strategies to mitigate vascular dysfunction are urgently needed. Hypothesis: We hypothesized that bromocriptine quick release (BCQR) therapy would improve vascular health in youth with T1D. Methods: This was a placebo-controlled, random-order, double-blinded, cross-over study investigating BCQR as adjunct therapy on central aortic stiffness as measured by phase-contrast MRI. Participants also underwent flow mediated dilation test and brachial distensibility evaluation using tonometry. Adolescents with T1DM were randomized 1:1 to phase-1 of 4-week BCQR (minimum dose 1.6 mg daily) or placebo therapy after which all vascular measurements were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment. Results: Forty-two adolescents (mean age 15.9 yrs, HbA1c 8.6%, BMI %ile 71.4, TD duration 5.8 yrs) with T1D were enrolled. BCQR therapy decreased systolic (Δ = -5 mmHg, p &lt; 0.001) and diastolic blood pressure (Δ = -2 mmHg, p = 0.039). BCQR therapy reduced ascending aortic PWV (Δ = -0.4 m/s, p = 0.005), and increased RAC (Δ = -2.6%, p = 0.022), and distensibility (Δ = 0.08 %/mmHg, p = 0.010). In the thoraco-abdominal aorta, BCQR decreased PWV (Δ = -0.2 m/s, p = 0.013) and increased distensibility (Δ = 0.05 %/mmHg, P = 0.032) (FIGURE). In contrast, BCQR decreased RHI (Δ = -0.34, p = 0.006). Conclusions: BCQR therapy improved central aortic stiffness and pressure hemodynamics in adolescents with T1D over 4 weeks. However, BCQR decreased peripheral RHI. BCQR therapy might serve as a potential clinical intervention to attenuate accelerated aortic stiffness in youth with T1D supporting future longer-term studies.