bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16654: Covid - 19 - Acute Myocardial Infarction and Heart Failure Mortality Trends in a Non-epicenter Region
Authors: Indaram Mahathi , Doyle Mark , Wiswall Sarah , Poornima Indu G
Published: May 2021

Introduction:
As the novel coronavirus gained acceleration, there are several reports of a decreasing number of hospital admissions for acute myocardial infarctions (AMI) worldwide. It is unclear if this is due to an actual decrease in their incidence or due to patients avoiding hospital visits during the pandemic. We examined the trends in admissions for AMI, acute decompensated heart failure (HF) and their associated mortality in an integrated health system (7 hospitals) in Pittsburgh (Pennsylvania), a non-epicenter region.

Hypothesis:
If patients are presenting late due to avoiding hospitals, AMI and HF would be associated with increased mortality rates.

Methods:
We collected data on the total number of admissions and deaths related to AMI (ST and non-ST elevation), HF using ICD-10 codes, during the period of January-April 2020. We compared this with data from the same period in 2018, 2019. Mortality rate was calculated as deaths per 100 admissions.

Results:
There were 505 AMI admissions in January-April 2020 and 37 died compared to 23 deaths amongst 645 admissions in the same period of 2018 and 2019 (averaged). Similarly, there were 1030 HF admissions in January-April 2020 and 46 died in comparison to 39 deaths amongst 1280 admissions in 2018 and 2019 (averaged). The absolute number of AMI and HF admissions was lower in 2020 (p<0.05, p<0.01). There was no difference in absolute number of deaths attributed to HF or AMI between 2020 and the preceding years (p=0.3). However, mortality rate was higher for HF in 2020 compared to prior 2 years.

Conclusions:
In this non-epicenter region, there was a significant decrease in admissions for AMI and HF in 2020 compared to 2018-2019 while the absolute number of deaths were similar. Similar mortality rates for AMI across the years suggests that patients were presenting appropriately and that the true incidence was likely low. However, higher mortality rate with HF may suggest a delayed presentation albeit without accounting for confounders.
Abstract 16664: Aortic Valve Calcification is Prognostic for Mild Cognitive Impairment
Authors: Chung Hojune E , Chen Jessica , Christensen Jared L , Ghosalkar Dhairyasheel S , Soares Cullen , Chu Alice , Shah Nishant R , Wu Wen-Chih , Choudhary Gaurav , Morrison Alan R
Published: May 2021

Introduction:
While an association between vascular disease and dementia has been identified, few studies have assessed the longitudinal relationship between aortic valve calcification (AVC) and mild cognitive impairment (MCI). We recently found AVC to be associated with increased atherosclerotic events, and we sought to determine the prognostic value of AVC derived from low dose, lung cancer screening computed tomography (LCSCT) for MCI in a moderate-to-high atherosclerotic risk cohort.

Methods:
This was a single site, retrospective analysis of 1401 U.S. veterans (65 years [IQI: 61, 68] years; 97% male), who underwent quantification of AVC from LCSCT indicated for smoking history. Exclusion criteria included lung cancer, prior aortic valve replacement and prior MCI diagnosis. The primary outcome was new diagnosis of MCI identified by objective testing (Mini-Mental Status Exam or Montreal Cognitive Assessment) or by ICD coding. Secondary outcome was nonfatal cerebrovascular accident (CVA). Time-to-event analysis was carried out using AVC as a continuous and a categorical variable, and multivariate adjustment included age, diabetes mellitus, glomerular filtration rate <60 mL/min, coronary artery disease, and prior CVA.

Results:
Over a 5-year follow up, 110 patients (8%) were newly diagnosed with MCI and 45 patients (3%) had CVA. By Cox regression, AVC was predictive of MCI (HR: 1.15 [1.07 -1.24], p<0.001) and the association remained significant after multivariate adjustment (HR: 1.09 [1.01-1.18], p=0.026). Non-zero AVC tertiles were: 0.1-115; 116-427; and ≥428 Agatston Units. AVC was associated with MCI at increasing tertiles, and after multivariate analysis, the association remained significant (HR: 1.89 [1.09-3.28], p=0.024 and HR: 1.80 [1.01-3.20], p=0.047; tertiles 2 and 3, respectively). AVC was also associated with CVA (HR: 1.17 [1.05-1.32], p=0.006); however, the association lost significance after multivariate adjustment (HR: 1.12 [0.99-1.26], p=0.080).

Conclusions:
To our knowledge, this is the first study demonstrating that quantification of AVC from LCSCT is predictive of MCI. The association may be in part due to atherosclerotic thromboembolic events as there was a trend toward increasing nonfatal CVA in this population.
Abstract 16670: Outcomes of Patients With St Elevation Myocardial Infarction and History of Prior Coronary Artery Bypass Graft Surgery
Authors: Karacsonyi Judit , Schmidt Christian W , Garcia Santiago , Henry Timothy D , Rangan Bavana V , Nikolakopoulos Ilias , Vemmou Evangelia , Xenogiannis Iosif , Goessl Mario , Sorajja Paul , Chavez Ivan , Mooney Michael R , Poulose Anil , TRAVERSE Jay , Wang Yale , Baran Kenneth , Bradley Steven M , Megaly Michael S , Garberich Ross , Ungi Imre , Burke Nicholas , Brilakis Emmanouil S
Published: May 2021

Introduction:
The outcomes of ST elevation myocardial infarction (STEMI) patients with prior coronary bypass graft (CABG) surgery have received limited study.

Methods:
We compared the clinical and procedural characteristics and outcomes of STEMI patients with and without prior CABG surgery in a contemporary STEMI registry of consecutive STEMI patients with STEMI or new left bundle-branch block within 24 hours of symptom onset presenting between March 2003 and April 2020. Morality and major cardiac adverse events (MACE: death, MI or stroke) were the primary outcomes of the study. Survival curves are depicted using the Kaplan-Meier method and compared with log-rank test.

Results:
Of the 6,311 patients included in the analyses, 6.9% had history of prior CABG. Mean age was 63.4 ± 13.9 years and most of the patients were men (71%), 21% had prior MI and 19% had diabetes mellitus. Prior CABG patients were older (70.4±11.7 vs. 62.9±13.9 years, p<0.001) and more likely to have diabetes (39% vs. 18%, p<0.001), prior MI (68% vs. 18%, p<0.001) and cardiogenic shock at presentation (14% vs. 9%, p=0.001) compared with patients without CABG. Median door to balloon time (69 [52, 88] vs. 55 [41, 79] min, p<0.001) as well as length of hospital stay (3 [2, 5] vs. 3 [2, 4] days, p=0.032) were longer in prior CABG patients. Survival evaluated by the Kaplan Meier method at 30 days, 1 year, and 5 years were significantly lower in patients with prior CABG (p<0.001, Figure). Landmark survival analyses, with landmark time of hospital discharge, were similar at 30 days (p=0.158) but showed lower survival rates at 1 year and 5 years. MACE occurred with similar incidence at 30 days follow up, but were more common at 1 year follow up. Outcomes were similar to saphenous vein graft and native coronary culprits.

Conclusions:
Patients with STEMI and previous CABG represent a higher risk cohort with worse in-hospital and long-term outcomes compared to those without previous CABG.
Abstract 16681: Ability of the Intermountain Risk Score Measured in 2019 (pre-COVID) to Predict Major Adverse Health Events in Patients Positive for SARS-CoV-2 in 2020
Authors: Horne Benjamin D , Muhlestein Joseph B , Bledsoe Joseph R , May Heidi T , Carlquist John F , Peltan Ithan D , Webb Brandon J , Bennett Sterling T , Rea Susan , Bair Tami L , Knight Stacey , Ronnow Brianna S , Le Viet T , Knowlton Kirk U , Anderson Jeffrey L
Published: May 2021

Background:
The Intermountain Risk Sore (IMRS) is a general health clinical decision tool based on the complete blood count (CBC) and basic metabolic profile (BMP). IMRS was developed to predict all-cause mortality. IMRS was validated previously in patients from the US and elsewhere, including in general medical and surgical patients and in diagnosis-specific populations. IMRS has been implemented at Intermountain Healthcare to guide clinical care in hospital settings. IMRS has not been tested as a predictor of major adverse health events after diagnosis of novel coronavirus disease (COVID)-19.

Methods:
Intermountain patients (ages ≥18 years) with a CBC and BMP measured in 2019 and with a COVID-positive test in 2020 (N=1,025) were evaluated to determine if the pre-2020 IMRS predicted a composite of hospitalization or mortality. All study subjects tested positive for COVID between March 3 and June 8, 2020. IMRS was calculated using original sex-specific variable weightings (see Horne BD et al,
Am J Med
2009).

Results:
Overall, 55 females and 54 males had a composite endpoint, respectively (5 and 10 deaths; 52 and 46 hospitalizations), with c-statistics of c=0.748 for females and c=0.669 for males using IMRS calculations from 2019 (see Table). For n=170 patients, IMRS was also calculated from 2020 CBC/BMP panels obtained at the time of COVID diagnosis, and it also predicted the composite endpoint at that timepoint (for females and males combined, odds ratios= 4.05, 2.46, and 1.53 for high-, moderate-, and mild-risk categories vs. low-risk; see Table for category thresholds).

Conclusion:
IMRS measured using 2019 CBC and BMP lab results predicted major adverse health events for patients diagnosed with COVID in 2020. Use of IMRS may empower population health with anticipation of COVID outcomes; for higher risk patients, the IMRS result may lead to enhanced preventive measures if the patient is free of COVID and, if COVID is diagnosed, it may lead to earlier, more aggressive care.
Abstract 16683: Profiling Cardiac Inflammation and Molecular Changes During the Transition of Hypertrophic to Dilated Cardiomyopathy
Authors: MOHAMMED ARIF Fnu , sadayappan Sakthivel , Owens Phillip , BECKER Richard
Published: May 2021

Introduction:
Hypertrophic cardiomyopathy (HCM) is a disease caused primarily by sarcomere gene mutations [like myosin-binding protein C3 (
MYBPC3
)], with several distinct phenotypes. Tissue-level inflammation has been reported in human HCM, tissue-specific neutrophil subsets, and their dysregulation cause inflammatory myopathies, and neutrophil extracellular traps (NETs) are associated with cardiac fibrosis in aged rodents. However, the mechanism(s) responsible for the broad phenotypic variability and changes observed over time transitioning from HCM to dilated cardiomyopathy (DCM) has not yet been elucidated.

Objective:
To determine the cardiac inflammatory signature of HCM and transition from HCM to DCM and its relationship to fibrosis and ventricular remodeling in an established
MYBPC3
(

cMyBP-C
t/t

) mouse model.

Method and Results:
Mixed-gender

cMyBP-C
+/+

(WT) and mutant mice (

cMyBP-C
t/t

) underwent echocardiography and were euthanized at one, two and three months of age (n=8) and blood and hearts were harvested. Echocardiography and histopathology examination confirmed significant heart dysfunction and tissue remodeling in

cMyBP-C
t/t

mice showing cardiac hypertrophy at one month of age (Left ventricular (LV) posterior wall systole 1.20 ±0.39
vs
1.51±0.49 and LV posterior wall diastole 0.96 ±0.22
vs
1.38 ±0.36 mm; *
p<0.05
), and DCM phenotype (LV internal diameter systole 2.40 ±0.41
vs
3.67 ±0.25 and LV internal diameter diastole 3.44 ±0.29
vs
4.30 ±0.39 mm; *
p<0.05
) along with myofibrillar loss and increased cardiac fibrosis at three months. Interestingly, LV dysfunction and hypertrophy resulted in a time-dependent increase in the activation of coagulation, as measured by plasma microvesicle tissue factor activity, thrombin antithrombin, and D-dimer.
In silico
analysis of RNA-Seq data from 3-months old

cMyBP-C
t/t

mice heart revealed key genes and pathways associated with HCM, DCM, tissue remodeling, renin-angiotensin-aldosterone signaling, fibrosis, apoptosis, NETosis, and inflammation.

Conclusions:
The transition from HCM to a DCM phenotype involves proinflammatory and profibrotic signaling. Therapies directed at tissue-specific inflammation and NETs may be a novel and impactful strategy for HCM.
Abstract 16684: Risk Prediction in Chronic Heart Failure: Comparison of the PREDICT-HF and MAGGIC Risk Scores in 4744 Patients in DAPA-HF
Authors: Simpson JoAnne , Docherty Kieran , Petrie Mark , Jhund Pardeep S , McMurray John J
Published: May 2021

Introduction:
Predicting outcomes in patients with heart failure (HF) is challenging. We compared the performance of the recently developed PREDICT-HF score with the established MAGGIC risk score in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).

Methods:
The MAGGIC risk score is the most commonly used risk score in heart failure and was derived using data from 39,372 patients enrolled in 30 clinical trials and cohort studies and includes 13 clinical variables. PREDICT-HF (www.predict-hf.com) incorporates demographic, comorbidity and laboratory variables, including natriuretic peptides, and was developed using data from PARADIGM-HF. The performance of both models was tested in in DAPA-HF i.e. in symptomatic patients with HFrEF receiving contemporary standard care. The outcomes examined included all-cause death and cardiovascular (CV) death at 1 and 2 years. Model discrimination and calibration were assessed by Harrell’s C statistic. For the PREDICT-HF model participants with missing values, median values from the derivation cohort were imputed.

Results:
The mean age of the 4744 patients in DAPA-HF was 66 years and 77% were male; 68% were in NYHA functional class II and 24% in class III. During a median follow-up of 18 months, 605 patients died, and 500 experienced CV death. Using PREDICT-HF, the C statistic at 1 and 2 years was 0.71 and 0.70 for all-cause death, and 0.73 and 0.72 for CV death, respectively. The MAGGIC risk score was available for 4740 patients in DAPA-HF. The C-statistic for all cause death at 1 and 2 years was 0.63 and 0.63, respectively. Model discrimination for PREDICT-HF and MAGGIC are shown in Table 1.

Conclusions:
PREDICT-HF performed well, and significantly better than the MAGGIC risk score, in predicting mortality in a contemporary cohort of patients receiving evidence-based treatment.
Abstract 16693: Heart Failure in the Caribbean: Phenotypes and Management Patterns
Authors: Feliz Edisson , Guzman Samuel , Mateo Jennifer , Rumardo Angelica , Nunez Ayala Elaine , Herrera Cesar
Published: May 2021

Introduction:
There is sparse published data on Heart Failure (HF) in the Caribbean region where cultural, ethnic and socioeconomical differences may play a role in all aspects of this entity. We sought to study clinical profiles and treatment characteristics of patients with HF in the Dominican Republic.

Methods:
Electronic records of a tertiary care CV center were used to recruit stable patients with HF from the outpatient cardiology clinic and immediately post hospital discharge.

Results:
From May 2015 to May 2020, 700 consecutive subjects with any form of HF were identified: 478 (68%) with Heart Failure with Reduced Ejection Fraction (HFrEF), 144 (21%) with Heart Failure with Mid Ejection Fraction (HFmEF) and 78 (11%) with Heart Failure with Preserved Ejection Fraction (HFpEF) constitute the study group; 391 (56%) were enrolled immediately post-discharge and 309 (44%) from the outpatient clinic. Gender (male): HFrEF 66% / HFmEF 63% / HFpEF 46% (p=0.003); mean age: 65±14 / 66±14 / 77±11 yrs. (p=0.01). Comorbidities: Hypertension 83% / 88% / 97% (p=0.002); Diabetes Mellitus 36% / 42% / 40% (p=0.45); Coronary Artery Disease 45% / 51% / 26% (p=0.009); Atrial fib 23% / 20% / 40% (p=0.002); CKD 23% / 20% / 40% (p=0.002). Etiology by clinical assessment: Ischemic Heart Disease 48% / 58% / 17%; Cardiomyopathies 32% / 15% / 0%; Hypertensive 5% / 9% / 83%; others 15% / 18% / 0% (all p=<0.001). Echo: Ejection Fraction (EF) 29±7% / 44±3% / 62±8%; mitral regurgitation ≥ moderate 30% / 15% / 8% (all p=<0.001). Management patterns for HFrEF: ACE inhibitors/Angiotensin II receptor blockers (ARB) 66%; Sacubitril/Valsartan 14%; aldosterone receptor antagonists (ARA) 63%; beta blockers (BB) 91%. On guideline-directed drugs at target doses: ARB/ACE/Sacubitril-valsartan 33%; BB 22%; and ARA 72%. Device use in eligible patients: ICD/CRT/CRT-D 17%.

Conclusions:
In this series, HFrEF was the most common form with suboptimal Guideline-directed therapy in many subjects, particularly device use. Those with HFmEF shared similarities with HFrEF in etiologies. Patients with HFpEF were older, more frequently women, and had a higher prevalence of CKD and Atrial Fib. Regional registries ought to better characterize the impact of these findings on outcomes among high-risk populations.
Abstract 16694: Left Ventricular Global Longitudinal Strain Predicts Ventricular Arrhythmias in Patients With Implanted Cardiac Devices
Authors: Asad Zain Ul Abideen , Kliewer Brian , Mao Tiffany F , Javed Isma N , Iqbal Abdul Ghani , Jafry Ali , Akhtar Khawaja , Elkholey Khaled , Ngo Phuong E , Stavrakis Stavros
Published: May 2021

Introduction:
Abnormal left ventricular ejection fraction (LVEF) is the traditional parameter used to assess the risk of sudden cardiac death (SCD), but most SCD events occur in patients with LVEF >40%.

Hypothesis:
We hypothesized that global longitudinal strain (GLS) can predict SCD in patients with heart failure and implantable cardiac devices.

Methods:
This was a retrospective cohort study. Device interrogation and chart review was done for demographic, clinical and echocardiographic characteristics and assessment of outcomes; ventricular tachycardia (VT) or ventricular fibrillation (VF), all-cause mortality, cardiac hospitalizations, non-sustained VT and new atrial fibrillation (AF). Cox-regression analysis was performed for the association between GLS, other clinical and echocardiographic parameters and outcomes.

Results:
A total of 180 patients were included with males 176 (98%), HFrEF (LVEF<40%) 58 (33%), HFmEF (LVEF 40-50%) 37 (21%), HFpEF 83 (46%), ischemic cardiomyopathy 78 (43%) and non-ischemic cardiomyopathy 39 (22%). Over a median follow up of 31 months, 29 (16%) developed sustained VT/VF, 33 (18%) died, 55 (31%) had cardiac hospitalization, 74 (41%) had non-sustained VT and 25 (14%) developed new AF. Abnormal GLS (≥-17%) predicted VT/VF (HR=4.0, 95% CI 1.2 - 13.3, p=0.02) and mortality (HR=4.2, 95% CI 1.5 - 11.9, p=0.008) in the entire population. Notably, in the HFpEF group, abnormal GLS was the only predictor of mortality (HR=3.5, 95% CI 1.1 - 10.8, p=0.02; Figure 1).

Conclusions:
Abnormal GLS is a predictor of ventricular arrhythmias and mortality in patients with heart failure. In patients with HFpEF, GLS may be used for risk stratification upon further validation in larger studies.
Abstract 16696: Racial Differences in Cardiometabolic Determinants of Natriuretic Peptide Levels in Clinically Referred Patients With and Without Heart Failure
Authors: Boakye Ansa Newman Kwame , Xu Meng , Reynolds Cassandra , Farber-Eger Eric , Dixon Debra , Agrawal Vineet , Collins Sheila , Wang Thomas , Gupta Deepak K
Published: May 2021

Background:
Relative natriuretic peptide (NP) deficiencies are associated with hypertension, diabetes, and obesity. The prevalence of these conditions varies by race, affecting more black than white individuals. We assessed whether circulating NP levels and factors associated with NP levels differ by race in clinically referred patients.

Methods:
Using Vanderbilt University Medical Center electronic health records from 2002 to 2013, we examined plasma B-type natriuretic peptide (BNP) levels and correlates in 30,487 black (17%) or white adult patients. Multivariable-adjusted models including interaction terms by race and stratification by heart failure (HF) status were used.

Results:
In 18,850 patients without HF, BNP levels were lower in black [median 58 pg/ml (25
th
, 75
th
percentile: 23, 179)] compared with white individuals [97 pg/ml (38, 247)], p< 0.001. Factors most strongly correlated with BNP differed between black (creatinine, age, chronic kidney disease, body mass index (BMI), left ventricular [LV] ejection fraction) and white (age, BMI, LV mass, chronic kidney disease, sex) patients (
Figure
). Lower BNP levels in black patients were observed across the spectrum of heart rate, blood pressure, body mass index, glucose, LV ejection fraction and mass, and renal function. The directional association of cardiometabolic risk factors with BNP levels was largely similar by race, with exceptions of significant interactions by BMI and creatinine. Higher BMI was associated with lower BNP levels in whites, while among black patients beyond a BMI of approximately 35 kg/m
2
, BNP levels did not decline any further. With higher creatinine, the rise in BNP levels was steeper in black compared with white patients. In contrast to patients without HF, among patients with HF (n = 11,637), BNP levels and its correlates were similar between black and white patients (
Figure
).

Conclusion:
The associations between cardiometabolic factors and BNP levels vary by race and HF status.
Abstract 16698: Cardiopulmonary Exercise Testing With an In-Line Filter During the COVID-19 Pandemic
Authors: Bhat Rohan R , Schoenike Mark W , Kowal Alyssa , White Casey , Rouvina Jennifer , Hardin Charles C , Malhotra Rajeev , Lewis Gregory D
Published: May 2021

Introduction:
During maximum incremental exercise expiratory flow rates increase > 10-fold and minute ventilation can exceed 100L/min, raising concern for possible spread of COVID-19 in asymptomatic patients undergoing exercise testing. Moreover, use of surgical or N95 masks that limit airflow are recognized to limit the ability to perform maximum exercise.

Hypothesis:
Use of an in-line filter during cardiopulmonary exercise testing is feasible and will not adversely impact measurements of exercise capacity.

Methods:
We conducted a proof-of-principle study in which a commercially available electrostat filter (Figure 1A), which has >99.9% viral efficiency without affecting spirometry measurements during pulmonary function testing, was placed in-line, upstream of the flow meter and gas analyzer sample line for use during cardiopulmonary exercise testing. A single healthy subject completed incremental exercise with a 3 min period of unloaded exercise followed by 4-min stages of exercise at 50, 100, 150, and 200W with and without the filter in place on the same day. Mechanical dead space was 53 ml with the filter and 45 ml without.

Results:
In comparison to no internal filter, use of an in-line filter resulted in VO
2
measurements of 99%, 97%, 98%, and 97% during 50W, 100W, 150W, and 200W, respectively (Figure 1A). VO
2
/work slope measurements and measurements of minute ventilation were also highly consistent throughout exercise with and without use of an in-line filter (Figure 1B).

Conclusions:
Exercise testing is an integral part of cardiovascular care delivery. Our findings require further validation but suggest that an in-line filtration system can be utilized in an effort to reduce droplet and viral dissemination without impacting measures of cardiopulmonary performance.
Abstract 16815: Female Sex and Its Relation With Poor Control of Oral Anticoagulation With Coumarin Derivatives: A Systematic Review and Meta-Analysis
Authors: Viana Catiane Costa , Praxedes Marcus Fernando da Silva , Sousa Waleska Jaclyn Freitas Nunes de , Bartolazzi Frederico , Vianna Mayara Sousa , da Silva José Luiz Padilha , Martins Maria A
Published: May 2021

Introduction:
Sex-differences in the quality of oral anticoagulation control have been reported,although with controversial evidence. Our hypothesis was that sex would be associated withoral anticoagulation control. We performed a systematic review and meta-analysis to investigatethis association.

Methods:
We searched for studies on MEDLINE, BVS, CINAHL, EMBASE,Cochrane and Web of Science. We included observational and experimental studies withparticipants aged >18 years of both sexes, on oral anticoagulation with warfarin or othercoumarin derivatives indicated for long-term use. The outcome of interest was time intherapeutic range (TTR), calculated by the Rosendaal method. We synthesized data from theselected studies and developed the meta-analysis. Odds ratios (OR) for binary variables andmean differences (MD) for continuous variables were pooled using the random-effects modelswith estimation via the DerSimonian-Laird method.

Results:
Thirteen studies with 89,745patients (45.08% women) were included. Nine studies were assessed in the meta-analysis frombinary variables (OR=0.89; 95% CI=0.80, 1.00; z=-1.96; p=0.05; I
2
=74%) (Fig. 1) and fourstudies with continuous variables (MD=-3.02; 95% CI=-4.43, -1.62; z=-4.22; p<0.0001; I
2
=0%)(Fig. 2). The pooled estimates indicated that women were associated with lower TTR than men.
Fig. 1
Analysis of sex effect on oral anticoagulation control.
Fig. 2
Analysis of sex effect on oral anticoagulation control. In conclusion, this systematic review showed that the female sex was associated with lowerTTR than male sex. Our results suggest the need for innovative strategies to improve healthcarefocused on women.
Abstract 16835: Targeted Disruption of Paraoxonase 3 in a Dahl Salt-Sensitive Rat Model of Chronic Kidney Disease Increases Renal Cortical Pro-Inflammatory Eicosanoids
Authors: Mohammed Chrysan J , Khalaf Fatimah K , Dube Prabhatchandra , Reid Tyler J , Connolly Jacob A , Khatibshahidi Bella Z , Kleinhenz Andrew L , Haller Steven T , Kennedy David J
Published: May 2021

Background:
Paraoxonase 3 (Pon3), is one of the three isoforms of the paraoxonase gene family. While Pon1 and Pon2 are widely studied, there is a paucity of knowledge regarding Pon3. Pon3 is synthesized in the liver and can circulate bound to high-density lipoproteins. There is significant expression in the kidney also. Pon3 has the ability to metabolize eicosanoids, which can act as signaling molecules and have known roles in the pathophysiology of some renal diseases. Decreased Pon activity is associated with elevated levels of eicosanoid metabolites and adverse clinical outcomes. We tested the hypothesis that targeted disruption of Pon3 results in elevated levels of pro-inflammatory eicosanoids and progression of renal injury.

Methods/ Results:
Ten week old male Dahl salt-sensitive (SS rats) and Pon3 mutant rats (SS
Pon3
KO) were maintained on 8% high salt diet for eight weeks, to initiate salt-sensitive hypertensive renal disease. Previously we observed that SS
Pon3
KO rats on eight weeks high salt diet demonstrated significantly increased phenotypic renal injury and mortality. In the current study, we noted that SS
Pon3
KO had significantly decreased (p<0.05) glomerular filtration rate compared to SS wild type. Blood pressure (radiotelemetry) as well as plasma angiotensin and aldosterone (LC-MS/MS) were not different between the two groups after high salt diet. We used targeted lipidomic profiling to determine eicosanoid content in renal cortex from SS
Pon3
KO and SS wild type rats at the end of eight weeks of high salt diet. We found that hydroxyl fatty acids 5-HEPE and 5-HETE (5-lipoxygenase dependent arachidonic acid metabolites) were significantly (p<0.05) elevated in the renal cortex of SS
Pon3
KO compared to SS wild type rats. In addition to being mediators of inflammation, these metabolites are associated with renal cell injury and death. Furthermore, prostaglandin 6-keto-PGF
1α
, which has known links to renal inflammation, was significantly (p<0.05) increased in renal cortex of SS-
Pon3
KO compared to SS wild type rats.

Conclusion:
These findings suggest that targeted deletion of Pon3 increases pro-inflammatory eicosanoids (5-HETE and 5-HEPE) and prostaglandins (6-keto-PGF
1α
), as well as increases renal damage independent of blood pressure.
Abstract 16838: Lipoprotein(a) is Weakly Associated With Coronary Artery Calcification in Molecularly Defined Heterozygous FH Subjects
Authors: Miname Marcio H , Novaes Betina , Remedio Bruna , Santos Raul D
Published: May 2021

Introduction:
Familial hypercholesterolemia (FH) is characterized by premature atherosclerosis (ATH). Coronary calcium score (CAC) reflects coronary plaque burden. Lipoprotein(a) [Lp(a)] increases ATH risk in FH. Little is known about the association of CAC and Lp(a) in heterozygous FH.

Hypothesis:
Lp(a) could be associated with CAC presence in HeFH independently of LDL-c and age.

Methods:
Molecularly confirmed primary prevention FH individuals that were submitted to CAC and Lp(a) evaluation were included. LDL-c was corrected by Lp(a)-cholesterol. Binary logistic regression analysis with CAC presence as dependent variable was used to evaluate determinants of CAC. Spearman correlation and area under ROC curve (AUC) were calculated for Lp(a) discrimination of CAC presence.

Results:
We included 217 FH [65.4% female, 43.9±13.6 years, LDL-c 237±76 mg/dL, median Lp(a) 29 mg/dL (interquartile range: 53)]. CAC was present in 98 (45.1%) individuals. In univariate analysis CAC associated with (OR, 95%CI): age (1.09, 1.062-1.120, p<0.001), LDL-c (1.005, 1.001-1.009, p=0.017), Lp(a) (1.010, 1.003-1.017, p=0.007), hypertension (3.99, 2.202-7.868, p<0.001), BMI (1.096, 1.030-1.166, p=0.004) and corneal arcus (3.20, 1.509-6.790, p=0.002). After multivariate logistic regression only age (OR: 1.086, 95%CI 1.052-1.121, p<0.001) and LDL-c (OR: 1.005, 95% CI 1.001-1.010, p=0.024) persisted associated with CAC. LDL-c was associated with CAC for those with Lp(a) below the median (OR=1.007, 95% CI 1.001-1.013, p=0.019) and this association persisted even including Lp(a) in the model (p=0.022). However, LDL-c was not associated with CAC for those with Lp(a) above the median (OR=1.003, 95%CI 0.997-1.008) and persisted not associated when including Lp(a) in the model (p=0.208). The reverse occurred with Lp(a), which was not associated with CAC for those with Lp(a) below the median (p=0.534) and was associated to CAC for those above median (p=0.013). Lp(a) correlation with CAC was weak (r=0.175, p=0.010) and the AUC was 0.581 (95% CI 0.503-0.659, p=0.040).

Conclusions:
Lp(a) is weakly correlated to CAC in FH and the association of LDL-c and Lp(a) with CAC is different according to Lp(a) levels. This suggests that Lp(a) may not be associated with plaque burden in FH.
Abstract 16850: Machine Learning Based Estimation of Systolic and Diastolic Arterial Blood Pressure From the Electrocardiogram and Oxygen Saturation Waveforms
Authors: Sevakula Rahul Kumar , Kassab Mohamad , Bollepalli Sandeep Chandra , Isselbacher Eric M , Armoundas Antonis
Published: May 2021

Introduction:
Accurate, continuous blood pressure (BP) monitoring requires invasive equipment. We investigate the utility of a machine learning algorithm (ML) to estimate the systolic (sys) and diastolic (dia) BP from the electrocardiogram (ECG) and oxygen saturation (SpO2) signals.

Methods:
We identified over 2,000 hours (~9.2 M heart-beats), of 4 lead ECG, arterial BP, and SpO2 waveforms, from 82 random ICU patients, with various diagnoses. The ECG, BP and SpO2 waveforms were delineated using a wavelet-transform-based algorithm. Features extracted from the ECG and SpO2 signals were used as input to the ML model, while the sys/dia BP values of the corresponding BP signal (range: 0-250 mmHg), served as the gold standard. Using these features, we trained two independent Random Forest (RF) models to estimate the sys/dia BP values, and measured their performance over five-fold cross-validation. To identify the optimal window-length (# heart beats) in estimating sys/dia BP values, the entire process of extracting features and training/testing of RF models was performed for window-lengths of {1,5,6,7,8,9,10,11,12,13,14,15,20,30,50} heart-beats.

Results:
The root-mean-square error (RMSE) at each window-length is shown in the Figure. The lowest RMSE for both estimated sys/dia BP, 5.81±4.61 mmHg and 3.73±3.26 mmHg, respectively, was achieved at 14 heart-beats. The corresponding RMSE values using a one-beat length-window were 7.73±5.93 mmHg and 5.28±4.42 mmHg, respectively. This result indicates the ability to estimate the instantaneous BP values even on a beat-to-beat basis, with low-error.

Conclusions:
In comparison to prior studies, our novel ML model, to the best of our knowledge, has been trained over the largest amount of data. Our ML model can accurately estimate the sys/dia values of the arterial BP.

Figure:
RMSE values obtained while estimating the mean sys/dia BP, across different window-lengths.
Abstract 16872: The Association of Mental Health Disorders With Heart Failure Outcomes and the Impact of Substance Abuse
Authors: Cazzulino Francesca , Nishimura Marin , Bhatia Harpreet S , Thomas Isac C
Published: May 2021

Introduction:
Depression is associated with adverse heart failure (HF) outcomes. Substance abuse disorders often co-occur with depression and other psychiatric disorders. It is unclear if associations of psychiatric disorders with HF outcomes are confounded, mediated or enhanced by substance abuse.

Methods:
Medical records and diagnosis codes of HF patients with reduced ejection fraction at UC San Diego between 2005 and 2016 were reviewed. Outcomes were total number of HF admissions, time to HF readmission, and all-cause mortality. Associations of mood and anxiety disorders were assessed using negative binomial regression or cox regression models with hierarchical adjustment for demographics, substance abuse, and medical co-morbidities. Effect modification by substance abuse was assessed by inclusion of multiplicative interaction terms.

Results:
Of 4529 patients (mean age 61.5 years, 69% male) included, 722 (16%) had an anxiety disorder and 222 (4.9%) had a mood disorder. Methamphetamine (6.6 %) and opioid (6.0%) abuse were common. Over a median follow up of 3.8 years (9999 HF admissions and 901 deaths), both anxiety and mood disorders were associated with total HF admissions and HF readmission; this was not attenuated by adjustment for substance abuse (Table, top). Adjustment for medical co-morbidities weakened the associations modestly. These associations did not vary significantly by abuse of any substance (Table, bottom). Mood disorders were associated with mortality only in patients with certain substance abuse disorders.

Conclusions:
Anxiety and mood disorders are associated with adverse HF outcomes. Their associations are independent of and do not vary with substance abuse, however some substances appear to enhance an association with total mortality. These results suggest that greater recognition and treatment of psychiatric disorders in HF patients, including in those with co-morbid substance abuse disorders, may improve clinical outcomes.
Abstract 16880: Exosomes From Dilated Cardiomyocytes Activate Fibrosis
Authors: Fu Xuebin , Jang Jihyun , Gunasekaran Muthukumar , Sharma Sudhish , Mishra Rachana , Saha Progyaparamita , Abdullah Mohamed , Wang Lina , Arfat Mir Yasir , Li Deqiang , Kaushal Sunjay
Published: May 2021

In dilated cardiomyopathy (DCM), exaggerated fibrosis reduces tissue compliance and accelerates the progression to heart failure. However, the mechanisms for fibrotic remodeling in DCM are not well understood. Exosomes are small extracellular vesicles that function as intercellular messengers. Our hypothesis is that exosomes from hypertrophic stimulated DCM cardiomyocytes activate fibrosis in the heart. We utilized iPSCs reprogrammed from DCM patients and healthy control individuals (CTL) to differentiate them into cardiomyocytes (iCMs). iCMs were stimulated by Angiotensin II, and conditioned media were collected to isolate exosomes thereafter. Fibroblasts were treated with CTL-exosomes and DCM-exosomes respectively in vitro. Meanwhile, we injected exosomes into the mouse hearts in vivo. Fibrotic markers and protein expression were examined by western blot and histology. Additionally, we also analyzed the microRNA profiles in the DCM-exosomes and CTL-exosomes by small RNA sequencing. The microRNAs expressions in exosomes were also confirmed by RT-PCR. We found DCM exosomes treatment significantly upregulated extracellular matrix proteins expressions in fibroblasts. Collagen I, collagen III, and CTGF were significantly upregulated in DCM exosomes treatment group compared to CTL exosomes treatment group. Intramyocardial injection of DCM exosomes into wild type mice (CD-1) caused impaired ejection fraction after 7 days compared to CTL exosomes injection (DCM = 51.5 ± 6.21%*, CTL =64.6 ± 3.99%; * = P < 0.05). Picro sirius red staining for extracellular matrix showed significant increase of fibrosis in DCM exosome injection group, compared to CTL exosomes and PBS group (DCM = 3.08 ± 0.24%*, CTL = 0.087 ± 0.02%, PBS = 0.053 ± 0.01%; * = P < 0.05). Next-generation sequencing of these exosomes exhibited upregulation of a group microRNAs in the DCM exosomes. microRNA-103a upregulation was confirmed in DCM exosomes. Overexpression microRNA-103a resulted in fibroblast activation and upregulation of Col I, Col III, and CTGF expression in vitro. Our findings uncovered a critical role for exosomal microRNA (microRNA-103a) mediating pathological fibrotic remodeling in DCM.
Abstract 16882: Exercise Prescription Patterns After Spontaneous Coronary Artery Dissection: Insights From a Large Multinational Registry
Authors: Chacin Suarez Audry , Bonikowske Amanda R , Medina-inojosa Jose R , Gulati Rajiv , Best Patricia J , Hayes Sharonne N , Tweet Marysia S
Published: May 2021

Introduction:
Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction in otherwise healthy and most times presumably fit young women. In the absence of evidence for benefit or harm, exercise prescription (EXP) after SCAD remains arbitrary. We assessed EXP patterns among participants in a large multinational SCAD registry.

Methods:
Participants with SCAD as confirmed by coronary angiography completed surveys detailing exercise (EX) habits prior to SCAD (initial survey), and EXP from their provider on initial and subsequent visits after SCAD (follow-up survey). Demographic and clinical characteristics were collected by electronic health record review by trained nurse abstractors. EXP was categorized according to EX components that include: type, intensity, frequency, time/session, and external conditions.

Results:
Among 950 participants, mean ± age was 46.8 ± 9.5 years, 96% were women and 77% reported attending ≥1 Cardiopulmonary Rehabilitation session. Prior to SCAD, 49% were aerobically exercising ≥ 3times per week, and only 32% performed strength-building EX regularly. Initial and subsequent post-SCAD visit details in 299/950 participants showed that most (93%) patients received some form of EX
(Figure 1-A)
counseling, namely: EXP, unspecific advice or were discouraged from any EX
(Figure 1-B)
. Limits regarding EX type and intensity were the most common advice received among EXP group
(Figure 1-C)
.

Conclusions:
Insights from our study show that only 40% of patients were achieving current exercise recommendations for adults prior to SCAD (vs 53% adult U.S population; CDC, 2018) which suggests that SCAD patients may not be as active as previously described. Most patients receive some form of EX counseling after SCAD; however, a structured EXP is needed to avoid overly cautious approaches that could lead to uncertainty, deconditioning, impaired quality of life, or increase risks associated with a sedentary lifestyle.
Abstract 16894: Utilization of H2FPEF to Predict One-Year Mortality in Decompensated Heart Failure With Preserved Ejection Fraction
Authors: Saith Sunil , trikha anuragh , Chkhikvadze Tamta , Khorolsky Ciril , Ha June , Chuquin J. D
Published: May 2021

Background:
The H2FPEF score is a validated scoring system to determine whether dyspnea may be due to heart failure with preserved ejection fraction (HFpEF). Recent evidence has suggested that H2FPEF scoring system may correlate with outcomes in established HFpEF. Its utilization for estimating mortality in patients who die within one year of discharge is not known.

Methods:
We collected clinical demographics and echocardiographic parameters from reports to calculate H2FPEF scores for 301 patients admitted with decompensated HFpEF between August 2016 and 2017. Patients were included if an echocardiographic report was available within 3 months, confirming an ejection fraction > 50%. E/E’ and filling pressures were scored as 0 if not recorded in the echocardiographic report.

Results:
Median age was 81 years (IQR: 71-89), with 62.9% female. One-year follow-up was confirmed for 268 patients, with 56 deaths (20.9%). Receiver operating curve analysis suggest borderline significance of H2FPEF in predicting one-year mortality (area under curve, 0.576, 95% CI: 0.493-0.658, p=0.073). Optimal H2FPEF cutpoint score was 4.5 (73% sensitivity, 50% specificity). On univariate analysis, body mass index (BMI) > 30, hypertension, atrial fibrillation (p<0.001) and pulmonary artery systemic pressure > 35 mmHg (p=0.038) were associated with one-year mortality. On stepwise logistic regression, only BMI > 30 and atrial fibrillation remained associated with mortality in multivariate analysis.

Conclusion:
The utilization of H2FPEF in established HFpEF might confer some ability to predict one-year mortality, driven by obesity (2 points) and atrial fibrillation (3 points). Validation in larger cohorts with longer follow-up is necessary to establish its potential role in discharge planning and transitions of care of decompensated HFpEF.
Abstract 16899: Sex Differences in Young Adults With Acute Myocardial Infarction
Authors: Nadadur Malini , Tank Rikin , Chen Cheng , ICHIUJI Anne , Shen Yuh-Jer A , Lee Ming Sum , Lin Bryan
Published: May 2021

Introduction:
There are important sex differences in the pathophysiology and clinical presentation of cardiovascular disease. Cardiovascular disease is understudied in women, despite it being the leading cause of mortality. The goal of this study is to report sex differences in clinical characteristics, treatment, and outcomes in young patients presenting with acute myocardial infarction.

Methods:
This is a retrospective observational study that included patients ages 18 to 40 hospitalized for acute myocardial infarction between 2006 and 2016 in Kaiser Permanente Southern California, a large integrated healthcare system. Differences in demographics, clinical characteristics, and management were examined between men and women. Multivariable Cox proportional hazard models were used to examine the association between sex and mortality.

Results:
Between 2006 and 2016, a total of 26,390 patients were hospitalized with a principal diagnosis of acute myocardial infarction and underwent coronary catheterization. In this cohort, 603 patients were young adults between age 18 to 40, of whom 144 (24%) were women. Women were more likely to be black. There were no significant sex differences in the prevalence of hypertension, hyperlipidemia, diabetes, heart failure and renal failure. There was a higher prevalence of obesity in women. Women were more likely to have no obstructive disease on coronary angiogram (43.4% vs. 33.2%, p=0.03). Treatment with percutaneous coronary intervention was less likely in women (38.2% vs. 56.2%, p<0.001). Mortality was low for both women and men during index hospitalization (0.7% vs 0.9%, p=0.84) and at one year (1.4% vs. 1.5%, p=0.91), with no significant differences (adjusted HR 1.3, 95% CI 0.5-3.1).

Conclusions:
Compared to young men, young women presenting with acute myocardial infarction as less likely to have obstructive coronary artery disease. Mortality rates for both men and women were low, with no significant differences observed.
Abstract 16920: Transcatheter Aortic Valve Replacement in Aortic Regurgitation: The U.S. Experience
Authors: Jani Chinmy T , Arora Shilpkumar , Lahewala Sopan , ZUZEK ZACHARY , Jaswaney Rahul , Thakkar Samarthkumar J , Patel Harsh P , Singh Anandita , Patel Raj , Bhyan Poonam , Hoit Brian , Osman Mohammed Najeeb , Attizzani Guilherme , Main Anthony , Panaich Sidakpal S
Published: May 2021

Background:
Transcatheter aortic valve replacement (TAVR) may be an effective option for high-risk AR patients. Although international experiences of TAVR for AR are published, U.S. data is limited. The primary objective of this study was to investigate periprocedural and 30-days outcomes in terms of mortality and post-procedural complications in patients undergoing TAVR for AR using large national U.S. databases.

Hypothesis:
TAVR is a promising option in AR

Methods:
Study cohorts were derived from Nationwide Inpatient Sample (NIS) and Nationwide Readmissions Database (NRD) 2016-17. TAVR and AR were identified using ICD-10-CM-codes. The key outcomes were all-cause mortality, disabling stroke, valvular complications, complete heart block (CHB)/ permanent pacemaker placement (PPM), open heart surgery, acute kidney injury (AKI) requiring dialysis, and vascular complications. Multivariate logistic regression was used to adjust for confounders.

Results:
915 patients from the NIS (male-71%, age 65-84.2%) and 822 patients from the NRD (male-69.3%, age 65-80.5%) underwent TAVR for AR. The median length of stay (LOS) was 4 days for both cohorts. In-hospital mortality was 2.7% in NIS and 30-day mortality was 3.3% in NRD. Disabling strokes were noted in 0.6% peri-procedurally and 1.8% at 30-days. Valve-related complications were 18-19% with paravalvular leak being the most common. Approximately 11% of patients developed CHB and/or needed PPM in both cohorts. In NRD, 2.2% of patients required dialysis for AKI, 1.5% developed vascular complications, and 0.6% required open-heart surgery within 30-days post-procedure. Anemia was predictive of increased overall complications and valvular complications, whereas, peripheral vascular disease was predictor of increased valvular complications and CHB/PPM.

Conclusion:
TAVR is a promising option in AR. Further studies are necessary for the expansion of TAVR as standard treatment in AR.
Abstract 16926: The Effects of a Mitochondrial Targeted Ubiquinone (MitoQ) on Vascular Function in Chronic Kidney Disease
Authors: Kirkman Danielle L , Shenouda Ninette , Stock Joseph M , Muth Bryce J , Chouramanis Nicholas , Townsend Raymond R , Edwards David G
Published: May 2021

Introduction:
Aberrant vascular function contributes to the substantially high cardiovascular burden of chronic kidney disease (CKD). Mitochondrial derived oxidative stress is a potential therapeutic target to ameliorate CKD related vascular dysfunction.

Hypothesis:
We hypothesized that a mitochondrial targeted antioxidant (MitoQ) would improve vascular function in Stage 3-5 CKD patients without overt cardiovascular disease.

Methods:
In this controlled, double-blind trial, 18 CKD patients (Mean±SEM: Age, 62±3 years; eGFR, 45±3 ml•min•1.73
2
) were randomized to receive an oral dose of MitoQ (20mg/day; MTQ) or a Placebo (PLB) for 4 weeks. Outcome measures were assessed at week 0 and week 4. Aortic pressure waves were synthesized from brachial artery waveforms acquired by oscillometry and the use of a generalized transfer function. The central pressure waveform was separated into forward and reflected waves using a triangular flow waveform. Conduit artery vascular function was assessed via brachial artery flow mediated dilation (FMD).

Results:
MitoQ was well tolerated and patient compliance was high (MTQ, 99.6±0.4%; PLB, 97.8±2.2%). Independent of peripheral (Baseline vs. Follow Up: MTQ, 140±6 vs. 137±6 mmHg; PLB, 136±4 vs. 134±6 mmHg; interaction p=0.7) and central (MTQ, 128±5 vs. 123±6 mmHg; PLB, 124±3 vs. 123±5 mmHg; interaction p=0.8) systolic blood pressures, MitoQ maintained forward wave amplitudes (MTQ, 31±3 vs. 29±1 mmHg; PLB, 29±3 vs. 36±3 mmHg; interaction p=0.05) and tended to reduce reflected wave amplitudes (MTQ, 18±2 vs. 16±1 mmHg; PLB, 19±2 vs. 21±2 mmHg; interaction p=0.04). MitoQ administration favored improvements in FMD (MTQ, 2.4±0.3 vs. 4.0±0.9%; PLB, 4.2±1.0 vs. 2.5±1.0%; interaction p=0.04).

Conclusions:
These results suggest that targeting mitochondrial derived reactive oxygen species holds promise as a potential therapeutic strategy to improve CKD related vascular dysfunction. Whether MitoQ related improvements in arterial hemodynamics are a result of augmented cardiac function or a reduction in vascular resistance warrants future investigation in larger studies.