bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19396: Impaired Autonomic Modulation During the Valsalva Maneuver Predicts Ischemia in Patients With Coronary Artery Disease
Authors: Shah Amit J , Alkhoder Ayman , Obideen Malik , Ramadan Ronnie , Wilmot Kobina , Al Mheid Ibhar , Kutner Michael , Quyyumi Arshed A , Bremner J. Douglas , Vaccarino Viola
Published: July 2021

Introduction:
Previous studies have found that lower resting short-term heart rate variability (HRV), a measure of autonomic dysfunction, predicts adverse cardiac events. Abnormal autonomic function may precipitate myocardial ischemia. Physiologic challenges like Valsalva and deep breathing may also provide important data by modulating preload/afterload and stimulating various autonomic receptors.

Methods:
We examined autonomic function in 166 patients with CAD using the ANSAR method (ANX 3.0, ANSAR Inc. Philadelphia, PA). HRV was measured in the sitting position, standing position, during deep breathing, and during Valsalva. After ANSAR testing, patients underwent
99m
Tc[[Unable to Display Character: ‐]]sestamibi myocardial perfusion imaging at rest and with exercise or pharmacological stress. A summed difference score (SDS) was computed to quantify ischemia using a 17-segment model with observer-independent software. Multivariable models adjusted for CAD risk factors, psychiatric comorbidities, and medications.

Results:
The mean (SD) age was 62 (9) years, 75% were men, and 31% had ischemia (SDS ≥ 4). Both low (LF) and high (HF) frequency HRV during all 4 conditions were associated with ischemia in unadjusted models (table), but after multivariable adjustment, only LF and HF HRV during Valsalva and deep breathing were still associated with ischemia. The strongest association was found with LF HRV during Valsalva, such that every 10% decrease in LF HRV during Valsalva (p=0.003, adjusted) associated with a 1 point increase in SDS. When dividing patients into 4 categories of SDS score (0, 1-3, 4-7, ≥ 8), the SDS ≥ 8 category had a lower LF HRV during Valsalva than all other categories, most notably compared to SDS=0 (78% reduction in LF HRV).

Conclusion:
Low HF and LF HRV are associated with increased risk of myocardial ischemia in CAD patients. Most notably, autonomic inflexibility during Valsalva may help uncover underlying vulnerabilities in autonomic reflexes that predict ischemia burden.
Abstract 19419: A Phase IIa Randomized Double-Blind, Placebo Controlled Study to Evaluate Plasmid Stromal Cell-Derived Factor-1 for Treatment of Critical Limb Ischemia - The STOP-CLI Trial
Authors: Kibbe Melina R , Yadav Ajay , Parakh Rajiv , Mendelsohn Farrell O , Alexander Jason Q , McShannic Joseph R , Pastore Joseph M , Fitzgerald Michael L , Aras Rahul , Penn Marc S
Published: July 2021

Background:
Stromal cell-derived factor-1 (SDF-1) promotes tissue repair by increasing cell survival, endogenous stem cell recruitment and vasculogenesis. Preclinical studies demonstrated that non-viral DNA plasmid encoding human SDF-1 (pSDF-1) is safe and increased vessel density in animal models of hindlimb ischemia versus placebo. Additionally, clinical studies have demonstrated safety of pSDF-1 and evidence of neovascularization at the microvascular level. A Phase IIa multi-center double blind randomized placebo-controlled dose escalation study (STOP-CLI) was initiated to evaluate the safety and efficacy of pSDF-1 administered via direct intramuscular injection in patients with critical limb ischemia (CLI).

Methods:
Forty eight CLI (Rutherford 4 or 5) patients who were poor candidates for surgical revascularization on stable medical therapy with ankle systolic pressure ≤70 mmHg or toe systolic pressure ≤50 mmHg were enrolled into 4 cohorts (n=12 each). Within each cohort, subjects were randomized 3:1 to receive a single set of direct intramuscular injections (8 or 16) to the ischemic limb of escalating doses of 1 mg/ml pSDF-1 (4, 8, 8 or 16mg) or placebo and were followed for 12 months post-dosing. Efficacy endpoints include: quality of life via SF-36, visual analog scale (VAS), Rutherford class, time to first/number of amputations, wound healing, and survival.

Results:
Enrollment was completed in July 2013. At baseline, patients were, 58.6±13.7 years, 88% male, and had an equal number of Rutherford 4 and 5 (n=24 each). To date, 482 follow up months have been completed with 36 Serious Adverse Events reported, none drug-related. Interim 12 month efficacy results show patients who received 8 injections (8 x 1 mg) totaling 8 mg pSDF-1 improved in rest pain (VAS -3.3±2.5 cm vs. -0.8±2.4 cm; 8 x 1 mg injections vs. placebo, p=0.12) and demonstrate improvements in SF-36 Overall Physical (22.4 ± 27 vs. -2.6 ± 29.7, p=0.22) and Mental (21.0 ± 12.7 vs. 0.26 ± 28.2, p=0.16) Health. Final 12 month data will be available in September 2014.

Conclusions:
STOP-CLI tests the hypothesis that delivery of pSDF-1 is safe and will improve the clinical status of patients with CLI. The interim results of STOP-CLI demonstrate safety and bioactivity of pSDF-1 for treatment of CLI.
Abstract 19466: Preliminary Experience Using Multiplexed Imaging of the Sympathetic Autonomic Nervous System - Impact on Outcome of Catheter Ablation of Atrial Fibrillation
Authors: Ernst Sabine , Menichetti Francesca , Baavour Rafael , Roth Nathaniel , Bomanji Jamshed , Ben-Haim Simona
Published: July 2021

Introduction:
Catheter ablation of ganglionated plexi (GP) as an add on to pulmonary vein (PV) isolation has been reported to significantly improve outcome of atrial fibrillation (AF) ablation. In order to facilitate localization of these GPs, a novel imaging study is proposed, assessing the uptake of iodine-123 metaiodobenzylguanidine (mIBG, an analog of norepinephrine)in combination with 3D surface reconstruction from contrast computed tomography (cCT) or cardiac magnetic resonance (CMR).

Methods:
A total of 8 patients (5 male, median age 58 yrs) underwent mIBG SPECT using a dedicated cardiac camera (D-SPECT, SUMO, Spectrum Dynamics). This data was merged with 3D CMR or cCT and finally imported into CARTO (Biosense Webster). Using the individual mediastinum uptake as a normalizing factor, high uptake sites in the epicardial fat pads around the left atrium (LA) were identified. Five patients had paroxysmal AF whilst 3 present in persistent (n=2) or longstanding persistent (n=1) AF. Only 3 patients were treated de-novo, with the remaining failing in median 2 previous ablation procedures. Invasively, high uptake sites were mapped using high frequency stimulation (HFS) to confirm GP locations, which were subsequently ablated. PV (re) isolation and CFAE ablation was performed as needed.

Results:
Both the mIBG and CT or CMR scans were performed without complications. Focal mIBG uptake sites corresponded to anatomical GP sites, but individual variations of additional GPs were observed. Using HFS stimulation, GP sites were confirmed, but exact localization was highly depending on accurate image registration. Median follow-up of 9.2 months with all PAF and persistent AF patients in SR (1 AT redo), while the long-standing AF relapsed.

Conclusion:
The combination of mIBG SPECT and 3D anatomical imaging (SUMO protocol) provides a novel type of “road map” for localizing GPs during AF ablation. GPs were variable in number and location and were invasively confirmed using high frequency stimulation. Addition of GP ablation to standard AF ablation strategies seems beneficial in patients with paroxysmal or persistent AF. Further studies in larger patient cohorts are needed to confirm these initial observations.
Abstract 19627: A National Perspective of the Influence of Do-Not-Resuscitate Orders on In-Hospital Mortality and Adverse Outcome after Intracerebral Hemorrhage
Authors: Patel Achint , Lahewala Sopan , Patel Neil , Nadkarni Girish N , Dhaduk Grishma , Busani Sudharani , Benjo Alexandre M , Pokhrel Narayan , Bambhroliya Chirag , Solanki Shantanu , Sabharwal Manpreet S , Arora Shilpkumar , Mahajan Abhimanyu , Patel Nilay , Badheka Apurva , Jani Vishal , Gidwani Umesh , Hussain Syed I
Published: July 2021

Background:
The impact of do-not-resuscitate (DNR) orders on outcomes has not been systematically evaluated in Intracerebral Hemorrhage (ICH).

Hypothesis:
We assessed the impact of DNR orders in ICH and its association to mortality/related adverse outcomes.

Methods:
We reviewed the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample(NIS) database of 2011 for ICH using ICD 9-CM codes(431).This represents 20% of all US hospital patients and weighted numbers represent national estimates. We defined patients’ DNR status with ICD code V49.86 and comorbid conditions by Deyo’s modification of Charlson’s Comorbidity Index (CCI). We only included adult patients in our analysis. Our primary outcomes of interest were in-hospital mortality and adverse outcome (composite of mortality & discharge other than home). We utilized chi-square test for univariable analysis for categorical variables and generated hierarchical multilevel regression models to determine independent predictors of mortality and adverse outcome.

Results:
We analyzed a total of 13440 pts (weighted n= 64617) with ICH of which 2029 (weighted n=9713) patients had DNR status. The proportions of mortality (56% vs. 19%, p<0.001) and adverse outcome(89% vs 70%) were higher in patients with DNR orders. Even after adjusting for confounders (demographics, Deyo’s modification of charlson’s co-morbidity index, admission type (elective vs emergent), hospital region, hospital teaching status, hospital ICH volume and primary payer), DNR status was associated with higher in hospital mortality (OR 6.98, 95% CI 6.58-7.41), p<0.001) and higher odds of adverse outcome (OR 3.98, 95% CI 3.64-4.34, p<0.001).

Conclusion:
DNR status in patients admitted with ICH appears to be a independent and significant predictor of substantially increased hospital mortality and adverse outcomes. The reasons for this are multifactorial and likely involve patient as well as systematic factors.Further studies including both quantitative/qualitative aspects are warranted to investigate these factors in detail.
Abstract 19678: Safety of Cryoablation of Atrial Fibrillation in the Presence of Mechanical Mitral Valve
Authors: Rajsheker Srinivas , Gujja Pradeep , Attari Mehran
Published: July 2021

Introduction:
Pulmonary vein isolation is an effective therapy for recurrent, symptomatic, drug-refractory atrial fibrillation (AF). Radiofrequency ablation (RFA) has long been the standard of care, while cryoballoon technology has emerged as a feasible approach with promising results in paroxysmal AF. There is risk of catheter entrapment during RFA in patients with mechanical mitral valve and the experience is limited. To the best of our knowledge pulmonary vein isolation (PVI) with cryoablation has never been reported in a patient with a mechanical mitral valve.

Case:
A 52 year old male presented with symptomatic paroxysmal AF, nonischemic cardiomyopathy biventricular defibrillator, mechanical aortic and mitral valve replacement for rheumatic valvular disease. The patient was highly symptomatic while on sotalol therapy. We proceeded with PVI using cryoablation technology.

Procedure:
After a single transseptal puncture, a 28 mm cryoballoon catheter and 20mm 8 pole circular recording catheter were advanced into the left atrium. All four pulmonary veins were isolated with the aid of intracardiac echo, fluoroscopy and Ensite 3-D mapping. Caution was maintained to minimize catheter manipulation and to keep the catheters away from the mechanical valvular plane.

Discussion:
The use of cryoablation for PVI has several potential advantages over radiofrequency ablation including greater improvement in fluoroscopic time and total procedure duration. The risk of prosthetic valve dysfunction due to trauma from ablation catheter, and entrapment of the circular mapping catheter in the mitral valve apparatus represent major concerns when performing PVI in patients with mitral valve replacement, however, less need for manipulation of catheter is an advantage of cryoablation compared to RFA in this case. This case illustrates that cryoablation can be successfully performed in a patient with a prosthetic mechanical mitral valve.
Abstract 19693: Modeling Adaptive Growth -- Biomimetic Culture of Neonatal Aortic Root Explants
Authors: Piechura Laura M , Guyette Jacques P , Gilpin Sarah E , Mathisen Douglas J , Ott Harald C
Published: July 2021

Background:
Heart valve disease afflicts individuals of all ages, but current treatments, involving replacement with non-viable prosthetics, are particularly suboptimal for young patients. To design “growing” valve replacements, postnatal growth mechanisms must be elucidated; models of adaptive growth are lacking, thereby hindering these investigations. We hypothesized that physiologic mechanical loading with growth factor stimulation would enable the adaptive growth of aortic root explants
in vitro.
To this end, we designed a biomimetic perfusion bioreactor that permits the concomitant delivery of these factors.

Methods and Results:
We constructed a chamber for culturing neonatal rat hearts under pulsatile flow conditions. Parameters were adjusted to mimic native physiology using ultrasound assessment of cusp motion and invasive measurement of left ventricular and aortic pressures. Culture medium was designed by quantification of key growth factor (IGF-1, TGF-β
2
, VEGF, EGF, BMP-2 and FGF-2) concentrations within age-matched serum via ELISA. Explants were cultured for five days. Controls were explanted from age- and size-matched pups. Dynamically-cultured samples exhibited similar proliferation rates at early time points when compared to those of valve cusps
in vivo
as assessed by EdU incorporation (10.5% vs. 14.9%, p=0.35). After five days of dynamic culture, native proliferation rates were achieved only with concomitant growth factor administration (13.3% control; 13.1% dynamic+GF; 3.1% dynamic alone). There was no evidence of proliferation in statically-cultured controls.

Conclusions:
We describe a novel biomimetic culture system that permits the modeling of adaptive growth in aortic root explants. Our results demonstrate recapitulation of
in vivo
cell proliferation rates in dynamically-cultured hearts and suggest a role for mechanical and humoral stimulation in mediating aortic valve growth. This system enables the elucidation and manipulation of the mechanisms driving postnatal heart valve growth, thereby informing the design of the ideal pediatric valve graft with adaptive growth potential.
Abstract 19700: Recent Trends in Procedure Type, Morbidity and In-hospital Outcomes of Patients With Peripheral Artery Disease: Data From the Brazilian Public Health System
Authors: Nascimento Bruno R , Brant Luisa C , Lana Maria Letícia L , Lopes Eduardo L , Ribeiro Antônio Luiz P
Published: July 2021

Introduction:
The prevalence of peripheral artery disease (PAD) is rising worldwide, with a considerable impact on health care systems. We aimed to characterize the recent trends in surgical, percutaneous and clinical therapeutic procedures and in-hospital outcomes of PAD among all hospitalized patients in the Brazilian Public Health System between 2008 and 2012.

Methods:
Nationwide data of all hospitalizations in the Brazilian Public Health System (DataSUS) database in 2008, 2010, and 2012 were analyzed regarding the frequency of hospitalizations due to PAD (endovascular - EVR, surgical revascularizations - SR and clinical treatment - CT), length of hospital stay and in-hospital mortality and associated costs to the health system.

Results:
The number of hospitalizations related to PAD (EVR, SR and CT) remained stable from 2008 to 2012: 28,091 and 28,151 respectively, accounting for 0.25% and 0.24% of all in-hospital procedures. However, there was a significant change in the proportions of treatment modalities used in this period. In 2008: SR = 8,001 (29%), EVR = 3,207 (11%) and CT = 16,887 (60%); in 2010: SR = 7,999 (30%), EVR = 4,020 (15%) and CT: 14,849 (55%); and in 2012: SR = 7,882 (28%), EVR = 5,044 (18%) and CT = 15,225 (54%); p<0.001. The results show a 57% increase in EVR, and a 9.8% decrease in CT in this period. Total costs raised 23%, from US$ 18.6 million in 2008 to R$ 22.9 million in 2012 (p< 0.001), with a marked 92% increase in EVR costs (R$ 5.3 to 10.0 million), compared to SR (11%) and CT (30%). Global mean hospital days did not change from 2008 to 2012 (5.8 to 5.7 days), whereas it decreased for EVR (5.7 to 4.8, p<0,001). Hospital mortality decreased from 2008 to 2012 for EVR (2.0 to 1.4%, p=0.048), increased for CT (5.1 to 5.8%, p=0.002) and remained stable for SR (8.5 to 8.8%, p=0.44). Overall mortality, however, increased from 6.2% in 2008 to 6.7% in 2012 (p=0.004).

Conclusion:
There is an increasing proportion of EVR for PAD in Brazil, with a concomitant increase in costs, mainly related to these procedures. Our administrative data-based analysis depicts the significant rise of overall PAD mortality in Brazil, especially in clinically treated patients, emphasizing the need of controlling PAD risk factors and promoting its early diagnosis and effective management.
Abstract 19769: Cardiac Injury and Stunning after Ischemia is Related to Loss of PBEF/Nampt Function and is Rescued by PTEN Inhibition
Authors: Li Jing , Shao Zuo-Hui , Li Chang-Qing , Chen Sy-Jou , Zhu Xiangdong , Harty Shaun , Vanden Hoek Terry L
Published: July 2021

Introduction:
Therapeutic hypothermia protection during cardiovascular resuscitation has been associated by us with preservation of heart tissue Pre-B-cell colony-enhancing factor (PBEF)/nicotinamide phosphoribosyltransferase (Nampt) level. This finding was associated with increased heart Akt activity that is negatively regulated by the phosphatase PTEN. We hypothesized that the PTEN inhibitor, VO-OHpic (VO), can improve heart cell survival and contractility via its role in energetic recovery following ischemia.

Methods:
Primary neonatal heart cells were exposed to 90 min ischemia and 180 min reperfusion to evaluate viability by propidium iodide uptake. Contractility was assessed in a stunning model of 30 min ischemia and 90 min reperfusion. VO (1μM) was given at reperfusion and PBEF/Nampt inhibitor FK866 (100 nM) was administered 1 h prior to ischemia. Akt phosphorylation and PBEF expression was detected by Western blot and ELISA assay, respectively. ATP content was measured by a fluorescent assay kit.

Results:
Compared to control cells, VO improved cell survival (56.3 ± 7.3 vs. 32.5 ± 7.6%,
p
< 0.05), a protective effect blocked by FK866. VO also rapidly improved contractile recovery following 30 min ischemia and decreased PBEF/Nampt release from heart cells, protective effects blocked by FK866. Improved contraction was related to increased Akt Thr308 and Ser473 phosphorylation and total ATP content.

Conclusions:
PTEN inhibition improves heart cell survival, ATP content and contractile recovery after ischemia. Protection is associated with attenuation of PBEF/Nampt cell release and is blocked by PBEF/Nampt inhibitors.
Abstract 19771: Persistent Thrombocytopenia after Myocardial Infarction is Associated with Increased Short- and Long-Term Mortality
Authors: Kumar Anirudh , Virani Salim , Bassett Scott , Alam Mahboob , Hira Ravi , Caruso Andrew , Paniagua David , Denktas Ali , Hamzeh Ihab , Levine Glenn , Ballantyne Christie , Deswal Anita , Bozkurt Biykem , Jneid Hani
Published: July 2021

Background:
Thrombocytopenia (TCP) occurs commonly in patients hospitalized with acute myocardial infarction (AMI). It is unclear whether persistent TCP after discharge among AMI survivors is associated with worse outcomes.

Methods:
We examined the impact of persistent post-discharge TCP on outcomes in a registry of consecutive AMI patients hospitalized between January 2004 and December 2007. In-hospital (IH) TCP was defined by a nadir platelet count < 150 x 109/L. Resolved TCP was defined as IH TCP which resolved within 3 months after discharge while persistent TCP was defined as IH TCP which did not resolve within 3 months.

Results:
Of 842 patients hospitalized for a first AMI, we examined data on 617 hospital survivors who had follow-up within 3 months of discharge and documented long-term outcomes. Of those, 474 (76.8%) patients did not experience IH TCP while 42 (6.8%) and 101 (16.4%) had persistent and resolved TCP, respectively (Table). Patients with persistent TCP were older, had worse comorbidities, and were more likely to have TCP at baseline and discharge. There were no inter-group differences in infarct size, major bleeding complications, revascularization, or ejection fraction at discharge. Mortality following discharge was higher at all time-points among AMI patients with persistent TCP compared to patients with resolved or without IH TCP (Figure). Patients with resolved TCP had comparable mortality to those without IH TCP.

Conclusion:
Persistent TCP within 3 months after hospital discharge for AMI is associated with significantly increased short- and long-term mortality compared to patients with recovered TCP or without IH TCP.
Abstract 19807: Pre-Superior Cavopulmonary Anastomosis Cardiac Catheterization at Altitude
Authors: Di Maria Michael V , Fagan Thomas E , Wilson Neil , Mitchell Max B , Campbell David N , Jaggers James , da Cruz Eduardo , Ivy D. Dunbar , Younoszai Adel K
Published: July 2021

Introduction:
Infants with single ventricle physiology typically undergo cardiac catheterization prior to superior cavopulmonary anastomosis (SCPA) to assess operative suitability. Predictors of poor outcome at sea level include elevated central venous pressure (CVP), transpulmonary gradient (TPG), pulmonary vascular resistance (PVR) and pulmonary artery (PA) size. Living at higher altitude has vasoconstrictive effects on the pulmonary vasculature, and a prior study suggested that higher PA pressure may predict worse outcomes. The goal of this study was to determine which elements of the pre-SCPA catheterization were useful in predicting successful Fontan operation at altitude.

Methods:
A retrospective review revealed 150 patients who underwent pre-SCPA catheterization over a 10-year period. Pre-SCPA catheterization data were abstracted and subjects were grouped by progression to Fontan vs. aborted palliation, heart transplant or death. Statistical analysis included Wilcoxon Rank Sum tests, uni-variable logistic regression and receiver operator characteristic (ROC) curve analysis.

Results:
Differences between groups at cardiac catheterization are summarized in Table 1. Logistic regression showed that larger PA diameter was protective; left PA: OR: 0.73, 95% CI: 0.6-0.9, p = 0.01; right PA: OR:0.73, 95% CI: 0.6-0.9, p = 0.02. ROC analysis defined thresholds for minimum left PA and right PA diameter of <4mm for poor outcome (area under the curve of 0.68 and 0.67, respectively).

Conclusions:
Our data suggest that pulmonary arterial size, more so than measured pressure or resistance, influences ability to achieve Fontan palliation at higher altitude. We hypothesize that this may be a feature of differences in pulmonary arterial growth. An alternative approach to evaluating pulmonary arterial morphology during palliation, such as cross-sectional imaging, may help optimize individual patient hemodynamics and provide better predictors of outcome.
Abstract 19924: National Cost Comparison of Trans Catheter Aortic Valve Replacement With Surgical Aortic Valve Replacement in Moderate to High Risk Patients With Severe Symptomatic Aortic Stenosis in New Zealand
Authors: Bhattacharyya Srija , Roskruge Matthew , Pasupati Sanjeevan , Devlin Gerard , Smyth David , Webster Mark , Ruygrok Peter
Published: July 2021

Introduction:
AS is a condition with an increasing prevalence in New Zealand (NZ). The natural history of severe AS is such that patients face a poor prognosis once the disease becomes clinically evident. Surgical aortic valve replacement (SAVR) is the standard of care, yet many are at high risk of poor outcomes due to comorbidity, frailty or anatomical limitations. Clinically TAVR may be an appropriate alternative treatment; however, at present it remains an expensive technology: the procurement cost of an Edwards Sapien trans catheter valve is NZD$30,000. Expansion of TAVR could have a major budget impact on the NZ public healthcare system. Conversely, the high cost of the transcatheter valve may be offset by intensive care unit stay and the cost of complications related to SAVR.

Methods:
To explore this further, we retrospectively compare index admission cost in AS patients with Euroscore 2 > 4 undergoing SAVR with those having TAVR. Patients were excluded if they had surgery outsourced to the private sector, if they had not had their procedure by 31/3/2014 or if full costing data could not be extracted from the hospital business department. Clinical variables include date of admission, date of procedure, age, gender, weight, Euroscore 2, renal function (GFR), LV function and previous sternotomy. Data was collected across the three TAVR centers in NZ. A total of 170 TAVR patients are compared with 168 SAVR patients.

Initial Results:
Mean Euroscore 2 was 9.8 +/- 5.4 in the TAVR group compared with 7.4 +/- 4.3 in the SAVR group. The mean cost of SAVR vs TAVR was $65,793 and $52,582 respectively. Median cost was $54,826 for SAVR and $46,899 for TAVR. 57% of the mean cost of TAVR was due to the valve. Average length of stay in TAVR patients was half that of SAVR patients. ICU cost in SAVR patients was $10,021 higher than in the TAVR patients. On average, TAVR required 10% of the blood product costs associated with SAVR.

Conclusions:
We show that the average index admission cost of SAVR is significantly higher than TAVR in this group of patients who were at moderate to high risk of surgery. Also, non-device costs are much higher in SAVR, suggesting higher hospital resource requirements compared to TAVR. This data has implications for TAVR funding in the NZ public healthcare system.
Abstract 19958: Evaluation of Tricuspid Regurgitation (TR) Severity Prior to and after Device Extraction in Patients with Cardiac Device Infection
Authors: Butler Thomas , Khan Akhlaq , Sengupta Abhishek , Sherman Jonathan , Denman Russell , Burstow Darryl , Sedgwick John F
Published: July 2021

Aim:
This study sought to evaluate the impact of device extraction on the severity of TR in patients with cardiac device related infection (CDI) and infective endocarditis (CDRIE).

Methods:
The medical and echocardiographic records of 142 patients who had undergone device extraction for suspected infection from 2007 - 2013 were reviewed. Data on clinical complications, echocardiographic documentation of TR severity prior to and after device removal and potential risk factors for change in TR severity was obtained. A paired t test was used to evaluate whether the TR mean grade changed significantly.

Patient Demographics:
A total of 56 patients out of the 142 patients had TTE and/or TOE imaging. Of these patients, 22 patients had ICD’s, 27 patients had PPM’s and 7 patients had BiV Devices. The mean age was 62 years (47 males). Clinical complications included decompensated heart failure (12.5%), septic shock (8.9%), septic arthritis (8.9%), splenic abscess (1.78%), septic pulmonary embolism (5.35%), leukocytoclastic vasculitis (1.78%).

Results:
The mean duration of device in situ prior to extraction was 64 months (5.33yrs). The mean grade of TR prior to device extraction was grade 1.35/4 (SD=0.901, C.I. 1.16 to 1.72). The mean grade of TR post extraction was 1.54/4 (SD= 0.96 with C.I. 1.26 to 1.89). The mean difference in mean TR grade was 0.13 (C.I. 0.37 to -0.106) p >0.05. One patient had a worsening of TR by at least 2 grades post extraction. This was due to valve perforation from infection rather than extraction related trauma. This was the only patient that required surgery for clinically significant TR.

Risk factors for worsening TR post extraction included the length of time leads were in situ and age of the patient. Time of Device in situ prior to extraction did not correlate significantly with severity of TR post procedure rho 0.12 (p value = 0.45). Furthermore, age at the time of the procedure did not correlate with tricuspid regurgitation severity post extraction rho 0.21 (p value = 0.18).

Conclusions:
Worsening of TR post extraction is uncommon and is more likely due to valve destruction from infection rather than trauma to the valve during extraction. Furthermore, a number of complications occur peri-procedurally that impacts on patient outcomes.
Abstract 20004: Long-term Risk of Mortality, Aortic Dissection and Thoracic Aortic Surgery After Isolated Aortic Valve Replacement in Patients With Bicuspid and Tricuspid Aortic Valves
Authors: Itagaki Shinobu , Chiang Yuting , Chikwe Joanna
Published: July 2021

Introduction:
The natural history of aortopathy after isolated aortic valve replacement (AVR) in patients with bicuspid aortic valves (BAV) is not well characterized.

Hypothesis:
The incidence of dissection and thoracic aortic surgery after isolated AVR in patients with BAV is higher than in patients with tricuspid valves.

Methods:
From 1995-2010, 2,203 bicuspid and 1,436 rheumatic tricuspid patients undergoing isolated AVR were identified from the Statewide Planning and Research Cooperative System which captures all inpatient admissions and emergency visits to every hospital in New York State. Deaths were identified from the Social Security Death Master File. Kaplan-Meier analysis of survival and competing risk analysis of aortic dissection and thoracic aortic surgery was performed.

Results:
BAV patients were younger than tricuspid aortic valve (TAV) patients (52.0 vs. 64.2 years, p<0.001). Survival at 15 years after AVR was 77% versus 58%, respectively (p<0.001). During median follow up of 8.0 years (range 0-19.0 years), aortic dissection occurred in 9 BAV patients versus 4 TAV patients. The 15-year cumulative incidence of dissection after AVR in BAV patients was 0.7% versus 0.4% in TAV patients (p=0.28) (Figure 1). Thoracic aortic surgery was performed in 33 BAV patients versus 9 TAV patients. The 15-year cumulative incidence of thoracic aortic surgery was 3.1% in BAV patients versus 1.1% in TAV patients (p<0.001) (Figure 2).

Conclusions:
Patients undergoing isolated AVR of bicuspid valves are at greater long-term risk of aortic dissection and thoracic aortic surgery than patients with tricuspid valves, and should be considered for life-long surveillance.
Abstract 20062: Predicting Sudden Cardiac Death in the General Population: Analysis of the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study
Authors: Deo Rajat , Lopez Faye , Katz Ronit , Adabag Selcuk , Chen Lin Y , deFilippi Christopher R , Folsom Aaron R , Heckbert Susan R , Kestenbaum Bryan R , Konety Suma , Kronmal Richard A , Patton Kristen K , Siscovick David , Sotoodehnia Nona , Shlipak Michael G , Alonso Alvaro
Published: July 2021

Introduction:
Most cases of sudden cardiac death (SCD) in the general population occur primarily among persons who do not have any prior history of clinical heart disease.

Hypothesis:
After evaluating a comprehensive panel of traditional and novel cardiovascular risk factors in two, large, racially diverse, population-based cohorts, we sought to develop a predictive model of SCD among US adults without a history of cardiovascular disease.

Methods:
We evaluated a series of 26 demographic, clinical, laboratory and electrocardiographic measures in participants who were free of baseline cardiovascular disease in the Atherosclerosis Risk in Communities (ARIC) Study (n=13,677) and the Cardiovascular Health Study (CHS) (n=3,650).

Results:
After a median follow-up of approximately 13 years, there were a combined total of 318 adjudicated SCD events for analysis. The following 11 risk factors were significant risk factors for SCD after meta-analyzing the findings from each cohort: age (per 5 years; HR 1.32, 95% CI [1.17 - 1.49]), male sex (HR 2.23; 1.70 - 2.93]), African American race (HR 1.62, 1.19 - 2.20), current smoking (HR 2.19, 1.65 - 2.92), low physical activity (HR 1.42, 1.09 - 1.85), hypertension (HR 1.82, 1.37 - 2.42), diabetes (HR 2.49, 1.86 - 3.34), low serum albumin (per 0.3 g/dL decrease; HR 1.38, 1.20 - 1.59), low HDL (<40 mg/dL in men and <50 mg/dL in women; HR 1.37, 1.05 - 1.80), eGFR<60 ml/min/1.73m2 (HR 1.77, 1.16 - 2.71), and a prolonged QTc interval (≥440 milliseconds in men or ≥460 milliseconds in women; HR 2.08, 1.54 - 2.80). Over a 10-year follow-up period, a model combining these risk factors showed good to excellent discrimination for SCD risk (C statistic 0.831 in ARIC and 0.745 in CHS). Serum biomarkers including C-reactive protein (CRP), NT-pro-brain natriuretic peptide (BNP) and high sensitivity troponin T were not significant risk factors and did not enhance SCD risk prediction when added to the final multivariate model.

Conclusions:
A prediction model including demographic, clinical, laboratory, and electrocardiographic variables provided accurate information on the future SCD risk in middle-aged and elderly populations.
Abstract 20074: Hemodynamic Profile of Prolonged Normothermic, Mild Hypothermic, and Deep Hypothermic Emergency Cardiopulmonary Bypass Reperfusion in Rats
Authors: Magnet Ingrid A , Ettl Florian , Schober Andreas , Warenits Alexandra-Maria , Testori Christoph , Grassmann Daniel , Wagner Michael , Clodi Christian , Schriefl Christoph , Teubenbacher Ursula , Högler Sandra , Weihs Wolfgang , Sterz Fritz , Janata Andreas
Published: July 2021

Background:
The hemodynamic profile of rats randomized into prolonged normothermic (NT, 37±0.5°C), mild hypothermic (MH, 33±0.5°C) or deep hypothermic (DH, 27±0.5°C) reperfusion with emergency cardiopulmonary bypass (ECPB), following refractory ventricular fibrillation cardiac arrest (VF CA) was explored.

Methods:
Fifty adult male Sprague-Dawley rats were put on bypass for 15 min, following 10 min of VF CA. The ECPB setup included a circulating water bath which temperature controlled all animals at target. After 15 min, rats were defibrillated, weaned from bypass, and controlled at 33°C (MH, DH) or 37°C (NT) externally. All rats received a single dose of epinephrine (30 μg/kg), heparin and sodium bicarbonate with the crystalloid priming of the ECPB circuit. ECPB flow rate was kept at 100 mL/kg in all groups. Mean arterial pressure (MAP) was continuously monitored in the femoral artery and is presented as median with 25th/75th quartile mmHg.

Results:
See figure. There was no difference in MAP before or during CA. For the first 5 min of resuscitation, MAP at a given ECPB flow rate was highest in the DH group (DH 84(69;89), MH 51(49;61), NT 48(37;55) , p = <.001). This was reversed during the last 5 min on bypass (DH 35(30;42), MH 44(37;64), NT 42(33;67), p = .034). For 10 min off bypass, the DH group was relatively hypotensive (DH 46(40;62, MH 64(60;77), NT 61(54;77), p = .005), which was again reversed for the remaining post resuscitation period (DH 68(60;78), MH 59(54;66), NT 53(49;62), p = .008).

Conclusions:
While the temperature profiles of NT and MH reperfusion were similar, DH caused initially higher pressures followed by a period of hypotension as compared to NT and MH groups at identical epinephrine doses and ECPB flow rates. Off bypass, DH animals were again relatively hypotensive, coinciding with their rewarming to mild hypothermia. Further experiments are needed to determine the cause of this, like hypothermic vasoconstriction, or altered pharmacokinetics.
Abstract 20168: Right Ventricular Global Longitudinal Strain is Correlated With Cardiovascular Magnetic Resonance Ejection Fraction and Provides Prognostic Value in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Onishi Tetsuari , Yoshii Kosuke , Tsuru Masato , Shimane Akira , Okajima Katsunori , Taniguchi Yasuyo , Kawai Hiroya
Published: July 2021

Introduction:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by functional abnormalities of the right ventricular (RV). RV ejection fraction (EF) determined by cardiac magnetic resonance (CMR) imaging is accepted as gold standard measure of RV systolic function.

Hypothesis:
RV global longitudinal strain (GLS) by 2-dimensional speckle tracking echocardiography (2DSTE) is correlated with CMR-RVEF, and associated with cardiac events in patients with ARVC.

Methods:
We studied 50 patients referred with suspected ARVC. Of them, 19 patients (Group A) were diagnosed as ARVC, while remaining 31 patients (Group B) were not diagnosed due to not meeting criteria. All patients underwent CMR for measurements of RVEF, and echocardiography with conventional assessment including tricuspid annular plane systolic excursion (TAPSE), RV end-diastolic and end-systolic area (RVEDA, RVESA) and RV fractional area change (RVFAC), and with 2DSTE analyses of GLS which was expressed as the absolute value. The cardiac events, defined as death, hospitalization for heart failure, fatal arrhythmia and appropriate defibrillator shock, were followed up for patients in Group A.

Results:
Patients in Group A had significantly smaller values of TAPSE, RVFAC, GLS and RVEF and significantly greater values of RVESV compared with patients in Group B (p<0.05 for all), while there were no significant differences in RVEDV between 2 groups. GLS were correlated with RVEF (P=0.001, r=0.4) as with RVEDA, RVESA, RVFAC and TAPSE (p<0.01 for all). 4 appropriate defibrillator shocks were observed during averaged 724 days followed-up period in Group A. Dividing patients in Group A into 2 groups with median value of CMR-RVEF or GLS, Kaplan-Meier curve analysis revealed that GLS was significantly associated with outcome (P=0.02), while CMR-RVEF was not.

Conclusions:
GLS in the RV was significantly correlated with CMR-RVEF, and was associated with cardiac events in patients with ARVC.
Abstract 20180: Erroneous Diagnosis of Brugada Syndrome: Advanced Multi-Modality Coronary Evaluation to Establish an Ischemic Etiology for Recurrent Ventricular Arrhythmia
Authors: Flatley Erin E , Beaser Andrew D , Balkhy Husam H , Nathan Sandeep , Moss Joshua D
Published: July 2021

Introduction:
Rapid diagnosis of ST-segment elevation (STE) myocardial infarction is mandatory for optimal treatment, but standard coronary angiography may occasionally result in misdiagnosis.

Case presentation:
A 54-year-old man was referred for second opinion on treatment of recurrent ventricular tachycardia (VT) and chest pain. Three years prior, he suffered a cardiac arrest requiring AED shock. Initial EKG showed 5-10 mm STE in leads V2-V6. Emergent coronary angiography at another facility reportedly showed non-obstructive disease, and STE resolved spontaneously. Procainamide challenge during a subsequent electrophysiology study elicited changes diagnosed as Brugada syndrome, and an ICD was implanted. Over the next several years, he had frequent episodes of VT, often associated with chest pain and terminated with anti-tachycardia pacing. Multiple antiarrhythmic drugs were ineffective, and VT ablation was recommended.

Based on the history and original EKG, we proceeded with multi-modality coronary evaluation and provocative testing for coronary vasospasm. An indistinct proximal LAD lesion was further evaluated with fractional flow reserve (FFR) testing, showing a baseline FFR of 0.90 that decreased to 0.67 after administration of intracoronary adenosine. Optical coherence tomography (OCT) revealed 90% eccentric ostial LAD stenosis (see Figure). Given the location and severity of the lesion, he underwent successful robotic totally endoscopic beating heart LIMA-LAD bypass grafting. Post-operatively, both chest pain and episodes of VT resolved.

Conclusions:
The differential diagnosis of transient STE includes several non-coronary etiologies. However, in the setting of dramatic STE across the precordium and recurrent ventricular arrhythmias, a comprehensive, multi-modality coronary evaluation should be employed to identify lesions that may be otherwise equivocal via angiography or sites of significant vasospasm.
Abstract 20211: Contrast Improvement of Biodegradable Stents for X-ray Computed Tomography Visualization
Authors: Winters James , Bennett James , Guelcher Manfred , Mathur Anthony , Martin John , Fahmy Tarek , Sinusas Albert
Published: July 2021

Introduction:
Biodegradable stents present challenges during percutaneous coronary intervention (PCI) because they are typically radiolucent. For the same reason they cannot be visualized in vivo with clinical CT. By impregnating a contrast agent in the stents’ polymer coating, the stents can be seen during PCI and their degradation can be tracked in vivo using serial CT imaging. We evaluated the degradation of a polymer coated magnesium (Mg) stent in a bioreactor using dual energy microCT.

Methods:
Bare Mg stents with 125 μm strut thickness were coated with either a mixture of poly(lactic-co-glycolic acid) (PLGA) and triiodobenzoic acid (TIBA) or PLGA and iodinated dendrimer (ID), deployed in latex tubing, and imaged using high resolution microCT (eXplore CT120, GE) at both 80kVp and 120kVp. Stents were exposed to physiological flow in a bioreactor for 5 days, removed and dual energy microCT was repeated using same protocol. Dual energy images were processed using a custom Matlab algorithm, and the iodinated polymer was digitally segmented from the Mg struts.

Results:
Images of stents at baseline coated with both PLGA-ID and PLGA-TIBA showed a marked increase in CT attenuation. Images of degraded stents coated with PLGA-TIBA showed a loss of attenuation in the polymer coating but little degradation, which suggests the small TIBA molecules was not retained in the polymer. Using dual energy CT enabled segmentation of the struts and polymers.

Conclusions:
We have demonstrated that the radio-opacity of polymer-coated biodegradable stents can be improved with the addition of an X-ray contrast agent during the process of polymer coating with microCT. The results suggest that the degradation of biodegradable stents could be tracked in vivo. This approach could help with stent deployment and determine when the standard dual anti-platelet therapy can be stopped based on degradation as assessed with dual energy CT.
Abstract 20227: Global Myocardial Injury as a New Criterion Independent of Infarct Size and Area-at-risk
Authors: Johnson Steven E , Lee Daniel C , Benefield Brandon C , Holly Thomas A , Arora Rishi , Fang Wei , Goldberger Jeffrey J , Zhao Ming
Published: July 2021

Introduction:
In acute coronary syndromes, the extent of myocardial injury can be substantially greater than the infarct zone. Existing imaging methods identify the infarct zone but do not assess “global myocardial injury” (GMI), which measures the total area of myocardium that sustained injuries including and beyond the infarct zone per se.

Hypothesis:
GMI can be detected based on changes in cellular membrane organization as a surrogate marker, using Tc-99m-duramycin.

Methods:
Balloon angioplasty was used for coronary occlusion in a pig model of myocardial ischemia and reperfusion (n = 9). Tc-99m-duramycin scans were acquired on a SPECT/CT scanner on day 1. On day 2, the infarct zone was assessed with Tc-99m-tetrofosmin. In an open-chest pig model of myocardial ischemia/reperfusion (n = 4) we used Evans Blue dye to facilitate the measurement of area-at-risk (AAR). Tc-99m-duramycin uptake was measured by gamma counting after tetrazolium (TTC) staining and physically dissecting the AAR, infarct zone and the noninfarcted-but-ischemically-damaged tissues. Histopathology was used to document cellular damages.

Results:
Quantitatively, Tc-99m-duramycin uptake delineated an area of myocardium that included but was substantially more extensive than the infarct zone. Under the current experimental condition, this area accounted for 81.0 ± 9.6% of the AAR, whereas the infarct zone was 25.5 ± 14.0% of the AAR. This was consistent with in vivo imaging, where the size of Tc-99m-duramycin positive tissue was visually larger than the perfusion defect in the Tc-99m-tetrofosmin scan. By histopathology, the noninfarcted-but-ischemically-damaged tissues contained features associated with cellular damages, and a heterogeneous mix of viable and dead cells.

Conclusions:
Tc-99m-duramycin has significant uptake in infarcted as well as noninfarcted-but-ischemically-damaged myocardium, thus reflecting global myocardial injury. The data support GMI as a new criterion independent of infarct size and AAR. The noninfarcted-but-ischemically-damaged myocardium is pathologically heterogeneous, thus a potential substrate for ventricular arrhythmias. The ability to detect such tissues may have important diagnostic and prognostic value.
Abstract 20373: Inhibition of Glycogen Synthase Kinase-3β Amplifies β-catenin Signaling to Promote Dedifferentiation of Endothelial Cells to Improve Neovessel Formation
Authors: Wary Kishore K , Kohler Erin E
Published: July 2021

Rationale:
Wnt signaling plays a key role in the development and the regeneration of neovessels, however, the underlying mechanisms of these processes are not clearly understood.

Goal:
To elucidate the mechanism of dedifferentiation of venous endothelial cells (VECs) to arterial (A)ECs.

Methods and Results:
Herein we demonstrate that 6-bromoindirubin-3'-oxime (BIO), an inhibitor of Glycogen Synthase Kinase (GSK)-3β elicits the stabilization and the nuclear accumulation of β-catenin, thereby its direct interaction with the transcription factor NANOG in the nucleus of ECs. In a ChiP experiment, NANOG protein bound to the
NANOG-,
BRACHYURY-,
CD133-
and
VEGFR2
-promoters in these cells. In a cell-based assay, BIO induced the activation of the
NANOG
-promoter-luciferase reporter system. Accordingly, stimulation of VECs with BIO increased Notch-1, Ephrin-B2 and Hey2 expressions, indicating dedifferentiation these cells to AECs. While NANOG-depletion decreased BIO-induced NOTCH-1 expression and neovascularization. BIO increased Matrigel plug neovessel formation in nude mice. Immunostaining of Matrigel plug sections prepared from these mice showed increased expression of Notch-1, Ephrin-B2 and Hey2, indicating dedifferentiation of a subset of VECs into AECs. In a mouse model of hind limb ischemia, BIO induced the incorporation of VECs into collateral neovessels as characterized by Ephrin-B2- and Hey2-positivities, and smooth muscle cell recruitment.

Summary:
Thus, we show that a subset of mature VECs may retain the ability to dedifferentiate into AECs
in vivo
and suggest critical roles of GSK-3β inhibition in this process.
Abstract 20450: Impact of Addressing Social and Behavioral Factors in Reducing Heart Failure Readmission
Authors: Milani Richard V , Lavie Carl J , Ventura Hector O
Published: July 2021

Background:
United States 30-day hospital readmission rate (RR) for heart failure (HF) is averaging 22.6% and represents a financial burden for CMS and now to hospitals via potential penalties leveraged by Medicare. Efforts to improve RR must identify and treat underlying causes, and these may include social and behavioral factors not heretofore discerned.

Methods:
We evaluated multiple social and behavioral factors using validated questionnaires in 74 consecutive patients admitted for HF to determine their prevalence and their possible influence over HF admissions including 30-day readmission. Measures included depression, medication adherence, quantified sodium consumption, heart failure quality of life, sleep-related concerns, and other socio-economic factors including medication affordability and family support. Specific problems were systematically addressed during hospitalization and follow-up. In addition, patients were closely monitored during the 30-days post-discharge with oral diuretics adjusted as needed based in change in daily weight.

Results:
The average age was 71±13 years, 61% were male, and the mean ejection fraction was 36 ±19%.

Frequently admitted patients (≥ 2 HF admissions in the last 12 months) differed from standard patients:

*p<0.05, †p=0.10

The combination of addressing and treating these factors reduced subsequent 30-day readmission from 25% to 12% (p<0.05).

Conclusions:
Social and behavioral issues are commonly found in HF patients and are more prevalent in patients with a high frequency of HF hospitalizations. Identifying and systematically addressing these factors can lead to a reduction in hospital utilization.