bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 35: Integrin alpha-5 beta-1 and Fibronectin Receptor-Ligand Pair Determines Reparative and Neovascularization Potential of Endothelial Progenitor Cells
Authors: Wary Kishore K , Mock Choun , Garean Sean , Zhao Yidan D , Malik Asrar B
Published: July 2021

Endothelial Progenitor Cell (EPC)-based therapy may be useful for the treatment of microvascular disorders associated with ischemic diseases and for therapeutic neovascularization. Here, we addressed whether mouse bone marrow derived EPCs (mEPCs) express integrins, synthesize and deposit fibronectin, requirements for EPC engraftment in injured microvessels. We used anti-CD34, anti-Flk-1, and anti-VE-cadherin antibodies as mEPC markers. Ex vivo expanded mEPCs were analyzed by fluorescent microscopy and Western blotting for expression of integrins, fibronectin, and von Willebrand Factor (ligands for integrins alpha-5 beta-1 and alpha-v beta-3). Fibronectin and vWF expression of mEPCs was compared with adult mouse lung endothelial cells (mECs). Fluorescent microscopy showed markedly increased fibronectin and vWF staining and Western blotting showed >20-fold increase in fibronectin and vWF expression in mEPCs compared with mECs. The appearance of polymerized fibronectin matrix suggested that mEPCs synthesized, deposited, and assembled fibronectin. Next, ex vivo expanded mEPCs were subjected to shRNA-mediated silencing of alpha-5 integrin, fibronectin and vWF genes. Silencing of alpha-5 integrin and fibronectin genes reduced the proliferative potential of mEPCs whereas vWF silencing had no effect. To evaluate the effectiveness of mEPCs treatment, we irradiated C57BL/6J mice (5.0 Gy) and challenged the mice i.p. with bacterial lipopolysaccharide (LPS) to induce endothelial barrier injury and pulmonary edema. Infusion of mEPCs induced greater survival (~50% at 7.5 mg of LPS/kg BW, n=6) and prevented pulmonary edema resulting from microvessel injury; in contrast, mECs infusion had no protective effect. Thus, EPC expression of alpha-5 beta-1 integrin and secretion of fibronectin matrix may be crucial determinants of engraftment of EPCs at sites of vascular injury, and their ability to promote repair of injured microvessels and neovascularization.
Abstract 63: Hands-On Defibrillation: An Analysis of Current Flow Through Rescuers In Contact With Patients During Biphasic External Defibrillation
Authors: Lloyd Michael S , Krivitsky Eric L , Walter Paul F , Langberg Jonathan J
Published: July 2021

Background:
During cardiopulmonary resuscitation, the need for rescuers to stand clear before a shock is delivered invariably interrupts chest compressions. Brief interruptions like these reduce the efficacy of defibrillation in animal models. Current flow through a rescuer in contact with a patient being shocked with modern biphasic waveforms and adhesive patch electrodes has not been investigated. We hypothesized that leakage current is low through a rescuer performing chest compressions at the time of shock delivery.

Methods:
During 18 elective cardioversions using truncated exponential biphasic waveforms (median energy 200 joules, range 100 –360 joules), an investigator serving as the rescuer placed a gloved hand on the patient’s anterior chest immediately adjacent to the defibrillating patch with approximately 20lbs of pressure to simulate chest compressions. Skin electrodes were used to connect the rescuer’s thigh to the patient’s posterior shoulder, simulating a worst-case return current pathway. During shock delivery, voltage and current through the rescuer (hand to thigh) were recorded using a digital storage oscilloscope during the shock delivery.

Results:
In no cases were shocks perceptible to the rescuer. Mean patient transthoracic impedance was 57 +/− 14 ohms (range 36 –79 ohms). Potential differences in volts (V) between the rescuer’s wrist and thigh ranged from 1.7 to 14 V (mean 6.7 +/− 2.7 V). Calculated impedances through rescuers ranged from 8,190 to 100,400 ohms (mean 30,100 +/− 20,400 ohms). The average leakage current flowing through the rescuer’s body for each phase of the shock waveform was 273 +/−191 microamperes (range 1 to 910 microamperes). All measured values in our series were well below 2,500 microamperes, an accepted safety standard for earth-leakage current in medical devices.

Conclusions:
Even in a simulated worst-case scenario, a rescuer performing chest compressions during biphasic external defibrillation is exposed to low levels of leakage current. Our findings demonstrate the safety and feasibility of uninterrupted chest compressions during shock delivery, which may enhance the efficacy of defibrillation and cardiocerebral perfusion.
Abstract 71: Is the new Basic Life Support protocol (2005) easier to learn?
Authors: Betlehem Jozsef , Nagy Gabor , Marton Jozsef , Gondocs Zsigmond
Published: July 2021

Objectives: The effective learning of basic life support (BLS) skills in the process of training is always an important expectation during the course. Each assessment of BLS training is a complex, continuous action where the evaluation should not be subjective by using the examiner’s experiences only. In order to reach the reliable standard of pedagogical assessment, our department developed a score to ensure more objectivity on BLS examination.

Methods: The developed scoring tool which is consistent with the steps of 2000 and 2005 ERC BLS protocols was introduced at the faculty. After a trial period we assessed in a cross sectional study design 156 students in 2005/2006 first semester based on 2000 ERC BLS, and 207 students in 2006/2007 first semester based on 2005 ERC BLS protocol. The volunteers are between the age 18 and 25 years, and all students studied the same BLS protocol in 28 hours/semester. The data were analyzed by Chi Square test and cross tabulation with SPSS 11.00.

Results: The positive results in all steps of 2005 BLS protocol were correlating with successful of BLS exams significantly. Comparing the five steps of 2005 BLS protocol to 2000 BLS protocol, the checking for responsiveness (p=0,001), shouting for help (p=0,013), checking for breathing (p=0,000; Phi 0,068 vs 0,459), chest compression (p=0,000; Phi: 0,443 vs 0,472), breathing (p=0,000 Phi: 0,360 vs 0,764), seemed to be influencing the successful exams in the 2005 ERC BLS protocol significantly, which made it easier to learn the new protocol, too. There was not significant correlation between the genders in case of 2000 or 2005 BLS protocol.

Conclusions: Our earlier developed score is useful in evaluating the 2005 BLS protocol and the new protocol can be learned more successfully.
Abstract 74: Prognostic markers in Myocardial Infarction complicated by Cardiogenic Shock
Authors: Prondzinsky Roland , Lemm Henning , Swyter Michael , Wegener Nicholas , Unverzagt Susanne , Carter Justin M , Schlitt Axel , Buerke Ute , Russ Martin , Werdan Karl , Buerke Michael
Published: July 2021

Objectives

. Despite aggressive therapy (including PCI and IABP use), survival following acute myocardial infarction complicated by cardiogenic shock (MI-CS) is poor. Early identification of survivors from non-survivors enables better, patient tailored therapy. We hypothesised that APACHE II scoring and other common markers may provide prognostic information in patients receiving contemporary, PCI based therapy for MI-CS.

Methods.

We conducted the IABP-shock-trial (a monocentric, prospective, randomized, controlled, IABP intervention trial) and analysed potential prognostic markers amongst the whole study population. Forty consecutive patients with acute MI-CS were enrolled and APACHE II scores, Cardiac index (CI), BNP and IL-6 levels were measured at enrolment and daily for 4 days before correlation with subsequent 28 day mortality.

Results

. The mean age was 64±1.9 years, 52% were mechanically ventilated, the mean ejection fraction was 27±2.1% and overall 28 day survival was 67%. The initial (on admission to hospital) and serial (over the 4 days) APACHE II scores successfully discriminated between survivors and non-survivors (initial APACHE II scores, 18.1±1.66 and 29.9±2.88, respectively, p<0.05). Following receiver operating curve (ROC) analysis, APACHE II scores were most predictive of survival followed (in order of predictive value) by CI, IL-6 and BNP (Table 1

). Values for APACHE II scores and cardiac index were significantly predictive of survival.

Conclusions

. We conclude that both initial and serial APACHE II scores provide reliable prognostic information for MI-CS patients treated with contemporary, PCI centred therapy. Cardiac index was also of some predictive value. However, in contrast to previous data (applicable mainly to chronic heart failure patients), serial BNP values were not predictive of mortality in this cohort of patients.

Table 1:

ROC analysis
Abstract 534: Large Tumor Suppressor 2 (Lats2), a Downstream Target of Mammalian Sterile 20 Like Kinase 1 (Mst1), Negatively Regulates Ventricular Mass.
Authors: Nakano Noritsugu , Matsui Yutaka , Sadoshima Junichi
Published: July 2021

Mst1 is an evolutionarily conserved serine threonine kinase which is a critical regulator of growth and death in cardiac myocytes. Mst1 forms a complex with hWW45 and Lats2, thereby activating Lats2. Lats2 partially mediates the proapoptotic effect of Mst1 in cardiac myocytes
in vitro
. In order to elucidate the cardiac function of Lats2
in vivo
, we generated transgenic mice with cardiac specific expression of Lats2 (Tg-Lats2, line #8) and dominant negative Lats2 (Tg-DN-Lats2). At 5– 6 months of age, Tg-Lats2 exhibited a greater left ventricular (LV) end-diastolic dimension (4.3 vs 3.7 mm, n = 8, n = 7,
p <
0.05) and lower LV ejection fraction (EF, 63 vs 72 %,
p <
0.05) than wild type (WT) mice. In addition, many Tg-Lats2 exhibited a remarkably enlarged right atrium with mural thrombus. Although LV weight /body weight (LVW/BW) in Tg-Lats2 was not significantly different from that in WT, right ventricular weight (RVW)/BW in Tg-Lats2 was significantly smaller than that in WT (0.65 vs 0.96,
p <
0.05). The LV myocyte cross sectional area (CSA) was significantly smaller in Tg-Lats2 than in WT (82 vs 100%,
p <
0.05) and the RV myocyte CSA showed a similar tendency. Significantly reduced RVW/BW and LVEF were also observed in Tg-Lats2 line #20 (milder expression). Tg-Lats2 exhibited greater levels of interstitial fibrosis (13.0 vs 3.4%,
p <
0.05) at baseline. Although the number of TUNEL positive myocytes was not different between Tg-Lats2 and WT at baseline, it was significantly greater in Tg-Lats2 after transverse aortic constriction for 4 weeks (0.12 vs 0.09%,
p <
0.05). In contrast, Tg-DN-Lats2 exhibited significantly greater LVW/BW (3.88 vs 3.27, n = 10, n = 10,
p <
0.05) and RVW/BW (0.96 vs 0.73,
p <
0.05), and normal LV function. Furthermore, adenovirally expressed Lats2 reduced both the relative cell size and protein/DNA content in cultured neonatal rat cardiac myocytes (53.5%, 63.2% vs LacZ control virus, n = 3, p < 0.05). Conversely, DN-Lats2 virus transduction significantly increased the cell size and protein/DNA content of cardiac myocytes (125.0%, 121.1% vs LacZ control virus, n = 3, p < 0.05). These results suggest that Lats2 is a critical negative regulator of ventricular mass and that stimulation of Lats2 leads to increases in cell death, fibrosis and cardiac dysfunction.
Abstract 90: Inhospital Outcome of 458 Patients with Acute Myocardial Infarction Requiring Mechanical Ventilation. Results of the BEAT Registry of the ALKK.
Authors: Zeymer Uwe , Kouraki Kleopatra , Schneider Steffen , Ludwigshafen Herzzentrum , Uebis Rainer , Aschaffenburg Klinikum , Tebbe Ulrich , Lippe-Detmold Klinikum , Klein Hermann , Idar-Oberstein Klinikum , Janssens Uwe , Senges Jochen , Ludwigshafen Herzzentrum
Published: July 2021

Background:
There is only limited information about characteristics and clinical outcome of patients with acute myocardial infarction (AMI) requiring endotracheal intubation and mechanical ventilation. Therefore we sought to evaluate the clinical course of a large cohort of patients with AMI and mechanical ventilation.

Methods:
The BEAT Registry of the ALKK prospectively enrolled all consecutive patients requiring mechanical ventilation, who were admitted to an internal intensiv care unit (ICU) of 45 participating German centers. Patient characteristics, treatment and complications until discharge were collected. For this analysis we created a subgroup of patients admitted with ST-segment elevation or non-ST Segment elevation myocardial infarction.

Results
: During the 9-month study period 458 consecutive patients with AMI were included. The mean age was 68±8 years and 71% were men. While 40% of the patients were intubated in the prehospital phase, 60% were intubated in the hospital. The initial cause for intubation was in 48% of the cases ventricular fibrillation/ tachycardia or sudden cardiac death, in 39% congestive heart failure and in 13% of the cases non-cardiac. Of the 458 patients 256 (56%) developed cardiogenic shock, 86 (19%) acute renal failure, 76 (17%) coma or brain damage, 64 (14%) severe infection, 46 (10%) sepsis, 28 (6%) MODS and 17 (4%) gastrointestinal bleeding. 204 (45%) patients underwent coronary angiography, 38% were treated with PCI and 5% with coronary artery bypass grafting. The inhospital mortality in the total group was 48% and in the subgroup of patients with cardiogenic shock 69%.

Conclusion:
Patients requiring mechanical ventilation as complication during the early phase of an AMI constitute a high risk subgroup with a mortality of 50%. Further research is necessary to improve the outcome of these patients.
Abstract 98: Spontaneous Refibrillation Following External Defibrillation of Long Duration Ventricular Fibrillation in Swine
Authors: Allred James D , Killingsworth Cheryl R , Allison Scott , Dosdall Derek J , Melnick Sharon B , Smith William M , Ideker Raymond E , Walcott Gregory P
Published: July 2021

Background:
Following successful defibrillation of the long duration ventricular fibrillation (LDVF) associated with sudden cardiac arrest (SCA), refibrillation occurs in over half of resuscitation attempts. In experimental animals with normal hearts, refibrillation almost never occurs following short duration VF lasting < 1 min (SDVF). It is not known if refibrillation following LDVF is due to the cardiac disease that caused the initial LDVF of SCA or if the LDVF itself causes abnormalities that can initiate VF. Further, the mechanism of refibrillation initiation is unknown. We tested the hypothesis that refibrillation occurs frequently following LDVF in previously normal hearts and propagates from a common area within the heart.

Methods
: In 6 pigs, 115–120 plunge needles containing 3– 6 electrodes each were inserted throughout the heart. With the chest closed, external defibrillation pads were placed in a left lateral to right lateral configuration. Following successful defibrillation of 20 s of SDVF, the animal was observed for spontaneous VF for at least 4 min. After termination of 7 min of LDVF, the animal was placed on cardiopulmonary bypass and observed for 15 min for spontaneous VF.

Results:
Following LDVF, 1.33 ±0.8 episodes of spontaneous VF occurred in each animal. The mean time to VF was 71 s (range 5 – 139 s) following defibrillation of LDVF. Three animals had a second episode of VF within 3 min of termination of LDVF. Earliest sites of origin of spontaneous VF occurred equally in the LV (3), RV (3), and septum (2) and arose equally from the endocardium (3), epicardium (2), and myocardium (3). Refibrillation originated in the posterior half of the ventricles 75% of the time. The first refibrillation cycle appeared focal in 75% of cases and reentrant in 25%. Premature ventricular beats arising out of the posterior RV base immediately preceded 75% of VF episodes.

Conclusions:

Spontaneous VF is common after defibrillation of LDVF but not SDVF in previously health swine, indicating that refibrillation does not require preexisting cardiac disease but can be caused by the detrimental effects of LDVF.

Most episodes of refibrillation begin as focal activity within the posterior half of the ventricles.
Abstract 105: Transferring Images via the Wireless Messaging Network using Camera Phones Shortens Time Required to Diagnose Acute Coronary Syndrome
Authors: Ohtsuka Masashi , Uchida Eiji , Nakajima Toru , Yamaguchi Hiroyuki , Takano Hiroyuki , Komuro Issei
Published: July 2021

The speed at which reperfusion treatment can begin is critical in cases of acute coronary syndrome. Electrocardiograms (ECG) are used to make the diagnosis. In the absence of a cardiologist in the emergency room (ER), the ECG image data must be sent to a cardiologist on stand-by outside the hospital. Up until now, ECG images were sent from the hospital to the cardiologist by fax, but if a fax machine is not readily available to the cardiologist, they must look for one in order to receive the image data. More recently, camera phones have become very advanced and are able to send and receive high quality images by e-mail. In this study, we examined whether sending ECG images to a cardiologist by camera phone was more efficient than by fax. ECG images were taken of 20 patients suspected to have acute coronary syndrome. Patients were divided alternately into two groups of ten patients each; the F group and the CP group. The F group’s ECG images were sent to a cardiologist by fax (n=10) and the CP group’s ECG images were sent by camera phone (n=10). We measured the time taken in transmitting the images from the ER to a cardiologist, the time taken to analyze that image and the total time elapsed from image transmission to diagnosis by the cardiologist. All data presented are mean±SD. Group comparisons were based on the Student’s t-test. The amount of time taken in transmitting the images from the ER to the cardiologist was longer in the F group (163.8±5.1 sec) than that taken by the CP group (71.5±4.6 sec). However, the amount of time taken by the cardiologist to analyze those images was shorter in the F group (12.9±1.8 sec) than that of the CP group (24.1±4.3 sec). Total time elapsed from image transmission to diagnosis was shorter in the CP group (95.6 ± 8.4 sec) than that of the F group (176.7 ± 4.9 sec). In conclusion, using camera phones to transmit ECG images to the cardiologist shortens the time taken to diagnose acute coronary syndrome. Furthermore, camera phones are more advantageous in regards to availability and cost in comparison to fax machines because of the recent popularization of camera phones. Therefore, image transmission by camera phones is more efficient in sending image data to a cardiologist than by fax.
Abstract 111: In-hospital Cardiac Arrest: Predictors Of Long Term Survival After Being Discharged Alive
Authors: Keuper Wessel , Dieker Hendrik-Jan , Brouwer Marc A , Verheugt Freek W
Published: July 2021

Background
Long term survival of patients discharged alive after cardiopulmonary resuscitation (CPR) for an in-hospital cardiac arrest (IHCA) has not been extensively studied. It is also largely unknown which of these patients are at high risk for poor survival. Therefore we studied survival and predictors of survival for these patients.

Methods
We retrospectively studied patients who suffered from an IHCA between 1997–2004 and who survived to discharge. Data were collected using an Utstein form. A Kaplan Meier curve was calculated for survival. Survivors were compared with non-survivors and Cox regression analysis was performed to determine predictors of survival.

Results
In this period 222 patients had an IHCA and 19% (n=42) was discharged alive. Known predictors of survival to discharge were confirmed, primarily initial rhythm. In the discharged patients, survival after a median follow-up of 2.9 years (IQR 1.5–7.2) was 57% (n=24). Non-survivors were significantly older, median age 69.3 (IQR 59.6 –75.2) versus 56.7 (IQR 48.1– 68.8) years and had significantly more often diabetes mellitus, arrhythmias, valvular disease and cancer in their medical history than survivors. Initial rhythm did not differ between groups. After adjustment for baseline differences it was found that cancer independently predicted a lower chance of survival (HR 2.8; 95% CI 1.1–7.5). Older age tended to predict a lower chance of survival as well.

Conclusion
Whenever a patient is discharged alive after an IHCA, the chance of survival is evidently reduced. Only cancer independently predicted a lower chance of survival. Long term survival seems to be determined more by comorbidity than arrest variables.
Abstract 541: Dyxin/Lmcd1, A Novel LIM Protein, Is Both Necessary And Sufficient For The Induction Of Cardiomyocyte Hypertrophy
Authors: Frank Derk , Hanselmann Christiane , Will Rainer , Katus Hugo A , Frey Norbert
Published: July 2021

Sustained cardiac hypertrophy may lead to heart failure and sudden death. While significant progress has been made in elucidating the underlying molecular mechanisms, it is believed that several molecules that modulate cardiomyocyte growth remain elusive. To identify novel candidates involved in hypertrophic signalling, we conducted a genome-wide screening experiment by subjecting neonatal rat cardiomyocytes (NRCM) to either biomechanical stretch or phenylephrine (PE) stimulation followed by microarray analyses. Among several other molecules (stretch: n=164; PE: n=238), the new LIM protein Dyxin/Lmcd1 was significantly upregulated both by stretch (5.6fold, p<0.001) and PE (2.5 fold, p<0.01). Moreover, Dyxin was markedly induced in hypertrophic hearts of transgenic mice overexpressing the phosphatase calcineurin (3.8fold on mRNA- and 2.9fold on protein level (both p<0.01)). To dissect the putative function of this novel molecule, we adenovirally overexpressed Dyxin in NRCM, which led to marked cellular hypertrophy (1.5fold increase in cell surface area, p<0.001) and induction of ANF (3.8fold, p<0.05). In addition, the calcineurin-responsive gene MCIP1.4 was found upregulated (3.2fold, p<0.001), suggesting that Dyxin activates the calcineurin pathway. In order to test whether Dyxin is also required for cardiomyocyte hypertrophy, we stimulated NRCVM with either PE or stretch and utilized adenovirus-encoded microRNAs to knock down Dyxin (−75% on protein, −85% on mRNA level). While both PE and stretch induced significant hypertrophy (+41% and +48%, p<0.001), the inhibition of Dyxin expression completely blunted the hypertrophic response to both stimuli (p<0.001). Consistently, induction of the “hypertrophic gene program” (including ANF, BNP, and alpha-skeletal actin) was abrogated. Likewise, PE-mediated upregulation of MCIP1.4 expression (7.3fold; p<0.001), was entirely prevented by the knockdown of Dyxin (0.8fold, p=n.s.). We show here that Dyxin, which has not been implicated in hypertrophy before, is significantly upregulated in cardiac hypertrophy. Moreover, it is both necessary and sufficient for cardiomyocyte hypertrophy, and this effect is mediated, at least in part by modulation of calcineurin signalling.
2007 Katharine A. Lembright Award and Lecture—Stage D Heart Failure: Quality-of-Life Outcomes After Transplantation and Mechanical Support
Authors: Grady Kathleen
Published: July 2021

Approximately 5 million individuals have heart failure in the United States. The 1-year mortality rate for patients with New York Heart Association class IV heart failure is 50%. Treatment options for patients with refractory symptoms and stage D heart failure include heart transplantation and mechanical circulatory support devices. Improved outcomes have been demonstrated in these advanced heart failure patients who undergo surgical therapies. Prolongation of life is relevant only if quality of life (QOL) is improved.

Improvement in QOL outcomes has been demonstrated before and after heart transplantation, including improved outcomes when bridged to transplantation with left ventricular assist devices (LVADs). While listed for transplantation, worse QOL is significantly related to more symptoms, psychological distress, and functional disability. Patients who are bridged to heart transplantation with an LVAD report significantly improved QOL and decreased symptoms from before to early after LVAD implantation, as well as fairly good and stable QOL outcomes through 1 year after implantation.

At 1 year after transplantation, better QOL is significantly related to less psychological distress, functional disability, and symptom distress; older age; and fewer complications. At 5 to 10 years after heart transplantation, QOL is positive and stable. Improved QOL is significantly related to biopsychosocial variables, including less depression, more positive emotions, more social support, and less fatigue. Thus, for stage D heart failure patients, heart transplantation conveys significant short-and long-term QOL benefit, including in those patients who are bridged to transplantation with an LVAD.
2007 James B. Herrick Award and Lecture—The Road Ahead
Authors: Holmes David
Published: July 2021

The road ahead always starts from where it began. For the field of interventional cardiology, the road began 30 years ago this past September, when a 38-year-old physician treated a 38-year-old man for symptomatic coronary artery disease. After this “disruptive” experience, using “disruptive” technology, by a “disruptive” young physician, the landscape has never been the same.

Andreas Gruentzig, that physician, revolutionized the practice of modern cardiovascular care, not just with the introduction of percutaneous transluminal coronary angioplasty, but even more with the concept that a person could work safely in an awake patient within a vascular tree to achieve a specific goal. This sentinel event spurred the development of an extensive family tree of discipline, including intravascular ultrasound; angioscopy; percutaneous treatment of structural heart disease, including among others valvular heart disease, hypertrophic obstructive cardiomyopathy, and atrial fibrillation; ablation; and treatment of carotid and peripheral arterial disease and, more recently, stroke.

In addition, Dr Gruentzig can be said to have encouraged the development of less invasive surgical revascularization approaches, such as “mid-cab” coronary bypass graft surgery. Now that we have broken the barrier of working therapeutically within the vascular tree, the road ahead will include continual assignments and miniaturization of techniques for identification, prevention, and treatment of disease. That road ahead will only be limited by our ability to imagine and create and then our ability to document improved outcome for society, in both individuals and as a whole.
2007 Stroke Council Award and Lecture—Influence of Health Behaviors, Social Factors, and Gender on Stroke Risk and Outcome
Authors: Kelly-Hayes Margaret
Published: July 2021

It is estimated that 1 in 5 women and 1 in 6 men will experience a stroke over their lifetime. As a major healthcare problem, stroke is the third leading cause of death and the leading cause of serious, long-term disability in the United States today. There are currently 5.7 million stroke survivors alive, with 15% to 30% having moderate to severe functional limitations and 20% needing constant care or institutionalization. New knowledge about genetics, treatment, and rehabilitation in stroke continues to make important gains in reduction of death rates. However, prevention is still the best strategy to reduce the burden of stroke. A number of factors have been established as independent contributors to stroke, including hypertension, smoking, diabetes, and atrial fibrillation. In addition to traditional risk factors, there is an increasing interest in the role of health behaviors and social factors in stroke risk. Epidemiological studies such as the Framingham Heart Study have recently suggested that women experience stroke at an older age, are more disabled and depressed before stroke, have limited social support systems, and are at high risk for institutionalization if they do survive. Better integration of established risk factors, health behaviors, and social dimensions can augment our understanding of those at highest risk for stroke and those most vulnerable for dependency. Public awareness of and education about this interrelationship is an important key to prevention of stroke and its aftermath.
Differential Regulation of Histone Deacetylase 4 by CaM Kinase II and Protein Kinase A in Response to Cardiac Beta-Adrenergic Signaling
Authors: Backs Johannes
Published: July 2021

Abstract 281

Johannes Backs, David Patrick, Thea Backs, Svetlana Bezprozvannaya, Xiaoxia Qi, Joseph A Hill, Eric N Olson, UT Southwestern Medical Center at Dallas, Dallas, TX

Johannes Backs, 2007 Finalist and Presenting Author
Granzymes: Major Players in Vascular Remodelling, Atherosclerosis and Longevity
Authors: Granville David J
Published: July 2021

Abstract 285

Rani P Cruz, Wendy A Boivin, Ciara M Chamberlain, Jonathan C Choy, Bruce M McManus, David J Granville, University of British Columbia, Vancouver, BC, Canada

David J Granville, 2007 Finalist and Presenting Author
Adenylate-Cyclase VI Transforms Ventricular Cardiomyocytes Into Biological Pacemaker Cells
Authors: Ruhparwar Arjang
Published: July 2021

Abstract 1744

Arjang Ruhparwar, Klaus Kallenbach, Univ of Heidelberg, Heidelberg, Germany; Gunnar Klein, Mahyar E Makoui, Christoph Bara, Hannover Medical School, Hannover, Germany; Daniel C Sigg, Medtronic Inc., Minneapolis, MN; Axel Haverich, Hannover Medical School, Hannover, Germany; Matthias Karck, University of Heidelberg, Heidelberg, Germany; Michael Niehaus, Hannover Medical School, Hannover, Germany

Arjang Ruhparwar, 2007 Finalist and Presenting Author
Objectively Measured, but Not Self-Reported, Medication Adherence Independently Predicts Event-Free Survival in Patients with Heart Failure
Authors: Wu Jia-Rong
Published: July 2021

Abstract 1729

Jia-Rong Wu, Debra K Moser, Misook Chung, Terry A Lennie, University of Kentucky, Lexington, KY

Jia-Rong Wu, 2007 Finalist and Presenting Author
2008 George E. Brown Memorial Lecture—Flow-Induced Vasodilation in the Human Heart: Unique Endothelial Mechanisms and Clinical Insights
Authors: Gutterman David
Published: July 2021

The most physiologically important stimulus for endothelium-dependent dilation is shear stress. Flow across the endothelial surface triggers a mechanochemical signal transduction pathway that results in release of nitric oxide (NO), prostacyclin, and/or endothelial-derived hyperpolarizing factors (EDHFs) such as hydrogen peroxide (H
2
O
2
) and epoxyeicosatrienoic acid (EET). In most normal arteries, NO is the prominent mediator; however, in disease states, NO may be quenched by an elevation in superoxide. In these situations, compensatory dilator mechanisms may emerge, using EDHFs. One mechanism of this compensation may involve an important dilator pathway interaction whereby NO inhibits CYP450 monooxygenase. This is particularly prominent in the microcirculation, where disease-induced loss of NO often results in enhanced endothelial CYP450 activity and generation of EET as an alternate dilator. Recent data indicate that H
2
O
2
can also inhibit CYP450.

In the human coronary microcirculation from subjects with coronary artery disease, NO and prostacyclin play little role in the dilation to most pharmacological agonists or to shear stress. Instead, EETs and H
2
O
2
are critical mediators of flow-induced dilation. Interestingly, the dilation requires ROS generation from the endothelial mitochondrial electron transport chain. Dual vessel bioassay studies suggest that H
2
O
2
is the transferable compound responsible for hyperpolarizing and relaxing the underlying vascular smooth muscle cells. In contrast, dilation to bradykinin also involves both H
2
O
2
and EET, but the H
2
O
2
originates from endothelial nicotinamide adenine dinucleotide phosphateoxidase oxidase, and EETs serve as an important transferable dilator agent.

Endothelial release of NO, EET, and H
2
O
2
has implications beyond vasodilation. NO and EETs have potent antiatherosclerotic properties. Hydrogen peroxide, on the other hand, although a potent dilator, has proatherogenic properties. Therefore, it is hypothesized that the profile of endothelial factors released by shear stress and other stimuli may help determine the balance between proatherosclerotic and anti-atherosclerotic factors in vascular homeostasis.
2008 Charles T. Dotter Memorial Lecture—More Surprises From the Healthy Donut
Authors: Rubin Geoffrey
Published: July 2021

In 1990, magnetic resonance imaging (MRI) techniques for imaging the cardiovascular system were ascendant, generating considerable enthusiasm throughout the imaging community. Simultaneously, computed tomography (CT) was considered to play a minimal role in cardiovascular imaging. However, the introduction of spiral CT and subsequent birth of CT angiography (CTA) in 1991 transformed the field by offering greater spatial detail, more reliable image quality, and a less complex workflow than MRI.

In 1998, multidetector-row CT (MDCT) revolutionized CTA by allowing high spatial resolution imaging of large vascular territories, including “whole-body” three-dimensional angiograms in less than 20 seconds. The volumetric acquisitions of CTA allowed the analysis of the arterial wall, juxta-arterial structures, and the arterial lumen, while revealing limitations of intra-arterial angiography, the previously undisputed standard for vascular imaging. MDCT also provided key breakthroughs for improving the temporal resolution of CT, enabling cardiac and coronary CTA to be performed on widely available scanning platforms.

Throughout the current decade, CT advances have followed a near exponential trajectory, and the question “Can we reliably perform coronary CTA?” has been replaced by “What impact does management based on CT findings have on patient outcomes?” In just 2 years, an unprecedented diversity in novel CT technology has emerged, including multiple x-ray sources, wide-area detectors, and energy-discriminating detectors that promise extraordinary advances in the assessment of tissue composition, fine detail visualization, tissue perfusion, functional characterization, artifact suppression, and radiation dose minimization. Together, we will explore the past, present, and future of CT in the diagnosis and characterization of cardiovascular health and disease.
2008 Distinguished Scientist Lecture—MicroRNA Control of Heart Disease: From New Biology to New Therapeutics
Authors: Olson Eric N.
Published: July 2021

MicroRNAs act as negative regulators of gene expression by inhibiting the translation or promoting the degradation of target mRNAs. Because individual microRNAs often regulate the expression of multiple target genes with related functions, modulating the expression of a single microRNA can, in principle, influence an entire gene network and thereby modify complex disease phenotypes. We have identified signature expression patterns of microRNAs associated with pathological cardiac hypertrophy, heart failure, and myocardial infarction in humans and mouse models of heart disease. Gain- and loss-of-function studies in mice have revealed profound and unexpected functions for these microRNAs in numerous facets of cardiac biology, including the control of myocyte growth, contractility, energy metabolism, fibrosis, and angiogenesis, providing glimpses of new regulatory mechanisms and potential therapeutic targets for heart disease. Especially intriguing is the discovery of a network of muscle-specific microRNAs embedded within myosin heavy chain genes, which control myosin expression and the response of the heart to stress and thyroid hormone signaling. Recent studies have demonstrated that disease-inducing cardiac microRNAs can be persistently silenced in vivo through systemic delivery of anti-miRs, allowing for the direct therapeutic modulation of disease mechanisms. The myriad roles of microRNAs in the control of cardiac function and dysfunction and therapeutic opportunities for manipulating microRNA biology in the setting of heart disease will be discussed.
Long-Term Effects of a Rapid Response Team on Hospital-Wide Code Rates and Mortality
Authors: Chan Paul
Published: July 2021

Abstract 502

Paul S. Chan, Adnan Khalid, Lance Longmore, Mid-America Heart Inst, Kansas City, MO; Robert Berg, Univ of Arizona at Tucson, Tucson, AZ; Mary Ann Peberdy, Virginia Commonwealth Univ, Charlottesville, VA; Mikhail Kosiborod, John A. Spertus, Mid-America Heart Inst, Kansas City, MO

Paul Chan, 2008 Finalist and Presenting Author
Polymer Injection Therapy to Reverse Remodel the Papillary Muscles: Efficacy in Reducing Mitral Regurgitation in a Chronic Ischemic Model
Authors: Solis-Martin Jorge
Published: July 2021

Abstract 1104

Jorge Solis-Martin, Benjamin Johnson, J.Luis Guerrero, Mark Handschumacher, Suzanne Sullivan, Massachusetts General Hosp, Boston, MA; G.J.C Braithwaite, Cambridge Polymer, INC, Boston, MA; O.k. Muratoglu, G.j Vlahakes, Robert A Levine, Judy Hung, Massachusetts General Hosp, Boston, MA

Jorge Solis-Martin, 2008 Finalist and Presenting Author
Geographical Analysis of Cardiac Interventional Services in Alabama
Authors: Graves Barbara
Published: July 2021

Abstract 1014

Barbara A Graves, Joseph Weber, Univ of Alabama, Tuscaloosa, AL

Barbara Graves, 2008 Finalist and Presenting Author
2008 Russell Ross Memorial Lectureship in Vascular Biology—Activating and Inhibitory Receptors in Blood and Vascular Cells
Authors: Newman Peter
Published: July 2021

The activation state of circulating blood cells is a tightly controlled process that is continuously influenced by both stimulatory and inhibitory events, and proper integration of the signals transduced by physical and chemical mediators to which cells are exposed is crucial for maintaining homeostasis. Studies carried out over the past 20 years has led to the identification of numerous plasma membrane receptors linked to intracellular signaling pathways that regulate cellular activation, signal transmission, and later, adaptation. Human platelets are both a valuable and clinically relevant model system in which to study such activating and inhibitory processes at the molecular level, as their dysregulation can lead to bleeding, inflammation, thrombosis, and cardiovascular disease. Platelets express G protein-coupled receptors, kinase- and phosphatase-linked receptors, and a host of adhesion molecules, and there is growing recognition that these are intricately intertwined, making rational intervention to control platelet activation and platelet aggregation an increasingly approachable, albeit challenging, possibility. This lecture will highlight our recent understanding of the complex interplay between immunoreceptor tyrosine-based activation motif (ITAM)–bearing and immunoreceptor tyrosine-based inhibitory motif (ITIM)–bearing receptors that exists in platelets and other vascular cells, with an emphasis on the role that such receptors play in human health and the treatment of cardiovascular disease.
Abstract 5781: Evaluation of Global and Regional Right Ventricular Systolic Function in Patient Prosthesis Mismatch after Mitral Valve Replacement using Velocity Vector Imaging
Authors: Tugcu Aylin , Tayyareci Yelda , Yildirimturk Ozlem , Aytekin Saide
Published: July 2021

The aim of this study was to compare right ventricular (RV) global and regional systolic function in patients with and without patient prosthesis mismatch (PPM) after isolated mitral valve replacement (MVR) using Velocity Vector Imaging (VVI) method. The PPM group consisted of 20 patients that underwent isolated MVR with an indexed effective orifice area (EOA) ≤ 1.2 cm
2
/m
2
determined by continuity equation and indexed for body surface area. The non-PPM group consisted of 20 patients that also underwent isolated MVR with an indexed EOA > 1.2cm
2
/m
2
. Echocardiographic images in apical planes were analyzed for RV volumes, ejection fractions, myocardial velocity, strain and strain rate at the basal, mid and apical segments of RV free wall and ventricular septum using VVI. The demographic and preoperative data were similar between PPM and non-PPM groups. Evidence of PA hypertension defined as systolic PA pressure > 40 mmHg was present in 50% of patients in PPM group, whereas none of the patients in non-PPM group had PA hypertension. RV volumes were significantly increased, and RV ejection fraction, peak systolic myocardial velocities, strain and strain rates were significantly impaired in patients with PPM compared to non-PPM group (p<0.001 for all). Indexed EOA correlated strongly with myocardial velocities, strain and strain rates in all segments of the RV (p<0.05 for all). Multivariate stepwise regression analysis demonstrated that indexed EOA and systolic PA pressure were the independent determinants of basal free wall peak systolic strain (β=0.547, p<0.001 and β=−0.304, p=0.033 respectively) and strain rate (β=0.497, p=0.001 and β=−0.332, p = 0.026 respectively). Using receiver-operating characteristics analysis cut-off values for basal free wall peak systolic strain and strain rate in determining patients with indexed EOA ≤ 1.2 cm
2
/m
2
were −25.62 % (sensitivity 85%, specificity 95%) and −1.87 1/s (sensitivity 95%, specificity 95%) respectively. PPM after MVR is associated with RV global and regional RV dysfunction. Two-dimensional echocardiography has some limitations in evaluating RV function due to its complex geometry. VVI is a feasible modality in assessment of RV global and regional RV function.
Abstract 5838: Successful Replacement of Aortic Valves by Decellularized Allografts in the Sheep: First Long-Term Results
Authors: Baraki Hassina , Cebotari Serghei , Tudorache Igor , Braun Maike , Hoeffler Klaus , Goerler Adelheid , Bara Christoph , Calistru Alex , Brandes Gudrun , Hilfiker Andres , Haverich Axel
Published: July 2021

Immunogenicity of human allografts leads to gradual valve degeneration. Pulmonal cell-free valvular scaffolds obtained by methods of tissue engineering have proved to induce in-vivo guided tissue regeneration and represent a promising valve substitute especially for children. Here we describe the successful orthotopic implantation of decellularized aortic valves in the systemic circulation in sheep. Allogenic detergent decellularized (0.5% sodium deoxycholate/0.5% SDS) aortic valve (AV) conduits (n = 12) were implanted orthotopically as root replacement in lambs (35–45 kg). Fresh native AV conduits served as controls (n = 6). After three and nine months follow-up the valves were investigated for functionality by echocardiography, for morphology and histological appearance. Decellularization resulted in complete loss of cells in AV wall, cusp and myocardial cuff, no influence on scaffold microarchitecture was observed. During 9 months follow-up no signs of conduit dilatation, aortic stenosis (transvalvular gradient max. 6.1 ± 5.1mmHg) or reduction of cusp mobility were observed in the decellularized group. Regurgitation in these valves was trivial in all cases. The grafts showed no histological signs of rejection and partial repopulation of the valvular scaffolds with autologous cells. In contrast, control animals developed mild to severe AV insufficiency. Histological investigation revealed significant calcific degeneration and massive rejection of these valves. Decellularized AV conduits may represent a durable AV substitute resistant to high systemic pressure. Furthermore, cell-removal prevents the allograft valve from immunologic deterioration and early graft degeneration.
Abstract 5853: Continuous Flow Left Ventricular Assist Device in Women with Advanced Heart Failure: Results After One Year of Support
Authors: Pamboukian Salpy V , Bogaev Roberta C , Russell Stuart D , Boyle Andrew J , Moazami Nader , Chen Leway , Farrar David J , Pagani Francis D
Published: July 2021

Small continuous flow left ventricular assist devices (LVAD) are providing new options for women in advanced heart failure who due to body size limitations were historically excluded from use of large first generation pulsatile devices. We report the experience of women one year after implantation with the new, HeartMate II continuous flow LVAD for bridge to transplantation. Patients (n=279), 24% female (F), 76% male (M) in NYHA Class IV heart failure, LV ejection fraction 16±7% (F), 16±6% (M), mostly inotrope dependent and about half on intraaortic balloon pump support (50% F, 43% M), who had been enrolled in the HM II clinical trial for at least 1 year as a bridge to cardiac transplantation at 33 centers were analyzed. Outcomes and causes of death in the first year of support between F and M recipients were determined. The percentage of patients who had undergone transplantation, recovery of the heart with device removal, or continued on HM II support after one year were the same (80%) between M and F. However, the percentage of patients who had received a heart transplant was significantly less for F (38%) than M (53%) (p<0.05). Median duration of support for F was 226 days (range 8–1004) vs. 143 days (range 0–1057) for M. Mortality on device support was 20% for F and 18% M. There were no statistically significant differences in leading causes of death: sepsis (1.5% F vs 4.2% M), ischemic stroke (3.1% F vs 1.9% M), hemorrhagic stroke (3.1% F vs 1.4% M), and right heart failure (3.1% F vs 1.9% M). Of 82 patients continuing on support at 1 year, 26 (32%) were F with median BSA of 1.65 vs 2.14 m
2
for M. Kaplan Meier survival at one year was similar for females (74%) and males (76%). The smaller, more durable HM II rotary LVAD may be especially advantageous to women with advanced HF as a bridge to cardiac transplantation, because of significantly smaller BSA and need for extended duration of mechanical support due to longer wait times for suitable organ donors.

Outcomes at one-year
Abstract 5861: BAY 58–2667, A Novel No-independent Activator Of Soluble Guanylate Cyclase Attenuates Myocardial Infarction Following Ischemia/reperfusion Injury Through Protein Kinase G Activation
Authors: Ockaili Ramzi A , Salloum Fadi N , Chau Vinh Q , Lall Sumeet K , Kukreja Rakesh C
Published: July 2021

Background:
BAY 58–2667 (4-[((4-carboxybutyl){2-[(4-phenethylbenzol) oxy]phenethyl} amino)methyl[benzoic]acid) is a soluble guanylate cyclase (sGC) activator that acts independent of the gaseous ligand NO. Preclinical data show that BAY 58–2667 induces cGMP generation and causes vasodilatation in the diseased vessel. Since cGMP-dependent PKG activation is an essential component of ischemic tolerance induced by preconditioning in the heart, we interrogated the potential role of this compound in cardioprotection.

Methods and Results:
Adult male ICR mice were pretreated with either BAY 58–2667 (10 μg/kg, ip) or 10% DMSO (vehicle) 30 min prior to regional ischemia for 30 min and reperfusion for 24hrs. PKG-specific inhibitor, KT5283 (1 mg/kg, ip) was given 10 min before BAY 58–2667 or vehicle. Infarct size (IS) was measured by computer morphometry of tetrazolium stained sections. IS (mean ± SE) was reduced with BAY 58–2667 as compared to vehicle (80% reduction). KT5283 blocked the cardioprotective role of BAY 58–2667 as shown by an increase in infarct size. KT5283 alone had no significant effect on infarct size. Similar results were obtained in the rabbit heart where this compound caused 62 % reduction in infarct size following 30 min of ischemia and 3 hrs of reperfusion

Conclusion:
For the first time, we show that novel NO-independent activator of sGC induces powerful protection against myocardial infarction in the adult heart. The infarct-limiting effect of BAY 58–2667 is mediated by PKG dependent signaling.