bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 1035: Analysis of the Mechanisms Responsible for the Genesis of the Complex Fractionated Atrial Electrogram During Atrial Fibrillation Using 3D Non-Contact Mapping System
Authors: Yamabe Hiroshige , Morihisa Kenji , Tanaka Yasuaki , Uemura Takashi , Enomoto Koji , Ogawa Hisao
Published: July 2021

Complex fractionated atrial electrogram (CFAE) region has been implicated as the substrate of atrial fibrillation (AF). However, how its electrogram morphology is generated has not been precisely evaluated. The purpose of this study was to investigate the mechanisms responsible for the genesis of the CFAE during AF. In 16 patients with paroxysmal AF, endocardial mapping of the left atrium was performed during AF using 3D non-contact mapping system (EnSite 3000). After localization of CFAE region, we examined the activation sequence of the wave during AF. Then, we compared the conduction velocity of the wave, frequency of wave break-up and wave fusion, and frequency of pivoting activation observed during AF between CFAE and non-CFAE regions. The CFAE was located in the roof (100%), anterior (50%), posterior (56%), pulmonary vein (PV) (81%), appendage (81%) and septum (81%), respectively. The area of CFAE was 13.4±5.0 cm2. During AF, 1 to 4 meandering reentrant waves with a maximum number of 2.3±0.7 were observed. The conduction velocity of the wave at the CFAE region was significantly slower than that at the non-CFAE region (0.65±0.38 vs. 2.31±0.89 m/second, p<0.0001). In addition, there were frequent episodes of pivoting conduction, wave break-up and wave fusion in the CFAE region, which were resulted in the generation of the multiple deflections of the local electrogram in the CFAE region. Thus, the frequency of the pivoting conduction (5.0±2.1 vs. 0.3±0.8 times/second, p<0.0001), wave break-up (5.5±3.8 vs. 0±0 times/second, p<0.0001) and wave fusion (6.5±5.8 vs. 3.6±3.1 times/second, p<0.05) at the CFAE region were significantly higher than those at the non-CFAE region. At the CFAE region, the wave break-up produced a new wave and the fused waves were organized into a new wave, then propagated to the next adjacent excitable region, resulted in the perpetuation of reentrant wave propagation. The multiple deflections of the electrogram at the CFAE region was generated by the slow conduction, frequent episodes of pivoting conduction, wave break-up and wave fusion. These features imply that CFAE region provide an important substrate for the perpetuation of reentrant wave propagation and maintenance of AF.
Abstract 1059: Left Atrial Volume and E/E′ Ratio are Most Predictive of Exercise Capacity in Hypertrophic Cardiomyopathy
Authors: Le Vy-Van , Perez Marco , Wheeler Matthew , Schnittger Ingela , Ashley Euan
Published: July 2021

Hypertrophic cardiomyopathy (HCM) is characterized by LVH and myocardial disarray which result in ischemia, diastolic dysfunction and arrhythmias. While many experience functional limitation, the precise mechanisms are still unknown. We aim to determine the relation between echocardiogram findings and exercise capacity. We studied 48 patients (48 ± 15 years; 15 females) referred for symptom-limited cardiopulmonary testing and stress echocardiography for clinical reasons: 23 had a proximal HCM pattern (group I), 7 had a classic reverse curvature pattern (group II), 4 had an apical pattern (group III) and 14 had a concentric pattern (group IV). At baseline, patients in group I were significantly older than in other groups (54 ± 13 (I) vs. 41 ± 12 (II), 38 ± 12(III) and 44 ± 17 years (IV); p=0.04). No other significant difference in clinical characteristics was noted between groups. The maximal septum thickness was higher in groups I and II than in III and IV (19 (16 – 23), 22 (17–33), 17, and 16 (13–18) mm, respectively; p=0.05). Groups I and II were more likely to have resting gradient of >10 mm Hg (68% and 18%, respectively vs. 14% in IV; p=0.01) and to present rest systolic anterior movement (74% and 15% vs. 11% in IV; p <0.001). A higher prevalence of abnormal transmitral inflow E to lateral E′ ratio (E/E′) was also noted in Group I (80%, p=0.05): high ratios are known to be associated with high pulmonary wedge pressure in non-HCM populations. At peak exercise, group I achieved a lower peak VO
2
(21.8 ±2.1 vs. 27.1±6.6 in II 36.6 ±5.1 in III and 29.4 ±2.7 ml/kg/min in IV; p=0.03). No significant differences in Valsalva and exercise gradients and delta rest-to-peak gradients were noted between patterns. In age-adjusted multivariate analysis, only negative correlations between E/E′ (R2=0.45; p=0.03) and indexed LA volume (R2=0.39; p=0.009) and peak VO
2
were significant. In contrast, no correlation was found between maximal exercise capacity and LV dimensions, conventional Doppler indices of diastolic function, lateral E′ or gradients. Lateral E/E′ and indexed LA volume are negatively correlated with functional capacity even after age-adjustment. Although patients with proximal HCM achieved the lowest peak VO
2
, gradient and morphology were not related to exercise capacity.
Abstract 1065: A New Method for Stem Cell Imaging Using Contrast Ultrasound
Authors: Cui Wenjin , Chen Xucai , Wang Jianjun , Fisher Andrew , Kim Kang , Carson Andrew , Kripfgans Oliver D , Haworth Kevin J , Wagner William R , Villanueva Flordeliza S
Published: July 2021

Background
: Mesenchymal stem cells (MSCs) are a promising new cardiac reparative therapy. The distribution of delivered MSCs is poorly understood due to limited methods to track them
in vivo
. To test the hypothesis that ultrasound can detect MSCs, gas-filled microbubbles (MBs) were developed for MSC uptake.

Methods
: Perfluorocarbon gas-filled MBs were synthesized from a biodegradable polymer. Cultured rat and human bone-marrow derived MSCs were dwelled with MBs (12 hrs), washed, and suspended in medium. MSC uptake of MBs and MB retention of gas were confirmed with transmission electron microscopy (TEM) and density centrifugation. Spectral analysis of free MB response to up to 10MHz ultrasound was performed. 2nd harmonic and contrast pulse sequence (CPS) 2D echo imaging (7MHz) of MB-labeled and unlabeled MSCs was performed at a mechanical index (MI) 0.3 and 1.9. Videointensity was measured in 200 frames/capture.

Results:
Frequency spectra of free MBs contained 2nd and 3rd harmonics, indicating MB non-linearity. TEM showed MBs within MSCs (Figure

). By density centrifugation, MSCs with MBs were less dense than MSCs alone, confirming intracellular MB gas retention. Videointensity (gray scale units) of MSCs containing MBs vs MSCs alone was higher at both low MI (35±2 vs 0±0 harmonic, p<0.005; 21±2 vs 15±0 CPS, p<0.005), and high MI (14±2 vs 6±1 harmonic, p<0.005; 6±2 vs 0±0 CPS, p<0.005).

Conclusions
: Our acoustically active polymer MBs are internalized by MSCs and render them detectable with ultrasound. Because the polymer degrades slowly, this approach may permit serial non-invasive
in vivo
ultrasound imaging of MSC fate, thus facilitating optimization of cell therapy strategies.
Abstract 1066: Ultrasound-targeted Plasmid Delivery of Vascular Endothelial Growth Factor and Angiopoietin-1: Combination Gene Therapy for Therapeutic Angiogenesis
Authors: Smith Alexandra H , Kuliszewski Michael A , Fujii Hiroko , Stewart Duncan J , Lindner Jonathan R , Leong-Poi Howard
Published: July 2021

We have previously shown that ultrasound-mediated (UM) delivery of vascular endothelial growth factor (VEGF) plasmid-bearing microbubbles promotes therapeutic angiogenesis. While VEGF is important during the initiation of angiogenesis, it results in primarily immature vessels, which are prone to late regression. Angiopoietin (Ang)-1 is a potent growth factor that acts to stabilize the neovasculature, later in the angiogenic process. We hypothesized that temporal delivery of VEGF and Ang-1 plasmid DNA would result in a more sustained angiogenic response, as compared to VEGF alone, in the setting of severe chronic ischemia.

Methods
: Unilateral hindlimb ischemia was produced by iliac artery ligation in 30 rats. At day 14 post-ligation, microvascular blood velocity (β) and flow (MBF) in the proximal hindlimb muscles were assessed by contrast-enhanced ultrasound (CEU). UM-delivery of plasmid (500 μg cDNA)-bearing microbubbles (1×109), was then performed at pre-specified time points, with treatment groups including

VEGF alone at day 14;

VEGF at day 14 followed by Ang-1 at day 28; and

control rats receiving no therapy (n=10 per group). β and MBF were re-assessed at day 28 and 8 wks post-ligation.

Results
: Relative MBF (normalized to the contralateral normal leg) remained reduced at all time points after ligation in the control group. In VEGF-alone treated animals, MBF in the ischemic leg increased 2 wks after delivery (0.48 ± 0.19 to 0.82 ± 0.23, p < 0.001), but regressed over the next 4 wks (0.61 ± 0.14 at 8 wk, NS vs. 2 wks). In the VEGF/Ang-1 treated animals, MBF in the ischemic leg also increased 2 weeks after VEGF delivery (0.39 ± 0.19 to 0.69 ± 0.28, p < 0.01); however, vascular regression was prevented by late Ang1 delivery (0.83 ± 0.20 at 8 wks, p < 0.005 vs. 2 wks and p<0.01 vs VEGF alone at 8 wks). At week 8, relative β values were greater in VEGF/Ang-1 treated compared to VEGF-alone treated animals (0.87 ± 0.33 to 0.60 ± 0.23, p < 0.05).

Conclusions
: Compared to delivery of VEGF alone, delivery of Ang-1 plasmid DNA at 2 wks post-VEGF gene delivery results in sustained improvement in MBF, with prevention of late vascular regression. The greater microvascular blood velocity in VEGF/Ang-1 treated muscle may signify improved vascular functionality with late Ang-1 therapy.
Abstract 1068: Evaluation of Malignant and Benign Cardiac Masses by Quantitative Real-Time Contrast Echocardiography
Authors: Uenishi Eliza K , Mathias Wilson , Caldas Marcia Azevedo
Published: July 2021

Primary tumors of the heart are rare, most of them benign. However the differential diagnosis between benign and malignant tumors is very difficult. Quantitative Real-time Contrast Echocardiography(QRTCE) can evaluate the vascularity of cardiac masses and therefore help in characterizing the nature of cardiac masses. To evaluate the perfusion of cardiac masses and to compare the quantitative perfusion parameters of malignant and benign cardiac tumors by QRTCE. We studied 42 patients with cardiac masses, 23(54.8%) women, mean age 47.2±17.9 years old, 23(54.8%) with malignant tumor and 19 (45.2%) with benign tumors. Contrast-enhanced images were obtained after intravenous administration of PESDA(perfluorocarbon-exposed sonicated dextrose and albumin) or Definity®(lipid-encapsulated microbubbles) contrast. Q-lab software was applied to quantitative the perfusion of mass and adjacent cavity. The CE-derived rate of microbubble velocity(β), blood volume(A), blood flow(A × β) and relative blood flow(A/Acavity × β) were obtained by curve fitting of videointensity versus time plots, after the transient destruction of microbubbles by high-energy ultrasound. All malignant cardiac and 16 benign masses were confirmed by pathology. Blood velocity (β) was greater in the malignant than benign mass (1.4±2.04 × 0.71±0.48 dB, p=0.001). Malignant and benign mass A, A×B and A/Acavity × β values were 4.11±3.99 × 3.4±2.53, p=0.095; 3.69±3.95 × 2.85±3.36, p=0.113; 0.18±0.24 × 0.13±0.17, p=0.442; respectively. The malignant tumors were primary cardiac lymphoma (n=2), mediastinal lymphoma (n=5), pericardial mesothelioma(n=1) and metastatic tumors(n=15). Myxoma (n=15), lypoma(n=1), paraganglioma(1) and rabdomyoma(n=2) constituted the benign masses. QRTCE provides important information to differentiate the nature of cardiac masses by the demonstration of higher values of resting myocardial blood flow.
Abstract 1070: Targeted Delivery of Macromolecules Using Ultrasound and Microbubbles is Regulated by Induction of Endocytosis and Pore Formation
Authors: Juffermans Lynda J , Meijering Bernadet D , Kooiman Klazina , Emmer Marcia , van Wamel Annemieke , Musters Rene J , Henning Rob H , Zuhorn Inge S , Deelman Leo E , van Gilst Wiek , de Jong Nico , Kamp Otto
Published: July 2021

Ultrasound (US) contrast microbubbles are promising vehicles for local drug and gene delivery. However, the exact mechanisms behind intracellular delivery of therapeutic compounds remain to be resolved. We hypothesized that endocytosis and pore formation are involved during US and microbubble targeted delivery (UMTD) of therapeutic compounds. Primary bovine aortic endothelial cells were subjected to UMTD of fluorescent dextrans (4.4 – 500 kDa) using 1-MHz US during 30s with 0.22 MPa peak-negative pressure. Duty cycle: 6.2%, pulse repetition frequency 20 Hz. Confocal laser microscopy showed the localization of 155 and 500 kDa dextrans in distinct vesicles after UMTD, indicating uptake via endocytosis. Independently inhibiting the main routes of active cellular uptake, i.e. clathrin- and caveolae-mediated endocytosis and macropinocytosis, caused significant decreases of 50 – 70% in intracellular delivery of 4.4 – 500 kDa dextrans (p<0.05). Furthermore, 3D immunofluorescence microscopy demonstrated dextran vesicles (500 kDa) to co-localize with both clathrin and caveolin-1. Finally, after energy depletion no uptake of 500 kDa dextran was observed after UMTD. In addition to triggering endocytosis, UMTD evoked transient pore formation, suggested by the homogeneous distribution through the cytosol of the 4.4 and 70 kDa dextrans. Formation of transient pores in the cell membrane was further supported by the influx of Ca2+ measured by live-cell fluorescence microscopy. This influx (peak mean fluorescence intensity (MIF) 186.4±3.4%) was not affected by the L-type Ca2+ channel blocker verapamil (MIF 172.5±3.2%), but significantly attenuated in a Ca2+ free buffer (MIF 111.1±2.0%, p<0.001). Finally, cells pre-loaded with fluorescent dextrans showed a significant decrease (p<0.05) of cytosolic fluorescence after US and microbubble exposure (4.4 kDa: 63.4±2.1%) and (155 kDa: 79.1±2.3%), compared to cells not exposed to US and microbubbles (100%). Endocytosis is a key mechanism of UMTD besides transient pore formation. The contribution of uptake via pores is dependent on molecular size. These findings are pivotal for optimizing US and microbubble intracellular delivery of therapeutic compounds.
Abstract 1096: Cytokine Enhancement with Hgf Or Vegf in the Infarct Border Zone is Key to Attenuating the Negative Remodelling after Myocardial Infarction
Authors: Schrepfer Sonja , Deuse Tobias , Peter Christoph , Stein William , Doyle Tim , Zimmermann Wolfram H , Eschenhagen Thomas , Pelletier Marc P , Wu Joseph , Robbins Robert C
Published: July 2021

Adult mesenchymal stem cell (MSC)-based treatment strategies have been proposed to alleviate the consequences of myocardial infarction (MI). The cytokine release of ischemic myocardium was investigated in vivo after LAD ligations in mice and in vitro in cultured cardiomyocytes. Of all cytokines that were at least 5-fold upregulated during ischemia, only HGF and VEGF proved to promote MSC proliferation, and chemotaxis in vitro. Homing of intranenously (IV) injected MSCs (0.5×106 per animal) into the infarct border zone after LAD ligation was inefficient (1±0.5 cells/HPF). Cytokine enhancement (CE) of HGF or VEGF by intramyocardial injection at the time of MI significantly facilitated MSC homing (11±4 cells/HPF and 7±4 cells/HPF, respectively; p=0.001). To our knowledge, this is the first study monitoring cardiac geometry and function over a long-term period of 6 months. using ECG-triggered contrast Micro-CT. It revealed that the progressive decrease in EF over time (to 19±1%) could be attenuated by CE with HGF (29±6%; p=0.003) or VEGF (28±4%; p=0.004) and subsequent IV MSC injection. However, LVEFs of animals treated with CE with HGF or VEGF only, but received no MSC injection, were similar to those groups that also received IV MSCs (p=0.127 and p=0.54, respectively). Best results were finally achieved by prolonged presence of HGF or VEGF, achieved by intramyocardial injection of MSCs stably transfected to produce HGF or VEGF and firefly luciferase into the infarct border zone. Duration of cytokine release was estimated by monitoring MSC survival using in vivo bioluminescence imaging (BLI). BLI signals were detectable for 10 days in contrast to the rapid fate of the cytokines after single dose administration in the CE group, resulting in preserved LVEFs at 6 months This study highlights the beneficial effect of HGF and VEGF to attenuate the negative LV remodelling after MI and diminishes the role of the MSCs to a pure delivery system for paracrine effects.
Abstract 1148: Local Hypercoagulability and Endothelial Dysfunction after Sirolimus-Eluting Stent Implantation: Implication for Late Stent Thrombosis
Authors: Yamaguchi Koji , Wakatsuki Tetsuzo , Niki Toshiyuki , Kusunose Kenya , Koshiba Kunihiko , Yagi Syusuke , Iwase Takashi , Yamada Hirotsugu , Soeki Takeshi , Akaike Masashi , Sata Masataka
Published: July 2021

Endothelial dysfunction is known to cause hypercoagulability. The long-term effects of sirolimus-eluting stent (SES) on endothelial function are not known. We evaluated endothelial function and local hypercoagulability more than six months following SES or bare metal stent (BMS) implantation. Forty-three patients treated six months earlier with a coronary stenting for isolated proximal left anterior descending (LAD) stenosis, with no evidence of restenosis, were studied. Sixteen patients had been stented with BMS, and 27 had been with SES. Changes in diameter at distal site of the stented LAD in response to intracoronary acetylcholine infusions (30μg/min) were assessed by quantitative angiography. We also measured plasma levels of prothrombin fragment F1+2 (F1+2) and D-dimer sampled in coronary sinus (CS) and sinus of Valsalva (V). The mean percent change in the diameter of the stented LAD was significantly more in the SES group than in the BMS group (−33.4±5.9 vs. −19.8±6.0%, p<0.05). The translesional F1+2 gradient [F1+2(CS) minus F1+2(V)] and D-dimer gradient were greater in the SES group than in the BMS group (0.52±0.68 vs. −0.10±0.29 nmol/l, p<0.05 and 0.22 ±0.38 vs. −0.12±0.35 μg/ml, p<0.05, respectively). An increased local coagulative response and more severe endothelial dysfunction were observed long term after SES implantation as compared to BMS. In the SES group, delay of endothelial regrowth might be associated with our findings.
Abstract 2006: Contrast-Enhanced MRI in the Hyperacute Phase of ST-Elevation Myocardial Infarction Predicts Late Myocardial Recovery
Authors: Larose Eric , Rodes Josep , Nguyen Can , Proulx Guy , Gleeton Onil , Dery Jean-Pierre , Noel Bernard , Barbeau Gérald , Roy Louis , Amyot Marc , Delarochellière Robert , Bertrand Olivier
Published: July 2021

Left ventricular ejection fraction (EF) late after myocardial infarction determines whether patients will benefit from cardioverter/defibrillator (CV/D) implantation. At present, patients with acute ST elevation myocardial infarction (STEMI) are evaluated several months later to determine EF and CV/D indication following initial recovery. We determined whether contrast-enhanced MRI (CE-MRI) in the hyperacute phase of STEMI could predict late myocardial recovery. 50 patients with STEMI underwent CE-CMR within 12 hours of primary angioplasty (median 4h). All had follow-up CE-CMR >6 months later. Global and segmental left ventricular function, morphology, perfusion and necrosis were determined and assessed by validated techniques (QMass, Medis, the Netherlands). In the hyperacute phase of STEMI, a greater cardiac output (4.2 vs 3.4 L/min, p=0.01) was measured due to significantly greater heart rate (72 vs 57 bpm, p<0.01) despite similar stroke volumes (59 vs 60mL, p=NS) compared to >6 months later. On average, LVEF did not significantly change from hyperacute STEMI to recovered phase (51 vs 54%, p=NS) but systolic wall thickening increased on average from 41 to 50% (p=0.01) due to compensatory increased systolic thickening of non-infarct related segments. LV mass decreased from 120 to 105 g (p=0.01) due to a decrease in mean wall thickness driven by infarct segment wall thinning (9.2 vs 8.4mm, p<0.01). Microvascular function improved significantly (time to 50% enhancement on first-pass CE-MRI: 24.3 vs 21.7ms, p=0.03). Contrary to prior reports of “scar shrinkage” comparing necrosis in the first week after STEMI and 6 months later, necrosis relative to total myocardial volume did not differ between the hyperacute phase and >6 months (20 vs 18%, p=0.46). Furthermore, the transmural extent of necrosis, a potent predictor of functional recovery, did not significantly change from the hyperacute to the recovered phase of STEMI (mean 17 vs 14%, p=0.38). CE-MRI in the hyperacute phase of STEMI is a powerful predictor of long-term myocardial function and necrosis which could prove useful for very early risk stratification and future targeting of appropriate therapies.
Abstract 2011: A Simple Nomogram to Predict the Probability of Successful Reperfusion with Pre-Hospital Thrombolysis
Authors: Bongard Vanina , Puel Jacques , Savary Dominique , Charpentier Sandrine , Belle Loic , Loubeyre Christophe , Miljkovic Darko , Ingelheim Boehringer , Cottin Yves , Steg Philippe G , Elbaz Meyer
Published: July 2021

In ST-elevation myocardial infarction (STEMI), coronary recanalisation is a prerequisite for deriving benefit from thrombolysis, but achieving myocardial reperfusion is also key to benefit. Data regarding the impact of thrombolysis on myocardial reperfusion are scarcer than for recanalisation, especially when pre-hospital thrombolysis is considered. To develop a nomogram for predicting myocardial reperfusion after pre-hospital thrombolysis. In 2004 – 05, 800 consecutive French patients with STEMI received pre-hospital thrombolysis within 6 hours of symptom onset (median delay of 110 minutes). The assessment of myocardial reperfusion was based on the measurement of ST resolution (STR) between a first electrocardiogram (ECG), recorded before thrombolysis, and a second one in the cath laboratory. Myocardial reperfusion was assessed when STR was 70%, at least, in the single lead with the greatest baseline ST-elevation. The sample comprised 18% of women and median age was 59. The median delay between the two ECGs was 110 minutes. The proportion of patients who achieved STR was 42%. The nomogram was based on the variables that were independently associated with STR in multivariate logistic regression analysis. For instance, a non-obese smoker patient, with a non-anterior STEMI and a maximum ST-elevation of 2 mm, for whom thrombolysis is possible within 1 hour of symptom onset, together with the administration of a thienopyridine, but no IV nitrates, has a probability of 0.87 to achieve STR. If thrombolysis is delayed after one hour, without thienopyridine administration, in case of anterior STEMI, the probability declines to 0.50. The probabilities of STR for the different situations covered by the nomogram range from 0.10 to 0.87. This nomogram, developed in a “real world” setting, is designed to predict a priori the probability of myocardial reperfusion following thrombolysis, based on simple clinical and electrocardiographic data.
Abstract 2017: A Single Bolus Intravenous Administration of Sodium Bicarbonate is Effective in the Prevention of Contrast-Induced Nephropathy in Patients with Renal Insufficiency Undergoing Diagnostic Coronary Arteriography or Elective Percutaneous Coronary Intervention
Authors: Tamura Akira , Miyamoto Kumie , Naono Shigeru , Kawano Yoshiyuki , Kotoku Munenori , Watanabe Toru , Kadota Junichi
Published: July 2021

BACKGROUND:
Recent prospective studies have demonstrated that intravenous hydration with sodium bicarbonate (SB) is effective in the prevention of contrast-induced nephropathy (CIN). However, it has not yet been invetigated whether a single bolus intravenous administration of SB immediately before exposure to contrast media can prevent CIN. Accordingly, this prospective, controlled, randomized trial was designed to examine the efficacy of a single bolus administration of SB in the prevention of CIN in patients with renal insufficiency undergoing diagnostic coronary arteriography (CAG) or elective percutaneous coronary intervention (PCI).

METHODS:
A total of 144 patients with a serum creatinine level of >1.1 mg/dl and <2.0 mg/dl scheduled for diagnostic CAG or elective PCI were enrolled in this study. The patients were randomly assigned to the following 2 groups: standard intravenous hydration with sodium chloride plus a single bolus intravenous administration of SB (20 ml = 20 mEq) 5 min before exposure of contrast media (group A, n = 72) and standard intravenous hydration with sodium chloride alone (group B, n = 72). The primary end point was the development of CIN, defined as an increase of ≥25% or ≥0.5mg in serum creatinine level within 3 days after the procedure. We also evaluated the incidence of adverse clinical events, including acute pulmonary edema, acute renal failure requiring dialysis, and death within the first 7 days after the procedure.

RESULTS:
There were no significant group differences in age, gender, the frequencies of diabetes mellitus and PCI, serum creatinine at baseline, the volume of contrast media, and drugs administered. The single bolus intravenous administration of SB led to a significant increase in arterial blood pH (7.41 ± 0.04 to 7.43 ± 0.03, p <0.001). The incidence of primary end point was significantly lower in group A than in group B (1.4% vs 12.5%, p = 0.017). The incidence of adverse clinical events did not differ significantly between the 2 groups (0% vs 1.4%).

CONCLUSIONS:
A single bolus intravenous administration of SB before contrast injection is effective in the prevention of CIN in patients with renal insufficiency undergoing diagnostic CAG or elective PCI.
Abstract 2018: Comparison of Risks and Clinical Predictors of Contrast Induced Nephropathy in Patients Undergoing Primary versus Elective Percutaneous Coronary Intervention
Authors: Chong Eric , Shen Liang , Poh Kian K , Ong Hean Y , Soon Chao Y , Tan Huay C
Published: July 2021

Background:
Contrast nephropathy (CIN) post percutaneous coronary intervention (PCI) increases adverse clinical outcomes. We examine and compare the risks and clinical predictors of CIN among patients who undergo primary versus elective PCI and the effectiveness of prophylactic treatments.

Methods:
A cohort of 8798 patients who underwent PCI from May 1996 to April 2008 were enrolled. We divided patients into 3 groups(Grp). A: STEMI patient undergoing primary PCI. B: NSTEMI patients undergoing early elective PCI. C: stable patients without myocardial infarction(MI) undergoing elective PCI. Prophylactic saline hydration and oral N-acetylcysteine (NAC) treatment were given to Grp B and C if they have baseline renal impairment (glomerular filtration rate, GFR ≤60ml/min/1.73m
2
). Grp A patients were unable to receive pre-PCI prophylaxis due to emergency situation. The occurrence of CIN and mortality were compared among 3 grps.

Results:
Mean age was 57.4±11.1 years. 3146(35.9%) were diabetics. CIN occurred in 12.0% vs. 9.2% vs. 4.5% p=<0.0005, in Grp A, B, C respectively. CIN correlated with increased mortality (15.5% vs. 1.3% p<0.0005) at 1 month. Significant risk predictors of CIN are shown in table

Incidence of CIN categorized according baseline renal function based on GFR range are shown in table

Clinical predictors of CIN Incidence of CIN categorized by different GFR subgroups

Conclusion:
Saline and NAC prophylaxis are effective in preventing CIN in milder renal impaired patients (GFR 40 – 60) but are less effective in the more severely renal impaired patients (GFR<40). Patients presenting with STEMI undergoing primary PCI are at the highest risk for development of CIN. Accelerated prophylactic therapy need to be developed to reduce CIN in this cohort.

Table 1

Table 2
Abstract 2029: The Incidence, Predictors and Outcome of New Lesions Treated With Percutaneous Coronary Intervention in Patients Presenting with Myocardial Infarction
Authors: Lemesle Gilles , de Labriolle Axel , Bonello Laurent , Roy Probal , Steinberg Daniel H , Slottow Tina L Pinto , Torguson Rebecca , Kaneshige Kimberly , Xue Zhenyi , Suddath William O , Sattler Lowell F , Kent Kenneth M , Lindsay Joseph , Pichard Augusto D , Waksman Ron
Published: July 2021

Patients presenting with ST elevation myocardial infarction (STEMI) often require percutaneous treatment of lesion not targeted at the time of the primary percutaneous coronary intervention (PCI). This study aimed to detect the incidence, predictors and outcome of recurrent PCI that was not staged and not related to the initial treatment of the STEMI. Between January 2003 and December 2005, 1007 consecutive patients presenting with a STEMI were screened. Of these 94 (10.5%) pts returned within 36 months for a second PCI, not planned and not related to the index procedure at the time of the primary PCI. The baseline and the angiographic features of these patients were compared to 913 patients who did not require a subsequent PCI. Patients who were subjected for subsequent PCI were followed clinically for additional 12 months for major adverse cardiovascular events (MACE) including death, MI and target lesion revascularization (TLR). The median time to the second PCI was 396 days. The clinical presentation at the time of the recurrent PCI was a non-ST-elevation ACS in 46.1% and a new ST elevation in 9.7%. Independent predictors of recurrent PCI occurrence are detailed in the table

. At 1 year after the recurrent PCI, there were 9 (9.6%) deaths, 4 Q-Wave MI (4.3%), 4 TLR (4.3%) and 17 MACE (18%). Following STEMI, nearly 10% of patients experiencing a cardiac event that requires subsequent unplanned PCI unrelated to the initial PCI. Patients with diabetes and peripheral vascular disease are at high risk to develop such an event which is associated with high mortality and morbidity. Aggressive preventive and medical management should be applied to this population for prevention of these subsequent events.

Table:

Independent predictors of recurrent PCI by multivariate Cox analysis.
Abstract 2053: Cardiac Arrest and Resuscitation Increases Nos3-Dependent Formation of Circulating Nitrosylhemoglobin (HbNO)
Authors: Beiser David G , Orbelyan Gerasim , Chalupsky Karel , Hamann Kimm , McNally Elizabeth M , Hoek Terry L Vanden
Published: July 2021

OBJECTIVE:
To characterize the enzyme-mediated nitrosylhemoglobin production following cardiac arrest.

METHODS:
Adult female wildtype (WT, n=5) and NOS3−/− (n=8) mice were anesthetized, intubated, ventilated, and instrumented with intravascular catheters. Arrest was induced with intravenous KCl. After 8 minutes of untreated arrest, chest compression and ventilations were performed. Hemodynamics were monitored for up to 120 minutes following return of spontaneous circulation (ROSC). Electron paramagnetic resonance spectroscopy was used to measure nitrosylhemoglobin (HbNO) in whole blood samples obtained from animals (WT and NOS3−/−, n=4 per time point) sacrificed at: baseline (BL), following 8 (CA8) or 20 (CA20) minutes of untreated arrest and at 60 (R60) or 120 (R120) minutes following ROSC. Heart tissue total-NOS3 and phospho-NOS3 were assayed by Western blot.

RESULTS:
At BL, NOS3−/−animals displayed higher maximum left-ventricular pressure (LVPmax) than WT animals (113.3 ± 13.19 mmHg vs. 86.8 ± 4.48 mmHg, p<0.05). In the R120 group, ROSC was achieved in 4 of 5 (80%) WT and 4 of 8 (50%) NOS3−/− animals. Following ROSC, NOS3−/−animals displayed lower LVPmax (51.97 ± 7.429 vs. 66.95 ± 4.394 mmHg, p<0.05) and left ventricular stroke work (132.5 ± 26.28 mmHg·μL vs. 456.5 ± 128.9 mmHg·μL, p<0.05) than WT. NOS3−/− animals displayed significantly higher left-ventricular relaxation time constants (tau = 25.82 ± 6.471 ms vs. 15.45 ± 2.223 ms, p<0.05) at R120. At BL, whole blood HbNO concentrations were similar in WT and NOS3−/− animals (0.75 ± 0.10 μM vs. 0.86 ± 0.11 μM, p=0.46). In WT animals, HbNO concentrations increased during untreated arrest at CA20 (1.42 ± 0.19 μM, p<0.05) and following resuscitation at R120 (1.66 ± 0.25 μM, p<0.05) relative to BL. HbNO concentrations were lower in NOS3−/− animals as compared to WT at all time points following cardiac arrest (p< 0.05). Heart tissue from WT animals displayed increased levels of heart tissue total-NOS3 and phospho-NOS3 at R60.

CONCLUSIONS:
Circulating HbNO increases following cardiac arrest and resuscitation. Such increases appear to be NOS3-dependent and are associated with improved cardiovascular function.
Abstract 2082: A Model of Quality of Life in Adolescents with Congenital Heart Disease
Authors: Moon Ju Ryung , Jeong Soo-ln , Huh June , Kang I-Seok , Park Seung Woo , Yang Ji-Hyuk , Jun Tae-Gook , Lee Heung Jae
Published: July 2021

Objective
: This study was examined to identify the variables related to quality of life (QOL) in adolescents with congenital heart disease (CHD).

Methods
: The subjects were 266 adolescents with CHD under observation following cardiac surgery in three cardiac centers in Korea. The adolescents each completed twenty questionnaires. The exogenous variables in the model were individual risk factors, individual protective factors, family protective factors and social protective factors, while QOL and resilience were an endogenous variable. These six theoretical variables were assessed by 20 measurable variables (anxiety, depression, symptom distress, NYHA Functional class, oxygen saturation, number of operations, self-esteem, hope, attitude toward CHD, body image, academic achievement, family cohesion, family function, parental support, parental overprotection, socioeconomic status, friend support, teacher support, resilience and QOL) and 15 paths were established. Data were analysed using structural equation modelling.

Results:
The overall fit indices of the hypothetical model were χ2=26.63, GFI=.96, RMR=.02, NFI=.95, RFI=.85, IFI=.98 and PNFI=.87. All 15 paths in the hypothetical model were found to be significant(all, p<0.01). Higher resilience (t=11.93), family (t=7.88), individual (t=5.75), and social (t=4.14) protective factors were associated with increased QOL, as were lower individual risk factors (t=−5.30). Resilience had the greatest impact on QOL. Individual protective factors correlated positively with both family (t=8.88) and social (t=8.33) protective factors, while family factors correlated positively with social protective factors (t=9.31). Individual risk factors correlated negatively with family (t=−7.13), individual (t=−7.00) and social (t=−4.69) protective factors. Thus, the higher each of these protective factors was, the smaller the effect of individual risk factors.

Conclusion:
To increase the QOL of adolescents with CHD, it is important to develop a strategy to increase resilience. Furthermore, nursing interventions that will enhance individual, family, and social protective factors must be developed and implemented in order to reduce the negative effects of individual risk factors.
Abstract 2145: Recovery of Cardiac Autonomic Dysfunction after Acute Myocardial Infarction as a Predictor of Fatal of Near-Fatal Arrhythmic Events
Authors: Huikuri Heikki V , Exner Derek V , Kiviniemi Antti , Tulppo Mikko , Raatikainen Pekka , Messier Marc , Becker Daniel , Kavanagh Katherine M , Thomsen Poul-Erik Bloch
Published: July 2021

Background.
Changes in cardiac autonomic function have been documented after myocardial infraction (MI), but their significance is unknown. We assessed the amount of recovery of autonomic dysfunction after MI and its significance among the patients with depressed left ventricular ejection fraction (LVEF ≤ 0.40 - CARISMA and ≤ 0.50 - REFINE).

Methods and Results.
Changes in heart rate variability (dHRV) and turbulence (dHRT) were measured from 24-hour ECG recordings performed 5–21 days and again at six weeks post-MI in 312 patients included in the Cardiac Arrhythmias and Risk Stratification after Myocardial Infarction (CARISMA) study. The primary endpoint was sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) recorded by an implantable device. Non-arrhythmic death was a secondary endpoint. HRV and HRT measures increased significantly from baseline to six weeks post-AMI (p<0.001 for dHRV and p=0.017 for dHRT slope). The patients with attenuated recovery of autonomic function had a higher incidence of VT/VF events (n=25), e.g. those with a dHRT slope < 2.0 ms/RRi (optimized cut-off) had a hazard ratio of 10.2 (95% CI from 1.35 to 77.9, p=0.03) of experiencing the VT or VF. The change of very-low (dVLF) and low-frequency (dLF) spectral components also predicted the VT/VF events (p=0.03 for dVLF and p=0.02 for dLF). Only one patient with a dHRT slope ≥2.0 mm/RRi (n=79) experienced VT/VF event (negative accuracy 99%). Validation was performed in the Risk Estimation Following Infarction Non-invasive Evaluation (REFINE) post-MI population (n=322). Of the 24 fatal or non-fatal cardiac arrests that occurred in REFINE, all but two were identified by a lack of improvement in HRT slope as defined in CARISMA (negative accuracy 98%). The risk of fatal or non-fatal cardiac arrest was 7.0-fold (95% CI from 1.6 to 29.6; p = 0.009) higher in patients without improvement in HRT. Lack of improvement in HRT was not predictive of non-arrhythmic death in either post-MI population.

Conclusions.
Autonomic function undergoes a substantial improvement early after MI, which is associated with vulnerability to VT or VF. A marked recovery of autonomic dysfunction protects from the occurrence of fatal or near-fatal arrhythmic events after MI despite depressed LVEF
Abstract 2151: Fragmented QRS in Body Surface Potential Mapping Predicts Cardiac Death and Hospitalizations after Myocardial Infarction
Authors: Korhonen Petri , Konttila Teijo , Husa Terhi , Tierala Ilkka , Mäkijärvi Markku , Väänänen Heikki , Toivonen Lauri
Published: July 2021

Increased QRS fragmentation in visual inspection of 12-lead ECG has shown association with cardiac events in post-myocardial infarction (MI) patients. We investigated if user-independent computerized intra-QRS fragmentation analysis predicts cardiac deaths (CD) and heart failure hospitalizations (HFH) after acute MI. Patients (n= 158) with acute MI and left ventricular ejection fraction (LVEF) < 50% were studied. Mean age was 61±10 years and left ventricular ejection fraction 40 ± 6%. A 120-lead body surface potential mapping was performed at hospital discharge. After signal-averaging and binomial filtering QRS fragmentation was computed as the number of extrema within the whole QRS (fragmentation index M). QRS duration (QRSd) was computed for comparison. During a mean follow-up of 51 months 15 patients suffered cardiac death and 23 were hospitalized for HF. Both M and QRSd were significantly larger in patients with events. Using the mean value + 1SD as cut-point both parameters were univariate predictors of CD and HFH. In multivariate analysis including age, sex, LVEF, bundle branch block, previous MI, atrial fibrillation, and diabetes M was an independent predictor for cardiac death and HFH (HR 8.7 for CD and 3.8 for HFH) whereas QRSd only predicted HFH (HR 4.6). M showed adequate positive (PPA) and excellent negative (NPA) predictive accuracy, which were further improved when combined to LVEF < 40% (Table

). Increased QRS fragmentation in post-infarction patients predicts cardiac deaths and progression of heart failure. A computer-based automatic fragmentation analysis is a stronger predictor than QRS prolongation.
Abstract 2162: Mechano-energetic Superiority Of Left Ventricular Apex And Left Ventricular Septal Pacing
Authors: Mills Robert W , Mulligan Larry J , Kuiper Marion , van Hunnik Arne , Lampert Anniek , Skadsberg Nick D , van Wijk Frank , Cornelussen Richard , Prinzen Frits W
Published: July 2021

Objective:
Previous studies showed hemodynamic benefits over right ventricular (RV) apex pacing by left ventricular (LV) septal or LV apex pacing. We investigated whether this benefit is also reflected in mechanical efficiency.

Methods:
After AV-nodal ablation, dogs received 16 weeks of VDD pacing at the RV apex (RVa; n = 8), LV apex (LVa; n = 7) or LV septum (LVs; n = 8; transventricular-septal approach). After chronic pacing, LV stroke work (SW; conductance catheter) was measured, as well as relative myocardial oxygen consumption (MVO
2
, coronary flow velocity and arterial-coronary sinus O
2
difference). Baseline efficiency (SW/MVO
2
) was assessed during implant site (IS), RVa, LVa, and RVa + LV lateral (BiV) pacing. In order to investigate the effect of pacing site udner different conditions, measurements were performed during baseline and dobutamine infusion +/− partial aortic occlusion. The O
2
cost of generating SW, corrected for end-systolic elastance and effective arterial elastance, was calculated using the Suga model of mechano-energetics.

Results:
RVa pacing after chronic LV pacing reduced SW/MVO
2
(Figure a

; mean ± SD, *p<0.05 vs. 1) and increased O
2
cost (Figure b

) in combination with a 12% fall in LV dP/dt-max. However, LVa or BiV pacing after chronic RVa pacing did not significantly alter efficiency, despite a 12% increase in LV dP/dt-max. LVa pacing improved efficiency over LVs and collectively over BiV pacing (p<0.05).

Conclusions:
Acutely, LVa pacing results in the greatest mechanical efficiency. The lack of improvement in efficiency despite increasing contractility when switching from chronic RVa pacing to LV based pacing may indicate contractile remodeling.
Abstract 2169: Chronic Intra-cardiac Parasympathetic AV-node Pacing In Goats With Chronic AF To Control Ventricular Rate
Authors: Kornet Lilian , Michels Koen , van Hunnik Arne , Verheule Sander , Scala Alberto Della , Cornelussen Richard
Published: July 2021

INTRODUCTION Drug therapy to reduce the ventricular rate during atrial fibrillation (AF) is effective in only 50% of the patients and limited by side effects. Currently available pacing algorithms are even less effective. The aim of this study was to test the feasibility of chronic AV-Node Inhibition (AVNI) by intra-cardiac parasympathetic nerve stimulation. Our ultimate goal is to develop a pacemaker device with a feature to inhibit AV node function to decrease ventricular rate during AF.

METHODS Leads were implanted in the right atrial appendage and right ventricular apex and connected to a pacemaker for AF induction. In addition, an atrial lead (’AVNI lead’) connected to an implantable high frequency neurostimulator was implanted at a site with a strong prolongation of the PQ-time. Immediately after implantation optimal settings, optimal location, acute effects of AVNI on ventricular rate and the possible pro-arrhythmic effects of AVNI were assessed. The ’safety window’ for AVNI was defined as the difference between the output at the AVNI lead that produced atrial capture and the output that produced AVNI. One week after implantation, AF was maintained for one week by burst pacing via the lead in the right atrial appendage. After this 2 week period, the chronic effects of AVNI were assessed weekly for periods ranging from 3 weeks to 7 months.

RESULTS In total, 5 goats were studied . The optimal location for AVNI was located at the junction of the coronary sinus and inferior vena cava. Optimal AVNI was found at a stimulation frequency of 30Hz and pulse width of 180 μs in each animal. During the implant procedure “a safety window” appeared to be present. However, it became smaller after a longer period of AVNS. The acute effect of AVNI (averaged over the experiments) was a prolongation of the median R-R interval of 37 % (SD = 21%), which was not significantly different from the chronic effect at the end of the study (average = 32% (SD = 18%).

CONCLUSIONS Chronic intra-cardiac AV-node inhibition to reduce the ventricular rate during AF is feasible. Atrial pro-arrhythmic effects can be avoided by optimization of the stimulus parameters and location.
Abstract 2205: Intraventricular Septal Intramural Asynchrony in Patients with Dilated Cardiomyopathy Using Tissue Velocity Imaging Correlates with the Severity of Myocardial Fibrosis
Authors: Tanaka Jun , Nakatani Satoshi , Amaki Makoto , Kanzaki Hideaki , Hashimoto Shuji , Ishibashi-Ueda Hatsue , Kitakaze Masafumi , Harada Kazumasa , Kuwajima Iwao
Published: July 2021

Dilated cardiomyopathy (DCM) is histologically characterized by myocardial fibrosis and cellular hypertrophy. These myocardial changes may affect timing of regional peak contraction. We investigated whether there was a correlation between intraventricular septal (IVS) intramural asynchrony based on tissue velocity imaging and the histologic changes. We obtained apical 4-chamber tissue velocity images in 27 normal subjects and 22 patients with DCM undergoing myocardial biopsy using Vivid 7 (GE). We set 6 tandem regions of interest (ROIs) on the mid level of the IVS and measured the time to peak myocardial contraction (Ts) from the QRS onset at each ROI. We defined the standard deviation of Ts (Ts-SD) as an index of IVS asynchrony. Further, we analyzed a correlation between Ts-SD and the degree of myocardial fibrosis and cellular hypertrophy. The degree of myocardial fibrosis and cellular hypertrophy was graded qualitatively (0 to 3 scale) according to the percent of fibrosis occupied of the tissue sample and cell size. Ts-SD was larger in patients with DCM compared with normal subjects (13.9±12.3 vs. 6.2±4.0 ms, p<0.05), suggesting asynchronous contraction of IVS in DCM. Ts-SD showed a significant correlation with the degree of myocardial fibrosis (grade 1, 6.9±3.5 ms; grade 2, 15.7±3.5 ms; grade 3, 25.9±5.3 ms; p<0.05), while not with that of cellular hypertrophy (p=0.50). There was intramural asynchrony in IVS in DCM. This method could predict the degree of myocardial fibrosis noninvasively. Because myocardial fibrosis is the substrate for heart failure in DCM, the present method should provide clinically important information.