bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19055: MicroRNA Gene Expression of Heart Transplant Endomyocardial Biopsy
Authors: Chang Eleanor , Fishbein Gregory , Bakir Maral , Bondar Galyna , Jackson Nicholas , Liem David , Litovsky Silvio , Tallaj Jose , Starling Charlotte , Ping Peipei , Reed Elaine , Deng Mario , Tabak Esteban , Cadeiras Martin
Published: July 2021

Introduction
Endomyocardial biopsy is the standard surveillance method to detect cardiac allograft rejection. While microRNAs (miRNA) play a major role in regulating mRNA, their nature and role in the biology is not well understood. We hypothesized that specific mRNA-miRNA networks can be identified underlying the clinical phenotypes of different forms of cardiac allograft rejection.

Method
Twenty one tissue samples from 14 post-HTx patients were subjected to genome wide miRNA sequencing. A non-parametric empirical Bayes framework removed batch effect and filtered genes with low variability. Weighted Gene Correlation Network Analysis (WGCNA) clustered genes into related eigengene modules based on their gene expression. Identified miRNAs were subjected to target prediction and compared with mRNA expression profiles previously identified on the same biopsies. Gene Ontology (GO) was used for biological interpretation of selected genes.

Results
1270 miRNAs were used to construct 9 eigengene modules. Module-Trait relationship were then investigated as shown in Figure. The top ten miRNA probe sets filtered by the highest intra-module correlation and statistical significance were hsa-miR-141-3p, hsa-miR-150-5p, hsa-miR-605, hsa-miR-582-5p, hsa-miR-3150b-3p, hsa-miR-508-3p, hsa-miR-652-5p, hsa-miR-26a-1-3p, hsa-miR-3667-3p and hsa-miR-3911. Target prediction analysis resulted in 724 gene targets. GO analysis revealed 184 categories enriched by these genes including regulation of protein kinase activity, cardiac muscle cell differentiation and epithelial cell migration among others. Compared to mRNA previously identified in the same heart biopsies showed 685 overlapping gene targets.

Conclusion
WGCNA identified miRNA modules correlated with different clinical phenotypes of rejection. MRNA-miRNA pairs were identified to help understand the biology of rejection and as interesting candidates for diagnostic or therapeutic applications.
Abstract 19094: Use of ACE Inhibitors or Angiotensin Receptor Blockers is Associated With a Significantly Lower Risk of 30-day All-cause and Heart Failure Readmissions and All-cause Mortality in Older Medicare Beneficiaries Hospitalized for Heart Failure Developing Acute Kidney Injury
Authors: Siddiqui Mohammed , Sanders Paul W , Arora Garima , Morgan Charity , Zhang Sijian , Prabhu Sumanth D , Agarwal Anupam , Cutter Gary , Mehta Ravindra L , Deedwania Prakash , Fletcher Ross D , Fonarow Gregg C , Butler Javed , Aronow Wilbert S , Wu Wen-Chih , Anker Stefan D , Allman Richard M , Ahmed Ali
Published: July 2021

Background:
We presented data that demonstrating that acute kidney injury (AKI) as defined by a rise in admission serum creatinine by ≥0.3mg/dL is associated with a 16% significant increase in 30-day all-cause readmission in hospitalized heart failure (HF) patients (Circulation. 2014; 130: A19999). We have previously published data suggesting that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is associated with improved outcomes in HF patients with chronic kidney disease (PMC3324926 and PMC3575519). However, these drugs are often avoided in HF patients with AKI.

Methods:
Of the 8049 Medicare beneficiaries hospitalized for HF and discharged alive from 106 U.S. hospitals (1998-2001), 6854 had data on admission, discharge, and highest serum creatinine, of which 2180 had AKI (a rise in admission serum creatinine by ≥0.3 mg/dL) and of these 1171 (54%) received a discharge prescription for ACEIs or ARBs. Using propensity scores for ACEI or ARB use, we assembled a matched cohort of 755 pairs of patients balanced on 33 baseline characteristics including baseline serum creatinine and rise of serum creatinine.

Results:
30-day all-cause readmission occurred in 21% and 27% of matched patients receiving and not receiving ACEIs or ARBs, respectively (HR, 0.77; 95% CI, 0.62-0.95; p=0.015). 30-day HF readmission occurred in 6% and 11% of matched patients receiving and not receiving ACEIs or ARBs, respectively (HR, 0.53; 95% CI, 0.37-0.76; p=0.001). 30-day all-cause mortality occurred in 5% and 9% of matched patients receiving and not receiving ACEIs or ARBs, respectively (HR, 0.89; 95% CI, 0.79-1.00; p=0.052). Both readmission and mortality benefits persisted for 12 months post-discharge (Figure).

Conclusions:
Among patients hospitalized for HF who developed AKI after hospital admission, discharge prescription of ACEIs or ARBs was associated with significant short- and long-term improvements in outcomes.
Abstract 19161: cAMP Regulated Transcriptional Coactivator 1 - A Novel Player in Cardiac Hypertrophy
Authors: Morhenn Karoline M , Quentin Thomas , Schroeder Sabine , Pahl Anja , Steinmetz Michael , Geertz Birgit , Eschenhagen Thomas , Schlossarek Saskia , Carrier Lucie , Cardinaux Jean-René , Zimmermann Wolfram-Hubertus , Lutz Susanne , Oetjen Elke
Published: July 2021

Maladaptive cardiac hypertrophy leads to heart failure, a common cause for hospitalization. Chronic β-adrenergic, PKA dependent signaling and calcineurin contribute to hypertrophy. These signals converge in many tissues on the cAMP Regulated Transcriptional Coactivator 1 (CRTC1).

We studied if CRTC1 promotes the development of maladaptive cardiac hypertrophy in human and murine hearts.

In cardiomyocytes, treatment with β-adrenoceptor agonist isoprenaline dephosphorylated, thus activated 59 ± 5 % of total CRTC1, as seen by immunoblot (n = 3-4). Activation was prevented by propranolol. CRTC1 was not activated by endothelin or angiotensin II. CRTC1 protein content was enhanced in human and murine heart tissue under conditions of acquired and inherited maladaptive hypertrophy, seen by immunoblot (n = 7-8).
Crtc1
-deficient mice (KO) showed a higher ratio of heart weight to tibia length than their wild-type littermates (WT) (8.6 ± 0.4 mg/mm vs. 10.9 ± 0.8 mg/mm in WT and KO, respectively, n = 12) and increased myocyte size (516 ± 8 μm
2
vs. 590 ± 11 μm
2
in WT and KO, respectively, n = 3 hearts). Echocardiographically assessed, the ejection fraction, fractional area shortening and cardiac output were reduced by 47 ± 8 %, 49 ± 12 % and 42 ± 9 %, respectively, in KO mice (n = 6-9). mRNA levels of
Nppa
,
Nppb
,
Acta1
,
Myh7
and the pro-fibrotic
Ctgf
did not differ between WT and KO mice (n = 12-15). By reducing G
αq
-protein induced signals in the heart, the Regulator of G-Protein Signaling 2 (RGS2) reduces hypertrophy. In KO mice the
Rgs2
mRNA and protein levels were reduced by 26 ± 10 % and by 38 ± 8 %, respectively (n = 8-10). In a luciferase reporter gene assay overexpression of CRTC1 stimulated
Rgs2
promoter transcriptional activity 1.8 fold (± 0.1); mutation of the CRTC1-interaction site, the cAMP-response element, prevented CRTC1-induced transcriptional activity (n = 6). In addition, chromatin immunoprecipitation showed the recruitment of endogenous CRTC1 to the
Rgs2
promoter in cardiac tissue.

In conclusion, our data indicate that increased CRTC1 protein content in maladaptive cardiac hypertrophy is a compensatory mechanism to delay disease progression, in part by upregulation of RGS2. Thus, CRTC1 represents a novel player of cardiac hypertrophy.
Abstract 19212: Racial Differences in Clinical Outcomes and Resource Utilization Associated With Heart Failure Hospitalizations in the United States: A Nationwide Analysis From 2011-2012
Authors: Kumar Nilay , Khera Rohan , Garg Neetika
Published: July 2021

Background and objectives:
Heart failure (HF) incidence is higher among Blacks compared to Whites. There is a paucity of recent data on racial differences in in-hospital mortality and resource utilization in a nationally representative, multiracial cohort of HF hospitalizations.

Hypothesis:
There are significant racial-ethnic differences in HF hospitalization outcomes.

Methods:
We used the 2011-2012 Nationwide/National Inpatient Sample to identify hospitalizations with a primary diagnosis of HF using relevant ICD-9 codes. Outcomes of interest were in-hospital mortality, length of stay (LOS) and mean inflation adjusted charges. The effect of race on outcomes was ascertained using logistic or linear regression.

Results:
375,740 primary HF hospitalizations representing 1.8 million hospitalizations nationwide were included. Mean age was 72.6 (SD 14.6) years and 50.1% were females. After adjusting for age, sex, hypertension, diabetes, APR-DRG mortality risk and socioeconomic status, in-hospital mortality was significantly lower for Blacks (OR 0.69, 95% CI 0.64 - 0.74; p<0.001), Hispanics (OR 0.82, 95% CI 0.75 - 0.91; p<0.001) and Asians or Pacific Islanders (OR 0.85, 95% CI 0.73 - 0.99; p=0.04) compared to Whites. Average inflation adjusted charges were significantly higher for all minorities compared to Whites except for Native Americans for whom charges were significantly lower than Whites (p<0.05 for Black, Hispanic, Asian, NA or Others vs. Whites). LOS was modestly higher for Blacks or Other races vs. Whites (p=0.01 B vs. W and Others vs. W) and lower for Native Americans vs. Whites (p<0.001).

Conclusions:
Blacks, Hispanics and Asians hospitalized for HF are significantly less likely to die in the hospital compared to Whites. Hospital charges for racial-ethnic minorities are significantly higher compared to Whites. The reasons for racial differences in HF hospitalization outcomes require further investigation.
Abstract 19225: Impact of Change in Resuscitation Guidelines on National Out-of-hospital Cardiac Arrest Outcomes: Fulfilled Expectations?
Authors: Eid Shaker M , Albaeni Aiham , Rios Rebeca , Baydoun May , Akinyele Bolanle , Raghavakurup Lekshmi N , Baydoun Hind , Chandra-Strobos Nisha
Published: July 2021

Background:
The intent of the 5-yearly Resuscitation Guidelines is to improve outcomes. Previous studies have yielded conflicting reports of a beneficial impact of the 2005 guidelines on out-of-hospital cardiac arrest (OHCA) survival. Using a national database, we examined survival before and after the introduction of both the 2005 and 2010 guidelines.

Methods:
We used the 2000 through 2012 National Inpatient Sample database to select patients ≥18 years admitted to hospitals in the United States with non-traumatic OHCA (ICD-9 CM codes 427.5 & 427.41). A quasi-experimental (interrupted time series) design was used to compare monthly survival trends. Outcomes for OHCA were compared pre- and post- 2005 and 2010 resuscitation guidelines release as follows: 01/2000-09/2005 vs. 10/2005-9/2010 and 10/2005-9/2010 vs. 10/2010-12/2012. Segmented regression analyses of interrupted time series data were performed to examine changes in survival to hospital discharge.

Results:
For the pre- and post- guidelines periods, 81600, 69139 and 36556 patients respectively survived to hospital admission following OHCA. Subsequent to the release of the 2005 guidelines, there was a statistically significant worsening in survival trends (β= -0.089, 95% CI -0.163 – -0.016,
p
=0.018) until the release of the 2010 guidelines when a sharp increase in survival was noted which persisted for the period of study (β= 0.054, 95% CI -0.143 – 0.251,
p
=0.588) but did not achieve statistical significance (Figure).

Conclusion:
National clinical guidelines developed to impact outcomes must include mechanisms to assess whether benefit actually occurs. The worsening in OHCA survival following the 2005 guidelines is thought provoking but the improvement following the release of the 2010 guidelines is reassuring and worthy of perpetuation.
Abstract 19240: Operative Indication for Chronic Dissecting Aneurysm in Descending Thoracic and Thoracoabdominal Aorta
Authors: ODA TATSUYA , Minatoya Kenji , Sasaki Hiroaki , Tanaka Hiroshi , Seike Yoshimasa , Itonaga Tatsuya , Inoue Yosuke , Kobayashi Junjiro
Published: July 2021

Background:
Because of a lack of information about the rupture size of chronic dissecting descending thoracic and thoracoabdominal aneurysms, we evaluated the natural history of those aneurysms.

Patiens and Methods:
Data on 422 patients (mean age, 63.3 ± 11.3; 272 male) with chronic dissection in descending thoracic and thoracoabdominal aorta treated at our institution from 2007 to 2014, were analyzed. Patients with connective tissue disorder, impending rupture of aneurysms, infected aneurysms, and an acute dissection without aneurysms were excluded. Chronic dissection was defined as a dissection more than 2 weeks from symptom onset. The aneurysm diameter at the time of the rupture was measured on CT scan in ruptured aneurysms group (n=21), and initial aneurysmal diameter on CT scan in non-ruptured aneurysms group (n=401). The measurements were performed at maximum short axis diameter of the aneurysm on three-dimensional CT.

Results:
Midian size of all aneurysms was 4.5 cm (range 3.5 to 9.0 cm) and that of in ruptured aneurysms was 5.9 cm (range 4.5-8.0 cm). The location of aneurysms was descending aorta in 303 patients, thoracoabdominal aorta in 119. Aortic surgery was performed in 150 patients (urgent in 20, elective in 130). Hospital mortality rate were 20% (5/20) in patients with ruptured aneurysms and 2.3% (3/130) in patients with non-ruptured aneurysms. Figure shows the incidences of rupture according to the aneurysm size. The incidence of a rupture increases with larger aortic size. At 3.5 to 3.9 cm, 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm and more than 6.0 cm, the incidence of rupture was 0%, 0%, 1.2%, 10.2%, 14.3% 20.8%, respectively. The aneurysms more than 5.0 cm were ruptured in 15.1% of patients.

Conclusions:
Because an elective operation is associated with low mortality, operative indication of chronic dissecting aneurysm in descending and thoracic-abdominal aorta should be considered when its size is 5.0 cm or larger in good-risk patients.
Abstract 19242: No Difference in Skill Acquisition and Retention When Teaching Laypersons Recovery Position Using Four-stage and Two-stage Teaching Technique: A Randomized Comparison
Authors: Bjørnshave Katrine , Krogh Lise Q , Hansen Svend B , Nebsbjerg Mette A , Rasmussen Stinne E , Thim Troels , Løfgren Bo
Published: July 2021

Introduction:
Resuscitation guidelines recommend that unconscious and spontaneously breathing persons are placed in the recovery position to secure airway patency. Techniques for teaching the recovery position require evaluation.

Aim:
To evaluate acquisition and retention of recovery position skills among laypersons taught using a four-stage and two-stage teaching technique.

Methods:
Laypersons were randomized to a standardized European Resuscitation Council (ERC) courses in BLS/AED including training in recovery position using a four-stage teaching technique compared to modified course with the same content using a two-stage teaching technique. Participants were tested immediately after training and three months (±five days) later to assess acquisition and retention of recovery position skills. Tests were video recorded and reviewed by two assessors blinded to teaching technique. A skill checklist in accordance with the ERC guidelines representing the eight steps of the recovery position was used. The primary endpoint was passing the test (8 out of 8 skills).

Result:
In total, 160 participants were included. Total average number of steps of eight performed correctly was 7.3±1.0 (n=70) vs 7.1±1.1 (n=72) (p=0.5) immediately after the course and 4.1 ±2.3 (n=64) vs 3.8 ±2.3 (n=64) (p=0.4) three month later when using the four-stage and the two-stage technique, respectively. Correct final recovery position was obtained by 91% vs 93% immediately after the course and 49% vs 42% three month later. Each separate step of the recovery position is shown in Table 1.

Conclusion:
There was no difference in skill acquisition and retention when teaching laypersons recovery position using the four-stage and two-stage teaching technique. There was a marked decrease in skill level three months after training, particularly keeping the airway patent by head tilt and checking breathing regularly in both groups.
Abstract 19271: Lack of Sufficient Pulsatile Flow in the Microvasculature May Contribute to Increased Microvascular Complications in Patients Implanted With Continuous Flow Left Ventricular Assist Devices
Authors: McDonnell Barry J , Castagna Francesco , Najjar Mark , Watkeys Laura , Kearney Maria , Yuzefpolskaya Melana , Topkara Veli , Garan Arthur R , Mancini Donna M , Takayama Hiroo , Naka Yoshifumi , Colombo Paolo C , Cockcroft John R
Published: July 2021

Background:
In patients on continuous flow left ventricular assist devices (CF-LVAD) support, low pulsatility has been implicated in the development of microvascular complications such as gastrointestinal bleeds and strokes. The aim of this study was to measure and compare the microvascular flow profiles of both CF-LVAD patients and age matched healthy controls.

Methods:
The cuff based Mobil-O-Graph system (IEM) was used to measure supine blood pressure (BP) in 6 patients implanted with a CF-LVAD. Using the captured brachial pressures and associated waveform, the inbuilt ARCSolver algorithm was used to calculate central systolic and diastolic pressures, augmentation index (AIx) and aortic pulse wave velocity (aPWV). Pulsatility index (PI) of the central retinal (CR) and mid cerebral artery (MCA) was measured using a 12MHz linear probe with vivid-Q ultrasound and 2MHz transcranial Doppler ultrasound, respectively. Similar measurements were recorded in 13 healthy, age, mean pressure and aPWV matched controls.

Results:
Brachial and central pulse pressures were both significantly lower in CF-LVAD patients compared to controls. In addition, PI was significantly lower in the CF-LVAD group compared to controls in the CR and MCA (Table).

Conclusion:
Our data provide the first evidence that pulsatile flow is significantly lower in the microcirculation of CF-LVAD patients compared to healthy controls. This lack of pulsatile flow to appropriately stimulate the endothelium and replicate normal healthy haemodynamics, may in part be responsible for the increased risk of microvascular complications in CF-LVAD patients. As this is a pilot study, more mechanistic studies assessing macro and microvascular flow haemodynamics in CF-LVAD patients are needed to understand these associations further.

Table.
Abstract 19324: Effects of Simulated Microgravity on Ckit+ Cardiac Progenitor Cells
Authors: Hatzistergos Konstantinos E , Takeuchi Lauro M , Balkan Wayne , Hare Joshua M
Published: July 2021

Introduction:
Space flight has profound negative impacts on cardiac health. Whereas microgravity appears to benefit cardiomyogenesis, long-duration space flight results in increased risk for cardiomyopathy. Here, we focused on cKit+ cardiac progenitor cells (CPCs) to elucidate the effects of microgravity in the heart.

Hypothesis:
Microgravity inhibits migration, proliferation and differentiation of CPCs.

Methods:
Adult heart tissue or induced pluripotent stem cells (iPSCs) from cKitCreErt2;IRG mice were grown for up to 24- (n=5) or 21-days (n=6), respectively, in static (SC) or a rotary cell-culture system (RCCS, simulated microgravity) in the presence of 4-OH tamoxifen to irreversibly label CPCs with EGFP. Expression of EGFP was quantified at selected time points in heart explants and iPSC-derived beating embryoid bodies (EBs). In addition, microarray analysis was performed on EBs at selected time points (n=11).

Results:
We found that, although explants in SC consistently produced EGFP+ CPCs with full capacity to proliferate and migrate, expression of EGFP was abolished in RCCS (p<0.05). Similarly, when day-4 EBs (formed via the hanging-drop method) were transferred to RCCS, they generated significantly fewer spontaneously beating EBs compared to EBs grown in SC (p=0.0005), whereas expression of EGFP in beating EBs was downregulated ~10-fold (p=0.01). Microarray analysis of EBs illustrated that the effect of CPs was accompanied by downregulation of genes related to migration, differentiation and development of the cardiac neural crest cell (CNC) lineage (i.e. Pax3, semaphorins, endothelin) without affecting the expression of cardiac mesoderm-related genes (i.e. GATA4, NKX2-5, MEF2C). Intriguingly, the effect of RCCS in CNC-related genes could be partly rescued upon transfer of EBs from RCCS to SC.

Conclusions:
cKit expression and CNC pathways are inhibited under simulated microgravity but can be reversed by returning to normal gravity. Our findings provide novel insights into the role of gravity in cardiomyogenesis and suggest that CPCs should be targeted therapeutically for the prevention and treatment of microgravity-induced cardiomyopathy.
Abstract 19336: Reported Stroke Rates in Patients With Nonvalvular Atrial Fibrillation in North America are Lower Than Those Cited in ESC and AHA Guidelines
Authors: Quinn Gene R , Singer Daniel E
Published: July 2021

Background:
Anticoagulants (OAC) decrease ischemic stroke rates in patients with atrial fibrillation (AF) but increase the risk of bleeding. The risk of ischemic stroke where the absolute benefit of anticoagulation outweighs the bleeding risk has been shown to be 1-2% per year. The American Heart Association/American College of Cardiology/Heart Rhythm Society and the European Society of Cardiology (ESC) guidelines have adopted the CHA2DS2-VASc stroke risk score; their recommendations assume the scheme’s point scores correspond to fixed stroke rates. However, reported rates of stroke vary widely across cohorts, placing in question the generalizability of guideline recommendations.

Objective:
To contrast the reported rates of stroke in North American (NA) patients with AF who do not take OAC with the Danish AF cohort used to create the ESC guidelines.

Methods:
We conducted a systematic review to identify all cohort studies and randomized controlled trials including patients with non-valvular AF not treated with OAC. We excluded studies that enrolled only patients undergoing surgical procedures or cardioversion, or only patients with specific comorbidities such as prior stroke or kidney disease.

Results:
Of the 3,552 studies screened, we identified 13 eligible NA studies representing 137,652 patients. Larger and more contemporary cohorts generally had lower stroke rates (Table). When weighted by number of subjects, the NA cohorts’ ischemic stroke rate averaged 1.88% per year, whereas the Danish cohort had a rate of 4.66% per year.

Conclusions:
Large variation exists in stroke rates across putatively representative cohorts. This may reflect true differences in rates or methodologic differences among studies. These differences could change the point score threshold for recommending OAC in lower risk regions. Reexamining the net benefit of OAC in patients with a CHA2DS2-VASc score of 1 or 2 seems warranted, particularly for those with weak 1-point risk factors.
Abstract 19379: Red Blood Cell Washing Increases Kidney Injury in Cardiac Surgery Patients - The Role of Oxidised Lipids and Oxidative Stress
Authors: Wozniak Marcin J , Sullo Nikol , Qureshi Saqib , Patel Nishith , Will Dott , Nielsen Pia , Kumar Tracy , Joel-David Lathishia , Wiltshire Michael , Cardigan Rebecca , Murphy Gavin
Published: July 2021

Introduction:
Allogeneic red blood cell (RBC) transfusion in cardiac surgery patients increases the risk of pulmonary and renal morbidity. These associations are attributable to the ‘storage lesion’ - accumulation of metabolites in the RBC supernatant that includes pro-inflammatory lipids, cell-free hemoglobin and energy depletion.

Hypothesis:
Storage lesion components trigger different events that lead to organ injury. Reducing storage lesion by RBC washing or rejuvenation will reduce organ injury.

Methods:
Samples from 60 cardiac patients participating in a randomized controlled trial of RBC washing prior to transfusion versus standard care were analysed for inflammatory markers. In a complementary experiment, 4 groups of pigs received crystalloid infusion or 14-day old RBC that were left untreated, washed or rejuvenated (Rejuvesol, Citra Labs, IN). Inflammatory markers, free hemoglobin and iron were measured in blood. Leukocyte invasion was determined by immunohistochemistry. The results were verified and further analysed in an in vitro inflammatory model.

Results:
Transfusion of stored RBC (~22 days) into humans or pigs was associated with leukocyte activation, and attenuated by washing. That was attributed to oxidised lipids on transfused RBC derived microvesicles that activated monocytes and platelets, as revealed in depletion experiments. Unexpectedly, transfusion of washed RBC increased kidney injury, which correlated with higher free haemoglobin levels, oxidative stress (confirmed by HMOX-1 levels and protein carbonylation), and endothelial injury in washed RBC recipients. Oxidative stress triggered non-standard endothelial activation defined by expression of VLA5 and fibronectin retention. Either pathway was reduced when rejuvenated blood was transfused.

Conclusion:
Monocytes/platelets and endothelium are activated by oxidized lipids/MV and reactive free haem, respectively, and can be alleviated by RBC rejuvenation.
Abstract 19385: Postprandial Hypotension, is it Real? The Preliminary Results of a Pilot Study
Authors: Lee Ju-Hee , Bae Dae-Hwan , Kim Sang-Min , Lee Sang-Yeub , Bae Jang-Whan , Hwang Kyung-Kuk , Kim Dong-Woon , Cho Myeong-Chan
Published: July 2021

Introduction:
Postprandial hypotension is an important hemodynamic abnormality but it is very under-recognized. We performed this pilot study to evaluate the prevalence of postprandial hypotension and the possible associations between postprandial blood pressure (BP) decline and other forms of BP variability in type 2 diabetes.

Methods:
We enrolled 21 patients with type 2 diabetes. All patients were examined with ambulatory BP monitoring and we recorded every meal time. Postprandial hypotension was defined as a systolic BP fall of at least 20 mmHg compared with baseline BP level.

Results:
Mean age was 64.4±11.8 years and 11 patients were female (52.4%). Overall systolic BP and diastolic BP are 127.4±13.2 mmHg and 73.4±9.8 mmHg. Overall systolic BP variability was 13.7±5.5. Average postprandial BP fall was 13.9±10.7 mmHg and the BP fall was most conspicuous after breakfast. Fourteen patients (67%) were experienced postprandial hypotension by definition. Among them, 6 patients (43%) were non-dipper, 5 patients (36%) were reverse dipper and a patient was extreme dipper. Average systolic BP variability was significantly higher in the patients with postprandial hypotension (15.1±6.2 vs. 10.9±1.9, P=0.02).

Conclusions:
Postprandial hypotension is common in type 2 diabetes and there is possible relationship between postprandial hypotension and other abnormal BP patterns. To clarify the clinical significance of postprandial hypotension, large sized long term prospective study is needed.
Abstract 19427: Epidemiology and Outcomes of Out-of-hospital Cardiac Arrest in Qatar
Authors: Irfan Furqan B , Bhutta Zain A , Tariq Tooba , Shaikh Loua A , Govender Pregalathan , Owen Robert C , Suwaidi Jassim A , Singh Rajvir , Djarv Therese , Thomas Stephen , Smith Karen , Castren Maaret , Cameron Peter
Published: July 2021

Aim:
There is a scarcity of population based studies on out-of-hospital cardiac arrest (OHCA) in the Middle East and the wider Asian region. This study describes the Epidemiology and outcomes of OHCA in Qatar, a Middle Eastern country.

Methods:
Data was extracted retrospectively from a national registry on all adult cardiac origin OHCA patients attended by Emergency Medical Services (EMS) in Qatar, from June 2012 - May 2013.

Results:
The annual crude incidence rate of cardiac origin OHCA attended by EMS was 23.5 per 100,000. The age-sex standardized incidence rate was 87.83 per 100,000 population. The annual sex-standardized incidence rate for males and females was 91.5 and 84.25 per 100,000 population respectively.

Of 447 adult, cardiac origin OHCA patients included in the final analysis, most were male (n=360, 80.5%) with median age of 51 years (IQR = 39-66). Frequently observed nationalities of OHCA cases were Qatari (n=89, 19.9%), Indian (n=74, 16.6%) and Nepalese (n=52, 11.6%).

Common initial cardiac arrest rhythms were asystole (n=301, 67.3%), ventricular fibrillation (n=82, 18.3%) and pulseless electrical activity (n=49, 11%).

OHCA was unwitnessed (n=220, 49%) in nearly half of the cases while bystanders witnessed it in 170 (38%) patients. Bystander CPR was carried out in 92 (20.6%) of the cases. Of 187 (41.8%) patients who were given shocks, bystander defibrillation was delivered to 12 (2.7%) patients.

Prehospital outcomes; 332 (74.3%) patients did not achieve return of spontaneous circulation (ROSC), 40 (8.9%) patients achieved unsustainable ROSC, 58 (13%) achieved ROSC till Emergency department (ED) handover and 5 patients achieved ROSC but rearrested again before reaching ED.

Survival to hospital discharge occurred in 38 (8.5%) patients. Neurological outcomes were assessed utilizing Cerebral Performance Category [CPC] scores with a favorable CPC score of 1-2 at discharge in 27 (6%) patients, while 11 (2.5%) patients had a poor CPC score of 3-4. Of those with CPC score 1-2 at hospital discharge, 59% and 26% had CPC score 1-2, at 1 and 3 years follow-up respectively. Overall survival was 9.7%.

Conclusion:
Standardized rates are comparable to western countries, there are significant opportunities to improve outcomes, including better bystander CPR.
Abstract 19439: Melatonin Blunts Pressure-overload Left Ventricular Hypertrophy and Improves Cardiac Performance in Pathologic and PPhysiologic Cardiac Hypertrophy
Authors: Offerhaus Joost , Lee Dong , Bedja Djahida , Cingolani Oscar
Published: July 2021

Introduction:
Reactive oxygen species (ROS) has been established as key mediators in cardiac hypertrophy and function through activation of redox-sensitive kinases, by stimulating NADPH oxidase. Melatonin has been described as having potent antioxidant properties in different tissues.

Hypothesis:
The hormone melatonin, would prevent pressure-overload (pathologic) hypertrophy,

Methods:
Mice (C57Bl6) were subjected to transverse aortic constriction (TAC), and treated with melatonin (MEL, 10 mg/Kg/day) in water (“TAC+MEL”) or placebo (TAC). A second group underwent intense treadmill exercise for 8 weeks and also received melatonin (EX-MEL) or water (EX). A sham operated group served as control (“sham”). After 7 weeks of TAC and 8 weeks of exercise, cardiac function was assessed by echocardiography and pressure –volumetric analysis. Cardiac ROS activity (TBARS, NRF2, Keap-1) was determined.

Results:
TAC promoted LVH in mice (LVMI: 6.38±0.38 mg/mm tibia length (sham), 8.11±0.63 (TAC) which was blunted by melatonin (LVMI: 6.34±0.31 (TAC+MEL) mg/mm, P<0.05). Increased LVH was associated with decreased endocardial shortening measured by echocardiography, from 61±2 (sham) to 54±1.8 % (TAC + placebo), P <0.05. This decrease in fractional shortening was less pronounced in the TAC+ MEL group (58±2.9%) as well as in PV loop analysis. The antioxidant action of MEL was evidenced by the decrease in myocardial lipid peroxidation (TBARS) from 0.35±0.02 (TAC) to 0.25±0.02 (TAC+MEL) nmol/mg of protein, P<0.05. Adult mice isolated myocyte studies revealed that Ang 2 (20nM) increased sarcomere shortening and calcium transient, both of which were blunted when cells were pre-incubated with melatonin (p< 0.005, Ang2
vs
MEL + Ang2). In the exercise group, melatonin had only a small, non-significant reduction in LVMI, but a marked improvement in cardiac performance (PV loop analysis).

Conclusion:
Melatonin prevents pressure-overload LVH and improves contractility due to its antioxidant action. In physiologic LVH (exercise), melatonin does not affect hypertrophy, but exerts a positive effect on cardiac performance. These effects seem to be, at least in part, mediated through melatonin interfering with the Keap-1- Nrf2 antioxidant pathway.
Abstract 19495: Compensatory Strategies Improve Medication Adherence in Heart Failure Patients With Mild Global Cognitive Impairment
Authors: Vehovec Anton M , Dolansky Mary A , Josephson Rich , Hughes Joel W
Published: July 2021

Introduction:
Mild cognitive impairment is common in patients with HF and is linked to poor medication adherence. Poor medication adherence is associated with higher mortality and hospitalizations. Medication adherence strategies to compensate for cognitive impairment are not well understood. The purpose of this secondary analysis is to identify the type and frequency of compensatory strategies used by patients with HF and mild cognitive impairment and to determine if compensatory strategy use is associated with medication adherence.

Methods and Results:
The parent study was a longitudinal descriptive study (N=379) to determine the relationships among cognitive impairment and self-management. The Modified Mental Status (3MS), a global measure of cognition and an electronic pill box (Medsignals) were used. A subsample of 156 patients with mild to moderate global cognitive impairment was selected based on a 3MS of less than 90. The frequencies of four compensatory strategies use were: pillbox (n=85, 57%), family reminders (n=17, 11%), reminders including calendars and alarms (n=17, 11%), and combining administration with other tasks (n=51, 33%). An independent samples t-test was performed to test the difference in medication adherence between persons that did and did not use each compensatory strategy. Pillbox use was associated with medication adherence (p<.05). The group that used a pillbox (n=80) had a mean medication adherence of 82.5%, while no pillbox use (n=90) had a mean of 74.8% No other compensatory strategies were related to better medication adherence.

Conclusion:
In clinical practice, global cognition screening and education on pillbox use to improve medication adherence is recommended. Although other compensatory strategies did not have a significant impact on medication adherence, more research is need to understand compensatory strategies to help patients with mild cognitive impairment improve medication adherence.
Abstract 19503: Durability of Antiplatelet Effect of a Novel Extended-release Formulation of Acetylsalicylic acid, Durlaza in Patients With Diabetes
Authors: Gurbel Paul A , Bliden Kevin Blide P. P , Patrick Jeff Patrick , Saadin Katayoon Saadin , Tantry Udaya
Published: July 2021

Background:
High platelet turnover (HPT) is implicated in incomplete platelet inhibition and high platelet reactivity (HPR) during immediate release aspirin therapy in type II diabetes patients (T2DM). Durlaza is a new, extended-release orally administered aspirin formulation developed to provide 24-hour antithrombotic effects with once-daily dosing.

Methods:
In this open-label, single-center study, T2DM patients (n=40) and a history of cardiovascular disease (CVD) or multiple CVD risk factors were treated with daily 162.5 mg Durlaza for 14±4 days and adverse events were collected. Antiplatelet effects were determined by conventional aggregation (LTA), Multiplate analyzer, thrombelastography with PlateletMapping, PlateletWorks ,VerifyNow Assay, and serum thromboxane B2 (TxB2) at 1, 12, 16, and 24 hrs after the last dose. HPT was defined as immature platelet fraction of ≥3.0% or MPV≥11.0 fl. Patients exhibiting HPT and/or HPR (based on previously published cutpoints in ≥2 assays) were treated with Durlaza at 325mg for 14± 4 days and platelet function testing was repeated.

Results:
Prevalence of HPT and HPR was 47% and 27%, respectively. There was no loss of antiplatelet effect at 12, 16 and 24 h versus 1 h by all assays (Table 1). All patients responded to 162.5mg Durlaza as measured by arachidonic acid-induced aggregation with LTA and platelet reactivity levels were low at all timepoints (Table). Serum TxB2 was lower at 12 h (p<0.03) as compared to 1 h after 162.5mg and was lower at all times with the 325 mg vs. the 162.5 mg Durlaza (p < 0.05). HPT did not affect the PD profile of Durlaza (Pts with HPT vs. no HPT, p=NS for all). Patients had no serious adverse events and low treatment related AE rate (<5%).

Conclusion:
In this first comprehensive assessment, a new, extended-release 162.5 Durlaza provided sustained antiplatelet effects over 24 h in T2DM patients with a favorable safety profile. Doubling the dose further lowered serum TxB2 in pts with HPT and/or HPR.
Abstract 19536: Lipid Oversupply to Cardiomyocytes Induces Sphingolipid-dependent Oxidative Stress and Induction of Mitophagy Through Ceramide Synthase 2
Authors: Law Brittany A , Roddy Patrick , Liao Xianghai , Schulze P. C , Cowart L. A
Published: July 2021

Introduction:
Diabetic cardiomyopathy (DbCM) contributes to the high risk of heart failure (HF) in diabetics, but mechanisms underlying DbCM remain unclear. We previously showed that highly saturated fat feeding in mice altered cardiomyocyte sphingolipid profiles leading to DbCM and that some of these maladaptations were dependent on autophagy and ceramide synthase 5 (CerS5).

Hypothesis:
In the present study, we sought to further understand the cellular processes in which lipid overload leads to DbCM in in the context of sphingolipids.

Methods:
Mice fed an obesogenic diet and in vitro studies using H9c2 cardiomyocytes were utilized in this study.

Results:
Increased oxidative stress and enhanced apoptosis were identified in the hearts of animals subjected to lipid overload, while animals treated with the sphingolipid synthesis inhibitor myriocin were protected. Similarly, cardiomyocytes treated with palmitate showed a sphingolipid-dependent increase of reactive oxygen species (ROS) and mitophagy. Treatment with mitochondria-targeted ceramide analogs induced cardiomyocyte cell death in an increasing chain length manner, which was exacerbated by inhibiting mitophagy. This suggested that lipotoxicity to cardiomyocytes occurs in part through oxidative stress in a sphingolipid-dependent manner, and mitophagy may occur to prevent further damage. Our observation that only longer chain ceramides led to these outcomes suggested involvement of CerS2 which specifically produces very long chain ceramides (C20 and higher). Overexpression of CerS2 showed increased mitophagy in cardiomyocytes and knockdown of CerS2 by CRISPR-CAS9 technology decreased mitophagy.

Conclusions:
Taken together, our data suggest that lipid overload induces mitophagy potentially as a protective measure in defense from CerS2-induced mitochondrial damage, oxidative stress and cell death in DbCM.
Abstract 19554: Lipoprotein(a) and Risk of Ischemic Stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Alexander Kristine S , Zakai Neil A , Unverzagt Fred , Wadley Virginia , Kissela Brett M , Judd Suzanne E , Glasser Stephen , Cushman Mary
Published: July 2021

Background:
Increased lipoprotein (a) (Lp(a)) is associated with coronary risk, but links with stroke have been less consistent. Blacks have 2-4-fold higher Lp(a) levels than whites, and have higher stroke incidence than whites, but have been under-represented in studies of Lp(a) and stroke to date.

Hypothesis:
Lp(a) is a risk factor for ischemic stroke, and this risk differs by race.

Methods:
REGARDS recruited 30,239 black and white U.S. men and women in 2003-7 to study regional and racial differences in stroke mortality. We measured Lp(a) by immunonepholometric assay in 572 cases of incident ischemic stroke and a 1,104-person cohort random sample. The hazard ratio of stroke by baseline Lp(a) was calculated using Cox proportional hazards models, stratified by race. Lp(a) was modeled both as a continuous variable (per sex- and race-specific SD) and in sex- and race-specific quartiles, given known differences in distributions by race and sex.

Results:
As shown in the Figure, being in the 4
th
vs 1
st
Lp(a) quartile was associated with ischemic stroke in black but not white participants, adjusted for age and sex (Model 1). The HRs were essentially unchanged with added adjustment for stroke risk factors (Model 2). There was no significant association between Lp(a) as a continuous variable and stroke, though race-specific patterns were similar. There remained no association between Lp(a) and stroke in whites when we used the sex- and race-specific 90
th
percentile as a cut-off (HR: 0.91 95% CI: 0.52, 1.60).

Discussion:
Lp(a) was associated with ischemic stroke risk in black but not white REGARDS participants, this might partly explain the black/white disparity in stroke. Further studies in racially diverse groups are necessary to confirm these findings.

Figure 1.
Hazard ratios for Lp(a) and stroke in blacks and whites, per quartile (compared with first quartile) and SD.
Abstract 19572: Elevated PETCO2 During Cardiac Resuscitation Without Return of Spontaneous Circulation
Authors: Hypes Cameron , Spaite Dan , Vadeboncoeur Tyler , Murphy Ryan A , Hu Chengcheng , McDannold Robyn , Silver Annemarie , Bobrow Bentley
Published: July 2021

Background:
Quantitative End-Tidal CO2 (PETCO2) measurement during cardiac arrest is recommended for monitoring the CPR quality to detect ROSC. While low ETC02 can reflect suboptimal CPR quality and increases in ETC02 are often associated with ROSC the significance of high values of PETCO2 without ROSC remain unclear.

Objectives:
To describe the population of OHCA victims with high PETCO2 (>50 mm Hg) during ongoing resuscitation including demographics, rhythm characteristics, occurrence of ROSC, the later occurrence of field termination of resuscitation and the presumed etiology.

Methods:
An observational analysis of adult OHCAs with available PETCO2 data occurring between Oct 2010 and Nov 2014 at two sites involved in the Save Hearts in Arizona Registry and Education (SHARE) quality improvement program. CPR and PETCO2 data were recorded using ZOLL E and X Series EMS monitors. PETCO2 is reported as the mean value for each minute. The cardiac rhythm and the presence of ROSC were determined for each minute using EMS provider reports, vital signs, ECG, and accelerometer data. The first recorded minute of PETCO2 and minutes with ROSC were excluded.

Results:
Study population included 654 OHCAs with PETCO2 data, 96 cases (58% male, age median 65 (IQR 54-75)) with at least 1 min of high PETCO2 in the absence of ROSC were identified. Of these, 31 (32%) had ROSC at least once during their resuscitation. Cases were of presumed cardiac etiology in 81 (84%), while 12% and 4% had presumed respiratory and other etiologies, respectively. A total of 322 minutes of PETCO2 >50 mm Hg in the absence of ROSC were identified. The mean PETC02 value was 67 (IQR 54-75). Of these 296 minutes (92%) occurred during PEA. Despite high PETCO2, resuscitation was terminated in the field in 21 (22%) patients. Only one subject survived to hospital discharge.

Conclusions:
In this observational study, high PETCO2 was frequently found during resuscitation without ROSC and PEA was the most common cardiac rhythm. Further study is warranted to determine the significance and possible reasons for this finding.
Abstract 19652: Gender Disparities Among Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Gaglia Michael A , Torguson Rebecca M , Lipinski Michael J , Ben-Dor Itsik , Satler Lowell , Pichard Augusto , Waksman Ron
Published: July 2021

Background:
Previous studies have suggested higher rates of mortality among female patients undergoing surgical aortic valve replacement, but gender disparities in transcatheter aortic valve replacement (TAVR) patients are not well-studied.

Objectives:
We sought to compare 30-day and 1-year outcomes in female vs. male patients undergoing TAVR for severe, symptomatic AS.

Methods:
Consecutive patients undergoing TAVR at a single center were stratified according to gender. We compared female v. male patients in regards to the incidence of comorbidities, in addition to 30-day and 1-year outcomes according to the Valve Academic Research Consortium (VARC) criteria. A Cox proportional hazards regression was performed to assess for an independent association of female gender and mortality at 1 year.

Results:
The study population included 362 female and 354 male patients. Females were less likely to suffer from a number of comorbidities than males, including a coronary artery disease (63.8% v. 84.3%, p<0.001), peripheral vascular disease (26.3% v. 41.8%, p<0.001), and chronic renal insufficiency (41.7% v. 53.6%, p=0.002). Despite this, females had a higher average STS score (9.9 v. 8.2; p<0.001). Females were more likely to have a life-threatening bleed (9.9% vs. 5.4%, p=0.03), although there was only a trend for more major vascular complications (11.8% vs. 8.2%, p=0.11). Females also had higher rates of in-hospital (7.8% vs. 3.7%, p=0.02) and 30-day mortality (9.7% vs. 5.6%, p=0.04), although there was no difference at 1 year (21.0% vs. 21.5%, p=0.88). Following multivariable adjustment, there was no independent association of gender and mortality at 1 year.

Conclusions:
Females undergoing TAVR suffer higher rates of short-term mortality, but outcomes at 1 year are similar to males. This suggests that there may be a hazard to female gender periprocedurally, but long term this difference is abolished because of a lesser burden of comorbidities.
Abstract 19715: Diabetes Abrogates the Cardioprotective Effects of Ischemic Postconditioning Cardioprotection by Impairing AdipoR1/Caveolin-3/STAT3 Signaling
Authors: Li Haobo , Yao Weifeng , Liu Zipeng , Wang Sheng , Irwin Michael G , Xia Zhengyuan
Published: July 2021

Introduction:
Ischemic postconditioning (IPo) protects against myocardial ischemia reperfusion (MI/R) injury by activating mitochondrial signal transducer and activator of transcription 3 (mitoSTAT3) through adiponectin (APN) in non-diabetes, but losses its effectiveness in diabetes whose cardiac APN is reduced. We postulated that malfunction of APN is the key mechanism whereby IPo losses cardioprotection in diabetes.

Methods and Results:
Four-week (4w) or eight-week (8w) streptozotocin-induced diabetic rats were treated with APN adenovirus (tail vein injection, 1*109 pfu) 1-week before inducing MI/R (30 minutes of left coronary artery ligation followed by 2 hours of reperfusion) with or without IPo (3 cycles of 10s of ischemia and 10s of reperfusion, n=6 per group). At the end of reperfusion, myocardial injury was more severe in both 4w and 8w diabetic rats evidenced as increased infarct size than age-matched control (43.4±3.3 in 4w diabetic vs. 30.6±2.2 in control, 55.4±2.0 in 8w diabetic vs. 38.0±1.9 in control, all P<0.05) concomitant with increased plasma CK-MB release and worse cardiac function (lower dP/dtmax and ejection fraction), and more severely impaired mitochondrial function (decrease in complex I, II+III, and IV activities), more severe reduction of activated mitoSTAT3 and colocolization of APN receptor-1(AdipoR1) and caveolin-3(Cav3), a molecule essential for APN signaling. These changes cannot be reversed by IPo alone in both 4w and 8w diabetic rats, while IPo in combination with APN significantly attenuated all the abovementioned changes in 4w diabetic but not in 8w diabetic rats whose baseline and post-ischemic cardiac AdipoR1 and Cav3 expression were more severely reduced than that in 4 w diabetic rats. The protective effects of joint IPo and APN treatment in 4w diabetes were abolished by inhibition of STAT3 irrespectiove of IPo and APN induced enhancement of AdipoR1 and Cav3 expression and colocalization.

Conclusion:
IPo loses cardioprotection in diabetes due to reduced APN and impaired AdipoR1/Cav3 signaling. APN supplementation by activating mitoSTAT3 restores IPo cardioprotection in 4w diabetic where AdipoR1 and Cav3 are functionally interactive, but not in 8w diabetic rats whose AdipoR1/Cav3 signaling impaired.