bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 21319: Racial Differences in the Prevalence of Atrial Fibrillation in Patients With Dual-Chamber Pacemakers
Authors: Wali Eisha , Deshmukh Amrish , Bukari Abdallah , Ozcan Cevher
Published: March 2022

Introduction:
Several cohort studies have reported racial differences in prevalence of atrial fibrillation (AF). This may be due to ascertainment bias. Thus, we aimed to determine incidence of AF with respect to race in patients with sinus node dysfunction and conduction disease.

Hypothesis:
Ethnicity may have significant impact on development of AF in patients with sinus node dysfunction and conduction disease requiring pacemaker.

Methods:
All patients followed at the University of Chicago with a dual-chamber pacemaker implanted between January 2005 to December 2011 and sinus node dysfunction (SND) or high-degree atrio-ventricular block (HGAVB) requiring dual chamber pacemaker were included. Patients were identified retrospectively. Electronic medical records, ECGs, device interrogation data, and procedure notes were examined. Logistic regression analysis was used to evaluate the association of race and device-detected AF incidence, controlling for clinical characteristics and medical comorbidities, including age, gender, HTN, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnea, coronary artery disease (CAD), chronic kidney disease (CKD), and valvular heart disease.

Results:
Three-hundred and twenty-four patients met criteria, including 125 (38%) Caucasians, 173 (53%) African Americans, 7 (2.2%) Hispanics, and 10 (3.1%) Asian-Americans. Average age was 68.9 +/- 14.8, 185 (57%) were female. Chi-squared analysis revealed no significant relationship between race and diabetes, CAD, or valvular disease in this population. Hypertension (p<0.01) and CKD (p=0.02) were associated with race; both were more common in African Americans and Hispanics. In a multivariate analysis, younger age (p=0.01; OR=1.02 (1.005-1.04)), African American race (p=0.03; OR=0.6 (0.3-0.9)), and Asian American race (p=0.04; OR=0.2 (0.03-0.8)) were associated with a decreased risk of device-detected AF.

Conclusions:
African American race was associated with a decreased incidence of AF in patients with continuous monitoring, despite a relatively increased rate of CKD and hypertension in this population. This suggests that racial differences in AF cannot be fully explained by ascertainment bias.
Abstract 21333: Persistent Decreased Survival in Diabetic Subjects With HFrEF Despite Advances in Therapy
Authors: Kamalesh Masoor , Ajam Tarek , Devaraj Srikant , Ajam Samer
Published: March 2022

Background:
With the advancement in diabetic management throughout the years, this study aimed to compare the effect of diabetes mellitus on mortality in patients with heart failure with reduced ejection fraction (HFrEF).

Methods:
The VA’s databases were queried to identify all patients diagnosed with HFrEF from 2007 to 2015. A total of 61,400 diabetic patients were matched to as many non-diabetic patients using propensity score matching with replacement. To estimate the impact of diabetic patients on overall mortality of HFrEF patients, the Cox proportional hazard model was used on the matched sample and adjusted for patient characteristics.

Results:
From the overall sample of 114,010 patients with HFrEF, 61,400 (54%) had diabetes mellitus. On the matched sample, after adjusting for patient characteristics such as age, sex, high beta blocker dose, heart rate quartile, carvedilol, metoprolol, comorbidities, and medications, we found that the diabetic patients were associated with a higher overall mortality compared to non-diabetic patients (HR: 1.50, 95% CI: 1.48-1.53, p<0.001).

Conclusions:
Diabetic HFrEF patients have a higher risk of mortality than non-diabetic HFrEF patients despite controlling for beta blocker dose, medications and comorbidities.
Abstract 21345: Diastolic Blood Pressure is the Predictors of Left Ventricular Myocardial Relaxation in Healthy Postmenopausal Women
Authors: Sekiguchi Haruki , Kimura Makiko , Hagiwara Nobuhisa
Published: March 2022

Introduction:
Previous studies that indicate metabolic syndrome (MetS) might be at risk for left ventricular (LV) diastolic dysfunction. However, little is known about which metabolic factors contribute to the development of LV dysfunction in postmenopausal women without obesity or overweight, diabetes mellitus, and/or cardiovascular disease.

Methods:
Participants without diabetes mellitus, systolic dysfunction, or other heart diseases underwent a thorough physical examination including tissue Doppler echocardiography. A peak early mitral annular velocity (e′) of <5.0 was designated as indicating abnormal LV myocardial relaxation (LVMR). We performed single and multiple logistic regression analyses of e′ and cardiovascular risk factors, including MetS factors and indicators of major organ dysfunction. Normal-weight subjects (body mass index <25 kg/m2) were also analyzed.

Results:
A total of 269 postmenopausal women (mean age, 70 ± 7 years) participated, of which 29 (10.8%) had MetS and 67 (23.8%) had abnormal LVMR. Multiple logistic regression analysis revealed high diastolic blood pressure: DBP (odds ratio [OR] 5.3, 95% confidential interval [CI] 1.89 - 15.0, P < 0.01), abnormal waist circumference (OR 2.4, CI 1.15 - 5.01, P < 0.01) and age (OR 1.1, CI 1.05 - 1.16, P < 0.01) to be predictors of abnormal LVMR. In normal-weight subjects (n = 232), high DBP (OR 5.1, CI 1.65 - 15.89, P < 0.01), and aging (OR 1.1, CI 1.06 - 1.17, P < 0.01) were predictors of abnormal LVMR.

Conclusions:
In postmenopausal women, only diastolic blood pressure was the independent risk factors for abnormal LVMR in both normal-weight and over-weight individuals, and therefore might be useful for predicting diastolic heart failure during routine physical checkups.
Abstract 21350: Outcomes With Steroid-Free Maintenance Immunosuppression After Heart Transplant: Results From the United Network for Organ Sharing Registry
Authors: Wayda Brian , Clemons Autumn , Givens Raymond C , Takeda Koji , Takayama Hiroo , Latif Farhana , Restaino Susan , Naka Yoshifumi , Garan A. Reshad , Yuzefpolskaya Melana , Farr Maryjane A , Colombo Paolo C , Topkara Veli K
Published: March 2022

Background:
Given their adverse effects, there is growing interest in omitting corticosteroids from the initial maintenance immunosuppression (IS) regimen after heart transplant (HT). However, evidence for the efficacy of this strategy is limited.

Hypothesis:
Steroid-free and steroid-containing maintenance regimens are associated with comparable outcomes following HT.

Methods:
We included patients who received HT between July 2004 and April 2014 and were discharged on an initial maintenance regimen with both tacrolimus and mycophenolic acid, with or without corticosteroids, and with no other IS medications. Patients with rejection or graft failure (death or re-transplant) prior to discharge were excluded. Survival analyses compared outcomes between steroid-free and steroid-treated patients, including time from discharge to graft failure, hospitalization, and infection and rejection requiring hospitalization.

Results:
Of 10,080 included patients, 15%, 22%, 11%, and 50% experienced graft failure, infection, rejection, and hospitalization, respectively during the follow-up period (2004 - 2014). Steroid-free regimens were used in 8.2%. Steroid-free patients had lower risks of hospitalization (HR = 0.78, p < 0.0001), infection (HR = 0.56, p < 0.0001), and rejection (HR = 0.66, p = 0.018). There was no significant difference in the risk of graft failure (p = 0.12).

Conclusions:
Steroid-free and steroid-treated patients have comparable graft survival after HT and differ with respect to other selected outcomes. Further research will determine whether this stems from differences in efficacy or patient mix. A steroid-free strategy is likely optimal for selected patients.
Abstract 21364: Multicenter Prospective Study Comparing Phased Multipolar versus Traditional Radiofrequency Ablation
Authors: Azizi Zahra , Verma Atul , Alipour Pouria , Khaykin Yaariv , Leong-Sit Peter , Sarrazin Jean-Francois , Sturmer Marcio , Patterson Sherri , Morillo Carlos , Amit Guy , Roux Jean-Francois , Essebag Vidal
Published: March 2022

Background:
Multipolar, phased radiofrequency (RF) catheter ablation (PVAC) has been associated with reduced procedural times compared to traditional RF. We performed a multicenter study to assess the efficacy and efficiency of using this catheter.

Methods:
This is a multicenter, sequential, prospective, cohort study between 2012 to 2016 in 6 tertiary care centers (NCT01562912). Patients were enrolled if they had symptomatic, paroxysmal AF (less than 7 days) refractory to at least one antiarrhythmic medication. Patients were enrolled in a 2:1 ratio of PVAC (group A) to control point-by-point RF with 3D mapping (group B). ECG and 48 hour Holter monitor were used to assess patients at 3, 6, 9 and 12 months post-ablation follow up. Recurrence was defined as any atrial arrhythmia >30 seconds excluding an initial 3 month blanking period.

Results:
Overall, 230 patients consisting of 162 males (70.4%) with mean age 57±11 years were analyzed. By Kaplan-Meier analysis, freedom from any atrial arrhythmia at 12 months was 49% and 69.2% in group A and B respectively (p=0.033) (Figure1). Among patients with recurrence, 14.7% (21) in group A and 7.7% (6) in group B had redo procedure within 12 month post procedure(p=0.12). Procedure time was significantly lower in Group A than Group B (P<0.0001). There was no significant difference in fluoroscopy time between the two groups (p=0.49). Stroke was not reported in any of the patients. Pulmonary Embolism, occurred in 1.3% of patients in group B. Pericardial effusion occurred in 1.4% in group A and 2.6% in group B. Tamponade occurred in 3.8% of patients in group B.

Conclusion:
This study demonstrated that the PVAC catheter is associated with significantly reduced procedure times for AF ablation, however, AF recurrence rates may be higher than contemporary point-by-point RF ablation with 3D mapping technology.
Abstract 21366: Atrial Fibrillation Adversely Affects Readmission Outcomes for Heart Failure: Observations From the Nationwide Readmissions Database
Authors: Joy Parijat S , Olshansky Brian , Gopinathannair Rakesh
Published: March 2022

Introduction:
Atrial fibrillation(AF) and heart failure (HF) often coexist. Readmissions in HF is a rising concern.

Hypothesis:
AF affects 90-day readmissions following admission for HF.

Methods:
The Nationwide Readmissions Database (NRD) for 2013 was analyzed for the first readmission within 90-days following discharge with a diagnosis of AF and HF. Clinical Classification Software (CCS) from the Health Care Utilization Project (HCUP) was utilized to investigate leading diagnoses and procedures for readmissions. ICD-9-CM codes were used to identify diagnoses not classified in the CCS. All estimates were weighted using the weight variable provided by HCUP for stratified sampling.

Results:
In 2013, 885,270 adults were admitted with a primary diagnosis of HF of which 364,447(41%) had AF. After discharge, 90-day all-cause readmission rates were significantly higher in HF patients with coexisting AF (41% vs 38%, p<0.001). Multivariate regression analysis showed that AF was independently associated with an increased likelihood of 90-day readmission after discharge for HF (OR: 1.18, CI: 1.14-1.21). In HF patients with coexisting AF, the primary readmission diagnoses were HF (36%), renal failure (4%), AF (4%), sepsis (4%) and respiratory failure (3%) and the most common procedures performed were cardioversion (16 %), echocardiogram (12 %), coronary revascularization (7%), blood transfusion (6%) and hemodialysis (5%). Mean length of stay during readmission in patients with and without coexisting AF was 5.0 vs 5.5 days (p<0.000, t-test). Mean cost of readmission during readmission in patients with and without coexisting AF was $8693 vs $9386 (p<0.000, t-test).

Conclusion:
In patients with HF, coexisting AF is associated with higher likelihood of 90-day readmission. Most common causes for such readmissions are decompensated HF, AF and renal failure. Adequately controlled AF may reduce readmissions in HF patients.
Abstract 21376: Apo A-I Mimetic Peptides Inhibit IBD In Multiple Mouse Models
Authors: Meriwether David , Volpe Carmen , Grijalva Victor , Trost Hanah , Mukherjee Pallavi , Martin Martin G , Fogelman Alan M , Reddy Srinivasa T
Published: March 2022

Introduction:
Inflammatory bowel disease (IBD) has been linked to an increased prevalence of early stage vascular disease. ApoA-I mimetic peptides including 4F and Tg6F (6F expressed in tomatoes) are potential therapeutic agents for the treatment of inflammatory diseases. We previously reported that 4F protects against the development of IBD in a COX2-deficient and cholate-dependent mouse model of Crohn’s disease.

Hypothesis:
We sought to determine, a) the mechanism by which 4F inhibits IBD, b) whether 4F is protective in additional mouse models of IBD, and c) whether Tg6F could also protect against IBD.

Methods:
We examined the effects of cholate on changes in barrier permeability and translocation of LPS into portal vein plasma, in COX2-deficient and wild-type mice. We studied the effects of both COX2 and 4F on the pro-inflammatory response of LPS-stimulated macrophages. We investigated the effects of 4F in the IL10
-/-
+ piroxicam model of colitis. Finally, we examined the protective effects of Tg6F in myeloid conditional COX2 KO mice that were challenged with cholate.

Results:
Cholate increased both barrier permeability and the translocation of LPS into portal vein plasma equally in both COX2-deficient and wild-type mice, while only COX2-deficient mice including myeloid COX2-deficient mice subsequently developed IBD. Bone marrow derived macrophages lacking COX2 expressed 10-15 fold higher pro-inflammatory cytokines including IL1-β compared to WT macrophages, when stimulated with LPS. Both pre-treatment and co-treatment of these macrophages with 4F significantly reduced the expression of pro-inflammatory cytokines, returning them to the level of WT. 4F significantly inhibited the development of colitis in IL10
-/-
mice challenged with the COX inhibitor piroxicam, as determined by colon length, colitis score, and H&E score. Furthermore, Tg6F significantly protected against the development of IBD in myeloid COX2 KO mice challenged with cholate, as determined by gross pathology and H&E score.

Conclusions:
4F protects against IBD in the COX2-deficient mouse model, in part, by inhibiting the pro-inflammatory phenotype of COX2-deficient macrophages. Our findings suggest a novel therapeutic role for ApoA-I mimetic peptides including Tg6F in IBD.
Abstract 21379: Transfemoral vs Transapical Transcatheter Aortic Valve Replacement: Analysis Of The Nationwide Inpatient Sample and National Readmission Database From 2011-2014
Authors: Mantha Aditya , Tariq Afnan R
Published: March 2022

Introduction:
Transfemoral (TF) and transapical (TA) techniques for transcatheter aortic valve replacement have been validated in clinical trials. However, the impact of the choice of approach modality on resource utilization, mortality, and readmissions in clinical practice remains unclear.

Methods:
Patients who underwent transcatheter aortic valve replacement (ICD 9: 35.05, 35.06) in the 2011-2014 National Readmission Database (NRD) and the Nationwide Inpatient Sample (NIS) Databases for whom readmission data was available were analyzed. The NRD and NIS are all-payer inpatient databases maintained by the Healthcare Cost and Utilization Project (HCUP) that estimate more than 35 million annual U.S. hospitalizations. Mortality, readmission, and GDP-adjusted cost were evaluated using hierarchical linear models adjusting for socioeconomic, demographic and comorbidity measured by Elixhauser Index.

Results:
38,929 patients underwent TAVR during the study period, 8,643 (22%) received a TA approach while 30,285 (78%) received a TF approach. TA patients were more likely female (52% vs 46%, P<0.001), more likely from ZIP codes with median income below the national median (48% vs 44%, P<0.001), and had higher Elixhauser Index (CI: 6.5 vs 6.1, P<0.001). The TA approach was associated with higher adjusted mortality at discharge (6.7% vs 3.8% OR=1.7, P<0.001), higher cost ($65,591 vs $56,595, β=0.14 , P<0.001), and longer stays (11 vs 8.3 days, IRR=1.28, P<0.001). All-cause readmission was significantly higher in TA patients within 30 days (20% vs 16%, OR=1.27, P<0.001).

Conclusion:
In this study of 38,929 U.S. patients who underwent TAVR from 2011-2014, after adjustment for demographics, comorbidities, and hospital level variation, the TA approach was 14% more expensive, had 27% higher odds of readmission within 30 days, 28% longer length of stay, and 70% greater odds of mortality compared to TF approach. Our findings support the preference for the TF approach where technically feasible.
Abstract 21391: Combined Aerobic and Inspiratory Muscle Training Versus Aerobic Training Alone in Heart Failure: A Meta-Analysis of Randomized Controlled Trials
Authors: Lin Yu-Shan , Wang Li-Ying , Huang Hsin-Yi , Chen Bo-Yan , Hsu Wei-Ning
Published: March 2022

Background:
Abnormal ventilatory response contributes to exercise intolerance in patients with chronic heart failure (CHF). Previous meta-analysis showed that inspiratory muscle training (IMT) is beneficial for improving respiratory muscle strength and functional capacity in patients with CHF. However, whether the combination of IMT and aerobic training (AT) could further improve ventilatory response during exercise in patients with CHF is not clear.

Purpose:
The aim of this meta-analysis was to investigate the effect of IMT in combination with AT on ventilatory response during exercise in patients with CHF.

Methods:
We searched the following electronic databases (from inception to January 2017): PubMed, Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (from January 2000 to January 2017) for relevant literature. We included randomized controlled trials (RCT) that compared IMT+AT with AT in which the outcomes was to assess ventilatory response (peak oxygen uptake and minute ventilation/carbon dioxide production (VE/VCO2) slope), and maximal inspiratory pressure (PImax)) during exercise in patients with CHF. A random-effects model was used for the main analysis.

Results:
Of 63 identified studies, three RCTs with a total of 94 CHF patients met the inclusion criteria. Compared to AT alone, combined IMT and AT significantly increased PImax (mean difference 18.7 cmH2O, 95% CI: 10.2 to 27.2; p<0.0001) but had no effect on peak oxygen uptake (mean difference 0.7; 95% CI: -1.3 to 2.7; p=0.49) or VE/VCO2 slope (mean difference -2.8; 95%CI: -8.1 to 2.6; p=0.31). Subgroup analyses showed intensive inspiratory training makes further improvement in PImax and Minnesota Living with Heart Failure Questionnaire (mean difference -4.22; 95% CI -7.69 to -0.75; p=0.02), irrespective of baseline inspiratory muscle strength and ejection fraction.

Conclusions:
The results showed that in patients with CHF, IMT in combination with AT training could improve respiratory muscle strength but had no impact on ventilatory response during exercise. These findings suggested that the inspiratory muscle insufficiency might not be the main cause for abnormal ventilatory response during exercise in patients with CHF.
Abstract 21395: The One-Stop Trans-Apical Device for Aortic Valvular Disease: 1-Year Results of the Multi-Centre Study on J-Valve System
Authors: Tung Ming Wui , Wang Wei
Published: March 2022

Objectives:
This study presents the first report of multi-centre outcomes of the J-Valve
TM
system with a novel designed positioning element and a two-step positioning mechanism for easy and accurate implantation in patients with AS or AR.

Methods:
This multi-centre, prospective study, conducted at three largest cardiac centers in China, enrolled 107 patients (mean age 74.4 ± 5.18). Preoperative Euro-SCORE was (27.5 ± 8.3%). Clinical and echocardiographic evaluations were performed at baseline, post-procedure, discharge and 30 days, and also at 6 and 12 months.

Results:
TA-TAVI with the J-Valve device was successfully implanted in 98 patients (procedural success rate 93.33%). The overall mortality at 30 days and 12months was 4.7% and 5.0% respectively. Conversion to surgery was necessary in 6 patients (5.6%). Among 58 patients with AS, 12-month follow-up echocardiography demonstrated a favorable reduction of mean transvalvular gradients from 51±17 mmHg to 15±8 mmHg. All patients with completed follow up (n=93) reported improvements in at least one of the NYHA classes. The majority of successfully treated patients remained no or mild paravalvular aortic regurgitation (98.7%); none of the patients had severe post-procedural regurgitation (>2+). The combined ratio of successful implantation without adverse events at 1-year was 85.0%.

Conclusions:
Transapical J-ValveTM implantation was safe and effective in the treatment of patients with AS or AR at high risk for surgery. Excellent hemodynamic performance during the one year follow-up was demonstrated with low incidence of post-operative complications.
Abstract 21407: Effect of Aspiration Thrombectomy on in Hospital Mortality in Patients With ST Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Insights From the U.S National Inpatient Sample Database
Authors: Vuddanda Venkat , Turagam Mohit K. , Yandrapalli Srikanth , Singla Atul , Katta Natraj , Balla Sudarshan
Published: March 2022

Introduction:
Aspiration thrombectomy (AT) during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has been widely used. Recent large multicenter trials have created uncertainty about the benefit of thrombus aspiration and suggested possible harm from increased stroke risk. There is lack of real world data regarding outcomes with AT when performed in addition to PCI of the culprit artery for STEMI.

Hypothesis:
We sought to investigate the effect of AT on in-hospital mortality when performed in addition to culprit artery PCI for STEMI.

Methods:
Using the U.S. National Inpatient Sample (NIS) database from 2007-14, we identified all discharge records with a primary diagnosis of STEMI (ICD-9-CM diagnosis codes 410.XX) undergoing PCI (ICD-9-CM procedure codes 00.66, and 36.0X). Patients receiving AT in addition to PCI during the hospitalization were identified using ICD-9-CM procedure code 36.09, and in-hospital mortality was compared in patients with and without AT. Statistical analyses were performed using R (Vienna, Austria). To account for the single cluster stratified random sampling design of NIS, R survey package was used to obtain national estimates. Proportions were compared with Chi-Square test, and p trend computed using Mann-Kendall test.

Results:
Of 951,322 PCIs for STEMI, 4299 (0.4%) had AT in addition to PCI. Use of AT remained consistent over the study period (0.53% vs. 0.70%; p trend = 0.896). We observed no statistically significant difference in the age adjusted in-hospital mortality in patients with and without AT (3.8% vs. 4.4 %; p = 0.06).

Conclusion:
In this nationally representative study population, aspiration thrombectomy is not associated with improvement in in-hospital mortality when performed in addition to PCI of the culprit artery for STEMI.
Abstract 21411: Coronary Endothelial ROS Protects Cardiac Function
Authors: Colantuono Bonnie , Harrington Elizabeth O , Sellke Frank W , Abid Ruhul
Published: March 2022

Introduction:
Recent findings from our lab demonstrated that modulation of NADPH oxidase-derived ROS for a short period (4 weeks), but not long period (20 weeks), improves coronary endothelial cell proliferation
in vitro
and aortic sprouting angiogenesis
ex vivo
.

Hypothesis:
We hypothesized that whereas short-term increase in endothelial ROS will improve post-MI cardiac function by increased coronary angiogenesis, long-term exposure to ROS will not.

Methods:
Tetracycline (Tet)-ON/Tet-OFF binary transgenic mice, Tet-Nox2:VE-Cad-tTA (Tg-Nox2), were used as a model for endothelium-specific increase in the expression of the catalytic subunit of NADPH oxidase resulting in increased ROS. Tet-ON and Tet-OFF Tg-Nox2 mice that were exposed to 4 weeks (short-term) and 16 weeks (long-term) of increased EC-ROS were subject to LAD ligation.

Results:
We demonstrate that there was an increase in capillary density (by 38± 6.45; p<0.05) and angiogenesis (by 2-fold) in short-term Tg-Nox2 post-MI myocardium but not in long-term Tg-Nox2. Short-term, but not long-term, Tg-Nox2 animals showed reduction in infarct size by Trichrome staining and improvement in cardiac function including EF, LVEDV and LVESV by echocardiography.

Conclusion:
These findings suggest that a short, but not long, exposure to increased EC-ROS play an important role in cardiovascular health and myocardial preservation in the post-MI heart.
Abstract 21421: Identification of Nherf1 as a Regulator of Right Ventricle Cardiomyocyte Hypertrophic Remodeling With Implications for Pulmonary Hypertension
Authors: Kelly Neil , Alhamaydeh Mohammad , Hoyt Alexander , Mutchler Stephanie , Yeung Megan , Baust Jeffrey , Al Ghouleh Imad
Published: March 2022

Introduction & Hypothesis:
The molecular mechanisms underlying right ventricle (RV) hypertrophic remodeling (both adaptive and maladaptive) in response to sustained pressure overload, such as that experienced during pulmonary hypertension (PH), are inadequately understood. Our previous work demonstrating a role for the cytosolic organizer protein p47
phox
in pressure overload-induced RV hypertrophy and our recent publication on a direct interaction between p47
phox
and ERM-binding cytoskeletal protein Nherf1 lead us to hypothesize that Nherf1 is a regulator of RV cardiomyocyte hypertrophy.

Methods & Results:
Cardiomyocyte-derived H9C2 cells and RV rat neonatal cardiomyocytes isolated from 1-day-old pup hearts (RV-RNCM) were subjected to neurohormonal hypertrophic stimulation using angiotensin II (AngII, 1 & 10 μM). RV pressure overload was induced in mice by pulmonary artery banding (PAB; 3wk). AngII treatment resulted in H9C2 and RV-RNCM hypertrophy and induced Nherf1 protein expression. The AngII-induced hypertrophy was attenuated by Nherf1 gene knockdown using siRNA. Moreover, Co-IP studies revealed an Nherf1-p47
phox
association in H9C2 cells that is enhanced by pro-hypertrophic AngII-treatment. Sequential loss of function strategies educated by novel
in silico
gene network analyses of PH gene intersected with cardiomyopathy gene networks, combined with a careful consideration of our previous findings and the literature, identified potential involvement of Hippo pathway transcriptional co-activators Yap/Taz, water channel aquaporin1 (Aqp1), and apoptosis signal-regulating kinase 1 (Ask1) in this pathway.
In vitro
, co-IP studies revealed a Nherf1-Yap association and interruption of Ask1 or Aqp1 reduced AngII-induced cardiomyocyte cellular hypertrophy.
In vivo
, PAB induced an increase in Nherf1 expression and association with p47
phox
.

Conclusion:
The present study supports a new role for Nherf1 in mediating pro-hypertrophic cardiomyocyte cellular responses and implicates a molecular network previously not connected to either the RV or Nherf1. These data identify potential therapeutic targets for RV dysfunction in PH and shed light on novel molecular mechanisms so far untested in the pressure overloaded right heart.
Abstract 23071: Hydroquinidine Abolishes Life-threatening Arrhythmic Events in Patients With Short QT Syndrome
Authors: Mazzanti Andrea , Maragna Riccardo , Vacanti Gaetano , Kostopoulou Anna , Marino Maira , Monteforte Nicola , Bloise Raffaella , Pagan Eleonora , Napolitano Carlo , Bagnardi Vincenzo , Priori Silvia G.
Published: March 2022

Background:
Short QT Syndrome (SQTS) is one of the rarest and most lethal inherited arrhythmogenic syndromes. Preliminary data have shown that hydroquinidine (HQ) is effective in prolonging the duration of QT interval and in preventing the induction of ventricular arrhythmias during programmed electrical stimulation in SQTS patients. No data exist regarding the efficacy of HQ in reducing cardiac events in SQTS patients.

Objective:
To determine whether HQ reduces the occurrence of Life-threatening Arrhythmic Events (LAE), defined as aborted cardiac arrest and sudden cardiac death, in SQTS patients.

Methods:
Cohort study on consecutive SQTS patients referred to our center and treated with HQ. The endpoint was to evaluate the antiarrhythmic efficacy of HQ, by comparing the percentage of patients with LAE, the number of LAE per patient and the annual rate of LAE before and after the beginning of therapy with HQ (mean duration of therapy 6±1 years).

Results:
The study population was comprised of 17 SQTS patients with the following characteristics: 13 (76%) males, age at beginning of therapy with HQ 29±3 years, QTc interval before treatment 331±3 ms. Therapy with HQ was ceased in 2 cases (12%) after 1 week due to gastrointestinal intolerance, while in the remaining 15 patients HQ was administered continuously for 6±1 years, at an average dose of 528±42 mg per day (7±0.6 mg/kg/day). HQ significantly prolonged the QTc interval in all patients, by a mean of 60±6 ms (p<0.001). HQ reduced to zero the percentage of patients with LAE (from 40% to 0%, p=0.03), the mean number of LAE per patient (from 0.73±0.3 to 0, p=0.026) and the annual rate of LAE (from 12.2% to 0%, p=0.028).

Conclusions:
We showed for the first time that HQ, besides normalizing the duration of the QT interval, is associated with a major reduction of life-threatening arrhythmic events in SQTS patients, thus representing an efficacious therapeutic approach in this group of individuals. Early discontinuation due to gastrointestinal intolerance occurred in 12% of patients.
Abstract 23072: Unrecognized Venous Injuries After Cardiac Implantable Electronic Device Transvenous Lead Extraction
Authors: Tarakji Khaldoun , Saliba Walid , Markabawi Danny , Rodriguez E Rene , Krauthammer Yoaav , Brunner Michael , Hussein Ayman , Baranowski Bryan , Cantillon Daniel , Kanj Mohamed , Niebauer Mark , Rickard John , Callahan Thomas , Shao Mingyuan , Martin David , Wazni Oussama , Wilkoff Bruce , Tan Carmela
Published: March 2022

Background:
Major complication rate of transvenous lead extraction (TLE) is estimated around 1-2.0%. Laceration of the central veins can be fatal.

Objectives:
to define the incidence and extent of venous injuries on a microscopic level after TLE and compare it with the incidence of clinically documented events of venous laceration.

Methods:
We studied all patients who underwent TLE at our tertiary center within 30 months via a variety of techniques. Extracted leads and tissue around them were fixed in formalin. Pathologic examination was standardized to examine the leads identifying the areas covered by tissue cuffs along the length of the lead. The cuffs were removed and sectioned transversely to their longitudinal axis. Microscopic examination was performed using H&E and Movat stains to identify the presence of vein tissue.

Results:
Four hundred sixty one patients (63±15 years) had a total of 861 leads extracted (585 pace/sense and 272 defibrillator leads) with an average of 1.9 leads per patient and a median lead age of 2,546 days. Upon microscopic review, 80 leads (9.3%) in 72 out of the total 461 patients (15.6%) demonstrated segments of vein, the majority of which were transmural (Venous tissue including adventitia). Despite this finding, only five (1.1%) catastrophic complications occurred that required emergent surgical intervention. Risk factors for venous injury included ICD lead, age of lead, and the use of laser sheath.

Conclusions:
Microscopic venous injuries during lead extraction are common but often not recognized clinically.
Abstract 23075: Machine Learning Outperformed ACC/AHA Pooled Cohort Equations Risk Calculator for Detection of High-Risk Asymptomatic Individuals and Recommending Treatment for Prevention of Cardiovascular Events in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Kakadiaris Ioannis , Vrigkas Michalis , Budoff Matthew , Yen Albert , Naghavi Morteza
Published: March 2022

Background:
Studies have shown that the status quo for atherosclerotic cardiovascular disease (ASCVD) prediction in the U.S. - using ACC/AHA Pooled Cohort Equations Risk Calculator - is inaccurate and results in overtreatment of low-risk and undertreatment of high-risk individuals. Machine Learning (ML) is poised to revolutionize healthcare. We used ML to develop a new ASCVD risk calculator and tackled the problem.

Methods:
We developed a ML Risk Calculator using the latest 13-year follow up dataset from MESA (Multi-Ethnic Study of Atherosclerosis) of 6,814 participants who were free of clinical CVD at baseline. We gave identical input to both calculators and compared their accuracy for recommending statin to 5,415 subjects (age 60.6 ± 9.7 years; 47.3% males) who were not on lipid lowering treatment at baseline.

Results:
Over 13 years, 775 (14.3%) “All CVD” and 381 (7.0%) “Hard CVD” events occurred. According to ACC/AHA Risk Calculator and a 7.5% 10-year risk threshold for treatment, 42.9% would be recommended to take statin. Despite the high proportion recommended for statin treatment, 25.7% of “Hard CVD” and 26.3% of “All CVD” events occurred in those not recommended statin, resulting in sensitivity (Sn) 0.74, specificity (Sp) 0.60, and AUC 0.72 for “Hard CVD” and Sn 0.73, Sp 0.62, and AUC 0.73 for “All CVD”. In sharp contrast, the ML Risk Calculator recommended only 10.6% to take statin, and only 15.0% of “Hard CVD” and 4.9% of “All CVD” events occurred in those not recommended statin, resulting in Sn 0.84, Sp 0.95, and AUC 0.92 for “Hard CVD” and Sn 0.95, Sp 0.88, and AUC 0.95 for “All CVD”.

Conclusions:
ML clearly outperformed the ACC/AHA Risk Calculator by recommending less drug therapy and missing fewer events. Further studies are underway to validate these findings in other cohorts. As we introduce our ML model to more data particularly to cases in which events occurred weeks or months following data collection instead of years, short-term risk prediction may be possible.
Abstract 23082: Gemcabene Add-On Therapy to High- and Moderate-Intensity Statin Stratums in Hypercholesterolemic Subjects (ROYAL-1, a Phase 2b Study)
Authors: Frias Juan , Kastelein John , Bakker-Arkema Rebecca , Masson Liz , Golden Lee , Bisgaier Charles , Stein Evan
Published: March 2022

Introduction:
Recent large cardiovascular event outcome trials with ezetimibe and a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to statins demonstrated benefit from additional LDL-C reduction. Despite availability of approved injectable PCSK9 inhibitors, there still remains a need for novel, efficacious, safe, well-tolerated, and cost-effective oral LDL-C lowering therapies. Gemcabene (GEM) has been shown to significantly lower LDL-C, non-HDL-C, ApoB, and hsCRP further in hypercholesterolemic subjects when added to background statin therapy. GEM neither interacts pharmacokinetically nor has shown increased adverse effects with statins.

Hypothesis:
GEM added to high- or moderate-intensity statin +/-ezetimibe therapy will provide additional LDL-C reduction for subjects not at goal.

Methods:
High-risk subjects including those with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease on appropriate diet and stable statin therapy for at least 12 weeks and LDL-C ≥ 100 mg/dL (2.59 mmol/L) and triglycerides < 500 mg/dL (5.65 mmol/L) were randomized into a 12-week, placebo-controlled, parallel-group, double-blind study to assess the efficacy of GEM 600 mg QD on LDL-C and other lipoproteins and hsCRP. Safety and tolerability were evaluated. The subjects were stratified by high- or moderate-intensity statin therapy, with or without ezetimibe, with a target of 52 subjects (26 GEM; 26 placebo) in each stratum. The study (NCT02634151) enrolled 105 subjects (53% women, 77% Caucasian, mean age 61 years). Mean baseline LDL-C for all subjects was approximately 134 mg/dL (3.48 mmol/L) with most subjects in the high-intensity statin stratum on atorvastatin and most subjects in the moderate-intensity stratum on either simvastatin or atorvastatin.

Results:
Data for the full cohort was previously reported. Data by statin-intensity stratum (high and moderate) including LDL-C, non-HDL-C, ApoB, Lp(a) and hsCRP as well as safety and tolerability will now be reported.

Conclusion:
The trial and data analysis by statin-intensity stratification, including efficacy and safety, will be completed in October 2017 in time for presentation at the American Heart Association Scientific Sessions.
Abstract 23084: Marked Global Variability in Cost Effectiveness of Lipid-Lowering and Combination Antihypertensive Therapies in Primary Prevention: Analyses of the HOPE-3 Trial
Authors: Lamy Andre , Tong Wesley , Lonn Eva , Swaminathan Balakumar , Jung Hyejung , Bosch Jackie , Yusuf Salim ,   on behalf of the HOPE-3 Investigators
Published: March 2022

Background:
The Heart Outcomes Prevention Evaluation (HOPE) - 3 trial demonstrated that low dose lipid-lowering medication alone or with an angiotensin receptor blocker (ARB)+ thiazide resulted in a significantly lower risk of cardiovascular events compared to placebo in intermediate risk persons without cardiovascular disease. Since use of these medications in primary prevention could have significant cost implication, we report the cost analysis of the HOPE-3 trial.

Methods:
Hospitalization events, procedures, medications and study drugs were extracted for each patient. We applied country-specific costs to healthcare resources consumed for each patient. We calculated average cost per patient for the length of the study (median follow-up 5.6 years). Costs are reported in US dollars and discounted at 3% per year. The costs of the study drugs vary considerably between countries and we use the most locally affordable (generic) lipid-lowering medication and ARB + diuretic combination.

Results:
In most regions, use of lipid-lowering medication in combination with antihypertensive drugs in HOPE-3 was cost-neutral or cost-saving as the cost of these medications was offset by savings in other costs (events, procedures, and usual medications). Surprisingly, in India and China, the cost of these medications is the main component of overall health expenditures, being more expensive than all other costs.

Conclusions:
The use of lipid-lowering medication alone or with antihypertensives agents is cost-saving in most regions by providing significant clinical benefit to intermediate risk persons without cardiovascular disease. Prices for these generic drugs in India and particularly in China are high relative to other costs and policies to reduce the prices of these are needed to ensure that generics are more affordable. Primary prevention using lipid-lowering medication and antihypertensive agents would be cost-neutral or cost-saving worldwide.
Abstract 23085: 30-Day Outcomes of Transseptal Transcatheter Mitral Valve Replacement for Failed Surgical Bioprostheses (Mitral Valve-in-Valve): The MITRAL Trial (Mitral Implantation of TRAnscatheter vaLves)
Authors: Guerrero Mayra , Pursnani Amit , Salinger Michael , Wang Dee Dee , Kodali Susheel , George Isaac , Hahn Rebecca T , Satler Lowell , Inglessis Ignacio , Eleid Mackram , Meduri Christopher , Rajagopal Vivek , Reisman Mark , Aldea Gabriel , Eng Marvin , Waksman Ron , Pichard Augusto , Palacios Igor , Russell Hyde M , Saucedo Jorge , Kar Saibal , Makkar Raj , O'Neill William , Rihal Charanjit , Leon Martin , Feldman Ted
Published: March 2022

Introduction:
Transcatheter mitral valve replacement (TMVR) using aortic transcatheter heart valves (THV) is developing as an alternative to surgery for patients with severely degenerated mitral valve (MV) bioprostheses. Retrospective self-reported registries have collected outcomes on these TMVR procedures in the STS/ACC Transcatheter Valve Therapy Registry and in the Valve-in-Valve International Database. Most reported TMVR procedures for failed surgical bioprostheses have been performed using a transapical access approach. A prospective comprehensive evaluation of mitral Valve-in-Valve (VIV) outcomes, including transseptal access has not previously been conducted.

Objectives:
To evaluate in-hospital and 30-day clinical outcomes of transseptal mitral VIV with SAPIEN 3 THV in patients with very high surgical risk.

Methods:
Prospective enrollment of very high surgical risk patients with symptomatic severely degenerated MV surgical bioprostheses in 30 patients at 15 sites in the U.S. Candidates were assessed by a case review committee prior to approval. Baseline qualifying echocardiograms and cardiac CT studies were analyzed by independent core labs. Echocardiograms, cardiac CT studies and neurology evaluations were also performed after mitral VIV procedures. Clinical events were adjudicated by a clinical events committee and safety was monitored by a data safety monitoring board.

Results:
26 patients have been enrolled between July 2016 and June 2017. Mean age was 83 years, 62% female, mean STS score was 10% and 62% were in New York Heart Association class III or IV. Transseptal access was used in all procedures. Technical success was achieved in all patients and there was no in-hospital mortality. There was no 30-day cardiovascular mortality and 4% (1 patient) 30-day all-cause mortality (1 patient died of asphyxia on day 29 after choking on pills at home), which was lower than the 30-day mortality in the TVT registry (9%). Detailed procedural, in-hospital and 30-day outcomes will be presented on the complete cohort of 30 patients.

Conclusions:
In patients without surgical alternatives, transseptal mitral ViV procedures in failed surgical bioprostheses are associated with high technical and procedural success and low 30-day mortality.
Abstract 23086: Impact of Rivaroxaban Alone or in Combination With Aspirin versus Aspirin in Preventing Graft Occlusion in Patients With CABG Surgery COMPASS CABG
Authors: Lamy Andre , Eikelboom John , Connolly Stuart , Bosch Jackie , Fox Keith A , Yusuf Salim ,   COMPASS Steering Committee and Investigators
Published: March 2022

Background:
Coronary artery bypass grafting (CABG) surgery reduces mortality in patients with severe ischemic heart disease. Patients with recent CABG surgery are at risk for early graft failure which is associated with an increased risk of myocardial infarction (MI) and death. Aspirin reduces the risk of graft failure and major adverse cardiovascular events (MACE) in patients with CABG, but is only modestly effective. We hypothesized that in patients with recent CABG surgery, rivaroxaban in combination with aspirin or rivaroxaban alone would be more effective than aspirin alone for the prevention of bypass graft failure.

Methods:
COMPASS CABG was designed to evaluate whether rivaroxaban 2.5mg twice-daily in combination with aspirin 100mg daily or rivaroxaban 5mg twice-daily is superior to aspirin 100mg daily for prevention of bypass graft failure and vascular events in patients with recent CABG surgery. The primary outcome was graft failure and the secondary outcome was a composite of MI, stroke, or CV death. Graft patency was assessed with a CT angiogram at 1 year after surgery.

Results:
Between March 2013 and May 2016, the COMPASS trial randomized 27,395 patients from 602 centers in 33 countries. Of these patients, 1,488 were randomized within 4-14 days after CABG surgery. Elective CABG was performed in 78.4% of these patients. Triple vessel disease was present in 77.8% of patients, double vessel disease in 17.1% and 24.1% of patients had a left main disease. The IMA was harvested as a pedicle in 70.9% of patients and with a skeletonized technique in 29.1%. Vein grafts were harvested in an open fashion in 87.8% of patients and with a minimally invasive approach in 12.2% of patients.

Conclusion:
The results of COMPASS CABG will be presented on the efficacy and safety of rivaroxaban, alone or in combination with aspirin on graft patency and MACE in the long-term management of patients with recent CABG surgery.
Abstract 23088: GLP-1 Loading During Percutaneous Coronary Intervention (GOLD PCI) trial
Authors: Giblett Joel P , Clarke Sophie , McCormick Liam M , Zhao Tian , Braganza Denise , Densem Cameron G , O'Sullivan Michael , West Nick E , Hoole Stephen P
Published: March 2022

Introduction:
Glucagon-like peptide 1 (7-36) amide (GLP-1) is an incretin hormone, which has been shown to protect against non-lethal cardiac ischemia-reperfusion injury. We sought to investigate whether GLP-1 protected against PCI-induced myocardial infarction (PMI) and attenuate cardiac troponin I (cTnI) release after elective PCI.

Methods:
A double-blind, randomised, placebo-control trial, stratified for diabetes mellitus, conducted in a single UK centre, administered an intravenous infusion of GLP-1 (1.2pmol/Kg/min) or saline to patients approximately 30-minutes before elective PCI. The primary endpoint was PMI defined as a cTnI elevation > 5xURL at 6-hours post-PCI. Secondary endpoints include, intra-procedural chest pain, TIMI flow and blush grade after PCI, rise in cTnI elevation and creatinine at 6-hours post-PCI and major adverse cardiovascular and cerebrovascular events (MACCE) at six months.

Results:
A CONSORT diagram for the study is shown in Figure 1. Of the 192 patients randomized, 152 (79%) were male, mean age 68.1±8.9 years. Patient demographics were similar between the groups. There was no inter-group difference in the incidence of PMI: GLP-1 9 (9.8%) vs. saline 8 (8.3%), p=0.28. Median [IQR] cTnI elevation between the groups was also similar: GLP-1 20 [0-88.5] vs. saline 10 [0-58.5] ng/L, p=0.28. Renal function was not impaired at 6 hours. Δ Creatinine was not significantly different. (GLP-1 -2.78±9.04 vs. saline -1.75±8.74 μmol/L, p=0.73). Other secondary end-point data will be available at time of presentation.

Conclusion:
GLP-1 did not confer cardioprotection against PMI after elective PCI, although the incidence of PMI in contemporary PCI is low.