bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13073: ECG, Clinical, and Imaging Characteristics of Arrhythmogenic Right Ventricular Cardiomyopathy With Fat and Fibrotic Invasion Into the Left Ventricular Myocardium Revealed by Four-dimensional (4D) Cardiac CT
Authors: FUNABASHI Nobusada , Kobayashi Yoshio
Published: May 2021

Introduction:
4D cardiac CT can reveal characteristics of arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) such as fat and fibrotic invasion into the RV and LV myocardium (RVM, LVM), an enlarged RV, reduced RV motion and bulging.

Hypothesis:
We could differentiate ARVC patients with fat and fibrotic invasion into the LVM from those without, using ECG, clinical, and other imaging characteristics.

Methods:
Retrospective analysis of 17 patients (11 males, 57±17 years) with suspected ARVC who underwent 4D cardiac CT.

Results:
9 patients met the 2010 ARVC task force criteria. 4 had fat and fibrotic invasion into the LVM (group 1) but 5 did not (group 2). The remaining 8 did not fulfill the ARVC criteria (group 3). The proportion of males and age did not differ between groups. In groups 1, 2 and 3, respectively, 3 (75%), 4 (80%), and 1 (13%) patients had epsilon waves in V1-3 (group 1>3, P=0.033, group 2>3, P=0.005). 2 (50%), one (20%) and 4 (50%) had complete right bundle branch block (CRBBB) (all P=NS). Three (75%), 3 (60%), and 1 (13%) had inverted T waves in V1-3 or beyond (group 1>3, P=0.033). One (50%), 3 (75%), and 2 (50%) had terminal activation duration of QRS ≥55 ms measured from the nadir of the S wave to the end of the QRS, including R’, in V1, V2, or V3, in the absence of CRBBB (all P=NS). One (25%), 4 (80%) and 1 (13%) had sustained ventricular tachycardia (SVT; group 2>3, P=0.005). Two (50%), 1 (20%), and 3 (38%) had non-SVT (all P=NS). 4 (100%), 2 (40%), and 2 (25%) had clinical heart failure (group 1>2, P=0.019, group 1>3, P<0.001). Finally, 4 (100% and 80%) and 6 (75%) had RV enlargement on TTE (all P=NS). On 4D CT, 4 (100%), 5 (100%), and 5 (63%) of patients in groups 1, 2 and 3, showed RV enlargement (all P=NS); 4 (100%), 2 (40%), and 1 (13%) showed reduced RV motion (group 1>2, P=0.019, group 1>3, P<0.001); 75, 100, and 0%, had RV fat invasion (group 1>3, P=0.002, group 2>3, P<0.001); and 25, 0, and 0% showed bulging (all P=NS).

Conclusions:
Most patients had RV enlargement on TTE and/or 4D CT. Presence of epsilon waves, reduced RV motion, and RV fat invasion on 4D CT may differentiate groups 1 and 2 from group 3, inverted T waves in V1-3 leads or beyond may differentiate group 1 from group 3, SVT may differentiate group 2 from group 3 but only clinical heart failure may differentiate groups 1 and 2.
Abstract 13077: Higher Occurrence of Right Ventricular Fibrosis in Right Ventricular Outflow Tract-dominant Than Diffuse Hypertrophic Types: A Pulmonary Hypertension Study Using Cardiac Computed Tomography
Authors: FUNABASHI Nobusada , Ozawa Koya , Kobayashi Yoshio
Published: May 2021

Introduction:
On cardiac CT of pulmonary hypertension (PH), two right ventricular (RV) hypertrophic (RVH) morphological types are seen, namely RV outflow tract-dominant and RV-diffuse. However, clinical significance of this difference is unclear.

Hypothesis:
These two morphological RVH types have different effects on myocardial characteristics, clinical severity and prognosis in PH patients.

Methods:
We retrospectively analyzed 43 PH patients (33 females, 55±15yrs, 31 chronic thromboembolic PH (CTEPH), 7 idiopathic pulmonary arterial (PA) hypertension). On CT, RV fibrosis was defined as contrast defects in early phase and abnormal enhancement in late phase. Cases were divided into 3 groups: RV outflow tract-dominant RVH (gp 1), RVH-diffuse (gp 2), and no RVH (gp 3). Mean follow up was 39.3±20.1, 58.3±17.7, 68.2±11.9 months, respectively.

Results:
There were 6, 26, 11 patients in gps 1, 2, 3, respectively. There were no significant differences in these percentages between CTEPH and idiopathic PA hypertension or between ages ≥60 and <60 yrs. There were no significant differences of R/S wave ratio on ECG V1 lead, maximum RV wall thickness on end-diastole (CT), plasma BNP and estimated PA systolic pressure (PASP) on TTE between gps 1 and 2. There were significant positive correlations between maximum RV wall thickness in end-diastole and plasma BNP in gp 1 (R=0.44) but no correlations in gp 2 (R=0.05). Similarly, there were significant positive correlations between maximum RV wall thickness in end-diastole and estimated PASP in gp 1 (R=0.38) but no correlations in gp 2 (R= -0.08). RV fibrosis was detected in 3 patients (50%) (gp1) and 1 patient (4%) (gp2) (P=0.003). Zero, 2, and 1 patients died due to PH during follow-up periods in gps 1, 2, 3 , respectively, and there were no significant differences in these percentages on Kaplan Meier analysis and log rank testing. Interobserver agreement between two observers was 91% in gp 1 and 77% in both gps 2 and 3.

Conclusions:
In PH patients, RV outflow tract-dominant RVH was relatively easy to diagnose and manifested with greater occurrence of RV fibrosis than diffuse-type. RV outflow tract-dominant RVH showed significant positive correlations of maximum RV wall thickness in end-diastole with plasma BNP and estimated PASP.
Abstract 13085: Post-icd Implant Intervention: Secondary Prevention and Partner Support Associated With Improved Physical and Psychological Outcomes
Authors: Sauer Liberato Ana Carolina , Thompson Frances Elaine , Dougherty Cynthia M
Published: May 2021

Introduction:
Health characteristics and symptoms of patients with an ICD differ based on ICD indication (primary or secondary prevention). The purpose of this study was to examine for differential effects of ICD indication on health outcomes in 2 post-implant interventions: a patient-only intervention (P-only) and a patient intervention that included the patient’s partner (P+P).

Hypothesis:
Intervention effects on patient health outcomes will be influenced by ICD indication.

Methods:
A prospective RCT (N = 301) compared the 2 interventions on:
Physical Function
(SF-36
Physical functioning
,
Vitality
and
Physical Component Score
- PCS; physical health,
Patient Concerns Assessment
- PCA) and
Psychological Adjustment
(SF-36
Social Functioning
and
Mental Component Score -
MCS; State Anxiety, STAI; and Depression, PHQ-9). Study participants were randomized to intervention condition, blocked by comorbidities and ICD indication. The 2 nurse-led social cognitive theory interventions (P-only or P+P) were delivered by telephone during the first 12 weeks post implant. Health outcomes were measured at baseline, 3, and 12 months. Using repeated measures ANOVA, comparisons were made among 4 study groups, defined by ICD indication (primary vs secondary) and intervention condition (P-only vs P+P).

Results:
The sample was primarily white (91%), male (88%), average age 64±11.90 years, BMI = 29.57±6.17, EF = 34.08±14.33, Charlson Comorbidity = 2.29±1.49, with 60% receiving ICD for primary prevention. Secondary, compared to primary, prevention patients in both interventions showed improved physical functioning, vitality, physical health, and depression (F = 8.5, P = <0.001; F = 5.75, P = 0.001; F = 6.15, P = < 0.001; F = 4.09, P = 0.007, respectively). The greatest improvements were observed at 3 months (end of interventions) and maintained or improved at 12 months. Secondary prevention patients participating in P+P showed the greatest improvement in vitality and depression across 12 months.

Conclusion:
Patients who received an ICD for secondary prevention and were also in the P+P intervention showed greatest improvement across recovery, indicating promising health outcomes for patients in intervention programs that include the partner.
Abstract 13109: Oral and Intravenous Iron Therapy for Iron Deficiency Anemia After Cardiac Surgery
Authors: Elio Venturini , Veronica Venturini , Giallauria Francesco
Published: May 2021

Introduction:
cardiac surgery is associated with a high risk to develop iron deficiency anemia (IDA) with impact on the Cardiac Rehabilitation (CR) program. Sucrosomial Iron (SI) is a new oral iron with good gastrointestinal compliance and bioavailability

Hypothesis:
to compare SI with Ferric Carboxymaltose (FCM) i.v. the gold standard treatment for IDA.

Methods:
67 consecutive patients admitted to a CR unit after cardiac surgery (27 CABG, 29 valves/aortic surgery, 11 CABG+valves) were alternately treated with SI or FCM. Blood parameters were assessed at the admission (8-10 days after surgery) (T1), at discharge (18-22 days after surgery) (T2) and 10 days from discharge (T3). The study design provides for a single dose of 1000 mg of FCM at T1 or a dose of 120 mg of SI per day for the first 8-10 days after T1; then SI was scaled to 30 mg/die up to T3. Two groups were comparable in terms of age (SI vs FCM: 67.3 ± 12.8 vs 70.2 ± 12.2) and ejection fraction (SI vs FCM: 52.7% ± 7.8 vs 53.9% ± 5.4). Because the small sample size, non-normal distributed longitudinal variables were logarithmically transformed, to guarantee the maximum possible power to the analysis.

Results:
data are shown in the following table. At T1, two treatment groups showed no statistically significant difference. Hemoglobin significantly increased in both groups, without significant difference at T3. Transferrin saturation and Sideremia significantly increase in both groups, although the correction is faster with FCM. Ferritin, elevated to baseline for inflammatory condition after surgery, is reduced in the SI group, while it increases significantly in FCM group.

Conclusions:
SI is able to correct post-surgical IDA in times and ways comparable to i.v. FCM. The hyperferritinemia observed with FCM at T2 may be due to a low-grade pro-inflammatory effect correlated to the high level of iron deposition in macrophages. SI is able to recover IDA and to achieve normal Ferritin values, avoiding the risk of hyperferritinemia.
Abstract 13127: Cardiac Metastasis of Lingual Squamous Cell Carcinoma, A Systematic Review of Presentation, Management, and Outcomes
Authors: Kerndt Connor C , Nessel Trevor , Bills John A , Shareef Zaid A , Balinski Alexander , Mistry Devin
Published: May 2021

Introduction:
Cardiac metastasis of lingual squamous cell carcinoma (LSCC) describes a rare oncologic progression of oral disease currently ill-defined by medical literature. In this systematic review, we aim to characterize the presentation, management, and outcomes associated with LSCC cardiac metastases.

Methods:
A comprehensive search of PubMed, Embase, and Cochrane Library databases was performed from inception until December 2019. Inclusion criteria included a histologically diagnosed LSCC, definitive location of cardiac metastasis, and Oxford evidence level of 4. Duplicate, non-English, animal studies, and non-original research were excluded. Patient demographics, presenting symptomology, imaging findings, interventions, and outcomes were collected and analyzed.

Results:
Twenty-seven articles containing 31 cases met the outlined inclusion criteria. The average age of patient presentation was 55.6 years, ranging from 23-77 years. Average time from primary cancer diagnosis to identification of cardiac metastasis was 2.2 years, varying from 0.2-11.0 years. Shortness of breath (29.0%) and chest pain (29.0%) were the most common presenting symptoms, while effusion (21.2%) and right ventricular outflow obstruction (18.2%) were the predominant echocardiogram findings. Right sided metastases (76.7%) were identified more commonly than left sided metastases (53.3%) and septal metastases (36.7%). Cardiac metastases most commonly presented within the right ventricle (56.7%), followed by the left ventricle (43.3%) (Figure 1). Surgical resection (80.6%) and radiotherapy (74.2%) were the most frequently utilized interventions. No patients obtained remission with treatment and all patients expired within one year of metastatic diagnosis.

Conclusions:
Cardiac metastases of LSCC demonstrate ventricular predominance and suggest a poor prognosis. Patients may benefit from palliative measures, rather than invasive intervention.
Abstract 13145: Differences of Cancer Types in Hospital Mortality in Patients With Venous Thromboembolism
Authors: Yuichiro Okushi , Kusunose Kenya , Ise Takayuki , Tobiume Takeshi , Yamaguchi Koji , Yagi Shusuke , Fukuda Daiju , Yamada Hirotsugu , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka
Published: May 2021

Introduction:
We sought to evaluate the clinical characteristics and outcomes of patients with cancer-associated VTE, compared with the matched cohort without cancer using real-world big data of VTE. Background: Cancer is associated with a high incidence of Venous Thromboembolism (VTE) and there are many guidelines/recommendations about VTE. However, the prognosis of cancer-VTE patients is not well known because of a lack of big data. Moreover, there is also no knowledge on how cancer type is related to prognosis.

Methods:
This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). We identified 28,247 patients who were first hospitalized with VTE from April 2012 to March 2017. 26.0% were cancer patients. Compared with national statistics of cancer incidence in 2015 from National Cancer Center of Japan, the proportion of gynecological cancer patients was higher, but other cancer types had similar prevalence rates. Propensity score (PS) was estimated with logistic regression model, with cancer as the dependent variable and 18 clinically relevant covariates.

Results:
We included 24,576 patients after exclusion. The median age was 71years (range: 59-80 years), and 42.0% were male. On PS-matched analysis with 12,418 patients, patients with cancer had higher total in-hospital mortality (9.5% vs. 3.8%, P<0.001; OR, 2.72, 95% CI: 2.33-3.19) and in-hospital mortality within 30days (6.8% vs. 3.2%, P<0.001; OR, 2.20, 95% CI: 1.85-2.62). On analysis for each type of cancer, in-hospital mortality in 10 types of cancer was significantly high, especially pancreas (OR: 9.65, 95%CI: 4.31-21.64), biliary tract (OR: 8.36, 95%CI: 2.42-28.89) and liver (OR: 7.33, 95%CI: 1.92-28.02).

Conclusions:
Patients with cancer had a higher in-hospital mortality for VTE than those without cancer, especially in pancreatic, biliary tract and liver cancers.
Abstract 13157: Deep Learning for Detection of Elevated Pulmonary Artery Wedge Pressure Using Standard Chest X-ray
Authors: Hirata Yukina , Kusunose Kenya , Yamada Hirotsugu , Tsuji Takumasa , Fujimori Kohei , Kotoku Junichi , Sata Masataka
Published: May 2021

Introduction:
Chest X-ray (CXR) is a useful and economical modality for the detection of congestive heart failure. However, the accuracy is limited by the subjective nature of its interpretation. Deep learning (DL) can be used to recognize diseases or findings objectively in various imaging modalities, and may outperform previous diagnostic techniques.

Hypothesis:
We hypothesized that DL-based analysis of CXR detect the presence of elevated pulmonary arterial wedge pressure (PAWP) in patients with suspected heart failure.

Methods:
We enrolled 1,013 patients with paired right heart catheterization and CXR performed from October 2009 to February 2020 in our hospital. DL algorithm for the detection of elevated PAWP was developed using the training dataset, based on a single CXR image. Independent evaluation cohort of 115 patients was performed using CXR-based DL model and echocardiographic data to detect the presence of high PAWP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the DL-based models compared with echocardiographic data.

Results:
The study included 1,013 patients (mean age, 67±13 years; 569 males [56%]). The mean PAWP was 12.5±6.4 mmHg and 218 patients (22%) had more than 18mmHg. To detect high PAWP, the AUC produced by DL algorithms was effective, and the DL algorithm with the largest AUC was ResNet50. In an evaluation cohort, to detect high PAWP, the AUC using the DL model with CXR was similar to the AUC produced by the echocardiographic left ventricular diastolic dysfunction algorithm (0.77 vs. 0.70; respectively; p=0.27), and significantly higher than the AUC by measurements of echocardiographic parameters (ResNet50 vs. other parameters; all compared p <0.05)
(Figure)
.

Conclusions:
The present results demonstrated that DL based on analysis of CXR can detect the presence of high PAWP. This finding suggests that the DL based approach may support an objective evaluation of CXR in the clinical setting.
Abstract 13167: Early Mobilization in Postoperative Cardiac Surgical Patients
Authors: Goldfarb Michael , Dima Diana , Langlois Yves
Published: May 2021

Introduction:
Early mobilization (EM) is recommended by cardiac surgical societies. However, the optimal method of EM delivery has yet to be determined. Our objective was to assess whether a bedside nurse-driven EM strategy is safe and associated with improved outcomes following cardiac surgery.

Methods:
Consecutive post-cardiac surgery patients in a cardiovascular intensive care unit (CVICU) at an academic tertiary care centre from 2017 to 2019 prior to and after EM program implementation were reviewed. Postoperative cardiac surgery patients were initially managed in a general ICU and transferred to the CVICU when hemodynamic stability was achieved, typically postoperative day 1 or 2. Functional status was assessed by the nurse on CVICU admission using the Level of Function (LOF) Mobility Scale, which ranges from LOF 0 (bed immobile) to LOF 5 (walks > 50 feet). The nurse uses the LOF score to guide twice-daily level-specific mobility activities. The primary outcome was hospital length of stay.

Results:
There were 504 patients included in the study (preintervention, N=329; Intervention, N=175). There was no difference in age, sex or comorbid illness between the groups (Table). The LOF was 4.7 ± 0.5 prior to surgery, 3.4 ± 1.1 on CVICU admission, and 4.3 ± 0.6 on CVICU discharge in patients undergoing EM. Patients were mobilized during nearly all mobilization opportunities (98.7%; 685/694). Adverse events were rare (0.4%; 8 events/1901 mobilization activities), minor and transient. There was no difference is postoperative hospital length of stay, in-hospital mortality, discharge home or 30-day hospital re-admission (all P>0.05).

Conclusion:
A nurse-driven EM program was safe and associated with improvement in functional status in postoperative cardiac surgery patients. The EM program was not associated with improved short-term outcomes. Further studies are needed to understand optimal delivery of EM in cardiac surgical patients.
Abstract 13169: US Prevalence Estimates of Individuals With Diabetes and Chronic Kidney Disease Indicated for SGLT-2 Inhibitor Initiation
Authors: Aggarwal Rahul , Lu Kimberly , Chiu Nicholas , Bakris George , Bhatt Deepak L
Published: May 2021

Introduction:
Since the CREDENCE trial results, the American Diabetes Association (ADA) recommends SGLT-2 inhibitors as first line therapy for patients with stage III Chronic Kidney Disease (CKD) or proteinuric CKD, regardless of baseline A1C. We project the number of US individuals with diabetes and renal disease that meets inclusion into the CREDENCE trial and that are recommended for SGLT-2 inhibitors based on the guidelines.

Methods:
Our initial cohort consisted of 48,710 individuals from the 2007-2016 National Health and Nutrition Examination Survey with survey weights designed to estimate the US population. CREDENCE eligible patients were patients with diabetes who had an eGFR of 30-90 and urine albumin-to-creatinine ratio (UACR) of >300 mg/g. Guideline eligible patients were stage III CKD individuals and those with a UACR > 30 mg/g.

Results:
In the US population, 21,411,059 (+/-708,233) individuals are >=18 years and have diabetes. Of these individuals, 578,514 (+/-72,385) are CREDENCE eligible. Based on the ADA recommendations, 7,504,508 (+/- 342,139) adults with CKD and diabetes are recommended for an SGLT-2 inhibitor, representing 35.0% of individuals with diabetes. The mean age of guideline eligible individuals is 64.4 years, with 3,886,904 males (51.8%) and 3,617,604 females (48.2%).

Conclusions:
In the United States, a large number of individuals--approximately 35% of adults with diabetes--have renal disease characteristics that give them a first-line indication for SGLT-2 inhibitor initiation.
Abstract 13179: Distinct Biomarker Profiles for Pediatric and Adult Dilated Cardiomyopathy
Authors: GROPLER Melanie R , Lipshultz Steven E , Wilkinson James D , Towbin Jeffrey A , Colan Steven D , Canter Charles E , Lavine Kory J , Simpson Kathleen E
Published: May 2021

Introduction:
Pediatric and adult dilated cardiomyopathy (DCM) represent distinct entities with divergent gene expression, histopathology, and response to medical therapies. Prognostically important serum biomarkers identified in adults have failed to provide similar diagnostic and prognostic information for children with DCM. We hypothesized that pediatric and adult DCM populations display different biomarker profiles.

Methods:
Pediatric control (≤18y), pediatric DCM, and adult DCM plasma samples were analyzed using the SOMAscan biomarker platform to simultaneously measure over 1300 known protein analytes. Pediatric control and DCM subjects were age- and gender-matched. Most samples were obtained within 2 years of diagnosis. Biomarkers were compared between groups with p-value <0.05 (false discovery rate) and fold change (ratio of means) >2 considered significant. Principal component analysis was used to visualize differences in proteomic data.

Results:
The study included 39 pediatric control (mean age 3y, IQR 1-14), 39 pediatric DCM (median age 2.7y, IQR 1-13), and 40 adult DCM (median age 53y, IQR 46-63) subjects. Twenty plasma peptides were upregulated in pediatric DCM compared to controls. Plasma renin and 6-phosphogluconate dehydrogenase represented potential pediatric-specific biomarkers. Pediatric DCM subjects clustered into 4 distinct subgroups with unique biomarker profiles and distinguishing clinical characteristics suggesting the pediatric DCM phenotype may represent a heterogeneous group of diseases.

Conclusions:
This feasibility study provides important evidence that distinct biomarker profiles are present in pediatric and adult DCM patients. These findings provide preliminary data to inform the design of larger prospective studies to validate pediatric DCM specific biomarkers and investigate their prognostic value.
Abstract 13199: Home Blood Pressure Monitoring Among Us Adults Without Hypertension: How Do Existing Patient and Physician Behaviors Correspond to Current Recommendations?
Authors: Bryant Kelsey B , Green Matthew B , Kronish Ian M , Zhang Yiyi , Sheppard James , McManus Richard , Moran Andrew E , Bellows Brandon K
Published: May 2021

Introduction:
Home blood pressure monitoring (HBPM) is an option recommended by the 2017 ACC/AHA guidelines to confirm a hypertension diagnosis or identify masked hypertension. Using clinic BP and patient characteristics, the Predicting Out-of-Office BP in the Clinic (PROOF-BP) algorithm can be used to guide HBPM decisions. It is unknown how existing patient use and physician recommendations for HBPM align with current screening recommendations.

Methods:
We used the 2009-2014 National Health and Nutrition Examination Survey (NHANES) to identify US adults aged ≥20 years without hypertension or antihypertensive medication use. We identified those who would have been recommended to undergo HBPM by ACC/AHA guidelines as those with a mean BP 120-159/<100 mm Hg and by the PROOF-BP algorithm as those with a predicted out-of-office BP 125-134/75-84 mm Hg. We required individuals to have complete data needed for the PROOF-BP algorithm (demographics, BP, smoking, alcohol use, kidney disease) and reported HBPM actual/recommended use. All analyses were weighted to be representative of the US population.

Results:
We included 7,185 NHANES adults without hypertension; weighted mean (SE) age was 41.5 (0.3) years, 48% female, and mean BP 117.0 (0.3)/70.4 (0.3) mm Hg. Overall, 50.3% of adults without hypertension would have been recommended to undergo HBPM by ACC/AHA guidelines and 29.7% by PROOF-BP (
Table
). Only 13.3% of those recommended HBPM by ACC/AHA guidelines used or were told to use HBPM, compared to 11.5% of those not recommended screening. Similar results were seen among those recommended HBPM by PROOF-BP (
Table
).

Conclusions:
Our analysis shows that prior to 2017 guidelines, a substantial proportion of US adults may have had their hypertensive status misclassified due to a lack of HBPM or undergo unnecessary monitoring. These findings suggest an opportunity for clinicians and health systems to more clearly target HBPM to those who need it given guidelines currently in use.
Abstract 13306: Impella Combined With Extracorporeal Membrane Oxygenation Synergistically Unloads the Left Ventricle and Reduces Infarct Size in a Model of Myocardial Infarction With Cardiogenic Shock
Authors: Sunagawa Genya , Saku Keita , Nishikawa Takuya , Suematsu Nobuhiro , Kubota Toru , Sunagawa Kenji , Tsutsui Hiroyuki
Published: May 2021

Introduction:
Extracorporeal membrane oxygenation (ECMO) supports hemodynamics in cardiogenic shock (CS) at the expense of left ventricular (LV) overload. LV assist device (LVAD) also supports hemodynamics, whereas LVAD unloads LV. Therefore, the combination of ECMO and LVAD would augment hemodynamic support and unload LV. We hypothesized that the combination therapy in acute myocardial infarct (AMI) in CS could synergistically improve hemodynamics and unload LV, which, in turn, reduces infarct size.

Methods:
In protocol 1, we ligated coronary arteries and created AMI with CS in 5 mongrel dogs (15.1±0.3 kg). We transvascularly introduced Impella CP into LV. We kept the ECMO flow constant at 1.8L/min. We compared hemodynamics and the LV pressure-volume area (PVA, an index of LV oxygen consumption) under 3 conditions; Control, ECMO, and ECMO+Impella (ECPELLA) in each dog. In protocol 2 (n=15), we ligated coronary arteries for 180 min and then reperfused. We activated Impella CP and/or ECMO from 60 min after the coronary ligation to the end of the experiment. We allocated dogs into 3 groups, no support (Control), ECMO, and ECPELLA and compared infarct size at 180 min after reperfusion among 3 groups.

Results:
In protocol 1, both ECMO and ECPELLA increased arterial pressure compared to Control (Control: 63±9, ECMO: 88±10 and ECPELLA: 97±18 mmHg, p < 0.05), and resolved the CS status. ECPELLA strikingly reduced PVA by 83% relative to Control (1500±326, 2038±357 and 258±182 mmHg*ml, p<0.001). In protocol 2, ECPELLA markedly reduced the infarct size (15±8%) compared to Control (53±7%, p<0.05) and ECMO (39±10%, p<0.05).

Conclusions:
ECPELLA before reperfusion markedly improved hemodynamics, reduced PVA, and limited infarct size in a dog model of MI with CS. ECPELLA could prevent ECMO-induced LV overload and synergistically exert powerful anti-infarct effects in AMI with CS.
Abstract 13307: An Oral Antisense Oligonucleotide for PCSK9 Inhibition in Humans
Authors: Gennemark Peter , Walter Katrin , Clemmensen Niclas , Rekic Dinko , Nilsson Catarina , Knoechel Jane , Holtta Mikko , Wang Yanfeng , Yu Rosie , riney stanley , Monia Brett P , Andersson Ulf , Jansson-Lofmark Rasmus , Rocha Cristina S , Linden Daniel , Ryden-Bergsten Kristina , Hurt-Camejo Eva , CROOKE Rosanne M , Tillman Lloyd , Carlsson Bjorn , Elebring Marie , Tivesten Anna , Davies Nigel
Published: May 2021

Current PCSK9 inhibitors are administered via subcutaneous (SC) injection. Here, we present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier ASO chemistries and intestinal permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by tri-antennary
N
-acetyl galactosamine (GalNAc) conjugation make this ASO highly potent. A single SC dose of 90 mg reduces PCSK9 by >90% in humans with elevated LDL-C (A), and a once monthly SC dose of 25 mg ([20, 30], 90% CI) is predicted to reduce PCKS9 by 80% at steady-state. To investigate the feasibility of oral administration, we developed an oral solid tablet wherein the ASO is co-formulated with a transient permeation enhancer. Repeated oral daily dosing of tablets to dogs resulted in a bioavailability of 7% in the liver (target organ), approximately 5-fold greater than the plasma bioavailability (B). Favourable liver uptake following oral administration is supported by similar bioavailability in plasma and kidney. Since the ASO is not active in rodents or dogs, we used a rat-specific GalNAc-
Malat-1
ASO with the same chemistry to confirm target engagement. Intrajejunal administration resulted in ≥78% mRNA knockdown in the liver for single doses of 3-40 mg/kg. A monkey tolerability study of the PCSK9 ASO further supports oral feasibility with all tested doses (28-56 mg/day) significantly reducing LDL-C already after 7 days of daily oral dosing. Based on available animal and human data, and an assumption of 5% oral bioavailability in humans, a daily dose of 15 mg ([10, 20], 90% CI) in man is predicted to reduce PCSK9 in plasma by 80% at steady-state. This supports the development of the compound for subcutaneous and oral administration to treat dyslipidemia.
Abstract 13328: Impact of Cascade Screening for Familial Hypercholesterolemia on Cardiovascular Events
Authors: Tada Hayato , Nohara Atsushi , Yamagishi Masakazu , Takamura Masayuki , Kawashiri Masa-aki
Published: May 2021

Background:
Familial hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the low-density lipoprotein (LDL) receptor or associated genes, resulting in elevated serum cholesterol levels and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Early diagnosis and timely treatment can substantially lower the risk of ASCVD. In this sense, cascade screening could be one of the most useful options. However, few data exist regarding the impact of cascade screening for FH on the reduction of risk of ASCVD events. We aimed to evaluate the prognostic impact of cascade screening for FH.

Methods:
We retrospectively investigated the health records of 1,050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened, who were referred to our institute. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiovascular events (MACE). The median period of follow-up was 12.3 years (interquartile range [IQR] = 9.1-17.5 years), and MACE included death from any causes or hospitalization due to ASCVD events.

Results:
During the observation period, 246 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr,
P
< 2.2 х 10
–16
), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.36; 95%CI = 0.22 to 0.60;
P
= 6.3 х 10
–5
) when compared with the probands, even after adjusting for those known risk factors.

Conclusions:
The identification of patients with FH via cascade screening appeared to result in better prognoses.
Abstract 13330: Intrarenal Doppler Ultrasonography Reflects Hemodynamics and Predicts Prognosis in Patients With Heart Failure
Authors: Watanabe Koichiro , YOSHIHISA Akiomi , Sato Yu , Hotsuki Yu , Ichijo Yasuhiro , KIMISHIMA Yusuke , Yokokawa Tetsuro , Misaka Tomofumi , Oikawa Masayoshi , KOBAYASHI ATSUSHI , Takeishi Yasuchika
Published: May 2021

Introduction:
We aimed to clarify clinical implications of intrarenal hemodynamics (congestion and hypoperfusion) assessed by intrarenal Doppler ultrasonography (IRD) and their prognostic impacts in patients with heart failure (HF).

Methods and Results:
We performed IRD and measured interlobar renal artery velocity time integral (VTI) and intrarenal venous flow (IRVF) patterns (monophasic or non-monophasic pattern) to assess intrarenal hypoperfusion and congestion in HF patients (n=341). These patients were categorized based on 1) VTI: high VTI (VTI ≥ 14.0 cm, n=231) or low VTI (VTI < 14.0 cm, n=103); and 2) IRVF: monophasic (n=36) or non-monophasic (n=305) pattern. We performed right-heart catheterization, and examined post-discharge cardiac event rate such as cardiac death and rehospitalization due to worsening HF. Regarding renal perfusion, cardiac index was positively correlated with VTI (R=0.270, P=0.040). Concerning renal congestion, levels of right atrial pressure were higher in monophasic pattern than in non-monophasic pattern (9.0 vs. 7.2 mmHg, P=0.029). Importantly, HF patients with low VTI and a monophasic IRVF pattern (subset 4) had the highest cardiac event rate (
Figure
). In the Cox proportional hazard analysis, the combination of low VTI and a monophasic IRVF pattern was found to be a strong predictor of cardiac events (HR 8.357, 95% CI 3.365-20.752).

Conclusion:
Intrarenal hypoperfusion and congestion assessed by IRD imaging reflected cardiac output and right atrial pressure, and was useful to risk-stratify HF patients.
Abstract 13342: Increasing Use of the Right Ventricle to Pulmonary Artery Shunt for Stage 1 Palliation: A Report From the National Pediatric Cardiology Quality Improvement Collaborative
Authors: Hill Garick , Heydarian Haleh , Marcuccio Elisa , Tepe Brooke , Stein Laurel H , Hill Garick D
Published: May 2021

Introduction:
Stage 1 palliation (S1P) of single ventricle heart defects with aortic hypoplasia consists of either the Norwood operation with a modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery shunt (RVPAS), or a hybrid procedure. Changes in national trends over time and factors influencing surgical approach remain unclear.

Hypothesis:
There has been an increase in national use of the RVPAS for S1P.

Methods:
Data from the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) phase 1 (6/2008-8/2016) and phase 2 (8/2016-9/2019) databases were used. S1P type was evaluated by year of operation. Factors influencing the choice of MBTS versus RVPAS, as well as length of stay after S1P and mortality prior to Stage 2 palliation (S2P) between shunt types, were evaluated. Sites were stratified by the number of patients in the database per year as small (<5), medium (<10) and large (≥10) centers.

Results:
The combined database included 3335 eligible patients; 1,028 (30.8%) with MBTS, 1,989 (59.7%) with RVPAS, and 318 (9.5%) with hybrid procedure. Overall, of 62 centers, 14.6% of S1P were at small centers (n=26), 40.6% at medium centers (n=24), and 44.7% at large centers (n=12). There was an increase in RVPAS use over time (p=0.02). In multivariable analysis, increasing hospital volume (OR 1.2 [95% CI 1.1-1.4], p=0.003) and absence of other organ system anomalies (OR 1.5 [95% CI 1.0-2.2], p=0.049) were associated with MBTS use over RVPAS. Median length of stay after S1P with MBTS was longer than with RVPAS (31 [95% CI 20-49] vs 29 [95% CI 19-47] days, p=0.054) and mortality was higher prior to S2P (12.3% vs 9.6%, p=0.03).

Conclusions:
Use of RVPAS with S1P has increased over time with a decrease in MBTS use and unchanged hybrid frequency. MBTS is used more commonly in centers with higher volume and in patients without other anomalies but is associated with longer post-op hospitalization and lower transplant-free survival to stage 2 palliation.
Abstract 13379: Cause-specific Mortality by Diffuse Coronary Artery Calcium Phenotypes: Results From the Coronary Artery Calcium Consortium
Authors: Dudum Ramzi , Dardari Zeina A , Feldman David , Berman Daniel , Budoff Matthew J , Miedema Michael D , Nasir Khurram , Rozanski Alan , Rumberger John A , Shaw Leslee J , Cainzos Achirica Miguel , Patel Jaideep , Blaha Michael J
Published: May 2021

Objectives:
We sought to assess characteristics of diffuse coronary artery calcium (CAC) phenotypes and their associations with cause-specific mortality.

Background:
CAC is a measure of subclinical atherosclerosis and improves risk stratification. CAC characteristics including vessel involvement, number of vessels, volume, and density have been shown to differentially impact risk. Less is known about clinical predictors of a diffuse CAC phenotype and its impact on cause-specific mortality.

Methods:
The CAC Consortium is a retrospective, multi-site cohort of 66,636 participants without CHD who underwent CAC scoring. Risk factor data were collected at enrollment or scan. Participants with CAC>0 were included—CAC area, CAC density, and the CAC index of diffusion (the percentage of total CAC in the vessel with the highest CAC score) were calculated and the association between CAC characteristics and CVD- and CHD-specific mortality was assessed.

Results:
In 28,147 study participants (mean age 58.3 years, 25% female, and 89.6% white), ~66% had ≥2 calcified vessels. Diabetes, hypertension, and hyperlipidemia were predictors of multivessel involvement (p<0.001). After controlling for CAC score, those with 4-vessel CAC had more CAC area involved with less dense calcification compared to those with 1-vessel involvement. After adjustment, those with CAC score 1-299 had a graded increase in CVD- and CHD-specific mortality with increasing vessel number compared with 1-vessel CAC. No difference was seen for individuals with CAC >300. Among those with multivessel CAC involvement, all-cause survival was significantly worse in diffuse compared to other phenotypes.

Conclusion:
Diffuse CAC involvement was characterized by less dense calcification, more CAC area, multiple coronary vessel involvement, and presence of certain traditional risk factors. Multivessel CAC is associated with increased CVD- and CHD-specific mortality, particularly among CAC scores 1-299.
Abstract 13382: Increased Adiposity is Associated With Risk of Adverse Clinical Events in Fontan Patients
Authors: Cao Jacob Y , Tran Derek , Briody Julie , Attard Chantal , Hassan Ebrahim B , Simm Peter , Burchill Luke , Twigg Stephen , Fiatarone-Singh Maria A , Ayer Julian , Celermajer David , d’Udekem Yves , Cordina Rachael L
Published: May 2021

Introduction:
Increased adiposity and reduced lean mass are prevalent in Fontan patients and could be impactful because of the reliance on the peripheral muscle pump and the importance of favourable pulmonary physiology in univentricular physiology. The current study aimed to determine the impact of body fat and lean mass on the risk of adverse outcomes in Fontan patients.

Methods:
Patients with dual-energy X-ray absorptiometry (DXA) scans from the Australian and New Zealand Fontan Registry were included; they had been consecutively recruited for 2 previous cohort studies. Regression analysis was used to characterize the association between body composition and the composite endpoint of Fontan failure (which included death, transplantation, New York Heart Association (NYHA) functional class III/IV, protein-losing enteropathy, and plastic bronchitis) and development of moderate or worse ventricular dysfunction.

Results:
131 DXA scans were analyzed, with mean follow-up of 2.5 (SD 2.2) years after DXA. Mean body fat percentage (%BF) was 29% (SD 10) with 48% having increased adiposity compared with local reference data. Mean appendicular lean mass index (ALMI) z-score was -1.5 (SD 1.1); one third of patients had skeletal muscle deficiency (defined as ALMI z-score between -1 and -2) and another third had Fontan-associated myopenia (defined as ALMI z-score < -2). Nine patients reached the composite endpoint during the follow-up period. Age and %BF were predictors of the endpoint in univariable regression (age: HR 1.09 per year, 95% CI 1.02-1.17,
p
= 0.01; %BF: HR 1.08, 95% CI 1.01-1.17,
p
= 0.03). On multivariable regression, %BF remained a significant predictor with every 1% increase conferring an 9% increased risk (HR 1.09, 95% CI 1.00-1.19;
p
= 0.045). ALMI was not a predictor of the endpoint (HR 1.40, 95% CI 0.71-2.76,
p
= 0.33). However, all patients who experienced a Fontan failure event (n=4) concurrently had increased adiposity and skeletal muscle deficiency.

Conclusions:
Increased adiposity is associated with increased risk for adverse clinical outcomes. Appropriate lifestyle interventions to optimise body composition should be an important aspect of routine care in this population.
Abstract 13398: 4D Flow Cardiac MRI Reveals Subtle Diastolic Dysfunction in Young Adults Born Premature
Authors: Corrado Philip A , Macdonald Jacob A , François Christopher J , Eldridge Marlowe W , Goss Kara , Wieben Oliver
Published: May 2021

Introduction:
Individuals born premature have smaller ventricular chambers volumes and a reduced cardiac reserve during exercise. Epidemiologic studies demonstrate increased risk of developing heart failure by young adulthood, though whether this is due primarily to systolic or diastolic dysfunction remains unresolved.

Hypothesis:
We hypothesize that either systolic or diastolic function, quantified as intraventricular kinetic energy (KE) during systolic and diastolic phases, respectively, will be altered in both ventricles of young adults born premature.

Methods:
A total of 56 young adults participated in this observational cardiac MRI study: 35 subjects born moderately to extremely premature (birth weight <1500 g or gestational age ≤32 weeks), and 21 age-matched term-born subjects. Each subject underwent cardiac MRI, including cine cardiac structure/function assessment and four-dimensional flow-encoded MRI (4D flow MRI). Five 4D flow parameters, normalized by end diastolic volume (EDV) to control for heart size, were extracted from each ventricle’s KE-time curve: average KE/EDV, peak systolic KE/EDV, early diastolic (E-wave) KE/EDV, late diastolic (A-wave) KE/EDV, and the ratio of E-wave KE to A-wave KE.

Results:
Average KE/EDV and peak systolic KE/EDV were similar between term and preterm subjects. Preterm-born subjects had increased A-wave KE/EDV in the RV and decreased E/A KE ratio in both ventricles (Table 1), indicating subtle diastolic dysfunction. The E/A KE ratio was moderately correlated with stroke volume index in both ventricles (LV: R=0.37, P=0.005; RV: R=0.32, P=0.02).

Conclusions:
Our results suggest that diastolic dysfunction, along with reduced chamber size, contributes to the reduced stroke volume seen in individuals born premature. In addition, diastolic dysfunction may further limit cardiac functional reserve and increase early heart failure risk in this population.
Abstract 13402: FHL-1 Contributes to and Colocalizes With Titin in Cardiac Hypertrophy
Authors: El-Bizri Nesrine , Liu Jing , Matt Rachel , Iyer Rugmani P , Raman Girija , Tanis Keith Q , Zhou Heather , Rosahl Thomas W , Sheth Payal , Swaminath Gayathri
Published: May 2021

Increased myocardial stiffness is a hallmark of impaired diastole in heart failure (HF). Hypo-phosphorylation of the N2B unique sequence (N2Bus) of titin (TTN), a giant myofilament protein, increases passive tension leading to diastolic dysfunction in HF. Enhancing the altered N2Bus phosphorylation improves cardiac stiffness and function. FHL-1, an interacting protein potentially modulating N2Bus phosphorylation is increased in HF. FHL-1 knockout mice display blunted cardiac hypertrophy and improved diastolic compliance in response to pressure-overload by transverse aortic constriction, TAC. FHL-1 also regulates skeletal muscle hypertrophy. We hypothesize that FHL-1 contributes to cardiac hypertrophy and colocalizes/interacts with TTN in heart failure. In house IHC data showed site-specific N2Bus hypo-phosphorylation at S4099, S4010 and S4185 in human HCM and/or DCM tissue samples. Longitudinal in-vivo studies showed that FHL-1 and cardiac hypertrophy markers genes were increased in left ventricles (LV) of TAC mice using RNA-seq. A persistently enhanced FHL-1 protein expression by immunoblotting and mass spectrometry strongly correlated with LV hypertrophy at 1, 4, and 6 weeks post-TAC. In addition, LV hypertrophy correlated negatively with function (fractional shortening). Increases in FHL-1 and hypertrophy markers mRNA levels were confirmed by RT-qPCR in neonatal rat ventricular myocytes (NRVM) under phenylephrine (PE) and endothelin-1 (ET-1) induced hypertrophy. Under similar conditions, FHL-1 protein levels were increased by immunofluorescence (IF) in cytoplasmic, perinuclear and nuclear regions of NRVM. Colocalization of phospho-TTN and FHL-1 was observed in NRVM and was enhanced under PE- and ET-1 induced hypertrophy. IF studies in human skeletal myotubes showed that FHL-1 expression was increased during myoblast differentiation and IGF1-E3R induced hypertrophy. Preliminary data using Microscale Thermophoresis showed binding affinity between N2Bus and FHL-1 proteins. Our studies show that FHL-1 contributes to hypertrophy in addition to N2B hypo-phosphorylation status contributing to diastolic dysfunction in HF. Targeting FHL-1 and TTN can be a potential strategy to improve diastolic compliance in HF.
Abstract 13405: Genetic Deletion of Stimulator of Interferon Genes Attenuates Atherogenesis in Apolipoprotein E-deficient Mice
Authors: Pham Phuong T , Fukuda Daiju , Sata Masataka
Published: May 2021

Introduction:
Recent studies show the contribution of innate immunity system to the pathogenesis of inflammatory diseases, including atherosclerosis. Stimulation of interferon genes (STING), originally known as a cytosolic DNA sensor, recognizes cytosolic DNA fragments, activating innate immunity. Here, we investigated whether STING contributes to the development of vascular inflammation and atherogenesis in apolipoprotein E-deficient (Apoe
–/–
) mice.

Methods and Results:
The expression of STING increased in the atherosclerotic aorta in both gene and protein expression levels. STING-deficient Apoe
–/–
(STING
–/–
Apoe
–/–
) mice reduced atherosclerotic lesions in the aortic arch (
P
<0.05), along with the reduction of lipid and macrophage accumulation in atherosclerotic plaques (
P
<0.05, respectively), and inflammatory molecule expression in the aorta compared with those in Apoe
–/–
mice after 20 weeks on a western-type diet. Also, pharmacologic blockade of STING in Apoe
–/–
mice for 12 weeks treatment attenuated atherogenesis in the aortic arch (
P
<0.05), reduced the accumulation of lipid in atherosclerotic plaques (
P
<0.05) with no alteration of metabolic parameters. Restoration of STING in bone marrow in STING
–/–
Apoe
–/–
mice promoted atherogenesis (
P
<0.05), lipid deposition (
P
<0.05), and vascular inflammation. cGAMP, a specific STING agonist, or mitochondrial DNA extracted from macrophages promoted expression of inflammatory molecules more effectively in Apoe
-/-
macrophages than in STING
–/–
Apoe
–/–
macrophages, while C-176, a specific STING inhibitor, attenuated these inflammatory responses. The results of western blotting showed the involvement of NF-κB and IRF-3 signaling in STING-associated vascular inflammation and macrophage activation. Furthermore, in humans, STING expression was confirmed in atherosclerotic lesions in the carotid artery.

Conclusion:
STING signaling activates macrophages, promotes vascular inflammation and atherosclerosis in Apoe
-/-
mice. Our results suggest that STING may serve as a potential therapeutic target for atherosclerosis.