bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17460: Anemia and Therapeutic Hypothermia Post-cardiac Arrest: Is There a Transfusion Threshold?
Authors: Borges Nyal , Young Michael N , Holmes Benjamin , Song Yanna , Zern Emily , McPherson John A
Published: March 2022

Introduction:
Profound anemia has been shown to have deleterious effects in critically ill patients (pts). Currently, no data exists regarding the effects of anemia on outcomes in pts post-cardiac arrest treated with therapeutic hypothermia (TH). We aim to evaluate whether a correlation between anemia and neurologic outcome exists in this high risk population.

Methods:
We performed a retrospective study of 260 consecutive comatose survivors of cardiac arrest treated with TH. Independent variables included hematocrit at time of admission, 24, 48 and 72 hrs post-admission as well as packed red blood cell transfusions. The outcome variable was Cerebral Performance Category (CPC) score at discharge. CPC scores 1-2 represented good neurologic outcomes while scores 3-5 represented poor outcomes. A Spearman correlation was computed between each of the above independent variables and discharge CPC, adjusting for the following risk factors: place of arrest, arrest rhythm, time to ROSC, witnessed arrest and presence of chronic kidney disease.

Results:
Of 260 pts, 101 (38.9%) had a good neurologic outcome (CPC≤2) at discharge. The mean hematocrit at admission for males and females was 40 ± 6.4 and 39.2 ±7 % respectively. The Spearman coefficient between hematocrit and CPC score at discharge was not statistically significant (Figure 1). Coefficient for hematocrit at admission and 72hrs with CPC score at discharge was 0.07 (p = 0.32) and 0.01 (p = 0.85) respectively. Coefficient for transfusions and CPC score was -0.11 (p =0.1).

Conclusion:
Our data suggest that neurological outcomes after cardiac arrest in pts treated with TH are unrelated to hematocrit levels or transfusions. Based on these findings, conservative transfusion strategies may be appropriate in this patient population.
Abstract 17469: Expanding the Donor Pool in Pediatric Heart Transplant With a Novel Three Dimensional Technique
Authors: Plasencia Jonathan , Ryan Justin , Lindquist Jacob , Sajadi Susan , VanAuker Micheal , Richardson Randy , Ellsworth Erik , Park Susan , Augustyn Robyn , Southard Richard , Nigro John , Pophal Stephen , Frakes David , Zangwill Steven
Published: March 2022

Introduction:
Heart transplant (HTx) outcomes continue to improve although organs remain limited. Donor-recipient (DR) size matching is critical in pediatrics. Usually, centers apply a subjective donor weight (wt) range based on recipient chest x-ray. DR wt ratios may vary from 0.7–4.

Hypothesis:
A novel 3D tool can be used to predict ideal donor size.

Methods:
A library of 3D reconstructed normal hearts was created from CT/MRI data. A linear fit of normal heart volume vs. body wt was determined for wts up to 22.5kgs (R
2
=0.983). The linear fit was used to predict donor heart volumes and ideal donor wt. Similarly, pre and post HTx hearts were reconstructed from 3 infant pts undergoing HTx.

Results:
[Table] The library was used to predict ideal donor wt targeting 1:1 DR heart volume ratio. Pt A had cardiomegaly and an ideal DR wt ratio of 3.5, which may be outside a center’s usual range. While all 3 Pts had DR wt ratios > 1, Pt A had a downsized graft while Pt B and C had upsized grafts (based purely on DR heart volumes). 3D reconstructions > 1 week post HTx suggest the downsized graft became larger and upsized grafts smaller.

Conclusion:
3D reconstruction has tremendous potential to improve DR size matching in HTx. As the virtual library grows, the ability to accurately predict DR heart volumes will improve. Further, retrospective analysis of transplant cases, wherein 3D matching was used, will allow us to predict the limits of under and oversizing. Finally, this technique has potential to allow “virtual transplantations” wherein we can model a particular donor (green) into a patient-specific recipient (red) and assess fit along with potential for mismatch related morbidity. [Figure]
Abstract 17476: Poloxamer 188 Prevents Mitochondrial Impairment Induced by ST Segment Elevation Myocardial Infarction in a Time and Route-dependent Manner
Authors: Bartos Jason A , Matsuura Timothy R , Tsangaris Adamantios , Debaty Guillaume , McKnite Scott H , Rees Jennifer N , Bates Frank , Metzger Joseph M , Yannopoulos Demetris
Published: March 2022

Introduction:
Poloxamer 188 (P188) is a nonionic copolymer known to prevent ischemia-reperfusion injury in cardiac tissue. The mechanism is unknown, though it is believed to prevent unregulated ion flux by sealing stress-induced gaps in sarcolemmal membranes. We hypothesized that immediate intra-coronary P188 infusion would prevent mitochondrial impairment after ischemia/reperfusion in a porcine model of ST segment elevation myocardial infarction (STEMI).

Methods:
STEMI was induced in 55 pigs by 45 minutes of endovascular coronary occlusion. Upon reperfusion, animals were randomized to four groups: control, immediate intra-coronary P188 treatment (I-P188), delayed P188 treatment (D-P188) initiated after 30 minutes of reperfusion through a peripheral intravenous catheter, or immediate intra-coronary infusion of polyethylene glycol (PEG). Mitochondria were harvested from non-ischemic and ischemic heart tissue after 4 hours of reperfusion. Mitochondrial respiration (RCI) and calcium retention capacity (CRC) were measured in the presence of complex I or complex II substrates. Infarct size was measured after 4 hours of reperfusion by TTC and Evans Blue staining.

Results:
Mitochondrial yield significantly improved with I-P188 treatment suggesting normalization of mitochondrial morphology whereas all other groups were similarly reduced. In control, D-P188, and PEG groups, the RCI was significantly reduced in ischemic compared to non-ischemic tissue for complex I and complex II. I-P188 treatment prevented the reduction in complex I RCI while it had no effect on reduction of complex II RCI. The CRC also increased in ischemic mitochondria from animals treated with I-P188 compared to all other groups. Infarct size was reduced by 66% or more with I-P188 treatment compared to the other groups. Serum troponin was similarly reduced only in the I-P188 treatment group.

Conclusions:
Immediate intra-coronary P188 treatment prevents mitochondrial damage and reduces infarct size after STEMI. This benefit is not observed when treatment is delayed and delivered through a peripheral IV. While the mechanism remains unknown, the amphipathic properties of P188 are necessary as PEG infusion did not provide a significant benefit.
Abstract 17509: The Influence of Chronic Total Occlusion Recanalization on Fractional Flow Reserve Value of Collateral Donor Artery
Authors: Sumiyoshi Akinori , Fujii Kenichi , Shibuya Masahiko , Imanaka Takahiro , Kawai Kenji , Tamaru Hiroto , Horimatsu Tetsuo , Saita Ten , Nishimura Machiko , Masuyama Tohru , Ishihara Masaharu
Published: March 2022

Background:
Although recent guidelines recommend the use of fractional flow reserve (FFR) measurements to make decisions for patients with multi-vessel disease and borderline lesions, the presence of a concomitant chronic total coronary occlusion (CTO) may alter the FFR of the interrogated vessel due to collateral circulation. The purpose of this study was to investigate the change in donor artery FFR associated with PCI of a concomitant CTO.

Methods:
Nineteen consecutive patients who underwent PCI for CTO lesions were prospectively enrolled. All patients underwent myocardial stress perfusion scintigraphy before PCI. An intracoronary pressure/temperature sensor-tipped wire was advanced through a guiding catheter to a point 7cm distal from the ostium of both non-target arteries. At steady-state hyperemia, hemodynamics including FFR and the hyperemic mean transit time (Tmn), which are inversely proportional to coronary flow velocity, were calculated before and immediately after PCI. Coronary blood flow (CBF) was calculated as 1/Tmn х π х (diameter/2)
2
. Coronary wedge pressure was also measured after 30 s of balloon occlusion within the stented segment of the target arteries after PCI.

Results:
The average FFR values of the donor artery before PCI were 0.89±0.09. None of patients had signs of ischemia in the territory of the donor arteries, even though five patients had an FFR value of <0.80 in the donor arteries. After the successful recanalization of the target arteries, FFR values in the donor artery increased to 0.95±0.06 (mean difference, 0.06 [0.04 to 0.09]: p <0.001). On the other hand, CBF in the donor artery significantly decreased from 35.5±15.7 to 25.7±13.8 (p=0.02). No linear correlation was identified between the change of FFR in the donor artery and coronary wedge pressure in the occluded artery (r= -0.05, p= 0.78).

Conclusions:
Revascularization of a CTO lesion provides moderate increase in the FFR value of the collateral donor artery as a result of the reduction of coronary blood flow. Therefore, the hemodynamic significance of intermediate stenosis in the donor artery by FFR should be carefully evaluated in the presence of CTO.
Abstract 17513: Strength of Acute Clinical Management and Weakness of Preventive Efforts - Results of Nationwide Myocardial Infarction Registry From Central Eastern Europe With a 3-year Follow-up
Authors: Zdrojewski Tomasz , Gierlotka Marek , Wojtyniak Bogdan , Polonski Lech , Kozierkiewicz Adam , Gasior Mariusz , Chlebus Krzysztof , Wierucki Lukasz , Kalarus Zbigniew , Opolski Grzegorz
Published: March 2022

Background and aim.
A significant bias of national AMI registries have been described recently. Therefore, to assess a comprehensive picture of AMI in Poland, we performed a study on nationwide data of all Polish AMI patients in 2009-2012 to assess incidence, quality of care, and cardiovascular events up to 3 years following AMI.

Methods.
The database of the only, public, obligatory, health insurer in Poland (NHF)together with the data from Ministry of the Interior, and Central Statistical Office were used (AMI-PL nationwide registry). The AMI cases were selected based on primary diagnosis coded in ICD-10 as I21 or I22. For years 2009-2012 all hospitalisations (N=311,813) in a given year and death records were analysed. Additionally, for 2009, data on hospitalisations, procedures, and deaths in a 3-year follow-up were obtained.

Results.
The age-standardized incidence of AMI in Poland in 2009 was 196 cases per 100,000 population (176 per 100,000 were hospitalized) with decreasing trend over time (80-90 thousands AMI patients each year per 38 mln of population). The incidence was 2.5 times higher in men than in women. Proportion of STEMI declined over time from 55% to 47% in 2012. The percentage of patients treated with invasive strategy raised from 72% to 81%. Decrease of in-hospital case fatality was observed, from 9.1% to 8.0% in 2012. Age-standardized fatality was essentially equal in women and men. Data for index hospitalization in 2009 and cardiovascular events up to 3 years following discharge are presented in the table. Total costs of index AMI hospitalizations for NHF insurer in 2009 were 203 mln EUR, and during 3 years following discharge additionally 162 mln EUR.

Conclusions.
In Poland standards of care and early outcomes in AMI are similar to Western countries. However high incidence of AMI in Polish population, approximately 35 to 50% higher when compared to reported in Denmark or England, indicates a need for intensifying primary prevention programmes.
Abstract 17541: Impact of Therapeutic Hypothermia on Hemodynamics and Prognosis of Acute Coronary Syndrome After Resuscitation From Out-of-hospital Cardiac Arrest
Authors: Yoshida Taiji , Sakata Kenji , Konno Tetsuo , Hayashi Kenshi , Kawashiri Masa-aki , Okajima Masaki , Taniguchi Takumi , Yamagishi Masakazu
Published: March 2022

Backgrounds:
Although therapeutic hypothermia is recommended for neurologically unconscious patients after resuscitation from cardiac arrest, few data exist regarding clinical management during therapeutic hypothermia in acute coronary syndrome (ACS), requiring emergent coronary intervention. Therefore, we analyzed the impact of hypothermia on hemodynamics and prognosis of unconscious ACS patients.

Methods and Results:
We investigated consecutive 21 ACS patients (16 men, mean age 62.8±9.1) who were unconscious and induced hypothermia after resuscitation from out-of-hospital cardiac arrest between April 2009 to March 2014. Invasive hemodynamic monitoring with a pulmonary artery catheter was used during hypothermia with the target body temperature 34°C. ACS was diagnosed with emergent coronary angiography before or during cooling in all cases, and 18 patients had underwent emergent percutaneous coronary intervention. Average required time for the target body temperature from cardiac arrest were 6.8±2.6 hours. During hypothermia, mean blood pressure and cardiac index decreased significantly from 91.3 to 72.7 mmHg and 2.5 to 1.5 l/min/m2, respectively (p<0.05), except for 5 patients with percutaneous cardiopulmonary support (PCPS). Under these conditions, 14 patients had hypokalemia and required potassium replacement and 7 patients had anemia and required a transfusion of red cell concentrates. Therapeutic hypothermia was discontinued early in 8 patients (fatal arrhythmia or circulatory instability in 5 patients, death in 3 patients with PCPS). Average length of stay in our hospital was 26.9 days (1-75 days). Importantly, 8 patients had a good functional outcome as defined by a cerebral performance category scale (CPC) 1-2, 7 patients had CPC 4 at the time of discharge, although there were still 6 death cases. Interestingly, of 8 patients with hypothermia early discontinued, 6 patients (75%) had a good functional outcome (CPC 1-2). Shorter time until return of spontaneous circulation was the most significant factor for a good neurological outcome.

Conclusions:
These results demonstrate that with hypothermia the outcome of ACS was favorable as far as maintaining hemodynamic state, probably due to less occurrence of fatal arrhythmias.
Abstract 17547: Syncope and Inferior ST Elevations: A Diagnosis Within the Heart
Authors: Chatterjee Neal A , Steiner Johannes K , Stone James R , Lewis Gregory D , Moore Stephanie A , Jannuzzi James L
Published: March 2022

A 53 year old woman with a history of diabetes and hypertension presented with syncope, hypotension, and electrocardiography demonstrating inferior ST elevations. The week prior to admission she treated an episode of left knee pain with an admixture of Chinese herbs. Two days prior to presentation she noted the onset of fevers, myalgias and dizziness culminating in syncope the day of admission. Initial electrocardiogram demonstrated complete heart block and junctional escape with inferior ST elevations. Cardiac catheterization demonstrated no epicardial coronary disease. Laboratory studies revealed acute kidney injury, elevated cardiac biomarkers, and a normal white blood cell count with normal differential. Upon transfer to our hospital, the patient was hypotensive requiring temporary ventricular pacing and vasopressor support. Echocardiogram demonstrated severe systolic dysfunction with LVEF of 31%. On arrival, she was noted to have episodes of monomorphic ventricular tachycardia. Etiologies of fulminant myocarditis considered included viral (lymphocytic), giant cell myocarditis, and sarcoid a well as acute eosinophilic myocarditis given recent ingestion of novel herbal mixture. Given the potential for steroid-responsive etiologies, endomyocardial biopsy was performed with institution of mechanical support ( intra-aortic balloon pump) and administration of parenteral steroids. Inotropic and mechanical support were weaned within 72 hours of administration of steroids and she demonstrated normalization of electrical conduction. Biopsy demonstrated acute necrotizing eosinophilic myocarditis (ANEM). Cardiac MRI demonstrated acute myocarditis, subacute inferior infarct, and no LV thrombus. ANEM represents an often fatal, fulminant form of eosinophilic heart disease and can present without systemic eosinophilia. Triggers can include antecedent viral illness and drug hypersensitivity (including herbal mixtures). Eosinophilic proteins can stimulate platelet aggregation and coronary vasoconstriction. Considered mechanisms of inferior infarct included LV thrombus with coronary embolism. The patient was treated with steroids and anticoagulation with recovery of baseline cardiopulmonary function.
Abstract 17550: Predictors of High DFT in Single and Dual Coil Leads: Is There Still a Role for DFT Testing in Current Practice?
Authors: Senfield Jeffrey J , Smith James , Cuoco Frank , Sturdivant J. L , Leman Robert , George Anil , Lewis Geoffrey , Gold Michael R
Published: March 2022

Background:
Two recent changes in implantable cardioverter defibrillator (ICD) practice are the increased use of single coil leads and less frequent defibrillation threshold (DFT) testing at implantation. Single coil leads have higher mean DFTs which is of unclear clinical significance. Such leads were used in only a minority of subjects in SIMPLE, which showed no benefit of DFT testing.

Hypothesis:
Clinical characteristics can be used to predict patients at increased risk of an inadequate defibrillation safety margin with single coil leads.

Methods:
This analysis included 174 consecutive patients undergoing de novo left pectoral, single coil ICD implantation. A standardized modified step down testing algorithm at implantation was used to determine the delivered energy DFT. Logistic regression was used to assess predictors of DFT and of a high DFT (> 25 J).

Results:
The patient population was 71.3 percent male and 35 percent African American (AA). The mean age was 60.8 ± 14.3 years and ejection fraction was 34.3 ± 15.6 percent. Of twelve clinical factors assessed, the univariate predictors of DFT were age (p < 0.001), male sex (p < 0.001) and AA race (p < 0.001). After covariate adjustment, race, age and ejection fraction were found to be associated with a high DFT. The mean DFT (J) among AA was 16.1 ± 8.8 compared with 13.3 ± 6.5 for the rest of the cohort (p < 0.05). Moreover, 13.1% of AAs had a high DFT compared with 1.7% for the rest of the cohort (p < 0.005).

Conclusions:
Age, race and sex predict DFTs with single coil leads. AA are at increased risk for a high DFT and thus an inadequate defibrillation safety margin (< 10 J) and should be considered for dual coil leads and/or defibrillation testing at implantation.
Abstract 17568: Phospholipase C Gamma-1 Mediated Akt-notch1 Signaling is Essential for Intima Formation
Authors: Zhuang Jianhui , Jiang Dongyang , Peng Wenhui , Lu Yuyan , Zhao Qian , Gao Lin , Chi Chen , Xu Xiangbing , Yan Chen , Xu Yawei , Ge Junbo , Pang Jinjiang
Published: March 2022

Introduction:
Vascular smooth muscle cell (VSMC) proliferation, migration and dedifferentiation are critical for vascular diseases, such as atherosclerosis and restenosis after angioplasty. Recently, it is demonstrated that after vascular injury Notch 1and Notch 3 knockout (KO) mice have decreased intima formation whereas Notch 2 KO mice have increased one. Therefore, it is important to investigate the specific regulatory pathways that activate the different Notch receptors.

Methods and Results:
There was a time and dose dependent activation of Notch1, as determined by western blot of N1-ICD but not Notch 2 and 3 in VSMC. As Akt activates Notch signaling in endothelial cells and phospholipase C gamma-1 (PLCγ1) binds to and activates Akt in tumor cells, we therefore propose that PLCγ1 mediated Akt -Notch1 pathway is critical for intima formation by increasing VSMC proliferation, migration and dedifferentiation. To test our hypothesis, we measured PLCγ1 and Akt interaction in VSMC. We observed an association between PLCγ1 and Akt, which was increased upon AngII or PDGF stimulation. Depletion of PLCγ1 by siRNA significantly inhibited Akt and Notch1 activation. As the major target gene of Notch1, Hey2 protein expression was increased 1.8 fold and 2.3 fold respectively after AngII and PDGF stimulation. PLCγ1 siRNA treatment inhibited it by 68.3% and 64.7%. Depletion of PLCγ1 significantly inhibited PDGF induced VSMC proliferation, migration and dedifferentiation but increased apoptosis. In vivo, PLCγ1 and control siRNA were delivered periadventitially in pluronic gel after carotid ligation. Morphometric analysis 21days after ligation demonstrated that PLCγ1 depletion attenuated intima area (2.2 ± 0.7 vs 4.3 ± 1.0, *104 μm2) and intima/media ratio (0.21 ± 0.09 vs 0.43 ± 0.12) compared to the control group.

Conclusions:
In conclusion, PLCγ1 mediated Akt-Notch1 signaling is crucial for intima formation. The PLCγ1 and Akt interaction will be a promising target for therapeutic stratergies that inhibit vascular remodeling.
Abstract 17577: Peripheral Blood Gene Expression in Acute Coronary Syndrome Reflects Acute Inflammatory Responses and Correlates With Residual Inflammation at Follow-up
Authors: Vanhaverbeke Maarten , Pastori Ambra , Huber Heinrich J , Petit Thibault , Trenson Sander , Adriaenssens Tom , Bennett Johan , Dubois Christophe , Desmet Walter , Janssens Stefan , Sinnaeve Peter
Published: March 2022

Introduction:
Previous research showed that peripheral blood gene expression profiles correlate with the extent of coronary artery disease (CAD) in stable non-diabetic patients. It remains unknown how these expression profiles change during an acute coronary syndrome (ACS), and whether they relate to residual inflammation at 30-days follow-up.

Methods:
Peripheral blood samples were prospectively collected from 34 unselected ACS patients (mean age 62 years, 20 STEMI and 14 NSTEMI) on admission and after 30 days. Total RNA was extracted from whole blood at both time points and micro-array analysis was performed (Affymetrix). The results were validated with qRT-PCR and correlated to clinical characteristics and biomarkers.

Results:
On admission, 170 inflammatory transcripts were differentially expressed when compared to 30 days after the event. Pathway analysis revealed IL-1ß and TNF-α as common upstream regulators of these transcripts. From the top 10 genes, we selected 4 significantly upregulated genes on admission for qRT-PCR validation:
CLEC4E
(fold change 2.2,
p
<0.001),
FKBP5
(fold change 2.3,
p
<0.001),
IL18RAP
(fold change 1.6,
p
=0.002) and the inflammasome-related
NLRC4
(fold change 1.8,
p
<0.001). These findings were consistent in STEMI and NSTEMI. The gene expression levels on admission were inversely related to hsCRP levels at 30 days. Patients with a high gene expression score on admission had a mean hsCRP of 0.56±0.11mg/l at 30-day follow-up, vs. 2.44±0.75mg/l in patients with a low gene expression score (
p
=0.035, figure 1). This difference was independent of peak troponin T or peak CRP.

Conclusion:
Peripheral blood gene expression profiles reflect acute inflammatory responses in ACS. Lower baseline gene expression levels, but not infarct size or peak CRP, were associated with higher hsCRP at 30 days, an important marker of residual cardiovascular risk. Whether these expression profiles correlate with outcome needs further investigation.
Abstract 17587: Implications of Angina Pectoris on Quality of Life, Functional Capacity and Clinical Outcomes in Chronic Heart Failure Patients: Insights From HF-ACTION
Authors: Mentz Robert J , Parikh Kishan , Coles Adrian , Schulte Phillip J , Kraus William E , Fleg Jerome L , Keteyian Steven J , Piña Ileana L , Fiuzat Mona , Whellan David J , O’Connor Christopher M
Published: March 2022

Background:
Angina pectoris (AP) is associated with worse outcomes in heart failure (HF) patients, but less is known about implications on health related quality of life (HRQoL) and functional capacity.

Methods:
We assessed HRQoL, functional capacity and outcomes in chronic HF patients with reduced EF in the HF-ACTION trial of usual care +/- exercise training based on whether patients had AP. AP was patient-reported based on recent symptoms or development during exercise testing. We assessed all-cause mortality/hospitalization in patients with AP vs. no AP using multivariable Cox proportional hazards regression. We assessed for an interaction between AP status and exercise training with respect to outcomes and the change in quality of life and functional capacity from baseline to 3 months.

Results:
In HF-ACTION, 406 (17%) patients had AP at baseline with 44% of these reporting ≥ class II symptoms. Patients with AP more often had ischemic etiology, but had similar EF, NT-proBNP and beta-blocker use. Baseline 6-minute walk distance and peak VO
2
were similar in both groups, but patients with AP had worse depressive symptoms and HRQoL. After risk adjustment, AP was associated with a 22% greater risk of all-cause mortality/hospitalization (Figure). There was evidence of an interaction between baseline AP and exercise training on change in peak VO
2
(P=0.019), but not for HRQoL or clinical outcomes. The median change in peak VO
2
with exercise training was 0.8 mL/kg/min with AP vs. 0.6 mL/kg/min without AP.

Conclusion:
AP was associated with worse HRQoL and more depressive symptoms. Despite a greater improvement in peak VO
2
with exercise training, patients with AP experienced more adverse events. Clinicians should consider routine assessment and management of AP in HF patients as well as the associated symptoms related to depression and implications on quality of life.
Abstract 17589: Use of a Wearable Cardioverter Defibrillator (WCD) to Protect Patients After ICD Explantation: Results From the National Registry
Authors: Wan Chingping , Ellenbogen Kenneth A , Love Charles J , Deshpande Sanjay , Szymkiewicz Steven J
Published: March 2022

Introduction:
The WCD is used to treat patients (pts) at high risk of VT/VF until ICD therapy can be implemented as well as for pts with ICDs who undergo device removal and treatment of an underlying infectious process. In non-pacemaker dependent pts for whom an ICD must be removed due to infection, the WCD is now routine therapy, allowing the pt to be managed as an outpatient until the infection is resolved. Re-implantation may be postponed for weeks to months depending upon the nature of the infection being treated. The current study sought to report the outcome of using a WCD in pts who underwent ICD explantation. We report on the time course of re-implantation and the use of the WCD in patients after ICD explantation.

Methods:
Medical orders from 1/2008 through 12/2013 were reviewed for pts prescribed a WCD after ICD explantation. Demographics and WCD-stored electrocardiogram were assessed. A shockable arrhythmia event was defined as all sustained VT or VF occurring within a single 24-hour period. Duration of WCD use and reason for ending use were also evaluated.

Results:
A total of 8,058 pts were identified. Mean age was 62 ± 14 years; male pts consisted of 75% of the study population. While wearing the WCD, 280 (3%) pts experienced 334 VT or VF events, of which 328 were successfully treated by the WCD. The 24-hour survival was 93% (310/334). VT or VF occurrence was highest in the initial weeks following ICD removal (0.7, 0.6 and 0.7 per pt-week for weeks 1, 2 and 3 respectively). Two-month cumulative event rate was 4%. Median time to re-implantation was 48 (IQR, 24-82) days. Thirty-nine percent of the pts wore the WCD for more than 2 months (Figure).

Conclusion:
After ICD explantation, pts were at highest risk of VT or VF during the initial 3 weeks. The WCD demonstrated a high efficacy for resuscitating pts from VT/VF events, with 30-day survival rate being 79% and 90-day being 71%.
Abstract 17601: Left Atrial function Assessed by Cardiac Magnetic Resonance Imaging in Patients With Heart Failure With Preserved and Reduced Left Ventricle Ejection Fraction With and Without Symptoms
Authors: Choudhary Naila , Passick Michael , Butler Javed , Reichek Nathaniel , Cao Jie J
Published: March 2022

Introduction:
Increased left atrial volume (LAV) is considered a barometer for impaired left ventricular (LV) relaxation. In this study we examined the LAV and LA emptying function in patients with LV systolic (LVSD) and diastolic dysfunction (LVDD) with and without clinical heart failure (HF).

Methods:
Prospectively enrolled study participants (n=66) underwent cardiac MR (CMR) in a 1.5 T scanner. Patients with atrial fibrillation were excluded. LAV was assessed at end systole (ES) and at end diastole (ED) using area-length methods in cine MR 4-chamber and 2-chamber planes and indexed to body surface area. HF status was based on clinical manifestations, elevated BNP or NT-BNP. Patients also underwent echocardiogram within 2 hours of CMR. LV ejection fraction (LVEF) by CMR < 50% was defined as LVSD. Echocardiographic criteria and/or elevated LVED pressure by catheterization were applied to define LVDD.

Results:
LAV was significantly increased in HF patients. The greatest increase was seen among those with HFrEF. When compared to normal controls the magnitude of increase in LAV in HF patients was greater at ED than ES. Patients having LVSD and LVDD without clinical HF demonstrated relatively normal LAV at both ES and ED. While LA emptying function was significantly reduced in all HF patients the greatest reduction was found in HFpEF. LA boost function in late diastole was significantly increased only in LVDD (Table). Of the three LA indices, LA emptying function had the strongest correlation with (logarithm transformed) BNP (r = -0.62, p <0.001) and NT-BNP (r = -0.58, p <0.001) supporting its relationship with adverse hemodynamics.

Conclusion:
Significantly increased LAV and reduced LA emptying function were present in HFrEF and HFpEF. Heightened LA boost function with relatively normal LAV and emptying function was characteristic of LVDD without HF. These LA features demonstrate the importance of atrioventricular interdependence and may be valuable in clinical diagnosis.
Abstract 17603: Transgenic Overexpression of Alanine-glyoxylate Aminotransferase 2 in Mice Lowers Asymmetric Dimethylarginine and Improves Vasomotor Function
Authors: Rodionov Roman N , Burdin Dmitrii , Brilloff Silke , Todorov Vladimir , Jarzebska Natalia , Martens-Lobenhoffer Jens , Demyanov Anton , Hilgers Karl , Cordasic Nada , Jacobi Johannes , Maas Renke , Hofmann Anja , Morawietz Henning , Bode-Böger Stefanie M , Hugo Christian P , Hohenstein Bernd , Weiss Norbert
Published: March 2022

Background:
ADMA (asymmetric dimethylarginine), an inhibitor of nitric oxide synthase, has been shown to be associated with the risk of cardiovascular diseases. There are two known pathways for ADMA catabolism: hydrolysis to citrulline by dimethylarginine dimethylaminohydrolases (DDAH) and transamination by alanine-glyoxylate aminotransferase 2 (AGXT2) with formation of asymmetric dimethylguanidino valeric acid (ADGV). In contrast to the first pathway, the second one is poorly characterized. The goal of our study was to test the hypothesis that transgenic overexpression of AGXT2 would lead to lowering of systemic levels of ADMA and improvement of vasomotor function.

Results:
We generated transgenic mice (TG) with ubiquitous overexpression of AGXT2 under control of the chicken beta actin (CAG) promoter. qPCR and Western Blot were used to confirm the ubiquitous expression of the transgene. We did not observe and developmental or phenotypic abnormalities in the TG animals. Biochemical data were generated using HPLC-MS/MS. AGXT2 TG mice had ADMA plasma levels decreased by 15% (p<0.05), whereas ADGV plasma levels were 6 times higher in comparison with wild-types (p<0.001). Lung and heart of TG animals exhibited 2 times lower tissue ADMA content in comparison with controls (p<0.05). Isolated aortic rings were used to estimate endothelium-dependent and -independent relaxation in response to acetylcholine (Ach) and sodium nitroprusside (SNP), respectively. Aortas from AGXT2 TG mice demonstrated an increase in maximal response to ACh (p<0.05). There was a similar relaxation in response to SNP in both groups. We did not observe any differences in mean arterial blood pressure measured by telemetry between the wild type and AGXT2 TG mice.

Conclusion:
In the current study we were able to demonstrate that upregulation of AGXT2 leads to lowering of ADMA levels and improvement in endothelial-dependent relaxation in vivo. AGXT2 thereby may be a potential drug target for long-term reduction of systemic ADMA levels in cardiovascular pathologies. This is especially important, because all the efforts to develop ADMA-lowering interventions by means of upregulation of DDAH have not been successful so far.
Abstract 17613: Defining Clinical Indexes of Good Basket Placement that Predict Successful Outcome From Atrial Fibrillation Rotor Ablation
Authors: Schricker Amir A , Baykaner Tina , Zaman Junaid , Lalani Gautam , Hopper Kenneth , Moyeda Antonio , Krummen David E , Narayan Sanjiv M
Published: March 2022

Introduction:
Ablation for atrial fibrillation (AF) needs improvement, yet it is unclear what to ablate beyond the pulmonary veins since trials question fractionated electrograms or lines. Ablation of rotors and focal sources guided by contact baskets is promising, but with recent disappointing results in one study in which basket contact was poor. We related basket position to fluoroscopic landmarks to determine indexes of optimal placement that predict successful AF rotor ablation.

Methods:
We studied 60 AF patients (62±10 years, 65% persistent) in whom AF was mapped by 64-pole baskets of 48-60 mm diameter, sized by echocardiography or computed tomography. Cineangiograms were used to determine in blinded fashion if left atrial (LA) baskets lay near the floor (coronary sinus, Fig A) or not (Fig B), or if RA or LA baskets were deformed by the atria in 1 image (static) or during multiple cardiac cycles (dynamic; arrows in Fig C). Ablation comprised rotor targeting then PVI, with follow-up per guidelines.

Results:
Using bi-atrial baskets, 205 sources (LA 138; RA 67) were ablated (3.6±1.4/patient). In static images, LA baskets reached the floor in 44 (73%) and were deformed in 54 (90%). Dynamic basket deformation was seen in LA in 39 (65%) and RA in 51 (85%). Presence of LA deformation directly correlated with LVEF, inversely correlated with NYHA functional class (each p=0.05), and was related to good LA coverage. Single procedure AF-freedom at 1 year was higher in patients with dynamic LA deformation than in those without (80% vs. 57%; p=0.07), but unrelated to other indices.

Conclusions:
Atrial basket positioning is a new but important skill for implementing AF rotor ablation. This study is the first to systematically examine optimal indexes of good basket contact, and found that dynamic deformation of basket splines during systole predicted successful AF rotor ablation more effectively than other indexes.
Abstract 17637: Combination Therapy With Hypothermic Target Temperature Management and Valproic Acid After Cardiac Arrest
Authors: Oh Joosuk , Jinka Tulasi , Ren Xiaodan , Neumar Robert W
Published: March 2022

Introduction:
While hypothermic target temperature management (HTTM) has been regarded as a reliable strategy for post-cardiac arrest treatment, there are no pharmacologic agents proved to be neuroprotective against post-cardiac arrest brain injury. In recent years, many studies have shown that valproic acid (VPA), a well-known antiepileptic drug, is neuroprotective against various brain insults. VPA inhibits histone deacetylase activity and causes hyperacetylation of histones, followed by transcriptional activation of anti-apoptotic genes. In this study we tested the hypothesis that combination therapy of hypothermia and VPA could enhance neuroprotection and improve outcome.

Methods:
Male Long-Evans rats were instrumented for continuous telemetric EEG recording with video and then subjected to 8-minute asphyxia cardiac arrest. Nine rats that achieved the return of spontaneous circulation (ROSC) were allocated into the following 3 groups. Controlled normothermia (N group, 36.5-37.5 °C, n=3), HTTM (H group, 32-33 °C for 24 hours, n=3) and HTTM with VPA administration (HV group, 32-33 °C for 24 hours, 300 mg/kg, IV, n=3). Three-day survival, best achieved neurologic function score (NFS), the number of seizure event was compared between the 3 groups.

Results:
The 3-day survival was 33.3% in N group, 33.3 % in H group and 100 % in HV group (p=0.12). The best NFS averaged 263.33 ± 36.67 in N group, 380 ± 64.29 in H group and 468.33 ± 15.90 in HV group (p=0.13). The total number of seizure events in each group averaged 0.33 ± 0.33 in N group, 4.33 ± 2.96 in H group, 0 in HV group (p=0.20).

Conclusions:
These early results suggest that the combination of HTTM and VPA is a promising strategy that could result in synergistic neuroprotection after cardiac arrest.
Abstract 17644: Noninvasive Assessment of Diastolic Myocardial Stiffness by Echocardiography in Patients With Cardiac Amyloidosis
Authors: Alashry Mahmoud , Luis Sushil A , Pislaru Sorin V , Pellikka Patricia A , Grogan Martha , Dispenzieri Angela , Pislaru Cristina
Published: March 2022

Background:
Cardiac amyloidosis (CA) results from extracellular deposition of insoluble amyloid fibrils in the myocardium, leading to myocardial stiffening, restrictive cardiomyopathy and poor prognosis. Thus, measurements of myocardial stiffness might help with identification of patients with cardiac amyloid deposition. The speed of wave transmission of myocardial stretch (Vm) is a novel measure of myocardial elasticity. Our aim was to investigate the behavior of Vm in the left ventricular (LV) myocardium of patients with CA. We hypothesized this wave speed will be increased in these patients and will partly explain the reduction in systolic myocardial function.

Methods:
We prospectively studied 23 consecutive patients with systemic amyloidosis, of whom 17 (age 59±13 years) had confirmed cardiac involvement (15 AL, 2 TTR), and compared to 18 control subjects (age 47±13 years) with normal LV function. Comprehensive transthoracic echocardiography was performed. Tissue Doppler cineloops (350-450 frames/s) were acquired from 6 LV walls from 3 standard apical views. Regional and global Vm were measured as the wave speed of the onset of myocardial stretch from LV base to apex (late diastole).

Results:
Subjects with CA (n=17) had higher Vm compared to normal subjects (2.5±0.8 vs 1.5±0.2 m/s; P<0.001, respectively). They also had lower LV ejection fraction (56±11 vs 65±4%; P=0.02), global longitudinal strain (GLS -14±5 vs -20±2%, P<0.001), and myocardial relaxation (mitral annulus septal e’ velocity 4.7±1.9 vs 9.2±2.4 cm/s; P<0.001) and higher LV mass (150±54 vs 87±18 g/m2; P<0.001), left atrial volume (44±7 vs 27±6 mL/m2; P<0.001), and estimated LV filling pressure (E/e’ 20±9 vs 8±3; P<0.001). There was a strong positive association between Vm and LV wall thickness (R=0.62; P<0.001), GLS (R=0.45; P=0.01) and septal E/e’ (R=0.42; P=0.02) and an inverse correlation between Vm and septal e’ (R=-0.39; P=0.03), but not with ejection fraction (P=0.37).

Conclusion:
This pilot study indicates that Vm is elevated in patients with CA compared to normal subjects, commensurate with the effects of amyloid deposition on LV structure and function. This novel measurement shows promise for noninvasive assessment of diastolic myocardial stiffness in patients with CA.
Abstract 17659: Leaflet Calcification and Matrix Damage Due to Transcatheter Heart Valve Crimping
Authors: Sinha Aditi , Kheradvar Arash
Published: March 2022

Introduction:
Previous studies suggest that crimping causes permanent structural damage to the leaflet tissues of transcatheter heart valves (THV). However, this damage is not yet known to facilitate calcification process.

Hypothesis:
Our hypothesis is to test whether crimp-induced damage promotes valvular calcification.

Methods:
Self-expandable THVs with Glutaraldehye-fixed bovine pericardial leaflets was used. The valves were divided into two groups; crimped and uncrimped, and each group was split into two to be exposed either to a calcifying solution or to a control -normal phosphate buffered saline- solution. For the crimped group, the valves were carefully crimped with a standard crimper at 14Fr and held crimped for 20 minutes. The calcifying solution contains ionic concentrations corresponding to normal human plasma. All groups were maintained at pH 7.5, 37°C, on an orbital shaker at 400 rpm for 7 weeks. At the end, each tissue sample was individually embedded, sectioned and stained for calcium stain (Von Kossa), Verhoff’s Van Geison (VVG) stain for elastin and collagen stain (trichrome III).

Results:
Fig 1A show the normal bovine pericardium with arranged collagen layers in blue whereas intermittent striations are seen across the collagen fibers in the crimped group (Fig 1B). VVG stains show similar results with continuous elastin fibers (black) in the uncrimped group (Fig 1C) versus fragmented elastin fibers in the crimped group (Fig 1D). Of most significance are the results from the von kossa stains where crimped samples in saline show minimal hydroxyapatite deposition (Fig 1E) while crimped samples in calcifying buffer show brown deposits of hydroxyapatite along the crimped regions (Fig 1F). No hydroxyapatite deposition was observed in uncrimped group exposed to calcifying solution.

Conclusions:
Our results indicate that severe structural changes due to crimping are associated with greater levels of calcium deposition along the crimped sites.
Abstract 17693: Metabolic and Hemodynamic Determinants of Progression of Mild to Moderate Aortic Stenosis in Patients With End Stage Renal Disease
Authors: Kim Darae , Shim Chi Young , Cho In Jeong , Chang Hyuk-Jae , Hong Geu-Ru , Hong Geu-Ru , Ha Jong-Won , Chung Namsik
Published: March 2022

Background:
We aimed to characterize progression of aortic stenosis (AS) with end stage renal disease (ESRD), and to determine metabolic and hemodynamic factors attributing to AS progression.

Method:A total of 73 ESRD (50 males, age 72±11 years) on dialysis with mild (n=56) to moderate AS (n=17) were enrolled. Age, sex and AS severity matched control group with eGFR above 60 mL/min/1.73m2 was selected (n=79). Transthoracic echocardiography was performed at baseline and during follow up (48±23 months). Severity of AS was accessed by aortic valve area (AVA) calculated by continuity equations. Acceleration of AS was assessed by annual AVA reduction rate. Accelerated group in ESRD patients was defined as those with the highest quartile of AVA reduction rate. Clinical outcomes included aortic valve intervention, hospital admission due to heart failure, and death.

Results:
Annual AVA reduction rate was significantly higher in ESRD compared to control group (0.36±1.9 vs. 0.05±0.14 cm2/yr, p<0.01). Significantly more patients from mild AS in ESRD progressed to moderate to severe AS compared to control group (32% vs. 9%, p=0.02), while moderate AS showed similar progression in both group (Figure). Accelerated AS group in ESRD patients had significantly larger left atrial volume Index (LAVI) (p<0.01), larger stroke volume (p<0.01) and higher log PTH (p=0.04) compared to non-accelerated group. In multivariate analysis, LAVI≥42ml/m2 (HR 2.2, 95% CI 1.10-4.80, p=0.04) and higher log PTH (HR 2.9, 95% CI 1.10-8.04, p=0.04) were associated poor clinical outcome even after controlling for age and baseline LDL cholesterol.

Conclusion:
AS in ESRD progress in more accelerated manner compared to those with normal kidney function, even in mild to moderate AS. Therefore, more frequent follow up with proper risk stratification by assessing hemodynamic and metabolic characteristics, such as LAVI and PTH, may benefit ESRD patients to reduce clinical events.
Abstract 17695: SCN5A H558R Polymorphism Counteracts Effects of SCN5A Mutations by Decrease Risk Allele Expression Level
Authors: Matsumura Hiroya , Nakano Yukiko , Suenari Kazuyoshi , Tokuyama Takehito , Sairaku Akinori , Kawazoe Hiroshi , Tomomori Shunsuke , Kihara Yasuki
Published: March 2022

The common SCN5A polymorphism, H558R (c.1673A>G,rs1805124), has been reported to be a genetic modulator of Brugada syndrome (BrS) carrying a SCN5A mutation. H558R has been known to improve the sodium channel activity in mutated channels by restoring the abnormal channel gating kinetics or membrane trafficking. The mechanisms by which H558R rescues the SCN5A mutations remain incompletely defined. We investigated the possible mechanism of why H558R modifies the effects brought by an SCN5A mutation. We investigated rs1805124 in 95 BrS patients (91 males, mean age 42 ± 14 years) and 1,875 normal controls (1546 male, mean age 54±18 years). We obtained the right atrial sections during aortic aneurysm operations from 21 patients and rs1805124 was also genotyped in them. Using cDNA of these patients, we examined the expression level of SCN5A by real time RT-PCR and whether splicing of exon 9 to exon 10 in SCN5A was correct by RT-PCR.and evaluate the difference between the genotypes of rs1805124. Additionally, we analyzed the expression ratio of the A allele and G allele separately by specific probes in heterozygous patients. H558R was less frequent in patients with BrS than in normal controls (4.7% vs. 10.3%, P = 0.01). We found strong Linkage disequibrium (LD) in c1141-3C>A (Intron 9) and H558R (r2=0.946). The genotype distribution of the rs1805124 of AA, AG, and GG genotypes in the 21 patients were 13 (61.9 %), 8 (38.1 %), and 0 (0%), respectively. The expression level of SCN5A was similar in the patients with and without H558R. There were not any splicing abnormalities of SCN5A despite of H558R existence. The A allele expression level was mean 1.38 fold higher than that for the G allele (P=0.004). The result suggested that the mutation effect was relieved if the heterozygous mutation rode on the risk allele G. We may have elucidated one reason why H558R modifies the effects brought on by SCN5A mutations.
Abstract 17697: Myocardial Response to Milrinone in Single Ventricle Heart Disease
Authors: Nakano Stephanie J , Nelson Penny , Sucharov Carmen C , Miyamoto Shelley D
Published: March 2022

Background:
Single ventricle heart disease (SV) is a subset of congenital heart defects characterized by a univentricular circulation. Despite surgical intervention, progressive heart failure (HF) is a common cause of death and indication for heart transplantation in children with SV. The exact mechanisms underlying SV HF are poorly understood, limiting the ability to identify effective therapies. Empiric treatment with milrinone, a phosphodiesterase 3 inhibitor (PDE3i), has become increasingly common in SV HF; however the response to milrinone has yet to be characterized in the pediatric SV population. The purpose of this study was to determine the myocardial response to PDE3i in children with SV.

Methods and Results:
Cyclic adenosine monophosphate (cAMP) levels, phosphodeisterase (PDE) activity, and phospholamban phosphorylation (pPLB) were determined in explanted human ventricular myocardium from non-failing pediatric donors (n=10) and pediatric patients transplanted secondary to SV HF (of right ventricular [RV] morphology). SV HF subjects were divided into those who received milrinone therapy (n=13) and those who did not (n=12). In comparison to non-failing RV myocardium, cAMP levels are lower in SV HF patients treated with milrinone (ANOVA, p=0.046). Chronic milrinone treatment does not alter total PDE or PDE3 activity in SV myocardium. Additionally, when compared with non-failing RV myocardium, SV myocardium (both with and without milrinone) demonstrates equivalent pPLB at the protein kinase A site (serine 16 residue).

Conclusions:
As evidenced by preserved pPLB, the molecular adaptation associated with SV HF differs significantly from that demonstrated in pediatric HF due to dilated cardiomyopathy. These alterations support a pathophysiologically distinct mechanism of HF in pediatric SV patients, which has direct implications regarding the putative response to PDE3i treatment in this population.