bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13702: A Novel Genetic Risk Score Predicts Ischemic Stroke in Patients With Cardiometabolic Disease
Authors: Patel Parth N , Marston Nicholas A , Kamanu Frederick K , Weng Lu Chen , Bonaca Marc P , Giugliano Robert P , Scirica Benjamin M , O'Donoghue Michelle L , Cannon Christopher P , ANDERSON Christopher D , Bhatt Deepak L , Steg Philippe G , Cohen Marc , Storey Robert F , Sever Peter S , Keech Anthony C , RAZ Itamar , Mosenzon ofri , Braunwald Eugene , Ellinor Patrick T , Lubitz Steven A , Sabatine Marc S , Ruff Christian T
Published: November 2020

Introduction:
Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for first ischemic stroke after accounting for traditional risk factors in four clinical trials across the spectrum of cardiometabolic disease.

Methods:
Subjects who had consented for genetic testing, were of European ancestry, and had no prior history of stroke from the SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, and FOURIER trials were included in this analysis. A recently validated GRS composed of 36 SNPs associated with ischemic stroke was calculated in each patient. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for age, sex, ancestry, hypertension, hyperlipidemia, smoking, diabetes mellitus, atrial fibrillation, coronary artery disease, and congestive heart failure.

Results:
In 23,089 subjects across the four trials, a total of 313 ischemic strokes occurred over a median follow-up of 3 years. Those with higher genetic risk were at significantly increased risk for ischemic stroke with an adjusted HR per 1-SD GRS of 1.12 (1.004-1.25; p=0.043). Individuals in the top 10% of genetic risk had a 42% greater hazard for ischemic stroke than those in the lower 90% of genetic risk (adjusted HR 1.42 [1.03-1.97]; p=0.034). The magnitude of risk conferred by high genetic risk was similar or greater than the risk provided by well-established clinical risk factors (Figure).

Conclusions:
Across four large clinical trials of subjects with cardiometabolic disease, a 36-SNP GRS was a strong, independent predictor of first ischemic stroke. The risk of stroke was particularly high in patients in the top 10% of genetic risk.
Abstract 13711: Coronary Artery Calcium, Ankle-brachial Index, High Sensitivity C-reactive Protein, and a Family History of Coronary Artery Disease as Predictors of Incident Cardiovascular Events at Different Stages of Hypertension: The Multi-ethnic Study of Atherosclerosis
Authors: Kanneganti Radha , Dardari Zeina , Blumenthal Roger S , Blankstein Ron , Agatston Arthur S , Budoff Matthew J , Watson Karol E , Burke Gregory , Michos Erin D , Nasir Khurram , Blaha Michael J , Tota-Maharaj Rajesh
Published: November 2020

Background:
Coronary artery calcium (CAC), ankle-brachial index (ABI), high-sensitivity CRP (hsCRP), and family history (FHx) of coronary artery disease (CAD) are used as complementary aids in cardiac risk stratification. The 2017 ACC/AHA hypertension guideline’s new Stage I hypertension group has created uncertainty regarding intensity of blood pressure (BP) treatment in this group. We evaluated the comparative utility of CAC, ABI, hsCRP and FHx CAD as risk predictors of cardiovascular (CVD) events within different BP strata.

Methods:
The MESA cohort was followed for a median of 13 years with regards to incident coronary heart disease (CHD) and CVD events. BP was categorized per ACC/AHA guideline: normal- <120/<80, elevated 120-129/<80, stage I 130-139/80-89, and stage II ≥140/≥90. Participants on BP medications were assigned stage II. Cox regression was used to compare prediction of CHD and CVD events by CAC>300, CAC>75
t
h
%, ABI<0.9, hsCRP>2 mg/L and FHx CAD, stratifying by BP groups after adjusting for demographics, CVD risk factors and use of BP and cholesterol medications.

Results:
Of 6268 persons, 539 incident CHD events and 572 incident CVD events were noted. CAC>300 and CAC>75
th
% predicted an increased CHD event risk throughout all BP groups. ABI<0.9 was predictive of CHD events in stage I and II, while hsCRP was not predictive in any group. CAC>300 predicted a 2-fold increased CVD risk in all BP groups after adjustment. In the Stage I group, CAC>300, CAC>75
th
% and ABI<0.9 showed additive predictive value in incident CHD and CVD events. Using the adjusted model to predict CHD survival, CAC>300 had a consistently higher C-statistic throughout all BP categories compared to other risk markers.

Conclusion:
CAC>300 was associated with increased CHD and CVD risk in all BP groups and demonstrated superior prognostic utility compared to other risk markers. CAC>300, CAC>75
th
% and ABI<0.9 showed potential as risk modifiers in the new Stage I hypertension group.
Abstract 13715: Pathophysiological Role of Dexmedetomidine for Monocrotaline-induced Pulmonary Arterial Hypertension in Rats
Authors: Yamaguchi Yohei , Hosokawa Susumu , Kajikawa Yusuke , Maejima Yasuhiro , Isobe Mitsuaki , Furukawa Tetsushi , Doi Shozaburo
Published: November 2020

Introduction:
The abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs) is one of pathological characteristics of pulmonary arterial hypertension (PAH). Inflammation is thought to play an important role for PASMCs proliferation in PAH. Dexmedetomidine (DEX) is a selective α2-adrenergic receptor agonist that is used as a sedative in clinical settings. It has been reported that DEX regulates certain inflammatory responses.

Hypothesis:
DEX ameliorates Monocrotaline (MCT)-induced PAH in rats through its anti-inflammatory effect.

Methods:
In vivo, 6-week-old male Sprague-Dawley rats were injected 60 mg/kg of MCT subcutaneously. At day 14 after MCT injection, continuous infusions of DEX (2μg/kg/hour) by osmotic pumps were started in one group (MCT + DEX group), and not in another group (MCT group). We performed cardiac catheterization to measure right ventricular systolic pressure (RVSP) and prepared rats paraffin embedded lung tissues for Immunohistochemistry at day 23. In vitro, we analyzed the effect of DEX on human PASMCs (hPASMCs) proliferation stimulated with fibroblast growth factor 2 (FGF2). In addition, we examined mRNA levels of proinflammatory cytokines in hPASMCs by FGF2 stimuation with/without DEX.

Results:
Both RVSP and survival rate markedly improved in MCT + DEX group compared with those in MCT group (RVSP; 34mmHg ± 4mmHg vs. 70mmHg ± 10mmHg, survival rate 42% vs. 0% at day 29). In histological analysis, medial hypertrophy of pulmonary arterioles and phosphorylated-p65 positive PASMCs significantly reduced in MCT + DEX group. DEX also inhibited hPASMCs proliferation dose dependently. Furthermore, IL-6 mRNA expression was suppressed by DEX in hPASMCs stimulated with FGF2.

Conclusions:
DEX improved MCT-induced PAH in rats by suppressing PASMCs proliferation through the anti-inflammatory effect, which may result from inhibition of NF-κB activation induced by IL-6. DEX can be a new therapeutic tool for PAH.
Abstract 13730: Electrical Axes of P and T but Not QRS Waves on ECG Are New Indicators of Successfulness of the Nuss Operation for Pectus Excavatum Considering Anatomical Severity as Indicated by the Haller Index Acquired by CT
Authors: FUNABASHI Nobusada , Kobayashi Yoshio
Published: November 2020

Introduction:
Pectus excavatum (PEX) is a depression of the sternum which can physically constrict the heart and cause abnormal ECGs. The Nuss operation is a minimally invasive technique for PEX repair.

Hypothesis:
As right (RA) and left atria (LA) are compressed in PEX, axes of P, QRS, and T waves are abnormal and the Nuss operation normalizes them. We also took the Haller index (HI) into to account.

Methods:
17 PEX patients (14 male, 12±6 years) underwent CT and ECG before and after the Nuss operation.

Results:
All Nuss operations were successful, and HI was significantly improved from 5.62±2.29 to 3.29±0.65 (P=0.0002). There were no significant differences before and after surgery for electrical axes of P waves (46±20 vs 65±55, P=0.20), and QRS waves (75±33 vs 76±23, P=0.72), but T waves were greater thereafter (22±27 vs 40±19, P=0.001). Correlation coefficients (CC) between the degree of axes of P, QRS and T waves, and HI before operation were -0.23, -0.06, and 0.11, respectively. These values after operation were -0.25, -0.06, and 0.19, respectively. As HI is an indirect indicator of heart compression, we evaluated the degree of RA and LA compression qualitatively as none, mild, and moderate/more. Of 17 patients, 5 had moderate/more compression of RA and/or LA by PEX (group 1); the remaining 12 did not show compression (group 2). Only P wave values were significantly smaller in group 1 than 2 before surgery, but these differences disappeared after surgery. In both groups, degree of axes of T waves was significantly greater after the operation.

Conclusion:
In patients with PEX, axes of T waves after the Nuss operation became significant greater than before the operation in patients with moderate or more compression of RA and/or LA by PEX. For P waves, this was smaller before the operation in those with compression but this was improved by the Nuss operation. P and T wave axes but not QRS could be therefore non-invasive indicators of Nuss operation success in addition to gross PEX appearance.
Abstract 13740: Validation of Paris Risk Score to Predict Long-term Bleeding Events After Percutaneous Coronary Intervention in Japanese Population
Authors: Shimizu Takeshi , Ando Takuya , Akama Joh , Anzai Fumiya , Muto Yuki , KIMISHIMA Yusuke , Kiko Takatoyo , YOSHIHISA Akiomi , Yamaki Takayoshi , Kunii Hiroyuki , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: November 2020

Introduction:
It has been reported that East Asian people have higher bleeding risks than Western people. The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) bleeding risk score was developed to estimate the bleeding risk after percutaneous coronary intervention (PCI). However, the utility of PARIS bleeding score for predicting long-term bleeding risks has not been validated in Japanese population.

Methods:
Consecutive 1061 patients who underwent PCI and survived to discharge were divided into three groups based on the category of PARIS bleeding risk score: low risk group (0-3 risk points), intermediate risk group (4-7 risk points) and high risk group (8-15 risk points), then we compared patient characteristics and followed bleeding events.

Results:
The numbers of patients at low, intermediate and high risk groups were 113 (10.7%), 420 (39.6%) and 528 (49.8%), respectively. Clinical characteristics for three groups were as follows: atrial fibrillation (low, intermediate and high risk groups; 8.2%, 8.9% and 21.6%, P < 0.001, respectively), peripheral artery disease (3.1%, 9.1% and 22.1%, P < 0.001), coronary multi-vessel disease (38.9%, 44.3% and 54.4%, P = 0.001), use of statin (97.3%, 89.6% and 71.7%, P < 0.001) and proton-pump inhibitors (69.1%, 72.5%, and 78.9%, P = 0.02). Among 1061 patients, a total of 74 bleeding events were occurred during the follow-up period (mean of 1742 days). In the Kaplan-Meier analysis, the cumulative incidence of bleeding events significantly increased from low risk group to intermediate and high risk group (P < 0.001). The risk score showed a significant prognostic value in predicting bleeding events (area under the receiver operating characteristic curve, 0.674; 95% confidence interval, 0.615-0.733).

Conclusions:
The PARIS bleeding risk score successfully stratified the long-term bleeding risk in patients with coronary artery disease after PCI in Japanese population.
Abstract 13747: Investigation of the Probability of Spontaneous Conversion From Atrial Fibrillation to Sinus Rhythm Utilizing Continuous Rhythm Monitoring
Authors: Ziegler Paul D , Charitos Efstratios I
Published: November 2020

Introduction:
Atrial fibrillation (AF) recurrence or spontaneous conversion to sinus rhythm (SR) are regarded as random events.

Hypothesis:
We hypothesized that the probability of spontaneous conversion to SR decreases as more time is spent in AF. We attempt to quantify this phenomenon and investigate factors that can affect this probability.

Methods:
Cardiac rhythm histories of 1195 patients (age 73.0 ± 10.1, follow-up: 349 ± 40 days; 14533 AF episodes) with implantable devices were reconstructed and analyzed. No patients received cardioversion, AF ablation, or any obvious AF therapies during follow-up. Patients with no AF recurrence or continuous AF during follow up were excluded. Hierarchical regression methods were employed to investigate the time course of the probability of rhythm change and factors that influence it.

Results:
Probabilities of spontaneous conversion from AF to SR (solid blue line) and recurrence of AF in patients with SR (solid red line) are shown in the Figure. For patients in AF , spontaneous conversion probability significantly decreases with time spent in AF and plateaus after ~7 days (dotted blue line). Similarly for patients in SR, increasing time in SR reduces the probability of developing AF (solid red line) and plateaus after ~7 days (dotted red line). Patient age (p<0.001), LVEF (p<0.05) and presence of coronary artery disease (p<0.01) significantly influence the spontaneous conversion probabilities independent from AF burden.

Conclusions:
Spontaneous SR conversion or AF recurrence diminishes with increasing time spent in AF or SR, respectively, and are influenced by several patient-related factors. These findings suggest that patients should be closely monitored after AF recurrence or SR conversion.
Abstract 13753: Early and Late Outcomes of Ambulatory Counter Pulsation Device: Novel Intravascular Ventricular Assist Device vs Conventional Axillary Intra-aortic Balloon Pump
Authors: Nishida Hidefumi , Koda Yojiro , Song Tae , Onsager David , Nguyen Ann , Grinstein Jonathan , Bow Chung , Smith Bryan , Kalantari Sara , Sarswat Nitasha , Kim Gene , Jeevanandam Valluvan , Ota Takeyoshi
Published: November 2020

Introduction:
Intravascular ventricular assist device (iVAS; NuPulse CV, North Carolina, USA) is a newly developed ambulatory and portable counter pulsation heart assist system.

Hypothesis:
Early and late clinical outcomes of iVAS is comparable to those of conventional axillary intra-aortic balloon pump (IABP) as a bridge to heart transplantation(BTT).

Methods:
Between April 2016 and January 2020, 33 patients underwent iVAS implantation (Group A) and 69 patients underwent axillary IABP (Group B) as a BTT. We reviewed perioperative data and late clinical outcomes including survival. Long-term survival was assessed with the Kaplan-Meier analysis.

Results:
The patients in Group A was significantly older than Group B (A: 58.8±8.1 vs B: 53.3±14.7 p=0.048). The use of inotropes at the time of device implantation was similar between two groups (A:22/33(66.7%) vs B: 47/69(68.1%), p=0.88). Almost all patients were able to ambulate and participate in physical therapy (A:100% vs B:97.1%, p=0.21). The duration of device support in Group A was significantly longer than Group B (A:83.3±93.7 vs B:19.0±13.3 days, p <0.01). After a FDA approval, eleven patients (44%) in Group A was able to be discharged with an iVAS. While waiting for transplantation, 3 patients expired in Group A and none in Group B. Two patients in Group A required an escalation of support (ECMO N=1, LVAD N=1) and 1 patients in Group B (percutaneous LVAD N=1). Balloon exchange due to device related complications was required less frequently in Group A compared to Group B (A: 2/33, 6.1% vs B: 20/69, 29.0% p <0.01). Adverse events during balloon exchange included aortic rupture (N=1) and type A aortic dissection (N=1) (all in Group B). The success rate of BTT was not significantly different between groups (A:27/32(84.4%), B: 64/68(94.1%),p=0.13). The long-term survival after heart transplantation did not differ between the groups (A: 78.1% at 3 years vs B: 83.8% at 3 years, log-rank=0.07).

Conclusions:
Both iVAS and conventional axillary IABP showed comparable long-term survival and decent success rates of BTT. The iVAS featured with the portable mechanism might be a promising option as a BTT.
Abstract 14066:
O
-GlcNAc Levels Stimulation is a New Potential Therapeutic Strategy at the Early Phase of Septic Shock in the Young
Authors: DUPAS Thomas , DENIS Manon , Dontaine Justine , Bultot Laurent , Persello Antoine , Erraud Angelique , Bigot Edith , Vertommen Didier , Lebreton Jacques , tessier Arnaud , De Waard Michel , Gauthier Chantal , Bertrand Luc , Rozec Bertrand R , Lauzier Benjamin
Published: November 2020

Background:
We have shown that increase in
O
-GlcNAc levels, a post-translational modification involved in the stress response, at the early phase of septic shock in adult (84 days old rats) is a potential new therapeutic strategy. Most studies focus in adults while the population most affected by septic shock, young children, is rarely studied. Considering that
O-
GlcNAc levels are higher in the young, the impact of
O-
GlcNAc on septic shock in the young should be tested.
Purpose:
Evaluate if
O-
GlcNAc stimulation could improve sepsis outcomes in young.

Methods:
Endotoxemic shock was induced in 28 days old rats with an
i.v.
injection of saline (CTRL, n=10) or LPS (O111:B4, 20mg.kg
-1
- LPS, n=9). 1 hour after LPS rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10ml.kg
-1
- LPS+R, n=10) ± NButGT (10 mg.kg
-1
- NButGT, n=11) to increase
O-
GlcNAc levels. 2 hours later, physiological functions and markers of severity were measured and used in adapted Pediatric RISk of Mortality score (PRISM score). The impact of treatment on survival was evaluated on n=16 per group. Mass spectrometry (MS) study was performed to identify
O
-GlcNAcylated proteins.

Results:
LPS induce a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1; mmHg; p<0.05), alter biological parameters (lactates: CTRL: 3.92 ± 0.26; LPS: 6.42 ± 0.45; mmol.l
-1
; pH: CTRL: 7.27 ± 0.02; LPS: 7.15 ± 0.02; p<0.05), PRISM score (p<0.05) and is associated with multi organs dysfunction (troponin T: CTRL: 19.7 ± 4.0; LPS: 45.4 ± 11.4; ng.l
-1
; creatinine: CTRL: 15.9 ± 1.5; LPS: 25.3 ± 2.6; μmol.l
-1
; p<0.05). LPS+R has no beneficial effect while NButGT improves MAP (p<0.05), PRISM score (p<0.05) and the median survival (NButGT: 36.0; LPS+R: 13.65; hours; p<0.001) compared to LPS+R treatment. MS highlight important variations of
O-
GlcNAcylation particularly that of mitochondrial proteins.

Conclusions:
Despite higher
O-
GlcNAc levels, we demonstrate that
O-
GlcNAc stimulation is also a potential new therapeutic strategy for septic shock in young. Our results show that it is the difference between the basal levels and the post-stimulation levels which induces a protection against sepsis. Proteins identify by MS will need to be specifically studied to decipher their impact in septic shock.
Abstract 14085: Population Health Delivery: A Community Health Needs Assessment Related to Physical Activity and Exercise
Authors: Sundaram Kavin , Podhajsky Erica , Maher Lisa
Published: November 2020

Introduction:
A community health needs assessment asks members to measure the health of their community by prioritizing problems and identifying the needs.

Methods:
There are 10 counties in the Cedar Valley Area of Northeast Iowa, USA. Healthcare providers and allied service organizations came together as partners to write online survey to identify the community health needs of Cedar Valley residents. The online survey for residents was posted from March 1-May 15, 2019 and drew 1,554 unique responses. The online Survey Monkey for residents was supplemented by paper surveys distributed to and collected from members of minority church congregations. Responses were tabulated and analyzed. Once the initial responses arrived, the partners reached out to gather additional responses from minority populations to help match the overall return to the market profile. The resident survey was extended 45 days past its original deadline to ensure additional returns. This report focuses on physical inactivity and exercise part of the multi question survey.

Results:
For the question of risky adult behavior, 45% of the residents identified physical inactivity. For question of what healthy behaviors would you like to start or do more often to improve your health, 77% of the residents identified more exercise. For the question of what prevents you from doing the healthy behavior, 63% identified lack of motivation, 61% identified not enough time. But only 5% said that they were not aware of the healthy options. For the question of what would help you or your family members to start or maintain a healthier lifestyle, 58% identified more affordable facilities, 36% identified employee wellness programs, 32% identified community exercise programs and 17% identified school wellness programs.

Conclusion:
These results indicate that there is clear awareness in this community that physical inactivity is a risky adult behavior and 95% of the population was aware of exercise as a healthy option. The results also identified specific perceived needs. To achieve high degree of physical activity and exercise and to maintain population health, more efforts need to be focused on wellness programs to improve the motivation and make available affordable facilities.
Abstract 14094: Gender Difference in Covid-19 Test Status and Disease Outcomes in Heart Failure Patients
Authors: Nedeltcheva Arlet V , Doukky Rami
Published: November 2020

Introduction:
Heart failure is a common health problem in older patients. As part of quality improvement study we analyzed the data of Heart failure patients admitted for COVID-19 infection in Cook County Health, Stroger Academic Hospital between March 19 and May 27, 2020.

Hypothesis:
1. To test if all patient admitted for Covid-19 will test positive. 2. To test if there is gender difference in the Heart failure patients affected by Covid-19 pandemic.

Methods:
Quality improvement clinical research.

Results:
For the period stated 74 patients with Heart failure were admitted for treatment of Covid-19 viral infection (31% female vs. 69% male), ages 29 to 88 (Mean 61+/-12).

From all Heart failure patients admitted for COVID-19 only 42% tested Covid-19 positive (19% female vs. 81% male).Table:1

From all Heart failure patients admitted (74) there were 3 deaths and they were in patients who tested positive for Covid-19. Their medical condition was complicated by severe comorbidity as HIV, multi-organ metastatic cancer, one patient had DNR/DNI status.

From the Heart failure patients admitted for Covid-19 symptoms 96% went home with improved health.

Conclusions:
Our analysis indicates that there is gender difference in magnitude Covid-19 virus affects Heart Failure patients and in their health outcome. This data may be used as base for individualized health care approach.
Abstract 14098: Comparisons of Advance Directive Attitudes, Perceived Susceptibility, and End-of-life Life-sustaining Treatment Preferences Between Patients With Heart Failure and Cancer Survivors and the Relationships
Authors: Heo Seongkum , Kim JinShil , Choi Jiin , Shin Mi-Seung , Kim Miyeong , Seo EunJu , An Minjeong , Shim Jae Lan
Published: November 2020

Introduction:
The needs for advanced care planning, including preferences to life-sustaining treatments (LSTs), in patients with heart failure (HF) are comparable to or higher than those in cancer survivors, but they had less access to such care than cancer survivors. Diagnostic context and patients’ attitudes and perceived susceptibility can impact preferences to LSTs, but there is limited evidence on these relationships.

Purpose:
To compare LST preferences, attitudes, and perceived susceptibility between patients with HF and cancer survivors, and to examine the associations of these variables with their preference for each LST (cardiopulmonary resuscitation [CPR], ventilation support, hemodialysis, and hospice care).

Methods:
Secondary data on LST preferences (the Korean-Advance Directive), attitudes toward advance directive (Advance Directive Attitude Survey), perceived susceptibility (Perceived Susceptibility subscale of the Advance Care Planning survey), and demographic characteristics were obtained from 36 outpatients with HF (mean age, 65.44 years; male, 69.4%) and 107 cancer survivors (mean age, 67.39 years; male, 32.7%). To compare LST preferences, attitudes, and perceived susceptibility between the wo diagnostic groups, chi-square test,
t
-test, and Wilcoxon rank sum test were used. To examine the relationships of diagnostic context, attitudes, and perceived susceptibility to preferences for each LST, controlling for sex, marital status, and educational level, multivariable logistic regression analyses were used.

Results:
More patients with HF preferred CPR than cancer survivors (41.7% and 15.9%,

χ
2

= 8.88,
P
= 0.003). Attitudes and perceived susceptibility were similar between the two diagnostic cohorts (
P
= .508 and
P
= .062, respectively). Patients with HF had greater odds of preferring CPR (odds ratio [OR] = 3.02, confidence interval [CI] = 1.19, 7.70) than cancer survivors. Patients with more positive attitudes had greater odds of preferring hospice care (OR = 1.14, CI = 1.06, 1.23).

Conclusions:
Diagnostic context and patients’ attitudes were associated with preferences for LSTs. Therefore, diagnostic context and improvement in attitudes need to be considered to facilitate informed decision-making for LSTs.
Abstract 14108: Does Primary Graft Dysfunction Increase First Year Intimal Thickness After Heart Transplantation?
Authors: Nishihara Keith , Azarbal Babak , Kransdorf Evan P , Benck Lillian , Patel Jignesh K , Kobashigawa Jon A
Published: November 2020

Introduction:
Primary graft dysfunction (PGD) has been reported in between 7-30% of heart transplant recipients with severe PGD known to have poor outcome. Due to graft dysfunction and potential for endothelial cell injury, it is not known whether all grades of PGD can increase first year intimal thickening, which may be a harbinger for clinical cardiac allograft vasculopathy (CAV).

Methods:
Between 2010 and 2017, we assessed 769 heart transplant patients and divided them into those patients with mild PGD (n=12), moderate PGD (n=35), severe PGD (n=36) and no PGD (n=686). Endpoints included 3-year survival and freedom from angiographic CAV (stenosis ≥30%) and non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, stroke); and 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), antibody mediated rejection (AMR). First year intravascular ultrasound (IVUS) was performed at baseline 4-8 weeks and at 1 year after transplant. IVUS parameters included first-year average change in MIT and change in MIT ≥0.5mm.

Results:
First year change in average MIT and MIT ≥0.5mm and 3-year freedom from CAV were not significantly different in all groups. The severe PGD group compared to all groups had significantly lower 3-year survival and freedom from NF-MACE. There was lower freedom from various types of rejection in the PGD groups compared to the no PGD group. Specifically, 1-year freedom from ACR was significantly lower in the mild PGD group compared to the moderate PGD group and the no PGD group (see table).

Conclusions:
PGD grades do not appear to lead to increased first year intimal thickening or angiographic CAV at 3 years. Lower freedom from ACR in the mild PGD group and ATR in the severe PGD group will need further study. Larger numbers of patients are needed to confirm these findings.
Abstract 14112: Apabetalone (RVX-208) Reduces ACE2 Expression in Human Cell Culture Systems, Which Could Attenuate SARS-CoV-2 Viral Entry
Authors: Gilham Dean , Fu Li , Tsujikawa Laura M , Rakai Brooke , Wasiak Sylwia , Stotz Stephanie , Sarsons Christopher , Sweeney Michael , JOHANSSON Jan , Wong Norman , Kulikowski Ewelina
Published: November 2020

Introduction:
Apabetalone is an orally available small molecule that affects gene transcription by inhibiting BET protein interactions with acetylated histones and transcription factors. Apabetalone is in late stage clinical development for the treatment of cardiovascular disease (CVD). Clinical trials show apabetalone is well tolerated and has a favorable safety profile. Recent evidence indicates this drug could be repurposed to treat COVID-19 by reducing expression of the angiotensin converting enzyme 2 (ACE2) receptor that is essential for SARS-CoV-2 viral entry and/or disrupting viral protein E interaction with BET proteins. The spike protein of SARS-CoV-2 engages with human ACE2 expressed in multiple organs such as lung, liver, kidney, heart and intestine to initiate infection in host cells. Ultimately, the infection leads to life threatening complications in COVID-19 patients.

Hypothesis:
Apabetalone downregulates ACE2 expression to protect human cells from SARS-CoV-2.

Methods:
Primary human kidney tubular epithelial cells (RPTEC) were stimulated with TNFα and co-treated with apabetalone overnight. Primary human hepatocytes (PHH) and the hepatoma cell line, HepG2, were treated up to 96 h with apabetalone or other BET inhibitors (BETi). Gene expression was analyzed by microarray or RT-PCR. Human aortic endothelial cells (HAEC) were pretreated with apabetalone for 1 h followed by TNFα stimulation for another 1h. Chromatin occupancy of the BET protein BRD4 was examined by ChIP-seq.

Results:
In RPTEC, 5μM apabetalone downregulated ACE2 mRNA by 50%. Apabetalone dose dependently reduced ACE2 gene expression in HepG2 or PHH from 3 independent donors by up to 90%. JQ1 is a pan BET inhibitor, whereas MZ1 promotes BET protein degradation. Both JQ1 and MZ1 treatments downregulated ACE2 in liver cells, indicating an on target BETi effect. In HAEC, apabetalone abolished BRD4 occupancy at an enhancer in proximity to the ACE2 gene.

Conclusions:
Apabetalone reduces ACE2 gene expression in multiple human cell types. ACE2 expression may be regulated by adjacent BRD4 enhancer occupancy. The impact of apabetalone on SARS-CoV-2 life cycle is under investigation. The results will provide mechanistic support for potential COVID-19 clinical trials.
Abstract 14115: A Multimorbidity-based, Risk-stratified Reanalysis of the Affirm Trial
Authors: Ruzieh Mohammed , Mandrola John , Dyer Anne Marie , Chinchilli Vernon M , Naccarelli Gerald V , Foy Andrew J
Published: November 2020

Introduction:
Multimorbidity is common in patients with cardiovascular disease. Clinical trials in cardiovascular medicine mostly enroll patients who are younger, healthier and more affluent than average patients with the condition of interest. These trials rarely account for patient-level multimorbidity in a systematic fashion. Further, treatment effect heterogeneity is usually tested across subgroups of patients based on the presence or absence of individual variables, not on the basis of summative risk scores which account for multimorbidity.

Objectives:
To describe the distribution of multimorbidity using a modified version of the Charleson comorbidity index (mCCI), scale 0-14, and to assess its impact on the original primary endpoint of all-cause mortality.

Methods:
We performed a multimorbidity-based risk-stratified reanalysis of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Trial. To do this, we created a mCCI risk score based on inclusion of patient clinical parameters documented at the time of trial enrollment. The variables included in our score are: Age, ischemic heart disease, heart failure, symptomatic bradycardia, stroke or TIA, peripheral vascular disease, diabetes, hepatic or renal disease, pulmonary disease, and polypharmacy.

Results:
We found that the majority of patients in the AFFIRM Trial had a mCCI score of ≤4 (55.5%) and there was no statistically significant difference in the risk of death for rate vs rhythm control in these patients (7.9% vs 8.8%;
p=0.44
). However, for patients with a mCCI ≥5 (44.5%), there was a strong trend toward a reduction in death with rate control that nearly reached statistical significance despite being underpowered (24.5% vs 28.3%;
p=0.07
), figure.

Conclusion:
This proof-of-concept study supports the idea that clinical trials in cardiovascular medicine should systematically assess for multimorbidity and investigate its potential impact on treatment effects.
Abstract 14117: Clinical Characteristics and Cardiovascular Outcomes in Childhood-Onset Hypertrophic Cardiomyopathy
Authors: Marston Nicholas A , Han Larry , olivotto iacopo , Day Sharlene , Ashley Euan A , Michels Michelle , Pereira Alexandre D , Ingles Jodie , Semsarian Christopher , Jacoby Daniel L , Colan Steven D , Joseph Rossano , Wittekind Samuel , Ware James S , Saberi Sara , Helms Adam S , Mital Seema , Ho Carolyn
Published: November 2020

Introduction:
The prevalence of childhood-onset hypertrophic cardiomyopathy (HCM) is lower than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM.

Methods:
We performed an observational cohort study of 6345 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe) and Toronto's SickKids hospital. HCM patients were stratified by age at diagnosis (<1 year (infancy), 1-18 years (childhood), >18 years (adulthood)) and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death.

Results:
Based on defined age of diagnosis stratification, 173 (3%) patients were diagnosed in infancy, 909 (14%) in childhood, and 5263 (83%) in adulthood. Childhood-onset HCM patients had a 2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following diagnosis, and HF and AF more common by the end of the 2nd decade (
Fig, a
). Sarcomeric HCM was more common in childhood-onset HCM (62%) and carried a worse prognosis than non-sarcomeric disease, including a >2-fold increased risk of HF (HR

adj

2.39 [1.36-4.20], p=0.003) and 67% increased risk of overall composite events (HR

adj

1.67 [1.16-2.41], p=0.006). When compared to adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias (HR

adj

1.36 [1.03-1.80]) and twice as likely to require transplant or ventricular assist device (HR

adj

1.99 [1.23-3.23]) (
Fig, b
).

Conclusion:
Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into disease biology and can help improve the precision of risk prediction.
Abstract 14143: Percutaneous Coronary Intervention in Very Elderly Patients With Prior Coronary Artery Bypass Grafts Presenting With Acute Myocardial Infarction
Authors: Phan Derek Q , ROSTOMIAN Ara , Lee Mingsum , moore naing a , mansukhani prakash , aharonian vicken , Brar Somjot S , Zadegan Ray
Published: November 2020

Introduction:
There is limited data on the benefits of percutaneous coronary intervention (PCI) in very elderly patients with prior coronary artery bypass grafts (CABG). Therefore, we sought to evaluate the outcomes of PCI versus medical therapy alone in very elderly patients with prior CABG who present with acute myocardial infarction (AMI).

Methods:
Retrospective study of patients ≥ 80 years old with prior CABG who underwent invasive coronary angiography for AMI at Kaiser Permanente Los Angeles Medical Center between June 2009 and February 2019. Patients were treated with PCI or medical therapy alone. Inverse Probability Treatment of Weighting (IPTW) was used to balance baseline characteristics between treatment groups and cox proportional hazard regression analysis was utilized. Outcomes evaluated were all-cause mortality and non-fatal MI.

Results:
There were 347 patients (average age 83.6±3.2 years, 18% female) analyzed. Of these 167 (48%) underwent PCI. Compared to medical therapy alone, the PCI group was more likely to have left main disease (15% vs 2.8%, p<0.01) and higher ejection fraction (48.0± vs 44.4± %, p=0.02); but less likely to have history of atrial fibrillation (31.7% vs 45.6%, p<0.01). To adjust for significant differences between groups, IPTW was utilized to balance covariates (all p>0.05). At a median follow-up of 27.6 months (interquartile range 9.7-52 months), there were no significant differences in all-cause mortality (Hazard Ratio [HR] 0.93, 95% Confidence Interval [CI] 0.88-1.32, p=0.5), and non-fatal MI (HR 0.95, 95% CI 0.72-1.26, p=0.7).

Conclusion:
PCI did not improve clinical outcomes over medical therapy alone in very elderly patients ≥ 80 years of age with prior CABG presenting with AMI. Further studies are needed to delineate the role of PCI in this high-risk unique population.
Abstract 14147: Vascular Complication of Distal Transradial Approach in Patients With Acute Myocardial Infarction
Authors: Yamada Takeshi , Matsubara Yuki , Washimi Soichiro , Hashimoto Sho , Taniguchi Norimasa , Nakajima Shunsuke , Hata Tetsuya , Takahashi Akihiko
Published: November 2020

Background:
The distal transradial approach (dTRA) for coronary catheterisation is a newly introduced alternative to the conventional transradial approach. This study investigated the incidence of vascular complication of the dTRA in patients with acute myocardial infarction (AMI) who underwent primary percutaneous coronary intervention (PCI).

Methods:
Consecutive 131 patients with AMI who underwent primary PCI between April 2018 and October 2019 were investigated. The dTRA was used as the primary approach whenever feasible in this study period. The bleeding complication after dTRA and the patency of the radial artery were investigated. The patency of the radial artery was examined using Doppler ultrasound in follow-up period.

Results:
Among the 131 AMI patients, 116 patients (88.5%) underwent successful primary PCI using the dTRA. The patients included 83 men (71.6%), and the mean age was 70.4 ± 12.9 years. A 5- or 6-French sheath (conventional or slender) was used in the primary procedure. The average time to achieving hemostasis was 5.0 ± 4.1 hours; TIMI minor bleeding was observed in 2 patients (1.5%) and there were no TIMI major bleeding. Color Doppler sonography of the radial artery was performed in 94 patients with the mean follow-up period of 273 ± 183 days, and the incidence of radial artery occlusion (RAO) was 1.1% (n=1).

Conclusions:
The application of dTRA is considered to have low incidences of bleeding complication and radial artery occlusion in the patients with AMI.
Abstract 14158: Ankle-brachial Index and Risk of Severe Ischemic Leg Outcomes in a Community-based Population: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Paskiewicz Amy , Wang Frances , Yang Chao , Ballew Shoshana , Kalbaugh Corey , Selvin Elizabeth , Salameh Maya , HEISS Gerardo M , Coresh Josef , Matsushita Kunihiro
Published: November 2020

Introduction:
Ankle-brachial index (ABI) ≤ 0.9 is used to define lower-extremity peripheral artery disease (PAD). However, the association between ABI and severe ischemic leg outcomes in the general population has not been investigated.

Hypothesis:
Lower ABI is independently associated with risk of severe ischemic leg outcomes.

Methods:
We studied 13,742 ARIC participants (median age 54 [SD 5.75] years, 45% males) without intermittent claudication or a history of revascularization for PAD at baseline (1987-89). We quantified the association of ABI with risk of severe ischemic leg outcomes using Cox regression. ABI was modeled as a restricted cubic spline allowing for potentially non-linear associations. Severe ischemic leg outcomes were ascertained through ICD codes and included critical limb ischemia (CLI) (defined as PAD with rest pain or tissue loss) and ischemic leg amputation (amputations with PAD diagnosis).

Results:
Over a median of 28 years of follow-up, there were 221 and 129 events of CLI and ischemic leg amputation, respectively. Lower ABI was linearly associated with both CLI and ischemic leg amputation (Figure). With ABI 1.25 as the reference, adjusted hazard ratios of CLI were 2.48 (95% CI 1.15-5.36) at ABI 0.7, 1.97 (1.30-2.99) at ABI 0.9, and 1.73 (1.18-2.54) at ABI 1.0. The corresponding hazard ratios of ischemic leg amputation were 3.57 (1.44-8.81), 2.63 (1.54-4.48), and 2.23 (1.34-3.70), respectively. The association was largely consistent in demographic and clinical subgroups, although the results were less evident in younger and female participants compared to their counterparts.

Conclusions:
In middle-aged adults without clinical PAD, lower ABI was independently and linearly associated with higher risk of severe ischemic leg outcomes. Our results support the value of ABI as an indicator for leg vascular condition and also indicate that ABI 0.9-1.1 should not be considered normal for ischemic leg prognosis.
Abstract 14177: Low Cholesterol Level Was a Risk for Stroke or Systemic Embolism in Elderly Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: Iguchi Moritake , Masunaga Nobutoyo , ISHII MITSURU , An Yoshimori , Ide Yuya , Fujino Akiko , Hamatani Yasuhiro , DOI KOSUKE , Ikeda Syuhei , Ishigami Kenjiro , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Ogawa Hisashi , Abe Mitsuru , Akao Masaharu
Published: November 2020

Introduction:
Hyperlipidemia is a well-established risk factor for cardiovascular disease. However, low cholesterol is also reported to be associated with poor outcome in chronic disease, which is called “cholesterol paradox”, and the impact of cholesterol level on the incidence of stroke or systemic embolism (SE) in atrial fibrillation (AF) remains unclear.

Methods:
The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. We obtained baseline total cholesterol level (TC) in 3,051 patients, and examined the relationship between TC and incidence of stroke/SE.

Results:
TC was inversely correlated with age and positively correlated with body weight. Patients with lower TC were more likely to be male, and had more diabetes, coronary artery disease, heart failure, prior stroke/SE, chronic kidney disease, and anemia. CHA
2
DS
2
-VASc score was inversely correlated with TC. Prescription of statin was higher in patients with lower TC, but that of oral anti-coagulants was not associated with TC. During the median follow-up of 1,476 days, stroke/SE occurred in 277 (9.1%) patients. After adjustment for the components of CHA
2
DS
2
-VASc score, body weight, and prescription of oral anti-coagulants and statins, TC had significant inverse association with the incidence of stroke/SE (hazard ratio (HR), 0.94; 95% confidence interval (CI) 0.91-0.98 for 10-mg/dl increase) (Table). TC was significantly associated with ischemic stroke/SE (HR, 0.95; 95% CI 0.91-0.99 for 10-mg/dl increase), but was not associated with intracranial bleeding (HR, 0.95; 95% CI 0.88-1.02 for 10-mg/dl increase). When we divided the patients into the elderly (≥75 years) and the young, low TC was a predictor for stroke/SE in the elderly (HR, 0.94; 95% CI 0.90-0.99 for 10-mg/dl increase), but was not in the young (HR, 0.95; 95% CI 0.90-1.01 for 10-mg/dl increase).

Conclusions:
Low TC might be an independent predictor for stroke/SE in elderly patients with AF.
Abstract 14191: Effect of Intensive Blood Pressure Lowering on Incident Atrial Fibrillation: A Systemic Review and Meta-analysis
Authors: Singleton Matthew J , Chen Lin , Whalen Sean P , Bhave Prashant , Beaty Elijah , Yeboah Joseph , Soliman Elsayed Z
Published: November 2020

Introduction:
The effect of intensive versus standard blood pressure (BP) lowering on the risk of atrial fibrillation (AF) is uncertain.

Hypothesis:
Intensive BP lowering is associated with a lower risk of AF among patients with hypertension.

Methods:
We searched PubMed, EMBASE, and CENTRAL for trials published between inception and June 5, 2020 for randomized controlled trials evaluating the effect of intensive versus standard (target systolic BP < 140 mmHg) BP lowering on incident AF. We assessed heterogeneity using the

I
2

statistic then used fixed-effects meta-analysis models to report pooled treatment effects and 95% confidence intervals. We also tested for publication bias by three funnel plot-based methods. The quality of each study was assessed with the Cochrane Risk of Bias tool.

Results:
We assessed 16 candidate studies for eligibility from 2,312 published articles, but only three randomized clinical trials were eligible for inclusion and included a combined 12,219 participants with hypertension: Cardio-Sis (Studio Italiano Sugli Effetti Cardiovascolari del Controllo della Pressione Arteriosa Sistolica), ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial), and SPRINT (Systolic Blood Pressure Intervention Trial). The target systolic BP in the intensive BP arm was <120 mmHg for participants in SPRINT and ACCORD-BP, but <130 mmHg for participants in Cardio-Sis. Participants randomized to intensive BP lowering had significantly lower risk of incident AF compared with those randomized tostandard BP lowering (AF incidence 2.2% vs. 3.0%, respectively; pooled hazard ratio (95% confidence interval ): 0.74 (0.59 - 0.93)).

Conclusions:
Intensive BP lowering is associated with a significantly lower risk of incident AF in patients with hypertension. These findings add to the current evidence supporting the benefits of intensive BP control.