bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18554: Short-term Melatonin Treatment Protects the Hearts of Obese Rats Independent of Changes in Body Weight and Visceral Fat Mass
Authors: Lochner Amanda , Nduhirabandi Frederic
Published: July 2021

Melatonin treatment has been shown to prevent the harmful effects of diet-induced obesity and reduce myocardial susceptibility to ischaemia-reperfusion injury (IRI) when administered from the onset of obesity. However, the exact mechanism whereby it exerts its beneficial actions on the heart in obesity and insulin resistance is unknown. In this study we investigated the effects of relatively short-term melatonin treatment on the heart in a rat model of diet-induced obesity. Control (C) and diet-induced obese (D) Wistar rats (fed for 20 weeks (wks)) were divided into 3 groups receiving drinking water with or without melatonin (4mg/kg/day) for the last 6 or 3 wks of experimentation. Isolated hearts were perfused in the working mode, subjected to regional (35min) or global ischaemia (15min) and reperfusion (2h); others were non-perfused (baseline). Myocardial infarct sizes as well as baseline and post-ischaemic activation of PKB/Akt, ERK42/44, GSK-3β and STAT-3 were determined. Blood was collected for study of metabolic parameters. Diet-induced obesity caused significant increases in body weight gain (14.5%), visceral adiposity (70.3%), fasting blood glucose (20%), serum insulin (55.6%) and triglyceride (84.2%) levels with a concomitant increase in post-ischaemic myocardial infarct size (41%) and a reduced cardiac output (12.7%). Melatonin treatment (both 3 and 6 wks) decreased serum insulin levels and the HOMA-index in the D group only (3 wks % reduction: 39%; 47.2%, p<0.05 vs untreated D respectively) with no effect on body weight gain, visceral adiposity, serum triglycerides and glucose levels. It also increased serum adiponectin levels in the D group (113% p<0.05 vs untreated D), reduced myocardial infarct sizes in both groups (3 wks %reduction: C 42.4%; D 61.6%) and activated baseline myocardial STAT-3, PKB/Akt, ERK42/44 and GSK-3β after 10 min reperfusion. Short-term melatonin administration to obese and insulin resistant rats reduced insulin resistance and protected the heart against
ex vivo
myocardial IRI independently of body weight gain and visceral adiposity. Melatonin-induced cardioprotection was associated with concomitant activation of the RISK and SAFE pathways.
Abstract 18577: Skin Autofluorescence is an Independent Predictor of the Coronary Artery Disease
Authors: Fujino Yusuke , Tahara Satoko , Takagi Kensuke , Naganuma Toru , Nakamura Shotarou , Ishiguro Hisaaki , Fukino Keiko , Kurita Naoyuki , Wang Wei , Nakamura Sunao
Published: July 2021

Aims:
Skin autofluorescence (SAF), a non-invasive measurement of the accumulation for glycation end products (AGEs) level of skin, has been reported as a useful marker for micro/macro vascular complications. However there is little data evaluating whether SAF can be the predictor of the patients with suspected a coronary artery disease (CAD) and indicating the coronary angiogram (CAG). The aim of this study was to evaluate association between SAF and CAD detected by CAG in the catheterization laboratory.

Methods:
From October/2013-March/2014, 333 patients with suspected the CAD and underwent CAG were enrolled prospectively. SAF were assessed with autofluorescence reader before CAG. Patients with the history of percutaneous coronary intervention, coronary artery bypass grafting were excluded. CAD was defined as if there was at least one coronary artery stenosis greater than or equal to 50% (AHA classification) by CAG. Association between SAF and existence of CAD was evaluated, and we also explored the relationship between SAF and number of diseased coronary artery.

Results:
Of the 333 patients, CAD was observed in 145 (43.5%) patients. In multivariate logistic regression analysis, age (odds ratio [OR]: 1.03; 95% con[[Unable to Display Character: ﬁ]]dence interval [CI]: 1.00 to 1.06; p = 0.049), gender (male as reference) (odds ratio [OR]: 0.46; 95% con[[Unable to Display Character: ﬁ]]dence interval [CI]: 0.28 to 0.75; p = 0.002), HbA1c (odds ratio [OR]: 1.45; 95% con[[Unable to Display Character: ﬁ]]dence interval [CI]: 1.10 to 1.91; p = 0.008) and SAF (odds ratio [OR]: 4.85; 95% con[[Unable to Display Character: ﬁ]]dence interval [CI]: 2.750 to 8.55; p <0.001) were considered to be the predictors of CAD. Furthermore patients with higher SAF showed more number of coronary artery disease (Figure 1). When we use the response variable greater equal to 2.3 to determine CAD, sensitivity is 0.655 (0.572, 0.732) and specificity is 0.713 (0.642, 0.776).

Conclusions:
SAF was independent predictor of CAD and showed a possibility of being the surrogate for the CAD as non-invasive methodology.
Abstract 18643: Role for RUNX2 in Pulmonary Arterial Hypertension
Authors: Ruffenach Grégoire , Chabot Sophie , Breuils-Bonnet Sandra , Ferraro Pasquale , Provencher Steeve , Bonnet Sébastien
Published: July 2021

Introduction:
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by enhanced pulmonary artery smooth muscle cells (PASMC) proliferation, calcification and suppressed apoptosis. Numerous biological pathways have been implicated in the sustainability of this phenotype, including P53/P21, Bcl-2 along with the STAT3/NFAT axis. Several studies have demonstrated that miR-204 is downregulated in PAH. Interestingly, miR-204 directly regulates the expression of the transcription factor RUNX2, which is implicated in many features characterizing PAH, including modulation of the BMPR2, P53/P21, and Bcl2 pathways.

Hypothesis:
Thus, we hypothesized that a miR-204 dependent upregulation of RUNX2 in PAH promotes PASMC proliferation, resistance to apoptosis and calcification.

Methods/Results:
Using human explanted lungs, fresh distal PAs and freshly isolated PASMC from both control and PAH patients (n=5 to 12), we demonstrated a significant (p<0.05) upregulation of RUNX2 (RT-qPCR, western blot and immunofluorescence) in PAH compared to controls. Gain and loss functions experiments in PASMC showed that downregulation of miR-204 in control PASMC increases RUNX2 expression, while increases in miR-204 in PAH-PASMC decreases it (n=3 to 5 p<0.05). Increased RUNX2 expression was associated with a downregulation of P53/P21 and an upregulation of Bcl2 (n=3 to 8 p<0.05). More importantly, restoring miR-204 or decreasing RUNX2 expression decreased calcification (red alizarin), proliferation (Ki67) and resistance to apoptosis (TUNEL) in human PAH-PASMC (n=3 p<0.05), while upregulating RUNX2 in control PASMC using an adenovirus mimicked PAH phenotype (n=3 p<0.05). Finally, in Sugen/hypoxia rat model of PAH, nebulization of RUNX2 siRNA (n=15) decreased mean PA pressure, pulmonary vascular resistance, and increased exercise tolerance and cardiac output (p<0.05).

Conclusions:
Taken together, our study uncovers a new miR-204-RUNX2 axis contributing to a P53/P21-dependent pro-proliferative and Bcl2-dependent anti-apoptotic phenotype in PAH-PASMC.
Abstract 18682: Inflammatory Biomarkers for Prognostication of Outcomes in Stable Coronary Artery Disease - Experiences From the STABILITY Trial
Authors: Held Claes , White Harvey D , Stewart Ralph A , Budaj Andrzej , Cannon Christopher P , Harrington Robert A , Koenig Wolfgang , Krug-Gourley Sue , Siegbahn Agneta , Steg Philippe Gabriel , Tarka Elizabeth , Östlund Olof Petter , Wallentin Lars
Published: July 2021

Introduction:
Prognostication of outcome in patients with stable coronary artery disease (CAD) is currently based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction and possibly cardiac biomarkers.

Hypothesis:
We assessed the incremental prognostic value of biomarkers of inflammation in the Stabilization of Atherosclerotic Plaque By Initiation of Darapladib Therapy (STABILITY) trial.

Methods:
In STABILITY, 15,828 patients with chronic CAD on optimal medical treatment were randomized to treatment with darapladib or placebo. Serum levels of hs-C-reactive protein (CRP) and Interleukin (IL)-6 were measured at randomization in 14,373 and 4733 patients, respectively. Centrally adjudicated outcome events were accumulated during a median of 3.7 years follow-up. The associations between levels of the biomarkers and outcomes were evaluated by multivariable Cox regression.

Results:
The impact of biomarker levels at baseline in relation to the composite endpoint, MACE (major adverse cardiovascular event), of cardiovascular (CV) death, myocardial infarction (MI) and stroke, and its individual components are presented in the Table. Both hs-CRP and IL-6 provided strong prognostic information in addition to clinical predictors for outcomes of MACE, CV death and MI, but not for stroke.

Conclusions:
In conclusion, the cardiac biomarkers hs-CRP and IL-6, provided important complementary prognostic information on the risk of CV mortality and MI, but not for stroke in patients with stable CAD on optimal medical treatment.
Abstract 18714: Role of 123 Iodine Metaiodobenzylguanidine Imaging in Prediction of Arrhythmic Events in Heart Failure Patients Candidate to ICD
Authors: Bruno Noemi , Salvi Nicolò , Scarparo Paola , Calvieri Camilla , Armato Alessandra , Cinque Alessandra , Bruno Pasqualina , Mancone Massimo , De Vincentis Giuseppe , Fedele Francesco
Published: July 2021

Background:
According to guidelines, implantable cardioverter defibrillator (ICD) is recommended in prevention of sudden cardiac death (SCD) in heart failure (HF) patients (pts). Guidelines have several limitations because ICD indication is based mainly on left ventricular ejection fraction (EF). Recent data showed that, independently from EF, 123-iodine metaiodobenzylguanidine imaging (123-I MIBG) could help to identify HF pts at high risk of SCD [heart/ mediastinum (H/M) ratio ≤1.6 and a summed score (SS) > 26], who may benefit of ICD.

Aim:
Our aim is to assess, in a real world registry, the role of 123-I MIBG for the prediction of ventricular tachyarrhythmia (VT) causing appropriate ICD therapy in HF pts.

Methods:
We consecutively enrolled 97 patients admitted to our hospital with diagnosis of HF, left ventricular ejection fraction (LVEF) ≤35% and indication to ICD. All patients underwent MIBG imaging. The patients were classified into two groups: Group 1 with H/M≤1.6 , SS> 26; Group2 with H/M>1.6, SS <26. All patients underwent 1 year follow-up.

Results:
65 pts were included in group 1 and 32 pts in group 2. All baseline characteristics were similar in 2 groups apart from the etiology (table 1). In group 1, H/M ratio was 1.37±0.3 vs 1.8 ± 0.2 in group 2 (p=0.0002); SS was 37.5± 9.7 vs 16 ±6 in group 2 (p = 0.0001). At 1 year follow-up VTs causing appropriate ICD therapy in group 1 were 13.4% vs 1.28% in group 2(p=0.02); overall cardiac events were in group 1 16.4 % vs 1.92% in group 2 (p=0.02).

Conclusion:
Our results suggest that 123 I-MIBG can identify patients at increased risk for arrhythmic death and can be useful in the decision-making of ICD implantation independently from ejection fraction.
Abstract 18738: Use of Antithrombotic Therapies and Outcomes in Patients with Atrial Fibrillation and Heart Failure: Insights from the GARFIELD Registry
Authors: Corbalan Ramon , Pereira Barretto Antonio C , Ambrosio Giuseppe , Al Mahmeed Wael , Le Heuzey Jean-Yves , Kayani Gloria , Jerjes-Sanchez Carlos , Stepinska Janina , Parkhomenko Alexander , Steffel Jan , Panchenko Elizaveta , Kakkar Ajay K ,   for the GARFIELD Investigators
Published: July 2021

Background:
Atrial fibrillation (AF) is commonly associated with heart failure (HF) and this combination is associated with a worse prognosis than either alone. However, it is unclear if these patients receive appropriate antithrombotic therapies and if they have a higher incidence of stroke or systemic embolism (SE).

Methods:
We compared clinical characteristics, antithrombotic therapies, and outcomes in patients with and without HF in the GARFIELD Registry, an ongoing, international, observational registry of consecutively recruited patients with newly diagnosed non-valvular AF and ≥1 additional stroke risk factor. A total of 12,458 prospective patients were enrolled in 30 countries between March 2010 and January 2013. Results are reported at 1-year follow-up. HF was defined at baseline as New York Heart Association (NYHA) I-II or III-IV. Antithrombotic therapy use and 1-year outcomes in patients with and without HF were analysed.

Results:
In total, 20% of patients had HF; they were older and had higher CHA2DS2-VASc and HAS-BLED scores compared with patients without HF. A higher proportion of patients with HF received antithrombotic therapies. The incidence of all-cause death was higher in HF patients than non-HF patients. Patients with NYHA class III-IV HF had a higher unadjusted incidence of all-cause death and stroke/SE compared with non-HF patients: 10.5 (95% confidence interval 8.8 to 12.7) vs 2.9 (2.7 to 3.2) per 100 person-years and 1.9 (1.2 to 3.0) vs 1.0 (0.8 to 1.2) per 100 person-years, respectively. Event rates slightly changed after adjustment for stroke risk factors.

Conclusion:
More AF patients with HF received antithrombotic therapies compared with those without HF. They also showed a higher incidence of all-cause death with increasing HF severity compared with AF patients without HF. After adjustment for stroke risk factors, this association was slightly attenuated.
Abstract 18822: Endoglin Selectively Modulates TRPC Expression in Response to Left or Right Ventricular Pressure Overload
Authors: Morine Kevin J , Paruchuri Vikram , Qiao Xiaoying , Pham Duc T , Huggins Gordon S , Denofrio David , Kiernan Michael S , Karas Richard , Kapur Navin K
Published: July 2021

Introduction:
Endoglin is an accessory receptor for the cytokine transforming growth factor beta. Reduced endoglin activity limits cardiac fibrosis due to left ventricular (LV) pressure overload. Recently, we reported that reducing endoglin activity also limits upregulation of the profibrogenic transient receptor potential canonical channel 6 (TRPC6) in the right ventricle (RV) during pressure overload. Few studies have compared TRPC channel expression in the RV versus LV.

Hypothesis:
We hypothesized that endoglin regulates TRPC upregulation in response to RV and LV pressure overload.

Methods:
To explore a functional role for endoglin as a regulator of TRPC expression in response to RV or LV pressure overload, endoglin haploinsufficient (Eng+/-) and wild-type (Eng+/+) mice were exposed to thoracic aortic (TAC) or pulmonary arterial (PAC) constriction for 10 weeks. Biventricular tissue was then analyzed by real-time polymerase chain reaction.

Results:
After TAC, LV levels of TPRC1 and 6 were increased in both Eng +/+ and Eng +/- mice compared to sham controls. LV levels of TRPC4 were increased in Eng +/+, not Eng +/- mice after TAC. After PAC, RV levels of TRPC1, 3, 4, and 6 were increased in Eng +/+ compared to sham controls. In contrast, chronic RV pressure overload did not increase RV levels of TRPC1, 3, 4, and 6 in Eng +/- mice compared to sham controls.

Conclusions:
Pressure overload induces distinct profiles of TRPC expression in the RV and LV and these effects in the RV require full endoglin activity. Taken together, these data support that endoglin may be an important and novel target of therapy to modulate RV responses to injury.
Abstract 18894: Standard Deviation of Segmental Left Atrial Strain is Impaired in Patients Treated by Pulmonary Vein Isolation With Late Failure
Authors: Grafe Michael , Kriatselis Charalampos , Gerds-Li Hong , Kaufmann Jan , Furundzija Vesna , Thanabalasingam Usan , Fleck Eckhart , Wellnhofer Ernst
Published: July 2021

Introduction:
Pulmonary vein isolation (PVI) has been established as effective interventional treatment in chronic atrial fibrillation (AF). Impairment of left atrial strain is considered a surrogate parameter of fibrosis. There is considerable variance of strain among different atrial wall segments. We hypothesized that early impairment of strain affects mobile segments and thus reduces inter-segmental variance of strain.

Methods:
We evaluated 89 consecutive PVI patients and 28 controls (mean age 60 ± 12 y, 33 female). The longitudinal strain of the left atrium in a 4-chamber apical window was determined by speckle tracking (Philips IE33 offline analysis by QLAB™). Success was defined as maintenance of sinus rhythm until last follow-up (minimum 3 months elapsed since PVI). Follow-up comprised repeated Holter-monitoring and echocardiography. Variance was evaluated as standard deviation of segmental strain before PVI (STD).

Results:
Atrial fibrillation recurred in 40 of 89 patients. STD was 16.5±7.9 in controls, 8.1±5.3 in PVI with persisting success and 4.6±2.2 in late PVI failure (see also box-plot).

The group differences between controls, PVI success and PVI failure were all significant (p<0.001 Kruskal-Wallis and median test) and improved prediction of PVI failure significantly in a binary logistic as well as linear discriminant model.

Conclusions:
Standard deviation of segmental left atrial strain is impaired in patients treated by pulmonary vein isolation with late failure and should be further evaluated as predictor for recurrence.
Abstract 18973: Left Ventricular Function Improvement After Recent MI in Patients Using a Wearable Cardioverter Defibrillator
Authors: Wan Chingping , Szymkiewicz Steven J
Published: July 2021

Introduction:
The wearable cardioverter defibrillator (WCD) has been used to protect AMI patients with reduced LVEF (≤35%) until ICD evaluation is recommended. The rate of EF improvement (e.g. EF>35%) over the initial 8-12 weeks after AMI has not been reported.

METHODS:
The manufacturer-maintained registry was searched for AMI patients who received a WCD shock for VT/VF between 05/2008 and 02/2013. The treated group was matched (1: ~4) with event-free WCD patients by ICD-9 code (410.*), gender, age and prescription date. Chart notes were reviewed for clinical characteristics. Follow-up was assessed through the registry and Social Security Death Master File.

RESULTS:
There were 992 (age=63±12, female=20.2%) AMI patients included in the final analysis, 206 treated by WCD and 786 event-free patients. Median follow-up was 334 days. Mean length of WCD use was 67±506 (median=38) days. Subgroup clinical characteristics are presented in Table 1. In the event-free group, 289 (38.9%) patients showed EF improvement to >35%. Nine (4.5%) in the treated group continued wearing the WCD until EF recovery, while 125 (60.7%) received ICD. Absence of recorded heart failure and/or diabetes were associated with LVEF recovery (p<.0001).

CONCLUSION:
In our study, almost 40% of AMI patients with initial EF ≤35% had EF improvement in two months. The EF recovery group had lower rates of heart failure and diabetes. WCD allows time for left ventricular function recovery in low EF post MI patients, optimizing ICD implantation decisions.
Abstract 18977: Non-Syndromic Mitral Valve Prolapse From Gene Mutations to Modifiable Mechanisms
Authors: Norris Russell , Sauls Kimberly , Durst Ronen , Peal David , Toomer Katelynn , Leyne Maire , Talkowski Michael E , Brand Harrison , Perrocheau Maelle , Lynch Stacey N , Bouaia-Naji Nabila , Delling Francesca N , Freed Lisa A , Le Tourneau Thierry , LeMarec Herve , Estivill Xavier , Fernandez-Friera Leticia , Dina Christian , Solis Jorge , Trujillano Daniel , Irvine Kenneth D , Mao Yaopan , Ossowski Stephan , Wessels Any , Menick Donald , Kasiganesan Harinath , Bromme Ann-Marie , Williams Katherine , Schott Jean-Jacques , Hagege Albert A , Jeunemaitre Xavier , Markwald Roger R , Milan David J , Levine Robert A , Slaugenhaupt Susan
Published: July 2021

Mitral valve prolapse (MVP) is a common disease affecting nearly 1 in 40 individuals. It is the leading surgical indication for mitral valve regurgitation. Despite a clear heritable component, the genetic etiology of non-syndromic MVP has remained elusive. Individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of a previously linked interval on chromosome 11. We found a novel missense mutation in DCHS1, the human homologue of the Drosophila cell polarity gene dachsous (ds) that segregates with MVP in the family. The familial mutation reduced protein stability in zebrafish and cultured cells. Morpholino knockdown of zebrafish dachsous1b yielded a regurgitant atrioventricular canal defect that could be rescued by wild-type human DCHS1 but not by mRNA with the familial mutation. Adult haploinsufficient Dchs1 mice had anatomic and functional prolapse of thickened, elongated leaflets recapitulating the human MVP phenotype. Dchs1 haploinsufficiency was associated with developmental defects in valve shape, cell migration and patterning during fetal morphogenesis, suggesting cell polarity as a previously unrecognized facet of valve morphogenesis. Studies of downstream changes identified increased MAP kinase activities and α-SMA+ cells (myofibroblasts) in the valves preceding myxomatous degeneration; these suggest potential future directions for blunting disease progression. Additional genetic studies identified a second family with a DCHS1 mutation and a significantly increased burden of novel DCHS1 mutations in sporadic MVP cases Interdisciplinary studies strongly support DCHS1 as the first identified disease-causing gene for non-syndromic MVP and suggest potential mechanisms for modifying disease natural history.
Abstract 18991: Salt Taste Detection and Recognition Thresholds - Reliability of a Rapid Sensory Analysis Method
Authors: Giguère Jean-François , Gallani Maria-Cecilia , Doré Michel , Proulx Bellhumeur Alexandra
Published: July 2021

Introduction:
Excessive sodium intake is clearly and independently associated with hypertension and cardiovascular diseases. The salt taste sensitivity is closely related to hedonic aspects of nutrition, and this is an important individual factor contributing to the nutritional behavior of salt intake.

Hypothesis:
The purpose of this study was to evaluate the reliability of an adapted-sensory analysis method for rapid determination of salt taste Detection Threshold (DT - the minimum concentration necessary to detect the stimulus) and Recognition Threshold (RT - the minimum concentration necessary to recognize the salty stimulus).

Methods:
The temporal stability of a rapid sensory analysis based on the 3-alternative forced-choice (3-AFC) method (ASTM E679) was tested with 30 adult volunteers. DT and RT for salt were determined using a 15 series of ascending concentrations of salt (from 1 to 290 mM; 1,5-fold steps). Intraclass correlation coefficient (ICC) was used to test the agreement between the results of the test-retest (1-week interval). For the analysis, the threshold values were log-transformed.

Results:
The average time of the trial per participant was 16.7 minutes. Standard deviation on log-transformed DT and RT values quite were variable among subjects. Means for both DT and RT were lower in the retest: 2,99 mM (test) vs. 2,41 mM (retest) for DT; and 19,04 mM (test) vs. 13,76 mM (retest) for RT. However, the test-retest results for both thresholds were reasonably in agreement, as confirmed by the ICCs observed: 0.599 (CI95%; 0,157 - 0,809) and 0.783 (CI95%; 0,545 - 0,897) for DT and RT, respectively.

Conclusions:
The sensory analysis method used in this study exhibited evidence of temporal stability, thus of a reliable measure. This observation and the fact of being fast and simple to perform for both experimenter and participant, reinforce its suitability for the determination of salt taste thresholds in studies involving large numbers of subjects. Linking between taste sensitivity to salt consumption and some clinical characteristics such as obesity and visceral fat, may help to understand the mutual influence of these variables, and suggest appropriate interventions to reduce salt intake among individuals at higher cardiovascular risk.
Abstract 19008: Is Cold Pressor Cardiac Magnetic Resonance Imaging Testing Useful for Detection of Coronary Endothelial Dysfunction?
Authors: Dela Cruz Sherwin , Wei Janet , Shufelt Chrisandra , Mehta Puja , Rogatko Andre , Zhang Xiao , Thomson Louise E , Petersen John , Anderson R. David , Pepine Carl J , Berman Daniel S , Bairey Merz C. Noel
Published: July 2021

Background:
Coronary endothelial dysfunction is typically assessed by invasive coronary reactivity testing (CRT) to measure coronary blood flow ([[Unable to Display Character: ∆]]CBF) and diameter responses to acetylcholine (Ach). We evaluated if cold pressor testing (CPT) during noninvasive cardiac magnetic resonance imaging (CMRI) measurement of myocardial perfusion reserve index (MPRI) reflects invasive measurements with Ach and CPT in subjects suspected of having endothelial dysfunction.

Methods:
CRT was performed in 137 symptomatic women using incremental infusions of Ach in the left coronary artery for 3 minutes and with CPT using ice pack on their hand and forearm for 2 minutes. Quantitative coronary angiography was performed 5 mm distal to the Doppler wire positioned in the proximal left anterior descending artery. In 132 women, [[Unable to Display Character: ∆]]CBF was calculated from average peak velocity and vessel cross sectional area. Invasive CPT could not be completed on 4 women. All women underwent CPT CMRI (1.5 T) to measure MPRI as a ratio of stress and rest upslopes of the whole myocardium. Five definitions of normal invasive CPT and Ach diameter response (dilation > 0, 5, 10, 15 or 20%) were compared to two abnormal definitions (≤ 0 or - 5%) of endothelial function. Normal [[Unable to Display Character: ∆]]CBF was defined as ≤ 50%. We used Wilcoxon Two-Sample statistical test to compare MPRI in each group.

Results:
CPT MPRI was significantly different in those with normal versus abnormal invasive Ach when Ach diameter response was defined as ≥ 20% or < - 5 % (p=0.04), though not with other thresholds (Table).

Conclusion:
Noninvasive CPT CMRI may not be useful for detection of endothelial dysfunction in symptomatic women as no significant difference in MPRI was found in those with normal and abnormal invasive CRT. However, there may be a role for CPT MPRI in detecting endothelial dysfunction at higher thresholds of normal diameter response. Additional investigation will evaluate CPT CMRI and cardiovascular outcomes.
Abstract 19022: Endothelial Cell Specific CD36 Deletion Reduces Uptake of Fatty Acids by the Heart
Authors: Willecke Florian , Son Ni-Huiping , Fang Xiang , Drosatos Konstantinos , Pietka Terri , Abumrad Nada A , Goldberg Ira J
Published: July 2021

Circulating fatty acids must cross the endothelial cell (EC) barrier to supply cardiomyocytes (CM). How this occurs is unknown. Cluster of differentiation (CD) 36 is a membrane associated protein whose total body deletion leads to reduced uptake of non-esterified fatty acids by heart, skeletal muscle and adipose tissue. To determine the contribution of EC versus CM CD36 in heart lipid uptake, we floxed CD36 and created EC- and CM-specific knockout (KO) mice. CD36 mRNA was reduced >50% in the heart, lung and skeletal muscle of EC-CD36 KO mice; CM-CD36 KO mice also had an ~50% reduction of CD36 mRNA levels in the heart. Both CM- and EC-specific CD36 ablation altered heart mRNA levels of glucose transport and oxidation genes (e.g. Glut1 ~2-fold increased, PDK4 ~0.5-fold decreased); these changes were similar to those found in mice with total body CD36 deletion. Loss of EC-CD36 led to increased plasma free fatty acid levels and prevented heart lipid droplet accumulation after an overnight fast (assessed by EM and oil red O staining). Lipid droplet accumulation was less affected in CM-CD36 KO hearts. To quantify the role of CD36 in the uptake of short chain vs. long chain fatty acids we simultaneously injected mice with radiolabeled [14C]hexanoic acid and [3H]oleic acid. Compared to both floxed-CD36 and CM-CD36 KO mice, plasma clearance of oleic acid was significantly delayed, and heart and quadriceps muscle uptake of oleic acid was reduced >50% in EC-CD36 KO and total-CD36 KO mice. Hexanoic acid uptake was not decreased by either deletion. Therefore, CD36 in EC is needed for the accumulation of long chain fatty acids in the heart and appears to be required for movement of fatty acids across the EC barrier.
Abstract 19116: Assessment of Perioperative Minute Ventilation in Obese versus Non-Obese Patient Using a Non-Invasive Respiratory Volume Monitor
Authors: Voscopoulos Christopher , Freeman Jenny , Campbell Kathleen , George Edward
Published: July 2021

Introduction:
Adequate respiration is critical to survival and can be influenced by opioids, sedatives and apnea. Direct monitoring of ventilation has previously not been available for non-intubated patients. Reliance on indirect measures (SpO2, RR) may delay needed interventions and obese patients may be at further risk. A non-invasive respiratory volume monitor (RVM) providing real-time direct measures of MV, TV & RR in non-intubated patients is used to assess respiratory status in obese and non-obese patients.

Methods:
Data collected from an impedance-based RVM (ExSpiron-1Xi, Respiratory Motion, Waltham, MA) in 62 orthopedic patients (65.4 ±12.0 yrs, BMI: 30.8 ±6.0 kg/m
2
) before, during & after surgery (PACU arrival & discharge) were compared to predicted MV (MV
PRED
) based on IBW. Ventilator MV (Apollo, Draeger, Telford, PA) during GA was assumed to be adjusted to maintain appropriate end-tidalCO
2
.

Patients were stratified based on obesity status (cutoff BMI=30). The distributions of MV at various times were compared (non-obese vs obese) using an un-paired 1-sided t-test & a 2-sample F-test.

Results:
Despite similar MV
PRED
in both groups (6.2±0.2; 6.1±0.2 L/min, p>0.3) obese patients were managed at a higher MV during surgery (6.1±0.2; 5.3±0.2 L/min, p<0.01). MV differences were far greater preoperatively (9.7±0.4 vs. 6.7±0.3 L/min), at PACU arrival (11.4 ±1.2; 6.8±0.7 L/min) & discharge (7.7±0.5; 5.0±0.6 L/min, p<0.01 all, Fig 1). Patient-to-patient variability in MV was similar in both groups pre-op, but larger in obese patients. Even with the large average MV in obese patients, 6% of them left the PACU with MV<40% MV
PRED
.

Conclusions:
On average, obese patients have greater MV than predicted by IBW formula, likely due to greater metabolic demand. Post-op, obese patients have greater variability in ventilation when treated with standard opioid doses & may be at greater risk for hypoventilation. RVM can provide data for individualized treatment plans.
Abstract 19134: Elevated Troponin T is Associated with Adverse Outcomes After Aortic Valve Replacement
Authors: Dhillon Ashwat , Poddar Kanhaiya , Tuzcu Murat , Roselli Eric , Svensson Lars , Kapadia Samir
Published: July 2021

Background:
Data regarding association of elevated cardiac enzymes and adverse outcomes in patients who undergo aortic valve replacement (AVR) has been inconclusive. Role of coronary revascularization prior to AVR remains uncertain. We sought to understand prognostic implication of post procedure troponin T (TnT) elevation in patients undergoing AVR.

Hypothesis:
We hypothesized that patients with significantly elevated TnT after AVR will have worse outcomes representing important coronary circulation which is not revascularized.

Methods:
We retrospectively studied 4648 consecutive patients who underwent AVR at a single tertiary care center between January 2007 and December 2013. These were divided into surgical AVR (SAVR) and transcatheter AVR (TAVR). Median post procedure peak TnT was identified in the SAVR and TAVR groups. Patients were divided into quartiles based on median TnT level.

Results:
Of 4648 patients who underwent AVR, 4200 (66% male) were SAVR and 448 (59% male) were TAVR. Median post procedure peak TnT values in the TAVR and SAVR group were 0.19 [0.08-0.39] & 0.36 [0.22-0.64] respectively (p<0.001). 6 month mortality was 1.5% (65/4200) in SAVR cases and 2.7% (12/448) in TAVR cases (p=0.08). In patients with TnT less than 50
th
percentile, 6 month mortality was 0.7% & 1.8% after SAVR & TAVR respectively (p=0.1). In patients with TnT higher than 50
th
percentile, 6 month mortality was 2.4% & 3.6% after SAVR & TAVR respectively (p=0.26). In the SAVR group, mortality was 0.7% in patients with TnT levels less than 50
th
percentile & 2.4% in patients with TnT higher than 50
th
percentile (p<0.001). See Figure.

Conclusion:
Peak troponin T was significantly higher after SAVR as compared to TAVR. Higher post procedure peak TnT is associated with increased 6 month mortality. These results are highly significant in the SAVR group. The mechanism and significance of these findings requires further studies.
Abstract 19158: Myocardial Function Abnormalities in Obesity: Assessment via Standard Doppler Indices, Myocardial Speckle-tracking and Kinematic Modeling of Early Diastolic Filling
Authors: Chirinos Julio A , Claessens Tom , Raja Muhammad W , Segers Patrick , Rietzschel Ernst , DeBuyzere Marc , Gillebert Thierry ,   Asklepios Investigators
Published: July 2021

Background:
Obesity is an established risk factor for heart failure. We aimed to comprehensively characterize early subclinical obesity-related abnormalities in diastolic and systolic function in a large general population sample.

Methods:
We studied 1,603 middle-aged adults enrolled in the Asklepios study. We assessed standard Doppler indices of diastolic function, speckle-tracking echocardiography-derived myocardial systolic deformation and parameters describing the elastic recoil-driven early diastolic suction attribute of the left ventricle (LV), obtained via kinematic modeling of early mitral inflow. All models were adjusted for, age, gender and LV size.

Results:
Speckle tracking echocardiography revealed decreased longitudinal peak systolic strain in obesity (-17.3; 95%CI=-17. 7 to -16.8; P=0.001), with preserved circumferential strain (P=0.35). Obesity was also independently associated with lower stored elastic strain energy (9013 vs. 10695 m
2
/s
2
; P<0.0001) available at mitral valve opening, resulting in a lower peak force driving early diastolic filling (1824 vs. 2013 m/s2; P<0.001). Despite exhibiting a lower early diastolic mitral annular tissue velocity (8.32 vs. 9.6 cm/s; P<0.001), obese subjects demonstrated a significantly greater early diastolic mitral inflow propagation velocity (81.5 vs. 73.8 cm/s; P<0.001) and a lower damping constant c (15.1 vs. 16.7 /s; P<0.01), which represents the dampening effects of slow LV relaxation and increased tissue viscoelasticity preventing rapid LV filling).

Conclusions:
Our results suggest that the main abnormality underlying abnormal early diastolic LV filling in obesity is a reduced stored elastic strain / potential energy during systolic contraction, leading to decreased mechanical recoil during early diastole. This may be related to loss of longitudinal (but not circumferential) systolic function. Our findings have implications for our understanding the underlying mechanisms of obesity-related LV dysfunction.
Abstract 19182: Epicardial Adipose Tissue Volume Selectively Predicts Myocardial Redox State in Patients With Ischemic Heart Disease
Authors: Antonopoulos Alexios S , Sabharwal Nikant , Shirodaria Cheerag , Kelion Andrew , Uberoi Raman , Anthony Suzan , Sayeed Rana , Neubauer Stefan , Channon Keith M , Antoniades Charalambos
Published: July 2021

Introduction:
Myocardial redox state is a strong determinant of heart biology. Epicardial adipose tissue (EpAT) is in close contact with the human heart and it is likely that by secreting a wide range of adipokines it may affect the biology of the underlying myocardium.

Hypothesis:
We hypothesised that EpAT volume may predict myocardial redox state and consequently myocardial function in ischaemic heart disease (IHD).

Methods:
We recruited 38 patients undergoing coronary artery bypass grafting surgery. Patients underwent transthoracic echocardiography to assess cardiac function and cardiac computerised tomography to determine the volume of EpAT, pericardial (PerAT) and subcutaneous (ScAT) AT, by using a strictly pre-defined protocol. Samples of right atrium appendage were collected during surgery and myocardial NADPH oxidase activity was assessed by lucigenin-enhanced chemiluminescence (using its substrate -NAPDH 100uM +/- its specific inhibitor VAS2870 40uM).

Results:
Increased EpAT volume index (EpAT volume/body surface area), but not PerAT or ScAT, was strongly associated with increased myocardial NADPH oxidase activity (Figure). EpAT volume index was not related with left ventricle (LV) mass index or LV systolic/diastolic function (p=NS for all). EpAT volume index was also unrelated to risk factors or body mass index (p=NS for all).

Conclusions:
These findings introduce the concept of a local cross-talk between EpAT and the underlying myocardium in humans. EpAT volume can be used as a surrogate of myocardial redox state, and this may have direct implications in risk stratification of patients undergoing coronary bypass surgery.
Abstract 19209: Utilization of Inpatient Cardiac Rehabilitation During a Hospitalization for a Cardiac Condition: A National Sample
Authors: Pack Quinn R , Priya Aruna , Lagu Tara , Pekow Penny , Berry Robert , Atreya Auras R , Lindenauer Peter K
Published: July 2021

Introduction:
Inpatient cardiac rehabilitation (ICR) programs provide important services to patients, including daily ambulation, risk factor education, and coordinated referral to outpatient cardiac rehabilitation. However, little is known about national current utilization or practice patterns.

Methods:
Utilizing a geographically and structurally diverse sample of US hospitals (PREMIER data warehouse, Inc.) we examined the use of ICR using detailed administrative data from January 2007 to June 2011. Patients with an ICD-9 principal diagnosis of myocardial infarction (MI) or heart failure (HF), or with a procedure code for coronary artery bypass surgery (CABG), valve (V) surgery, or percutaneous coronary intervention (PCI) were included. Any patient with ≥ 1 service code for ICR was considered to have received ICR.

Results:
We evaluated 1,343,537 qualifying admissions from 458 hospitals. The overall ICR utilization rate was 20.8%. ICR utilization was highest in patients with surgical procedures with 45.5%, 37.0%, 40.7% for CABG, V, CABG+V, with rates of 23.7%, 31.3%, 23.7%, 15.6%, and 10.6% for elective PCI, urgent PCI, MI + PCI, MI alone, and HF respectively. Of 458 hospitals, 223 (49%) hospitals provided any ICR, with a median (10-90%) hospital ICR rate of 18.8% (0.06% - 74.1%). Hospitals in urban areas had significantly higher rates of ICR compared to hospitals in rural areas (30.1% vs. 18.6%) as did hospitals with presence of interventional services (surgical services: 31.5% vs. 20.2%, p = 0.006; PCI services: 30.3% vs. 14.7%, p =0.003).

Conclusions:
There appears to be substantial variation in the delivery of ICR across US hospitals. Less than half of hospitals with cardiac patients provide ICR and only a minority of patients ever receives ICR. This substantial gap in the secondary prevention of heart disease appears to warrant further investigation and intervention.
Abstract 19312: A Follow-up Study of Coronary Vasomotor Function in Ischemic and Remote Myocardium Following Successful Percutaneous Revascularization for Acute Myocardial Infarction - a [15O]H2O PET Study
Authors: Teunissen Paul F , Timmer Stefan A , Danad Ibrahim , Harms Hans J , Raijmakers Pieter G , Lammertsma Adriaan A , van Rossum Albert C , van Royen Niels , Knaapen Paul
Published: July 2021

Introduction:
In patients with acute myocardial infarction (AMI), coronary vasomotor function is not only impaired in the myocardial territory supplied by the culprit-artery but also in remote myocardium supplied by angiographically normal vessels.

Aims:
The aim was to investigate the temporal evolution of coronary vasodilatory reserve in patients with AMI by use of [15O]H2O PET, after successful percutaneous coronary intervention (PCI).

Methods:
Fourty-four patients with AMI and successful revascularization by PCI were included (i.e. TIMI II or III flow after coronary stenting). Subjects were examined one week and three months after AMI with [15O]H2O PET to assess the coronary flow reserve (CFR). CFR was defined as the ratio of myocardial blood flow during hyperemia (hMBF) and rest (MBF). Additionally, 45 age and sex matched subjects without a prior cardiac history underwent similar scanning procedures and served as a control group.

Results:
At baseline, CFR averaged 1.77 ± 0.63 in infarcted myocardium versus 2.41 ± 0.79 in remote myocardium (p < 0.001). In comparison, CFR in the control group averaged 4.16 ± 1.45 (p = 0.001 versus both). During follow-up, the CFR increased from 1.77 ± 0.63 to 2.75 ± 0.89 in infarcted myocardium (p < 0.001), and from 2.41 ± 0.79 to 2.85 ± 0.75 in remote myocardium (p = 0.001). This was predominantly due to an increase in hMBF, from 1.64 ± 0.54 to 2.19 ± 0.74 mL/min/g in infarcted myocardium (p < 0.001), and 2.20 ± 0.56 to 2.61 ± 0.65 mL/min/g in remote myocardium (p = 0.001).

Conclusions:
Coronary vasodilatory reserve is impaired in both ischemic and remote myocardium directly after AMI. Following successful revascularization, the coronary vasodilatory reserve significantly improved in both regions. As a consequence, these early and late post-infarct alterations in remote myocardium may also affect temporal infarct evolution and recovery of left ventricular function.
Abstract 19335: Not Your Typical Atrial Flutter
Authors: Olson Matthew D , Adabag Selcuk
Published: July 2021

Case:
Mr M. presented to the emergency room with two months of progressive shortness of breath and was found to be in atrial flutter with 2:1 conduction at a rate of 140 bpm. His medical history was significant for tobacco use, etoh abuse, and hypertension. Key objective findings included tachycardia, hypoxia an elevated JVP, bibasilar crackles, a summation gallop, and lower extremity edema. His work up included an echocardiogram that illustrated a globally depressed EF (15-20%) and a large “worm like” mass that was free floating and extended into the RV.

Management:
A heparin drip was already infusing as the initial plan included cardioversion. Since the patient remained hemodynamically stable and there was no evidence of concurrent deep vein thrombosis, a TEE was performed to fully evaluate the mass and to assess the intra-atrial septum for right to left shunting. The TEE with 3D renderings demonstrated a mobile 0.8 x 10 cm mass most consistent with a thrombus that intermittently prolapses through the tricuspid valve into the RV. CT surgery was consulted and discussed the options of thrombolysis vs surgical thrombectomy. Due to the size and apparent dense organization of the thrombus, surgical thrombectomy was performed. When the right atrium was opened after initiation of bypass, there was no visible clot. The main PA was explored and without evidence of the thrombus. As bypass flow decelerated, the clot proceeded into the RA from the IVC cannula. The attached picture illustrates the thrombus removed from the RA and associated echo images.

Discussion:
Right atrial or ventricular thrombi in transit in hypoxic patients create a challenging clinical dilemma, as distal embolization may be fatal. In this case we chose to surgically remove the thrombus instead of the more commonly employed thrombolytic therapy. The determining factors included clot organization, relative patient stability, and surgical candidacy.
Abstract 19363: Migration of MicroRNAs From Cardiomyocytes to Cancer Cells Interferes With Tumor Formation in the Adult Heart
Authors: Graciotti Laura , Hosoda Toru , Sanada Fumihiro , Borghetti Giulia , Arranto Christian , Valeriani Fiorenza , Wybieralska Ewa , Ogorek Barbara , Rota Marcello , Goichberg Polina , Anversa Piero , Leri Annarosa
Published: July 2021

The low incidence of cardiac tumors has been attributed to tissue pressure dictated by myocardial mechanics and large coronary blood flow. These variables, however, have failed to consider the possibility that the rare occurrence of heart neoplasms may be dictated by the molecular characteristics of cardiomyocytes. We have shown that miR-1, miR-133a, and miR-499 translocate from myocytes to co-cultured MCF7 breast cancer cells, inhibiting their growth. The transfer of miRs is mediated by gap junction channels and is abolished by Cx43 and Cx45 silencing. Although these in vitro results provided important information on the inhibitory function of miRs in cell proliferation, co-culture of myocytes and cancer cells does not mimic the in vivo organization of the myocardium that allows the formation of multiple sites of coupling between myocytes and tumor cells. To reproduce, at least in part, the in vivo condition, we developed first a physiological model of organ culture. Thick vibratome-cut myocardial slices were placed on a multiwell plate containing an oxygen-saturated sponge. At 24-48 hours, the cultured tissue was viable and myocytes showed a well organized sarcomere structure. Two hours after plating of the organ slices, control MCF7 cells or MCF7 cells in which Cx43 and Cx45 were silenced (MCF7-shCx43-shCx45) were seeded on the myocardium. Control MCF7 cells showed a slower growth rate than MCF7-shCx43-shCx45 cells, a finding consistent with miR translocation and its blockade, respectively. Second, 1 x 106 MCF7 or MCF7 cells overexpressing miR-1, miR-133a, and miR-499 (MCF7-miRs) were injected subcutaneously in NOD-SCID mice; ~45 days later, the tumors developed from MCF7 cells were more than 10-fold larger and 3-fold heavier than those originated from MCF7-miRs cells. Third, these studies were complemented with the intramyocardial injection of 1 x 105 control MCF7 cells. Five weeks later, no neoplastic lesions were identified. However, when an excessive number of MCF7 cells were injected, 1 x 106, tumor formation was apparent. In conclusion, our results indicate that transfer of miR-1, miR-133a, and miR-499 from cardiomyocytes to cancer cells plays a critical role in preventing the generation of tumors in the myocardium.