bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16680: Endovascular Therapy of Svc Syndrome-a Systematic Review
Authors: Azizi Abdul Hussain , Shafi Irfan , Zhao Matthew , Lakhter Vladimir , Bashir Riyaz
Published: May 2021

Background:
Superior vena cava (SVC) syndrome is caused by the occlusion of the SVC and can result in significant morbidity and mortality. Recently, endovascular therapy (ET) has become the standard of care for majority of these patients. We performed a systematic review of available literature to assess the contemporary technical success rate, restenosis rate, and recurrence rate of SVC syndrome following endovascular intervention.

Methods:
We searched PubMed, Cochrane Library, and Embase databases from 1988 to 2019 for studies on Endovascular Therapy for SVC syndrome. After screening 709 records, 13 studies were included. Screening was conducted using Rayyan QCRI software for systemic reviews. Studies included full-length journal articles on SVC syndrome and ET among adults (18+ years). Case reports, or case series with <20 patients were excluded. Data analysis was performed using OpenMeta software. Proportions and 95% confidence intervals (CIs) were calculated using random effects models. Heterogeneity among studies was assessed using Q and I
2
statistics. We evaluated the end-points of the technical success, restenosis rate and recurrence rates in SVC syndrome patients after endovascular stenting

Results:
A meta-analysis of 13 studies included a total of 1024 patients. The results of our meta-analysis show a weighted technical success rate of 98.6% (95% CI 0.97 – 0.99) (Fig. 1A), restenosis rate of 11.8% (95 CI 0.08-0.14) (Fig 1B) and recurrence rate of 9.9% (95% CI 0.06-0.13) (Fig 1C). Our studies had a substantial heterogeneity (I
2
) of 52-80%.

Figures:Figure 1A

Figure 1B

Figure 1C

Conclusions:
Our systematic review revealed high technical success rate, low restenosis, and recurrence rates after endovascular therapy supporting the paradigm of endovascular therapy as first line treatment for patients with SVC syndrome.

Disclosures:
Dr. Bashir has equity interest in Thrombolex Inc.
Abstract 16692: Spontaneous Coronary Artery Dissection Associated With Pregnancy
Authors: Lobo Angie S , Hayes Sharonne N , Best Patricia J , Rose Carl , Gulati Rajiv , Tweet Marysia
Published: May 2021

Introduction:
Spontaneous coronary artery dissection (SCAD) is a rare but life threatening cause of acute coronary syndrome and a common etiology of pregnancy-associated myocardial infarction (PAMI).

Hypothesis:
We aimed to examine the clinical presentation, treatment, and outcomes of the largest pregnancy associated-SCAD (P-SCAD) patient cohort to date.

Methods:
A total of 128 women enrolled in the Mayo Clinic SCAD Registry between 2010-2020 who were pregnant or up to 1 year postpartum at time of P-SCAD were identified. We subdivided P-SCAD in an “early” group with <12 weeks of delivery and a “late” group presenting between >12 weeks -12 months following delivery.

Results:
Among the 128 women with P-SCAD, 7(5%) occurred during pregnancy (2/7 first trimester, 5/7 third trimester). Of the 121 women with postpartum P-SCAD, 88/121(72%) occurred <12 weeks of delivery and 33/121(27%) at 12 weeks to 1 year postpartum. The mean age of P-SCAD was 35.3 +/- 4 years (26-48). The most common symptom on presentation was chest pain 118/128(92%); 62/128(48%) presented with ST elevation MI and 58/128(45%) presented with non-ST elevation MI. Multivessel involvement occurred in 40/128(31%), left anterior descending artery (LAD) in 88/128(69%), and left main (LM) in 28/128(22%) of all P-SCAD. Percutaneous coronary intervention (PCI) was performed in 52/128(41%) with a success rate of 81%. Coronary artery bypass grafting was performed in 24/128(19%) of which 6/24 patients had an unsuccessful PCI, 14/24 had proximal or multivessel SCAD, and 4/24 had persistent or extension of initial SCAD. Of those treated conservatively 52/128(40%), 11/52(21%) had LM and LAD. Among all the P-SCAD patients, 84/128 (66%) were screened for an underlying arteriopathy, of whom 44 (52 %) were diagnosed with fibromuscular dysplasia. At a median follow up of 3 years (IQR 1 to 6), 12/128 (9%) of all P-SCAD survivors had a recurrent SCAD event and 7/12 (58%) were within 1 year postpartum. There were no deaths.

Conclusions:
P-SCAD most commonly presents with ST-elevation MI and multivessel involvement within the initial 12 weeks postpartum. Clinicians need to be familiar with this etiology of PAMI to avoid delay in diagnosis and appropriate management.
Abstract 16806: Changes in Wall Stress in Ascending Thoracic Aortic Aneurysms From Systole to Diastole
Authors: Liu Andrew , Wang Zhongjie , XUAN Yue , Hope Michael D , Ge Liang , Tseng Elaine E
Published: May 2021

Introduction:
Aortic rupture or dissection of ascending thoracic aortic aneurysms (aTAA) is a life-threatening pathology that can occur when wall stress exceeds wall strength. Surgical guidelines for repair is when aneurysm max diameter ≥5.5 cm. However, rupture has been documented at various sizes, including 60% <4.5cm. Wall stress may be a better predictor of dissection than diameter, using finite element analysis (FEA) of patient-specific aTAA models to assess patient-specific risk of dissection. The purpose of this study was to determine changes in aneurysm FEA peak wall stresses in patients during the cardiac cycle from systole to diastole.

Methods:
Preoperative aTAA patients (n = 20) underwent ECG-gated computed tomography (CT) scans at systolic and diastolic phases. Patient-specific 3D aneurysm geometries were reconstructed from the imaging data at both phases and after accounting for pre-stress, underwent FEA using LS-DYNA solver. Wall stress distribution and magnitude were determined using user-defined fiber-embedded material model at systole (120mmHg) and diastole (80mmHg). Aortic volume changes during the cardiac cycle were determined using computer-aided design tools.

Results:
From the diastolic model, the 99
th
percentile circumferential stresses were 348.8 ±105.6 kPa and 186.6 ±31.4 kPa for the sinus and ascending aorta respectively, while for the systolic model, they were 500.7 ±183.7 kPa (p=0.00072) and 296.5 ±64.4 kPa (p < .00001), respectively. The 99th percentile longitudinal stresses from the diastolic model were 223.2 ±75.4 kPa and 126.1 ±20.4 kPa for the sinus and ascending aorta, respectively, while for the systolic model, they were 336.3 ±78.4 kPa (p < .00001), and 235.2 ±48.0 kPa (p < .00001), respectively. Mean volume change of the ascending aorta in percentage between systolic and diastolic phases was 6.34%.

Conclusions:
Peak circumferential and longitudinal stresses changed significantly from systole to diastole. For patients with significant hypertension, these differences in wall stress may be magnified such that sudden or significant hypertension may result in wall stress values that exceed tissue strength leading to dissection.
Abstract 16829: Isolated Left Atrial, Biatrial or Right Atrial Dilatation - Association With Low Voltage Areas in Patients With Atrial Fibrillation
Authors: Seewoester Timm , Dinov Borislav , Nedios Sotirios , Hindricks Gerhard , Kornej Jelena
Published: May 2021

Background:
Left atrial volume (LAV) and low voltage areas (LVA) are markers for impaired outcome after ablation of atrial fibrillation (AF). Some studies reported the importance of increased right atrial volume (RAV) as a predictor for arrhythmia recurrences in AF patients.

Hypothesis:
to investigate association between the LAV/RAV ratio and LVA presence.

Methods:
Patients undergoing first AF ablation with pre-procedural cardiovascular magnetic resonance (CMR) imaging were included. LVA were assessed peri-procedurally using high-density 3D maps and defined as <0.5 mV. LAV was determined using a biplane model based on cine 4- and 2-chamber views, RAV using a monoplane model based on the cine 4-chamber view. Both volumes were indexed to body surface areas, and the LAV/RAV ratio was calculated. LAV/RAV ratio >1 indicated isolated LA dilatation, ratio ≤1 was defined as biatrial/isolated RA dilatation.

Results:
The study population included 184 patients (Age 63±10 years, 34% women, 58% persistent AF, 22% LVA). There were 148 (80%) patients with isolated LA dilatation. In univariable analysis, isolated LA dilatation was associated with LVAs (OR 6.803, 95% CI 1.395-26.514, p=0.016). This association remained robust in multivariable model after adjustment for persistent AF, CHA
2
DS
2
-VASc score, renal function, and heart rate (OR 5.981, 95%CI 1.256-28.484, p=0.025). Using ROC analysis, LAV/RAV ratio (AUC 0.668, 95% CI 0.585-0.751, p<0.001, Figure) was significant predictor for LVA. Biatrial/isolated RA dilatation occurred in 36 (20%) patients. On multivariable analysis, after adjustment for age, persistent AF, and renal function, male sex remained significantly associated with biatrial/isolated RA dilatation (OR 3.040, 95% CI 1.050-8.802, p=0.040).

Conclusions:
LAV/RAV ratio is useful for the prediction of LVA in AF. Isolated LA dilatation was associated with LVA presence, while male sex remained associated with biatrial/isolated RA dilatation and less LVA.
Abstract 16831: Effect of a Virtual Cardiac Rehabilitation Program on Functional Capacity and Risk Factor Modification in Veterans With Ischemic Heart Disease
Authors: Harzand Arash , Vakili Alexander A , Davis-Watts Michelle , Nazar Rene , Wright Phyllis , Parrish Cate G , Rout Pratik , Alrohaibani Alaaeddin , Shah Amit J
Published: May 2021

Background:
Cardiac rehabilitation (CR) is a comprehensive lifestyle change program proven to reduce cardiovascular disease (CVD) risk and improve quality of life in patients with ischemic heart disease but remains highly underutilized (<20% of eligible patients) due to the inconvenience and cost of attending a facility-based program. We evaluated the efficacy of a home-based, virtual CR program using mobile health (mHealth) in veterans with coronary artery disease (CAD) on improving functional capacity, CVD risk factors, and depressive symptoms.

Methods:
We enrolled 196 Veterans with a qualifying CR diagnosis between May 2016 and April 2020. All participants underwent baseline functional evaluation with a 6-minute walk test (6MWT), followed by a 12-week home-based, virtual CR program delivered via the Movn smartphone app (Movn by Moving Analytics). The Movn app featured daily alerts to exercise, a digital diary to record activity and vital signs, and connectivity with a health coach who remotely monitored participants through an integrated dashboard and scheduled weekly phone visits. We compared the risk factor profile pre-intervention versus post-intervention with paired t-tests.

Results:
Among enrolled Veterans, the mean (SD) age was 61 (9) years, 95% were male, and 50% were black. A majority (63%) completed the full 12-week virtual CR program including an exit visit. Participants completed an average of 10.4 ± 1.9 (range 3–13) phone visits with the coach. There were concurrent improvements in 6MWT distance (443.9 vs. 481.9 meters; mean difference [MD], 38 meters; 95% CI, 26.6 – 50.8, P<0.001), low-density lipoprotein cholesterol (80 vs. 69 mg/dL, MD, -10.9; 95% CI, -17.9 to -3.9, P=0.003), body mass index (31.1 vs 30.8; MD, -0.33; 95% CI, -0.60 to -0.06; P=0.001), and PHQ-9 depression scores (7.4 vs. 6; MD, -1.4, 95% CI, -2.4 to -0.44; P=0.005) among program completers.

Conclusions:
Among veterans with ischemic heart disease, a virtual CR program results in moderate improvements in functional capacity, CVD risk factors, and mood. The durability of these effects and whether virtual CR improves longer-term outcomes such as readmissions, survival, and cost remain to be determined.
Abstract 16836: Quantitative Speckle Tracking Strain Analysis of Border and Remote Left Ventricular Regions After an Infero-Lateral Myocardial Infarction in a Chronic Swine Model
Authors: Onohara Daisuke , Kono Takanori , Suresh Kirthana , Amedi Alan , Padala Muralidhar
Published: May 2021

Introduction:
A myocardial infarction (MI) imposes a significant pathological load on the viable myocardium, leading to an acutely adaptive response and chronically maladaptive remodeling. In patients with an inferolateral MI, the mechanical load on the remote regions is significant, and thus the resulting ventricular remodeling is extensive and often leading to congestive heart failure. In this study, we used 3D echocardiography combined with speckle tracking strain to quantify the myocardial strains of the remote and border zone in an inferolateral MI swine.

Hypothesis:
An inferolateral MI imposes significant changes in myocardial strains is not only the border zone but also the remote regions.

Methods:
Six swine were induced with an inferolateral MI by ethanol injection. The animals were survived to 10 weeks post-infarction. Nine healthy swine were used as controls. Both animal groups underwent cardiac echocardiography with Siemens, by tunneling of a transesophageal probe into the thoracic cavity for direct placement onto the left atrium, such that the entire left heart was imaged. Strain analysis was performed with eSie LV analysis (Figure A).

Results:
EF was significantly lower than the control group (43.0±8.2% vs 52.2±5.2%, p=0.0190). EDV and ESV in the MI group were greater compared to the control group (127.8±32.0 ml vs 81.9±19.2 ml, p=0.0040, and 74.5±28.6 ml vs 38.5±6.8 ml, p=0.0027, respectively) indicative of remodeling. Circumferential end-systolic strains of basal- and mid-inferolateral wall in the MI group were significantly reduced compared to the control group (24.1±20.0% vs 48.0±18.6%, p=0.0339 and 10.5±11.4% vs 27.8±12.8%, p=0.0186, respectively). Similarly, longitudinal strain in mid-inferolateral wall in the MI group was significantly reduced (-7.8±5.8% vs -16.3±12.8%, p=0.0120) (Figure B, C).

Conclusion:
Reduction in both circumferential and longitudinal strains were observed in the border zone, but not in the remote zone.
Abstract 16837: Exosomes Derived From Podoplanin Positive Cells Induce Serum Amyloid A3 Amyloidosis in Healthy Mouse Heart
Authors: Cimini Maria , garikipati venkata naga srikanth , Elia Andrea , Wang Chunlin , TRUONGCAO MAY , Huang Grace , Mallaredy Vandana , Benedict Cindy , Kishore Raj
Published: May 2021

The extra-cellular-matrix (ECM) composition of scar tissue after myocardial infarction (MI)has been largely investigated; although fibronectin and collagen are favorable for newmyocyte formation there is a missing component that increase the stiffness and reducethe remodeling of the ischemic area. We identified a primary Serum Amyloid A3 (Saa3)extracellular accumulation that contribute to the chronic alteration of the tissue. Serumamyloid amyloidosis (AA) are characterized by deposition of hepatic misfolded protein,Saa3 is the only amyloid protein that is released locally after inflammation, mostly bymesenchymal progenitor cells. We already described that two days after MI,mesenchymal and endothelial progenitor cells express Podoplanin (PDPN) a plateletaggregation-inducing type I transmembrane glycoprotein as a signal of activation. Exosomes derived from this cohort of cells actively release Saa3 in the ECM affecting thebiology of fibrosis beyond the inflammation. Specific histological staining such asthioflavin t and Congo red, showed amyloid deposition in mouse hearts 1 month after MI;furthermore, immunohistochemistry for Saa3 detected the deposition of the misfoldedprotein alongside fibronectin and collagen. PDPN+ cells were isolated 2 days after MI,cultured expanded and activated with TNFα and AngiotensinII. Activated PDPN positivecells highly expressed Saa3 and exosomes derived from activated PDPN+ cellsconditioned media were used in vivo for the treatment of healthy mouse hearts. Treatedmice developed an extended epicardial fibrosis and amyloidosis with a subsequentimpairment in the contractility and increase of the end diastolic and systolic volumes. Thefibrotic area was characterized by infiltrating CD45+ cells. Novel therapies aimed atpromoting clearance of existing amyloid deposits may be an effective approach in thenear future in the treatment of scar remodeling after MI.
Abstract 16842: Cost-Effectiveness of Antibiotic-Eluting Envelopes for Prevention of Infections Associated With Cardiac Implantable Electronic Devices
Authors: Modi Ronuk , Zimetbaum Peter , Isaza Nicolas , Calvachi Paola , Raber Inbar , Bellows Brandon , Kramer Daniel B , Kazi Dhruv
Published: May 2021

Introduction:
Infections of cardiac implantable electronic devices result in substantial morbidity and healthcare costs. Using an antibiotic-eluting envelope (AEE) during implantation may reduce the incidence of device-related infection. We examined the cost-effectiveness of an AEE in patients receiving CRT-D devices.

Methods:
This analysis was conducted independent of the trial sponsor. We developed a state-transition Markov model to compare the use of an AEE with usual care during CRT-D initial implantation or reimplantation. Effectiveness of the AEE (unit cost $1000) was estimated from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial. Other inputs were derived from prior trials, registries, vital statistics, and nationally representative datasets. Long-term survival was projected using a non-parametric approach. The model reported incidence of infections, mortality, quality-adjusted life years (QALYs), and direct healthcare costs. Future costs and QALYs were discounted by 3% annually. The primary outcome was the incremental cost-effectiveness ratio (ICER) of AEE use from the US healthcare sector perspective over a lifetime analytic horizon. We assumed a cost-effectiveness threshold of $100,000 per QALY gained.

Results:
Use of an AEE at initial CRT-D implantation added 0.008 QALYs per patient at an incremental cost of $918 (ICER $118,000/QALY). Due to higher infection rates, the use of AEE in reimplantation procedures was more economically attractive (ICER $55,900/QALY). One-way sensitivity analyses showed an inverse relationship between ICER and rate of infection. The ICER was less than $100,000/QALY with infection rate greater than 2.42% in the first year after new CRT-D (Figure 1).

Conclusions:
At current prices, use of AEE is cost-effective for CRT-D reimplantation procedures but not for initial CRT-D implants. Cost-effectiveness of AEEs may be improved by restricting use to patients at increased risk of infection.
Abstract 16875: Cystatin C- versus Creatinine- Based Assessment of Renal Function in Patients Admitted With Heart Failure: Insights From DOSE, ROSE and CARRESS-HF
Authors: Wang Yu Chiang , Pinsino Alberto , Braghieri Lorenzo , Pang Li , Fabbri Matteo , Katamreddy Adarsh , Arfaras Melainis Angelos , Li Weijia , Faillace Robert
Published: May 2021

Introduction:
Serum creatinine (sCr) is routinely used to calculate estimated glomerular filtration rate (eGFR) in heart failure (HF) pts. However, changes in muscle mass may limit the accuracy of sCr as marker of renal function in this population. Cystatin C (CysC) is independent of muscle mass and provides an alternative measure of eGFR. In prior studies, higher sCr/CysC ratio has been associated with higher muscle mass. Herein, we compared CysC- and sCr-based eGFR at serial time points among pts admitted with HF. We hypothesized that muscle mass would decline during HF admission and this would result in a decrease of sCr/CysC ratio.

Methods:
We pooled pts from 3 trials performed in pts admitted with HF (DOSE, ROSE and CARRESS-HF). eGFR was calculated using CKD-EPI-CysC equation (eGFRCysC) and sCr-based MDRD equation (eGFRsCr). The relative difference between eGFRCysC and eGFRsCr (ΔeGFR) was calculated as follows: (eGFRCysC-eGFRsCr)/ eGFRsCr. To control for confounders, we analyzed changes in sCr/CysC ratio and in ΔeGFR among pts with samples available at both admission and a subsequent time point.

Results:
A total of 2849 samples were available in 841 pts (age 68 ± 13, 26% female, left ventricular ejection fraction 36 ± 17%). Compared with eGFRsCr, eGFRCysC reclassified 50% of the samples to different GFR categories, mainly to more advanced renal dysfunction (Fig. A). eGFRCysC was significantly lower than eGFRsCr at all time points (Fig. B). From time of admission to all subsequent time points, sCr/CysC ratio declined while ΔeGFR widened (all p-values<0.001). At time of enrollment in CARRESS-HF, each additional day of HF admission was associated with a decline in sCr/CysC ratio of 1.5% (p=0.04).

Conclusions:
The use of CysC reclassifies a large proportion of pts admitted with HF to more advanced renal dysfunction when compared to sCr-based assessment. The discrepancy between CysC- and sCr-based eGFR appears to widen during HF admission, likely due to muscle mass wasting.
Abstract 16878: Cardiac Overexpression of RXFP1 via AAV9 Gene Therapy Sensitizes Myocardial Inotropic Response to Serelaxin
Authors: Devarakonda Siva Teja , Mauro Adolfo G , Cain Chad , Salloum Fadi N
Published: May 2021

Background:
The pleiotropic hormone relaxin has been shown to mediate physiologic responses during pregnancy by facilitating increases in vascular compliance and cardiac output. While relaxin signaling has been attributed to increases in atrial inotropy, the hormonal effects on ventricular contractility have not been explored
in vivo
. In this study, we investigated the dose-response effects of recombinant human relaxin (serelaxin) on ventricular mechanics.

Methods and Results:
Adult male CD1 mice were anesthetized and mechanically ventilated prior to Millar cardiac catheterization. A pressure-volume catheter was advanced into the left ventricle (LV), and baseline systolic and diastolic pressure/volume (PV) loops were recorded (Pre). Mice were injected with either saline, 10 μg/kg (low dose) or 1 mg/kg (high dose) of serelaxin, and PV loops were obtained after stabilization (Post) . Mice injected with 1 mg/kg demonstrated significantly higher LV contractility (
Fig A
) independent of preload (
Fig B
). These responses were not observed with low dose. In order to further examine the role of RXFP1 in modulating these responses, healthy CD1 were injected with AAV9-RXFP1 or empty vector as control and receptor overexpression was confirmed four weeks later via qPCR (
Fig C
). PV loop analysis showed an increased inotropic response [ΔP
Max
, Δ(dP/dt)
Max
] and improved relaxation kinetics [Δ(dP/dt)
Min
, Δτ] in RXFP1-overexpressing mice at a lower dose of serelaxin, when compared to empty vector mice (
Fig D
).

Conclusions:
Our data show a novel, dose-dependent correlation between serelaxin and ventricular inotropic and lusitropic responses in mice. These responses were observed at a lower drug dose in cardiac RXFP1-overexpressing mice. We propose that further investigation of this phenomenon could advance the therapeutic, cardioprotective effects associated with relaxin therapy in different etiologies of heart failure that may exhibit changes in RXFP1 expression.
Abstract 16893: Thrombotic Events During Extended Microaxial Mechanical Circulatory Support for Cardiogenic Shock
Authors: Lopes Mathew S , Silva Danuzia , Loriaux Daniel , Berg David , Levangie Michael , Bohula Erin A , Morrow David A
Published: May 2021

Background:
Percutaneous ventricular assist devices (VAD) are used in ~1/3 of patients (pts) with cardiogenic shock (CS). A percutaneous microaxial intracardiac VAD can offer hemodynamic support weighed against a risk of vascular complications. However, few studies have addressed the incidence of thrombotic complications, particularly in pts who require extended mechanical circulatory support (MCS).

Methods:
We conducted an observational cohort study to quantify the risk of thrombotic events during MCS in pts managed with a microaxial VAD for CS or mixed shock from 2015-2020 in a quaternary referral center. All consecutive pts were captured in a prospective registry of MCS and retrospectively reviewed for potentially device-related thrombotic events by 2 physician adjudicators. All pts received systemic anticoagulation with unfractionated heparin and/or bivalirudin.

Results:
The study included 106 pts (72% male, mean age 59.8). Peripheral artery disease, and a significant smoking history were present in 12% and 44% of cases respectively. The duration of microaxial VAD use was 5.3 days on average and >7 days in 25%. A concurrent microaxial VAD and other MCS were used in 28% of cases. Thrombotic/ischemic events were observed in 24.5% and were subcategorized into limb ischemia with visualized thrombus (n=6), limb ischemia without visualized thrombus (n=6), systemic embolism (n=6), intraventricular thrombus (n=2), device thrombus (n=6), and device dysfunction (n=3). Three pts had more than one complication. Moderate to severe thrombocytopenia (<100mcg/dL) was observed in 78% of pts. In-hospital mortality was 51% and was not higher in pts with thrombotic events (p=0.14).

Conclusion:
Thrombotic events are common with a microaxial intracardiac VAD with an observed rate that was higher than previously reported. Larger studies of all-comers with MCS for CS are needed to better define the rate of MCS-associated complications.
Abstract 16930: Despite Prior Results, Heart Transplant Recipients Over 70 Have Worse Survival Outcomes Based on the 2019 United Network for Organ Sharing Database
Authors: Kanaparthi Jay , Kashem Mohammed , Suryapalam Manish , Toyoda Yoshiya
Published: May 2021

Introduction:
As the prevalence of heart failure increases by age, it is critical we understand the role of heart transplantation (HTx) in older patients. Recent long term studies have indicated no difference in HTx outcomes between recipients 70 years or older and those ages 60-69. But these studies included data from the 1980-90s, introducing significant variance due poorer outcomes across age groups in that era. We analyzed the most recent United Network for Organ Sharing (UNOS) database, stratified by time frames before and after 2000, to demonstrate this statistical discrepancy and derive a more representative comparison of modern survival by age group.

Hypothesis:
HTx recipients 70+ years old may not actually have comparable survival to those 60-69 years of age, when assessing more recent HTx data.

Methods:
All UNOS HTx recipients over 60 years of age (n=20,446) were divided into 2 cohorts: those 60-69 and those ≥70 years old, which were analyzed over two time frames: transplant date 1987-1999 and 2000-2019. Demographic data (gender, ethnicity, BMI) as well as peri-operative factors (ICU stay, ischemic time, and length of stay) were evaluated for significance using Chi-Squared and H-Tests as appropriate. Kaplan-Meier Curve with log-rank tests were used to assess 10 year survival outcomes.

Results:
19,129 patients were 60-69 years old, and 1,317 were ≥70 years old, with mean ages of 64.0±2.7 and 71.3±1.6 years respectively. The distribution of demographic and peri-operative factors was significantly different between the cohorts, with p<0.05 for values. Survival analysis indicated no significance in the earlier timeframe (1987-1999) with p=0.341, but indicated significance in the later timeframe (2000-2019), with p=0.004.

Conclusion:
The results indicate that since 2000, recipients 60-69 years of age have better 10- year post transplant survival than older recipients, a relationship previously obscured by worse outcomes in early data.
Abstract 16939: Metabolic and Electrophysiological Alterations Underlie Proarrhythmic Properties of Highly Reactive Isolevuglandins in Atrial Cardiomyocytes
Authors: Subati Tuerdi , Yang Zhenjiang , Christopher Isis L , Van Amburg Joseph C , Murphy Matthew B , Stark Joshua M , Trykall David Z , Barnett Joey V , Murray Katherine
Published: May 2021

Background:
Hypertension is one of the most common risk factors for atrial fibrillation (AF), although the precise cellular and molecular mechanism(s) by which hypertension leads to AF are not well understood. Isolevuglandins (IsoLGs) are highly reactive dicarbonyl products of lipid peroxidation responsible for a major component of oxidative stress-related injury. In a mouse model of hypertension, we recently demonstrated that IsoLGs are elevated in hypertensive mouse atria and that an IsoLG scavenger reduced both IsoLG burden and AF susceptibility.

Hypothesis:
In this study, we hypothesized that IsoLGs can promote AF by inducing proarrhythmic metabolic and electrophysiologic (EP) changes in atrial cardiomyocytes.

Methods and Results:
Using standard patch clamp methods, we found significant changes in action potential properties of isolated mouse atrial cardiomyocytes exposed to IsoLGs (1μM, n=15 cells), including elevation of resting membrane potential, shortening of APD and reduction of V
max
. Acute IsoLG treatment led to a reduction of intracellular ATP production in atrial HL-1 cardiomyocytes, as measured by using a luminescence assay. Employing TMRM and Mitotracker Green staining for confocal and high-throughput screening (HTS) live-cell imaging assays, we also found that IsoLGs decreased mitochondrial membrane potential (compared to control, TMRM fluorescence decreased by 23%, 28%, 36% and 42%, respectively, when exposed to 0.01, 0.1, 0.5 and 1μM concentrations of IsoLG) accompanied by increased apoptosis (Cell Event Caspase-3/7 Green Detection Reagent) in a concentration-dependent manner, suggesting a prolonged mitochondrial transition pore opening. Moreover, cell metabolism assays performed using Agilent’s Seahorse XF96 extracellular flux analyzer revealed that IsoLGs exert a concentration dependent decrease in basal oxygen consumption rate and ATP production in HL-1 atrial cardiomyocytes.

Conclusion:
Together, these findings indicate that IsoLGs promote proarrhythmic EP and mitochondrial effects in atrial cells and thus may provide a novel therapeutic target for AF.
Abstract 16940: Missed Opportunities for Screening and Management of Dysglycemia After Myocardial Infarction: The Prospective NORIN STEMI Registry
Authors: Vaduganathan Muthiah , MP Girish , Gupta Puneet , Hendrickson Michael , Qamar Arman , Arora Sameer , Pandey Ambarish , BANSAL ANKIT , Batra Vishal , Mahajan Bhawna , Safal Safal , Tyagi Sanjay , Bhatt Deepak L , gupta mohit
Published: May 2021

Background:
Dysglycemia is a major and increasingly prevalent cardiometabolic risk factor worldwide, but often is undiagnosed even among high-risk patients with cardiovascular disease. New risk reduction strategies for DM are available, but little is known about their uptake in low middle-income countries.

Methods:
We conducted a prospective NORIN STEMI registry-based study of patients presenting with STEMI to 2 government-funded tertiary care medical centers in New Delhi, India from January to November 2019. Hemoglobin A1c was collected as a part of the study protocol, irrespective of baseline glycemic status. Prediabetes and DM were defined as screening HbA1c 5.7-6.4% and ≥6.5%, respectively.

Results:
Among 3,635 patients with STEMI (median age 55[45-62] with 33% ≤50 years, 16% women, 54% BMI≥30kg/m
2
), 855 (24%) reported a prior history of DM. Among patients with known DM, median HbA1c (available in n=826) was 7.4% (6.4-8.2%). At presentation, 1 patient (0.1%) and 21 patients (2%) were treated with an SGLT2i and GLP-1RA, respectively. Among patients without known DM, median HbA1c (available in n=2,668) was 5.5% (5.1%-5.9%) with 737 (28%) newly identified to have prediabetes and 339 (13%) to have DM. Compared with patients with euglycemia (42%), patients with known or newly detected prediabetes (49%) and DM (49%) experienced higher rates of post-MI LV dysfunction EF≤40% (P<0.0001). In-hospital mortality (4.3%, 5.6%, 8.8%) and 30-day mortality (6.6%, 8.1%, 11.7%) were similarly higher among patients with dysglycemia (P<0.0001 for both).

Conclusion:
Among patients presenting with STEMI in North India, protocolized HbA1c screening doubled the proportion of patients with known dysglycemia. These patients faced higher rates of LV dysfunction and mortality out to 30 days. Treatment with SGLT2i or GLP-1RA was infrequent.
Abstract 16946: Radial versus Femoral Access for Coronary Procedures in Patients With Prior Coronary Artery Bypass Grafting Surgery: An Updated Study-Level Meta-Analysis
Authors: Nikolakopoulos Ilias , Vemmou Evangelia , Xenogiannis Iosif , Karacsonyi Judit , Rangan Bavana V , Rao Sunil V , Alaswad Khaldoon , Tsigkas Grigorios , Anastasios Milkas , Bradley Steven M , Goessl Mario , Wang Yale , Chavez Ivan , Garcia Santiago , Burke M. Nicholas , Brilakis Emmanouil S
Published: May 2021

Introduction:
The preferred access site for cardiac catheterization in patients with prior coronary artery bypass surgery (CABG) continues to be debated.

Methods:
We performed a systematic review and meta-analysis of two randomized trials and eighteen observational studies, including 58,237 patients with prior CABG (27,063 in the radial group; 31,174 in the femoral group) that underwent cardiac catheterization with or without intervention. Outcomes included (1) access-site complications rate; (2) crossover rate to a different vascular access; (3) procedure time; and (4) contrast volume. Data were extracted by two independent authors; using a random effects model, standardized mean differences (SMD) and 95% confidence interval (CI) were calculated for continuous outcomes, whereas odds ratio (OR) and 95% CI were calculated for binary outcomes.

Results:
Among randomized trials, the crossover rate (OR:12.63; 95% CI: 1.57,101.62; p=0.021) was higher in the radial group, while contrast volume (SMD: 0.15; 95% CI: -0.52, 0.82, p=0.66), procedure time (SMD: 0.49; 95% CI: -0.64, 1.62, p=0.4) and the incidence of access site complications (OR:1.21; 95% CI: 0.36, 4.07; p=0.76) and were similar. Among observational studies, access site complication rates (OR:0.46; 95% CI: 0.25,0.86; p<0.001) and contrast volume (SMD: -0.14; 95% CI: -0.20, -0.07; p=0.03) were lower and crossover rates were higher (OR: 4.79; 95% CI: 1.99, 11.52, p=0.02) in the radial group, while procedure time was similar (SMD: 0.13; 95% CI: -0.08, 0.34, p=0.02).

Conclusions:
Most data published for radial vs. femoral access in prior CABG patients are observational with only two randomized-controlled trials performed to date. Radial access is associated with lower vascular access complication rates and contrast volume in observational studies and higher rates of crossover to femoral access in both observational and randomized studies.
Abstract 16955: Contrasting Effects of Smooth Muscle TRPV4 Channels on Vascular Function
Authors: CHEN YEN LIN , Daneva Zdravka , Sonkusare Swapnil K.
Published: May 2021

Introduction:
Transient receptor potential vanilloid 4 (TRPV4) channels are a major Ca
2+
entry pathway in vascular endothelial cells. TRPV4 channels are also expressed in vascular smooth muscle cells (SMC). However, the effect of SMC TRPV4 (TRPV4
SMC
) channels on vascular resistance and blood pressure remains controversial.

Hypothesis:
We hypothesized that TRPV4
SMC
channels are essential regulators of vascular function and blood pressure.

Methods:
Inducible, SMC-specific TRPV4 knockout (TRPV4
SMC
-/-
) mice were used. Blood pressure was monitored using radiotelemetry catheters. SMC Ca
2+
signals were recorded with a spinning disk confocal imaging system. Pressure myography studies assessed vascular reactivity in MAs.

Results:
Resting diastolic blood pressure and mean arterial pressure were lower in TRPV4
SMC
-/-
mice when compared to control mice. Selective TRPV4 channel agonist, GSK1016790A (GSK101), induced Ca
2+
influx signals in SMCs that were inhibited by TRPV4 channel inhibitor GSK2193874 and were absent in MAs from TRPV4
SMC
-/-
mice. In pressure myography studies, GSK101 constricted the MAs in control mice, but not in TRPV4
SMC
-/-
mice. Moreover, MAs from TRPV4
SMC
-/-
showed lower vasoconstriction in response to phenylephrine, a α1 adrenergic receptor agonist. These results indicated that Ca
2+
influx through TRPV4
SMC
channels contributes to vasoconstriction and increased vascular resistance. However, studies of pressure-induced constriction or myogenic tone indicated that MAs from TRPV4
SMC
-/-
mice exhibit a higher myogenic constriction at pressures ≥ 60 mm Hg. Moreover, membrane depolarization-induced vasoconstriction (KCl, 33 and 60 mM) was also increased in TRPV4
SMC
-/-
mice when compared to the control mice, indicating that TRPV4
SMC
channels oppose pressure- or membrane depolarization-induced vasoconstriction.

Conclusions:
TRPV4
SMC
channels are essential regulators of resting blood pressure. While TRPV4
SMC
channels contribute to α1 adrenergic receptor-induced vasoconstriction, they negatively regulate pressure-induced vasoconstriction. The divergent effects of TRPV4
SMC
channels on vascular function may be determined by the selective stimulus-TRPV4
SMC
channel coupling and downstream signaling mechanisms.
Abstract 16965: Paraoxanase-1 Modulates Cardiotonic Steroid Induced Cardiac Inflammation and Fibrosis in Dahl Salt Sensitive Model of Chronic Kidney Disease
Authors: Dube Prabhatchandra R , Khalaf Fatimah , Patel Mitra , Khatibshahidi Bella , DeRiso Armelle , Lad Apurva , Mohammed Chrysan J , Kleinhenz Andrew , Fedorova Olga , Haller Steven , Kennedy David J
Published: May 2021

Objective:
Cardiotonic steroids (CTS) are known ligands of the Na+/K+-ATPase (NKA) and chronic elevations in volume expanded conditions such as hypertension and chronic kidney disease (CKD) can mediate a pro-inflammatory and pro-fibrotic phenotype. Paraoxonase1
(PON1)
is a lactonase enzyme that circulates bound to HDL and possesses antioxidant, anti-inflammatory and anti-atherogenic properties. PON1 can hydrolyze CTS to inactive open-ring forms making them incapable of stimulating NKA and initiating pro-inflammatory signaling cascades. Diminished PON1 activity results in detrimental clinical outcomes in the context of CKD but whether reduced
PON1
activity is mechanistically linked to adverse cardiovascular events in CKD remains unknown. We hypothesized that PON-1 can attenuate progression of cardiac inflammation in CKD via modulating the pathogenic pathways induced by CTS signaling using a well characterized Dahl salt-sensitive rat model of hypertensive renal disease and elevated CTS.

Methods:
Dahl salt-sensitive wild type (
SS-WT
), PON1 knockout (
SS-PON1KO
), and PON1 knockout rats treated with 3E9 anti-CTS antibody (3E9 mAb,50μg/kg i.p. every week for a total of 4 injections) were fed a high salt (8%) diet for five weeks to induce hypertensive renal disease and elevate CTS levels. H&E staining was performed on hearts to analyze immune cell infiltration. Real-time PCR (RT-PCR) analysis was performed for markers of inflammation (IL6, IL1β, and CCL2), hypertrophy (Myh7, NPPA, and Slc8a), and fibrosis (Timp1).

Results:
RT-PCR analysis revealed significantly increased (≥1.5 fold) expression of cardiac inflammatory (p<0.005), hypertrophy (p<0.0005), and fibrotic markers (p<0.05) in
SS-PON1 KO
compared to
SS-WT
rats after high salt feeding. Treatment of
SS-PON1 KO
rats with 3E9 mAb significantly decreased (≥ 2.5 fold) expression of Timp1, IL6, Ccl2, IL1β, NPPA, Myh7 and Slc8a (all p<0.005). H&E analysis of hearts revealed significantly decreased immune cell infiltration in
SS-PON1KO rats treated with
3E9 mAb compared to
SS-PON-1 KO
rats (3.5±0.5 VS1.813±0.4094,p<0.005).

Conclusion:
Our findings suggest that PON-1 via its counter-regulatory mechanism of the CTS signaling axis exhibits a cardioprotective role in chronic kidney disease.
Abstract 16977: Coronary Chronic Total Occlusions: Insights on Upstream Management
Authors: Swat Stanley , Hebbe Annika , Waldo Stephen , Valle Javier A
Published: May 2021

Introduction:
Percutaneous coronary intervention (PCI) of coronary artery chronic total occlusions (CTO) has increased over time, despite representing higher procedural risk than traditional PCI. While guidelines for stable ischemic heart disease recommend antianginal therapy prior to attempted revascularization, the frequency with which this occurs for CTO PCI remain unknown. We propose to assess the frequency and variability in upstream use of antianginal therapy prior to CTO PCI attempt over time.

Methods:
This study identified all patients who underwent a CTO PCI attempt from January 2012 to September 2018 across the Veterans Affairs Healthcare System using the Veterans Affairs Clinical Assessment, Reporting and Tracking (CART) program. Patients were categorized by upstream management: (A) <2 antianginal medications prescribed in year prior to CTO PCI, (B) ≥ 2 antianginals (C) Stress testing within 3 months of CTO PCI attempt and (D) ≥2 antianginals AND stress testing. Antianginal medications included beta blockers, nitrates, calcium channel blockers, and ranolazine. Multivariable logistic regression was used to estimate the propensity for receiving each category of treatment over time.

Results:
During the study period, 4250 patients underwent CTO PCI, with 1716 (40%) on ≥2 antianginal medications, 2534 (60%) on <2 antianginals, 1023 (24%) with stress testing, and 338 (8%) on ≥2 antianginals with stress testing. Trends in upstream medical management of patients undergoing CTO PCI were unchanged over each fiscal year (Figure 1A) while odds of preprocedural stress testing decreased across fiscal years (Figure 1B).

Conclusions:
The majority of patients were on low intensity antianginal medical therapy prior to CTO PCI. Utilization of preprocedural stress testing decreased over time while patterns of upstream medical management remained constant, suggesting an opportunity to improve guideline compliance among patients undergoing attempted CTO PCI.
Abstract 16981: Proteomic Profiles of Diabetic Heart Failure Report on Myocardial Metabolism, Ventricular Hypertrophy, and Endothelial Dysfunction
Authors: Truby Lauren K , Kwee Lydia , Regan Jessica A , Bowles Dawn E , Milano Carmelo A , Grass Elizabeth , Bristow Michael R , McGarrah Robert W , Holley Christopher L , Shah Svati H
Published: May 2021

Introduction:
There is a complex epidemiologic relationship between type two diabetes mellitus (DM) and heart failure (HF), and it is unclear whether the biochemical basis of HF differs in patients with and without DM.

Hypothesis:
Proteomic profiling of myocardial tissue from patients with and without DM will identify unique signatures of diabetic HF.

Methods:
Using the Olink aptamer-based platform, we performed proteomic profiling of 552 proteins on 37 myocardial tissue samples: 9 controls, 10 with HF, 7 with DM, and 11 with HF+DM. One-way ANOVA was first used to identify proteins that differed across the four groups. Associated proteins were then tested for differences between HF+DM and each other group independently; we retained proteins with the same direction of effect for each comparison. Each analysis was controlled for false discovery rate (q<0.1).

Results:
We identified 12 proteins that differed significantly between HF+DM and all three other groups. Among these, six proteins were significant after FDR adjusted ANOVA and had the same direction of effect. These included 5’-NT (q=5.35E-07), a regulator of intracellular energy utilization, and carboxypeptidase A2, a metalloprotease that cleaves peptides during digestion (q=0.0003). Expression of myocardial leptin receptors (q=0.001), complement factor H related protein (q=0.003), and carbonic anhydrase (q=0.006) were also upregulated in diabetic HF, and have previously been linked to myocyte hypertrophy. Markers of endothelial dysfunction - ESM-1 (q=5.62E-06) and VEGFR-3 (q=0.024) - were also increased in HF+DM myocardium as compared to other groups (Figure 1).

Conclusions:
Proteomic profiling of HF, DM, and HF+DM myocardial tissue suggest alterations in intracellular energy substrate utilization as well as increased expression of tissue biomarkers previously associated with ventricular hypertrophy and myocardial remodeling.
Abstract 16986: Reduced Medical Spending Overtime With Use of a Home Blood Pressure Monitoring Program
Authors: James Roberta , Lu Wei , Schnieder Jennifer , Shah Bimal R
Published: May 2021

Background:
Livongo’s Applied Health Signals Home Blood Pressure Monitoring Program (HBMP) offers patients a Bluetooth connected blood pressure cuff, hypertension (HTN) management education, and access to health coaches. Previous studies have demonstrated the clinical benefits of HBPM so the objective of this study was to also evaluate the impact on U.S. medical spending within the first year.

Methods:
People younger than 65 years with continuous enrollment in health benefits for the 12 months before and 12 months after launch of the HBMP and use of the program for at least three months were selected. Medical spending for those participants was compared to eligible but non-HBMP participant controls who were identified utilizing propensity score with nearest-neighbor matching methodology on age, gender, and pre-period medical spending with exact matching on Charlson Comorbidity Score Index in a 1:1 ratio. People with medical spending exceeding $50,000 monthly or $100,000 annually were excluded from the analysis. The HBPM participant baseline blood pressures were compared to BP values at 12-months to assess improvement in BP management. Mean medical spending based on the total allowed amounts per member per month (PMPM) was compared between the HBPM and non-HBPM groups using intention-to-treat difference-in-difference (DiD) analysis.

Results:
There were 1,417 HBPM participants with mean age of 51 years, 52% female, 64% with uncontrolled HTN (BP > = 130/80) at baseline, and mean pre-period medical spending of $490 PMPM. For participants with uncontrolled HTN, mean systolic and diastolic BP reductions were 14.2 mmHg and 10.1 mmHg, respectively, with 54% decreasing in HTN stage or considered controlled. The HBPM group had a 1% reduction in medical spending to $474 PMPM while the non-HBPM group had an 18% increase in medical spending from $410 PMPM to $486 PMPM resulting in a medical savings of $81 PMPM. The HBPM group also had a reduction of 33% in inpatient utilization and 14% in ED visits.

Conclusion:
HBPM participants experienced improved BP control and a reduction in total medical cost savings resulting in a positive return on investment. The main drivers of medical savings were a reduction in ED and inpatient hospital utilization.
Abstract 17007: Cardiac Magnetic Resonance Assessment of Right Ventricular Remodeling After Anthracycline Therapy
Authors: Ferreira de Souza Thiago , Quinaglia Thiago , Antunes-Correa Ligia , Drobni Zsofia , Costa Felipe , Nadruz Wilson , Brenelli Fabrício , Sposito Andrei , Mattos-Souza José , Neilan Tomas , Jerosch-Herold Michael , Coelho-filho Otavio R
Published: May 2021

Introduction:
There are limited data characterizing the effect of anthracyclines on right ventricular (RV) structure and function.

Hypothesis:
The goal of this study was to test the effect of anthracyclines on RV myocardial remodeling using cardiac magnetic resonance (CMR).

Methods:
This was a prospective CMR and serum biomarker study of 27 women with breast cancer (BC) (51.8±8.9 years) who underwent a CMR prior, and up to 3-times after anthracycline therapy (240 mg/m
2
). The primary measure of interest was the RV extracellular volume (ECV) and cardiomyocyte mass index (1-ECV). Additional measures of interest were the left ventricular (LV) ECV, and the LV and RV mass. Biomarkers included high-sensitive troponin T, and creatinine-kinase MB isoenzyme (CKMB).

Results:
Before anthracyclines, all subjects had normal LV ejection fraction (EF) (69.4±3.6%) and RVEF (55.6±9%). At 351-700 days after anthracyclines, the LVEF and LV mass index declined to 58±6% (P<0.001) and 36±6g/m
2
(P<0.001). Similarly, the RVEF and RV mass index also decreased, reaching 46.3±6.8% at (222-350] days (P<0.001) and 8.13±2g/m
2
at (350-700] days (P<0.001) after anthracycline, respectively (Figure 1). At (350-700] days after anthracycline, both LV and RV ECV increased by 0.037 to 0.36±0.04 (P=0.004) and by 0.12 to 0.40±0.07 (P<0.001), respectively (Figure 2). In parallel, both the LV and RV cardiomyocyte mass also decreased after anthracyclines (Figure 2).

Conclusions:
In a prospective observational study among women with breast cancer, anthracyclines were associated with a decrease in the RV EF, an increase in the RV ECV and a decrease in the RV cardiomyocyte mass.