bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 24071: A Peptide Of The Amino-terminus Of Grk2 Induces Hypertrophy And Yet Elicits Cardioprotection After Pressure Overload.
Authors: Schumacher Sarah M , Gao Erhe , Chuprun J Kurt , Koch Walter J
Published: March 2022

Heart failure (HF) is a leading cause of death worldwide and a growing burden on public health, and the underlying mechanisms of cardiac remodeling and decompensation to HF remain a focus of research efforts towards therapeutic development. Signaling via G protein-coupled receptors (GPCRs) is critical for normal heart function and is tightly controlled by GPCR kinases (GRKs) with GRK2 (originally βARK1), being intimately involved in HF progression. In addition to its well-characterized role in regulating GPCRs, ongoing research has demonstrated great diversity in the functional roles of GRK2. I have recently investigated GRK2 amino terminal binding interactions through the generation of transgenic (Tg) mice with cardiac-targeted expression of the amino-terminal peptide βARKnt (residues 50-145). In a murine model of trans-aortic constriction (TAC)-induced pressure overload, echocardiography revealed increased left ventricular (LV) posterior wall thickness (1.57 versus 1.37 ± 0.02; n = 16) and LV mass in TgβARKnt compared to non-transgenic littermate controls (NLC) 4 weeks after TAC or Sham surgery. Interestingly, despite enhanced hypertrophy at baseline and after acute pressure overload, the progression to HF was paradoxically inhibited in TgβARKnt mice during chronic pressure overload with preserved cardiac function (% Ejection Fraction 57.3 versus 37.3 ± 2.0; n = 11, 10). Further, βARKnt expression limited adverse left ventricular remodeling, with reduced interstitial fibrosis (% area fibrosis 4.1 versus 9.2 ± 0.8; n = 11, 9 hearts) and preserved β-adrenergic receptor density 4 weeks after surgery. The effect of cardiac βARKnt expression was not consistent with alterations in GRK2 activity at GPCRs as neither GRK2 peptide inhibition (TgβARKct) nor GRK2 overexpression alter hypertrophy, and overexpression hastens HF development. Further, TgβARKnt mice exhibit reduced epididymal white adipose content and altered mitochondrial respiration, suggesting altered cardiac metabolism. These data support the idea that the βARKnt peptide embodies a distinct functional interaction and that βARKnt-mediated regulation of β-adrenergic receptor density may provide a novel means of cardioprotection during pressure-overload induced HF.
Abstract 10001: The Systemic Inflammation-Based Glasgow Prognostic Score Predicts Prognosis in Acute Decompensated Heart Failure Patients with Preserved Left Ventricular Ejection Fraction: A Multicenter Study
Authors: Yoshima Shohei , Nagai Yoshiyuki , Shutta Ryu , Masuda Daisuke , Tamaki Shunsuke , Muraki Ryosuke , Abe Makoto , Sako Koji , Yamashita Shizuya , Seo Masahiro , Yamada Takahisa , Nakagawa Akito , Yasumura Yoshio , Nakagawa Yusuke , Yano Masamichi , Hayashi Takaharu , Hikoso Shungo , Sotomi Yohei , Sakata Yasushi ,   the OCVC-Heart Failure Investigator
Published: March 2022

Background:
A systemic inflammatory state caused by comorbidities has been shown to play a key role in pathophysiology of heart failure with preserved ejection fraction (HFpEF). The inflammation-based prognostic score termed Glasgow prognostic score (GPS), combining C-reactive protein and albumin, has been reported to provide prognostic information in patients with cancer or heart failure. However, little is known about the usefulness of the GPS for the prediction of prognosis in patients with HFpEF who are admitted with acute decompensated heart failure (ADHF).

Methods:
Patients' data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT-HFpEF) study, which is a prospective multicenter observational registry for ADHF patients with LVEF ≥50% in Osaka area. We studied 1017 patients who survived to discharge. The GSP was calculated at discharge as follows: patients with both elevated C-reactive protein (>1.0mg/dL) and hypoalbuminemia (<3.5g/dL) were allocated a score of 2, patients with one of these abnormalities were allocated a score of 1, and patients with neither of these were allocated a score of 0. The endpoint was all-cause death.

Results:
During a follow-up period of 1.5±1.2 years, 178 patients had all-cause death. At multivariate Cox analysis, GPS 1 (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.14-2.56, p=0.0090) and GPS 2 (HR 2.42, 95% CI 1.51-3.88, p=0.0003) were independently associated with all-cause death after the adjustment for major confounders. There was significant difference in the rate of all-cause death when the patients were stratified according to the GPS (Figure).

Conclusions:
In this multicenter study, the systemic inflammation-based GPS was shown to be useful for the prediction of prognosis in HFpEF patients admitted for ADHF.
Abstract 10013: PRDs Are Multifunctional Oral Inhibitors of PCSK9 and ACAT2
Authors: Paolo Parini , Ahmed Osman , Pedrelli Matteo , Oshiro Taichi , Pramfalk Camilla , Eriksson Mats , Mejia Erika
Published: March 2022

Introduction and Hypothesis:
PCSK9-inhibition reduces the residual cardiovascular risk associated with LDL-cholesterol (LDL-C), but the wide-spread use of the antibody-based therapies is affected by the costs, especially in low- and middle-income countries. Hence, there is a need to identify affordable and effective drugs to inhibit PCSK9.

Methods:
Female and male C57BL/6J mice were fed a high fat diet prior to and during eight weeks of oral treatment with PRD125 (10 mpk/day), a molecule originally developed as a selective inhibitor of ACAT2. Also, HepG2 cells were incubated with PRD125 or PRD017 (1 and 10 μg/mL) in the presence or absence of atorvastatin (5 μmol/L).

Results:
PRD125 significantly reduced serum concentrations of LDL-C (-30% to -50%) and PCSK9 (>-60%), without significantly affecting
PCSK9
mRNA levels. Additionally, significant decreases in fasting glucose (-17%) and HOMA-IR (-50%) were also observed. As the effects by PRD125 on serum concentrations of PCSK9 were posttranscriptional, we studied whether PRD125 or PRD017 may exert similar effects in human hepatocyte-like HepG2 cells. While atorvastatin significantly increased cellular PCSK9 protein levels (~40%), significant decreased levels (~40%) were observed by PRD125 or PRD017, regardless of the presence or absence of atorvastatin. Contrary to atorvastatin, and in line with the observation in mice, PRD125 and PRD017 did not affect
PCSK9
mRNA levels.

Conclusion:
PRD125 and PRD017 are non-species-specific posttranscriptional inhibitors of PCSK9, that exert their functions in the presence or absence of cholesterol synthesis inhibition by atorvastatin. As PRD125 also improves glucose tolerance and decreases atherosclerosis in mice by inhibiting ACAT2, PRD125 can be considered as a progenitor of a new group of multifunctional orally active molecules with great potential for treatment and prevention of atherosclerosis and cardiometabolic diseases.
Abstract 10014: Prognostic Value of the Combination of Aortic Pulsatility Index and Fibrosis-4 Index in Patients Admitted for Acute Decompensated Heart Failure
Authors: Yamada Takahisa , Watanabe Tetsuya , Morita Takashi , Kawasaki Masato , Kikuchi Atsushi , Kawai Tsutomu , Seo Masahiro , Nakamura Jun , Kayama Kiyomi , UEDA KUMPEI , Sakamoto Daisuke , Tamura Yuto , Fujita Takeshi , Kogame Takehiro , Nishigaki Keisuke , Fukuda Yuto , Kokubu Yuki , Fukunami Masatake
Published: March 2022

Backgrounds:
Aortic pulsatility index (API), calculated as (systolic - diastolic blood pressure)/pulmonary capillary wedge pressure, is a novel hemodynamic measurement representing cardiac filling pressures, and contractility and has been shown to be associated with adverse clinical outcome in patients with advanced heart failure (HF). On the other hand, cardiohepatic interactions have been a focus of attention in HF, and liver dysfunction in HF patients is caused by liver congestion, which is related to liver stiffness. It has been recently reported that liver stiffness assessed by non-invasive fibrosis marker such as Fibrosis-4(FIB4) index predicts the poor outcome in HF patients. However, there is no information available on the prognostic value of the combination of API and FIB4 index in patients with acute decompensated heart failure (ADHF).

Methods and Results:
We studied 238 patients admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. API was obtained at the admission. FIB4 index was calculated by the formula: age(yrs) х AST[U/L]/(platelets [10
9
/L] х (ALT[U/L])
1/2
). FIB4 index >2.67 was defined as abnormal, as previously reported. During a follow up period of 5.2±4.4 yrs, 58 patients had cardiovascular death (CVD). At multivariate Cox analysis, API and FIB4 index were significantly associated with CVD, independently of serum creatinine level and prior heart failure hospitalization, after the adjustment with hemoglobin and serum albumin levels. The patients with both lower API ≤1.905 (AUC 0.665[0.584-0.546]) and abnormal FIB4 index had a significantly increased risk of CVD than those with either lower API or abnormal FIB4 index and none of them (50% vs 23% vs 16%, p=0.0003, respectively).

Conclusion:
The combination of API and FIB4 index might be useful for stratifying ADHF patients at higher risk for CVD.
Abstract 10021: Prediction of Intracerebral Hemorrhage in Out-of-Hospital Cardiac Arrest Patients with Post-Resuscitation Electrocardiogram
Authors: Kaichi Ryota , Ishii Masanobu , Mikami Takafumi , Ikebe Sou , Takae Masafumi , Mori Takayuki , Komaki Soichi , Toida Reiko , Kurogi Kazumasa , Nagamine Yasuhiro , Matsuyama Masakazu , Yamaguchi Tetsuro , Yano Takao , Tsujita Kenichi , Yamamoto Nobuyasu
Published: March 2022

Introduction:
The appropriate patient selection for urgent coronary angiography after return of spontaneous circulation (ROSC) are still unclear. Hence intracerebral hemorrhage (ICH) show non-specific ST-changes on post-resuscitation electrocardiogram (ECG) and lead to misdiagnosis and incorrect therapeutic decisions. Therefore, we evaluated the characteristics of patients with ICH in nontraumatic out-of-hospital cardiac arrests (OHCA) after ROSC to identify patients who need brain computed tomography (CT) as the next diagnostic work-up.

Methods and Results:
We studied 1303 consecutive patients who transported to our hospital due to OHCA between 2008 and 2020, and 1,235 (95%) were assessed their cause of death by CT. After excluding 126 patients with obvious extracardiac causes, 329 patients with ROSC were finally included, and categorized into 2 groups: those with ICH (n=32, 10%) and those with suspected cardiac origin group (n=297). Logistic regression analyses showed that younger age (<75 years), female, no shockable rhythm change, tachycardia (≥100bpm), lateral segment elevation, inferior segment depression on ECG were independently associated with ICH. We developed a new predictive model for ICH by adding 1 point for each of the 6 factors. The ICH positive rate increased by a factor of 2.36 for each 1-point increase (P<0.001). Three points or less corresponded to a negative predictive value of 94% and 4 points or more corresponded to a positive predictive value of 31% for ICH (Figure).

Conclusion:
Our new predictive model might be useful for risk stratification of ICH in OHCA patients with ROSC.
Abstract 10044: Efficacy of Sacubitril-Valsartan in Patients with Reduced Left Ventricular Ejection Fraction
Authors: Ueyama Hiroki , Kuno Toshiki , Briasoulis Alexandros
Published: March 2022

Introduction:
Angiotensin receptor-neprilysin inhibitor (ARNI) reduces death and heart failure (HF) hospitalization in patients with HF and reduced ejection fraction (HFrEF). In addition to the PARADIGM-HF, PARADISE-MI and LIFE trial has recently tested the safety and efficacy of ARNI in subgroups of patients with reduced left ventricular ejection fraction (LVEF) such as those patients at risk for HFrEF after myocardial infarction (without prior HF) and advanced HF patients.

Methods:
We performed a random-effects model meta-analysis of three randomized controlled trails investigating the effect of ARNI in patients with reduced LVEF. The main endpoints were the composite of cardiovascular death and HF hospitalization, and HF hospitalization.

Results:
A total of 14,395 patients were included in our analysis. The characteristics of the included studies are demonstrated on Table 1. The composite endpoint and HF hospitalization were non-significantly reduced with ARNI compared with angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers (composite endpoint adjusted hazard ratio [HR] 0.9, 95% confidence intervals 0.75-1.08 and HF hospitalizations: HR 0.87, 0.72-1.04, Figure 1). The heterogeneity among trials was high (I
2
>50%).

Conclusions:
In line with the recently reported trials, our findings support the use of ARNI in patients with HFrEF that meet the inclusion criteria of PARADIGM-HF trial. It is important to tailor medical therapy by matching individual patient profiles to inclusion criteria of the published randomized clinical trials.
Abstract 10057: Subclinical Atrial Fibrillation is More Prevalent in Heart Failure with Preserved Ejection Fraction Compared to the General Population
Authors: Yang Eunice , Heckbert Susan , Ding Jie , Spragg David D , Calkins Hugh G , Shah Sanjiv J , Szklo Moyses , Post Wendy , Sharma Kavita
Published: March 2022

Introduction:
Atrial fibrillation (AF) is a common in patients with heart failure with preserved ejection fraction (HFpEF), and is associated with higher filling pressures, reduced exercise capacity, and reduced survival. The prevalence of subclinical AF in HFpEF remains unknown.

Hypothesis:
We hypothesized that subclinical AF was more prevalent in individuals with HFpEF when compared to individuals without clinical heart failure history.

Methods:
We evaluated subclinical AF in 101 HFpEF patients with no prior diagnosis of clinical AF using 14 day ambulatory ECG patch monitoring (Ziopatch XT, iRhythm Technologies). We compared the prevalence of subclinical AF in HFpEF with controls drawn from 3303 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) exam 6 follow-up, excluding those with known heart failure or high H2FpEF score who underwent the same ECG patch monitoring. Case-control comparisons of participants between the ages of 55 to 93 years were performed using multivariable logistic regression to adjust for demographic and clinical comorbidities, as well as patch monitoring duration.

Results:
80 HFpEF patients and 1356 MESA participants were included. The HFpEF patients were younger (69 [63, 76] v. 72 [66, 80], p=0.02), more obese (BMI of 36 [30, 45] v. 27 [24, 30], p<0.001) and more likely to have diabetes (34 v. 21%, p=0.01). There was a higher proportion of African Americans in the HFpEF group (57.5 v. 22.8%, p<0.001). The prevalence of subclinical AF was 9.8% in HFpEF group and 6.2% in MESA participants. After multivariable adjustment for age, sex, race, body mass index, hypertension, diabetes, smoking pack-years and total analyzable time on ECG monitor there was a significantly higher odds of subclinical AF in HFpEF compared to MESA (OR 4.26 [1.2, 16.2], p=0.03).

Conclusions:
HFpEF patients have a higher prevalence of subclinical AF than the general population. Screening for atrial arrhythmias may be appropriate in HFpEF patients for timely initiation of thromboembolic prophylaxis, and may identify individuals at greater risk for clinical decompensation in light of the well documented risks associated with AF in HFpEF.
Abstract 10058: Increased Prevalence and Worsened Outcomes of Peripheral Vascular Disorders Hospitalizations in Young Adults: A National Decade Apart Analysis, 2007 vs. 2017
Authors: Desai Rupak , Chintalapalli Patta Harika Varma , Shenwai Priya , Srikanth Sashwath , Yar Khan Nibras , Rida Taherunnisa , Asfeen Ummul , Gandhi Zainab J , Jain Akhil
Published: March 2022

Background:
Prevalence and trends in peripheral vascular disease (PVD) admissions among young adults have been infrequently evaluated on a large scale. We aimed to study the demographics, comorbidities, and outcomes of PVD in young adults from data selected from two nationwide cohorts a decade apart (2007 vs 2017).

Methods:
We queried National Inpatient Sample (2007 & 2017) to identify PVD admissions among young adults (18-44 years) and compare the burden, demographics, comorbidities between 2017 and 2007 cohorts. Primary outcomes were all cause mortality, MACE (all-cause mortality, AMI, cardiogenic shock, cardiac arrest, ventricular fibrillation/flutter, pulmonary embolism, coronary intervention) and stroke, and secondary outcomes were hospital resource utilization.

Results:
There was an increase in young PVD hospitalizations in 2017 (0.5%/n=46,760) vs. 2007 (0.4% /n=37,099). The 2017 cohort often included younger (37 vs 40 years), white (54.8% vs 57.7%), female (48.6% vs 47.5%), Medicaid enrollees admitted non-electively (85.2% vs 80.0%) (p<0.05) vs. 2007 cohort. Comorbidities like smoking, drug abuse, fluid and electrolyte disorders, and pulmonary circulation disorders were the most frequent comorbidities in 2017 cohort vs. 2007 cohort. Despite lower rate of hypertension, renal failure, hyperlipidemia, complicated diabetes decreased in young PVD admissions from 2007 to 2017 (p<0.001), there was alarming increase in all-cause mortality (1.5% vs 3.4%, aOR1.39, 95%CI:1.23-1.59) and stroke (4.2% vs. 10.4%, aOR2.43, 95%CI:2.25-2.63) on adjusted multivariable analysis (p<0.001) with comparable MACE (8.9% vs 10.4%, aOR0.99, p=0.697) in 2017 vs. 2007. There was fewer routine discharges, prolonged hospital stay and charges in 2017 PVD cohort.

Conclusion:
The comparison of two national cohorts selected a decade apart showed an increased frequency of admissions of young PVD with higher substance abuse and higher all-cause mortality and stroke.
Abstract 10067: A Nitric Oxide Donor Binds to SARS-CoV-2 Papain-Like Protease with Therapeutic Implications
Authors: Schmedtje John F , Assar Zahra , Ciske Fred
Published: March 2022

Novel compounds developed as nitric oxide (NO) donors for cardiovascular diseases were created by linking an urea-like NO donor to the 5-carbon of the generic agent isosorbide-2-nitrate. NO also appears to have antiviral effects on SARS-CoV-2. A study of drug-protein interactions was undertaken
in silico
using Maestro, Schrödinger Suite software to determine if the novel compounds could be antivirals. SARS-CoV-2 papain-like protease (PL
pro
) was a primary target as it mediates viral replication and inhibition of host interferon-based responses. Compared with known antiviral drugs, including the known PL
pro
inhibitor GRL-0617, CR-0305 had a better Glide Score (a predictor of ligand affinity) against PL
pro
. Molecular Mechanics / Generalized Born Surface Area (MM/GBSA) calculations and Molecular Dynamics simulations predicted CR-0305 binding to the PL
pro
catalytic pocket where it makes the most of key residues in the catalytic site. Subsequently, CR-0305, or (3S,3aS,6R,6aR)-6-((3-(2-hydroxyacetamido)propyl)amino) hexahydrofuro[3,2-b]furan-3-yl nitrate, was synthesized by ligating a (TBDPS) Tert-Butyldiphenylsilyl-protected side chain to the 5-carbon of 1,4:3,6-Dianhydro-L-Iditol Triflate Mononitrate followed by a de-protection reaction that removed TBDPS. Toxicity of CR-0305 was examined using MitoCheck Complex I-V activity assays in an Agilent Seahorse XFe96 analyzer in isolated mitochondria with mitochondrial stress tests in HMEC-1 human dermal endothelial cells and measurement of the effect of drug on ATP synthesis in HMEC-1 cells. No significant toxicity was identified at 10-100 μM concentrations. GRL-0617, CR-0202 and CR-0305 were tested in Vero E6 and A549-ACE2 cells exposed to SARS-CoV-2 using a drug dose response regimen from 20 μM down to 40 nM in 2-fold serial dilution. There was no evidence of cytotoxicity. GRL-0617 gave an approx. 50% reduction in SARS-CoV-2 infection compared to vehicle at the highest dose tested (20 μM), as measured by virus N protein staining with a specific antibody. CR-0305 gave a consistent but weak effect on total N protein expression in A549-ACE2 cells. In conclusion, CR-0305 binds
in silico
to SARS-CoV-2 PL
pro
and appears to inhibit viral replication
in vitro
, justifying further development.
Abstract 10074: Cardiovascular Outcomes in Patients with Concurrent Atrial Fibrillation and Myeloproliferative Neoplasms
Authors: Leiva Orly , Jenkins Andrew , Rosovsky Rachel P , Karp-Leaf Rebecca , Goodarzi Katayoon , Hobbs Gabriela
Published: March 2022

Introduction:
Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocytosis (ET) and myelofibrosis (MF), are clonal stem cell neoplasms. Therapy is instituted to prevent thrombosis, a leading cause of morbidity/mortality in this population. Atrial fibrillation (AF) is also associated with increased risk of thromboembolism. Risk scores, including CHA
2
DS
2
VASC, are used to determine benefit of anticoagulation (AC) but have not been validated in patients with MPN.

Methods:
This is a single-center, retrospective cohort study of patients with concurrent MPN and AF from 2000 to 2020 (n = 142; 62 ET, 54 PV, 26 MF). Outcomes included composite of arterial thrombotic events (ATE; MI, ischemic stroke, or peripheral arterial embolism) and cardiovascular (CV) death, bleeding requiring hospitalization, and all-cause mortality (ACM).

Results:
AC was used in 69% of all MPN patients (73% of ET/ PV, 50% of MF). CHA
2
DS
2
VASC scores were significantly higher in patients with ET/PV compared with MF (4 ± 2 vs 3 ± 1, p = 0.0019). After median follow-up (FU) of 49 months (IQR 18, 86) the composite outcome occurred in 39% of patients with MPN (ET/PV 36%, MF 50%). Bleeding occurred in 30% of patients (ET/PV 29%, MF 30%) and ACM in 45% of all patients (ET/PV 40%, MF 83%). Patients with MF had worse composite-free survival (log-rank p = 0.0043, Fig-A) and no difference in bleed-free survival (Fig-B) compared with ET/PV patients. After multivariable logistic regression including CHA
2
DS
2
VASC, age, sex, MF, AC, CAD, hypertension, diabetes, prior stroke, aspirin use, MPN treatment and FU time as co-variables, MF was associated with the composite (aOR 4.1, 95% CI 1.2-14.9), CHA
2
DS
2
VASC was not (aOR 1.3, 95% CI 0.8-2.1).

Conclusions:
Patients with MPN and AF have high rates of adverse outcomes with MF having worse composite-free survival compared to ET/PV. Traditional risk scores may underperform in this patient population underscoring the need for further investigation.
Abstract 10078: Facilitators and Barriers to Chronic Care Among Patients with Heart Failure in Rural Haiti: A Qualitative Study
Authors: Basow Elizabeth , Isaac Benito , Fenelon Darius , Toussaint Evyrna , Calixte Dawson , Ibrahim Michel , Hirschhorn Lisa , Drainoni Mari-Lynn , Adler Alma , Clisbee Mary , Bukhman Gene , Kwan Gene F
Published: March 2022

Introduction:
Heart failure (HF) is a leading cause of hospitalizations in rural Haiti. However, few patients hospitalized for HF return for outpatient care. The factors that contribute to chronic HF care access are poorly understood.

Objective:
To investigate the facilitators and barriers to accessing care for chronic HF from the patients’ perspectives.

Methods:
We conducted three group interviews and one individual interview with thirteen patients with HF. We recruited patients after discharge from a non-governmental organization-supported academic hospital in rural Haiti. We employed thematic analysis using emergent coding and categorized themes using the socioecological model.

Results:
Facilitators of chronic care included participants’ knowledge about the importance of HF treatment and engagement with health systems to manage symptoms. Strong social support networks helped participants access clinic visits. Participants reported low cost of care at this subsidized hospital, good medication accessibility, and trust in the healthcare system. Participants expressed the strong spiritual belief that the healthcare system is an extension of God’s influence. Barriers to chronic care included participants' misconceptions about adherence to medications and the need to take HF medications with food. Lack of social support prevented clinic access, and non-healthcare costs associated with clinic visits were prohibitive. Participants expressed low satisfaction regarding the clinic experience. Another barrier to healthcare was the belief that heart disease caused by supernatural spirits is incurable.

Conclusions:
We identified several facilitators and barriers to chronic HF care with implications for HF management in rural Haiti. Future interventions to improve chronic HF care should address misconceptions and foster patient support systems for visit and medication adherence. Leveraging local spiritual beliefs may promote care engagement.
Abstract 10083: Deaths in Acute Myocardial Infarction; Us Location Trends
Authors: Minhas Abdul , Ariss Robert , Ullah Waqas , Arshad Hassaan , Khan Muhammmad , Fudim Marat , Nasir Khurram
Published: March 2022

Introduction:
The need for increased utilization of hospice in the dying patients has been recognized in multiple fields including cardiology recently. The aim of this study to examine the trends in location of deaths in acute myocardial infarction (AMI) related deaths in the United States from 2003 to 2019.

Methods:
The CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) was used to access the National Vital Statistics System data from 2003 to 2019. AMI related deaths in patients ≥ 25 years of age were identified from multiple causes of death. Joinpoint regression was used to examine changes in trend, annual percentage change (APC), and average annual percentage change (AAPC). Location of death was categorized as home, medical facility, hospice facility, nursing home/long term care (NH/LTC) and other/unknown.

Results:
Of AMI related deaths, 23.62% occurred at home, 0.94% at hospice facility, 39.64% at medical facility and 13.30% at NH/LTC. From 2003-2019, the number of deaths has increased at hospice facility (AAPC 24.7[95% CI, 18.1 to 31.6]) and decreased at both medical facilities (AAPC -3.1[95% CI, -3.5 to -2.8]) and NH/LTC (AAPC -4.3[95% CI, -4.6 to -3.9]). The number of deaths initially decreased at home till 2009 (APC -1.9[95% CI, -2.5 to -1.3]) followed by increase till 2019 (APC 1.5[95% CI, 1.2 to 1.8]).

Conclusion:
Although there was an increasing trend in AMI related mortality at hospice and home locations, rates of utilization of hospice facility remain very low.
Abstract 10085: Risk Profiles and Outcomes of Patients Receiving Antibacterial Cardiovascular Implantable Electronic Device Envelopes
Authors: Woodard David , Kim Grace , Murrow Jonathan R , Nilsson Kent R
Published: March 2022

Background:
Antibacterial cardiovascular implantable electronic device (CIED) envelopes provide short-term local antibiotic delivery and can reduce implant site infection risk. Available antibacterial CIED envelopes are either fabricated from biologic material (extracellular matrix hydrated with antibiotics by the user) or from non-biologic material (synthetic mesh coated with antibiotics by the manufacturer).

Objective:
To compare the risk profiles and outcomes of CIED procedure patients receiving no envelope vs an antibacterial envelope.

Methods:
Records of consecutive CIED procedure patients at one center were reviewed through 12 months follow-up. Procedures used either no envelope, a biologic envelope pre-hydrated with vancomycin and gentamicin (BIO) [CanGaroo®, Aziyo Biologics], or a non-biologic envelope coated with minocycline and rifampin (Non-BIO) [TYRX™, Medtronic].

Results:
CIED procedures were performed on 248 patients (191 with envelope, 89 BIO, 102 Non-BIO). Patients receiving envelopes were younger, had significantly more comorbid risk factors (p<0.001), and received high powered devices and reoperative procedures more often (p<0.001)(Table 1). BIO envelopes were used more often in higher risk patients (84% vs 78%) and reoperative patients (62% vs 38%) compared to Non-BIO envelopes. CIED implant site pocket infection rates were low (envelope 0.5%, no envelope 0%, p=0.584), with no significant difference between BIO and Non-BIO envelopes.

Conclusion:
Antibacterial envelopes were used more often to treat patients with multiple comorbid risk factors. Biologic envelopes were used more often in higher risk patients. There was no significant difference in CIED implant site pocket infection rates for patients receiving biologic or non-biologic antibacterial envelopes.
Abstract 10090: Cost-Effectiveness of Management for Hospitalized Patients; Gender Difference Between Female and Male Cardiologists
Authors: Nakayama Atsuko , Kodera Satoshi , Morita Hiroyuki , Takeda Norifumi , Komuro Issei
Published: March 2022

Introduction:
The cost and/or cost-effectiveness for inpatient management according to the gender of attending physicians remain to be elucidated.

Hypothesis:
The treatment by female cardiologists may be cost-effective.

Methods:
The hospitalization costs were extracted from the Diagnosis Procedure Combination (DPC) -based payment system. Using the dataset of 7,457 hospitalized patients with cardiovascular diseases in our hospital from 2012 to 2018, we compared the actual cost of inpatient management by female cardiologists with that by male cardiologists. Next, we estimated the cost-effectiveness of inpatient management according to the gender of attending cardiologists.

Results:
The cost of initial hospitalization per patient was similar between the patients treated by a female middle-grade cardiologist and those treated by a male middle-grade cardiologist ($17,527 ± 14,158, vs. $17,358 ± 15,183, P=0.69). As an analysis on cost-effectiveness, the incremental cost of hospitalization managed by male middle-grade cardiologists was $67 per patient as compared with that by female middle-grade cardiologists. Concordantly, the evaluation on incremental cost-effectiveness ratio per quality-adjusted life year gained showed that the inpatient management by female cardiologists was dominant over that by male cardiologists (less cost and better effect).

Conclusions:
Inpatient management by female cardiologists was more cost-effective as compared with that by male cardiologists. Physicians’ gender might have a considerable effect on the medical economics.
Abstract 10092: Prophylactic Ventricular Tachycardia Ablation in Ischemic Cardiomyopathy: An Updated Meta-Analysis of Randomized Controlled Trials
Authors: Rattanawong Pattara , Shipman Justin N , Fatunde Olubadewa , Sorajja Dan
Published: March 2022

Introduction:
Catheter ablation of the arrhythmogenic substrate reduces the recurrence of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillator (ICD). However, the all-cause mortality benefit in this population is unclear.

Hypothesis:
Prophylactic ablation of the arrhythmogenic substrate decreases all-cause mortality and prevents the recurrence of VT/ventricular fibrillation (VF) in patients with ischemic cardiomyopathy.

Methods:
We searched the MEDLINE and EMBASE databases from inception through May 2021. We included randomized controlled trials that compared all-cause mortality and ventricular arrhythmia recurrence in patients with ischemic cardiomyopathy who underwent ICD implantation with and without prophylactic ablation. The data from each study was combined using a fixed effects model to calculate the hazard ratio and 95% confidence interval (CI).

Results:
Four randomized controlled trials during 2007-2020 involving 505 patients (249 patients with and 256 patients without prophylactic VT ablation) were included in our meta-analysis. Compared with control, prophylactic VT ablation did not decrease the all-cause mortality (pooled hazard ratio = 0.94, 95% CI 0.54-1.63, p = 0.818, I2 = 5.8%). However, prophylactic VT ablation significantly decreased appropriate ICD therapy (pooled hazard ratio = 0.58, 95% CI 0.41-0.82, p = 0.002, I
2
= 26.1%) and VT/VF recurrence (pooled hazard ratio = 0.70, 95% CI 0.52-0.93, p = 0.015, I
2
= 0.0%).

Conclusions:
Prophylactic VT ablation in patients with ischemic cardiomyopathy did not decrease all-cause mortality; however, it did lead to decreased appropriate ICD therapy and VT/VF recurrence.
Abstract 10113: Improving Safety of Direct Oral Anticoagulant Dosing in Patients with Advanced Chronic and End-Stage Renal Disease
Authors: Upadhyay Naman , Mohammed Rahed , Kochar Kirpal , Ruge Max , Dikdan Sean , lev yair
Published: March 2022

Introduction:
Direct oral anticoagulants have become a mainstay in therapy for venous thromboembolism as well as mitigation of stroke and systemic embolism risk in atrial fibrillation. Although guidelines have been put forth for dose reduction in renal impairment, significant inconsistency in dosing practices exists. No study has directly evaluated the dosing practice of apixaban and rivaroxaban in those with advanced chronic kidney disease (stage 4 and 5) and end-stage renal disease at a quaternary care institution.

Methods:
We screened 853 patients from 1/1/2017 to 3/21/2020 with advanced chronic kidney disease and end-stage renal disease and identified 312 patients on either apixaban or rivaroxaban. Clinical data collected include anticoagulation indication, dosing, serum creatinine, age, weight, and creatinine clearance (calculated by the Cockcroft-Gault equation).

Results:
A total of 312 patients were studied (268 apixaban, 44 rivaroxaban). Among all patients with advanced chronic kidney disease and end-stage renal disease, a total of 123 patients (46%) were incorrectly dosed with apixaban compared to 17 patients (38%) with rivaroxaban. Among those with advanced chronic kidney disease, 57 patients (41%) were dosed incorrectly with apixaban compared to 10 patients (27%) with rivaroxaban. Among those with end-stage renal disease, 66 patients (50%) were dosed incorrectly with apixaban. (Figure 1).

Conclusion:
We demonstrate that there is significant variance in the dosing practice of direct oral anticoagulants among patients with advanced chronic kidney disease and end-stage renal disease. We hope to develop a checklist within the electronic medical record to promote adherence to guidelines when determining whether a patient requires dose reduction in the setting of renal dysfunction. Further investigation is being carried out to determine differences in outcomes among those properly dosed and those incorrectly dosed.
Abstract 10126: Lifetime Cardiovascular Risk Model to Identify Individuals with Low 10-Year Risk but High Lifetime Risk
Authors: Lee Hokyou , Yano Yuichiro , Allen Norrina , Park Yu Rang , Kim Dong Wook , Park Sungha , Lee Eun Jig , Lloyd-jones Don , Kim Hyeon Chang
Published: March 2022

Introduction:
Young adults with poor lifestyle and multiple risk factors (RF) still have low predicted 10-y cardiovascular (CV) risks as existing models are largely age-driven. This is exaggerated in low-risk populations (eg, Asians), often understudied for similar reasons. Using the Korean National Health Insurance (NHI) data, we developed CV risk models to identify individuals with low 10-y risk but high lifetime risk.

Methods:
Models were derived from a 50% sample of 2004-2005 NHI health examinees of age 20-89 free of CV disease. We built sex-specific Cox models with age as time scale and age-varying coefficients for CV events (myocardial infarction, stroke, or CV death) and competing non-CV death. We defined 10-y and lifetime CV risks as the cumulative risks at baseline age+10 and 90 years of age, respectively. We examined distributions of predicted risks and identified individuals with low 10-y/high lifetime risks using nationwide complex-survey data.

Results:
The derivation set included 4 894 098 participants (median age, 44 y; 56.9% male; median follow-up, 15.1 y), in whom 238 292 new CV events occurred before age 90. Age-varying coefficients were introduced to account for differential relative hazard contributions from high RF burden by age (Fig A and B). Models were validated in the 50% holdout set (age, 20-80; C-index, 0.821-0.854) and the 3 external prospective cohorts (age, 40-80; C-index, 0.701-0.763); calibration plots showed good agreement between predicted vs observed risks. Examples of calculated 10-y/lifetime risks are in Fig C. At the population-level, lifetime risks remained stable across age, whereas 10-y risks exponentially increased with age (Fig D). People with low 10-y risk but high lifetime risk had high RF burden despite young age (Fig E).

Conclusions:
The lifetime CV risk model can be used to guide preventive strategies in young, low-risk population, whose 10-y risk may not fully reflect potential lifetime benefit from CV disease prevention.
Abstract 10140: Atrial Natriuretic Peptide Deficiency Associated with Greater Cardiometabolic Disease in Males
Authors: Ichiki Tomoko , Iyer Seethalakshmi R , Scott Christopher , CANNONE Valentina , Sangaralingham Jeson , Bailey Kent , Goetze Jens P , Tsuji Yoshihisa , Rodeheffer Richard J , Burnett John C
Published: March 2022

Introduction:
The cardiac hormone atrial natriuretic peptide (ANP) plays a key role in blood pressure (BP) and metabolic homeostasis through guanylyl cyclase receptor-A. While the role of ANP in cardiovascular disease (CVD) has been extensively investigated, its role in metabolic regulation has only recently emerged. A genetic variant of the ANP gene (rs5068), which increases production of ANP and NT-proANP, is associated with lower blood pressure (BP), reduced risk for hypertension and a decreased prevalence of obesity and metabolic syndrome.

Hypothesis:
We hypothesized that sex differences in ANP may have an important role in cardiometabolic disease together with cardiovascular (CV) morbidity and mortality.

Methods:
We studied 1176 subjects (age > 45 years) in the general population from Olmsted County MN. Plasma ANP molecular forms were quantified. Metabolic and cardiorenal parameters, and detailed medical records were reviewed. The cardiometabolic protective action of the ANP gene variant rs5068 was also assessed. Subjects were followed for all-cause mortality and morbidity for 12 years.

Results:
Plasma ANP molecular forms were significantly lower in males compared to females. Males had higher BMI and greater incidence of myocardial infarction (MI), coronary artery disease and heart failure (HF). Males also had lower EF and HDL cholesterol and higher LA volume and LV mass, serum glucose, insulin and diastolic pressure. The presence of the rs5068 minor allele improved the cardiometabolic phenotype including BP and widespread metabolic parameters in males but not females. After adjustment by age, males had increased risk of all-cause mortality, HF, MI, and stroke.

Conclusions:
Males are characterized by a relative ANP deficiency compared to females and widespread prevalence of cardiometabolic disease and increased CV morbidity and mortality in the general population. We demonstrate that the cardiometabolic protective action of the ANP gene variant rs5068 minor allele is sex dependent and protective in males. These findings have diagnostic and therapeutic implications, particularly in males.
Abstract 10177: Optimal Reperfusion Strategy in Acute High-Risk Pulmonary Embolism Requiring Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-Analysis
Authors: Chopard Romain , Nielsen Peter B , Ius Fabio , Ecarnot Fiona , Pilichowski Hugo , Piazza Gregory , Meneveau Nicolas
Published: March 2022

Introduction:
The optimal pulmonary revascularization strategy in acute high-risk pulmonary embolism (PE) requiring the implantation of extra corporeal membrane oxygenation (ECMO) remains controversial.

Methods:
We conducted a systematic review and meta-analysis of available evidence comparing mechanical reperfusion and other strategies, including systemic or catheter-directed thrombolysis and ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes.

Results:
The literature search identified 835 studies, 17 of which were included, totaling 321 PE patients with ECMO. Overall, 31.1% were treated with mechanical pulmonary reperfusion, while 78.9% received other strategies. The mortality rate was 23.0% in the mechanical reperfusion group and 43.1% in the other strategy group. The pooled OR for mortality with mechanical reperfusion was 0.46 (95%CI, 0.213-0.997; I
2
= 28.3%) versus other reperfusion strategies (Figure). The rate of bleeding in PE patients under ECMO was 29.1% in the mechanical reperfusion group and 26.0% in the other reperfusion group (OR, 1.09; 95% CI, 0.46-2.54; I
2
, 0.0%) among 10 eligible studies with available bleeding data. The meta-regression model did not identify any relationship between the covariates “more than one pulmonary reperfusion therapy” and “ECMO implantation before pulmonary reperfusion therapy”, and outcomes.

Conclusions:
The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, yields the best results, regardless of the timing of ECMO implantation in the reperfusion timeline, and regardless of whether thrombolysis has been administered or not.
Abstract 10189: A Novel Hypothermia-Triggered and Controlled-Release Hydrogen Sulfide Delivery System Exerts Myocardial Protection from Ischemia-Reperfusion Injury
Authors: Yan Tao , Xia Wenyi , Wen Lianlei , Zhu Shijie , Zhu Miao , Lang Meidong , Wang Chunsheng , Guo Changfa
Published: March 2022

Introduction:
Hydrogen sulfide is a cardio-protective gas molecule, which prevents cardiocytes from ischemia-reperfusion injury, and then further improves the transplanted heart performance. However, the instability of hydrogen sulfide restricts its application in cryogenic heart reserving solution. The present study aimed to construct a novel hypothermia-triggered mesoporous silica nanoparticles (HT-MSN) for controlled hydrogen sulfide release.

Methods:
A polymer as hypothermia trigger was synthesized through free radical copolymerization of N-n-propylacrylamide and N-tert-butylacrylamide with azodiisobutyronitrile as the initiator. The selected diallyl trisulfide, as the hydrogen sulfide donor, was encased in mesoporous silica nanoparticles (MSN) to obtain controlled-release and drug-loaded particles. In order to controllably release hydrogen sulfide from drug-loaded particles in hypothermia, the polymers were coated on the surface of drug-loaded MSN. Characteristics of obtained HT-MSN were evaluated. Cytotoxicity and effects on myocardial protection were further assessed.

Results:
Combination of nuclear magnetic resonance spectroscopy and gel permeation chromatography determined the synthesized success of the hypothermia-triggered polymer. Further, through adjusting composition of those co-monomers, the polymer showed a lower critical solution temperature of around 7
o
C estimated by ultraviolet, indicting the potential for application at lower temperatures. Transmission electron microscope identified characteristics of obtained HT-MSN with uniform size and regular mesoporous. Furthermore, the novel HT-MSN system exhibited low cytotoxicity and acceptable myocardial protection, including anti-apoptosis and antioxidant activities.

Conclusion:
This study provided a novel hypothermia-triggered platform for controlled hydrogen sulfide release to protect cardiocytes against ischemia-reperfusion injury.
Abstract 10220: CSL112 (Apolipoprotein A-I (human)) Infusion Rapidly Increases ApoA-I Exchange Rate via Specific Serum Amyloid-Poor HDL Sub-Populations When Administered to Patients Post Myocardial Infarction
Authors: Didichenko Svetlana A , Velkoska Elena , Navdaev Alexey V , Greene Brandon H , Lorkowski Shuhui W , Mears Jenny J , Wright Samuel D , Gibson C M , Smith Jonathan D , Kingwell Bronwyn A
Published: March 2022

Background:
Apolipoprotein A-I (apoA-I) exchange rate (AER) into plasma high density lipoprotein (HDL) may represent a cell-free measure of HDL function, and predict recurrent major adverse cardiovascular events post-acute myocardial infarction (AMI).

Purpose:
To characterise the effects of CSL112 (apoA-I (human)) on AER and the relationships with specific HDL subpopulations when administered in the 90-day high-risk period post AMI.

Methods:
Patients from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study received either placebo, 2g or 6g CSL112 post AMI. The rate of apoA-I exchange into HDL was measured in AEGIS-I plasma samples incubated with fluorescent apoA-I-NBD (7-nitrobenz-2-oxa-1,3-diazole) lipid-sensitive reporter for 30 min at 37°C. HDL particle size distribution was assessed by native gel electrophoresis followed by fluorescent imaging and detection of apoA-I and serum amyloid A (SAA1/SAA2) by western blotting.

Results:
CSL112 infusion increased AER peaking 2 h post infusion and returning to baseline by 24 h. AER was correlated with cholesterol efflux capacity, HDL-C, apoA-I and phosphatidylcholine (all p<0.001). CSL112 infusion induced transient changes in HDL particle size distribution. Small remodelled HDL (S-HDL
rem
) derived from CSL112 were detected in plasma 2-4 h after infusion. Large remodeled HDL species (L-HDL
rem
) accumulated 2-12 h post infusion. The apoA-1-NBD reporter was confined to distinct HDL subpopulations that contained little SAA. In plasma samples characterized by the baseline pattern of HDL particle size distribution (0 h and 24-48 h post infusion), the apoA-I-NBD reporter predominantly exchanged into the HDL3 subpopulation, but not into large HDL2.

Conclusion:
Infusion of CSL112 increased AER via exchange into SAA-poor HDL particles. AER may represent a clinically amenable biomarker of HDL functionality.
Figure:
HDL particle remodelling and AER in a representative subject infused with 6g CSL112
.
Abstract 10226: Bioactive Adrenomedullin for Assessment of Venous Congestion in Heart Failure
Authors: Egerstedt Anna , Czuba Tomasz , Bronton Kevin , Lejonberg Carl , Ruge Toralph , Wessman Torgny , Radegran Goran , Schulte Janin , Hartmann Oliver , MELANDER Olle , Smith Gustav
Published: March 2022

Introduction:
Bioactive adrenomedullin (bio-ADM) is a vascular-derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF).

Hypothesis:
We aimed to evaluate diagnostic and prognostic performance of bio-ADM for HF in comparison to amino-terminal pro-B-type natriuretic peptide (NT-proBNP), with decision thresholds derived from invasive hemodynamic and population-based studies.

Methods and Results:
Normal reference ranges (95% prediction interval) for bio-ADM were derived from a community-based cohort (n=5060): 8-39 pg/mL. In a cohort of HF patients undergoing right heart catheterization (n=346), bio-ADM was correlated with mean right atrial pressure (mRAP, r=0.55) and followed a concordant trajectory to mRAP after heart transplantation. In contrast, NT-proBNP was correlated with pulmonary arterial wedge pressure (PAWP). The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mRAP and PAWP was 0.74 (95%CI=0.67-0.79) and 0.70 (95%CI=0.64-0.75), respectively, with optimal bio-ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT-proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95%CI=0.68-0.79] and 0.68 [95%CI=0.61-0.75]). In a cohort of patients presenting with acute dyspnea (n=1534), including patients with decompensated HF (n=570), a bio-ADM decision cutoff of 39 pg/mL was associated with 30- and 90-day mortality and conferred a 2-fold increased odds of HF diagnosis, independently from NT-proBNP.

Conclusions:
Bio-ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT-proBNP. Our findings support utility of bio-ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.