bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 603: Cardioprotection by p300 During Myocardial Ischemia-Reperfusion and Infarction in vivo
Authors: Wei Jianqin , Llanos Alexander , Rodrigues Claudia , Steen Dylan , Webster Keith , Bishopric Nanette
Published: April 2024

Introduction: The acetyltransferase p300 is a critical regulator of cardiac growth and MEF-2- and GATA-4-dependent gene expression. We have previously shown that p300 is inducible by adrenergic stimulation and pressure overload in both in vitro and in vivo models. The p300 promoter contains 2 consensus HIF-1 binding sites.

Hypothesis: p300 induction is an early survival signal during myocardial stress.

Methods: A previously described mouse line expressing a cardiac-restricted p300 transgene (p300TG) with ~2.5x of control p300 levels was subjected to permanent left coronary occlusion (MI) or 40 min occlusion/24h reperfusion (I/R). Control mice from each genotype received thoracotomy without coronary ligation (sham). Cardiac function was assessed at 1h, 3d, 8d, and 6 wk by 30 MHz ultrasonography, and myocardial infarction size was assessed by histologic and biologic (TTC staining) assays at 6 wk. Infarct size was determined by TTC staining of coronal sections from apex to base and evaluated by planimetry.

Results: In wt mice, p300 protein levels increased markedly by Western analysis in ischemic myocardium compared with remote non-ischemic tissue (2.0 fold at 3 d, 2.5 fold at 8d; n=34, p<0.001 for both) and with sham-operated hearts (n=9, p <0.001). Infarct size was reduced by 32% in p300TG mice compared to WT littermates (26.5%Ã‘Â =0.9 vs 38.6 Ã‘Â ±1.3 infarcted myocardium, p<0.001, N=28). TUNEL analysis revealed extensive apoptosis in WT myocardium that was markedly reduced in p300TG hearts (N= 4). Similarly, p300TG mice experienced less cardiac functional loss from MI than wt littermates (fractional shortening=63.9 Ã‘Â ±2.6 vs. 44.3 Ã‘Â ±1.4 %, p <.001, n= 10). In I/R mice, injury area was 29.2% less in p300TG vs. WT littermates (23.6 Ã‘Â ±1.7 vs. 33.8 Ã‘Â ±1.1% of total LV, p<0.001, n=10). STAT3, HIF-1 and ERK1/2 protein levels were all induced by both ischemic and I/R injury, and this induction was significantly greater in p300TG myocardium (STAT-3, HIF-1, ERK1/2{1.5, 1.4, 2.1fold,p<0.001 respectively).

Conclusions: p300 is induced by ischemic stress, and exerts protection against ischemic injury in vivo. This effect is likely through induction of specific pro-hypertrophic, pro-angiogenic and anti-apoptotic signals.
Abstract 604: Atorvastatin Activates Cycloxygenase-2 in the Heart via S-Nitrosylation by Inducible Nitric Oxide Synthase
Authors: Birnbaum Yochai , Ye Yumei , Lin Yu , Freeberg Sheldon Y , Martinez Juan D , Uretsky Barry F , Perez-Polo Jose R
Published: April 2024

Background:
Atorvastatin (AT) increases myocardial expression of phophorylated Ser-1777 endothelial nitric oxide synthase (P-eNOS), inducible NOS (iNOS) and Cycloxygenase-2 (COX2). Although AT increases the expression of COX2 in eNOS
−/ −
mice, there is no increase in COX2 activity as occurs in wild-type (WT) mice. In the rat, COX2 activation occurs by iNOS mediated S-nitrosylation.

Aim:
To investigate whether the difference in COX2 activity between the AT-treated WT and eNOS
−/ −
is related to S-nitrosylation.

Methods:
WT, eNOS
−/ −
, and iNOS
−/ −
mice received AT 10 mg/kg/d (AT+) or water alone (AT-) for 3 days. Hearts were harvested and subjected to ELISA and immunoblotting. Snitrosylation of COX2 was assessed by the “Biotin Switch” assay. To verify that the immunoprecipitates contained COX2, membranes were stripped and blots with anti-COX2 antibodies.

Results:
COX2 expression in the AT- groups was very low. AT increased COX2 expression in WT (4,287±104%) and eNOS
−/ −
(4,354±101%), but not iNOS
−/ −
mice (101±3%). However, myocardial 6- keto-PGF
1α
levels (81.4±0.2 vs. 15.7±0.1 pg/ml; p<0.001) were increased by AT only in WT mice, but not in eNOS
−/ −
(16.5±0.1 vs. 15.6±0.1 pg/ml) or iNOS
−/ −
(15.9±0.2 vs. 15.3±0.1 pg/ml) mice. The “Biotin Switch” assay shows that COX2 was S-nitrosylated only in WT mice. Although eNOS is activated by AT in the iNOS
−/ −
mice, there is no S-nitrosylation and activation of COX2.

Conclusions
: COX2 is activated by S-nitrosylation only in WT mice. Although iNOS is intact in eNOS
−/ −
mice, it is not activated and therefore, does not S-nitrosylate the AT-induced upregulated COX2.
2006 William W. L. Glenn Lecture–Rebuilding the Heart: New Horizons for Cardiac Surgeons
Authors: Weisel Richard
Published: April 2024

Cardiac surgery is changing today, as it was during the time of Dr William Glenn. In those days, cardiac surgeons were trained to do thoracic and vascular surgery.Today, cardiac surgeons are retraining to do intravascular and minimally invasive cardiac and vascular procedures. However, today’s cardiac surgeons should also retrain to employ gene-enhanced cell therapy to modify both the heart and the vasculature to improve the outcomes of their interventions. Cell transplantation has come of age and is undergoing extensive clinical trials. The implantation of precursor cells induces angiogenesis, improves regional and global function, and enhances the recruitment of reparative cells to the heart. In addition to correcting anatomic cardiac lesions, surgeons may be able to restore function to the heart by a combination of cardiac regeneration and rejuvenation of the response to injury. Tissue engineering may restore heart function without synthetic materials, provided the surgeon employs the right combination of cells and biodegradable scaffolds. These grafts may be ideal for the surgical repair of congenital cardiac defects, and clinical trials are underway. The implanted grafts grow and remodel as the child becomes an adult. Cardiac surgeons are retraining to acquire new skills to correct cardiovascular defects. In addition, surgeons should acquire the knowledge required to regenerate and rebuild the heart and vasculature.
2006 Ancel Keys Memorial Lecture—Diet and Heart Disease: The Seven Countries and Beyond
Authors: Willett Walter
Published: April 2024

Studies of different populations worldwide and of migrants from low- to high-risk regions indicate that coronary heart disease (CHD) is potentially almost entirely preventable. Mechanistic studies during the past decade have indicated that many biological pathways can lead to CHD, and the opportunities for prevention have thus been expanded. Smoking accounts for about one third of myocardial infarctions in Western countries, and overweight and obesity contribute similarly. Reducing intake of total fat as a percent of calories is not an effective means for prevention, but multiple lines of evidence indicate that the type of dietary fat has a major impact on risk of CHD. Intake of
trans
fat from partially hydrogenated vegetable oils most strongly increases the risk, saturated fat is weakly associated with greater risk, monounsaturated fats moderately decrease risk, and polyunsaturated fats strongly decrease risk. Both N-6 and N-3 polyunsaturated fatty acids contribute to lower risk. The form of dietary carbohydrate also appears to influence risk of CHD importantly: Highly refined starches are related to increased risk, but consumption of whole-grain, high-fiber cereal products consistently have been associated with lower risks. Higher consumption of fruits and vegetables contributes to lower risk, probably by multiple mechanisms. Many issues remain to be settled, including the optimal mix of mono- and polyunsaturated fatty acids, the optimal amounts of N-3 and N-6 fatty acids, the amount and source of protein, and the effects of antioxidants, other phytochemicals and minerals. From our long-term studies, we have calculated that modest dietary changes, together with avoidance of smoking, regular physical activity, and maintenance of a healthy body weight, can reduce rates of CHD by more than 80%. Failure to take advantage of dietary and lifestyle means of preventing these diseases represents a tremendous lost opportunity for improved health and well-being.
2009 Katharine A. Lembright Award and Lecture—The Evolving Picture of Women With CHD
Authors: McSweeney Jean
Published: April 2024

Although coronary heart disease is the No. 1 killer of women, an evidence-based picture of prodromal and acute myocardial infarction symptoms in ethnically diverse women is underdeveloped. This contributes to disparate outcomes, especially in minority women. Lack of recognition of early presenting symptoms associated with coronary heart disease and acute myocardial infarction on the part of women and their healthcare providers contributes to these poor outcomes because delayed recognition of symptoms limits options for efficacious treatment. This presentation will focus on the development of the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS) that has been used with more than 2800 racially diverse women. This instrument, based on qualitative findings, includes 33 symptoms of prodromal coronary heart disease and 37 symptoms of acute myocardial infarction and questions related to frequency and severity of the symptoms. Women’s symptom experiences and difficulty receiving a diagnosis of coronary heart disease will be discussed. Comparison of both prodromal and acute myocardial infarction symptoms in black, Hispanic, and white women will be presented. The presentation will conclude with a cluster analysis, based on prodromal and acute myocardial infarction symptom scores calculated from symptom reports from more than 1500 women, that examines the association between racially diverse women’s characteristics and symptom clusters. These data make a significant contribution to the evolving picture of women’s prodromal and acute myocardial infarction symptoms.
2009 Charles T. Dotter Memorial Lecture—Cardiovascular Molecular Imaging of Gene and Cell Therapies
Authors: Gambhir Sanjiv
Published: April 2024

Regenerative medicine with the use of stem cells has appeared as a potential therapeutic alternative for many disease states. Numerous questions remain with regard to the viability and biology of transplanted stem cells in the living subject. Recent advances in molecular biology and imaging have allowed the successful noninvasive monitoring of transplanted stem cells in the living subject. I will review the different imaging strategies that can be adopted to study the viability and biology of transplanted stem cells. These include the use of multimodality reporter gene imaging (eg, fusion reporters), including clinical translation of such strategies. Use of these strategies will be critical as the different regenerative therapies are being tested for clinical use.
2009 Laennec Clinician/Educator Lecture—Diastolic Function: Past, Present, and Future
Authors: Grossman William
Published: April 2024

One hundred years ago, research by Otto Frank, Carl Wiggers, and Yandell Henderson identified cardiac tonus and variable diastolic relaxation as important aspects of cardiac function. Belief in the existence of cardiac tonus and variable relaxation then went into eclipse from 1930 to 1970, during which time the application of A.V. Hill’s equations of muscle mechanics (derived from experiments on skeletal muscle) to cardiac physiology assumed that cardiac muscle was basically a “twitch” muscle and was completely passive between contractions. For the past 40 years, there has been a resurgence of interest in and experimental support for the concept of variable diastolic relaxation. At the same time, improved clinical measurement techniques have allowed simultaneous measurement of left ventricular pressure and volume, establishing firmly the existence and importance of rapidly occurring shifts in the diastolic left ventricular pressure–volume relation. Today, it is clear that up to 50% of patients presenting with acute heart failure manifest as pulmonary edema are exhibiting increased resistance to diastolic left ventricular filling as their primary problem, rather than impaired contractile function and reduced left ventricular systolic emptying. Many causes of increased resistance to diastolic left ventricular filling occur clinically, including myocardial hypertrophy, ischemia, diabetes, and increased coronary venous pressure, and may be modifiable with appropriate therapy. Examples will be presented.
2009 Ancel Keys Memorial Lecture—Drug Therapies for the Prevention of CVD Events: Trials and Errors
Authors: Psaty Bruce
Published: April 2024

Drug therapies for risk factors such as high levels of blood pressure, lipids, and glucose represent, in Geoffrey Rose’s terms, a high-risk approach to a population-based problem. The purpose of these therapies is to prevent cardiovascular events, yet the US Food and Drug Administration generally approves new medications for these conditions on the basis of premarket studies that use surrogate end points. It is not feasible to address all questions about the efficacy and safety of drugs during the premarket phase, so postmarket evaluation is crucial. Historically, however, drug approval separates the period of intense evaluation from the period of intense marketing. Between 1980 and 2005, prescription drug expenditures increased from $12 to $200 billion. The expansion of the pharmaceutical industry in the second half of the twentieth century has provided a number of safe and effective medications for many conditions. The health of Americans has clearly benefited in quality and duration of survival. With several notable exceptions, however, the NIH has largely turned the evaluation of drug treatments over to industry, and the results of key NIH trials must often contend with industry marketing to influence practice. The duty to provide a return on investment to shareholders tends to create for industry an asymmetric interest in safety and efficacy. As a result, the design, conduct, and reporting of some industry-funded studies remain a public health problem. The current approach to the evaluation of the safety and efficacy of medications occasionally provides an unreliable patchwork of evidence about health outcomes and incomplete information about the risk–benefit profiles of new drug therapies. For medications that are well evaluated, single–risk-factor approaches to treatment decisions may limit their benefit to the population.
2009 Distinguished Scientist Lecture—Highlights of Hormones and Heart Disease: Forty Years in Forty Minutes: The Rancho Bernardo Study
Authors: Barrett-Connor Elizabeth
Published: April 2024

The Rancho Bernardo Study began in 1972 as one of 12 Lipid Research Clinic Prevalence Studies sponsored by the National Heart Institute. Each site was allowed to select its own epidemiologist, who could then select a cohort of 5000 to 6000 individuals. I was given the great opportunity to choose the San Diego LRC cohort. I chose Rancho Bernardo for several reasons, of which perhaps the most important was that it was a new town with many “old people” over the age 50 years. Beyond any expectation, Rancho Bernardo is now in its fortieth year of continuous funding from the NIH, plus intermittent and critically important additional grants to junior faculty and visiting scholars from the American Heart Association.

In the beginning, I knew little about cohort studies or heart disease epidemiology. I did know that heart disease had 6 accepted risk factors: age, male sex, cholesterol, smoking, blood pressure, and diabetes. Every clinician knew male sex was a strong heart disease risk factor, but clinical studies of sex differences were few. The LRC had not planned to study diabetes, which “belonged to another institute,” but I managed to add fasting glucose and 2 pages about noncholesterol risk factors, including diabetes, to the baseline 2-page questionnaire. During the next 40 years, that small beginning allowed me and many new colleagues the opportunity to try to understand the interface between sex differences in coronary heart disease and diabetes.

This talk summarizes cardiovascular insights based on epidemiological data from the Rancho Bernardo Study. I am grateful to the many scholars at diverse levels of training who began their careers using Rancho Bernardo data and the many who continue to do so.
Cyclophilin A Augments ROS Production and Angiotensin II–Induced Cardiac Hypertrophy in Mice
Authors: Satoh Kimio
Published: April 2024

Abstract #3090

Kimio Satoh, Dept of Cardiovascular Med, Tohoku Univ Graduate Sch of Med, Sendai, Japan; Patrizia Nigro, Fabrice Jaffré, Michael R. O’Dell, New New Soe, Zhaoqiang Cui, Amy Mohan, Burns C. Blaxall, Bradford C. Berk, Aab Cardiovascular Res Inst and Dept of Med, Univ of Rochester, Rochester, NY

Kimio Satoh, 2009 Finalist and Presenting Author
Dichloroacetate Reverses the Impaired Cardiac Function and the Electrical Remodeling in Right Ventricular Hypertrophy by Inhibiting Pyruvate Dehydrogenase Kinase
Authors: Piao Lin
Published: April 2024

Abstract #2362

Lin Piao, Yong-Hu Fang, Univ of Chicago, Chicago, IL; Virgilio J Cadete, Univ of Alberta, Edmonton, AB, Canada; Christian Wietholt, Dalia Urboniene, Peter T Toth, Glenn Marsboom, Hannah Zhang, Idith Haber, Jalees Rehman, Univ of Chicago, Chicago, IL; Gary D Lopaschuk, Univ of Alberta, Edmonton, AB, Canada; Stephen L Archer, Univ of Chicago, Chicago, IL

Lin Piao, 2009 Finalist and Presenting Author
The Mitochondrial Permeability Transition Pore Opens During Ventricular Fibrillation in a Rat Model of Closed Chest Resuscitation
Authors: Ayoub Iyad M.
Published: April 2024

Abstract #2364

Iyad M. Ayoub, Jeejabai Radhakrishnan, Madhav P. Upadhyaya, Raul J. Gazmuri, Rosalind Franklin Univ of Med and Science, North Chicago, IL

Iyad M. Ayoub, 2009 Finalist and Presenting Author
Impact of Primary Coronary Angioplasty Delay on Myocardial Salvage, Infarct Size and Microvascular Damage in Patients With ST-Elevation Myocardial Infarction: Insight From Cardiovascular Magnetic Resonance
Authors: Bucciarelli-Ducci Chiara
Published: April 2024

Abstract #249

Chiara Bucciarelli-Ducci, CMR Unit, Royal Brompton Hosp and Cardiovascular and Respiratory Sciences, Univ “La Sapienza” Rome, London, United Kingdom; Marco Francone, Iacopo Carbone, Radiological Sciences, Univ Rome La Sapienza, Rome, Italy; Emanuele Canali, Raffaele Scardala, Cardiovascular and Respiratory Sciences, Univ Rome La Sapienza, Rome, Italy; Francesca Calabrese, Radiological Sciences, Univ Rome La Sapienza, Rome, Italy; Gennaro Sardella, Massimo Mancone, Cardiovascular Sciences, Univ Rome La Sapienza, Rome, Italy; Carlo Catalano, Radiological Sciences, Univ Rome La Sapienza, Rome, Italy; Francesco Fedele, Cardiovascular and Respiratory Sciences, Univ Rome La Sapienza, Rome, Italy; Roberto Passariello, Radiological Sciences, Univ Rome La SapienzaSciences, Univ, Rome, Italy; Jan Bogaert, Dept of Medical Imaging, Gasthuisberg Univ Hosp, Leuven, Belgium; Luciano Agati, Cardiovascular and Respiratory Sciences, Univ Rome La Sapienza, Rome, Italy

Chiara Bucciarelli-Ducci, 2009 Finalist and Presenting Author
Resveratrol Improves Myocardial Perfusion in a Swine Model of Hypercholesterolemia and Chronic Myocardial Ischemia
Authors: Robich Michael P.
Published: April 2024

Abstract #4220

Michael P. Robich, Beth Israel Deaconess Med Ctr, Boston, MA; Frank W. Sellke, Alpert Medical Sch of Brown Univ, Providence, RI

Michael P. Robich, 2009 Finalist and Presenting Author
Chromosome 9p21 Variant Predicts Mortality After CABG Surgery
Authors: Muehlschlegel Jochen D
Published: April 2024

Abstract #4222

Jochen D Muehlschlegel, Kuang-Yu Liu, Tjörvi E Perry, Amanda A Fox, Harvard Medical Sch, Boston, MA; Charles D Collard, Baylor Coll of Med, Houston, TX; Stanton K Shernan, Simon C Body, Harvard Medical Sch, Boston, MA; CABG Genomics Investigators

Jochen D Muehlschlegel, 2009 Finalist and Presenting Author
Biomarkers of Myocardial Stress and Systemic Inflammation Are Lower in Patients Who Engage in Heart Failure Self-Care Management
Authors: Lee Christopher S
Published: April 2024

Abstract #904

Christopher S Lee, Univ of Pennsylvania, Philadelphia, PA; Debra K Moser, Terry A Lennie, Univ of Kentucky, Lexington, KY; Nancy C Tkacs, Kenneth B Margulies, Barbara Riegel, Univ of Pennsylvania, Philadelphia, PA

Christopher S Lee, 2009 Finalist and Presenting Author
The Impact of Attained Educational Level on Incident Cardiovascular Events Differs Between High-Income Countries and Low-and-Middle-Income Countries
Authors: Goyal Abhinav
Published: April 2024

Abstract #899

Abhinav Goyal, Emory Rollins Sch of Public Health and Emory Sch of Med, Atlanta, GA; Deepak L Bhatt, VA Boston Healthcare System and Brigham and Women’s Hosp, Boston, MA; Ph. Gabriel Steg, INSERM U-698, Univ Paris 7, AP-HP, Paris, France; Bernard J Gersh, Mayo Clinic, Rochester, MN; Mark J Alberts, Northwestern Univ Feinberg Sch of Med, Chicago, IL; E Magnus Ohman, Duke Clinical Res Inst, Durham, NC; Ramón Corbalán, Pontificia Univ Católica, Santiago, Chile; Kim A Eagle, Univ of Michigan Medical Ctr, Ann Arbor, MI; Efrain Gaxiola, Ctr Especializado en Terapia Endovascular, Jardínes Hosp de Especialidades, Guadalajara, Mexico; Runlin Gao, Fuwai Hosp, Beijing, China; Shinya Goto, Tokai Univ Sch of Med, Kanagawa, Japan; Ralph B D’Agostino, Boston Univ, Boston, MA; Robert M Califf, Duke Clinical Res Inst, Durham, NC; Sidney C Smith Jr, UNC Ctr for Cardiovascular Science and Med, Univ of North Carolina–Chapel Hill, Chapel Hill, NC; Peter W Wilson, Emory Sch of Med, Atlanta, GA

Abhinav Goyal, 2009 Finalist and Presenting Author
Use of Contraindicated Anti-Thrombotics in Dialysis Patients Undergoing Percutaneous Coronary Interventions: Insights From the NCDR Cath-PCI Registry
Authors: Tsai Thomas T
Published: April 2024

Abstract #895

Thomas T Tsai, Thomas M Maddox, Denver VA Medical Ctr/Univ of Colorado Denver, Denver, CO; Matthew T Roe, David Dai, Karen P Alexander, Duke Univ Medical Ctr, Durham, NC; P, Michael Ho, Denver VA Medical Ctr/Univ of Colorado Denver, Denver, CO; John C. Messenger, Univ of Colorado Denver, Denver, CO; Brahmajee K Nallamothu, Univ of Michigan Hosp, Ann Arbor, MI; Eric D Peterson, Duke Univ Medical Ctr, Durham, NC; John S. Rumsfeld, Denver VA Medical Ctr/Univ of Colorado Denver, Denver, CO

Thomas T Tsai, 2009 Finalist and Presenting Author
QT Dynamics Early After Exercise as a Predictor of Mortality
Authors: Johnson Nils P
Published: April 2024

Abstract #2373

Nils P Johnson, Thomas A Holly, Jeffrey J Goldberger, Northwestern Univ, Chicago, IL

Nils P Johnson, 2009 Finalist and Presenting Author
Abstract 4756: Evaluation of the Peri-strut Low Intensity Area Following Sirolimus- and Paclitaxel-Eluting Stents Implantation: Insights From an Optical Coherence Tomography Study in Humans
Authors: Otake Hiromasa , Ikeno Fumiaki , Shinke Toshiro , Teramoto Tomohiko , Sawada Takahiro , Miyoshi Naoki , Ako Junya , Honda Yasuhiro , Yock Paul G , Fitzgerald Peter J , Hirata Ken-ichi
Published: April 2024

Background:
In previous pathological studies, paclitaxel-eluting stents (PES) showed greater fibrin deposition around stent struts, while sirolimus-eluting stent (SES) showed predominance of inflammatory cells with less fibrin deposition than PES. However, there are limited in-vivo data clarifying those qualitative differences in the process of vascular healing after 1st-generation drug-eluting stents (DES) implantation. A recent animal study has shown that peri-strut low intensity area (PLIA) seen in optical coherence tomography (OCT) imaging might represent the process of hyaluronic acid and proteoglycan replacing fibrin.

Methods:
A total of 60 patients who underwent 6-month follow-up OCT after SES (n=34) and PES (n=26) implantation were enrolled. PLIA was defined as a region around stent struts with a homogenous lower intensity appearance than surrounding tissue on OCT images without significant signal attenuation (Figure

). To evaluate longitudinal extent of PLIA, %PLIA was calculated for each lesion as follows: stent length with PLIA/entire stent length × 100.

Results:
PLIA was identified by OCT in 19 lesions in SES and 22 lesions in PES. PES showed a higher incidence of PLIA (85% vs. 56%; p=0.03, respectively) with a greater %PLIA than SES (43.0±25.6% vs. 27.8±23.1%; p=0.05, respectively). There was a positive correlation between average neointimal thickness and %PLIA in SES, while only a weak correlation was observed in PES (Figure

).

Conclusions:
PES showed a higher incidence of PLIA with a greater longitudinal extent of PLIA than SES. The presence and extent of PLIA appeared to be associated with neointimal proliferation after 1st-generation DES implantation.
Abstract 4758: Multiple Inter-strut Hollow, a Unique Finding of Optical Coherence Tomography After Sirolimus Eluting Stent Implantation: The Prevalence and Clinical Characteristics
Authors: Hosogi Shingo , Shimizu Hayato , Tanaka Hiroyuki , Fuku Yasushi , Yamamoto Hiroyuki , Goto Tsuyoshi , Kadota Kazushige , Mitsudo Kazuaki
Published: April 2024

Background: It has been reported that Optical Coherence Tomography (OCT) revealed cavities formation between and outside of the stent strut, Multiple Inter-strut Hollow (MIH) after Sirorimus eluting stent (SES) implantation. However, the incidence and the clinical characteristics of MIH are unknown.

Methods: We analyzed the findings of OCT, in 60 cases with in-stent restenosis (ISR) after SES (n=52) and bare metal stent (BMS) (n=8) implantation. MIH was defined as multiple cavity formation which maximum depth was over 0.3mm between and outside of the stent strut in OCT. Furthermore, we examined the relation between the maximum depth of MIH and the clinical characteristics of the lesions with MIH, such as, original lesion type (AMI/UAP, stable AP, CTO or ISR) and period to restenosis (more than 1 year or less than 1 year).

Results: The incidence of MIH was significantly higher in SES group compared with BMS group (42.3% v.s. 0.0%; p<0.05) and also showed the tendency to increase in the group which original lesion type was CTO. Regarding the maximum depth of MIH, there was no significant difference between more and less than 1 year groups (0.62+−0.24mm v.s. 0.53+−0.12mm; p=0.34), however, the depth of MIH tended to increase in CTO group.

Conclusions: MIH is peculiar phenomenon after SES implantation on OCT findings. Further careful follow-up is needed to reveal the clinical implication of MIH.

Incidence of MIH
Abstract 4849: The Dual Rho-GEF Kalirin Promotes Vascular Smooth Muscle Cell Migration and Proliferation
Authors: Zhang Lisheng , Sharma Krishn , Wu Jiao-Hui , Smith Liisa S , Brian Leigh , Exum Sabrina T , Eipper Betty A , Mains Richard E , Freedman Neil J
Published: April 2024

Vascular smooth muscle cell (SMC) migration and proliferation are regulated by signaling through the Rho family GTPases, RhoA and Rac, which are activated by GTP exchange factors (GEFs). One such Rho-GEF was recently associated with human atherosclerosis by genetic epidemiology: kalirin, a 340 kDa protein containing both Rac- and RhoA-GEF domains. We tested the hypothesis that SMC kalirin promotes Rac or RhoA signaling, and thereby atherogenic SMC activity. By immunoblotting (IB) and quantitative immunofluorescence microscopy, we found that kalirin is expressed abundantly in SMCs, and is up-regulated 1.6±0.2-fold (p<0.03) in the media of atherosclerotic, as compared with normal arteries. To test kalirin’s role in regulating SMC signaling, we compared 3 independent lines of SMCs from congenic WT and kalirin
−/+
mice (with 45±5% of WT kalirin levels), as well as SMCs transfected with non-targeting or kalirin-targeting siRNA (43±9% protein knockdown). We assessed Rac and RhoA activation by G-LISA (Cytoskeleton, Inc.), and by IB for (respectively) phospho-Thr
423
-p21-activated kinase (activated Rac effector), and phospho-Ser
695
-MYPT1 of myosin light chain phosphatase (targeted only by RhoA-activated kinase). In response to FBS or PDGF, SMCs with kalirin deficiency ((−/+) or RNAi-mediated) showed reduction in the activation of Rac (by 50±10%, p<0.05), but not RhoA. Moreover, SMC migration toward FBS or PDGF (8–15-fold/basal, Transwell chambers) was reduced by 30 –50% in kalirin-deficient SMCs (p<0.05). FBS-induced proliferation (assessed by SMC counting) was also reduced in kalirin
−/+
SMCs, by 20±5% (p<0.05), even though ERK activation was not altered. To test kalirin action on SMCs in vivo, we denuded the common carotid artery endothelium with a 0.36-mm wire, a procedure we have shown (by bone marrow transplant) produces neointimal hyperplasia comprising SMCs derived only from the arterial media. Neointimal area 4 wk after wire injury was 60±10% less (p<0.05) in kalirin
−/+
(0.012±0.003 mm
2
) than in WT mice (0.03±0.01 mm
2
) matched for gender, age, and weight, even though medial area was equivalent. We conclude that kalirin is an important Rac-GEF in SMCs, and promotes SMC migration and proliferation in a manner that may prove pro-atherogenic.
Abstract 4850: Improved Myocardial Energetics Following Chronic Treatment Using an Implantable Device in Resistant Hypertension: Results From European and United States Trials of the Rheos
®
System
Authors: de Leeuw Peter , Bisognano John D , Bach David S , Lovett Eric G , Kaufman Christopher L
Published: April 2024

Background:
The Rheos System provides Baroreflex Activation Therapy (BAT
™
) and has been shown to chronically reduce blood pressure and improve left ventricular (LV) structure and function in patients with resistant hypertension (HTN). The effect of BAT on myocardial energetics and mechanical efficiency is unknown.

Methods:
Resistant HTN (stage II) patients (systolic BP ≥160 mmHg) taking ≥3 anti-HTN drugs were implanted with the Rheos System which was activated 1 month after implant. Baseline data were acquired before implant. Follow-up echocardiograms were performed after 3 and 12 months of BAT. Echocardiograms were reviewed at a blinded core lab. Stroke work was calculated as systolic BP × stroke volume × 0.0144 and eMVO
2
was defined as heart rate × systolic BP. Myocardial mechanical efficiency was defined as the ratio of stroke work/eMVO
2
. Changes at follow-up vs. pre-implant were analyzed with paired t-tests. Data are presented as mean ± SEM.

Results:
34 subjects (19 M/15 F, Age 52.5±1.8 yr) were implanted at 8 centers. Pre-implant myocardial mechanical efficiency was normal. A 15% reduction in stroke work was observed at 3 months and was sustained after 12 months of BAT despite a reduction in anti-HTN medications (table

). eMVO
2
was significantly reduced with BAT. Myocardial mechanical efficiency was preserved. Cardiac structure, as indexed by LV mass index and left atrial dimension, was abnormal at pre-implant but was significantly improved after BAT.

Conclusions:
In addition to previously documented blood pressure reduction, chronic BAT improves myocardial energetics, as indicated by reduced stroke work and eMVO
2
, while maintaining normal myocardial efficiency in resistant hypertensive patients. Concomitant improvements in cardiac structure were also observed. These data suggest that BAT provide benefits beyond blood pressure reduction and are under further investigation in a large placebo-controlled clinical trial.

Changes in Cardiac Function and Structure & Medication with BAT
Abstract 4851: Three-year Target Systolic Blood Pressure Less Than 120 mmHg for More Than 65 Aged Hypertension Patients With Chronic Renal Disease
Authors: Zeng Xianghong , Li Yunyun , Zeng Xianghong , Liu Zhaohuan , Zeng Xiangji , Chen Xiaoyun
Published: April 2024

Background: Many studies demonstrate that systolic blood pressure (SBP) ≥140 mm Hg does not provide renal protection in renal disease with hypertension, but SBP≤120 mmHg may be able to slow progress of renal disease. However, target SBP≤150 mmHg in elderly hypertension patients was recommended in Chinese hypertension guideline in 2005.The safety and efficacy of SBP≤120 mmHg in elderly hypertension patients with chronic renal disease is hardly reported.

Methods: In a prospective, controlled open-label studies, the authors have evaluated the safety and efficacy of three-year treatment on progress of renal disease and risk of development of cardiovascular disease in 122 >65 aged hypertension patients with chronic renal disease. Before randomization, all patients have already been treated for one-year with angiotensin converting enzyme inhibitors (ACEI) or angiotensin AT
1
receptor blockade(ARBs) and other antihypertensive drugs, but their SBP are above 140 mmHg but less than 150 mmHg. Blood pressure, serum creatinine(Cr) and potassium were monitored every 14 days in the period of follow-up..

Results: By the end of three years, Cr clearance increased from 51±2.0 to 63±3.2 ml/min, p<0.001,in the group of strict control of SBP, By contrast, Cr clearance decreased significantly from 52±1.9 to 42±2.1 ml/min, P<0.01, in the controls. During this time, urine protein excretion decreased from 1.4±0.5 to 0.4±0.4g every 24 hours (P<0.01) in the treatment group, but urine protein excretion decreased slightly (from 1.3±0.4 to 1.2±0.5, P>0.05) in the controls. Nine patients had got ACS, 10 patients stroke, three patients died in SCD and 2 patients died in chronic heart failure in controls but one patient had ACS, two patients stroke, one died in non-cardiac cause and 2 patients had mild dizzy who can continue to take theses drugs in the treatment group(p<0.01).However, the incidence of hyperkalaemia was similar between two groups.

Conclusions: Long-term SBP≤120 mmHg is safe and was more apparently in decreasing proteinuria, slowing the progress of renal disease and reducing the risk of development of acute cardiovascular events in elderly hypertensive patients with chronic renal disease.
Abstract 4862: ST-Segment Depression in Lead aVR: A Useful Predictor of Impaired Myocardial Reperfusion in Patients With Anterolateral ST-Segment Elevation Acute Myocardial Infarction
Authors: Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi , Morita Satoshi , Ishikawa Toshiyuki , Uchino Kazuaki , Tsukahara Kengo , Iwahashi Noriaki , Okuda Jyun , Umemura Satoshi , Kimura Kazuo
Published: April 2024

Background:
ST-segment depression in lead aVR during ST-segment elevation acute myocardial infarction (STEMI) theoretically represents a reciprocal change in response to an opposite vector resulting from ST-segment elevation in the apical and inferolateral walls. We hypothesized that ST-segment depression in lead aVR during anterolateral STEMI is associated with less successful myocardial reperfusion, because of more extensive area at risk.

Methods:
We studied 301 patients with a first anterolateral STEMI who underwent coronary recanalization (TIMI grade 3 flow) by fibrinolysis or percutaneous coronary intervention within 6 h after symptom onset. Patients were divided into the 3 groups according to ST-segment deviation in lead aVR on admission ECG: group A, 71 patients with ST-segment elevation of ≥ 0.5 mm; group B, 131 patients without ST-segment deviation; and group C, 99 patients with ST-segment depression of ≥ 0.5 mm. Myocardial blush grade was assessed immediately after recanalization.

Results:
There were no differences in age, sex, coronary risk factors, time from symptom onset to admission, or multivessel disease among the 3 groups. In groups A, B, and C, the incidence of Killip class ≥ 2 was 6%, 6%, and 15% (p=0.03); the sum of ST-segment elevation in leads I, aVL, and V1– 6 was 20±11, 23±9, and 33±14 mm (p<0.01); the rates of initial TIMI grade 0 or 1 flow was 56%, 70%, and 78% (p=0.01); good collateral circulation was 43%, 39%, and 22% (p=0.03); impaired myocardial reperfusion (defined as myocardial blush grade 0 or 1) was 14%, 23%, and 65% (p<0.01); peak creatine kinase level was 3432±1995, 4045±2144, and 5986±2550 mU/ml (p<0.01); and predischarge left ventricular ejection fraction was 56±13%, 51±11%, 44±12% (p<0.01), respectively. Multivariate analysis showed that ST-segment depression in lead aVR was an independent predictor of impaired myocardial reperfusion (odds ratio 3.31, 95% CI 1.98 to 5.52, p<0.001); but sum of ST-segment elevation in leads I, aVL, and V1– 6 was not.

Conclusions:
In patients with anterolateral STEMI, ST-segment depression in lead aVR on admission ECG is associated with less successful myocardial reperfusion and larger infarct. Assessment of ST-segment deviation in lead aVR is useful for acute risk stratification.
Abstract 4867: Circulating Chemical and Cellular Injury/Repair Responses Are Linked to the Extent of Heart Injury in Human Myocardial Infarction
Authors: McGeoch Ross , McGarrity Anne , Payne Alexander R , Watkins Stuart , Steedman Tracey , Davie Andrew P , Lindsay Mitchell M , Robb Stephen D , Rheaume Eric , Tardif Jean-Claude , Oldroyd Keith G , Berry Colin
Published: April 2024

Introduction:
Circulating injury and repair pathways in human myocardial infarction (MI) are incompletely understood. We investigated rheological and regenerative pathways acutely and in the longer term post-MI.

Methods:
Blood constituents implicated in myocardial injury (e.g. red cell volume distribution width, hemoglobin) and repair (circulating CD34
+
progenitor cells, serum vascular endothelial growth factor (VEGF), serum thymosin
β
4 and AcSDKP excreted in urine) were quantified in patients 2 days and 3 months after ST elevation MI (STEMI). Coronary collateral flow was measured invasively during emergency percutaneous coronary intervention. Cardiac function and remodeling were quantified by gadolinium contrast enhanced MRI at 1.5T at these time-points.

Results:
Thirty-five consecutive STEMI patients (mean±SD age 58±10 years; 3(9%) women) were included. Mean (SD) thymosin
β
4 concentration was lower at day 2 compared to at 3 months post-MI (3.0±1.6 vs. 7.0±2.9
μ
g/L; P<0.0001). Two days post-MI, AcSDKP correlated negatively with white cell count (R=−0.54; P=0.024) and VEGF (R=−0.57; P=0.038). After adjustment for white cell count, AcSDKP two days post-MI negatively predicted left ventricular (LV) ejection fraction (R
2
=0.43; P=0.024) and positively predicted LV end-systolic volume index (R
2
=0.56; P=0.011) at 3 months. At follow-up, CD34
+
count negatively predicted myocardial infarct mass (R
2
=0.29; P=0.015) and LV end-systolic volume index (R
2
=0.20; P=0.02). Delta CD34
+
negatively predicted infarct mass (R
2
=0.13; P=0.049) at 3 months. Mean red cell volume at day 2 negatively predicted LV end-systolic volume index (R
2
=0.24; P=0.038) and infarct size (R
2
=0.13; P=0.045) at 3 months. In multivariable analyses, VEGF at day 2 predicted LV end-diastolic volume index at follow-up (coefficient of variation (95% CI) −0.021 (−0.038, −0.035); P=0.021). Coronary collateral supply was negatively predicted by hemoglobin (−0.04 (−0.06, −0.11); P=0.006) and positively predicted by red cell volume distribution width (0.06 (0.02, 0.10); P=0.004) and platelet count (0.001 (0.0001, 0.002); P=0.001) at day 2.

Conclusions:
Circulating injury/repair responses predict coronary collateral recruitment and cardiac function and remodeling post-MI.
Abstract 4876: Leptin Reverses Hyperlipidemia and Vascular Dysfunction in Mice Exposed to Intermittent Hypoxia
Authors: Yang Ronghua , Sikka Gautam , Reinke Christian , Miller Karen , Liu Xiaolin , Vandegaer Koenraad M , Polotsky Vsevolod Y , O’Donnell Christopher P , Berkowitz Dan E , Barouch Lili A
Published: April 2024

Obesity and sleep apnea contribute to poor vascular health. Lack of leptin and exposure to intermittent hypoxia (IH) both lead to greater vascular stiffness and endothelial dysfunction, accompanied by dyslipidemia. We previously showed that leptin deficient ob/ob mice exposed to IH showed greater vascular stiffness, fully reversed with leptin repletion. In this study, we tested the hypothesis that leptin treatment in lean mice exposed to IH can improve dyslipidemia, vascular compliance and endothelial function. C57BL6/J mice with or without leptin infusion (0.3 mg/kg/day via subcutaneous osmotic pumps) were exposed to IH or room air for 4 weeks. Pulse wave velocity (PWV) was measured by Doppler to assess vascular stiffness (n=8–20). Vascular relaxation response to acetylcholine (ACh) was measured in preconstricted aortic rings (n=10–21) to indicate endothelial function. In mice exposed to room air, leptin did not affect PWV (3.53±0.07 vs. 3.48±0.04 m/s in control, p=NS) or endothelium-dependent relaxation (Emax 79.7±2.1 vs. 77.5±3.4 % in control; p=NS). Mice exposed to IH had higher PWV, i.e. increased vascular stiffness, vs. control (3.92±0.06 m/s; p<0.001). There was a trend toward improved PWV in IH+leptin mice (3.74±0.08 m/s; p=0.08 vs. IH, p<0.05 vs. control). ACh-induced aortic ring relaxation was attenuated in IH (Emax 65.5±2.0 %; p<0.001 vs. control) but normal in IH+leptin (Emax 78.1±1.8 %; p<0.001 vs. IH, p=NS vs. control). Fasting serum total cholesterol was lower in IH+leptin vs. IH mice (82.6±3.2 vs. 102.6±5.1 mg/dL, p<0.001), as was total triglycerides (26.3±3.5 vs. 38.3±3.4 mg/dL, p<0.05). Hepatic protein expression of stearoyl-Coenzyme A desaturase 1 (SCD-1), which catalyzes monounsaturated fatty acid synthesis and is transcriptionally inhibited by leptin, was also lower in IH+leptin vs. IH by Western blot (0.65±0.07 vs. 1.00±0.05 arb. units; p<0.01). In summary, we describe a novel role for leptin in protecting against IH-induced vascular stiffness and endothelial dysfunction, associated with improved dyslipidemia and reduced SCD-1 in mice. Leptin’s inhibitory actions on fatty acid synthesis may provide vascular benefits in sleep apnea and hyperlipidemia and offer new therapeutic strategies in patients with these conditions.
Abstract 4897: Right Ventricular Diastolic Dysfunction in Upper-normal and Mildly Hypertensives: A Tissue Doppler Imaging Study
Authors: Canale Maria Laura , Talini Enrica , Giannini Cristina , Bendinelli Stefano , Dell’Omo Giulia , Di Bello Vitantonio , Pedrinelli Roberto
Published: April 2024

Background:
Systemic hypertension is known to affect the right ventricle in addition to its wide-ranging effects on left ventricular structure and function. Whether upper-normal increments in systemic blood pressure (BP), sampled by ABPM, exert any effect on right ventricular function is, however, unknown at this point.

Methods:
Left (LV) and right ventricular (RV) diastolic longitudinal function were assessed by pulsed-wave TDI sampled at mitral (early:Em
MIT
and late:Am
MIT
) and tricuspid (Em
TRIC
and Am
TRIC
) annular level in a group of 98 (37F/61M, age: 46 ± 14yrs) otherwise normal subjects with office BP values ranging from the optimal (< 120/80 mmHg) to the mild hypertensive (140–160/90–100 mmHg) range. RV free wall (FWT) and interventricular septum thickness (IVST), LV ejection fraction (EF), TRIC annulus plane systolic excursion (TAPSE, an index of RV systolic function), LV mass index (MI, g/m
2.7
) were evaluated by standard methods. The sample was stratified by ascending 24-hr systolic(S) BP tertiles (cutoffs:117 and 130 mmHg, I:110 ± 7/68 ± 7, II:125 ± 4/77 ± 7, III:139 ± 7/87 ± 8 mmHg) and analyzed accordingly.

Results
: Em
TRIC
decreased significantly at each increasing 24-hr SBP stratum (I:15.9 ± 2.8, II:12. ± 3.1, III:10.9 ± 3.6 cm/sec, I vs II p < 0.01, II vs III p < 0.01) in parallel with consensual reductions in Em
MIT
(I:11.1 ± 2.8, II:8.7 ± 2.9, III:8.3 ± 2.6 cm/sec, I vs II & III p < 0.001). RVFWT (I:3.5 ± 0.6, II:4.0 ± 1.1, III:3.6 ± 0.9 mm, NS) and LVMI (I:38.6 ± 8.3, II: 41.3 ± 6.6, III: 43.0 ± 9.1 g/m
2.7
, NS) did not change in contrast to the graded, BP-related thickeness of IVS (I: 7.9 ± 1.1, II: 9.3 ± 1.25, III: 10.3 ± 1.34 mm, I vs II: p = 0.001, II vs III: p = 0.001). Intra-individually (n = 98), Em
TRIC
associated with 24-hr SBP (r =−0.52, p < 0.001), IVST (r = −0.63, p < 0.001) and Em
MIT
(r = 0.41, p < 0.001) but only the two latter (IVST: t = 5.5, p < 0.0001; Em
MIT
: t = 2.8, p = 0.006) were independent predictors of Em
TRIC
when entered in a multiple regression model.

Conclusions
: Systemic BP increments still within the normal range associate with echocardiographic evidence of RV diastolic longitudinal dysfunction. Interventricular septum thickening appears to be the main determinant of that behavior, possibly as an expression on interventricular dependence.
Abstract 4903: Control of Hypertension in All Age Groups in a Large Multiyear Multicenter Analysis From the Department of Veterans Affairs
Authors: Fletcher Ross D , Papademetriou Vasilios , Amdur Richard , Faselis Charles , McManus Christopher , Jones Ronald
Published: April 2024

Introduction:
Benefits of blood pressure (BP) control have been well elucidated, but overall BP control remains poor. Elderly patients are considered resistant or difficult to control. Thus, we assessed the effect of organized interventions to control blood pressure in a large cohort of patients in the Department of Veteran Affairs.

Methods:
From January of 2000 to December 2007, we assessed BP control in 478,099 patients from 15 VA hospitals in various geographic locations around the United States. Patients were divided in 4 groups based on age: G1 <55 (N = 105,119), G2 55- <70 (N = 174,418), G3 70- <80 (N = 129,516), G4 ≥ 80 (N = 69,046). Medical interventions to control BP included use of electronic medical records with automated reminders, medical regimen adjustments, and frequent visits to both specialty and nurse run clinics.

Results
: Control rates (BP ≤ 140/90) at baseline were: 49.5% in G1, 43.6% in G2, 43.5% in G3 and 44.0% in G4. After 7 years of follow up BP control improved to 69.9% in G1, 70.9% in G2, 72.3% in G3 and 71.6% in G4 (p <0.0001 for all groups compared to baseline). Average blood pressure changes are shown (figure

). Patients over the age of 70 achieved the greatest systolic BP reduction. Diastolic BP decreased in all age groups over the age of 55, but remained unchanged in the younger age group. BP levels were lower during the summer time as compared to winter in all age groups.

Conclusions:

High rates of BP control can be achieved even among the very old.

Older patients respond well to appropriate interventions.

Diastolic BP decreased in all age groups over the age of 55, but remained unchanged in younger patients.

Seasonal BP variation is seen independent of age.