bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2504: Plasma Asymmetric Dimethylarginine (ADMA) Levels And Short Outcome In Elderly Patients With Severely Exacerbated Heart Failure
Authors: Ishibashi Yutaka , Tokumaru Atsushi , Shimada Toshio
Published: July 2021

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is elevated in congestive heart failure, associated with the severity of heart failure. We investigated the association between plasma ADMA level and early prognosis in elderly patients with severely exacerbated heart failure. Plasma ADMA, symmetric dimethylarginine (SDMA), arginine (Arg), plasma BNP and serum interleukin 6 (IL-6) concentrations were measured at admission in 52 elderly patients (82Â ± 2 years, 38 women) with exacerbated heart failure (pulmonary congestion and hypoxemia). ADMA was measured with HPLC (0.47Â ± 0.09 Â μmol/L in normal control). Patients with infection and renal failure (serum creatinine > 2.0 mg/dl) were excluded from the study. Eight patients (Group A) died without improvement of heart failure. Other 44 patients (Group B) were able to discharge. Although SDMA was not different between the 2 groups, ADMA was significantly higher in the Group A than in the Group B (0.62Â ± 0.19 vs. 0.53Â ± 0.15 Â μmol/L, respectively, p < 0.05). Furthermore, Arg was significantly lower in Group A than in Group B, resulting in higher ADMA/Arg ratio in the Group A (1.61Â ± 0.88 vs. 1.04Â ± 0.64 x10–2, respectively, p < 0.001) (0.61Â ± 0.11 in normal control). The ADMA/Arg ratio in the group B was not affected by heart failure treatment. The ADMA/Arg ratio was positively correlated with BNP and IL-6 levels (p < 0.05 for both), and both BNP and ADMA/Arg ratio were independent predictors of cardiac death (p < 0.001 in logistic regression analysis). In conclusion, these findings suggest that ADMA metabolism closely correlates with pathophysiology of heart failure in elderly patients, and supports the need for future studies examining the administration of L-arginine for treatment of elderly heart failure patients.
Abstract 2558: Outcomes of Children with Cardiomyopathy Listed for Heart Transplant: A Multi-Institutional Study
Authors: Dipchand Anne I , Naftel David C , Feingold Brian , Spicer Robert , Yung Delphine , Kaufman Beth , Allain-Rooney Tina , Hsu Daphne
Published: July 2021

BACKGROUND: Dilated (DCM), restrictive (RCM), and hypertrophic (HCM) cardiomyopathies (CM) in children have widely varying clinical courses and therapeutic options. For all types, heart transplant (HTx) offers a chance for long-term survival, but clinical outcomes following listing and predictors to guide in the optimal timing of listing have not been well defined.

METHODS AND RESULTS: A multi-institutional, prospective, event-driven registry of pts<18 years of age listed for HTx from 01/93 to 12/05 (n=2,792) was used to compare outcomes of DCM (n=965; 84%); RCM (n=126; 11%); and HCM (n=63; 5%). Waitlist mortality for all pts was 12% with no difference by diagnosis (p=0.69). At listing, more DCM were Status 1 (p<0.0001), on high dose inotropes (p<0.0001), ventilated (p<0.0004), or on an assist device (VAD, p=0.0081). At the time of HTx, Status 1 (p<0.0001) or VAD (p=0.0003) were more common in DCM pts. Despite being more acutely unwell, overall survival from listing was higher in DCM pts (p=0.05), which was most dramatic for those listed in infancy (p<0.0001).[Fig

] Survival was particularly poor in RCM and HCM pts who were <1 yr of age at listing.[Fig

] Late (10 yr) survival post-HTx was also higher in DCM pts (82%) compared with RCM (76%) and HCM pts (65%, p=0.02).

CONCLUSION: Children with CM awaiting HTx have a low waitlist mortality and good survival post-HTx with DCM pts demonstrating a consistent, modest survival advantage from listing. The relatively poor survival in select groups of RCM and HCM pts suggests the need for further study to better understand the causes and timing of death, timing of listing, and influence of patient characteristics on survival.s
Abstract 2559: Impact of Stent Thrombosis On MACE In The ARTS-II Study
Authors: Serruys Patrick W , Daemen Joost , Vranckx Pascal , Smits Peter , Hanet Claude , Herrman Jean-Paul , Wittebols Kristel , Stoll Hans-Peter
Published: July 2021

PURPOSE: There is still scarce data about the incidence of (late) stent thrombosis (ST) following implantation of drug-eluting stents in patients treated for multivessel coronary artery disease (MVD). Recent concerns were raised about a possible erosion of the long-term treatment benefit of sirolimus-eluting stents (SES) due to ST. Our aim was to assess the impact of ST on Major Adverse Cardiac Events (MACE) up to 3 years in patients treated with SES for MVD in the Arterial Revascularization Therapies Study part II (ARTS-II) trial.

METHODS: ARTS-II is a non-randomized, open label, stratified trial with 607 patients exclusively treated with SES for multivessel coronary artery disease including mandatory involvement of the LAD. The 3-year clinical data from ARTS-II were re-adjudicated by an independent clinical events committee for the incidence of ST according to the definitions recently proposed by an Academic Research Consortium (ARC) using the categories of definite (angiography or autopsy), probable (myocardial infarction in target area, unexplained death within 30 days), and possible ST (unexplained death).

RESULTS: The majority of patients (53.5%) had 3-vessel disease. Total stented length was 72.5 ± 32.1mm, and 3.7 ± 1.5 stents were implanted per patient on average. At 3 years, 18/607patients died (3.0%), and MI was observed in 49/607 patients (8.1%). Stent thrombosis occurred in 39/607 patients (6.4%), 21 patients had ``definite” ST, and 32 patients had ``definite or probable” ST according to the ARC classification. From the 39 patients experiencing ST only 8 died, 7 of which were contributed by the ARC ``possible” ST category.

CONCLUSIONS: In ARTS-II, the majority of deaths in patients with ST was contributed by the ARC possible category. The final impact of ST on the individual MACE categories will be presented at the conference.
Abstract 2565: Predictors For Very Late Stent Thrombosis After Drug-eluting Stent Implantation In Diabetic Patients.
Authors: Voudris Vassilis , Karyofillis Panagiotis , Thomopoulou Sophia , Patsilinakos Sotitrios , Manginas Athanasios , Spargias Constantinos , Pavlides Gregory , Cokkinos Dennis V.
Published: July 2021

Background:
Despite encouraging results with drug-eluting stents (DES) reported in diabetes mellitus (DM) patients (pts) with coronary artery disease, the long-term safety is unknown, because of late-onset stent thrombosis (LST). We investigated the incidence, risk factors and association of antiplatelet treatment (APLT) interruption for the development of LST in DM pts treated with DES during long-term clinical follow-up (FU).

Methods:
A total of 610 consecutive DM pts (male 80%, mean age 65 ± 9 years) had been treated with DES (sirolimus 80%, paclitaxel 10%, zotarolimus 2% combination 8%); 133 (22%) were on insulin treatment. Dual APLT treatment for 12 months received 93%, more than 12 months 72% and statin treatment 93% of pts. Clinical FU at least 12 months post-PCI (median 29 months, interquartile range 21 to 40) was obtained in 597/610 (98%) of pts. LST was defined as angiographic documentation of stent occlusion associated with an acute ischemic event, unexplained sudden cardiac death (D) or myocardial infarction (MI) not clearly attributable to another coronary lesion.

Results:
The incidence of LST was 2.18% (13 of 597 pts) and 6 additional pts (1%) developed stent thrombosis before 12 months (EST). All pts with LST (median time 19 months, interquartile range 14 to 24) had unexplained sudden cardiac D and 2/6 pts with EST non-fatal MI. Eleven out of 13 pts (85%) were on dual antiplatelet treatment at the time of LST. There was no difference in the incidence of LST between pts on oral antidiabetic medications and insulin treatment (2,1% vs. 2.3%, p:ns). In a multivariate model including clinical and angiographic factors, the only predictor for LST was ejection fraction <40% (OR 0.10, 95% CI 0.03– 0.43, p<0.05).

Conclusion:
LST in DM pts occurred in 2.18% after DES implantation; most of these pts were on dual APLT treatment. The only predictor of LST was depressed left ventricular function.
Abstract 2567: Paclitaxel Eluting Stents are associated with a high rate of Stent Thrombosis compared to Bare Metal Stents in an Underserved Hispanic Population Presenting with Acute ST Segment Myocardial Infarction
Authors: Shah Atman P , Shavelle David M , Swenson Kathleen , Jaquez Sandra , Martinez Michelle , Choi Jae , French William J
Published: July 2021

Background:
Paclitaxel-eluting stents (PES) are shown to reduce restenosis and target lesion revascularization (TLR). The effectiveness of PES in Hispanic patients who present with acute myocardial infarction with ST segment elevation (STEMI) is not well established.

Methods:
A non-randomized, retrospective analysis was performed on 236 Hispanic patients presenting with STEMI between 8/2002 and 4/2006 at an academic tertiary care hospital serving a primarily indigent population. 150 patients received a PES and 86 received an uncoated stent (BMS). The incidence of cardiac death, myocardial infarction (MI), TLR, subacute thrombosis (SAT), and a composite of these major adverse cardiac events (MACE) was assessed at 1 year.

Results:
Baseline clinical characteristics in both groups revealed no statistically significant differences. All patients had clinical follow up at one year. There were statistically significant reductions in MI [2.0% (n=3 PES) vs. 10.5% (n=9 BMS), p=0.037] and TLR [6.0% (9) vs. 18.6% (16), p=0.04]. There was no difference in death [0.7% (1) vs. 1.1% (1), p=0.99]. SAT was increased in the PES group (6.0%, n=9) compared to the BMS group (1.1%, n=1, p=0.03). MACE was 14.7% in the PES group and 31.2% in the BMS group (p=0.017). Premature clopidogrel discontinuation (<6 months) was the etiology of SAT in 8 of the 9 patients.

Conclusions:
Use of DES is associated with lower rates of MI and TLR in Hispanics presenting with STEMI. There is an increased incidence of SAT in this population primarily due to premature clopidogrel discontinuation. The role of socioeconomic factors in premature antiplatelet discontinuation and its effects on SAT need further evaluation.
Abstract 2580: Potential Role of Circulating Progenitor Cells in Coronary Microvascular Dysfunction of Heart Transplant Patients with Normal Coronary Angiograms
Authors: Tona Francesco , Fadini Gianpaolo , Caforio Alida , Baesso Ilenia , Agostini Carlo , Angelini Annalisa , Napodano Massimo , Gerosa Gino , Avogaro Angelo , Iliceto Sabino
Published: July 2021

Peripheral blood progenitor cells (PCs) may play a role in the early stages of cardiac allograft vasculopathy (CAV). We assessed the relationship between PCs and coronary microvascular function in heart transplant (HT) patients (pts) with normal coronary angiograms.

Methods
: We studied 41 pts with (36 M, aged 50 ± 12 years) at 6 ± 3 years from HT and 40 age and sex matched healthy subjects. Six subpopulations of PCs were determined by flow cytometry as follows: uncommitted (CD34
+
, CD133
+
, CD34
+
CD133
+
) and endothelial PCs (EPCs, CD34
+
KDR
+
, CD133
+
KDR
+
, CD34
+
CD133
+
KDR
+
). Coronary flow velocity in the LAD was detected at rest and during i.v. adenosine by transthoracic echocardiography. Coronary flow reserve (CFR) was the ratio of hyperemic diastolic mean velocity (DMV) to resting DMV. CFR <2.5 was considered abnormal. CFR was measured in 10 pts (8 M, aged 50 ± 12 years) and was abnormal in 3 (group A) and normal in 7 (group B).

Results
: EPCs were lower in pts than in controls (p<0.05). CD34
+
cell count was higher in group A than in group B (583 ± 100 vs 282 ± 185 cells/10
^
6 cytometric events, p=0.01). CD34
+
cell count was also inversely correlated with CFR as shown in the figure

. At multivariable analysis, adjusted for time from HT, diabetes, hypertension and hypertrophy, CD34
+
cell count was the only independent predictor of CFR (β=-0.773, p=0.006).

Conclusion
: EPCs were reduced in HT pts with normal angiograms, in keeping with their immunosuppressed status. Levels of CD34
+
cells were inversely related with CFR. Mobilization of uncommitted PCs may be involved in the pathogenesis of CAV, possibly by PCs capacity of differentiation into neointimal and medial cells.
Abstract 2593: Noninvasive Coronary Angiography by Dual Source Computed Tomography in patients with an intermediate pretest likelihood for coronary artery disease
Authors: Leber Alexander , Ovrehus Kristian , Tittus Janine , Johnson Thorsten , Becker Christoph , Becker Alexander
Published: July 2021

Introduction: Multislice CT has gained acceptance as a noninvasive tool to evaluate coronary arteries but its utility is limited by the occurrence of motion artifacts in patients with heart rates exceeding 70bpm. Furthermore little is known about the accuracy of MSCT in patient populations with an intermediate pretest likelihood for obstructive coronary artery disease.

Objectives: The aim of the present study was to assess the clinical performance of a dual x-ray source MSCT with high temporal resolution without using negative chronotropic pretreatment.

Methods: Dual source CT angiography (DSCT) (Siemens Definition) was performed in 130 patients with an intermediate likelihood for coronary artery disease, according to the Morise Scoring method, who were referred for invasive coronary angiography.

Results: DSCT generated datasets with diagnostic image quality in overall 127/130 patients. In 13 of 15 patients with atrial fibrillation and in 63 of 65 patients with heart rates > 65 bpm image quality was diagnostic. 13/13 patients with at least 1 stenosis > 75% (Sensitivity 100%) were correctly identified and in 110/114 patients (Specificity 96%, positive predictive value 76%) coronary stenosis >75% were correctly excluded. The accuracy to detect patients with coronary stenoses > 75% was not significantly different among patients with heart rates > 65bpm and < 65bpm.

Conclusion: This is one of the first studies using Multislice CT to assess the coronary status of patients with an intermediate pretest likelihood for coronary artery disease. We have shown that Dual Source Multislice CT (DSCT) allows to rule out coronary artery stenoses in such patients with excellent sensitivity. Due to a trend to overestimate the stenosis severity the positive predictive value of this technique is moderate in patient cohorts with a low prevalence of coronary stenoses. Fast heart rates and arrhythmias are no limitations for this technique anymore.
Abstract 2606: A Meta-Analysis of Glucose-Insulin-Potassium Therapy for Treatment of Acute Myocardial Infarction (1966:–2007:)
Authors: Mamas Mamas , Neyses Ludwig , Fath-Ordoubadi Farzin
Published: July 2021

Glucose-Insulin-Potassium (GIK) therapy has been proposed to provide metabolic support to the ischaemic myocardium through a shift from potentially harmfully free fatty acid metabolism to glucose metabolism. Our metanalysis published 10 years ago of 9 trials with 1932 patients demonstrated that GIK had an important role in reducing mortality post AMI. Since then, a number of larger randomised trials including CREATE ECLA, ECLA pilot, GIPS-I, GIPS-II, Pol-GIK and REVIVAL have been published investigating the role of GIK in the setting of AMI in modern thrombolysis / primary PCI era. Hence, we repeated our metanalysis to include these trials. A MEDLINE search for all randomized placebo-controlled studies of GIK therapy in AMI and meta-analysis of the mortality data was performed. We included 15 trials from 1966 to 2007 enrolling 25,635 patients. 30 day mortality in the GIK group was 1263 out of 12881 (9.8%) and in the placebo group 1259 out of 12748 (9.9%). Metanalysis of these 15 randomised trials did not reveal any benefit from GIK treatment, odds ratio 1.0, 95% CI 0.92 -1.08, P>0.05; see figure

. Subgroup analysis of patients receiving high dose GIK or where reperfusion was not achieved still did not demonstrate any benefit of GIK. In conclusion, our current metanalysis performed on 15 randomised trials spanning over 40 years with 25,635 patients does not demonstrate any benefits of GIK on mortality post AMI. This may reflect differences in patient cohorts between modern era of AMI management and studies performed 20 –30 years ago used in our last metanalysis where control group mortality was 21%.
Abstract 2612: Derived Fibrinogen Versus Brain Natriuretic Peptide and C-Reactive Protein as a Predictor of Events After Myocardial Infarction
Authors: Ketch Terry R , Turner Samuel J , Sacrinty Matthew T , Lingle Kevin C , Applegate Robert J , Kutcher Michael A , Sane David C
Published: July 2021

Multiple biomarkers have been studied to assess risk for future coronary events. Fibrinogen is involved in platelet aggregation, thrombus formation, and is a marker of inflammation. Furthermore, prothrombin time-derived fibrinogen levels are widely available with routine coagulation assays. We retrospectively evaluated admission derived fibrinogen, BNP and CRP levels as well as baseline clinical and procedural characteristics of 475 consecutive patients admitted with acute myocardial infarction who subsequently underwent stent placement. Major adverse cardiac event (MACE) outcomes data were collected to two years after index admission. Higher quartiles of admission fibrinogen levels were associated with increased hazard of death from any cause (log-rank p-value <0.001), non-fatal myocardial infarction (log-rank p-value <0.001), and any MACE (log-rank p-value = 0.004) at two years. In a Cox proportional hazards multivariate model including the covariates age (10 years), heart failure class, smoking status, diabetes, hypertension, cerebrovascular disease, history of renal failure, previous PCI and/or CABG, multivessel coronary disease, BNP and CRP, increased admission derived fibrinogen remained a significant predictor of increased hazard of MACE at two years [HR 2.22 (1.03– 4.77)]. In the same model, BNP [HR 0.95 (0.82–1.08)] and CRP [HR 1.22 (1.01–1.47)] were less robust prognosticators. In patients admitted with an acute myocardial infarction who undergo PCI with stent placement, admission derived fibrinogen levels, a widely available analyte, are more strongly predictive of future major adverse cardiac events than BNP and CRP.
Abstract 2627: High Energy Defibrillation Impairs Myocyte Contractility and Intracellular Calcium Dynamics
Authors: Ristagno Giuseppe , Wang Tong , Tsai Min-Shan , Sun Shijie , Tang Wanchun , Weil Max H
Published: July 2021

Introduction.
High energy defibrillation is recognized to increase postresuscitation myocardial dysfunction. We examined the effects of defibrillation energies on contractility and intracellular Ca
2+
dynamics at the single cardiomyocyte level.

Hypothesis.
Increasing the defibrillation energy would produce correspondent reduction in myocyte contractility and impairment of intracellular Ca
2+
dynamics.

Methods.
Ventricular cardiomyocytes, obtained from adult Sprague-Dawley rat hearts, were loaded with Fura-2/AM. The myocytes were then placed in a chamber mounted on an inverted microscope and superfused with a buffer solution at 37 °C. The cells were field stimulated to contract at 0.5 Hz with a field stimulator (IonOptix Corporation, Milton, MA). Mechanical properties were assessed using a video-based edge-detection system (IonOptix Corporation, Milton, MA) and expressed as cell shortening percentage. Intracellular Ca
2+
dynamics were evaluated with a dual-excitation fluorescence photomultiplier system (IonOptix Myocam System) and inferred from the ratio of the fluorescence intensity at the two different wavelengths. Myocytes were randomized into 4 groups of 10 cells each, to receive:

a single 0.5 Joule biphasic shock;

a single 1 Joule biphasic shock;

a single 2 Joule biphasic shock; and

a control group without shock. The myocytes were paced for additional 4 min after the shock.

Results.
A 0.5 Joule shock did not have effects on cardiomyocyte contractility and intracellular Ca
2+
dynamics. Higher energy shock, i.e. 1 or 2 Joule, significantly impaired cardiomyocyte contractility and intracellular Ca
2+
dynamics (p < 0.01). These adverse effects were greater when higher energy was employed (p < 0.01). Table

Conclusions.
Higher defibrillation energy significantly impairs myocyte contractility. Reductions in cardiomyocyte shortening and intacellular Ca
2+
dynamics abnormalities were greater when higher energy shock was employed.

Results
Abstract 2647: Analysis of the Anatomical and Electrophysiological Characteristics of Tachycardia Circuit in Atrioventricular Nodal Reentrant Tachycardia Accompanied by the Block in the Upper Common Pathway
Authors: Morihisa Kenji , Yamabe Hiroshige , Tanaka Yasuaki , Uemura Takashi , Ogawa Hisao
Published: July 2021

We examined the anatomical and electrophysiological characteristic of the atrioventricular nodal reentrant tachycardia (AVNRT) accompanied by the ventriculo-atrial block during tachycardia, suggesting the presence of upper common pathway in 8 patients. Tachycardia was induced by the atrial burst and/or extrastimulation followed by the AH jump and the earliest atrial electrogram was observed at the His bundle (HB) site in all patients. The HA block was observed after gradual prolongation of the HA interval in 2 patient and abruptly in 6 patients. After administration of isoproterenol, 1:1 HA conduction was resumed in all patients. The tachycardia cycle length, AeHe interval and HeAe interval were 357±89, 275±55 and 80±44 msec, respectively. Single extrastimulus delivered from the HB site reset the tachycardia as soon as it was delivered during late diastole. However, single extrastimulus delivered from the inferior portion of the coronary sinus ostium (I-CSOS) was unable to reset the tachycardia without capturing the earliest atrial electrogram at the HB site, suggesting that atrium is not involved in the circuit. Thus, the longest coupling interval of single extrastimulus that reset the tachycardia at the HB site was significantly longer than that at I-CSOS (347±89 msec vs. 324±109 msec, p=0.012). The following return cycle after extrastimulation at the HB site did not differ from the tachycardia cycle length (357±89 msec, vs. 357±89 msec, p=NS), however, that at I-CSOS was significantly longer than the tachycardia cycle length (398±85 msec, vs. 357±89 msec, p=0.012). Catheter ablation was performed in a stepwise fashion starting at the inferior CSOS. Although the results of single extrastimulation showed that the atrial myocardium at I-CSOS was out of the reentry circuit, ablation near the I-CSOS, distant from HB site, selectively eliminated slow pathway conduction in all patients without impairment of fast pathway conduction.

Conclusions: The AVNRT with upper common pathway has the characteristic of relatively long HA interval during tachycardia. Sub-atrial tissue, but not the atrium, extending from the HB site to I-CSOS forms the upper common pathway in AVNRT. It was shown that upper common pathway has an anatomical structure of a certain range.
Abstract 2654: Persistent Diastolic Dysfunction Late After Valve Replacement In Severe Aortic Regurgitation
Authors: Sossalla Samuel , Villari Bruno , Ciampi Quirino , Petruzziello Bruno , Turina Juraj , Turina Marko , Hess Otto M
Published: July 2021

Introduction:
Regression of left ventricular (LV) hypertrophy with normalization of diastolic function has been reported in patients with aortic stenosis. The purpose of the present study was to evaluate the effect of aortic valve replacement (AVR) on LV systolic and diastolic function an LV structure in chronic aortic regurgitation (AR) early and late after AVR.

Methods:
25 patients were included in the present analysis. Ten patients with severe AR were studied before, early (21 months) and late (89 months) after AVR using LV biplane angiograms, high-fidelity pressure measurements, and endomyocardial biopsies. Fifteen healthy subjects were used as controls. LV systolic function was determined from biplane ejection fraction (EF) and midwall fractional shortening, LV diastolic function from the time constant of LV relaxation, peak filling rates, and myocardial stiffness constant. LV structure was assessed from muscle fiber diameter, interstitial fibrosis and volume fraction of myofibrils.

Results
: LV muscle mass was significantly increased preoperatively but decreased by 38% early and 55% late after surgery, but remained (ns) elevated compared to controls. LV EF and midwall fractional shortening did not change after AVR. LV relaxation was significantly prolonged before (89±28 ms vs. controls 47±11 ms, p<0.001) and early (67±19 ms) but normal late after AVR (42±14 ms). Early and late peak filling rates were increased preoperatively and were normalized early after surgery. Myocardial stiffness constant was increased in AR patients before surgery (22±6 vs. controls 9±3, p<0.001) but decreased significantly after AVR. However, it remained increased at late follow-up (15±4, p<0.05). Muscle fiber diameter decreased significantly early and late after AVR, but remained hypertrophied at late follow-up. Interstitial fibrosis was increased preoperatively and increased even further early but decreased only late after AVR.

Conclusions
: Patients with AR show normalization of macroscopic LV hypertrophy late after AVR, altough fiber hypertrophy persists. These changes in LV myocardial structure late after AVR are accompanied by a change in passive elastic properties with persistent diastolic dysfunction due to the increased interstitial fibrosis.
Abstract 2657: The Increased Local Insulin-like Growth Factor-1 To IGF Binding Protein-3 Ratio In The Pathogenesis Of The Left Ventricular Hypertrophy In Humans: Augmentation By Matrix Metalloproteinase-2 Activity
Authors: Abe Naoki , Matsunaga Toshiro , Kameda Kunihiko , Tomita Hirofumi , Osanai Tomohiro , Fukui Kozo , Fukuda Ikuo , Okumura Ken
Published: July 2021

Insulin-like growth factor (IGF)-1 is a potent mitogen and is said to enhance ventricular hypertrophy. IGF-1 is present as an IGF-1-IGF binding protein-3 (IGFBP-3) complex, and its free form shows bioactivity. Recently, the matrix metalloproteinases (MMPs) were shown to facilitate IGF-1 bioactibity through the degradation of IGFBP-3. To clarify the relation of IGF-1 and IGFBP-3 to MMPs and their roles in human cardiac hypertrophy, we measured levels of total IGF-1, IGFBP-3, MMP-2, and MMP-9 in the pericardial fluid, which reflects the myocardial interstitial fluid, obtained from 51 patients with aortic valvular disease (AVD) (n=36) (aortic stenosis (n=24), aortic regurgitation (n=12)) and mitral valvular disease (MVD) (n=15) (mitral stenosis (n=6), mitral regurgitation (n=9)) who underwent open heart surgery. Levels of total IGF-1 and IGFBP-3 were measured by enzyme immunoassay, and the activities of MMP-2 and MMP-9 by gelatin zymography. Left ventricular mass index (LVMI) was estimated by echocardiography. Pericardial total IGF-1 level (ng/ml) in AVD (32±19) was higher than that in MVD (20±17) (p<0.05). Pericardial IGFBP-3 level (ng/ml) was not different between AVD (715±318) and MVD (857±441). When total IGF-1/IGFBP-3 ratio, indicative of potency of IGF-1 action, was estimated in each patient, it was significantly higher in AVD than in MVD (p<0.017). There was no difference in MMP-9 activity between AVD and MVD, while MMP-2 activity in AVD was higher than that in MVD (p<0.05). LVMI in AVD was significantly greater than in MVD (p<0.05). In the linear regression analysis for all patients, pericardial total IGF-1/IGFBP-3 ratio was positively correlated with LVMI (r=0.3, p<0.05). To further clarify the relationship among total IGF-1, IGFBP-3 and MMP-2, we examined the effect of IGF-1 on smooth muscle cell (SMC) proliferation. IGF-1 (250 ng/ml) induced SMC proliferation, and this was inhibited by IGFBP-3 (2500 ng/ml). This inhibiting effect of IGFBP-3 was reversed by co-treatment with MMP-2 (0.005 unit). These findings suggest that cardiac IGF-1/IGFBP-3 system, which is augmented by MMP-2, plays an important role in the pathogenesis of LV hypertrophy.
Abstract 379: Enhancement of TRPC6-mediated Ca
2+
Entry in Pulmonary Artery Smooth Muscle Cells of Idiopathic Pulmonary Arterial Hypertension Patients
Authors: Yu Ying , Safrina Olga , Platoshyn Oleksandr , Cahalan Michael D , Rubin Lewis J , Yuan Jason X
Published: July 2021

Background & Hypothesis:
Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and sustained pulmonary vasoconstriction are thought to play critical roles in the development of idiopathic pulmonary arterial hypertension (IPAH). Recently, we demonstrated that upregulation of the canonical transient receptor potential 6 (TRPC6) channel contributes to excessive proliferation of PASMCs isolated from IPAH patients. This study aimed at characterizing whether up-regulated TRPC6 expression affects resting cytosolic [Ca
2+
] ([Ca
2+
]
cyt
) level and Ca
2+
entry in PASMCs of IPAH patients.

Methods & Results:
[Ca
2+
]
cyt
was measured by fluorescence ratio video imaging with the Ca
2+
indicator fura-2. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a cell-permeable diacylglycerol analog that activates TRPC6 channels, was used to stimulate channel activities in the presence of extracellular Ca
2+
. The resting [Ca
2+
]
cyt
andOAG-mediated increase in [Ca
2+
]cyt were significantly higher in PASMCs from IPAH patients compared to PASMCs isolated from secondary pulmonary artery hypertension and normotensive patients. In PASMCs from IPAH patients, inhibition of TRPC6 expression by adenovirus-mediated siRNA specifically targeted the human TRPC6 gene led to an approximately 90% reduction of TRPC6 mRNA and protein levels and significantly attenuated OAG-mediated increase in [Ca
2+
]
cyt
. Treatment of the IPAH-PASMCs with siRNA also decreased the resting [Ca
2+
]
cyt
and significantly inhibited cell proliferation in comparison to cells treated with scrambled control siRNA. Furthermore, exogenous overexpression of human TRPC6 increased the resting [Ca
2+
]
cyt
and enhanced OAG-mediated Ca
2+
entry in normal PASMCs.

C

onclusions:
These results suggest that upregulation of TRPC6 channels in PASMC from IPAH patients serves as an important pathway for agonist-mediated Ca
2+
entry, mitogen-mediated PASMC proliferation and, ultimately, pulmonary vascular remodeling. Targeting TRPC6 expression and function in PASMCs would help develop novel therapeutic approaches for IPAH patients.
Abstract 2665: Cellular Cardiomyoplasty: Optimizing Cellular Dosage and Retention by Microencapsulation
Authors: Kindi Adil H AL , Chen Guang Yong , Asenjo Juan Francisco , Ge Yin , Bhathena Jasmine , Chiu Ray C , Prakash Satya , Shum-Tim Dominique
Published: July 2021

Objective:
There is no consensus regarding the optimal dose of marrow stromal cells (MSCs) for cellular cardiomyoplasty via direct intramyocardial implantation. Previous studies also demonstrated massive cells loss after injections due to myocardial contraction. Here we studied the dosage at which there is functional improvement, and hypothesized that cellular washout may be reduced by increasing the size of the injectate using microencapsulation.

Methods:
In
Experiment I
, 5 groups of rats (n=9/grp) underwent coronary ligation; Grp. I had no treatment; Grp. II to V received escalating 0.5x10
6
, 1.5x10
6
, 3x10
6
and 5x10
6
cells each. Echocardiogram was performed at baseline, 2 days and 6 weeks after surgery to measure ejection fraction ( EF) in a blinded fashion. In
Experiment II
, fluorescent cell-sized microspheres (10 μm) were encapsulated in Alginate-Poly-l-Lysine-Alginate microcapsules in two different sizes. Each rat received intramyocardial injection of 1x10
6
microspheres. In Grp. A (n=16/grp), rats received bare microspheres, Grp. B, microspheres within 200 μm microcapsules and in Grp. C, microspheres within 400 μm microcapsules were given. After 20 minutes, hearts were harvested and the microspheres retained in the myocardium quantified.

Results:
In Experiment I
, baseline LVEF was 71 ± 1.4%. Two days post MI, EF was 30.5± 10.1% and no statistical difference between groups. EF at 7 weeks was 30± 4.3 in Grp. I, 30.2± 9.4% in Grp. II, 53.8± 11.8% in Grp. III, 54±8.2% in Grp. IV and 52.6 ± 7.5% in Grp. V. The improvement in LVEF was statistically significant between Grps. I-II and Grps. III - V. (p< 0.05, ANOVA and Tukey’s) In
Experiment II
, the microspheres retention rate was 4.3 ± 3.5% (Grp. A), 16.5 ± 7.7% (Grp. B) and 13±6.3% (Grp. C). The difference between Grp. A vs B and C was statistically significant but not between Grp. B and C . (p< 0.05, ANOVA and Tukey’s)

Conclusion:
We concluded that functional improvement in this animal model starts at 1.5 x10
6
cells, but is far from optimal. Micoencapsulation increased the retention by 4 folds. Thus this study suggests that improving mechanical retention is possible by microencapsulation of donor stem cells which may facilitate functional improvement of the damaged heart.
Abstract 2686: Can Real-Time 3D Echocardiography Be Used to Assess Myocardial Perfusion?
Authors: Bhan Amit , Kapetanakis Stamatis , Rana Bushra S , Ho Emily , Wilson Karen , Monaghan Mark J
Published: July 2021

Introduction: 2D low mechanical index (LMI) contrast specific myocardial perfusion imaging is now an accepted technique. Advancements in technology now allow us to use this technique in combination with real-time 3D echo. We assessed the hypothesis that real time 3D myocardial contrast echo (RT3DMCE) is feasible in a clinical setting.

Methods: 46 consecutive patients (24 male) referred for contrast enhanced echocardiography were imaged using a 3D scanner equipped with novel 3D LMI power modulation software. All patients underwent 2D contrast echo and real-time 3D apical full volume acquisition, during contrast infusion. Datasets were taken in left ventricular opacification (LVO) and LMI perfusion modes. These were then evaluated segmentally for wall motion and myocardial contrast enhancement, relative to the LVO mode.

Results: A total of 736 left ventricular segments were analysed. Wall motion and perfusion could be assessed in 726 (98.6%) and 721(98%) respectively of the 2D segments and 708 (96.2%) and 701(95.2%) of the 3D segments. Although p=<0.05 for these comparisons, they showed good agreement: 97.6% (
kappa
0.52) for wall motion and 97.3% (
kappa
0.61) for perfusion. 661 segments had normal wall motion and thickening in 2D. Of these, normal 3D myocardial opacification was seen in 91.8% of apical, 85% of mid and 77.2% of basal segments. 34 segments were akinetic with no 2D evidence of perfusion and of these RT3DMCE successfully identified a perfusion defect in 31 (91% p=NS).

Conclusion: Evaluation of myocardial perfusion using RT3DMCE is feasible in most segments. In the future it has the potential to specify accurate location of perfusion defects and quantify volumes.
Abstract 2707: The Magnitude of Health Care Resource Utilization by Medicare Beneficiaries with Heart Failure
Authors: Page Robert L , Strongin Kara B , Mills Roger M , Hogan Christopher , Lindenfeld JoAnn
Published: July 2021

Introduction:
By 2010, the number of individuals ≥ 65 years with a heart failure (HF) diagnosis should increase by an additional 700,000. As the financial burden of HF is expected to substantially increase, we examined health care expenditures of Medicare beneficiaries with HF to estimate the current healthcare costs and resource allocation.

Methods:
An analysis of 2005 Medicare claims was conducted, using a 5% sample standard analytic and denominator file, limited data set version to extrapolate the 34,150,200 Medicare beneficiaries. The cohort was defined by the Centers for Medicare and Medicaid Services Hierarchical Condition Categories Model which requires one HF diagnosis from a physician or hospital outpatient department/inpatient bill. HMO enrollees, persons without Part A and Part B coverage, and those outside the United States were excluded.

Results:
Based on inclusion criteria, 260,076 beneficiaries were identified. Beneficiaries with HF accounted for 13% of the total beneficiary population and 37% of all Medicare spending. Reimbursement for hospital inpatient admissions, physician visits, and hospital outpatient visits accounted for $12,556; $5,875; and $2,753 per-capita, respectively. In one year, 22% of all beneficiaries required hospitalization compared to 59% of beneficiaries with HF. Thirty-one percent of beneficiaries with HF had ≥ 2 inpatient admissions. Twenty-four percent of all hospital discharges were for HF, either as a principal diagnosis or co-morbidity, accounting for $30.4 billion. On average, 8.3 different outpatient and inpatient providers ordered services for a single beneficiary. Beneficiaries with at least two prior HF hospitalizations within the index period had on average 3.04 physician visits every three months. Only 26% of these visits were conducted by a cardiologist.

Conclusion
: Medicare beneficiaries with HF impose a tremendous burden on Medicare, consisting of over one-third of Medicare spending. It will be important to determine how much of this burden is due to HF and how much to comorbid conditions. Development of specialized Medicare HF Management Programs, also providing comprehensive care for co-morbidities, could curtail these admissions and potentially reduce costs.
Abstract 2710: Emergency Room Utilization of Continuous Intravenous Furosemide Together With the American Heart Association Get With the Guideline Heart Failure Care (GWTG-HF) Decreases Length of Stay for Hospitalized Heart Failure Patients at St. Joseph’s Regional Medical Center (SJRMC)
Authors: Faillace Robert T , Pruden James , Adinaro David , Marut Lorraine , Matza Ilene , Sarimento Lucena , Cahill Kathleen , Bogdanowicz Eileen , Smith Deborah , Manke John
Published: July 2021

The main goals of therapy for hospitalized congestive heart failure (CHF) patients are to achieve euvolemia and to administer optimal standards of care. No study to date has examined ways to implement use of continuous intravenous furosemide (IVF) in the Emergency Room (ER) and ensure that each CHF patient consistently receives optimal standards of care throughout their hospitalization. Therefore, we hypothesized that a multi-disciplinary team approach with coordination of care from ER arrival to discharge (DC) with use of the AHA GWTG-HF Program will decrease length of stay (LOS) and provide optimal care for CHF patients as compared to usual care.

METHODS:
GWTG-HF was operational in 2006 with a multi-disciplinary team consisting of a Physician Champion, Advanced Practice Nurses (APNs), Case Managers and RNs. In June of 2006 the IVF program was implemented in coordination with the ER, Cardiology and Medicine Departments. ER physicians were prompted by an electronic medical record provider order entry (EMR-POE) CHF order set. GWTG-HF APNs followed these patients throughout their hospitalization. We compared the average LOS of CHF patients who received usual care in 2005 (Group I) to CHF patients who received IVF and GWTG-HF care from 6/06 to 4/07 (Group II).

RESULTS:
CHF cases in Group I equaled 773 as compared to 212 cases in Group II. Average LOS in I was 6.7 days as compared to 5.5 days in II (p = 0.001). Overall compliance with GWTG-HF Core Measures in 2006 was 98%.

CONCLUSIONS:
1. Implementation of IVF in the ER with an EMR-POE order set helps ensure utilization of IVF in the ER at time of admission for CHF patients; 2. A multi-disciplinary team approach with use of IVF along with GWTG-HF is associated with a significant decrease in the LOS as compared to usual care; 3. A multi-disciplinary team approach to care for the CHF patient is superior to usual care with regards to LOS; and 4. GWTG-HF is associated with a high compliance with standards of hospitalized CHF care.
Abstract 2722: Large Scale Mutation Discovery Screen Identifies Functionally Variant UGDH Alleles in Patients with Atrioventricular Valve Defects
Authors: Bakkers Jeroen , Chocron Sonja , Gouriev Victor , Smith Kelly , Deprez Ronald Lekanne dit , Joziasse Irene C , Doevendans Pieter A , Mulder Barbara J , Simpson Melanie , Barycki Joseph , Cuppen Edwin
Published: July 2021

Background: Congenital heart defects are the most common birth defects. Although genetic dispositions are believed to cause CHDs, only few genes have been identified that harbour mutations causing such defects. Studies in model organisms have identified many essential genes for cardiac development. UDP-glucose dehydrogenase (UGDH) enzymatic activity is required for the signal transduction of FGF and Wnt ligands and zebrafish jekyll/ugdh mutations lack AV valves.

Methods and Results: From literature candidate genes were selected that are essential for AV canal-, septum-, and valve formation. By large scale sequencing we analysed the coding regions of 36 candidate genes in 192 patients with reported AVSDs. As a result we identified 457 genetic variations of which 207 variants are in flanking non-coding regions, 156 variants are in coding regions but silent and 94 variants are non-synonymous variants that alter the protein sequence. Comparison with the available databases such as HapMap and screening 350 control individuals resulted in the validation of 49 non-synonomous missense mutations in 23 genes only present in the patient group. These included novel GATA4 missense mutations (R285C and M224V) located in the highly conserved DNA binding domains, which by in vitro analysis significantly reduce transcriptional activity of the protein. Three patients with mitral valvar prolapse and mitral regurgitation were identified with novel missense mutations in the UDP-glucose dehydrogenase (UGDH) gene (R141C and E416D). In vitro experiments demonstrated a negative affect on enzyme activity and stability by a change in protein conformation. Furthermore, experiments in zebrafish jekyll/ugdh mutants showed that UGDH R141C and UGDH E416D couldn’t rescue the defects in AV formation demonstrating an inactivating effect of these missense mutations in vivo.

Conclusions: A model organism based candidate gene screen in CHD patients resulted in the identification of novel functional missense mutations in the UGDH gene not previously implicated in congenital heart defects.
Abstract 385: Endothelial Vasomotor Dysfunction in Brachial Artery Predicts Early Renal Dysfunction in Patients with Coronary Artery Disease
Authors: Nakamura Takamitsu , Hirano Mitsumasa , Kitta Yoshinobu , Kodama Yasushi , Obata Jun-ei , Takano Hajime , Kawabata Ken-ichi , Sano Keita , Mende Akira , Kugiyama Kiyotaka
Published: July 2021

There is an intimate relation between coronary artery disease (CAD) and chronic kidney disease. Endothelial function in renal vasculature plays an important role in regulation of renal hemodynamics in normal and pathological states. Endothelial dysfunction is a systemic disorder, and there may be possible relation of endothelial function between brachial artery and renal vasculature. We examined whether endothelial vasomotor dysfunction in brachial artery may predict early renal dysfunction in patients with CAD.

Methods and Results:
Flow-mediated endothelium-dependent dilation (FMD, % increase in diameter from baseline) in brachial artery was measured by ultrasound in 558 consecutive patients with CAD. Patients with advanced renal failure (glomerular filtration rate [GFR] < 50 mL/min/1.73 m
2
) were not included. A subgroup of 402 patients with normal renal function at the enrollment (normo-albuminuria [< 30 mg/day] and normal serum creatinine levels [< 1.0 mg/dL]) were prospectively followed up for 1 year. The end point was the occurrence of either microalbuminuria (≥ 30 mg/day) or serum creatinine levels > 1.5 mg/dL. At the enrollment, patients with impaired FMD (≤ 4.4%, 50
th
percentile of the distribution in all study patients) had higher levels of urine albumin excretion (24 ± 2 vs. 17 ± 1 mg/day, p < 0.05) and serum creatinine (0.8 ± 0.1 vs. 0.5 ± 0.1 mg/dL, p <0.05), and lower GFR (72 ± 3 vs. 80 ± 2 mL/min/1.73 m
2
, p < 0.05) than patients with preserved FMD (> 4.4%). Over 1 year follow up, 30 (17%) patients with impaired FMD had an end point (12 patients, increase in serum creatinine levels; 18, microalbuminuria), while 15 (6.7%) patients with preserved FMD had an end point (6, increase in serum creatinine levels; 9, microalbuminuria) (p < 0.01). Using multivariate logistic analysis, impaired FMD was the most strongest predictor of occurrence of either increase in serum creatinine levels or microalbuminuria during 1 year follow up (OR; 2.8, 95% CI; 1.5 – 5.5, p < 0.01) among covariates including hypertension, diabetes, age.

Conclusion:
Endothelial vasomotor dysfunction in brachial artery is an independent predictor of development of early renal dysfunction in patients with CAD. Measurement of FMD is useful for stratification of risk for future renal dysfunction.
Abstract 2753: Predicting Success of Prospective Gating in Dual Source Coronary CTA: Development of a Model and Initial Experience
Authors: Gutstein Ariel , Lee Cynthia , Wolak Arik , Dey Damini , Oba Muneo , Gransar Heidi , Slomka Piotr , Suzuki Yasuyuki , Suzuki Shoji , Friedman John , Thomson Louise E , Hayes Sean , Berman Daniel S
Published: July 2021

Background:
Prospectively gated (PG) coronary CTA (PG-CCTA) with dual source CT (DSCT) allows dramatic reduction of radiation burden, but requires prospective phase selection and assessment of likelihood of adequate image quality. We developed and tested the model for predicting success of PG-CCTA

Methods:
Retrospectively gated (RG) CCTA was acquired with DSCT in 103 consecutive pts. Two experienced assessed by consensus whether diagnostic quality images could have been obtained in a single predefined phase (70% of RR interval), thereby identifying pts in whom PG scan would be successful. Potential predictors of success entered in a model included age, BMI, coronary calcium score (CCS), beta-blocker use, average HR (HR), and HR variation during CCS acquisition before CCTA. The model was subsequently applied in 9 consecutive pts

Results:
Of 1633 coronary segments (segs) assessed in 103 pts with RG-CCTA, 28 (0.2%) in 12 pts were unevaluable, and 63 segs (0.4%) in 16 pts required phase change. HR was ≤ 70 BPM during CCS acquisition in 83 pts (80.6%), of whom 59 (71%) could be analyzed with a single 70% RR phase compared to only 10% of pts with HR>70. By logistic regression HR ≤ 70 ( OR= 0.024, p<0.0001), HR variation / 5 BPM ( OR = 0.88, p=0.04), CCS / 100 ( OR=0.84, p=0.01) and BMI (OR 0.9, p=0.04) were independent predictors of a successful single phase CCTA. Over 90% of pts with HR<70 and CCS<100 could be analyzed with 70% RR phase (Figure

). Applying this model, 9 consecutive pts had excellent PG CCTA with low radiation dose (3.1±0.4 mSv) vs 15.9±5.2mSv for RG-CCTA (p<.0001).

Conclusion
: PG-CCTA drastically reduces radiation dose and is feasible with HR 3 70, low pre-scan HR variation and low CCS.