bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 21413: Molecular Basis of Maternal Obesity Induced Fetal Cardiac Contractile Dysfunction
Authors: Wang Qiurong , Odhiambo John F , Pankey Chris , Ghnenis Adel , Nathanielsz Peter W , Ford Stephen P , Guo Wei
Published: March 2022

One third of the women at reproductive age are overweight or obese in US. Epidemiological studies in humans and studies on animals have shown that obesity during pregnancy (
i.e.
maternal obesity, MO) increases incidences of cardiovascular diseases in offspring. Uterus environment is essential for fetal cardiac development and MO as a stress condition in uterus could program cardiovascular disease in prenatal and postnatal offspring. However, the mechanisms of the origin and development of MO-induced cardiovascular disease later in life remain unclear. For this purpose, we use sheep (sharing many similarities with human pregnancy) as a model to study the impact of MO on fetal heart contractile function. Previously, we have demonstrated that MO impaired fetal sheep cardiomyocyte contractility by reducing the peak shortening and velocity of shortening/relengthening and prolonged the time to peak shortening/relengthening. We also found that MO disrupted the calcium homeostasis in fetal cardiomyocytes by increasing intracellular Ca
2+
level and inducing the calcium insensitivity in the cell. In current study, we found that MO increased the phosphorylation of protein kinase A (PKA) as well as the phosphorylation of Ca
2+
/calmodulin-dependent protein kinase II (CaMKII), which further promoted phosphorylation level of ryanodine receptor type 2 (Ryr2) at Ser2808 and Ser2814 respectively. Expression level of FKBP12.6, a key protein interacting with Ryr2 for calcium releasing, was upregulated in MO fetal myocardium. On the other hand, MO reduced expression of myosin heavy chain in fetal myocardium. Moreover, the cardiac troponin T and troponin I expression level was upregulated in MO fetuses, whereas MO downregulated the expression of troponin C in fetal myocardium. Taken together, our findings suggest that increased CaMKII and PKA phosphorylation of Ryr2 plays a critical role in the development of MO-induced sarcoplasmic reticulum Ca
2+
leak in fetal cardiomyocytes. Furthermore, our data indicate that the change in expression levels of myosin heavy chain and troponin C, I and T is the cause of calcium insensitivity and contractile dysfunction in MO fetal cardiomyocytes. Our studies have provided a fundamental molecular basis of MO programmed heart disease.
Abstract 23074: The Department of Justice Investigation and ICD Implantations Not Meeting Medicare’s National Coverage Determination
Authors: Desai Nihar R , Parzynski Craig , Brindis Ralph , Spatz Erica , Masters Claire , Minges Karl , Peterson Pamela , Masoudi Fred , Oetgen William , Buxton Alfred , Zipes Douglas , Curtis Jeptha
Published: March 2022

Background:
In 2010, the Department of Justice (DOJ) announced an investigation into the placement of implantable cardioverter defibrillators (ICDs) outside CMS’ National Coverage Determination (NCD). Recently, more than 500 hospitals reached settlements with the DOJ totaling $250 million. We sought to examine the potential impact of the DOJ investigation on clinical practice.

Methods:
Within the NCDR ICD registry, we calculated the proportion of initial primary prevention ICDs among Medicare beneficiaries not meeting NCD criteria between January 2007 and December 2015 stratified by whether the implanting hospital eventually paid a settlement to the DOJ. To examine changes in primary and secondary prevention ICD volume, we restricted to facilities implanting at least 10 ICDs in each year of the study.

Results:
A total of 331,349 ICD procedures from 1820 hospitals were included; 452 of these hospitals settled with the DOJ. Prior to announcement of the DOJ investigation in 2010, hospitals that eventually settled had significantly higher proportions of primary prevention ICDs that did not meet NCD criteria (P< 0.001, Figure left panel). Following the announcement of the DOJ investigation, the proportion of implantations not meeting NCD criteria declined at all hospitals, but the pace of decline accelerated and was significantly larger in hospitals that settled (P
int
= 0.009). Over the study period, there was a 33% decline in primary prevention ICD volume at hospitals that settled with DOJ as compared with a 17% reduction at hospitals that did not settle. In contrast, the volume of secondary prevention ICDs remained relatively constant over time (Figure, right panel).

Conclusion:
The proportion of primary prevention ICDs not meeting NCD criteria has declined at all hospitals. Announcement of the DOJ investigation was associated with more rapid and larger reductions at hospitals that settled without evidence of unintended consequences on secondary prevention ICDs.
Abstract 23081: Anti-inflammatory Effect of Whole-Food Plant-Based Vegan Diet vs the American Heart Association - Recommended Diet in Patients With Coronary Artery Disease: The Randomized EVADE CAD Trial
Authors: Shah Binita , Newman Jonathan , Woolf Kathleen , Ganguzza Lisa , Guo Yu , Fisher Edward A , Allen Nicole , Hazen Stanley L , Larigakis John , Zhong Judy , Gianos Eugenia , Ujueta Francisco , Slater James
Published: March 2022

Background:
The effect of a whole-food plant-based vegan diet vs an AHA-recommended diet on inflammatory, lipid, and glucometabolic profiles remains uncertain.

Methods:
This prospective blinded end-point trial randomized 100 patients with invasive angiographically-defined coronary artery disease (CAD) to 8 weeks of a vegan or AHA diet. Participants were provided weekly groceries for their assigned diet strategy, sample 2-week menus, tools to measure portion size, and on-going consultation with the study dietitian. Dietary adherence was measured by two weekly 24-hour dietary recalls and plasma and urine trimethylamine-
N
-oxide levels. Participants also completed a 4-day food record during the week prior to the baseline, 4-, and 8-week study visits. The primary endpoint was serum hsCRP concentration. A linear mixed effect model was used to model the log-transformed endpoints (to correct for skewness), evaluate the change in endpoint over time within treatment group, and test the interaction between time and treatment. The primary analysis was also covariate-adjusted.

Results:
Baseline characteristics are shown in Table 1. Two subjects withdrew from the vegan group after randomization, but dietary adherence remained higher in the vegan vs AHA group at the 4-week (96% vs 84%, p=0.09) and 8-week (94% vs 70%, p=0.003) visits. Endpoints are shown in Table 2.

Conclusion:
A vegan diet significantly reduced systemic inflammation, as evidenced by hsCRP, in patients with CAD on guideline-directed medical therapy, while an AHA diet did not. This is the first rigorous study to comprehensively assess multiple indices of cardiovascular risk between a vegan and AHA diet.
Abstract 23083: Glycemic Therapies, Atherothrombotic And Heart Failure Risk, And Outcomes By Baseline Cardiovascular Disease Status: Meta-analysis of Large CV Outcome Trials
Authors: Udell Jacob A
Published: March 2022

Purpose/Background:
Recent glycemic therapy CV outcome trials have demonstrated risk reduction on the composite of CV death, MI or stroke (atherothrombotic MACE) and heart failure (HF). We investigated whether effects are modified by weight change, an indirect marker of intravascular volume status and explored among effective therapies heterogeneity by baseline CVD status.

Methods:
Random-effects metaanalysis among glycemic therapy CV outcome trials on the relative risk (RR) of MACE and HF.

Results:
Among 21 trials of 149,916 patients, 5,749 (3.8%) HF and 15,357 (10.2%) MACE events occurred during a mean 3.9 years of follow-up (range 1.5-10 years). Across classes of glycemic therapy there was substantial heterogeneity for the risk of HF (I
2
=74%; P-interaction <0.0001) but not MACE (I
2
=31%; P-interaction=0.08). Among effective therapies, reduction in MACE risk was confined to patients with established CVD (HR 0.82, 95% CI, 0.77-0.89) with no effect among patients without CVD (HR 1.06, 95% CI, 0.86-1.31; P-interaction=0.02; Figure). Meta-regression showed that every 1 kg change in weight between therapies modified the RR for HF by 4.8% (95% CI 2.5-7.0; P=0.00002).

Conclusion:
An effect on MACE appears confined to secondary prevention whereas an effect on HF appears related to achieved weight change between glycemic therapies.
Abstract 23094: Titin Truncating Variants Predict Life-threatening Arrhythmias in Patients With Dilated Cardiomyopathy
Authors: Corden Ben , Jarman Julian , Whiffin Nicola , Tayal Upasana , Buchan Rachel , Sehmi Joban , Harper Andrew , Midwinter William , Lascelles Karen , Markides Vias , Mason Mark , Pennell Dudley J , Barton Paul J , Prasad Sanjay K , Wong Tom , Cook Stuart A , Ware James S
Published: March 2022

Introduction:
There is an urgent need for better arrhythmic risk stratification in non-ischaemic dilated cardiomyopathy (DCM), where the benefit of ICD implantation is unclear. Titin truncating variants (TTNtv) are the commonest genetic cause of DCM and are associated with early onset non-sustained ventricular tachycardia (NSVT) and atrial fibrillation (AF) in these patients.

Hypothesis:
We hypothesize that TTNtv status can predict potentially life threatening ventricular tachycardia (VT) or fibrillation (VF) and development of new persistent AF in DCM patients with CRT-D or ICD devices.

Methods:
We studied 117 DCM patients with an ICD or CRT-D and documented device-recorded arrhythmia over a median period of 4.2 years. Patients were stratified by TTN genotype (28 positive for a TTNtv, 89 negative). The primary outcome was time to first device-treated VT >200bpm or VF. Secondary outcome measures included time to first development of persistent AF.

Results:
TTNtv predicted the risk of receiving an appropriate ICD therapy for VT/VF (hazard ratio [HR] = 4.9, 95% confidence interval [CI]=2.3-10.7, P<0.0001). This association was independent of all covariates, including replacement fibrosis measured by late-gadolinium enhancement (LGE), (adjusted HR = 8.2, 95% CI 1.9-36.5, P=0.005). Individuals with both a TTNtv and fibrosis had a markedly greater risk for appropriate device therapy than those with neither (HR = 16.6, CI 3.5-79.3, P<0.0001). TTNtv were also a risk factor for developing new persistent AF (HR = 4.4, 95% CI = 1.45-13.1, P=0.006).

Conclusion:
TTNtv status is an important risk factor for clinically significant arrhythmia in patients with DCM and CRT-D or ICD devices. TTNtv status alone, or more powerfully in combination with fibrosis imaging by MRI, may provide an effective approach for risk stratifying the need for ICD therapy in DCM patients.
Abstract 23928: Microrna-125b-5p Protects The Heart From Acute Myocardial Infarction By Repressing Pro-apoptotic Bak1 And Klf13 In Cardiomyocytes
Authors: Aonuma Tatsuya , Bayoumi Ahmed S , Kim Il-man
Published: March 2022

Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy and has been proposed as a biomarker of heart failure. We previously showed using the β-arrestin-biased β-blocker, carvedilol that β1-adrenergic receptor-mediated cardioprotective signaling through β-arrestin1 stimulates processing of miR-125b-5p in the mouse heart (Figure A-C). We hypothesize that β1-adrenergic receptor/β-arrestin1-responsive miR-125b-5p confers cardioprotection against acute myocardial infarction. Using cultured cardiomyocyte (CM) and
in vivo
approaches, we show that miR-125b-5p is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125b-5p exhibit an increased sensitivity to stress-induced apoptosis, while CMs overexpressing miR-125b-5p have increased phospho-AKT pro-survival signaling. Moreover, we demonstrate that loss-of-function of miR-125b-5p in the mouse heart causes abnormalities in cardiac structure and function after acute myocardial infarction. Mechanistically, cardioprotection elicited by miR-125b-5p is in part attributed to repression of the pro-apoptotic genes
Bak1
and
Klf13
in CMs (Figure D). In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction.
Abstract 24015: Genome-Wide Association Study of Vasodilator Response in Pulmonary Arterial Hypertension
Authors: Karnes Jason H , Batai Ken , Arora Amit , Kaye Justin , Steiner Heidi , Nair Vineet , Garcia Joe GN , Yuan Jason , Pauciulo Mike , Nichols William , Desai Ankit
Published: March 2022

Introduction:
Pulmonary arterial hypertension (PAH) is a rare and fatal disease associated with variable therapeutic response, suggesting a genetic contribution. Vasodilator-responsive PAH accounts for a minority of PAH cases and is associated with dramatically improved survival over vasodilator-nonresponsive PAH. The objective of our study was to identify genetic influences on vasodilator drug response in PAH.

Methods:
Two cohorts of patients with Group I PAH confirmed by right heart catheterization were derived from the PAH Biobank (NHLBI R24HL105333), representing over 40 US institutions. Differences between hemodynamics at rest (baseline mean pulmonary arterial pressure, mPAP) and after vasodilator (nitric oxide, prostacyclin) administration were determined to define acute vasodilator drug response (with unchanged cardiac index) as a continuous measure. All cases were genotyped using HumanOmni5 with single nucleotide polymorphism (SNP) call rate >99%, minor allele frequency (MAF)>3%, and Hardy-Weinberg p-value>0.01. Analysis was restricted to cases with European ancestry. We performed linear regressions in an additive model for acute vasodilator drug response with adjustment for baseline mPAP, age, gender, and first 3 principal components. A Bonferroni-corrected alpha=5x10
-8
was used in the discovery cohort and alpha=0.05 was used in the replication cohort.

Results:
The discovery cohort included 434 PAH cases and the replication cohort included 49 less severe PAH cases. QQ-plots showed no evidence of genomic inflation (lambda=1.00). Association of the intronic SNP rs8057488 (MAF 0.05) in the sorting nexin 29 gene (
SNX29
) with acute vasodilator drug response reached genome-wide significance in the discovery cohort (beta= -7.03 mmHg, p=3.39x10
-8
). A significant association between rs8057488 and acute vasodilator drug response was also observed in the replication cohort (beta = -6.48 mmHg, p=0.03).

Conclusion:
These findings implicate a novel association between
SNX29
variation and differential responses to vasodilator treatment in Group I PAH. While requiring further replication in a larger independent cohort, these observations advance our understanding of the molecular underpinnings in PAH.
Abstract 24036: Inhibition Of Prolyl-tRNA Synthetase As A Novel Mediator Of Cardiac Fibrosis
Authors: Park Joon Seok , Lee Caroline H , Yoon Sungjin , Kim Jong Hyun , Kim Sunghoon , Lee Bongyong
Published: March 2022

Introduction:
Prolyl-tRNA synthetase (PRS), a member of aminoacyl tRNA synthetases (ARS), is an enzyme that conjugates amino acid proline to its cognate tRNA to generate prolyl-tRNA to be used in protein synthesis. Since ARS are essential for protein synthesis and viability, dysregulation of ARS has been proposed to many human diseases. Cardiac fibrosis is characterized by excess production and deposition of ECM proteins by activated fibroblast. Although proline is a main component of collagen and ECM proteins, the exact mechanism and involvement of PRS in cardiac fibrosis has not yet been elucidated.

Hypothesis:
We hypothesized that suppression of PRS would down-regulate collagen synthesis, which could be beneficial in cardiac fibrosis.

Results:
To validate our hypothesis, we investigated the expression levels of pro-fibrotic markers by overexpression or knockdown of PRS in vitro. We showed that PRS is closely related to the expression of collagen I and α-SMA. Then, we showed that treatment of DWN12088, a novel small molecular selective inhibitor of PRS, reduced expression levels of pro-fibrotic markers in TGFβ-induced fibrotic environments using various cell-lines and primary fibroblasts. Interestingly, we showed that down-regulation of pro-fibrotic markers by DWN12088 is independent of TGFβ signaling pathway, although TGFβ is required for induction of pro-fibrotic markers. In vivo study, we performed transverse aortic constriction in C57BL/6 mice to evaluate the effect of DWN12088 in cardiac fibrosis. TAC results in pressure overload-induced left ventricular hypertrophy and fibrosis, and it is one of the most widely used models to study cardiovascular diseases. 2-week oral treatment of DWN12088 markedly reduced cardiac fibrosis with ED
50
of 0.4 mg/kg, based on histological examinations. In addition, we demonstrated that 2-week oral treatment of DWN12088 showed reduction in infiltration of inflammatory cells, left ventricle thickness and accumulation of collagen fiber.

Conclusion:
These results suggest that inhibition of PRS attenuates pressure-overloaded cardiac fibrosis and a selective inhibitor of PRS, DWN12088, could serve as a potent anti-fibrotic agent without affecting critical cellular signaling cascade.
Abstract 24070: Cardiac-Specific Overexpression Of Caveolin-3 Expedites Cardiac Relaxation After Adrenergic Stimulation
Authors: Zemljic-Harpf Alice E , Busija Anna R , Joshi Mugdha A , Alas Basheer F , Schilling Jan M , Roth David M , Insel Paul A , Patel Hemal H
Published: March 2022

Introduction:
Caveolae are membrane localized signaling platforms that compartmentalize signal transduction proteins such as GPCRs. Previous studies from our laboratory have demonstrated that overexpression of caveolin-3 in cardiac myocytes (Cav3 OE) protects against pressure-overload induced heart failure. Additionally, Cav3 OE mice present increased heart rate variability with lower nocturnal heart rates, but the mechanisms behind these phenotypes remain unclear.

Hypothesis:
Since Cav3 OE mice are protected from stressful cardiac stimuli, we tested the rationale that Cav3 OE hearts may show altered parasympathetic control of cardiac responses to adrenergic stimulation.

Methods:
Cav3 OE mice and transgene negative littermate controls (Ctrl) (12-16-week-old, n=10-11 each) were anesthetized with isoflurane and cardiac contractility was assessed by echocardiography at baseline. Isoprenaline (Isuprel USP [Iso], 300 nM i.p.) was administered ~10 min after baseline recordings and cardiac function recorded at 2 min, 5 min, and 10-15 min after Iso. The same animal cohort received a single atropine injection (2 mg/kg i.p) 20 min before isoflurane anesthesia and Iso challenge echocardiography was performed as described above.

Results:
At baseline, no differences in cardiac contractility (% ejection fraction, %EF±SD) were detected between the two groups ~68±8 %EF. After Iso injection cardiac contractility was increased to ~91±3 %EF in both genotypes at 2 min; however, in Cav3 OE mice cardiac contractility recovered to 83±3 %EF by 5 min post Iso challenge whereas Ctrl animals maintained increased contractility of 92±3 %EF (p < 0.001). Importantly, Cav3 OE mice pre-treated with atropine no longer showed increased recovery at 5 min or 10-15 post Iso (p = 0.007). A three-way ANOVA of the time-course after Iso injection found a significant effect of atropine on the responses of Cav3 OE versus Ctrl hearts to Iso (p = 0.007).

Conclusion:
We show for the first time that Cav3 OE mice show a faster recovery from hypercontractility after isoproterenol stimulation. Since atropine abrogated this recovery, these data suggest that Cav3 OE mice exhibit increased parasympathetic tone that may be responsible for improved stress adaptation and heart rate variability.
Abstract 24073: Need of Treating Residual Inflammatory Activity in Coronary Heart Disease: the value of high sensitive CRP and LDL in a Real World Cohort.
Authors: Peikert Alexander , Kaier Klaus , Merz Julian , Hassanin Ibrahim Ahmed Fadel Ali , Wolf Dennis , Hilgendorf Ingo , Willecke Florian , Stachon Peter , Zirlik Andreas
Published: March 2022

Introduction:
Inflammation drives atherosclerosis and its complications. Thus, CANTOS as the first anti-inflammatory outcome trial in this population produced positive results. However, it is unclear how many patients qualify for an anti-inflammatory therapy in everyday practice.

Hypothesis:
This study analyzes how many patients with coronary heart disease (CHD) on guideline conform therapy show an increased residual inflammatory as opposed to an increased residual lipid risk in order to define the need for an anti-inflammatory treatment in a real world setting.

Methods:
High sensitive C-reactive protein (hsCRP) and low density lipoprotein (LDL) levels were determined in 700 all comer patients between June 2016 and June 2017 in our center. Patients lacking CHD, such with chronic-inflammatory diseases, acute inflammation, and on immunosuppressive medication were excluded. Patients were divided in the following groups: elevated hsCRP (≥2mg/dl), normal hsCRP (<2mg/dl), off target LDL-cholesterol (≥70mg/dl), on target LDL-cholesterol (<70mg/dl). Univariate logistic regression and backward selection was performed in order to define factors influencing hsCRP.

Results:
From 700 patients 221 fulfilled the inclusion and exclusion criteria. HsCRP was increased in 45% of these patients. Patients with on target LDL Levels showed lower hsCRP concentrations than those with off target values of LDL confirming a positive association between both (1,92mg/dl vs. 3,15mg/dl, p=0.005). However, despite guideline-conform LDL-control 34% of patients with a LDL-cholesterol <70mg/dl had elevated levels of hsCRP (≥2mg/dl) suggestive of residual inflammation. After logistic univariate regression LDL-cholesterol ≥70mg/dl (OR 2.15, p=0.014), heart failure (OR 3.07, p<0.001) and diabetes mellitus (OR 2.22, p=0.021) independently predicted elevated levels of hsCRP. Heart failure (OR 4.56, p<0.001) and diabetes together (OR 3.04, p=0.012) identified as co-predictors increased hsCRP following backward selection.

Conclusions:
A substantial part of patients with CHD shares a residual inflammatory risk defining a need for an anti-inflammatory therapy. Residual inflammation is particularly prevalent in patients with heart failure and diabetes.
Abstract 10002: Risk Factors and Clinical Outcomes of Non-Home Discharge in Patients with Acute Decompensated Heart Failure: An Observational Study
Authors: Washida Koichi , Kato Takao , Ozasa Neiko , Morimoto Takeshi , Yaku Hidenori , Seko Yuta , Yamamoto Erika , Yoshikawa Yusuke , Yamashita Yugo , Kimura Takeshi
Published: March 2022

Background:
No clinical studies have focused on the factors associated with discharge destination in patients with acute decompensated heart failure.

Methods and Results:
Of 4,056 consecutive patients hospitalized for ADHF in the KCHF registry, we analyzed 3,460 patients hospitalized from their homes and discharged alive. There were 3009 and 451 patients who were discharged to home (home discharge) and non-home (non-home discharge), respectively. We investigated the factors associated with non-home discharge and compared the outcomes between home discharge and non-home discharge. Factors independently and positively associated with non-home discharge were age ≥80 years (odds ratio [OR]:1.76, 95% confidence interval [CI]:1.28-2.42), body mass index ≤22 kg/m
2
(OR:1.49, 95%CI:1.12-1.97), poor medication adherence (OR:2.08,95%CI:1.49-2.88), worsening heart failure (OR:2.02, 95%CI:1.46-2.82), stroke during hospitalization (OR:3.74, 95%CI:1.75-8.00), functional decline (OR:12.24, 95%CI:8.74-17.14) and length of hospital stay >16 days (OR:4.14, 95%CI:3.01-5.69), while those negatively associated were diabetes mellitus (OR:0.69, 95%CI:0.51-0.94), cohabitants (OR:0.62, 95%CI:0.46-0.85), and ambulatory state before admission (OR:0.25, 95%CI:0.18-0.36). The cumulative 1-year incidence of all-cause death was significantly higher in the non-home discharge group than in the home discharge group. The non-home discharge group compared with the home discharge group was associated with a higher adjusted risk for all-cause death (HR:1.66, P <0.001).

Conclusions:
The discharge destination of acute decompensated heart failure patients is influenced by factors such as pre-hospital social background, age, body mass index, low self-care ability, events during hospitalization (worsening heart failure, stroke, etc.), functional decline, and length of hospital stay; moreover, the prognosis of non-home discharge patients is worse than that of home discharge patients.
Abstract 10011: Oral Rivaroxaban versus Subcutaneous Enoxaparin in the Prophylaxis of Covid-19 Induced Coagulopathy in Mild to Moderate Sars Cov-2 Infection
Authors: Km Vaishnavi , - Sheeba Chandralekha , Lalchandani Janvi , Kumar Dhiraj
Published: March 2022

Introduction:
Preliminary data highlights the importance of anticoagulation therapy in the prevention and treatment of thromboembolism in SARS CoV-2 infection. There is insufficient data comparing the safety and efficacy of direct oral anticoagulants (DOACs) and subcutaneous enoxaparin in the prophylactic management of COVID-19 associated thromboembolic disease, particularly in mild to moderate cases of COVID-19 infection.

Hypothesis:
Oral rivaroxaban is superior to subcutaneous enoxaparin in the prophylaxis of COVID-19 induced coagulopathy in mild to moderate SARS CoV-2 infection.

Methods:
In this randomized, open-label, prospective, superiority trial involving hospitalized patients with confirmed mild or moderate COVID-19 disease, we began enrolment of 230 patients from 1
st
August 2020 to receive either once-daily oral rivaroxaban (10mg or 15mg) or once-daily subcutaneous enoxaparin (40mg or 60mg) for duration of in-hospital stay (median: 8 days). Patients were randomised in a 1:1 ratio into groups by computer-generated allocation software. The primary outcome was a composite of all major, clinically relevant haemorrhagic and thrombotic events. An intention-to-treat analysis was carried out on the dataset. The trial was registered with Clinical Trials Registry of India (CTRI/2021/05/033871).

Results:
The primary efficacy outcome occurred in 4 of 115 patients in the rivaroxaban group (3.5%) versus 16 of 113 patients in the enoxaparin group (14.2%) (hazard ratio 0.207, 95% confidence interval [CI], 0.069 to 0.621, P=0.005). Adverse events developed in 4.3% of patients in the study group and 12.4% in the enoxaparin group (hazard ratio 0.328; 95% CI, 0.118 to 0.910; P=0.032). Major bleeding was seen in 1 patient (0.9%) in the rivaroxaban group and 3 patients (2.7%) in the enoxaparin group.

Conclusions:
Rivaroxaban alone was superior to enoxaparin for the prophylactic management of coagulopathy associated with mild to moderate SARS CoV-2 infection.
Abstract 10022: Young Adults Hospitalized with Diabetes Remain at 25% Higher Risk of Acute Myocardial Infarction with Cannabis Use Disorder: A Nationwide Matched Analysis
Authors: Desai Rupak , Dyutima Dr , Valdez Confesora , Rueda Maria J , Sanchez Lorannys Y , Spasova Violeta , Castillo Zaymis D , Igbenabor Christiana A , Galan Mirian D , Gandhi Zainab J , Singh Sandeep
Published: March 2022

Background:
The impact of cannabis use on diabetes mellitus and associated cardiovascular events remains understudied. Rising trends in recreational cannabis use in the young prompted us to evaluate the risk and outcomes of acute myocardial infarction (AMI) in young diabetics with cannabis use disorder (CUD).

Methods:
We queried the National Inpatient Sample (2015 October-2017) to identify young adult admissions with diabetes. Demographically (age, sex, and race) matched (1:1) cohorts (CUD+ vs. CUD) were compared for comorbidities and risk of AMI and subsequent inpatient outcomes among young diabetics. Multivariable regression analysis was performed adjusting for confounders.

Results:
Of young adults admitted with diabetes (median 35 [29-40] years, 59.3% male, 42.3% white), demographically matched CUD+ (n=32170) and CUD- (n=32170) cohorts were obtained
(Table 1).
The CUD+ cohort often consisted of non-elective admissions (91.7% vs. 85.45%), Medicaid enrollees (51.6% vs. 38.7%), patients from lower household income quartile (47.9% vs. 43.1%) vs. CUD- cohort and had higher burden of smoking, alcohol abuse, chronic pulmonary disease, depression, psychosis and neurological disorders (p<0.001). On adjusted multivariable analysis, the risk of AMI was 25% higher (OR:1.25, 95%CI:1.02-1.51, p=0.03) in CUD+ cohort, however, there was no significant difference in the subsequent inpatient mortality. Male sex (aOR1.35), non-elective admission (aOR2.46), Medicaid/self-pay enrollment (aOR 2.0/3.8), AIDS (aOR6.24), coagulopathy (aOR1.85), peripheral vascular disease (aOR 1.82), hypertension (aOR 2.12), hyperlipidemia (aOR2.53), smoking (aOR1.78), and obesity (aOR1.36) were independent predictors of AMI.

Conclusion:
Young diabetics with CUD may have 25% higher risk of AMI hospitalizations. Male sex, cardiovascular comorbidities, tobacco smoking, AIDS and coagulopathy independently predicted higher risk of AMI among young diabetics with CUD.
Abstract 10036: An Investigation of Plant-Based, Mediterranean, Paleolithic and Dash Diets on Cardiovascular Disease Risk (VA Beach Diet Study)
Authors: Alex Talreja , Talreja Sophie , Talreja Deepak
Published: March 2022

Introduction:
Cardiovascular disease (CVD) is the leading cause of death in the United States for middle-aged men and women despite the fact that prevention and control of CVD is achievable by modifying risk factors through lifestyle changes and diet therapy. We examined the impact of four diet programs (plant-based (Vegan), Mediterranean, Paleolithic (Paleo) and DASH diets) on the CV risk factor profile of adults in the Hampton Roads area of Virginia.

Hypothesis:
Among the Diets studies, there will be a variable response with regards to impact on lipids.

Methods:
Nondiabetic adults (ages 35-85) with one or more risk factors for CVD were invited to participate in 1 of the 4 diet arms. Participants underwent a comprehensive nutrition education program prior to a 60-day diet intervention in which they kept a daily food log and met weekly with a multi-disciplinary study team. An initial health screen was performed to assess weight, blood pressure (BP), fasting glucose (FPG), A1C, lipids and lipoprotein particles, and repeated after 60 days on the diet and at 6-months follow-up.

Results:
279 subjects completed the 60-day dietary intervention (58 Vegan, 80 Mediterranean, 76 Paleo, 65 DASH), and 199 returned for 6-month follow-up. Most subjects were female, Caucasian, mean age 56, mean BMI 33 kg/m2. At baseline, mean FPG, TG and HDL-C were within the normal range, whereas LDL-P and BP were elevated. After 60 days on the respective diets, subjects lost an average of 9 lbs (4.7% body weight, total 2,576 lbs), which was associated with improvements in BP across all groups. Subjects on the Vegan and Paleo diets lost the most weight (~6.5%) and showed the greatest improvement in lipid risk factors (11-14% decrease in LDL-P; 10-20% decrease in VLDL and TG).

Conclusions:
All four diets promoted weight loss and improved BP but had variable effects on lipid risk factors.
Abstract 10038: Cardiovascular Impact of Immune Checkpoint Inhibitors: A Systemic Review and Meta-Analysis
Authors: Ayub Muhammad , Farooq Muhammad , Arif Abdul Wahab , Ba Aqeel Sheeba , Almani Muhammad , Mangla Ankit , Okwuosa Tochi M , Santos Volgman Annabelle
Published: March 2022

Introduction:
Immune checkpoint inhibitors (ICIs) have become the cornerstone for treatment of advanced malignancies and have led to long-term tumor responses and improved survival. The body’s immune response to ICIs can lead to unintended consequences (immune-related cardiovascular adverse effects) sometimes involving the heart.

Methods:
Embase, Ovid, PubMed, and Scopus were searched for ICI randomized phase II or III clinical trials reporting adverse cardiovascular events with combination or monotherapy ICIs (experimental arm) and placebo or standard of care chemotherapy (control arm). The primary outcome was cumulative incidence of cardiovascular adverse effects, and secondary outcomes were isolated incidence of hypertension, myocardial infarction, myocarditis and pericardial effusion. Statistical heterogeneity was quantified using

I
2

statistics. Publication bias was assessed with Egger’s regression test. P-value of 0.05 was deemed as statistically significant.

Results:
Twenty studies (N=13,525) met the inclusion criteria. The studies included 1 small cell and 8 non-small cell lung, 3 renal cell, 1 head & neck, 1 colorectal and 1 prostate cancer with 2 malignant melanoma, 2 multiple myeloma, and 1 mesothelioma. There were 7434 (54.96%) and 6091 (45.04%) patients in the ICI and non-ICI arms, respectively. There was no statistically significant difference in reported cardiovascular toxicity with ICI compared to placebo or standard of care (OR 0.953 95% CI 0.542-1.675, I
2
=89.49 p<0.001). There was no statistical difference in incidence of HTN (OR 0.543, 95% CI 0.219-1.346. I
2
=94.98, P<0.001), pericardial effusion (OR 1.44, 95% CI 0.72-2.90. I
2
=0%, P=0.613), MI (OR 0.76, 95% CI 0.76-3.298 I
2
0%, P=0.83) and myocarditis (OR 2.12, CI 0.638-7.055, I
2
=0%, P=0.185).

Conclusions:
This meta-analysis demonstrates no significant difference in cardiovascular adverse effects in ICI group when compared to placebo or standard of care.
Abstract 10045: Higher Morbidity, Mortality and Healthcare Resource Utilization in Admissions for Congestive Heart Failure with Concomitant Aspiration Pneumonia: National Inpatient Sample Analysis
Authors: Jain Akhil , Jindal Rishabh , Agarwal Charu , Mudgal Gaurav , Varughese Vivek Joseph , Raju Athul Raj , Jnaneswaran Geethu , Gandhi Zainab J , Desai Rupak
Published: March 2022

Introduction:
Data on the burden of congestive heart failure (CHF) in aspiration pneumonia (AP) patients is sparse. Our aim is to study the burden, morbidity and outcomes of CHF on AP patients.

Methods:
We queried the National Inpatient Sample (2015 October-2017) to identify admissions for AP in patients with CHF vs without CHF using relevant ICD-codes. Primary outcomes reported were all-cause mortality and pulmonary morbidity. Secondary outcomes included patient disposition, LOS and utilization of hospital resources.

Results:
We included 14,38,034 aspiration pneumonia (AP) hospitalizations amongst which 3,33,975 had associated CHF (23.2%). AP-CHF cohort often included older (79 [68-87]), white (74.8% vs 72.6%), male (54.7% vs 45.3%) patients admitted non-electively with Medicare insurance at Urban teaching facilities compared to AP only cohort (p<0.001)
(Table 1)
. AP-CHF cohort was more often associated with valvular disease, pulmonary circulation disease, peripheral vascular disease, chronic pulmonary disease, hypertension (secondary/complicated), diabetes mellitus, hyperlipidemia and obesity compared to AP-only cohort. AP-CHF cohort had lower rates of alcohol abuse, drug abuse and smoking. AP- CHF cohort had higher adjusted odds of all-cause mortality (aOR 1.14 95% CI 1.13-1.15, p<0.001), ARDS (aOR 2.27), respiratory failure (aOR 1.77), severe sepsis with septic shock (aOR 1.34) and requirement of respiratory support (aOR 1.40) compared to AP only cohort. AP-CHF cohort was more often discharged to short-term or intermediate facility and had longer stay with higher hospital charges compared to AP only cohort.

Conclusion:
Based on our analysis it can be concluded that nearly one-fourth of AP hospitalizations have concomitant CHF and that is associated with higher morbidity, mortality and complications ultimately leading to higher hospital resource utilization.
Abstract 10079: Risk of Cardiovascular and All-Cause Mortality in Patients with Myeloproliferative Neoplasms Following Heart Failure Hospitalization
Authors: Leiva Orly , Bhatt Ankeet , Jenkins Andrew , Rosovsky Rachel , Karp-Leaf Rebecca , Goodarzi Katayoon , Hobbs Gabriela
Published: March 2022

Introduction:
Myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocytosis (ET) and myelofibrosis (MF), are clonal stem cell neoplasms that commonly harbor the JAK2V617F mutation. Recent preclinical studies suggest that the JAK2V617F mutation in hematopoietic stem cells accelerates pathologic cardiac remodeling, potentially contributing to HF. However, the prognostic significance of HF hospitalization in MPNs has not been studied.

Methods:
Single-center, retrospective cohort study of patients with MPN with ≥ 1 HF hospitalization after MPN diagnosis from 2000-2020 (N = 105, 39 ET, 39 PV, 27 MF). Our outcomes were death (cardiovascular [CV] and all-cause mortality [ACM]) and recurrent HF hospitalization after index hospitalization. To assess predictors of CV death and ACM, we used a multivariable logistic regression using age, sex, LVEF ≥ 50% at index event, cardiology follow-up 3 months after index, pulmonary hypertension (PH) before index, MF, treatment of MPN, NT-proBNP at index, CAD, hypertension, prior stroke, diabetes, and arterial thrombosis (AT) after index (stroke or MI) as co-variables.

Results:
After median follow-up time of 19 months (IQR 5, 19, full characteristics in Table), CV death, ACM, recurrent HF, AT occurred in 30%, 55%, 54%, 12%, respectively. After multivariable regression, recurrent HF (aOR 5.3, 95% CI 1.7-19.3), PH (aOR 3.2, 95% CI 1.0-10.7) and AT (aOR 4.4, 95% CI 1.1-21.5) were associated with increased odds of CV death. Close cardiologist follow-up (aOR 0.2, 95% CI 0.05-0.7) and LVEF ≥ 50% (aOR 0.3, 95% CI 0.1-0.9) were associated with decreased odds of CV death. Only recurrent HF was associated with increased odds of ACM (aOR 2.5, 95% CI 1.0-6.5).

Conclusions:
Patients with MPN who have multiple HF hospitalizations have high rates of CV death and ACM. Closer cardiology follow-up pre and post HF hospitalization may improve outcomes in this population and more research is needed to improve cardiovascular outcomes.
Abstract 10091: Fine Fibrillatory Wave as a Risk Factor for Heart Failure Event in Atrial Fibrillation Patients: The Fushimi Af Registry
Authors: Kawaji Tetsuma , Ogawa Hisashi , Hamatani Yasuhiro , Kato Masashi , Yokomatsu Takafumi , Miki Shinji , Abe Mitsuru , Akao Masaharu ,   the Fushimi AF Registry investigators
Published: March 2022

Introduction:
The clinical significance of fibrillatory (F) wave on electrocardiogram during atrial fibrillation (AF) is poorly understood.

Hypothesis:
We assessed the hypothesis that fine F wave was associated with heart failure (HF) event in AF patients.

Methods:
The current study enrolled 2442 AF patients whose baseline electrocardiogram during AF rhythm was available from a Japanese community-based prospective survey, the Fushimi AF Registry. The impact of fine F wave, defined as the amplitude of F waves less than 0.1mV, on the primary composite HF endpoint (a composite of hospitalization due to HF and cardiac death) was examined.

Results:
Fine F wave was observed in 589 patients (24.1%). Patients with fine F wave were older, and had higher prevalence of sustained AF, pre-existing HF and larger left atrial diameter than those with coarse F wave. During the median follow-up duration of 5.9 years, the cumulative incidence of a composite of hospitalization due to HF and cardiac death was significantly higher in patients with fine F wave than in those with coarse F wave (33.3%, and 23.9% at 8 years, log-rank P<0.001: Figure). The higher risk associated with fine F wave was consistent even for individual components of the primary composite HF endpoint. By multivariable analysis with 11 clinically relevant variables, fine F wave became an independent predictor for the primary composite HF endpoint (hazard ratio 1.31, 95% confidence interval 1.07-1.61, P=0.01).

Conclusions:
Compared with coarse F wave, fine F wave was more prevalent in patients with larger left atrial diameter or those with sustained AF, and was independently associated with higher risk for HF events.
Abstract 10094: National Trends in Deaths Due to Heart Disease and Cancer in the Elderly: 20 Year-Data
Authors: Minhas Abdul , Qavi Ahmed H , NAZIR SALIK , Dani Sourbha , Siddiqi Tariq Jamal , Usman Muhammad , Figueredo Vincent M , Fudim Marat
Published: March 2022

Heart disease and cancer are the two leading causes of death in the United States. The aim of this study was to examine the trends in heart disease and cancer-related deaths in the elderly population in the United States from 1999 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 1999 to 2019. Heart and cancer-related deaths, age >/=75 years, and sex were identified. Deaths were represented as age-adjusted mortality rates (AAMR) per 100,000 population. Joinpoint regression was used to examine changes in trend and annual percentage change (APC) overall.

Results:
AAMR related to heart disease decreased from 4587 in 1999 to 3235.6 in 2019 (average APC -1.8[95% CI, -1.9 to -1.6]). AAMR was higher in men (4375.6) than women (3287). Among the racial/ethnic groups, AAMR was highest in non-Hispanic Blacks (NHBs) (3926.2). APC in AAMR decreased across all the subgroups. After initial decline, the decrease in APC in AAMR decelerated overall (-0.7) and in both women (-0.9) and men (-0.7) since 2011.

AAMR related to cancer decreased from 1770.51 in 1999 to 1379.91 in 2019 (average APC -1.3[95% CI, -1.3 to -1.2]). AAMR was higher in men (2104) than women (1262.7). Among the racial/ethnic groups, AAMR was highest in NHBs (1695.2). APC in AAMR decreased across all the subgroups. After an initial decline, the decrease in APC in AAMR accelerated overall (-1.5) and in men (-1.9) since 2007 and in women (-1.3) since 2006.

Conclusion:
Heart disease and cancer related mortality in elderly has been decreasing at a variable pace over the last twenty years. The decrease in the heart disease related mortality has decelerated in last several years whereas the decline in cancer related mortality has decelerated. Further research with targeted interventions in both these diseases is needed.
Abstract 10102: Duration of Disease and the Quality of Life of the Patients with Atrial Fibrillation
Authors: Nakamaru Ryo , Ikemura Nobuhiro , Spertus John , Kimura Takehiro , Katsumata Yoshinori , Fujisawa Taishi , Miyama Hiroshi , Fukuda Keiichi , Takatsuki Seiji , Kohsaka Shun
Published: March 2022

Introduction:
Several recent studies have reported that early rhythm control for atrial fibrillation (AF) was associated with a lower risk of adverse cardiovascular outcomes than usual care. However, the effects of early intervention for AF on patients’ reported quality of life (QOL) in real-world patients, outside of selected clinical trials, have not been investigated.

Methods:
We analyzed 2,892 patients from a prospective, multicenter registry of consecutive AF patients (KiCS-AF) enrolled between 2012 to 2018 in Japan. Patients were divided into quartiles according to their AF duration (time interval between AF diagnosis and referral to the cardiology service; Q1 median 0 days [IQR:0-0], Q2 14 [7-22], Q3 119 [55-329], Q4 1968 [1122-3590]). The quartiles of AF duration were then compared with patients’ QOL improvement, as assessed by changes in the Atrial Fibrillation Effect on Quality-of-Life-overall summary score (AFEQ-OS [0 to 100]; higher score reflecting better QOL) over 1 year after the treatment initiation with analysis of covariance adjusted for differences in baseline characteristics.

Results:
Patients with the shortest duration of AF (Q1) were more likely to be older, female, and to have a higher incidence of heart failure compared with other groups. At 1 year, patients had improved AFEQT-OS scores, regardless of AF duration (adjusted difference [standard error], Q1, 8.2 [0.6], Q2 8.7 [0.6], Q3 8.7 [0.5], Q4 8.0 [0.5], p=0.67). The adjusted differences were similar in patients that underwent rhythm- (Q1 12.3 [0.7], Q2 12.2 [0.7], Q3 10.9 [0.7], Q4 12.2 [0.7], p=0.41) or rate-control strategy (Q1 3.3 [0.7], Q2 4.4 [0.8], Q3 4.5 [0.7], Q4 3.7 [0.8], p=0.64: Figure).

Conclusions:
The duration of AF was not associated with QOL improvement, regardless of treatment strategy. For symptomatic patients, the duration of AF should not be a deterrent to treatment.
Abstract 10103: The Prognostic Impact of D-dimer on Long-Term Mortality in Patients with Coronary Artery Disease After Percutaneous Coronary Intervention
Authors: Kurosawa Yuta , Shimizu Takeshi , Muto Yuki , Kimishima Yusuke , Misaka Tomofumi , Yoshihisa Akiomi , Yamaki Takayoshi , Kunii Hiroyuki , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: March 2022

Background:
D-dimer is one of common measurable coagulation markers, that is associated with the risk of thrombotic events in vascular diseases. However, the impact of D-dimer on long-term mortality in coronary artery disease (CAD) patients remains unclear. Here we investigated the association between D-dimer and long-term mortality in CAD patients.

Methods and Results:
Consecutive 1440 patients with CAD who underwent percutaneous coronary intervention and survived to discharge were enrolled. We divided these patients into three groups based on plasma D-dimer levels at admission: first (D-dimer < 0.7 μg/ml, n = 455), second (0.7 ≤ D-dimer < 1.2, n = 453), and third (1.2 ≤ D-dimer, n = 532) tertiles. We compared clinical characteristics among three groups, and prospectively followed all-cause, cardiac, non-cardiac and cancer mortalities. Clinical characteristics for three groups were as follows; mean age (first tertile, second tertile, third tertile; 61.3 ± 11.3, 69.0 ± 10.8, 72.4 ± 10.8 years, P < 0.001), prevalence of chronic kidney disease (31.6%, 36.0%, 61.3%, P < 0.001), anemia (25.1%, 39.7%, 64.5%, P < 0.001), atrial fibrillation (10.8%, 14.1%, 19.7%, P < 0.001), peripheral artery disease (4.8%, 12.4%, 18.8%, P < 0.001) and heart failure (27.0%, 33.1%, 51.9%, P < 0.001). In the Kaplan-Meier analysis (mean follow-up periods 1572 days), all-cause, cardiac, non-cardiac and cancer mortalities were significantly higher in third tertile than others (P < 0.01, P < 0.01, P < 0.01 and P < 0.01, respectively). In the multivariable Cox proportional hazard analyses after adjusting for confounding factors, the high D-dimer level was an independent predictor of all-cause, cardiac, non-cardiac and cancer mortalities (HR 3.62, P < 0.01; HR 3.50, P < 0.01; HR 3.69, P < 0.01; and HR 3.17, P = 0.02).

Conclusion:
D-dimer is associated with long-term cause-specific mortality in CAD patients.