bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16830: Early Cardiac Biomarker Changes Following Myocardial Injury
Authors: Fisher Marilee , Maruta Toyoaki , Yano Takeshi , Li Tian , McQuillan Jay , Setren Adam , Blood Jane , Morrissey Jeremiah J , Tsuneyoshi Isao , Bach Richard G , Boyle Walter A
Published: March 2022

Introduction:
Levels of cardiac troponin I (cTnI), now used routinely to identify myocardial infarction, typically rise slowly following an acute myocardial injury (AMI), and early detection remains challenging, as does early identification of large AMI events that may benefit most from early invasive management.

Methods and Results:
Plasma samples were obtained preceding and at frequent intervals following septal myocardial ablation (PTSMA) in HCM patients (n = 20) to identify putative early cardiac biomarkers (CBs). Immunoassays for CBs of interest were developed and validated. Three CBs with markedly different time-dependent profiles following AMI were identified (Figure 1): cTnI rose slowly and peaked late (16-24h); fatty acid binding protein 3 (FABP3) rose and peaked much earlier (4-6h); while myosin light chain 3 (MYL3) peaked and declined very rapidly (<2h). Quantification of time-dependent changes in the levels of CBs, d[CB]/dt and d2[CB]/dt2, revealed dynamic early signals with the potential to time the onset and course of injury (Figure 2).

Conclusions:
These data demonstrate significantly different time courses for increased plasma levels of CBs following an AMI event. While cTnI is the most cardiac specific, MYL3 and FABP3 levels, as well as changes in levels of all 3 CBs, provide additional early information that may allow for improved ability to diagnose AMI at earlier time points, as well as to identify time elapsed since the AMI event. Such analyses of novel CBs and their rapid changes may enhance early identification of AMI and help distinguish larger AMIs that could benefit most from early intervention.
Abstract 16857: Design and Implementation of a Prehospital Electrocardiogram Remote Transmission and Data Recording App for Acute Myocardial Infarction Based on WeChat in China
Authors: Li Yuxi , Zhang Yan , Liu Hongmei , Li Dou , Li Jianping , Huo Yong ,   China STEMI Care Project
Published: March 2022

Introduction:
There were evidences showing prehospital electrocardiogram (ECG) remote transmission could reduce door-to-balloon (D2B) time in ST-segment elevation myocardial infarction (STEMI) care. There is spacious room for improvement due to low ratio of tele-ECG transmission usage in China. Meanwhile, the collection of prehospital clinical data, especially key time points during emergency care is not sufficient. The existing systems for ECG transmission require unique hardware leading to poor cost-benefits. We designed a mobile app to solve these problems based on WeChat, the most popular messaging communication app in China, which can transmit clear images of high quality and has a monthly-active-user of 549 million.

Hypothesis:
We assessed the hypothesis that such an app could solve the problems above in China.

Methods:
Firstly, we included 192 PCI hospitals together with their global positioning system (GPS) coordinates and telephone numbers into the database throughout China. Once an ECG image is sent through the app, ECG image, transmission time and sender’s GPS coordinates will be automatically recorded onto the server; the app will reply with a multimedia message listing nearby PCI hospitals, which can be contacted by clicking the specific link easily. At the same time, the on-call physician in the PCI hospital will receive a short message containing the ECG. Furthermore, an automatically generated electronic form evaluating prehospital treatment delay is also provided, in which the key time points can be recorded by clicking.

Results:
We performed a field test for a STEMI case, it took 20 seconds sending ECG and feedback message was received in 2 seconds, the responding physician in the PCI hospital stated ECG image was clear enough to interpret and all key time points were traceable. A pilot study is being conducted in a regional network including 4 PCI hospitals and 13 non-PCI hospitals in Tianjin.

Conclusions:
In conclusion, this is a low cost novel digital system integrated with daily communication service app on prehospital emergency care for STEMI to solve the problems of prehospital ECG remote transmission and prehospital clinical data recording in China. The effect on D2B time and outcomes requires further study.
Abstract 16872: Increased Production of Oxidized Phosphatidylcholine Molecules in Patients Presenting With ST Elevation Myocardial Infarction (STEMI)
Authors: Searle Rachael , Allen David , Hasanally Devin , Chaudhary Rakesh , Ravandi Amir
Published: March 2022

Introduction:
Despite restoration of blood flow to myocardium after ischemia, a large percentage of myocardial cells die after reperfusion. This phenomenon is termed ischemia/reperfusion injury (I/R). Oxidized phosphatidylcholines (OxPC) are generated in the presence of reactive oxygen species, which are abundant during I/R. We aimed to determine the change in OxPC in patients presenting with STEMI who undergo primary Percutaneous Coronary Intervention (PCI).

Methods:
Blood samples were collected from subjects with STEMI (n=27) and subjects with non-obstructive CAD (n=20) prior to, and at completion of PCI/angiography respectively. The complete oxidative lipidomic profile at the onset of STEMI and after PCI was compared to control prior to and after diagnostic angiography. The oxidative lipidomic profile was established and compared using high-performance electrospray mass spectrometry.

Results:
Seventy nine distinct OxPCs were identified in human plasma which included fragmented OxPCs, terminal furans, isoprostanes and long-chain products. There were 17 compounds that showed a significant increase in the STEMI population when compared to control. The largest changes seen overall were in the fragmented OxPCs. Fragmented OxPCs in control vs pre PCI STEMI had a significant rise from 8.9 vs 21.8 ng/ml of plasma, (p = 0.0001) and STEMI post PCI increased to 8.9 vs 29.7 ng/ml of plasma, (p = 7.1x10-5). When organizing molecules by functional group, fragmented carboxylic acid OxPCs were the most abundant in plasma with pre vs post PCI levels increasing from 12.8 to 22.2 ng/ml of plasma (p= 0.03).

Conclusion:
We have shown for the first time that OxPC molecules are present in patients with STEMI and are increased when compared to control patients. There is also a significant increase in OxPC levels after PCI in the STEMI population. These changes represent increases in OxPC during ischemia and a further increase after reperfusion injury. Given the potent biological activity of OxPCs, the attenuation of their activity may be a novel therapeutic approach to reduce the deleterious effects of I/R.
Abstract 16891: Beat-to-beat Systolic as Well as Diastolic Blood Pressure Variability is High in Atrial Fibrillation
Authors: Olbers Joakim , Gille Adam , Östergren Jan , Ljungman Petter , Rosenqvist Mårten , Witt Nils
Published: March 2022

Background:
Atrial fibrillation (AF) is associated with an increased risk for cardiovascular morbidity and mortality, beyond thromboembolism. The underlying mechanisms for this association are not fully understood but may involve effects on artery walls and endothelial function. High blood pressure (BP) incurs an increased risk of cardiovascular events. The interplay between AF and BP is insufficiently studied.

Material and methods:
We studied 33 patients, 21 in AF and 13 in sinus rhythm (SR), during coronary angiography. After catheterization of the radial artery invasive BP was recorded four times at three locations (radial artery, brachial artery (twice) and ascending aorta). BP was recorded for a minimum of 15 consecutive beats. BP variability defined as mean beat-to-beat BP difference was calculated for systolic and diastolic BP at each site.

Results:
There was a significant difference (p<0.001) in mean systolic and diastolic beat-to-beat BP variability between the AF and SR groups at all locations, see figures. No significant difference in BP variability was seen between locations. RA = Radial Artery; BA = Brachial Artery; AA = Ascending Aorta

Conclusions:
Beat-to-beat BP variability in patients with AF is substantially higher than in patients with SR. Systolic BP variability was almost twice as high and diastolic BP variability was almost seven times as high in AF as compared to SR. Hemodynamic effects of this beat-to-beat variation in BP may have negative effects on vascular structure and function, possibly contributing to the disproportionate increase in cardiovascular morbidity and mortality seen in AF patients.
Abstract 17006: Is White Rice Consumption a Risk for Cardiovascular Disease? A Systematic Review and Meta-analysis
Authors: Krittanawong Chayakrit , Tunhasiriwet Anusith , Bisanz Kimberly J , Zhang HongJu , Marysia Tweet S , Prokop Larry J , Chirapongsathorn Sakkarin , Wang Zhen , Hayes Sharonne N
Published: March 2022

Introduction:
Current proposed Dietary Guidelines for Americans, 2015 suggested replacing refined grains (e.g., white rice) with whole grains (e.g., brown rice) for improved health outcomes; however, the association between white rice consumption and risk of cardiovascular disease (CVD) was not fully investigated. The purpose of this study was to explore the associations between rice consumption, metabolic syndrome and cardiovascular disease.

Methods:
We conducted a comprehensive search of MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from database inception through May 2015. Observational studies were included if the studies reported hazard ratios (HRs) or odd ratios (ORs) of the associations between rice consumption, metabolic syndrome and cardiovascular disease. Data were extracted by one reviewer and then reviewed by two independent reviewers. Conflicts were resolved through consensus. Using the DerSimonian and Laird random effects models, we calculated pooled HRs and pooled ORs with 95% confidence intervals (95% CIs). Subgroup analyses were performed to explore potential sources of heterogeneity. The quality of the included studies and publication bias were assessed.

Results:
Out of 343 retrieved articles, we identified 6 cross-sectional and 9 prospective studies with a total of 575,852 individuals with 24,649 total CVD events and 4,409 metabolic syndrome cases. The highest category of white rice consumption (≥5 times/week) was associated with a 37% higher risk of metabolic syndrome (pooled OR, 1.37; 95% CI: 1.03-1.84; p<0.001; I
2
= 78.7%) but not a higher risk of cardiovascular disease (pooled HR, 1.01; 95% CI: 0.95-1.08; p=0.65; I
2
= 0%), compared to the lowest category (≤1 time/month).

Conclusions:
Higher white rice consumption has not been shown to increase the risk of cardiovascular diseases but may be associated with increased risk of metabolic syndrome.
Abstract 17021: Association Between Regulatory Review Times and Adverse Event Reports in New Cardiovascular Devices
Authors: Stern Ariel D , Kramer Daniel B , Ouellet Melissa D , Kesselheim Aaron S
Published: March 2022

Introduction:
The Food and Drug Administration (FDA) approves new high-risk medical devices after reviews of safety and effectiveness data gathered in clinical trials. Some have advocated for shorter review times to encourage innovation. We evaluated whether regulatory review time and product novelty predict adverse events involving high-risk cardiovascular devices.

Methods:
All high-risk cardiovascular devices approved between 2000-2009, grouped by FDA-assigned product codes were linked to regulatory review data and adverse events reported in the FDA’s Manufacturer and User Facility Device Experience database over the four years following FDA approval. Adverse events were classified according to severity, and linear probability / logistic regression models evaluated whether regulatory review times or product novelty predicted adverse event reporting.

Results:
Regulatory review times for 106 devices averaged 14.6 (SD: 9.77) months. Only 48/106 (45%) of devices in 28 product codes had at least 1 reported adverse event (mean: 182, range: 1-2706), yielding a total of 8,721 adverse event reports. Shorter regulatory review times were associated with a higher probability of any adverse event, as well as a higher probability of patient injury/death: a one standard deviation decrease in regulatory review time was associated with a 13.7% absolute/30.4% relative increase in risk of any adverse event reporting (95% CI: 6.8-20.5, p<0.001), a 9.8% absolute/39.1% relative increase in absolute risk of adverse events involving serious injury or death (95% CI: 2.0-17.6, p=0.02), and a 9.8% absolute/39.1% relative increase in probability of being in the top quartile of the count of total adverse events involving injury or death (95% CI: 2.0-18.6, p=0.02). Controlling for review time, novelty of a product was not predictive of the presence or frequency of adverse event reports.

Conclusion:
High-risk cardiovascular devices with shorter FDA reviews were associated with a higher probability of any reported adverse events, of events involving serious injury or death, and were more likely to be among those with the highest number of adverse event reports of injury or death. These data should inform current proposals aimed at expediting the review of high-risk devices.
Abstract 17041: Impact of Different Patterns of Left Ventricular Ballooning in Patients With Stress (Takotsubo) Cardiomyopathy: Single Center Clinical Experience
Authors: Kim Ju Hyeon , Jeong Yeong jin , Park Jinoh , Lee Pil Hyung , Jang Jeong Yoon , Lee Sahmin , Cho Min Soo , Kim Yu Na , Bae Jae Seok , Lee Cheol Hyun , Kim Dae-Hee , Song Jong-Min , Kang Duk-Hyun , Song Jae-Kwan , Choi Kee-Joon
Published: March 2022

Introduction:
Stress cardiomyopathy (SCMP) is characterized by acute reversible left ventricular (LV) dysfunction, and it is well accepted that SCMP can show various patterns with or without apical involvement. However, clinical data describing characteristics and outcomes according to the patterns of LV ballooning are lacking.

Methods:
We retrospectively identified 549 consecutive patients (age, 64±15 years; 328 female) with SCMP in a single tertiary hospital from Jan 2009 to June 2014. They were divided into 2 groups with typical apical ballooning (group 1) and atypical patterns sparing the LV apical segment (group 2). Clinical characteristics and outcomes including in-hospital mortality were explored.

Results:
Apical ballooning was most common (n=394, 71.8%) and group 2 included mid-ventricular ballooning (21.7%), basal ‘inverted’ ballooning (2.9%), global hypokinesia (1.8%), localized ballooning (1.1%), and isolated right ventricular ballooning (0.7%). Group 1 was characterized by higher mean age (67±13 vs. 55±17 years, p<0.001) with higher prevalence of coronary risk factors including obesity, hypertension, hyperlipidemia and diabetes mellitus. Emotional stress was a triggering event in a very limited patients comprising < 5%, whereas physical stress associated with underlying medical conditions comprised more than 70%. Distribution of triggering events was similar between groups. ECG abnormalities including T wave inversion, ST segment elevation, QT prolongation and atrial fibrillation were more frequent in group 1 than group 2 with lower LV ejection fraction. However, in-hospital mortality was comparable between groups (24% vs. 21%, p=0.52).

Conclusions:
Apical sparing ballooning develops in up to 30% of patients with SCMP. Younger age, favorable medical conditions, less severe ECG changes, and higher LV ejection fraction cannot translate to lower mortality in this group. Physicians’ vigilance is needed to improve clinical outcomes.
Abstract 17072: A Novel Algorithm for Quantification of Mitral Valve Regurgitation Based on Pixel Density Analysis of Continuous Wave Doppler Imaging
Authors: El Haddad Milad , De Backer Tine , De Buyzere Marc , Swillens Abigail , Segers Patrick , Timmermans Frank
Published: March 2022

Introduction:
Echocardiography is important for the assessment of mitral valve regurgitation (MR) and to guide clinical decision making. Echocardiographic methods are being used to quantify MR severity but their applicability, accuracy, and reproducibility have been debated.

Hypothesis:
To test the feasibility and in vitro validation of a novel custom-made transthoracic echocardiographic method for the assessment of MR severity based on pixel density analysis (PDA) of the continuous wave (CW) envelope in digital images.

Methods:
MR was prospectively assessed in 290 patients on a VIVID E9 echo machine (GE) with fixed settings. MR severity was evaluated according to international guidelines using color doppler, vena contracta (VC) width, proximal iso-velocity surface area (PISA) method, and PDA. The applicability, inter-observer, and intra-observer variability of all methods were compared. For validation of the PDA algorithm, a pulsatile in vitro cardiac phantom was used with prosthetic mitral valves with different regurgitant orifices (13.2, 27.2, 54.7, and 86.5 mm2). Regurgitant volume (RV) was calculated by multiplying the regurgitant orifice with the time velocity integral.

Results:
The PDA method showed a linear correlation with color doppler (r=0.82), VC width (r=0.67), PISA-effective regurgitant orifice area (EROA, r=0.72), and PISA-RV (r=0.67); p<0.001 for all. The PDA was significantly more applicable than VC width (n= 275/290, 95% vs. 218/290, 75% p<0.001) and PISA-based methods (n=191/290, 65% p<0.001). Additionally, PDA showed a stronger intra- and inter-observer agreement compared to the VC, PISA-EROA, and PISA-RV (intra-observer ICC = 0.96 vs. 0.79, 0.87, and 0.82 respectively; inter-observer ICC = 0.96 vs. 0.46, 0.89, and 0.85 respectively). In the in vitro validation, PDA showed a strong linear correlation with regurgitant volumes (r=0.92, p<0.001).

Conclusions:
We showed the clinical feasibility and in vitro validation of a novel digital quantitative echocardiographic method to assess MR severity. This method is more applicable and has less inter- and intra-observer variability compared to current quantitative methods. Patient follow-up is ongoing to validate the novel methods against clinical endpoints in MR.
Abstract 17084: Clinical Experience With the Subcutaneous Implantable Cardioverter Defibrillator in Paediatric Patients
Authors: Knops Reinoud , Brouwer Tom
Published: March 2022

Introduction:
In pediatric patients prevention of Sudden Cardiac Death (SCD) using Implantable Cardioverter Defibrillators (ICD) is associated with a higher risk of complications than in the adult population. Surgical re-interventions due to infection, lead dislocation or migration and inappropriate shocks on intra and extracardiac oversensing are the most prevalent complications. The Subcutaneous ICD (S-ICD) has been introduces as a less invasive and extravascular alternative to overcome some of these complications. The scientific data that has led to the approval of the S-ICD did not include pediatric patients. Contradicting reports in small cohorts have been published on the effectiveness of S-ICD therapy in the pediatric population. We here report the largest pediatric cohort with the longest follow up to date where the S-ICD has been used for SCD prevention.

Hypothesis:
The S-ICD is safe and effective for the prevention of SCD in a diverse pediatric population.

Methods:
We retrospectively studied all consecutive pediatric patients (age<18 yrs)that were implanted with a S-ICD in our center.

Results:
Fifteen S-ICDs were implanted in 14 patients (mean age 14, range 8-17), 71% were male, mean BMI was 18.8 (range 17.2-28.8), 57% had a secondary prevention indication, 77% had a genetic arrhythmia diagnosis and the median follow up was 21 months (range 1- 57).

The first shock efficacy of induced and spontaneous episodes was 100% (n=13 and n =2 respectively). Inappropriate shocks due to intracardiac oversensing occurred in 3 (21%) patients. No lead failures or dislocations were observed. Two patients (14%) experienced a complication requiring re-intervention: one infection and one pocket erosion. After the pocket erosion the S-ICD has been successfully re-implanted. In one patient the S-ICD was removed after cardiac transplantation. None of the patients died during follow up.

Conclusions:
The S-ICD is safe and effective in a diverse pediatric populations. There was a very high efficacy of defibrillation therapy (100%) and a relative low and mild occurrence of complications. The S-ICD should be considered as a viable alternative for transvenous ICD's in pediatric patients.
Abstract 17096: Assessing the Prevalence of Atherogenic Dyslipidemia in EURIKA Patients
Authors: Halcox Julian P , Roy Carine , Henriksson Karin M
Published: March 2022

Introduction:
Atherogenic dyslipidemia (AD), a condition identified by high triglyceride (TG) and/or low high-density lipoprotein cholesterol (HDL-C) levels, is associated with worse cardiovascular disease (CVD) outcomes.

Methods:
We used data from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, NCT00882336) to analyze the prevalence of AD according to patients’ CVD risk levels, determined using AHA/ACC (risk of atherosclerotic cardiovascular disease [ASCVD]; Table 1) and European (systematic coronary risk evaluation-HDL [SCORE-HDL]; Table 2) criteria. Patients in EURIKA were free from CVD but had at least one CVD risk factor (N=7641). AD was defined as TG ≥200 mg/dL and/or HDL-C <40 mg/dL in men and <50 mg/dL in women.

Results:
A large proportion of patients from EURIKA have high TG and/or low HDL-C levels characteristic of AD (Tables). Using AHA/ACC criteria to assess patients not receiving statin treatment and at high risk for CVD (type 2 diabetes [T2DM]; ASCVD risk ≥7.5%), the proportions with high TG, low HDL-C or both were 28.9%, 31.7% and 16.3%, respectively; for patients at low risk (without T2DM; ASCVD risk <7.5%), the respective proportions were 11.6%, 17.9% and 4.9%. Similarly, a higher proportion of patients defined as being at high risk by European criteria (T2DM, or SCORE-HDL ≥5%) had signs of AD than those at low risk (without T2DM, or SCORE-HDL <5%). Prevalence of AD was greater in patients with T2DM, but similar in those receiving statins and those who were not.

Conclusions:
Many patients at high risk of CVD also have signs of AD and may benefit from more intensive preventive measures.
Abstract 17113: Transaortic Edge-to-edge Mitral Valve Repair for Functional Mitral Regurgitation in Patients Undergoing Aortic Valve Replacement: A 13-year Experience
Authors: Mihos Christos G , Laurrari-Reyes Maiteder , Hung Judy , Santana Orlando
Published: March 2022

Objective:
The study aim was to evaluate the safety and efficacy of a transaortic edge-to-edge mitral valve repair (Alfieri stitch) for moderate or greater (≥2+) functional mitral regurgitation (MR) in patients undergoing aortic valve replacement, who were deemed to be high risk for conventional double valve surgery.

Methods:
We retrospectively evaluated all patients who underwent aortic valve replacement combined with a transaortic edge-to-edge mitral valve repair for ≥2+ functional MR, between February 2002 and April 2015. The MR was graded as 0 (trace/none), mild (1+), moderate (2+), moderate-to-severe (3+), or severe (4+).

Results:
There were 40 consecutive patients identified; 32 had aortic stenosis and 8 aortic regurgitation. The mean age was 77.5 ± 5 years, and 34 (85%) were male. Coronary artery disease was present in 26 (65%) patients, while 14 (35%) had no or non-obstructive disease. Sixteen (40%) patients had a prior history of cardiac surgery, and the mean EuroSCORE II was 14.3% ± 12.9. Nine patients (22.5%) underwent concomitant coronary artery bypass grafting. At a median of 1 month (IQR 0.75-10) follow-up, there were significant improvements in preoperative versus postoperative median MR grade (3 versus 1, p<0.001), and mean left ventricular ejection fraction (34% versus 41%, p=0.018), left ventricular end-diastolic dimension (54mm versus 49mm, p=0.005), and pulmonary artery systolic pressure (49mmHg versus 35mmHg, p<0.001). Persistent 3-4+ MR occurred in 2 (5%) patients. In 12 patients with at least 6 month echocardiographic follow-up (mean = 18 ± 11 months), a sustained improvement in median MR grade (4 versus 1, p<0.001), and mean left ventricular ejection fraction (40% versus 53%, p=0.003), left ventricular end-diastolic dimension (53mm versus 41mm, p=0.005), and pulmonary artery systolic pressure (46mmHg versus 33mmHg, p<0.039) was observed, with persistent 3-4+ MR occurring in 1 (8.3%) patient. Actuarial survival at 1, 3, and 4.5-years was 82% ± 6, 71% ± 8, and 65% ± 10, respectively.

Conclusions:
A transaortic edge-to-edge repair for ≥2+ functional MR can be safely performed during aortic valve replacement, and confers early and mid-term improvements in MR grade, left ventricular remodeling, and pulmonary hemodynamics.
Abstract 17161: Reduced Ventilatory Function and Gas Exchange are Associated With Cardiac Remodeling and Changes in Systolic and Diastolic Function in the Community
Authors: Nayor Matthew , Stevenson Meredith D , Xanthakis Vanessa , Tsao Connie W , Mitchell Gary F , Vasan Ramachandran S , Cheng Susan , O'Connor George T
Published: March 2022

Introduction:
Chronic lung disease and heart failure have been reported to be associated, but the pathophysiologic relations between cardiac and pulmonary structure and function in the community are not well understood. We evaluated cross-sectional associations between measures of pulmonary function and echocardiographic traits related to cardiac remodeling and systolic and diastolic function in a large, community-based sample.

Hypothesis:
We hypothesized that lower ventilatory function and diffusion capacity would be associated with adverse cardiac remodeling and reduced left ventricular (LV) systolic and diastolic function.

Methods:
Forced expiratory volume in 1 second (FEV1), single-breath carbon monoxide diffusion capacity (DLCO), and comprehensive echocardiographic measures were obtained in approximately 2500 participants (mean age 67±9 years; 55% women) attending the 8
th
Framingham Offspring examination cycle.

Results:
Using multivariable-adjusted linear regression models, we observed lower DLCO to be associated with lower fractional shortening, relatively higher early LV filling (E/A ratio), greater LV filling pressures (E/e’ ratio), and smaller right ventricular (RV) size (
Table)
. Similarly, lower FEV1 was associated with smaller left atrial size, relatively higher early LV filling (E/A ratio), smaller RV size, and smaller right atrial area (
Table
).

Conclusions:
Lower ventilatory function and diffusion capacity are associated with smaller cardiac chamber dimensions, worse LV systolic function, and changes in measures of LV diastolic filling. The mechanisms responsible for these relations require further investigation, but these associations provide evidence for a pathophysiologic association between chronic lung disease and abnormalities in cardiac structure and function in the community.
Abstract 17167: Risk Stratification for Long-term Survival Benefit With Cardiac Resynchronization Therapy in Mild Heart Failure Patients
Authors: Biton Yitschak , Goldenberg Ilan , Zareba Wojciech , Costa Jason , Mcnitt Scott , Polonsky Bronislava , Moss Arthur J , Kutyifa Valentina
Published: March 2022

Background:
Cardiac resynchronization therapy (CRT) has been shown to reduce heart failure (HF) events or death in mild HF patients with left bundle branch block (LBBB) ECG pattern. However, risk stratification for long-term mortality benefit with CRT in this cohort is currently lacking.

Methods:
The study population comprised 1266 patients with LBBB enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). A clinical risk score was developed using best-subset proportional hazards regression analysis in patients randomized to CRT with defibrillator (CRT-D) to predict survival benefit. Cox proportional hazards regression analysis was used to evaluate risk reduction of death by CRT-D versus an implantable cardioverter defibrillator (ICD)-only among the risk score groups.

Results:
We identified four clinical variables predicting outcome in CRT-D patients: age≥65, creatinine≥1.4 mg/dl, coronary artery bypass graft [CABG] in the patient history, and left ventricular ejection fraction [LVEF] < 26%. Five-year risk of mortality was 4% with no risk factor (low risk, n=357), 6% with 1 risk factor (n=500), 12% with 2 risk factors, and 27% with 3 risk factors (n=123); there were no patients with 4 risk factors. The mortality benefit from CRT-D vs. an ICD-only showed a U-shaped pattern with no significant benefit in patients with no risk factor (HR=0.77, CI 0.32-1.85, p=0.553), 46% reduction with 1 risk factor (HR=0.54, CI 0.32-0.89, p=0.017), 45% reduction with 2 risk factors (HR=0.55, CI 0.34-0.90, p=0.018), and no benefit with 3 risk factors (HR=0.77, CI 0.32-1.85, p=0.553).

Conclusions:
In MADIT-CRT, mild HF patients with LBBB with an intermediate mortality risk derived long-term survival benefit from CRT-D vs. an ICD-only. However, no survival benefit was observed in patients with low risk or a very-high risk.
Abstract 17218: Radiation Therapy is not Associated With Incident Atrial Fibrillation in Patients With Thoracic Cancer
Authors: Lentz Robert , Chalazan Brandon , Kolek Matthew , Farber-Eger Eric , Wells Quinn , Moslehi Javid , Darbar Dawood
Published: March 2022

Introduction:
Radiotherapy for thoracic cancer causes incidental cardiac exposure and increases risk of ischemic heart disease. Less clear is whether radiotherapy similarly increases risk of arrhythmias. Radiotherapy induces cardiac inflammation and fibrosis, which are risk factors for atrial fibrillation (AF).

Hypothesis:
In patients with thoracic tumors, radiotherapy is associated with incident AF.

Methods:
We conducted a retrospective study of electronic medical records (EMR) of patients who had a primary tumor of the breast, lung, mediastinum, or esophagus diagnosed between 1994 and 2014, did not have AF at time of diagnosis, and did not have previous thoracic radiotherapy. Patients were followed for incident AF until the end of the EMR or death. Incident AF was determined using a validated algorithm with a positive predictive value of 95.6%. After multiple imputation of missing variables, the association between radiotherapy and incident AF was assessed using Cox proportional hazards models.

Results:
4163 patients were included in the analysis. Mean (SD) age was 61.2 (13.3) years and 71% were women; 600 underwent radiotherapy. After a median (25
th
-75
th
percentile) 796 (255-2032) days of follow-up, the incidence of AF was 6.8% with and 6.2% without radiotherapy (P=0.538). After adjustment for potential confounders, radiotherapy was not associated with incident AF [hazard ratio (HR): 1.02, 95% confidence interval: 0.72-1.44]. Age [HR (per year): 1.05 (1.04-1.06), P=6.0*10
-15
], male sex [HR: 2.44 (1.80-3.30), P=9.5*10
-9
], coronary artery disease [HR: 1.42 (1.06-1.92), P=0.02], hypertension [HR: 6.44 (2.04-20.3), P=0.001], and heart failure [HR: 3.20 (2.31-4.44), P=3.4*10
-12
] were associated with incident AF. Among 3908 patients with unilateral breast or lung tumors, radiotherapy was not associated with incident AF [HR: 1.23 (0.79-1.92)] and tumor laterality did not modify the effect (P for interaction: 0.201).

Conclusions:
In this large retrospective cohort study, radiotherapy for thoracic tumors was not associated with incident AF. Rather, previously described AF risk factors were the most important drivers of AF risk. Larger studies with extended follow-up may further elucidate whether thoracic radiotherapy is a risk factor for AF.
Abstract 17227: Late Hepatic Complications Following Fontan Conversion Surgery
Authors: Deal Barbara J , Johnson Joyce , Webster Gregory , Tsao Sabrina , Marino Bradley S , Costello John M , De Freitas Andrew , Ganger Daniel R
Published: March 2022

Introduction:
Fontan conversion surgery has extended survival for patients with univentricular heart, yet raised concerns regarding durability of hepatic function.

Methods:
We reviewed liver outcomes among transplant-free survivors of Fontan conversion with arrhythmia surgery at our institution. Hepatic screening included a combination of annual liver function testing with clinically indicated imaging and/or biopsy.

Results:
Between 1994 - 2014, 145 patients underwent Fontan conversion surgery at a median age of 23 (3-47) years, following initial Fontan surgery at median age of 6 (1 -35) years. Initial Fontan surgery types were atriopulmonary (79%), atrioventricular (13%), and lateral tunnel (8%). Early mortality was 2% following Fontan conversion surgery, with 10-year transplant free-survival of 84%. During median follow-up of 9 (1-20) years among 130 transplant-free survivors, significant liver disease developed in 6 patients (4.6%): hepatocellular carcinoma in 5 patients (primary 4, metastatic from appendix 1), and fulminant liver failure in one patient. Median age at diagnosis of hepatocellular carcinoma/liver failure was 35 (28-47) years, a median of 27 (22-33) years following initial Fontan surgery. Carcinoma was detected on annual hepatic screening with ultrasound in 3, and by elevated alpha-fetoprotein level prompting imaging in 2 patients. None of the patients had clinical variceal bleeding. Preoperative status included heterotaxy syndrome in 2, NYHA Classification III-IV in 5, and long standing ascites in 2 patients. Death occurred in 3/6 patients at a mean of 1.4 years following diagnosis of hepatic disease.

Conclusion:
Late hepatocellular carcinoma/liver failure was found in 4.6% of non-transplanted Fontan conversion patients, indicating the need for serial monitoring of liver status. Early detection of carcinoma with routine screening using American Association for the Study of Liver Diseases guidelines may allow for improved treatment strategies and prolonged survival.
Abstract 17253: Chest Compression Hemodynamics are Dependent on Chest Compression Rate
Authors: Lampe Joshua W , Yin Tai , Bratinov George , Shoap Wes , Lin Yuxi , Kaufman Christopher L , Becker Lance B
Published: March 2022

Introduction:
The mechanisms through which chest compressions (CC) generate blood flow remain controversial. The thoracic pump model is CC rate insensitive in the range 60 - 150 compressions per minute (cpm) but is sensitive to change in CC duty cycle with the prediction that increasing duty cycle would result in a modest, but linear, decrease in minute blood flow at a constant rate. Thus, the recently reported relationship between CC rate and outcomes may be due to changes in duty cycle instead of changes in rate.

Methods:
CPR was performed on nine domestic swine (∼30 Kg) using standard physiological monitoring. Flow was measured in the abdominal aorta, the inferior vena cava (IVC), the right renal artery and vein, the right common carotid and external jugular. Ventricular fibrillation (VF) was electrically induced. Mechanical CC were started after ten minutes of VF. CC were delivered at a rate of 50, 75, 100, 125, or 150 cpm and at a depth of 2” for a total of 54 min. CC rates were changed every 2 min and were randomized. The compression time was held constant at 350 ms.

Results:
CC generated blood flow showed a significant rate/duty cycle dependence and time dependence in all measured blood vessels. Early in the resuscitation, blood flows were optimized by rates above 100 cpm. As CC continued both the net blood flow and the optimal CC rate decreased as shown in Figure 1. Using previously collected data at 100 cpm and varying duty cycles, we found that minute blood flow did not decrease linearly with duty cycle, as predicted by the thoracic pump model.

Conclusions:
The optimal CC rate during CPR changes as a function of time suggesting that a fixed CC rate is not optimal. However, the data support the choice of ∼100 cpm as the “best” choice for a fixed CC rate. While some aspects of the observed rate effect may be explained by changes in CC duty cycle, these data do not support the idea that CC generated blood flow is independent of rate in the range 60-150 cpm.
Abstract 17282: Concordance of Mitral Leaflet Chordal Measurements Using Different Echocardiographic Techniques and Surgical Approaches: Implications for Mitral Valve Repair
Authors: Javadikasgari Hoda , Gillinov A M , Mihaljevic Tomislav , Griffin Brian P , Desai Milind Y
Published: March 2022

Objectives:
In patients with significant primary mitral regurgitation (PMR), the success of mitral valve repair (MVr) depends upon precise preop planning, including accurate assessment of chordal length. Both 2-dimentional (2D) & 3-dimentional (3D) transthoracic (TTE) & transesophageal (TEE) echocardiography visualize anterior and posterior chords. We sought to assess concordance of echo-based MV chordal measurements against direct intraop (robotic vs. midline) measurements.

Methods:
After informed consent, we prospectively enrolled 56 consecutive patients (59±11 years, 86% men) who underwent MVr (52% robotic, 48% sternotomy) between 12/14-6/15 by a single experienced surgeon. The lengths of anterior & posterior MV chords were measured in 2-, 3-, & 4-chamber views on preop 2D/3D TTE & 2D/3D TEE (Philips & General Electric) & were compared to intraop length of the most perpendicular normal anterior & posterior chords. All measurements were performed in a blinded manner & noninvasive measurements were compared against intraop measurements using intraclass correlation coefficient (ICC).

Results:
Intraoperatively, the mean lengths of anterior & posterior chords were 2.02±0.4 & 1.81±0.4 cm, respectively. For the anterior chords, the mean lengths on 2D & 3D TTE were 1.96±0.3 & 1.96±0.3 cm, respectively, while they were 1.99±0.3 & 1.93±0.3 cm on 2D & 3D TEE, respectively. Similarly, for posterior chords, the mean length on 2D & 3D TTE was 1.90±0.3 & 1.89±0.3 cm, while they were 1.91±0.3 & 1.90±0.3 cm on 2D & 3D TEE, respectively. Data on ICC’s (for the concordance of the whole group & separated on different surgical approaches) are shown in Figure.

Conclusion:
There is high concordance in measurement of anterior MV chords by 2D/3D TTE/TEE with surgical techniques. However, concordance for posterior chord measurement is less accurate, especially when a robotic approach is used. In such patients, precise preop planning using imaging (including tomography) may be crucial.
Abstract 17287: Increase in Utilization of High-intensity Statin Among New Users After the Release of the 2013 ACC/AHA Cholesterol Management Guideline
Authors: Olufade Tope , Anzalone Deborah , Kern David M , Tunceli Ozgur , Zhou Siting , Willey Vince , Cziraky Mark J
Published: March 2022

Introduction:
To characterize changes in statin utilization patterns after the release of the 2013 ACC/AHA cholesterol management guideline.

Methods:
Using administrative claims and laboratory results data from the HealthCore Integrated Research Database, statin use was captured during the 4 quarters before and after release of the 2013 ACC/AHA guideline. Individuals were classified into 4 statin benefit groups (SBG), as described in the ACC/AHA guideline. Patients new to statins were identified independently during each quarter.

Results:
An average of 205,358 patients were identified across the 4 SBG groups during each quarter, of whom an average of 3,658 were new statin users. New users were 41% women and 61 years old on average. Results are shown in Figure 1. In SBG 1, high-intensity statin use in patients <75 years increased from an average of 19.6% per quarter before the guideline to 24% in the quarters afterward. In SBG 2, there was a gradual increase in high-intensity statin use following introduction of the guideline. In SBG 3, high-intensity statin use for patients with 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% increased during the post-guideline period, but little change was seen for moderate-intensity statin use for patients with ASCVD risk <7.5%. In SBG 4, a small increase in moderate- to high-intensity statin use was observed.

Conclusions:
The 2013 ACC/AHA guideline appeared to have a modest effect in the utilization of high-intensity statins among new users in the period immediately following its release. The increase was most marked in the use of high-intensity statins in ASCVD patients and in patients treated by specialists. Follow-up in future years to assess the impact of the ACC/AHA guideline is warranted.
Abstract 17343: Innate T Cells Improve Brain Injury and Mortality After Cardiac Arrest and Resuscitation
Authors: Kim Edy Y , Ikeda Kohei , Hayashida Kei , Brenner Michael B , Ichinose Fumito
Published: March 2022

Introduction:
Systemic inflammation may contribute to brain injury and mortality after cardiac arrest and resuscitation (CA/CPR). The early increase of inflammatory cytokines (such as interferon-γ [IFNγ]) suggests a role for innate immunity in CA/CPR. Natural Killer T (NKT) cells, a type of innate T cell, are “master regulators” of IFNγ and other facets of the early innate immune response in other disease models. To study the regulation of innate immunity after CA/CPR, we examined CD1dKO mice (which lack both invariant NKT cells and diverse NKT cells) and Jα18 KO mice (which lack only invariant NKT cells).

Hypothesis:
NKT cells control inflammation, brain injury, and mortality in CA/CPR.

Methods:
Mice were mechanically ventilated, underwent 8 min. of normothermic CA with potassium chloride i.v. and were resuscitated with chest compressions and epinephrine i.v.

Results:
Surprisingly, normally pro-inflammatory NKT cells had a protective effect. After CA/CPR, pan-NKT cell-deficient (CD1d KO) mice had markedly worsened brain injury and mortality compared to wild-type (WT) mice; but Jα18 KO mice (which only lack invariant NKT cells) had similar outcomes as WT mice. These results suggested that diverse NKT cells had a protective role after CA/CPR. Pan-NKT cell-deficient (CD1d KO) mice had exaggerated IFNγ production by NK and innate lymphoid cells (ILC1s) after CA/CPR. In line with the increased IFNγ and worsened outcomes in NKT cell-deficient mice, IFNγ-deficient (IFNγ KO) mice had improved brain injury and mortality after CA/CPR, compared to WT mice. Finally, NKT cell-deficient mice were rescued by IFNγ deficiency (Cd1d-/- Ifng-/- double KO mice).

Conclusions:
Unexpectedly, diverse NKT cells were anti-inflammatory and protective in CA/CPR. In CA/CPR, diverse NKT cells reduced IFNγ levels, and reduction of IFNγ improved mortality and brain injury. Innate T cells and IFNγ may be targets for therapeutic intervention in CA/CPR.
Abstract 17354: A Canadian Pilot Randomized Controlled Trial for a Decision Support Intervention in de novo Implantable Cardioverter Defibrillator Candidates - Main findings
Authors: Carroll Sandra , McGillion Michael H , Stacey Dawn , Healey Jeff S , Foster Gary , Hutchings Sarah A , Arthur Heather M , Arthur Heather M , Browne Gina , Thabane Lehana
Published: March 2022

Introduction:
Patient decision aids (PtDA) support quality decision making and improve patient reported outcomes. This pilot randomized controlled trial aimed to evaluate the use of an ICD specific PtDA on patient’s decisional conflict and ICD knowledge.

Methods:
In accordance with the International Patient Decision Aid Standards (IPDAS), a PtDA was developed. We conducted a single-centre non-blinded RCT with concealed allocation to evaluate the effect of a PtDA in patients offered an ICD for primary prevention. Exclusions: 1) inability to read English and complete a PtDA, 2) ICD for secondary prevention, 3) biventricular devices. Consented patients were randomized to 1) usual care, 2) PtDA intervention. Prior to specialist consultation the PtDA intervention group received the PtDA. The primary outcome of decisional conflict was measured before consultation and post-ICD implantation. The decisional conflict scale measures patient’s perception of difficultly making a decision, uncertainty regarding the decision and factors contributing to uncertainty. Higher scores are indicative of greater decisional conflict. Knowledge was measured as a secondary outcome using 5 questions related to ICD treatment, benefits and risks.

Results:
Eighty-two patients were randomized to usual care (n=41) or PtDA intervention (n=41). Mean age (SD) was 66.76 (11.05), 27% female. Baseline characteristics between groups were balanced. Patients receiving the PtDA intervention scored significantly lower on the DCS scale with a total mean score of 27.32 (18.37) when compared to usual care, scoring 49.53 (18.62) (p<0.0001). This difference remained post implantation, 21.16 (11.71) PtDA intervention, 29.89 (13.32) usual care, (p=0.0041)). The PtDA intervention group were more knowledgeable, with 47.50% scoring greater than 3/5 of the knowledge questions correct, compared to 23.09% receiving usual care (p=0.023).

Conclusion:
The results of this pilot study suggest that use of an ICD-specific PtDA reduced patient’s decisional conflict both pre and post implantation and improved knowledge. In the context of making decisions regarding life prolonging interventions, our findings suggest evidence based decision support results in improved patient decision quality.
Abstract 17356: Anti-arrhythmic Effect of Exosomes Secreted by Cardiosphere-derived Cells: Reduction in Inducible Ventricular Arrhythmias in a Porcine Model of Chronic Myocardial Infarction
Authors: Dawkins James F , Gallet De Saint Romain , Valle Jackelyn , Cingolani Eugenio , Marban Eduardo
Published: March 2022

Introduction:
Myocardial infarction (MI) survivors are at increased risk for ventricular arrhythmias and sudden death; risk directly correlates with infarct size and scar heterogeneity. The regenerative effects of cardiosphere-derived cells (CDCs),which are now in phase 2 clinical trials, are mediated by exosomes (CDC
exo
).Like CDCs, CDC
exo
reduce scar size and increase viable mass in chronic MI. These naturally secreted nanoparticles mediate cell-cell signaling by transfer of bioactive payloads including microRNAs. Hypothesis: We hypothesized that post-MI hearts treated with CDC
exo
exhibit reduced inducibility of ventricular tachycardia (VT).

Methods:
An angioplasty balloon was inflated in the left anterior descending coronary artery for 150 minutes followed by one month of reperfusion in 7 female Yucatán minipigs. Electroanatomical mapping (EAM) was then performed to define the MI border zone (4.1-7mV NOGA tip potentials), after which we injected either CDC
exo
(7.5mg/1 ml n=4) or phosphate-buffered saline(PBS, 1ml, n=3), in 12-15 border zone sites via MYOSTAR catheter. Four weeks later, EAM was repeated and arrhythmia susceptibility was probed using both programmed ventricular stimulation and burst pacing (train of 8 beats from 400 to 200ms in 10 ms decrements) at the infarct border zone, and in healthy tissue near the posterolateral wall (>10mv). Arrhythmia morphology was characterized by 12 lead ECG. Final infarct size was quantified by histology (TTC).

Results:
In CDC
exo
-injected pigs, infarct size was lower (11.4% vs 7.8%, p=0.05) and viable mass was higher (69.3g vs 79.3g, p=0.03) than in PBS controls. No sustained VT was induced by programmed ventricular stimulation. Burst pacing elicited VT which rapidly degenerated into ventricular fibrillation in all control animals (n=3), but in only 1 of 4 CDC
exo
-treated animals (p=0.04),when paced at both the infarct border and healthy myocardium.

Conclusions:
Exosomes from CDCs regenerate myocardium post-MI. Pigs treated with CDC
exo
exhibit reduced inducibility of sustained ventricular arrhythmias by burst pacing. This first demonstration of an anti-arrhythmic effect of exosomes motivates more extensive investigation of the effects of these nanoparticles on rhythm disorders.