bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18486: Serial Measurements of High-Sensitive Cardiac N-terminal Pro B-type Natriuretic Peptide Predict Prognosis of Ambulant Chronic Heart Failure Patients: Results of the Bio-shift Study
Authors: van Boven Nick , Battes Linda C , Akkerhuis K M , Caliskan Kadir , Langstraat Jannette , Rizopoulos Dimitris , Boersma Eric , Umans Victor A , Kardys Isabella
Published: July 2021

Introduction:
N-terminal pro B-type natriuretic peptide (NT-proBNP) has prognostic value in chronic heart failure (CHF) patients, but most studies evaluated single or few measurements only.

Hypothesis:
We think that longer term NT-proBNP patterns in CHF patients facilitate assessing prognosis.

Methods:
From 2011 to 2013, 263 ambulant CHF patients were included in 2 hospitals. NT-proBNP was measured at baseline and every 3 months. The primary endpoint (PE) comprised heart failure (HF)-hospitalization and cardiovascular mortality. The association between NT-proBNP pattern and the PE was assessed by a statistical method that combines a mixed model, describing temporal evolution of NT-proBNP, with Cox proportional hazards regression.

Results:
Mean age was 67 (SD 13) years, 72% were men and 27% were NYHA class III-IV. During a median follow-up of 1.0 (IQR 0.6-1.4) years 885 samples (median 3 (IQR 2-5) per patient) were drawn. The PE was reached in 41 patients (16%). Median baseline NT-proBNP was 137 (IQR 50-274) ng/L, which was higher in patients with PE than in those without (297 (IQR 186-687) ng/L vs. 110 (IQR 38-235) ng/L; age- and sex adjusted hazard ratio (HR) for doubling of baseline NT-proBNP: 1.21; 95% CI 1.13-1.30). The median of the last NT-proBNP before a PE was 308 (IQR 201-831) ng/L. Age- and sex adjusted NT-proBNP increased before an event, and this temporal pattern was associated with increased risk of PE: doubling of NT-proBNP over time resulted in 2.09 times increased risk (95% CI 1.71-2.56).

Conclusions:
Temporal patterns of NT-proBNP are associated with HF-hospitalizations and cardiovascular mortality in CHF patients. NT-proBNP was steady in stable patients, but increased before an event. This pattern was expected based on clinical experience, yet has never been quantified prospectively.
Abstract 18521: Sensory Neuropathy Jeopardizes Nociceptive-mediated Liberation and Homing of Stem Cells in Mice and Patients With Diabetes
Authors: Dang Zexu , Maselli Davide , Spinetti Gaia , Sambataro Maria , Seganfreddo Elena , Quaini Federico , Rowlinson Jonathan , Lorusso Bruno , Reni Carlotta , Fadini Gian P , Madeddu Paolo
Published: July 2021

Introduction:
Diabetic sensory neuropathy (SN) causes either unbearable pain or lack of ischemic pain perception. It remains unknown if SN affects bone marrow (BM) with consequence for stem cell (SCs) liberation upon tissue injury. We reported that ischemia induces the liberation of Lineage
-
Sca-1
+
c-kit
+
(LSK)SCs co-expressing the SP receptor NK1 (LSK-NK1)
via
a neuronal circuitry projecting to the BM and a humoral mechanism consisting of the generation of a chemoattractant gradient of Substance P (SP) between the circulation and BM. We hypothesize that SN might contribute to faulty SC liberation in diabetes.

Results:
Nociceptive fibers coexpressing SP and NGF are reduced in BM of type 1 (T1D, streptozotocin-induced) and type 2 diabetic (T2D, Leptin-receptor knockout) mice compared with controls. BM SN was prevented by systemic AAV-mediated NGF gene therapy. Upon induction of limb ischemia, a gradient of SP is created between skeletal muscle>circulation>BM in non-diabetic mice, which associates with LSK-NK1 cell liberation and homing to the ischemic limb. These phenomena are abrogated in T1D mice. Furthermore,
in vitro
SP-induced migration of BM LSK-NK1 cells is reduced in T1D mice (
P
<0.05 vs. ND mice). For clinical translation, we studied the association of SN and SC liberation in T2D with or without vascular complications. Sensory fibers were found reduced in BM of T2D patients. In addition, critical limb ischemia fails to create an SP gradient and induce CD34+NK1+ SC release. Pain is an acknowledged side effect of BM stimulation by granulokines. We found that BM stimulation with G-CSF fails to induce CD34+NK1+ SC liberation in T2D patients, with this phenomenon being directly correlated to pain score and increase in SP levels.

Conclusions:
We are the first to show that diabetes is associated with NGF-sensitive BM SN in animal models and humans. Two nociceptive mechanisms fail following ischemia or granulokine stimulation: the ability of nerve terminals to coordinate SP release between periphery and BM and responsiveness of NK1 SCs to SP-induced chemoattraction. These findings open new avenues to rescue diabetic SC mobilopathy and thereby encourage vascular repair.
Abstract 18525: Effects of Statin Therapy on Ascending Aorta Aneurysms Growth: a Propensity-matched Analysis of 828 Patients
Authors: Angeloni Emiliano , Refice Simone , Vitaterna Angelo , Lombardo Paola , Pirelli Michele , Melina Giovanni , Sinatra Riccardo
Published: July 2021

Introduction:
Pleiotropic effects of statins have been advocated for remodelling of the vascular wall.

Hypothesis:
Whether statin therapy influences the growth rate of ascending aorta (AA) aneurysms.

Methods:
A total of 1348 patients was referred to our outpatient clinic for initial AA ectasia from September 2005 to December 2010. A propensity score was built to perfectly match (1:1) patients administered (Group A) or not (Group B) with statin therapy. Clinical and echocardiographic follow-up was 100% completed at 3 years after the first visit. Treatment groups were investigated for differences in AA maximum diameter, furthermore rates of survival free from death and/or complications were assessed by Kaplan-Meyer analysis.

Results:
Finally, two fairly-comparable groups of 414 patients each were obtained (Propensity model c-statistic 0.84, p<0.0001). No significant differences were noted in baseline characteristics, mean AA diameters were 40.9±2.6 mm and 40.7±2.5 mm in Group A and B, respectively. At 3-years, similar rates of hypertension control (84±9% vs. 83±11%) were found, whilst growth rate of AA diameter was +22.3±9.4 mm in Group A (+7.4 mm/year) and +26.5±8.4 mm (+8.8 mm/year) in Group B (p=0.0001). Three-year survival free from the composite outcome (death, dissection/rupture, need for operative repair) was found to be significantly improved in Group A (64±4%) rather than in Group B (53±5%), with a log-rank p=0.002 (HR 0.41, 95%CI 0.37 to 0.48).

Conclusions:
In this study, statin treatment is associated with reduced growth rate of ascending aorta aneurysms. The latter resulted in better survival free from complications for patients receiving statins.
Abstract 18543: Whole Exome Sequencing in Sudden Infant Death Syndrome Identifies a High Proportion of Putative Pathogenic and Functionally Significant Rare Variants Related to Inherited Cardiac Conditions
Authors: Wong Leonie C , Simpson Michael A , Tester David J , FitzPatrick David R , Tfelt-Hansen Jacob , Bevan Steve , Ware James S , Evans Margaret J , Fleming Peter J , Platt Craig C , Jeffrey Iona J , Cohen Marta C , Ackerman Michael J , Behr Elijah R
Published: July 2021

Introduction:
Sudden Infant Death Syndrome (SIDS) is defined as the sudden death of an infant which remains unexplained after comprehensive clinical and pathological assessment. Prior studies have implicated inherited cardiac conditions (ICC).

Hypothesis:
Whole exome sequencing will identify a significant burden of putative pathogenic (PP) and rare functionally significant (RFS) cardiac genetic variants in SIDS.

Methods:
96 SIDS cases with complete phenotypic data were selected from 434 cases. Prone sleeping position was excluded to enrich for genetic risk. Genomic DNA underwent target enrichment using Agilent SureSelect Human All Exon v5 kit and sequencing on Illumina HiSeq. Reads were aligned to GRCh37 reference genome with Novoalign and variants called with SAMtools. Principal component analysis identified 82 cases of North European (NE) ancestry. Variants were annotated with Annovar and compared to control data from a local exome database, 1000 Genomes and ESP. Analysis focused on 83 known ICC susceptibility genes (27 channelopathy-associated [CH]; 56 cardiomyopathy-associated [CM]). PP was defined as ultra rare nonsense or frameshift mutations or other variants previously reported as disease-associated and absent in controls. RFS was defined as variants with abnormal functional characterization and <0.5% prevalence in controls.

Results:
20/82 cases (24%) carried at least 1 PP/RFS variant: 12 CH variants in 9 genes (AKAP9, ANK2, CACNB2, CAV3, KCNE2, RYR2, SCN5A, SNTA1, TRDN) in 13 cases; 7 CM variants in 5 genes (ABCC9, ACTN2, CSRP3, TCAP, TTN) in 8 cases. Variants were most commonly identified in the 3-6 months age group (p=0.009). There were no other significant phenotypic differences between variant-positive and negative cases (Table 1).

Conclusions:
There was an 11% yield of PP variants in non-prone sleeping SIDS cases of NE ancestry, with an additional 13% hosting RFS variants. These may provide a potential substrate in the pathophysiology of SIDS.
Abstract 18572: Sleep Duration is Associated with Degree of Insulin Resistance in a High Risk Population: the Baptist Employee Healthy Heart Study
Authors: Ali Shozab S , Oni Ebenezer , Aneni Ehimen C , Roberson Lara , Post Janisse , Nagi Gagandeep , Shaharyar Sameer , Jamal Omar , Malik Rehan , Aziz Muhammad , Younus Adnan , Rosell Beatriz , Guzman Henry , Cury Ricardo , Fialkow Jonathan , Agatston Arthur S , Veledar Emir , Feldman Theodore , Nasir Khurram
Published: July 2021

Introduction:
Metabolic syndrome, the clustering of multiple cardiovascular risk factors, is established as a risk factor for CVD. Shorter or longer sleep duration has been reported to be associated with increased risk of metabolic syndrome (MS) and diabetes mellitus (DM) through increased insulin resistance (IR). However, it is not known if impaired sleep alters IR in a high-risk population with known MS/DM.

Methods:
The Baptist Employee Healthy Heart Study is an ongoing lifestyle intervention study examining the effects of web-based interventions on reducing CVD risk in individuals with MS/DM. Sleep duration was self reported by the participants. Daily sleep duration was categorized into sleep <7 hours (short), 7 to 8 hours (normal) and >8 hours (long). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting insulin and fasting glucose level.

Results:
The population consisted of 182 participants (74% women, 49% Hispanic, mean age 52 ± 9 years). In this study the mean sleep duration was 7±5 hours and mean HOMA-IR was 5.2 ± 5.6 units. Systolic and diastolic blood pressure, BMI, waist circumference, total cholesterol level and LDL cholesterol level did not apparently differ across the groups. Both short and long sleepers tended to have lower HDL cholesterol level and higher triglyceride level (p<0.05). The mean HOMA-IR was significantly higher in short and long sleepers {7-8hrs (4.09±4.8); <7hrs (5.36±4.7); >8hrs (9.52±10.7), p<0.001}, and were more likely to have HOMA-IR in the highest quartile as compared to normal sleepers. In ordinal logistic regression, after adjustment for traditional risk factors, short and long sleepers were at 2-3 fold higher risk of increasing levels of HOMA-IR.

Conclusions:
In this study of high metabolic risk individuals, sleep duration was associated with increased insulin resistance and highlights the importance of improving sleep hygiene in the clinical management of high risk individuals with MS and DM.
Abstract 18615: Subclinical Thyroid Dysfunction, Rather than Low-T3 Syndrome, is an Independent Predictor of Adverse Cardiac Events in Patients with Acute Decompensated Heart Failure
Authors: Hayashi Tomohiro , Hasegawa Takuya , Kanzaki Hideaki , Funada Akira , Amaki Makoto , Ohara Takahiro , Sugano Yasuo , Yasuda Satoshi , Ogawa Hisao , Anzai Toshihisa
Published: July 2021

Background:
Altered thyroid hormone metabolism characterized by low triiodothyronine (T3) levels is a common finding in patients with severe systemic diseases, called low T3 syndrome (LT3-S). Additionally, subclinical thyroid dysfunction, defined as abnormal thyroid-stimulation hormone (TSH) and normal thyroxine (T4) levels, causes left ventricular dysfunction. However, the prevalence and prognostic impact of LT3-S and subclinical thyroid dysfunction in patients with acute decompensated heart failure (ADHF) have not been investigated.

Methods:
We examined consecutive 287 patients with ADHF who received thyroid function tests and no thyroid medications at admission (age 69±15 years, 166 male). Thyroid dysfunction was defined as follows: LT3-S as free T3< 4.0 pmol/L; euthyroidism as TSH of 0.45 to 4.49 mIU/L; subclinical hypothyroidism (Sc-hypo) as TSH of 4.5 to 19.9 mIU/L; subclinical hyperthyroidism (Sc-hyper) as TSH< 0.45mIU/L with normal free T4 levels for the last two. We sought to investigate the impact of the indices of thyroid function and the thyroid disorders above to predict cardiac death and re-hospitalization for heart failure after discharge.

Results:
At admission for ADHF, 155 patients (54%) showed LT3-S, and 62 (22%) Sc-hypo, and 5 (2%) Sc-hyper, and 196 (68%) euthyroidism. Cox proportional hazards model analysis revealed that TSH and fT4, not fT3, were independent predictors of adverse cardiac events among variables including age, sex, estimated glomerular filtration rate, left ventricular ejection fraction and B-type natriuretic peptide. Indeed, Sc-hypo was an independent predictor (HR 2.21, 95% CI 1.41-3.43, p< 0.001), whereas LT3-S and SC-hyper was not (p = 0.49 and 0.24, respectively).

Conclusion:
Although LT3-S was observed in about half of ADHF patients, the presence of LT3-S did not indicate poor prognosis after discharge. Meanwhile, Sc-hypo at admission was an independent predictor of adverse cardiac events in ADHF patients.
Abstract 18631: Delayed Recognition of Cardiac Arrest in Emergency Medical Dispatch - Best Source of Key Information for System Improvement?
Authors: Hardeland Camilla , Soilammi Linda , Hansen Andreas E , Olasveengen Theresa M
Published: July 2021

Background:
Measuring emergency medical dispatch performance is important for both quality control and clinical outcome. Recognition of cardiac arrest is one of the key metrics when evaluating performance as it is essential for initiation of bystander CPR. It is commonly reported as either recognized or not recognized without any benchmarked definition or time limit. Little is known about the extent of delayed recognition, and if these initial delays lead to clinically relevant delays in CPR.

Methods:
Prospective, observational study of cardiac arrest calls during a 1 year period in Oslo and Akershus Emergency Services. Dispatch logs, ambulance records and audio files were analyzed. Recognition of cardiac arrest was reported as (1) recognized, (2) not recognized and (3) delayed recognition. Delayed recognition was defined as failure to initially clarify consciousness or abnormal breathing before moving on to further questioning regarding other symptoms or patient history. Calls across all three groups were purposefully selected, and respective dispatchers invited for interviews based on the calls they had experienced.

Results:
500 cardiac arrest calls were processed of which 289 calls were included for further analysis as the dispatcher had the opportunity to recognize cardiac arrest and initiate CPR instructions. 74% of cases were recognized, 13% were not recognized and in 13% recognition was delayed. Median time to bystander CPR (first compression performed) was 2,6 (range 0.9,12.3) minutes when cardiac arrest was recognized and 5,1 (range 2.9,9.7) minutes when recognition was delayed. Interviews after calls where cardiac arrest was not recognized or delayed in recognition yielded insight into challenging areas for the dispatchers such as agonal breathing, handling health care workers as callers and non-compliance with protocol that have impacted future training and education.

Conclusion:
Delayed dispatch recognition of cardiac arrest is common and leads to significant delays in chest compressions. Emergency medical dispatch systems committed to improving cardiac arrest outcomes need to identify and explore all calls that challenge the system, not only those where cardiac arrest is not recognized.
Abstract 18651: Osteopontin RNA Aptamer Reverses Heart Failure and Increases Plasma HDL Levels
Authors: Li Jihe , Singh Jayanti , Kurlansky Paul , Shehadeh Lina A
Published: July 2021

Objective:
Osteopontin (OPN) expression increases in the heart during hypertrophy and heart failure and in the aorta during atherosclerosis. OPN KO mice were reported to have a reduced hypertrophic response after trans-aortic constriction (TAC), and a reduced plaque burden on an APOE-/- background. We hypothesized that an RNA aptamer targeting OPN protein would effectively modulate the responses to TAC and atherogenesis.

Method and Results:
C57BL6 male mice were subjected to sham or TAC surgeries. TAC mice were injected starting day1 with OPN RNA aptamer or mutant OPN aptamer. At 4wks, OPN aptamer treatment increased %EF (25%) relative to mut control (n=13, p<.01). This significant cardiac improvement was sustained at 8 wks (n=7) and 12wks (n=4-7). WGA and PR staining showed respectively that the OPN aptamer significantly reduced myocyte size (.8 fold at 4wks and 0.7 fold at 12 wks) and cardiac fibrosis (0.4 fold at 4wks and 0.3 fold at 12 wks). In 4 and 12wk LVs and RVs, OPN aptamer reduced Nppb, Nppa, Opn, Fn1, Col3a1, and Lum transcripts (n=3-6 - p<.05). At 12 wk, FN1 protein was reduced in the LVs and RVs by the OPN Apt (n=3 p<.05) and serum HDL was increased (20% p=.001; n=5-7). In 6 mo APOE-/- mice, systemic injections of OPN aptamer also increased plasma HDL (13%; p=.02; n=8-10).To assess effect of OPN aptamer on reversal of cardiac remodeling, at 8 wks post TAC (n=3-4), cardiac function was assessed followed by a total of 7 OPN aptamer injections (one every other day), and then assessed again at 10 wks. The OPN aptamer improved %EF in TAC mice (.6 fold p=.02 TAC vs Sham before treatment to .85 fold p=NS after treatment). In wild type but not OPN KO neonatal mouse cardiomyocytes-fibroblast co-culture, 16h treatment with FAM-labeled OPN aptamer, followed by Phalloidin and TNT staining, showed successful intracellular uptake of the OPN aptamer by cardiac myocytes and more so by fibroblasts.

Conclusion:
OPN RNA aptamer protected against and reversed cardiac dysfunction in a mouse TAC model of cardiac hypertrophy, and increased serum HDL in WT and APOE-/- mice. The cardioprotective effect of the OPN aptamer, together with the efficient uptake by cardiac myocytes and fibroblasts make it a promising therapeutic molecule and a potential platform for targeted RNA delivery into the heart.
Abstract 18655: Efficacy of Cardiac Computerized Tomographic Angiography in the Evaluation of Patients with Cocaine-Induced Chest Pain: A Pilot Randomized Trial
Authors: Peralta Richard , Yoon Andrew , Atoui Moustapha , Mejia Karomibal , Afshar Maryam , Min James , Bella Jonathan N.
Published: July 2021

Background:
Cocaine-induced chest pain (CICP) is reported in 40% of patients using cocaine and is associated with frequent emergency room visits and hospital admissions.

Hypothesis:
Coronary computed tomographic angiography (CCTA) has better outcomes than standard-of-care (SOC) for the evaluation of patients with CICP.

Method:
CICP patients were randomized to CCTA protocol or SOC. The primary outcome of the study was a composite of recurrent emergency room visits and hospital admissions. Secondary outcomes included length of stay, major adverse cardiovascular events and all-cause mortality.

Results:
The study population consisted of 202 patients with CICP (CCTA=23 and SOC=179). As compared to SOC, the number of emergency room visits in the CCTA group were lower at 30 days (1.04±0.1 vs. 1.24±0.5, p=0.012) and 1 year (2.43±0.9 vs. 2.61±2.1, p=0.008), but not at 3 years (5.04±3.3 vs. 4.87±1, p=0.112) findings that were independent of CCTA results. Mean admission rates for the CCTA group were slightly but not significantly lower than the SOC group at 30 days (0.91±0.1 vs.1.10±0.2 p=0.438) and 1 year (1.52±0.3 vs. 1.82±0.3 p=0.187), but not at 3 years (3.22±0.6 vs. 2.95±0.5, p=0.111). Hospital length of stay was also lower in CCTA patients than in SOC patients (2.61±0.5 vs. 3.34 ± 0.5 p<0.001). After 3 year follow-up, there was 1 major adverse cardiovascular event in the CCTA group compared to 22 in the SOC group (p=0.024). No patient died in the CCTA while 3 patients died from any cause in the SOC group (p=0.776) after 3 years of follow-up.

Conclusion:
In this prospective randomized trial, CCTA reduced near and intermediate-term but not long-term rates of emergency room visits and hospitalizations. When compared to SOC, the use of CCTA was associated with a reduction of major adverse cardiovascular events. Larger randomized controlled trials to further assess the efficacy of a CCTA-based strategy for CICP appear warranted.
Abstract 18662: Aortic Valve Orientation Angle is Associated With Aortic Morphology and Dissection Risk
Authors: Hardikar Ashutosh A , Iannaccone Andrea , Marwick Thomas H
Published: July 2021

Introduction:
Asymmetric aortic root enlargement may lead to unequal thinning of the aortic wall, differential shear stresses and dissection. We sought the association of aortic root morphology with aortoventricular angle (AVAng), LVOT-root angle (RootAng), root-aorta angle (AortAng) [Fig 1] and outcomes.

Methods:
Demographic, morphometric and epidemiological parameters were gathered in 100 patients with aortic disease over last 6 years and 50 age and sex matched controls undergoing aortic CT. Two observers measured AVAng, RootAng, AortAng between the proximal aorta, aortic annulus and LV outflow tract [Figure 1] and orthogonal diameters along the thoracic aorta, noting the type of arch and other pathologies. The root axis was taken by joining the midpoints of aortic annulus and sinotubular junction, and asymmetry index (AI) [Fig 1] was calculated as the ratio of the maximal distance between axis and right wall, and axis to left wall in coronal view. There were 22 aortic dissections in the study group, and follow up was 32.3 months.

Results:
AortAng was different between TAV and BAV, but AI and AVAng were similar. AortAng [P= 0.008], AI [P= 0.004] and AVAng [p=0.013] had the strongest correlation with aortic dilatation [>40 mm], and were different in the dissection group (Table). The AI correlated well with root dilatation while AortAng and AVAng correlated with ascending aortic dilatation. TAV had a diffuse pattern of aortic dilatation as compared to BAV.

Conclusions:
AVAng and RootAng correlate with aortic dilatation patterns, and also aortic dissection. The AVAng and AortAng may explain the differential shear stresses seen along the 2 curvatures in aortic pathologies.
Abstract 18692: Association of Sleep Medication with Cardiorespiratory Fitness in Normotensives, Prehypertensives and Hypertensives
Authors: Routledge Faye S , Gary Rebecca , Rogers Ann E , Paul Sudeshna , Dunbar Sandra B
Published: July 2021

Background:
Recent studies link insomnia with increased risk of hypertension. The reasons for this association are unknown but may be related, in part, to decreased levels of physical activity and cardiorespiratory fitness. Additionally, sleep medication often has multiple deleterious side effects that may impact a person’s engagement in physical activity. We hypothesized that insomnia symptoms and sleep medication use were associated with reduced cardiorespiratory fitness.

Methods:
Adults (n=606) enrolled in the Emory-Georgia Tech Predictive Health Institute study completed baseline demographic, clinical, depression (Beck Depression Inventory II; BDI-II), sleep (Pittsburg Sleep Quality Index , PSQI) and cardiorespiratory fitness (maximal oxygen consumption; VO2max) measures. Insomnia symptoms (sleep latency of ≥30 minutes, nighttime or early morning awakenings) and sleep medication use ≥1 times/week were derived from the PSQI. Multiple linear regression was performed to test for associations between cardiorespiratory fitness and insomnia symptoms or sleep medication use.

Results:
The sample was 68% female, 25% African American, 41% normotensive, 33% prehypertensive, 26% hypertensive with a mean age of 48±11 years and mean body mass index (BMI) 27.6±6.3 kg/m2. Sleep medication use was reported in 11.9% of normotensives and was inversely associated with VO2max adjusting for age, gender, ethnicity, BMI, and heart rate (β=-0.12, p=.03, adjusted R2=.36) and remained significant after further adjustment for blood pressure, HDL cholesterol, depression and smoking (β=-0.11, p=.03, adjusted R2=.41). Sleep medication use was reported in 18.4% of prehypertensives and 22.8% of hypertensives but was not significantly associated with VO2max in either group. No evidence of association between insomnia symptoms and VO2max was found.

Conclusion:
Sleep medication was related to reduced cardiorespiratory fitness in normotensives. People who use sleep medication may be less physically active placing them at greater cardiovascular risk which has important clinical implications for risk reduction. This relationship is attenuated in prehypertension or hypertension and may reflect the influence of pathophysiology and other variables.
Abstract 18720: The Impact of Prolonged Clopidogrel Use Beyond 12 Months After Coronary Stenting in Smokers and Non-smokers
Authors: Depta Jeremiah P , Smoot Kyle , Cho Kelly , Sokolovskaya Galina , Gagnon David R , Ly Samantha , Temiyasathit Sara , Do Jacquelyn , Nava Adrianna , Ostrowski Simon , Gaziano Michael , Faxon David P , Kinlay Scott
Published: July 2021

Background:
Cigarette smoking potentiates the antiplatelet effect of clopidogrel. Guidelines recommend clopidogrel for 12 months after percutaneous coronary intervention (PCI) with bare-metal (BMS) or drug-eluting (DES) stents. Whether smoking affects the risk of ischemic events related to clopidogrel use beyond 12 months after PCI is unknown

Methods:
We identified all PCIs performed in the Veterans Affairs (VA) health system from 2002-2006 and linked the information with the VA pharmacy database. VA and non-VA clinical outcomes were identified by ICD-9 codes from the VA National Patient Care and CMS/Medicare databases. All patients who were event-free at 12 months were followed for death, myocardial infarction (MI), or target vessel revascularization (TVR) up to 4 years following PCI. Prolonged (i.e., > 12 months) vs. clopidogrel use for
<
12 months was assessed for each outcome within each stent type using propensity score adjusted inverse probability of weighting (IPW) Cox-proportional hazards analyses.

Results:
From 2002-2006, 28,507 patients included in the study underwent PCI and were event free at 12 months. Of these, 42% were smokers (n = 11,989) at the index PCI, 51% received a DES (n = 14, 594) and 45% were treated with prolonged clopidogrel use (n = 12,968). Following a 12-month landmark period, 2,194 deaths, 2,288 death or MIs, and 2,010 TVRs occurred. In smokers, prolonged clopidogrel use was associated with a lower risk of death and death or MI with both stent types (interaction p ≤ 0.10). In non-smokers, prolonged clopidogrel use was associated with a lower risk of death (interaction p = 0.04) and death or MI (interaction p = 0.03) in patients receiving DES only (Table).

Conclusions:
Prolonging clopidogrel more than 12 months after PCI may lower the risk of death or MI in smokers irrespective of stent type and in non-smokers receiving DES only. This study suggests that the duration of clopidogrel use after PCI may be tailored to smoking status and stent-type.
Abstract 18727: RAGE-HMGB-1 Expression in the Ascending Aorta of Bicuspid Aortic Valve (BAV) Patients Correlates With Circulating SRAGE and May Predict Vascular Dysfunction Associated With BAV Disease
Authors: Branchetti Emanuela , Bavaria Joseph E , Grau Juan , Updhayay Aseem , Lai Eric , Shaw Richard , Gorman Joseph , Gorman Robert , Ferrari Giovanni
Published: July 2021

Introduction:
Bicuspid Aortic Valve (BAV) is associated with premature valve and vascular complications. Thirty to 50% of BAV patients require surgery for valve diseases and/or ascending aorta (AA) dilatation. Increasing studies suggest that the measure of AA diameter, as criteria for aortic surgery, is an imperfect predictor of dissection and rupture. Therefore there is a need to identify reliable markers of dysfunctional AA to guide the decision for surgery. Recently, Advanced glycation end products (AGEs), such as HMGB-1 and S100A12, and their binding to the Receptor for AGE (RAGE) have been associated to mechanisms of valve and vascular degeneration. We previously demonstrated that BAV patients have higher plasma levels of the soluble form of RAGE (sRAGE) when compared with tricuspid aortic valve (TAV) patients. We also showed that the AA of BAV patients with higher circulating sRAGE is characterized by severe elastin degradation and matrix disorganization when compared to those with lower sRAGE.

Hypothesis:
We hypothesized that the level of circulating sRAGE may be related to the expression of AGEs and RAGE in the AA.

Methods:
HMGB-1 and S100A12 plasma values were measured by ELISA in BAV (N=20) and TAV (N=20) patients previously tested for sRAGE. Logistic regression and multivariate analysis were performed. AA tissue from BAV patients with sRAGE concentration ranging from 491 pg/mL to 5978 pg/mL were tested for the expression of RAGE, HMGB-1 and S100A12 by immunohistochemistry and Western blotting.

Results:
RAGE expression linearly increased in the AA of BAV patients with higher plasma sRAGE (R2=0.5). RAGE and sRAGE levels correlate with the expression of HMGB-1. S100A12 was minimally detected and restricted to inflammatory infiltrates in both BAV and TAV patients with AA dilatation. Plasma level of S100A12 and HMGB-1 were not significantly different in BAV patients when compared to TAV and did not correlate with sRAGE concentration.

Conclusions:
These results suggest that HMGB1-mediated RAGE activation in the AA of BAV patients may be responsible for tissue degeneration and increased sRAGE release in the bloodstream. The interaction AGE-RAGE in the AA of BAV patients may help in evaluating the risk for rapid AA degeneration independently of dilation.
Abstract 18749: CD34+ Circulating Progenitor Cell Levels for Prediction of Subclinical Atherosclerotic Disease
Authors: Lopes Joao Pedro , Zidar David , Ishikawa Masakazu , Alaiti Mohamad , Nascimento Bruno , Ribeiro Antonio Luiz , Padilha Jose Luiz , Wang Yunmei , Jain Mukesh , Simon Daniel , Costa Marco
Published: July 2021

Introduction:
The public health burden of atherosclerosis remains unacceptably high despite existing measures aimed at primary prevention. Although the detection of subclinical atherosclerotic disease as measured by quantification of coronary artery calcium score (CACS) by computed tomography (CT) refines risk estimation, this approach is costly and may not be feasible as a global strategy. We sought to analyze peripheral blood mononuclear cells (PB-MNC) using polychromatic flow cytometry in patients undergoing cardiac CT to determine cellular correlates of early atherosclerosis.

Methods:
We enrolled 286 patients with recent CT for CACS determination (125 CACS=0 / 161 CACS>0). PB-MNCs were isolated for flow cytometry determination using a panel of cell markers, to quantify CD34+CD45dim circulating progenitor cells (CPC). We performed multivariable logistic regression analysis to identify independent predictors of CACS=0. Integer chance weights were assigned to each independent risk variable as a point scoring system. Summed scores were used to define chance groups in quartiles. Predicted chances of CACS=0 were compared with the observed chances and a score calibration test (Hosmer-Lemeshow) was performed.

Results:
High levels of circulating CPC independently predicted the absence of subclinical atherosclerosis in addition to age, female gender, and nonsmoking status. A risk score calibration test demonstrated the predicted and observed chances of this outcome were similar by risk group (p > 0.05). The area under the ROC for the model indicates a 78% chance that the model assigned a lower probability to a patient with CACS=0 than to a patient with subclinical atherosclerosis.

Conclusion:
In our sample, the proportion of CPC was shown to be an independent predictor of absence of coronary disease and the generated score showed a robust correlation between predicted and observed values of CACS.
Abstract 18759: N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein and Infarct Size Measured With Delayed Enhancement Multidetector Computed Tomography
Authors: Sim Doo Sun , Ahn Youngkeun , Kim Yun Hyeon , Seon Hyun Ju , Park Keun Ho , Yoon Hyun Ju , Yoon Nam Sik , Kim Kye Hun , Hong Young Joon , Park Hyung Wook , Kim Ju Han , Jeong Myung Ho , Cho Jeong Gwan , Park Jong Chun
Published: July 2021

Background:
There is a paucity of information on the time-dependent relationship of cardiac biomarkers to infarct size and left ventricular (LV) remodeling after myocardial infarction (MI). We sought to investigate the relationship between levels high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and indices of infarct size and LV volume after acute MI.

Methods:
A total of 86 patients with ST-elevation MI within 12 hours after the symptom onset underwent delayed enhancement multi-detector computed tomography (DE MDCT) immediately after percutaneous coronary intervention (PCI) to determine infarct size. LV function and remodeling were assessed by echocardiography. Hs-CRP and NT-proBNP were serially measured at admission, 24 hours, and 2 months. DE MDCT and echocardiography were repeated at 2 months after PCI.

Results:
Levels of both hs-CRP and NT-proBNP at 24 hours showed positive correlation with infarct size at baseline and at 2 months, and negative correlation with LV ejection fraction at baseline and at 2 months. NT-proBNP at 2 months correlated with infarct size (r=0.561, p=0.007), LV ejection fraction (r= - 0.539, p=0.010), and LV end diastolic and systolic volume indices at 2 months (r=0.796, p=0.032 and r=0.831, p=0.021, respectively). NT-proBNP was higher in patients who developed LV remodeling at 2 months: 929 pg/mL vs. 134 pg/mL,
p
= 0.002. In contrast, hs-CRP at 2 months showed no relationship to infarct size, LV function, or LV volumes at 2 months.

Conclusions:
Elevated hs-CRP during active myocardial necrosis was associated with infarct size and LV dysfunction, whereas elevated levels of NT-proBNP early and late after the onset of acute MI were both correlated with infarct size, LV dysfunction, and LV remodeling.
Abstract 18819: Graded Benefit of EDTA Chelation in Post-MI Patients with Diabetes Treated with Different Hypoglycemic Strategies
Authors: Lamas Gervasio A , Escolar Esteban , Boineau Robin , Nahin Richard , Goertz Christine , Mark Daniel , Rosenberg Yves , Lindblad Lauren , Lee Kerry
Published: July 2021

Introduction:
The NIH-funded Trial to Assess Chelation Therapy (TACT) reported a clinical benefit of EDTA-based chelation on cardiovascular (CV) outcomes in post-MI patients with diabetes (DM). We assessed the benefit of therapy by severity of diabetes.

Methods:
TACT, a multi-center, double-blind, placebo-controlled, 2 X 2 factorial trial of EDTA chelation and high-dose vitamins, enrolled pts age > 50 years with an MI at least 6 weeks prior and creatinine < 2.0. Median duration of follow-up was 55 months. The primary endpoint was death from any cause, MI, stroke, coronary revascularization, or hospitalization for angina. The major secondary clinical endpoint was cardiovascular death, MI, or stroke. The type of hypoglycemic therapy (insulin, oral, or none) was used as a surrogate for severity of diabetes. The log rank test and Cox model were used for treatment comparisons. This is a non-prespecified subgroup comparison.

Results:
TACT enrolled 1708 pts. Among the 633 (37%)with diabetes, 162 (26%) were on insulin, 301 (48%) not on insulin, but on oral hypoglycemic, and 170 (27%) on neither. For the overall subgroup of 633 pts with diabetes EDTA chelation significantly reduced the primary endpoint (HR 0.59 95% confidence intervals (CI) 0.44-0.79, p<0.001). For pts on insulin, the benefit was qualitatively greatest (HR 0.42 95% CI 0.25-0.74, p=0.002), compared with the effect on patients receiving oral hypoglycemic therapy (HR 0.66 95% CI 0.43-1.01, p=0.053), or none (HR 0.69 95% CI (0.39-1.20), p=0.19). For the key secondary endpoint, the best results were in the patients on insulin (HR 0.53) or on oral drugs (HR 0.54), whereas the smallest effect was seen in the patients on neither type of medication (HR 0.82).

Conclusions:
In post-MI pts with DM treated with standard therapies, the clinical benefit of EDTA-based chelation therapy was most pronounced among the patients with the most severe diabetes, those on insulin therapy. Additional work to understand mechanisms will be necessary.
Abstract 18838: Inhibition and Genetic Deficiency of Trem-1 Receptor Reduces Development of Experimental Atherosclerosis in Mice
Authors: Joffre Jérémie , Potteaux Stephane , Boufenzer Amir , Loyer Xavier , Mellak Safa , Laurans Ludivine , Bruneval Patrick , Tedgui Alain , Mallat Ziad , Gibot Sebastien , Ait Oufella Hafid
Published: July 2021

Introduction:
Innate immunity, particularly monocytes / macrophages and neutrophils, play a major role in the development and the complications of atherosclerosis. TREM-1 is a recently discovered receptor expressed by myeloid cells that amplifies the inflammatory response by increasing chemokines and pro inflammatory cytokines production. The aim of this study was to determine the role of TREM-1 in experimental atherosclerosis.

Methods and results:
TREM-1 is not present in healthy artery but is expressed (mRNA and protein) in human carotid atherosclerotic plaques, mainly by macrophages. 8 week-old Ldlr-/ - mice were lethally irradiated and transplanted with a bone marrow graft Trem-1 + / + or Trem-1-/ - and put on a fat diet (FD) during 14 weeks. Cholesterol levels were not different between the two groups. In Ldlr-/-/Trem-1-/ - chimeric mice, we observed a 60% reduction of the lesion size in the aortic sinus (120100 ± 139600 vs 479116 ± 70229 μm2, P = 0.006) and a 49% reduction on the thoracic aorta (9.5 ± 2.2 vs 4.8 ± 1.6% surface ratio, P = 0.02). In Ldlr-/-/Trem-1-/- chimeric mice, plaques showed a significant decrease in macrophage infiltration (MOMA +, P=0.029) and a reduction in necrotic core size (Masson’s trichrome, P=0.003). In vitro, splenocytes from Ldlr-/-Trem-1-/- stimulated by oxidized LDL produced less IL-12 (ELISA) than control chimeric splenocytes (126 ±104 vs 1185 ± 795 pg/ml, P = 0.001).

We have developed a dodecapeptide (LR-12) wich inhibits TREM-1 binding to its endogenous ligand. Apoe-/- mice were treated by daily intraperitoneal injections of LR-12 (100μg) or scramble peptide during 4 weeks. We observed that LR-12 treatment reduced atherosclerosis development on a chow diet (-30%, P <0.05) and on a high fat diet (-42%, P = 0.005).

Conclusion:
TREM-1 is expressed in human and mouse atherosclerotic plaques. TREM-1 genetic invalidation and pharmacological inhibition reduce the development of atherosclerosis and induce a more stable plaque phenotype.
Abstract 18842: Point of Care Testing Overestimates INR in CF-LVAD Patients
Authors: Dionizovik-Dimanovski Marija , Levin Allison P , Mody Kanika P , Simonich Erica , Fried Justin , Kalesan Bindu , Garan Arthur R , Yuzefpolskaya Melana , Naka Yoshifumi , Takayama Hiroo , Colombo Paolo C , Uriel Nir , Jorde Ulrich P
Published: July 2021

Background:
Long-term anticoagulation therapy with warfarin is used in pts. with continuous-flow LVAD (CF-LVAD) to minimize the occurrence of thromboembolic events. Patient self-testing (PST) of INR with home monitoring devices has been shown to improve time within therapeutic INR range as well as patient satisfaction in other settings. However, PST devices have never been tested in pts. with CF-LVADs. The purpose of this study was to determine the reliability of PST devices in patients supported with CF-LVADs.

Methods:
A correlation study was performed in 50 CF-LVAD pts. who were on stable warfarin therapy for a minimum of 3 weeks. Simultaneous INR values were determined from capillary whole blood samples using the Alere home monitoring PST device and venous blood samples processed in the core laboratory at a large volume CF-LVAD center. Hematocrit, liver function tests, TSH, and amiodarone use were also recorded on patients due to their propensity to affect warfarin metabolism and INR results.

Results:
Fifty LVAD pts with a mean age of 60 (±14) years were included in the study. Forty-one (82%) were male, and the mean time on CF-LVAD support at the time of INR measurement was 12 months, ranging from 1 to 56 months. There was a moderate correlation between the venous and capillary INR values with a correlation coefficient of 0.83 (r
2
=0.68, p<0.001; Fig 1a). The median difference between the methods was 0.39, with 44/50 pts. having higher INRs with Alere (Fig 1b). Results remained the same after controlling for the use of amiodarone, abnormal hematocrit and liver enzymes, creatinine and TSH.

Conclusion:
Point of care testing with Alere consistently overestimates INR when compared to conventional laboratory testing in CF-LVAD patients. While our data requires large scale validation, similar results have been reported with point of care testing in other patient populations. Once validated, failure to adjust for this difference may lead to unintentional subterapeutic INR.
Abstract 18883: High Sensitivity Troponin T in Acute Heart Failure: Insights from RELAX-AHF
Authors: Felker G. Michael , Mentz Robert J , Teerlink J R , Voors A A , Pang P S , Ponikowski P , Greenberg B H , Filippatos G , Davison B A , Cotter G , Prescott M F , Hua T , Severin T , Metra M
Published: July 2021

Background:
Elevations of cardiac troponin are common in acute heart failure (AHF), but their clinical importance is uncertain. We examined the association between serial high-sensitivity troponin T (hs-cTnT) and outcomes in the RELAX-AHF study, a randomized trial of IV serelaxin in AHF.

Methods:
hs-cTnT (Roche Diagnostics) was measured at baseline and days 2, 5, and 14. Patients with clinical evidence of ACS were excluded by protocol. 1074 patients (93% of total cohort) with data available for both baseline and at least 1 follow-up hs-cTnT measurement were analyzed. We assessed the relationship between baseline hs-cTnT and peak change from baseline hs-cTnT with outcomes. Models were adjusted for other clinical variables and treatment assignment. Differential effect of serelaxin by troponin levels was assessed by interactions terms.

Results:
The median baseline troponin was 0.033 mcg/L, and 95% were above the 99
th
upper reference limit (URL). Patients with elevated hs-cTnT were more likely to be men with ischemic heart disease, worse renal function, and higher natriuretic peptides. Both higher baseline hs-cTnT and greater peak hs-cTnT were associated with increased risk for adverse outcomes even after adjustment (
Table
). Treatment effect of serelaxin did not differ based on troponin status.

Conclusion:
Consistent with prior data, hs-cTnT was elevated above the 99% URL in the vast majority of AHF patients at baseline, and was associated with markers of disease severity. Both baseline and peak change from baseline hs-cTnT were associated with worse clinical outcomes, but relationships were generally strongest for 180-day CV mortality. Treatment effect of serelaxin did not differ based on troponin status.
Abstract 18891: Prospective Evaluation of Diagnostic Performance and Safety of Implementing a Biventricular Approach for Endomyocardial Biopsy in Patients With Suspected Myocarditis
Authors: Lurz Philipp , Foehrenbach Felix , Luecke Christian , Urban Daniel , Boudriot Enno , Thiele Holger , Desch Steffen , Klingel Karin , Kandolf Reinhard , Schuler Gerhard
Published: July 2021

Background:
Previous retrospective analyses have suggested that biventricular (BV) endomyocardial biopsy (EMB) is superior to right (RV) or left ventricular (LV) EMB only in diagnosing patients with suspected myocarditis.

Aim:
To prospectively assess the feasibility, safety and diagnostic yield of BV EMB in consecutive patients with suspected myocarditis.

Methods:
Five to six EMBs were taken from the RV and LV under fluoroscopic guidance. Biopsies were analyzed in a core lab by highly experienced investigators (KK, RK) Myocarditis/myocardial in[[Unable to Display Character: ﬂ]]ammation was de[[Unable to Display Character: ﬁ]]ned as the detection of ≥14 infiltrating leukocytes/mm2 (CD3 T-lymphocytes and/or CD68 macrophages) in addition to enhanced HLA class II expression in professional antigen-presenting immune cells.

Results:
100 consecutive patients (mean age 44 ± 15 years) with clinically suspected myocarditis were included. RV EMB was attempted in 100 patients, in 3 the procedure was abandoned due to unsatisfying positioning on the guiding catheter, in 1/97 RV EMBs were inadequate with no myocardial tissue obtained. LV EMB was attempted in 97 patients, in 3, LV EMB was not performed due to presence of LV thrombi, in 1/97 patient LV EMBs were inadequate with no myocardial tissue obtained. Major complication rate for LV EMB was 0% and for RV EMB, 1% (pericardial tamponade requiring surgical revision). Results of adequate BV EMBs were analyzed in 92 patients. On BV EMB, myocarditis was diagnosed in 61/92 patients. When considering LV EMB only, the diagnosis would have been missed in 3/61, when considering RV EMB only in 7/61 patients.

Conclusion:
BV EMB is feasible and safe in the majority of patients with suspected myocarditis and yields in a superior diagnostic performance as compared to a single ventricle EMBs.