bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16004: Clinical and Hemodynamic Correlates of Exaggerated Metabolic Cost of Exercise Initiation
Authors: Schoenike Mark W , Shah Ravi V , Armengol de la Hoz Miguel Á , Cunningham Thomas F , Blodgett Jasmine B , Tanguay Melissa , Sbarbaro John A , Rouvina Jennifer N , Kowal Alyssa , Houstis Nicholas , Nayor Matthew G , Baggish Aaron L , Ho Jennifer E , Hardin Corey , Malhotra Rajeev , Lewis Gregory
Published: May 2021

Introduction:
Exercise intolerance is common in cardiovascular disease and is a cardinal manifestation of heart failure with preserved ejection fraction (HFpEF). Decreased exercise capacity is often attributed to cardiac limitations, though HFpEF is increasingly recognized to be both a metabolic and a cardiovascular disorder.

Hypothesis:
Patients with HFpEF will have exaggerated metabolic cost of exercise initiation with associated high expenditure of hemodynamic reserve capacity.

Methods:
We quantified the workload-equivalent cost of initiating exercise using cardiopulmonary exercise testing in patients with HFpEF (N=184, age 62±13, 47% women, peak VO2 13.8±3.3 ml/kg/min). Individualized VO2-work rate relationships during loaded exercise were used to derive the work-equivalents required to move extremities with zero external resistance (0 watts)—termed “internal work” (IW). Standard linear regression techniques were used for comparisons.

Results:
In individuals with HFpEF, the internal work (42±28 W) was often a large portion of the total workload achieved. BMI accounted for the greatest variance in IW (23%), suggesting a metabolic basis for IW. Resting measures of myocardial function and biventricular filling pressures did not measurably contribute to explanatory variance in IW, suggesting a non-cardiac origin. Individuals with HFpEF in the fourth quartile of IW (76±28W) had a dramatic hemodynamic response to exercise in pulmonary capillary wedge and mean pulmonary arterial pressures. Changes in hemodynamic measurements were more modest between quartiles of IW in the submaximal ramp period following unloaded exercise.

Conclusions:
Internal work is a new measure that captures the metabolic cost of initiating movement. Internal work is associated with limitations in achievable external workload as well as steep early increases in cardiac filling pressures in HFpEF. Further investigation into the pathophysiology of elevated IW is needed.
Abstract 16010: Congestive Heart Failure and Coronavirus Disease 2019 Illness Severity
Authors: Ruge Max , Gomez Joanne Michelle D , Nair Gatha G , Fugar Setri , du Fay de Lavallaz Jeanne , jahan nusrat , Lavani Prutha , Simmons J. Allan , Rao Anupama , Marinescu Karolina , Williams Kim A , Volgman Annabelle S , Suboc Tisha Marie
Published: May 2021

Introduction:
The coronavirus disease 2019 (COVID-19) pandemic has killed hundreds of thousands worldwide. Those with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. Congestive heart failure (CHF) may lead to worsening COVID-19 symptoms. However, it is unclear if CHF is an independent risk factor for severe COVID-19 infection or if other accompanying comorbidities are responsible for the increased risk.

Methods:
From March to June 2020, data was obtained from adult patients diagnosed with COVID-19 infection who were admitted in the Rush University System for Health (RUSH) in Illinois. Heart failure patients, determined by ICD code assignments extracted from the electronic medical records, were identified. Multivariable logistic regression was performed between predictor variables and a composite outcome of severe infection consisting of Intensive Care Unit (ICU) admission, intubation, or in-hospital mortality.

Results:
In this cohort (n=1136), CHF [odds ratio (OR) 1.02] alone did not predict a more severe illness. Prior myocardial infarction [(MI), OR 3.55], history of atrial fibrillation [(AF), OR 2.14], and male sex (OR 1.55) were all significantly (p<0.001) associated with more severe COVID-19 illness course when controlling for CHF (Figure 1). In the 178 CHF patients, more advanced age (68.8 years vs. 63.8 years; p<0.05) and female sex (54.5% vs. 39.1%; p<0.05) were associated with increased severity of illness.

Conclusions:
Prior MI, history of AF, and male sex predicted more severe COVID-19 illness course in our cohort, but pre-existing heart failure alone did not. However, CHF patients who are females and older in age are at risk for severe infection. These findings help clinicians identify patients with comorbidities early at risk for severe COVID-19 illness.
Abstract 16040: High-risk Percutaneous Coronary Intervention Without Mechanical Circulatory Support in Acute Coronary Syndrome
Authors: Khalid Nauman , Javed Hasan , Zhang Cheng , Shea Corey , Shlofmitz Evan , Chen Yuefeng , Musallam Anees , Case Brian C , Yerasi Charan , Forrestal Brian , Chezar Azerrad Chava , Rogers Toby , Hashim Hayder , ben-dor itsik , Bernardo Nelson L , Satler Lowell F , Waksman Ron
Published: May 2021

Background:
Use of mechanical circulatory support (MCS) for high-risk percutaneous coronary intervention (HRPCI) remains controversial with lack of randomized evidence and associated complication risks from these devices. We investigated whether performing HRPCI without elective MCS in patients with acute coronary syndrome (ACS) is safe and feasible.

Methods:
A single-center, retrospective analysis was done for patients presenting with ACS meeting HRPCI criteria (defined by Interventional Council of American College of Cardiology) including unprotected left main disease, last remaining conduit, left ventricular ejection fraction<35%, 3-vessel coronary artery disease, severe aortic stenosis or severe mitral regurgitation. Clinical, procedural, major in-hospital and 30-days cardiovascular outcomes were assessed.

Results:
From 2003-2018, 1992 patients (2887 lesions) with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI) and 920 patients (1328 lesions) with ST-segment elevation myocardial infarction (STEMI) underwent HRPCI. The study population had 64.8% men and 52.9% Caucasians in UA/NSTEMI-group and 64.3% men and 53.7% Caucasians in STEMI-group. Mean age for UA/NSTEMI and STEMI patients were 68.6+/-12.69 and 64.52+/-13.54 years respectively. Procedural success was achieved in 96.5% of UA/NSTEMI and 97.9% of STEMI patients. In-hospital and 30-day all-cause mortality was 2.1% for UA/NSTEMI and 4.7% for STEMI patients. Bailout MCS was required in 2.4% of UA/NSTEMI and 9.9% of STEMI patients. Rates of major complications for UA/NSTEMI and STEMI were low, except for renal failure (Panel A). Panel B provides HRPCI criteria distribution.

Conclusions:
HRPCI without elective MCS is safe and feasible in majority of ACS patients challenging the current practices of professional societies. A randomized trial comparing unprotected vs. protected HRPCI for ACS patients is warranted to identify patients that would benefit from MCS.
Abstract 16046: Conventional versus Right Mini-thoracotomy versus Robotic Mitral Valve Replacement/repair; Insights From a Network Meta-analysis
Authors: Yokoyama Yujiro , Takagi Hisato , Kuno Toshiki
Published: May 2021

Background:
Benefits and risks of minimally invasive cardiac surgery (MICS) through right mini-thoracotomy and robotic surgery for mitral valve are not fully understood. We conducted a network meta-analysis comparing the perioperative and long-term outcomes of mitral valve surgery via conventional sternotomy, MICS and robot.

Methods:
MEDLINE and EMBASE were searched through March 15th, 2020 to identify randomized controlled trials (RCTs) and propensity-score matched (PSM) trials that investigated perioperative and long-term outcomes after mitral surgery via conventional sternotomy, MICS and robot. Subanalyses were conducted by restricting trials, in which mitral valve repair was tried first for all patients.

Results:
Our systematic literature search identified 2 RCTs and 21 PSM trials. MICS was related to significant decrease in PM ([RR] [95% confidence interval [CI] =0.56 [0.40-0.78]] and SSI (RR [95%CI] =0.53 [0.33-0.85) compared to conventional sternatomy. Re-exploration for bleeding was significantly higher in robot compared to sternotomy (RR [95% CI] =1.56 [1.03-2.37]), and transfusion was higher in sternotomy compared to MICS (RR [95%CI] =1.63 [1.27-2.08]). No significant differences were observed in perioperative mortality, MI, stroke, and LCOS among there procedures. Similarly, there were no significant differences in long-term survival and mitral valve reoperation. Suanalyses by restricting trials in which mitral valve repair tried first for all patients showed MICS was related to significant increase in mitral valve reoperation compared to conventional sternotomy (hazard ratio [95%CI] =7.33 [1.54-34.97]) (Figure).

Conclusion:
Our network meta-analysis demonstrated similar long-term survival and mitral valve reoperation. However, MICS was related to significant increase in mitral valve reoperation after mitral valve repair compared to conventional sternotomy.
Abstract 16061: Antihypertensive Therapy Prescribing Pattern Among Patients With Markedly Elevated Blood Pressure in a Real-world Setting
Authors: Lu Yuan , Huang Chenxi , Mahajan Shiwani , Caraballo Cesar , Spatz Erica S , Schulz Wade , Krumholz Harlan M
Published: May 2021

Introduction:
Combination therapy with two or more antihypertensive agents is recommended for management of patients with markedly elevated blood pressure (systolic blood pressure [SBP] ≥160 mmHg or diastolic blood pressure [DBP] ≥100 mmHg) by the 2017 AHA/ACC hypertension guideline. Using electronic health records (EHR) data from a large health system, we characterized real-world antihypertensive drug prescribing patterns and assessed guideline adherence among ambulatory patients with markedly elevated BP.

Methods:
Our cohort included patients aged 18-85 years with at least 2 outpatient visits in the Yale New Haven Hospital System between January 1
st
, 2013 and December 31
st
, 2018, resulting in a total of 665,691 patients. We defined the phenotype of markedly elevated BP as two consecutive outpatient visits with SBP ≥160 mmHg or DBP ≥100 mmHg. We described the number and class of antihypertensive drugs (previously taken and newly prescribed) at the second visit with BP ≥160/100 mmHg.

Results:
We identified 38,098 patients with markedly elevated BP with a mean age of 62.4 (SD: 13.7) years; 47.9% were male; and 67.8%, 20.9%, and 9.3% were White, Black and Hispanic. Among them, 49.3% were not on any antihypertensive drugs at the end of the second visit, 26.2% had one active antihypertensive drug prescription, and 24.5% had two or more agents prescribed (Figure). Among patients with two or more antihypertensive drug prescriptions, the most common drug class combination prescribed was diuretic/ACE inhibitor (10.2%), followed by diuretic/ARB (9.3%), and ACE inhibitor/calcium channel blocker (6.5%). The low prescription of combination therapy was consistent across age, gender, and race subgroups.

Conclusions:
Prescribing of guideline-recommended combination antihypertensive drugs for patients with markedly elevated BP is suboptimal. Major opportunities exist for improving the guideline adherence of antihypertensive drug prescription in this population.
Abstract 16064: Mechanical Left Ventricular Venting is Associated With Improved Survival in Adults Undergoing Venoarterial Extracorporeal Life Support: An ELSO Registry Analysis
Authors: Nunez Jose I , Willar Brooks , Kennedy Kevin , Rycus Peter , Tonna Joseph , Sabe Marwa , Kapur Navin K , Shaefi Shahzad , Garan Arthur R , Grandin Edward W
Published: May 2021

Introduction:
Venoarterial extracorporeal life support (VA-ECLS) imposes increased afterload on the left ventricle (LV), potentially provoking LV distension and impaired ventricular recovery. Prior studies have suggested a survival benefit with LV mechanical venting (MV), but multi-center data are lacking.

Methods:
We queried the ELSO registry for adults undergoing VA-ECLS and stratified them by the use of MV, including intra-aortic balloon pump and percutaneous ventricular assist device. We excluded patients with pulmonary embolism, heart transplant, congenital and valvular heart disease, aortic disease, and central cannulation. The primary outcome was in-hospital mortality. Secondary outcomes were on-support mortality and major adverse events, including bleeding, hemolysis, ischemic stroke, limb ischemia, and renal injury. We used multivariable logistic regression modeling to adjust for relevant clinical covariates.

Results:
Among 12734 patients undergoing VA-ECLS, 3353 (26.3%) received MV devices. Patients with MV were older (mean age 56.3 vs 52.7 years), more often male (76.3% vs 68.5%), and more often supported for acute myocardial infarction (43.0% vs 21.7%), p<0.001 for all. Prior to ECLS, patients with MV had lower rates of cardiac arrest (51.7% vs 55.1%) but more commonly needed >2 vasopressors (41.8% vs 27.2%) and had a higher incidence of acute renal (17.1% vs 10.5%), liver (4.4% vs 3.1%), and respiratory failure (20.9% vs 15.9%), p<0.001 for all. Crude on-support (41.6% vs 47.8%, p<0.001) and in-hospital (56.7% vs 59.2%, p=0.01) mortality were lower in the MV group. In multivariable modeling, MV was associated with a significantly lower odds of mortality but higher odds of adverse events including medical and cannula site bleeding, hemolysis, limb ischemia and renal injury (Figure).

Conclusions:
Among adults supported with peripheral VA-ECLS, LV MV was associated with lower mortality despite a higher rate of important adverse events.
Abstract 16082: Machine Learning to Improve Left Ventricular Scar Quantification in Hypertrophic Cardiomyopathy Patients
Authors: Ghaziani Zeinab N , Sun Jesse , Chan Raymond H , Rakowski Harry , Maron Martin S , Rowin Ethan J , WANG BO , Tsang Wendy
Published: May 2021

Introduction:
Accurate and reproducible scar quantification of late gadolinium enhancement (LGE) images from cardiac magnetic resonance imaging (CMR) is important in risk stratifying hypertrophic cardiomyopathy (HCM) patients. Previous machine learning algorithms for CMR LGE quantification deployed three-dimensional convolutional neural network (CNN) architecture, which required image cropping and custom graphic processing units (GPUs) to function, thus limiting their general applicability. We aim to develop a deep two-dimensional (2D) CNN model that contours the left ventricle (LV) endo- and epicardial borders and quantifies LGE.

Hypothesis:
We hypothesize that a deep 2D CNN model, which uses commercially available GPUs, could be used to efficiently and accurately contour LV endo- and epicardial borders and quantify CMR LGE in HCM patients.

Methods:
We retrospectively studied 296 HCM patients (2423 images) from the University Health Network (Toronto, Canada) and Tufts Medical Center (Boston, USA). LGE images were manually segmented by an expert reader. Scar was defined as 5 standard deviations higher than the mean of the annotated normal region pixels. A 2D U-net CNN variant was used to train a model on 80% of the datasets. Testing was performed on the remaining 20%. We applied a 5-folds cross validation algorithm for training to improve model robustness. Model performance was assessed using the Dice Similarity Coefficient (DSC).

Results:
We were able to develop a deep learning model that could successfully perform both LV segmentation and scar quantification using a generally available GPU card. Our algorithm did not require image cropping and processed one image every 60 milliseconds. DSC scores averaged across the 5-folds was excellent at 0.89+0.22 for the endocardium and 0.81+0.17 for the epicardium, and good at 0.57+0.31 for scar.

Conclusions:
Using novel 2D CNN methods, we have successfully developed an automatic algorithm that rapidly provides LV endo- and epicardial contours and scar quantification on LGE CMR images that is superior to previously published studies. Unlike previous algorithms, our program does not require the use of custom CPUs or image cropping, potentially allowing it to be integrated into routine clinical practice.
Abstract 16090: Mitochondrial Fission Related Mirnas Plays a Role in the Etiology of Pulmonary Artery Diseases
Authors: Iwatani Noriko , Kubota Kayoko , Ikeda Yoshiyuki , Miyanaga Sunao , Tokushige Akihiro , Ohishi Mitsuru
Published: May 2021

Background:
Mitochondria play a crucial role in developing cardiovascular diseases through reactive oxygen species production. Mitochondria are dynamic organelles that undergo fission and fusion and mitochondrial fission is reported to cause pulmonary artery diseases (PH). This study examined whether and how mitochondrial fission-related miRNA are involved in the etiology of PH.

Methods:
We enrolled 41 patients with PH (mean age: 61.2±13.4, 31 female) and 30 control patients (mean age: 67.4±12.0, 14 female). PH patients were then categorized as group 1 (n=12), group 3(n=7) and group 4 (n=22). We isolated total RNAs from blood samples and measured circulating miR-140 regulating mitochondrial dynamics to fission and miR-30, miR-485 and miR-499 which induce mitochondrial fusion by real-time PCR.

Results:
The circulating miRNA levels of miR-140-3p was higher and that of miR-485-3p and miR-485-5p were lower in PH compared to Ctr, whereas miR-30 and miR-499 did not change between the two groups. Among PH patients, circulating levels of miR-140 was highest in patients with group1, and that of miR-485was lowest in patients with group3. These results suggest that circulating miRNA which regulate mitochondrial dynamics to fission is related to PH. Moreover, the levels of miR-140 was co-related to SvO2 (p=0.0065) and the change in cardiac index in PH(p=0.0385), indicating that circulating miR-140 may play a crucial role in the etiology and severity of PH.

Conclusion:
Circulating miRNA which regulate mitochondrial dynamics to fission may Plays a crucial role in developing PH.
Abstract 16113: CT Pulmonary Angiography Yield in Patients With an Active Malignancy: Lack of Non-invasive Screening
Authors: Lamping Olivia , Yarra Pradeep , Stratton Austin , Pidakala John , Bhalla Vikas
Published: May 2021

Patients with an active malignancy are at increased risk of venous thromboembolism due to the production of pro-coagulant factors causing a hypercoagulable state. Providers must keep their index of suspicion high for a pulmonary embolism in these patients because of the high prevalence and often vague symptoms. This is a retrospective study of 2226 patients who underwent CT pulmonary angiography (CTPA) in the emergency department. We compared the diagnosis of PE in patients with and without an active malignancy within the past 6 months. Of those patients without an active cancer, 133/1788 (7.4%) patients were diagnosed with a PE. This is not significantly different from the cohort with cancer where 37/437 (8.5%) patients were diagnosed with a PE (p=0.468). During diagnosis, patients with a history of cancer were less likely to have a chest x-ray, d-dimer or troponin performed prior to the CTPA scan (Table 1). These tests are less invasive and much cheaper than the CTPA and can help identify other pathologies that a patient may be experiencing. Not surprisingly, patients with a malignancy have a higher Wells’ score, revised Geneva score and PERC rule (Table 2), leading providers further down diagnostic algorithms towards CTPA. While many of these high-risk patients should immediately undergo CTPA, patients at low or moderate risk of PE should first be evaluated with less invasive testing such as a chest x-ray or d-dimer. In conclusion, in order to decrease the number of patients unnecessarily undergoing CTPA, patients with an active malignancy should be risk stratified in a similar manner as those patients without a malignancy, including the use of non-invasive testing where appropriate.
Abstract 16122: Comparative Risk of Incident Coronary Heart Disease Across Multiple Chronic Inflammatory Diseases
Authors: Sinha Arjun , Rivera Adovich , Chadha Simran , Prasada Sameer , Pawlowski Anna , Thorp Edward B , Deberge Matthew , Ramsey-Goldman Rosalind , Lee Yvonne , Achenbach Chad , Lloyd-jones Donald M , Feinstein Matthew J
Published: May 2021

Introduction:
Inflammation plays an important role in the pathogenesis of coronary heart disease (CHD). Chronic inflammatory diseases (CIDs) may serve as models to provide insights into the relationships between immune dysfunction, inflammation, and CHD. To investigate this further, we analyzed the risk of incident CHD across different CIDs.

Methods:
We created a cohort of individuals with CIDs and non-CID controls (frequency-matched on demographics and CHD risk factors), free of baseline CHD, receiving regular outpatient care in a large medical system from 2000 to 2019. CIDs included psoriasis, rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and inflammatory bowel disease (IBD). CHD was defined as myocardial infarction (MI), angina, or coronary revascularization. We used adjusted hazards models to determine incident CHD risk for each CID relative to controls. We also analyzed incident CHD risk by severity of inflammation (baseline C-reactive protein) or immune dysfunction (baseline CD4 T cell level in HIV).

Results:
Of 18,129 individuals with CIDs and 18,988 controls, there were 1,011 incident CHD events over a median of 3.5 years. After adjusting for demographics and CHD risk factors, CHD risk was significantly elevated in SLE [hazard ratio (HR) 2.85, 95% confidence interval (CI) 2.19-3.71, p<0.01], SSc (HR 2.14, 95% CI 1.54-2.99, p<0.01), HIV (HR 1.38, 95% CI 1.12-1.69, p<0.01), and RA (HR 1.22, 95% CI 1.00-1.49, p=0.05). Findings were similar with MI as the lone outcome. When CIDs were categorized by inflammation or immune dysfunction, there was a pattern of higher CHD risk with higher levels of inflammation/immune dysfunction across CIDs (Figure).

Conclusions:
Our results show that SLE, SSc, HIV, and RA were associated with significantly elevated risks of incident CHD and MI. Higher levels of inflammation or immune dysfunction were associated with heightened CHD risk within CIDs.
Abstract 16127: Peripheral Artery Disease Guideline Operative With Patient-Reported Outcomes (PAD GO PRO): A Report From the PAD GO PRO Quality Program
Authors: Bunte Matthew C , Vupputuri Sravanthi
Published: May 2021

Introduction:
Peripheral artery disease (PAD) is a public health epidemic, driven by surging rates of diabetes and an aging population. Poor disease recognition and inconsistent medical care account for suboptimal outcomes.

Methods:
Using an administrative code algorithm, patients over age 40 years evaluated during an ambulatory visit were screened for diagnostic codes indicating PAD. Patients with PAD were assessed for optimal medical care (OMC) per 2016 American Heart Association Guidelines on the Management of Patients with Lower Extremity PAD, including (1) antiplatelets, (2) statins, (3) antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and (4) tobacco abstention. OMC was defined as achieving all 4 quality metrics at first visit. Rates for a composite endpoint of all-cause mortality, myocardial infarction, and stroke (MACE) were compared between OMC and non-OMC groups. Cox proportional hazard modeling was used to assess the relationship between OMC and outcomes.

Results:
In a population of 353,738 unique ambulatory patients, 15,690 had PAD (4.4%). Among those with PAD, the mean (SD) age was 72.5+/-11.0 years, 46.2% were female, and 11.2% used tobacco. Patients with PAD receiving OMC (n=4,371), compared to those with non-OMC (n=11,319), had a significantly reduced rate of the composite endpoint (19.9% vs 26.9%; hazard ratio (HR): 0.65; [95% confidence interval (CI), 0.60-0.71]; p<0.001) during a mean 26.7 months follow-up (Figure). The benefits of OMC on MACE was driven by a reduction in all-cause death (7.1% vs 15.5%; HR: 0.41, [95% CI, 0.36-0.46]; p<0.001). Rates of myocardial infarction (12.5% vs 15.41%; HR 0.96 [95% CI, 0.86-1.08]; p=0.532) and stroke (3.3% vs 3.8%; HR 1.06 [95% CI, 0.87-1.30]; p=0.556) were not significantly reduced.

Conclusions:
In a large, real-world cohort of patients identified to have PAD, guideline-directed OMC significantly reduces all-cause death and MACE.
Abstract 16130: Plasma Proteomic Analysis of Association Between Atrial Fibrillation, Coronary Microvascular Disease and Heart Failure
Authors: Ozcan Cevher , DIXIT GUNJAN , Blair John
Published: May 2021

Introduction:
Atrial fibrillation (AF) commonly occurs in patients with heart failure with preserved ejection fraction (HFpEF). Recent studies showed a high prevalence of coronary microvascular dysfunction (CMD) in patients with HFpEF and a likely association with AF. Yet, the biomarkers and mechanisms of their association have not been characterized.

Hypothesis:
Plasma proteomic analysis can identify novel biomarkers of the association between AF, CMD and HFpEF, and mechanistic pathways of their association.

Methods:
We studied the plasma samples from the patients with AF, CMD and/or HFpEF. Liquid chromatography-mass spectrometry based untargeted and label-free quantification proteomic analysis was performed. Circulating plasma proteins were screened to determine candidate biomarkers and the mutual mechanistic pathways in these disease processes.

Results:
We identified 130 dysregulated proteins across the groups with the independent patient replicates. Discovery-based untargeted plasma proteomic analysis identified 35 proteins in association with AF, CMD and HFpEF candidate biomarkers of their association (Fig). SAA1, LRG1 and APOC3 were significantly elevated in the coexistence of AF, CMD and HFpEF. LCP1, PON1 and C1S were markedly downregulated in their associations. Combined downregulation of PON1 and C1S was a marker of the HFpEF and CMD. Low PON1 was associated with HFpEF. Low C1S was a marker of CMD. Reduced levels of LCP1, KLKB1 and C4A were associated with AF in patients with CMD and HFpEF. These dysregulated proteins are associated with inflammatory processes, coagulation pathways, oxidative stress, metabolism, complement system and extracellular matrix remodeling.

Conclusions:
Plasma proteomic profile provides biomarkers and mechanistic insight into the association of AF, CMD and HFpEF. Circulation dysregulated proteins can be clinically useful for risk stratification.
Abstract 16164: Left Ventricular Ejection Fraction Matters in Transthyretin Amyloidosis Cardiomyopathy
Authors: Rashdan Lana , Chandrashekar Pranav , Dale Zack , Elman Miriam , Nazer Babak , Heitner Stephen B , Masri Ahmad
Published: May 2021

Introduction:
Patients with transthyretin cardiac amyloidosis (ATTR-CM) are risk stratified using the Mayo Clinic Prognostic Model. Prior studies showed global longitudinal strain’s (GLS) role in predicting mortality. However, frequently, arrythmias and poor image quality limit GLS quantification. Given GLS and LVEF correlation, we sought to assess the prognostic value of LVEF in addition to Mayo staging in patients with ATTR-CM.

Methods:
A single center observational cohort study of patients who had been seen at our Amyloidosis Center with ATTR-CM diagnosed between 2005-2019. LVEF was assessed using Simpson’s bi-plane method. Mayo Stages were classified as follows (NTproBNP and Troponin I thresholds 3000 pg/ml and 0.1 ng/ml, respectively): Stage I (both values < threshold), Stage II (either ≥ threshold) and Stage III (both ≥ threshold). The primary outcome was all-cause mortality.

Results:
Ninety-one patients with ATTR-CM (mean age 73±10 years, 92% male) had a median (IQR) follow-up of 28 (15, 45) months, and 25 (28%) patients died. Mayo Stage distribution in patients with LVEF <50% vs LVEF ≥50% was 33% vs 66% (Stage I), 40% vs 24% (Stage II), and 27% vs 10% (Stage III) (Fisher’s exact, p=0.03). Thirty-seven (41%) had LVEF <50% of whom 35% died as compared to 53 (59%) with LVEF ≥50% of whom 23% died, (log-rank, p=0.02; Figure). Results from univariable and multivariable Cox Proportional Hazard models are shown in Table.

Conclusions:
LVEF provides incremental prognostic information to the Mayo classification.
Abstract 16165: Inorganic Arsenic Induces Sex-Dependent Pathological Cardiac Hypertrophy
Authors: Kabir Raihan , Sinha Prithvi , Mishra Sumita , Ebenebe Obialunanma V , Taube Nicole , Oening Christian , KECELI Gizem , Chen Rui , Paolocci Nazareno , Rule Ana M , Kohr Mark J
Published: May 2021

Exposure to inorganic arsenic (iAS) through drinking water is well-associated with adverse cardiovascular outcomes, yet the mechanisms through which it induces these effects are not fully understood. Recent epidemiological findings highlight an association between iAS exposure and altered left ventricular geometry in both the presence and absence of hypertension. We therefore tested the hypothesis that iAS exposure has a bimodal impact on cardiac-intrinsic and hemodynamic mechanisms that together induce pathological remodeling of the myocardium. Adult male and female mice were exposed to an environmentally relevant dose of 615 μg/L NaAsO
2
for eight weeks. Males (n=9-10 mice/group) exhibited increased systolic blood pressure (115.1±3.0 vs. 106.0±2.3 mmHg, p=0.0350) via tail cuff photoplethysmography, left ventricular wall thickening (0.98±0.01 vs. 0.88±0.01 mm, p<0.0001) via transthoracic echocardiography, increased heart weight to tibia length (8.56±0.21 vs. 7.15±0.24 mg/mm; n=24 mice/group), and increased plasma atrial natriuretic peptide (47.85±12.0 vs. 15.14±3.73 pg/mL, p=0.0379) via enzyme immunoassay. Myocardial mRNA transcript levels (n=10 hearts/group) of
Acta1
(1.36±0.18 vs. 0.73±0.11, p=0.0037),
Myh7
(1.53±0.15 vs. 1.04±0.10, p=0.0138), and
Nppa
(2.40±0.29 vs. 1.02±0.07, p=0.0001) were increased, and
Myh6
(0.92±0.17 vs. 1.14±0.23, p=0.0001) was decreased, evidencing pathological hypertrophy in the male heart. Female hearts, however, were largely protected at this eight-week timepoint as similar changes were not detected. Further investigation found that
Rcan1
was upregulated (1.47±0.19 vs. 0.97±0.04, p=0.0161; n=10 hearts/group) in male hearts, suggesting that calcineurin-NFAT was activated. Interestingly, iAS was sufficient to activate NFAT (0.82±0.11 vs. 0.46±0.05, p=0.0214; n=8 wells/group) independent of blood pressure via luciferase assay. In conclusion, these results demonstrate for the first time that iAS may cause pathological cardiac hypertrophy not only by increasing hemodynamic load, but also by activating calcineurin-NFAT and inducing fetal gene expression in the male heart, thus providing novel mechanistic insight into the threat of iAS exposure to the cardiovascular system.
Abstract 16191: Association of Left Ventricular Mass Progression With Heart Failure Events: Implications for Understanding the Hispanic Paradox
Authors: Vasquez Nestor , Castro-Diehl Cecilia , Lee Un Jung , Burke Gregory , Bertoni Alain G , Wagenknecht Lynne E , Ac Lima Joao , Bluemke David A , Rodriguez Carlos J
Published: May 2021

Introduction:
Hispanics have been described as paradoxically having a higher prevalence of cardiovascular (CV) risk factors (RFs) but lower CV mortality compared to non-Hispanic Whites (NHW). The association of left ventricular mass (LVM) change with heart failure (HF) has not been well studied and variability across race-ethnic groups is unknown.

Methods:
MESA participants with LVM measurements by cardiac MRI at baseline and exam 5 (10-year interval) were included and followed for HF events after exam 5. LVM was calculated as the percentage of the predicted value based on height, weight and sex in a healthy population. LVM absolute (exam 5 - baseline) and relative change were compared across race-ethnic groups (Hispanics, non-Hispanic blacks [NHB], NHW, Chinese). HF RFs included hypertension, diabetes and obesity. The association between LVM change with incident HF events was evaluated using age-gender adjusted Cox proportional hazard models.

Results:
Among 2,981 participants (mean age 60 years, 53% female, 20% Hispanics, 42% NHW, 25% NHB, 13% Chinese) LVM at both exams was higher in NHB followed by Hispanics, whereas NHW and Chinese had the lowest LVM
(Table)
. Over 10-years, NHB had the highest LVM relative change (+4.4%) and Hispanics had the lowest (+1.7%). HF RFs were more prevalent in NHB and Hispanics compared to the other groups (p<0.01). After a mean follow-up time from exam 5 of 6.4 years, an 18% increase in HF risk was seen per 5-unit increase in LVM in the total population. In race-ethnicity stratified analyses, this association was seen only in NHB (22% increase in HF risk per 5-unit LVM increase, p=0.01), and Hispanics (34% increase in HF risk per 5-unit LVM increase, p<0.01).

Conclusions:
Hispanics and NHBs had a high burden of HF risk factors and higher baseline LVM relative to other groups. Hispanics paradoxically exhibited the lowest whereas NHB had the highest degree of LVM change over time, and yet both groups had similarly increased HF risk associated with LVM change.
Abstract 16206: An Atypical Presentation of Spontaneous Coronary Artery Dissection in a Young Male Patient
Authors: Sami Farhad , Campos Enrique , Acharya Prakash , Dalia Tarun , Hocsktad Eric
Published: May 2021

Background:
Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in women but rare in young healthy males. We report a case of a young male who presented with left hand tingling/numbness and was ultimately diagnosed with SCAD.

Case Presentation:
A 24-year-old male with history of asthma developed left hand tingling/numbness while playing basketball. This progressed to cold left upper extremity, prompting him to go to emergency room. Doppler ultrasound showed acute left brachial thrombus and emergent embolectomy of left brachial artery was done. Transesophageal echocardiogram, performed to investigate possible cardiac source of thrombus, showed normal ejection fraction, dyskinetic apex and biventricular thrombus (Figure 1A). Cardiac MRI revealed a large transmural MI in distribution of a wraparound left anterior descending artery (LAD) with associated regional akinesis of the left ventricular apex and an infarct in the right ventricular apex. Subsequent angiography revealed normal coronary arteries (Figure 1B) except a heterogenous linear filling defect in the apical LAD consistent with Type 1 SCAD (Figure 1C). No intervention was performed and the patient was treated conservatively. It was postulated that patient sustained an apical MI after SCAD of LAD, leading to formation of ventricular thrombi which then embolized to cause acute brachial artery thrombosis.

Discussion:
SCAD in young males is rare and can be a diagnostic challenge. Type 1 “pathognomic” angiographic finding in SCAD, is the classic appearance of multiple radiolucent lumens or arterial wall contrast staining. In case of inconclusive angiography, intravascular ultrasound or optical computed tomography can confirm diagnosis. Interventionalists should be familiar with angiographic appearance of SCAD as advanced imaging might not be available and in many cases, conservative management is preferred to percutaneous coronary intervention.
Abstract 16433: Quality Initiative Tied to Physician Reimbursement Significantly Improves Sacubitril/valsartan and Spironolactone Use Among Patients With Heart Failure With Reduced Ejection Fraction
Authors: Minciunescu Andrei , Baez-Quintana Laira , Yantz Rebecca , del Castillo Therese , Calcagno Manuel , Soderstrom Lynn T , Overbeck Deanna , Myhera Tiara , Levy Warren S , O'Connor Christopher M , Haddad Tariq M
Published: May 2021

Introduction:
Despite data showing reductions in risk of death and heart failure hospitalization in heart failure patients with reduced ejection fraction (HFrEF), sacubitril/valsartan (SV) and mineralocorticoid-receptor antagonist (MRA) adoption rates have remained low. We hypothesized that instituting a quality initiative (QI) that prospectively identified SV/MRA candidacy in HFrEF patients and tied successful use of MRA/SV in eligible patients to total health system compensation would improve utilization rates.

Methods:
A HFrEF QI was implemented whereby a portion of a large outpatient cardiology practice’s total compensation by the health system was tied to successful SV and MRA use in HFrEF patients (EF<40%) with NYHA class II-IV symptoms. Quality metric goals that triggered maximum reimbursement were set at >25% SV use and >60% MRA use in eligible HFrEF patients, given the low rates of appropriate SV and MRA use nationally.

Following QI introduction, patients with the above eligibility criteria were prospectively identified over one year. Providers were sent daily e-mails notifying them of eligible patients that day, and during the patient visit were prompted to complete a form, documenting use of SV, MRA, and/or any contraindications to their use including blood pressure, renal function, potassium level, ACE/ARB intolerance, or financial obstacles. To serve as a control arm, data was retrospectively collected on 6 months of consecutive HFrEF patients with the same eligibility criteria prior to QI initiation.

Results:
Of 1345 retrospectively identified HFrEF patients prior to initiating the QI, 855 (63.5%) and 964 (71.7%) met SV and MRA eligibility criteria. Of these, 324 (37.9%) were prescribed SV, 365 (37.9%) an MRA. Following QI implementation, 3792 patients with HFrEF were prospectively identified, and of these 2550 (67.2%) and 2589 (68.2%) met eligibility criteria for SV and MRA initiation. SV use in eligible patients increased from 37.9% pre-QI, to 72.1% post-QI (p < 0.001). MRA use increased from 37.9% pre-QI to 66.2% post-QI (p < 0.001).

Conclusions:
A quality initiative linking successful implementation of SV and MRA use in eligible HFrEF patients to physician compensation resulted in a significant increase in SV and MRA adoption rates.
Abstract 16436: Targeting Store Operated Calcium Entry in Vascular Smooth Muscle Cells by a Novel Small-molecule Inhibitor
Authors: Shawer Heba , Hemmings Karen , Porter Karen , Foster Richard , Beech David J , Bailey Marc A
Published: May 2021

Vascular smooth muscle cells (VSMC) are physiologically quiescent cells optimised for vascular contractility and the modulation of vascular tone. Platelet-derived growth factor (PDGF) signalling is a critical driver of pathological remodelling of native VSMC to a proliferative synthetic state, which is a process associated with vascular pathologies. Here, we studied the role of store operated calcium entry (SOCE) through Orai1 channels in VSMC plasticity utilizing novel small molecule inhibitor of Orai1 channels. We developed small-molecule Orai1 inhibitor, 4-(2,5-dimethoxyphenyl)-N-[(pyridin-4-yl)methyl]aniline, called JPIII, evaluated its effects on SOCE, and its functional impact in human primary VSMC (hVSMC) from saphenous vein and rat thoracic aorta VSMC cell line. Our Orai1 inhibitor potently suppressed SOCE in hVSMC (IC
50
of 297 nM, n=3) and rat VSMC (IC
50
of 819.5 nM, n=3), leading to significant impairment of PDGF-induced cell migration in hVSMC by 31% (P=0.0071, n=6) and rat VSMC by 24% (P=0.04, n=3). Orai1 inhibition also reduced PDGF-induced proliferation of hVSMC by 20% (P=0.02, n=5) and of rat VSMC by 26% (P=0.003, n=4) at concentration of 30 μM JPIII relative to controls. RNA-Seq analysis of PDGF-stimulated primary human aortic VSMC (n=4/group) was performed to investigate the effects of Orai1 inhibition on the transcriptional response of cells and showed significant downregulation of genes involved in inflammation (C-X-C motif chemokine ligand (CXCL) 1, CXCL3, CXCL5, CXCL6), downregulation of matrix degrading enzymes (metalloproteinase (MMP) 12 and MMP16), and upregulation of cholesterol biosynthesis pathways by Orai1 inhibition. Consistent with the observed functional phenotype, our results revealed an inhibitory effect on transcriptional networks involved in cell proliferation and migration. The effects of Orai1 inhibition on the transcription of genes involved in inflammation, MMPs expression, cholesterol metabolism, cell proliferation, and migration powerfully associate Orai1 signalling with VSMC remodelling. Our results provide insight into the role of Orai1 in VSMC remodelling and the possible therapeutic potential of a small molecule inhibition approach in targeting pathologic remodelling.
Abstract 16439: Is Pulmonary Venous Flow Pulsatility a Critical Determinant of Left Atrial Appendage Blood Stasis Risk?
Authors: Sanatkhani Soroosh , Nedios Sotirios , Jain Sandeep K , Saba Samir , Menon Prahlad G , Shroff Sanjeev G
Published: May 2021

Introduction:
Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, most commonly in the left atrial appendage (LAA), and a resultant five-fold increase in the risk of ischemic stroke. The current standard of stratifying stroke risk, based on the CHA
2
DS
2
-VASc score, does not consider subject-specific LAA hemodynamics and blood stasis risk. We have developed a methodology for computing mean residence time of blood-borne particles in the LAA (

t
m

), an index of LAA blood stasis, using 3D left atrial (LA) and LAA geometries and pulmonary venous (PV) inlet blood flow data. While subject-specific 3D geometry can be obtained readily, it is not easy to measure all LA inlet blood flow waveforms
in vivo
. Therefore, a sensitivity study of LAA

t
m

to the inlet blood flow waveform characteristics (shape and magnitude) is needed.

Hypothesis:
PV flow pulsatility does not affect LAA

t
m

.

Methods:
Cardiac computed tomography images of 10 AF subjects were obtained and LA and LAA geometries were reconstructed in 3D and subsequently meshed for computational fluid dynamics (CFD) analysis. We employed CFD analysis, modeling blood cells as neutrally buoyant tracers transported in the blood and used a systems-based approach, to quantify LAA

t
m

. Each subject was simulated using four PV blood flow characteristics: (1)
Normal-S
, steady PV flow with cardiac output (CO) of 5.5 L/min; (2)
AF-S
, steady PV flow with reduced CO of 4.4 L/min; (3)
Normal-P
, normal pulsatile PV flow with normal CO = 5.5 L/min; and (4)
AF-P
, a typical AF pulsatile waveform where systolic phase and the reversal phase are diminished with reduced CO of 4.4 L/min.

Results:
Comparing the two steady flow groups, LAA

t
m

significantly increased as CO was decreased (
Normal-S:
2.6±0.3 s,
AF-S:
3.1±0.3 s,
P
=0.02). However, the presence of pulsatility did not affect LAA

t
m

at both levels of CO:
Normal-P:
2.4±0.2 s;
Normal-S:
2.6±0.3 s,
P
=0.2 and
AF-P:
2.9±0.3 s;
AF-S:
3.1±0.3 s,
P
=0.3.

Conclusions:
LAA blood stasis risk, as quantified by LAA

t
m

, is significantly affected by the steady PV flow magnitude (i.e., cardiac output) and not by PV flow pulsatility. Therefore, the subject-specific LAA blood stasis risk can be reliably estimated using subject-specific LA and LAA 3D geometries and subject-specific CO.
Abstract 16462: Using Geospatial Mapping to Target Risk and Facilitate Placement of Community Health Workers, Educational Tools, and AHA Field Teams
Authors: Zwecker Zoe L , Spratt Susan , Goldstien Benjamin A , Granger Bradi B
Published: May 2021

Introduction:
Diabetes is a chronic condition that affects 34.2 million Americans. Long-lasting or undiagnosed diabetes increases the risk of developing cardiovascular disease (CVD). Geographic Information Systems (GIS) inform healthcare delivery interventions to target patients, clinicians, health systems and communities at highest risk. A gap remains in how data and GIS are applied and leveraged in the context of value-based care delivery systems. This spatial analysis demonstrates the application of a generalizable methodology for allocating resources such as AHA Field Teams, community health workers (CHWs), and educational tools to areas most burdened by diabetes and CVD.

Methods:
The automated geocoding infrastructure from the Duke Medicine electronic data warehouse was developed to standardize and scale geocoding addresses for a population of people with type 2 diabetes from the Southeastern Diabetes Initiative (SEDI) in 2017. While maintaining accuracy and assuring that patients’ protected health information was secure, we used geocoded data and public data (public health data, census tract data, and information on the built environment) to assess risk and identify accessible resources.

Results and Discussion:
Using this method to understand racial distribution, level of education, and income,we identified high risk communities in Durham County. We correlated geospatial patterns of health risk, illness burden, and determined accessible resources for diabetes and CVD.We calculated a resource ratio of one CHW to 100 patient-population and identified a central hub for fixed resource access. Using neighborhood boundaries, we identified a community where the burden of diabetes reached 17%, 60% of inhabitants were African American, median income was $55,945, and just 17.7% had a bachelor’s degree. Understanding risk using these social determinants (Figure 1) supports the intentional allocation of resources and hiring of CHWs.
Abstract 16507: Complex Percutaneous Coronary Intervention Features Worsen Prognosis in Diabetic Patients: Insights From a Large Single-center Registry
Authors: Nicolas Johny , Cao Davide , Claessen Bimmer E , Chiarito Mauro , Sartori Samantha , Qiu Hanbo , Nardin Matteo , Power David , Roumeliotis Anastasios , Goel Ridhima , Chandiramani Rishi , Zhang Zhongjie , Baber Usman , Sweeny Joseph , Krishnan Prakash , Kini Annapoorna , Sharma Samin K , Dangas George , Mehran Roxana
Published: May 2021

Introduction:
Despite the increasing number of complex percutaneous coronary interventions (CPCI), data regarding outcomes following CPCI in patients with diabetes mellitus (DM) are scarce.

Hypothesis:
Compared to the general population, diabetic patients undergoing CPCI have worse prognosis.

Methods:
We analyzed data of patients who underwent PCI in a tertiary-care center between 2009 and 2017. Patients were divided into 2 groups (CPCI and non-CPCI) stratified by presence of DM. CPCI was defined as having ≥1 of the following: stent length >60 mm, ≥3 stents implanted, ≥3 lesions, ≥3 target vessels, bifurcation with ≥2 stents, or chronic total occlusion. The main outcome was major adverse cardiac events (MACE), a composite of death, myocardial infarction (MI) and target vessel revascularization (TVR) at 1 year.

Results:
Out of 20,412 patients included, 5,038 (24.7%) underwent CPCI. Patients with DM constituted 46.5% (n=9,494) of the overall cohort and 44.5% (n=2,240) of CPCI group. Among patients undergoing CPCI, diabetics were younger, more likely to be female, and had more cardiovascular risk factors (kidney disease, dyslipidemia, and hypertension) than non-diabetics. In addition, diabetic patients had more advanced coronary disease (multivessel disease, high syntax score, and longer lesion length). At 1 year, diabetic patients had higher risk of MACE than non-diabetic, regardless of PCI complexity (
Figure 1
). Nonetheless, there was a significant interaction between CPCI and diabetes in terms of mortality at 1 year (p-interaction=0.009). In contrast, compared to non-diabetics, a higher risk of TVR (
adj
HR 1.49, 95% CI [1.24 - 1.78], p <0.001) and bleeding (
adj
HR 1.45, 95% CI [1.05 - 1.98], p=0.02) was observed in diabetics undergoing non-CPCI but not CPCI.

Conclusion:
Diabetic patients are at higher risk of MACE than the general population regardless of PCI complexity. Yet, 1-year mortality is substantially higher in diabetics undergoing CPCI than non-CPCI.