bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16570: Systemic Inflammation Alters the Bleeding-Ischemic Balance in High-Bleeding Risk Patients Undergoing Percutaneous Coronary Interventions
Authors: Nicolas Johny , Cao Davide , Claessen Bimmer E , Chiarito Mauro , Sartori Samantha , Qiu Hanbo , Nardin Matteo , Camaj Anton , Roumeliotis Anastasios , Zhang Zhongjie , Goel Ridhima , Chandiramani Rishi , Baber Usman , Sweeny Joseph , Krishnan Prakash , Kini Annapoorna , Sharma Samin K , Dangas George , Mehran Roxana
Published: May 2021

Introduction:
Prognosis in high-bleeding risk (HBR) patients after percutaneous coronary intervention (PCI) is largely dependent on risk of ischemic/bleeding events. Inflammation is known to increase the ischemic risk following PCI in the general population, yet its impact on HBR patients remains unknown.

Hypothesis:
We assessed the hypothesis that inflammation, as reflected by elevated high-sensitivity C - reactive protein (hsCRP), increases the risk of ischemic and bleeding events in HBR patients undergoing PCI.

Methods:
We included patients who underwent PCI at a tertiary care center between 2014 and 2017. Patients were classified as HBR if they met ≥1 major or ≥2 minor criteria according to the Academic Research Consortium (ARC)-HBR consensus. Patients were then stratified into high (≥3 mg/l) and low (<3 mg/ml) baseline hsCRP level; those presenting with myocardial infarction (MI) or hsCRP >10 mg/l were excluded. The main outcomes of interest were major adverse cardiac events (MACE) (composite of all-cause death, MI, and target vessel revascularization) and bleeding events.

Results:
Out of 7,186 patients included, 3,403 (42.3%) fulfilled the ARC-HBR definition of whom 1,046 (34.4%) had high hsCRP. These patients were frequently female, younger, and had more cardiovascular risk factors (diabetes, kidney disease, and peripheral artery disease) yet similar angiographic features (multivessel disease, syntax score, and lesion length) than those with low hsCRP. Although risk of MACE at 1 year was similar in HBR patients with either high or low hsCRP, mortality risk was significantly higher in the former group (
Figure 1
). In addition, HBR patients with high hsCRP were more likely to have periprocedural bleeding (OR 1.72, 95% CI [1.14-2.58], p=0.01) but similar risk of 1-year major bleeding as HBR patients with low hsCRP (
Figure 1
).

Conclusion:
In conclusion, inflammation is associated with periprocedural bleeding and 1-year mortality in HBR patients undergoing PCI.
Abstract 16604: Significant Correlation Between Arterial Velocity Pulse Index and Muscle Sympathetic Nerve Activity in Hypertensive Patients
Authors: sugimoto hiroyuki , Murai Hisayoshi , Hamaoka Takuto , Mukai Yusuke , Okabe Yoshitaka , tokuhisa hideki , Usui Soichiro , Sakata Kenji , Takamura Masayuki
Published: May 2021

Introduction:
Augmented sympathetic nerve activity (SNA) in hypertension (HT) is regarded as a therapeutic target, but there is few non-invasive markers to evaluate SNA in clinical practice. It is reported to associate with SNA which increased arterial reflected wave plays the important role in disease progression in HT, and it is reported to associate with SNA. Recently, Arterial Velocity Pulse Index (AVI) are developed as an index of arterial reflected waves, however the relationship between AVI and SNA is still uncertain.

Methods:
Patients with essential HT and matched non-hypertensive control subjects were included in this study. HT was diagnosed as systolic blood pressure (SBP) ≧ 140 mmHg or diastolic blood pressure (DBP) ≧ 90 mmHg. Patients with secondary HT was excluded. AVI was measured from left upper arm by NAS-1000 (Nihon Koden, Japan). SNA was evaluated by direct recording of muscle sympathetic nerve activity (MSNA) from peroneal nerves.

Results:
50 HT patients and 50 control subjects were included. Age, SBP and DBP were significantly increased in HT group compared to control (Age 63±14 vs 42±16 years, p<0.001; SBP 144±16 vs 115±9 mmHg, p<0.001; DBP 80±14 vs 67±9 mmHg, p<0.001). MSNA and AVI were significantly increased in HT group compared to control (MSNA 34±10 vs 25±8 bursts/min, p<0.05; AVI 28±9 vs 17±5, p<0.05). In univariate analysis, AVI was significantly correlated with MSNA, age, and SBP in HT group. However, no significant relationship was observed between AVI and MSNA in multivariate analysis. Therefore, HT group was divided into two groups according to their severity (group 1, SBP<160mmHg, N=30; group 2, SBP>160 mmHg, N=20). AVI in group 1 showed significantly correlation with MSNA (r=0.49, p<0.05), but no correlation was seen in group 2.

Conclusions:
AVI was significantly increased in patients with HT compared to control, and AVI is significantly associated with MSNA in HT patients with SBP<160mmHg. These results indicate that AVI is helpful to estimate augmented SNA in patients with mild or moderate hypertension. Further study is warranted to exam the relationship AVI and SNA in reality.
Abstract 16606: Home Blood Pressure Monitoring Postpartum Detects Masked Hypertension in Women With a History of Preeclampsia
Authors: Nuckols Virginia R , Stroud Amy K , Brandt Debra , Santillan Mark K , Santillan Donna A , Catov Janet M , Hubel Carl A , Pierce Gary L
Published: May 2021

Introduction:
One-third of women with a history of preeclampsia (hxPE), a hypertensive pregnancy disorder, develop chronic hypertension (HTN) within five years postpartum. Twenty-four hour ambulatory blood pressure monitoring (ABPM) shows that 12% of women with hxPE have ‘masked’ HTN. Masked HTN is undetected in routine clinical assessment but is associated with elevated cardiovascular disease risk. ABPM (gold-standard) or home blood pressure monitoring (HBPM) is needed to identify masked HTN. HBPM is a well-tolerated, inexpensive alternative to ABPM. However, the ability of HBPM to detect masked postpartum HTN using new AHA/ACC HTN guidelines is unknown. The purpose of this study was to compare ABPM and HBPM in the identification of masked and sustained HTN among young women with hxPE and healthy pregnancy (HP) controls 1-3 years postpartum.

Methods:
Women with hxPE (N=22; age 33 ± 5 yrs) and HP controls (N=26; age 34 ± 4 yrs) were assessed 18 ± 6 months postpartum. Seated office blood pressure (BP) was collected with an automated brachial cuff and averaged over three trials. ABPM (Mobil-o-graph) was conducted with a portable, automated brachial cuff and averaged over 38 ± 2 awake and asleep BP recordings. Participants completed HBPM (Microlife) morning and evening for seven consecutive days. BP thresholds for HTN were determined according to 2017 AHA/ACC clinical guidelines.

Results:
HTN was more prevalent among women with hxPE compared with HP assessed by office BP (59 vs. 15 %, P=0.002) and ABPM (68 vs. 31 %, P=0.01) but not HBPM (41 vs 19 %, P=0.10). The prevalence of masked HTN did not differ between women with hxPE and HP (14 vs. 19%, P=0.71) assessed by ABPM. In the entire cohort, HBPM detected 50% of masked HTN cases identified by ABPM. HBPM agreed with ABPM on HTN status (κ = 0.49, P=0.002). HBPM and ABPM detected uncontrolled HTN in three of four women with hxPE prescribed anti-hypertensive medication.

Conclusion:
HxPE is associated with a higher prevalence of HTN 1-3 yrs postpartum compared with controls, but the prevalence of masked HTN did not differ. ABPM and HBPM showed concordant classification of HTN using current BP guidelines. These findings indicate that HBPM may be a valuable pre-screening tool for early identification and management of HTN postpartum.
Abstract 16627: Coronary Artery Calcium Scoring and Cardiovascular Events in Patients With Cancer: Analysis of CLARIFY Registry
Authors: Al-Kindi Sadeer , Tashtish Nour , Guha Avirup , Rashid Imran , Cainzos Achirica Miguel , Nasir Khurram , Rajagopalan Sanjay
Published: May 2021

Introduction:
Cardiovascular disease and cancer co-exist due to shared risk factors. The utility of coronary artery calcium (CAC) scoring in this population to predict cardiovascular events is not certain.

Methods:
We studied all patients enrolled in the CLARIFY registry of no-charge CAC (Clinicaltrials.gov NCT04075162) with diagnosis of any cancer. We followed patients for major adverse cardiovascular events (myocardial infarction, stroke, heart failure, coronary revascularization or mortality).

Results:
A total of 3,432 patients with cancer were identified. Mean age was 64±9 years, 1965 (57%) were women and 2937 (86%) were white. Overall distribution of CAC scores were as follows: CAC 0 in 35%, CAC 1-99 in 31%, CAC 100-399 in 20%, and CAC ≥ 400 in 15%. CAC distribution varied by cancer type (figure A). At a median follow-up of 663 [294-1086] days, 343 patients had MACE event. Compared with CAC 0, patients with CAC ≥ 400 had increased unadjusted risk of MACE (HR 2.57 [1.93-3.41], P<0.001), which was not attenuated after adjusting for age and sex (HR 2.09 [1.50-2.90], P<0.001).

Conclusions:
In this large cohort of patients with cancer, coronary artery atherosclerotic calcifications are common, vary by cancer type, and are associated with major adverse cardiovascular events, independently of age and sex. Further research should focus on utility of routine CAC for cardiovascular risk stratification in patients with cancer.
Abstract 16629: Endothelial Caveolin-1-trpv4 Regulation of Pulmonary Arterial Pressure and Impairment in Pulmonary Hypertension
Authors: Daneva Zdravka , Marziano Corina , Ottolini Matteo , CHEN YEN LIN , Hong Kwangseok , Zhang Aimee , Baker Thomas , Mihalek Andrew , Goncharova Elena , Minshall Richard D , Laubach Victor , SONKUSARE Swapnil K
Published: May 2021

Background:
Pulmonary hypertension (PH) is a degenerative disorder that is characterized by elevated vascular resistance and pulmonary arterial pressure (PAP). Endothelial transient receptor potential vanilloid 4 (TRPV4
EC
) ion channels represent an important Ca
2+
influx signaling mechanism that promotes vasodilation of small pulmonary arteries (PAs). Scaffolding protein caveolin-1 (Cav-1) has been shown to precipitate with TRPV4 channels in pulmonary endothelial cells in culture.

Hypothesis:
We hypothesized that the endothelial Cav-1-TRPV4 channel signaling in small PAs lowers PAP, and is impaired in PH.

Methods:
Inducible endothelium-specific KO mice for TRPV4 channel or Cav-1 were used to study the role of Cav-1-TRPV4 signaling in the regulation of resting PAP. Endothelium-specific P2Y2 receptor KO mice were used to test if Cav-1 provides a signaling scaffold for purinergic activation of TRPV4
EC
channels. Endothelial Cav-1-TRPV4 signaling was assessed in PAs from two PH mouse models and PH patients. The role of NADPH oxidase (NOX1)- and inducible nitric oxide synthase (iNOS)-mediated peroxynitrite (PN), an oxidant molecule, in impairing Cav-1-TRPV4 signaling in PH was evaluated using NOX1-/- and iNOS-/- mice and pharmacological inhibitors.

Results:
We show that endothelial Cav-1-TRPV4 signaling in small PAs lowers resting PAP, and protects against the pathogenesis of PH. Endothelial Cav-1 provides a signaling scaffold for the activation of TRPV4 channels by endogenous purinergic receptor signaling. Moreover, TRPV4
EC
channel activity and Cav-1-TRPV4 signaling are impaired in small PAs from two mouse models of PH and PH patients. Elevated levels of NOX1 and iNOS enzymes in caveolae resulted in PN formation close to Cav-1 in PH. Elevated PN targeted Cav-1 to lower Cav-1-TRPV4 signaling, thereby contributing to impaired vasodilation and increased PAP. Pharmacological inhibition of NOX1, iNOS, or PN rescued TRPV4
EC
channel activity and vasodilation in PH.

Conclusion:
This study provides novel evidence that endothelial Cav-1-TRPV4 signaling lowers PAP and is impaired in PH. Inhibiting NOX1 or iNOS activity, or lowering endothelial PN levels may represent a novel strategy for restoring TRPV4
EC
channel activity, vasodilation, and PAP.
Abstract 16649: Natural History of Ascending Aortic Aneurysms With Bicuspid and Tricuspid Aortic Valves
Authors: Tharakan Serena , Bellaire Christopher , Roy Jordan , Bravo Miguel , Puskas John , Di Luozzo Gabriele
Published: May 2021

Introduction:
Patients with bicuspid aortic valves (BAV) and tricuspid aortic valves (TAV) with ascending aortic aneurysms (AAA) are at risk for aortic complications. Meticulous follow-up and assessment of risk factors can mitigate the adverse aortic events.

Hypothesis:
We hypothesized that BAV and TAV with AAA can be managed conservatively with acceptable survival, low aortic complication rate, and timely surgery.

Methods:
From 2016 to 2018, 188 patients were seen for an isolated AAA. 147 patients had two or more CT scans (631-patient-years) which allowed measurement of aortic growth. We used a 1:1 greedy matching algorithm in R to identify similar cohorts of BAV and TAV patients matched by age, sex, hypertension, family history of aortic disease, coronary artery disease, and hyperlipidemia. Univariate and multivariate analysis of the unmatched cohorts were performed. Echocardiogram data was evaluated for each patient.

Results:
Initial mean AAA diameter was 4.3±0.58 cm (Table 1). The mean time between scans was 4.2 ± 3.3 years. 20 patients had an ascending aortic aneurysm ≥ 5cm with mean diameter 5.2 ± 0.23 cm (range 5.0-6.0 cm). Five patients had an aortic event (1 BAV and 4 TAV). Three of these aortic events lead to patient deaths (1 BAV and 2 TAV), in addition to one death (TAV) unrelated to aortic pathology. From time of enrollment, survival at 10 years was 90 ± 32%. Our model suggests that given the absence of known high risk factors, BAV patients do not have an accelerated ascending or root growth rate in comparison to their TAV counterparts. BAV patients do have higher rates of aortic stenosis (p <.05), a factor that influenced the need for aortic repair.

Conclusion:
In conclusion, regardless of aortic valve type, the associated AAA has a similar natural history and low adverse event rate. In the absence of risk factors, conservative management of AAA can be accomplished with minimal risk to the patient.
Abstract 16653: Ventricular Arrhythmias With Ibrutinib Use: A Systematic Review and Meta-Analysis
Authors: Khallid Yaser , Dasu Neethi , Shah Ankit , Fradley Michael G , Dasu Kirti , Levine Adam
Published: May 2021

Introduction:
Ibrutinib is a widely used treatment option for patients with chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. There is limited investigation on the relationship between ibrutinib and the development of ventricular arrhythmias.

Hypothesis:
We hypothesized that the incidence of ventricular arrhythmias in patients taking ibrutinib compared to the patients on other treatment regimens would be higher.

Methods:
We performed an aggregate data meta-analysis on nine studies to examine the incidence of ventricular arrhythmias. We further assessed a meta-regression analysis to evaluate the effect of duration of therapy on incidence of ventricular arrhythmias. Relative risk (RR) and 95% confidence intervals (CI) were estimated using a random-effects model.

Results:
Of 3809 patients being treated with ibrutinib, the incidence of ventricular arrhythmias was almost 8-fold higher in patients being treated with ibrutinib compared to other tyrosine kinase inhibitors (TKIs), other chemotherapies, or immunotherapy. (RR 8.13, 95% CI 4.37-15.10, p <0.0001). On meta-regression analysis, the incidence increased further with longer duration of treatment (coefficient = 0.0206, p=0.049); patient populations greater than 60 years have a higher incidence of ventricular arrhythmias (coefficient = 0.0237, p=0.044). Over 50% of patients diagnosed with ventricular arrhythmias on ibrutinib died of sudden death.

Conclusions:
For patients treated with ibrutinib, there was a markedly higher rate of ventricular arrhythmias and an increased incidence with longer duration of treatment. These data highlight the need for guidelines on surveillance and management for ventricular arrhythmias for patients taking ibrutinib.
Abstract 16661: Fluid Challenge During Right Heart Catheterization for Evaluation of Pulmonary Hypertension Identifies Patients With Decreased Right Ventricular Function
Authors: Agrawal Vineet A , Muhs Amelia , Assad Tufik , Robbins Ivan M , Newman John , Pugh Meredith E , Tedford Ryan J , Hemnes Anna R , Brittain Evan , Agrawal Vineet
Published: May 2021

Introduction:
Fluid challenge during right heart catheterization (RHC) identifies occult left heart diastolic dysfunction (Occ-DD) in 10-20% of patients initially diagnosed with pre-capillary pulmonary hypertension (PH). The prognostic implications of the response to fluid challenge are not known. Abnormal right ventricular (RV) function is a poor prognostic indicator in all forms of PH.

Hypothesis:
We hypothesized that fluid challenge during RHC identifies patients with worse RV function and survival.

Methods:
Consecutive patients referred for RHC with fluid challenge from 2009-2016 were studied. Occ-DD was defined by a resting pulmonary arterial wedge pressure (PAWP) < 15 mmHg, and a PAWP > 18 mmHg after 500cc fluid challenge. Resting DD was defined by resting PAWP > 15 mmHg. RV function was assessed by pulmonary artery pulsatility index (PAPi) or RV stroke work index (RVSWI). Statistical analysis was conducted using Kruskal Wallis test. Survival analysis was conducted by log rank test.

Results:
Of the 310 patients identified, 83% were female with a mean age of 54 + 14 years. The cohort consisted of 204 (66%) patients without DD, 30 (10%) with Occ-DD, and 76 (24%) with resting DD. Patients with Occ-DD were older (59 + 12 vs 51 + 14, p < 0.0001) with greater BMI (31 + 6 vs 28 + 7, p < 0.0001), but had similar prevalence of obesity, hypertension, diabetes mellitus, and coronary disease to all groups. Patients with Occ-DD had lower PAPi (7.8 + 0.4 vs 8.5 + 0.4, p < 0.0001), lower RVSWI (9.9 + 0.8 vs 17.8 + 0.7 mmHg*ml/m2, p < 0.0001) (Figure), and decreased survival (3.7 + 3.5 vs 4.9 + 3.5 years, p < 0.0001) compared to those without DD. After adjustment for RV function, survival was no longer different between groups.

Conclusions:
Patients with Occ-DD after fluid challenge during RHC have decreased survival due to worse RV function compared to patients without DD. These findings suggest important prognostic implications for fluid challenge in the evaluation of patients with PH.
Abstract 16677: Real World Screen Failure Rates for Transcatheter Mitral Valve Repair and Replacement for Mitral Regurgitation
Authors: Safren Lowell , Nasher Nayeem , Reddin Gemma , Forrestal Brian , Khan Jaffar , Case Brian C , Collins Erin , ben-dor itsik , Shults Christian , Satler Lowell F , Rogers Toby , Waksman Ron
Published: May 2021

Background:
Despite an expanding armamentarium of devices, many patients with mitral regurgitation referred for transcatheter mitral valve repair or replacement are not eligible to participate in the clinical trials or receive a commercially available device. We sought to understand the reasons why patients were excluded from receiving therapy.

Methods:
We retrospectively analyzed the medical charts, and correspondence related to patients referred to our tertiary valve center for transcatheter mitral valve replacement (TMVR) or transcatheter mitral valve repair (TMVr) between June 2016 to September 2019. Patients were screened for eligibility by our structural Heart Team for either TMVR or TMVr. If TMVR or TMVr was not offered the reason for screen failure was recorded and categorized.

Results:
Over the 3-year period, 564 patients were referred for TMVR/TMVr. Of these, 15.9% were determined to be eligible for and underwent surgical repair or replacement. 440 patients (78.0%) were considered for TMVR/TMVr. 92 patients (16.3%) underwent TMVR/TMVr. The majority of patients (348/564, 61.7%) ultimately did not undergo intervention (Panel A). The reasons for exclusion were clinical in 78%, issues related to patient preference of care delivery in 49% of patients, anatomical in 37% and futility in 25% of patients (Panel B).

Conclusions:
The majority of patients with mitral regurgitation referred for transcatheter mitral therapy are excluded for a variety of reasons. Clinical trials testing new transcatheter mitral valve devices should be encouraged to follow patients who are excluded to better understand optimal timing of intervention, address challenging anatomies, and ultimately improve penetrance of these novel therapies.
Abstract 16801: Papillary Muscle Tip Approximation in Repair of Ischemic Mitral Regurgitation in a Chronic Swine Model
Authors: Kalra Kanika , Zhan Moodie Samantha , Xu Dongyang , Padala Muralidhar
Published: May 2021

Introduction:
Mitral valve (MV) repair with undersized annuloplasty (UMA) for ischemic mitral regurgitation (IMR) is being abandoned in favor of valve replacement (MVR) following CTSN trial results. However, in patients with durable repair, survival and left ventricular function (LVF) were significantly better than MVR. Achieving a durable repair with UMA is challenging as it draws leaflets away from papillary muscle (PM) insertions, causing unphysiological tethering and unicuspid configuration that fails (FigA-B).

Hypothesis:
Drawing PM tips together with an approximating stitch (PMT-A) can relieve leaflet tethering and enable better repair (FigC). A chronic swine model of IMR was used to compare effects of isolated PMT-A, UMA and PMT-A+UMA on MV and LV at 3 months post surgery.

Methods:
Twenty-five farm swine underwent catheterization and occlusion of left circumflex artery, resulting in postero-lateral myocardial infarction (MI). Two months after MI, IMR severity of >2+ was confirmed on echo, and animals underwent one of the 3 repairs: PMT-A (n=6), UMA (n=8), PMT-A+UMA (n=11). Echo was performed postoperatively and repeated with MRI at 3 months (FigD). MV kinematics, coaptation geometry, and LVF were assessed.

Results:
IMR was eliminated after all repairs and did not recur through the study. Annulus continued to grow after PMT-A, but not in UMA or PMT-A+UMA group (FigE1) without increasing severity of IMR. Compared to prerepair, tenting depth was significantly reduced only in PMT-A and PMT-A+UMA groups (FigE2). Both leaflet excursion angles (diastolic minus systolic angles) increased after PMT-A, but not in other groups (FigE3-4). LV size and LVF was similar between groups, confirming that PMT-A did not perturb diastolic filling.

Conclusions:
In this model of IMR, PMT-A improved leaflet mobility, compared to isolated UMA or PMT-A+UMA. PMT-A is a simple technique that can potentially improve durability of MV repair by restoring valvular kinematics.
Abstract 16821: An ECG Derived Risk Score Predicts In-Hospital Death in Patients With COVID-19
Authors: McCullough Stephen , Goyal Parag , Krishnan Udhay , Vohra Adam , Huang Jennifer , Zhang Lisa , Choi Justin , Safford Monika M , Okin Peter M
Published: May 2021

Introduction:
COVID-19 is a respiratory syndrome with high rates of mortality, and findings from the ECG on hospital presentation have been shown to increase the odds of death. We thus hypothesized that findings from the presenting ECG could discriminate the risk of death in high risk subgroups, and sought to create an ECG risk score for death in COVID-19.

Methods:
We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics were manually abstracted from the electronic health record; ECG data were digitally extracted from the first ECG in each patient, and Bazett-corrected QT interval and ST segment deviation at the M-point (STm, in μV) were quantified in all 12 leads. Our primary outcome was death.

Results:
710 patients who presented to a large teaching hospital with COVID-19 underwent an ECG. The mean age was 63 ± 16 years, 37% were women, 62% of patients were non-white, and 56% had hypertension; 78 (11%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (OR=3.56, 95% CI 1.80-7.02, p<0.001), a right bundle branch block or intraventricular block (OR=2.73, 95% CI 1.41-5.32, p=0.003), maximal STm in V5 or V6 (STmV5V6) ≤ -50 μV (OR=3.01, 95% CI 1.41-6.41, p=0.004), STmV2 <0 μV (OR=3.41, 95% CI 1.88-6.18, p<0.001), and QTc ≥480 ms (OR=2.84, 95% CI 1.52-5.29, p=0.001) predicted death. When each variable was assigned a point value of 1, in additive fashion an ECG score=1 or ≥2 similarly predicted death (OR=4.49, 95% CI 2.17-9.25, p<0.001 and OR=11.23, 95% CI 5.27-23.93, p<0.001, respectively), and discriminated risk within high risk age groups (<60, 70-80, >80,
Figure
).

Conclusions:
A simple ECG risk score (including APCs, RBBB/IVB, STmV5V6 ≤ -50 μV, STmV2 <0 μV, and QTc ≥480 ms) on initial hospitalization predicted in hospital death in COVID-19, and further discriminated risk of death in high risk age groups.
Abstract 16822: Growth Curves Describing a Single Ventricle Population After Fontan Procedure
Authors: Runkel Bethany , Staggs Vincent , Hosey Cojocari Chelsea , Wagner Jonathan B
Published: May 2021

Introduction:
Complex single ventricle congenital heart disease (CHD) patients are subject to multiple stressors early in life that affect somatic growth. Pre-Fontan growth patterns are well-described, but post-Fontan growth has not been extensively studied in the current era. We sought to describe post-Fontan growth patterns by creating sex-specific body mass index (BMI)-for-age curves.

Hypothesis:
There is no difference in the growth of post-Fontan pediatric patients when compared to published normative data.

Methods:
A single-center, preexisting database was retrospectively queried for all patients who underwent Fontan procedure between 2006 and 2018. Patients with a genetic syndrome, a primary endocrine disorder, or significant prematurity were excluded. BMI-for-age curves were created for both male and female patients using anthropometric data extracted from the electronic medical record. Curves were then visually compared with Centers for Disease Control and Prevention (CDC) growth charts.

Results:
Of 227 patients who underwent primary Fontan operation, 37 were excluded. Of the remaining 190 patients, 59% were male. All had an extracardiac conduit, half had right-ventricular dominant CHD, and 15% had a Fontan fenestration. Median age and weight at surgery were 3.9 years and 15 kilograms, respectively. BMI curves were similar in appearance to CDC BMI-for-age growth charts, with adiposity rebound at age 6. BMI increased more rapidly in teen boys compared with girls, and a total of five patients (2.6%) had BMI values greater than 25 kg/m
2
at 16 years of age.

Conclusion:
Post-Fontan patients at our institution demonstrate BMI-for-age patterns similar to those of the general population during childhood and early adolescence, with adiposity rebound occurring at a typical age. Though excess weight gain does not completely spare patients with single ventricle CHD, overweight status appears to be less common than in the general pediatric population.
Abstract 16828: Risk of Hematopoietic Cancer in Congenital Heart Diseased Children With or Without Genetic Syndromes
Authors: Sazzad Hasan Mohammad , Liu Aihua , Guo Liming , Ganni Elie , Kaufman Jay S , Marelli Ariane J
Published: May 2021

Background:
Individuals with genetic syndromes can manifest both congenital heart disease (CHD) and cancer due to possible common underlying pathways. However, reliable risk estimates of hematopoietic cancer (HC) among children with CHD based on large population-based data are scant.

Method:
We conducted a population-based analysis to estimate the cumulative incidence of HC in a cohort of children (0-18) born between 1999 and 2017 with at least one hospitalization records of CHD diagnosis or CHD-related procedural code. The data source was the Canadian Institute for Health Informatics-Discharge Abstract Database which regularly collects hospitalization and day surgery records in all Canadian provinces except Quebec, comprising over 30 million people. Hematopoietic cancer and syndromes were both identified by hospitalization diagnoses. We used modified Kaplan-Meier curve analysis to estimate the cumulative incidences [with 95% confidence intervals (CI)] up to 18 years of age, with death as a competing risk and stratified by the binary indicator of genetic syndrome status.

Result:
We followed 92815 CHD children from birth for 921,866 person-years. In this study population,10.5% had genetic syndromes and 461 cases of HC were observed, yielding incidence rates of HC 22.5 (95% CI: 19.4-25.4) and 3.0 (2.6-3.3) per 10,000 person-years for children with and without genetic syndrome, respectively. Cumulative incidence of HC up to age 18 was 2.6% (95% CI: 2.2-2.9%) among children with a genetic syndrome, and 0.40% (0.34-0.46%) without the syndrome. It was higher in the first 6 years of life (2.1%) than the subsequent 6-years intervals up to adulthood (0.4% in 6-12 years and 0.2% in 12-18 years of age).

Conclusion:
This is the first population-based analysis documenting that genetic syndromes in CHD children are a powerful predictor of hematopoietic cancers. The finding is important in informing risk-stratified policy recommendations to protect CHD children from cancer.
Abstract 16849: Extracellular Vesicles Derived From Mesenchymal Stem Cells Protects Mice From Monocrotaline-Induced Pulmonary Hypertension and Improve Echocardiographic Parameters
Authors: Blume Corssac Giana , Teixeira Rayane , Karbasiafshar Catherine , Liang Olin D , Abid Ruhul
Published: May 2021

Introduction:
Pulmonary hypertension (PH) is a currently incurable disease with high morbidity and mortality. Treatment with extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) appeared to be effective and promising.

Objective:
We aimed at evaluating whether MSC-EVs could improve right ventricle (RV) and pulmonary artery (PA) functions in mice with PAH induced by monocrotaline (MCT).

Methods:
FVB mice (M/F – 6 weeks) received MCT injections 1x/week for 4 weeks (60mg/kg sc.) and were treated with MSCs-EVs 24 hours after each MCT injection (3x10
6
cells in 100μL PBS 1x, iv.). The experimental groups were: Control (vehicle-vehicle; n=9); MCT (MCT-vehicle; n=10); Control EVs (vehicle-EVs; n=8); MCT EVs (MCT-EVs; n=10); PA acceleration time (PAT), PA ejection time (PET) and tricuspid annular plane systolic excursion (TAPSE) were assessed by echocardiography 28 days after first MCT injection; Fulton index was used to calculate RV hypertrophy, and pulmonary vascular remodeling (WT/D) was assessed by histology.

Results:
PAT and PAT/PET were decreased by 22.6±5.7% and 15.6±4.9%, respectively, in MCT group compared to Control (p<0.01 and p<0.02). PAT was increased in Control EVs and MCT EVs groups when compared with MCT group (by 28.2±7.6%, p<0.01 and 20±6.9%, p<0.04, respectively). TAPSE (figure 1) was decreased in the MCT group compared with Control (42.9±6.7%, p<0.0001) and increased in both Control EVs (62.8±12.2%, p<0.0001) and MCT EVs (52.7±11.1%, p<0.0005) groups compared with MCT group. In addition, MCT group presented RV hypertrophy 49.4±16.5% higher than Control (p<0.03), and 29.1±10.4% higher than MCT EVs group (p<0.05). The WT/D was increased in MCT compared to Control (63.7±7.6%, p<0.0001), but decreased in Control EVs (44.9±4.6%, p<0.0001) and MCT EVs (44.3±5.4%, p<0.0001) in relation to MCT group.

Conclusion:
Treatment with MSC-EVs protects against the development of PH and improves PA and the RV function in MCT-treated mice.
Abstract 16853: Retrograde Peripheral Limb Perfusion for Formidable Femoral Arterial Access in Veno-Arterial ECMO Treatment
Authors: Gobolos Laszlo , Hogan Maurice , Kakar Vivek , Sanger Stefan , Raposo Nuno , BHATNAGAR GOPAL , Park Woosup
Published: May 2021

Introduction:
VA ECMO has emerged to a well-established therapeutic method in severe acute heart failure. In the case of peripheral ECMO placement, especially applying direct arterial cannulation, the limb perfusion is often compromised by an occlusive effect of the cannula positioned in the femoral artery. The classical proximal femoral arterial reperfusion branch provides sufficient blood flow via a small auxiliary cannula, but in patients with severe peripheral arterial vasculopathy or with significant tissue depth resulting from obesity, the placement of a peripheral arterial perfusion loop may pose a technical challenge.

Methods:
In case of emerging peripheral ischemic symptoms at femoral VA ECMO placement, ultrasound scanning of the lower limb vessels is performed. In an uncomplicated vascular situation, antegrade distal perfusion can be established. If a significant vasculopathy is present in the proximal vessels, or any further hindrances, including extreme obesity, physically not allowing a subtle perfusion cannula placement resulting from the discrepancy between the tissue depth and cannula length, retrograde peripheral perfusion could be established via the dorsal pedal artery utilising the Seldinger method. An ultrasonographic guidance is essential; hence there is sometimes no backflow present on the inserted cannula in a critically ischemic limb. Following sufficient de-airing manoeuvres, the retrograde femoral flow can be safely established; NIRS confirms the successful reperfusion in a short timeframe. If the dorsal pedal artery is not sufficient for cannulation purposes, the postmalleolar posterior tibial artery segment or the anterior tibial artery through the similarly named muscle can be utilised for cannulation purposes.

Results:
Two patients showed a pre-reperfusion calf saturation of 29% and 38%, which has increased to 61% and 64% after re-establishing the distal flow within minutes, respectively. We have experienced no complications emerging during the application of the above method.

Conclusions:
In case of peripheral vascular disease or the body habitus does not allow safe installation of an antegrade flow device, our retrograde perfusion option can save the affected limb on VA ECMO therapy.
Abstract 16854: Left Atrial Dysfunction and Prediction of Atrial Fibrillation in LMNA Cardiomyopathy
Authors: Tremblay Gravel Maxime , Parikh Victoria , Kawano Yumeko , Picard Kermshlise , Tucker Brianna , Haddad Francois , Lakdawala Neal K , Wheeler Matthew T
Published: May 2021

Introduction:
LMNA
cardiomyopathy is characterized by a high incidence of atrial fibrillation (AF) and an increased risk for AF-related stroke. AF commonly occurs before apparent cardiomyopathy, and the ability to predict its incidence in asymptomatic
LMNA
mutation carriers is limited. We sought to evaluate the presence of echocardiographic features specific to
LMNA
and whether they predict AF incidence.

Methods:
Patients harboring
LMNA
mutations (n=77) from two referrals centers between 2000 and 2017 were retrospectively included. Comparator groups included patients with
TTN
cardiomyopathy (n=35) and healthy subjects (n=36). Echocardiograms at first clinical contact were analyzed for routine metrics and LA strain and related to incident AF.

Results:
Patients with
LMNA
mutations were assessed at median age 47 years (IQR, 32-62) with median LVEF 51% (41-61). In
LMNA
patients with LVEF ≥55% (n=20) and healthy subjects matched for LVEF, LA contractile strain was lower in
LMNA
patients (-10% vs -16%, respectively;
P
= 0.047), whereas other parameters did not significantly differ (Figure, panel A). Comparison of LVEF-matched
LMNA
and
TTN
cardiomyopathy patients showed LA contractile strain as the only distinguishing feature (-5.8% vs -12.8%, respectively;
P
= 0.01) (Figure, panel B).
LMNA
patients without previous AF (n=35) were followed for a total of 133 patient-years during which 11 (31%) developed AF. In Cox regressions adjusted for clinical and echocardiographic variables, decreased LA contractile strain (<
Abstract 16855: NOX4 NADPH Oxidase Mediates Diastolic Dysfunction in Stress Cardiomyopathy via Regulation of Inflammation and Fibrosis
Authors: Vendrov Aleksandr E , Xiao Han , Lozhkin Andrey , Madamanchi Nageswara R , Zhang Youyi , Runge Marschall
Published: May 2021

Acute sympathetic stress in adults results in catecholamine overload and often leads to development of stress cardiomyopathy complicated by long-lasting diastolic dysfunction. We previously reported that activation of β-adrenergic signaling in the heart increases reactive oxygen species-mediated inflammasome activation and IL-18 release, inducing myocardial inflammation, fibrosis, and dysfunction. Here we tested the hypothesis that NOX4 NADPH oxidase is a primary mediator of myocardial inflammation and diastolic dysfunction in the setting of acute stress. Acute stress in wild-type and mice with cardiomyocyte (CM)-specific
Nox4
deletion (
Nox4
CM-/-
) was induced with a single dose of β-adrenergic receptor agonist isoproterenol (ISO; 5 mg/kg) injection. After 3 days, ISO-treated wild-type mice had higher myocardial H
2
O
2
, inflammasome activation and IL-1β, IL-18, IL-6, CCL2, and TNF-α levels and enhanced myocardial interstitial macrophage infiltration compared with vehicle-treated or
Nox4
CM-/-
mice (p<0.001). Wild-type mice left ventricles had increased presence of activated fibroblasts (periostin
+
) and myofibroblasts (α-actin-2
+
) and significantly higher interstitial collagen deposition compared with
Nox4
CM-/-
mice 7 days post-ISO. Assessment of left ventricular function showed significantly increased mitral valve E, decreased deceleration time, decreased tissue Doppler E’ and increased E/E’ without changes in ejection fraction and end systolic or diastolic volumes, suggesting restrictive pattern of diastolic dysfunction with increased filling pressure in wild-type compared with control or
Nox4
CM-/-
mice. ISO treatment of ventricular CMs isolated from wild-type mice significantly increased levels of H
2
O
2
and expression of NLRP3 and cleaved caspase-1 and IL-18 as compared with
Nox4
-deficient or wild-type CMs pretreated with NOX4/NOX1 inhibitor GKT137831. These data suggest that NOX4 NADPH oxidase is a critical mediator of CM sympathetic overstimulation inducing inflammasome activation and cytokine release, myocardial inflammation, and fibrosis, resulting in impaired diastolic function. Inhibiting myocardial NOX4 during acute sympathetic stress may be beneficial to preserve cardiac function.
Abstract 16866: Artificial Neural Networks as Prediction Tools: Predicting Permanent Pacemaker Implantation (PPMI) in Patients Undergoing Transcatheter Aortic Valve Replacement (TAVR) Utilizing a Shallow Feed-Forward Neural Network
Authors: Parulkar Anshul , Sheikh Wasiq , Ahmed Malik B , Singal Sachit , Lima Fabio V , Sharma Esseim , Parulkar Sanchita S , Chu Antony F
Published: May 2021

Introduction:
Despite increasing TAVR volumes after a series of recent favorable clinical trials, adverse outcomes remain frequent, including new or worsened conduction disease requiring PPMI, life-threatening bleeding, paravalvular leak, and stroke. PPMI carries a reported incidence ranging from 8.8-14.6% and is of particular concern given the increased risk of mortality and rehospitalization. New techniques in signal processing may inform novel statistical approaches to better predict PPMI from a set of clinical variables. Artificial neural networks (ANN) comprise a family of algorithms that utilize non-linear activation functions to enable improved prediction of PPMI in TAVR patients.

Objective:
To examine the predictive utility of a feed-forward neural network in classifying PPM implantation in patients undergoing TAVR.

Methods:
Pre and post-operative data from a single institution were collected for all patients undergoing TAVR without prior pacemaker implantation from January 2016 to December 2019. Data was imported into Matlab, partitioned into training, validation, and test sets, and processed in a two-layer feed-forward neural network with sigmoid hidden and softmax output neurons. Performance data included confusion matrices and receiver operating characteristic (ROC) curves.

Results:
The total sample size for the cohort was 513 patients with a PPMI incidence of 8.6%. The training set contained 40 variables and 359 patients, while the validation and test sets contained 77 patients each. The final optimized model showed cross-entropy of 0.25 with 6 iterations and an area under ROC curve of 0.73. Overall model accuracy was 92.7% in the validation set and 88.3% in the test set.

Conclusions:
In summary, we show that feed-forward neural networks can be useful in processing multiple interdependent variables to aid clinical prediction. Our network demonstrated modest discriminatory ability in predicting the need for PPMI after TAVR.
Abstract 16868: Conditional Renal Tubule Specific Deletion of
KDM6a
Gene Causes Hypertension in Mice
Authors: Han Xiaobin , Akinseye Leah , Chen Kai , Sun Zhongjie
Published: May 2021

Objective:
Aging-associated downregulation of Klotho is partly due to epigenetic upregulation of H3K27me3 in the kidney. The purpose of this study is to investigate the potential role of KDM6a, a demethylase of histone 3 lysine (K) 27 trimethylation (H3K27me3), in the regulation of blood pressure and explore the related molecular pathways that may influence the kidney function during aging.

Methods and Results:
Wild type and Ksp-Cre/KDM6a-floxed mice were divided into vehicle control and tamoxifen (10 mg/kg/mouse/7days) treated cohorts (WT mice: KDM6a floxed or Ksp-Cre only and Ksp-Cre/KDM6a -loxed mice). Blood pressure (BP) was measured by tail cuff method and confirmed by carotid artery cannulation at the end of study. Deletion of the
KDM6a
gene (KDM6a-cKO) significantly increased BP at day 7. BP remained elevated throughout the study. We found that the H3K27me3 level was significantly increased in the kidneys of KDM6a-cKO mice compared to control mice confirming that KDM6a is an important H3K27 demethylase in the control of methylation levels in the kidney. Elevation of BP was likely due to upregulation of the Na
+
:K
+
:2Cl
-
co-transporter (NKCC2) in the thick ascending limb of Henle's loop and NaCl co-transporter (NCC) in the distal convoluted tubule confirmed by qPCR and immunohistochemistry. Accordingly, we found that the urine sodium level was decreased in KDM6a-cKO mice compared to KDM6a-con mice. We showed that expression of aquaporin 2 (AQP2) was increased in the kidney of KDM6a-cKO mice, suggesting that AQP2 may also contribute to increased BP through modulation of body water homeostasis. Furthermore, we demonstrated that expression of Klotho was downregulated by 50%, which blocked FGFR1/Klotho/ERK signaling in the kidney of KDM6a-cKO mice. Notably, expression of aging markers including p53, p21, and p16 was significantly increased in the kidney of KDM6a-cKO mice, indicating that deletion of KDM6a in the renal tubule results in kidney aging.

Conclusion:
KDM6A is essential to the maintenance of normal kidney function and blood pressure. Renal-specific KDM6A knockout-induced hypertension is likely attributed to increased H3K27me3 levels and the resultant dowregulation of Klotho gene expression which impairs the FGFR1/Klotho/ERK signaling.
Abstract 16874: Papillary Muscle Approximation Relieves Tethering Forces and Improves Systolic Mitral Valve Kinematics in an Ex-Vivo Model of Functional Mitral Regurgitation
Authors: Zhan Moodie Samantha , Sreerangathama Suresh Kirthana , Xu Dongyang , Padala Muralidhar
Published: May 2021

Introduction:
Undersizing annuloplasty (UA), which is the current standard to correct functional mitral regurgitation (FMR) is effective, but the resulting unphysiological systolic geometry causes FMR recurrence. On the other hand, papillary muscle approximation (PMA), a sub-annular technique, reduces inter-papillary separation and tethering forces, mobilizing the leaflets.

Objective:
To investigate the effect of PMA on mitral valve tethering forces and systolic coaptation geometry, compared to UA.

Methods:
A left heart model with pig mitral valves was used to create a tethered mitral valve geometry and to perform surgical repairs (
Fig. A
). Mitral valve geometry, and marginal and strut chordal forces acting on both leaflets were measured. Eight individual pig valves (n=8) were studied, with hemodynamic and mechanics data acquired at normal geometry (BASELINE) (
Fig. B)
, after tethering (FMR) (
Fig. C)
, undersizing annuloplasty (UA) to size 34 (Edwards Lifesciences Physio ring) (
Fig. D)
, papillary muscle approximation (PMA), and combination (PMA+UA).

Results:
Tenting height, which increased after FMR, was least with PMA (0.46 cm± 0.21) and PMA+UA (0.50± 0.16) but remained significantly high with UA (0.73±0.21, p=0.03) (
Fig. E
). Excursion angles of anterior and posterior leaflets were restored close to baseline values after PMA and PMA+UA but remained significantly tethered after UA (
Fig. F & G
). Tethering of the valve increased the strut and marginal chordae forces from 0.47 and 0.14 N to 0.89 and 0.21 N, an increase of 89% and 50% respectively. PMA reduced the forces by 47% and 34%, and PMA+UA reducing it by 43% and 34%to 0.51 while UA only reduced it by 15% and 20% (
Fig. H & I
).

Conclusion:
PMA significantly reduced the tethering forces on both marginal and strut chordae of both leaflets. Decrease in tethering forces restored the physiologically favorable valve geometry enabling better leaflet mobility and coaptation compared to UA.
Abstract 16884: Evaluating the Effectiveness of Atrial Fibrillation Ablation Guided by Spatiotemporal Electrogram Dispersion
Authors: Liu Brian , Nunez-Garcia Arismendy , Tran Cao , Wu Michael
Published: May 2021

Introduction:
Catheter ablation of atrial fibrillation (AF) guided by spatiotemporal dispersion (SD) of electrograms has been proposed as an ablation strategy to treat patients with persistent AF. However, external validation of this technique is lacking. Here we report a single center experience using ablation by SD.

Hypothesis:
Targeting regions with SD is associated with a high rate of termination and favorable freedom from AF among patients with persistent AF.

Methods:
Patients with persistent AF who underwent SD from November 2018 to January 2020 were included in this study. All patients underwent pulmonary vein isolation (PVI) in addition to targeting areas of SD. Lesions on areas of electrogram dispersion were anchored to the PVI or to mitral or posterior wall lines where appropriate. EKG, Holter, event monitors or device interrogations were obtained at 3 and 6 months to assess for arrhythmia recurrence.

Results:
44 patients met the inclusion criteria and were included in the study. The patients had a mean age of 69±8 years and were 68 % male. The prevalence of comorbidities was as follows: hypertension (89%), diabetes (21%), OSA (37%) and CAD (26%). Average CHADSVASC score was 2.9±1.4, LVEF was 53±11% and left atrium (LA) diameter was 5.2±1 cm. The recurrence rate of AF at 6 months was 14% whereas the recurrence of atrial tachycardia was 20%. Acute AF termination was observed in 73% of the patients. Termination to sinus occurred in 38% of the patients and the remaining terminated to atrial tachycardia which was subsequently ablated to sinus. The mean procedure duration was 240±90 minutes. Univariate analysis showed recurrence was associated with LA diameter (r=.52; p<.001). No recurrences were observed among patients with a LA diameter < 5 cm. Termination rates were higher among patients with LA diameter < 5 cm when compared to LA diameter ≥ 5 cm. However, it did not reach statistical significance (80% vs. 60%; p=.21).

Conclusions:
The target of electrograms with SD during AF ablation added to PVI was associated with a high termination rate and a good freedom from AF recurrence at 6 months. The ideal candidate for this procedure may be those with LA diameter < 5 cm among persistent AF. The long-term efficacy of this technique merits further studies in larger populations.