bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16145: Reduced Ejection Fraction at Diagnosis is an Independent Predictor of Mortality in Transthyretin Amyloid Cardiomyopathy
Authors: Bukhari Syed , Bashir Zubair , Shpilsky Daniel , Eisele Yvonne S , Soman Prem
Published: May 2021

Introduction:
The prevalence of reduced ejection fraction (HFrEF) in transthyretic cardiac amyloidosis (ATTR-CA) and its prognostic implications have not been well studied.

Hypothesis:
We hypothesized that reduction in ejection fraction in ATTR-CA is associated with poor prognosis.

Methods:
We analyzed all patients with the diagnosis of ATTR-CA. ATTR-CA was diagnosed by positive PYP and negative serum studies for AL amyloidosis. The transthoracic echocardiogram (TTE) at the time of PYP was used to identify patients with reduced EF <50% (ATTR-rEF) and preserved EF ≥ 50% (ATTR-pEF). Kaplan-Meier curve for survival between the two groups and adjusted cox proportional hazard models were generated.

Results:
Of the 124 ATTR-CA patients (mean age of 79.9 ± 7.4, 87% men, 90% Caucasians), 51 (41%) were ATTR-rEF. Compared to ATTR-pEF, at the time of PYP, ATTR-rEF were more symptomatic ( NYHA-FC ≥ 3, 61% vs 26%, p<0.001), had lower prevalence of obstructive coronary artery disease (CAD)(37% vs 55%, p=0.05), worse mean diastolic dysfunction (3 vs 2.15, p<0.01), lower tricuspid annular plane systolic excursion (TAPSE <1.7, 59% vs 25%, p<0.001) and reduced renal function ( creatinine, 1.63 ± 0.85 vs 1.27 ± 0.55 mg/dl, p<0.01). There was no difference in terms of biomarkers (BNP, p=0.1 and troponin, p=0.3) and interventricular septal thickness (p=0.2). Over a mean follow up period of 1.5 years, 27 (22%) patients died. ATTR-rEF was associated with higher mortality compared to ATTR-pEF (35% vs 12%, p=0.002; HR 3.7, 95%CI 1.62-8.63, p<0.01, fig. 1A). After adjustment for multiple cofounders including TAPSE and serum creatinine, reduced EF was an independent predictor of mortality (HR 3.02, 95% CI 1.30-7.10, p=0.01). When divided into EF≥ 50%, EF 41-49% and EF ≤ 40%, there was stepwise increase in the risk of mortality (p<0.01, fig. 1B).

Conclusion:
HFrEF is present in more than one-third of patients with ATTR-CA at the time of diagnosis, and is an independent predictor of mortality in ATTR-CA.
Abstract 16160: Invasive Approach for Cocaine Associated Non-ST-Elevation Myocardial Infarction is Associated With Reductions in Major Adverse Cardiac Events and Worsening Emergent Revascularization
Authors: ZUZEK ZACHARY , Arora Shilpkumar , Jaswaney Rahul , Jani Chinmay , PANAICH SIDAKPAL , Osman Mohammed , Hoit Brian , Josephson Richard A , Zidar David A , Shishehbor Mehdi
Published: May 2021

Introduction:
Impact of an invasive approach in patients with cocaine associated non-ST-elevation myocardial infarction (CANSTEMI) is unknown.

Hypothesis:
To determine the effects of an invasive approach on patients with CANSTEMI.

Methods:
Nationwide Readmissions Database (NRD) from years 2016-2017 was utilized for hypothesis. We utilized ICD-10 CM codes I21.4 in primary diagnosis field and F14 in secondary fields to identify CANSTEMI. Coronary angiogram (CA) with or without percutaneous coronary intervention (PCI) was considered an invasive approach. The primary outcome was a composite of major adverse cardiac events (MACE) at one year. Secondary outcomes included all-cause mortality, MI readmission, stroke readmission, and emergent revascularization at one year. Cox-Proportional Hazard regression was used to adjust for demographic and comorbid confounders.

Results:
A total of 7,372 patients were identified of which 4,332 (58.8%) underwent invasive treatment. Patients with obesity, hyperlipidemia, tobacco use, and a personal and family history of CAD were more likely to undergo an invasive approach. Conversely, patients with CKD stage 3 or more and anemia were less likely to undergo invasive treatment. The primary outcome was significantly reduced with an invasive approach compared to a non-invasive approach. Similarly, all-cause mortality and MI readmission were also significantly reduced with an invasive approach. An invasive approach was associated with increased emergent revascularization compared to a noninvasive approach. On further stratification of an invasive approach, CA and PCI both were individually associated with improved MACE outcomes and PCI only was associated with increased emergent revascularization.

Conclusions:
In conclusion, an invasive approach with CA with or without PCI for CANSTEMI was associated with reductions in morbidity and mortality. PCI only was associated with an increase in emergent revascularization.
Abstract 16173: Clinical Characteristics and Short-term Outcomes of Hospitalized Patients With Sars-cov-2 Infection and Reduced Left Ventricular Ejection Fraction
Authors: Nair Gatha G , Gomez Joanne Michelle M , Fugar Setri S , du Fay de Lavallaz Jeanne , Ruge Max , Hlepas Alexander , Rahman Annas , Patel Priya P , jahan nusrat , Simmons Alan , Rao Anupama , Bai Charlotte J , Marinescu Karolina , Williams Kim A , Volgman Annabelle S , Suboc Tisha
Published: May 2021

Introduction:
Early studies of coronavirus disease 2019 (COVID-19) patients suggested that heart failure (HF) may lead to poorer prognosis. We evaluated demographics and short-term clinical outcomes of patients with evidence of left ventricular systolic dysfunction (LVSD) in comparison to those with preserved LV systolic function (PSF).

Methods:
In this retrospective study of patients hospitalized for COVID-19 between March and June 2, 2020 at Rush Health Systems in Metro Chicago, demographics, comorbidities and clinical outcomes of patients who demonstrated LVSD (ejection fraction [EF] <50%) on transthoracic echocardiogram (TTE) were compared to that of controls with PSF.

Results:
Out of 1,312 hospitalized patients, 225 underwent TTE, and 44 patients showed LVSD. Demographics were similar between two groups, with exception of a higher prevalence of African American (AA) race (48 % vs. 29%; p=0.03) in the LVSD group. While 82% of patients in the LVSD cohort had history of chronic HF, only 26% of patients in the PSF had pre-existing HF (p<0.001). Underlying comorbidities were similar between groups: obesity (39% vs. 36%; p=0.86), diabetes (57% vs. 57%; p=1.0), hypertension (70% vs. 66%; p=0.72) and end-stage renal disease (20% vs. 19%; p=0.83). Coronary artery disease trended toward a higher frequency (50% vs. 34%; p=0.058) in the LVSD group. Troponin elevation (18% vs. 12%; p=0.43), vasopressor use (57% vs. 56%; p=1.0), endotracheal intubation (59% vs. 57%; p=0.87), myocardial infarction (30% vs. 23%; p=0.43), ICU admission (75% vs. 75%; p=1.0), hospital length of stay (median 11 days vs. 15 days; p=0.4), and death (25% vs. 23%; p=0.84) were similar between groups. Patients with LVSD had higher incidence of sustained ventricular tachycardia or fibrillation than those with PSF (18% vs. 6%; p=0.016).

Conclusions:
In our COVID-19 admissions, LVSD was more common in AA patients. Patients with LVSD had a higher risk of ventricular arrhythmias. However, there were no differences between need for ICU admission or intubation, vasopressor requirements, length of stay or death between patients with LVSD and those without. Longitudinal follow-up studies are needed to identify differences in long-term sequelae of COVID-19 infection with evidence for LVSD.
Abstract 16183: Predictors of Myocardial Injury in Patients With Negative Stress Echocardiogram
Authors: Bou Chaaya Rody G , El-Am Edward A , Sabra Mohamad , Rachwan Rayan Jo , Mshelbwala Fakilahyel S , jaradat ziad , Batal Omar
Published: May 2021

Background:
A negative result on stress echocardiography (SE) is generally associated with a low risk of cardiovascular events and carries a favorable prognosis. The present study was conducted to identify clinical and echocardiographic characteristics associated with increased risk of myocardial injury following a negative SE (NSE).

Methods:
We retrospectively identified a total of 4130 SEs performed between 2013 and 2017 at a tertiary care center. NSE was defined as the absence of a new or worsening wall motion abnormality (WMA) with stress. Patients with resting WMA on SE were excluded. The occurrence of myocardial injury following index SE within 1 year was then recorded. Myocardial injury was defined as an elevated (>99
th
percentile of the upper reference limit of normal) and changing troponin value (a rise and/or fall of the troponin value observed) following index SE.

Results:
During the study period, 2962 patients with NSE met inclusion criteria (median age 58 years-old; 50% females). Baseline characteristics were as follows: 35% diabetic, 49% hyperlipidemic, 62% hypertensive, 41% had a history of smoking, 21% had a history of coronary artery disease (CAD), 24% had end-stage liver disease (ESLD), 5% had end-stage renal disease (ESRD) and 1.5% had a left ventricular ejection fraction (LVEF) < 50%. Around 5% of patients developed myocardial injury within 1 year of NSE. Age, diabetes mellitus, ESLD and a LVEF <50% were significantly associated with an increased risk of myocardial injury on univariate and multivariate analysis (p<0.013) (Table).

Conclusion:
Patients with age > 65 years, diabetes mellitus, ESLD and a LVEF <50% were found to be at increased risk of myocardial injury within 1 year of a NSE. These characteristics should be accounted for during the interpretation of SE as these patients warrant intensive risk factor modification and close follow-up.
Abstract 16205: MKP-5 Deficiency Attenuates Pressure Overload-induced Cardiac Hypertrophy
Authors: Min Kisuk , Huang Yan , Giordano Frank J , Bajpeyi Sudip , Bennett Anton M
Published: May 2021

Introduction:
Cardiac remodeling occurs in response to pathological stimuli including chronic pressure overload, subsequently leading to heart failure. Despite considerable research efforts, the molecular mechanisms responsible for heart failure have yet to be fully elucidated. One of the prominent signaling pathways involved in the development of pathological cardiac hypertrophy is the mitogen-activated protein kinases (MAPKs) pathways. The MAPKs are inactivated by the MAPK phosphatases (MKPs) through direct dephosphorylation. Growing evidence suggests the importance of MKP-5 signaling mechanisms in physiological and pathological processes. However, the role of MKP-5 has not been explored in cardiac muscle. The objective of this study is to investigate how MKP-5-mediated MAPK activity contributes to mechanisms responsible for pressure overload-induced cardiac hypertrophy.

Hypothesis:
We tested the hypothesis that MKP-5 serves as a central regulator of MAPKs in pressure overload-induced cardiac hypertrophy.

Methods:
To investigate the role of MKP-5 in cardiac muscle, we caused pressure overload-induced cardiac hypertrophy in wild type (mkp-5
+/+
) mice and MKP-5 deficient mice (mkp-5
-/-
) through transverse aortic constriction (TAC). Cardiac function was evaluated by echocardiographic analysis at 4 weeks after TAC. Cardiac hypertrophy was measured by heart-to-body weight ratio. Interstitial myocardial fibrosis was evaluated by Sirius red stains and expression of fibrogenic genes was determined by quantitative PCR.

Results:
Echocardiographic analysis showed that the ejection fraction and fractional shortening of

mkp-5
+/+

mice significantly decreased by at 4 weeks after TAC. Heart-to-body weight ratio increased in

mkp-5
+/+

mice. However, MKP-5-deficient heart was protected from cardiac dysfunction and cardiac hypertrophy induced by TAC. Importantly, the fibrogenic genes were markedly reduced in

mkp-5
-/-

mice as compared with

mkp-5
+/+

mice at 4 weeks after TAC.

Conclusions:
Collectively, our study demonstrates that MKP-5 deficiency prevents the heart from pressure overload-induced cardiac hypertrophy and suggests that MKP-5 may serve as a novel therapeutic target for treatment of heart disease.
Abstract 16215: Ventricular Dyssynchrony is Associated With Arrhythmic Mitral Prolapse Prior to Chamber Remodeling
Authors: Pandis Dimosthenis , Miller Marc , El-Eshmawi Ahmed , Grapsa Ioulia A , Boateng Percy , Trivieri Maria Giovanna , Lerakis Stamatios , Pedrizzetti Gianni , Anyanwu Ani , Adams David H
Published: May 2021

Introduction:
Asymptomatic patients on active surveillance for degenerative mitral regurgitation are at risk of ventricular arrhythmia and sudden death.

Hypothesis:
Abnormal myocardial mechanics may precede ventricular remodeling and may help identify at-risk patients.

Methods:
Multi-directional myocardial mechanics and LV dyssynchrony were assessed in 204 consecutive patients awaiting surgical mitral repair for severe degenerative MR in a quaternary mitral reference center.

Results:
The mean age was 58 ±12.5 years and 40% were females. The mean EF was 63% ± 6% and 92% had compensated LV function (EF>60% and LVESD<4cm) and only 24% had elevated LV filling pressures (E/e'≥13). Indexed LV wall stress-to-LVEDD, relative wall thickness and indexed LV mass-to-BSA were similar amongst males-females, although males had higher mean blood pressure (94 Vs. 90, P=0.02) . The peak global longitudinal strain (GLS) was -25.2% ± 3.3% and the mid-ventricular circumferential and radial strains were -33.5%±6.7% and 56%±25% respectively. Ventricular ectopy was present in 24.5% of patients and only 17% had atrial fibrillation (Afib) despite the significantly dilated left atria (mean LAVi 70±26.6 ml/m
2
). The median LV mechanical dispersion was 40msec (IQR 30.7-56.5) but increased significantly with ventricular ectopy (65msec, P<0.01) and further influenced by concomitant Afib (p=0.001 for 2-factor interaction). Diastolic LV function did not correlate with dispersion (r=0.02 and 0.01 for E/A and E/e', P=NS) but was associated with the duration of LV diastolic filling (mean 502±140msec; r=0.2, P=0.004). Interpapillary radial strain delay was noted in the study cohort (mean delay 52.8msec, range 0-335msec) while intepapillary activation delay was manifested with concomitant ventricular ectopy (mean time-to-peak LS delay 57.5±48msec).

Conclusions:
Left ventricular dyssynchrony manifested by increased mechanical dispersion and imbalanced interpapillary mechanics are observed prior to overt chamber remodeling in significant degenerative MR and is associated with ventricular ectopy. Further studies are needed to assess the related clinical implications and potential impact on risk stratification in this patient group.
Abstract 16235: Rhythmic Disturbances in Patients With Cardiac Amyloidosis: Analysis From Cedars-Sinai Amyloidosis Registry
Authors: Cho Jae Hyung , Cuk Natasha , Leong Derek , Ehdaie Ashkan , Cingolani Eugenio , Shehata Michael , Patel Jignesh
Published: May 2021

Introduction:
Cardiac arrhythmias are frequent complications of patients with cardiac amyloidosis. The burden and nature of cardiac arrhythmias in patients with cardiac amyloidosis have not been investigated in a large patient population.

Hypothesis:
Cardiac amyloidosis is a highly arrhythmogenic disorder requiring implantation of cardiac electronic devices.

Methods:
Cedars-Sinai amyloidosis registry was analyzed to investigate the prevalence and nature of cardiac arrhythmias in patients with cardiac amyloidosis. Ambulatory ECG monitoring data, implantable cardioverter-defibrillator or pacemaker implantation, and interrogation data were reviewed to study the burden of cardiac arrhythmias in patients with cardiac amyloidosis.

Results:
A total of 156 patients were analyzed in the registry: 51 patients (32.7%) with AL amyloidosis, 101 patients (64.7%) with ATTR amyloidosis, and 4 patients with AA amyloidosis (2.6%). Thirty-seven patients (23.7%) were implanted with cardioverter-defibrillator; 23 patients (14.7%) for primary prevention, 11 patients (7.1%) for secondary prevention of ventricular tachycardia, and 3 patients (1.9%) for secondary prevention of ventricular fibrillation. Twenty-two patients (12.1%) needed pacemaker implantation; 9 patients (5.8%) for high-grade or complete heart block, and 13 patients (8.3%) due to sick sinus syndrome. The most common arrhythmias were atrial fibrillation occurring in 80 patients (51.3%) followed by first-degree AV block in 31 patients (19.9%). Sustained ventricular tachycardia occurred in 14 patients (8.9%) during hospitalization, device interrogation or ambulatory monitoring.

Conclusions:
Both atrial and ventricular arrhythmias are common manifestations of cardiac amyloidosis, frequently necessitating implantation of cardiac electronic devices.
Abstract 16403: Prevalence and Sex Differences in Early-onset Atrial Fibrillation - A Nation-wide Primary Care Study in Norway
Authors: Kalstø Silje M , Nygård Ståle , Tveit Arnljot , Ariansen Inger , Christophersen Ingrid E
Published: May 2021

Background:
Several studies have reported a male:female ratio of 4:1 in lone atrial fibrillation (AF) populations. However, there have been few reports on the young population with AF, and no reports from a primary care setting. Here, we describe prevalence and sex-differences in early-onset AF in a nation-wide register-based study in the primary care sector in Norway.

Methods:
In Norway, with a population of 5.4 million, healthcare is publicly financed and all general practitioner (GP) claims have been recorded in the Norwegian Control and Payment of Health Reimbursement (KUHR) registry, since 2006. We identified all individuals aged ≥18 and <50 years registered with ≥1 AF diagnosis code (International Classification of Primary Care (ICPC) K78), from 2006-2019 in the KUHR registry. Based on population estimates from Statistics Norway, we calculated the prevalence of early-onset AF in 2019, as a total, by sex, and by age groups: 18-29, 30-39, 40-49.

Results:
We identified 5563 individuals (28.5% women, age 18-49 years) aged 18-49 in 2019 with AF diagnosed <age 50 years. In 2019, the prevalence of early-onset AF registered in all individuals up to age 50 was 0.24% (women: 0.14% (1585/1114821), men 0.34% (3978/1176555), p=1.4x10
-205
) with a ratio of 2.5 men:women. In individuals aged 18-29 the prevalence was 0.05% (women 0.04% (164/410367), men 0.07% (292/435001), p=79x10
-8
). For the age group 30-39 years the prevalence was 0.19% (women 0.12% (408/349639), men 0.27% (985/367730), p=3.9x10
-49
). For the age group 40-49 years the prevalence was 0.51% (women 0.29% (1013/354815), men 0.72% (2701/373824), p=1.39x10
-155
).

Conclusion:
We show that the prevalence of early-onset AF in a nation-wide primary care population is 0.24% and that the sex-difference in prevalence is smaller than previously reported in early-onset and lone AF studies. Our findings underline the need of increased awareness of AF as a disease in the young, and particularly to women in the youngest age-groups.
Abstract 16407: Plasma Omega-3 Fatty Acids Predict Cardiovascular Events Stratified by Coronary Artery Calcium
Authors: Alfaddagh Abdulhamied , Kapoor Karan , Dardari Zeina , Bhatt Deepak L , Budoff Matthew J , Nasir Khurram , Miller Michael , Welty Francine K , Miedema Michael D , Shapiro Michael D , Blumenthal Roger S , Blaha Michael J
Published: May 2021

Background:
In REDUCE-IT, high-dose eicosapentaenoic acid (EPA) was beneficial in high-risk patients without clinical CVD independent of triglyceride levels. Whether the benefit of higher plasma EPA extends to those without subclinical CVD is unclear.

Hypothesis:
In those without clinical CVD, plasma omega-3 fatty acid (O3FA) levels predict long-term CVD events, and subclinical CVD measured by coronary artery calcium (CAC) modifies the effect such that individuals with the highest CAC attain the greatest benefit from higher O3FA.

Methods:
We examined 6568 MESA participants with plasma EPA and docosahexaenoic acid (DHA) levels measured at baseline and classified them by tertiles of EPA and DHA and by CAC category (0, 1-99, ≥100). Our outcome was time to CVD event (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Cox regression models were used to assess the associations between log-transformed EPA and DHA and CVD events adjusted for demographic factors, CVD risk factors, and medication use.

Results:
Mean age was 62.1±10.2 and 52.9% were females. Higher log(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.93;
P
= 0.002) and log(DHA) (aHR = 0.80; 95% CI, 0.66-0.96;
P
= 0.019) were independently associated with fewer CVD events. The difference in absolute CVD event rates between the lowest and highest EPA tertile increased at higher CAC levels (Figure). The adjusted HR for highest compared to lowest EPA tertile within CAC 0 was 1.02 (95% CI, 0.72-1.45), CAC 1-99 was 0.71 (95% CI, 0.51-0.98), and CAC≥100 was 0.66 (95% CI, 0.52-0.83). A similar association was seen in tertiles of DHA by CAC category. These findings were consistent by sex and race category and after adjusting for O3FA supplement use.

Conclusion:
In an ethnically diverse population free of clinical CVD at baseline, higher plasma O3FA levels were associated with fewer CVD events. The absolute reduction in CVD events with higher O3FA levels was more apparent at higher CAC scores.
Abstract 16412: The Predictors of Hemodynamic Response to Phosphodiesterase-5a Inhibition in Advanced HFrEF
Authors: Melenovsky Vojtech , Reichenbach Adrian , Monzo Luca , Al-Hiti Hikmet , Jurcova Ivana , Havlenova Tereza , Kotrc Martin , Kautzner Josef
Published: May 2021

Introduction:
In advanced HFpEF, acute phosphodiesterase 5 (PDE5) inhibition leads to favorable change in pulmonary vascular resistance (PVR) and to an increased cardiac output (CO) of variable degree. The determinants of the response are poorely understood.

Methods:
47 HFrEF patients (85% males, 57±11 years, NYHA 2.9±0.5, 55% non-ischemic, PAmean 42±8 mmHg, 43% RV dysfunction) underwent clinical exam, echocardiography, biochemical tests and right heart catheterization (RHC) before and after I.V. administration of sildenafil (20 mg). Baseline predictors of absolute and relative (%diff) change of PVR and CO were studied.

Results:
PDE5i led to highly significant (p<0.001) reduction of pulmonary artery (PA) mean pressure (-11±9 mmHg), PVR (-2.2±1.6 WU;-42±24%), PA wedge pressure (-5.2±7.3 mmHg), CVP (-3.2±2.3 mmHg) and to increase in cardiac output (+0.6±0.7 l/min; +18±23%). PVR decreased more than systemic resistance (PVR/SVR -27±30%diff). Predictors of high CO response (COdiff%) were: low BMI, no diabetes, low baseline CO and severity of mitral or tricuspid regurgitation (r=0.53 or =0.43, both p<0.003). The strongest predictor of high PVR%diff was plasma potassium level. HF etiology, renal function, gender, RAAS inhibitor dose, renin or aldosterone levels were unelated to pulmonary vasoreactivity. Patients who dropped PVR<3 WU after PDE5i had higher plasma K+ (4.1±0.5 vs 4.5±0.3 mmol/L, p=0.01) than those who did not, similar relation was found for K+ and PDE5i-induced change of transpulmonary gradient.

Conclusions:
The largest increase in CO after PDE5i is observed in HFrEF patients with severe mitral (or tricuspid) regurgitation, probably due to chamber unloading and reduction of regurgitant SV. Pulmonary vasodilator response to PDE5i may be influenced by plasma potassium level. High-normal plasma potassium levels may preserve normal pulmonary vasoreactivity in HFrEF, perhaps by influencing K-channels in pulmonary vascular smooth muscle cells.
Abstract 16413: The Development of Care Curves Following the Stage 1 Palliation: A Comparison of Intensive Care Among Five Centers
Authors: Sperotto Francesca , Davidson Jesse , Smith-Parrish Melissa N , Elhoff Justin , Sinha Anjuli , BLINDER Joshua J , Ehrmann Daniel , Marino Bradley S , Kheir John N
Published: May 2021

Introduction:
Comparisons of care among centers is currently limited to major endpoints, such as mortality, length of stay, or complication rates.

Hypothesis:
We hypothesized that comparing individual elements of intensive care over time using classical statistics and “care curves” may highlight important modifiable differences among centers.

Methods:
We retrospectively reviewed data of key elements of postoperative care after stage-1-palliation (S1P) among 5 US centers during 2009-2018. Minimum mandatory ventilation rate (MMVR), opioid total daily dose (TDD) and fluid balance (FB) were computed from postoperative day (POD) 0 to 28. Cox regression, mixed random effect models and growth chart-like care curves were used to analyze data variability and trajectory over time.

Results:
During the study period, 502 patients underwent S1P (median age 5 [IQR 3-6] days). Patients were weaned from MMV by POD 8 (IQR 5-16), with significant differences among centers (P<0.001). Opioid administration peaked on POD 2 (3.7 [IQR 1.5-7.5] mg morphine equivalents/kg/day), and freedom from opioids was achieved in a median of 13 (IQR 8-25) days (P<0.001 among centers). After adjusting for patient-level characteristics, center affiliation was independently predictive of time to freedom from MMV and from opioids. The median daily FB per patient was +23 (IQR -3 to +39) ml/kg/day (P<0.001 among centers). Center affiliation was independently predictive of both trajectories over time and daily variation in MMVR, opioid TDD, and FB. Growth chart-like care curves can be used to visualize variation in elements over time (Fig1).

Conclusions:
Both “care curves” and classical statistics highlighted important modifiable differences in the elements of care among centers. MMVR, opioid TDD, and FB following S1P significantly differ even after adjusting for patient and operative factors. Care curves may be used to guide collaborative quality improvement initiatives in the intensive care unit.
Abstract 16442: Cardiac Mitochondrial Dynamic-related LncRNA (CMDL)-1 Protects Cardiomyocytes Against Apoptosis in Doxorubicin-induced Cardiotoxicity
Authors: Aung Lynn-Htet-Htet , Chen Xiatian , Liu Ziqian , Li Zhe , Li Peifeng
Published: May 2021

Introduction:
With the rapid development of sequencing technologies, several long non-coding RNAs (lncRNAs) have been identified; among which many are significant players in cardiac physiology and pathology. Doxorubicin (Dox), a commonly used anticancer agent, in the long-term can induce cardiotoxicity, limiting its clinical use. Despite the multiple signaling pathways involved in Dox cardiotoxicity, most of them ultimately lead to the activation of apoptosis, contributing to the progressive cardiomyocyte loss, and hence ensuring heart failure.

Methods and Results:
Microarray analysis showed that multiple lncRNAs were differentially expressed between control and doxorubicin-treated groups, denoting that lncRNAs may play a critical role in Dox cardiotoxicity. Functional enrichment analysis displayed that the differentially expressed genes are annotated to MAPK signaling and cardiac hypertrophic pathways. CMDL-1 is first characterized in rat cardiomyocytes and is the most significantly downregulated lncRNA after doxorubicin exposure. CMDL-1 is located upstream to the transient receptor potential cation channel, subfamily M, member 7 (Trpm-7), which can function as a kinase by phosphorylating itself or other substrates. Mechanistic analysis indicated that lentiviral overexpression of CMDL-1 decreased Dox-induced mitochondrial fission (MitoTracker Red CMXRos) and apoptosis (TUNEL and flow cytometry) in cardiomyocytes. Bioinformatic and experimental data showed that CMDL-1 could bind to Drp1. Overexpression of CMDL-1 promoted its association with Drp1, as well as with phosphorylated (p)-Drp1, evidenced by RNA immunoprecipitation analysis. However, overexpression of CMDL-1 couldn’t effectively reduce mitochondrial fission if Drp1 was minimally expressed by siDrp1. These findings suggest that CMDL-1 could prevent mitochondrial fission and apoptosis by impairing Drp1 phosphorylation.

Conclusions:
Collectively, we demonstrated that a novel lncRNA CMDL-1 could play a protective role in cardiac injury and could be a potential therapeutic target in Dox cardiotoxicity. Our study is additional evidence of the less appreciated mechanism of lncRNAs, modulating the phosphorylation status of its interacting proteins.
Abstract 16464: Coronary Artery Calcium Score and Incidence of Clinically Significant Carotid Stenosis
Authors: Singh Aditya , Stys Tom , Bares Valerie , Wilson Jeffrey , Stys Adam
Published: May 2021

Introduction:
Coronary artery calcium (CAC) has been found to be associated with coronary artery plaque burden and is a major predictor of coronary heart disease (CHD) events. The data on its role in predicting carotid artery stenosis (CAS) is limited.

Methods:
Participants age ≥ 18 years with heart screen done from Nov 2008- Feb 2019 were selected and were assessed for documented diagnosis of carotid artery stenosis after their heart screen. Only the most recent heart screen per person and earliest documented CAS was considered. The chi-squared test and Welch’s 2-sample t-test was used to test for significant association between CAS and the nominal variables and mean calcium score respectively.

Results:
A total of 35,084 patient were screened for CAC score and 1439 (4.1%), were recorded to have a diagnosis of carotid artery stenosis. 53.5% being females and mean age of 63.69±9.31 years. The mean time between heart screen and documented diagnosis of CAS was 1529.4 ± 1211.0 days. The presence of CAS was significantly higher in patients ≥ 60 years (8.5%) as compared to those age <60 years (2%). There was a significant difference in mean CAC score between those with CAS as compared to non- carotid stenosis group (324.2, vs 107.27, p<.0001). In patient with elevated CAC ≥ 100, 9.98% had diagnosis of CAS, as compared to 2.82% in patients with CAC <100, however among patients with diagnosis of CAS 46.6% had elevated CAC ≥ 100.

Conclusions:
The presence of carotid artery stenosis (CAS) was significantly associated with elevated coronary artery calcium score (≥100) and was significantly higher in patients with age ≥ 60 years, which in correct clinical context is helpful in suspecting CAS.
Abstract 16476: Visit-to-Visit Blood Pressure Variability is Associated With Incident Frailty: The Multidomain Alzheimer Preventive Trial (MAPT)
Authors: Rouch Laure , de Souto Barreto Philipe , Hanon Olivier , Amar Jacques , Rolland Yves , Vellas Bruno
Published: May 2021

Introduction:
Visit-to-visit blood pressure variability (BPV) has been associated with greater cardiovascular and all-cause mortality, cognitive impairment, and incident dementia. It may also represent a decline in homeostatic mechanisms in blood pressure (BP) regulation associated with frailty, one of the most problematic expression of population aging.

Hypothesis:
We hypothesized that visit-to-visit systolic (SBPV), diastolic (DBPV), mean arterial (MAPV) and pulse pressure (PPV) variability are associated with greater incident frailty.

Methods:
We included 1,394 non-frail community-dwelling participants aged ≥ 70 years from the Multidomain Alzheimer Preventive Trial (MAPT) who underwent repeated clinical examinations over a 5-year follow-up period. SBPV, DBPV, MAPV and PPV were evaluated using standard deviation, coefficient of variation (CV), average real variability, successive variation, variation independent of mean and residual standard deviation. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses.

Results:
Higher SBPV was significantly associated with increased risk of incident frailty (1-sd increase of CV: HR = 1.18, 95% CI [1.02-1.37], p=0.03) after adjustment for demographics, body mass index, stroke, ischemic heart disease, diabetes, heart failure, antihypertensive drugs, systolic BP, MAPT intervention groups and baseline pre-frail status. Similar results were observed with all indicators of variability. DBPV and MAPV were not associated with incident frailty (p=0.6 and p=0.2, respectively). Interestingly, higher PPV was also associated with a greater risk of developing frailty over time (1-sd increase of CV: HR = 1.17, 95% CI [1.01-1.35], p=0.03).

Conclusion:
Independently of BP, higher SBPV and PPV are major clinical predictors of incident frailty. Our findings support the concept of BP physiological dysregulation underlying the frail state and suggest that controlling BP instability could be a promising interventional target in preventing frailty.
Abstract 16484: Primary Prevention Implantable Cardioverter Defibrillator Utilization for Hypertrophic Cardiomyopathy in US vs Non-US: Findings From the Share Registry
Authors: Nauffal Victor , Marstrand Peter , Han Larry , olivotto iacopo , Helms Adam S , Saberi Sara , Ingles Jodie , Pereira Alexandre , Wittekind Samuel , Ashley Euan A , Ware James S , Michels Michelle , Rossano Joseph , Jacoby Daniel L , Day Sharlene , Ho Carolyn
Published: May 2021

Introduction:
Risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) has evolved with notable differences in international practice trends and US vs European guidelines.

Hypothesis:
Utilization of primary prevention implantable cardioverter defibrillators (ICD) is higher in the US.

Methods:
We examined rates of primary prevention ICD implantation in 5,063 HCM patients in the international SHaRe registry from 2000 - 2020 (NUS=2,390; Nnon-US=2,673). Using multiple logistic regression we compared probability of ICD implantation for US vs non-US sites adjusting for standard SCD risk factors (Figure 1A). Interaction tests were performed to identify risk factors differentially associated with ICD implantation in US vs non-US sites after 2014 when the European Society of Cardiology (ESC) risk score was introduced.

Results:
The odds of ICD implantation were 3-fold higher in US sites [ORUS/non-US=3.11 (2.54 -3.81)] (Figure 1A). Odds remained similar after adjustment for ESC risk score [OR =3.17 (2.57 -3.91)]. Implantation rates were higher in the US throughout the study period with a notable drop in rates in both US and non-US sites after 2014 and a reduction in the magnitude of the difference in ICD utilization between US and non-US sites (ORUS/non-US (<2014) =4.20 (3.05-5.78) vs. ORUS/non-US (≥2014)=2.55 (1.89-3.44); pinteraction<0.001) (Figure 1B). Non-sustained ventricular tachycardia was a stronger predictor of ICD implantation in US sites [ORUS=4.9 (3.4-7.0) vs ORnon-US= 2.1 (1.2-3.6); pinteraction=0.005], whereas, left atrial diameter (> 40 mm) was a stronger predictor in non-US sites [ORNon-US=2.9 (2.1-4.0) vs ORUS=1.3 (1-1.6); pinteraction <0.001].

Conclusions:
ICD utilization rates vary globally. In this study, primary prevention ICD utilization rates were 3-fold higher in the US despite adjustment for standard SCD risk factors. Further studies are needed to evaluate outcomes of these practice differences.
Abstract 16504: Low Disturbed Flow Induces Dynamic Immune Compartment Alterations in Atherogenesis as Revealed by Single Cell Rna-seq
Authors: Qu Lili , Li Chuan , Matz Alyssa , Rodriguez-Oquendo Annabelle , Vella Anthony , Murphy Patrick , Zhou Beiyan
Published: May 2021

Low disturbed blood flow (LDF) is a critical contributing factor to atherogenesis but its direct impact on the immune compartment was not well-depict. To fill this knowledge gap, we adopted scRNA-seq to capture sheer-stress induced immune responses during atherogenesis. A partial carotid artery ligation (PCAL) model was selected for its paired comparison of carotid arteries with normal flow (NF) or LDF. Indeed, we observed drastic changes in both endothelial and immune compartment. Macrophages were the most significantly increased population induced by LDF (from 4% to 12% of CD45+ cells) with two well-separated subsets (Mac-c8, Mac-c9). MacSpectrum analyses revealed that Mac-c8 displayed higher inflammatory states than the lipid-laden Mac-c9. Interestingly, three T subtypes displayed unique flow-induced enrichment patterns that were selectively enriched in LDF but not in the NF condition. Furthermore, we created an original algorithms to evaluate the impact of sheer-stress on membrane protein-mediated cell-cell interaction among all cell types in the atheroma. Several pairs of molecular interactions were identified, including multiple APP-ligands interaction pairs and those in BAG2 Signaling. Moreover, signature genes identified in these LDF-induced T cells displayed high correlation to the plaque severity in human artery-aorta samples. Collectively, our study provided a high-resolution and focused analyses of sheer-stress induced immune cell action during atherogenesis. This is also the first identification of unique T subsets, to our knowledge, that are enriched in arterial wall exposed to low and disturbed flow. Further characterization of these cells will provide valuable information to understand and therapeutically treat atherogenesis.
Abstract 16511: Isocaloric Fructose Restriction Improves Postprandial Chylomicron and VLDL Excursions in Adolescents With Obesity by Reducing Angiopoietin-Like Protein 3 and Apolipoprotein CIII
Authors: Bains Yasmin , Erkin-Cakmak Ayca , Caccavello Russell , Mulligan Kathleen , Noworolski Susan , Schwarz Jean-Marc , Lustig Robert , Gugliucci Alejandro
Published: May 2021

Introduction:
Delayed postprandial triglyceride-rich lipoprotein (TRL) metabolism is associated with increased atherogenic risk. Dietary fructose is a preferred lipogenic substrate which contributes to NAFLD and dyslipoproteinemia.

Hypothesis:
Isocaloric fructose restriction reduces postprandial TRL excursions in part by affecting the modulation of lipoprotein lipase (LPL) activity and peripheral clearance rates.

Methods:
We determined the effect of 9 days of isocaloric fructose restriction on fasting and postprandial TRL metabolism markers in obese Latino and African American children (9-18 years old; n=30) with high habitual sugar consumption (>50 g/d). Metabolic assessments were performed on day 0 and day 10 of isocaloric fructose restriction (starch substituted for sugar, same macronutrient composition). To follow postprandial TRL metabolism, after an initial double-sized meal, single-sized meals (providing 67% of daily calories, 15% protein, 35% fat, 50% carbohydrate) were fed every 30 minutes, with blood sampled every hour for 8 hours. Fructose content of meals reduced from 12% on day 0 to 4% on day 10. Paired t-tests compared change from day 0 to day 10 within each child.

Results:
Fasting TG, apoCIII, and ANGPTL3 reduced by 25%, 28% and 26% respectively (p <0.01). Postprandial AUC of TG, apoCIII, ANGPTL3, VLDL, chylomicrons (apoB48) reduced by 35%, 34%, 40%, 17%, 19% (p <0.01), while no changes were found in fasting or AUC for ANGPTL4, ANGPTL8 nor LPL mass.

Conclusions:
Short-term isocaloric fructose restriction improved postprandial chylomicron and VLDL metabolism in children with obesity. Specific and selective improvements in ANGPTL3 and apoCIII suggest differential modulation of LPL activity as a putative mechanism that deserves further exploration.
Abstract 16541: Clinical and Imaging Phenotypes From a Registry of Segmental Arterial Mediolysis
Authors: Pandey Arvind K , Gerhard-Herman Marie
Published: May 2021

Background:
Segmental arterial mediolsyis (SAM) is a non-inflammatory arteriopathy that is increasingly being recognized; however, its clinical characteristics and natural history remain poorly defined.

Methods:
A retrospective, single-institution review of 20 patients presenting with arterial dissection, intramural hematoma, aneurysm, or occlusion between 2015 and 2020 was performed. To establish a non-invasive diagnosis of SAM, patients with FMD, inflammatory, or genetic arteriopathy were excluded by clinical, laboratory, and imaging criteria according to multidisciplinary guidelines. Patient demographics, clinical features, imaging findings, and management were assessed.

Results:
The average age of patients was 56 years; 75% were male. CAD was present in 15% of patients and 45% had hypertension; 55% were current or prior smokers. In patients without diagnosed CAD, the 10-year ASCVD risk score was 8.7% and the Framingham risk score was 6.8%. The average hemoglobin A1c was 5.6%. Acute onset abdominal pain (70%) was the most frequent presenting symptom. On average, two different arterial beds were affected at the time of diagnosis, most often in the abdomen. Arterial dissection was present in 75% of patients, and intramural hematoma was seen in 35% of cases. The most affected vessel was the superior mesenteric artery (50%), followed by the celiac, renal, and iliac arteries (35% each). Over a mean follow-up period of 20 months, all patients survived; two patients required intervention due to worsening clinical symptoms. Anticoagulation (AC) was utilized in 50% of cases, most commonly for one month. Long-term follow-up imaging was available in 11 patients; 3 patients (27%) had progression in lesion size over the first month. By 1 year, only 1 patient continued to show enlargement, with all others showing regression.

Conclusions:
This cohort provides longitudinal follow-up on both clinical and imaging characteristics of non-invasively diagnosed SAM. The condition shows a male predominance, typically manifesting in middle-aged patients with low to intermediate cardiovascular risk. While a subset of patients shows growth in size of the affected vascular segment over the first month, longer follow-up imaging demonstrates regression.
Abstract 16545: Sinus Rhythm Dynamics and Ventricular Ectopy in an Experimental Model of Aging
Authors: Comelli Martina , Pizzo Emanuele , Meo Marianna , Cervantes Daniel O , Plosker Aaron , Faltas Bridget , Jacobson Jason T , meste olivier , Rota Marcello
Published: May 2021

Aging is coupled with alterations of heart rate and heart rate variability (HRV), together with increased incidence of arrhythmias and sudden cardiac death. But whether changes of sinus rhythm properties of the aged heart correlate with enhanced occurrence of ventricular ectopic discharge remains unclear. Thus, we studied the effects of aging on heart rate, HRV, and occurrence of premature ventricular complexes (PVCs) in aging C57Bl/6 mice. Electrocardiograms (ECG) were obtained in male and female conscious mice at ~4, ~12, ~18, and ~24 months of age (n=37-66). Heart rate was preserved at ~4, ~12, and ~18 months (729±30, 730±22, and 725±20 bpm) and reached a minimum at ~24 months (708±37 bpm). Standard deviation of RR intervals, an indicator of HRV, was maximal at ~4 months (3.5±1.7 ms) and was reduced at ~12, ~18, and ~24 months (2.6±1.5, 2.5±1.3, and 2.6±1.3 ms). By frequency domain analysis, high-frequency components of RR interval variations, indicative of parasympathetic influence, were preserved with aging. In contrast, low frequency components, comprising the influence of sympathetic and parasympathetic axis, were maximal in young animals and progressively decrease at ~12, ~18, and ~24 months. PVCs were observed in only 3% of mice at ~4 months, a fraction that increased to 11%, 10%, and 22% at ~12, ~18, and ~24 months, respectively. For each age interval, heart rate and HRV parameters for animals with PVCs were distributed within the range observed in mice not experiencing ventricular ectopy. Moreover, for animals with PVCs, parameters of HRV before the occurrence of ectopic beats were comparable to those observed during undisturbed sinus rhythm, although a tendency for lower heart rate was seen. To address the role of the autonomic nervous system on incidence of ectopic events, ECGs were collected before and after block of the sympathetic and parasympathetic axis in mice at ~4 months (n=30) and ~24 months (n=26). This intervention reduced heart rate in both groups of animals and attenuated HRV exclusively in young. Moreover, combine autonomic block decreased incidence of PVCs by 50% and 57% in young and old animals, respectively. Collectively, these results suggest that occurrence of ventricular ectopy does not correlate with heart rhythm dynamics.
Abstract 16551: Transcatheter Closure of Patent Ductus Arteriosus in Premature Infants - How Young is Too Young?
Authors: Chakraborty Abhishek , Philip Ranjit , Naik Ronak , Abdulmajeed Huma , Harsono Mimily , Waller Rush , Sathanandam Shyam
Published: May 2021

Background:
Transcatheter patent ductus arteriosus (PDA) closure (TCPC), has been shown to be feasible and safe for infants as small as 700 grams or even smaller.

Hypothesis:
The corrected gestational age of the infant may be a better representation of tissue maturity than the weight of the infant. This study was aimed to explore the outcomes of TCPC based not just on weight, but also on the age of the infant.

Methods:
This was a retrospective study including infants born at gestational age < 28 weeks who underwent TCPC between Jan-2012 and May-2020 and weighed < 3 kg at the time of the procedure. The study period was divided into four-time blocks. Success and complication rates were compared for those who underwent the procedure at < 28 days to those infants that underwent TCPC >28 days of age.

Results:
In study period, TCPC was attempted on 241 infants that satisfied the inclusion criteria, with a 99.1% success rate. There was no difference in success rates based on the age at TCPC (99.3% vs. 99% for procedural age < 28 days vs. >28 days respectively; P=0.82). Overall, 140 infants underwent TCPC at < 28 days of age, 29 of whom were < 14 days, and 54 infants underwent TCPC between 15 and 21 days of age. The median age at TCPC progressively decreased from 60 days of life (14-211 days) between January 2012 and December 2014 to 18 days (8-38 days) between August 2019 and May 2020 (P < 0.00001). Similarly, the weight at TCPC decreased over the same time periods (median 1985 grams vs. 900 grams; P < 0.00001). Procedure-related complication rates were similar for those < 28 days vs. >28 days of age at the time of TCPC (2.8% vs. 4.9% respectively; P=0.42).

Conclusions:
It is feasible and safe to perform TCPC after the first week of life for infants born < 28 weeks’ gestation. As experience grows, more infants are referred to earlier after birth which translates to performing TCPC on smaller infants. The benefits of early TCPC have to be determined in order for this therapy to be advocated routinely for all premature infants.
Abstract 16558: The Burden of Arrhythmia in Cardiac Amyloidosis Hospitalizations: Perspective From a Nationwide Study
Authors: Thakkar Samarthkumar J , Patel Harsh P , Patel Raj , Chowdhury Medhat , Kumar Ashish , Doshi Rajkumar P , Tan Bryan E-Xin , Barssoum Kirolos , Arora Shilpkumar , Patel Brinda , Baibhav Bipul , Rao Mohan
Published: May 2021

Introduction:
Cardiac amyloidosis (CA) is a significantly underdiagnosed cause of infiltrative and restrictive cardiomyopathy, which leads to rapidly progressive heart failure associated with poor outcomes.

Hypothesis:
There is a paucity of data on the incidence and outcomes of arrhythmia among CA hospitalizations.

Methods:
Nationwide Inpatient Sample from 2016 to 2017 was used for the present analysis. CA hospitalizations with concurrent arrhythmia were identified by using appropriate ICD-10 CM codes, and it was compared with CA hospitalizations without arrhythmia. The primary outcome was all-cause in-hospital mortality, and secondary outcomes were the length of stay and total hospital cost. The adjusted odds ratio was calculated by multivariable regression analysis after adjusting for baseline characteristics and comorbidities.

Results:
A total of 5030 hospitalizations with CA were identified, of which 1570 had associated arrhythmia. CA hospitalizations with arrhythmia had higher mortality compared to without arrhythmia (150 (10.82%) vs. 215 (6.21%), P=0.012) (Table 1). Length of stay (9.74 days vs. 8.20 days, P=0.02) and total cost of hospitalization (avg. $ 112840 vs. $88638, P=0.02) were significantly higher in CA hospitalizations with concomitant arrhythmia (Table 1). Among arrhythmia, atrial fibrillation was the most common (89.38%) (Figure 1). Adjusted odds of in-hospital mortality due to any arrhythmia (aOR (adjusted odds ratio) = 1.83, CI (confidence interval) = 1.14 - 2.92, P=0.012) or atrial fibrillation (aOR= 1.73, CI= 1.075-2.277, P= 0.02) were significantly higher in CA hospitalization (Table 2).

Conclusions:
CA hospitalizations with arrhythmia had a higher adjusted odds of in-hospital mortality as compared to without arrhythmia. Additionally, CA hospitalization with arrhythmia had a longer length of stay, and cost of care. Among all arrhythmia, atrial fibrillation was the most common.