bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 64: Association Between Blood Pressure Measurements, Vasopressor Use and Outcome in Post--Cardiac Arrest Patients Treated with Therapeutic Hypothermia from 4 Sites (COMICA Study Group)
Authors: Perman Sarah M , Grossestreuer Anne V , Leary Marion , Donnino Michael W , Cocchi Michael N , Peberdy Mary Ann , Ornato Joseph P , Clore John N , Callaway Clifton W , Rittenberger Jon C , Abella Benjamin S , Gaieski David F
Published: April 2024

Introduction: Specific hemodynamic optimization strategies have not been clearly described nor defined for post-cardiac arrest syndrome (PCAS) patients undergoing therapeutic hypothermia (TH).

Hypothesis: Patients who suffer worse neurologic outcomes will have more significant hemodynamic derangements in the early hours post-arrest than those with good neurologic outcome.

Methods: This is a collaborative study amongst 4 centers with aggressive TH protocols (BID, Penn, Pitt, VCU). It is a secondary analysis from prospectively collected data of out-of-hospital cardiac arrest patients who underwent TH. The primary outcome is neurologic status at hospital discharge measured as cerebral performance category (CPC), dichotomized into “good” (1 or 2) or “poor” (3, 4, or 5). Demographic information, initial rhythm and co-morbid conditions were obtained. Study variables were abstracted at baseline, 12, 24, 36 and 48 hrs. Variables recorded were systolic blood pressure (SBP) at baseline; MAP at each time point; worst, highest and lowest mean arterial pressure (MAP) for each 24 hr interval; vasopressor use.

Results: A total of 111 patients were enrolled. Patients were 61 ± 16.8 years, 59.5% male, with an initial rhythm of VF/VT in 50.5% of cases. The initial SBP for patients with good vs. poor outcome was 150 ± 37 mmHg vs. 128 ± 32 mmHg respectively (p=0.037). Patients in both groups had comparable MAPs at 12 hrs (91 vs. 87, p= 0.34) and at 36 hrs (86 vs. 81, p=0.113); however, the vasopressor use at these time points differed. At 12 hrs, vasopressors were used in 20% of patients with good outcome, versus 43.4% of patients with poor outcome (p=0.017). At 36 hrs, 31.4% of patients with a good outcome were on vasopressors vs. 50.7% with a poor outcome (p=0.06). In the first 24 hrs, subjects with good and poor outcome had equal distributions of their worst MAPs into the “low” (90 mmHg) categories. Conversely, in the second 24 hrs, patients with a poor outcome had a higher proportion of patients where their worst MAP was “low” versus those who had a good outcome (67% vs. 76%, ns).

Conclusions: Patients with poor neurologic outcomes have lower initial SBPs and a higher percentage of vasopressor use during TH versus patients with good neurologic outcomes.
Abstract 66: Association of Initial Neurological Examination with Survival Following Out-of-Hospital Cardiac Arrest
Authors: Rittenberger Jon C , Guyette Francis X , Doshi Ankur A , Clore John , Gaieski David F , Grossestreuer Anne V , Abella Benjamin S , Donnino Michael , Cocci Michael , Peberdy Mary Ann , Ornato Joseph P , Callaway Clifton W , National Post-Arrest Resuscitation Consortium
Published: April 2024

Introduction: Following resuscitation from out-of-hospital cardiac arrest (OHCA), failure to awaken from coma remains a common cause for withdrawal of care. Prior investigations have demonstrated initial organ system dysfunction is associated with survival and neurologic outcome.

Hypothesis: We hypothesized that initial neurologic examination would be associated with survival following resuscitation from cardiac arrest.

Methods: We conducted a retrospective study of 111 comatose OCHA subjects treated with dedicated post-arrest protocols, including therapeutic hypothermia and hemodynamic optimization. These subjects were prospectively enrolled in a multicenter clinical study examining mitochondrial dysfunction from ischemia-reperfusion injury (COMICA Study Group). Subjects not receiving sedation during the initial examination were eligible for analysis. Neurologic examination was classified using the motor and brainstem subscores of the Full Outline of UnResponsiveness (FOUR). For analysis, subjects were dichotomized as deep coma (FOUR Motor+ Brainstem<4) or not. Survival and good neurologic outcome, defined as a Cerebral Performance Category (CPC) of 1-2 and Modified Rankin Scale (mRS) of 0-3 were compared using chi-squared tests.

Results: Mean age was 61 (SD 17) years, 66 (59%) male, witnessed in 91 (82%), and received bystander CPR in 49 (44%) of cases. The predominant rhythm was VF/VT in 56 (50%) and low flow time was 19 (IQR 9, 28) minutes. The initial neurologic examination was obtained without sedation in 54 (49%) of subjects. Subjects with deep coma on initial examination were less likely to survive (18% vs. 65%; p<0.001), or have a good outcome using CPC (15% vs. 45%; p=0.01) or mRS (15% vs. 45%; p=0.01).

Conclusions: Deep coma on initial neurologic examination is associated with death prior to discharge and poor neurologic outcome. However, depth of coma alone is insufficient to rule out good outcome.
Abstract 70: External Validation of the Hypothermic to Ischemic Ratio as a Predictor of Survival from Out-of-Hospital Cardiac Arrest for Patients Presenting with a Shockable Rhythm
Authors: Sawyer Kelly N , Kurz Michael C , Elswick RK , Zhan Chun , Gaudio Michelle , Morrison Laurie J
Published: April 2024

Objectives: The Hypothermic to Ischemic Ratio (H/I Ratio = total hypothermic time (THT) / total ischemic time (TIT)) was derived to predict survival after out-of-hospital cardiac arrest (OHCA) and found to be highly significant in multivariable models. We sought to externally validate these findings.

Methods: Adult, non-traumatic, OHCA patients presenting with a shockable rhythm (VF/pVT) and surviving to hospital admission between September 1, 2007, and December 31, 2011, were considered for inclusion. Structured data were abstracted from a population-based dataset (Strategies for Post Arrest Care (SPARC) Network database (Toronto, Canada)). THT was measured from initiation in the ED, through therapeutic hypothermia (TH) and rewarming to at least 36.5°C. TIT was estimated from call to 911 or EMS witnessed collapse to return of spontaneous circulation (ROSC). Patients were excluded for age >90 years, TIT <5 or >90 minutes, cooling initiated >6 hours after ROSC, rewarming time >30 hours, or missing relevant intervals. Stepwise logistic regression was used to fit the most parsimonious model. Results: Overall, 1,170 OHCA patients received TH, average age 65 years (SD 15.4), 71% male, 85% witnessed, and 43% with bystander CPR. A total of 497 VF/pVT patients met our criteria, with 52.5% surviving to discharge. In multivariable modeling (Table), TIT, age, and H/I Ratio were the most significant predictors for survival (Chi-Sq 123.43, p<0.0001, R² = 0.25, area under curve = 0.82).

Conclusions: External validation of the H/I Ratio confirmed it is a significant predictor for survival in OHCA patients presenting with a shockable rhythm. Prospective studies should consider H/I Ratio as a potential predictor for investigation.
Abstract 8857: Iron Restriction Prevents the Progression of Diabetic Nephropathy in db/db Mice
Authors: Ikeda Yasumasa , Enomoto Hideaki , Tajima Soichiro , Izawa-Ishizawa Yuki , Kihira Yoshitaka , Ishizawa Keisuke , Tomita Shuhei , Tsuchiya Koichiro , Tamaki Toshiaki
Published: April 2024

Background:
Iron is well-known as an essential trace metal for all living body. On the other hand, excess iron causes oxidative stress through catalyzing highly toxic hydroxyl radical via Fenton/Haber-Weiss reaction. Recent studies have shown that iron reduction ameliorates diabetic condition and prevents development of adipocyte hypertrophy. In the present study, we studied the protective effect of iron reduction against diabetic nephropathy, a diabetic complication.

Methods and Results:
We employed male db/db mice, a model of diabetic nephropathy and male db/m mice as control mice. db/db mice were divided into 2 groups, normal diet group (ND)(Fe 100mg/kg food) and iron-restricted diet group (ID)(Fe 10mg/kg food). Urinary albumin excretion was increasing in db/db mice with ND compared with db/m mice with ND, which was suppressed in db/db mice with ID. In renal histological analysis, increased glomerular volume and mesangial area expansion in ND-fed db/db mice were reduced in ID-fed db/db mice. Deposition of extracelluar matrix such as collagen IV and fibronectin was decreased in db/db mice with ID. Upregulated glomerular desmin expression in db/db mice with ND was diminished in db/db mice with ID. In terms with oxidative stress, ID diminished increased superoxide production in kidney of ND-fed db/db mice. Renal expression of NADPH oxidase components, p22phox and NOX4, were augmented in db/db mice with ND-fed, which was abolished by ID-fed. In terms with renal iron transporter, there were no differences of expression of transferrin receptor and divalent metal transporter-1 between db/m mice and db/db mice, increased ferroportin expression in db/db mice with ND- was reversed by ID to the same level as db/m mice. Urinary iron excretion was significantly higher in ND-fed db/db mice, which was reduced with ID administration.

Conclusion:
These findings suggest that dietary iron restriction exert preventive effect against development of diabetic nephropathy via the reduction of oxidative stress.
Abstract 8898: Oxygenation-induced Postnatal Remodeling of the Ductus Arteriosus
Authors: MeiHua Jin , Utako Yokoyama , Ryo Ishiwata , Susumu Minamisawa , Yoshihiro Ishikawa
Published: April 2024

Introduction:
Intimal thickening (IT) is an important remodeling for anatomical closure of the ductus arteirosus (DA). Although the immediate rise of oxygen tension at birth contracts DA smooth muscle, the role of oxygen in vascular remodeling remains unknown.
Hypothesis:
Raising oxygen tension promotes IT and anatomical DA closure.

Methods:
Tissues and vascular smooth muscle cells (SMCs) were obtained from the DA and aorta of rat fetuses on the 21st day of gestation. To examine the effect of raising oxygen tension, SMCs were cultured in a hypoxic chamber (1% O
2
, 5%CO
2
, pO
2
: 20 mmHg) for 3 days and then transferred to a normoxic chamber (21% O
2
, 5% CO
2
, pO
2
: 120 mmHg).Production of basic fibroblast growth factor (bFGF) and H
2
O
2
were measured by ELISA. The area of IT was evaluated by Elastica van Gieson stain. Immunohistochemical analysis was performed using human DA tissues from eight patients with various congenital heart diseases.

Results:
bFGF was highly expressed in the part of IT in human and rat neonatal DA. Oxygenation increased production of bFGF {1.6-fold (1h), 4.2-fold (6h), n=4-8,
P
<0.001}, H
2
O
2
{1.8-fold (10 min), n=6,
P
<0.01} and phosphorylation of ERK1/2 { 2.2-fold (15 min), n=5-9,
P
<0.001} in rat DA SMCs, but not in aortic SMCs. Inhibition of reactive oxygen species (ROS) by apocinin or rotenone, or ERK inhibitor U0126 attenuated oxygen-induced bFGF production. Oxygenation and recombinant bFGF promoted DA SMC migration (1.8-fold, n=6,
P
<0.001). Neutralizing antibody against bFGF, apocynin or rotenone attenuated oxygen-induced migration. In vivo study, intraperitoneal administration of anti-bFGF antibody, ROS inhibitor
N
-acetylcysteine or ERK1/2 inhibitor U0126 attenuated postnatal IT in full-term rat DA (0.8-fold, 0.8-fold, or 0.8-fold, respectively, n=4-10,
P
<0.01). Furthermore, administration of bFGF promoted IT in preterm rat DA (1.4-fold n=4,
P
<0.01). Co-administration of bFGF with a cyclooxygenase (COX) inhibitor, rather than a COX inhibitor alone, significantly enhanced IT and promoted closure of rat preterm DA.

Conclusions:
These results suggest that raising oxygen tension and subsequent induction of ROS induced bFGF secretion via ERK1/2, leading to postnatal anatomical losure of the DA.
Abstract 8948: ST-Segment Elevation in Lead aVR Strongly Predicts 3-Year Adverse Outcomes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi , Tsukahara Kengo , Iwahashi Noriaki , Maejima Nobuhiko , Endo Mitsuaki , Morita Satoshi , Umemura Satoshi , Kimura Kazuo
Published: April 2024

Background:
In non-ST-segment elevation acute coronary syndrome (NSTE-ACS), lead aVR is referred to as a “cavity lead” and ST-segment elevation in this lead (ST↑aVR) may reflect global subendocardial ischemia in NSTE-ACS. We evaluated the prognostic value of ST↑aVR on admission ECG in patients with NSTE-ACS.

Methods:
We studied 548 patients with NSTE-ACS who underwent coronary angiography during initial hospitalization. Patients with bundle branch block and left ventricular hypertrophy were excluded. Patients were divided into the 3 groups according to the degree of ST↑aVR on admission ECG: no ST↑aVR (n=378, G-A); ST↑aVR <1.0 mm (n=98, G-B); and ST↑aVR ≥1.0 mm (n=75, G-C). Troponin T (TnT), hemoglobin (Hb), high-sensitivity C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), brain natriuretic peptide (BNP), TIMI risk score, and summed ST-segment depression in other leads were also measured on admission.

Results:
There were no differences in sex or coronary risk factors except for diabetes mellitus in the 3 groups. In G-A, G-B, and G-C, age was 66±11, 68±11, and 70±11 years; the rates of diabetes mellitus were 29%, 48%, and 51%; Killip ≥2 was 5%, 20%, and 33%; positive TnT was 30%, 45%, and 56%; TIMI risk core was 3±1, 4±1, and 4±2; the levels of Hb were 14±2, 13±2, and 12±2 g/dl; hsCRP was 0.349±1.594, 0.640±1.936, and 0.830±1.740 mg/dl; eGFR was 67±24, 59±28, and 53±27 ml/min/1.73 m
2
; BNP was 149±248, 385±339, and 445±407 pg/ml; summed ST-segment depression was 2±2, 6±4, and 13±7 mm; the rates of left main or 3-vessel disease were 8%, 44%, and 72%; and major adverse events (death, [re]infarction, urgent revascularization, or congestive heart failure) at 3 years were 15%, 38%, and 55%, respectively (all p<0.01). After adjusting for baseline characteristics, multivariate analysis showed that as compared with no ST↑aVR, the hazard ratios (95% CI) for 3-year adverse events associated with ST↑aVR <1.0 mm and ST↑aVR ≥1.0 mm were 1.71 (1.08-6.69; p=0.030) and 3.29 (1.39-7.76; p=0.007), respectively.

Conclusions:
In patients with NSTE-ACS, greater ST↑aVR on admission ECG is strongly associated with poorer clinical outcomes at 3 years. Our findings suggest the importance of ST↑aVR in early risk stratification.
Abstract 8987: Strain Determination by a High Resolution DENSE 3D Speckle Tracking Method Using a New Nongated 4D Echo Image Loops: Validation Against Sonomicrometry
Authors: Mandi Kaavya , Truong Kevin , Kang Christine , Chen Vivian , Ashraf Shahryar , Streiff Cole , Roundhill David , Zhang Zhijun , Song Xubo , Zhu Meihua , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
We tested our DENSE 3D speckle tracking method for strain computation on new nongated 4D echocardiography images, which is a significant resource for 3D imaging of fetal hearts without requiring EKG gating.

Methods:
We studied freshly harvested rabbit hearts (n=5) due to their smaller size, in a water tank to facilitate ultrasound scanning. Each heart was connected to a calibrated pulsatile pump through a latex balloon in the LV cavity secured at the mitral annulus. Two 0.7mm sonomicrometry crystals were secured into myocardium along the long axis of the LV. Pulsatile heart motion was generated by injecting 5 different stroke volumes (SV; 1,2,3,4 and 5ml) into the LV with the calibrated pump. At each SV, sonomicrometry displacement data was recorded and 4D images acquired with an X6-1probe on a Philips iU22 ultrasound system. Image data was exported in AVS format and processed in our MatLab based DENSE speckle tracking method for strain computation.

Results:
Increasing SV increased stretching of myocardial tissue which was detected as well as correlated increases in longitudinal strain both by sonomicrometry and the DENSE speckle tracking strain method. Sonomicrometry derived strains showed a good correlation with 3D DENSE derived strains at all SVs studied (r=0.85, p<0.05).

Conclusions:
New nongated 4D echocardiography is feasible for strain determination in imaging of small hearts.
Abstract 8989: Left Atrial Appendage Volume as a Predictor of Left Atrial Appendage Thrombus and Sludge in Patients With Nonvalvular Atrial Fibrillation: A Three-Dimensional Transesophageal Echocardiographic Study
Authors: Harada Kenji , Tanaka Jun , Tolstrup Kirsten , Gurudevan Swaminatha V , Siegel Robert J , Shiota Takahiro
Published: April 2024

Background:
Clinical and echocardiographic predictors for detecting left atrial appendage (LAA) thrombus are well characterized. However, whether the size of LAA measured by two-dimensional transesophageal echocardiography (2D-TEE) predicts the risk of thrombus formation in LAA has been the subject of much controversy.

Purpose:
The aim of this study was to investigate the ability of LAA volume derived from real-time three-dimensional transesophageal echocardiography (RT3D-TEE) to predict LAA thrombus and/or sludge in patients with nonvalvular atrial fibrillation (NVAF).

Methods and Results:
A total of 71 patients with NVAF lasting ≥ 1 month and without severe valvular regurgitation, who underwent 2D-TEE and RT3D-TEE, were included in the study. They were divided into two groups according to the presence of LAA thrombus and/or sludge. LAA thrombus and/or sludge were detected in 28 patients (39%). In these patients, the prevalence of LAA thrombus and that of LAA sludge were 54% and 100%, respectively. All 2D and 3D measurements of LAA were performed at ventricular end-systole.A trend was only seen for a significant correlation between LAA volume measured by RT3D-TEE and LAA area in the longitudinal section imaged (usually between 60 and 90 dgrees) by 2D-TEE (r = 0.31, p = 0.08). On multivariable analysis, LAA volume and the ratio of early transmitral flow velocity to peak early diastolic mitral annular velocity (E/e') were found to be significantly predictive of LAA thrombus and/or sludge. Conversely, LAA emptying flow velocity predicted freedom from them (Table 1). Receiver operating characteristic analysis yielded an optimal cutoff value of 14.7 cm
3
for LAA volume to detect LAA thrombus and/or sludge (area under the curve 0.89). The sensitivity and specificity of this model were 79% and 89%, respectively.

Conclusion:
Our data suggest that increased LAA volume measurements by RT3D-TEE can assist in the detection of LAA thrombus and/or sludge in the patients with NVAF.
Abstract 9: Total Liquid Ventilation Provides a Combined Neuro- and Cardioprotection After a Shockable Cardiac Arrest Occurring After Regional Myocardial Ischemia in Rabbits
Authors: Darbera Lys , Chenoune Mourad , Lidouren Fanny , Kohlhauer Matthias , Adam Clovis , Bruneval Patrick , Carli Pierre , Vivien Benoît , Ricard Jean-Damien , Dubois-Randé Jean-Luc , Ghaleh Bijan , Berdeaux Alain , Tissier Renaud
Published: April 2024

Introduction: Total liquid ventilation (TLV) with perfluorocarbons has been shown to induce a rapid and protective cooling in animal models of cardiac arrest (CA). In these models, the heart was arrested without underlying myocardial ischemia.

Hypothesis: We assessed whether TLV could provide a combined neuro- and cardioprotection after a CA occurring after previous myocardial ischemia, as commonly observed in the clinical arena.

Methods: Rabbits instrumented with cardiac output (CO) probes were submitted to coronary artery occlusion. Two minutes later, ventricular fibrillation was induced and let untreated during 8 min. Rabbits were subsequently resuscitated and randomly submitted to a normothermic follow-up (Control) or 3 h of hypothermia (32°C) with either TLV or external cold blankets combined to saline infusion (30 ml/kg at 4°C i.v.; Saline group). Coronary artery reperfusion was instituted after 40 min of myocardial ischemia. After awakening, surviving rabbits were followed during 7 days.

Results: Ten rabbits were included and resuscitated in each group. Under cooling, the target tympanic and esophagus temperatures of 32°C were achieved within 5-10 min in TLV vs 30-45 min in Saline group. In the latter group, hypothermia failed to improve subsequent survival, CO or neurological recovery but slightly reduced infarct size vs Control (41±5% vs 54±3% of risk zone, respectively). Conversely, TLV potently reduced infarct size (13±1% of risk zone) and improved CO (e.g., 133±11 vs 84±19 ml/min/kg in survivors at day 1 in TLV vs Control, respectively). As shown in Figure, TLV also improved survival and neurological outcome.

Conclusions: Ultra-fast cooling with TLV induced a potent cardio- and neuroprotection in a rabbit model of CA with underlying myocardial ischemia, whereas conventional hypothermia was less efficient.

Left: Neurological dysfunction score (0%: normal; 100%: death). Right: survival after the cardiac arrest.*, p<0.05 vs Saline and Control
Abstract 90: Systolic and Diastolic Function in Cardiac Arrest Patients During Therapeutic Hypothermia
Authors: Call Shawn L , Milosavljevic Staci L , Gaglianello Nunzio , Widlansky Michael E , Kleczka James F , Choi Byung-il (Bill) W
Published: April 2024

BACKGROUND: Previous studies and experience have suggested that the LVEF might be depressed in patients (pts) undergoing therapeutic hypothermia (TH) after cardiac arrest. We evaluated LV function by echocardiography (echo) during TH in pts with return of spontaneous circulation(ROSC) after cardiac resuscitation to observe whether TH may preserve cardiac function and contractile reserve compared to the patients without TH.

METHOD: Retrospective chart review on 54 out of 292 pts with ROSC between 2007 and 2010 including echo reports performed prior to, during admission, and follow-up period; excluding 125 pts with no ROSC, and 113 pts with clear non-cardiac cause for arrest, age <18 years, and no echo within 24 hrs of presentation post cardiac arrest.

RESULTS: 32 non-TH patients and 22 TH patients were included in the study after applying the exclusion criteria. The two groups differed by location of arrest, with the non-TH group having 13/32 (41%) and the TH group having 16/22 (73%) out of hospital arrests, (p-value=0.028). 17 (53%) non-TH patients and 7 (31%) TH patients survived to discharge. Systolic function after ROSC in pts undergoing TH (average core temperature: 33.3
o
C) and non-TH were 43 +/- 17% vs. 50 +/- 18% (P:NS), with normal EF (50-55%) in 7 vs. 17 pts (P:NS) and depressed EF (15-49%) in 15 vs. 15 pts (P:NS).Diastolic function in pts with TH and non-TH were normal in 6 vs. 10 pts, mild dysfunction in 3 vs. 6 pts, moderate dysfunction in 5 vs. 4 pts, severe dysfunction in 3 vs. 0 pts, and un-interpretable in 5 vs. 12 pts. (P:NS).Other echo variables i.e.systolic and diastolic dimension and LV mass indices were not statistically different in two groups.

CONCLUSION: There was a trend of reduction in LVEF, but no significant deterioration of LV systolic and diastolic function, suggesting TH may not adversely affect cardiac performance during the procedure. A long term improvement in cardiac function in this population linked to TH warrants further investigation to prove the hypothesis that a reduced LVEF may be related to cardioprotective features associated with decreased demand and consumption of energy in the myocardium during TH following cardiac arrest.
Abstract 9000: Long-term Outcomes After Sirolimus-Eluting Stent Implantation for Calcified Coronary Lesions: Insights From the j-Cypher Registry
Authors: Nishida Koji , Kimura Takeshi , Seki Syuichi , Kubokawa Syoichi , Kawai Kazuya , Hamashige Naohisa , Miyano Ichiro , Morimoto Takeshi , Mitsudou Kazuaki
Published: April 2024

Background:
The long-term clinical outcomes of drug-eluting stents for calcified coronary lesions in patients with and without dialysis have not yet been adequately addressed.

Methods:
Among 10,717 patients (16,947 lesions) who were exclusively treated with sirolimus-eluting stents (SES) in the j-Cypher registry, 5-year clinical outcome was compared between patients with at least 1 lesion with moderate to severe calcification (Calc group), and patients with non-calcified (no to mild calcification) lesions only (Non-calc group). Analyses were made separately according to dialysis status (non-dialysis stratum [Calc group: 3208 patients, and Non-calc group: 6919 patients], and dialysis stratum [Calc group: 419 patients, and Non-calc group: 171 patients].

Results:
Cumulative incidence of adjusted risk for 5-year mortality was significantly higher in the Calc group than in the Non-calc group in both non-dialysis stratum (13.5% versus 8.3%: P<0.0001, and hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.07-1.41, P=0.004) and dialysis stratum (49.4% versus 38.6%: P=0.016, and HR 1.53, CI 1.12-2.09, P=0.008). Regardless of dialysis status, the Calc group as compared with the Non-calc group had a significantly higher cumulative incidence of target lesion revascularization (TLR) (non-dialysis, 14.0% versus 11.2%, P<0.0001; dialysis, 33.4% versus 18.7%, P<0.0001) and major adverse cardiac events (MACE) (non-dialysis, 30.4% versus 22.9%, P<0.0001; dialysis, 69.2% versus 53.8%, P<0.0001). In non-dialysis stratum, the cumulative incidence of late TLR beyond 1 year was similar between the Calc and Non-calc groups (7.2% versus 7.0%, P=0.84). However, dialysis patients with calcified lesions had a significantly higher late TLR rate (17.2% versus 8.1%, P=0.014). Stent thrombosis was unrelated to both dialysis and calcification (non-dialysis, 1.5% versus 1.2%, P=0.23; dialysis, 2.6% versus 0.6%, P=0.076).

Conclusion:
Regardless of dialysis status, patients with calcified coronary artery lesions have an increased long-term risk for adverse events, such as mortality, TLR, and MACE, after SES implantation. Lesion calcification in dialysis patients was associated with higher risk for late TLR through 5 years.
Abstract 9121: Does AF Burden Measured By Implantable Loop Recorder During Post-ablation Blanking Period Predict Response At 12 Month Follow-up?
Authors: Pokushalov Evgeny , Romanov Alexander , Losik Denis , Artyomenko Sergey , Turov Alexey , Shirokova Natalia , Karaskov Alexander , Mittal Suneet , Steinberg Jonathan S
Published: April 2024

Introduction:
The aim of this study was to identify if there is a threshold of AF burden during the first months post-ablation obtained through continuous subcutaneous monitoring that can identify patients at risk of subsequent AF recurrences.

Methods:
613 patients with symptomatic drug refractory AF (17% with persistent AF) were enrolled in this retrospective analysis. All patients underwent circumferential pulmunary vein isolation (PVI) and were implanted with an ILR for collecting data on AF burden during 12-month follow-up. AF freedom (Responders) was defined as AF%<0.5% during follow-up period. A ROC curve analysis was performed to identify the value of AF burden during the first 2 months post ablation (Blanking Period, BP) that was predictive of late recurrence of AF.

Results:
After the first ablation procedure, 396 (65%) of the 613 patients were AF-free at 12-month: 346 out of 508 (68%) in the paroxysmal AF group and 50 out of 105 (47%) in the persistent AF group. Using the ROC curve (Fig 1), the specificity corresponding to 90% sensitivity was 75%. The corresponding threshold in the AF burden during the blanking period able to identify patients at risk of late recurrences was 7.1%, corresponding to 102h (= 4.25 days) in AF during the 2 months BP. At the multivariate analysis, a threshold in the AF burden <7.1% during BP was still highly significant (p<0.0001) and the odds of responders/non-responders was 21.5 (10.8 - 42.9).

Conclusions:
The BP AF pattern predicted response to catheter ablation. An AF burden ≥7.1% assessed by continuous monitoring was a powerful predictor of subsequent AF recurrence after initial ablation, and thus be an appropriate guide for early re-intervention.
Abstract 9181: Does a Low Ejection Fraction Predict Mortality? Insights From the ASCEND-HF Trial
Authors: Toma Mustafa , Ezekowitz Justin A , O'Connor Christopher M , Hernandez Adrian F , Bakal Jeffrey A , Sardar Muhammad Rizwan , Zolty Ronald , Massie Barry M , Armstrong Paul W , Starling Randall C
Published: April 2024

Background:
Acute heart failure (AHF) is associated with significant morbidity and mortality. Limited data exist assessing the relationship between left ventricular ejection fraction (EF) and outcomes in patients with AHF.

Methods:
We explored the association between EF and 30-day and 180-day mortality in AHF patients enrolled in the Acute Studies of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial. EF was analyzed as a continuous variable and as 3 categories: 50%(PresEF).

Results:
Of the 7007 patients in the trial, EF was available in 5687 (81.2%) patients: 4474 (78.7%) had LowEF, 674 (11.9%) had IntEF, and 539 (9.5%) had PresEF. Compared to LowEF patients, those with IntEF and Pres EF were older, more likely to be female, have atrial arrhythmias, diabetes, and higher systolic blood pressure, and lower heart rate, respiratory rate and BNP. The unadjusted 30-day and 180-day mortality was similar for LowEF (3.7%, 12.3%), IntEF (3.4%, 13.1%), and PresEF (4.3%, 14.1%), respectively (p>0.05). After multivariable adjustment, the hazard ratio (HR) for 180-day mortality remained similar for the LowEF (HR 0.96, 95% CI: 0.75-1.24; p = 0.77), and IntEF (0.91, 95% CI 0.66-1.3; p = 0.58) compared to the PresEF group. By contrast, when EF was evaluated as a continuous measure, it exhibited a U-shaped relationship, i.e. the lowest risk of 30-day and 180-day death occurred at an EF of 35%. After matching for age and sex, the mortality risk attributed to EF was attenuated for patients with an EF > 35%, but the mortality risk increased exponentially if the EF was < 35%. (Fig.

Conclusions:
Among patients with AHF, 30-day and 180-day mortality is similar for those with IntEF or PresEF but increases exponentially for those with LowEF after accounting for key patient variables. Prior observations of a similar mortality risk for AHF patients with a higher EF need to be reevaluated.
Abstract 9232: Admission Heart Rate and In-Hospital Outcomes in Patients Hospitalized for Heart Failure
Authors: Bui Anh L , Grau-Sepulveda Maria V , Hernandez Adrian F , Peterson Eric D , Yancy Clyde W , Bhatt Deepak L , Fonarow Gregg C
Published: April 2024

Background:
Prior studies have suggested an association between higher heart rate (HR) and higher mortality, particularly in chronic heart failure (HF). Whether this relationship holds true in patients hospitalized with HF and differs between those in sinus rhythm (SR) and those in atrial fibrillation (AF) and by ejection fraction (EF) and has not been well studied.

Methods:
We examined 145,211 admissions for HF from 295 hospitals enrolled in Get With The Guidelines-Heart Failure from January 2005 through September 2011.

Results:
The median admission HR was 82 (IQR 70-97). Patients presenting at higher HR tended to be younger, have less comorbidities, and lower ejection fraction. In-hospital mortality had a J-shaped relationship with HR, with the lowest mortality rate with HR 70-75 (Figure). However, the relationship of mortality and HR differed between patients presenting in SR and AF: at HR above 100 bpm, the mortality curve for AF plateaued, whereas that for patients in SR continued to rise. The J-shaped curves remained similar for patients in HF with reduced EF and those with preserved EF, although patients in HF with preserved EF had a higher risk of mortality with increasing HR above 105 compared to those with reduced EF, but a lower risk of mortality below that cutpoint. After adjusting for patient and hospital characteristics, higher HR was associated with higher mortality (adjusted odds ratio [aOR] 1.26, 95% CI 1.22-1.31 per 10 bpm increase in HR) and longer length of stay (aOR 1.10, 95% CI 1.09-1.12 for LOS > 4days).

Conclusions:
Higher admission HR is independently associated with worse outcomes in patients admitted for HF, in those in SR and AF and preserved and reduced EF. Whether early reduction in HR will improve short-term outcomes in patients hospitalized with HF is worthy of investigation. -.
Abstract 9256: Improving the Sensitivity for Left Ventricular Hypertrophy in Obese Patients by Normalizing Electrocardiographic Criteria to Body Mass Index
Authors: Anaya-Cisneros Mauricio , Purice Gabriel , Cardenas-Garcia Jose L , Mazimba Sula , Goldberg Ythan
Published: April 2024

Introduction:
The electrocardiogram (ECG) has low sensitivity for the diagnosis of LVH in obese patients. We hypothesized that adjusting the voltage on ECG to body mass index (BMI) would increase the sensitivity in this population.

Methods:
From our institutional database we identified patients over age 35 who underwent ECG and transthoracic echocardiography within 6 months. Those with prolonged QRS duration, paced rhythm and significant acute cardiopulmonary disease were excluded. Three ECG criteria for LVH- Sokolow, Cornell and Romhilt-Estes- were compared to echocardiographically derived left ventricular mass index using the Devereux formula. LVH was defined as 134g/m
2
for men and 110 g/m
2
for women. We then performed an adjustment of individuals' summed ECG voltage for each criterion by normalizing to a BMI of 25 with the formula: Adjusted voltage = ECG voltage*BMI/25.

Results:
Of 476 patients studied (255 male, 221 female, mean age 62.5) 36.8% were obese (BMI≥30), and 41.7% had LVH based on echocardiogram (34.1% in the non-obese and 41.7% in the obese group). The sensitivity of all ECG criteria was lower in the obese population. The sensitivity for identifying LVH by Sokolow was 37.7 % vs. 25.0 %, by Cornell 47.7% vs. 41.1 and by Romhilt-Estes 54.6% vs. 37.5% for non-obese and obese patients, respectively (p>0.05). Adjusted Sokolow augmented the sensitivity substantially in from 40.9% to 81.8% (p<0.001) in men and from 14.7% to 38.2% (p=0.001) in women, respectively. Similarly, the adjusted Cornell criterion increased the sensitivity from 40.9% to 86.4% in men (p<0.001) and 41.2% to 73.5% in women (p=<0.001). Adjusted Romhilt-Estes did not show statistically different results. Overall accuracy was not significantly reduced with the adjusted ECG criteria.

Conclusion:
Normalizing Cornell and Sokolow criteria to the BMI significantly improves the sensitivity of ECG to identify LVH in obese patients.
Abstract 9305: Integrating Palliative Care into the Outpatient Heart Failure Disease Management Setting: A Feasibility Study
Authors: Lombardo Dawn , Evangelista L orraine S , Malik Shaista , Ballard-Hernandez Jennifer , Motie Marjan , Liao Solomon
Published: April 2024

BACKGROUND:
There is limited research on the effectiveness of palliative care (PC) programs on symptom distress and quality of life (QOL) in patients with advanced heart failure (HF).

PURPOSE:
We conducted this prospective, comparative study to determine whether a shared care model that integrates PC with standard HF care in an outpatient setting versus standard HF care alone impacts symptom burden, depression, anxiety, and QOL (physical, emotional, overall).

METHODS:
Thirty-six patients (mean age 53.9 ± 68.0; predominantly male [72%]; White [61%]; married [69%]; New York Heart Association class II [69%]) were referred for an outpatient PC consultation in conjunction with their post-discharge follow-up visit with their HF provider. Changes in symptom burden, depression, anxiety and QOL at three months were compared to 36 patients with advanced HF matched on age, gender, race, and NYHA functional class.

RESULTS:
Significant improvements were observed in symptom burden (P < .001), depression (P = .002), emotional QOL (P = .001) and overall QOL (P < .001) in both groups over time; anxiety and physical QOL improved for patients receiving PC but worsened for patients in the comparison group (Table 1). A multivariate model that included PC accounted for 57%, 23%, 75%, 37% and 50% of variance in symptom burden, depression, physical, emotional, and overall QOL, respectively.

CONCLUSIONS:
Our findings support the interpretation that participation in a PC intervention may reduce symptom burden and depression and enhance QOL in patients hospitalized with acute HF exacerbation. Larger scale, prospective, randomized clinical trials sufficiently powered to assess clinical outcomes, are warranted to assess the efficacy of a shared care model that integrates PC with standard HF care in outpatient settings on symptom distress, psychological outcomes, and QOL in patients with advanced HF.
Abstract 9344: Tobacco Smoke Exposure is Associated with Alterations of Cerebrovascular Flow Velocities and Regulation in Children
Authors: Harada Kenji , Abe Tomohiro , Harada Yukiko
Published: April 2024

Background:
Passive smoking (PS) is associated with increased risk for cerebrovascular and cardiovascular events, however, there has been little focus on cerebrovascular function. The purpose of this study is to assess cerebrovascular flow velocities and regulation in PS children.

Methods:
Noninvasive ultrasonographic measurements were made in 51 children (age:9 ± 4years) who have been exposed to tobacco smoking since intrauterine life and 35 age-matched children without PS. Using transcranial color Doppler sonography, peak systolic (PSV), end-diastolic (EDV), and average peak flow (APV) velocities of middle cerebral artery were measured during supine rest and 3 minutes-upright posture. Pulsatile index as a parameter of vascular resistance was calculated. Pulsatile index was defined as (PSV-EDV)/APV. Quantitative B-mode ultrasound scans were used to measure intima-media thickness and diameters of the common carotid artery. Urine cotinine concentrations were assessed.

Results:
Flow velocities and pulsatile index were not significantly different between controls and PS children (p > 0.05). In controls and PS children with urine cotinine concentrations <5ng/ml (n = 26), pulsatile index did not change during upright position (p > 0.05). However, in PS children with urine cotinine concentrations ≥ 5ng/ml (n = 25), there was a significant increase in pulsatile index during upright position (0.93 ± 0.14 vs. 0.87 ± 0.12, p < 0.01), because APV and EDV were significantly lower (69 ± 16 vs. 76 ±17 cm/sec and 44 ± 9 vs. 50 ± 11 cm/sec, p <0.05, respectively), although PSV was not significantly different. The percent change in pulsatile index during an upright position correlated significantly with urine cotinine level (r =0.57, p < 0.01). Intima-media thickness at carotid artery and stiffness did not correlate with cerebral blood flow velocities.

Conclusions:
The present study indicates that passive smoking can adversely affect cerebral blood flow and regulation in the cerebrovascular bed in childhood. Passive smoking not only is a risk factor for later cardiovascular disease, but also is associated with significant impairment of cerebral flow dynamics.
Abstract 9357: Combined Antihypertensive Regimen, Sexual Function, Oxidative Stress and Hypertension: A Randomized Controlled Trial
Authors: YU JING , Yang Longquan , Ma Ruixin , Zhao Feng , Lin Xin , Liu Peijun , Bai Feng
Published: April 2024

Combinations of a calcium channel blocker with either an angiotensin II receptor blocker or a beta-blocker are recommended as effective therapies for hypertension. However, it remains unclear whether these two of combinations have similar effects on sexual function in men with hypertension. This prospective, randomized, parallel open label study (

ClinicalTrials.org.
NCT01238705

) compared the effects of a felodipine-irbesartan combination with those of a felodipine-metoprolol combination on the sexual function and on markers of oxidative stress in men with mild to moderate hypertension. Two-hundred and eighteen participants aged 25 to 60 years were randomly assigned to receive a once daily treatment of either felodipine combined with irbesartan or felodipine combined with metoprolol for 48 weeks. Sexual functioning was evaluated using the International Index of Erectile Function (IIEF) questionnaire at baseline and after 48-weeks of therapy. Levels of serum testosterone, sex hormone binding globulin (SHBG), 8-Hydroxy-2’-deoxyguanosine (8-OHdG), 4-hydroxynonenal (HNE) and malondialdehyde (MDA) were measured. There were no statistical differences of prevalence of erectile dysfunction (ED) between pre- and post-treatment in two groups (P>0.05), also did the levels of serum testosterone, SHBG and HNE. On the other hand, in felodipine-irbesartan group, scores of erectile functions (EF) and sexual desire (SD) were improved. The concentrations of serum 8-OHdG and MDA raised up after treatment (133.47±32.31 versus 130.70±31.25 ng/L, 6.82±1.17 versus 6.59±1.14 nmol/ml). The results suggested that felodipine-irbesartan may be more benefic to EF of hypertensive male patients than felodipine-metoprolol. This effect was possibly relevant to irbesartan, which could prevent oxidative stress. However, further investigations are needed.
Abstract 9358: Accelerated Progression of Coronary Atherosclerosis in Patients With Ultrasonic Features of Plaque Vulnerability
Authors: Kataoka Yu , Wolski Kathy , Balog Craig , Uno Kiyoko , Puri Rishi , Tuzcu E.Murat , Nissen Steven E , Nicholls Stephen J
Published: April 2024

Backgrounds:
Vulnerable plaques typically contain large lipid cores accompanied by expansive vascular remodeling and spotty calcification. While non-occlusive plaque rupture has been proposed as a mechanism for sudden disease progression, the natural history of atheroma progression in patients with vulnerable plaques have not been well characterized.

Methods:
3460 patients with angiographic coronary artery disease underwent serial intravascular ultrasound imaging to monitor atheroma progression in 7 clinical trials of anti-atherosclerotic therapies. Patients with (n=1063) and without (n=2397) focal vulnerable plaques, defined as the combination of percent atheroma volume (PAV) >40%, expansive vascular remodeling and spotty calcification, were compared with regard to clinical characteristics and the rate of atheroma progression.

Results:
Patients with vulnerable plaques were less likely to be female (24 v. 31%, p<0.001) and more likely to have hypertension (82 v. 78%, p=0.01) and diabetes (38 v. 30%, p<0.001). Vulnerable plaque patients harbored more extensive atherosclerotic disease at baseline, with a greater PAV (42.5±7.4 v. 36.9±9.2%, p<0.001) and total atheroma volume (TAV, 207.6±82.7 v. 184.6±82.7 mm3, p<0.001). On serial evaluation, less progression of PAV (0.25±0.28 v. 0.46±0.27%, p=0.08) and TAV (-4.6±2.2 v. -3.0±2.2mm3, p=0.03) was observed in vulnerable plaque patients. Use of statins and optimal control of risk factors including LDL-C and HDL-C levels were associated with the slowest disease progression in patients with vulnerable plaques (Figure).

Conclusions:
While focal vulnerable plaques are associated with more extensive atherosclerotic burden, these patients demonstrate the greatest benefit of risk factor interventions. These findings suggest that while vulnerable lesions have the propensity to promote ischemic syndromes, they present a modifiable substrate that is sensitive to intensive use of medical therapies.
Abstract 9385: Percutaneous Carbon Dioxide Treatment Using a Gas Mist Generator Accelerates Angiogenesis in the Ischemic Hindlimb
Authors: Izumi Yasukatsu , Yamazaki Takanori , Nakamura Yasuhiro , Yamaguchi Takehiro , Hanatani Akihisa , Shimada Kenei , Yoshiyama Minoru , Iwao Hiroshi
Published: April 2024

Background:
Although highly-concentrated carbon dioxide (CO
2
) is thought to be useful for ischemic diseases, devising an artificial CO
2
-rich bath is difficult. Hypothesis: We hypothesized that the treatment with a few micrometers of CO
2
particles atomized by double-fluid nozzles (CO
2
mist) would exert an angiogenic effect in the ischemic hindlimb.

Methods and Results:
(1) Lower bodies of rats with unilateral hindlimb ischemia were wrapped in a polyethylene bag filled with CO
2
gas alone or CO
2
mist by a gas mist generator (Advance Biotron). Near-infrared spectroscopy revealed that CO
2
mist-treatment increased oxygenated hemoglobin and decreased deoxygenated hemoglobin in the ischemic leg of rats. However, CO
2
gas-treatment did not change these parameters. (2) Mice with unilateral hindlimb ischemia were divided into the untreated (UT) group and CO
2
mist-treated (CM) group. CO
2
mist was treated to mice in the same way as rats for 10 minutes a day. By a laser Doppler analysis, ischemic hindlimb blood flow in the CM group was higher persistently after 7th days of induction of ischemia than that in the UT group. Furthermore, capillary density by immunostaining with anti-CD31 was also significantly increased in the CM group at day 28, compared with the UT group. These effects were abolished by administration of Nω-Nitro-L-arginine, an inhibitor of nitric oxide synthase. Vascular endothelial growth factor mRNA expression at days 4 and 7 was increased in the CM group but not in the UT group. (3) At 4 days after ischemia, digested proteins of muscles from the nonischemic, UT or CM group were labeled with isobaric tag for relative and absolute quantitation (iTRAQ) reagents, and proteomic analysis was performed by liquid chromatography - tandem Mass spectrometry (LC/MS/MS). Sixty-eight and 62 of identified 195 proteins were increased and decreased by ischemia, respectively. The treatment of CO
2
mist downregulated some of the 68 increased proteins, which were mainly signal transduction-related proteins. On the other hand, CO
2
mist-treatment upregulated some of the 62 decreased proteins, which were mainly metabolic enzyme-related proteins.

Conclusion:
Percutaneous CO
2
mist therapy may be a potentially useful for ischemia-induced angiogenesis.
Abstract 9396: Bayesian Methods Affirm the Use of Percutaneous Coronary Intervention to Improve Survival in Patients with Unprotected Left Main Coronary Artery Disease
Authors: Bittl John A , He Yulei , Jacobs Alice K , Normand Sharon-Lise T
Published: April 2024

Introduction:
Several randomized clinical trials (RCTs) have supported the Class I recommendation for coronary artery bypass grafting (CABG) for unprotected left main coronary artery disease (ULMCAD). In the absence of RCTs directly comparing percutaneous coronary intervention (PCI) with medical therapy (MT) for this indication, the new Class IIa recommendation for PCI to improve survival in selected patients with ULMCAD has been statistically inferred from several studies comparing CABG with PCI.
Hypothesis:
We tested whether Bayesian approaches supported the recommendation for PCI to improve survival in patients with ULMCAD.

Methods:
We performed a Bayesian cross-design and network meta-analysis of 12 studies (4 RCTs, 4 observational matched studies and 4 other cohort studies) comparing CABG with PCI (N=4,574 patients) and of 7 studies (2 RCTs and 5 observational studies) comparing CABG with MT (N=3,224 patients).

Results:
The odds ratios (ORs) for 1-year mortality after PCI versus CABG using Bayesian cross-design meta-analysis were not different among RCTs (OR 0.99, 95% Bayesian credible interval [BCI] 0.67-1.43), matched cohort studies (OR 1.10, 95% BCI 0.76-1.73), and other types of cohort studies (OR 0.93, 95% BCI 0.58-1.35). A network meta-analysis suggested that MT alone is associated with higher 1-year mortality than the use of PCI for patients with ULMCAD (Figure).

Conclusions:
Bayesian methods support the current revascularization guidelines and suggest that PCI may improve survival over MT alone for patients with ULMCAD. An integrated approach analyzing data from both observational and randomized studies using Bayesian methods may yield new insights to enhance the translation of trial data into clinical practice.