bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14382: Outcomes of Heart Transplantation in the Smallest Infants: To List or Let Grow?
Authors: Bock Matthew J , Pahl Elfriede , Eltayeb Osama , Costello John M , Gossett Jeffrey G
Published: April 2024

Introduction:
Waitlist and post-transplant outcomes for heart transplantation (HTx) in infants below 5 kg are not well defined.

Hypothesis:
We hypothesize that lower listing weight leads to higher waitlist and post-HTx mortality in the smallest infants.

Methods:
All children <5 kg listed for primary (1°) HTx between 10/87-12/14 were identified in the United Network for Organ Sharing database. Demographic and clinical covariates, along with waitlist and post-HTx survival, were compared between weight groups. Waitlist and post-HTx survival differences were assessed via the Kaplan-Meier method and a Cox proportional hazards model assessed independent risk factors for mortality.

Results:
Over the 27 year study period, 2,785 infants <5 kg were listed for 1° HTx. Median waiting time was 25 days [IQR 9-57]. The majority had congenital heart disease (79%) and 205 (7%) were <2.5 kg. Waitlist death or removal due to deterioration was more common in infants <2.5 kg (37%), compared to 31% in those 2.5-5 kg (p <0.01). Waitlist survival was worse for patients with progressively lower listing weight (p <0.01; Fig. 1a). In addition, 30-day and 1-year post-HTx survival were worse in the <2.5 kg cohort [77%, 64% (<2.5 kg) vs. 89%, 79% (2.5-5 kg), respectively] (p <0.01; Fig. 1b). However, 1-year conditional survival after HTx was not different between the groups (p=0.82; Fig. 1c). In the <2.5 kg group, pre-HTx ECMO requirement was an independent risk factor for waitlist and post-HTx mortality [waitlist adjusted HR 4.3 (CL 2.0, 9.2), post-HTx adjusted HR 11.3 (CL 4.0, 31.8); p <0.01].

Conclusions:
For small infants, lower listing weight is associated with increasing waitlist mortality. Early post-HTx mortality is worse for infants weighing <2.5 kg and the need for ECMO while listed greatly increases these risks. Despite elevated waitlist and early post-HTx mortality, long term conditional survival for infants <2.5 kg is similar to that achieved in patients weighing 2.5-5 kg.
Abstract 14689: Effects of Statin Therapy on Three-Dimensional Morphology of Fibrous Caps in Lipid Plaques: Analysis Using a Newly Developed Algorithm for OCT
Authors: Wang Zhao , Cho Young-Seok , Soeda Tsunenari , Xing Lei , Jia Haibo , Aguirre Aaron , Vergallo Rocco , Minami Yoshiyasu , Lee Hang , Fujimoto James G , Yu Bo , Jang Ik-Kyung
Published: April 2024

Background:
The exact dose-dependent mechanism of plaque stabilization with statin therapy remains unclear. The objective of this study is to compare the effects of different doses of statin therapy on 3D morphology of fibrous caps using optical coherence tomography (OCT).

Methods:
Patients with coronary artery disease were randomized into two groups of treatment: atorvastatin 20 mg/day (moderate intensity) and atorvastatin 60 mg/day (high intensity), and were imaged by OCT at baseline and 12-month follow-up. A total of 31 lipid plaques from 21 patients were analyzed. Fibrous caps were quantified in 3D using a novel computer algorithm. 3D metrics provided comprehensive information on the distribution and surface area of fibrous caps in a thickness category (e.g. <80 μm). Fibrous caps were reconstructed in 3D to assess plaque vulnerability (Fig. 1).

Results:
Both high and moderate intensity statin therapy increased fibrous cap thickness at follow-up. However, only high intensity statin therapy reduced thin cap (<80 μm) area significantly at follow-up. Conventional metrics such as the minimum cap thickness failed to reveal the differences between the treatment groups (Fig. 2). Instead, 3-D metrics, in particular the thin cap area change showed dose-dependent differences between the treatment groups (p<0.001). 3-D reconstructions further revealed that high intensity statin treatment induced a more rapid transition from thin to thick caps.

Conclusions:
High intensity statin therapy more effectively stabilized fibrous caps. Thin cap area can be used as a better metric than minimum cap thickness for characterizing vulnerable plaque evolution.
Abstract 14693: Incremental Utility of BNP and LV Global Longitudinal Strain in Predicting Post-operative LV Systolic Dysfunction and Outcomes in Asymptomatic Patients With Significant Primary Mitral Regurgitation Undergoing Mitral Valve Surgery
Authors: Alashi Alaa , Mentias Amgad , Patel Krishna , Gillinov A Marc , Popovic Zoran B , Mihaljevic Tomislav , Rodriguez L Leonardo , Sabik Joseph F , Griffin Brian P , Desai Milind Y
Published: April 2024

Background:
Outcomes after mitral valve (MV) surgery for primary mitral regurgitation (PMR) are excellent. However, some patients have a drop in post-op left ventricular ejection fraction (LVEF), despite preserved pre-op LVEF. In asymptomatic patients with ≥3+ PMR with preserved pre-op LVEF (≥60%) who underwent MV surgery for class IIa indications, we assessed the incremental ability of brain natriuretic peptide (BNP) & LV-global longitudinal strain (LV-GLS) to predict a) a reduction in post-op LVEF & b) long-term mortality.

Methods:
We included 448 such patients (61±12 years, 69% men) who had MV surgery between 2005-08. Clinical (including logBNP), baseline (including LV-GLS using Velocity Vector Imaging) & follow up echo (LVEF) data were recorded. Post-op LVEF <50% was considered abnormal. Society of Thoracic Surgeons (STS) score was calculated. Death during follow-up was recorded.

Results:
At baseline, atrial fibrillation, angiotensin inhibitors and betablockers & MV flail were observed in 21%, 55%, 40% & 45%, while mean STS score, logBNP, MV efective regurgitant orifice, LVEF, right ventricular systolic pressure & LV-GLS were 4.1±1, 4.1±1, 0.55±0.2 cm2, 62±2%, 37±15 mm Hg & -20.6±2%. 92% underwent MV repair (11% with coronary bypass) & 94 (21%) had abnormal post-op LVEF. At 7.7±2 years, there were 30 (7%) deaths. Figure 1a shows logistic regression of association between abnormal post-op LVEF & various factors. On multivariable Cox survival analysis, higher STS score (Hazard ratio or HR 1.55), lower LV-GLS (HR 1.17) & higher logBNP (HR 2.26) were independent predictors of long-term mortality (all p<0.05). Figure 1 b-c shows curves for long-term survival, based on LV-GLS & log-BNP better or worse than median.

Conclusions:
In asymptomatic patients with ≥3+ PMR & baseline LVEF ≥60% who underwent MV surgery, lower baseline LV-GLS & higher logBNP were associated with abnormal post-op LVEF. Both, higher logBNP & LV-GLS were associated with higher long-term mortality.
Abstract 14791: Mitral Annular Calcification is Not Associated With Survival After Percutaneous Edge-to-Edge Repair of Mitral Regurgitation
Authors: Tat Emily , Cheng Richard , Arsanjani Reza , Siegel Robert J , Hussaini Asma , Trento Alfredo , Kar Saibal
Published: April 2024

Introduction:
Mitral annular calcification (MAC) has been associated with age, hemodialysis (HD) status, coronary disease, and mortality. While MAC is seen frequently in pts undergoing percutaneous edge-to-edge repair of mitral regurgitation (MR) its impact on survival is unknown.

Hypothesis:
MAC is not associated with mortality after percutaneous MR repair.

Methods:
Pts who underwent MitraClip repair of MR between Apr 2009 and May 2014 were included. Kaplan-Meier survival was plotted between pts with no MAC and pts with MAC. A multivariate Cox regression of all-cause mortality was performed simultaneously adjusting for MAC, age, HD status, and prior myocardial infarction (MI).

Results:
173 pts were included. Mean age at percutaneous repair was 76.9 ± 12.6 yrs and 40.8% were females. MAC was present in 86/173 (49.7%) of pts, and was mild in 61/86 (70.9%) cases and moderate or severe in the remaining cases. In pts with MAC prevalence of prior MI was higher 28/86 (32.6%) vs. 16/87 (18.4%) p=0.037 but ejection fraction was similar 51.8 ± 17.1 vs. 50.4 ± 18.6 % p=0.603. Age was increased in pts with MAC 79.9 ± 10.1 vs. 74.3 ± 14.0 yrs p=0.003. MR was moderate-to-severe in 35/173 (20.2%) of pts and severe in 138/173 (79.8%) of pts. MR improved by 2 grades or more in 165/173 (95.4%) of pts after repair. Survival was decreased in pts with MAC as compared to pts with no MAC by Log Rank p=0.049 (Figure 1A). However, in a multivariate Cox regression model of all-cause mortality, MAC, after adjusting for age, HD status, and prior MI, was not associated with mortality with a hazard ratio of 1.166 (95% CI 0.707 - 1.922) p=0.548 (Figure 1B). In this model age and prior MI were associated with mortality with hazard ratios of 1.048 (95% CI 1.021 - 1.077) p=0.001 and 1.798 (95% CI 1.052 - 3.075) p=0.032, respectively.

Conclusions:
The presence of MAC was not associated with mortality after adjusting for age, HD status, and prior MI and should not preclude the MitraClip procedure. Procedural success was equally high.
Abstract 14799: Clinical Outcomes and Health-related Quality of Life of Catheter Ablation vs. Anti-arrhythmia Drug Therapy Among Atrial Fibrillation Patients in China
Authors: Du Xin , Wu Jiahui , Guo Xueyuan , Li Songnan , Sang Caihuai , Yu Ronghui , Long Deyong , Dong Jianzeng , Jia Yu , Xuan Jianwei , Ma Changsheng
Published: April 2024

Introduction:
Although catheter ablation of atrial fibrillation(AF) has been demonstrated to be associated with significantly better rhythm control compared with anti-arrhythmia drug therapy (AAD),whether this treatment can improve Health-Related Quality of Life (HRQOL) remains unknown.

Methods:
This is a prospective, single center study conducted in Beijing Anzhen Hospital. Patients were treated at the discretion of their physician and propensity score matching was performed to ensure the comparability of patients in the ablation and AAD arms. HRQOL evaluated at each 3-month follow up period was the primary endpoint of this study. The first 3 month after enrollment was excluded as a blanking period. HRQOL were measured using Short Form-36 (SF-36) and Atrial Fibrillation Effect on Quality-of-life questionnaire (AFEQT).

Results:
This study enrolled 318 and 151 subjects in the drug treatment and catheter ablation arms respectively. For the matched 75 pairs of paroxysmal AF subjects, 82.0% in the ablation arm and 22.4% in the AAD arm was in sinus rhythm at 12 month follow up. For the matched 57 pairs of persistent AF, 65.3% and 19.3% patients was in sinus rhythm in the ablation and AAD arms respectively. In the ablation arm, the subjects showed significant improvement in their SF36 and AFEQT scores compared with subjects in the AAD arm (all p<0.001 when compared with AAD subjects at the same follow up period, Figure 1)

Conclusion:
The ablation treatment has demonstrated significantly improved quality of life compared with
anti-arrhythmia
drug therapy in Chinese AF patients.

Table of Contents
Abstract 14869: Survivors of Adult Out-of-Hospital Cardiac Arrest Are Likely to be Neurologically Intact Despite Prolonged Prehospital Resuscitation
Authors: Williams Jefferson G , Bachman Michael W , Box James W , O'Neal D. Alan , Myers J. Brent
Published: April 2024

Introduction:
Preliminary data suggest that adult out-of-hospital cardiac arrest (OHCA) patients may survive neurologically intact with duration of prehospital resuscitation (DOPR) exceeding previous guidelines. We assess how DOPR affects neurologically intact survival (NIS) from OHCA.

Methods:
We conducted an observational study of all OHCA patients in our urban/suburban advanced life support EMS system (pop 1,000,000) from 2005-2014. Excluded were resuscitations not attempted, age < 16, trauma patients, and EMS-witnessed arrests. DOPR was measured from time of dispatch to end of prehospital resuscitation, defined by first return of spontaneous circulation, en-route hospital, or death. Primary outcome was NIS, defined as cerebral performance category (CPC) 1 or 2. Multiple modelling approaches including decision trees and multivariate logistic regression were used to determine predictors of NIS.

Results:
Of 3814 eligible OHCA, patients were: mean age 64.3 years and 60.4% male, 38.2% bystander witnessed, and 43.3% bystander assisted. Median time to first arriving professional response unit was 4.6 min (IQR 3.4-6.0). We controlled for resuscitation protocol changes over time, with median CPR fraction of 96% (IQR 93-96) and median compression rate 114 (103-137) during the most recent phase. Overall, 467 survived (12.2%) and 392 had NIS (83.9% of survivors). The median DOPR for NIS was 18 min (12-25), and the 90th percentile for NIS was 35 min, with 39 patients surviving neurologically intact with DOPR > 35 min. The adjusted OR (95% CI) for the continuous variable DOPR was 0.99 (0.99-1.00) for NIS and 1.00 (0.99-1.00) for overall survival. The length of time that EMS was on scene also had an adjusted OR of 1.00 (1.00-1.00) for both survival and NIS. Significant predictors of NIS include age, initial rhythm, witnessed, basic airway, prehospital ROSC, and therapeutic hypothermia phase. Intermittent physiologic parameters such as End Tidal CO2 measured at 30 minutes after dispatch were not predictive. Limitations include the observational study design. CONCLUSIONS: In this retrospective analysis of OHCA, a majority of survivors were NIS regardless of DOPR. Further study should examine predictors of paramedics’ decision to extend resuscitation.
Abstract 14960: Left Ventricular Native T1 Time and the Risk of Arial fibrillation Recurrence After Pulmonary Vein Isolation in Patients With Paroxysmal Atrial Fibrillation
Authors: Kato Shingo , Roujol Sébastien , Basha Tamer , Berg Sophie , Kissinger Kraig V , Goddu Beth , Manning Warren J , Nezafat Reza
Published: April 2024

Introduction:
Native T1 mapping has emerged as a noninvasive non-contrast magnetic resonance imaging (MRI) method to assess for diffuse myocardial fibrosis. However, LV native T1 time in atrial fibrillation (AF) patients and its clinical relevance are unclear.

Hypothesis:
We hypothesized that native T1 time is elevated in AF patients and elevated native T1 time is associated with higher rate of AF recurrence after pulmonary vein isolation (PVI).

Methods:
Fifty paroxysmal AF patients referred for PVI (60±8 years, 37 male) and 13 healthy control subjects (57±8 years, 10 male) were studied. All patients were in sinus rhythm during the MRI scan. Native T1 mapping images were acquired using a Modified Look-Locker imaging (MOLLI) sequence in 3 short-axis planes (basal, mid and apical slices) using an electrocardiogram triggered single-shot acquisition with a balanced steady-state free precession readout.

Results:
LV ejection fraction was similar between groups (AF: 61±6%; controls: 60±5%, p=0.31). No LV myocardial scar was observed in any patient on LGE. Myocardial native T1 time was greater in AF patients (1099±52 vs 1047±26 msec, p=0.001). During a mean follow-up period of 233 days, 7 of 50 (14%) patients experienced recurrence of AF. Kaplan Meier curve demonstrated significant difference in AF recurrence between patients with elevated LV native T1 time and patients with non-elevated LV native T1 time (p=0.032 by Log-rank test, elevated native LV T1 time was defined as >2SD of controls: 1099msec). Cox proportional hazard analysis identified native T1 time as an independent predictor of recurrence of AF (HR: 1.21, 95% CI: 1.05-1.40, p=0.009).

Conclusions:
There are differences in the native LV myocardial T1 time between AF patients with preserved LV function referred for PVI and normal controls. Native T1 time is an independent predictor of recurrence of AF after PVI in patients with paroxysmal AF.
Abstract 14982: Comparison of Hybrid Endovascular and Open Surgical Repair for Proximal Aortic Arch Diseases
Authors: Oh Pyung Chun , Kang Woong Chol , Ko Young-Guk , Shin Eak Kyun , Choi Donghoon , Park Chul-Hyun , Youn Young Nam , Lee Do Yun , Moon Jeonggeun , Kim Sihun , Chung Wook-Jin
Published: April 2024

Background:
To compare the outcomes of hybrid endovascular and open surgical repair for proximal aortic arch diseases.

Methods:
A total of 55 consecutive patients with an aortic arch aneurysm or aortic dissection involving any of zone 0 to 1 (39 male, age 63.4±14.3 years) who underwent a hybrid endovascular repair (n=35) or open surgical repair (n=20) from 2006 to 2014 were included in a retrospective analysis. Perioperative and late outcomes were compared.

Results:
The two groups had similar baseline characteristics, except age and EuroSCORE II, which were higher in the hybrid group. Perioperative mortality or stroke did not differ significantly between the two groups, but tended to be lower in the hybrid repair group than in the open repair group (11.4% vs. 30.0%, p=0.144). Incidences of other morbidities did not differ. During follow-up, similar over-all survival was observed between the hybrid group and the open repair group (87.3% vs. 79.7% at 1 year and 83.8% vs. 72.4% at 3 years; p=0.319). However, significantly lower reintervention-free survival was observed for hybrid repair compared with open repair (83.8% vs. 100% at 1 year and 65.7% vs. 100% at 3 years; p=0.022).

Conclusions:
Comparable perioperative and late outcomes were observed for hybrid endovascular repair of proximal aortic disease compared with open surgical repair, despite a higher reintervention rate during follow-up. Therefore, hybrid repair may be considered as an acceptable treatment alternative to surgery, particularly in patients at high surgical risk.
Abstract 15079: Complete Revascularization for Multivessel Disease ST Elevation Myocardial Infarction: Insights From an Updated Meta-Analysis
Authors: Kundu Amartya , Sardar Partha , Chatterjee Saurav , Giri Jay , Mukherjee Debabrata
Published: April 2024

Introduction:
Multivessel Disease is commonly seen in ST Elevation Myocardial Infarction (STEMI). Current guidelines recommend primary percutaneous coronary intervention (PCI) on only the culprit vessel , unless the patient is hemodynamically unstable. Recent trials have reported significant benefit on cardiovascular endpoints with complete revascularization of vessels during STEMI. The purpose of this meta analysis was to assess the benefit of complete revascularization (either single setting or staged PCI) compared to culprit only PCI in STEMI patients with multivessel disease.

Methods:
We searched PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science ,CINAHL databases and presentations at major cardiovascular scientific sessions from inception through June 5th, 2015. Randomized Trials comparing complete revascularization strategies (single-setting PCI or staged PCI) and culprit-only PCI were included. The primary outcome of interest was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, new myocardial infarction (MI) and repeat revascularization.

Results:
Seven trials enrolling a total of 2006 patients were included in the final analysis. Complete revascularization (single-setting PCI + staged PCI) was associated with a significant reduction in MACE, when compared to culprit only PCI [OR 0.52; 95 % CI 0.32 to 0.85; P = 0.009]. However, there was no significant difference in all cause mortality [OR 0.75; 95 % CI 0.51 to 1.12] or recurrent MI [OR 0.74;95 % CI 0.4 to 1.39] with complete revascularization.

Conclusion:
In patients with STEMI and multivessel disease, complete revascularization is associated with a significant reduction in major adverse cardiovascular outcomes, driven primarily by a reduction in repeat revascularization, with no evidence of significant difference in all cause mortality or recurrent MI when compared to culprit only PCI.
Abstract 15101: Does Echocardiography Provide Additional Insight Into Outcome in Patients Admitted With Acute Respiratory Decompensation?
Authors: Gumber Divya , Sanghi Vedha , Young Laura , Zdradzinski Michael , Sasidhar Madhu , Krasuski Richard A
Published: April 2024

Background:
Hospitalization for decompensated lung disease is known to portend a poor prognosis. Scoring systems can predict clinical outcome, though few have included cardiac features. Whether echo provides additional prognostic benefit is unknown.

Methods:
We manually reviewed the electronic medical records of patients admitted with acute respiratory failure to a special pulmonary recovery unit. We examined demographic characteristics and echos performed during hospitalization. When available we also reviewed echos prior to admission. All death certificates were reviewed, as were the discharge summaries.

Results:
Among 327 patients only 241 (74%) survived to discharge. Survivors were similar to descendents with respect to age (64 years), sex (42% vs. 49%), obstructive lung disease (70 vs. 61%), diabetes (41% vs. 51%) and coronary disease (33% vs. 25%). Patients who died had more chronic kidney disease (35% vs. 19%, p=0.007), lower albumin (3.2±0.7 vs. 3.0±0.7, p=0.018), lower sodium (136±7 vs. 139±5, p=0.003) and higher serum lactate (2.4±2.0 vs. 1.5±1.4, p=0.001). Interestingly there were no differences in left ventricular size, function or valve disease based on survival. Similarly right ventricular size and function were not different, and right ventricular systolic pressure was comparable. Right atrial dilatation was present in 11% of descendents, compared with 28% of survivors (p=0.007); similarly right atrial pressure was lower in descendents (6.0±3.6 vs. 7.1±3.9, p=0.013). Renal function worsened more frequently in descendents (p=0.005), suggesting possible prerenal azotemia. Different multivariable models each demonstrated right atrial dilatation as the most potent predictor of outcome. Interestingly on the prior echo no difference was seen in right atrial dilatation (35% vs. 34%), again suggesting transient volume depletion.

Conclusions:
In patients admitted with respiratory decompensation, mortality is high (>25%). Echo provides independent prognostic information, surprisingly not related to pulmonary pressure or biventricular size and function, but by presence of right atrial enlargement. The latter appears protective, suggesting an important role for properly maintaining volume status in these patients.
Abstract 15155: Good Exercise Capacity Alleviates the Effect of High Coronary Atherosclerotic Burden on All-cause Mortality
Authors: Sung Jidong , Yoon Ji Hyun , Choi Su-Yeon , Chang Hyuk-Jae
Published: April 2024

Introduction:
Both exercise capacity and coronary artery calcium score (CACS) have been reported to be important prognostic factors. It has not been well studied whether there is significant interaction between these two factors in influencing clinical outcome.

Hypothesis:
The effect size of CACS on all-cause mortality is reduced by higher level of exercise tolerance.

Methods:
From multicenter registry of health screening cohort, 26,286 subjects were included in the final dataset for analysis who underwent both coronary calcium scoring and treadmill exercise test. All-cause mortality data were obtained from national mortality registry.

Results:
The mean age of study subjects was 54 ± 8 years and proportion of male subjects 81%. Median follow-up duration was 5.5 (interquartile range 3.6 - 7.5) years and 232 (0.9%) deaths occurred. In fully adjusted Cox’s proportional hazard model with interaction term, exercise capacity ≥ 10 METs (hazard ratio (HR) 0.684, 95% CI 0.483 - 0.971) and CACS ≥ 400 (HR 3.328, 95% CI 1.850 - 5.988) were significant predictors of mortality and the HR of CACS ≥ 400 in those with lower exercise capacity is estimated to be about three times of that in those with higher exercise capacity. (HR 3.328 in < 10 METs vs. 1.108 in ≥ 10 METs, p for interaction = 0.024) after adjustment for age, gender, fasting glucose, serum creatinine, serum ALT and serum albumin.

Conclusions:
In subjects with higher exercise capacity, the effect of very high CACS on all-cause mortality was significantly smaller than in those with lower exercise capacity. Good physical fitness is likely to override, at least partially, the adverse effect of high coronary atherosclerotic burden.
Abstract 15229: Critical Protective Role of Endogenous Nitric Oxide in Established Severe Pulmonary Arterial Hypertension in Rats
Authors: Tanaka Mariko , Abe Kohtaro , Oka Masahiko , Schwenke Daryl O , Shirai Mikiyasu , Kuwahira Ichiro , Hirooka Yoshitaka , Hoka Sumio , Sunagawa Kenji
Published: April 2024

Background:
It is widely believed that impared bioavailability of endothelium-derived nitric oxide (NO) contributes to the development of pulmonary arterial hypertension (PAH). However, there are reports that show high pulmonary endothelial NO synthase (eNOS) expression in PAH patients, and the functional roles of endogenous NO in established PAH remain unclear.

Hypothesis:
We tested the hypothesis that pulmonary eNOS expression is increased, and that endogenous NO plays an important functional role in a rat model of PAH.

Method and Results:
Adult male Sprague Dawley rats (BW: 150 - 200g) were injected subcutaneously with Sugen5416 (20 mg/kg; VEGF receptor blocker), and exposed to hypoxia (10% O2) for 3 weeks followed by a return to normoxia for 5 weeks. Hemodynamic examination was performed at the 1-, 3-, 5- and 8-week (wk) time points after Sugen5416 injection. RV systolic pressure increased time-dependently (RVSP: 47 ± 6, 83 ± 14, 101 ± 22, and 122 ± 16 mmHg at 1-, 3-, 5- and 8-wk time points, n=4-6) compared with normal rats (31 ± 2 mmHg, n=4, p<0.01, respectively). Blockade of NOS with Nω-nitro-L- arginine methyl ester (L-NAME, 30 mg/kg, iv) further increased RVSP acutely (ΔRVSP from each baseline: 7 ± 11, 25 ± 11, 52± 21, and 43 ± 13 at 1-, 3-, 5- and 8-wk time points) compared with normal rats (0.8 ± 1.1 mmHg). At the 8-wk time point, inhibition of NOS caused a marked RVSP elevation (165 ± 11 mmHg), leading to RV failure and death in all rats tested. In vivo pulmonary angiogram using the synchrotron radiation microangiogram system showed severe small pulmonary arterial narrowing in response to L-NAME. Western blot analysis showed increased eNOS protein levels in PAH rat lungs (n=4 each time point; p<0.01 vs. normal) and immunohistochemisty revealed high expression of eNOS in remodeled pulmonary arteries at the 5- and 8-time points.

Conclusion:
Based on our findings that L-NAME caused marked pulmonary vasoconstriction and further elevation in RVSP and that there was high lung eNOS protein levels in advanced PAH rats, we conclude, contrary to the general assumption, that endogenous NO presumably via eNOS may play a critical protective role by counteracting severe pulmonary vasoconstriction in established PAH.
Abstract 15237: Inhibition of the Kynurenine Pathway Improves Neurological Recovery in a Rat Model of Cardiac Arrest
Authors: Affatato Roberta , Lucchetti Jacopo , Ceriani Sabina , Fumagalli Francesca , Fracasso Claudia , Staszewsky Lidia , Letizia Teresa , Masson Serge , Gobbi Marco , Latini Roberto , Ristagno Giuseppe
Published: April 2024

Introduction:
Kynurenine pathway (KP), the major route of the tryptophan (TRP) catabolism, is involved in the pathogenesis of numerous cerebral disorders. We have previously demonstrated that KP is activated following cardiac arrest (CA) and correlates with neurological injury both in animals and humans. We thus hypothesized that inhibition of the enzyme initiating the TRP catabolism into kynurenine (KYN), i.e. indoleamine-2,3-dioxygenase (IDO), could prevent KP activation and improve neurological recovery.

Methods:
Twenty-two rats received oral administration of 1-Methyl-Tryptophan (1-MT, 800mg/Kg of racemate) (n=10) or corresponding vehicle (n=12), 24h and 2h before CA. Ventricular fibrillation was induced and untreated for 8 min. CPR was then performed for additional 8 min prior to defibrillation. Blood samples were obtained for assay of plasma levels of: 1-MT, TRP, KYN, high-sensitive cardiac troponin T (hs-cTnT), and neuron specific enolase (NSE). Rats were observed up to 96h for assessment of neurological recovery by the neurological deficit score (NDS).

Results:
High plasma levels of 1-MT were observed up to 96h after drug administration (Fig). CA induced a significant and long-lasting KP activation (reported as KYN/TRP) and this was significantly reduced in rats treated with 1-MT (Fig). 90% of animals treated with 1-MT were successfully resuscitated compared to 75% of those treated with vehicle. Lower levels of hs-cTnT (5186 vs. 9207 ng/L) and NSE (0.44 vs. 0.76 ng/mL) were observed in treated animals compared to vehicles. 1-MT also significantly reduced the KP activation in the hippocampus, restoring the KYN/TRP ratio to the values observed in naïve rats. The severity of CA-induced neurological deficit was significantly reduced by 1-MT (Fig), and correlated with level of KP activation, both in plasma (Fig) and in the hippocampus (r=0.73, p=0.019).

Conclusions:
In this model, inhibition of KP was feasible and improved neurological recovery after CA.
Abstract 15292: Quantitative Waveform Measures Predict Survival From Out-of-hospital Cardiac Arrest Independent of Prior Cardiovascular Disease
Authors: Hulleman Michiel , Blom Marieke T , Salcido David D
Published: April 2024

Introduction:
Quantitative waveform measures (QWM) of ventricular fibrillation (VF) can predict survival from out-of-hospital cardiac arrest (OHCA). However, cardiovascular disease (CVD) can change QWM as well as outcome from OHCA. We assessed the hypothesis that risk factors for and the presence of CVD were associated with changes in VF amplitude spectrum area (AMSA) and survival from OHCA.

Methods:
Data from ARREST, a registry of all OHCAs in North-Holland, the Netherlands, were used. Medical history was collected from the general practitioner using a questionnaire. AMSA was calculated for the first artifact free VF segment (mean segment duration 4.8 sec, sample frequency 125 Hz) and prior to every shock. Linear regression was used to assess the association between AMSA, risk factors and CVD, adjusting for resuscitation characteristics. Logistic regression was used to associate AMSA, resuscitation characteristics, risk factors and CVD with survival to hospital discharge.

Results:
We included 693 patients with an OHCA between 2006 and 2010, available medical history and VF on ECG recording with AED (n=163) or manual defibrillator (n=530), receiving a total of 2675, median 3 defibrillation shocks. Time from EMS call to first rhythm recording was median (IQR) 8.8 min (5.7-11.6), and 295 patients survived to hospital discharge (43%). Mean AMSA for the first analyzable segment was 12.7 (±16.0) mV-Hz, significantly lower for cardiomyopathy and obesity, and higher for known familial sudden cardiac death (SCD) (Table 1). Higher AMSA per mV-Hz increase (adjusted for resuscitation characteristics, risk factors and CVD) was significantly associated with higher survival to discharge (OR 1.04; 95% CI 1.02-1.06; P<0.001).

Conclusions:
Changes in AMSA due to reported CVD and risk factors are of small magnitude. AMSA remains an independent predictor of survival to hospital discharge, even when adjusting for resuscitation characteristics, risk factors and CVD.
Abstract 15305: Feasibility and Performance of a Diagnosis-only Cardiac Implantable Electronic Device Interrogation System and Process for Use in a Hospital Environment
Authors: Mittal Suneet , King-Ellison Kelly , Younge Kevin , Stein Kenneth
Published: April 2024

Introduction:
Interrogation of cardiac implantable electronic devices (CIEDs) typically requires in-person evaluation. When needed urgently in a hospital environment, the need for a company representative and/or specially trained physician/nurse delays diagnosis and increases resource utilization. A diagnosis-only remote interrogation device and process for Boston Scientific (BSC) CIEDs was developed to address this situation.

Methods:
LATITUDE Consult is a read-only interrogator that provides 24/7 access to expert technical review of data retrieved from a BSC CIED without requiring on-site access to a full-function programmer or specially trained personnel. Usage metrics, reason and results for each interrogation were recorded during the initial launch of the system.

Results:
53 communicators were used in hospitals and clinics across 15 states. There were 509 discrete transmissions (ICD in 39%; PPM 35%; CRT-D 26%), most commonly from the ER (n=294, 58%) or PACU (n=145, 28%). A third of transmissions occurred outside of “working hours”. Results were communicated within 15 minutes in 89% of cases. The most common reasons for device check were evaluation of symptoms, post-procedure check, and shock evaluation. Transmissions were categorized as: no episodes in past 72 hours and no out of range measurements (n=174, 34%); episodes in past 72 hours but no out of range measurements (n=170, 33%); further review recommended (n=130, 26%). Overall, only 53 (10%) transmissions were classified as urgent and required immediate attention (Table).

Conclusions:
We demonstrate the feasibility of a stand-alone system that can rapidly interrogate a BSC CIED in a variety of hospital settings, even outside of traditional business hours. For 90% of all device interrogations, immediate attention was not required; this allows resources to be efficiently focused on the small minority of patients with an urgent device related issue.
Abstract 15439: Obese Children With Concentric Hypertrophy and Impaired Cardiac Strain: A Potentially High-risk Subgroup Identified With Cardiac Magnetic Resonance
Authors: Jing Linyuan , Friday Cassi M , Suever Jonathan D , Umasankar Nivedita , Haggerty Christopher M , Wehner Gregory J , Hamlet Sean M , Powell David K , Radulescu Aurelia , Kirchner H. Lester , Epstein Frederick H , Fornwalt Brandon K
Published: April 2024

Objectives:
Obesity affects nearly one in five children and is associated with increased risk of premature death. Heart disease may contribute to this premature death. We aimed to use cardiac magnetic resonance (CMR) to comprehensively assess the prevalence and severity of heart disease in obese children, with the hypothesis that obese children have cardiac remodeling and impaired cardiac function compared to healthy weight children.

Methods and Results:
Twenty obese (age 12 ± 3 years, 60% female) and 20 healthy weight children (age 13 ± 3 years, 50% female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, obese children had a 27% increase in LV mass (p <0.001, Figure 1A) and a 12% increase in LV thickness (obese = 5.5 ± 0.7 mm, healthy = 5.0 ± 0.7 mm, p = 0.01). This evidence of cardiac remodeling was present in obese children as young as age 8. Forty percent of obese children had concentric hypertrophy, 40% had normal geometry and 20% had either eccentric hypertrophy or concentric remodeling. LV ejection fraction and peak strains were not different between the healthy weight and obese groups. However, peak longitudinal strain showed a significant relationship with the type of LV remodeling, and was most impaired in obese children with concentric hypertrophy (Figure 1B).

Conclusions:
Obese children show evidence of significant heart disease, which begins as young as age 8. The presence of concentric hypertrophy in 40% of obese children along with the association with impaired cardiac strain in these children may represent a high-risk subgroup. Given the associations between pediatric obesity and early mortality, these early signs of heart disease in obese children demand further investigation.
Abstract 15529: Aspirin and Renal Insufficiency Progression in Patients With Atrial Fibrillation and Chronic Kidney Disease
Authors: Pastori Daniele , Pignatelli Pasquale , Perticone Francesco , Sciacqua Angela , Carnevale Roberto , Farcomeni Alessio , Basili Stefania , Corazza Gino R , Davì Giovanni , Lip Gregory , Violi Francesco ,   ARAPACIS study group
Published: April 2024

Introduction:
Thromboxane (Tx)A2 is an eicosanoid with aggregating and vasoconstrictor properties. In experimental models, TxA2 reduces renal perfusion and accelerates renal failure, but its role in human pathophysiology is unclear.

Hypothesis:
To test the association between the use of aspirin, which inhibits TxA2 production, and the incidence of an estimated Glomerular Filtration Rate (eGFR) <60 and <45 ml/min/1.73 m2 in a long-term follow-up.

Methods:
Prospective multicentre observational cohort study including 800 atrial fibrillation (AF) patients affected by chronic kidney disease (CKD) from I Clinica Medica of “Sapienza” University of Rome, from University Magna Græcia of Catanzaro, and from the ARAPACIS study.

CKD was defined as an eGFR <90 ml/min/1.73 m2 by CKD-EPI formula; eGFR was calculated at baseline and after a median of 28.0 months. In 401 patients, urinary 11-dehydro-TxB2 was measured.

Results:
Baseline median eGFR was 64.9 ml/min/1.73 m2; 147 and 91 AF patients had an incident eGFR <60 and <45 ml/min/1.73 m2, respectively; 16.5% AF patients were treated with aspirin (100 mg/day) in addition to oral anticoagulants. At multivariable analysis, aspirin was inversely associated with incident eGFR<45 ml/min/1.73 m2 (odds ratio [OR]: 0.367, 95% confidence interval [CI] 0.153-0.880, p=0.025), but not with incident eGFR<60 ml/min/1.73 m2. The effect of aspirin persisted after propensity score adjustment (OR: 0.920, 95%CI 0.857-0.988, p=0.022). Median TxB2 levels were higher in patients with (123.0 ng/mg creatinine) compared to those without incident eGFR <45 ml/min/1.73 m2 (90.0, p=0.031) and significantly associated with incident eGFR<45 ml/min/1.73 m2 (log TxB2 OR 2.239, 95%CI 1.056-4.747, p=0.036). TxB2 was significantly lower in aspirin-treated patients (p=0.014).

Conclusions:
TxA2 may be implicated in renal function deterioration in AF patients with CKD.
Abstract 15538: Serial Measurements of Neuron-specific Enolase and Prediction of Poor Neurological Outcome in Comatose Patients After Out-of-hospital Cardiac Arrest - A TTM Substudy
Authors: Wiberg Sebastian , Erlinge David , Kjaergaard Jesper , Wanscher Michael , Devaux Yvan , Stammet Pascal , Kuiper Michael , Nielsen Niklas , Friberg Hans , Hassager Christian
Published: April 2024

Purpose:
Neuron-specific enolase (NSE) has been established as a predictor of poor neurological outcome after out-of-hospital cardiac arrest (OHCA). The optimal strategy for evaluation of serial NSE measurements remains unknown.

Methods:
The Target Temperature Management (TTM) trial biobank holds serial blood samples of OHCA patients, drawn at 24 hours, 48 hours and 72 hours after randomization to targeted temperature of either 33°C or 36°C. We included all patients being comatose at day 3 and investigated the value of NSE to predict poor neurological outcome and death (i.e. cerebral performance category 3-5) at 180 days follow-up. Multiple logistical regression and C-statistics models were used to establish the optimal use of the NSE-values.

Results:
A total of 550 comatose OHCA patients were included in the study (mean age 65 years, 80% men). At 180-day follow-up 333 (61%) of the patients had a CPC-score of 3 to 5. C-statistics revealed that the strongest predictor for poor CPC-score was the NSE value at 72 hours (AUC=0.85, see table).

In a multiple logistic regression model adjusted for sex, age, time to return of spontaneous circulation, shock-able rhythm and lactate-levels at admission the area under the NSE-curve from 24 to 72 hours had the highest odds ratio (OR=4.2, p<.0001).

Conclusions:
In patients being comatose at day three after OHCA the biomarker NSE is a strong predictor for poor neurological function and death (CPC 3-5) at 180-day follow-up. Adjustment for pre-hospital factors associated with a poor prognosis suggests that the area under the NSE-curve from 24 to 72 hours is a strong independent predictor.
Abstract 15544: GRK2 RGS Domain-Specific Interaction With Gαq Inhibits Hypertrophy and Cardiac Dysfunction During Pressure Overload
Authors: Schumacher Sarah M , Gao Erhe , Cohen Maya , Lieu Melissa , Chuprun J. Kurt , Koch Walter J
Published: April 2024

G protein-coupled receptor (GPCR) kinases (GRK) play a critical role in cardiac function through regulation of GPCR activity. Canonically, GRK2 phosphorylates active GPCRs leading to desensitization and down-regulation of the receptors to regulate signaling in the heart. Mounting evidence, however, supports non-canonical regulation of cardiac function by GRK2 through a dynamic “interactome” in which GRK2 can uncouple GPCRs via novel protein-protein interactions. Several GRK2 interacting partners are important for adaptive and maladaptive myocyte growth including Gq, the signaling trigger for maladaptive cardiac hypertrophy, leading to HF. Importantly, GRK2 contains a putative amino-terminal Regulator of G protein Signaling (RGS) domain, that directly interacts with Gq and appears to inhibit signaling without altering Gq enzymatic activity. In the present study we generated transgenic (Tg) mice with cardiac-specific expression of the RGS domain of GRK2 (βARKrgs) and subjected them to a trans-aortic constriction (TAC) model of pressure overload hypertrophy. The βARKrgs Tg mice exhibited a marked anti-hypertrophic effect, with reduced left ventricular wall thickness and hypertrophic gene expression relative to their littermate controls. Use of genetically engineered lines demonstrated that this was through an interaction of the βARKrgs peptide with Gq-mediated signaling that inhibited hypertrophy as well as the progression to heart failure (HF). These data support our hypothesis that the RGS domain of GRK2 may serve as a non-canonical inhibitor of Gq-mediated hypertrophic signaling in the heart and highlight how this research may pave the way for novel GRK2-based therapeutic approaches to prevent hypertrophy and HF.
Abstract 15623: Transplantation of Adipose-derived Stem Cells Sheet for Accelerated Neovascularization and Engraftment in Acute Myocardial Infarction Rats
Authors: Kim Jong-Ho , Joo Hyung Joon , Kim Mina , Choi Seung-Cheol , Park Chi-Yeon , Lee Jeong Ik , Hong Soon Jun , Lim Do-Sun
Published: April 2024

Background:
Transplantation of adipose-derived stem cell (ADSCs) has been suggested to improve cardiac function after acute myocardial infarction (AMI). Poor retention rate and differentiation ability of the implanted ADSCs limited their therapeutic potential. This study investigated the application of cell sheet technology for ADSC to improve engraftment and functional recovery in rat AMI model.

Methods:
Mouse ADSC (mADSC) sheets were successfully obtained by using the thermo-responsive dishes. Three groups of sham (n=10), suspended mADSC myocardial injection (n=10) and mADSC sheet transplantation (n=10) were compared in rat AMI model of left anterior descending coronary artery ligation. Final analyses were performed at day 28 after cell implantation.

Results:
In rat AMI model, mADSC sheet showed higher cellular engraftment in the infarcted heart compared to suspended mADSCs and sham control (signal unit; 227.3±18.3, 2.0±2.0 and 0; p<0.05). Cytokine analysis of the cell-implanted myocardial tissues showed that higher expression of IGF-1, bFGF, TGF-β1, and EGF in mADSC sheet compared to suspended mADSCs and sham control (p<0.05). Microvascular density of the peri-infarct zone was also higher in mADSC sheet compared to suspended mADSCs and sham. Interestingly, the transplanted cell-derived microvessels determined by mouse specific anti-vWF antibody were detected only in mADSC sheet. Echocardiography showed the significant improvement of ejection fraction (EF) in both suspended mADSCs and mADSC sheet compared to sham control (ΔEF; 15.60±0.44%, 15.24±0.62% and 3.53±%0.18; p<0.05).

Conclusions:
Although the functional recovery was comparable between ADSC sheet transplantation and suspended ADSC injection, ADSC sheet transplantation improved the cellular engraftment, paracrine effect of growth factor and cytokine secretion, and in-vivo neovascularization compared to suspended ADSC injection.
Abstract 15686: Coagulation-Independent Effects of Factor Xa on Protease-Activated Receptor 2 (PAR-2) in Pulmonary Hypertension
Authors: Joseph Christine , Berghausen Eva M , Behringer Arnica , Vantler Marius , Rosenkranz Stephan , Baldus Stephan
Published: April 2024

Factor Xa (FXa) is a key molecule in the coagulation cascade. Besides, FXa exerts direct effects on cells via protease-activated receptor 2 (PAR-2), inducing proliferation and migration.

Pulmonary hypertension (PH) is a fatal disease, defined by increased pulmonary vascular resistance, causing pulmonary arterial pressure elevation and finally right heart failure. Aberrant proliferation and migration of smooth muscle cells (SMCs) are crucial for underlying vascular remodeling processes in the pulmonary vasculature.

We hypothesize that FXa contributes to vascular remodeling in PH via PAR-2 in pulmonary arterial SMCs (PASMCs).

In vitro proliferation was assayed via BrdU incorporation, migration via modified Boyden chamber, respectively.

Human PASMCs (hPASMCs), as well as murine PASMCs (mPASMCs) from WT and PAR-2-/- mice were used. FXa (0.1-1.5U/ml) and the following inhibitors were applied: Vorapaxar (PAR-1), U0126 (ERK), and SKI-178 (sphingonsine-kinase-1).

Adult male WT and PAR-2-/- mice were exposed to normoxia vs. hypoxia to develop PH. After 21 days, right ventricular systolic pressure (RVSP) was measured. Right heart hypertrophy was determined by ratio of right ventricle to left ventricle plus septum (RV/(LV+S)).

FXa mediated hPASMC proliferation (2.78±0.60 fold vs. ctrl, n>4) via ERK and sphingosine-kinase-1. Whereas, vorapaxar did not affect FXa-mediated proliferation in hPASMCs (n=3). FXa-induced proliferation was significantly impaired in PAR-2-/- vs. WT PASMCs (1.41±0.11 vs. 1.79±0.05, n=6).

FXa induced chemotaxis of hPASMCs (1.46±0.13 fold vs. ctrl, n=6). PAR-2-/- PASMCs displayed impaired basal migratory responses (1.45±0.46 cells) and decreased chemotaxis towards FXa vs. WT cells (1.37±0.81 vs. 9.958± 0.29 cells, n=3).

PAR-2 deficiency protected from hypoxia-induced elevation of RVSP compared to WT mice (30.86±1.315 mm/Hg vs. 40.38±1.257 mm/Hg; n≥7). However, RV/(LV+S) was not decreased in PAR-2-/- vs. WT animals (0.392±0.026 vs. 0.413±0.0142; n≥7).

Conclusively, PAR-2 plays an important role in experimental PH in mice. Additionally, we elucidated that F-Xa exerts direct mitogenic and chemotactic effects in PASMCs via PAR-2 activation, indicating a direct link between F-Xa and PAR-2 in pulmonary hypertension.
Abstract 11151: Vascular Pulsatility During Mechanical Actuation of the Fibrillating Heart is Equivalent to the Native Beating Heart
Authors: Schmitt Benjamin A , Wright Nathan V , Zhou Yirong , Reynolds David B , Anstadt Mark P
Published: April 2024

Introduction:
Direct Mechanical Ventricular Actuation (DMVA) is a non-blood-contacting direct cardiac compression device shown to resuscitate both humans and animals without myocardial injury. The purpose of this study was to determine if DMVA support during ventricular fibrillation (VF) generates pulsatility similar to the native heart.

Methods:
Large canine (n=10) and swine (n=10) were anesthetized, underwent sternotomy, and instrumented for hemodynamic monitoring and intracardiac echocardiography. VF was induced for 5 mins of circulatory arrest and DMVA applied for 15 mins. Hearts were then defibrillated and allowed to recover. Repeated periods of arrest were used to increase cardiac dysfunction post-resuscitation. Paired t-tests were used to compare the post-sternotomy baseline, supported VF, and unsupported post-resuscitation states. Mean pressures and flows were statistically equalized between supported arrest and unsupported post-resuscitation. Previously described metrics of pulsatility were calculated using 10 sec flow and pressure intervals.

Results:

Conclusions:
DMVA was able to generate physiologic levels of pulsatility even during support of the fibrillating heart across a range of heart sizes. Differences in overall energy (EEP) between the possibly hyperdynamic baseline and support can be explained by discrepancies in mean (continuous) pressures and flows given observed similarities in the pulsatile component (PP, PI, SHE). Mechanical actuation of the fibrillating heart was shown to provide superior pulsatility compared to post-resuscitation hearts with comparable hemodynamic means and power curves.