tbuckley/cabot-search huggingface dataset:
Abstract 11370: Comparing Coronary Artery Cross-Sectional Area Among Asymptomatic South Asian, White, and Black Participants: The Masala and Cardia Studies
Authors: Robert T Short, Jeffrey Carr, Sangeeta Nair, James G Terry, Donald M Lloyd-Jones, Namratha Kandula, Alka M Kanaya, Feng Lin
Journal: Circulation (2023)

Introduction: South Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible. Hypothesis: We hypothesized that South Asian participants would have smaller left anterior descending artery (LAD) cross sectional area (CSA) than Black and White participants, and that this association would be attenuated after adjusting for body size (BMI and height) and cardiovascular risk factors. Methods: We compared the LAD CSA (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America study with White and Black participants in the Coronary Artery Risk Development in Young Adults study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to explore differences by race/ethnicity in LAD CSA after adjusting for demographic, BMI, height, coronary artery calcium (CAC), and ASCVD risk factors. Results: We included 3,353 participants: 513 South Asian (44% women), 1286 Black (60% women), and 1554 White (54% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian and White participants by sex. However, South Asian participants had smaller LAD CSA compared to Black participants by sex. After full adjustment for ASCVD risk factors, LAD CSA values were: South Asian women (19.9 mm 2 , 95% CI [18.8 - 20.9]) and men (22.3 mm 2 , 95% CI [21.4 - 23.2]; White women (20.0 mm 2 , 95% CI [19.4 - 20.5]) and men (23.6 mm 2 , 95% CI [23.0 - 24.2]); and Black women (21.6 mm 2 , 95% CI [21.0 - 22.2]) and men (26.0 mm 2 , 95% CI [25.3 - 26.7]) ( Figure 1 ). Conclusions: After accounting for differences in body size, South Asian participants had smaller LAD CSA compared to Black participants, but similar to White participants. Future studies should determine whether LAD CSA is associated with future ASCVD events.
Abstract 11323: Improving Risk Assessment With Generalized Cardiovascular Disease Risk Score
Authors: Jeremy B Sussman, TIMOTHY HOFER, David Ratz, Wyndy Wiitala, David Flood, Jennifer Burns, Stephanie Visnic, Bradley Youles, Rodney Hayward
Journal: Circulation (2023)

Introduction: Clinical practice usually divides cardiovascular (CV) disease prevention patients into distinct primary (1 o ) and secondary (2 o ) prevention groups. Hypothesis: That a generalized CVD risk prediction model will find overlap in risk between primary and (2 o ) prevention patients and variation within them, allowing better targeting of interventions for CV risk. Methods: We followed all patients aged 40-75 who visited a Veterans Affairs outpatient clinic during the year 2010. The primary outcome was having a new ASCVD event in 5 years of follow-up. We used one risk score based on existing risk scores (traditional model) and developed a second using elastic net logistic regularization that with over 100 variables from the electronic health record (VARS+). All models were assessed for predictive accuracy. Models were developed on an 80% sample of the dataset and tested on the remaining 20%. Results: The sample had 742,787 patients, over 20,000 of whom were women. 7.7% had a history of heart attack, 5.2% stroke, and 27% had diabetes. 30% of male participants and 23% of women an event during follow-up. The c-statistic is 0.75 for the traditional model and 0.77 for the VARS+ model, with good calibration in both. There was substantial overlap between 1 o and 2 o prevention (Figure). There was a wide range of risk, such that secondary prevention patients in the 25 th and 75 th percentiles for overall risk had 5-year event rates of 14.1% and 32.1%, respectively. Discussion: CV disease prevention could be better targeted in some cases by reducing the distinction between 1 o and 2 o prevention in favor of a focus on generalized risk.
Abstract 11913: Prognostic Value of Right Ventricular-Pulmonary Arterial Coupling in Adults With Repaired Coarctation of Aorta
Authors: Snigdha Karnakoti, Omar Abozied, Ahmed Younis, Sriharsha Kandlakunta, Marwan Ahmed, Alexander C Egbe
Journal: Circulation (2023)

Introduction: Right ventricular (RV) systolic dysfunction and pulmonary hypertension is present in 20% of adults with repaired coarctation of aorta (COA). However, the prognostic value of RV to pulmonary artery (RV-PA) coupling in this population is unknown. Objective: The purpose of this study was to assess the relationship between RV-PA coupling and clinical outcomes (heart failure hospitalization and all-cause mortality) in this population. Methods: Retrospective cohort study of adults with repaired COA and normal RV systolic function defined as RV-free wall strain ≥-24%. RV-PA coupling was assessed using tricuspid annular plane systolic excursion/ RV systolic pressure (TAPSE/RVSP) ratio. Results: Of 509 patients (median age 32 [20-45] years; men 290 [57%]), the average TAPSE and RVSP were 22±5 mm and 33±9 mmHg, respectively, and TAPSE/RVSP ratio was 0.78 (0.56-0.96) mm/mmHg. Of 509 patients, 51 (10%) died and 43 (8%) were hospitalized for heart failure. TAPSE/RVSP was associated with all-cause mortality (hazard ratio 0.82, 95% confidence interval 0.78-0.86, per 0.1 mm/mmHg), and heart failure hospitalization (hazard ratio 0.86, 95% confidence interval 0.79-0.83, per 0.1 mm/mmHg) after adjustment for anatomic lesions, cardiovascular interventions, comorbidities, and echocardiographic indices. The inclusion of TAPSE/RVSP ratio in the risk models improved the prognostic power of the models to predict all-cause mortality (C-statistics difference 0.046, p&lt;0.001), and heart failure hospitalization (C-statistics difference 0.031, p=0.007). Conclusions: TAPSE/RVSP ratio was associated with outcomes in COA patients with normal RV systolic function, suggesting that abnormal RV-PA coupling may be present prior to the onset of overt RV systolic function in this population.
Abstract 11906: Targeting Metabolic Alterations in Smooth Muscle Cells Associated With an <i>Acta2</i> Pathogenic Variant Prevents Moyamoya-Like Cerebrovascular Disease
Authors: Anita Kaw, TING WU, Zhen Zhou, Zbigniew Starosolski, Albert J Pedroza, Kaveeta Kaw, Sean P Marrelli, Ketan Ghaghada, Callie Kwartler, Dianna M Milewicz
Journal: Circulation (2023)

Pathogenic variants disrupting arginine 179 ( R179 ) in ACTA2 (encodes smooth muscle α-actin) predispose to moyamoya ( MMD )-like cerebrovascular disease, characterized by occlusion of the distal internal carotid arteries by cells that stain positive for smooth muscle cell ( SMC ) markers. SMCs explanted from mice with a SMC-specific knock-in of the Acta2 R179C mutation ( Acta2 SMC-R179C/+ [PMID: 35878552]) fail to fully differentiate, maintain stem cell marker expression, and proliferate and migrate faster than wild-type ( WT ) SMCs. Consistent with a stem cell-like phenotype, Seahorse assays and metabolomics analyses found that Acta2 SMC-R179C/+ SMCs have increased glycolytic flux and decreased oxidative respiration ( OXPHOS ) associated with reduced mitochondrial DNA ( mtDNA ) and complex I activity when compared to WT SMCs. Exposing Acta2 SMC-R179C/+ SMCs to nicotinamide riboside ( NR ), a NAD+ analogue, decreases glycolysis and increases OXPHOS by enhancing complex I activity, and with this metabolic switch, Acta2 SMC-R179C/+ SMCs increase differentiation and decrease migration. With left carotid artery ligation ( LCAL ), 21% of Acta2 SMC-R179C/+ mice die of strokes within 5 days, and at postop day 21, 100% of the surviving Acta2 SMC-R179C/+ mice have enlarged left carotid arteries occluded with cells positive for SMC marker; compared to only 8% of the WT mice. The Acta2 SMC-R179C/+ mice 21 days post LCAL also have increased leptomeningeal collateral remodeling and Circle of Willis (CoW) narrowing and straightening based on CT imaging with liposomal-iodinated contrast agent. NR treatment reduces deaths with LCAL in the mutant mice (p=0.20), resolves intraluminal occlusive lesion formation (p&lt;0.05), attenuates CoW narrowing and straightening (p&lt;0.05), and prevents aberrant collateral remodeling (p&lt;0.001). These results define the pathogenesis of MMD lesions associated with ACTA2 R179 variants: the mutation disrupts the differentiation of stem cells into SMCs, leading to increased SMC migration and proliferation and MMD-like lesions with LCAL, and identify a potential therapeutic that alters SMC metabolism to drive differentiation and decrease migration, and ultimately attenuate MMD-like cerebrovascular disease in Acta2 SMC-R179C/+ mice.
Abstract 11836: A Rare Cause of Recurrent Myocardial Infarction: Genetic Testing Cracks the Case
Authors: John A Bostrom, Ashvin N Pande, Frederick Ruberg, Omar Siddiqi, Pavel Kopach, Darae Ko, Monica Ahluwalia
Journal: Circulation (2023)

A 29-year-old man presented to our institution with acute, severe substernal chest pain. An ECG on arrival revealed 3mm ST-elevations in the lateral leads with reciprocal depressions in the inferior leads. Troponin-I was above assay (&gt;50 ng/mL). Emergent coronary angiography showed normal coronary arteries, and left ventriculogram showed no wall motion abnormalities. A transthoracic echocardiogram showed normal biventricular size, wall thickness, and ejection fraction (EF). This was his fifth episode of chest pain over the past 10 years, consistent with prior presentations of ST-elevation myocardial infarction and angiographically normal coronary arteries. A prior cardiac magnetic resonance imaging (MRI, 6 years before the current presentation) revealed increased T2 signal intensity and subepicardial late gadolinium enhancement (LGE) in the septum, inferior, and inferolateral walls, suggestive of nonischemic acute myocardial injury. A repeat cardiac MRI during the current presentation showed mildly reduced biventricular systolic function (LVEF 52%, RVEF 36%), and again showed increased T2 signal intensity and subepicardial LGE involving the septum, inferior and inferolateral walls. The anterior and anterolateral walls were also now involved. Endomyocardial biopsy (EMB) showed focal interstitial fibrosis with no evidence of active myocarditis. On telemetry he was noted to have runs of non-sustained ventricular tachycardia (NSVT). Serologic evaluation was negative for parvovirus, cytomegalovirus, and Chagas disease. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Genetic testing was performed at our newly established cardiovascular genetics program, which showed a pathogenic truncating mutation in the desmoplakin gene (DSP). DSP cardiomyopathy (CM) is an LV-predominant arrhythmogenic CM, which can present with episodic myocardial injury, and has a high disposition for ventricular arrhythmias with subepicardial LGE pattern often proceeding LV systolic dysfunction. A primary prevention implantable cardioverter-defibrillator was placed given extent of LGE and NSVT burden in the context of DSP variant. This case illustrates the importance of genetic testing in identifying rare CM phenotypes.
Abstract 111: Combination Therapy of Hydrogen Inhalation and Hypothermic Temperature Control Improves Neurological Outcomes After Out-of-Hospital Cardiac Arrest
Authors: Tomoyoshi Tamura, Hiromichi Narumiya, Masaru Suzuki
Journal: Circulation (2023)

Background: In a randomized trial, we demonstrated that hydrogen (H 2 ) inhalation improves outcomes after cardiac arrest (CA). All patients underwent target temperature management (TTM), but the selection of a target temperature between 32 and 36 °C varied per institutional protocol. Hypothesis: The combination of hypothermic TTM and H 2 improves neurological outcomes after CA. Aims: This study aimed to investigate the interaction of H 2 and hypothermic TTM on neurological outcomes after CA. Methods: This post-hoc analysis of a randomized controlled trial (HYBRID II Trial; jRCTs031180352) included comatose patients after cardiogenic out-of-hospital CA (OHCA). They received either 2% H 2 mixed oxygen (H 2 group) or oxygen alone (control group) for 18 hours under hypothermic TTM (&lt;35°C) or normothermic TTM (35-36°C). A target temperature was reached quickly, maintained for 24 hours, and rewarmed over 48 hours. A good neurological outcome was defined as a Cerebral Performance Category (CPC) of 1 or 2 at 90 days. The neurological outcomes were compared between the H 2 and control groups under hypothermic or normothermic TTM. Results: The analysis included 72 patients with outcome data (39 and 33 patients in the H 2 and control group, respectively). Hypothermic TTM was implemented in 25 (64%) and 24 (73%) patients in the H 2 and control group, respectively (P=0.46). Under hypothermic TTM, 17 (68%) and 9 (38%) patients achieved CPC 1 or 2 in the H 2 and control group, respectively (relative risk 1.81 [95%CI: 1.05-3.66]). In contrast, under normothermic TTM, CPC of 1 or 2 was achieved in 5 (36%) and 4 (44%) patients (P&gt;0.99) in the H 2 and control group, respectively. A multivariable logistic regression analysis indicated that the interaction between H 2 and hypothermic TTM was independently associated with CPC 1 or 2 at 90 days (adjusted odds ratio 3.71 [95%CI: 1.14-12.1]) after adjusting for confounding factors including age, sex, witness status, bystander CPR implementation, shockable rhythm, CA duration, and time from the return of spontaneous circulation to gas inhalation. Conclusions: H 2 in combination with hypothermic TTM improved neurologicaloutcomes after cardiogenic OHCA. However, the favorable effects of inhaled H 2 were not observed under normothermic TTM.
Abstract 13763: Reducing Cardiovascular Disease Risk by Estrogen Treatment After Surgical Menopause in Combination With the Suppression of Interferon Gamma Pathway in <i>Ldlr</i> Null Mice
Authors: Lin Zhu, Bridget Litts, Julia An, Jeffrey Rein, Sivaprakasam Chinnarasu, Macrae F Linton, John M Stafford
Journal: Circulation (2023)

Atherosclerotic cardiovascular disease (ASCVD) risk is increased in women after menopause, which has not been shown to be reversed by postmenopausal hormone therapy. To understand the underlying mechanism for the lack of improvement in ASCVD with hormone therapy, Ldlr -/- mice with established atherosclerosis were subjected to procedures of surgical menopause (ovariectomy, ovx), 17β-estradiol (E 2 ) treatment after ovariectomy (ovx+E 2 ), or sham. In all groups, hyperlipidemia was normalized with a chow diet. Ten weeks later, atherosclerosis burden and ASCVD risk were evaluated. Atherosclerosis was reversed by the resolution of hyperlipidemia in sham but not ovx nor ovx+E 2 mice. While E 2 treatment improved lipid management in ovx mice, we observed persistent inflammation, which presented as high levels of IFNγ, IL-6, and C-PEP2 as well as impaired HDL anti-atherogenic functions and unresolved inflammation in the atherosclerosis lesion. To further investigate the role of inflammation in persistent ASCVD during hormone therapy, the interferon gamma (IFNγ) pathway was suppressed in a second cohort of Ldlr -/- mice that were constituted with bone marrow from Ifn γ -/- mice following lethal irradiation. Similar to the 1 st cohort of mice, E 2 treatment improved ASCVD risk factors including hyperlipidemia and insulin actions. In mice carrying IFNγ -/- bone marrow, atherosclerosis lesion size was reversed with E 2 treatment, which was associated with decreased IFNγ and IL-6 in the blood. We are further investigating the HDL functions and lesion inflammation in this cohort. Our studies indicate that limiting inflammation may be needed in order to restore the cardiovascular benefits of menopause E 2 treatment.
Abstract 108: Mitochondria-Targeted S-Nitrosothiol MitoSNO Improves Neurological Recovery and Survival After Asphyxial Cardiac Arrest in Rats
Authors: Yusuke Endo, Lance B Becker, Ryosuke Takegawa, Tomoaki Aoki, Eriko Nakamura, Michael P. Murphy, Kei Hayashida
Journal: Circulation (2023)

Introduction: Mitochondria-targeted S-nitrosothiol MitoSNO offers protection against ischemia-reperfusion injury by attenuating the reverse electron transport of mitochondrial complex I during reperfusion. This study aimed to assess whether administration of MitoSNO after ROSC improves neurological and survival outcomes following cardiac arrest (CA). Methods: Adult male rats were subjected to 10 minute of asphyxial CA followed by mechanical ventilation and manual CPR. After successful CPR, animals were assigned to one of two experimental groups: receiving respiration buffer as a vehicle or MitoSNO (100 ng per dose). Based on our preliminary study, two doses of each drug were intravenously injected via femoral vein: immediately after ROSC and at 60 minutes post-ROSC. The survival time and neurological function score (NFS) were recorded for up to 72 h. Surgery, CPR, drug injections, echocardiography, and immunohistochemistry were performed in a blind manner. Results: MitoSNO significantly improved NFS and survival rate ( Fig A ). Echocardiography revealed that MitoSNO improved left ventricular ejection fraction 2 h post-ROSC compared to the vehicle. In another set of experiments, relative cerebral blood flow (rCBF) compared to baseline was invasively monitored at 2 h post-CA using a laser speckle imaging. The imaging showed CA caused a reduction in rCBF 2 h post-CA in the vehicle group, which was markedly improved by MitoSNO ( Fig B ). Western blotting assay showed, in brain 2 h post-CA, MitoSNO significantly mitigated protein levels of 3-NT, a marker for nitrogen free radical-modified proteins, and cleaved Caspase-3, an indicator of programmed cell death. Immunohistochemistry revealed that MitoSNO suppressed neuronal degeneration in vulnerable brain regions of surviving animals. Conclusions: Our study demonstrated that MitoSNO inhibited the production of oxidative stress in the brain and improved neurological and survival outcomes following CA in rats.
Abstract 12680: Analysis of the Impact of Cardiovascular Disease on the Early Post-COVID Period Based on the ACTIV SARS-CoV-2 International Registry
Authors: Akhmetzhan Sugraliyev, Galiya Aimakhanova, Elizaveta Gordeychuk, Roman Bashkinov, Aleksandr Arutiunov
Journal: Circulation (2023)

Introduction: Cardiovascular disease (CVD) is a leading cause of mortality worldwide. The early post-hospitalization period following COVID-19 infection is critical due to high incidences of rehospitalization and deaths. Aim: To study the impact of CVD on the first 3 months after hospitalization for COVID-19. Methods: An international registry "ACTIV SARS-CoV-2" (NCT04492384) was established to characterize the course of COVID-19 in the Eurasian region and included 7 countries. The presented subanalysis used data of patients hospitalized during the acute phase of COVID-19. The post-COVID period was assessed based on telephone surveys of the patients 3 months (n=3099) after recovery. Results: 79.8% of patients required unscheduled medical care in the first three months post-recovery from SARS-CoV-2 infection, with 11.8% necessitating rehospitalization. Decompensation of various CVDs was the most common reason for unscheduled medical care (Table 1). The presence of CVD in people who had COVID-19, significantly increased the likelihood of death in the first 3 months after discharge from the infectious diseases hospital (OR 4.93; 95% CI 2.53-10.8; p&lt;0.001). The predominant causes of death were cardiovascular events, such as acute heart failure (22.4%; n=13), acute coronary syndrome (10.3%; n=6), acute cerebrovascular accident (10.3%; n=6), pulmonary embolism (3.4%; n=2), in addition to end-stage chronic kidney disease (5.2%; n=3). Conclusions: Analysis of data from the "ACTIV SARS-CoV-2" registry showed that CVD may be a risk factor for a more severe course of the early post-COVID period. Moreover, cardiovascular conditions were the leading cause of unscheduled healthcare encounters and death in the first 3 months after recovery from COVID-19, which may underscore the contribution of this infection to decompensation of CVD.
Abstract 13759: Impact of Shock Network Protocols on Reducing Cardiogenic Shock Death in STEMI Cases: A Middle Eastern Study
Authors: Fabrizio Clementi, Musab T Egaimi, Pierfrancesco Corvo, heeyoung seo, Alghafek Almorraweh, Wonsuk Choi, Kamil Vallabh, Lateefa Aidam, Sumera Haque, Abdulmajeed Al Zubaidi
Journal: Circulation (2023)

Introduction: The optimal use of mechanical circulatory support (MCS) in managing acute myocardial infarction with cardiogenic shock (AMICS) treated with percutaneous coronary intervention (PCI) remains a complex clinical challenge. In response to this, our study seeks to explore the implementation of a systematic Shock Protocol that integrates pre-PCI MCS in patients presenting with STEMI and SCAI class C and above. Hypothesis: Utilizing a prospective, multi-centre STEMI database, our study aimed to assess the impact of the Shock Protocol on survival at hospital discharge. Methods: From January 2022 to February 2023, five participating sites within our STEMI network committed to the study, adhering to a standardized protocol for AMICS treatment. The selection criteria mirrored those of the "SHOCK" trial. The survival rate at hospital discharge for this cohort was compared to pre-protocol implementation (October 2020-December 2021). Results: Of 745 STEMI cases, 418 and 327 were treated before and after protocol implementation. AMICS diagnoses were in 10.5% and 10.7% in the BSP and ASP groups, respectively. The mean ages were 53 (BSP) and 51 (ASP), with 90% males. Approximately 83% and 85% of BSP and ASP patients, respectively, were on vasopressors or inotropes at Cath-Lab arrival. Pre-Cath-Lab cardiac arrests (CA) occurred in 20% (BSP) and 33% (ASP), while post-arrival CA incidence was 30% (BSP) and 12% (ASP). MCS was used in 27% (BSP) and 87% (ASP). In ASP, 85% of devices were implanted pre-PCI. Median FMC-to-balloon times were 104 ±28.2 (BSP) and 77 ±41.6 (ASP) minutes. Discharge survival rates were 77% (BSP) and 82% (ASP). Mortality predictors: TIMI flow &lt;3 post-PCI, post-Cath-Lab CA, and SCAI class D/E. In SCAI class D/E patients, protocol implementation enhanced survival at hospital discharge. Conclusions: In our STEMI network, upfront MCS use in AMICS patients improved post-discharge survival.