bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15682: A Novel Antibiotic Delivery Approach Enhances Salvage of Infected Cardiovascular-implantable Electronic Devices
Authors: Topaz Moris , Kazatsker Mark , Ashkenazi Itamar , Schwartz Arie L , Carmel-Neiderman Narin N , Topaz Guy , Rosso Raphael , Glikson Michael , Viskin Sami , Shotan Avraham
Published: May 2021

Introduction:
Infection of cardiovascular-implantable electronic devices (CIED) is a serious complication. Systemic antibiotic therapy is considered ineffective, justifying the current guidelines proposing total CEID and lead extraction.

Objective:
To evaluate the safety and efficacy of continuous in-situ-targeted, ultra-high concentration of antibiotics (CITA) in CIED infections limited to the subcutaneous pocket.

Methods:
Infected CIED were treated with CITA, delivered to the CIED pocket following minimally invasive surgery (MIS). The CIED were submerged in a 10
2
-10
3
minimal inhibition concentration (MIC) solution of vancomycin and/or gentamicin as per daily conventional dosing. Serum antibiotic levels were regulated by adjusting the concentration and flow of pocket irrigation. CIED salvage rate was assessed.

Results:
A total of 937 and 481serum assays of vancomycin and gentamicin, respectively, from 83 infected CIED was evaluated (Figure). Target antibiotic serum levels were obtained at 12-48 hours. Median treatment was 8 days (IQR 5,12). Parallel intravenous (IV) vancomycin treatment was applied in 6 (7%) infections. Vancomycin serum levels exceeded a trough limit of 20μg/ml in 20 (2.1%) assays, of which 19/20 received parallel IV treatment. No peak gentamicin levels were recorded. Gentamicin exceeded trough serum level reaching 2-3μg/ml in 80 (16.6%), reached potentially toxic levels of 3-5μg/ml in 33 (6.9%), and exceeded 5μg/ml in 10 (2.1%) assays. CITA resulted in a 1-year salvage of 71 (86%) CIED. Treatment failed in 12 infections, resulting in 8 uneventful total CIED extractions. The 30-day mortality rate was 2.4%.

Conclusions:
CITA provided ultra-high pocket antibiotic levels, with its safety confirmed by systemic level assays. CITA combined with MIS enabled salvage of 86% of infected CIED. The CITA-MIS approach may serve as an initial therapeutic option prior to the extraction of locally infected CIED, especially in high-risk patients.
Abstract 15684: Discordance Between Severity of Heart Failure as Determined by Patient Report versus Cardiopulmonary Exercise Testing
Authors: Michelis Katherine C , Grodin Justin L , Zhong Lin , Pandey Ambarish , Toto Kathleen , Thibodeau Jennifer T , Drazner Mark H
Published: May 2021

Introduction:
Although patient-reported outcomes are increasingly emphasized, symptoms may be discordant to objective parameters of heart failure severity. The frequency of such discordance, associated characteristics, and its influence on clinical outcomes is unknown.

Methods:
This is a post-hoc analysis of the HF-ACTION trial (N=2062). Participants were divided by median baseline values for Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ, subjective measure) and V
E
/VCO
2
slope (objective measure) into 4 groups: “concordant-lower severity” (high KCCQ, low V
E
/VCO
2
slope), “concordant-higher severity” (low KCCQ, high V
E
/VCO
2
slope), “symptom magnifier” (low KCCQ, V
E
/VCO
2
slope), and “symptom minimizer” (high KCCQ, V
E
/VCO
2
slope). Baseline characteristics were compared, and the relationship between group and clinical outcomes over a median follow-up of 442 days was assessed in adjusted Cox models.

Results:
Discordance of patient-reported and objective illness severity was common (46%). Depression was more prevalent among symptom magnifiers (N=480) versus concordant-lower severity (N=566) and symptom minimizer (N=465) groups (30%, 18%, 14%, respectively; P<0.001). Compared to concordant-lower severity participants, those who were symptom magnifiers, symptom minimizers, or concordant-higher severity were at increased risk of hospitalization (Table). Concordant-higher severity participants and symptom minimizers, but not symptom magnifiers, were at an increased risk of death versus concordant-lower severity participants.

Conclusion:
A high rate of discordance was observed between patient-reported and objective heart failure severity. Depression was associated with symptom magnification. Hospitalization was influenced by patient-reported severity but mortality tracked more closely with objective data, highlighting potential limitations of static patient-reported outcomes for risk stratification.
Abstract 15701: Relationship Between Cardiac Biomarkers and Major Adverse Cardiovascular Events in DECLARE-TIMI 58
Authors: Zelniker Thomas A , Morrow David A , Mosenzon ofri , Goodrich Erica , Jarolim Petr , Cahn Avivit , Bhatt Deepak L , Leiter Lawrence A , McGuire Darren K , WILDING JOHN , Averkov Oleg V , Budaj Andrzej , Parkhomenko Alexander , Ray Kausik K , Gause-nilsson Ingrid A , Langkilde Anna Maria , Fredriksson Martin , RAZ Itamar , Sabatine Marc S , Wiviott Stephen D
Published: May 2021

Introduction:
Biomarkers of hemodynamic stress and myocardial injury are associated with the risk of CV death & heart failure in patients with atherosclerotic vascular disease (ASCVD). Here we explore the association between cardiac biomarkers and ASCVD outcomes in patients with type 2 diabetes (T2DM).

Methods:
This was a nested biomarker study in DECLARETIMI 58, a randomized, blinded, placebo-controlled trial of dapagliflozin in T2DM and either multiple risk factors (MRF, ~60%) or established ASCVD (~40%). The relationship between baseline NT-proBNP and hsTnT levels (TIMI Biomarker Laboratory, n=14,565) and the composite of myocardial infarction, ischemic stroke, and CV death (MACE), was modeled within the placebo arm using Cox models adjusted for age, sex, race, smoking, baseline eGFR, BMI, T2DM duration, insulin use, history of CAD, MI, ischemic stroke, PAD, HF, dyslipidemia & hypertension. Interaction testing was applied to assess the effect of dapagliflozin according to baseline biomarker value.

Results:
NT-proBNP and hsTnT were significantly associated with MACE (Adjusted hazard ratio (aHR) per 1-SD in log-transformed biomarker, NT-proBNP: aHR 1.62; hsTnT aHR 1.59). The magnitude of the relationship was similar in patients with ASCVD (NT-proBNP aHR 1.60; hsTnT aHR 1.62) and MRF (NT-proBNP aHR 1.62; hsTnT: aHR 1.51)
[Fig A]
. Moreover, both biomarkers remained independently associated with MACE when combined in the multivariable model (NT-proBNP aHR 1.46, hsTnT aHR 1.39). The risk of MACE by baseline biomarker level and stratified by treatment arm is shown in
Fig B.

Conclusions:
In patients with T2DM both with and without ASCVD, higher baseline NT-proBNP or hsTnT levels identified patients at increased risk of MACE. The difference in MACE rates between dapagliflozin and placebo tended to be more pronounced in ASCVD patients with higher baseline or NT-proBNP or hsTnT levels.
Abstract 15707: Histone Deacetylase Inhibition Reverses Preexisting Diastolic Dysfunction and Blocks Covert Extracellular Matrix Remodeling
Authors: Travers Joshua G , Wennersten Sara A , Pena Brisa , Bagchi Rushita A , Smith Harrison E , Hirsch Rachel A , Vanderlinden Lauren A , Lin Ying-Hsi , Dobrinskikh Evgenia , Demos-Davies Kimberly M , Cavasin Maria A , Mestroni Luisa , Steinkuhler Christian , Houser Steven R , Lin Charles Y , Lam Maggie P , McKinsey Timothy A
Published: May 2021

Introduction:
Diastolic dysfunction is associated with the development of heart failure with preserved ejection fraction and other cardiac maladies, including atrial fibrillation. Inhibition of histone deacetylase (HDAC) activity has previously been shown to prevent diastolic dysfunction by enhancing myofibril relaxation. Here, we further addressed the therapeutic potential of HDAC inhibition in a model of established diastolic dysfunction with preserved ejection fraction.

Methods:
Four weeks following uninephrectomy (UNX) and implantation with deoxycorticosterone acetate (DOCA) pellets, when diastolic dysfunction was clearly evident, one cohort of mice was administered the clinical-stage HDAC inhibitor ITF2357/Givinostat. Serial echocardiography, blood pressure measurements, and endpoint invasive hemodynamic analyses were performed, along with the evaluation of pathological cardiac fibrosis and remodeling.

Results:
HDAC inhibition completely normalized diastolic function without lowering blood pressure in this model of systemic hypertension. Cardiac fibrosis was not evident in any mouse cohorts based on picrosirius red staining or second harmonic generation microscopy. However, mass spectrometry revealed induction in the expression of more than one hundred extracellular matrix (ECM) proteins in LVs of UNX/DOCA mice, which correlated with profound tissue stiffening based on atomic force microscopy. Remarkably, ITF2357/Givinostat treatment entirely blocked ECM expansions and LV stiffening. The HDAC inhibitor was subsequently shown to suppress cardiac fibroblast activation, at least in part, by blunting recruitment of the pro-fibrotic chromatin reader protein, BRD4, to key gene regulatory elements.

Conclusions:
These findings demonstrate the potential of HDAC inhibition as a therapeutic intervention to reverse existing diastolic dysfunction, and establish blockade of ECM remodeling as a second mechanism by which HDAC inhibitors improve ventricular filling. Additionally, our data reveal the existence of pathophysiologically relevant ‘covert’ cardiac fibrosis that is below the limit of detection of histochemical stains, highlighting the need to evaluate fibrosis of the heart using diverse methodologies.
Abstract 15710: Myocardial Ischaemia in Cardiac Amyloidosis, Changing Perspectives
Authors: Chacko Liza , Kotecha Tushar , Martinez-Naharro Ana , Brown James , Rezk Tamer , Knott Kristopher , Knight Daniel , Patel Niket , Moon James C , Gonzalez Arantxa , Rapezzi Claudio , Gilbertson Janet , Leone Ornella , Xue Hui , Hawkins Philip , Gillmore Julian D , Kellman Peter , Fontana Marianna
Published: May 2021

Introduction:
Cardiac involvement determines outcome in systemic amyloidosis, but the relationship between amyloid deposits and outcomes is poorly understood. Many clinical observations are not explained by the simple concept of physical, mechanical replacement of the interstitium by amyloid material.

Hypothesis:
Preliminary studies in patients with cardiac amyloidosis (CA) support the hypothesis that myocardial ischaemia contributes to cell damage. This study assesses the presence and mechanisms of myocardial ischaemia using CMR with multiparametric mapping and histopathological assessment.

Methods:
92 patients with CA (41 AL, 51 ATTR) and 73 without CA (26 with unobstructed coronary arteries; 47 with 3VD) underwent CMR with T1, T2, Extracellular volume (ECV) mapping and adenosine stress with myocardial blood flow (MBF) mapping. 25 cardiac biopsies and 3 explanted hearts with CA were analysed histopathologically.

Results:
CA patients had severe reductions in stress MBF and myocardial perfusion reserve (MPR)- (1.03ml/g/min±0.50;1.54±0.59
)
compared to patients with unobstructed coronary arteries (2.82 ml/g/min±0.53; 2.94±0.59, p<0.001), and comparable only to 3VD (1.32±0.47ml/g/min, p=0.04;1.49±0.44, p=1.00). Myocardial perfusion abnormalities correlated with amyloid burden, systolic function and blood biomarkers (p<0.001). Biopsies showed evidence of diffuse hypoxia with abnormal VEGF staining in cardiomyocytes and endothelial cells. Amyloid infiltration in intramural arteries was associated with severe lumen reduction in 20% of vessels, with severe reduction in capillary density in areas with and without amyloid deposits.

Conclusion:
CA is associated with severe myocardial ischaemia demonstrable by histology and CMR perfusion mapping. Histological evaluation indicates a complex pathophysiology, where direct disruption of the vessels by amyloid deposits and reduction in epicardial flow contribute to myocardial ischaemia.
Abstract 15714: Intra-cardiac Pressure Estimation Using Subharmonic Aided Pressure Estimation (SHAPE) - A Clinical Evaluation
Authors: Esposito Cara , Savage Michael P , Mehrotra Praveen , Cohen Ira , Fischman David L , Machado Priscilla , McDonald Maureen , Ruggiero Nicholas J , Walinsky Paul , Vishnevsky Alec , Forsberg Flemming , Davis Marguerite , Dickie Kristopher , Dave Jaydev K
Published: May 2021

Introduction:
Subharmonic aided pressure estimation (SHAPE) utilizes ambient pressure sensitivity of subharmonic signals from ultrasound contrast agents. The objective was to evaluate SHAPE with Definity (Lantheus Medical Imaging, Inc.) and Sonazoid (GE Healthcare) microbubbles for intra-cardiac pressure estimation.

Hypothesis:
Errors between SHAPE and pressures obtained during cardiac catheterization ≤ 5 mmHg.

Methods:
IRB approved this study. Consenting patients received an infusion of Definity (56 patients; 2 vials in 50 mL of saline; infusion rate: 4-10 mL/min) or Sonazoid (77 patients; rate (mL/hour) = 0.18 x weight in kg co-infused with saline at 120 mL/hour) during cardiac catheterization. Subharmonic data was acquired using a SonixTablet (PA 4/2 array; BK Ultrasound) synchronously with pressures from the left and right ventricles and the aorta (for left heart catheterizations only). Subharmonic data (in dB) was converted to pressure values (in mmHg) using calibration factors (mmHg/dB) based on data obtained from the aorta - utilizing pressures from the aorta either during the catheterization procedure or pressures obtained using a SphygmoCor (AtCor Medical Pty. Ltd.) device after the catheterization procedure. Clinically relevant pressures between the SHAPE technique and the pressure catheter were compared.

Results:
Correlation coefficient between the subharmonic and pressure data was -0.8 ± 0.1. With Definity, mean absolute errors ranged from 2.9 ± 1.5 to 5.0 ± 4.2 mmHg and from 4.4 ± 5.7 to 23.7 ± 28.3 mmHg for calibration factors utilizing aortic pressures from pressure catheter and SphygmoCor, respectively. For Sonazoid microbubbles, these errors ranged from 7.9 ± 12.0 to 10.1 ± 12.4 mmHg and from 7.2 ± 11.5 to 15.0 ± 23.2 mmHg, respectively. Two adverse events occurred during Definity infusion; these were resolved with return to baseline conditions.

Conclusion:
SHAPE may be useful for estimating intra-cardiac pressures noninvasively.
Abstract 15719: Levosimendan Improves Liver Function in Patients With Advanced Chronic Heart Failure
Authors: Zemljic Gregor , Anzic Drofenik Ajda , Cerar Andraz , Frljak Sabina , Poglajen Gregor , Sebestjen Miran , Okrajsek Renata , Knezevic Ivan , VRTOVEC Bojan
Published: May 2021

Introduction:
Although there is evidence of beneficial effects of levosimendan on heart and renal function in patients with advanced chronic heart failure, the impact of levosimendan on liver function remains undefined.

Hypothesis:
We investigated the effects of levosimendan on liver function in patients with advanced chronic heart failure.

Methods:
We enrolled 299 patients with chronic heart failure (NYHA class 3) and left ventricular ejection fraction <30%, aged between 18 and 80 years. 150 patients were randomized to receive levosimendan (0.1 mcg/kg/min infusion for 24 hours; LS Group), and 149 received no levosimendan (Controls). Liver function was evaluated at baseline and again at 3 months by measuring total bilirubin, direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gGT) and lactate dehydrogenase (LDH).

Results:
At baseline, the groups did not differ in age (59±11 years in LS Group vs. 60±10 years in Controls; P=0.74), sex (male: 77% vs. 75%; P=0.36), heart failure etiology (ischemic: 45% vs. 47%; P=0.64), left ventricular ejection fraction (27±2% vs. 26±3%; P=0.97), and plasma NT-proBNP levels (4758±3912 pg/mL vs. 5111±4271 pg/mL; P=0.71). Liver function tests of both groups at the time of enrollment were comparable. At 3 months we found a significant improvement in liver function in LS Group, but not in Controls, with a decrease in total bilirubin (21.9±16.4 μmol/L to 18.5±13.1 μmol/L in LS Group vs. 22.1±17.1 μmol/L to 22.0±17.3 μmol/L in Controls; P<0.001), direct bilirubin (8.6±6.4 μmol/L to 7.1±5.2 μmol/L vs. 8.7±6.6 μmol/L to 8.8±6.7 μmol/L; P<0.001), AST (1.18±0.98 μkat/L to 0.42±0.40 μkat/L vs. 1.16±0.92 μkat/L to 1.15±0.87 μkat/L; P=0.03), ALT (0.73±0.71 μkat/L to 0.50±0.49 μkat/L vs. 0.75±0.77 μkat/L to 0.74±0.70 μkat/L; P=0.006), gGT (2.25±2.30 μkat/L to 1.87±1.94 μkat/L vs. 2.23±2.18 μkat/L to 2.22±2.16 μkat/L; P=0.003) and LDH (3.66±2.46 μkat/L to 3.36±1.96 μkat/L vs. 3.58±2.77 μkat/L to 3.62±2.82 μkat/L; P=0.006).

Conclusions:
Levosimendan appears to improve long-term liver function in advanced chronic heart failure patients. Thus, repetitive levosimendan infusions may potentially slow the progression of cardio-hepatic syndrome to cardiac cirrhosis.
Abstract 15720: Transmembrane Stem Cell Factor Delivered in Nanocarriers Promotes Angiogenesis in Ischemia Without Mast Cell Activation
Authors: Takematsu Eri , Srinath Sanjana , Sherman Michael , Dunn Andrew K , Baker Aaron
Published: May 2021

Introduction:
The current standard cares for peripheral artery disease (PAD) include surgical revascularizations with bypass grafting or percutaneous interventions. However, these interventions cannot be performed in a significant portion of patients, and many do not respond to these surgical procedures. Protein therapy to stimulate the body to create new vasculature is another alternative, which is minimally invasive to patients. Stem cell factor (SCF) is a candidate protein for treating PAD, but clinical use of SCF has been limited due to toxicity related to mast cell activation. SCF also exists in a transmembrane form (tmSCF), possessing differential activities from soluble SCF and has not been explored as a therapeutic agent.

Results:
To develop tmSCF as a therapeutic we created tmSCF embedded in liposome or lipid nanodisc
(Fig. A)
. Hindlimb ischemia model on WT and ob/ob mice showed that tmSCF proteliposome (tmSCFPL) and nanodisc (tmSCFND) improved blood flow recovery significantly more than control
(Fig. B, C)
. Mouse model of anaphylaxis revealed that tmSCF-based therapies did not activate mast cells
(Fig. D, E)
. Colocalization assay of c-Kit and clathrin/caveolin revealed that mast cells preferentially use clathrin-mediated pathways to internalize SCF and caveolin-mediated pathways for tmSCF-based therapies
(Fig. F, G)
. Surface c-Kit internalization study on mast cells showed faster uptake of SCF in comparison to tmSCF-based therapies
(Fig. H)
. Previous study indicates that clathrin-mediated internalization causes increased activation of mast cells. Our studies together with the previous finding suggest that mast cell activation does not occur for tmSCF-based therapies because of the slower uptake, greater utilization of the caveolin internalization pathway and weaker activation of mast cells.

Conclusions:
TmSCF-based therapies can provide therapeutic benefits without off-target effects on mast cells by tuning activation with nanocarriers.
Abstract 15732: Transcatheter Aortic Valve Replacement as a Path to Transplant: Similar Short-term Outcomes in Liver and Renal Failure
Authors: Caughron Hope , Parikh Devang , Allison Zev , Mahadevan Vaikom
Published: May 2021

Introduction:
Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement in patients with predicted poor surgical outcomes due to end stage liver disease (ESLD) or end stage renal disease (ESRD), though there remains minimal data regarding outcomes and treatment strategy in this population. This study evaluates in-hospital, 30-day, and 1-year outcomes after TAVR in a cohort of patients with ESLD and/or ESRD compared to a cohort without these comorbidities.

Methods:
We retrospectively compared 317 consecutive patients (N=37 ESLD and ESRD, N=286 without ESLD or ESRD) age >18 who underwent transfemoral or transssubclavian TAVR at University of California San Francisco Medical Center from August 1
st
, 2014 to April 1
st
, 2020.

Results:
The ESLD and ESRD group had younger patients (69.8±11.5 vs 79.1±9.8, p<0.01), a higher incidence of diabetes mellitus (54.8% vs 28.3%, p<0.01), and higher STS-PROM scores (7.8±6.5 vs 4.7±3.9, p<0.01). Comparing the ESLD and ESRD to the control group, there were similar rates of in-hospital cerebrovascular events (3.2% vs 3.5%, p=0.94), vascular complications (6.5% vs 7.0%, p=0.91), and mortality (0.0%, vs 1.7%, p=0.46) with more bleeding events at discharge (9.7% vs 2.1%, p=0.01) and 1-year (29.2% vs 10.4%, p=0.01). Mortality rates were similar at 30-days (3.2% vs 2.1%, p=0.69) and 6-months (3.4% vs 2.8%, p=0.83), with a trend towards higher mortality in the ESLD and ESRD group at 1-year (16.7% vs 7.8%, p=0.15) from primarily noncardiac causes. Readmission rates were higher in the ESLD and ESRD cohort at 6-months (58.6% vs 27.2%, p<0.01) and 1-year (66.7% vs 40.6%, p=0.02).

One patient received dual kidney-liver transplant, 1 patient received a liver transplant, and 8 patients remain on the transplant wait-list.

Conclusion:
Patients with ESLD and ESRD who underwent TAVR had higher rates of bleeding events and noncardiovascular readmissions with similar rates of mortality at discharge, 30-days, and 6-months when compared to patients without these comorbidities. This study suggests that TAVR may be a safe path to transplant in patients with liver or renal failure and aortic valve pathology, though additional studies are necessary to confirm these findings.
Abstract 15742: An Open-label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution Shows Acute Conversion of Recent-onset, Symptomatic Atrial Fibrillation to Sinus Rhythm in a Dose- and Concentration-dependent Manner
Authors: Crijns Harry , Ruskin Jeremy N , Elvan Arif , Al-Windy Nadea , Tuininga Ype , Badings Erik , Aksoy Ismail , Van Gelder Isabelle C , Camm John , Kowey Peter R , Belardinelli Luiz ,   on behalf of the INSTANT Investigators
Published: May 2021

Introduction:
Oral and intravenous (IV) flecainide are recommended as first line therapy for pharmacological cardioversion of recent-onset atrial fibrillation (AF) in patients without known relevant structural heart disease. In the present open-label, dose-escalation study, the feasibility of using flecainide acetate inhalation solution (FlecIH) for acute conversion of recent-onset AF to sinus rhythm (SR) was evaluated.

Hypothesis:
We hypothesized that FlecIH quickly gives rise to plasma concentrations sufficient to rapidly restore SR in patients with recent-onset AF.

Methods:
Patients (n=95) with symptomatic AF (for ≤ 48 hours) were enrolled and self-administered FlecIH using a breath-actuated nebulizer (30 mg [n=10], 60 mg [n=20], 90 mg [n=21], 120 mg [n=17], and 120 mg in a formulation containing saccharin [n=27]). Blood samples were collected for flecainide plasma concentrations, electrocardiograms were obtained, cardiac rhythm with a 4-hour Holter and vital signs were monitored, and adverse events (AEs) were recorded. Patients who did not convert to SR were offered alternative treatment per the investigator’s discretion.

Results:
Conversion rates increased with dose and maximum plasma concentrations (C
max
) of flecainide. At the highest dose, 45% of patients converted to normal SR. Patients with C
max
> 300 ng/mL had a conversion rate of 53% whereas those with C
max
< 200 ng/mL had a conversion rate of 33%. The median time to conversion was 3.5 min after FlecIH administration. AEs were typically mild and transient. Commonly reported AEs associated with inhalation of flecainide included: cough, throat pain, and throat irritation; at the highest dose with the formulation containing saccharin, these AEs were reported for 37%, 11%, and 4% of patients, respectively. Cardiac AEs consistent with those observed with oral and IV flecainide and considered serious were uncommon and included 2 post-conversion pauses and 1 bradycardia, and 1 atrial flutter with 1:1 atrioventricular conduction; none required treatment and all resolved without sequelae.

Conclusions:
FlecIH was well tolerated. Inhalation of FlecIH at the 120 mg dose yielded therapeutic plasma levels and conversion rates within the range reported for oral and IV administration.
Abstract 15744: Contemporary Rhythm Monitor Utilization Following Acute Ischemic Stroke
Authors: Li Xinye , Khurshid Shaan , Ashburner Jeffrey M , Atlas Steven J , Singer Daniel E , Lipsanopoulos Ana T , Lee Priscilla R , Lin Aimee K , Ellinor Patrick T , Benjamin Emelia J , Schwamm Lee H , ANDERSON Christopher D , Trinquart Ludovic , Lubitz Steven A
Published: May 2021

Introduction:
Post-stroke rhythm monitoring can detect occult AF, but contemporary utilization is not well-understood. We sought to quantify monitor deployment in a real-world stroke population and assess whether it is calibrated to clinical AF risk.

Methods:
We performed a single-center analysis of consecutive patients with acute ischemic stroke 10/2018-6/2019 and no AF history and assessed monitor utilization (Holter/ECG, event/patch, and implantable loop recorder [ILR]) at 6 months. We evaluated predictors of monitor deployment using Cox proportional hazards modeling with the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) AF risk score, stroke subtype, and discharge disposition. We estimated the cumulative incidence of monitoring both overall and in stroke subtype and discharge disposition subgroups, accounting for the competing risk of death and with adjustment for other factors using inverse probability weighting.

Results:
Of 532 acute stroke patients (mean age 65, 47% female), the 6-month incidence of monitoring was 36.2% (95% CI 31.5-40.9,
Figure
). Monitoring included Holter/event monitor (74.3%), ILR (21.2%) or both (4.5%). Monitoring was more likely after cryptogenic (hazard ratio 4.36, 95%CI 3.12-6.1; 6-month monitor incidence 69.3%) and cardioembolic (1.80, 1.00-3.22; 37.3%) stroke, as opposed to other/unknown subtype (24.3%). Monitoring was also more likely after discharge home (1.92, 1.39-2.66; 47.6%) versus facility (27.7%). Monitoring was not associated with AF risk (1.08, 0.93-1.27, per 1 SD increase in CHARGE-AF), even though AF risk was associated with AF (1.67, 1.3-2.15, per 1 SD increase in CHARGE-AF).

Conclusions:
Rhythm monitors are underutilized after stroke. Interventions to encourage monitor deployment according to AF risk may improve the efficiency of post-stroke monitoring.

Figure.
Cumulative incidence of monitoring overall and within strata of stroke subtype and discharge disposition
Abstract 15745: Health Outcomes in Pulmonary Arterial Hypertension Patients With COVID-19: A Real-world Analysis
Authors: feldman jeremy , wilson melisa , Kantorovich Alexander , DeRuiter Alexander , Schreur Kevin , Classi Peter , Nelsen Andrew
Published: May 2021

Introduction:
Patients with underlying chronic conditions, including PAH, are predicted to have worse outcomes with COVID-19. This analysis aimed to assess the impact of COVID-19 on outcomes in PAH patients.

Methods:
Over a 5-month period starting 1/1/2020, PAH patients with COVID-19 were compared to PAH patients without COVID-19. In addition, COVID-19 patients with and without PAH were analyzed. Differences in all-cause mortality, all-cause hospitalization, and need for mechanical ventilation (MV) at any time after COVID-19 diagnosis were evaluated. Similar analyses were performed between subgroups of hospitalized patients. PAH and COVID-19 patients were identified by ICD and CPT codes along with PAH-specific medications from the TriNetX Dataworks Network of 35 international healthcare organizations. Cohorts were compared using unmatched and propensity-matched data (PMH, demographics, labs, and non-PAH medications) with categorical variables evaluated using χ
2
/Fisher’s Exact tests.

Results:
A total cohort of 566 patients were identified with a diagnosis of PAH; 510 without COVID-19 and 56 with COVID-19. In PAH patients with COVID-19, there were significantly higher rates of all-cause mortality, all-cause hospitalization, and need for MV (p<0.00001) compared to PAH patients without COVID-19. Mortality in the PAH with COVID-19 cohort was 16% compared to 2% in the PAH group without COVID-19. After matching, significance was maintained in all-cause hospitalization (P=0.0013) and need for MV (P=0.0009). Adjusting for disease severity examining only matched all-cause hospitalized patients, death and need for MV was significantly higher in the PAH patients with COVID-19. When comparing PAH patients with COVID-19 versus a matched COVID-19 cohort without PAH, there were no differences in any evaluated outcomes.

Conclusions:
This real-world analysis demonstrates that PAH patients with COVID-19 have worse outcomes, including a higher rate of all-cause mortality at 5 months, compared to PAH patients without COVID-19. Additionally, no differences were observed between COVID-19 patients with or without PAH. In a subset of patients with more severe disease that were hospitalized, the results were consistent to those from the overall cohort.
Abstract 15748: Failure of Subcutaneous Implantable Cardioverter Defibrillator in a Patient With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Desai Anish K , Glover Annie , Krebsbach Angela , Henrikson Charles
Published: May 2021

Introduction:
The subcutaneous ICD is an attractive option in ARVC patients as they rarely require pacing, it preserves vascular access, and it avoids the long-term morbidity related to intravascular lead placement. However, the limitations of the S ICD have not been fully demarcated by clinical trials.

Case:
After her father presented with a cardiac arrest, a 16-year-old female was diagnosed with ARVC on MRI after initially presenting with palpitations. This was corroborated via genetic testing, and an S ICD was placed after she passed pre-implant screening. Initially she did well, but she suffered inappropriate shocks approximately seven months after implant, in the setting of “hugging her boyfriend”. Interrogation revealed apparent noise, which was felt to be most likely due to lead fracture or possibly generator malfunction. At reoperation, first her lead was replaced, but continued noise was demonstrated intra-operatively, and thus her generator was also replaced. However, she was found again to have noise in each vector causing recurrent inappropriate shocks. Further testing ultimately determined that the noise was due to myopotentials, which were present in all vectors and unable to be programmed around. Ultimately, the S ICD was removed and replaced with a transvenous device.

Discussion:
While the S ICD is an attractive option in ARVC patients, the limitations of the technology must be acknowledged. The far-field nature of the sensing algorithm in the S ICD leads to a risk of myopotential oversensing. If this occurs, sometimes the system cannot be salvaged and the patient must be converted to a transvenous system. Recognizing this at the initial presentation with inappropriate shocks can avoid unsuccessful attempts at S ICD system modification and morbidity from future inappropriate shock events.
Abstract 15760: Survival Following Durable Ventricular Assist Device Implantation is Associated With Provider Teamwork: A Social Network Analysis
Authors: Funk Russell J , Fetters Michael D , Pagani Francis D , Hou Hechuan , Zhang Min , Yang Guangyu , Aaronson Keith D , Hollingsworth John M , Chandanabhumma P. P , Cabrera Lourdes , Likosky Donald S
Published: May 2021

Introduction:
Health systems with more robust provider teamwork have lower mortality rates for coronary artery bypass grafting. Patients undergoing durable ventricular assist device (VAD) therapy have complex comorbidities and develop adverse events requiring multidisciplinary provider teamwork.

Hypothesis:
Provider teamwork is associated with 180-day mortality following durable VAD implantation.

Methods:
Data (linked Medicare claims+INTERMACS) were analyzed from primary durable VADs implanted across 119 hospitals over a five-year period. Claims were used to identify provider interactions (cardiac surgeons, cardiologists, anesthesiologists, intensivists, nurse practitioners, physician assistants) for previously shared VAD patients during the 1-year period ending 6-months before each patient’s VAD implant admission. Provider teamwork was assessed at the hospital level using a clustering coefficient (range: 0-1; higher values = greater teamwork), an established and validated measure capturing the prevalence of tightly connected groups in a network. Provider teamwork level was associated with a patient’s 180-day mortality rate using multivariable regression adjusting for baseline characteristics reported to INTERMACS.

Results:
The study cohort included 2,807 VAD patients (mean age 63 years, 53% for destination therapy, 19% female, 74% white) with 10.8% identified as INTERMACS Profile 1. There were 468 deaths (16.7%) within 180 days of implantation. Provider teamwork (clustering coefficient) was inversely associated with 180-day mortality (beta=-0.79; 95%CI: -1.26, -0.11). A 1SD increase in provider teamwork was associated with a 13.4% decrease in the predicted probability of 180-day mortality, Figure.

Conclusions:
Social networks characterized by greater provider teamwork are important determinants of mortality following VAD implantation and may serve as targets for optimizing outcomes and greater adoption for this therapy.
Abstract 15765: Clinical Significance of Submaximal Parameters of Exercise Stress Test in Characterizing Post-Fontan Patients
Authors: Kernizan Daphney , DAloisio Gina , Robinson Bradley , Tsuda Takeshi
Published: May 2021

Background:
Fontan patients have diminished exercise capacity relative to healthy peers. Peak oxygen consumption (pVO2) is a useful marker for maximum exercise capacity, though it may not be achievable in certain patients. We studied clinical validity of submaximal parameters in exercise stress test (EST) in post-Fontan patients.

Methods:
We retrospectively analyzed EST of post-Fontan patients and age-matched controls by cycle ergometer. We obtained peak values of heart rate (pHR), VO2, oxygen pulse (pOP), respiratory quotient (pRQ), and work rate (pWR). Submaximal parameters included ventilatory anaerobic threshold (VAT), slopes of VO2/HR changes (ΔVO2/ΔHR) and HR/WR changes (ΔHR/ΔWR), and oxygen uptake efficiency slope (OUES). Data are shown as mean ± standard deviation.

Results:
Twenty four single right ventricle (SRV), 12 single left ventricle (SLV), and 24 controls were studied (Table 1).pHR, pVO2, pOP, and pWR were significantly lower in Fontan patients than in controls, but with no significant difference between SRV and SLV. ΔVO2/ΔHR and OUES were significantly lower in Fontan group than controls, whereas VAT and pRQ were comparable in all three groups. VAT was preserved in Fontan groups. Lower slope of ΔVO2/ΔHR and decreased OUES in the Fontan group suggests an intrinsic exercise limitation or limited stroke volume (SV) increase. This was compensated by a higher HR response up to AT, exhibited by the higher slope of ΔHR/ΔWR despite lower pHR in the Fontan group.

Conclusions:
Peak exercise parameters were significantly lower in Fontan patients although pRQ and VAT were comparable among the three groups. The lower ΔVO2/ΔHR and pOP in Fontan patients suggest limited SV reserve in response to exercise. A combination of lower ΔVO2/ΔHR and higher ΔHR/ΔWR characterizes Fontan patient. Inclusion of submaximal exercise parameters brings additional value in specifying the physiological responses to exercise.
Abstract 15771: Recovery of Left Ventricular Function on Lvad Support is Associated With Improved Outcomes
Authors: Olsen Cameron , Mandawat Aditya , Triana Taylor , Samsky Marc D , Chiswell Karen , Karra Ravi -
Published: May 2021

Introduction:
For select patients, support with a left ventricular assist device (LVAD) can be used as a bridge to recovery of ventricular function. While rates of explant are low, improvement of left ventricular ejection fraction (LVEF) on LVAD support is more common.

Hypothesis:
We hypothesize that LVAD recipients whose LVEF recovers have better outcomes compared to those whose LVEF does not recover.

Methods:
Data from INTERMACS was merged with the Duke Echo Lab Database for all patients who underwent LVAD implantation between March 2006 and June 2017 at Duke Hospital. 286 patients with a continuous flow LVAD also had serial echocardiograms performed. Based on our prior work in HFrEF, we defined recovery as an LVEF >= 40%. INTERMACS data and manual chart review was used to identify hospitalizations for recurrent heart failure (HF), gastrointestinal bleeding (GIB), and pump thrombosis along with mortality.

Results:
9.8% of patients had an LVEF >= 40% within 2 years of implant. LVEF recovery was associated with female gender [53.6% vs 21.7%. p < 0.001], lower serum Cr prior to implant [1.30 mg/dL (IQR 1.00-1.60) vs 1.40 mg/dL (IQR 1.10-1.90), p = 0.05], and absence of an ICD [53.6% vs 79.8%, p = 0.002]. Within 1-year of the follow-up echo with the highest reported LVEF, patients whose LVEF was >= 40% had a reduced incidence for a composite of hospitalizations for HF, GIB, pump thrombosis, and mortality [12.8% vs 39.8%, p = 0.013] as well as reduced rate of recurrent composite endpoint events [4.7 vs. 49 events per 100 person years, p = 0.020]. Of the individual endpoints, subjects with an LVEF >= 40% had a lower, but non-significant, incidence of hospitalizations for HF [0% vs 10%, p = 0.122] and GIB [4.8% vs 18.2% p = 0.081]. Importantly, those who went on to recover their LVEF did not have a lower rate of recurrent composite endpoint events between the time of implant and time to follow-up echo (88 events per 100 person years in the recovery group vs 53 per 100 person years in the non-recovery group, p =0.052), suggesting that recovery of LVEF is temporally related to the improvement in outcomes.

Conclusions:
Recovery of LVEF on LVAD support in not uncommon. Strategies to facilitate recovery have the potential to improve outcomes of LVAD recipients beyond pump explant.
Abstract 15774: Site Variation and Early Outcomes for Coronary Revascularization in Patients Undergoing TAVR in Northern New England
Authors: Young Michael N , Dauerman Harold L , Malenka David J , Robich Michael P , Lahound Rony , Devries James T , Iribarne Alexander , Flynn James M , Magnus Patrick , Huang Yi-Ling , Ross Cathy S , Butzel David W ,   The Northern New England Cardiovascular Disease Study Group
Published: May 2021

Introduction:
It is unclear whether or not percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) yields an incremental benefit to patients with concomitant coronary artery disease (CAD).

Hypothesis:
We hypothesized that unprotected left main (LM) or proximal left anterior descending artery (pLAD) PCI conducted prior to TAVR is not associated with improved post-procedural clinical outcomes in a Northern New England patient population.

Methods:
We performed a retrospective study of 2,729 patients undergoing TAVR at 6 medical centers in Northern New England from 2012-2018. From this cohort, we identified patients with unprotected LM >50% and/or pLAD >70% CAD (n=160). We analyzed site variability and compared early outcomes of patients who underwent PCI ≤60 days before TAVR to those who did not.

Results:
Across 6 hospitals, there was significant variation in the use of PCI before TAVR (range 50%-76%, p for trend=0.361); this variation did not correlate with site TAVR volumes. In this 160 patient cohort, 36.2% had isolated LM>50% and 76% had pLAD>70% disease. The comparator groups were well-matched with respect to age, sex, and medical complexity. There were no significant differences between PCI and non-PCI groups with respect to early mortality, MI, or stroke after TAVR (Table).

Conclusion:
There is significant variation in revascularization practices before TAVR. The routine performance of unprotected LM or pLAD PCI before TAVR does not affect early post-valve outcomes in patients of Northern New England.
Abstract 15776: Outcomes of Atrioventricular Septal Defects in Patients With and Without Trisomy 21: Analysis of the Inpatient Sample Database
Authors: Aly Safwat A , Qattea Ibrahim , Aly Hany Z
Published: May 2021

Introduction:
Atrioventricular septal defect (AVSD) is among the most common congenital heart diseases especially in infants with trisomy 21 (T21). However, the clinical outcomes of AVSD are largely limited to institutional reports.

Aim:
Using U.S.A. national database, the purpose of this study was to a) to assess the prevalence, mortality and outcomes of AVSD, and b) to determine the impact of T21 on its outcomes.

Methods:
We queried The US National Inpatient Sample from the Healthcare Cost and Utilization Project for patients with AVSD with and without T21 in the period 2002-2017. Patient characteristics, comorbidities, mortality, and healthcare utilization were evaluated for AVSD comparing those with and without T21.

Results:
During the study period, a total of 20,628,538 infants were born in the in the US, of them 67,020 (0.3%) had AVSD. T21 was diagnosed in 34,825 (52%). The incidence of AVSD ranged from 4.5-7.4/year. Common associated CHD were transposition of great arteries, tetralogy of Fallot, and truncus arteriosus at 10.9%, 4%, 0.4% respectively. The association with CHD was not different between AVSD with and without T21. During study period, 92% of patients underwent surgical repair. AVSD patients with T21 had greater mortality (4.4% vs 1.1%, p<0.001) more frequent pulmonary hypertension (4.8% vs 2.7%, p<0.001), longer median length of hospital stay (7 vs 3 days), and less incidence of arrhythmia (2.8% vs 6%, p<0.001). Comparisons between AVSD with and without T21 are outlined in table 1.

Conclusion:
Almost half of infants with AVSD had T21. T21 is associated with greater mortality and pulmonary hypertension, longer hospitalization and less arrhythmia.
Abstract 15791: Evaluation of Medicare Claims for Heart Failure Diagnostic Development: A Multisense-linkage Feasibility Analysis
Authors: Wariar Ramesh , Wen Gezheng , Jacobsen Caroline , Ruble Stephen B , Boehmer John
Published: May 2021

Introduction:
The validity of utilizing claims data for the development of worsening heart failure (HF) diagnostics has not been previously reported. Therefore, we linked data from the MultiSENSE study, in which the HeartLogic diagnostic was first reported, with claims data in order to validate claims HF events and compare diagnostic performance.

Methods:
Identifiers from 791 United States study patients were directly linked with Medicare claims to produce 320 patients with continuous Medicare Part A/B fee-for-service (FFS) coverage during study participation. Claims HF events were defined using primary HF diagnosis codes (DRG and ICD-9-CM) and included inpatient events as well as outpatient events with intravenous decongestive therapy. We matched events by patient and date, calculated agreement between events (Cohen’s kappa coefficient κ), and evaluated HeartLogic diagnostic performance using sensitivity and false positive rate (FPR).

Results:
The linked cohort was older than the remaining patients and had greater disease burden. Study deaths (N=14) matched exactly with claims. In contrast, matching of 207 study hospitalizations with 197 acute inpatient events resulted in a total of 239 events of which 193 matched with claims (81%), 32 (13%) were claims-unique, and 14 (6%) were study-unique. Claims HF events had substantial agreement with study adjudicated hospitalizations (observed = 93.3%, κ = 0.823). The HeartLogic algorithm detected claims-derived events with a sensitivity of 75.6% and an FPR of 1.539 alerts/pt-year, which was not different from performance derived using study events (sensitivity = 77.6% and FPR = 1.528,
P
= 0.82 and 0.92). HeartLogic detected events contributed to 91% of HF event costs used for performance evaluation ($605,000 out of $663,000).

Conclusions:
The agreement between claims and study events, and equivalence of HeartLogic diagnostic performance suggest that claims data may have utility for future diagnostic development/enhancement. Additional data are needed to demonstrate safety, efficacy, and cost-effectiveness of HeartLogic-directed interventions.
Abstract 15951: B-type Natriuretic Peptide and Prognosis of Covid-19 in New York City
Authors: Takahashi Mai , Egorova Natalia , Kuno Toshiki
Published: May 2021

Background:
The association of B-type natriuretic peptide (BNP) and in-hospital outcomes of Coronavirus disease 2019 (COVID-19) remains unknown. Our aim of this study was to investigate the independent predictors for mortality, especially cardiac history and serial assessment of cardiac markers (B-type natriuretic peptide [BNP] and troponin I).

Methods:
We obtained the medical records for hospitalized patients with laboratory confirmed COVID-19 from the Mount Sinai Health System. 929 patients with BNP data were divided into 3 groups, BNP ≤ 20 pg/mL, 20 pg/mL < BNP ≤ 100, and 100 pg/mL < BNP. The Cox proportional hazard model was constructed with the three BNP groups and troponin-I, d-dimer and C-reactive protein at admission and peak level.

Results:
Each BNP category was divided almost equally (BNP ≤ 20 pg/mL (29.9%, N=278), 20 < BNP ≤ 100 pg/mL (35.5%, N= 330), 100 < BNP pg/mL (34.6%, N=321). Patients with high BNP are older and have more co-morbidity including cardiac disease and chronic kidney disease. Patients with high BNP had higher d-dimer, troponin-I than control group. At 4 weeks, death rates were significantly different among the 3 groups (BNP ≤ 20 pg/mL versus 20 < BNP ≤ 100 pg/mL versus 100 < BNP pg/mL: 4.7% versus 13.6% versus 18.4%, P<0.0001). After the Cox model adjustments were done with the initial lab, troponin-I (>0.030 ng/mL) and d-dimer were found to be independent predictors for in-hospital mortality (troponin-I: HR [95%CI]: 1.72 [1.23-2.41], P=0.002), d-dimer: 1.03 [1.00-1.05], P=0.025), but not BNP. Notably, the Cox model with peak lab had better predictability of in-hospital mortality than those with lab at admission.

Conclusions:
Although higher BNP showed higher in-hospital mortality with unadjusted data with hospitalized COVID-19, BNP was not an independent predictor for in-hospital mortality after adjustment. Serial lab measurements could provide better predictability for in-hospital mortality.