bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10427: Length of Stay After Atrial Fibrillation Ablation in a U.S. Ambulatory Surgical Setting Compared to a Hospital Setting
Authors: Zagrodzky William , Zagrodzky Jason , Kueffer Fred , Kulstad Erik B
Published: March 2022

Introduction:
Atrial ablation for the treatment of atrial fibrillation has traditionally been performed in the hospital setting. Recently, the Centers for Medicare and Medicaid Services (CMS) announced the Hospitals Without Walls program, allowing ambulatory surgery centers (ASCs) to conduct procedures such as atrial ablations. As a result, the first cases of ablations in an ASC have recently been completed. This study aimed to compare patient length of stay (LOS) and between the ASC setting to a traditional hospital setting.

Hypothesis:
LOS in the ASC setting is shorter than in the traditional hospital.

Methods:
Data from all patients treated with cryoballoon pulmonary vein isolation (PVI) in a single ASC were analyzed. A random sample of patients treated by the same provider during the same timeframe in the hospital setting were then acquired and compared. Procedural approaches were similar, with transeptal puncture performed under intracardiac echo, contrast venography and pressure waveform analysis performed prior to ablation to ensure good venous seal. No 3D mapping was used at either site. Intraprocedural emergency protocols were established prior to ablations.

Results:
A total of 13 patients received treatment in the ASC, with a mean age of 71 ± 8 years, 38% female, 9 patients had paroxysmal atrial fibrillation and 4 persistent atrial fibrillation. The mean number of cryoablation applications per pulmonary vein was 1.4 ± 0.7 with average application duration of 187 ± 37 seconds. The mean procedural duration was 52 ± 10 minutes and mean time in the ASC was 5.4 ± 1.5 hours. No acute adverse events occurred; however, one patient later presented with a sore throat and a groin hematoma without active bleeding or pseudoaneurysm. A total of 13 patients were analyzed in the hospital setting. Mean time in the hospital was longer than in the ASC (13.0 ± 13.0 hours, p<0.01). This is inclusive of 2 patients staying overnight. The mean hospital length of stay was also longer than in the ASC for the 11 patients with same day discharge (8.2 ± 6.6 hours, p<0.01).

Conclusions:
Cryoballoon PVI performed in an ASC setting resulted in a shorter overall length of stay than in the traditional hospital setting, with no acute complications occurring.
Abstract 10428: Bad Fall, Good Catch: Diagnosing a Rare Condition Presenting as Acute Coronary Syndrome
Authors: Haghighat Leila , Hamilton Barbara , Urisman Anatoly , Beygui Ramin , Tolstrup Kirsten
Published: March 2022

A 72 year-old mountain bicyclist suffered a biking accident. The following week, he presented to the emergency room with abdominal pain, where he was treated for superior mesenteric artery thrombosis and new-onset atrial fibrillation. Two months later, he presented with intermittent left scapular pain that radiated to the chest. Pharmacologic stress testing revealed a large reversible perfusion defect in the anterior wall with an ejection fraction of 41%. Left heart catheterization showed narrowing of the distal left main coronary artery and the proximal left anterior descending (LAD) and circumflex arteries, by what appeared to be external compression. Follow-up CT angiogram demonstrated two sinus of Valsalva aneurysms (SOVA) originating from the left and right coronary cusps. A transesophageal echocardiogram confirmed these findings and showed tremendous thrombus within the larger aneurysm. The patient was admitted to cardiothoracic surgery. Troponin was elevated to 0.16 μg/L, with EKG showing 1 mm ST-segment depressions in V4-6, prompting treatment for a non-ST segment myocardial infarction. He underwent complex surgery involving thrombus extraction and closure of the SOVA with pericardial patch repair, and coronary artery bypass grafting of the LAD and obtuse marginal arteries. After a prolonged ICU course in which the patient was managed for cardiogenic shock, he was discharged to a hospital equipped with a rehabilitation facility. Unfortunately, he developed profound lactic acidosis from ischemic bowel and passed away. SOVA are rare lesions that arise from congenital or acquired etiologies, such as this patient’s biking accident. Multi-modality imaging is important for quantifying size and anatomy. Unruptured SOVA can present as embolic phenomenon from thrombus, valvular regurgitation, or chest pain from compression of the coronary arteries. Rupture is a highly morbid condition, and so urgent referral to cardiothoracic surgery is recommended.
Abstract 10430: Characteristics and Outcomes Surrounding Out-of-Hospital Cardiac Arrests Due to Drug Overdose in the United States
Authors: Shekhar Aditya C , Adabag Selcuk
Published: March 2022

Introduction:
Sudden deaths due to drug overdose have increased significantly in the US in the last decade. However, little is known about the characteristics and outcomes of out-of-hospital arrests in these patients. Two important factors that predict survival include the rates of pre-EMS CPR and return of spontaneous circulation (ROSC) achievement.

Methods:
We assessed the circumstances and outcomes of out-of-hospital arrests due to drug overdose, from January 2017 to December 2019 using a nationwide database of EMS calls in the United States (NEMSIS). The comparison group included patients documented to have had an out-of-hospital cardiac arrest due to presumed cardiac causes. Special attention was paid to whether or not pre-EMS CPR was performed, the first monitored arrest rhythm, and whether ROSC was achieved.

Results:
There were a total of 10,094 out-of-hospital cardiac arrests that were determined by EMS to have been caused by a drug overdose and 189,031 that were presumed to be due to cardiac causes (Table 1). Rates of pre-EMS CPR were similar for both overdose-related arrests (55.0%) and presumed cardiac-related arrests (54.5%) (p=0.35). First monitored rhythms that were shockable were significantly more common in presumed cardiac-related arrests (17.7 %) than overdose-related arrests (5.2%) (p<0.001). Despite this, ROSC achievement was more common in overdose-related arrests (30.3%) than presumed cardiac-related arrests (26.0%) (p<0.001).

Conclusions:
Out-of-hospital cardiac arrests due to drug overdose are less likely to involve shockable first monitored arrest rhythms but are more likely to result in ROSC achievement than those due to presumed cardiac causes. Further studies should more closely examine factors surrounding cardiac arrests due to drug overdose.
Abstract 10435: A Plea for Inclusion of Surface Echocardiography for Acute Coronary Syndrome in the Advanced Cardiac Life Support Algorithm
Authors: WILBEN VIJU , Kanchi Muralidhar , Kumar Vinil , Kumar Srinath
Published: March 2022

Background:
The AHA/ACC guidelines algorithm for Acute Coronary Syndrome (ACS) does not include echocardiographic evaluation in the assessment of chest pain. Such patients may be subjected to interventions based on ECG leading invasive procedures which may prove unnecessary. This study was performed to determine if a bedside echocardiography would help identify the conditions that do not need intervention and might possibly change the treatment pathway at the right time.

Methods:
In a prospective observational study design, adult patients presenting to acute emergency care with chest pain were included in the study. Patients exhibiting a significant ST change on a 12-lead ECG were subjected to bedside echocardiography, i.e. 2D transthoracic echocardiography (2D-TTE) The findings of echocardiography were correlated with ECG and coronary angiography for possible percutaneous coronary intervention.

Results:
Among the 385 patients in the study, 312 suffered acute coronary syndrome. In 18.7% patients presented to acute emergency care with chest pain, ST-T changes and were found to have causes other than ACS; and bedside echocardiography (2D-TTE) was able to identify 90.4% of those cases. From this study we conclude that bedside echocardiography had high specificity (90.4%) and sensitivity (97.43%) in identifying regional wall motion abnormality (RWMA) due to ACS and exclude non-ischemic causes of chest pain.

Conclusion:
Bedside echocardiography is recommended in patients with chest pain and ST-segment abnormality to avoid unnecessary delay in diagnosis and invasive interventions in non-acute coronary syndrome (ACS). Hence it is reasonable to include bedside echocardiography in either box 3 or 4 in the ACS algorithm.
Abstract 10459: Adenosine versus Diltiazem in Stable Supraventricular Tachycardia Unresponsive to Vagal Maneuver
Authors: P R Nithin , WILBEN VIJU , Kumar Vinil , Kanchi Muralidhar
Published: March 2022

Introduction:
The treatment of stable supraventricular tachycardia (SVT) in the emergency department includes intravenous adenosine. There is evidence to show that calcium channel blockers such as diltiazem have a better conversion rate. This study was conducted to determine the relative effectiveness and to examine the adverse effects of these drugs on converting stable SVT into sinus rhythm.

Methods:
A prospective randomized controlled study with one group receiving an intravenous bolus dose of 6mg adenosine followed by 12mg if conversion not achieved, and followed by diltiazem if not reverted, and other group receiving diltiazem 0.25mg/kg IV followed by 0.35mg/kg if conversion is not achieved which was followed by continuous infusion. Heart rate and blood pressures were continuously monitored for 1-hour post-conversion with monitoring of other adverse events results: A total of 52 patients with stable SVT were enrolled and were randomized into two groups. Of these 26 patients were given IV Adenosine in one arm and 26 patients were given IV Diltiazem. The conversion rates with adenosine 76.9% were statistically lesser than the diltiazem group 100% with the statistically significant p value of 0.023. The mean change in the blood pressures in either group was statistically insignificant and also the adverse events in either group had no significance.

Conclusion:
Calcium channel blockers such as diltiazem may be superior to adenosine in the emergency department in the treatment of stable SVT. In this study IV Diltiazem had better conversion rates than the IV adenosine bolus with minimal adverse events. Hence calcium channel blockers are found to be better, safe, and cost-effective in converting stable SVT.
Abstract 10460: Urinary Fatty Acid Binding Protein 1 is a Biomarker for Impaired Proximal Tubular Protein Reabsorption and is Synergistically Enhanced by Concurrent Liver Injury
Authors: Kawakami Ryo , Matsui Miki , Konno Ayumu , Kaneko Ryosuke , Sunaga Hiroaki , Hanaoka Hirofumi , Obokata Masaru , Matsui Hiroki , Koitabashi Norimichi , Hirai Hirokazu , Kurabayashi Masahiko , Iso Tatsuya
Published: March 2022

Introduction:
Urinary fatty acid binding protein 1 (FABP1, also known as liver-type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs).

Methods and Results:
Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1-deficient mice with liver-specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver-derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT-R) either in a hepatocyte- or PTEC-specific manner, or both. Upon diphtheria toxin (DT) administration, massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion.

Conclusions:
Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver-derived FABP1 through a megalin-mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function.
Abstract 10462: Increased Bone Morphogenetic Protein 10 Activity is Associated with Increased Right Atrial Wall Stress and Disease Severity in Pulmonary Hypertension
Authors: Llucià-Valldeperas Aida , Van Wezenbeek Jessie , Groeneveldt Joanne A , Sanchez-Duffhues Gonzalo , Smal Rowan , Pan Xiaoke , vonk noordegraaf anton , Bogaard Harm J , Goumans Marie Jose , De Man Frances S
Published: March 2022

Background:
Pulmonary Hypertension (PH) is characterized by increased right atrial (RA) stretch and pressure. The major predisposing risk factor for PH involves mutations in bone morphogenetic protein (BMP) receptor 2 (BMPR2), for which BMP9 and BMP10 are ligands. In adults, BMP10 is produced by RA cardiomyocytes, however, the mechanism to BMP10 release is unknown. We hypothesize that RA wall stress may be a trigger for BMP10 secretion.

Methods:
We determined BMP10 and BMP9 levels in plasma samples from PH-patients (22 idiopathic pulmonary arterial hypertension (iPAH), 14 hereditary PAH (hPAH) and 11 chronic thromboembolic PH (CTEPH)) and 16 controls by ELISA. To study BMP10 and BMP9 activity, we exposed endothelial cells to 10% serum and analyzed BMP-activity as read out of the BRE-luciferase reporter assay. Serum was incubated with trap antibodies: anti-BMP9 to inhibit BMP9 ligand, and ALK1-Fc to inhibit both BMP9 and BMP10 ligands. BMP9 and BMP10 activity were deducted from the difference
vs
baseline and BMP9-activity, respectively.

Results:
Circulating BMP10 levels were higher in PH-patients: 16.5 [9.5-69.7] pg/mL in iPAH, 17.1 [1.4-113.4] pg/mL in hPAH and 37.8 [10.7-87.1] pg/mL in CTEPH,
vs
6.1 [0-8.7] pg/mL in controls (A). No differences were observed in BMP9 levels (B). BMP10 and BMP9 activity appeared lower in iPAH, only a trend was seen in BMP9-activity in iPAH
vs
hPAH (C,D). Next, we divided the PH cohort on median BMP10-activity. Higher active BMP10 in PH was associated with an increase in RA volume and pressure, and reduced RA compliance (E). Further, higher BMP10-activity in PH-patients was associated with worse disease status, shown by worse right ventricular function, lower stroke volume and increased NTproBNP (F).

Conclusions:
BMP10 circulating levels were increased in PH, whereas no difference in circulating BMP10-activity was observed. High BMP10-activity was associated with increased RA wall stress and disease severity in PH-patients.
Abstract 10465: Prevalence, Predictors and Outcomes of Pericardial Tamponade In Influenza Virus Infection: A Nationwide Inpatient Analysis
Authors: Desai Rupak , Gandhi Zainab , Neha , , Rahim Naima , Chhina Arashpreet , Raju Athul Raj , Jnaneswaran Geethu , Gawde Rashmi , Jain Akhil
Published: March 2022

Introduction:
Pericardial Tamponade (PT) is a rare, yet fatal complication of influenza virus infection (IVI). Considering the pertaining data remaining limited to case reports, we evaluated the frequency of PT and associated demographic variations, predictors and outcomes of PT in IVI using national multicenter datasets.

Methods:
We identified adult IVI admissions complicated by PT using National Inpatient Sample (2015Oct-2017) and relevant ICD-10 codes. Primary outcomes for frequency and predictors of PT in IVI and secondary outcomes of all-cause in-hospital mortality and patient discharge were analyzed. The multivariable analysis was performed adjusting for confounders to assess the independent predictors of PT in IVI.

Results:
Of 380,730 admissions with IVI, 130 (0.03%) patients experienced PT. Overall, young, female, non-white patients more frequently suffered PT during admissions for IVI. Compared to IVI admissions without PT, admissions with PT had significantly nearly six times higher all-cause mortality (23.1% v. 3.4 %, p<0.001). IVI-PT cohort had fewer routine discharges compared to those without PT (30.8% vs. 59.8%, p<0.001). IVI-related admissions who were Hispanics (OR 2.85 [CI 1.66-4.89] p<0.001) in highest income quartile (OR 4.02 [CI 2.40-6.74] p<0.001) with comorbidities like metastatic cancer(OR 6.60 [CI 3.70-11.79] p<0.001), peripheral vascular disease (OR 4.69 [CI 2.65-8.29] p<0.001), prior radiation therapy (OR 3.66 [CI 1.38-9.70] p=0.009), congestive heart failure (OR 3.65 [CI 2.41-5.52] p<0.001), pulmonary circulation disease (OR 3.23 [CI 1.30-8.02] p=0.011), and obesity (OR 2.41 [CI 1.56-3.72] p<0.001) had higher odds of developing PT
(Figure 1)
.

Conclusions:
In this multicenter analysis, we found IVI-related admissions among non-whites, patients from high-income quartile with cardiometabolic and oncologic comorbidities had a higher prediction of PT on multivariate analysis.
Abstract 10472: Impact of Polygenic Risk Scoring for Coronary Artery Disease on the Incidence of Chronic Kidney Disease and Acute Kidney Injury in Patients Undergoing Off Pump Coronary Artery Bypass Surgery
Authors: Kanchi Muralidhar , Vedam Ramprasad , Mishra Sangamitra , Menon Ramesh , Anjanappa Ram Murthy
Published: March 2022

Background:
This study aims to determine the applicability of genome-wide polygenic risk score (GPS
CAD
) to patients who underwent off-pump (OP-CABG) in South-Asian population and influence, on kidney dysfunction and incidence of AKI in OP-CABG.

Methods:
Study participants were categorized into four cohorts: 1) patients with normal renal function undergoing OP-CABG (eGFR>60ml/min/m
2
) (n=754; AKI
-
81, Non-AKI-673); 2)patients with renal dysfunction (eGFR<60ml/min/m
2
; not needing dialysis) undergoing OP-CABG (n=263; AKI-169, non-AKI-89); 3) patients with renal dysfunction with no symptomatic/known heart disease (n=92);4) control population (with normal kidney function, without symptomatic/known heart disease) (n=826). Genotyping was performed using Infinium Global Screening Array-24 v3.0 BeadChip from Illumina, which included 6,54,027 markers. The genotype data were imputed using the GenomeAsia reference panel and GPS
CAD
was determined. The GPS
CAD
was applied to all patients in the cohort. The following were determined (i) relationship between GPS
CAD
and CAD (ii) association between GPS
CAD
and incidence of preoperative renal dysfunction (iii) influence of GPS
CAD
on development of postoperative AKI and (iv) influence of a composite genetic predisposition to AKI in OP-CABG and GPS
CAD
on the surgical outcome.

Results:
The GPS
CAD
was generated for all samples in the four groups and was binned into 10 groups (deciles), in the ascending order of GPS
CAD.
The first decile (lowest GPS
CAD
bin) comprised ~60% of healthy controls, and 22% group A, 11% group B, and 7 % group C.
.
No difference was observed in GPS
CAD
between AKI and non-AKI samples belonging to group A.

Conclusions:
In summary, our results suggest no impact of GPS
CAD
on the presence of kidney dysfunction and incidence of AKI after off-pump CABG.
Abstract 10474: The Bet Protein Inhibitor Apabetalone Rescues Diabetes Induced Impairment of Angiogenic Response
Authors: Mohammed Shafeeq Ahmed A , Albiero Mattia , Ambrosini Samuele , Gergely Karsai , Wenzl Florian , Gorica Era , Calderone Vincenzo , Madeddu Paolo , Spinetti Gaia , Luscher Thomas F , Costantino Sarah , Fadini Gian P , Paneni Francesco
Published: March 2022

Introduction:
Therapeutic modulation of blood vessel growth is a promising therapeutic strategy for the prevention of limb ischemia in diabetic (DM) patients with peripheral artery disease (PAD). Epigenetic changes, namely posttranslational histone modifications, participate in angiogenic response suggesting that chromatin-modifying drugs could be beneficial in this setting. Apabetalone (APA), a selective inhibitor of bromodomain (BRD) and extra-terminal (BET) proteins, prevents BRD4 interactions with chromatin thus modulating transcriptional programs in different organs.

Hypothesis:
We sought to investigate whether APA affects angiogenic response in diabetes.

Methods:
Primary human aortic endothelial cells (HAECs) were exposed to normal glucose (NG, 5 mM) or high glucose (HG, 20 mM) for 48 hours in presence of RVX-208 (20μM) or vehicle (DMSO). Streptozotocin-induced diabetic mice were orally treated with APA or vehicle for 5 days. Hindlimb ischemia was induced in diabetic mice and blood flow recovery analyzed at 30 minutes, 7, & 14 days by laser Doppler imaging. Gastrocnemius muscle samples from patients with and without diabetes were employed to translate our experimental findings.

Results:
APA restored tube formation and migration in human endothelial aortic cells (HAECs) exposed to HG levels. Expression profiling of angiogenesis genes showed that APA prevents HG-induced upregulation of the anti-angiogenic molecule thrombospondin (THBS1). ChIP-seq and chromatin immunoprecipitation (ChIP) assays in HG-treated HAECs showed the enrichment of both BRD4 and active regulatory marks (H3K27ac) on THBS1 promoter, whereas BRD4 inhibition by APA prevented chromatin accessibility and THBS1 transcription. Mechanistically, we show that THBS1 inhibits angiogenesis by suppressing VEGFA signaling, while APA prevents these detrimental changes. In diabetic mice with hindlimb ischemia, epigenetic editing by APA restored THSB1/VEGFA axis thus improving limb vascularization and perfusion. Finally, epigenetic regulation of THSB1 by BRD4/H3K27ac was also reported in DM patients with PAD as compared to non-diabetic controls.

Conclusion:
Our findings set the stage for clinical trials testing APA in DM patients with PAD.
Abstract 10479: Genome Wide Association Study For Acute Kidney Injury In Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery
Authors: Kanchi Muralidhar , Menon Ramesh , Mishra Sangamitra , Vedam Ramprasad
Published: March 2022

Introduction:
In this study, we evaluated the genetic predisposition to AKI using genome-wide association study (GWAS) in patients undergoing elective off-pump-CABG (OP-CABG).

Methods:
Patients of South Asian ancestry were categorized into four cohorts as follows: (A) patients with normal renal function undergoing OP-CABG (eGFR>60ml/min/m2) (n=754; AKI
-
81, Non-AKI-673); (B) patients with renal dysfunction (eGFR<60ml/min/m2; not needing dialysis) undergoing OP-CABG (n=263; AKI-169, non-AKI-89); (C) patients with renal dysfunction with no symptomatic/known heart disease (n=92); (D) age-matched healthy control population (with normal kidney function, without symptomatic/known heart disease) (n=826). Renal function was considered to be normal, if the serum creatinine was less than 1.3mg% and/or estimated glomerular filtration rate was greater than 60ml/min/1.7 m
2
. Genotyping was performed using Infinium Global Screening Array-24 v3.0 BeadChip from Illumina, which included 6,54,027 markers. GWAS analysis was performed using age, genders and top10 principal components as covariates using logistic regression using PLINK 2.0. Postoperative AKI was defined based on Kidney Disease Improving Global Outcomes guidelines.

Results:
There were 754 participants with good renal function undergoing OP-CABG; among them, 81 subjects developed AKI postoperatively. The GWAS analysis revealed 607 markers with a suggestive significance p-value threshold of 1e-4. A modest signal was observed on chromosome 11 region, covering genes such as COX8A, NAA40, RCOR. The gene-based test in FUMA annotation revealed genes, MARCOD2, CNTN4, MAGI2 etc. as top hits. However, none of the markers remained significant after multiple testing corrections using Bonferroni and Benjamini-Hochberg.

Conclusions:
The GWAS revealed an association signal on chromosome 11, which is suggestive and needs to be pursued further in a larger sample set.
Abstract 10486: Single-Beat Estimation Right Ventricular End Diastolic Pressure Relationship
Authors: Oakland Hannah , Sugeng Lissa , Joseph Phillip , Amendola Ray , Crandall Ian , Raza Amjad , Izzi Daniel , Zalik Felicia , Elassal Ahmed , Heerdt Paul M , Singh Inderjit
Published: March 2022

Introduction:
An abnormal right ventricular (RV) end-diastolic pressure-volume relationship (EDPVR) is an early marker of poor prognosis in pulmonary arterial hypertension (PAH). Prior studies assessing RV diastolic impairment utilized pressure (P) measured at right heart catheterization (RHC) and non-simultaneous volume (V) measured by cardiac magnetic resonance imaging (cMRI), which serves as the current reference standard for V. Our aims were: (a) to validate a single-beat (SB) method to assess RV EDPVR in an animal model against multi-beat (MB) measurements during preload variation, and (b) to use V obtained via transthoracic 3D echocardiography (3DE) during simultaneous RHC.

Methods:
In six anesthetized swine under an Institutional Animal Care & Use Committee-approved protocol, a SB method was used to derive EDPVR as V
15
, the previously described predicted ventricular V at a theoretical EDP of 15 mmHg. A multi-beat (MB) reference EDPVR was defined using conductance/micromanometer catheter-measured RVP and V during preload variation. The V
15
value derived from the SB method was compared by Bland-Altman analysis to that defined by the reference EDPVR. Clinically, the SB method was applied to 13 patients with PAH and 10 age- and gender-matched controls who underwent RHC with simultaneous transthoracic 3DE. V
15
values between groups were compared by t-test.

Results:
In the animal model there was strong correlation between MB and SB estimates of V
15
(r=0.95; p<0.0001) with acceptable accuracy and precision (bias -4.2±6.1 mL, overall error 8.4%). Consistent with previous reports using cMRI, PAH patients exhibited greater V
15
(166±43 mL vs. 131±30 mL; p=0.04)
(Figure 1)
.

Conclusion:
This study demonstrates validity of a SB assessment of RV EDPVR using data obtained from transthoracic 3DE performed during RHC, obviating the need for non-simultaneous cMRI. Further studies are needed to examine SB assessment of RV EDPVR across the spectrum of PH phenotypes.
Abstract 10487: Right Thoracotomy versus Conventional Median Sternotomy in Redo Cardiac Surgery: A 10-Year Single-Centre Experience
Authors: Ng Yin Ling Clarissa , Chacko Jacob , Bleetman David , Khan Habib , Whitaker Donald , Deshpande Ranjit , Wendler Olaf , Baghai Max
Published: March 2022

Introduction:
Minimally invasive cardiac surgery (MICS) has been gaining popularity over conventional sternotomy due to reduced invasiveness. However, in redo cardiac surgery when the risks are higher due to adhesions, few studies compare long-term outcomes.

Objective:
We aim to compare the perioperative and long-term mortality and stroke/TIA rate in patients undergoing median sternotomy and right thoracotomy for redo cardiac surgery. Secondary outcomes were post-operative and total hospital stay, blood products used, return to theatre and new renal replacement therapy (RRT).

Methods:
We retrospectively analysed a cohort of 127 sternotomy patients and 29 right thoracotomy patients for redo cardiac surgery between 2010-2020. All patients underwent valve repair or replacement. Patients requiring concomitant cardiac procedures were included.

Results:
In-hospital and long-term follow-up were 100% and 98.1% complete and a maximum of 10.4 years. There were 52 deaths (33.3%) within the follow-up period. Perioperative mortality was 16.5% in sternotomy versus 3.45% in MICS, although this difference was insignificant after adjustment for logistic EuroSCORE (HR 0.38, [0.05-2.79]). In multivariate analysis, long-term mortality was significantly lower in MICS (HR 0.30 [0.10-0.85]). Adjusted Kaplan-Meier curves revealed lower long-term mortality in the MICS group (p<0.0001). Differences in stroke/TIA rates were insignificant (odds ratio 3.23 [0.85-12.8]). There were significantly less RBC (p=0.0001) and total blood products (p=0.0032) used in the MICS group. All 12 patients who returned to theatre for bleeding complications were in the sternotomy group. Although mean post-operative and total hospital stay and new RRT were lower in the MICS group, these differences were insignificant.

Conclusion:
MICS for redo cardiac surgery is a safe and effective alternative to median sternotomy without compromising both short-term and long-term clinical outcomes.
Abstract 10488: Overexpression of MFN2 Alleviates Sorafenib-Induced Cardiomyocyte Necroptosis via the MAM-CaMKIIδ Pathway
in vitro
and
in vivo
Authors: Song Ziping , song haixu , Liu Dan , Tian Xiaoxiang , Yan Chenghui , Yaling Han
Published: March 2022

Background:
The continued success of oncological therapeutics is dependent on the mitigation of treatment-related adverse events, particularly cardiovascular toxicities. As such, there is an important need to understand the basic mechanisms of drug toxicities and to explore the differences in the fundamental signaling pathways between cancer cells and non-cancer cells for the maintenance of function and survival of these cells. Our aim in this study was to elucidate the underlying mechanisms of sorafenib (Sor)-induced cardiomyocyte damage.

Methods:
Primary mouse cardiomyocytes were prepared and treated with Sor and various other treatments. Cardiomyocyte necroptosis was detected by flow cytometry, western blotting, and CCK8 assays. Mitochondrial Ca
2+
uptake was detected by Rhod-2 probes using confocal imaging. Morphological changes in mitochondria and mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) were imaged using transmission electron microscopy (TEM) and confocal microscopy.

Results:
We reported that RIP3/MLKL cascade activation, mitochondrial Ca
2+
overload, and the subsequent increase in calmodulin-dependent protein kinase II delta (CaMKIIδ) contributed to Sor-induced cardiac necroptosis. Excess MAM formation and close ER-mitochondria contact were key in the pathogenesis of Sor-induced Ca
2+
overload. Furthermore, we found that reduced mitofusin-2 (MFN2) levels corresponded to repressed MAM biogenesis and increased mitochondria-MAM tethering in cardiomyocytes. Sor-induced Mammalian Target of Rapamycin (mTOR) inactivation, followed by the activation and nuclear translocation of Transcription Factor EB (TFEB), contributed to mitophagy and MFN2 degradation. In an
in vivo
model, we reported that an increase in MFN2 expression specifically improved Sor-induced cardiomyocyte necroptosis by repressing the MAM-CaMKIIδ-MCU pathway.

Conclusions:
Sorafenib mediated cardiomyocyte necroptosis through the mTOR-MFN2-MAM-Ca
2+
-RIP3-CaMKIIδ pathway
in vitro
and
in vivo
. The overexpression of MFN2 could rescue Sor-induced cardiomyocyte necroptosis without disturbing the anti-tumor effects.
Abstract 10492: Preclinical Evaluation of Transient and Cardiomyocyte Specific Gene Therapy for the Treatment of Subacute Ischemic Heart Failure
Authors: Abouleisa Riham , Salama Abou B , Ou Qinghui , Tang Xian-liang , Solanki Mitesh , Guo Yiru , Nong Yibing , Kassem Kamal M , Hammad Sally , Abdulwali Fareeha , Dastagir Muzammil L. , Bolli Roberto , Mohamed Tamer
Published: March 2022

Rationale:
Treatment of heart failure is limited due to the limited regenerative capacity of cardiomyocytes. Our group has shown that ectopic expression of Cdk1/CyclinB1 and Cdk4/CyclinD1 (named 4F) via adenovirus vector promotes cardiomyocyte proliferation in 20% of infected cardiomyocytes
in vitro
and
in vivo
and improves cardiac function after myocardial infarction (MI).

Objective:
To introduce 4F specifically and transiently into cardiomyocytes to induce selective cardiomyocyte regeneration and limit any tumorigenic potential in other organs.

Methods and Results:
A polycistronic non-integrating lentivirus encoding 4F, each driven by a TNNT2 promoter (TNNT2-4F-NIL), was generated to induce transient and specific expression of 4F cardiomyocytes. TNNT2-4F-NIL promotes proliferation of 15% of cardiomyocytes in vivo after MI as assessed in lineage-tracing mice (α-MHC-Cre-MADM). Rats and pigs were subjected to coronary occlusion/reperfusion to induce MI. One week later, animals were injected (intramyocardially) with either TNNT2-4F-NIL or control-NIL. Four weeks after injection, TNNT2-4F-NIL treated rats and pigs showed a significant improvement in left ventricular ejection fraction (EF) compared to controls (TNNT2-4F-NIL rats 54.3±1.78% vs control-NIL 42.97±2.60%; n=9/group,
p
=0.003, TNNT2-4F-NIL pigs 37±2.3% vs control-NIL 28.4±1.2%; n=6/group,
p
=0.01). Histological analyses showed a 25-30% reduction in scar size in both rats and pigs treated with TNNT2-4F-NIL vs. control-NIL (p<0.05). To assess the long-term efficacy and safety of TNNT2-4F-NIL, a 4-months follow-up experiment after MI and virus treatment was performed during which cardiac function was assessed monthly. TNNT2-4F-NIL treated rats showed sustained improvement in cardiac function (EF in TNNT2-4F-NIL 48.4±3% vs in control-NIL 33.6±3%; n=6/group,
p
=0.008). There was no obvious development of arrhythmias and no evidence of oncogenicity or toxicity in other organs in TNNT2-4F-NIL treated rats or in the control group.

Conclusion:
This study provides a novel approach to treat heart failure, with the use of transient and cardiomyocyte-specific gene therapy that promotes long-term functional improvement after a single treatment with no obvious adverse effect.
Abstract 10493: Prognostic Value of Right Ventricular Longitudinal Strain in Transthyretin Amyloid Cardiomyopathy
Authors: Usuku Hiroki , Takashio Seiji , Yamamoto Eiichiro , Yamada Toshihiro , Oike Fumi , Fujisue Koichiro , Sueta Daisuke , Matsushita Kenichi , Tsujita Kenichi
Published: March 2022

Introduction:
This study was performed to investigate whether right ventricular global longitudinal strain (RV-GLS) provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM).

Methods and Results:
Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 111 patients who had enough information for two-dimensional speckle tracking imaging were retrospectively analyzed in this study. During a median follow-up of 615 days (25
th
-75
th
percentile; 318-1082 days), 26 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group had significantly lower RV-GLS (10.9±2.7% vs. 12.8±3.5%, p<0.05) and right ventricular free wall longitudinal strain (13.1±3.3% vs. 15.5±3.8%, p<0.01). However, conventional echocardiographic findings, such as left ventricular ejection fraction and E/e’ ratio were not significantly different between these two groups. Receiver operating characteristic analysis showed that the area under the curve of RV-GLS for cardiovascular death was 0.668 and that the best cutoff value of RV-GLS was 11.59% (sensitivity 69.2%; specificity, 63.5%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low RV-GLS (<11.59%) had a significantly higher probability of total cardiovascular death (p<0.01). After adjusting for conventional predictive factors (age, history of heart failure, hs-cTnT, and B-type natriuretic peptide), low RV-GLS was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (odds ratio, 3.40; 95% confidence interval, 1.26-9.18; p<0.05).

Conclusions:
RV-GLS has significant prognostic value in patients with ATTRwt-CM and provides greater prognostic power than conventional echocardiographic parameters.
Abstract 10501: Clinical Outcomes After Transcatheter Edge-to-Edge Repair of the Mitral Valve with the Mitraclip
TM
System in Cancer Survivors
Authors: Agrawal Nikhil , Lin Kevin , Battel Lucas , Garcia-Sayan Enrique , Lopez-Mattei Juan , Arain Salman A , Charitakis Konstantinos , Iliescu Cezar , Smalling Richard W , Dhoble Abhijeet
Published: March 2022

Introduction:
Valvular diseases, especially Mitral regurgitation (MR) confer a high cardiovascular burden in cancer survivors. Transcatheter Edge-to-Edge Repair (TEER) with the MitraClip
TM
system has shown promising results in the management of severe MR regardless of etiology. However, little is known about the impact of cancer history on patient outcomes.

Methods:
We studied 456 consecutive patients (cancer: 86; non-cancer: 370) with severe mitral regurgitation who underwent mitral valve TEER at our institution from 2005 to 2020. In addition to pre-and post-procedural characteristics, we examined imaging parameters and outcome data including all-cause mortality. We used Cox regression analysis to identify factors associated with mortality.

Results:
Patients were followed for a mean of 9.2 months (SD 19). Table 1 shows the baseline and follow-up characteristics for both groups. At 1-year follow-up, only 4 (5%) cancer survivors and 23 (6%) non-cancer patients had died. In a Cox regression analysis, short-term (<90 days) and long-term (1 year) mortality were similar in both cohorts (HR 0.8 and 1.2, respectively; p>0.05). Age and sex were also not significantly associated with mortality (p>0.05). In subgroup analyses, at 1-year follow-up, cancer survivors who had received prior radiation therapy were more likely to have died (11% vs 0; X2=5.07, p=0.024) and cancer survivors with solid tumors were more likely to have an NYHA functional class III-IV at 1-year follow-up than those with hematologic malignancies (X2=4.75, p=0.029).

Conclusions:
In this large retrospective study, short- and long-term all-cause mortality after mitral valve TEER were similar in both cancer survivors and non-cancer patients. Prior radiation therapy and history of solid tumors may be poor prognostic markers.
Abstract 10502: Impact of Norwood Shunt Type on Cardiac Function and Clinical Outcomes in Survivors to Early Adolescence with Hypoplastic Left Heart Syndrome and Other Single Right Ventricular Anomalies: A Report from the Single Ventricle Reconstruction (SVR) III Study
Authors: Goldberg Caren S , Trachtenberg Felicia , Gaynor J William , Mahle William T , Ravishankar Chitra , Schwartz Steven , Cnota James F , Ohye Richard G , Gongwer Russell , Taylor Michael , Paridon Stephen , Frommelt Peter C , Afton Katherine , Atz Andrew M , Burns Kristin , Detterich Jon A , Hill Kevin D , Cabrera Antonio G , Lewis Alan B , Pizarro Chritian , Shah Amee , Newburger Jane W ,   On Behalf of the Pediatric Heart Network Investigators
Published: March 2022

Introduction:
The SVR Trial demonstrated that the right ventricle-to-pulmonary artery shunt (RVPAS)
vs.
modified Blalock-Taussig-Thomas shunt (MBTTS) at Norwood operation was associated with better early survival for children with hypoplastic left heart syndrome (HLHS). However, it remains unclear if shunt type is associated with cardiac function, morbidities or survival in older children.

Methods:
SVR Trial survivors were followed annually. Cardiac MRI and cycle ergometry were performed at 10-12 years (y) of age for SVR III participants. Outcomes were compared by shunt type received (presented) and intention to treat, using linear, Poisson and Cox proportional hazards regression.

Results:
Among 549 children in the SVR Trial, 237 of 313 eligible transplant-free survivors returned for follow-up at median (IQR) 10.9 (10.4-11.5) y. Transplant-free survival at 12 y was 59% for the RVPAS
vs
54% for the MBTTS, with no difference in survival conditional on Stage II survival. Ejection fraction (EF) was measured by MRI in 168 participants, with no difference between groups (RVPAS median 53 [IQR 46-58] and MBTTS 52 [IQR 48-56], p=.38). In multivariable modeling, the percent variance in EF explained by pre-Norwood and Norwood variables including shunt type was low (R
2
< .2). Cycle ergometry was performed in 181 participants with no difference by shunt type in peak VO
2
(ml/kg/minute) (RVPAS 30 [IQR 25-36] vs. MBTTS 29 [IQR 24-33], p=.26) or in peak work rate (RVPAS 67±24 watts vs MBTTS 66±20 watts, p=.61). By age 12 y, the RVPAS group had a higher rate of PLE (5% vs. 2%, p =.04) and catheter interventions (14 vs 10 per 100 pt-y; p=0.01). Otherwise the cumulative incidence of events and complications were similar for shunt groups with stroke in 7%, seizure 14%, plastic bronchitis 1%, atrial tachyarrhythmias 7% and ventricular tachyarrhythmias 3%.

Conclusion:
By 12 y after Norwood, shunt type has minimal effect on post-Stage II transplant-free survival, cardiac function or exercise performance. EF is preserved in most transplant-free survivors. However, low and declining transplant-free survival, poor exercise performance, and accruing morbidities highlight the critical need for innovative strategies to improve long-term outcomes in patients with HLHS.
Abstract 10509: Aquaporin 1 Differentially Controls Endothelial Cell Senescence by Epigenetic and SASP Modulation
Authors: Saeedi Soheil , Karsai Gergely , Camici Giovanni G , Lüscher Thomas F , Jürg Beer H
Published: March 2022

Introduction:
Aquaporin 1 (AQP1) has been implicated in oxidant sensing, but little is known about its differential role in metabolism and function of proliferating (PEC) and senescent (SEC) endothelial cells. We sought to investigate

1)

role of AQP1 in modulation of epigenetic modification and senescence-associated secretory phenotype (SASP) in PEC and SEC, and

2)

reversal effects of Aqp1 deletion/inhibition on endothelial senescence and dysfunction.

Methods:
We executed Aqp1 deletion or selective blockade of AQP1 pore (with Bacopaside II 10 μM) to inhibit H
2
O
2
transport in human aortic endothelial cells (PEC
p.5 vs
SEC
p.15
) and examined its effects on cellular senescence (via SA-β-galactosidase staining) and function (via
in vitro
angiogenesis and migration assays), and H
2
O
2
-modulated epigenetic modification and SASP (via biochemical assays).

Results:
We found that AQP1 facilitates physiological H
2
O
2
supply which is necessary for angiogenesis and cell migration in PEC accompanied by marked increase in AMPK
T172
phosphorylation and inhibition of acetyl-coA carboxylase (ACC) that provides acetyl-coA for an increased histone 3 (H3) acetylation. Importantly, Aqp1 deletion/inhibition significantly induced senescence and mitochondrial dysfunction in PEC associated with increased SA-β-gal positive cells, upregulated SASP (TNF-α and ICAM-1), and downregulated Idh2. By contrast, decreased AMPK
T172
phosphorylation and H3 acetylation accompanied by increased SA-β-gal positive cells, upregulated SASP and mitochondrial dysfunction seen in SEC were reversed by Aqp1 deletion/inhibition. In SEC, we have shown that Aqp1 deletion restores angiogenesis and migration comparable to PEC.

Conclusion:
We conclude that AQP1 differentially controls metabolism and function in young and senescent ECs via epigenetic and SASP modulation and that AQP1 inhibition represent new possibilities for rejuvenating senescent ECs and treating cardiovascular disease.
Abstract 10514: Inguinal Fat Tissue Biopsy to Identify Transthyretin Amyloidosis in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Muto Yuki , Yoshihisa Akiomi , Sugawara Yukiko , Abe Satoshi , Oikawa Masayoshi , KOBAYASHI ATSUSHI , Kunii Hiroyuki , Nakazato Kazuhiko , Fujimiya Tsuyoshi , Takase Shinya , Takeishi Yasuchika
Published: March 2022

Background:
Several studies have recently reported that transthyretin (ATTR) amyloidosis is present in patients with aortic stenosis (AS). This study aimed to 1) examine the utility of inguinal fat tissue biopsy in AS patients who underwent transcatheter aortic valve implantation (TAVI) to detect ATTR amyloidosis, 2) compare clinical characteristics between AS patients with ATTR (ATTR group) and those without ATTR (non-ATTR group).

Methods and Results:
We prospectively analyzed consecutive 56 patients who underwent transfemoral TAVI from December 2018 to December 2020 in our hospital. To screen ATTR in these patients, we performed inguinal fat tissue biopsy from cut down or puncture site during TAVI. Of 56 AS patients, 5 (8.9%) patients were diagnosed as ATTR by inguinal fat biopsy. Compared with non-ATTR group, ATTR group presented higher levels of B-type natriuretic peptide (BNP, 566.4 vs. 242.5 ng/ml, P=0.0045), higher levels of troponin I (0.053 vs. 0.024 ng/ml, P=0.003), lower left ventricular ejection fraction (LVEF, 49.3 vs. 60.3%, P=0.0035), larger left ventricular mass index (150.2 vs. 115.5 g/m
2
, P=0.019), larger aortic valve area (0.84 vs. 0.63 cm
2
, P=0.029) and lower peak velocity of aortic valve (3.8 vs. 4.4 m/s, P=0.041). In contrast, age, sex, STS score, clinical frailty scale, prevalence of diabetes, chronic kidney disease and AF, levels of albumin, and eGFR were comparable between the two groups. Electrocardiogram and other echocardiographic parameters including interventricular septal wall thickness, posterior wall thickness, stroke volume index and E/A ratio did not differ between the two groups. Although TAVI was successfully completed in all patients, the incidence of life-threatening bleeding and 30-day readmission was higher in ATTR group than in non-ATTR group (40.0 vs. 5.9%, P=0.011 and 20.0 vs. 0.0%, P=0.001). There was no difference in occurrence of myocardial infarction, stroke, acute kidney injury, major vascular complication, pacemaker implantation and 30-day mortality.

Conclusions:
In AS patients, especially in those with increased BNP and troponin I levels and low-flow low-gradient pattern, ATTR should be considered. In this population, inguinal fat tissue biopsy is a novel and safe approach to identify ATTR.
Abstract 10533: Greater Left Ventricular Mass And Abnormal Diastolic Myocardial Function In Neonates Of Pre-eclamptic Pregnancies
Authors: Benvenuto Victor , Nies Melanie , Barnes Benjamin , Long Rita , Everett Allen D , Kutty Shelby
Published: March 2022

Introduction:
Maternal pre-eclampsia (PEC) is a placental insufficiency syndrome with potential effects on neonatal cardiac function.

Hypothesis:
We tested the hypothesis that neonatal exposure to maternal PEC results in systolic and diastolic myocardial dysfunction on echocardiogram.

Methods:
Neonates exposed to maternal PEC (N=142) were matched 1:1 for gestational age and gender (N=142) with neonates concurrently enrolled in our center during the same study period (2009-2019). Echocardiograms performed in first 30 days of life were analyzed. Image analysis was done retrospectively and included LV and RV global peak longitudinal strain, mitral and tricuspid inflow and tissue Doppler, and LV mass indexed to body surface area. Analyses included two-sample t-test, Wilcoxon rank sum, chi-squared, and Bonferroni correction testing.

Results:
The average gestational age was 28 weeks, with slight male predominance of 54.9%. Birth weight was 885g in PEC group, compared to 1100g in the control (p=0.003). Median age at echocardiogram was 8 days for PEC and 6 days for control.In the PEC group, systolic function demonstrated decreased longitudinal 2-chamber average peak strain and higher mean LV mass. There was no difference in 4-chamber average peak strain, circumferential mid-LV average peak strain, or longitudinal RV 6-segment average strain. Mitral and tricuspid valve E-wave deceleration times were shorter in the PEC group. There were no differences in other markers of diastolic function, including E/A and E/e’ ratio.

Conclusions:
PEC neonates have increased RV and LV stiffness, indicated by reduced E-wave deceleration time of the mitral and tricuspid valves. This is suggestive of grade 2 diastolic dysfunction. LV mass was increased in the PEC group. We did not find compelling evidence of systolic dysfunction with strain analysis. In conclusion, maternal PEC exposure results in neonatal diastolic abnormalities that may have long term effects on cardiac function.