bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17888: A Dynamically Updated Cardiac Transplant Waitlist Mortality Score
Authors: Cruz Vincent B , Steffen Robert , Starling Randall , Taylor David O , Hoercher Kathy , Rajeswaran Jeevanantham , Smedira Nicholas , Soltesz Edward , Blackstone Eugene H , Moazami Nader
Published: July 2021

Introduction:
U.S. heart allocation policies are currently under review. However, investigations into prioritization schemes for patients waiting for transplantation are hampered by the paucity of post-listing event data and complicated by widespread Mechanical Circulatory Support (MCS) usage.

Hypothesis:
A dynamic score can predict mortality and inform prioritization of patients awaiting heart transplant or considered for listing at time of MCS implant using clinical data, time-varying exposures, and laboratory values during listing.

Methods:
From 1/2008 to 6/2013, patients listed for transplant (n=314, 76%) or implanted with a MCS device with intention to list (n=101, 24%) were identified. Factors for a predictive, time-varying hazard model were selected from 74 pre-listing variables, 8 events and complications, and routine laboratory results after listing.

Results:
Seventy-eight deaths and 381 adverse events occurred during listing. A score based on 17 variables was developed, including black race, actual listing (vs. MCS), pulmonary artery pressure, history of coronary artery disease, diabetes, and ventricular tachycardia at listing, MCS implant and complications, dialysis, respiratory events, and neurologic events on the waitlist, and time-varying serum total bilirubin and creatinine. The figure shows a sample of predicted mortality scores varying over time as events and changes in biomarkers occur.

Conclusions:
We demonstrated a dynamic, updatable mortality risk score that predicts urgency among patients waiting for hearts independent of most demographics, heart failure etiology, symptoms, and cardiac function. This score tracks dynamic changes with time as biomarkers change and adverse events occur. MCS-related complications, neurologic events, and kidney failure significantly affect mortality. Future changes to U.S. heart transplant policies could use this newly developed tool as part of a larger allocation system.
Abstract 17913: The Long Non-coding Rna Malat1 Regulates Atherosclerosis in vivo
Authors: Michalik Katharina M , Cremer Sebastian , Fischer Ariane , Muhly-Reinholz Marion , Pfisterer Larissa , Poller Wolfgang , Boon Rainier , Zeiher Andreas M , Dimmeler Stefanie
Published: July 2021

Long non-coding RNAs (lncRNAs) have been described to play a role in many biological processes, including epigenetic regulation of gene expression. We previously showed that the lncRNA MALAT1 regulates angiogenesis. Since MALAT1 is induced by atheroprotective laminar shear stress, we determined whether MALAT1 regulates atherosclerosis.

To address this question, we generated MALAT -/- ApoE -/- mice that were fed with a high fat diet for 12 weeks. Genetic deletion of MALAT1 in ApoE-/- mice increased plaque size as defined by oil red positive area in the aortic arch (+28.4+12%; n=5, p<0.05). However, pharmacological inhibition of MALAT1 by GapmeRs, which were directed against MALAT1 and injected every second week for 12 weeks, did not significantly affect plaque load or plaque size. To explain the discrepant results, we analyzed the expression of MALAT1, which was fully deleted in all analyzed cell types and tissues obtained from MALAT1-/- mice, whereas GapmeR-MALAT1 treatment efficiently silenced MALAT1 expression in all organs except circulating and splenic monocytes. These data suggest that inhibition of MALAT1 in inflammatory cells, which is not sufficiently accomplished by MALAT1 GapmeRs, may be necessary to modulate atherosclerotic disease progression. In line with this, infiltration of CD45+ cells was significantly augmented in MALAT1-/-ApoE-/- mice (+35.5+8.6%, n = 10, p<0.05) but not in GapmeR-treated ApoE-/- mice (-5.6+12.3%, n=10, ns).

Moreover, MALAT1 deletion significantly increased macrophages (+60.4+22.8%, n=10, p<0.05) and dendritic cells in the spleen (+37.4+17.5%, n=10) and augmented circulating monocytes (+70.2+70.2%, n=5, ns).

In conclusion, we show that genetic deletion but not pharmacological inhibition of MALAT1 enhances atherosclerotic lesion formation and augments splenic monocytes and hematopoietic cell recruitment to atherosclerotic plaques.

The causal involvement of MALAT1 expression in hematopoietic cells in atherogenesis is currently elucidated by bone marrow transplantation experiments.
Abstract 17915: Brainstem Neuronal Networks for Breathing Control Involve a Disinhibitory Projection From the Dorsal Medulla
Authors: Zhang Shuang , Wu Yang , Cui Ningren , Jiang Chun
Published: July 2021

The critical neuronal networks for breathing control known to be located in the brainstem are still not fully understood. γ-Aminobutyric acid (GABA) is a neurotransmitter that not only plays an important role in the networks, but also allows investigational interventions to the networks. To gain a fast, local and reversible access to brainstem GABAergic neurons, we developed a strain of transgenic mice that expressed channelrhodopsin in a tandem with eYFP in GABAergic neurons directed by the
glutamic acid decarboxylase 2
promotor, the Gad2-ChR mouse. We firstly studied eYFP fluorescence in brainstem tissue sections. Several groups of previously known GABAergic neurons were positively labelled. Breathing response to optostimulation and CO
2
challenge were then studied in the anesthetized mice
in vivo
. When the optostimulation was applied to the ventral surface of the brainstem, especially the medulla, phrenic nerve activity was remarkably inhibited. Surprisingly, we found that optostimulation to the dorsal surface of the brainstem induced significant augmentation of both breathing activity and CO
2
chemosensitivity in the Gad2-ChR mice. Both breathing frequency and integrated phrenic amplitude were augmented. The effect was reversible and fast reaching peaking activation within 1 min. With respect to ventilation responses, optostimulation was nearly as potent as the response to 6% CO
2
. In the presence of 6% CO
2
, optostimulation was still capable of enhancing breathing activity. The breathing stimulation effect of optical GABA activation was located to the medulla. These observations suggest that respiratory neuronal networks involve a disinhibitory projection from dorsal GABAergic neurons in the medulla to a group of unidentified inhibitory neurons that are actively inhibit central breathing activity.
Abstract 17989: Evolution of At-risk Aortic Tissue in Patients With Bicuspid Aortic Valve After Valve or Aorta Replacement
Authors: Bollache Emilie , Fedak Paul W , van Ooij Pim , Guzzardi David , Malaisrie S. Chris , McCarthy Patrick M , Carr James , Collins Jeremy , Markl Michael , Barker Alex J
Published: July 2021

Objectives:
Bicuspid aortic valve (BAV) is associated with increased risk of aortopathy requiring surgery. However, to date, there is no clear consensus on aortic resection extent. Our objective was to study in BAV patients the evolution of ascending aortic (AA) ‘at-risk’ tissue, as defined by elevated wall shear stress (WSS) estimated using 4D flow MRI acquired at baseline and follow up.

Methods:
Eighteen BAV patients (49±15yrs) were included who underwent AA repair and MRI before surgery and at follow up (mean duration: 154±250 [7-977] days). For each patient and exam, 3D aortic systolic WSS was estimated from 4D flow MRI and at-risk tissue area was defined as the treatable region with high WSS, when compared to an atlas of physiologically normal values (as previously established in healthy controls).

Results:
The baseline sinus of Valsava and mid-AA diameters were both 4.5±0.6cm. Eight patients had severe aortic stenosis or regurgitation. Three patients had aortic valve replacement without aortic resection, 8 had AA repair without hemiarch repair, and 7 had AA and hemiarch repair. In the 8 AA repair patients, 3D area of elevated WSS increased at baseline from 25±29% to 52±37% at follow up, when expressed in percentage of the AA tissue remaining after surgery up from graft to the first branch (Figure). Little change in at-risk tissue area was observed in hemiarch repair patients.

Conclusions:
Our preliminary study demonstrates feasibility of 4D flow MRI to provide data regarding at-risk aortic tissue progression in BAV patients who underwent AA repair. Larger studies in a variety of clinical conditions are warranted to further understand the implications of these findings.
Abstract 17992: Observed versus Predicted Myocardial Infarction Among Individuals With Human Immunodeficiency Virus by American College of Cardiology/American Heart Association Pooled Cohort Equation Risk Strata: Center for AIDS Research Network of Integrated Clinical Systems
Authors: Feinstein Matthew J , Drozd Daniel R , Ning Hongyan , Delaney Joseph A , Nance Robin , Matthews William C , Achenbach Chad J , Crane Heidi , Lloyd-Jones Donald M
Published: July 2021

Background:
Human immunodeficiency virus (HIV)-infected individuals are at elevated risk for cardiovascular disease (CVD) due to an interplay between traditional CVD risk factors, chronic inflammation persisting despite HIV viral suppression, and side effects of antiretroviral therapy. Previous studies evaluating CVD risk prediction models in HIV populations have generally been small in size and assessed non-U.S. cohorts. The 2013 ACC/AHA ASCVD Risk Estimator has not been evaluated in a large, multi-center HIV cohort.

Hypothesis:
Our primary hypothesis was that the ACC/AHA ASCVD Risk Estimator would underestimate ASCVD risk across risk strata for HIV-infected patients.

Methods:
We evaluated this risk prediction tool in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) multi-center U.S.-based cohort of approximately 30,000 HIV-infected adults with rigorous central adjudication of myocardial infarction (MI) and differentiation between type I and II MI. We compared MI and ASCVD risks predicted by the ASCVD Risk Estimator to actual rates of MI observed in the CNICS cohort.

Results:
A total of 132 MIs were observed during follow-up, compared with 103 MIs that would have been expected based on the ASCVD risk estimator. Observed MI rates were higher than expected across most predicted risk levels, particularly among black participants and those with low (<5%) predicted 10-year ASCVD risk. This under-prediction was relatively uniform across risk strata among white men; the observed MI rates were 68%, 68%, 67%, and 67% greater than expected, respectively, for white men with <5%, 5% to <7.5%, 7.5% to <10%, and 10% or greater predicted 10-year ASCVD risk.

Conclusions:
These data suggest that the ACC/AHA Risk Estimator under-predicts MI risk among HIV-infected individuals. The under-prediction was relatively uniform across risk strata for white men. These data highlight the need for accurate HIV-specific CVD risk prediction tools.
Abstract 18021: Functional Substrates as the Strongest Predictor of Outcomes in Patients Presenting for Ventricular Arrhythmia Ablation
Authors: Hayase Justin , Faiwiszewski Yonatan , Vampola Stephen , Bender Aron , Ho Gordon , Baykaner Tina , Lalani Gautam , Schricker Amir , Rappel Wouter-Jan , Narayan Sanjiv , Krummen David
Published: July 2021

Introduction:
Recent work has shown that rotor characteristics can distinguish sustained versus non-sustained ventricular fibrillation (VF). However, the significance of functional VF substrates on patient outcomes is not studied.

Methods:
In 26 consecutive patients presenting for ventricular arrhythmia ablation procedures, 64-electrode basket catheters were inserted into both the left and right ventricles and VF was induced and defibrillated at 11±3 seconds. Computational phase analysis was performed and each VF cycle was characterized as rotor, focal, or disorganized activation. Follow-up data were analyzed for arrhythmia recurrence and compared to rotor stability. Forward stepwise regression analysis incorporating age, history of CHF, history of a-fib, history of prior MI, number of VTs induced, and presence of post-procedure inducible VT was performed to determine the strongest predictor of procedural outcome.

Results:
Of 26 patients, 19 had sustained VF, and 16 underwent attempted ablation (7 VT, 9 PVC). Optimization of the Youden index for the ROC analysis regarding rotor stability and procedural outcome demonstrated that maximum rotor stability of > 14.5 rotations (corresponding to total rotor prevalence of 71%) provided optimal sensitivity of 85% and specificity of 87% for arrhythmia recurrence. Among these, greater rotor stability was significantly associated with ventricular arrhythmia recurrence (86% versus 11%, p = 0.01) (Table 1), and was the strongest predictor of outcomes. Recurrence was independent of presenting arrhythmia.

Conclusions:
Functional VF/VT metrics were the strongest predictor of ventricular arrhythmia outcomes compared to traditional predictors in this series of patients. This suggests that functional substrate characteristics may provide added insight into recurrence mechanisms. Whether they may identify a target for future interventions requires further study.
Abstract 18025: Systematic Screening is Necessary to Detect Post-operative Thrombosis and Evaluate Risk in Children Undergoing Cardiac Surgery: A Prospective Observational Study
Authors: Manlhiot Cedric , Brandao Leonardo R , Holtby Helen M , Sivarajan V. Ben , Russell Jennifer L , Mertens Luc , Rand Margaret L , Gruenwald Collen E , Schwartz Steven M , Mital Seema , Stenyk Lia , Rolland Martha , O'Shea Sunita , Van Arsdell Glen S , Caldarone Christopher A , Chan Anthony K , McCrindle Brian W
Published: July 2021

Introduction:
Postoperative thrombosis in children undergoing cardiac surgery with cardiopulmonary bypass (CPB) is a frequent, under-diagnosed and clinically detrimental complication.

Methods:
Pediatric patients were prospectively enrolled before surgery with CPB in an observational cohort study. Children <1 year old and cyanotic patients were oversampled. All subjects had serial lab assessment of hemostatic status and standardized vascular ultrasound for surveillance of post-operative thrombosis. Eligible non-enrolled patients were retrospectively reviewed as concurrent controls without study surveillance. All imaging findings underwent blinded adjudication to confirm the presence and clinical importance of identified thrombi.

Results:
Of 400 enrolled patients (54% males, 55% <1 year, 25% cyanotic), 398 (99%) completed the study, and 339 (85%) had protocol vascular ultrasound prior to or within 1 week of hospital discharge. Post-operative thrombosis was diagnosed in 99 study patients (25%) vs. 10% of the 1,019 control patients (p<0.001). Clinical evaluation alone missed 59% of all postoperative thrombi and 20% of clinically important thrombi. Multivariable factors associated with higher odds of postoperative thrombosis in study patients included 4 factors reflective of reduced heparin sensitivity and/or anticoagulation levels during CPB (Table). Postoperative thrombosis was associated with longer ICU stay (5 vs. 2 days, p=0.008), longer hospital stay (6 vs. 10 days, p<0.001), increased odds of reintervention or post-operation ECMO (OR: 2.7, p=0.005) and mortality (OR: 5.9, p=0.002).

Conclusions:
Given the poor performance of relying on clinical suspicion for detecting post-operative thrombosis, children <1 year old undergoing surgery with CPB should be systematically screened for thrombosis post-operatively. Individualization of thromboprophylaxis should consider both preoperative clinical factors and heparin sensitivity.
Abstract 18039: Resource Utilization for Initial Hospitalization in Pediatric Heart Transplantation in the United States
Authors: Boucek Dana M , Lal Ashwin K , Pinto Nelangi M , Weng Hsin-Yi Cindy , Wilkes Jacob F , Menon Shaji C
Published: July 2021

Background:
Pediatric heart transplantation (HT) is resource intensive. Event driven pediatric HT databases do not capture data on resource use. The objective of this study was to evaluate resource utilization and identify associated factors during initial hospitalization for pediatric HT in a large multi-institutional cohort.

Methods:
This is a multicenter retrospective cohort study using the PHIS database (43 US children’s hospitals) of children ≤ 19 years of age who underwent HT between 1/07 and 7/13. Data collected: Demographic variables including site, payer, distance and time to center, clinical pre and post-transplant variables, mortality, cost and charge. Total length of stay (LOS) and charge for initial hospitalization were used as surrogates for resource use. Charges were inflation adjusted to 2013 $. Gamma regression analysis was performed to evaluate factors associated with resource use.

Results:
Of 1629 subjects, 54% were male, and the median age at HT was 5 years (IQR 0-13). The median total and ICU LOS were 51 (IQR: 23-98) and 23 (IQR: 9-58) days respectively, and mortality occurred in 82 (5%). Total charge and cost for hospitalization were $852,713 ($464,900-$1,609,300) and $383,600 ($214,900-$681,000) respectively. Factors associated with resource use on multivariate analysis are shown in Table 1. Younger age, lower center volume, southern region, and comorbidities prior to HT were associated with higher resource use. In later years, costs increased despite shorter LOS.

Conclusions:
This large multicenter study provides novel insight into factors associated with resource use in pediatric HT that cannot be assessed in alternative event driven transplant databases. Peri-transplant morbidities are associated with increased cost and LOS. Reducing costs in line with LOS will improve health care value. Regional and center volume differences need further investigation for optimizing value-based care and efficient use of scarce resources.
Abstract 18060: Risk Stratification Following Mitral Valve Surgery for Chronic Ischemic Mitral Regurgitation: A Very Long-term Study
Authors: Fino Carlo , Bellavia Diego , Miceli Antonio , Malouf Joseph , Iacovoni Attilio , Cugola Diego , Calabrese Alice , Simon Caterina , Delia Emilia , Caputo Massimo , Merlo Maurizio , Galletti Lorenzo , Senni Michele , Traina Marcello , Magne Julien
Published: July 2021

Background:
Very few long-term data are available on patients undergoing mitral valve surgery for chronic ischemic mitral regurgitation (CIMR). Objective:to identify determinants of survival and adverse cardiovascular events, at very long-term outcome.

Methods and Results:
We reviewed complete left and right ventricular echocardiographic data, six-minute walking test (6-MWT) and BNP levels at pre, peri and follow-up, on 137 consecutive patients who underwent restrictive mitral annuloplasty (RMA) or mitral valve replacement (MVR) and CABG, for CIMR.

Combined adverse cardiovascular events were defined as composite of death, heart failure, angina, myocardial infarction and re-hospitalization. Mean age was 67±0.7. Preoperative EF was 35±06%. Among 137 patients, 46% underwent RMA and 54% had MVR. Median follow- up was 7 years (range: 0.3-15.4). Early mortality was 7% (p=NS). In the RMA 42% of patients experienced MR recurrence. Overall survival at 5, 10 and 15 years were 84, 76 and 62% in RMA, and 87, 62 and 54% in MVR (p=0.65). At univariate analysis, preop B-blocker, 6-MWT, mean transmitral gradients and RV size were predictors of adverse events.The Cox Hazard multivariate analysis identified preoperative atrial fibrillation (p=0.005), preop BNP (p=0.025) as independent predictors of long-term mortality.Freedom from cardiovascular events at 5, 10 and 15 years were 90, 75 and 48% in RMA, and 90, 62 and 45% in MVR (p=0.57). .

The Cox Hazard multivariate analysis identified preop B-blocker therapy (p=0.001), atrial fibrillation (p=0.01), postoperative mean transmitral gradients (p=0.047 ) and indexed effective orifice area (p=0.02) as independent predictors of adverse cardiovascular events.

Conclusions:
Our study confirms an high rate of true MR recurrence, at very long-term follow-up. Among collected variables, preoperative BNP and atrial fibrillation were independent predictors of survival, whereas B-blocker therapy, atrial fibrillation, postoperative mean transmitral gradients and indexed effective orifice area were independent predictors of adverse cardiovascular events. Type of surgery did not affect the very long-term outcome.
Abstract 18091: Growth and Puberty in Fontan Survivors (GAPS study): A Multicenter Cross-sectional Study
Authors: Menon Shaji C , Presson Angela P , McCrindle Brian , Goldberg David J , Sachdeva Ritu , Goldstein Bryan , Seery Thomas , Uzark Karen C , Chelliah Anjali , Butts Ryan , Henderson Heather , Johnson Tiffanie , Williams Richard V
Published: July 2021

Introduction:
Chronic diseases may result in growth impairment and delayed puberty that contribute to psychosocial maladjustment. There are no data on the prevalence of short stature or delayed puberty in children and adolescents after Fontan operation, a cohort characterized by chronic low cardiac output.

Methods:
This was a cross-sectional study of 299 Fontan patients (8-18 years) from 11 Pediatric Heart Network centers. We collected demographic data, anthropometric measurements and Tanner stage using a validated self-assessment questionnaire. Anthropometric measurements and pubertal stage were compared to United States normative data. Short stature was defined as height <5% and abnormal BMI as <5% or >95%. Delayed puberty was defined as failure to reach a stage of development at an age greater than the median age in the subsequent Tanner stage. Comparisons were made between study population and contemporary normal population data.

Results:
Of the 299 subjects [42% female, median age at enrollment 13.9 years (IQR: 11.3, 16.1)], 98 (33%) had hypoplastic left ventricle and 24 (8%) had heterotaxy syndrome. Median age at Fontan was 3 years (IQR: 2, 4). PLE was present in 16 subjects (5%). Fontan survivors had a higher prevalence of short stature relative to normative data (20% vs. 5%, p<0.0001) and an increased prevalence of abnormal BMI (18% vs. 10%, p<0.0001). Abnormal BMI were split between low BMI (43%) and high BMI (57%). Both males (58%) and females (58%) had delay in ≥1 Tanner stage parameter with at least 2 yr differences between Fontan patients and population norms for most parameters (Figure).

Conclusion:
Compared to the normal population, Fontan survivors have a 4-fold increase in the prevalence of short stature and nearly 2 fold abnormality in in BMI. Delayed puberty was common in both genders. As these factors may have a negative psychosocial impact, routine screening and management of short stature and delayed puberty should be a priority in Fontan survivors.
Abstract 18162: Children First Study II: How an Educational Program in Cardiovascular Prevention at Public Schools Can Improve Parents’ Cardiovascular Risk
Authors: Pinto Cristiano J , Oyama Silvia M , Rodrigues Maria M , Davanço Taciana , Calderaro Daniela , Caramelli Bruno , Fornari Luciana S
Published: July 2021

Objective:
To evaluate whether a multidisciplinary educational program in cardiovascular prevention for children could improve the Framingham cardiovascular risk (FCR) of their parents after one year, in public schools in Brazil.

Methods:
We performed a prospective community-based study in Brazil during 2013 that randomized students aged 6 to 10 years old to two different approaches to receiving healthy lifestyle information. The control group received written educational material (EM) for their parents about healthy lifestyle. The intervention group received the same EM for parents and children were exposed to a weekly educational program in cardiovascular prevention with a multidisciplinary health team. At onset and end of the study we collected data from parents and children (clinical information, weigh, height, arterial blood pressure and laboratorial tests).

Results:
We studied 265 children and 419 parents. Analyzing the parents’ FCR we found that 9% of the control group and 13% of the intervention group had more than a 10% year risk of cardiovascular heart disease over the next 10 years (intermediate/high FCR). After the children educational program during one year in public schools, the intervention group had a reduction of 30% in the intermediate/high FCR group compared with a 0% reduction in the control group (p<0.008). The risk factor that mainly contributed for FCR reduction in the intervention group was blood pressure, with a reduction in SBP of 122.45 to 118.46 mmHg (p<0.001), and DBP of 84.59 to 80.03 mmHg (p<0.001), with no reduction in the control group (117.47 to 118.01 mmHg for SBP, p=0.7241, and 76.60 to 77.45 mmHg for DBP, p=0.1387).

Conclusion:
An educational program for cardiovascular prevention directed to school age children in public schools can reduce the FCR risk of their parents, especially in the intermediate/high risk categories, like we observed in private schools.
Abstract 18208: Intraindividual Variation of Tissue Doppler Velocities as Predictors of Cardiac Events in the General Population
Authors: Wang Joanna N , Biering-Sørensen Tor , Jørgensen Peter G , Jensen Jan S , Møgelvang Rasmus
Published: July 2021

Introduction:
Despite of Tissue Doppler imaging (TDI) being an important diagnostic tool for early detection of reduced myocardial function, there is still not a clear consensus on the site of measurement. It is complicated by the fact that the velocities vary between sites even within healthy individuals.

Objectives:
The aim of this study was to evaluate the predictive value of each mitral site along with the predictive value of the intraindividual variation between sites with respect to cardiac events.

Methods:
Cardiac function was evaluated by TDI in 2,064 participants within a large community-based population study. Peak systolic (s’), early diastolic (e’) and late diastolic (a’) velocities were obtained from 6 mitral annular sites. To assess global variation, two parameters were calculated using all 6 sites. One as their standard deviation divided by their mean, the other as their range divided by their median. To assess the variation within each apical projection, the difference between its two sites was divided by their mean. The end point was combined of admission with acute myocardial infarction, heart failure or cardiac death.

Results:
During a median follow-up of 10.9 years the endpoint occurred in 277 participants. In multivariable Cox proportional hazards regression adjusted for age and sex we found that a decrease in s’, e’ or a’ from any mitral site was associated with a significantly increased risk of the combined end point. However, neither the global variation nor the variation within each apical projection retained significant associations with the end point (Table).

Conclusions:
In the general population, systolic and diastolic TDI velocities at all mitral annular sites are important predictors of cardiac events. Along with the lack of association between intraindividual TDI variations and these events, it suggests that for the evaluation of cardiac prognosis the choice of site is of less importance.
Abstract 18230: Wringing Pump or Roller Pump? Insights From Rotational Mechanics in Children With Left Ventricular Noncompaction Cardiomyopathy
Authors: Nawaytou Hythem , Yubbu Putri , Miller Kelley , Banerjee Anirban
Published: July 2021

Introduction:
Left ventricular noncompaction (LVNC) is a rare form of cardiomyopathy in children, characterized by abnormal endocardial myofiber arrangement. This may result in an altered pattern of LV rotation depicted by a “roller pump” like motion and described as rigid body rotation (RBR). This pattern, is characterized by the apex and the base rotating in the same direction.

Hypothesis:
To describe the LV rotational patterns in children with LVNC using speckle tracking echocardiography and detect the relationship between the different rotational patterns and measures of LV systolic function.

Methods:
We prospectively studied 19 children (age 0.9 to 17.8 years) with LVNC and compared them with age-matched controls. Apical and basal rotations, peak twist and peak torsion were analyzed as indices of systolic function. Peak apical recoil rate was measured as an index of diastolic function.

Results:
Children with LVNC had significantly lower apical rotation (6.26°± 3.09°, 8.59°± 2.19° p=0.01) than controls. In 7 out of 19 (36.8%) patients a pattern of RBR was detected. Twelve patients exhibited the typical “wringing” motion of the LV, where the apex rotated counterclockwise and the base clockwise. Patients with LVNC and RBR had significantly lower ejection fraction than patients with LVNC without RBR (49.1 ± 9.2% vs 60.3 ± 10.2%, p<0.05). There were no significant differences in the remainder of the systolic and diastolic indices between LVNC patients and controls.

Conclusions:
Children with LVNC can exhibit an abnormal LV rotational pattern characterized by RBR that is associated with impaired systolic function.
Abstract 18236: Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC): Six Month Safety and Exploratory Efficacy Results
Authors: Chakravarty Tarun , Makkar Raj R , Kittleson Michelle , Friedman John , Berman Daniel S , George Richard , Siegel Robert , Slipczuk Leandro , Hamer Andrew , Smith Rachel R , Smith Shane , Kacena Katherine , Marbán Linda , Henry Timothy D , Marbán Eduardo
Published: July 2021

Background:
In the CADUCEUS trial, autologous cardiosphere-derived cells (CDCs) decreased infarct size and increased viable tissue in post-MI subjects. In ALLSTAR Phase I, allogeneic CDCs (CAP-1002) were safe and well-tolerated. The DYNAMIC trial is an open-label dose escalating safety trial of multi-vessel intra-coronary CAP 1002 in subjects with dilated cardiomyopathy.

Methods & Results:
Subjects were matched with CAP-1002 cell lines to which they had no donor specific antibodies by single antigen bead testing. Fourteen subjects (mean age 60.6 yr; range 32-76 years) with NHYA Class III symptoms and echo EF ≤35% (Screening Cardiac CT: mean 26.9%; range 16-34%) due to ischemic (n=7) or non-ischemic cause (n=7) were prospectively enrolled. Four escalating total CAP-1002 doses from 37.5M to 75M were infused via a sequential non-occlusive intracoronary catheter technique, divided among the 3 major coronary arteries (LAD, RCA and circumflex). Post-procedural cardiac enzymes (troponin and CKMB) were measured, with no clinically-significant increases observed in the 24 hr post-infusion. No pre-specified primary safety endpoints occurred; (post infusion reduction of TIMI flow for > 3 minutes, VT/VF, sudden death, major adverse cardiac (MACE) events within 72 hours of infusion, or acute myocarditis within 1 month). Further safety data and exploratory efficacy endpoints include BNP, 6 minute walk and VO2max as well as EF and volumes measured by both echo and cardiac CT at 6 and 12 months.

Conclusion:
Multi-vessel non-occlusive intracoronary infusion of CAP 1002 in subjects with dilated cardiomyopathy appears to be safe. Six month safety endpoint and adverse event data, as well as exploratory efficacy measures, will be available for presentation November 2015.
Abstract 18240: Poor Sexual Outcome Among Male ICD Patients Who Have Received Shock and Antitachycardia Pacing Therapy
Authors: Palm Johansen Pernille , Zwisler Ann-Dorthe , Hastrup Svendsen Jesper , Berg Selina K
Published: July 2021

Purpose:
To investigate (i) the prevalence of erectile dysfunction (ED) in male patients with implantable cardioverter defibrillator (ICD), and (ii) the association between ICD, indication, therapy and poor sexual outcome.

Methods:
This cross-sectional study included male patients with ICD. Inclusion criteria were NYHA I-II. Exclusion criteria were no partner and no known urinary tract diseases. Participants completed the International Index of Erectile Function questionnaire that concerns sexual function and meet psychometric criteria for test reliability and validity. The study was conducted as a postal survey and questionnaires were mailed out to 818 patients from two university hospitals. Data on indication (primary prevention vs secondary prevention) and therapy (shock and antitachycardia pacing ) was collected from local databases.

Results:
Data from the 370 responders (response rate 45.2 %) were analyzed. Mean age of patients was 63.9 ± 12.1. International Index of Erectile Function total mean score was 39.6 ± 24.2 (scale range 5 to 75, with higher score indicating better function). The Erectile Function domain mean score was 14.5 ± SD 11.5 (Scale range 1 to 30). The Erectile Function domain was distributed between 48.9 % having severe ED, 7.6 % moderate ED, 7.0 % moderate to mild ED, 7.0 % mild ED and 29.5 % having no ED. Age was highly associated with ED (OR 0.91, 95% CI: 0.88-0.93). Adjusted for age, ED was associated with therapy from the ICD (OR 1.84, 95% CI: 1.07-3.2) and primary prevention indication (OR 1.90, 95% CI: 1.19 - 3.06) compared to patients having an ICD on secondary prevention indication.

Conclusions:
Erectile dysfunction was present in more than 70 % of male patients with ICD and more than 48 % had severe erectile dysfunction, resulting in inability to perform a sexual intercourse. Age, primary prevention indication and therapy from the ICD were all associated with a poor sexual outcome.
Abstract 18251: Establishment of an in vitro Platform, the Hydrogel Mattress, to Enhance Maturation and Evaluate Contractile Function of Individual hiPSC-CMs
Authors: Feaster Tromondae K , Williams Charles H , Wang Lili , Cadar Adrian G , Chun Young W , Lim Chee C , Knollmann Bjorn C , Hong Charles C
Published: July 2021

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have great potential as tools for cell based therapy, disease modeling and drug discovery. However, their contractile properties have not been routinely evaluated; as methods to do so are cumbersome and not easily translated to standard laboratories. We sought to develop a more efficient protocol to evaluate hiPSC-CM mechanical properties, at the single cell level. Individual hiPSC-CMs were cultured on a hydrogel based platform, termed the hydrogel mattress, and their cellular contractile properties were evaluated using video based edge detection (Figure A). We found individual hiPSC-CMs maintained for 5 days on the mattress assumed an elongated shape (Figure B) and exhibited robust, reproducible cell shortening (~10% versus <1% for standard culture). We further found hiPSC-CM cellular contraction and peak cell shortening amplitude was comparable to that of freshly isolated adult rabbit and mouse ventricular CMs (Figure C). In addition, hiPSC-CMs maintained on the mattress exhibited characteristics of mature CMs including action potential waveform, calcium handling and pharmacological response to myofilament calcium sensitizers. We further show a positive correlation with the established traction force microscopy method. We demonstrate the hydrogel mattress platform enables routine characterization and quantification of contractile performance of isolated hiPSC-CMs. This platform can be extended to in vitro disease modeling, drug discovery and drug induced cardiotoxicity testing. Further, the mattress can be easily adapted to virtually any laboratory, thus streamlining cellular mechanical evaluation of individual hiPSC-CMs in vitro.
Abstract 18283: Left Ventricular STIFFness vs. Fibrosis Quantification by T1 MAPping in Heart Failure With Preserved Ejection Fraction - STIFFMAP-HFpEF
Authors: Rommel Karl-Philipp , von Roeder Max , Stiermaier Thomas , Latuscynski Konrad , Oberueck Christian , Sandri Markus , Lücke Christian , Gutberlet Matthias , Schuler Gerhard , Lurz Philipp
Published: July 2021

Introduction:
Heart Failure with Preserved Ejection Fraction (HFpEF) is an increasing public health problem. To tailor successful treatment strategies it is essential to identify patients’ individual pathologies contributing to HFpEF. Cardiac magnetic resonance (CMR) derived T1-Mapping has been suggested as non-invasive tool to quantify diffuse myocardial fibrosis. Invasive tracings of pressure-volume relations represent the gold-standard for assessing load-independent mechanical diastolic properties of the left ventricle.

Hypothesis:
Aim of this study was therefore to elucidate the diagnostic performance of T1-Mapping in HFpEF patients by examining the relationship between the extracellular volume fraction (ECV) and invasively measured parameters of diastolic function and to study the potential of ECV to differentiate between different pathomechanisms in HFPEF.

Methods:
We performed CMR T1-Mapping in 21 patients with HFpEF and 11 patients without heart failure symptoms (further referred to as controls). Pressure volume loops were obtained with a conductance catheter during basal conditions and handgrip exercise. Transient preload reduction was used to extrapolate the diastolic stiffness constant.

Results:
Patients with HFpEF showed a higher extra cellular volume fraction (p=0.001), an elevated load-independent passive LV stiffness constant - ß (p<0.001) and a longer time constant of active LV-relaxation Tau (p=0.04). ECV correlated well with ß (r =0.75, p <0.001). After multivariate analysis, ECV remained the only independent predictor of ß.

Within the HFpEF cohort, patients with ECV over median showed higher left ventricular masses (p=0.04) and a higher LV stiffness (p=0.05). ECV < median identified patients with a prolonged active LV relaxation (p=0.008) and a marked hypertensive reaction to exercise due to a pathologic arterial elastance (p=0.05).

Conclusions:
Diffuse myocardial fibrosis, assessed by CMR derived T1-Mapping independently predicts invasively measured LV stiffness in HFpEF. In addition, ECV helps to non-invasively distinguish the role of impaired active relaxation and passive stiffness and refines characterization of patients, which represents a prerequisite for any successful therapy in the future.
Abstract 18293: Unique Features of Cortical Bone Stem Cells Associated With Enhanced Cardiac Repair
Authors: Mohsin Sadia , Troupes Constantine D , Starosta Timothy , Sharp Thomas E , Smith Shavon , Agra Elorm J , Kubo Hajime , Berretta Remus M , Houser Steven R
Published: July 2021

Rationale:
Adoptive transfer of multiple stem cell types into failing human hearts has demonstrated modest beneficial effects in patients with cardiovascular disorders that damage the heart. Despite increasing use of stem cell based therapies, consensus on the optimal stem cell type is still not clear. Modest repair and improvement in cardiac function in patients with cardiac complications warrants identification of a novel stem cell population that possesses enhanced proliferative capacity and can effectively survives the harsh myocardial environment.

Objective:
To characterize surface marker expression, proliferation, survival, migration and differentiation capacity of CBSCs relative to known and extensively studied stem cell types including MSCs and CDCs.

Methods and Results:
CBSCs, MSCs and CDCs were isolated from Gottingen miniswine. CBSCs possess a unique cell surface marker profile versus CDCs and MSCs. Additionally CBSCs were morphologically distinct from MSCs and CDCs and showed enhanced proliferation capacity versus CDCs and MSCs. Concurrently CBSCs had significantly increased percentage of survival after exposure to an apoptotic stimuli as compared to MSC. A significantly greater percentage of CBSCs expressed markers of cardiac lineage commitment. Additionally, CBSCs can form functional gap junction with adult ventricular myocytes. CBSCs, CDCs and MSCs showed differential response towards ATP and histamine further strengthening the differences between the three cell types.

Conclusion:
CBSCs have enhanced proliferative capacity and cardiac lineage commitment versus CDCs and MSCs that could account for their enhanced effects on cardiac regeneration after myocardial infarction. Ultimately, this understanding would help us to develop viable cellular therapy options for treatment of heart failure patients.
Abstract 18294: Left Ventricular Systolic Dysfunction Early After Resuscitation From Cardiac Arrest is Associated With Shockable Arrest Rhythm
Authors: Jentzer Jacob C , Abu-Daya Hussein , Shafton Asher , Chonde Meshe , Chalhoub Didier , Althouse Andrew , Rittenberger Jon
Published: July 2021

Introduction:
Left ventricular systolic dysfunction (LVSD) is common after resuscitation from cardiac arrest (CA). The association of echocardiographic LVSD with cardiac rhythm during CA is not well described.

Hypothesis:
Patients with a shockable rhythm (VT/VF) will have a greater degree of LVSD by echocardiography after CA.

Methods:
Prospective registry of patients resuscitated from CA underwent transthoracic echocardiography (TTE) within 24 hours after CA. We determined 2D measurements, LVEF, spectral Doppler of mitral inflow and LV outflow, systolic and diastolic tissue Doppler of the mitral annulus velocity, and tricuspid plane annular excursion (TAPSE). We collected data on in-hospital mortality as well as vasopressor doses and troponin I levels. TTE parameters and clinical characteristics were compared between patients with a shockable (VT/VF) arrest rhythm and a non-shockable (asystole/PEA) arrest rhythm and between survivors and non-survivors using t-tests and ANOVA.

Results:
Of the 55 patients, the 23 (42%) with shockable CA rhythms had significantly higher LV end-systolic dimension (4.1cm vs. 3.3cm, p = 0.0073), lower LV fractional shortening (0.15 vs. 0.28, p <0.0001), and lower LVEF both by visual estimate (36.2% vs. 52.3%, p = 0.0012) and by Simpson’s biplane method (37.5% vs. 52.3%, p = 0.0506). Other measured TTE parameters did not differ between groups, including TAPSE (shockable 1.53 vs. non-shockable 1.82, p = 0.1731). Admission and peak 24 hour vasopressor requirements did not differ between groups. Peak troponin levels were higher (22.26 vs. 3.88, p = 0.0198) in patients with shockable CA rhythms, but admission troponin levels were no different (0.88 vs. 0.51, p = 0.1527). TTE parameters did not differ between survivors and non-survivors (visual LVEF 47.0% vs. 44.2%, p = 0.5968; LV fractional shortening 0.19 vs. 0.25, p = 0.0916).

Conclusions:
Patients with shockable CA rhythms have more severe LVSD on 24 hour echocardiography despite similar vasopressor requirements and admission troponin levels. Echocardiographic parameters at 24 hours did not predict in-hospital mortality. Early echocardiography after CA appears more useful for differentiating primary CA rhythm than for predicting mortality.
Abstract 18304: Are Prolonged Resuscitation Efforts Worthwhile? Patient Outcomes by Time to Restoration of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest Patients
Authors: Kragholm Kristian , Anderson Monique , Malta Hansen Carolina , Schulte Phillip J. , Kurz Michael C. , Fosbol Emil L. , Rajan Shahzleen , Wissenberg Mads , Stiell Ian , Nichol Graham , Peterson Eric
Published: July 2021

Introduction:
How long resuscitation attempts should be continued before termination of efforts is not clear in patients with out-of-hospital cardiac arrest (OHCA). We studied outcomes in patients with return of spontaneous circulation (ROSC) across quartiles of time from 9-1-1 call to ROSC.

Hypothesis:
Survival with favorable neurological outcome is seen in all time intervals from 9-1-1 call to ROSC.

Methods:
Using data from Resuscitation Outcomes Consortium (ROC) Prehospital Resuscitation clinical trials: IMpedance valve and an Early vs. Delayed analysis (PRIMED) available via National Institute of Health, patients with ROSC not witnessed by the emergency medical service (EMS) were identified and grouped by quartiles of time from 9-1-1 call to ROSC. We defined favorable neurological outcome as modified Rankin Scale (mRS) scores of ≤3.

Results:
Included were 3,431 OHCA patients with ROSC. Median time from 9-1-1 call to ROSC was 22.8 min (25%-75% 17 min–29.2 min); 953 (27.8%) survived to discharge (20.4% mRS ≤3). Significant survival and favorable neurological outcome were seen in each quartile (Figure). In patients who received bystander cardiopulmonary resuscitation (CPR), survival rates were 60.9%, 33.2%, 18.3% and 11.1% across quartiles of time to ROSC versus (vs.) 51.5%, 25.6%, 13.3% and 8.9% in patients without bystander CPR; corresponding rates of favorable neurological outcome were 50.7%, 23.8%, 12.2% and 9.1% vs. 40.1%, 16.6%, 8% and 4.8%. Correspondingly, survival rates in defibrillated patients were 70.1%, 45.9%, 25.5% and 16.4% vs. 36.3%, 9.5%, 6% and 3.4% in non-defibrillated patients; corresponding rates of favorable neurological outcome were 59.8%, 33.4%, 18.3% and 11.4% vs. 24.4%, 4.1%, 1.9% and 1.8%.

Conclusions:
Survival with favorable neurological outcome was seen in all quartiles of time to ROSC, even in cases without bystander CPR or shocks delivered. This suggests that EMS personnel should not terminate resuscitation efforts too early.
Abstract 18323: Complication Rates of Ventricular Tachycardia Ablation: Comparison of Safety Outcomes From Real World to Contemporary Clinical Studies
Authors: Pothineni Naga Venkata K , Deshmukh Abhishek , Padmanabhan Deepak , Kovelamudi Swathi , Mulpuru Siva , Noseworthy Peter A , Paydak Hakan
Published: July 2021

Introduction:
The availability, national scope and perceived unbiased nature of administrative claims data makes it an attractive choice by health care policy makers for evaluating quality and outcomes. We calculated Ventricular tachycardia (VT) ablation complication rates from national administrative data and compared them with data from randomized trials and prospective studies.

Methods:
A PUBMED database search was done to identify existing studies of VT ablation. Studies were divided into clinical (randomized controlled trials (RCTs) and prospective studies). Pooled rates of vascular, cardiac, neurological complications and procedure related mortality were computed and compared to reported complication rates from administrative database studies

Results:
We identified two administrative database studies of VT ablation that included a total of 14,352 procedures and 18 clinical studies with a total of 1,705 procedure. Overall complication rate in administrative studies was higher than in clinical studies (9.39% vs. 7.97%). Rates of cardiac/pericardial (4.47% vs. 2.29%) and vascular access complications (6.9% vs. 3.0%) were higher in real world studies. Neurological complications (1.17% vs. 0.45%) and procedure related mortality (1.53% vs. 1.29%) were higher in clinical studies. Among clinical studies, RCTs had the lowest reported complication rate.

Conclusion:
Despite substantial improvement, “real-world” complication rates from administrative data remain higher than those reported in RCTs. The discrepancy may be attributable to differences in operator skills, selection bias and variation in data quality. Use of large databases provides an important analytical resource as we embark on improving national health care efficacy and safety in the current challenging environment.