bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 190: Groups IIA, IVA and V Phospholipase A
2
in Coronary Thrombus Are Associated With Recurrent Cardiac Events and Development of Atherosclerosis in the Culprit Coronary Artery After Acute Myocardial Infarction
Authors: Takahashi Soichiro , Suzuki Koji , Tamaru Shun , Watanabe Yosuke , Mishina Hideto , Watanabe Kazuhiro , Fujioka Daisuke , Nakamura Takamitsu , Obata Jun-ei , Kawabata Kenichi , Kugiyama Kiyotaka
Published: April 2024

Background:
The intracoronary thrombus is a source of active lipid mediators including eicosanoids that play critical roles in the pathogenesis of acute myocardial infarction (AMI). Eicosanoids are derived from arachidonic acid generated by phospholipase A
2
(PLA
2
). This study examined whether PLA
2
were expressed in aspirated coronary thrombi and whether PLA
2
expression in the thrombi may be related to the recurrence of cardiac events and development of atherosclerosis in the culprit coronary artery after AMI.

Methods:
Intracoronary thrombi were obtained using an aspiration catheter at the emergent PCI from 48 patients with AMI who had successful treatment with PCI. The presence of groups IB, IIA, IID, IIE, IIF, III, IVA, V, VI, VII, X and XIIA PLA
2
was examined using immunohistochemical staining in all of the thrombi obtained. Repeated intravascular ultrasound in the culprit coronary artery was performed at emergent PCI and 6 months later in a subgroup of 20 patients.

Results:
Each of the 12 subtypes of PLA
2
was detected by its immunoreactivity in 2 - 6% of total nucleated cells and 16 - 39% of platelet area (CD42b-positive area). COX-1, COX-2 and 5-LOX, downstream enzymes for PLA
2
in the arachidonic acid cascade, were co-localized with PLA
2
. During 6 months of follow-up, 11 patients had cardiac events. Percentages of platelet areas immunopositive for groups IIA, IVA and V PLA
2
were significantly higher in patients with cardiac events (n = 11) than without (n = 37) (% of CD42b-positive areas: 36% vs. 14%, 55% vs. 32% and 54% vs. 27%, respectively, p < 0.05 in all). Similarly, percentages of nucleated cells immunopositive for groups IIA, IVA and V PLA
2
were also higher in thrombi from patients with cardiac events than without (p < 0.05 in all). Percentagesby which atheroma volumes and vessel volumes increased in the native coronary segments distal to the culprit coronary lesion were significantly and positively correlated with percentages of nucleated cells immunopositive for groups IIA (r = 0.60 and 0.52, respectively), IVA (r = 0.55 and 0.46) and V PLA
2
(r = 0.45 and 0.48).

Conclusion:
Groups IIA, IVA and V PLA
2
in coronary thrombi may play a role in recurrence of cardiac events and development of atherosclerosis in the culprit coronary artery in AMI survivors.
Abstract 19014: Significant Major Complication Occurrence in Extracting Riata Compared to Sprint Fidelis Leads
Authors: Sheth Harshal , Broman Michael , Mehrotra Amit , Sparano Dina , Shin John , Moss Joshua , Nayak Hemal , Burke Martin
Published: April 2024

Introduction:
Medtronic Sprint Fidelis and St. Jude Medical Riata defibrillator leads have been subject to class I recall. Extraction of these leads is a complex clinical decision with a case by case analysis. We compared the difference in the occurrence of major complications to understand the morbidity and mortality risk extracting either of these leads.

Methods:
We retrospectively reviewed 86 consecutive cases (59 men, 27 women) of Sprint Fidelis (n = 72) or Riata (n = 14) lead extraction from 2007 to 2012 and compared the rate of major complications between the two. The only exclusion criteria were pocket infection or endocarditis as an indication for extraction. Major complications were defined as death, cardiac/vascular avulsion or tear, cardiac tamponade requiring pericardiocentesis and/or stroke. Minor complications were defined as pericardial effusion not requiring intervention, pneumothorax and/or hematoma at surgical site.

Results:
The main indications for extraction included lead fracture (n = 36, 42%) and elective removal at pulse generator change (n = 28, 33%). There was a significant difference in occurrence of major complications with extraction of Riata as compared to Sprint Fidelis leads (2/14 vs. 1/72, p = 0.016). All 3 major complications occurred in dual coil leads. Within the Riata family of leads, there was no statistical difference in occurrence of major complications (1500 series 2/7 vs. 7000 series 0/7, p = 0.127). There was also no difference in patients with component failure versus prophylactic extraction (1/36 vs. 2/50, p = 0.76).

Conclusions:
Major complication occurrences in extraction are higher with Riata as compared with Sprint Fidelis leads based on this large, single-center experience. There was no statistical difference between the 8-Fr 1500 and 7-Fr 7000 Riata series of leads.

Further investigation is needed to help guide clinical decision-making for patients presenting with these recalled leads.
Abstract 19015: Loss of Plasma Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) After LDL Apheresis
Authors: Tavori Hagai , Giunzioni Ilaria , Linton MacRae F , Fazio Sergio
Published: April 2024

Low-density lipoprotein (LDL) apheresis (LDL-A) is used to reduce LDL levels in patients with severe familial hypercholesterolemia (FH). We, and others, have previously reported that up to 40% of plasma PCSK9 is bound to LDL, while the rest is with the apoB-deficient fraction. Therefore, we examined whether LDL-A treatment using dextran-sulfate columns (Liposorber®) affects plasma PCSK9 levels. Pre and post apheresis plasma from five FH patients in three consecutive treatment cycles was used to determine changes in PCSK9 levels. Lipid, albumin, CK-MB, and creatinine levels were also evaluated.

LDL-A treatment, as expected, significantly reduced plasma LDL (by 85±6%). In addition, PCSK9 levels fell by 52±7%, and this decrease was significantly correlated with the LDL drop (p=0.02, r
2
=0.304
),
but not with decreases in triglyceride or HDL levels. Levels of other plasma analytes (albumin, creatinine, CK-MB) did not show changes after apheresis treatment. Similar to LDL, PCSK9 levels returned to pre-treatment values between cycles (2-week intervals). Fractionation of pre and post plasma showed that 87±4% of LDL-bound PCSK9 and 38±14% of the PCSK9 associated with the apoB-deficient fraction were removed. From the column eluate we recovered more than 80% of the PCSK9 removed from the circulation. Running human plasma, isolated LDL and apoB-deficient plasma through a scaled-down apheresis column we again found a loss of 57% of total PCSK9, including 89% of LDL-bound PCSK9 and 41% of the PCSK9 associated with the apoB-deficient fraction. These decreases in PCSK9 levels are in the range of what is accomplished with current anti-PCSK9 antibody therapies.

These results show for the first time that dextran-sulfate LDL apheresis substantially reduces levels of plasma PCSK9. This likely represents an additional benefit of the apheresis treatment in keeping LDL levels down over time and may contribute to the prevention of cardiovascular events in FH patients undergoing apheresis. We also provide additional proof that more than one third of plasma PCSK9 is on the circulating LDL. These findings may guide use of future anti-PCSK9 therapies in LDL-A patients, and should lead to wider indications for LDL-A, beyond the most severe FH presentations.
Abstract 19043: Novel Bioactive Peptide Amphiphiles Nanofibers for Enhancement of Human Cd34+ Cell Mediated Ischemic Tissue Repair
Authors: Yu Yang , Sleep Eduard , Stupp Samuel I , Qin Gang J
Published: April 2024

Background:
CD34+ cells have shown unprecedented promise for ischemic tissue repair in recent clinical trials; however, their recruitment, retention, and survival in the injured tissue remain one of the major barriers to the success of this novel therapeutic strategy.

Methods and Results:
In this study, we have developed a self-assembling bioactive peptide amphiphile (PA) nanofiber that displays the integrin-recognized cell adhesion epitope RGDS and then tested this novel scaffold material for therapeutic delivery, retention, and functional support of human CD34+ cells in a mouse model of critical hind-limb ischemia (CLI). In culture, PA nanofibers, but not non-bioactive nanostructures or nanostructures with scrambled DGRS epitope, significantly enhanced the adhesion and survival of human CD34+ cells under a number of cellular stresses. In CLI nude mice, intramuscular injection of human CD34+ cells contained in the RGDS nanostructures led to a significantly better blood perfusion, motor ability, limb salvage, and treadmill endurance when compared with those of CD34+ cells contained in DGRS nanostructures, cells alone or RGDS alone. Histology analyses revealed a higher viability and retention of CD34+ cells in the limb tissue of the RGDS nanostructures/CD34+ cells group than in the RGDS nanostructures alone or cells alone group. In consistent with the improved functional recovery, the density of capillaries in the ischemic limb of RGDS nanostructures/CD34+ cells group was significantly greater than in other groups.

Conclusions:
Our data demonstrate that integrin-specific binding epitope RGDS nanostructure enhances viability, adhesion, and angiogenic capability of human CD34+ cells. This pre-clinical study provides a rationale for further investigation of combining RGDS PAs with human CD34+ cells to enhance the effectiveness of cell therapy for ischemic limb disease.
Abstract 19061: Kca3.1 Regulates Monocytosis and Monocyte Adherence in Atherosclerosis
Authors: Lemaitre Vincent , Redelman Douglas , Miura Hiroto
Published: April 2024

Introduction:
Atherosclerosis is associated with a monocytosis of an inflammatory subset (Ly-6Chi in mice), which is preferentially recruited to lesions and gives rise to pro-atherosclerotic macrophages (MΦ). We have shown that the intermediate-conductance Ca2+-activated K+ channel KCa3.1 is predominantly expressed in blood Ly-6Chi monocytes (MONO) and lesion MΦ, and KCa3.1 blockade or knockout reduces the development of atherosclerosis in mice. To further study the function of KCa3.1 in atherogenesis, we investigated its role in monocytosis and in MONO adherence to the endothelium in vivo.

Methods and Results:
Flow cytometric analyses of peripheral blood and bone marrow from Apoe-/- and Apoe-/- KCa3.1-/- mice showed that KCa3.1 deficiency decreased circulating MONO (8.8±1.5% of leukocytes, p<0.05 vs. 15.4±2.1%; n=7-8) and Ly6Chi MONO (4.2±0.7% of leukocytes, p<0.05 vs. 9.8±1.5%, n=7-8), with unchanged Ly6Clo MONO (4.6±1.3% of leukocytes, p=ns vs. 5.6±0.7%) and polymorphonuclar (11.7±1.4% of cells, p=ns vs. 12.5±1.2%; n=7-8). Apoe-/- KCa3.1-/- mice had reduced hematopoietic stem and multipotential progenitor cells (HSPCs) (2.4±0.5% of lineage negative cells, p<0.05 vs. 3.0±0.5%, n=7). In vivo confocal endomicroscopic analysis of leukocyte adherence was performed in anesthetized mice 4 hours after topical application of 0.5 μg TNF-α and 0.125 μg IL-1β onto the right external carotid artery where an imaging probe (Cellvizio®, field of view=8x105 μm2) was placed. Blood and circulating leukocytes were stained by intravenous injection of 200 μg FITC-dextran and 0.02% acrydine orange, respectively. KCa3.1 deficiency markedly inhibited leukocyte rolling (4±2 vs. 52±15 cells/min, contact time: 1.6±0.5 vs. 2.7±0.2 sec, distance: 78±11 vs. 165±5 μm, and velocity: 145±24 vs. 119±5 μm/sec) and adhesion (0.5±0.3 vs. 2.0±0.6 cells/min, p<0.05 for all data, n=6). Immunohistochemistry of lesions showed that Apoe-/- KCa3.1-/- mice had less CD68-positive MONO/MΦ compared to Apoe-/- mice (616±101, p<0.05 vs. 937±90 cells/mm2, n=8-9).

Conclusion:
KCa3.1 modulates monocytosis and plays a major role in MONO adherence to the endothelium in vivo. Thus KCa3.1 constitutes a promising therapeutic target for the prevention of atherosclerosis.
Abstract 19074: Multi-Vessel Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells in a Porcine Model of Myocardial Infarction
Authors: Tseliou Eleni , Kanazawa Hideaki , Dawkins James , Chowdhury Supurna , Middleton Ryan , Smith Rachel , Kreke Michelle , Marbán Linda , Makkar Raj , Marbán Eduardo
Published: April 2024

Background:
Single-vessel, intracoronary cardiosphere derived cells (CDCs) have been shown to be safe and effective in both preclinical and clinical studies. However, the potential utility of multivessel intracoronary delivery to target global left ventricular remodeling post-myocardial infarction (MI) has not been studied.

Objective:
We sought to evaluate the safety and efficacy of multivessel intracoronary delivery of allogeneic CDCs in a porcine model of subacute MI.

Methods:
MI was created in adult female Yucatan minipigs. Three weeks later, 12.5M allogeneic CDCs were infused sequentially in each of the three coronary vessels; LAD, LCX and RCA under stop-flow (Group 1) or nonocclusive-flow conditions (Group 2). Animals infused with vehicle under stop flow conditions served as the control group (Group 3; n=5 per group). Animals underwent MR imaging at baseline (just before infusion) and 4 weeks post-infusions. Left ventricular ejection fraction, scar mass and viable mass were evaluated at both time points.

Results:
Ejection fraction (EF) did not differ among the three groups at baseline. However, LV function was better preserved in both CDC infusion groups compared to vehicle at 1 month follow-up (ΔEF=-4+/-1.6% in Group 1, p=0.13; ΔEF =-1.1+/-2.2% in Group 2, p=0.7; ΔEF=-4.6+/-2.3% in Group 3, p=0.05). In terms of scar mass, CDCs under both stop-flow and non-occlusive infusion technique reduced 1 month post-treatment compared to the vehicle group (Δscar mass= -2.9+/-0.6gr in Group 1, p=0.012; Δscar mass= -1.2+/- 0.4gr in Group 2, p=0.028; Δscar mass =-1.9+/-1.1gr in Group 3, p=0.16). Viable mass was not changed significantly in any of the groups (p=ns). No humoral response (by circulating antibodies) or additional cell inflammatory response (by histopathological analysis) were detected 1 month post infusion in the continuous flow CDCs group. Serum troponin I measured at 24 hrs was routinely elevated in the stop-flow group, but not in the nonocclusive flow group.

Conclusions:
Nonocclusive multivessel delivery of allogeneic CDCs is safe and effective to preserve left ventricular function as soon as 1 month post-delivery, paving the way for future applications targeting global left ventricular remodeling.
Abstract 19077: Correlation of Renal Insufficiency With Left Ventricular Diastolic Dysfunction: How Medications Impact This Association?
Authors: Sharif Roozbeh , Kumar Arnav , Mutnuri Sangeeta , Khan Adnan , Bangura Lamin , Morsy Mohammad , Kuo Yong-Fang , Khalife Wissam
Published: April 2024

Background:
Increasing evidence between the association of chronic kidney disease (CKD) and left ventricular diastolic dysfunction (LVDD) has been emerging, however the impact of medications on this association has not been well studied.

Methods:
In a cross-sectional study, we reviewed the medical records of patients who presented to the echocardiographic lab in a tertiary care academic center between 2008 and 2011. CKD staging was categorized based on the estimated glomerular filtration rate (eGFR). Diastolic function was evaluated based on echocardiographic characteristics. Using logistic regression analysis, the association between CKD severity and LVDD was examined after adjusting for potential demographic and clinical confounders. Then, we hypothesized that medications (i.e. angiotensin converting enzyme inhibitors [ACE-inh]/ Angiotensin II receptor blockers [ARB], statins, beta blockers, or any combination of these) might modify this association and examined the interaction term of medications in regards to the association between CKD severity (eGFR) and LVDD.

Results:
Among 2443 patients, 1018 (41.7%) had normal eGFR, 757 (31%) had stage II, 443 (18.1%) stage III, 106 (4.3%) stage IV, and 119 (4.9%) stage V. LVDD was found in 1697 patients. Our data suggested that patients with CKD stage V have higher likelihood of developing LVDD (OR: 2.63, 95%CI 1.48-4.67, p=0.0006). Besides, higher CKD stage was associated with more severe LVDD (6.5%, 12.3%, 13.8%, 17.0%, and 20.2% patients with CKD stage I, II, III, IV, and V had LVDD stages II or higher, respectively).

The analysis of potential effect modifier indicated a significant interaction between CKD staging and treatment with statins, in regard to its association with LVDD (p=0.0008). Therefore, we categorized the patients based on the medications. The stratified analyses indicated that patients on Statins had weaker association between CKD stage V and LVDD (OR of 0.77 vs. 6.85).

Conclusions:
Higher CKD stage is associated with presence and severity of LVDD. Statins can play a protective role, particularly in the higher stages of CKD.
Abstract 19086: Gene Recruitment to the Nuclear Periphery
Authors: Egecioglu Defne , Brickner Jason
Published: April 2024

The regulation of gene expression plays an essential role in cellular function and behavior. Heart conditions that arise as a result of response to various forms of stress, as well as altered cholesterol levels are both associated with changes in transcriptional programs. Transcriptional regulation is therefore a crucial step before the progression of any cellular response to stress. Recent work has shown that the localization of genes in the nucleus plays an important role in regulating transcription; a gene’s location can impact its transcriptional activity and its chromatin structure. In brewer’s yeast, many genes are targeted from the nucleoplasm to the nuclear periphery, through association with the Nuclear Pore Complex (NPC), upon activation. Similar phenomena have been reported in metazoans. Targeting to the NPC promotes transcription and is controlled by cis-acting “DNA zip codes” in the promoters of these genes. Interestingly, the two zip-code harboring genes we have closely analyzed are both induced as a response to various forms of stress. To determine the molecular basis of zip code-mediated targeting, we have identified the transcription factor Put3 as a DNA zip code binding protein. We seek to determine how the DNA binding properties of Put3 affect the movement of chromosomal loci to the NPC, and how this singular transcription factor can have two distinct roles in the yeast nucleus: the activation of PUT genes, and relocalizing genomic loci by binding to zip codes. By assaying for the binding properties of Put3 to various zip codes in both in vitro and in vivo contexts, we have mapped the important residues within and flanking the DNA zip code core sequence. A number of upstream zip code residues play an important role for Put3-based gene targeting, as demonstrated by live yeast cell microscopy. The two nuclear roles for Put3 suggest that this protein associates with distinct groups of other proteins for each of its functions, and possibly in different conformations. Mutations within Put3 can separate these two functions. On the broader scale, this work aims to provide important fundamental insight into how eukaryotic genomes regulate their expression through alteration of their spatial organization within the nucleus.
Abstract 19118: Coronary Artery Dissection After Blunt Chest Trauma
Authors: Ng Chee Yuan , Choe David , Khan Hammad
Published: April 2024

Coronary artery dissection is a rare complication of blunt chest trauma. We present an unusual case of coronary artery dissection and our approach to treatment. A 28 year-old previously healthy male presented initially to Urgent Care with chest pain for 5 days after being hit on the chest with a soccer ball. Electrocardiogram (ECG) was unremarkable and he was sent home but he returned 5 days later with worsening intermittent chest pain. Physical examination was normal. ECG showed ST elevation in leads V2-V5. Prompt coronary angiography showed a dissected and heavily thrombotic proximal to mid left anterior descending artery (LAD). AngioJet thrombectomy was performed followed by placement of three drug eluting stents: 4 x 28 mm, 4 x 16 mm and 4 x 38 mm. Transient no reflow happened which was treated via intracoronary adenosine. The final angiographic result was satisfactory but the very distal LAD remained occluded though with resolution of symptoms and ECG changes. The distal LAD recanalized on a follow up angiogram done for recurrent chest pain. The patient was placed on bivalirudin periprocedure and eptifibatide for 24 hours and was loaded with prasugrel. Troponin T peaked at 1.63 ng/mL. Echocardiogram showed ejection fraction of 35% with anteroapical hypokinesis with preserved thickness. The patient was discharged home after 3 days. Trauma-related myocardial infarction can be caused by coronary artery dissection and compression due to epicardial hematoma. We present a case of coronary artery dissection that could be easily missed in a young individual and should be suspected early on so that prompt intervention could be performed.
Abstract 19126: Novel Linkage Between Metabolic Sensor Mechanistic Target of Rapamycin (mTOR) and Canonical NF-kB Signaling Pathway Preserves Mitochondrial Integrity in Ventricular Myocytes During Hypoxia
Authors: Kirshenbaum Lorrie A. , Dhingra Rimpy , Gang Hongying , Wang Yan , Biala Agnieszka
Published: April 2024

Background:
TNFα and other pro-inflammatory cytokines activate the canonical NF-kB pathway through the IkBa kinase (IKK) signaling complex. IKKβ kinase is also critical for Akt-mediated NF-κB activation in ventricular myocytes. Akt activates the kinase (mechanistic target of rapamycin (mTOR), which mediates important processes such as metabolism protein synthesis and autophagy. However, mTOR’s role in regulating cardiac myocyte cell survival is unknown.

Methods and Results:
Herein, we demonstrate bi-directional regulation between NF-kB signaling and mTOR, the balance of which determines ventricular myoctye survival. Overexpression of IKKβ resulted in mTOR activation and conversely overexpression of mTOR lead to NF-κB activation. Loss of function approaches demonstrated that endogenous levels of IKKβ and mTOR also signal through this pathway. NF-kB activation by mTOR was medated by phosphorylation of the NF-kB p65 subunit at S276 increasing p65 nuclear translocation and activation of gene transcription. This circuit was also important for NF-κB activation by the canonical TNFα pathway. Inhibition of mTOR with rapamycin or during hypoxia decreased NF-kB activation resulting in increased mitochondrial PTP opening, maladaptive autophagy and necrotic cell death. Conversely, mTOR over-expression suppressed mitochondrial injury, autophagy and cell death of ventricular myocytes during hypoxia as well as nutrient deprivation.

Conclusions:
To our knowledge, these data provide the first evidence for a bi-directional link between NF-kB signaling and mTOR that is critical in the regulation of cardiac myocyte death. Hence, modulation of this axis may be cardioprotective in attenuating metabolic stress induced during hypoxia.
Abstract 212: Synthesized 18-Lead Electrocardiogram in Patients Treated in the Emergency Department
Authors: Ashida Tadashi , Nagao Ken ,   Eizo Tachibana, Tukasa Yagi, Singo Furuya, Sigemasa Tani,,   Soga Taketomo, Kikushima Kimio, Watanabe Kazuhiro,Surugadai Nihon Univ Hosp, Tokyo
Published: April 2024

Background:
Standard 12-lead electrocardiogram (ECG) speed the diagnosis and shorten the time to reperfusion for acute coronary syndrome (ACS). However, there is insufficient information of posterior (V7-V9) and/or right (V3R-V5R) ventricular area in which data are not routinely recorded. Recently, a non-invasive standard 12-lead ECG system with an additional 6 leads (Synthesized 18-Lead ECG; Nihonkoden Co. Ltd.) has been developed.

Methods:
We conducted a prospective, blind, observational study of patients who treated in the emergency department (ED) of our hospital. From symptoms and signs on arrival at the ED, physicians judged whether ECG was necessary for diagnosis and primary care. We entrusted the medical examination and primary care to the physicians. When physicians suspected a patient with emergency cardiovascular disease, a synthesized 18-lead ECG was recorded within 10 minutes of ED arrival. The primary endpoint was a diagnosis of acute ST-elevation myocardial infarction (STEMI).

Results:
Of the 7,638 patients treated in the ED, 6,041 were adults. Of the 6,041 adults, 1,546 (26%) underwent synthesized 18-Lead ECG within 10 minutes of ED arrival. Of the 1,546 patients undergoing synthesized 18-Lead ECG, 407 (26%) were judged as possible cases of emergency cardiovascular disease with chest discomfort in 31%, disturbance of consciousness in 21% and dyspnea in 16% etc. Of these 407 patients with possible emergency cardiovascular disease, 25 (6%) were diagnosed as ACS, including 13 STEMI, 5 Non-STEMI and 7 unstable angina. Of the 13 STEMI patients, 2 (15%) were diagnosed as STEMI complicated by right ventricular infarction, including one moderate right ventricular dysfunction and one syncope.

Conclusion:
Synthesized 18-Lead ECG with right-sided and posterior precordial leads (V3R-V5R and V7-V9), was useful in the rapid diagnosis of STEMI within 10 minutes of ED arrival, especially in the early detection of right ventricular infarction.

1684
Abstract 290: Low Minute Ventilation Volume During CPR Disturbs the Relationship between End-Tidal CO2 and Coronary Perfusion Pressure
Authors: Ordelman Simone , van Berkom Paul , Aelen Paul , Woerlee Pierre , Noordergraaf Gerrit J
Published: April 2024

End-tidal CO
2
(ETCO
2
) is important for monitoring CPR quality as a surrogate for coronary perfusion pressure (CPP) and flow. We hypothesized that sufficient minute volume ventilation is not only needed to control CO
2
buildup, but also for the exhaled CO
2
to CPP relationship to remain valid.

To test our hypothesis, we measured minute volume ventilation together with CPP, arterial PCO
2
(PaCO
2
), and ETCO
2
in a pig model. Ventricular fibrillation was induced in 24 pigs, after which automated CPR (5 cm, 100 cpm) followed for 20 minutes. Animals were ventilated manually using a bag-mask-valve, either continuously at 10 min
-1
(group 1, n=8) or 30:2 mode (group 2, n=16). Correlation coefficients between CPP and ETCO
2
were calculated for each pig during the CPR interval.

Minute volume ventilation during CPR was 3.4 ± 1.0 L/min for group 1 and 2.2 ± 0.3 L/min for group 2 pigs. In group 1, PaCO
2
changed little during CPR (41.1 ± 7.6 mmHg initially vs. 38.6 ± 16.5 mmHg at 20 minutes), indicating suitable minute volume ventilation. ETCO
2
decreased concurrently with CPP. The correlation coefficient between CPP and ETCO
2
was 0.52 ± 0.39. Group 2 pigs showed a large increase in PaCO
2
(49.8 ± 6.6 mmHg initially vs. 58.0 ± 13.6 mmHg at 20 minutes), consistent with small minute volume ventilation. This increase in PaCO
2
was accompanied by a progressively increasing ETCO
2
, while the CPP consistently decreased. The CPP to ETCO
2
correlation coefficient showed a low, but negative (-0.18 ± 0.51) relationship, strongly supporting that the indicator function of ETCO
2
was lost. The figure shows an example.

In conclusion, insufficient ventilation affects ETCO
2
and can disturb the relationship between ETCO
2
and CPR quality as measured by CPP. This is reminiscent of hyperventilation effects. Ventilation minute volumes should therefore be monitored, and hypoventilation avoided, to prevent clinical misinterpretation of ETCO
2
values.
Abstract 304: Conversion of Ventricular Fibrillation to an Organized Rhythm Without a Defibrillator
Authors: Steinberg Mikkel T , Olsen Jan-Aage , Bendz Bjorn , Persse David , Sterz Fritz , Lozano Michael , Brouwer Marc A , Westfall Marc , Souders Chris M , Malzer Reinhard , van Grunsven Pierre M , Travis David T , Lerner E Brooke , Wik Lars
Published: April 2024

Background:
Reports of pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF) converting to an organized rhythm without defibrillator use are rare. We wish to report a series of such cases in the randomized Circulation Improving Resuscitation Care (CIRC) trial comparing outcome between integrated AutoPulse CPR (iA-CPR) and Manual-CPR (M-CPR) in patients with out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology.

Methods:
Defibrillator ECGs were studied to determine rhythm one minute after defibrillation attempts and rhythm immediately before the next defibrillation attempt. Rhythms were categorized as VF, pulseless VT, asystole or an organized rhythm. Organized rhythms were classified as either pulseless electrical activity (PEA) or as return of spontaneous circulation (ROSC) if accompanied by a steep increase in EtCO2, trans-thoracic impedance showing typical “dips,” and a detectable pulse.

Results:
In 1603 patients with analyzable date and a shockable rhythm there were 13 cases of VF/VT (10/3) conversions to PEA or ROSC during periods with external chest compressions without defibrillation attempts. In eight of the 10 VF cases chest compressions converted VF to PEA (5 iA-CPR vs 3 M-CPR) and in two to ROSC (2 iA-CPR vs 0 M-CPR). With VT one case converted to PEA (M-CPR ) and two to ROSC (2 iA-CPR vs 0 M-CPR). Examples will be presented.

Conclusion:
This study documents that conversion of VF or VT to an organized rhythm during CPR without electrical assistance is possible but rare.
Abstract 305: ECPR Indication Criteria -From the Cost Effective Analysis in SAVE-J Study-
Authors: Takahiro Atsumi ,   SAVE-J Study Group, Sakamoto Tetsuya , Morimura Naoto , Nagao Ken , Asai Yasufumi , Yokota Hiroyuki , Tahara Yoshio , Hase Mamoru , Nara Satoshi , Ariyoshi Koichi , Asaka Yoko , Aoki Noriaki
Published: April 2024

Background:
Last year, we have reported extracorporeal cardiopulmonary resuscitation (ECPR) improves the outcome of out-of hospital cardiac arrest. (SAVE-J study)

Objectives:
The aim is to determine the most effective indication criteria of ECPR.

Method:
The registered cases of SAVE-J from December 2008 to September 2011 were evaluated for cost effective analysis. The age, time to arrival, 6months outcome and the hospitalization costs were evaluated. The Quality Adjusted Life Years (QALY) and costs were evaluated for accumulation of Incremental Cost-Effectiveness Ratios (ICER). Different age groups and time to hospital arrival were sorted to extract data, and cost effectiveness of each group was compared.

Result:
The ICER of overall SAVE-J inclusion criteria was $85,800. By restricting to below the age of 50, the ICER was $54,800 and below the age of 40 was $38,300. With the sortation by arrival time, ICER was $64,100 within 25 minutes, and was $43,800 within 20 minutes.

Conclusion:
In Japan, implementation of new treatment is said to be about $50,000~60,000 per QALY. From cost-effectiveness point of view, the inclusion criteria for ECPR are below the age of 50, or arrival time to hospital within 20 minutes seems reasonable.
Abstract 319: Duration of Resuscitation Efforts and Functional Outcome After Out-of-Hospital Cardiac Arrest: When Should We Change to Novel Therapies?
Authors: Reynolds Joshua C , Frisch Adam , Rittenberger Jon C , Callaway Clifton W
Published: April 2024

Objectives:
Strategies such as extracorporeal life support yield favorable outcomes in select OHCA patients who fail traditional CPR. However, it is unclear how long to attempt CPR before switching to more intensive strategies. We hypothesized that most patients with good outcome after traditional CPR achieve return of spontaneous circulation (ROSC) quickly, and determined the maximal CPR duration (DUR) required to restore pulses in the majority (75%, 95% or 99%) of patients with good outcome.

Methods:
Retrospective cohort study of subjects with atraumatic OHCA and attempted resuscitation from 2005-2011. Good outcome was defined as a modified Rankin scale (mRS) 0-3. We determined DUR until ROSC for subjects with mRS 0-3 (good outcome), mRS 4-5 (poor outcome), or mRS 6 (in-hospital death) with Kaplan-Meier curves, and the association between DUR and good outcome with logistic regression.

Results:
Of 1,014 patients, 47% had ROSC, 11% survived, and 6% had mRS 0-3. DUR for each outcome are in Table 1. Cumulative proportions of good outcomes versus DUR are in Figure 1. Adjusting for prehospital and inpatient covariates, DUR (min) is associated with mRS 0-3 (OR 0.84; 95%CI 0.72, 0.98;p=0.02).

Conclusions:
Novel strategies should be considered early, because 75% and 90% of patients with good outcome have ROSC within 10 and 16 minutes of traditional resuscitation, respectively.
Abstract 345: Effects of Cannula Size in Venoarterial Extracorporeal Membrane Oxygenation
Authors: Czobor Peter , Parikh Kishan , Nathan Sandeep , Karol Janet , Shah Atman P
Published: April 2024

Background:
The degree of circulatory support that patients treated with veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) receive is limited by the size of the arterial cannula. However, the use of ECMO is associated with significant morbidity related to complications of cannulation, including limb ischemia and need for blood transfusion. We investigated the relationship between cannula size and clinical outcomes as well as transfusion needs in patients treated with VA ECMO.

Methods:
We performed a retrospective review of all patients treated with percutaneous VA ECMO at the University of Chicago Medical Center from January to December 2012. Baseline characteristics, size of arterial cannula, blood transfusions, and outcomes were recorded. Fisher’s exact test was used to compare the association between survivor status and cannula size (15 vs greater than 15 Fr). Association between cannula size and transfusion of packed red blood cells over the first 24 hours of treatment was determined using a quadratic regression model.

Results:
Percutaneous VA ECMO was initiated in 15 patients. 7 patients were alive at 30 days after ECMO initiation. The use of a smaller cannula was significantly associated with survival (P < 0.01) There was an association between the size of the arterial cannula and blood transfusion needs (P <0.01). Two patients experienced significant hemorrhage related to cannulation. Other major complications included HIT (1) and DIC (1). Limb ischemia was not seen as all patients underwent anterograde cannulation at time of ECMO initiation.

Conclusions:
Use of smaller arterial cannulae in VA ECMO was associated with increased survival and there was a correlation between cannula size and need for transfusion. Smaller cannulae result in lower flow rates, but also in reduced vascular complications. Further study is warranted to determine the balance between providing circulatory support and reducing complications in patients treated with VA ECMO.
Abstract 363: Dantrolene Decreases Susceptibility to Refibrillations by Restoring Vf Dependent Cardiac Calcium Handling Dysfunction
Authors: Zamiri Nima , Kusha Marjan , Massé Stephane , Azam Mohammad Ali , Lai Patrick , Meyer Chris , Dorian Paul , Nanthakumar Kumaraswamy
Published: April 2024

Background:
Ventricular refibrillation frequently occurs after successful defibrillation of Ventricular Fibrillation (VF) and negatively affects outcomes. Diastolic elevation in cytosolic calcium and dysfunction in calcium handling is proposed to underlie post-shock arrhythmias. Ryanodine Receptor 2 (RyR2) is the major calcium handling protein in cardiomyocytes. its dysfunction causes diastolic calcium leak from sarcoplasmic reticulum and calcium transient amplitude alternans (Ca-Alt), which can lead to arrhythmias. We hypothesized Dantrolene protects against refibrillations by restoring cardiac calcium handling and stabilizing RyR2 after VF.

Methods and Results:
Hearts from 14 healthy New-Zealand rabbits were excised and perfused using Langendorff method; VF(+ISO) was induced by burst pacing and left untreated for 4 min. Hearts received either Dantrolene (20μM) or saline during VF. Upon defibrillation, 4 more VF episodes were attempted. Sustainability (VF≥60 sec) and inducibility of refibrillations (VF≥10 sec) was evaluated. Calcium mapping using RhoD-2 was performed to assess Ca-Alt and diastolic Spontaneous Calcium Elevation (SCaE). Ca-Alt was defined as ≥10% variability in Calcium transient amplitudes. SCaE amplitude was measured during diastolic pause after termination of pacing.

In total, 83.33% of attempts to induce refibrillation in controls were successful compared to 41.18% in Dantrolene-treated hearts. (P=0.007)

Dantrolene (20μM) significantly decreased SCaE amplitude post VF. (Table 1) Ca-Alt emerged at shorter PCL in Dantrolene-treated hearts with 10% decrease from 195±9.5ms at baseline to 173±6.7ms post-VF compared to 11% increase in controls from 215±20ms to 235±8ms. (P=0.05)

Conclusion:
Dantrolene ameliorated arrhythmogenic diastolic SCaE caused by VF and increased calcium alternans threshold and may be the basis for the decreased susceptibility of treated hearts to refibrillations.
Abstract 15062: Circulating Brain-derived Neurotrophic Factor concentrations and the risk of cardiovascular disease in the community
Authors: Kaess Bernhard M , Preis Sarah R. , Lieb Wolfgang , Beiser Alexa S. , Yang Qiong , Cheng Tai C. , Vorgas Demetrios , Hengstenberg Christian , Erdmann Jeanette ,   on behalf of CARDIoGRAM, Schunkert Heribert , Seshadri Sudha , Vasan Ramachandran S.
Published: April 2024

Bernhard M. Kaess, 2013 Finalist and Presenting Author
Building Successful International Cardiovascular Nursing Research in Heart Failure Care
Authors: Jaarsma Tiny
Published: April 2024

International collaboration is vital to address the causes and deal with the impacts of many of the global challenges that society faces. One example of this is an international approach to fighting cardiovascular disease and its consequences for patients and their families. Selective national initiatives might not always be an optimal use of recourses, but instead international collaboration in cardiovascular caring research can help us in seeking excellence, build capacity and improve political influence, all needed to ultimately improve patient care. However, several countries worldwide have different health care systems, medical and nursing education programs and professional roles, and responsibilities, posing a major challenge to optimal collaboration and implementation of research findings.

An example of successful international teamwork is illustrated by research in the area of self-care in heart failure patients with collaboration in the area of empirical research, theory development and instrument development. Several intervention studies on improving self-care are conducted in different parts of the world, strengthening the evidence base of nursing interventions to improve outcomes of heart failure patients. Current international professional guidelines for the management of heart failure patients include advices on self-care. However, to transcend above post hoc pooling of data or adding a new data collecting site in another country, other structural forms of collaboration should be considered. Capacity building, including joint proposal writing, funding and joint policy statements need to be extended globally if it is to optimize reach and impact.
Calcium: Nodal Regulator of Contractility and Hypertrophy in Cardiac Myocytes
Authors: Houser Steven
Published: April 2024

This lecture will discuss Calcium (Ca
2+
) influx pathways involved in the regulation of cardiac contractility and cardiac responses to pathological stress. The lecture will review the data showing that the persistent increases in Ca
2+
influx required for myocytes that have persistently increased contractile demands can induce pathological cardiac myocyte hypertrophy and can induce myocyte death signaling pathways. The respective sources of Ca
2+
that activate contractile proteins (to produce enhanced force development) and hypertrophic or death signaling cascades will be discussed. Recent data suggests that the sources of Ca
2+
for regulation of contractile function and hypertrophy signaling are distinct. L-type Ca
2+
channels (LTCCs) and Transient Receptor Potential (TRP) channels appear to be sources of Ca
2+
for signaling and LTCCs are the primary source of Ca
2+
to activate excitation contraction coupling. The idea that TRP and LTCCs are housed in cellular microdomains to locally activate partner proteins that lead to either contraction or activation of signaling cascades will be discussed. Data to be presented suggests that housing the same molecules, LTCCs and TRP channels, in separate membrane microdomains allows the same class of ion channels to affect either excitation contraction coupling or signaling partners.
Abstract 77: CPC 1-2 and Modified Rankin <3 Scoring at Discharge Underestimates the Prevalence and Severity of Cognitive Deficits Seen in Cardiac Arrest Survivors at 3 Months
Authors: Artman Laura K , Peberdy Mary Ann , Ornato Joseph P , Gossip Michelle R , Wilder Schaaf Kathryn P , Kreutzer Jeffrey S ,   Virginia Commonwealth Univ ARCTIC Investigators
Published: April 2024

Background:
Cerebral performance category (CPC) and Modified Rankin (MRS) scoring are used commonly to document neurocognitive (NC) function after cardiac arrest (CA) with CPC1-2 or MRS <3 representing "good" neurological outcomes. This non-focused testing may be insensitive for deficits resulting from injury to brain areas most susceptible to global ischemia see in CA.

Hypothesis:
CPC 1-2 and MRS <3 at discharge does not adequately identify important NC deficits in survivors of CA.

Methods:
One hundred forty-four consecutive CA patients (pts) underwent bundled post arrest care including therapeutic hypothermia (TH) from 2-1-11 through 1-15-13. Fifty-three percent survived to discharge. Three months post discharge, 27 pts underwent a battery of neuropsychological assessments focused on multiple domains known to be sensitive to NC impairment. Reasons for not testing were: unable to perform test due to deficits(17); coma (12); refused (11); no-show (10). Individual pt results were normed for age and education level. Impairment for memory is reported as binomial (impaired vs. not). Impairment in other domains is reported as severely impaired (below the 10th percentile) and mildly impaired (below expectations).

Results:
The study population is 24 of the 27 pts who underwent testing at 3 months and were CPC 1-2 and MRS <3 at discharge. Pts were 75% male; mean age 51 (95%CI;45, 57) years; 92% VF; 92% witnessed; 79% bystander CPR; total ischemic time 18.5 (95%CI;17.1, 32.3)min; initial pH 7.19 (95%CI; 7.13, 7.24); initial lactate 8.5 (95%CI; 4.3, 12.6). The most commonly impaired cognitive domains are represented in the table.

Conclusions:
NC impairment is common after CA in pts treated with TH and a comprehensive post arrest program. Despite "good" neurologic outcome on traditional measures, CPC and MRS scoring significantly underestimates the prevalence and severity of these deficits at 3 months post discharge.
Abstract 9273: Meta-Analysis of Stroke After Transradial Versus Transfemoral Artery Catheterization
Authors: Patel Vishal G , Brayton Kimberly M , Kumbhani Dharam J , Banerjee Subhash , Brilakis Emmanouil S
Published: April 2024

Objectives:
To assess the risk of stroke after transradial (TR) versus transfemoral (TF) artery cardiac catheterization.

Background:
TR catheterization is gaining popularity due to its association with lower bleeding and access site complications, improved patient comfort, and lower costs compared to TF catheterization; however, there is concern that TR catheterization may be associated with an increased risk of neurological complications.

Methods:
We conducted a meta-analysis of randomized studies published until 2013 reporting risk of stroke in TR vs. TF catheterization.

Results:
Data from 11,273 patients in 13 studies were collated. The majority of patients were men, and 8,987 (79.7%) were enrolled in acute coronary syndrome trials. Very few patients had a history of prior coronary artery bypass grafting, and approximately 2/3 of patients underwent percutaneous coronary intervention. Stroke occurred in 25 of 5,659 patients in the TR group, vs. 24 of 5,614 patients in the TF group. There was no difference in stroke rates between the TR and TF groups (
Figure
, risk difference 0.00%, 95% confidence interval -0.29% - 0.25%, p=0.88). This finding was consistent in a number of sensitivity analyses (excluding non-ST elevation acute coronary syndrome (ACS) trials, non-ACS trials, trials reporting in-hospital events or 30-day events, trials requiring radial expertise).

Conclusions:
TR catheterization is not associated with a significant increase in stroke compared to TF catheterization.
Abstract 9333: Prognostic Value of Stress Echocardiography In Patients Achieving a High Exercise Workload (=10 Metabolic Equivalents) and Submaximal Heart Rate Response
Authors: Yao Siu-Sun , Agarwal Vikram , Supariwala Azhar , Chaudhry Farooq
Published: April 2024

Background:
High exercise capacity (≥10 metabolic equivalents, METS) is a predictor of favorable prognosis. Submaximal studies (<85% maximum predicted heart rate, MPHR) may lead to non-diagnostic results and indeterminate outcomes. The purpose of this study was to examine the prognostic value of stress echocardiography (SEcho) in patients achieving high exercise capacity and submaximal heart rate response.

Methods:
We evaluated 81 patients (50 ± 13 years; 62% male) achieving nine minutes (≥10 METS) and <85% MPHR with treadmill SEcho. Resting left ventricular ejection fraction and regional wall motion were assessed. The left ventricle was divided into 16 segments and scored on 5-point scale of wall motion. Abnormal SEcho was defined as stress-induced ischemia (wall-motion score of ≥1 grade). Followup (3.4 ± 1.5 years) for non-fatal myocardial infarction and cardiac death (n = 2) were obtained.

Results:
By univariate analysis, the number of new ischemic wall motion abnormalities (hazard ratio = 2.5, confidence interval 1.2 - 5.3, p = 0.02) was the most significant predictor of cardiac events. Cumulative survival in patients achieving nine minutes (≥10 METS) and <85% MPHR was significantly worse in patients with abnormal (ischemic) vs. normal (nonischemic) SEcho (1.1%/year vs. 0.2%/year, p = 0.02)[Graph].

Conclusions:
The ability to achieve nine minutes (≥10 METS), despite <85% MPHR by treadmill SEcho was associated with a benign prognosis (~1.0%/year). In the setting of high achieved exercise capacity and <85% MPHR, SEcho results (presence or absence of ischemia) were further able to sub-stratify this low risk group.