bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17062: A Novel Non-Invasive Index to Characterize Right Ventricle-Pulmonary Arterial Vascular Coupling in Children
Authors: Levy Philip , Woo Kel Vin , Hauck Amanda T , Hamvas Aaron , Singh Gautam K
Published: July 2021

Introduction:
The right ventricle (RV) is a pulsatile pump, the efficiency or work of which depends on proper hemodynamic coupling with the compliant pulmonary arterial vasculature (PV). RV-PV coupling derived by right heart catheritization (RHC) measures the ratio of ventricular elastance (Ees, contractility) to arterial elastance (Ea, afterload) and is based on the work-energy principle that states a change in energy is equal to the work expended by a force through displacement. Non-invasive echocardiography derived surrogates to the Ees/Ea ratio that account for the length-force relationship have been proposed, but their clinical correlation as estimates of RV-PV coupling remain to be established.

Hypothesis:
We hypothesize that the non-invasive index of RV length-force relationship is a reliable measure of invasive RV-PV coupling (Ees/Ea) in children.

Methods:
Prospectively acquired simultaneous echocardiography-derived ratio of tricuspid annular plane systolic excursion to pulmonary artery acceleration time (TAPSE/PAAT) and RHC-derived Ees/Ea were compared using regression analysis in a cohort of 125 children (median age, 5 years; IQR, 1-13 years) with a wide range of pulmonary hemodynamics. Ees/Ea was calculated using the single beat method from RHC measures with the following equation: (RV systolic pressure - mean pulmonary artery pressure) / mean pulmonary artery pressure. TAPSE (mm), as a measure of RV contractile reserve, was substituted for length, and PAAT (msec), a reliable estimate of RV afterload, was exchanged for force. PAAT was adjusted for RV ejection time (PAATi=PAAT/RVET) to account for heart rate variability.

Results:
TAPSE/PAAT and TAPSE/PAATi both correlated with invasive Ees/Ea (r = 0.81, p<0.01 and r=0.76, p<0.01, respectively, Figure). TAPSE/PAAT and TAPSE/PAATi were both decreased (p<0.001) in children with pulmonary hypertension by RHC (mPAP>25 mmHg and PVRi>3 WU.m2). With ROC analysis, TAPSE/PAAT < 0.13 m/sec and TAPSE/PAATi < 38 mm detected Ees/Ea < 1.0 with sensitivity of 95% and specificity of 91% with an AUC of 0.90 (95% CI, 0.85-0.96).

Conclusions:
TAPSE/PAAT and TAPSE/PAATi , non-invasive indices of the length-force relationship, provide reliable estimates of invasive RV-PV coupling in children.
Abstract 17063: The Potential Role of Sentinel Cerebral Protection System in Improving Outcomes of Transcatheter Aortic Valve Replacement Patients: A Meta-Analysis
Authors: Ndunda Paul M , Vindhyal Mohinder , Muutu Tabitha M , Khayyat Sinan , Srinivasan Sachin , Fanari Zaher
Published: July 2021

Introduction:
Stroke is still a major complication that is reported in 2-5% of patients at 30 days, after a transcatheter aortic valve replacement (TAVR). The Sentinel Cerebral Protection System (CPS) (Claret Medical Inc., Santa Rosa, CA. USA) is the only FDA approved cerebral embolic protection device (CEPD). This meta-analysis aims to assess the potential benefits of the routine use of CPS after TAVR.

Methods:
The Cochrane library, PubMed and Web of science were searched for relevant studies. Two authors independently screened and included studies that were randomized controlled trials or controlled observational studies comparing the use of Sentinel CPS with no CEPD in TAVR. Data was extracted and the risk of bias assessed using the Cochrane Collaboration tools (RoB2.0 and ROBINS-I).

Results:
Four studies (3 randomized controlled trials and 1 quasi experimental study) comparing 847 patients in whom sentinel CPS was used to 483 in whom it was not used. Two of the studies had low risk of bias and 2 had some concerns for risk of bias. The primary outcomes were the number or size of ischemic lesions on brain MRI in 2 studies, major cardiac and cerebrovascular events in 1 study and a composite of mortality or stroke in 1 study. Patients in whom Sentinel CPS was used had lower rates of 30-day clinical stroke (3.5% vs 6.1%; RR 0.51 [95% CI 0.29, 0.90] I
2
= 0%), 30-day mortality (0.8% vs 2.7%; RR 0.34 [95% CI 0.12, 0.92] I
2
= 0%) and major or life-threatening bleeding (3.3% vs 6.6%; RR 0.50 [95% CI 0.26, 0.98] I
2
= 16%). There was no significant difference between the two arms in the incidence of acute kidney injury (0.8% vs 1%; RR 0.85 [95% CI 0.22, 3.24] I
2
= 0%) and major vascular complications (5.1% vs 6%; RR 0.74 [95% CI 0.33, 1.67] I
2
= 45%).

Conclusion:
Sentinel CPS use in TAVR can be helpful in reducing the risk of stroke, mortality and major or life-threatening bleeding at 30 days.
Abstract 17066: Indications for Implantable Cardioverter-Defibrillator Placement in Pediatric Patients With Hypertrophic Cardiomyopathy
Authors: Lizano Santamaria Ramiro W , Fan Chun-Po S , Runeckles Kyle , Grosse-Wortmann Lars , Stephenson Elizabeth , Benson Lee
Published: July 2021

Background:
Sudden cardiac death (SCD) is the most common cause of death in children and adolescents with hypertrophic cardiomyopathy (HCM). Implantable cardio-defibrillators (ICD) are highly effective in preventing SCD, however, indications for ICD placement in the young is mainly guided from the adult experience.

Methods:
We conducted a retrospective single institution study of all children with HCM who had an ICD implanted from July 1999 through February 2016.

Results:
Thirty-three patients were identified. The mean age at ICD placement was 12.3±3 years with a mean follow up of 3.6±2.5 years. The mean maximal septal wall thickness Z score was 9.3± 2.9 and mean peak LV outflow tract gradient 17±12 mmHg. The median number of indications for ICD placement per patient was 3 (21%, 52%, 15% and 12% of the patients had 2, 3, 4 and 5 indications respectively). The most common indications were: severe HCM (Z-score ≥ + 6) (84%), abnormal blood pressure response to exercise (51%) and late gadolinium enhancement (LGE) (27%). Using the European Society of Cardiology HCM SCD risk calculator, the 5-year SCD risk was highest when the indication was ventricular tachycardia (VT). However, no patient with VT received ICD therapy (shock or anti tachycardia pacing (ATP)) during the study period. Fifteen patients received ICD therapy; 73% appropriately (73% a shock, 9% ATP and 18% both). Inappropriate shocks were delivered to 67% of the patients. One patient had slow rate VT (below the therapy zone) and one patient had ventricular fibrillation that did not elicit ICD therapy and required external defibrillation. The incidence rate ratios for appropriate ICD therapy were higher when the indication for the ICD placement was LGE (3.69), severe HCM (2.3) or compound heterozygosity (1.2) p <0.05. The majority of patients (>95%) were alive and free of transplant at 1 and 5 years after ICD placement.

Conclusions:
The risk stratification and selection of patients for ICD placement in the pediatric population is challenging. LGE, severe HCM and compound heterozygosity are associated with higher rate of appropriate ICD therapy. Optimal functioning of the ICD device in children and adolescents is difficult. The overall immediate survival and freedom from transplant is excellent.
Abstract 17069: Inhibition of Autophagy Attenuates Klotho Gene Deficiency-Induced Arterial Stiffening and Hypertension
Authors: Chen Kai , SUN Zhongjie
Published: July 2021

Background and Objective:
Klotho is an anti-aging gene which shortens lifespan when disrupted and extends lifespan when overexpressed. The objective of this study is to investigate whether autophagy plays a role in Klotho gene deficiency-induced arterial stiffening and hypertension.

Methods and Results:
Klotho mutant heterozygous (KL+/–) mice and age- and sex-matched wild-type (WT) mice were used. Pulse wave velocity (PWV), a direct measure of arterial stiffness, and blood pressure (BP) were increased significantly in KL+/– mice. The autophagy level, as measured by LC3II expression and autophagy flux, was increased in aortas of KL+/– mice, indicating that Klotho deficiency upregulated autophagy. Interestingly, chloroquine attenuated Klotho deficiency-induced increases in PWV and BP. Chloroquine abolished the upregulation of autophagic flux in KL+/– mice. Klotho deficiency-induced arterial stiffness was associated with accumulation of stiffer collagen and degeneration of compliant elastin which were accompanied by upregulation of MMP9, TGF-β1, TGF-β3, RUNX2 and ALP. These changes were effectively attenuated by chloroquine. Chloroquine also abolished the increase in scleraxis expression in aortas of Klotho
+/–
mice. In cultured mouse aortic smooth muscle cells, Klotho deficiency increased autophagy which led to upregulation of scleraxis, a key transcription factor of collagen synthesis. Klotho deficiency failed to upregulate scleraxis expression when autophagy was inhibited, suggesting that autophagy is a critical mediator of Klotho deficiency-induced upregulation of scleraxis.

Conclusion:
Suppression of autophagy by chloroquine attenuates Klotho gene deficiency-induced arterial stiffening and hypertension by abolishing upregulation of MMP9 and scleraxis. The enhanced autophagic activity plays a critical role in Klotho deficiency-induced arterial stiffening and hypertension.
Abstract 17073: Intraprocedural Use of Dopamine During Ventricular Tachycardia (VT) Ablation is Associated With Greater Number of VTs Induced and Increased Need for Cardioversions
Authors: Graham Jeffrey D , Rosenberg Michael , Sandhu Amneet , Tumolo Alexis , Tzou Wendy , Sauer William , Borne Ryan , Nguyen Duy
Published: July 2021

Introduction:
Hemodynamic drugs are frequently used in patients with heart failure, despite arrhythmogenic effects. In certain situations, dopamine has been associated with increased arrhythmias and mortality. There are no known studies reviewing the impact of hemodynamic drugs used during VT ablations on procedural outcomes.

Hypothesis:
We sought to determine whether intra-procedural use of dopamine, dobutamine, or phenylephrine affected the number of induced VTs, required cardioversions, or the acute success of VT ablations.

Methods:
We conducted a retrospective review for all VT ablations from 2013-17 at our institution. Patient and procedural details were collected for 149 VT ablations.

Results:
The cohort was 81% male, and 67% had cardiomyopathy of which 53% were ischemic with a mean EF of 29.1% (CI 26.7- 31.4). Vasoactive drugs were used in 87% of patients undergoing VT ablation: phenylephrine (67%), dopamine (40%), dobutamine (37%). After adjusting for heart failure and procedural time, use of dopamine, but not phenylephrine or dobutamine, was associated with a greater number of induced VTs (p =0.02, Fig. 1a). Adjusting for the same factors, dopamine and dobutamine were significantly associated with increased need for cardioversions (p < 0.01). Dobutamine, but not dopamine or phenylephrine, was associated with lower acute procedural success (OR 0.25, CI 0.08-0.77, P = 0.01).

Conclusions:
Different vasoactive drugs may have differential effects on VT ablation outcomes. The focus of VT ablation is usually on VT mechanism and substrate, but attention to other factors, such as vasoactive drugs, may be warranted to determine their effect on procedural outcomes.
Abstract 17077: Acute Hemodynamic Effects of Oral Nitrite in Pulmonary Hypertension Related to Heart Failure With Preserved Ejection Fraction (PH-HFpEF)
Authors: Levine Andrea R , Helbling Nicole L , Chien Nydia , Bachman Timothy N , Simon Marc A , Gladwin Mark T
Published: July 2021

Introduction:
Pulmonary hypertension (PH) occurs in 35-83% of patients with heart failure with preserved ejection fraction (HFpEF) and is associated with worse outcomes. There are no effective therapeutic options for these patients. Oral nitrite has demonstrated promise in pre-clinical models of PH-HFpEF. Recently, a phase 2 clinical trial showed that a single dose of inhaled nitrite significantly lowered pulmonary, right atrial, and pulmonary artery wedge pressures and substantially increased pulmonary artery compliance in patients with PH-HFpEF. We are currently evaluating the efficacy of chronic oral nitrite as a novel therapeutic agent in PH-HFpEF. We report, for the first time, our initial findings of the acute hemodynamic effects of a single dose of oral nitrite.

Methods:
This is part of an ongoing blinded 10-week cross-over treatment trial of oral nitrite in PH-HFpEF (NCT03015402). Patients were defined as having PH-HFpEF based on an ejection fraction > 40% and right heart catheterization (RHC) with a mPAP≥ 25 mmHg, PAWP ≥15 mmHg and TPG ≥ 12 mmHg. Patients who met criteria based on a screening RHC were given a single open label dose of 40 mg of sodium nitrite. Cardiopulmonary hemodynamics were obtained by RHC at baseline and after a single dose of oral nitrite. We are actively enrolling patients with the intent to provide open label oral sodium nitrite to ten patients.

Results:
Eight patients have currently been enrolled in the cross-over trial, of which four have required a screening RHC and have been given open label oral nitrite. Oral nitrite was well tolerated in all patients without any adverse events. Acute cardiopulmonary hemodynamic are presented in Figure 1.

Conclusion:
Administration of oral nitrite acutely results in an improvement of right ventricular and left ventricular filling pressures without any significant reduction in cardiac output, cardiac index, or mean arterial pressure. Oral nitrite may be a novel therapeutic agent for patients with PH-HFpEF.
Abstract 17088: Role of Caregiver Participation in Outcomes for Patients With Advanced Ambulatory Heart Failure: An Analysis of the Revival Registry
Authors: Gilotra Nisha A , Robinson, Shawn W , Kittleson Michelle , Shah Keyur , Pamboukian Salpy , Haas Donald C , Horstmanshof Douglas A , McNamara Dennis , Forde-McLean Rhondalyn , Taddei-Peters Wendy C , Khalatbari Shokoufeh , Spino Catherine A , Richards Blair , Mann Douglas L , Stevenson Lynne W , Stewart Garrick C , Aaronson Keith D
Published: July 2021

Introduction:
Advanced HF requires tremendous resources, and family caregivers generate significant health related cost-savings. Earlier work in the REVIVAL study demonstrated that increased baseline caregiver (CG) burden is associated with subjects exhibiting lower preference for ventricular assist device (VAD) therapy.

Hypothesis:
We examined whether 1) CG study participation and 2) CG burden predict combined outcome of death, VAD or UNOS 1 transplant in ambulatory advanced HF patients.

Methods:
We compared REVIVAL subjects with and w/o a participating CG, defined as a consented CG who completed at least one baseline quality of life (QOL) survey. Baseline characteristics were evaluated and the hazard ratio for CG vs. no CG for the combined outcome was determined by a Cox model.

Results:
Of 337 subjects, 95 (28%) identified participating CGs. CGs were 59 ± 14 yrs old, more commonly female (80%), a spouse/domestic partner (76%), and lived in the same home (86%). Subjects with a participating CG were older (62± 12 vs 59 ± 11 yrs, p=0.025). There were no differences in INTERMACS profile, NYHA class, HF risk scores, renal function or QOL. . Subjects without a participating CG were numerically more likely to experience the outcome of death, VAD or transplant by 1 year compared to those with a participating CG (26% vs. 17%), but the difference in event rate was not statistically significant (HR 1.65, CI 0.96-2.83, p=0.07). (Figure) There was no significant difference in primary endpoint based on CG burden or CG QOL as assessed by Oberst scale or EQ-5D index.

Conclusions:
In the REVIVAL study, less than one third of ambulatory advanced HF patients had a participating CG, raising the question of whether patients are more likely to progress to advanced HF if lacking a CG. Additionally, not having a participating CG may be related to worse HF outcomes. These data emphasize the need for larger studies to better understand the complex dynamics of the patient-caregiver dyad.
Abstract 17111: Genetic Influences on Human Plasma Metabolites That Determine Mortality in Heart Failure Patients
Authors: Lanfear David E , Gui Hongsheng , Li Jia , She Ruicong , Peterson Edward , Williams L. K , Sabbah Hani N
Published: July 2021

Background:
Heart failure with reduced ejection fraction (HFrEF) continues to be a global health burden. We recently reported a strong association of plasma metabolite profile (thirteen different metabolites) with survival among patients with HFrEF but the mechanism of this association is unclear. We studied the genetic associations of plasma metabolite to try to illuminate the disease mechanisms at work.

Methods:
A prospective genetic registry including 1032 HFrEF with genome-wide genotyping and imputation of single nucleotide polymorphisms (SNP; ~7 millions) and targeted metabolomics profiling. Genome-wide (GW) association analyses were performed to investigate the genetic impact of each SNP on the 13 metabolites of interest. Analyses were performed using linear models stratified by race (European Americans [N=516] and African Americans [N=516] and including the top five principal components (PC) for each population to avoid spurious associations due to population stratification. A fixed-effect meta-analysis was then used to combine results from the two populations. Threshold for GW significance was p<5E-8. As a second step, Cox proportional hazard regression models of overall survival were tested for each SNP that met GW significance.

Results:
We found at least one SNP reaching GW significance for 6 metabolites metabolites (a-KG, C5.Isovaleryl, Fumarate, Leucine, Succinate and X3.HBA). The most significant SNP (rs77836784, an intronic variant within PACRG) was associated with X3.HBA in African American HF patients (Beta estimate=22.82, P-value=7.14E-14). A cross-checking of SNP associations on both metabolites and HF survival identified 13 independent SNPs that may partially explain the contribution of the metabolites on HF mortality (Table 1) and seem to have biologic plausibility including for example a G-protein coupled receptor (GPR68) and protein kinase C (PRKC1).

Conclusion:
Genetic variants are associated with predictive plasma metabolites and survival. This may be useful to understand the underlying pathways connecting metabolites to HF progression. A complete investigation of genomic and metabolomics determinants including causal mediation and pathway analyses are on-going.
Abstract 17114: CHA
2
DS
2
-VASc Score is a Poor Predictor of Thromboembolic Events in Heart Failure Patients With and Without Atrial Fibrillation
Authors: Rivner Harold , Marzouka George R , Tang Fei , Goldberger Jeffrey J
Published: July 2021

Introduction:
Recent evidence suggests that the CHA
2
DS
2
-VASc score could be used to predict thromboembolic events (TE) (both CVA and noncerebral thromboembolism) in heart failure (HF) patients without atrial fibrillation (AF). This non-American cohort study had several limitations. We performed a retrospective analysis using the national Veteran Affairs database to externally validate the findings.

Hypothesis:
The CHA
2
DS
2
-VASc score can be used equally to predict TE in HF patients with or without AF.

Methods:
A retrospective cohort of the national Veteran’s Affairs database was used to identify HF patients discharged between 2002-2010. Rates for TE were calculated at both 1 and 5 years. C-statistics were calculated to test the performance of CHA
2
DS
2
-VASc in predicting the rate of TE in HF patients with and without AF. Patients who developed AF during the follow-up period (crossovers) and those on anticoagulation where excluded. Negative predictive value was calculated using cutoff value of 1.

Results:
A total of 77,601 patients were included in this analysis: 51,667 without AF and 15,630 with AF. 10,294 crossover patients were excluded. Baseline characteristics and medications are listed in Table 1. Event rates are reported in Table 2—there is a small trend towards higher incidence with increasing score in both groups. However, C-statistics were overall poor but similar for predicting TE in both groups (Table 3)

Conclusion:
Our analysis suggests CHA
2
DS
2
-VASc is a poor predictive model for TE in HF with or without AF. We found that previous conclusions regarding the predictive ability of CHA
2
DS
2
-VASc are not generalizable to our large American cohort. Like previously published studies, we show that the predictive ability of CHA
2
DS
2
-VASc was similar in both HF patients with or without AF, despite excluding patient receiving anticoagulation. This suggests that AF may not be the main predictor of TE in HF patients. There is a need for better predictive models for TE in HF.
Abstract 17119: Sufficient Pulmonary Vascular Bed Before Fontan Surgery Secures Favorable Fontan Hemodynamics
Authors: Kuwata Seiko , Saiki Hirofumi , Takanashi Manabu , Sugamoto Kenji , Senzaki Hideaki
Published: July 2021

Introduction:
While improvement of perioperative care markedly expanded candidacy of Fontan surgery, increasing number of Fontan patients is currently subjected to advanced heart failure therapies. Low pulmonary flow before Fontan procedure has been considered to be acceptable as it keeps pulmonary resistance low, however, compromised growth of pulmonary vascular bed after Fontan completion may deteriorate potential to preserve better Fontan circulation later. We tested our hypothesis that sufficient growth of pulmonary vascular bed before Fontan surgery chronically preserves favorable Fontan hemodynamics and prevents patients from cardiovascular remodeling.

Methods and Results:
Consecutive 33 patients who had undergone Fontan operation (median year after the surgery: 5.3years) were enrolled in this study. During cardiac catheterization, pulmonary arterial index (PAI) as the representative of vascular bed both before and after Fontan procedure was measured and hemodynamics as well as blood samples as a marker for end-organ dysfunction were analyzed. Before Fontan procedure, PAI ranged 74-426 and resistance of pulmonary artery (PAR) ranged 0.4-3.1. After median of 5.3 years of Fontan procedure, CVP exhibited modest decline with preserving cardiac index (CI). Interestingly, central venous pressure (CVP) with chronic Fontan circulation was negatively correlated with PAI of pre-Fontan procedure (P=0.02) whereas it was independent of PAR. Consistent with this, higher PAI before Fontan procedure was also significantly associated with higher CI (P<0.01) and lower levels of plasma brain natriuretic peptides (P=0.03). Importantly, patients with low PAI showed markedly elevated activation of renin-angiotensin-aldosterone (RAAS) activation and elevation of serum gamma-gltamyl transferase (P<0.01), a surrogate marker of liver congestion. Multivariate analysis revealed that high PAI was determinant of low CVP in the chronic Fontan patients, independent of body size, postoperative interval and pulmonary arterial resistance.

Conclusion:
Sufficient pulmonary vascular bed before Fontan procedure independently lowers CVP, may prevent cardiovascular remodeling by RAAS suppression as well as end organ dysfunction in chronic Fontan patients. Our result suggested importance of strategies to accelerate pulmonary vascular growth before Fontan procedure.
Abstract 17121: Predictors of Death and Major Adverse Cardiovascular Events in the ACCORD Trial Identified by Random Survival Forest Based Machine-Learning
Authors: Shamsuzzaman Md , Navarro Almario Eileen , Patel Tejas , Csako Gyorgy , Wu Colin O , Tian Xin , Tesfaldet Bereket , Fleg Jerome , Kettermann Anna , Gandotra Charu , Sopko George , Sviglin Helena , Cooper Lawton , Coady Sean , Banerjee Avantika , Farooque Nashwan , Dandi Gauri , Hoque Laboni , Cure Carlos , Kirby Ruth , Liu Lijuan , Chen Jue , Yan Ye , Chowdhury Iffat , Burkhart Keith , Calis Karim , Leifer Eric , Szarfman Ana , Domanski Michael , Pucino Frank , Rosenberg Yves , Hasan Ahmed A ,   for the Meta-AnalyTical Interagency Group (MATIG)
Published: July 2021

Background:
Patients with type 2 diabetes (T2D) are at high risk of cardiovascular (CV) morbidity/mortality. The ACCORD trial (NCT00000620) tested intensive glycemic, lipid and blood pressure interventions on major CV events in 10,251 T2D patients with baseline HbA1c concentration >7.5%. Despite its landmark findings, a data-driven systematic evaluation of predictors for major cardiovascular events among hundreds of ACCORD variables has not been conducted.

Methods:
Random Survival Forest (RSF), a machine-learning method for survival analysis, identified important predictors for total mortality (TM), CV death (CVd), hospitalization/death due to heart failure (hdHF), fatal/non-fatal stroke (CVA), non-fatal myocardial infarction (MI) and MACE (composite of CVd, MI and CVA). Among 378 risk factors, including some highly correlated features, the top-ranked predictors (collected at baseline or derived from repeated measures prior to events) were selected, resulting in a hierarchy of predictive variables. Effects of RSF-selected predictors were then evaluated by multivariate Cox Proportional Hazards Models.

Results:
Table 1 presented the top ten predictors for six major events. Variables associated with changes in renal function predicted TM, CVd, and hdHF with ~90% accuracy. Insulin use was an important predictor along with predefined composite renal microvascular events for MI, CVA and MACE (74-79% accuracy). The Cox regression models based on RSF variable selection yielded similar findings for these important predictors of events.

Conclusions:
RSF approach revealed that insulin use and overt renal microvascular events were predictors for the occurrence of MI, stroke, and MACE in T2D patients. Moreover, dynamic changes in urinary renal function biomarkers had additional predictive values for fatal events. These results provide important clinical insights for reducing CV events in Type 2 diabetes patients.
Abstract 17130: Variables Associated With Uncontrolled Blood Pressure Early After Stroke
Authors: Achilike Saviour , Wang Austin , Cooksey Gabretta , Hinojosa Evelyn , Okpala Munachi , Denny M C , Savitz Sean I , Sharrief Anjail
Published: July 2021

Introduction:
Uncontrolled blood pressure (BP) is a major risk factor for recurrent stroke; however, up to 50% of stroke survivors have uncontrolled BP 6 months after stroke. Characterization of factors associated with uncontrolled BP early after stroke discharge (DC) may help to identify patients for BP interventions.

Hypothesis:
We sought to identify factors associated with uncontrolled BP in the first month after stroke discharge. We hypothesized that African American (AA) race, insurance status, medication complexity, and hospital BP prior to discharge would be associated with uncontrolled BP.

Methods:
We identified hypertensive patients with ischemic or hemorrhagic stroke or transient ischemic attack scheduled to follow-up in the stroke clinic 2 to 4 weeks after hospital DC. Office BP was obtained using BpTRU, an automated machine that averages five unattended BP measures. Uncontrolled BP was defined using 2017 American College of Cardiology Guidelines as BP ≥ 130/80 mmHg. We used univariate logistic regression to assess relationships between uncontrolled BP and selected variables. Variables with statistically significant associations in the univariate models and variables associated with uncontrolled BP in the literature were included in the multiple logistic regression model.

Results:
Of the 230 patients identified, 55.7% had uncontrolled BP at clinic follow-up. In univariate and multivariable analyses, AA race, young stroke (age < 50), and systolic BP (SBP) 24-hours prior to DC were significantly associated with uncontrolled BP early after stroke DC. BP medication complexity was not associated with uncontrolled BP in this study.

Conclusions:
AA race, young age, and elevate SBP in the 24 hours prior to of stroke DC were associated with uncontrolled BP early after stroke. These variables can be used to identify patients who may benefit from early interventions aimed at reducing the risk of uncontrolled BP after stroke and stroke recurrence.
Abstract 17133: A Novel, Shear-Thinning and Rapidly Self-Healing Polymer Nanoparticle Hydrogel Diminishes Post-Operative Adhesions in Rodent and Ovine Models of Cardiac Adhesion Formation
Authors: Stapleton Lyndsay M , Steele Amanda N , Wang Hanjay N , Paulsen Michael J , Hernandez Hector L , Lucian Haley J , Smith Anton A , Yu Anthony C , Thakore Akshara D , Eskandari Anahita , Farry Justin M , Williams Kiah N , Hironaka Camille N , Totherow Kailey P , Jaatinen Kevin J , Appel Eric A , Woo Y. J
Published: July 2021

Objective:
Adhesions develop after 95% of operations, represent a major clinical challenge, and cost the U.S healthcare system $2.5B annually. In cardiac surgery, adhesions are problematic during re-operations, increasing operative times and posing risks of hemorrhage and injury to the heart and lungs during sternal reentry and cardiac dissection. We hypothesized that shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would provide a viscoelastic barrier, effectively preventing adhesion formation (Fig 1A).

Methods:
Multiple PNP formulations underwent rheologic characterization. Male Sprague Dawley rats (n=52) underwent permanent ligation of the LAD to induce robust postinfarct adhesions, followed by epicardial application of PNP (200L), Seprafilm®(1cm
2
), or no treatment. Male Dorset sheep (n=8) underwent an anterolateral epicardial abrasion followed by application of PNP (25mL), Seprafilm® (12 cm
2
), or no treatment. Degree of adhesion formation, standardized dissection time, heart function, and immune response were assessed 4-weeks following surgery.

Results:
PNP exhibited formulation-dependent mechanical properties indicating the effect of hydrogel stiffness on adhesion barrier efficacy (Fig 1B). Infarct size and heart function were controlled to ensure similar inflammatory responses contributing to adhesion formation across treatment groups. Treatment with certain PNP formulations significantly reduced the development of adhesions compared to controls (Fig 1C). Ovine hearts treated with the PNP 1:10 revealed a pristine epicardial surface (Fig 1D, 1E, and 1F) and resulted in a shorter dissection time relative to the controls (Fig 1G).

Conclusion:
Administration of a shear-thinning, self-healing hydrogel reduces the extent of adhesion formation in the thoracic cavity following surgery in small and large animal models. PNP provides an easily delivered, scalable solution for post-operative adhesion prevention.
Abstract 17140: Nitric Oxide Production is Decreased in the Left Ventricle of Diabetic Subjects Undergoing Coronary Artery Bypass Grafting
Authors: Kosta Angela , Ryzhov Sergey V , Kramer Robert S , Quinn Reed D , Sawyer Douglas , Robich Michael P
Published: July 2021

Introduction:
Dysregulation of endothelial nitric oxide synthase (eNOS) and generation of nitric oxide (NO) are critical early indicators for diabetes-induced endothelial dysfunction and cardiovascular complications. We hypothesize that levels of NO production and eNOS expression by endothelial cells are decreased in DM subjects when compared to non-DM subjects.

Methods:
The study cohort consisted of 9 non-DM subjects and 6 DM subjects undergoing myocardial biopsy at the time of coronary artery bypass grafting surgery. The non-myocyte cell suspensions from the left ventricle (LV), right atrial appendages (RAA), and skeletal muscle (SKM) tissue were analyzed by flow cytometry to measure production of nitric oxide in subpopulations of endothelial and non-endothelial cells. Cells in suspension were incubated with DAF-2DA in the presence or absence of NO synthase inhibitor, L-NAME. Flow cytometry was used to determine production of NO in subpopulations of endothelial and non-endothelial cells from biopsies. Measurements of eNOS and phospho-eNOS (ser1177) were performed using western blot.

Results:
Basal Nitric oxide production was measurable in non-diabetic subjects \ in 55%, 80% and 65% of unstimulated endothelial cells obtained from RAA, LV and SKM biopsies, compared to 40%, 40%, and 66%, respectively in diabetic subjects (
P
< 0.02, DM vs Non-DM). No differences were found in the number of NO-producing non-endothelial cells between DM and non-DM subjects. The level of eNOS showed a trend towards decreased protein expression in DM subjects compared to non-DM.

Conclusions:
Generation of NO by endothelial cells and level of eNOS expression are decreased in left ventricular endothelial cells of DM patients compared to non-DM. Left ventricular biopsies can be used safely for assessment of NO dysregulation and endothelial dysfunction, and whether these can be improved with interventions targeting diabetic cardiovascular disease.
Abstract 17143: An Updated Meta Analysis Comparingtranscatheterpatent Foramen Ovale Closure versus Medical Therapy to Prevent Recurrent Cryptogenic Stroke
Authors: Patel Krunalkumar , Patel Nirav , Doshi Rajkumar , Shah Jay , Miyani Tapankumar , Patel Palakkumar , Meraj Perwaiz
Published: July 2021

Background:
The closure of patent foramen ovale (PFO) by percutaneous transcatheter approach is controversial in a patient with cryptogenic stroke. Here in, we reviewed the literature and analyzed the data on safety and efficacy of standard medical therapy (MT) compared to mechanical closure by the percutaneous trans-catheter approach after recently published DEFENSE-PFO trial.

Hypothesis:
Transcatheter PFO closure decreases incidence of recurrent stroke compared to standard MT.

Methods:
We systematically searched PubMed, SCOPUS and EMBASE for the articles that compared overall mortality, efficacy in preventing recurrent stroke, and transient ischemic attack (TIA) after transcatheter PFO closure compared to standard MT. We also evaluated potential complications such as bleeding and development of atrial fibrillation.

Results:
A total 6 studies with 3,403 patients met pre-defined inclusion criteria. Mean follow-up was 3.75 years. Overall mortality was indifferent between transcatheter closure compared to MT (RR: 0.74, 95% CI 0.35-1.6, P=0.45, I
2=
0%). However, PFO closure reduced the rate of recurrent stroke by at least 60% (RR: 0.39, 95% CI 0.18-0.82, P=0.01, I
2=
56%), while did not reduce the risk of TIA compared to MT (RR: 0.76, 95% CI 0.52-1.12, P= 0.17, I
2
=0%). Higher incidence of atrial fibrillation was evident in mechanical closure (RR: 4.64, 95% CI 2.37-9.09, p<0.00001, I
2
=11%) but no increase in bleeding (RR: 0.88, 95% CI: 0.4-1.93, p=0.74, I
2
=28%).

Conclusions:
Mechanical PFO closure by transcatheter approach is a viable option in the prevention of recurrent stroke and TIA with an increased risk of development of atrial fibrillation without the risk of bleeding.
Abstract 17148: Association of Atrial Fibrillation With Short-Term Outcomes in Patients Hospitalized for Heart Failure With Preserved Ejection Fraction
Authors: Yandrapalli Srikanth , Ojo Amole , Harikrishnan Prakash , Vuddanda Venkat L , Karim Mohammed , Aronow Wilbert S , Frishman William , Ahmed Ali , Fonarow Gregg C , Lanier Gregg M , Iwai Sei , Jacobson Jason T
Published: July 2021

Background:
Atrial fibrillation (AF) is frequently present in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The association of AF with short term outcomes in patients hospitalized for HFpEF is not well studied.

Methods:
We queried the United States Nationwide Readmissions Database year 2014 using appropriate ICD-9 codes to identify a weighted sample of adult patients hospitalized for HFpEF. Patients with concomitant diagnoses of HF with reduced ejection fraction (HFrEF) were excluded. The primary outcome was a composite of in-hospital death or a 30-day readmission for HF. Secondary outcomes studied were individual outcomes along with composites of in-hospital death or a 30-day readmission for any cause or cardiac etiologies. Survey specific adjusted multivariable logistic regression models were used to analyze the association of AF with outcomes.

Results:
Of 229,098 patients (mean age 76 years, 38% men) who were hospitalized for HFpEF during the study period, AF was present in 45.3% (N=103,852). Patients with AF were older (mean age 80 vs 72 years, p<.001) and more likely men (39% vs 37.5%, p<.001) compared to patients without AF. Primary outcome occurred in 9.5% patients with AF and in 8.0% patients without AF (p<0.001). After adjusting for patient demographics, comorbidities, complications, and hospital characteristics, AF was associated with 17% higher odds of the primary outcome (OR 1.17, 95% CI 1.11-1.23), 20% higher odds of in-hospital death (OR 1.20, 95% CI 1.07-1.34), and 17% higher odds of a 30-day readmission for HF (OR 1.17, 95% CI 1.10-1.25). Similar results were noted for other outcomes;
TABLE
.

Conclusion:
AF was associated with significantly worse short-term outcomes in patients hospitalized for HFpEF. Additional strategies are needed to improve outcomes in HFpEF patients with AF. Future prospective studies need to examine if AF ablation in HFpEF may improve outcomes as in HFrEF.
Abstract 17159: Comparing Functional Status in Home-Based to Facility-Based Cardiac Rehabilitation Participants
Authors: Schopfer David W , Whooley Mary A , Allsup Kelly , Duvernoy Claire S , Forman Daniel E
Published: July 2021

Introduction:
Cardiac rehabilitation (CR) remains underutilized in patients with ischemic heart disease (IHD). Home-based CR (CR) has been promulgated as a model of delivery that may improve participation, but its impact on functional status is unclear.

Hypothesis:
We sought to compare change in 6-minute-walk-distance (6MWD) among patients enrolled in home-based vs. facility-based CR after myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery.

Methods:
We evaluated change in 6MWD among 231 Veterans with IHD via home-based vs. facility-based CR after an IHD event. Between 9/2015 and 9/2017, all eligible patients enrolling in home-based (San Francisco VA) or facility-based CR (VA Ann Arbor and VA Pittsburgh) were invited to participate. 6MWD was assessed at baseline, 3-, and 6-months.

Results:
Median baseline 6MWD were similar in 116 patients who completed home-based vs. facility-based CR (1155 vs. 1160 ft, p=0.52). Median time from referral to enrollment was shorter for home-based vs. facility-based CR (14 vs. 42 days, p<0.001). At 3 months, patients participating in home-based CR demonstrated greater increase in 6MWD (324 vs. 128 feet; p<0.001). After adjusting for demographics, comorbidities, and clinical indication, the mean 3-month change in 6MWD remained significantly greater (330 feet vs. 127 feet; p<0.001). However, the difference was no longer statistically significant at 6 months of follow-up (295 vs. 191 feet; p=0.10).

Conclusions:
Participants in home-based CR experienced faster time to enrollment and greater 3-month increases in 6MWD than those in facility-based CR, but differences were no longer significant at 6 months. The early superiority of HBCR may relate to shorter delay from referral to participation. Both groups demonstrated similar safety and efficacy. These findings suggest that among selected patients who cannot attend facility-based CR, home-based CR may provide a reasonable alternative.
Abstract 17174: Discrepancies in Development of Cardiac Myopathy in Males vs. Females
Authors: Kaur Gagandeep , Kheirkhahan Mobin , Marrouche Nassir F
Published: July 2021

Introduction:
Heart disease has proven to be the leading cause of mortality in women. Sudden Cardiac Death being responsible for 1 in 4 female deaths, of these women 64% display no prior symptoms. Structural remodeling associated with fibrosis, however, has been strongly linked to development of cardiovascular disease (CVD), risk factors, and co-morbidities. This study aims to provide a preliminary assessment of fibrosis manifestation in women in comparison to their male counterparts.

Methods & Results:
Atrial Fibrillation (AF) patients (370 male, 197 female) with Late-Gadolinium Enhanced MRIs (LGE-MRI) were processed for fibrosis. Collected data included: CHADS-VASc factors, age and AF type. These two groups were matched in terms of cardiovascular co-morbidities. The LGE-MRI pre-ablation showed women had significantly higher LA fibrosis than men (17.2 ± 9.5 vs 14.6 ± 7.6, p <0.001), this difference remained true even after stratifying based on Paroxysmal (women 15.6 ± 7.9 vs men 13.8 ± 6.5, p =0.04) and Persistent types of AF (women 19.9 ± 11 vs men 15.3 ± 8.4, p =0.002). Women at the time of LGE-MRI scan were older (72.2 ± 11.1 vs 67.8 ± 11.6, p <0.001) and a majority of them were older than 75-years-old (40.1%), whereas the majority of men were 65 to 74-years-old (41.6%). After adjusting for age, the result of our regression model showed female gender contributes to 3.5% more LA fibrosis (CI 95% 0.53 - 6.6%, p =0.02).

Conclusions:
Given the obtained results, it can be concluded that women should be screened for cardiac symptoms starting at an early age. Women present with CVD symptoms at an older age along with higher fibrosis percentage at their initial visit in comparison to their male counterpart. Further research is recommended to determine what factors are associated to this discrepancy.
Abstract 17186: Left Atrial Strain Predicts Adverse Outcomes in Hypertrophic Cardiomyopathy
Authors: Vasquez Nestor , Ostrander Benjamin , Lu Dai-Yin , Ventoulis Ioannis , Haileselassie Bereketeab , Goyal Sagar , Vakrou Styliani , Abraham Theodore P , Abraham M. Roselle
Published: July 2021

Introduction:
Hypertrophic cardiomyopathy (HCM) patients are at increased risk for heart failure (HF), stroke, death, and paroxysmal atrial fibrillation (PAF) development. There is no consensus whether atrial fibrillation (AF) is a marker or mediator of adverse outcomes in HCM patients.

Hypothesis:
We hypothesized that PAF and left atrial (LA) remodeling predict adverse outcomes in HCM.

Methods:
Echocardiography (2D and speckle tracking) was used to assess LA size, function, and mechanics in a cohort of HCM patients with history of PAF (PAF group, n=45) and age/gender-matched HCM patients without history of AF (No-AF group; n=59). AF was diagnosed by review of EKGs, event recorder/holter monitor data, and ICD interrogation. Patients were followed for a mean of 53 months for development of the composite endpoint of HF, death, and stroke.

Results:
Clinical/demographic characteristics were similar in the 2 groups; 67% of PAF group had a CHADS
2
VASC score ≤ 1. The PAF group had higher LA volume, lower LA ejection fraction, and higher E/A ratio (reflecting LV diastolic dysfunction) compared to the No-AF group. LA contractile and reservoir strain/strain rate (SR) were significantly lower in the PAF group (Table 1). Male gender, LA reservoir and conduit strain/SR (not PAF presence) were associated with the development of the composite endpoint in univariate analysis. Only LA conduit and reservoir strain/SR independently predicted the composite endpoint in a multivariate model. Kaplan Meier survival analysis showed greater event-free survival among HCM patients with LA conduit strain >10.2% (Figure 1a) and LA reservoir strain >23.8% (p < 0.01) (Figure 1b).

Conclusions:
PAF is associated with greater degree of LA myopathy in HCM. LA myopathy assessed by conduit and reservoir strain/SR may be useful for risk stratification for HF, stroke, and death in HCM.
Abstract 17198: Asymmetric Bifurcation Angle of Common Iliac Artery is Associated With Unilateral Calcified Nodule Lesion of Common Iliac Artery
Authors: Yoshihara Nagataka , Akahori Hirokuni , Imanaka Takahiro , Kawai Kenji , Miki Kojiro , Yanaka Koji , Tanaka Takamasa , Masuyama Tohru , Ishihara Masaharu
Published: July 2021

Background and aim:
It has been known that bifurcation angles of common iliac artery (CIA) are not always bilateral symmetry. Previous study reported that mechanical stress initiate calcification in aortic valve. The aim of this study was to investigate the impact of CIA anatomical features on lesion characteristic of CIA.
Methods and results:
This study enrolled 72 patients with intermittent claudication who had undergone endovascular-therapy (EVT) for de novo CIA atherosclerotic lesions in our hospital during April 2012 to March 2017. Anatomical analysis of CIA bifurcation was assessed by frontal view of initial angiography at EVT. We calculated the bilateral CIA angles between axis of terminal aorta and axis of proximal CIA, and bilateral symmetry was expressed as absolute value of the difference between both CIA angles (Δangle). The patients were divided into 2 groups: symmetry group (Δangle≦10 degrees, n=40) and asymmetry group (Δangle>10 degrees, n=32), according to the mean of Δangle. Distribution characteristics were classified into 2 patterns: bilateral lesions pattern and unilateral lesion pattern, furthermore we assessed calcified nodule of CIA lesion using intravascular ultrasound. There was no difference between 2 groups about patient characteristics. Unilateral lesion was observed in asymmetry group much more than symmetry group (63% vs 22%, P<0.05). Calcified nodule lesion was observed in asymmetry group much more than symmetry group (28% vs 5%, P<0.05).

Conclusions:
These findings suggested that asymmetric bifurcation angle of CIA was associated with unilateral lesion and calcified nodule lesion. Asymmetry of CIA bifurcation might be predictor of unilateral calcified nodule lesion of CIA.
Abstract 17214: Prediction of Mitral Valve Repair: Pre-Repair versus Virtual Repair versus Post-Repair
Authors: Yeo MyungGu , Nguyen Tom T , McPherson David D , Kim Hyunggun
Published: July 2021

Introduction:
Partial leaflet resection followed by ring annuloplasty is a reliable and reproducible mitral valve (MV) repair technique for the treatment of severe mitral regurgitation (MR) due to posterior chordal rupture.

Hypothesis:
We have developed a novel computational virtual MV repair strategy to predict the biomechanical and physiologic characteristics of post-repair MV dynamics to help with optimal surgical planning.

Methods:
Computational MV models were created using pre- and post-repair 3D echocardiographic data of a patient having posterior chordal rupture and severe MR. Virtual resection was designed by removing a pre-defined triangle-shaped leaflet portion in the P2 scallop and merging the excised leaflet edges. Virtual ring annuloplasty with the same ring size as the post-repair MV was performed following the triangular leaflet resection. Computational simulations of MV function (pre-repair, virtual repair, and post-repair) were performed using dynamic finite element methods. Leaflet coaptation across the MVs were quantitatively determined and compared.

Results:
The pre-repair MV with P2 chordal rupture showed severe P2 prolapse and leaflet malcoaptation. The post-repair MV demonstrated markedly reduced prolapse and sufficiently restored leaflet coaptation. The virtually repaired MV revealed a similar coaptation ratio as the post-repair MV indicating effective restoration of normal MV function. Both virtual repair and post-repair MVs showed improved coaptation not only in the P2 region but also in the A1-P1 and A3-P3 regions.

Conclusions:
We have quantitatively evaluated patient-specific MV function before and after potential MV repair using a novel virtual MV repair protocol. Both virtual repair and post-repair MVs decreased posterior leaflet prolapse and restored normal coaptation. This virtual MV repair strategy has the potential for improved pre-surgical planning to predict and optimize post-repair MV function.