bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 52: An Evidence Based Animal Model Of Prolonged Ventricular Fibrillation Cardiac Arrest
Authors: Mader Timothy J
Published: July 2021

Background: Promising basic science findings in cardiac resuscitation often do not translate into improved outcomes when studied in humans. One explanation is that the current animal models do not adequately reflect the out-of-hospital cardiac arrest (OHCA) clinical trial environment. The author sought to review the literature and devise a new model of prolonged VF with time intervals that more accurately simulate OHCA conditions.

Methods: A systematic review of the literature (01/90 –12/06) was conducted using PUBMED and a comprehensive list of appropriate MESH headings. All OHCA human clinical trials were included. The most relevant studies underwent explicit and detailed review. Mean values with 95%CI were calculated for each specified interval. Suitable conditions and establishment of appropriate times were then devised.

Results: Twenty-two papers with adequate detail for evaluation were examined, leading to the following recommendations: the duration of non-treatment (assuming no bystander CPR or first-responders) is 11” (3” for recognition and EMS activation, 7” response interval and 1” for paramedics to reach the patient); chest compressions are initiated immediately with passive oxygen insufflation; assuming they can be done simultaneously, IV access and intubation (ETI) are accomplished 4” after arrival; drugs are delivered by minute 16 - well into the metabolic phase; and 2” of CPR are needed to circulate the drugs for the first rescue shock (RS) at minute 18.

Conclusions: This proposed evidence based experimental model of prolonged untreated VF cardiac arrest has conditions and time intervals that simulate those of human OHCA clinical trials.
Abstract 56: Ventilation Is Necessary During Cardiopulmonary Resuscitation In A Rat Model Of Cardiac Arrest Induced By Airway Obstruction
Authors: Kurita Akihide , Taniguchi Takumi , Yamamoto Ken
Published: July 2021

Recent studies have showed that hypoventilation during cardiopulmonary resuscitation (CPR) improved the rates of return of spontaneous circulation (ROSC) and prognosis. However, there are few studies about the ventilation strategies during CPR in cardiac arrest caused by airway obstruction. To compare the effects of the three ventilation strategies during CPR in an animal model of cardiac arrest induced by airway obstruction, we investigated the rates of ROSC, survival rates, plasma cytokine levels, and lactate levels. thirty-six male Sprague Dawley rats were anesthetized with intraperitoneal injection of pentobarbital. Cardiac arrest was induced by airway obstruction. After 3 minutes of cardiac arrest, animals were randomized to receive one of the three ventilation strategies during CPR (n = 12 per group): normoventiraion (28 breaths/min), hypoventilation (14 breaths/min), or no-ventilation. The rates of chest compression (CC) was 240 –260 compressions/min and the depth of CC adjusted to maintain mean arterial pressure more than 25 mmHg in all groups. After 5 minutes of CPR, epinephrine (0.02 mg/kg) was administered, and all rats were ventilated at the rates of 28 breaths/min in FiO2 1.0. The rates of ROSC were 83%, 58%, 0% for the normoventilation, hypoventilation, and no-ventilation groups, respectively. The PaCO2 levels immediately after ROSC were 74mmHg and 88 mmHg for the normoventilation, and hypoventilation groups, respectively. The increases of plasma cytokine (TNF-a, and IL-6) levels and lactate levels after ROSC in the normoventilation group were significantly less than those in the hypoventilation group. The present study showed that normoventilation during CPR improved the rates of ROSC and the survival rates after ROSC in the animal cardiac arrest model induced by airway obstruction. Moreover, normoventilation attenuated the elevation of cytokine and lactate responses. These findings suggest that ventilation may be necessary during CPR in cardiac arrest caused by airway obstruction.
Abstract 66: Effectiveness Of Cardiac-only CPR Training by Self-learning Video, a 1-hour program, or Both
Authors: Nishiyama Chika , Iwami Taku , Kawamura Takashi , Ando Masahiko , Berg Robert A , Yonemoto Naohiro , Fukuda Risa , Yuasa Haruyuki , Kada Akiko , Yokoyama Hiroyuki , Nonogi Hiroshi
Published: July 2021

[Introduction]
Despite present efforts to train the general public in CPR, the proportion of bystander CPR is still low. Length of CPR training program and complexity of CPR skills may be barriers to bystander CPR performance. Recently, simple video self-learning has been shown to be an effective CPR training technique.

[Objective]
To evaluate the effectiveness of cardiac-only CPR training program by a self-learning video, a 1-hour practical course, or both.

[Method]

Designs

: A randomized controlled trial.

Participants:

General public aged 18 years or older.

Intervention:

In the video (V) group, participants received the self-learning video before CPR training and then attended a 1-hour cardiac-only CPR training program; in the control (C) group participants attended the training program without a self-learning video.

Data collection:

Before and immediately after the training, a 2 minute scenario-based test was conducted and CPR skills were recorded.

Outcomes:

The primary outcome measure was the number of correct chest compressions immediately after the training. We also calculated the achievement of correct chest compressions, which meant the proportion of correct chest compressions in relation to the ideal number of chest compressions based on 2005 CPR guideline.

[Result]
214 participants were randomly assigned to V (108) and C (106) groups. Before the training, the proportion of attempting chest compression, attempting AED operation, and calling for an AED, and the total number of chest compressions were significantly grater in the V group. After the training, all measured CPR skills of both groups improved substantially compared with pre-training skills, but there were no differences between groups (Table

).

[Conclusion]
A self-learning video improved CPR skills. However, a 1-hour practical training course was substantially more effective and the addition of a self-learning video did not improve its effectiveness.

Table:

CPR Skills of Pre- and Post-training
Abstract 532: Effect of 3-hydroxy-3-methylglutaryl-CoA Reductase Inhibitors on Renal Function
Authors: Sukhija Rishi , Bursac Zoran , Sachdeva Rajesh , Mehta Jawahar
Published: July 2021

Background
: 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) reduce serum cholesterol, and cardiovascular morbidity and mortality. The role of lipids in the progression of kidney disease and the potential beneficial effects of statins on renal function is unknown. Oxidative stress and inflammation may be the missing link between CAD and chronic kidney disease. Statins may protect the kidney through both lipid lowering properties and pleiotropic effects.

Methods
: We analyzed data in 197, 551 patients (mean age 64.8 ± 13.6 years, 95% males, 29.5% (58,332) statin users, and 70.5% (139, 219) non-statin users), who had baseline creatinine less than 3.5 mg/dl, from the cross-sectional data mined from the Veterans Affairs VISN 16 database. Deterioration of renal function was defined as doubling of the baseline or increase in creatinine of 0.5 mg/dl over at least 90 days.

Results
: Based on this definition, 3.4% of patients developed renal deterioration over 5 year of follow-up. After adjustment for demographics, diabetes mellitus, smoking, and other medications (especially use of angiotensin-converting enzyme inhibitors, calcium channel blockers and aspirin, all of which were confounders of the statin-renal deterioration relationship), use of statins reduced the odds of deterioration in renal function by 15% (OR 0.85, 95% CI = 0.80 – 0.89, p < 0.0001). This effect was independent of cholesterol lowering effect of statins. Impact of other variables was as follows: age (OR = 1.04, CI = 1.03–1.04, p < 0.0001), diabetes (OR = 1.76, CI = 1.67–1.85, p < 0.0001), and smoking (OR = 1.76, CI = 1.05–1.23, p = 0.0014).

Conclusion
: Statin use may retard the progression of renal disease. Although the precise mechanism is not known, lowering of LDL-cholesterol and improvement in endothelial function by statins may relate to reno-protective effect.
Abstract 540: Effects Of Altered Levels Of Adenylyl Cyclase Type 5 In Cardiac Myocytes From Chimeric Mice
Authors: Hu Che-Lin , Gao Shumin , Hong Chull , Liu Jing , Reinhardt Heather , Holle Eric , Wagner Thomas E , Vatner Dorothy E , Vatner Stephen F
Published: July 2021

The role of adenylyl cyclase (AC) isoforms in the heart has remained controversial in regards to their ability to enhance or impair cardiac function. We examined the effects of chronic pressure overload (aortic banding) in transgenic (TG) mice with cardiac overexpressed AC isoform type 5 (AC5TG), a major cardiac AC isoform. In AC5TG, the hypertrophic response, as assessed by LV/tibia length (TL), was greater, p<0.05, in AC5TG (6.6±0.2) than wildtype (WT) (5.1±0.2). In addition, cardiac decompensation occurred, as reflected by decreased LV ejection fraction and increased lung/body weight, which could exert systemic effects through reflexes and hormones. We sought to examine whether the effects of overexpressed AC5 on the response to pressure overload is due to the affects on the myocyte or its environment. Chimeric mice from fusion between embryos from the transgenic overexpressed AC5 parents and the Rosa26 parents, which ubiquitously express beta-galactosidase in all tissues and can be identified histologically with X-gal staining, were developed. The proportion of the AC5TG (FVB background) cells in the myocardium ranged from 2% to 75% (n=9). We subjected these animals to 2 wk aortic banding at 4 – 6 months of age and examined the physiological and histological changes in the heart. There was a direct correlation (r= 0.91) between the percentage of AC5OE cells and LV hypertrophy index (LV weight/BW) including LV end diastolic and systolic wall thickness (r=0.98 and 0.92, respectively). We then determined the myocyte cross-sectional cell size from different cell origin micrographically. After 2wk banding, myocytes originating from the Rosa26 (C57/BL6) and FVB background were similar in size, but myocytes overexpressing AC5 were significantly larger (33%, p<0.05). Conversely, there was a negative correlation between the amount of AC5OE cells and heart function: LV ejection fraction and contractility decreased in mice with a higher percentage of AC5OE myocytes (r = −0.89 and r = −0.81, respectively). Thus, overexpression of AC5 even in only a small fraction of total myocytes in the heart induced myocyte hypertrophy independent of any systemic influences.
Magnetic Resonance Imaging Reveals Novel Phenotypic Expression of Desmosomal Mutation in First-Degree Relatives of Patients with Arrhythmogenic Right Ventricular Dysplasia (ARVD). Prevalence and Clinical Significance in Patients Evaluated For ARVD
Authors: Tandri Harikrishna
Published: July 2021

Abstract 1768

Harikrishna Tandri, Darshan Dalal, Aditya Jain, Daniel P Judge, Theodore Abraham, Cynthia James, Samanthapudi K Daya, Crystal Tichnell, Stuart Russell, Hugh Calkins, David A Bluemke, Johns Hopkins University, Baltimore, MD

Harikrishna Tandri, 2007 Finalist and Presenting Author
Challenges of Using Peri-procedural Myocardial Infarction as a Quality Measure Among Patients Undergoing Percutaneous Coronary Intervention
Authors: Wang Tracy Y
Published: July 2021

Abstract 1754

Tracy Y Wang, David Dai, Eric D Peterson, Sunil V Rao, Matthew T Roe, Duke University, Durham, NC; on behalf of the National Cardiovascular Data Registry

Tracy Y Wang, 2007 Finalist and Presenting Author
2008 Alexander S. Nadas Lecture—Repaired, Not Cured
Authors: Rosenthal Amnon
Published: July 2021

A large number of patients with congenital cardiac disease have a repaired but not cured malformation. Although some mild cardiac defects may heal spontaneously, others persist or progress with advancing age. Among those with a major or complex defect repaired by interventional and/or surgical procedures, few are cured. Whereas major cardiac defects often occur as an isolated anomaly, many patients have serious extracardiac congenital defects, systemic syndromes, genetic abnormalities, or other handicaps. In caring for the patient, the pediatric cardiologist, in addition to directing cardiac therapy, is often called upon to coordinate the diverse care, plan, and guide for the patient’s future. It is a chronic disorder often recognized in the fetus, proceeding through infancy, childhood, and into adulthood, thus requiring long-term care. The medical and surgical therapy is usually provided by subspecialist colleagues within the field. However, delivery of appropriate, comprehensive, and optimal care requires a “quarterback” cardiologist concerned with diverse, frequently inevitable issues, such as prematurity, nutrition, growth, or genetic screening. Important concomitant problems may be related to associated extracardiac anomalies, exercise capacity, school, health or life insurance, employment, pregnancy, and family life. A primary care physician might be uncomfortable advising on many of these issues and the responsibility falls to the cardiologist. Anticipated medical advances may further impact the care and require yet greater coordination of services and close empathetic attention. These changes may include further cardiologist subspecialization, primary care provided by nurse clinicians, fetal cardiac intervention, increase in regionalization of specialty care, or more complex laboratory procedures—all not infrequently replacing the careful medical history and physical examination.
Large Tumor Suppressor 2, a Downstream Target of Mammalian Sterile 20 Like Kinase 1, Is an Endogenous Regulator of Myocyte Size and Apoptosis in the Heart
Authors: Matsui Yutaka
Published: July 2021

Abstract 484

Yutaka Matsui, Noritsugu Nakano, Hiromitsu Takagi, Dan Shao, Shumin Gao, Chull Hong, Peiyong Zhai, UMDNJ, New Jersey Medical Sch, Newark, NJ; Norikazu Yabuta, Osaka Univ, Osaka, Japan; Wufan Tao, Univ of Minnesota, Minneapolis, MN; Hiroshi Nojima, Osaka Univ, Osaka, Japan; Junichi Sadoshima, UMDNJ, New Jersey Medical Sch, Newark, NJ

Yutaka Matsui, 2008 Finalist and Presenting Author
Obstructive Sleep Apnea Increases the Risk of Sudden Cardiac Death: A Longitudinal Study of 10,701 Adults
Authors: Gami Apoor
Published: July 2021

Abstract 505

Apoor S Gami, Eric J Olson, Win K Shen, R Scott Wright, Karla V Ballman, David O Hodge, Regina M Herges, Daniel E Howard, Virend K Somers, Mayo Clinic, Rochester, MN

Apoor Gami, 2008 Finalist and Presenting Author
Biatrial Enlargement and Recurrent Cardioembolism in a 55 Year-Old Man With Atrial Fibrillation
Authors: Nallamshetty Shriram
Published: July 2021

Abstract 1124

Shriram Nallamshetty, Byungdoo A Yi, James Stone, Massachusetts General Hosp, Boston, MA; Patrick T O’Gara, Brigham and Women’s Hosp, Boston, MA; Calum A MaCare, Massachusetts General Hosp, Boston, MA

Shriram Nallamshetty, 2008 Finalist and Presenting Author
Abstract 5779: Quantification of Right Ventricular Dyssynchrony in Acute Pulmonary Embolism and Right Ventricular Pressure Overload Using Speckle-Tracking Strain Imaging
Authors: Ogawa Emiyo , Dohi Kaoru , Onishi Katsuya , Takamura Takeshi , Nakajima Hiroshi , Tanabe Masaki , Ota Satoshi , Tamada Hiroya , Yamada Norikazu , Miyahara Masatoshi , Nakamura Mashio , Ito Masaaki
Published: July 2021

Acute right ventricular (RV) pressure overload can alter RV systolic synchronicity associated with RV expansion and wall motion abnormalities in patinets with acute pulmonary thrombo-embolism (APTE). Twenty patients with massive or sub-massive APTE (mean age 57 ± 18 years, estimated peak systolic pulmonary pressure 51 ± 16mmHg) had echocardiography with speckle-tracking strain imaging on admission. RV dyssynchrony was defined as the time difference from earliest to latest peak strain among 6-sites (basal septum, mid septum, apical septum, apical free wall, mid free wall, basal free wall) form apical 4-chamber view using speckle-tracking longitudinal strain imaging. All intervals were corrected for heart rate (corrected interval = measured interval/(RR interval)
1/2
). Twenty normal subjects (Control: mean age 58 ± 10 years) were also assessed RV function and synchronicity for comparison. APTE had significantly low RV fractional area change (29 ± 10%* vs. 50 ± 7%), low global RV strain (−13 ± 4%* vs. −25 ± 3%), and large RV dyssynchorny (220 ± 103msec* vs. 78 ± 39msec) compared with Control (*p<0.05 vs. Control). After hemodynamic recovery from acute RV pressure overload by primary thrombolysis and/or anticoagulation therapy, both global RV strain and dyssynchrony were improved (−18 ± 4%† and 130 ± 53msec†, †p<0.05 vs. APTE on admission, respectively). Acute RV pressure overload induced reversible RV systolic dyssynchrony associated with RV systolic dysfunction in patients with APTE.
Abstract 5825: Association between Patterns of FDG Uptake and Arterial Wall Calcification on PET/CT and Atherogenic Risk Factors in Healthy Subjects
Authors: Narumi Hiroya , Yoshida Katsuya , Funabashi Nobusada , Hashimoto Naotake , Umehara Isao , Yoshida Shouji , Komuro Issei
Published: July 2021

Background: Augmented metabolic activity of macrophages leads to enough F-18 Fluorodeoxyglucose (FDG) uptake to allow visualization by positron emission tomography (PET). A large body of data, based on computed tomography (CT), has also accumulated concerning the relevance of vascular calcification to the atherosclerotic process. FDG PET/CT can localize both inflammatory changes and vascular calcification. The purpose of this study was to investigate risk factors contributing to these changes in the aorta in healthy subjects.

Materials and Methods: A total of 66 consecutive healthy subjects (44 men, 22 women; age range, 30–82 years, mean age, 55.8 years) participating in a health check protocol including FDG PET/CT were evaluated retrospectively. We placed regions of interest on the arterial wall to measure FDG uptake by PET images. To assess arterial calcification, the calcium score of the aorta was measured on CT images.

Results: FDG uptake was observed most commonly in proximal, followed by descending, thoracic, and abdominal segments. On the other hand, the most common site of vascular calcification was the descending thoracic aorta, followed by abdominal and, proximal segment. Whole aortic calcification (total calcium score of the whole aorta) was significantly correlated with age (r= 0.353, P= 0.004). On the other hand, FDG uptake (total SUV max of the whole aorta) was significantly correlated with systolic blood pressure (SBP) (r= 0.303, P= 0.013), triglyceride (TG) (r= 0.281, P= 0.022), fasting plasma glucose (FPG) (r= 0.317, P= 0.010), HbA1c (r= 0.433, P< 0.001), visceral abdominal fat area (r= 0.319, P= 0.005), and was negatively correlated with high density lipoprotein (HDL) (r= −0.317, P= 0.010), and adiponectin (r= −0.273, P= 0.029).

Conclusions: Aortic calcification was significantly correlated with age. On the other hand, FDG uptake was significantly correlated with the components of metabolic syndrome such as SBP, TG, FPG, HbA1c, visceral adipose fat area and negatively correlated with HDL and adiponectin, but not with age. Our results may suggest that the components of metabolic syndrome and aging affect the progression of atherosclerosis differently.
Abstract 5826: MicroSPECT-CT Imaging Demonstrates Impairment of Matrix Metalloproteinases Activation in Ischemic Peripheral Angiogenesis in Type-1 Diabetes Associated with Glycation
Authors: Dobrucki Lawrence W , Dione Donna , Kalinowski Leszek , Sinusas Albert J
Published: July 2021

We previously demonstrated an impairment of ischemic peripheral angiogenesis (IPA) in a murine model of hindlimb ischemia using a radiolabeled RGD peptide targeted at alpha-v integrin in type-1 diabetes mellitus (DM) in association with advanced glycation endproducts (AGE). Glycation of the extracellular matrix (ECM) in DM inhibits ECM degradation by matrix metalloproteinases (MMPs), and impairs IPA. We hypothesized that targeted microSPECT-CT imaging of MMP activation with
99m
Tc-labeled peptidomimetic (RP805; Lantheus, USA) would demonstrate impaired MMP activation during IPA in DM in association with AGE accumulation. Right femoral artery was surgically ligated on C57BL/6 male non-DM mice (n= 12) and DM mice (n= 17) 4–6 wks after STZ treatment (40 mg/kg i.p. for 5 days). DM mice demonstrated glycosuria and fasting glycemia (>200 mg/dL). RP805 (1.6± 0.5mCi) was injected and microSPECT-CT imaging performed 60 min later in mice 1 week (non-DM: n= 5; DM: n= 9) and 2 weeks (non-DM: n= 7; DM: n= 8) post-ligation. Blood was collected in additional non-DM (n= 4) and DM (n= 4) mice for measurement of HbA1c, an index of AGE accumulation. MicroSPECT-CT images were analyzed for RP805 activity within hindlimb distal to ligation, and ischemic-to-nonischemic (I/N) activity ratios calculated. DM mice demonstrated ~3-fold increase in glucose levels, and ~2.7-fold increase in AGE. Quantitative RP805 imaging demonstrated an impairment of MMP activation (~47%, P< 0.05) in DM at 1 week post-ligation, which normalized at 2 weeks. RP805 microSPECT-CT imaging provides a novel non-invasive approach for evaluation of impaired MMP activation during IPA in DM, and was associated with AGE accumulation.
Abstract 5839: Living Tissue Engineered Heart Valves Based On A Composite Self-Expandable Sandwich-Structured Scaffold And Autolgous Adult Stem Cells: First In Vivo Experiences Towards A Complete Minimally Invasive Approach
Authors: Schmidt Doerthe , Mariani Christine , Puolakka Arja , Rissanen Marja , Kelm Jens , Deichmann Thorsten , Zund Gregor , Hoerstrup Simon P
Published: July 2021

Background
: A clinically relevant heart valve tissue engineering concept requires minimally invasive techniques for both cell harvest and valve implantation. Here, we present first experiences with autologous tissue engineered heart valves fabricated from composite self-expandable biodegradable scaffolds and adult stem cells implanted by minimally invasive procedures in a sheep model.

Methods
: Sandwich-structured heart valve scaffolds (n= 12) were fabricated from non-woven PLDLA meshes coated with electrospun PLDLA nanofibers and integrated in self-expanding nitinol stents. Scaffolds were seeded with either autologous ovine bone marrow (BMC; n= 4) or jugular vein-derived cells (JVC; n= 8) and cultured in bioreactors. After 9d, heart valves were endothelialized with autologous peripheral blood-derived endothelial progenitor cells and jugular vein-derived endothelial cells, respectively. After additional 3d, heart valves (n= 6) were implanted trans-apically in pulmonary position. Controls were analysed (n= 6) as to tissue formation and composition (histology, biochemical assays). Mechanical properties were determined by tensile tests. In vivo performance was assessed by echocardiography up to 4 weeks.

Results
: Histology revealed cell attachment and ingrowth into the scaffold material resulting in layered tissues with endothelialized, eNOS positive surfaces. Amounts of GAG and cell number were similar in all heart valves, comparable to native tissues. Collagen production was higher in BMC based heart valves compared to JVC-derived tissues (Hydroyproline amount 34% vs. 20% of native tissues). Mechanical profiles demonstrated physiological tissue strength (max. tensile stress 0.41± 0.21 MPa) but less elasticity (E-Moduli 1.89± 0.79 MPa) independent of the cell source. Echocardiography displayed in vivo functionality (transvalvular mean pressure gradient 10.36± 3.17 mm/Hg) with more flexibility of BMC based heart valves leaflets.

Conclusions
: These results demonstrate that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve implantation is feasible. This clinically relevant approach is currently investigated in long-term animal studies.
Abstract 5845: Are Aortic Bioprostheses an Increasingly Good Option in Selected Patients Below the Age of 65?
Authors: Stoica Serban , Goldsmith Kimberley , Demiris Nikolaos , Punjabi Prakash , Faichney Alan , Berg Geoffrey , Sharples Linda , Large Stephen
Published: July 2021

To characterize contemporary long-term results of AVR as a function of type of prosthesis and subsequent competing risks. 5470 consecutive patients had AVR ± CABG at 3 centers between 1993–2006. Microsimulation survival models were developed combining perioperative mortality estimates from multivariable modeling of individual patient data, UK survival and random effects meta-analyses of valve-related events. Outputs were predicted and event-free life expectancy, and lifetime event rates according to patient characteristics of age, sex, creatinine, valve type, and concomitant CABG. In multivariable analysis long-term survival was significantly influenced by age (hazard ratio, HR, 1.52 per 10-year increment), male sex (HR 1.20), bioprosthesis (HR 1.25) and pre-operative creatinine, but not by concomitant CABG. Recipients of bioprostheses had longer average life expectancy for implant ages from 59 onwards in both men (see figure

) and women. The improvement in event-free survival for mechanical prostheses was greater at younger ages (3.4 years for implant age 50) and extended to implant age 65. Concomitant CABG increased operative mortality but conferred only slightly shorter life expectancy and event-free life expectancy than for those having AVR alone. Creatinine also had only a small absolute effect on outcomes. Structural bioprosthetic valve degeneration was the most common long-term complication. Predictions from simulation models were in excellent agreement with UK Heart Valve Registry survival data. Aortic bioprostheses could be implanted in many UK patients aged 59–65 without significant long-term hazards.
Abstract 5867: The Beneficial Effect of Raloxifene in Aortic Valve Calcification is Associated with Up-Regulation of Gas6-Axl Pathway
Authors: Shuvy Mony , Abedat Suzan , Daher Sameh , Valitsky Michael , Beeri Ronen , Lotan Chaim
Published: July 2021

Aortic valve calcification (AVC) is an inflammatory regulated process. Growth arrest-specific 6 (Gas6) is involved in atherosclerosis and inflammation; in addition the Gla domain of Gas6 directly inhibits mineralization. We sought to assess the role of Gas6 in AVC using our unique animal model of reversible AVC based on a uremia-inducing diet. We also evaluated the possible role of raloxifene (a selective estrogen modulator), which has demonstrated anti inflammatory effects on blood vessels, in the pathogenesis of AVC. Aortic valves were obtained from four groups of rats (n=10 each): calcified valves- from rats fed with the uremia-inducing diet for 7 weeks (group A), valves after calcification resolution following diet cessation (group B), valves from rats fed with the same diet who also received subcutaneous raloxifen (1 mg/kg/day) (group C), and control valves. Valves were examined using multislice computed tomography (MSCT), histology, RT-PCR and western blot. Histological evaluation of calcified valves (group A) revealed positive staining for calcium deposits and osteoblast’s markers (osteopontin, Runx-2). Gene expression analyses of these valves revealed 2.5 times decrease in Gas6 level compared to control valves (p<0.01). Western blot confirmed these results, and further showed a significant decrease of 33 % in Axl (Gas6 receptor) level along with down-regulation of the AKT survival pathway. Resolution of AVC (group B) was demonstrated using MSCT and histology; it was associated with down-regulation of osteoblast features, and up-regulation of both Gas6-Axl and AKT pathways. MSCT of raloxifene treated rats (group C) showed only minimal valve calcification compared with group A (Agatston score 23 ± 7 vs. 105± 15; p< 0.05). The beneficial effect of raloxifene was also confirmed by histology and was associated with up-regulation of Gas6 and Axl (30% and 40% increase respectively compared with group A; p<0.05) and of the AKT pathway. Down-regulation of the Gas6-Axl pathway is a critical step in inducing AVC. The reversibility of AVC was associated with up-regulation of the Gas6-Axl and AKT pathways. These pathways were significantly restored by raloxifene, which may be a promising treatment for AVC.
Abstract 5914: The Prognostic Value of the Initial Heart Rate Increase during Progressive Exercise Testing in Heart Failure
Authors: Guazzi Marco , Myers Jonathan , Peberdy Mary Ann , Bensimhon Daniel , Chase Paul , Arena Ross
Published: July 2021

The increase in heart rate during the first minute of a progressive exercise test (HR
1
) has been shown to be prognostically significant in a large cohort at risk for or diagnosed with cardiovascular disease. This issue, however, has not been specifically investigated in patients diagnosed with heart failure (HF). We assessed the hypothesis that HR
1
would possess prognostic value in a large HF cohort. Three-hundred and ninety two subjects diagnosed with HF (207 ischemic/185 non-ischemic, 279 male/113 female, age: 57.2 ±13.2 years, ejection fraction: 33.4 ±12.5) underwent cardiopulmonary exercise testing. Two-hundred and thirty three subjects were prescribed a beta-blocking agent at the time of testing. The difference between resting HR and HR after the first minute of exercise was defined as HR
1
. Ventilatory efficiency (VE/VCO
2
slope), the presence of oscillatory ventilation (EOV) and peak oxygen consumption (VO
2
) were also determined. Subjects were tracked for major cardiac events following exercise testing. There were 93 major cardiac events (82 deaths, 8 heart transplants, 3 left ventricular assist device implantations) during the 24.5 ±21.2 month tracking period (annual event rate: 10.5%). A HR
1
threshold of >13 beats per minute was a significant univariate predictor of adverse events in the overall group (Hazard ratio: 6.5, 95% CI: 3.6–11.4, p<0.001) as well as the subgroup receiving a beta-blocking agent (Hazard ratio: 4.0, 95% CI: 1.9 – 8.1, p<0.001). Moreover, in a multivariate analysis, HR
1
(>13, chi-square: 53.5, p<0.001), the VE/VCO
2
slope (<34, residual chi-square: 18.0, p<0.001) and EOV (yes/no, residual chi-square: 7.3, p<0.007) were all significant predictors of major cardiac events while peak VO
2
(>14 mlO
2
·kg
−1
·min
−1
, residual chi-square: 0.42, p=0.52) was not. Others have postulated that a greater HR
1
reflects a more rapid withdrawal of parasympathetic stimulus during exercise and a higher vagal tone at rest. These results demonstrate HR
1
during a progressive exercise test is prognostically valuable in patients with HF. Consideration of HR
1
for prognostic purposes may therefore be warranted in patients with HF during both submaximal and maximal exercise testing.
Abstract 5793: Novel Semi-Automatic Quantitative Assessment of The Aortic Valve and Aortic Root from Volumetric 3D Echocardiography: Comparison to Volumetric Cardiac Computed Tomography (CT)
Authors: Choi Jung Hyun , Georgescu Bogdan , Ionasec Razvan , Raman Subha , Hong Geu-Ru , Liu Shizhen , Houle Helene , Vannan Mani A
Published: July 2021

Accurate anatomical and functional assessment of AV and aortic root is crucial to understand the pathophysiology of abnormalities and management decision-making in patient with aortic valve diease and aortic aneurysm. The aim of this study was to evaluate the feasibility of novel semi-automatic assessment of AV and aortic root from volumetric 3-D Echo compared to CT. Volume-rendered 3-D TEE data were obtained using V5M transducer(Sequoia, Siemens). 6 points(commisures and valve tips) at ED and ES were identified on the 3-D TEE data. Volumetric CT images were acquired using 64-Slice CT(Avanto, Siemens). A dynamic 3-D model of the AV and root were obtained by standard mathematical modeling approach (non-uniform rational B-splines). This enabled automatic visualization and quantification of AV and root. We measured phasic change of the AVA(cm2), diameter of sinotubular junction(d-STJ, mm), sinus of Valsalva(d-SV, mm) and basal ring(d-BR, mm). 364 CT volumes from 41 patients and 23, 3-D TEE volumes from 15 patients with normal to mild AR were acquired. 3-D TEE data about AV and root showed strong correlation with CT data(table

). Figure

showed representative examples of 3-D Echo and CT modeling. This novel automated 3-D Echo approach provides accurate dimensions of the AV and the aortic root and may aid in valve and root repair procedures.

Comparison of AVA and aortic diameter between 3-D TEE and CT

Figure 1.

Top; Aortic root model, Bottom; Aortic valve model

Figure 2.

Automatic calculation from 3D TEE data (left; AVA, right; Aortic root diameter)

Figure 3.

Aortic root model segmentation (left two; 3D TEE, right two; CT)
Abstract 5796: Real-Time 3D Transesophageal Echo Enhances the Diagnostic Capabilities of Patent Foramen Ovale in Patient’s with Cerebral Vascular Accidents
Authors: Gill Edward A , Chen Michael A , Paramsothy Pathmaja , Cawley Peter J , Kim Francis , Buckler Joshua M
Published: July 2021

Real-time 3D transesophageal echo (RT3D TEE) is a novel technology whereby RT3D rendering of ultrasound images is performed resulting in unique views of cardiac structures. We have presented initial data reporting the incidence of optimal en face visualization of cardiac structures including the fossa ovalis (FO). We aimed to further characterize the FO. Therefore, our hypotheses were that the FO could be seen en face in full circumferential view (CV) in most patients and saline contrast RT3D TEE would enhance the accuracy of patent foramen ovale (PFO) diagnosis compared to contrast 2D TEE. Therefore, in an unselected series of 124 patients referred for TEE, we performed RT3D TEE with specific views of the FO using the Philips x7–2t RT3D TEE transducer. Images of the FO were acquired in the real-time 3D, 3D zoom, and full volume modes. Visualization of the FO was scored by 2 separate observers using the following scale:

full CV of the FO

>1/2 CV

<1/2 CV

no visualization.

The visualization score was 1.44. The average maximal and minimal diameters of the FO during the cardiac cycle were 1.46±0.90 and 1.12±0.12cm and an average maximum area of 169±20mm2. The sensitivity of saline contrast RT3DTEE for PFO diagnosis was 100% with specificity of 96% due to 3 cases where PFO was seen only by RT3D TEE.

RT3DTEE allows complete circumferential visualization of the FO in the majority of cases.

Our determination of the size of the FO compares favorably with pathologic series

Some cases of PFO can be expected to be detected only by RT3DTEE and therefore this technique should be performed when 2D TEE is negative for PFO but clinical suspicion remains high.
Abstract 6014: Impact of Metabolic Risk-factors Clustering on Post-Procedural Myocardial Injury and Clinical Outcomes in Patients Underwent Elective Coronary Intervention with Drug-Eluting Stents
Authors: Uetani Tadayuki , Amano Tetsuya , Kunimura Ayako , Kumagai Soichiro , Ando Hirohiko , Yokoi Kiminobu , Yoshida Tomohiro , Kato Bunichi , Kato Masataka , Marui Nobuyuki , Nanki Michio , Matsubara Tatsuaki , Ishii Hideki , Izawa Hideo , Murohara Toyoaki
Published: July 2021

The metabolic syndrome (MS) is associated with higher incidence of cardiovascular events. However association between clustering of MS components and clinical outcomes after elective PCI was unclear. We prospectively evaluated 438 consecutive patients who underwent elective PCI with drug-eluting stents. The metabolic factors were defined according to NCEP-ATPIII definition except for west circumference (≥90cm for men and ≥80cm for women; ethnic specific value of Japanese). Patients were divided into three stratified groups according to MS factors (0 –1, 2–3 and 4 –5). Post-procedural myocardial injury was evaluated by analysis of troponin-T (TnT) 18 hours after PCI. Cardiac event was defined as the composite end-point of death of any cause, MI and revascularization. Number of MS factors significantly correlated with post-procedural TnT after adjusting for age, gender and coronary risk factors in multivariate regression analysis (beta-coefficient 0.122, t-value 2.224, p=0.03). Increased accumulation of MS factors is associated with higher post-procedural TnT and worse clinical outcomes after PCI (Figure

). In Cox proportional hazard models, the number of MS factors was a significant predictor of cardiac events after adjusting for age, gender and coronary risk factors (OR 1.397, 95%CI 1.174 –1.663, p<0.01) Accumulation of MS factors associated with worse clinical outcome even in patients treated with drug-eluting stents.
Abstract 6017: Long-Term TAXUS Paclitaxel-Eluting Stent Outcomes in the Elderly Patients
Authors: Forman Daniel E , Wei Jeanne Y , Friedman Mark I , Dawkins Keith D , Baim Donald S
Published: July 2021

Although percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is widely used for treating elderly patients (pts), there are limited data regarding PCI outcomes in this high-risk patient population. To determine the impact of age on long-term safety and efficacy following implantation of the TAXUS Express
2
paclitaxel-eluting stent, we analyzed the TAXUS and ARRIVE studies. The 2,797 pts in TAXUS I, II SR, IV and V randomized trials and 7,492 pts in ARRIVE 1 and 2 “real world” registries were divided into three groups based on age: <60, 60 –70 and >70 years. Safety and efficacy outcomes were compared among these age groups.

Results:
While the 5-year death rate increased with age in the TAXUS trials, the rates of target lesion revascularization (TLR) and myocardial infarction (MI) were comparable, and the rate of stent thrombosis (ST) decreased with age. Moreover, the bare metal stent pts >70 (not shown) had similar rates of death and MI and a higher rate of TLR and ST than the corresponding TAXUS cohort. In “real world” higher risk ARRIVE pts, the 2-year death rate and cardiac death rate also increased with age while the rates of TLR, MI, and ST actually decreased with age. Elderly pts (age >70) treated with the TAXUS Express
2
stent had higher long-term death rates, but comparable TLR and MI rates and reduced ST rates compared to their younger counterparts. Collectively, these results indicate that despite the high-risk clinical and angiographic characteristics commonly observed in elderly pts, this patient population derives similar safety and efficacy from TAXUS stent treatment and such treatment should not be withheld on the basis of age alone when clinically and anatomically appropriate.
Abstract 6053: Long-Term Outcome of Percutaneous Transluminal Angioplasty in Chronic Hemodialysis Patients with Peripheral Arterial Disease
Authors: Aoyama Toru , Ishii Hideki , Tanaka Miho , Takahashi Hiroshi , Kawamura Yoshihiro , Kumada Yoshitaka , Toriyama Takanobu , Murohara Toyoaki
Published: July 2021

Chronic hemodialysis (HD) patients are at an increased risk for peripheral artery disease (PAD). Although percutaneous transluminal angioplasty (PTA) has become a widely used therapeutic intervention for PAD, its outcome in HD patients remains poorly understood. The aim of this study was to clarify the long-term outcome after PTA in HD patients with PAD. Consecutive 241 HD patients with 418 lesions and 152 non-HD patients with 201 lesions who underwent successful PTA as a first-choice therapeutic option for PAD were enrolled. They were followed for 8 years. Outcome measures included target lesion revascularization (TLR), major amputation, and all-cause mortality. Mean age was younger and prevalence of coronary artery disease and femoropopliteal lesion were significantly more frequent in HD patients (66±10years vs. 71±10years, p=0.0001, 52% vs. 41%, p=0.035 and 71% vs. 52%, p=0.0002, respectively). Prevalence of critical limb ischemia and TASC C+D lesion types were comparable in both groups (45% vs. 34% and 37% vs. 38%, respectively). During 46±38months, the 8-year freedom from TLR (64% vs. 76%, p=0.0057) limb salvage (82% vs. 97%, p=0.0001) and survival rates (52% vs. 87%, p<0.0001) were significantly lower in HD patients, respectively. On Cox multivariate analysis, HD status was strongly predictive of major amputation (HR 4.69, 95%CI 1.34 –16.39, p=0.015) and all-cause death (HR 5.13, 95%CI 2.14 –12.35, p=0.0002) but not of TLR (HR 1.54, 95%CI 0.85–2.78, p=0.15). In HD patients, ulceration/gangrene were independent predictors for all outcome (HR 2.50, 95%CI 1.22–5.09, p=0.0003 for TLR, HR 6.71, 95%CI 2.78 –16.13, p<0.0001 for amputation, and HR 1.95, 95%CI 1.11– 4.20, p=0.017 for all-cause death, respectively). Additional stenting was an independent predictor to reduce TLR in HD patients (HR 0.51, 95%CI 0.28 – 0.94, p=0.031). The long-term outcome after PTA was still poorer in HD patients compared with non-HD patients, but it might be acceptable in HD patients. Ulceration/gangrene was deeply associated with any outcome, thus, the detection at the earlier stage of PAD is important in this population who are at the highest risk for arteriosclerosis. Additional stenting was useful to reduce TLR.
Abstract 6074: Vitamin K Epoxide Reductase Genotype Alters Warfarin Dose Requirements in Pediatric Patients
Authors: Takao Cheryl M , Takahashi Masato , Pravica Vera , Barton Cheryl , Burckhart Gilbert
Published: July 2021

Warfarin is an oral anticoagulant used for prevention of thromboembolism in children. Its dosing is difficult due to the narrow therapeutic index & individual variability in effective dosage. Genetic polymorphism in 2 enzymes involved in warfarin metabolism, vitamin K epoxide reductase (VKORC) & cytochrome P450 isoenzyme 2C9 (CYP2C9), have been associated with lower dose requirements in adults. Testing for these polymorphisms is now recommended and being performed to guide dosing in adult patients(pts). Currently there is no information available on these polymorphisms & warfarin dosing in children. To examine the relationship between warfarin dosing & polymorphisms of CYP2C9 & VKORC1 in pediatric patients. Pts 0 –18 years old on warfarin for minimum 2 weeks were included. Data included ethnicity, age, weight, body surface area, gender, indication, dose, INR, target INR, medical illness or medications & adverse effects. Blood sample tested for CYP2C9 & VKORC1 genotypes & correlated with above variables. Dose at time of stable INR was compared to genetic alleles. Multivariate linear regression analysis was performed to identify factors associated with warfarin dosing. 29 pts were studied(62% males). There were 18 Hispanics, 7 Caucasian, 2 African Americans & 2 Mixed ethnicities. Indication for warfarin included Congenital heart disease(CHD) 45% & non CHD 55%. Mean age 5yrs 2mo(6mo-18yrs) & wt 22kg(6.9 – 84). For VKORC1, there were 13 AA(44%), 9 GA(31%), & 7 GG (24%) alleles. For CYP29, 4/23 were *2(17%) & 0 *3 alleles. There was no relationship between ethnicity & VKORC1 alleles. Pts with VKORC1 AA + AG allele required a significantly lower dose/kg(0.10mg/kg) compared to GG allele(0.19mg/kg)(p <0.001) even after adjusting for target INR. In this study, pts with VKORC1 AA + AG alleles require a 47% lower dose/kg compared to pts with GG alleles. This preliminary data suggest that VKORC1 status is an important factor in dosing requirements in pediatric pts. A study using a larger pediatric population is necessary to construct a dosing nomogram based on presence of genetic polymorphism.
Abstract 6094: Alterations in Blood Flow Reserve Secondary to Decompensated Diabetes Mellitus - Preliminary Results Obtained by Myocardial Contrast Echocardiography
Authors: Moraes Natanael V , Oliveira Carolina P , Tsutsui Jeane , Lerário Antônio C , Mathias Wilson
Published: July 2021

Diabetes mellitus (DM) is one of the most important health problems in developed countries. Poor blood glucose control is known to be associated with clinical symptoms and increased risk for cardiovascular complications. Myocardial contrast echocardiography (MCE) has been demonstrated to be valuable for assessing myocardial blood flow reserve (MBFR) in patients with obstructive coronary artery disease and in those with microcirculatory alterations. We hypothesized that DM would result in impairment of MBFR, as measured by MCE, even in patients without obstructive coronary artery disease.

Methods:
We studied 30 patients with DM (mean age 55 years, 13 men) and 10 control subjects (mean age 53 years, 5 men) with normal global and regional systolic function. MBFR was determined by quantitative contrast echocardiography during dipyridamol (0.84 mg/Kg) stress using intravenous commercialy available microbubbles contrast (Definity, Bristol-Myers Squibb). Diabetic patients were studied in a decompensated state, with mean glycosylated hemoglobin of 9.0% (ranging from 8.5% to 13.0%). Quantification of peak myocardial intensity (A), microbubble velocity (Beta) and MBFR (peak dipyridamol/baseline AxBeta) were measured off line using Q-Lab software (Philips Medical Imaging). All patients underwent computed tomography coronary angiography (64 slices) which demonstrated no obstructive coronary artery disease.

Results:
Values of A (dB), Beta (1/s), and AxBeta (dB/s) both at baseline and during dipyridamol stress are described in Table

. MBFR was significantly lower in patients with decompensated DM than in control subjects (1.58 versus 2.87; p<0.001).

Conclusion:
These preliminary results suggest that diabetic patients with poor blood glucose control and no obstructive coronary artery disease have impaired MBFR. MCE may be a useful noninvasive technique for evaluating changes in MBFR in this group of patients.
Abstract 6140: Value of Baseline Inferolateral Myocardial Contractile Function Assessed by Tissue Doppler Imaging to Predict Reduction of Functional Mitral Regurgitation with Low-Dose Dobutamine in Patients with Dilated Cardiomyopathy
Authors: Tatsumi Kazuhiro , Kawai Hiroya , Omar Salem , Fukuda Yuko , Okada Mariko , Norisada Kazuko , Furuki Maky , Onishi Tetsuari , Hirata Ken-ichi
Published: July 2021

Dobutamine (DOB) has the ability to reduce functional mitral regurgitation (FMR) in dilated cardiomyopathy (DCM) and DOB stress echocardiography might be useful to make an optimal selection of surgical treatments such as isolated myocardial revascularization or in combination with valve repair. The purpose of this study was to investigate the relationship between baseline echocardiographic parameters including regional myocardial function and reduction of FMR with DOB. We studied 38 DCM patients with reduced left ventricular ejection fraction (LVEF) (33±11%) and FMR. Standard and tissue Doppler echocardiography were performed at rest and with low-dose DOB (10 μg/kg/min), and we obtained LV volume, LVEF, tenting area of mitral valve (enclosed between the annular plane and leaflets), mitral annular area (MAA), FMR fraction and, longitudinal peak systolic strain rate (Ssr; absolute value) in the 6 segments at mid-LV level using apical images. According to the reduction of FMR with DOB, patients were divided into a large reduction group (%FMR reduction ≥ 30%) and a small reduction group (<30%), 17 and 21 patients, respectively. DOB increased LVEF and Ssr in all segments, and decreased LV volumes, tenting area, MAA, and FMR fraction (%FMR reduction = 28±19%) in all subjects. Regarding the baseline parameters, tenting area and FMR fraction in large reduction group were significantly smaller, and anterolateral Ssr and inferolateral Ssr in large reduction group were significantly larger than those in small reduction group. However, there was no difference in baseline LV volume, LVEF, MAA, nor Ssr in any other segments. In ROC curve analysis, the area under the curve for tenting area, FMR fraction, anterolateral Ssr, and inferolateral Ssr were 0.69, 0.70, 0.72, and 0.81, and baseline inferolateral Ssr > 1.00/s was the best predictor of DOB-induced %FMR reduction ≥30% with a sensitivity of 88% and a specificity of 75%. Baseline inferolateral myocardial contractile function was associated with DOB-induced reduction of FMR, suggesting that assessment of inferolateral myocardial preserved function is important for an optimal selection of surgical treatment in patients with FMR.