bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 108: Effect of a Medical Decision Support Device on Quality of Basic Life Support
Authors: Hunt Elizabeth A , Nelson Kristen L , Heine Margaret , Shilkofski Nicole A
Published: July 2021

Background:
As cardiopulmonary arrest (CPA) can occur anywhere, laypersons may need to initiate CPR. However, recent literature reveals the quality of basic life support (BLS) provided during CPA is poor. There is increasing interest in whether devices can support laypeople, as well as others, to manage medical emergencies.

Methods:
We performed a prospective, randomized, controlled trial of simulated out of hospital CPA in which each subject was asked to manage a standardized event using the Laerdal Resusci-Anne simulator. A study member played a second rescuer to help as directed. The intervention was a device with audiovisual prompts designed to assist with decision making. Study subjects included laypeople and nursing and medical students. The primary outcome measure was the proportion of subjects who performed compressions and ventilations at a 30:2 ratio. Secondary outcome measures were proportion of subjects who insisted on switching roles with the second rescuer after 2 minutes and other measures of quality BLS.

Results:
Thirty-one subjects were enrolled, 16 in the intervention arm and 15 in the control arm, with similar baseline characteristics. Subjects in the intervention arm were more likely to perform compressions to ventilations at a ratio of 30:2 than controls, [15/16 (94%) vs. 4/15 (27%), p<0.001], even with stratification by rescuer background: laypeople [8/9 (89%) vs. 0/4 (0%), p=0.02], medical or nursing student [7/7 (100%) vs. 4/11 (36%), p=0.01]. Intervention subjects were also more likely to insist that the second rescuer switch roles with them than controls, [12/16 (75%) vs. 2/15 (13%), p=0.001]. However, there was a delay in mean time (± standard deviation) to initiation of compressions in the intervention arm, [159.5 (±53) vs. 78.2 (± 20) seconds, p < 0.001] and the no-flow fraction was very high in both arms, [72.2% (± 0.1) vs. 75.4 (± 0.8), p = 0.35].

Conclusions:
The device resulted in a behavior change as intervention subjects were more likely to perform 30:2 and switch providers. Unfortunately, the device slowed the initial response time. These results are promising, but future studies should concentrate on decreasing latency time, periods without compressions and possible incorporation into automated external defibrillators.
Abstract 542: Mice with Cardiomyocyte-Restricted IGF-1 Receptor Deletion Exhibit Diminished Cardiomyocyte Size and Resistance to Exercise-Induced Cardiac Hypertrophy
Authors: Kim Jaetaek , Wende Adam R , Sloan Crystal , Wayment Benjamin E , Litwin Sheldon E , LeRoith Derek , Abel E. Dale
Published: July 2021

Insulin-like growth factor 1 (IGF-1) and IGF-1 receptors are expressed in murine hearts, and IGF-1 receptor signaling in cardiac muscle has been proposed to play a role in growth, differentiation, and cell survival, but mechanisms by which IGF-1 modulates myocardial structure and function are only partially understood. To investigate the role of IGF-1 signaling on cardiac development and physiology, we generated mice with cardiomyocyte-restricted knockout of the IGF-1receptor (IGF-1R −/−) by crossing α-MHC-Cre mice with mice containing a floxed exon 3 of the IGF-1R gene. Ablation of IGF-1 receptors in cardiomyocytes did not alter baseline heart weight to tibia length (HW/TL) ratios at 8 weeks or 12 weeks of age. However, wheat germ agglutinin (WGA-FITC) staining revealed that myocyte cross-sectional area was reduced by 18.8% (P < 0.05). To define the contribution of IGF-1 receptor signaling in the development of physiological hypertrophy; mice [WT (n = 7) or IGF-1R −/− (n = 9)] were subjected to 4 weeks swim (Sw) training and compared with Sedentary (Sed) wild type (WT) (n = 5) or IGF-1R −/− (n = 7) mice. HW/TL ratios increased by 19.2% in WT animals after swim training (5.19 ± 0.26 vs. 6.18 ± 0.2, P < 0.05), but only by 5.5% in Sw IGF-1R −/− mice (5.58 ± 0.18 vs. 5.89 ± 0.22, P = 0.32) and the fold increase in HW/TL was significantly greater in Sw WT vs. Sw IGF-1R −/− (P < 0.05). Despite resistance to hypertrophy, cardiac systolic function assessed by ejection fraction was preserved in Sw IGF-1R −/− (before Sw 0.71 ± 0.02 vs. after Sw 0.67 ± 0.02, P = 0.12). Phosphorylation of Akt was significantly increased in both trained WT and IGF-1R−/− mice at Ser473 [fold-change 1.61 ± 0.09 (P < 0.05) and 2.11 ± 0.19 (P < 0.01), respectively] and Thr308 [2.42 ± 0.24 and 2.61 ± 0.59 (P < 0.01), respectively] vs. Sed. Surprisingly Ser (473) Akt phosphorylation was greater in Sw IGF-1R−/− vs. Sw WT (P < 0.05). These data define an essential role for IGF-1 signaling in mediating physiologic cardiomyocyte hypertrophy, and indicate that although Akt signaling might be necessary for mediating physiological cardiac hypertrophy it is not sufficient in the absence of myocardial IGF-1R signaling.
Abstract 546: Postconditioning Fails to Limit Infarct Size in the Setting of Type-2 and Type-1 Diabetes
Authors: Przyklenk Karin , Maynard Michelle , Smith Craig S , Whittaker Peter
Published: July 2021

Relief of ischemia in a stuttering manner (postconditioning: PostC) has been shown to limit infarct size, due in part to activation of ERK 1/2 during the early minutes of reflow. However, it is unknown whether the efficacy of PostC is maintained in the setting of clinically relevant co-morbidities such as diabetes. To address this issue, isolated buffer-perfused hearts were obtained from:

healthy adult C57BL/6J mice (mean blood glucose [mg/dL]: 178±7);

age-matched BKS.Cg-m+/+
Lepr

db

/J
mice (genetic model model of type-2 diabetes; hyper-glycemic with blood glucose of 480±23); and

adult C57 mice injected 2 weeks previously with streptozotocin (model of type-1 diabetes; blood glucose: 556±15).

All hearts underwent 30 min global ischemia and received either:

complete, abrupt reperfusion (controls);

PostC with 3 10-sec cycles of stuttered reflow; or

an amplified (6 cycle) PostC stimulus.

Experiments were conducted with both standard perfusate and fatty acid-supplemented buffer (1.5 mM palmitate). In hearts from healthy mice, PostC:

was cardioprotective (infarct size [delineated by tetrazolium staining] was 27±3% and 29±5% of the LV in PostC groups vs 50±3% in controls; p<.05); and

was associated with an up-regulation of ERK signaling (including significant, >2-fold increases in expression of phospho-ERK and downstream targets of ERK [i.e., p70S6-kinase phosphorylated at Thr421/Ser424]).

Similar data were obtained, irrespective of the presence or absence of palmitate in the buffer. Moreover, the infarct-sparing effect of PostC was blocked by the ERK inhibitor PD98059 (infarct size: 68±7% vs 63±4% in PD-treated PostC vs control groups), consistent with a requisite role of ERK signaling in PostC-induced protection. In contrast, in the type-2 diabetic model, PostC did not activate ERK signaling and
exacerbated
(rather than reduced) infarct size (57±3%, 61±3% and 74±4%* in control, 3- and 6-cycle PostC groups; *p<.05 vs control) – outcomes that were not mitigated by addition of palmitate to the buffer. Similar loss of PostC-induced protection was seen with type-1 diabetes. Thus, PostC fails to reduce infarct size in the setting of both type-2 and type-1 diabetes, possibly due to impaired up-regulation of ERK signaling.
Abstract 552: Mitochondrial KCa and Anion Channels Influence Mitochondrial Volume and Respiratory Rate: Relevance to Cardioprotection
Authors: Cortassa Sonia , Aon Miguel A , Brown David A , Sidor Agnieszka , Sorarrain Nicolas , O’Rourke Brian
Published: July 2021

Ion channels in the mitochondrial inner membrane influence the response of the heart to ischemia and reperfusion - the opening of mitochondrial K
+
channels (mitoK
Ca
or mitoK
ATP
) induce cardioprotection while the excessive activation of an inner membrane anion channel (IMAC) contributes to post-ischemic contractile and electrical dysfunction. Here we examined the effects of K
Ca
channel openers and inhibitors on mitochondrial volume and respiration in KCl-based medium in energized isolated guinea-pig heart mitochondria. Inhibition of IMAC with a mitochondrial benzodiazepine ligand was also assessed. Mitochondrial swelling and contraction were evoked by the sequential addition of 5mM glutamate (Glu) and 5mM malate (Mal), respectively. Both the swelling and contraction responses involved energy-dependent fluxes of K
+
and Cl
−
. The Glu-induced swelling response was suppressed by preincubation with either the K
Ca
channel toxin paxilline, or by the IMAC blocker 4′-chlorodiazepam (4-Cl-DZP). The K
Ca
opener NS1619, at concentrations <10μM, initiated mitochondrial swelling responses either in the absence or presence of substrates. This effect was blocked by paxilline or charybdotoxin. Massive and irreversible swelling was induced by [NS1619] >10μM. Under similar conditions, mitochondrial respiratory control (State3/State4 VO
2
ratio) was maintained at >15 for [NS1619] <10μM, but was strongly suppressed above 20μM due to an increase in state4- and a decrease in state3-respiration. 4-Cl-DZP did not affect respiration and only slightly increased the K
0.5
for ADP. The findings indicate that mitochondrial matrix volume is modulated by mitoK
Ca
channel activity under normal conditions and in the presence of K
Ca
channel openers, while IMAC channels underlie compensatory anion movements in response to K
+
flux. Physiological regulation of mitochondrial volume by ion transport is in turn linked to altered respiratory flux, with important implications for cardioprotection and recovery of mitochondrial function in the post-ischemic heart.
2007 George L. Duff Memorial Lecture—The Immune Response in Atherosclerosis
Authors: Hansson Göran K.
Published: July 2021

Immune responses participate in every phase of atherosclerosis. Indeed, atherosclerosis can be viewed as an immune/inflammatory response to lipoprotein retention in the artery wall. There is increasing evidence that both adaptive and innate immunity tightly regulate the atherosclerotic process. Specific antigens and pathogen-like molecular patterns initiate the 2 aspects of immunity by ligating T- and B-cell receptors and pattern recognition receptors, respectively. Effector responses of vascular immune reactions include macrophage activation, cellular immunity, antibody formation, and vascular inflammation. Whereas experimental studies in gene-targeted models have identified major roles for innate immunity and Th1 responses in plaque initiation and progression, clinical, epidemiological and genetic studies suggest that plaque activation, rupture, and atherothrombosis also depend on immune reactions. This lecture will focus on the role of immune mechanisms in the formation and activation of atherosclerotic plaques.
2007 Charles T. Dotter Memorial Lecture—Renal Artery Stenosis and Cardiovascular Risks—The New Paradigms in Diagnosis and Treatment
Authors: Sos Thomas
Published: July 2021

Renal artery stenosis (RAS), hypertension, and renal insufficiency are each frequently present especially in the elderly population. RAS is often present without any clinical signs or symptoms, and even when hypertension or renal insufficiency is also present, these conditions may be coincidental rather than causally related. However, when RAS is physiologically significant (10% peak systolic trans-stenotic pressure gradient), it is one of the few potentially reversible causes of renal insufficiency and hypertension.

RVH is mediated by angiotensin II, a powerful vaso-constrictor producing systemic hypertension, cellular hypertrophy, proliferation of vascular smooth muscle cells, vascular and left ventricular hypertrophy, accelerated atherosclerosis, and progressive glomerular sclerosis, independent of the level of hypertension. Physiologically significant RAS also has direct effects on sympathetic nerve activity, nitric oxide production, and intrarenal prostaglandin concentration. Patients with atheromatous RAS (ARAS) and end-stage renal disease have a significantly higher mortality rate than the general dialysis population.

Some advocate prophylactic intervention for asymptomatic and hemodynamically insignificant ARAS; however, ARAS is a
marker for
but
not an independent risk factor
for major adverse cardiac events. Aggressive statin therapy arrests progression and produces regression of coronary and carotid atheroma.

Patients with asymptomatic and hemodynamically nonsignificant ARAS should be treated with aggressive statin and glucose control therapy, aspirin, and lifestyle modifications. This would likely produce all the potential benefits of prophylactic stenting, the very long-term durability and fate of which are unknown, and without any of its known major risks such as cholesterol embolisation and the 15% to 20% restenosis that can occur even in “low-risk” patients.

In summary, appropriately selected patients with ARAS and renal insufficiency benefit from interventional therapy, whereas those with clinically and hemodynamically nonsignificant stenoses should be treated by aggressive medical therapy, including statins and life style modifications.
2007 Donald Seldin Lecture—Fructose, Uric Acid, and the Pathogenesis of the Epidemic of Hypertension and Metabolic Syndrome
Authors: Johnson Richard J.
Published: July 2021

There has been a remarkable increase in the frequency of hypertension, obesity, diabetes, and kidney disease since the early 1900s, and this is largely responsible for the dramatic rise in cardiovascular disease during the past century. While physical inactivity and excessive energy intake play an important role, there is also concern that specific foods in the Western diet may contribute. In this lecture, we revisit the hypothesis that sugar, and in particular fructose, may have a key role in the epidemic. We will review the experimental and clinical evidence linking fructose to the epidemic, as well as recent data suggesting that the effects may be driven in part by the unique ability of fructose to raise uric acid. We will also briefly discuss the evidence that uric acid may be a true cardiovascular risk factor, with attention to its actions on the kidney and vasculature. Although more definitive studies need to be performed, the resurrection of these 2 old risk factors (fructose and uric acid) may allow for new insights into how to both prevent and interrupt the ongoing cardiorenal epidemic.
Sirt1 Controls Endothelial Angiogenic Functions During Vascular Growth And Maturation
Authors: Potente Michael
Published: July 2021

Abstract 286

Michael Potente, Laleh Ghaeni, Molecular Cardiology, Frankfurt, Germany; Danila Baldessari, Zebrafish Group, Milan, Italy; Raul Mostoslavsky, Howard Hughes Medical Inst, The Children’s Hosp, Boston, MA; Lothar Rossig, Molecular Cardiology, Frankfurt, Germany; Franck Dequiedt, Cellular and Molecular Biology Unit, Gembloux, Belgium; Judith Haendeler, Molecular Cardiology, Frankfurt, Germany; Marina Mione, Zebrafish Group, Milan, Italy; Elisabetta Dejana, IFOM-FIRC Inst of Molecular Oncology, Milan, Italy; Frederick W Alt, Howard Hughes Medical Inst, The Children’s Hosp, Boston, MA; Andreas M Zeiher, Stefanie Dimmeler, Molecular Cardiology, Frankfurt, Germany

Michael Potente, 2007 Finalist and Presenting Author
Transcriptomic based Biomarkers Contain Diagnostic and Prognostic Information about Patients with new onset Heart Failure
Authors: Heidecker Bettina
Published: July 2021

Abstract 1753

Bettina Heidecker, University of Miami, Miller School of Med, Miami, FL; Kenneth L Baughman, Brigham and Women’s Hosp, Boston, MA; Edward K Kasper, Ilan S Wittstein, Elayne Breton, Johns Hopkins Hosp, Baltimore, MD; Joshua M Hare, University of Miami, Miller School of Medicine, Miami, FL

Bettina Heidecker, 2007 Finalist and Presenting Author
A 35-Year-Old Female with Anterior ST Segment Elevation and Cardiogenic Shock
Authors: Bonaca Marc
Published: July 2021

Abstract 1757

Marc Bonaca, David Morrow, Carolyn Ho, Brigham and Women’s Hospital, Boston, MA

Marc Bonaca, 2007 Finalist and Presenting Author
2008 Ancel Keys Memorial Lecture—Screening for Coronary Artery Disease: Is It Too Soon to Think Clinically?
Authors: Lauer Michael
Published: July 2021

Screening is a mainstay of modern preventive medicine. Physicians routinely screen patients for breast or colorectal cancer, as well as hypertension, hypercholesterolemia, and abdominal aortic aneurysm. In each of these cases, randomized trials demonstrated that screening saves lives or prevents major morbidity. As coronary artery disease remains the number one cause of death in Western society, there is interest in screening for the disease itself, as opposed to just its risk factors. Some investigators have argued for routine screening of adults with coronary artery calcium testing; proponents have used direct-to-consumer advertising, legislative lobbying, and appeals in the mass media. Although it is true that coronary calcium scores correlate well with clinical events, the evidence base has not yet reached the level of established tests. We may fall into a too-often ignored trap, where strategies based on logic or risk markers turn out to be ineffective or even dangerous. When a seemingly healthy person undergoes a screening test and is found to have disease, that person becomes a patient subject to clinical thinking. If this translates into improved outcome, clinical thinking is appropriate. We must remember, though, that screening is supposed to prevent clinical events. When it merely detects subclinical disease, leading to unnecessary tests or procedures, it instead exposes people to the risks of thinking clinically. We must have the ambition, willingness, and patience to develop the evidence base needed to introduce new screening technologies to the clinic at the right time.
Predictors of 30-Day Mortality in Patients With Refractory Cardiogenic Shock Following Acute Myocardial Infarction Despite a Patent Infarct Artery
Authors: Katz Jason
Published: July 2021

Abstract 503

Jason N Katz, Duke Univ Medical Ctr & Duke Clinical Res Inst, Durham, NC; Amanda L Stebbins, Duke Clinical Res Inst, Durham, NC; John H Alexander, Duke Univ Medical Ctr & Duke Clinical Res Inst, Durham, NC; Harmony R Reynolds, New York Univ, New York, NY; Karen S Pieper, Duke Clinical Res Inst, Durham, NC; Witold Ruzyllo, Natl Inst of Cardiology, Warsaw, Poland; Karl Werdan, Martin-Luther-Univ Halle-Wittenberg, Halle-Wittenberg, Germany; Alexander Geppert, Wilhelminen hospital Vienna, Vienna, Austria; Vladimir Dzavik, Univ of Toronto, Toronto, ON, Canada; Frans Van de Werf, Univ Hosp of Gasthuisberg, Leuven, Belgium; Judith S Hochman, New York Univ, New York, NY; TRIUMPH Investigators

Jason Katz, 2008 Finalist and Presenting Author
A Multimarker Strategy for Risk Prediction in Heart Failure: Application of Novel Methods in a Community Cohort
Authors: Dunlay Shannon
Published: July 2021

Abstract 1252

Shannon M Dunlay, Yariv Gerber, Susan A Weston, Jill M Killian, Margaret M Redfield, Mayo Clinic, Rochester, MN

Shannon Dunlay, 2008 Finalist and Presenting Author
Predictive Value of Brachial Flow-Mediated Dilation for Incident Cardiovascular Events in Population Based Adults Free of Cardiovascular Disease at Baseline: The Multi-Ethnic Study of Atherosclerosis
Authors: Yeboah Joseph
Published: July 2021

Abstract 1255

Joseph Yeboah, Gregory L Burke, John R Crouse, Wake Forest Univ Sch of Med, Winston Salem, NC; Joao A Lima, John Hopkins Univ, Baltimore, MD; Craig Johnson, Univ of Washington, Seattle, WA; Joseph F Polak, Tufts-New England Medical Ctr, Boston, MA; Aaron Folsom, Univ of Minnesota, Minneapolis, MN; Wendy Post, John Hopkins Univ, Baltimore, MD; David M Herrington, Wake Forest Univ Sch of Med, Winston Salem, NC

Joseph Yeboah, 2008 Finalist and Presenting Author
It’s All in the Family: A Treatable Cause of Late-Onset Hypertrophic Cardiomyopathy
Authors: Daly Ryan
Published: July 2021

Abstract 1121

Ryan P Daly, E. Rene Rodriguez, Allan L Klein, Cleveland Clinic, Cleveland, OH

Ryan Daly, 2008 Finalist and Presenting Author
Abstract 5817.5: Assessment of Global Left Ventricular Function and Volumes with 320-Slice MSCT: A Comparison with 2D Echocardiography
Authors: de Graaf Fleur R , Schuijf Joanne D , van Werkhoven Jacob M , Jukema J Wouter , Nucifora Gaetano , Boogers Mark M , Scholte Arthur J , de Roos Albert , van der Wall Ernst E , Bax Jeroen J
Published: July 2021

Background.
Multi-slice computed tomography (MSCT) has been demonstrated as a feasible imaging modality for non-invasive assessment of coronary artery disease and left ventricular (LV) function analysis. Recently, 320-slice systems have become available with 16 cm anatomical coverage allowing prospective image acquisition of the entire heart within a single rotation or heart beat. However, limited data are currently available with these systems. The purpose of the present study therefore was to evaluate the accuracy of 320-slice MSCT in the assessment of global LV function as compared to 2-dimensional (2D) echocardiography.

Methods.
A head-to-head comparison between 320-slice MSCT and 2D echocardiography was performed in 40 patients (24 male; mean age 61 ± 9 years) with known or suspected coronary artery disease (CAD). During intravenous contrast agent administration, the entire heart was imaged in a single heartbeat, using prospective dose modulation (full dose during 65–85% of R-R interval). The following parameters were used: gantry rotation time 350 ms, tube voltage 120 kV, tube current 300–500mA. LV end-diastolic volumes (LVEDV) and LV end-systolic volumes (LVESV) were determined and the LV ejection fraction (LVEF) was derived. Two-dimensional echocardiography served as the gold standard.

Results.
Average LVEF was 59% ± 8% (range 31%–77%) as determined on 2D-echocardiography, compared with 61% ± 8% (range 33%–78%) on MSCT. Evaluation of LVEF by linear regression analysis showed a good correlation between MSCT and 2D-echocardiography (r = 0.84; p < 0.001). A close correlation between MSCT and 2D-echocardiography was also demonstrated for the assessment of LVEDV (r = 0.81; p < 0.001) and LVESV (r = 0.89; p < 0.001). At Bland-Altman analysis, mean differences (± SD) of 20.88 ml ± 23.07 ml (p < 0.01) and 6.83 ml ± 13.01 ml (p < 0.01) were observed between MSCT and 2D-echocardiography for LVEDV and LVESV respectively. As a result, LVEF was slightly overestimated with MSCT (1.98% ± 4.54%; p < 0.01).

Conclusion.
Accurate assessment of LV function and volumes is feasible with 320-slice MSCT in patients with known or suspected CAD.
Abstract 5856: Long-term Outcomes and Costs of Ventricular Assist Devices among United States Medicare Beneficiaries
Authors: Hernandez Adrian F , Shea Alisa , Milano Carmelo A , Rogers Joseph G , Hammill Bradley G , Schulman Kevin A , Peterson Eric D , Curtis Lesley H
Published: July 2021

BACKGROUND: Little is known about long-term outcomes and costs associated with VAD therapy among Medicare beneficiaries.

METHODS: Using the 100% inpatient and denominator files from 2000–2006, we identified Medicare fee-for-service beneficiaries as VAD only or VAD post-cardiotomy (at time of or within 30 days of cardiac surgery) and followed outcomes. Cumulative incidence of VAD reimplantation, explantation, cardiac transplantation, readmission and death were estimated accounting for censoring and competing risks. Cox proportional hazards model was used to determine factors associated with time-to-death. Inpatient costs–total and per survived day outside of the hospital were calculated from Medicare payments.

RESULTS: From 2000 through 2005, 2701 patients received a VAD from 549 hospitals; 1379 (51%) VADs post-cardiotomy and 1322 (49%) VAD only. Overall index hospital survival rate was 67% for VAD only and 39% for VAD post-cardiotomy. By one year these survival rates declined to 52% and 31% respectively (Figure

). Mean inpatient cost to Medicare in the first year was $178,626 (± $143,120) for VAD only and $112,013 (± $95,473) for VAD post-cardiotomy. For all VAD recipients, Medicare inpatient expenditures per day survived and out of the hospital were $1,021 for year 1 and $466 over 3 years.

CONCLUSIONS: VAD therapy is being used more commonly for end stage heart failure among Medicare beneficiaries; however, mortality and costs remains high. Advances in technology, and improved patient selection are needed before the use of VADs can expand more widely.
Abstract 5858: Role of Oxygen Tension and Oxidative Stress in Human Saphenous Vein Remodeling
Authors: Joddar Binata , Reen Rashmeet K , Firstenberg Michael , Gooch Keith J
Published: July 2021

Vessels cultured ex vivo maintain viability and vasoactivity for weeks and can remodel in response to mechanical cues. When cultured in the presence of 5% CO2/balance air veins develop neointimal hyperplasia (IH) while arteries do not suggesting that exposure to significant increases in pO2 levels might stimulate IH. Neointimal hyperplasia (IH) is a known mechanism by which saphenous veins have a decreased patency compared to arterial conduits when used for coronary artery bypass. We sought to explore the role of oxygen tension and oxidative stress in IH. Test the hypothesis that exposure of human saphenous veins (HSV) to arterial pO2 stimulates IH via ROS-mediated pathways. Almost 40 HSV remnants acquired following CABG were cultured ex vivo with arterial (~95mmHg) pO2 or venous (~40mmHg) pO2 for 14 days. All differences reported have a p<0.05 via Student’s t-test.

Results: HSV cultured at arterial pO2 exhibited

significant IH as evidenced by disruption of the IEL, invasion of cells from the media, and a 2.8-fold greater intimal area than fresh HSV,

a 5.8-fold increase in cell proliferation compared to fresh HSV,

increased ROS levels and oxidative stress as evidenced by 4-fold increase in 4-HNE level (a marker of oxidative stress), increased DHE staining (indicative of superoxide generation), and a progressive increase in total ROS levels with time as assessed by DCF fluorescence, and

a 3-fold increase in phosphorylated p38-MAPK, which is implicated in SMC proliferation.

In stark contrast vessels culture at arterial pO2, HSV cultured with venous pO2 did not develop increased IH and were indistinguishable from fresh vessels with respect to proliferation, markers of oxidative stress, and MAPK expression levels. Supplementing culture medium with antioxidants including Tiron or NAC blocked the pO2-induced changes. These data indicate that exposure to arterial pO2 increases cellular proliferation and stimulates IH, potentially via oxidative stress or ROS signaling and also suggest that exposure to elevated arterial pO2 might stimulate pathological remodeling of veins grafted into the arterial circulation.

This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).
Abstract 5871: Chronic Organic Mitral Regurgitation Results in Myofibrillar Degeneration and Oxidative Stress with Post-Surgical Left Ventricular Impairment Despite Pre-Surgical Left Ventricular Ejection Fraction > 60%
Authors: Ahmed Mustafa I , Gladden James D , Lloyd Steven G , Litovsky Silvio H , Gupta Himanshu , Inusah Seidu , Denney Thomas , McGiffin David C , Dell’Italia Louis J
Published: July 2021

Background:
Current guidelines recommend valve repair for chronic organic mitral regurgitation (MR) if LVEF drops below 60% to preserve LV function and maximize outcome. Post-operative drop in LVEF is typical, and widely believed to be due to alteration in loading conditions. Here we address whether cardiomyocyte damage may contribute to postoperative dysfunction.

Methods:
Three-dimensional magnetic resonance imaging (3D-MRI) with tissue tagging was performed in 23 MR patients, prior to and six months following mitral valve repair. LV biopsy was obtained from all MR patients at time of surgery. Immunohistochemistry was performed to assess for signs of oxidative stress, specifically lipofuscin deposition, and presence and quantity of xanthine oxidase (XO). Plasma XO levels were measured before, and six months post-surgery.

Results:
MR patients (n=23) demonstrated decreased LVEF (62 ± 1 to 54 ± 2% p=0.0002) and LV end-diastolic volume (116 ± 5 to 79 ± 5 ml/m
2
p<0.0001) six months after mitral valve (MV) repair. LV circumferential and longitudinal strain rates decreased below normal (6.54 ± 0.21 vs. 5.24 ± 0.24 p=0.0001, and 6.56 ± 0.26 vs. 5.41 ± 0.27 p=0.0084) despite no change in blood pressure and 3-dimensional LV end-systolic radius/wall thickness ratios. LV biopsies demonstrated marked cardiomyocyte myofibrillar degeneration vs. normals (2.32 ± 1.09 vs. 1.25 ± 0.45, p=0.0016, mean degeneration grade [1–4]). Immunostaining for xanthine oxidase (XO), a prominent oxidative enzyme, was increased in MR vs. normals (88 ± 7 vs. 33 ± 4%, p <0.01), as plasma XO decreased post-MV repair (2.12 ± 0.46 to 0.49 ± 0.25 μU/mL, p=0.008). Lipofuscin deposition, a product of oxidative stress, was increased in cardiomyocytes of MR vs. normals (0.62 ± 0.04 vs. 0.33 ± 0.04%, p <0.01).

Conclusions:
Decreased LV strain rates 6 months post MV repair indicate myocyte contractile dysfunction in chronic MR patients despite pre-surgical LVEF >60%. This is supported by marked cardiomyocyte myofibrillar degeneration and oxidative damage at the time of surgery. While raising questions regarding timing of surgery for MR, these findings generate hypothesis concerning XO and oxidative stress-related myocyte damage in the pathophysiology of LV contractile dysfunction in MR.
Abstract 5872: Argatroban And Bivalirudin Compared To Unfractionated Heparin In Preventing Thrombus Formation On Mechanical Heart Valves, Results Of An
In Vitro
Study
Authors: Maegdefessel Lars , Linde Torsten , Michel Thomas , Steinseifer Ulrich , Raaz Uwe , Friedrich Ivar , Werdan Karl , Buerke Michael , Schlitt Axel
Published: July 2021

Introduction
Argatroban and bivalirudin both selectively inhibit thrombin at its active site. In patients with heparin-induced thrombocytopenia, and HIT complicated by thrombosis (HIT II), argatroban and bivalirudin are recommended due to their ability to significantly decrease the risk of thrombembolic complications in comparison to other treatments. The aim of the present study was to investigate the efficacy of argatroban and bivalirudin in comparison to unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves using an
in vitro
system.

Materials and Methods
Blood (220 ml) from young and healthy male volunteers was anticoagulated either by UFH, argatroban bolus, argatroban bolus + continuous infusion, bivalirudin bolus, or bivalirudin bolus + continuous infusion. St. Jude Medical 27 mm prosthesis were placed in a newly constructed
in vitro
thrombosis tester, and exposed to a continuous circulation rate of 80 beats per minute to anticoagulated blood samples. The total exposure time was 60 minutes. To quantify the thrombi that developed, electron microscopy was performed. Using a Data Acquisition Unit (DAQ), flow- and pressure differences, before and after the heart valve, could be measured and compared between the five groups. And finally each valve was weighed before and after the experiment.

Results
The mean thrombus weight in group 1 (UFH) was 117 ± 93 mg, in group 2 (argatroban bolus) 722 ± 428 mg, in group 3 (argatroban bolus + continuous infusion) 162 ± 98 mg, in group 4 (bivalirudin bolus) 758 ± 323 mg, and in group 5 (bivalirudin bolus + continuous) 166 ± 141 mg (p-value: <0,00 for comparison between groups 2 and 4 to the other 3 groups). Electron microscopy showed higher rates of thrombus formation in groups 2 and 4.

Conclusion
Argatroban and bivalirudin were as efficient as UFH in preventing thrombus formation on mechanical heart valves in our
in vitro
experiments, when they were administered continuously. We hypothesize that either the continuous infusion of argatroban or bivalirudin are an optimal treatment option for patients with HIT after mechanical heart valve replacement for adapting oral to parenteral anticoagulation or
vice versa
.
Abstract 5916: Delayed Mortality in Peripartum Cardiomyopathy Indicates Need for Long-Term Follow-Up
Authors: Gollapudi Kranti , Forster Olaf , Libhaber Elena , Tibazarwa Kemi , Tshani Winnie , Sliwa Karen
Published: July 2021

Introduction: Peripartum cardiomyopathy (PPCM) is a rare form of cardiomyopathy occurring in women between one month antepartum and five months postpartum. It has been shown to carry a substantial risk of mortality within the first six months after diagnosis but few studies have outlined prospective long-term morbidity and mortality. The aim of this study is to assess long-term clinical outcome and mortality over a two-year period. Methods: Eighty consecutive women with PPCM were enrolled at diagnosis at a single center in a prospective study over a period of two years. Patients were started on standard heart failure therapy and detailed assessments, including echocardiography, were made at six-month intervals for twenty four months in surviving cases. Results: At baseline, the mean age of this cohort was 29.7 ± 6.4 years and 30 of 80 (38%) were in their first pregnancy. Overall, 71 (89%) patients presented in NYHA functional class III–IV at baseline and mean left ventricular ejection fraction (LVEF) was 29.7% ± 8.7%. During the two-year study period, 4 patients were lost to follow-up, 9 moved to remote areas, and 8 had a subsequent pregnancy, predisposing them to additional myocardial risk. In the remaining cases, mean LVEF was 45.1 ± 11.3, 46.3 ± 13.0 and 50.4 ± 13.5 at six, twelve, and twenty four months, respectively. Within two years, 22 women had died (28%), confirming the poor prognostic implications of PPCM. However, the majority of fatal events occurred between six and twenty four months (15 of 22; 68%). At six months, 7 of 80 (9%) patients had died. During extended follow-up, a further 15 of 69 (22%) died despite apparent recovery of left ventricular function. Conclusion: First, our findings emphasize the poor prognosis of PPCM. Furthermore, the fatality rate was higher than expected over a two-year period. The delayed mortality beyond six months observed in our study suggests the need for long-term clinical follow-up in women with PPCM.
Abstract 5923: Increased Frequency of High Heart Rate Episodes is Associated with Heart Failure Decompensation
Authors: Cho Yong K , Reynolds Dwight W , Germany Robin E , Kueffer Fred J , Taepke Robert T , Bourge Robert C , Bennett Tom D
Published: July 2021

The time course of cardiac arrhythmia occurrences and heart failure decompensation (HFD) events has not been well understood. To determine whether high heart rate (HHR) episodes occur more frequently prior to HFD events, the temporal relationship between HHR episodes and HFD events was analyzed from the COMPASS-HF study. The COMPASS-HF study included 274 NYHA class III-IV patients with an implantable hemodynamic monitor (IHM). In addition to monitoring hemodynamic status, the IHMs were set up to detect and store HHR episodes defined as a sensed ventricular HR > 150 bpm for at least 12 of 16 consecutive cardiac cycles. The number of IHM detected HHR episodes during the first 6-months of enrollment in the study was compared to HFD events by two methods:

within patients, by comparing HHR episode rate before and after a HFD event in patients with a single HFD event and

between patients, by comparing HHR episode rate in patients with HFD events (prior to the first HFD event) to HHR episode rate in patients without HFD events.

For those patients with one HFD event (n = 53 patients), HHR episode rates (# of HHR episodes/day) were 0.36 ± 0.82 and 0.05 ± 0.11 (p < 0.01) before and after the HFD event, respectively. Monitoring durations were 94 ± 4 days for before the HFD event and 91 ± 50 days for after the event. HHR episode rates were 0.30 ± 0.77 and 0.19 ± 0. 61 (p < 0.01) for patients with HFD events (n = 104 patients) and without HFD events (n = 170 patients), respectively. Monitoring durations prior to the first HFD event, and in patients without HFD events were 77 ± 46 days and 178 ± 41 days. IHM detected HHR episodes occurred seven times more frequently prior to HFD events than after HFD events. While the IHM could not differentiate the types of HHR rhythms, these data demonstrate a clear association between the rate of HHR episodes and HFD events. The cause and effect relation remains to be more clearly defined.
Abstract 5929: Evaluation of Myocardial Substrate with MRI Late Gadolinium Enhancement Allows for Earlier Detection of Cardiac Involvement Compared with Morphological Assessment in Primary AL Amyloidosis
Authors: Syed Imran , Glockner James , Feng DaLi , Araoz Philip A , Martinez Matthew , Gertz Morie A , Dispenzieri Angela , Oh Jae K , Grogan Martha
Published: July 2021

Objective:
In AL amyloidosis, early detection of cardiac involvement is desirable because of prognostic and therapeutic implications. Recent pilot MRI studies have demonstrated that late gadolinium enhancement (LGE) is a common finding in cardiac amyloidosis (CA) and reflects interstitial expansion due to amyloid infiltration. However it is not known whether evaluation of the myocardial substrate via LGE MRI may allow for earlier detection of CA compared with morphological assessment on the basis of increased left ventricular thickness (LVT).

Methods:
Between January 2006 and December 2007, 100 patients with confirmed AL amyloidosis underwent LGE MRI at our institution to evaluate for CA. Morphological evidence of CA was considered to be present when LVT was increased (mean of septum and inferolateral wall > 12 mm). LGE images were analyzed for presence and pattern of LGE. Clinical data was also reviewed.

Results:
Increased LVT was present in 69 patients. Abnormal LGE images were present in 76 patients (global diffuse transmural or subendocardial LGE in 43, suboptimally nulled myocardium in 18, and focal patchy LGE in 15 patients). LGE was present in 21 of 22 patients with a diagnosis of CA on cardiac biopsy. Seven patients (10%) with increased LVT did not have LGE. Conversely of 31 pts with normal LVT, 14 (45%) had abnormal LGE on MRI (usually suboptimally nulled myocardium or focal patchy LGE) and also had significantly higher incidence of low voltage ECG (50% vs. 0%), lower absolute limb lead voltage (6.5±3 vs. 9.7±2.6 mm), increased RV thickness (4.9±1.1 vs. 4.1±1) and higher BNP (316±376 vs. 107±103) compared to 17 patients without LGE (Table 1

).

Conclusions:
MRI LGE is common in patients with CA and evaluation of the myocardial substrate using this technique may allow for earlier detection of cardiac involvement in AL amyloidosis compared with morphological assessment on the basis of increased LVT.
Abstract 5931: The Presence and Pattern of Late Gadolinium Enhancement on cardiac MRI in Amyloidosis is Associated with Other Markers of Prognosis
Authors: Syed Imran , Glockner James , Araoz Philip A , Feng DaLi , Martinez Matthew , Gertz Morie A , Dispenzieri Angela , Oh Jae K , Grogan Martha
Published: July 2021

Objective:
Recent MRI studies have demonstrated the common occurrence of late gadolinium enhancement (LGE) in cardiac amyloidosis (CA). However, the association of LGE presence and pattern with other clinical, morphological, functional, and biochemical parameters has not yet been demonstrated. It is important to define this association, since many of these parameters (NYHA class, ventricular thickness, cardiac biomarkers) have prognostic implications.

Methods:
Of 151 patients with confirmed systemic amyloidosis who underwent LGE cardiac MRI between January 2006 and December 2007 to evaluate for possible CA, 120 (AL 100, senile 9, and familial 11) were included after meeting of inclusion and exclusion criteria. Cine MRI images were analyzed for morphologic and functional data. LGE images were analyzed for presence and pattern of LGE. Clinical data including ECG’s and cardiac biomarkers was obtained.

Results:
LGE evidence of CA was present in 95 patients and absent in 25 patients. Three main patterns of LGE were observed. These were

global diffuse transmural (homogenous or heterogenous) or subendocardial,

suboptimally nulled myocardium without clear hyperenhancement, and

focal patchy LGE. Symptoms, morphologic/functional variables, ECG voltages, and cardiac biomarker levels were worst in patients with global diffuse LGE, followed by suboptimally nulled myocardium, focal patchy LGE, and absent LGE groups (Table 1

).

Conclusions:
The presence of LGE in amyloidosis patients is associated with worse clinical, morphologic, functional, and biochemical parameters. Amongst patients with abnormal LGE, global diffuse (transmural or subendocardial) LGE is associated with the worst profile. This provides initial evidence that the presence and pattern of LGE in CA is associated with other markers of prognosis.
Abstract 5936: Can Apoptosis Predict Functional Recovery in Acute Myocarditis?
Authors: Abbate Antonio , Sinagra Gianfranco , Bussani Rossana , Hoke Nicholas N , Toldo Stefano , Barresi Elena , Salloum Fadi N , Silvestri Furio , Vetrovec George W , Kukreja Rakesh C , Baldi Alfonso
Published: July 2021

Background. Acute myocarditis is characterized by acute cardiac dysfunction followed by a variable recovery over time. Recent data have shown the presence of apoptosis in acute myocarditis. We hypothesized that the presence and extent of apoptosis evaluated at endomyocardial biopsy (EMB) could predict functional recovery in patients with acute myocarditis, with more apoptosis predicting less recovery.

Methods. Sixteen patients with acute myocarditis were studied with EMB. Baseline and follow up echocardiography was obtained in all cases. The patients were retrospectively divided in 2 groups according to the final left ventricular ejection fraction (LVEF): LVEF>40% [recovery] and LVEF≤40% [no recovery]. Co-staining for DNA fragmentation (TUNEL) and caspase-cleaved cytokeratin-18 (CytoDeath) were performed to quantify the cardiomyocyte apoptosis in EMB specimens. Four subjects dying of non-cardiac causes were selected as control hearts at time of autopsy.

Results. Six patients showed functional recovery (38%) while 8 did not (62%). The apoptotic rate (AR, expressed as % of double positive cardiomyocytes on total number per field) was significantly higher in the hearts of patients with acute myocarditis (1.1%[0.7–2.2] vs 0.01%[0.01–0.01] in control hearts, p<0.001). Unexpectedly, patients with functional recovery had a significantly higher AR than patients without recovery (3.2%[1.1–8.0] vs 0.5%[0.3–1.0], p=0.001), and the AR correlated with follow-up LVEF (R=+0.54, p=0.030). Six of the 8 patients (75%) with AR above average showed functional recovery vs 0 of the 8 patients (0%) with AR below average (p=0.007).

Conclusions. This study surprisingly shows that the presence of greater apoptosis at EBM in patients with acute myocarditis predicts functional recovery at 12 months. Whether this represents a true cause-effect association or it simply represents a non-causal association remains unclear and warrants further studies.
Abstract 5988: Can We Reduce the Use of DES without Compromising Efficacy? Results of a Strategy Combining a Simple Selection Process and the Use of Thin Strut Cobalt Chromium Bare Metal Stents
Authors: Stella Pieter , Nathoe Hendrik , HoseyniGuyomi Siyrous , Wildbergh Thierry , Meijburg Huub W , Doevendans Pieter A , van Belle Eric
Published: July 2021

The introduction of drug eluting stents (DES) has been a breakthrough in the prevention of restenosis following PCI. However, the high rates of late stent thrombosis observed with these devices make alternative preventive strategies mandatory. The use of thin struts cobalt chromium (TSCC) bare metal stents has been associated with promising clinical results. We hypothesized that the use of a strategy combining a simple selection of clinical indications and the use of TSCC BM stents could achieve very low restenosis rates without compromising safety. From September 2005 to June 2006, among patients referred for a PCI procedure in our centre, we prospectively selected those in which at least one of the 2 inclusion criteria was met:

de novo coronary lesion not exceeding 20 mm in length;

vessel diameter more than 2.6 mm; and excluded

those with diabetes mellitus unless vessel diameter > 3.5 mm; to undergo implantation of TSCC bare metal stents.

Twelve months follow-up was obtained in all patients. 511 patients; 30% of the total population referred for PCI; matched the selection criterions and were part of the study. Despite the selection process, the study population was at relatively high risk including 22% of patients with a history of MI, 50% with multivessel coronary artery disease and 59% undergoing PCI for an acute coronary syndrome. The procedural success rate was 99.6%. A single stent was implanted in 88% of patients. A peri-procedural myocardial infarction occurred in 7 (1.4 %) patients. Clinically driven TLR and TVR at 12 months were observed in 8 (1.6%) and 13 (2.5%) patients, respectively. Cumulative In stent-thrombosis at 1 and 12 months occurred in 4 (0.08%) and 6 (0.1%) patients, respectively. Our results demonstrate that a simple selection process, applying to 30% of a routine PCI population, combined with the use of TSCC bare metal stents can be associated with a very favourable long-term clinical outcome. The use of TSCC bare metal stents is an attractive alternative to DES in such a population.
Abstract 5995: Efficacy Of The Everolimus-eluting Stent in Diabetic Patients: Comparison With The Paclitaxel-eluting Stent
Authors: Otake Hiromasa , Ako Junya , Yamasaki Masao , Tsujino Ichizo , Shimohama Takao , Hasegawa Takao , Sakurai Ryota , Waseda Katsuhisa , Yock Paul G , Honda Yasuhiro , Sood Poornima , Sudhir Krishnankutty , Stone Gregg W , Fitzgerald Peter J
Published: July 2021

Background:
In the diabetic subgroup of the Spirit III trial (randomized, multicenter trial comparing Everolimus-eluting XIENCE
™
V stent (EES) to Paclitaxel-eluting Taxus
™
stent (PES) in de novo native coronary artery lesions), PES showed a trend toward fewer major adverse cardiac event compared with EES during 1 year follow-up in patients with diabetes despite lower observed late loss with EES at 8 months.

Methods:
The Stanford University IVUS Core Laboratory database was queried to evaluate the efficacy of EES in diabetics compared with PES. A total of 113 lesions treated with EES (n=58) and PES (n=55) undergoing 8 or 9 months follow up 3-D intravascular ultrasound (IVUS) were enrolled. Volume index (volume/length) was calculated for vessel (VVI), peri-plaque (PVI), neointima (NIV), and lumen (LVI). %NIV was calculated as neointimal volume / stent volume × 100. Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). Late lumen area loss was calculated as minimum lumen area (MLA) at post-intervention (Post) minus MLA at follow-up (FUP). Late incomplete stent apposition (LISA) was defined as separation of at least 1 strut from the vessel wall with blood speckle behind the strut, where Post IVUS revealed well apposition.

Results:
Average stent length was significantly longer in EES. EES showed less neointimal hyperplasia and smaller LVI loss than PES (Table

), whereas no statistical interactions were observed between EES and serial changes for VVI and PVI. PES showed a significant increase in PVI (Post: 7.6±3.1, FUP: 8.4±3.1; p=0.049) and a trend toward increase in VVI (Post: 14.8±5.5, FUP: 15.5±4.2; p=0.07) between Post and FUP. One case with LISA was observed in EES group.

Conclusions:
EES demonstrated significant suppression of neointimal hyperplasia in diabetic patients without vessel expansion compared with PES up to 8 months follow up.

Figure 1

Intra Individual matched In-Stent Late Luminal Loss[mm]