bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13227: Safety and Effectiveness of Trans-Catheter Mitral Valve Repair in the Elderly and Very Elderly Patients
Authors: Mahnkopf Christian , Schnupp Steffen , Amami Majdi , Oudeh Mahmoud , Mady Hesham , Ajmi Issameddine
Published: April 2022

Introduction:
Symptomatic mitral regurgitation (MR) is associated with a high mortality rate and high HF-related hospitalization. Symptomatic therapy in the elderly and very elderly patients remains weak in controlling severe MR. Patients with an increased risk of surgical repair of the MR seemed to benefit from MitraClip procedures.

Hypothesis:
Therefore, we thought to analyze the postprocedural safety and success of the MitraClip in octogenarians and older patients.

Methods:
Elderly patients with severe and symptomatic MR were presented and evaluated in the heart team. Patients with high surgical risks underwent MitraClip (Abbot, USA) procedure in our center. Post-procedural transthoracic echocardiography (TTE) procedure was performed to determine the MR grade and exclude procedure-related complications.

Results:
Two hundred eleven consecutive patients, older than 80 years (83.75 ±2.95, 106 Men (83.5±3.06) and 105 Women (84.01±2.83)), who received MitraClip between May 2015 and May 2020 were enrolled. The baseline characteristics are presented in table 1. Procedural success, defined as reducing the MR to grad I-II, was achieved in 93% of the patients (3.11±0.34 vs. 1.25±0.46, P = 0.002). All patients improved in the New York Heart Association functional class (3.04±0.40 vs. 1.92±0.76 one year after the intervention). No procedure-related death was registered. 81% (n=168) survival rate was achieved one year after the intervention. No clip embolization was detected in 3 months echocardiography control, Table 2.

Conclusions:
Our preliminary results indicate that MitraClip is a safe and effective therapeutic option in Elderly and very elderly patients with severe MR and high surgical risks. Therefore, this therapy should be considered despite age and comorbidities for effective symptomatic treatment in this particular cohort.
Abstract 13266: Prognostic Impact Of Low On-treatment Diastolic Blood Pressure On The First Episode Of Stroke/Systemic Embolism In Japanese Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: Ikeda Syuhei , Iguchi Moritake , Ogawa Hisashi , Minami Kimihito , Ishigami Kenjiro , DOI KOSUKE , Hamatani Yasuhiro , Yoshizawa Takashi , Ide Yuya , Fujino Akiko , ISHII MITSURU , Masunaga Nobutoyo , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: April 2022

Background:
Atrial fibrillation (AF) is associated with an increased risk of cardioembolic stroke and systemic embolism (SE). A secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that low diastolic blood pressure (DBP) was not related to risk of the first episode of stroke in hypertensive patients who received prescription of any antihypertensive agents. However, data regarding the impact of low on-treatment DBP on the first episode of stroke or SE in AF patients are limited.

Methods:
The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available in 4,472 patients, and hypertensive patients who received prescription of any antihypertensive agents, and without prior stroke or SE were examined (n=1,934).We divided these patients into four groups based on the quartile of DBP; Q1 (DBP< 63 mmHg, n=463), Q2 (63 mmHg≤DBP<71 mmHg, n=463), Q3 (71 mmHg≤DBP<80 mmHg, n=484), Q4 (80 mmHg≤DBP, n=524), and compared the clinical background and the incidence of clinical events.

Results:
Patients in Q1 group were older (Q1 vs. Q2 vs. Q3 vs. Q4; 77.2±0.45 vs. 74.2±0.45 vs. 73.6±0.44 vs. 71.0±0.42; p<0.01), and had lower systolic blood pressure (SBP, 113.9±0.73 mmHg vs. 124.4±0.73 vs. 130.2±0.71 vs. 141.3±0.68; p<0.01). During the median follow-up of 3,005 days, the incidence rates of stroke/SE were higher in patients in Q1 group, and other groups were comparable (Q1: 1.7% per person-year vs. Q2: 1.1% vs. Q3: 1.0% vs. Q4: 1.1%; p<0.01). Multivariate Cox proportional hazards regression analysis revealed that lower DBP(<63 mmHg) was an independent determinant of the incidence of stroke/SE (adjusted hazard ratio: 1.47, 95% confidence interval: 1.05-2.06).

Conclusion:
In Japanese AF patients without prior stroke or SE, low on-treatment DBP was associated with the incidence of stroke or SE.
Abstract 13269: Combination Therapy With Sodium Nitrite and Hydralazine Ameliorates the Severity of Heart Failure With Preserved Ejection Fraction
Authors: Lapenna Kyle B , Li Zhen , Sharp Thomas E , Hidalgo Hunter A , Xia Huijing , Wang John S , Moles Karl H , Koul Kashyap , Alahari Nikhilesh , Goodchild Traci T , Lefer David J
Published: April 2022

Background:
Recent studies suggest that nitrosative stress resulting from an imbalance in nitric oxide (NO) is the primary driver of heart failure with preserved ejection fraction (HFpEF); however, many of the comorbidities present in HFpEF patients are driven by oxidative stress. Due to the failure of nitric oxide (NO) based therapeutics in HFpEF clinical trials and the role of oxidative stress in each of the different HFpEF comorbidities, we sought to investigate the effects of sodium nitrite (NaNO2) therapy alone or in combination with the antioxidant and peroxynitrite scavenger, hydralazine, in a novel, “two-hit” murine model of HFpEF.

Methods:
HFpEF was induced in nine-week-old C57/BL6N mice (n = 13-15 per group) by high fat diet and L-NAME (0.5 g/L/day) via drinking water for 10 weeks. At 5 weeks, mice were treated with vehicle, sodium nitrite(75 mg/L) via drinking water, hydralazine (2 mg/kg/day B.I.D., I.P, or a combination of sodium nitrite + hydralazine. Cardiac structure and function via echocardiography and exercise capacity were measured at baseline, week 5 (prior to treatment), and week 10 (final endpoint). At week 10, invasive hemodynamic and
in-vitro
vascular reactivity studies were performed.

Results:
Sodium nitrite and hydralazine combination therapy resulted in significant (p < 0.01) improvement inE/E’ that was superior to either therapy alone. Hydralazine as a monotherapy and in combination with NaNO2lowered the E/A ratio compared to NaNO2 monotherapy (p <0.05). Aortic vasorelaxation maximal responses to acetylcholine were significantly improved in all study groups with the greatest improvement observed withNaNO2 + hydralazine. Left ventricular end-diastolic pressure (LVEDP) was significantly (p < 0.01) reduced with either therapy alone, but our data indicate that combination therapy was superior to either drug alone.

Conclusion:
Our data suggest that antioxidant therapy is required in combination with NO based therapeutics in HFpEF.
Abstract 13273: Late Senolytic Therapy Improves Cerebrovascular Endothelial Function but Not Cognition in Middle-Aged Severely Atherosclerotic Mice
Authors: Lambert Melanie , Miquel Geraldine , Thorin-Trescases Nathalie , Thorin Eric
Published: April 2022

Introduction:
Age-related and atherosclerosis-related vascular dysfunction contributes to neuro-vascular uncoupling, which induces neuronal damage and leads to precocious cognitive loss. This dysfunction could be partially explained by the accumulation of senescent cells (SnC) that remain metabolically active and release many pro-inflammatory factors.

Hypothesis:
Targeted elimination of SnC with a senolytic restores cerebrovascular function, maintains neuro-vascular coupling and slows cognitive decline.

Methods and Results:
Nine-month old male atherosclerotic mice (ATX, LDLR
-/-
;hApoB
+/+
) were treated (n=13), or not (n=11), for 3 months with navitoclax (50mg/kg), a Bcl2 inhibitor that stimulates global elimination of SnC overexpressing this antiapoptotic pathway. Twelve-month old vehicle-treated ATX mice developed atheroma plaques up to the upper neck portion of the carotid arteries, but not in the cerebral circulation. Three months treatment with navitoclax reduced aortic plaques size (-32%, p<0.001) from 40±2% in vehicle-treated mice to 27±2% in navitoclax mice. At 12 months, endothelial dysfunction was severe in vehicle-treated ATX mice, as evidenced by a strong reduction in flow-mediated dilation (FMD) of pressurized posterior cerebral arteries
ex vivo
; navitoclax improved endothelium-dependent dilatation by 50% (for example, FMD at 20 dyn/cm
2
: 58±10%) compared to vehicle-treated mice (FMD: 29±7%; p<0.05). Two cognitive tests were performed: the Y-maze and the novel object recognition tests, to assess exploratory behavior and executive function, respectively. A gradual decline of both exploratory and executive memory was observed from 3 to 6, 9 and 12 months in vehicle-treated ATX mice; navitoclax, however, did not prevent this cognitive decline.

Conclusion:
Global elimination of SnC slowed atherosclerotic plaque development and restored cerebral endothelial function, demonstrating that senescence contributes to vascular dysfunction. The absence of cognitive improvement with navitoclax suggests an irreversible state of neuronal damage that could not be affected by the late senolytic treatment. To demonstrate the role of SnC in cognitive impairment, an earlier senolytic therapy will be needed.
Abstract 13294: Percutaneous Coronary Intervention in Cancer Patients Using Drug Eluting Stent Compared With Bare Metal Sent
Authors: Moussa Pacha Homam , Ahmad Talha , Addoumieh Antoine , Agrawal Nikhil , Song Juhee , Gilchrist Susan C , Arain Salman A , Dhoble Abhijeet , Iliescu Cezar
Published: April 2022

Introduction:
It is unclear whether bare-metal stent (BMS) use in cancer patient is associated with similar outcome compared with drug-eluting stent (DES). We aim to compare outcome of percutaneous coronary intervention (PCI) in cancer patient who were treated with BMS versus DES.

Methods:
We identified cancer patients who underwent PCI using BMS or DES between 2013 and 2020. Outcome of interest was overall survival and number of revascularizations. Kaplan-Meier method was used to estimate the survival probability. Multivariate Cox regression model were utilized to compare overall survival between BMS and DES.

Results:
We included 347 cancer patients who underwent PCI with median follow-up of 34.1 months (95% CI, 28.4-38.7). 42 patients were treated with BMS (12.1%) and 305 with DES (87.9%). Age and gender were similar between BMS and DES groups (p = 0.08 and 0.94 respectively). DES use was more frequent in Caucasians while African American patients had more BMS (p=0.03). There was no significant difference in number of revascularizations between BMS and DES groups (p=0.36). Median survival was 46 months (95%CI, 34-66) with no significant difference in overall survival between BMS and DES groups in multivariate analysis (p = 0.37). Independent predictors for survival include age > 65 (hazard ratio [HR]:1.53 [95% CI, 1.046-2.240]), BMI > 30 (HR:0.58 [95% CI, 0.374-0.895) and hemoglobin level > 12 mg/dl (HR:0.44 [95% CI, 0.303-0.639]).

Conclusions:
PCI using bare-metal stent in cancer patients appears to be associated with similar overall survival and number of revascularizations compared with drug-eluting stent.
Abstract 13306: Predictors of All-Cause Mortality in Heart Transplant Recipients With COVID-19
Authors: De Sirkar Sovik , Yu Mingxi
Published: April 2022

Introduction:
Heart transplant recipients are among the most vulnerable to suffer complications from Covid-19, yet there remains no standard of treatment. The primary objective of this study was to identify predictors of all-cause mortality in heart transplant recipients infected with Covid-19 to better tailor management for these medically complex patients.

Methods:
A retrospective analysis of 28 heart transplant recipients with Covid-19 infections was performed at Loyola University Medical Center, a large tertiary care academic center located in the Chicago metropolitan area. Numerical data was assessed using two-tailed t-tests and bivariate logistical regression. Categorical variables were analyzed using chi-squared tests. Statistical analysis was performed using JMP Pro 15.

Results:
Between March 1, 2020 and April 30, 2021, 28 heart transplant recipients with Covid-19 sought care at our hospital. The inpatient cohort consisted of 19 patients, 10 (53%) of whom met the primary endpoint of all-cause mortality. Those in the mortality arm (mean age 58.7 ± 21.5 vs 54.3 ± 13.1 in survival arm, p=0.58) were more likely to present closer to symptom onset with an elevated RR, INR, lower MAP, cough, or ESRD. Patients admitted to an ICU with superimposed infections or shock, requiring antibiotics, vasopressors, dialysis, or convalescent plasma were more likely to meet the primary endpoint. Azathioprine appeared protective against all-cause mortality.

Conclusions:
This is the only known study to assess clinical outcomes in heart transplant recipients based in the American Midwest, a region with a high infection burden but equipped with commensurate clinical resources and access to evolving Covid-directed therapies. Our study demonstrated a considerably high mortality rate (53%) among heart transplant recipients with Covid-19 despite these measures. Further studies are warranted to identify key predictors of mortality in this population to guide management.
Abstract 13312: Comprehensive Sequencing of Small Non-Coding RNA Reveals Plasma Circulating Biomarkers of Hypertrophic Cardiomyopathy and Dysregulated Signaling Pathways
Authors: Shimada Yuichi J , Hasegawa Kohei , Fifer Michael A
Published: April 2022

Background:
Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes essential in normal myocardial contraction. However, it remains unclear through which signaling pathways gene mutations mediate the development of HCM. Growing evidence indicates that small non-coding RNAs (snRNAs) play important roles in post-transcriptional regulation of gene expression.

Hypothesis:
Comprehensive sequencing of snRNAs in plasma reveals circulating HCM biomarkers and differentially regulated signaling pathways.

Methods:
We conducted a multicenter case-control study of cases with HCM and age-, sex-, and body mass index-matched controls with hypertensive left ventricular hypertrophy. We carried out RNA-seq of 3293 snRNAs in plasma. We performed a sparse partial least squares discriminant analysis to develop snRNA-based discrimination model using samples retrieved during the first two-thirds of the study period (the training set). We prospectively tested the discriminative ability in independent samples that were collected thereafter (the test set). We also identified signaling pathways associated with snRNAs that were significantly dysregulated in HCM with Bonferroni-adjusted P<0.05.

Results:
The study included 324 patients (165 cases and 159 controls; n=224 in the training set, n=100 in the test set). Using the transcriptomics-based model derived from the training set, the area under the receiver-operating-characteristic curve in the test set was 0.89 (95%CI 0.81-0.96;
Figure
). Pathway analysis revealed that the Ras-MAPK pathway was upregulated in HCM (false discovery rate [FDR]=0.000002). Pathways involved in inflammation and fibrosis - e.g., TNF (FDR=0.000003) and TGF-β (FDR=0.002) - were also upregulated.

Conclusions:
This study serves as the largest-scale investigation to reveal circulating snRNA biomarkers of HCM and exhibits both novel (e.g., Ras-MAPK) and known (e.g., TNF, TGF-β) pathways that are differentially regulated in HCM.
Abstract 13314: Development of a Computational Fluid Dynamics Model for Assessing Hemodynamics in Aortic Arches in Human Fetuses
Authors: Evangelos Steven , Wei Zhenglun , Ge Shuping
Published: April 2022

Background and Objective:
The hemodynamics of fetal circulation and its alterations, as in cases of congenital heart defects (CHD), have been investigated in instrumented animal models or in human fetuses by noninvasive fetal echocardiography and Doppler (FED). There is little data in computational modeling of fetal circulation due to challenges in fetal cardiac imaging and the availability of validation methodologies. This study aims to develop and validate a computational model for assessing hemodynamics in aortic and ductal arches in human fetuses.

Methods:
Figure 1 shows our computational workflow. The process started by preparing a reconstructed 3D aortic and ductal arch anatomy derived from 3D FED. Then, the computational model was built and validated using clinical data from five human fetuses. The primary output was the velocity waveform at the aortic isthmus (AoI), validated using tracings from spectral Doppler.

Results:
Upon superimposing the reconstructed fetal aortic arch anatomies onto the original 3D FED stack, our results demonstrated a precise rendering of each subject’s unique vessel structure. Simulations were run for ten cardiac cycles, with each velocity waveform at the AoI showing a discrepancy of less than 15% when compared with the Doppler echocardiography tracings. These findings indicate a good agreement between our computational model and the FED data.

Conclusion:
This study presents the development and validation of a computational model for assessing patient-specific hemodynamics in the aortic arches of human fetuses. Continued investigation is warranted to further validate and apply this approach to improve the diagnosis, prognosis, and treatment of CHD in human fetuses.
Abstract 13326: Racial Differences in Non-Elective Implantable Cardioverter-Defibrillator Placement in Older (≥ 66) Medicare Patients With Heart Failure
Authors: Kuhrt Nathaniel , Akhabue Ehimare , Shalmon Uri , Bates Benjamin , Rua Melanie , Visaria Aayush , Lee Eileen , Dave Chintan , Gandhi Poonam , Setoguchi Soko
Published: April 2022

Introduction:
Racial and ethnic disparities in ICD use for primary prevention among HF patients have dissipated in recent years. While HF patients who received ICDs non-electively during unplanned or shortly after acute hospitalization were shown to have worse outcomes, racial and ethnic disparities in such non-elective ICD placement have not been described.

Methods:
We identified older (age≥66) HF patients with ICD placements in 20% random sample Medicare data (2008-2018) and defined ICD placement as: 1) non-elective - during unplanned or after recent (<3 month) hospitalization or 2) elective - during planned hospitalization or as ambulatory procedure. We described the temporal trends in elective vs non-elective ICD placement over time and by racial and ethnic subgroups. Adjusted rate ratios (RRs) for non-elective ICD placement were estimated using multivariable modified Poisson regression.

Results:
Among 97,925 ICD patients (mean age 76, 67% male, 85% White), Black and Hispanic patients had more comorbidities and were more often dual eligible for Medicaid (
Table
). The rate of non-elective placement for all patients has decreased over time (56% in 2008 to 34% in 2018). Black and Hispanic patients had a higher rate of non-elective placement compared to White patients (
Figure
) which persisted after multivariable adjustment [RR = 1.10 (95% CI: 1.07 - 1.13) for Black and RR = 1.09 (95% CI: 1.04 - 1.14) for Hispanic vs. White patients].

Conclusions:
Racial and ethnic disparities in non-elective ICD use persist after adjustment. Future work is needed to understand how these disparities may impact outcomes after ICD placement in racial and ethnic minorities.
Abstract 13336: Investigating the Effects of Physiological Shear Stress on Monocyte Phenotype for Therapeutic Development in Atherosclerosis
Authors: Aldarondo Dasia , Huynh Chris , Wayne Elizabeth
Published: April 2022

Introduction:
Monocytes are highly plastic immune cells which play a significant role in atherosclerosis development and progression. Monocyte phenotype is modulated by stimuli including physical parameters like the shear stress induced by blood flow. Atherosclerotic plaque formation impedes blood flow thereby impacting the shear stress applied to monocytes. The altered shear stress could contribute to the abnormal monocyte phenotype populations in atherosclerotic patients.

Aim:
To understand the relationship between monocyte phenotypic response to varying physiological shear stresses.

Methods:
To investigate the dynamics of monocytes under inflammatory stresses, THP-1wt cells were exposed to 40 dyne/cm
2
and 5 dyne/cm
2
which represent above normal and below-normal, atherosclerotic shear stress conditions respectively. Monocytes were either untreated or stimulated with lipopolysaccharide (LPS) to simulate low-grade inflammation. To evaluate the phenotypic response, ELISA and qPCR measurements of pro-inflammatory (TNF-α IL-12, NOS2, MAC-1, CCL2, CD40), anti-inflammatory (IL-10), and adhesion molecules (ICAM-1, VCAM-1, CCR2) were taken directly after, and four hours post shearing.

Results:
Shear stresses of 5 dyne/cm
2
or 40 dyne/cm
2
show differential response profiles in monocytes. At both stresses, THP-1wt cells downregulated expression of inflammatory and adhesion molecules after 4hrs. However, pre-stimulation with LPS resulted in either maintained or increased levels of expression. Notably, LPS stimulation for both shear stresses saw a 40-fold or greater increase in TNF-α, CCL2, CD40, and VCAM-1 after 4-hour incubation. In all conditions angiotensin converting enzyme 2 (ACE2), a molecule important for blood pressure regulation, was downregulated.

Conclusion:
The data concludes that shear stress has an impact on the activation of monocytes in both unstimulated and stimulated conditions. LPS data suggests that monocytes which are already in proinflammatory conditions are more susceptible to sustained activation from shear stress.
Abstract 13346: Sociobehavioral and Clinical Risk Factors Associated With Severe Asymptomatic Hypertension: A 1999-2018 National Health and Nutrition Examination Survey Analysis
Authors: Visaria Aayush , Akhabue Ehimare , Setoguchi Soko
Published: April 2022

Introduction:
Individuals with severe asymptomatic hypertension (SAH) are at high risk of CVD. It is unclear which risk factors are associated with SAH and whether they are different in patients with & without awareness of hypertension (HTN). We hypothesized self-reported HTN status would significantly modify the effect of factors associated with SAH.

Methods:
We included adults ≥20 years from the 1999-2018 National Health and Nutrition Examination Surveys. Mean BP was calculated as the average of 3 consecutive BP readings 30 seconds apart. SAH was defined as mean SBP≥180 or DBP≥120. We used survey design-adjusted multivariable logistic regression to identify demographic, behavioral, comorbid, and medication-related factors for SAH. We then determined the modifying effect of self-reported HTN on the independent associations between covariates and SAH.

Results:
Among the 44,622 participants (mean age 47, 51% female, 69% White, and 30% HTN), 0.9% had SAH. Nearly 26% with SAH did not report HTN diagnosis and 62% were taking ≤1 BP medication. SAH individuals were more likely to be older, female, non-Hispanic Black, of lower socioeconomic status, have CVD, and report lower alcohol and salt intake than those without SAH (Table). The significant associations between Black race, female sex, lower income, & BMI and SAH were not different by self-reported HTN (Table). Self-reported HTN significantly modified the effect of older age (OR [95% CI]; HTN: 1.07 [1.06, 1.08], No HTN: 1.10 [1.08, 1.13]), lower education (HTN: 1.04 [0.77, 1.42], No HTN: 2.26 [1.15, 4.44]), lack of insurance (HTN: 2.82 [1.86, 4.28], No HTN: 1.01 [0.52, 1.96]), and CKD (HTN: 1.49 [1.12, 1.98], No HTN: 2.24 [1.25, 4.03]) on SAH.

Conclusions:
Regardless of self-reported HTN status, non-Hispanic Blacks, females, and lower socioeconomic individuals were independently associated with SAH in the U.S. Older age, low education level, and CKD may confer greater risk of SAH in patients lacking HTN awareness.
Abstract 13385: Prediction of Patient Comfort for Extravascular and Subcutaneous Implantable Cardioverter-Defibrillation Devices Using Modeling
Authors: Mathiesen Danielle , Bhatia Varun , Formosa Elizabeth , Portway Bridget
Published: April 2022

Introduction:
Implanted medical devices may exert pressure on patients’ tissues, generating discomfort. Depending on implant location and device design, the pressure generated will vary. The investigational extravascular implantable cardioverter-defibrillator (EV ICD) device volume is 33 cubic centimeters (cc), while the commercially available subcutaneous (SQ) ICD is 59 cc. The objective of this work is to compare the pressure on the subcutaneous and muscular tissue over a device in a tissue pocket through computer simulation.

Method:
Finite element modeling was performed for the EV ICD and SQ ICD in three implant locations: subcutaneous, submuscular, and intermuscular. A pocket condition was simulated with tissue above the device being displaced by the thickness of the device; the resulting pressures were calculated. Device contact pressure on the subcutaneous and muscular tissue above the device was used as a surrogate for potential patient discomfort caused by the device pushing against tissue.

Results:
In all three implant locations, the tissue pressure of the EV ICD was lower than that of the SQ ICD. Larger areas of high pressure were present on the tissue surface near the edges of the SQ ICD device compared to the EV ICD. The reduction observed in the EV ICD relative to the SQ ICD device was 24% in subcutaneous, 12% in submuscular, and 44% in intermuscular. See figure.

Conclusion:
Simulation shows that the EV ICD exerts less pressure on the tissue over the device than the SQ ICD across clinically relevant locations, with the potential to improve patient comfort.
Abstract 13389: Critical Role of Electron Leak From Mitochondrial Electron Transport Chain Complex I in Oxygen Sensing in the Rabbit Ductus Arteriosus
Authors: Read Austin , Bentley Rachel , Martin Ashley , Dunham-Snary Kimberly J , Mewburn Jeffrey , Thebaud Bernard , Sharp Willard W , Archer Stephen L
Published: April 2022

Introduction:
The ductus arteriosus (DA) allows placentally oxygenated blood to bypass the non-ventilated fetal lungs and enter the systemic circulation. The fetus’ systemic pO
2
is ~40 mmHg, maintaining the DA in a state of hypoxic vasodilation. As pO
2
rises, with the first breath, the DA constricts and achieves functional closure within minutes. We have identified a mitochondrial O
2
-sensor controlling functional closure within DA smooth muscle cells (DASMC). Increased pO
2
leads to increased reactive oxygen species (ROS) production by complexes I and III of the electron transport chain (ETC). These ROS are diffusible signaling molecules and inhibit redox sensitive potassium channels causing DASMC depolarization and vasoconstriction. We propose this reflects electron leak from ETC complexes. Using the term rabbit model, we investigated the differential function of ETC I vs III complex-specific electron leak suppressors (S1QEL vs S3QEL) on vascular tone in DA rings.

Methods:
DA’s from term rabbits (n=11 rabbits, n=29 individual DA rings) were mounted on a force transducer at ~800 mg in Krebs at a PO
2
of ~40mmHg. DA’s were subject to varying pO
2
levels (from 35-155 mmHg) and at peak O
2
constriction were treated with ETC leak suppressors, ETC complex inhibitors or vehicle controls (DMSO).

Results:
Exposure to normoxia caused an average 1100±62 mg increase in DA tension. S1QEL (50 μM) caused an average 20.9±6.2% reduction in DA tension (n=8) whereas S3QEL (100 μM) only reduced DA tension by 4.4±2.2% (n=4). Rotenone (complex I inhibitor) and antimycin A (complex III inhibitor) also relaxed the DA while vehicle had minimal effect (-2.6±1.5%).

Conclusions:
Electron leak from complex 1, but not complex 3, is implicated in DA O
2
-sensing.
Abstract 13407: Validation of the MIRACLE2 Score for Prognostication After Out of Hospital Cardiac Arrest
Authors: Cheese Francine , Leadbetter Zoe , Sunderland Nicholas , Johnson Thomas
Published: April 2022

Background:
Early prediction of long-term outcomes after out-of-hospital cardiac arrest (OOHCA) remains a diagnostic challenge. MIRACLE2 is a points-based risk score that has been derived as a simple tool to aid clinicians in prognosticating those at high risk of poor neurological outcomes. To date, the score has been validated in two independent cohorts in the MIRACLE2 study. The aim of this study was to validate the MIRACLE2 score in a further independent cohort, with the primary outcome poor neurological outcome at 6 months (Cerebral Performance Category (CPC) 3-5).

Methods:
We retrospectively identified all patients treated at the Bristol Royal Infirmary from January 2019 to July 2020 with a primary or secondary ICD-10 diagnosis code for cardiac arrest. Patients were screened against the inclusion and exclusion criteria used in the MIRACLE2 study and the data required to calculate the MIRACLE2 and CPC scores were extracted from medical records.

Results:
198 patients met the OOHCA inclusion criteria and were included for analysis. Multivariable logistical regression confirmed 6 out of the 7 MIRACLE2 components as independent predictors of poor neurological outcome at 6 months: age category (60-80 years, OR 6.4, p=0.005; >80 years, OR 148.1, p<0.001), initial non-shockable rhythm (OR 36.9, p<0.001), non-reactivity of pupils (OR 13.7, p=0.002), low pH <7.20 (OR 5.1, p=0.014), adrenaline administration (OR 4.1, p=0.024), changing intra-arrest rhythms (OR 3.4, p=0.048). The MIRACLE2 score had an area under the curve of 0.89. The risk of poor neurological outcome in this cohort, across the previously described MIRACLE2 score risk groups (low <=2, intermediate 3-4, and high >=5), was comparable to that in the MIRACLE2 study (low: 15% vs. 6%; intermediate: 54% vs. 55%; and high: 93% vs. 92%, respectively).

Conclusion:
The MIRACLE2 score has been externally validated in an independent cohort as an accurate predictor of poor neurological outcome following OOHCA.
Abstract 13409: A Substantial Proportion of Patients With Transthyretin Cardiac Amyloid (ATTR) Present With Impaired Left Ventricular Ejection Fraction: Implications for Diagnosis and Race Disparities
Authors: Martyn Trejeeve M , Saef Joshua , Khedraki Rola , Ives Lauren , Jaber Wael A , Estep Jerry , Hanna Mazen A , Tang Wai Hong W
Published: April 2022

Background:
ATTR cardiomyopathy is classically described in patients with heart failure with preserved ejection fraction (HFpEF). We sought to understand the prevalence, characteristics, and survival of patients at the time of diagnosis, had heart failure with HFpEF (≥50%), HfmrEF: (41-49%), HFrEF ( ≤40%).

Methods:
A retrospective institutional amyloid registry study of 585 patients diagnosed with wild-type (WT) or variant ATTR-CM from 2011-2020. Cox proportional hazards models were used to assess probability of transplant-free survival.

Results:
In our cohort, (median age 77 [71,83], 84% male, 25% African-American (AA), median eGFR 58 [46,73], 28% had HFrEF (n= 165), 17% HFmrEF (n=97), and 55% with HFpEF (n=323). After adjusting for Age, sex, race, NT-proBNP, and eGFR, HFrEF patients had worse survival than those with HFpEF (HR, 0.47[95% CI, 0.33-0.68, p<0.001]) and HmrEF (HR, 0.47[95% CI, 0.29-0.77, p=0.002])
(Fig 1a)
AA patients had higher rates of HTN, DM, and variant TTR (72% vs. 9%, p<0.001) as well as lower rates of CAD compared to Caucasian patients. AA patients were predominantly V122I variant (n=109/146, 74%) and more likely to present with HFrEF (n=60/146, 41%) than Caucasian patients (n=102/440, 23%), p<0.001. AA WT (n=18/41, 44%) patients were also more likely to present with HFrEF than Caucasian WT (n=98/400, 25%), p=0.017
(Fig 1b).
AA variant (43/108,41%) were more likely to present as HFrEF than Caucasian variants (4/41, 9.8%), p=0.001.

Conclusions:
Forty-five percent of patients diagnosed with ATTR-CM presented with LVEF ≤50% at the time of diagnosis, confirming that clinical suspicion for diagnosis of ATTR-CM should extend beyond HFpEF presentation. Reduced LVEF is an independent prognostic factor in patients with ATTR-CM. Racial disparities in the LVEF at presentation are present in both variant and WT ATTR. Further investigation into co-morbid, genetic, and racial factors associated with the presenting phenotype of ATTR amyloid is needed.
Abstract 13413: Obstructive Sleep Apnea Increases Costs but Not Length of Stay in First Instance Heart Failure Hospitalizations
Authors: Zachariah Ashvin , Larned Joshua
Published: April 2022

Introduction:
Sleep-related breathing disorders have a high prevalence in the heart failure (HF) population. Although causality has not explicitly been established, obstructive sleep apnea (OSA) appears to increase risk for the development and progression of heart failure. A single-center study by Sommerfeld et. al. reported OSA as the strongest predictor for hospital readmission among HF patients. The goal of this study was to employ the use of a nationwide database to evaluate the possible effect of OSA on length of stay and costs associated with HF hospitalization.

Hypothesis:
Patients with history of OSA admitted for HF will have higher costs and longer length of stay associated with hospitalization, compared to controls without history of OSA hospitalized for HF.

Methods:
We conducted a retrospective matched cohort analysis using records from the Medicare Standard Analytical Files in the PearlDiver database. Using the International Classification of Diseases, ninth revision (ICD-9) codes, we queried for patients with history of obstructive sleep apnea hospitalized for heart failure from 2005-2014. We matched to controls (without history of OSA) based on age, gender, and Elixhauser Comorbidity Index. We sought to compare length of stay (LOS) and costs attributed to first-instance HF exacerbation. Costs were reported as the average amount paid per patient, as this more accurately reflects cost rather than amount billed by the hospital.

Results:
Matching yielded two cohorts of 464,620 patients in each group. Average amount paid per patient in the OSA group was greater by a statistically significant amount when compared to the group without OSA hospitalized for HF ($15,447 vs $9,555, p<0.0001). Length of stay was however noted to be shorter in the OSA cohort compared to the non-OSA cohort (5.7 days vs 8.1 days, p<0.0001).

Conclusions:
Patients with OSA who were hospitalized for HF suffered higher cost of hospitalization, although length of stay was not impacted. The effect on costs is in line with existing literature regarding the relationship between OSA and HF. Possible reasons for decreased LOS in the sleep apnea cohort include more rapid/aggressive treatment course, respiratory support, or death leading to reduction of LOS.
Abstract 13415: Initial Diuretic Dosing and Length of Stay in Patients Hospitalized for Congestive Heart Failure
Authors: Bradley Steven M , Thomas Chelsey , Rush Pam , Madrid Shaina , Strauss Craig
Published: April 2022

Background:
Among patients hospitalized for heart failure, a prior randomized trial suggests the initial dose of diuretics may have implications on time to decongestion and length of hospital stay. Little is known about the dosing of intravenous loop diuretics in routine clinical practice and the association between diuretic dosing and hospital length of stay.

Methods:
We identified 12,209 patients admitted with heart failure at 12 Allina Health hospitals in central Minnesota and western Wisconsin between January 1, 2017 and December 31, 2020. We excluded patients on observational status, no or unknown home loop diuretic dosing, no intravenous loop diuretic within 24 hours of admission, and patients who received inotropes or dialysis within 24 hours of admission. Initial diuretic dose was compared to home dose in furosemide equivalents using the Diuretic Strategies in Patients with Acute Decompensated Heart Failure trial logic and categorized into below home dose, equivalent to home dose, or above home dose. We describe patient characteristics and length of stay by category of initial diuretic dose.

Results:
Among 3,580 admitted for heart failure, initial diuretic dose was below home dose in 555 (15%) patients, equivalent to home dose in 756 (21%) patients, and above home dose in 2269 (64%) patients. Baseline characteristics by category of initial diuretic dose are presented in the Table. Mean length of stay was longest in patients receiving a diuretic dose that was below home dose (6.4 days) and shortest in patients receiving a dose above home equivalent (5.0 days) (Table).

Conclusions:
In a cohort of patients admitted for heart failure, more than 1 in 3 patients received an initial dose of intravenous loop diuretics that was equivalent to or below their home diuretic dose and this was associated with a longer length of hospital stay. These findings may represent a quality improvement opportunity in the care of patients hospitalized for heart failure.
Abstract 13421: Spontaneous Coronary Artery Dissection in Patients With and Without Chronic Systemic Inflammatory Diseases
Authors: Alfadhel Mesfer , Samuel Rohit , Mcalister Cameron , Nestelberger Thomas , Argote Parolis Johandra , Grewal Tejana , Saw Jacqueline
Published: April 2022

Background:
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction (MI). Chronic systemic inflammatory diseases (CIDs) are common amongst SCAD patients. Whether they contribute to the cause of SCAD or were simply bystanders remain unknown.

Methods:
We compared the baseline demographics, presentation characteristics and cardiovascular outcomes between patients with and without CIDs in the Canadian SCAD Study. CIDs included systemic inflammatory disorders as well as autoimmune diseases. Patients completed questionnaires along with detailed history of CIDs. Blood biomarkers for inflammation (e.g. C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], white blood cell counts) were obtained at the discretion of the treating physicians. Major adverse cardiovascular events (MACE) were defined as the composite of all-cause mortality, stroke or transient ischemic attack, MI, hospitalization for heart failure and unplanned revascularization.

Results:
Of 1225 patients with SCAD, 96 (7.8%) had a history of CIDs. Patients with CIDs were of similar age (52.5 vs.51.8 yrs, p=0.51), but were more likely to be women (96.9% vs 89.2%, p=0.02). There were no significant differences in baseline demographics, ECG, or angiographic findings between CID or non-CID cohorts. Among patients with biomarkers performed, there was no difference in CRP (9.6 vs. 12.9mg/L, p=0.54), ESR (10 vs. 13.9, p=0.42), white cell count (12.6 vs. 11.3, p=0.80), neutrophil count (5.1 vs. 5.6, p=0.70), or lymphocyte count (1.7 vs. 2.0, p=0.41), in CID versus non-CID groups, respectively. The proportion of patients treated conservatively or with revascularization were not different between groups. At median follow up of 3.0yrs (IQR 2.0-3.8), in hospital and overall MACE were not significantly different between CID and non-CID patients (8.4% vs. 6.1%, p=0.38) and (23% vs. 16.8%, p=0.12), respectively.

Conclusion:
In our large SCAD cohort, there were no significant differences in presentation or outcomes in SCAD patients with or without CID. Importantly, there was no difference in levels of inflammatory biomarkers, supporting the hypothesis that active inflammation was not an important contributor of SCAD.
Abstract 13425: Relationship Between Social Vulnerability and Case Fatality Rate at the Level of Counties and County-Equivalents in the Contiguous United States During the COVID-19 Pandemic
Authors: Mukherjee Sohini , Mukherjee Deblina
Published: April 2022

Introduction:
Pandemics prior to the COVID-19 pandemic have been known to disproportionately affect counties and county-equivalents with high social vulnerability. Social vulnerability refers to the potential negative effects on communities caused by external stresses on human health. Such stresses include natural or human-caused disasters, or disease outbreaks. On the other hand, case fatality rate estimates the proportion of deaths among identified confirmed cases.

Hypothesis:
A higher social vulnerability is associated with a higher case fatality rate at the levels of counties and county-equivalents in the contiguous United States during the COVID-19 pandemic.

Methods:
Data from 2990 counties and county-equivalents such as independent cities, districts, and parishes that are considered county-equivalents for census purposes was analyzed. Counties and county-equivalents from the non-contiguous states of Alaska and Hawaii were excluded as well as 59 counties and county-equivalents without available SVI data and/or available CFR data. Available SVI public source data was collected from the Centers for Disease Control and Prevention, while available CFR public source data was collected from the Emory Clinical Cardiovascular Research Institute.

Results:
Median SVI was 0.5185 [Range: 0.0006-1] and median CFR was 1.56% [Range: 0%-8.77%]. A vaccination rate ratio (RR) and 95% CI for SVI was calculated using Wald’s unconditional maximum likelihood estimation to compare CFRs of counties and county-equivalents with low social vulnerability (SVI: 0%-33%), moderate social vulnerability (33%-66%), and high social vulnerability (66%-100%). A higher SVI was associated with a higher CFR such that the RR for relative differences in CFR between counties and county-equivalents with a low social vulnerability and counties and county-equivalents with a high social vulnerability was 0.83, while the RR for relative differences in CFR between counties and county-equivalents with a moderate social vulnerability and counties and county-equivalents with a high social vulnerability was 0.89.

Conclusions:
Public policy interventions need to target counties and county-equivalents with a higher social vulnerability to help the most vulnerable of people.
Abstract 13426: CRISPR Guide RNA Design is Able to Use for Studying Splicing and Circadian Gene Expression
Authors: Mattapally Saidulu , Zhang Eric , Fast Vladimir G , Pollard Andrew E , Mattapally Chandrakala , Zhang Jianyi
Published: April 2022

Introduction:
CRISPR editing of genomic regulatory elements with the intention of direct exon/intron splicing is a hopeful means of everlastingly alleviating genetic diseases. Cas9-induced DNA double-stranded break, non-homologous end-joining repair pathways frequently introduce variable indel mutations at the cut site. Circadian rhythms control cell proliferation and differentiation, however circadian control of Human induced pluripotent stem cells (hiPSCs) remains study at the molecular level.

Hypothesis:
Elucidation of circadian rhythms in hiPSCs differentiated cardiomyocytes.

Methods:
In the current investigation, hiPSCs carrying knockout mutations for Per1, Per2, and connexin43 were generated via CRISPR/Cas9 gene-editing technology. hiPSCs were differentiated into cardiomyocytes (CM) and spheroid cultured was performed as previously described. We evaluated different guide RNAs Cas9-induced DNA double-stranded break were analyzed using Sanger sequencing and bioinformatics. Optical mapping was used to measure the electrical properties of individual spheroids and monolayers of WT, connexin 43 KO, and overexpression of connexin 43 (WT, Cx43 KO, and Cx43 OV). We also study in the hiPSCs CMs of monolayer resistivity and reactivity and compared them with rabbit ventricular myocardium.

Results:
To determine the genomic regulatory elements that control exon splicing we designed several guides Per1, Per2, and Connexin 43. Our sequencing and bioinformatics analysis found untranslated region or coding region designed guide RNA found changes in splicing but protein truncation observed in connexin 43 of the coding region. To further understand the differential expression of Cx43 in hiPSC-CMs optical mapping in monolayers and spheroids were observed decreased conduction velocities. To further understand we also perform impedance measurement in WT, Cx43 KO, and Cx43-OV. We found resistivity and reactivity were significantly changed between groups. We will look these mechanisms has any role in the spheroid treatment is associated with significant changes in arrhythmogenicity of swine studies.

Conclusions:
Our study established the CRISPR gRNA design can be used study splicing and circadian pattern regulated by connexin 43.
Abstract 13438: Obesity is Uncommon in Patients With Transthyretin Cardiac Amyloidosis
Authors: Poterucha Timothy J , Kurian Damian , Raiszadeh Farbod , Teruya Sergio , Elias Pierre , Kogan Rebecca , Chiuzan Codruta , Einstein Andrew J , Ruberg Frederick , Maurer Mathew S
Published: April 2022

Background:
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome that includes distinct subtypes with different pathophysiologies, genetics, and treatment. Distinguishing HFpEF due to transthyretin cardiac amyloidosis (ATTR-CA) is critical given its specific treatable pathophysiology. Obesity is a common driver of HFpEF, but it has been noted clinically that low body mass index (BMI) is a common finding in ATTR-CA.

Methods:
A single center, retrospective study of patients undergoing 99mTc-pyrophosphate (PYP) scans from 2010-2019 was analyzed for BMI association with ATTR-CA and the Val122Ile variant. BMI differences were prospectively evaluated in the ongoing multicenter Screening for Cardiac Amyloidosis Using Nuclear Imaging for Minority Populations (SCAN-MP) study. The association of BMI with ATTR-CA/Val122Ile was compared by Wilcoxon rank sum analysis and combined with age, sex, and maximum LV wall thickness in a multivariable logistic regression in both the retrospective and SCAN-MP cohorts.

Results:
In the retrospective analysis, BMI (in kg/m
2
) among those with ATTR-CA/Val122Ile (n=198, 40%) was lower (25.8, IQR 23.4-28.9) than in other patients (27.1, IQR 23.9-32.0) (p<0.001). In multivariable logistic regression, BMI < 30 (OR 2.60, 95% CI 1.49-4.54), remained independently associated with ATTR-CA/Val122Ile. In the first 221 patients enrolled in SCAN-MP, 18 (8%) had ATTR-CA (n=11) or were carriers of the Val122Ile variant (n=7) with negative PYP scans. Among those subjects, BMI was significantly lower (25.6 [IQR 24.3-28.3]) than in other patients (32.6 [27.9-38.1]) (p<0.001). BMI did not differ between ATTR-CA patients (27.5 [25.3-28.9]) and Val122Ile allele carriers with negative 99mTc-pyrophosphate scans (25.3 [24.3-28.2]). When combined with age, sex, and maximum LV wall thickness, BMI<30 (OR 11.8 [CI 2.47-56.14]) and maximum LV wall thickness (OR 1.38/mm [95% CI 1.10-1.74]) were associated with ATTR-CA/Val122Ile.

Conclusions:
Lower BMI is associated with a diagnosis of ATTR-CA/Val122Ile in heart failure with increased LV wall thickness and may be useful in selecting patients benefiting from evaluation for ATTR-CA.