bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 81: The Impact of Pre-Arrival Dispatch-Assisted CPR on Bystander CPR Rates, Time to Starting CPR and Survival From Out-of-Hospital Cardiac Arrest
Authors: Bobrow Bentley , Panczyk Micah , Stolz Uwe , Heagerty Nathan , Dameff Christian , Tully Jeffrey , Murphy Ryan Anne , Vadeboncoeur Tyler , Spaite Daniel
Published: April 2024

Background:
Bystander CPR (BCPR) strongly influences survival from OHCA yet is provided in a minority of cases. The AHA has promulgated guidelines on provision of pre-arrival Hands-Only dispatcher-assisted telephone CPR (TCPR) instructions to increase the proportion of arrests receiving early BCPR; however, the impact of those guidelines is unknown.

Objective:
Evaluate the impact of implementing the TCPR guidelines on: recognition of OHCA by 911 dispatchers, time from call receipt to start of TCPR instructions, time to first chest compression (CC), prehospital ROSC, survival, and favorable neuro outcome (FNO).

Methods:
Dispatch audio records of OHCA in 3 large dispatch centers in Arizona (10/10-3/13) were reviewed using a standardized time-stamp methodology. Data were entered into a structured TCPR database linked to EMS and hospital outcome data. Intervention: Implementation of a 3.5-hour staff training and a guideline-based change in dispatch protocol.

Results:
There were 860 pre-implementation (P1) and 799 post-implementation (P2) cases. A total of 1265 cases met inclusion criteria. Outcome data collection and linkage is ongoing: ROSC, survival and neuro outcomes were available in 26%, 24% and 22% of cases, respectively. The proportion of cases receiving TCPR increased: P1 (28.7%); P2 (49.9%, p<0.001). Median time to beginning TCPR instructions decreased significantly: P1 (153 sec); P2 (129 sec, p<0.001) as did median time to first CC: P1 (198 sec); P2 (162 sec, p<0.001). Outcomes - see Table.

Conclusion:
The implementation of the AHA pre-arrival TCPR guidelines was associated with a significant improvement in the time-to-CPR instructions and time-to-first CCs and rate of provision of telephone-assisted bystander CPR. This small, preliminary analysis of prehospital ROSC, survival, and FNO revealed higher, but statistically non-significant, rates after the interventions.
Abstract 85: Development of a Readily Translatable Model of Resuscitation From Ischemic Cardiac Arrest to Assess Regional and Global Arrhythmia Substrates and Outcomes
Authors: Cheng Aurelia , Fukaya Hide , Wilson Lance , Piktel Joseph S
Published: April 2024

Background:
Little is known about the effect of therapeutic hypothermia (TH) on arrhythmias in the resuscitated heart. TH has a beneficial effect on defibrillation thresholds and ROSC. However, there are no studies investigating why TH might be anti-arrhythmic during resuscitation from ischemia-induced cardiac arrest, the most common clinical scenario. Our goal was to develop a novel translational porcine model of resuscitation from regional ischemia-induced VF with the ability to identify differences in both regional and global arrhythmia substrates in order to determine mechanisms of the antiarrhythmic effect of TH and improve outcomes.

Methods:
Pigs underwent anesthesia and thoracotomy, and a large LAD occlusion was made. VF was induced after 30 min if spontaneous VF did not occur. CPR was started after 8 min with defibrillation and cardiac massage to achieve ROSC. Infarct was continued for a total of 60 min then reperfusion was continued for 60 min. Electrograms (EG) were recorded from multipolar needle (transmural) plunge electrodes at multiple sites and monophasic action potential (MAP) recordings were used to determine transmural and regional heterogeneities of repolarization and conduction. All spontaneous arrhythmias were recorded. Outcomes were compared between control (temp 37oC, CT), Pre-ischemia TH (TH 33oC), and post-infarct TH (TH-infarct). Cooling was induced using a cooling blanket, cold saline IV infusion, and ice packs.

Results:
Hemodynamic parameters were recorded during ischemia, during CPR, and reperfusion. Appropriate CPR was verified by BP and CO2 monitoring. 2/4 animals survived to the end of protocol in the CT group, 4/5 in the TH group, and 0/2 in the TH-infarct group. Total ROSC time was 9.8±7 for CT vs 37.5±6 (p<.04) for TH group (no ROSC for TH-infarct). EG’s were used to assess activation recovery intervals at transmural sites in the infarct, noninfarct, and border zones. Regional VF waveforms were obtained.

Conclusions:
We developed a translatable model of resuscitation from ischemic cardiac arrest using regional and global electrophysiologic monitoring to assess arrhythmia substrates. These data suggest improved outcomes during resuscitation with TH.
Abstract 86: AED Allocation: Creating Rules for AED Placement Based on Urban Risk Maps
Authors: Chrisinger Benjamin W , Grossestreuer Anne V , Curtis Meredith L , Ting Nancy , Wiebe Douglas , Branas Charles , Merchant Raina M
Published: April 2024

Background:
Although the prompt use of automatic external defibrillators (AEDs) in out of hospital cardiac arrest (OHCA) can be lifesaving, policies to guide placement of publicly accessible AEDs are not clearly defined.

Objectives:
To use location-based risk, location density, and presence of a designated responder to create a risk-based mapping framework to guide urban AED placement.

Methods:
Literature reporting frequency of OHCA by location type in urban areas was used to create a list of candidate sites in downtown Philadelphia, PA. Location-based risk areas were plotted using ArcGIS with a kernel density surface that reflected walking time of approximately 1.5 minutes. Locations were identified through available public records and the Google search engine. Designated responder status was assigned by location type. Sites were weighted by risk of arrest and multiplied by density of designated responders to create a composite “opportunity” layer. Hypothetical sites for 20 new AEDs were then mapped by selecting the point with the highest opportunity score, “placing” an AED, and recalculating opportunity scores for the entire study area. This process was iterated until 20 hypothetical AEDs were sited.

Results:
Thirty types of locations with previously-studied frequency of OHCA were identified. Figure 1 identifies several high-risk areas for OHCAs with AED caretakers present to use devices in an emergency that could benefit from close proximity to an AED.

Conclusions:
A location-based risk map for OHCA identifies specific higher-risk locations to locate AEDs in an urban area. The metrics to build this theoretical framework for device allocation can be used by cities to guide more strategic AED placement based on their unique cardiac arrest data and current AED placement.

Figure 1:
Abstract 9244: A Novel Phosphorylating Mechanism of STAT3 in Protection against Ischemia/reperfusion by Pharmacological Preconditioning With Tadalafil, a PDE Inhibitor
Authors: Kumar Sanjay , Okada Motoi , Chang Dehua , Ashraf Muhammad
Published: April 2024

Background:
Phosphodiesterase (PDE) inhibition enhances Protein Kinase G-I (PKG-I) activity leading to stem cell survival and cardioprotection against ischemia/reperfusion injury. We previously reported phosphorylation of STAT3 ser727 during late phase of protection. We aimed to investigate the specificity of STAT3 in regulation of PKG-I and cardioprotection using heart specific conditional knockout mice.

Methods and Results:
Heart specific conditional knockout mice were made by breeding STAT3fl/fl with tamoxifen inducible cre (MCM) transgenic mice. MCM transgene was cloned downstream to heart specific myosin heavy chain promoter (MHC). Cre positive mice (MCM:STAT3fl/fl) were selected from genotyping and tamoxifen (20mg/kg) was administrated for 10 days. KO mice were pretreated with tadalafil (1mg/kg) 1h before LAD coronary artery ligation for 30 min followed by reperfusion. Echocardiographic analysis showed abrogation of cardioprotection in STAT3 knockout mice with decreased ejection fraction and fraction shortening as compared to non-transgenic mice. Mitogen activated protein kinases ERK and P38 were known to phosphorylate STAT3 at ser727. On contrary, western blot analysis with heart tissue lysate showed reduced phosphorylation/activation of ERK both in control and tadalafil treated cells with no change in total ERK (P<0.05). Expression of pP38 and total P38 (p<0.01) were unaltered. Two fold increase in expression of PKG-I (P<0.05) during the late phase of protection was observed with tadalafil. Inhibition of PKG-I with KT5823 or antisense abolished STAT3 phosphorylation at ser727. Results were also replicated in vitro with mesenchymal stem cells isolated from adult male Fischer-344 rats by flushing the cavity of femur and cultured, purity was checked by CD44+ and CD73+ surface markers (flow cytometry). Cells were pretreated 1 h with tadalafil (100μM) then subjected to 2 h hypoxia (1% O2) and reoxygenation for 2 h/24 h.

Conclusion:
The study showed novel mechanism of phosphorylating STAT3 at ser727 by PKG-I leading to its entry inside nucleus and transcriptional activation of PKG-I by binding onto promoter making it a positive feedback loop. Heart specific STAT3 knockout mice showed abrogation of cardioprotection with tadalafil.
Abstract 9296: Three-Stage Fontan Without Cardiopulmonary Bypass
Authors: Mainwaring Richard D , Reddy V. M , Hanley Frank L
Published: April 2024

Objectives:
The 3-stage surgical approach is now accepted as the gold standard for management of children born with functional single ventricle. However, there is little consensus on the cardiopulmonary bypass strategies employed for these procedures. We have attempted to avoid cardiopulmonary bypass in single ventricle patients whenever possible to eliminate the adverse effects that are induced by this process. The purpose of this study was to review our experience in patients who underwent all 3 stages of the Fontan pathway without ever being exposed to bypass.

Methods:
52 single ventricle patients underwent "off-pump" treatment at all 3 stages of their surgical management. The time period of the study was from 2002 to 2013. There were 31 males and 21 females. Anatomic diagnoses included: double outlet left ventricle (n=11), pulmonary atresia with intact ventricular septum (n=11), tricuspid atresia (n=10), double outlet right ventricle (n=9), and other (n=11).

42 of 52 patients underwent a neonatal off-pump palliative procedure, including systemic-to-pulmonary artery shunt in 33 and pulmonary artery band in 9. 52 patients underwent an off-pump bi-directional Glenn: 38 had a single superior vena cava (facilitated by construction of a veno-venous shunt) and 14 had bilateral superior vena cavae. All 52 patients underwent an off-pump extra-cardiac conduit Fontan.

Results:
There was no operative mortality in the 52 patients undergoing Fontan completion. The patients have been followed for an average of 5.1± 2.5 years, with one late mortality. The median length of hospital stay for the 3 stages was 17, 5, and 9 days, respectively. 47 of the 52 patients were able to undergo all 3 stages without the need for a blood transfusion.

Conclusions:
This series demonstrates the feasibility of achieving a Fontan circulation without patients exposed to cardiopulmonary bypass. There was no operative mortality and very low mid-term mortality, and it is notable that less than 10% of patients ever had a blood transfusion. We believe that elimination of cardiopulmonary bypass does have clinical benefits in this highly select subset of single ventricle patients.
Abstract 9424: Coronary Artery Disease-Related Death May Be Associated With Higher Critical Plaque Wall Stress: A Multi-Patient 3D Fluid-Structure Interaction Study Comparing Plaque Wall Stress, Flow Shear Stress, and Plaque Burden as Risk Indicators
Authors: Huang Xueying , Yang Chun , Zheng Jie , Bach Richard , Muccigrosso David , Woodard Pamela K , Tang Dalin
Published: April 2024

Introduction:
Plaque burden has been used to predict cardiovascular events. However, many patients without flow-limiting atherosclerosis and without prior symptomatology develop catastrophic syndromes including stroke, or sudden cardiac death. We hypothesized that plaque wall stresses play an important role in vulnerable plaque rupture and may serve as a risk factor for cardiovascular event. The objective of this study was to compare plaque wall stress, flow shear stress, and plaque burden and identify their possible association with coronary artery disease (CAD)-related death.

Methods:
Ex vivo MRI data of coronary plaques from 12 patients (6 died from CAD cause and 6 died from non-CAD cause, based on autopsy reports) were used to construct 3D fluid-structure interaction models. Plaque wall stress and flow shear stress were extracted from all nodal points on the lumen surface of each 3D plaque model for analysis. The maxima of plaque wall stress and flow shear stress from all local maxima (excluding those on healthy sites) of each plaque were defined as the 3D critical plaque wall stress (CPWS) and 3D critical flow shear stress (CFSS), respectively. Plaque burden was calculated as plaque+media area/total vessel area bounded by the out-boundary. Two-sided Student t-test was used to compare the difference of CPWS, CFSS and plaque burden between the CAD and non-CAD groups.

Results:
Table 1 shows that mean 3D CPWS from CAD Group was 94.3% higher than that from non-CAD Group (265.6 vs. 136.7 kPa, P=0.0029). No difference was found for 3D CFSS values (p=0.851) and plaque burden (p=0.552) between the two groups.

Conclusion:
The results showed that plaques from the CAD group were associated with higher critical plaque wall stresses compared with plaques from the non-CAD group, suggesting that CPWS may serve to predict event risk, and may provide more accurate plaque vulnerability assessment. Prospective and large-scale studies are needed to further validate our findings.
Abstract 9609: Impact of Mesenchymal Stem Cell Left Ventricular Implantation on Heart Rate Variability: Results From the POSEIDON Trial
Authors: Shah Sachil , Brodt Chad , DiFede Darcy L , Ramireddy Archana , Coffey James O , Viles Gonzalez Juan F , Atapattu Suresh , Heldman Alan W , Myerburg Robert J , Hare Joshua M , Mitrani Raul D
Published: April 2024

Introduction:
Patients (pts) with ischemic cardiomyopathy (ICM) may have impaired heart rate variability (HRV) which is associated with worse prognosis. We tested the hypothesis that cardiac mesenchymal stem cell (MSC) implantation is associated with improvement in HRV in patients with severe LV dysfunction and abnormal HRV at baseline

Methods:
The POSEIDON Trial evaluated transendocardial MSC implantation in pts with ICM. We examined 24-48 hour ambulatory monitoring data from 25 pts at baseline, immediately post MSC implant, and intermittently up to 13 months following implantation. HRV was assessed using 3 parameters: (1) standard deviation of NN intervals (SDNN), (2) the square root of the mean squared differences of successive NN intervals (RMSSD), and (3) standard deviation of the average normal NN intervals (SDANN). HRV indices were correlated to changes in ejection fraction (EF), end systolic volumes (ESV), end diastolic volumes (EDV), and sphericity index (SI) using t-test.

Results:
The cohort had a mean age of 62 ± 10 years, EF 26.5 ± 9.4%, ESV 204.2 ± 80.6 ml and EDV 271.5 ± 85.4 ml. Compared with pre-implantation values, RMSSD trended to improve in the cohort (30.2 ± 15 to 51.9 ± 39.3 msec, p=0.08), significantly improved in the group with EF improvement (24.6 ± 10 to 57.3 ± 43.5, p= 0.04) and tended to improve in the group with improved EDV, ESV, SI (Table). SDNN and SDANN also tended to improve in the cohort, but showed significant improvement in the group with less structural improvement noted by EDV or ESV decrease by <5% (Table).

Conclusions:
There was a trend towards improvement in HRV after MSC implant. RMSSD, a variable more closely related with vagal tone, correlated better with greater improvements in EF, EDV, ESV and SI and may be a better marker of anatomical improvement. In contrast, SDNN and SDANN, which track not only vagal tone but diurnal variation, tended to improve in the overall cohort but showed improvement in the group with less structural improvement.
Abstract 9810: Relationship Between Time of Day and Periprocedural Myocardial Infarction After Elective Angioplasty
Authors: Fournier Stephane , Puricel Serban , Morawiec Beata , Eeckhout Eric , Mangiacapra Fabio , Trana Catalina , Tapponnier Maxime , Iglesias Juan Fernando , Michiels Vincent , Stauffer Jean-Christophe , Beggah Ahmed , Monney Pierre , Gobet Stephanie , Vogt Pierre , Cook Stephane , Muller Olivier
Published: April 2024

Introduction:
Recent studies have suggested an influence of circadian rhythms on myocardial infarction size and mortality among patients with ST-elevation myocardial infarction. The aim of the study is to investigate whether periprocedural myocardial infarction (PMI) is influenced by the time of day in elective patients undergoing percutaneous coronary intervention (PCI).

Hypothesis:
The time of day influences the occurrence of type 4A myocardial infarction in elective patients undergoing PCI.

Methods:
All consecutive patients undergoing elective PCI between 2007 and 2011 at our institutions with known post-interventional troponin were retrospectively included.Patients (n=1,021) were divided into 2 groups according to the starting time of the PCI: the morning group (n=651) between 07:00 and 11:59, and the afternoon group (n=370) between 12:00 and 18:59. Baseline and procedural characteristics as well as clinical outcome defined as the occurrence of PMI were compared between groups. In order to limit selection bias, all analyses were equally performed in 308 pairs using propensity score matching.

Results:
In the overall population, the rate of PMI was statistically lower in the morning group compared to the afternoon group (20% vs. 30%, p<0.001). This difference remained statistically significant after PS-matching (21% vs. 29%, p=0.03). Multivariate analysis shows that being treated in the afternoon independently increases the risk for PMI with an odds ratio of 2.0 (95%CI: 1.1-3.4; p=0.02).

Conclusions:
This observational propensity score-matched study suggests that the timing of an elective PCI influences the rate of periprocedural myocardial infarction.
Abstract 9820: Catheterization Diastolic Pressures Correlate With Diastolic Dyssynchrony in Patients With Single Right Ventricles
Authors: Stiver Corey , Gokhale Janaki , Husain Nazia , Nicholson Lisa , Cordier Joyce , Van Lente Lindsey , Holzer Ralf J , Cua Clifford L
Published: April 2024

Introduction:
Diastolic dyssynchrony is increasingly being recognized in both the adult and pediatric population. Increasing diastolic dyssynchrony has correlated with increased pulmonary capillary wedge pressures and worse clinical outcomes in patients with normal cardiac anatomy. No data exist in patients with single right ventricle (sRV) physiology. Goal of this study was to determine if diastolic dyssynchrony in patients with sRV physiology correlates with ventricular end-diastolic pressures (VEDP) obtained via cardiac catheterization.

Methods:
Tissue Doppler imaging (TDI) and strain rate (SR) analysis of sRV patients undergoing catheterization were performed. TDI analysis was performed at the level of the atrioventricular valve. Time interval from onset of QRS to peak TDI e’ wave of the respective walls was obtained. Differences in intervals were calculated: QRS(RV) - QRS(IVS) and QRS(RV) - QRS(LV). The sRV was separated into a six segment model for SR analysis. Time interval from onset of QRS to peak SR early diastolic wave (SRe) wave was obtained for the six segment model sRV. Standard deviation of the six SRe time intervals was calculated. VEDP was obtained from the catheterization report. Correlation of VEDP with timing intervals was analyzed via Pearson correlation.

Results:
Forty sRV patients were evaluated: 27 hypoplastic left heart syndrome, 9 double outlet right ventricles, 4 unbalanced atrioventricular septal defects. Age was 2.8 ± 3.5 years. Catheterization VEDP of the sRV was 9.3 ± 3.9 mmHg (median 8 mmHg range 4 - 24 mmHg). QRS(RV) - QRS(IVS) was 22.3 ± 18.1 msec and QRS(RV) - QRS(LV) was 23.7 ± 19.0 msec. SRe standard deviation of the sRV was 61.6 ± 23.9 msec. There was no significant correlation with VEDP and QRS(RV) - QRS(VS) (r = 0.1, p = NS) or with QRS(RV) - QRS(LV) (r = 0.2, p = NS). There was a significant correlation of VEDP with the SRe standard deviation value (r = 0.4, p < 0.05).

Conclusion:
Diastolic dyssynchrony, measured via SR analysis, correlated with VEDP in patients with sRV physiology. Future studies are needed to determine if this measurement is beneficial for either monitoring or treatment purposes in this complex patient population.
Abstract 9822: Semi-Automatedly Derived Total Atherosclerotic Plaque Burden by CT Angiography for Predicting Clinically Driven Coronary Artery Revascularization: A Comparison With Expert Stenosis Assessment in the CORE320 Multicenter Study
Authors: Kishi Satoru , Magalhaes Tiago , Cerci Rodrigo , Friedman Lisa A , Tanami Yutaka , Kitslaar Peter , Lemos Pedro A , Niinuma Hiroyuki , Cox Christopher , Reiber Johan H , Lima Joao A , Arbab-Zadeh Armin
Published: April 2024

Aims:
We investigated the performance of a semi-automated arterial contour algorithm by CT angiography (CTA) for assessing total coronary atheroma burden in patients with suspected coronary artery disease.

Methods:
A total of 373 patients referred for invasive coronary angiography (ICA) in the CORE320 multicenter study were included in this study. Patients underwent 320-row detector CT scanning for coronary angiography. In addition to quantitative CTA stenosis assessment, a novel arterial contour detection algorithm was used to quantify total coronary atheroma volume by subtracting lumen volume from vessel wall volume for the entire coronary tree using a 19-segment model. Atheroma volume was defined as the difference between vessel and lumen volume. For atheroma burden quantification in each patient, we used three parameters: 1) length normalized total atheroma volume (length normTAV) = total atheroma volume/total coronary length; 2) percent atheroma volume (PAV) = (total atheroma volume/total vessel volume) х 100; 3) Normalized total atheroma volume (TAVnorm) = (total atheroma volume/total coronary length) х mean coronary length in study population. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy for predicting clinically driven coronary revascularization within 30 days from ICA compared to an assessment based on CTA stenosis evaluation.

Results:
Of 373 patients, 76 patients underwent coronary revascularization. The median CTA stenosis, length normTAV, PAV, and TAVnorm were 62%, 5.8 m3/m, 54.2%, and 2845.4 mm3, respectively. The AUC of CTA stenosis assessment to predict coronary revascularization was 0.73 (95% CI, 0.69-0.78) compared to 0.69 (95% CI, 0.64-0.73) by PAV (p = 0.11). Accuracy was lower (p = 0.002) for TAVnorm and length norm TAV (AUC, 0.62; 95% CI, 0.57-0.67 for both indices). Interobserver agreement for atheroma volume was high (r = 0.99; p < 0.0001).

Conclusions:
A semi-automatedly derived index of atheroma volume by CTA performs similarly to expert CTA stenosis assessment for identifying patients who undergo clinically driven coronary revascularization. These results convey promise for a rapid, reliable assessment of clinically relevant coronary artery disease.
Abstract 9856: Left Atrial Passive Emptying Function Determined by Cardiac Magnetic Resonance Predicts Atrial Fibrillation Recurrence After Pulmonary Vein Isolation
Authors: Dodson John A , Neilan Thomas , Abbasi Siddique , Shah Ravi , Farhad Hoshang , Blankstein Ronald , Jerosch-Herold Michael , Kwong Raymond Y
Published: April 2024

Background:
While pulmonary vein isolation (PVI) has become a mainstream therapy for selected patients with AF, late AF recurrence is common and its risk factors remain poorly defined. The purpose of our study was to test the hypothesis that reduced left atrial passive emptying function (LAPEF) has a strong association with late recurrent AF after PVI.

Methods:
346 patients with AF referred for CMR pulmonary vein mapping prior to PVI from 9/2005-6/2011 were included. Left atrial volumes (LAV) were determined by the biplane area-length method. LA maximum volumes (VOLmax) and volumes before atrial contraction (VOLbac) were measured, and LAPEF was calculated as (VOLmax - VOLbac)/VOLmax x 100. The primary outcome was late recurrent AF (≥ 3 months after PVI). Late AF-free survival curves stratified by LAPEF quintiles were plotted using the Kaplan-Meier method. Cox proportional hazards assessed the prognostic association of LAPEF with recurrent AF, adjusting for known markers of AF recurrence (BSA, VOLmax, hypertension, non-paroxysmal AF, diabetes, heart failure, ≥1 PVI procedure, sleep apnea).

Results:
Over a median follow-up of 27 months, 124 patients (35.8%) experienced recurrent AF. Patients with recurrence were more likely to have non-paroxysmal AF (75.8% vs. 51.4%, P<0.01), larger mean LA volumes (60.2 ml/m2 vs. 52.8 ml/m2, P<0.01), and lower mean LAPEF (19.1 vs. 26.0, P<0.01). Patients in the lowest quintile of LAPEF (worst function) were at the highest risk of developing recurrent AF (Figure); at two years, the recurrence rate was 60.5% in the lowest quintile, compared to 17.3% in the highest quintile. After adjusting for historic markers of recurrent AF, patients with low LAPEF remained significantly more likely to recur (HR lowest vs. highest = 3.92, 95% CI 2.01-7.65).

Conclusions:
We found a strong association between LAPEF and recurrent AF after PVI that persisted after multivariable adjustment. LAPEF may be used to risk stratify PVI candidates for late recurrence.
Abstract 9907: Cardiac Adiponectin Resistance Develops Early After MI and Contributes to Heart Failure Progression
Authors: Wang Yajing , Ma Xin , Wang Xiaoliang , Lau Wayne Bond , Yuan Yuexing , Lopez Bernard , Christopher Theodore , Gao Erhe , Koch Walter
Published: April 2024

Deficiency of adiponectin (APN), a cardioprotective adipokine, as a risk factor of cardiovascular disease is well-defined. Recent clinical studies report that plasma APN levels are increased in heart failure (HF) patients, suggesting APN resistance might be another unrecognized risk factor. However, direct evidence supporting cardiac APN resistance during HF progression is currently lacking. Adult male mice were subjected to HF by coronary artery occlusion. The biological functions of APN were determined during the course of HF development (0-6 weeks). Plasma APN levels were reduced 3 days post-MI (P<0.01), gradually recovered thereafter, and reached a level greater than control 14 days post-MI (P<0.05). Consistent with APN level reduction, cardiac AMPK phosphorylation (a readout of APN intracellular signaling) was decreased 3 days post-MI (P<0.05). However, cardiac AMPK phosphorylation remained lower than control 14 days post-MI (P<0.01), despite significantly increased plasma APN levels at this time, suggesting reduced cardiac response to endogenous APN. APN administration via osmotic pump beginning 14 days post-MI for the remaining duration of MI did not protect against MI/R injury, in contrast to numerous previous studies demonstrating the cardioprotective effects of APN in acute MI/R. At the molecular level, APN treatment significantly increased both GLUT4 membrane recruitment and
18
F-FDG uptake in the normal heart (P<0.01). However, these responses were dramatically reduced 14-days post-MI. To gain more direct evidence demonstrating impaired cardiomyocyte response to APN during HF development, left ventricular cardiomyocytes were isolated from normal or MI mice (14 days), and incubated with human recombinant APN. APN-induced AMPK phosphorylation and PKA activation were significantly reduced in CM from MI mice compared to control (P<0.01). Together, these results demonstrate that APN resistance develops 2 weeks after MI, a critical period when the transition from adaptive to pathological remodeling occurs. APN resistance renders a potent endogenous cardioprotective molecule ineffective, thus facilitating HF progression. Interventions restoring cardiac APN response may be a novel approach against post-MI HF development.
Abstract 9908: Transcatheter Aortic Valve Replacement for High-risk Severe Aortic Stenosis: An Analysis of Incidence, Predictors and Prognostic Impact of New-onset Postprocedural Atrial Fibrillation- Mayo Clinic Experience
Authors: Melduni Rowlens M , Greason Kevin L , Suri Rakesh M , Nkomo Vuyisile T , Rihal Charanjit S , Sarano Maurice E , Gersh Bernard J , Holmes David R , Mathew Verghese
Published: April 2024

Introduction:
Atrial fibrillation (AF) is a serious complication, which occurs in 30% to 40% of patients after surgical aortic valve replacement (SAVR) and contributes to adverse outcomes. Advanced technology has enabled transcatheter aortic valve replacement (TAVR) in patients with High-risk Severe Aortic Stenosis (HRSAS). In these patients, the compliance of the systemic vasculature is an independent predictor of diastolic dysfunction, a known predictor of postoperative AF (POAF). We hypothesize that patients with HRSAS undergoing TAVR represent a population at increased risk for POAF.

METHODS:
The medical records of 195 TAVR patients at the Mayo Clinic from November 2008 to January 2013 were analyzed. All patient demographic, clinical, pre- and post-procedural outcomes were collected from the patients’ medical records, and reviewed to ascertain all cases of POAF (AF ≤30 days of surgery). Patients with a prior history of AF (n= 75 (38.5%)) were excluded. Logistic regression analysis was used to identify clinical predictors of POAF after TAVR.

Results:
The mean age of the study population was 80.8±7.8 years and 60.8% (n=73) were men. The mean STS risk score was 8.9±5.1. Of the 120 patients without prior AF, 20.8% (n=25) developed new-onset POAF after TAVR. Patients who developed POAF were more likely to have undergone a transapical or transaortic TAVR approach (OR 3.20; 95% CI (1.3-8.0), had a higher incidence of renal complications (52.0% vs 21.5%; p= 0.003), greater hospital length of stay (7.4±2.58 vs 5.0±2.6 days; p= 0.0003, and a trend toward higher 30-day mortality (28.0% vs 13.7%; p= 0.09) and pulmonary complications (16.0% vs 5.4%; p= 0.08) compared with those who did not develop POAF, respectively. Neurologic complications were not different between the 2 group (4.0% vs 3.2%; p= 0.85).

Conclusions:
Patients with High-risk Severe Aortic Stenosis undergoing TAVR have increased risk of POAF, primarily associated with a transapical or aortic surgical approach. Patients who develop POAF had higher incidence of post-procedural complications and longer hospitalizations. Therefore, perioperative strategies aimed at prevention of POAF are as important in TAVR patients as in those undergoing SAVR.
Abstract 10092: Renal Evidence of Remote Ischemic Conditioning for Elective Coronary Revascularization: A Meta-analysis of 13 Randomized Trials
Authors: Zhou Chenghui , Li Lihuan , Li Yuehua , Hausenloy Derek , Jeon Yunseok
Published: April 2024

Background:
Several early small trials have concerned about the renal effect of periprocedural remote ischemic conditioning(RIC) in patients with coronary artery disease(CAD), however, negative results were widely obtained. Hence, we sought to summarize the renal evidence of RIC in patients undergoing coronary artery bypass grafting(CABG) or percutaneous coronary intervention(PCI).

Methods:
A systematic search was performed in Pubmed, Embase, Cochrane library, and scientific sessions of AHA, ACC and ESC (up to April 2015). Randomized controlled trials with data on postoperative acute kidney injury(AKI) during elective coronary revascularization were included. Odds ratio(OR) with 95% confidence interval(CI) was calculated. Random-effect models were used for the potential clinical inconsistency. Publication bias assessment and sensitivity analysis were performed to evaluate the robustness of the results.

Results:
Thirteen RCTs with a total of 1861 CAD patients were identified and selected. Compared with controls, RIC significantly reduced the incidence of AKI (6.61% vs 11.6%;OR= 0.54; 95% CI, 0.37 to 0.78; P=0.001; I2=8.5%; Figure 1). No evidence of significant publication bias were observed (P=0.784, Begg’s test; P=0.096, Egger’s test). Sensitivity analysis of mortality excluding each included study at one time revealed that most individual study was consisted with the direction and size of the overall effect (All P≥0.01).There was no significant difference between CABG subgroup (9.8% vs 16.6%;OR=0.54;95%CI, 0.32 to 0.92; P=0.02; I2=0.0%) and PCI subgroup(5.3% vs 9.4%;OR=0.54; 95% CI, 0.30 to 1.00;P=0.05; I2=36.5%) (P=1.00 for subgroup difference).

Conclusions:
Based on the available evidence, RIC provides renal protection by reducing the postprocedural AKI in elective coronary revascularization. Such effect is similar between CABG and PCI.
Abstract 10114: Cardiovascular Magnetic Resonance Measurement of Myocardial Extracellular Volume by T1 Mapping Differentiates Athlete's Heart From Hypertrophic Cardiomyopathy
Authors: Swoboda Peter P , Mcdiarmid Adam K , Erhayiem Bara , Broadbent David A , Lyall Gemma K , Lancaster Rosalind E , Dobson Laura E , Ripley David P , Musa Tarique A , Garg Pankaj , Ferguson Carrie , Page Stephen P , Greenwood John P , Plein Sven
Published: April 2024

Introduction:
Athletes who train regularly can develop left ventricular (LV) hypertrophy, which can be difficult to differentiate from hypertrophic cardiomyopathy (HCM), the leading cause of sudden cardiac death in young athletes. Cardiovascular magnetic resonance (CMR) T1 and extracellular volume (ECV) mapping provide quantitative assessment of myocardial composition.

Hypothesis:
ECV can differentiate athletic from pathological remodelling.

Methods:
35 athletes, 25 HCM patients and 35 volunteers underwent 3.0T CMR protocol including 5b(3s)3b Modified Look-Locker Inversion (MOLLI) T1 maps before and 15 minutes after administration of 0.15mmol/kg intravenous gadobutrol. Native T1 and ECV were measured for each subject and each segment of the American Heart Association model.

Results:
Native T1 and ECV were both significantly lower in athletes than HCM (1182.8±38.1ms vs 1264.6±50.3ms, P<0.001 and 23.2±2.9% vs 32.3±5.9%, P<0.001 respectively). On receiver operator curve analysis the area under the curve (AUC) to differentiate HCM from athlete for native T1 was 0.91 and ECV 0.95. The AUC to differentiate indeterminate 8-15mm thick segments (Figure) were native T1 0.83, ECV 0.92 and segment thickness 0.80 (P<0.001 for all). The diagnostic accuracy of ECV was superior to native T1 and segment thickness (P=0.001 for both). The optimal cut-off to diagnose HCM in an indeterminate segment was ECV>24.7% (sensitivity 91.7% & specificity 83.2%) and native T1>1226ms (sensitivity 60.0% & specificity 96.7%).

Conclusions:
ECV measurement by CMR is able to distinguish HCM and athletic remodelling with high diagnostic accuracy and has a potential role in the exclusion of HCM in athletes presenting with left ventricular hypertrophy.

Figure:
ROC curves for segmental wall thickness (mm), native T1 (ms) and ECV (%) for the detection of HCM against athletes in intermediate wall thickness segments (8-15mm thick). AUCs were 0.80, 0.83, and 0.92 respectively (P<0.001 for all).
Abstract 10123: Evidence Against the J-shaped Curve in Treated Hypertensive Patients With Increased Cardiovascular Risk: The VALUE Trial
Authors: Kjeldsen Sverre E , Bangalore Sripal , Messerli Franz , Mancia Giuseppe , Holzhauer Björn , Hua Tsushung A , Zappe Dion , Weber Michael A , Julius Stevo
Published: April 2024

Introduction:
It has been postulated that low blood pressure (BP) during treatment is associated with increased risk for cardiovascular (CV) disease.

Hypothesis:
We tested whether low BP had unfavorable effect on CV outcomes in a high risk population of 15,244 hypertensive patients of whom 45% had a coronary heart disease (CHD) history.

Methods:
Patients were followed for 4.2 years (mean) in the VALUE Trial with no difference of the primary endpoint between valsartan and amlodipine arms. Cox proportional hazard models were used to evaluate relationships between average on-treatment BP and clinical outcomes, unadjusted and adjusted for baseline covariates such as age, BMI, history of CHD, history of stroke, left ventricular hypertrophy, diabetes mellitus, smoking, cholesterol and proteinuria.

Results:
Diastolic BP ≥90 mmHg but not diastolic BP <70 mmHg was associated with increased CV outcomes after covariate adjustment. We had similar results for death, myocardial infarction (MI), heart failure and stroke. Nadir for MI was at diastolic BP of 76 mmHg and for stroke 60 mmHg. The ratio of MI to stroke increased with lower diastolic BP (fig), but there was no significant J-curve regardless of CHD history. Also, systolic BP ≥140 but not <130 mmHg was associated with increased risk for CV outcomes, and systolic BP <130 mmHg significantly prevented stroke.

Conclusions:
Patients in BP strata ≥140/90 mmHg, but not patients in BP strata <130/70 mmHg, were at increased risk for adverse outcomes in this hypertensive, high risk population. Our data provide evidence against a J-curve in the treatment of hypertensive patients with high risk and support the concept “of the lower the better” in stroke prevention. However, the increase in the ratio of MI to stroke with lower diastolic BP indicates target organ heterogeneity in that the optimal on-treatment diastolic BP for cerebroprotection is below the one for cardioprotection.
Abstract 10198: Endothelin B Receptor Agonist, IRL-1620 is an Effective Neurovascular Remodeling Agent in Diabetic Rats With Cerebral Ischemia
Authors: Husby Monica , Leonard Mary G , Gulati Anil
Published: April 2024

Endothelin B (ETB) receptor agonist, IRL-1620 administered at 2, 4, 6 hr post-cerebral ischemia, has been shown to significantly aid in neuroprotection and neurovascular remodeling in normal rats. The incidence of type 2 diabetes mellitus (diabetes) is on the rise and it can be expected that there will be an upsurge of associated diseases, such as ischemic stroke in patients with diabetes. The present study was conducted to determine the efficacy and neurovascular remodeling effect of IRL-1620 in normal (non-diabetic) and diabetic rats following cerebral ischemia induced by right middle cerebral artery (MCAO). The induction of diabetes was achieved through a high-fat diet and single low dose (45 mg/kg) of streptozotocin. IRL-1620 (5 μg/kg) was administered intravenously at 4, 6, and 8 hr after MCAO on day 0, 3 and 6 (total of 15 μg/kg in three divided doses on day 0, 3 and 6). A mortality of 46% was observed by day 7 in normal rats with MCAO when treated with vehicle, while it was 17% when treated with IRL-1620. In diabetic rats 90% mortality was observed by day 7 post-MCAO when treated with vehicle, while it was 45% when treated with IRL-1620. Functional outcome for the IRL-1620 group was significantly better in both non-diabetic and diabetic rats compared to the vehicle group. In both non-diabetic (80.81%; p=0.02) and diabetic (69.58%; p=0.04) rats a significant reduction in infarct volume was seen in the IRL-1620 group compared to the vehicle group. Significantly more blood vessels/30μm brain slice were observed in the IRL-1620 versus vehicle group. Immunofluorescence staining revealed a significant increase in ETB receptor expression for rats treated with IRL-1620, compared to vehicle. Co-localization of VEGF+ve and endothelial cells in diabetic rats was higher (p=0.0009) in the IRL-1620 group (15.5±1.1%) compared to the vehicle group (10.2±0.81%). In diabetic rats, the IRL-1620 group had significantly (p=0.0012) more neurons in the cortex compared to the vehicle group as well as the highest levels of neuronal replication. Administration of BQ-788, a specific ETB receptor antagonist, attenuated the effects of IRL-1620. It is concluded that IRL-1620 is an effective neurovascular remodeling agent and may be useful in the treatment of cerebral ischemia.
Abstract 10826: GBT1118, a Potent Allosteric Modifier of Hemoglobin Oxygen Affinity Increases Tolerance to Hypoxia in Mice
Authors: Cabrales Pedro , Dufu Kobina , Hutchaleelala Athiwat , Xu Qing , Lehrer-Graiwer Josh , Sinha Uma
Published: April 2024

Introduction:
Adaptation to hypoxia involves several mechanisms that influence oxygen (O2) transport and utilization, including a reduction in hemoglobin (Hb) O2 affinity to favor the release of O2 to tissues. Paradoxically, increased Hb O2 affinity has been observed to have beneficial effects during severe hypoxia. Hypothesis: This study was designed to test the hypothesis that pharmacologically increasing Hb O2 affinity with GBT1118 can augment O2 transport during severe hypoxia (10 and 5% O2). Method: Mice were orally dosed with GBT1118 (70 or 140 mg/kg) or only vehicle (Control), and Hb O2 affinity was determined by hemoximetry. During hypoxia, changes in systemic and microvascular hemodynamics, tissue partial pressure of O2 (PO2) and tissue hypoxia were evaluated. At each timepoint, mice with adequate systolic blood pressure (BP) were counted as survived and mice with severe hypotension (BP ≤60 mmHg) were counted as non-survived and were euthanized.

Results:
Similar trends were observed at 10 and 5% O2 hypoxia. GBT1118 at 70 and 140 mg/kg decreased the P50 (PO2 at which blood is 50% saturated with O2) by 29 and 35 mmHg, respectively. During 5% O2 hypoxia, GBT1118 at 70 and 140 mg/kg increased SaO2 from 40% (Control) to 57% (70mg/kg) and 80% (140mg/kg), respectively. Moreover, mean BP and heart rate (HR) decreased to 50 mmHg and 375 bpm in control mice, whereas GBT1118-dosed mice sustained higher mean BP and HR in a dose-dependent fashion and improved survival (Figure 1). In addition, GBT1118 preserved microvascular blood flow and tissue oxygenation; consequently, GBT1118 reduced heart and brain hypoxic areas compared with control groups during hypoxia.

Conclusion:
Under severe hypoxia, GBT1118-mediated increase in Hb O2 affinity increases SaO2. At the tissue level, local milieu allows for efficient O2 extraction leading to improved oxygenation as measured by decreased lactic acidosis, improved cardiovascular function and ultimately, survival.
Abstract 10869: Role of Myocardial Perfusion, Sympathetic Denervation, and Scar Size in Predicting Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy
Authors: Rijnierse Mischa T , Allaart Cornelis P , de Haan Stefan , Harms Hendrik J , Huisman Marc C , Beek Aernout M , Lammertsma Adriaan A , van Rossum Albert C , Knaapen Paul
Published: April 2024

Introduction:
Myocardial perfusion, scar size, sympathetic denervation and innervation-perfusion mismatch, obtained from positron emission tomography (PET) and late gadolinium enhanced cardiovascular magnetic resonance imaging (LGE-CMR), may all provide better risk prediction of ventricular arrhythmias (VA). There may, however, be overlap between these risk markers, as some are based on similar pathophysiology. The aim of this study was to assess the role of PET and LGE-CMR derived risk markers in predicting VA inducibility in the same patient population.

Methods:
Patients (n=52, 66 ± 9 years, 90% male, LVEF 29 ± 6%) with ischemic cardiomyopathy and left ventricular ejection fraction (LVEF) ≤35% who were referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation were included. LGE-CMR was performed to assess LV volumes, function, and scar size. [
15
O]H
2
O PET and [
11
C]HED PET were performed to assess both resting and hyperemic myocardial blood flow (MBF), and sympathetic innervation. Perfusion and innervation defects, and mismatch were calculated. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA.

Results:
Patients with positive EPS (n=25) showed lower hyperemic MBF (1.36 ± 0.39 vs. 1.71 ± 0.39 mL·min
-1
·g
-1
,
P
=0.003), larger innervation defect size (28 ± 12 vs. 21 ± 13%,
P
=0.048), and tended to have larger scar size (24 ± 13 vs. 18 ± 9 g,
P
=0.07) and perfusion defect size (22 ± 13 vs. 15 ± 11%,
P
=0.06) compared with EPS negative patients (n=27). No differences were observed in LV volumes, LVEF, and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperemic MBF was the only independent predictor for VA inducibility (OR 0.78, 95% CI 0.65-0.94,
P
=0.007). A combination of risk markers did not yield incremental predictive value over hyperemic MBF alone.

Conclusion:
Of all previously validated risk markers for VA, impaired hyperemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value. These results may suggest that quantitative PET perfusion imaging may be promising for risk prediction of VA.
Abstract 10925: The Impact of a Positive Gene Test on Presentation and Disease Progression of Arrhythomogenic Right Ventricular Cardiomyopathy in Childhood
Authors: Chungsomprasong Paweena , Hamilton Robert , Fatah Meena , Manlhiot Cedric , Yoo Shi-Joon , Seed Mike , Elders Bernadette , McCrindle Brian W , Grosse-Wortmann Lars
Published: April 2024

Background:
The impact of a pathogenic mutation on the presentation and disease progression in arrhythmogenic right ventricular cardiomyopathy (ARVC) during childhood is unknown. The aim of this study was to compare gene-positive (GP) and gene-negative (GN) patients who were evaluated for ARVC.

Methods:
For this retrospective study, serial clinical data for patients with a known pathogenic mutation for ARVC (GP) were compared to those for GN patients. Magnetic resonance, echocardiography, ECG, signal average ECG (SAECG), Holter, and clinical findings were recorded during each serial evaluation. Patients were classified into possible, borderline or definite ARVC according to the revised Task Force Criteria (rTFC). Patients with ‘no’ ARVC at the last visit were excluded from the follow-up analysis.

Results:
We included 23 GP and 94 GN patients. GN and GP patients were similar in age at presentation. More patients in the GN group (75% vs. 30%, p=0.001) were symptomatic at presentation. The groups did not differ in their initial rTFC category or in their rate of progression to more severe diagnostic categories . Z-scores for RV end-diastolic volume (EDV) tended to progress faster in the GP group (p=0.06), as did the RV outflow tract diameter by echocardiography (p=0.04). Z-scores for RV ejection fraction deteriorated faster in the GP group (p=0.03) and Z-scores for LV EDV increased more rapidly (p=0.04). Patients who were symptomatic on presentation did not progress more quickly in terms of rTFC grading as compared to asymptomatic patients. During a median follow-up of 3.6 years (0-13.9), 2 patients developed ventricular tachycardia, 3 out of 20 with an implanted defibrillator experienced appropriate shocks, and 2 underwent heart transplantation. There were no deaths. GP did not predict adverse events.

Conclusion:
Gene negative and gene positive children who undergo a work-up for ARVC are referred at similar ages to a tertiary care centre. GP patients experience a faster growth of LV and RV size and a more rapid deterioration of RV function. However, being GP is not associated with a faster progression to higher rTFC categories , development of symptoms, or adverse outcomes in the pediatric age group.